Chemical Senses by Alexandros G. Sfakianakis: Μαρτίου 2017

Τρίτη 28 Μαρτίου 2017

On the Communicative Function of Body Odors.

On the Communicative Function of Body Odors.

Perspect Psychol Sci. 2017 Mar;12(2):306-324

Authors: de Groot JH, Semin GR, Smeets MA

Abstract
Humans use multiple senses to navigate the social world, and the sense of smell is arguably the most underestimated one. An intriguing aspect of the sense of smell is its social communicative function. Research has shown that human odors convey information about a range of states (e.g., emotions, sickness) and traits (e.g., individuality, gender). Yet, what underlies the communicability of these states and traits via smell? We fill this explanatory gap with a framework that highlights the dynamic and flexible aspects of human olfactory communication. In particular, we explain how chemical profiles, associative learning (i.e., the systematic co-occurrence of chemical profiles with state- or trait-related information), and top-down contextual influences could interact to shape human odor perception. Our model not only helps to integrate past research on human olfactory communication but it also opens new avenues for future research on this fascinating, yet to date poorly understood, field.

PMID: 28346117 [PubMed - in process]

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Calcium Homeostasis Modulator 1-Like Currents in Rat Fungiform Taste Cells Expressing Amiloride-Sensitive Sodium Currents.

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Calcium Homeostasis Modulator 1-Like Currents in Rat Fungiform Taste Cells Expressing Amiloride-Sensitive Sodium Currents.

Chem Senses. 2017 Mar 10;:

Authors: Bigiani A

Abstract
Salt reception by taste cells is still the less understood transduction process occurring in taste buds, the peripheral sensory organs for the detection of food chemicals. Although there is evidence suggesting that the epithelial sodium channel (ENaC) works as sodium receptor, yet it is not clear how salt-detecting cells signal the relevant information to nerve endings. Taste cells responding to sweet, bitter, and umami substances release ATP as neurotransmitter through a nonvesicular mechanism. Three different channel proteins have been proposed as conduit for ATP secretion: pannexin channels, connexin hemichannels, and calcium homeostasis modulator 1 (CALHM1) channels. In heterologous expression systems, these channels mediate outwardly rectifying membrane currents with distinct biophysical and pharmacological properties. I therefore tested whether also salt-detecting taste cells were endowed with these currents. To this aim, I applied the patch-clamp techniques to single cells in isolated taste buds from rat fungiform papillae. Salt-detecting cells were functionally identified by exploiting the effect of amiloride, which induces a current response by shutting down ENaCs. I looked for the presence of outwardly rectifying currents by using appropriate voltage-clamp protocols and specific pharmacological tools. I found that indeed salt-detecting cells possessed these currents with properties consistent with the presence, at least in part, of CALHM1 channels. Unexpectedly, CALHM1-like currents in taste cells were potentiated by known blockers of pannexin, suggesting a possible inhibitory action of this protein on CALMH1. These findings indicate that communication between salt-detecting cells and nerve endings might involve ATP release by CALMH1 channels.

PMID: 28334404 [PubMed - as supplied by publisher]

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Sweetener Intake by Rats Selectively Bred for Differential Saccharin Intake: Sucralose, Stevia, and Acesulfame Potassium.

Sweetener Intake by Rats Selectively Bred for Differential Saccharin Intake: Sucralose, Stevia, and Acesulfame Potassium.

Chem Senses. 2017 Mar 15;:

Authors: Dess NK, Dobson K, Roberts BT, Chapman CD

Abstract
Behavioral responses to sweeteners have been used to study the evolution, mechanisms, and functions of taste. Occidental low and high saccharin consuming rats (respectively, LoS and HiS) have been selectively outbred on the basis of saccharin intake and are a valuable tool for studying variation among individuals in sweetener intake and its correlates. Relative to HiS rats, LoS rats consume smaller amounts of all nutritive and nonnutritive sweeteners tested to date, except aspartame. The lines also differ in intake of the commercial product Splenda; the roles of sucralose and saccharides in the difference are unclear. The present study extends prior work by examining intake of custom mixtures of sucralose, maltodextrin, and sugars and Splenda by LoS and HiS rats (Experiment 1A-1D), stevia and a constituent compound (rebaudioside A; Experiment 2A-2E), and acesulfame potassium tested at several concentrations or with 4 other sweeteners at one concentration each (Experiment 3A-3B). Results indicate that aversive side tastes limit intake of Splenda, stevia, and acesulfame potassium, more so among LoS rats than among HiS rats. In addition, regression analyses involving 5 sweeteners support the idea that both sweetness and bitterness are needed to account for intake of nonnutritive sweeteners, more so among LoS rats. These findings contribute to well developed and emerging literatures on sweetness and domain-general processes related to gustation.

PMID: 28334357 [PubMed - as supplied by publisher]

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An Examination of the Role of L-Glutamate and Inosine 5'-Monophosphate in Hedonic Taste-Guided Behavior by Mice Lacking the T1R1 + T1R3 Receptor.

An Examination of the Role of L-Glutamate and Inosine 5'-Monophosphate in Hedonic Taste-Guided Behavior by Mice Lacking the T1R1 + T1R3 Receptor.

Chem Senses. 2017 Mar 17;:

Authors: Blonde GD, Spector AC

Abstract
The heterodimeric T1R1 + T1R3 receptor is considered critical for normal signaling of L-glutamate and 5'-ribonucleotides in the oral cavity. However, some taste-guided responsiveness remains in mice lacking one subunit of the receptor, suggesting that other receptors are sufficient to support some behaviors. Here, mice lacking both receptor subunits (KO) and wild-type (WT, both n = 13) mice were tested in a battery of behavioral tests. Mice were trained and tested in gustometers with a concentration series of Maltrin-580, a maltodextrin, in a brief-access test (10-s trials) as a positive control. Similar tests followed with monosodium glutamate (MSG) with and without the ribonucleotide inosine 5'-monophosphate (IMP), but always in the presence of the epithelial sodium channel blocker amiloride (A). Brief-access tests were repeated following short-term (30-min) and long-term (48-h) exposures to MSG + A + IMP and were also conducted with sodium gluconate replacing MSG. Finally, progressive ratio tests were conducted with Maltrin-580 or MSG + A + IMP, to assess appetitive behavior while minimizing satiation. Overall, MSG generated little concentration-dependent responding in either food-restricted WT or KO mice, even in combination with IMP. However, KO mice licked less to the amino acid stimuli, a measure of consummatory behavior in the brief-access tests. In contrast, both groups initiated a similar number of trials and had a similar breakpoint in the progressive ratio task, both measures of appetitive (approach) behavior. Collectively, these results suggest that while the T1R1 + T1R3 receptor is necessary for consummatory responding to MSG (+IMP), other receptors are sufficient to maintain appetitive responding to this "umami" stimulus complex in food-restricted mice.

PMID: 28334294 [PubMed - as supplied by publisher]

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Functional and Nonfunctional Forms of CquiOR91, an Odorant Selectivity Subunit of Culex quinquefasciatus.

Functional and Nonfunctional Forms of CquiOR91, an Odorant Selectivity Subunit of Culex quinquefasciatus.

Chem Senses. 2017 Mar 03;:

Authors: Hughes DT, Pelletier J, Rahman S, Chen S, Leal WS, Luetje CW

Abstract
In Culex quinquefasciatus, CquiOR91 is the ortholog of 2 larvae-specific odorant receptors (ORs) from Anopheles gambiae (Agam\Or40, previously shown to respond to several odorant ligands including the broad-spectrum repellent N,N-diethyl-3-methylbenzamide, DEET) and Aedes aegypti (Aaeg\Or40). When we cloned full-length CquiOR91 from a Culex quinquefasciatus larval head RNA sample, we found 2 alleles of this OR, differing at 9 residues. Functional analysis using the Xenopus oocyte expression system and 2-electrode voltage clamp electrophysiology revealed one allele (CquiOR91.1) to be nonfunctional, whereas the other allele (CquiOR91.2) was functional. Receptors formed by CquiOR91.2 and Cqui\Orco responded to (-)-fenchone, (+)-fenchone, and DEET, similar to what has been reported for Agam\Or40. We also identified 5 novel odorant ligands for the CquiOR91.2 + Cqui\Orco receptor: 2-isobutylthiazole, veratrole, eucalyptol, d-camphor, and safranal, with safranal being the most potent. To explore possible reasons for the lack of function for CquiOR91.1, we generated a series of mutant CquiOR91.2 subunits, in which the residue at each of the 9 polymorphic residue positions was changed from what occurs in CquiOR91.2 to what occurs in CquiOR91.1. Eight of the 9 mutant versions of CquiOR91.2 formed functional receptors, responding to (-)-fenchone. Only the CquiOR91.2 Y183C mutant was nonfunctional. The reverse mutation (C183Y) conferred function on CquiOR91.1 , which became responsive to (-)-fenchone and safranal. These results indicate that the "defect" in CquiOR91.1 that prevents function is the cysteine at position 183.

PMID: 28334229 [PubMed - as supplied by publisher]

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Comparative Study of Chemosensory Organs of Shrimp From Hydrothermal Vent and Coastal Environments.

Comparative Study of Chemosensory Organs of Shrimp From Hydrothermal Vent and Coastal Environments.

Chem Senses. 2017 Feb 22;:

Authors: Zbinden M, Berthod C, Montagné N, Machon J, Léger N, Chertemps T, Rabet N, Shillito B, Ravaux J

Abstract
The detection of chemical signals is involved in a variety of crustacean behaviors, such as social interactions, search and evaluation of food and navigation in the environment. At hydrothermal vents, endemic shrimp may use the chemical signature of vent fluids to locate active edifices, however little is known on their sensory perception in these remote deep-sea habitats. Here, we present the first comparative description of the sensilla on the antennules and antennae of 4 hydrothermal vent shrimp (Rimicaris exoculata, Mirocaris fortunata, Chorocaris chacei, and Alvinocaris markensis) and of a closely related coastal shrimp (Palaemon elegans). These observations revealed no specific adaptation regarding the size or number of aesthetascs (specialized unimodal olfactory sensilla) between hydrothermal and coastal species. We also identified partial sequences of the ionotropic receptor IR25a, a co-receptor putatively involved in olfaction, in 3 coastal and 4 hydrothermal shrimp species, and showed that it is mainly expressed in the lateral flagella of the antennules that bear the unimodal chemosensilla aesthetascs.

PMID: 28334209 [PubMed - as supplied by publisher]

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The Impact of Pregnancy on Taste Function.

The Impact of Pregnancy on Taste Function.

Chem Senses. 2017 Feb 23;:

Authors: Choo E, Dando R

Abstract
It is common for women to report a change in taste (for instance an increased bitter or decreased sweet response) during pregnancy, however specifics of any variation in taste with pregnancy remain elusive. Here we review studies of taste in pregnancy, and discuss how physiological changes occurring during pregnancy may influence taste signaling. We aim to consolidate studies of human pregnancy and "taste function" (studies of taste thresholds, discrimination, and intensity perception, rather than hedonic response or self-report), discussing differences in methodology and findings. Generally, the majority of studies report either no change, or an increase in threshold/decrease in perceived taste intensity, particularly in the early stages of pregnancy, suggesting a possible decrease in taste acuity when pregnant. We further discuss several non-human studies of taste and pregnancy that may extend our understanding. Findings demonstrate that taste buds express receptors for many of the same hormones and circulating factors that vary with pregnancy. Circulating gonadal hormones or other contributions from the endocrine system, as well as physiological changes in weight and immune response could all bear some responsibility for such a modulation of taste during pregnancy. Given our growing understanding of taste, we propose that a change in taste function during pregnancy may not be solely driven by hormonal fluctuations of progesterone and estrogen, as many have suggested.

PMID: 28334158 [PubMed - as supplied by publisher]

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Corrigendum.

Corrigendum.

Chem Senses. 2017 Feb 21;:

Authors:

PMID: 28334146 [PubMed - as supplied by publisher]

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The Effect of Stimulus Duration on the Nostril Localization of Eucalyptol.

The Effect of Stimulus Duration on the Nostril Localization of Eucalyptol.

Chem Senses. 2017 Feb 20;:

Authors: Frasnelli J, Gingras-Lessard F, Robert J, Steffener J

Abstract
The trigeminal system is a chemosensory system participating in the perception of most odorants, which allows for the perception of diverse sensations including the freshness of eucalyptus or the spiciness of pepper. The lateralization task, that is, the identification of the stimulated nostril in a monorhinal stimulation paradigm is only possible following trigeminal stimulation and allows therefore for the assessment of the trigeminal sensitivity also in a clinical setting. In this study, we aimed to determine the effects of the duration of stimuli on the lateralization task. To this end, we asked 32 young and healthy subjects perform the lateralization task while being exposed to eucalyptol stimuli ranging between 100 and 1250 ms. We found that participants performed on average at chance for stimuli shorter than 500 ms, and observed increasing accuracy for stimuli with longer durations. In conclusion, these data suggest that 500 ms represents a threshold for the lateralization of eucalyptol stimuli. Therefore, when trigeminal sensitivity is tested in a clinical setting, eucalyptol stimuli should have a duration of at least 500 ms.

PMID: 28334125 [PubMed - as supplied by publisher]

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Phantom Smells: Prevalence and Correlates in a Population-Based Sample of Older Adults.

Phantom Smells: Prevalence and Correlates in a Population-Based Sample of Older Adults.

Chem Senses. 2017 Feb 20;:

Authors: Sjölund S, Larsson M, Olofsson JK, Seubert J, Laukka EJ

Abstract
Loss of olfactory function is common in old age, but evidence regarding qualitative olfactory dysfunction in the general older population is scarce. The current study investigates the prevalence and correlates of phantom smell experiences (phantosmia) in a population-based study (Swedish National Study on Aging and Care in Kungsholmen [SNAC-K]) of Swedish adults (n = 2569) aged between 60 and 90 years. Phantosmia was assessed through a standardized interview and defined as reporting having experienced an odor percept in the absence of any stimuli in the surrounding environment that could emit the odor. The relationships between phantosmia and demographic, genetic, health-related, and behavioral variables were analyzed with hierarchical logistic regression analyses. The overall prevalence of phantom smells was 4.9%, and was associated with female gender, carrying the met allele of the BDNF gene, higher vascular risk burden, and reporting distorted smell sensations (parosmia). Olfactory dysfunction was, however, not related to phantosmia. The most frequently reported phantom smell was smoky/burnt. A novel finding was that some individuals reported phantom smells with an autobiographical connotation. The results from this study indicate that the prevalence of phantosmia in the general older population is not negligible and that some factors that are beneficial for preserved olfactory function, such as female gender and the BDNF met allele, are also associated with the occurrence of phantom smells.

PMID: 28334095 [PubMed - as supplied by publisher]

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Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration.

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Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration.

Cell Stem Cell. 2017 Mar 13;:

Authors: Ambrosi TH, Scialdone A, Graja A, Gohlke S, Jank AM, Bocian C, Woelk L, Fan H, Logan DW, Schürmann A, Saraiva LR, Schulz TJ

Abstract
Aging and obesity induce ectopic adipocyte accumulation in bone marrow cavities. This process is thought to impair osteogenic and hematopoietic regeneration. Here we specify the cellular identities of the adipogenic and osteogenic lineages of the bone. While aging impairs the osteogenic lineage, high-fat diet feeding activates expansion of the adipogenic lineage, an effect that is significantly enhanced in aged animals. We further describe a mesenchymal sub-population with stem cell-like characteristics that gives rise to both lineages and, at the same time, acts as a principal component of the hematopoietic niche by promoting competitive repopulation following lethal irradiation. Conversely, bone-resident cells committed to the adipocytic lineage inhibit hematopoiesis and bone healing, potentially by producing excessive amounts of Dipeptidyl peptidase-4, a protease that is a target of diabetes therapies. These studies delineate the molecular identity of the bone-resident adipocytic lineage, and they establish its involvement in age-dependent dysfunction of bone and hematopoietic regeneration.

PMID: 28330582 [PubMed - as supplied by publisher]

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Olfactory function and the social lives of older adults: a matter of sex.

Olfactory function and the social lives of older adults: a matter of sex.

Sci Rep. 2017 Mar 22;7:45118

Authors: Boesveldt S, Yee JR, McClintock MK, Lundström JN

Abstract
Social factors play a critical role in a panoply of health processes, including, as recently demonstrated, olfaction. Here, we investigated sex-dependent differences in the relationship between social lives and ability to identify odors in a large sample of nationally representative older US adults (n = 3005, National Social Life and Aging Project (NSHAP)). Social life was measured by the number of friends and close relatives as well as frequency of socializing. We here confirm the association between social lives and olfactory function and extend the notion by showing specifically that olfactory identification ability is modulated by sex in older adults. The connection between olfactory performance and social lives could reflect social modulation of aging as has been reported for health in general. Future studies are necessary to elucidate the precise mechanisms underlying this association and sex difference.

PMID: 28327569 [PubMed - in process]

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Twenty Shades of Chemosensory Perception.

Twenty Shades of Chemosensory Perception.

Perception. 2017 Mar-Apr;46(3-4):241-244

Authors: Lundström JN, Arshamian A, Olofsson JK

PMID: 28325137 [PubMed - in process]

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The long tale of the calcium activated Cl(-) Channels in olfactory transduction.

The long tale of the calcium activated Cl(-) Channels in olfactory transduction.

Channels (Austin). 2017 Mar 16;:0

Authors: Dibattista M, Pifferi S, Boccaccio A, Menini A, Reisert J

Abstract
Ca(2+)-activated Cl(-) currents have been implicated in many cellular processes in different cells, but for many years, their molecular identity remained unknown. Particularly intriguing are Ca(2+)-activated Cl(-) currents in olfactory transduction, first described in the early 90s. Well characterized electrophysiologically, they carry most of the odorant-induced receptor current in the cilia of olfactory sensory neurons (OSNs). After many attempts to determine their molecular identity, TMEM16B was found to be abundantly expressed in the cilia of OSNs in 2009 and having biophysical properties like those of the native olfactory channel. A TMEM16B knock-out mouse confirmed that TMEM16B was indeed the olfactory Cl(-) channel but also suggested a limited role in olfactory physiology and behavior. The question then arises of what the precise role of TMEM16b in olfaction is. Here we review the long story of this channel and its possible roles.

PMID: 28301269 [PubMed - as supplied by publisher]

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A Small Regulatory RNA Contributes to the Preferential Colonization of Escherichia coli O157:H7 in the Large Intestine in Response to a Low DNA Concentration.

A Small Regulatory RNA Contributes to the Preferential Colonization of Escherichia coli O157:H7 in the Large Intestine in Response to a Low DNA Concentration.

Front Microbiol. 2017;8:274

Authors: Han R, Xu L, Wang T, Liu B, Wang L

Abstract
Enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 (O157) is one of the most notorious human pathogens, causing severe disease in humans worldwide. O157 specifically colonizes the large intestine of mammals after passing through the small intestine, and this process is influenced by differential signals between the two regions. Small regulatory RNAs (sRNAs) are able to sense and respond to environmental changes and regulate diverse physiological processes in pathogenic bacteria. Although some sRNAs of O157 have been extensively investigated, whether these molecules can sense differences between the small and large intestine and influence the preferential colonization in the large intestine by O157 remains unknown. In this study, we identified a new sRNA, Esr055, in O157 which senses the low DNA concentration in the large intestine and contributes to the preferential colonization of the bacteria in this region. The number of O157 wild-type that adhered to the colon is 30.18 times higher than the number that adhered to the ileum of mice, while the number of the ΔEsr055 mutant that adhered to the colon decreased to 13.27 times higher than the number adhered to the ileum. Furthermore, we found that the expression of Esr055 is directly activated by the regulator, DeoR, and its expression is positively affected by DNA, which is significantly more abundant in the ileum than in the colon of mice. Additionally, combining the results of informatics predictions and transcriptomic analysis, we found that several virulence genes are up-regulated in the ΔEsr055 mutant and five candidate genes (z0568, z0974, z1356, z1926, and z5187) may be its direct targets.

PMID: 28289405 [PubMed - in process]

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Volatile secondary metabolites as aposematic olfactory signals and defensive weapons in aquatic environments.

Volatile secondary metabolites as aposematic olfactory signals and defensive weapons in aquatic environments.

Proc Natl Acad Sci U S A. 2017 Mar 13;:

Authors: Giordano G, Carbone M, Ciavatta ML, Silvano E, Gavagnin M, Garson MJ, Cheney KL, Mudianta IW, Russo GF, Villani G, Magliozzi L, Polese G, Zidorn C, Cutignano A, Fontana A, Ghiselin MT, Mollo E

Abstract
Olfaction is considered a distance sense; hence, aquatic olfaction is thought to be mediated only by molecules dissolved in water. Here, we challenge this view by showing that shrimp and fish can recognize the presence of hydrophobic olfactory cues by a "tactile" form of chemoreception. We found that odiferous furanosesquiterpenes protect both the Mediterranean octocoral Maasella edwardsi and its specialist predator, the nudibranch gastropod Tritonia striata, from potential predators. Food treated with the terpenes elicited avoidance responses in the cooccurring shrimp Palaemon elegans Rejection was also induced in the shrimp by the memory recall of postingestive aversive effects (vomiting), evoked by repeatedly touching the food with chemosensory mouthparts. Consistent with their emetic properties once ingested, the compounds were highly toxic to brine shrimp. Further experiments on the zebrafish showed that this vertebrate aquatic model also avoids food treated with one of the terpenes, after having experienced gastrointestinal malaise. The fish refused the food after repeatedly touching it with their mouths. The compounds studied thus act simultaneously as (i) toxins, (ii) avoidance-learning inducers, and (iii) aposematic odorant cues. Although they produce a characteristic smell when exposed to air, the compounds are detected by direct contact with the emitter in aquatic environments and are perceived at high doses that are not compatible with their transport in water. The mouthparts of both the shrimp and the fish have thus been shown to act as "aquatic noses," supporting a substantial revision of the current definition of the chemical senses based upon spatial criteria.

PMID: 28289233 [PubMed - as supplied by publisher]

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Κυριακή 26 Μαρτίου 2017

The ins and outs of molecular pathology reporting

Abstract

The raid evolution in molecular pathology resulting in an increasing complexity requires careful reporting. The need for standardisation is clearer than ever. While synoptic reporting was first used for reporting hereditary genetic diseases, it is becoming more frequent in pathology, especially molecular pathology reports too. The narrative approach is no longer feasible with the growing amount of essential data present on the report, although narrative components are still necessary for interpretation in molecular pathology. On the way towards standardisation of reports, guidelines can be a helpful tool. There are several guidelines that focus on reporting in the field of hereditary diseases, but it is not always feasible to extrapolate these to the reporting of somatic variants in molecular pathology. The rise of multi-gene testing causes challenges for the laboratories. In order to provide a continuous optimisation of the laboratory testing process, including reporting, external quality assessment is essential and has already proven to improve the quality of reports. In general, a clear and concise report for molecular pathology can be created by including elements deemed important by different guidelines, adapting the report to the process flows of the laboratory and integrating the report with the laboratory information management system and the patient record.

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The Esthetic and Psychologic Benefits of an Intraoperative Provisional Restoration

Abstract

Objective

When multiple visible teeth are prepared, the prolonged treatment time may lead to patients needing a break that requires them to leave the operatory. Such a situation allows the patient to view their prepared teeth, a process that can be disconcerting to some patients.

Clinical Considerations

An intraoperative provisional restoration can be made by using a thermoplastic vacuum-formed matrix of the patient's teeth that is filled with white-colored impression material and then placed over the prepared teeth to form a provisional restoration.

Conclusions

The use of an intraoperative provisional restoration can be effectively used to cover prepared teeth while providing normal tooth morphology and facial appearance after preparation of visible teeth.

Clinical Significance

When visible teeth are prepared, an intraoperative provisional restoration can be used to cover the prepared teeth and prevent concerned patients from viewing their prepared teeth.

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Semi-supervised classification trees

Abstract

In many real-life problems, obtaining labelled data can be a very expensive and laborious task, while unlabeled data can be abundant. The availability of labeled data can seriously limit the performance of supervised learning methods. Here, we propose a semi-supervised classification tree induction algorithm that can exploit both the labelled and unlabeled data, while preserving all of the appealing characteristics of standard supervised decision trees: being non-parametric, efficient, having good predictive performance and producing readily interpretable models. Moreover, we further improve their predictive performance by using them as base predictive models in random forests. We performed an extensive empirical evaluation on 12 binary and 12 multi-class classification datasets. The results showed that the proposed methods improve the predictive performance of their supervised counterparts. Moreover, we show that, in cases with limited availability of labeled data, the semi-supervised decision trees often yield models that are smaller and easier to interpret than supervised decision trees.

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Chronic hepatitis B: Immunological profile and current therapeutic vaccines in clinical trials

Publication date: Available online 25 March 2017
Source:Vaccine
Author(s): Yadira Lobaina, Marie-Louise Michel
More than 250million people worldwide are chronically infected with hepatitis B virus (CHB), and over half a million die each year due to CHB-associated liver complications such as cirrhosis and hepatocellular carcinoma. The translation of immunological knowledge about CHB into therapeutic strategies aiming to a sustainable hepatitis B virus (HBV) clearance has been challenging. In recent years, however, the understanding on the immune effectors required to overcome chronicity has notably increased thanks to preclinical and clinical research. Therapeutic vaccination may prove to be useful for treating CHB patients when coupled with current antiviral agents and other immunomodulatory strategies. This review summarizes current data and future perspectives on therapeutic vaccination. Other treatment alternatives that could be combined with vaccines for a complete cure from hepatitis B virus infection are also discussed.

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Cognitive testing to evaluate revisions to the Vaccine Adverse Event Reporting System (VAERS) reporting form

Publication date: Available online 25 March 2017
Source:Vaccine
Author(s): Tiffany A. Suragh, Elaine R. Miller, Beth F. Hibbs, Scott K. Winiecki, Craig Zinderman, Tom T. Shimabukuro
IntroductionThe Vaccine Adverse Event Reporting System (VAERS) is the spontaneous (passive) reporting system CDC and FDA use to monitor vaccine safety. We used cognitive testing to evaluate proposed revisions to the current VAERS form.MethodsWe conducted in-person cognitive interviews with 22 volunteers to evaluate proposed revisions in a prototype VAERS 2.0 form (new VAERS form). We analyzed data using thematic analysis.ResultsRepeating themes included preferences for: brevity, simplicity and clarity; features to minimize time requirements and facilitate ease of completion; logical ordering of questions by topic and importance; and visual cues like color-coded highlighting. Interviews identified instances of discordance between the intended meaning questions (from the perspective of CDC and FDA) and interpretation by volunteers.ConclusionsCognitive testing yielded useful information to guide further revisions of the VAERS form. Cognitive testing can be an effective tool for public health programs interested in developing surveys and reporting forms.

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Prevalence of factor H Binding Protein sub-variants among Neisseria meningitidis in China

Publication date: Available online 25 March 2017
Source:Vaccine
Author(s): Fenglin Shi, Aiyu Zhang, Bingqing Zhu, Yuan Gao, Li Xu, Yixing Li, Zundong Yin, Junhong Li, Na Xie, Zhujun Shao
ObjectiveTo study the prevalence of the fHbp genes in Neisseria meningitidis (N. meningitidis) isolates for further evaluation and development of serogroup B meningococcal vaccines in China.MethodsA panel of 1012 N. meningitidis strains was selected from the national culture collection from 1956 to 2016, according to the years of isolation, locations, and strain sources. These were tested by FHbp variant typing. Multi-locus sequence typing (MLST) was performed on 822 of these samples, including 242 strains from clinical strains and 580 carrier-derived strains. Analysis based on sequence types, serogroups, and FHbp variations were used to summarize the prevalence and characteristics of N. meningitidis.ResultsThere were 8 serogroups of N. meningitidis as well as a collection of nongroupable strains in this study. 1008 of 1012 N. meningitidis strains tested were positive for the fHbp gene. Serogroup A N. meningitidis (MenA) strains belonging to ST-1 and ST-5 clonal complexes harbored genes only encoding variant 1 (v1) FHbp. All MenW strains encoded v2 FHbp. 61.9% of clinical MenB strains were positive for v2 FHbp vs. 32.1% that were positive for v1. Among fHbp-positive carrier-derived MenB strains, v2 FHbp accounted for 90.8%. 79.7% of clinical MenC strains were positive for v1 FHbp and 20.3% were positive for v2 FHbp. Among carrier-derived MenC strains, v2 FHbp predominated. The number of major serogroups of N. meningitidis analyzed by MLST was 822, and the encoded FHbp showed CC- or ST-specific characteristics.ConclusionfHbp genes were detected in almost all N. meningitidis strains in this study. Therefore, it is possible that a vaccine against MenB or meningococci irrespective of serogroups, which includes FHbp, could be developed. Meningococcal vaccine development for China is a complex issue and these findings warrant further attention with respect to vaccine development.

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Moving the needle on nursing staff influenza vaccination in long-term care: Results of an evidence-based intervention

Publication date: Available online 25 March 2017
Source:Vaccine
Author(s): Cori L. Ofstead, Miriam R. Amelang, Harry P. Wetzler, Litjen Tan
PurposeInfluenza vaccination rates among healthcare providers (HCPs) in long-term care facilities (LTCFs) are commonly below the Healthy People 2020 goal of 90%. This study was conducted to develop and evaluate an intervention program designed to increase influenza uptake among HCPs in LTCFs.MethodsThis study was conducted in four Midwestern LTCFs. Baseline interviews, surveys, and administrative data analysis were performed following the 2013–2014 influenza season. Interventions implemented during the 2014–2015 season were based on the health belief and ecological models and included goal-setting worksheets, policy development, educational programs, kick-off events, incentives, a vaccination tracking roster, and facility-wide communication about vaccine uptake among HCPs. Outcomes were evaluated in 2015.ResultsAt baseline, 50% of 726 nursing staff employed during the 2013–2014 influenza season had documented receipt of influenza vaccine (Site A: 34%; Site B: 5%; Site C: 75%; Site D: 62%), and 31% of 347 survey respondents reported absenteeism due to respiratory illness. At follow-up, 85% of HCPs had documented receipt of influenza vaccine (p<0.01) and 19% of 323 survey respondents reported absenteeism due to respiratory illness (p<0.01). Vaccination rates among respondents' family members increased from 31% at baseline to 44% post-intervention (p<0.01). Reasons for declining vaccination did not change following exposure to educational programs, but HCPs were more likely to recommend vaccination to others after program implementation.ConclusionsVaccination rates among long-term care HCPs and their family members increased significantly and HCP absenteeism decreased after the implementation of multifaceted interventions based on an ecological model. The findings suggest that major increases in HCP vaccination can be achieved in LTCFs. More research is needed to evaluate the impact of increased HCP vaccination on the health and productivity of LTCF employees, their family members, and residents.

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Neonatal Diabetes

Journal of Investigative Medicine High Impact Case Reports, Volume 5, Issue 1, January 2017.

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«Separated Root Canal Instruments – An overview of incidence, localisation, treatment strategies and outcome»

«Separated Root Canal Instruments – An overview of incidence, localisation, treatment strategies and outcome»

Swiss Dent J. 2017 03 24;127(3):233-237

Authors: Suter B

Abstract
The dreaded fracture of a root canal instrument is in fact a rare adverse event. Most instrument fractures occur in molar teeth with the highest degree of root curvature. Various treatment options (leaving the fractured instrument with or without apicoectomy, bypassing or removing the fragment) and removing techniques (using ultrasonics, hollow tubes or bypassing and removing with debriders) are discussed. The clinical prognosis for teeth with fractured instruments is not necessarily compromised if appropriate further treatment is undertaken. Indeed, it is the timing of instrument fracture and the associated level of infection that will dictate treatment outcomes.

PMID: 28338300 [PubMed - as supplied by publisher]

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Chronic Automaticity in Addiction: Why Extreme Addiction is a Disorder

Abstract

Marc Lewis argues that addiction is not a disease, it is instead a dysfunctional outcome of what plastic brains ordinarily do, given the adaptive processes of learning and development within environments where people are seeking happiness, or relief, or escape. They come to obsessively desire substances or activities that they believe will deliver happiness and so on, but this comes to corrupt the normal process of development when it escalates beyond a point of functionality. Such 'deep learning' emerges from consumptive habits, or 'motivated repetition', and although addiction is bad, it ferments out of the ordinary stuff underpinning any neural habit. Lewis gives us a convincing story about the process that leads from ordinary controlled consumption through to quite heavy addictive consumption, but I claim that in some extreme cases the eventual state of deep learning tips over into clinically significant impairment and (so) disorder. Addiction is an elastic concept, and although it develops through mild and moderate forms, the impairment we see in severe cases needs to be acknowledged. This impairment, I argue, consists in the chronic automatic consumption present in late stage addiction. In this condition, the desiring self largely drops out the picture, as the addicted individual begins to mindlessly consume. This impairment is clinically significant because the machinery of motivated rationality has become corrupted. To bolster this claim I compare what is going on in these extreme cases with what goes on in people who dissociate in cases of depersonalization disorder.

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Actogram analysis of free-flying migratory birds: new perspectives based on acceleration logging

Abstract

The use of accelerometers has become an important part of biologging techniques for large-sized birds with accelerometer data providing information about flight mode, wing-beat pattern, behaviour and energy expenditure. Such data show that birds using much energy-saving soaring/gliding flight like frigatebirds and swifts can stay airborne without landing for several months. Successful accelerometer studies have recently been conducted also for free-flying small songbirds during their entire annual cycle. Here we review the principles and possibilities for accelerometer studies in bird migration. We use the first annual actograms (for red-backed shrike Lanius collurio) to explore new analyses and insights that become possible with accelerometer data. Actogram data allow precise estimates of numbers of flights, flight durations as well as departure/landing times during the annual cycle. Annual and diurnal rhythms of migratory flights, as well as prolonged nocturnal flights across desert barriers are illustrated. The shifting balance between flight, rest and different intensities of activity throughout the year as revealed by actogram data can be used to analyse exertion levels during different phases of the life cycle. Accelerometer recording of the annual activity patterns of individual birds will open up a new dimension in bird migration research.

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Erratum to: Application of Green Manure and Pig Manure to Cd-Contaminated Paddy Soil Increases the Risk of Cd Uptake by Rice and Cd Downward Migration into Groundwater: Field Micro-Plot Trials

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The independent influences of heat strain and dehydration upon cognition

Abstract

Purpose

Many researchers have addressed the potential effects of hyperthermia and dehydration on cognition, often revealing contradictory outcomes. A possible reason for this inconsistency is that experiments may have been inadequately designed for such effects. In this study, the impact of hyperthermia, dehydration and their combination on cognition were evaluated in eight young males, after accounting for a range of experimental limitations.

Methods

Passive heating and thermal clamping at two mean body temperatures (36.5, 38.5 °C) were performed under three hydration states (euhydrated, 3 and 5% dehydrated) to assess their effects on difficulty-matched working memory and visual perception tasks, and on a difficulty manipulated perceptual task. Data were analysed according to signal detection theory to isolate changes in response sensitivity, bias and speed.

Results

Neither moderate hyperthermia (P = 0.141) nor dehydration (P > 0.604) modified response sensitivity, nor did they significantly interact (P > 0.698). Therefore, the ability to distinguish correct from incorrect responses was unaffected. Nevertheless, hyperthermia, but not dehydration (P = 0.301), reduced the response bias (−0.08 versus 2.2 [normothermia]; P = 0.010) and reaction time (mean reduction 49 ms; P < 0.001), eliciting more liberal and faster responses (P = 0.010). Response bias was reduced for the memory relative to the perceptual task (P = 0.037), and this effect was enhanced during hyperthermia (P = 0.031).

Conclusions

These observations imply that, once potentially confounding influences were controlled, moderate hyperthermia, significant dehydration and their combined effects had insufficient impact to impair cognition within the memory and perceptual domains tested. Nonetheless, moderate hyperthermia elicited more liberal and rapid responses.

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G9a governs colon cancer stem cell phenotype and chemoradioresistance through PP2A-RPA axis-mediated DNA damage response

Publication date: Available online 25 March 2017
Source:Radiotherapy and Oncology
Author(s): Chi-Wen Luo, Jaw-Yuan Wang, Wen-Chun Hung, Guang Peng, Ya-Li Tsai, Tsung-Ming Chang, Chee-Yin Chai, Chih-Hung Lin, Mei-Ren Pan
Background and purposeNeoadjuvant concurrent chemoradiotherapy (CCRT) is a standard treatment of locally advanced colon cancer cell (CRC). In order to maximize efficacy and minimize toxicity, new drugs have been developed and used in combination with CCRT. Recently, it has been shown that G9a plays a role in mediating phenotypes of cancer stem cells (CSCs). This study aimed to characterize G9a as a biomarker in predicting therapy response to prevent overtreatment and adverse effects in CRC patients.Experimental designThe primary tumors from 39 patients who received CCRT for rectal cancer were selected. In vivo tumor xenograft models for tumorigenic properties in immunodeficient mice were developed. In vitro stemness ability was performed by tumor-sphere assays, cell response to anti-cancer agents and stemness-related genes analysis.ResultsCells survived from radiation treatment, and displayed high levels of G9a. A significantly positive correlation was shown between G9a and CSCs marker CD133 in locally advanced rectal cancer patients with CCRT. Knockdown of G9a increased the sensitivity of cells to radiation treatment and sensitized cells to DNA damage agents through PP2A-RPA axis.ConclusionsOur study theorized that G9a might serve as a novel target in colon cancer, which offers exciting potential in prediction of response to preoperative chemoradiotherapy in patients with advanced CRC.

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Quality assessment of delineation and dose planning of early breast cancer patients included in the randomized Skagen Trial 1

Publication date: Available online 25 March 2017
Source:Radiotherapy and Oncology
Author(s): Giulio Francolini, Mette S. Thomsen, Esben S. Yates, Carine Kirkove, Ingelise Jensen, Egil S. Blix, Claus Kamby, Mette H. Nielsen, Mechthild Krause, Martin Berg, Ingvil Mjaaland, Andreas Schreiber, Unn-miriam Kasti, Kristian Boye, Birgitte V. Offersen
Background and purposeTo report on a Quality assessment (QA) of Skagen Trial 1, exploring hypofractionation for breast cancer patients with indication for regional nodal radiotherapy.Material and methodsDeviations from protocol regarding target volume delineations and dose parameters (Dmin, Dmax, D98%, D95% and D2%) from randomly selected dose plans were assessed. Target volume delineation according to ESTRO guidelines was obtained through atlas based automated segmentation and centrally approved as gold standard (GS). Dice similarity scores (DSC) with original delineations were measured. Dose parameters measured in the two delineations were reported to assess their dosimetric outcome.ResultsAssessment included 88 plans from 12 centres in 4 countries. DSC showed high agreement in contouring, 99% and 96% of the patients had a complete delineation of target volumes and organs at risk. No deviations in the dosimetric outcome were found in 76% of the patients, 82% and 95% of the patients had successful coverage of breast/chestwall and CTVn_L2-4-interpectoral. Dosimetric outcomes of original delineation and GS were comparable.ConclusionsQA showed high protocol compliance and adequate dose coverage in most patients. Inter-observer variability in contouring was low. Dose parameters were in harmony with protocol regardless original or GS segmentation.

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Dynamic conformal arc radiosurgery for arteriovenous malformations: Outcome and influence of clinical and dosimetrical data

Publication date: Available online 25 March 2017
Source:Radiotherapy and Oncology
Author(s): Karen Clement-Colmou, Vincent Roualdes, Stéphane-André Martin, Stephanie Josset, Hubert Desal, Loïc Campion, François Thillays
PurposeTo assess efficacy, toxicity, and their predictive factors for dynamic conformal arc arteriovenous malformations (AVM) stereotactic radiosurgery.MethodData concerning 90 consecutive patients were retrospectively studied. Clinical, radiological, dosimetrical data and quality indexes were computed.ResultsAVM median volume was 1.06cc. Median prescribed dose was 22Gy. Total occlusion was obtained for 69% of patients. Post-radiosurgery annual hemorrhage rate was 2.2%. Predictive factor for total occlusion was delivered dose. Undesirable events occurred for 28% of patients. Predictive factors for adverse events were AVM revealing mode with seizure or headache, age≤28, AVM diameter≥3cm Spetzler–Martin score≥4, V12Gy≥2cc, large target volume and low homogeneity index (p<0.05). Brain parenchymal radiological reactions concerned 23% of patients, and their predictive factors were AVM revelation by seizure, deep localization, AVM diameter≥3cm, Spetzler–Martin score≥4, previous radiosurgery, numerous embolization, target volume, V12Gy and low homogeneity index (p<0.05).ConclusionOcclusion rate and toxicities are comparable to other series. Specific attention must be paid on pre-treatment clinical data, and target volume should be as small as possible, without reducing the delivered dose.

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Three-dimensional-guided perineal-based interstitial brachytherapy in cervical cancer: A systematic review of technique, local control and toxicities

Publication date: Available online 25 March 2017
Source:Radiotherapy and Oncology
Author(s): Lucas C. Mendez, Yonatan Weiss, David D'Souza, Ananth Ravi, Lisa Barbera, Eric Leung
ObjectiveTo evaluate local control and toxicities of perineal-based interstitial brachytherapy (P-ISBT) in cervical cancers treated with three-dimensional (3D) image-based planning through a systematic review. The secondary objective of this review is to summarize the implant and dosimetric techniques in 3D P-ISBT.MethodsSystematic review of the literature using the PRISMA guideline was conducted through a search of Medline, EMBASE and Cochrane databases. This search resulted in 19 relevant manuscripts. Selected studies evaluated the role of perineal ISBT in cervical tumours treated using 3D planning. Eleven of nineteen manuscripts contained sufficient information for LC and toxicity calculations. Data were extracted by at least two investigators.ResultsA total of 672 cervical cancer patients were treated with P-ISBT and planned with 3D image-based planning. Clinical outcomes could be identified for 392 patients and 60% were staged IIIB or higher. Most patients received 45–50.4Gy EBRT to the pelvis followed by a P-ISBT boost with a range of dose between 28 and 48Gy EQD2Gy. Overall LC was 79% (310/392) with a median follow-up ranging from 14 to 55months. Almost half of the patients (48%) had a median follow-up ≥35months. Patients treated to a lower tumour EQD2Gy total dose had inferior LC. Procedure-related complications were rare (7 infections and 7 episodes of bleeding) and limited. Combined late gastro-intestinal, genitourinary and vaginal grade 3 and 4 toxicity was 12.1%.ConclusionPromising LC rates were found in patients with cervical cancers treated with perineal ISBT with 3D image-based planning. In this systematic review, 60% had stage IIIB disease or higher and yet a LC rate of 79% was found. LC seemed to correlate with the dose delivered to the tumour, while toxicity rates were similar to other cervical cancer series using 3D image-based brachytherapy. Perineal ISBT with 3D planning seems to be an effective and safe treatment for large advanced cervical tumours and may be a reasonable alternative to the increasingly more standard and modern intracavitary/interstitial (IC/IS) approaches such as the 'Vienna' applicator.

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Patient safety in external beam radiotherapy, results of the ACCIRAD project: Current status of proactive risk assessment, reactive analysis of events, and reporting and learning systems in Europe

Publication date: Available online 25 March 2017
Source:Radiotherapy and Oncology
Author(s): Julian Malicki, Ritva Bly, Mireille Bulot, Jean-Luc Godet, Andreas Jahnen, Marco Krengli, Philippe Maingon, Carlos Prieto Martin, Kamila Przybylska, Agnieszka Skrobała, Marc Valero, Hannu Jarvinen
PurposeTo describe the current status of implementation of European directives for risk management in radiotherapy and to assess variability in risk management in the following areas: 1) in-country regulatory framework; 2) proactive risk assessment; (3) reactive analysis of events; and (4) reporting and learning systems.Material and MethodsThe original data were collected as part of the ACCIRAD project through two online surveys.ResultsRisk assessment criteria are closely associated with quality assurance programs. Only 9/32 responding countries (28%) with national regulations reported clear "requirements" for proactive risk assessment and/or reactive risk analysis, with wide variability in assessment methods. Reporting of adverse error events is mandatory in most (70%) but not all surveyed countries.ConclusionsMost European countries have taken steps to implement European directives designed to reduce the probability and magnitude of accidents in radiotherapy. Variability between countries is substantial in terms of legal frameworks, tools used to conduct proactive risk assessment and reactive analysis of events, and in the reporting and learning systems utilized. These findings underscore the need for greater harmonisation in common terminology, classification and reporting practices across Europe to improve patient safety and to enable more reliable inter-country comparisons.

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Can real-time RGBD enhance intraoperative Cone-Beam CT?

Abstract

Purpose

Cone-Beam Computed Tomography (CBCT) is an important 3D imaging technology for orthopedic, trauma, radiotherapy guidance, angiography, and dental applications. The major limitation of CBCT is the poor image quality due to scattered radiation, truncation, and patient movement. In this work, we propose to incorporate information from a co-registered Red-Green-Blue-Depth (RGBD) sensor attached near the detector plane of the C-arm to improve the reconstruction quality, as well as correcting for undesired rigid patient movement.

Methods

Calibration of the RGBD and C-arm imaging devices is performed in two steps: (i) calibration of the RGBD sensor and the X-ray source using a multimodal checkerboard pattern, and (ii) calibration of the RGBD surface reconstruction to the CBCT volume. The patient surface is acquired during the CBCT scan and then used as prior information for the reconstruction using Maximum-Likelihood Expectation-Maximization. An RGBD-based simultaneous localization and mapping method is utilized to estimate the rigid patient movement during scanning.

Results

Performance is quantified and demonstrated using artificial data and bone phantoms with and without metal implants. Finally, we present movement-corrected CBCT reconstructions based on RGBD data on an animal specimen, where the average voxel intensity difference reduces from 0.157 without correction to 0.022 with correction.

Conclusion

This work investigated the advantages of a C-arm X-ray imaging system used with an attached RGBD sensor. The experiments show the benefits of the opto/X-ray imaging system in: (i) improving the quality of reconstruction by incorporating the surface information of the patient, reducing the streak artifacts as well as the number of required projections, and (ii) recovering the scanning trajectory for the reconstruction in the presence of undesired patient rigid movement.

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Geometry calibration between X-ray source and detector for tomosynthesis with a portable X-ray system

Abstract

Purpose

Tomosynthesis is attracting attention as a low-dose tomography technology compared with X-ray CT. However, conventional tomosynthesis imaging devices are large and stationary. Furthermore, there is a limitation in the working range of the X-ray source during image acquisition. We have previously proposed the use of a portable X-ray device for tomosynthesis that can be used for ward rounds and emergency medicine. The weight of this device can be reduced by using a flat panel detector (FPD), and flexibility is realized by the free placement of the X-ray source and FPD. Tomosynthesis using a portable X-ray device requires calibration of the geometry between the X-ray source and detector at each image acquisition. We propose a method for geometry calibration and demonstrate tomosynthesis image reconstruction by this method.

Methods

An image processing-based calibration method using an asymmetric and multilayered calibration object (AMCO) is presented. Since the AMCO is always attached to the X-ray source housing for geometry calibration, the additional setting of a calibration object or marker around or on the patients is not required. The AMCO's multilayer structure improves the calibration accuracy, especially in the out-of-plane direction.

Results

Two experiments were conducted. The first was performed to evaluate the calibration accuracy using an XY positioning stage and a gonio stage. As a result, an accuracy of approximately 1 mm was achieved both in the in-plane and out-of-plane directions. An angular accuracy of approximately \(0.5^{\circ }\) was confirmed. The second experiment was conducted to evaluate the reconstructed image using a foot model phantom. Only the sagittal plane could be clearly observed with the proposed method.

Conclusion

We proposed a tomosynthesis imaging system using a portable X-ray device. From the experimental results, the proposed method could provide sufficient calibration accuracy and a clear sagittal plane of the reconstructed tomosynthesis image.

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Brain edema with clasmatodendrosis complicating ataxia telangiectasia

Publication date: Available online 25 March 2017
Source:Brain and Development
Author(s): Konomi Shimoda, Masakazu Mimaki, Shuhei Fujino, Masato Takeuchi, Rumi Hino, Hiroshi Uozaki, Masaharu Hayashi, Akira Oka, Masashi Mizuguchi
Ataxia-telangiectasia is a chronic progressive disorder affecting the nervous and immune systems, caused by a genetic defect in the ATM protein. Clasmatodendrosis, a distinct form of astroglial death, has rarely been reported in ataxia-telangiectasia. Neuropathology of our patient disclosed diffuse edema of the cerebral and cerebellar white matter with prominent clasmatodendrosis, implicating ATM in the regulation of astroglial cell death.

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Increased cortisol awakening response after completing the summer treatment program in children with ADHD

Publication date: Available online 24 March 2017
Source:Brain and Development
Author(s): Rumiko Okabe, Hisayoshi Okamura, Chiyomi Egami, Yasuhiro Tada, Chizuru Anai, Akiko Mukasa, Akiko Iemura, Shinichiro Nagamitsu, Junichi Furusho, Toyojiro Matsuishi, Yushiro Yamashita
ObjectiveLittle is known about the cortisol awakening response (CAR) in children with attention deficit hyperactivity disorder (ADHD). Here, we examined the CAR in children with ADHD and their mothers before, immediately after, and 4months after an intensive summer treatment program (STP).MethodsParticipants were 37 children aged 7–12years who completed the STP in 2009 and 2010, and their mothers. Daily saliva samples for cortisol measurement were collected twice daily at awakening and 30min afterwards at pre-STP, post-STP, and during a follow-up measurement period. ADHD symptom scores were evaluated by parents, and participants completed the Kid-KINDL^R QOL questionnaire.ResultsCAR was low in children with ADHD before the STP, and increased to the control range 4months after STP. Maternal CAR also tended to increase after STP. Changes in the CAR in children tended to correlate with an improved ADHD inattention scores (p=0.091), physical health (p=0.070), and school life subscales scores in the Kid-KINDL^R (p=0.079).ConclusionWe demonstrated that STP improved the behavior and QOL of children with ADHD. Our results indicate that STP could lead to improvements in HPA axis function, as reflected by increased CAR after STP.

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macrophage; +62 new citations

62 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

macrophage

These pubmed results were generated on 2017/03/26

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Lung-RADS Category 4X: Does It Improve Prediction of Malignancy in Subsolid Nodules?

Lung-RADS Category 4X: Does It Improve Prediction of Malignancy in Subsolid Nodules?

Radiology. 2017 Mar 24;:161624

Authors: Chung K, Jacobs C, Scholten ET, Goo JM, Prosch H, Sverzellati N, Ciompi F, Mets OM, Gerke PK, Prokop M, van Ginneken B, Schaefer-Prokop CM

Abstract
Purpose To evaluate the added value of Lung CT Screening Reporting and Data System (Lung-RADS) assessment category 4X over categories 3, 4A, and 4B for differentiating between benign and malignant subsolid nodules (SSNs). Materials and Methods SSNs on all baseline computed tomographic (CT) scans from the National Lung Cancer Trial that would have been classified as Lung-RADS category 3 or higher were identified, resulting in 374 SSNs for analysis. An experienced screening radiologist volumetrically segmented all solid cores and located all malignant SSNs visible on baseline scans. Six experienced chest radiologists independently determined which nodules to upgrade to category 4X, a recently introduced category for lesions that demonstrate additional features or imaging findings that increase the suspicion of malignancy. Malignancy rates of purely size-based categories and category 4X were compared. Furthermore, the false-positive rates of category 4X lesions were calculated and observer variability was assessed by using Fleiss κ statistics. Results The observers upgraded 15%-24% of the SSNs to category 4X. The malignancy rate for 4X nodules varied from 46% to 57% per observer and was substantially higher than the malignancy rates of categories 3, 4A, and 4B SSNs without observer intervention (9%, 19%, and 23%, respectively). On average, the false-positive rate for category 4X nodules was 7% for category 3 SSNs, 7% for category 4A SSNs, and 19% for category 4B SSNs. Of the falsely upgraded benign lesions, on average 27% were transient. The agreement among the observers was moderate, with an average κ value of 0.535 (95% confidence interval: 0.509, 0.561). Conclusion The inclusion of a 4X assessment category for lesions suspicious for malignancy in a nodule management tool is of added value and results in high malignancy rates in the hands of experienced radiologists. Proof of the transient character of category 4X lesions at short-term follow-up could avoid unnecessary invasive management. (©) RSNA, 2017.

PMID: 28339311 [PubMed - as supplied by publisher]

from Head and Neck on PubMed via xlomafota13 on Inoreader http://ift.tt/2o5P3yd

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Interictal Ripples Nested in Epileptiform Discharge Help to Identify the Epileptogenic Zone in Neocortical Epilepsy

Publication date: Available online 25 March 2017
Source:Clinical Neurophysiology
Author(s): Shuang Wang, Norman K. So, Bo Jin, Irene Z. Wang, Juan C. Bulacio, Rei Enatsu, Shenyi Dai, Zhong Chen, Jorge Gonzalez-Martinez, Imad M. Najm
ObjectiveThis study aimed to identify the subtype of interictal ripples that help delineate the epileptogenic zone in neocortical epilepsy.MethodsTotally 25 patients with focal neocortical epilepsy who had invasive electroencephalography (EEG) evaluation and subsequent surgery were included. They were followed up for at least 2 years. Interictal ripples (80–250 Hz) and fast ripples (250–500 Hz) during slow-wave sleep were identified. Neocortical ripples were defined as type I ripples when they were superimposed on epileptiform discharges, and as type II ripples when they occurred independently. Resection ratio was calculated to present the extent to which the cortical area showing an interictal event or the seizure onset zone (SOZ) was completely removed.ResultsFast ripples and types I and II ripples were found in 8, 19, and 21 patients, respectively. Only the higher resection ratio of interictal fast or type I ripples was correlated to the Engel 1a surgical outcome.ConclusionsType I ripples could assist in localizing the epileptogenic zone in neocortical epilepsy.SignificanceType I and fast ripples both may be pathological high-frequency oscillations.

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Exploration of the effect of probiotics supplementation on intestinal microbiota of food allergic mice.

Exploration of the effect of probiotics supplementation on intestinal microbiota of food allergic mice.

Am J Transl Res. 2017;9(2):376-385

Authors: Yang B, Xiao L, Liu S, Liu X, Luo Y, Ji Q, Yang P, Liu Z

Abstract
Environmental factor-induced alterations in intestinal microbiota have been demonstrated to be associated with increasing prevalence of food allergy. However, it is not clear to what extent oral administration of probiotics can affect gut microbiota composition, thus inhibiting food allergy development. Using ovalbumin (OVA)-sensitized murine model, it was demonstrated that probiotics ameliorated allergic symptoms, including reducing OVA specific-IgE, and -IgG1 levels in the serum, Th2 cytokines release in spleen, and occurrence of diarrhea. Moreover, 16S rRNA analysis showed that the probiotics-mediated protection was conferred by an enrichment of Coprococcus and Rikenella. The present study supports the theory that probiotics can treat food allergy by modulating specific genera of the gut microbiota.

PMID: 28337267 [PubMed]

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Understanding the naturalization of Eucalyptus globulus in Portugal: a comparison with Australian plantations

Abstract

Despite the potential utility of a biogeographical approach to understanding the naturalization of exotic species, studies using this approach are scarce. Eucalyptus globulus is an economically important Australian tree species that has become naturalized in a number of countries where it was introduced. Portugal is an ideal territory to study the naturalization of E. globulus owing to: a long introduction history, the antipodal location compared to Australia and the large cultivated area. Wildling density was assessed in 116 E. globulus plantations in central Portugal through 213 transects established along plantation borders. Boosted regression trees were used to model the influence of plantation-scale variables. Results from this survey were compared with data obtained in plantations from seven Australian regions, where a similar sampling protocol had been used. In Portugal, wildlings were more abundant in plantations that were: located in moist aspects, coppiced, with older tree stems and corresponding to intermediate site growth indexes. The overall density (127 plants ha⁻¹) was 14.9 times higher than in the Australian estate, but this ratio was reduced to 3.1 in a more comparable subset of unburnt, first rotation plantations. A generalized linear model fitted using a dataset combining the two surveys showed that country influenced wildling density, together with plantation rotation and stem age. These results provide insights into the naturalization of a widely cultivated tree species, pointing to a fundamental role of the introduction history, possibly acting along with the biogeographical characteristics of the introduced range.

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Exploration of the effect of probiotics supplementation on intestinal microbiota of food allergic mice.

Exploration of the effect of probiotics supplementation on intestinal microbiota of food allergic mice.

Am J Transl Res. 2017;9(2):376-385

Authors: Yang B, Xiao L, Liu S, Liu X, Luo Y, Ji Q, Yang P, Liu Z

PMID: 28337267 [PubMed]

} http://ift.tt/2nSQpiu

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Exploration of the effect of probiotics supplementation on intestinal microbiota of food allergic mice.

Exploration of the effect of probiotics supplementation on intestinal microbiota of food allergic mice.

Am J Transl Res. 2017;9(2):376-385

Authors: Yang B, Xiao L, Liu S, Liu X, Luo Y, Ji Q, Yang P, Liu Z

PMID: 28337267 [PubMed]

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Oxidative Stress and Autophagy in Metabolism and Longevity.

Oxidative Stress and Autophagy in Metabolism and Longevity.

Oxid Med Cell Longev. 2017;2017:3451528

Authors: Vikram A, Anish R, Kumar A, Tripathi DN, Kaundal RK

PMID: 28337248 [PubMed - in process]

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Hydroxychloroquine sensitizes chronic myeloid leukemia cells to Vγ9Vδ2 T cell-mediated lysis independent of autophagy.

Hydroxychloroquine sensitizes chronic myeloid leukemia cells to Vγ9Vδ2 T cell-mediated lysis independent of autophagy.

Int J Oncol. 2017 Mar 24;:

Authors: Han B, Zhao Y, Lin Y, Fu S, Wang L, Zhang M, Tie R, Wang B, Luo Y, Liu L, Yu J, Huang H

Abstract
Hydroxychloroquine (HCQ) is the only autophagy inhibitor in clinical use and it has shown great potential in treating chronic myeloid leukemia (CML). By inhibiting autophagy, HCQ enhances the anti-CML efficiency of chemotherapy. In the present study, we demonstrated that HCQ sensitized CML cells to Vγ9Vδ2 T cell-mediated lysis. HCQ inhibited autophagy in CML cells, but the sensitizing effects of HCQ were autophagy-independent. Since the sensitization was not mimicked by ATG7 knockdown and even occurred in the absence of ATG7. We revealed that in a time-dependent manner HCQ induced the expression of NKG2D ligand ULBP4 on the surface of CML cells. This marks the leukemia cell for recognition by Vγ9Vδ2 T cells. Blocking the interaction of NKG2D with its ligands deleted the sensitizing effects of HCQ. In addition, we showed that HCQ did not affect the synthesis or degradation of ULBP4, but induced the translocation of ULBP4 from the cytoplasm to the cell membrane. Our results uncovered a previously unknown mechanism for HCQ in CML treatment that underlines the ability of HCQ to modulate the immune visibility of CML cells, and pave the way to the development of new combination treatments with HCQ and Vγ9Vδ2 T cells.

PMID: 28339029 [PubMed - as supplied by publisher]

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MiR-9 enhances the sensitivity of A549 cells to cisplatin by inhibiting autophagy.

MiR-9 enhances the sensitivity of A549 cells to cisplatin by inhibiting autophagy.

Biotechnol Lett. 2017 Mar 23;:

Authors: Zhang Y, Meng X, Li C, Tan Z, Guo X, Zhang Z, Xi T

Abstract
OBJECTIVES: To demonstrate that miR-9 inhibits autophagy by down-regulating Beclin1 and thus enhances the sensitivity of A549 cells to cisplatin.
RESULTS: MiR-9 inhibited Beclin1 expression by binding to its 3'UTR. The inhibition decreased the cisplatin-induced autophagy in A549 cells, evidenced by the decreased expression of LC3II and GFP-LC3 puncta and the increased expression of P62. Upregulation of miR-9 level enhanced the sensibility of A549 cells to cisplatin and increased the cisplatin-induced apoptosis. Overexpression of Beclin1 reversed above effects of miR-9 mimics, cisplatin-induced autophagy was increased and apoptosis was decreased.
CONCLUSIONS: MiR-9 inhibits autophagy via targeting Beclin1 3'UTR and thus enhances cisplatin sensitivity in A549 cells.

PMID: 28337557 [PubMed - as supplied by publisher]

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RIN4 recruits the exocyst subunit EXO70B1 to the plasma membrane.

RIN4 recruits the exocyst subunit EXO70B1 to the plasma membrane.

J Exp Bot. 2017 Feb 20;:

Authors: Sabol P, Kulich I, Žárský V

Abstract
The exocyst is a conserved vesicle-tethering complex with principal roles in cell polarity and morphogenesis. Several studies point to its involvement in polarized secretion during microbial pathogen defense. In this context, we have found an interaction between the Arabidopsis EXO70B1 exocyst subunit, a protein which was previously associated with both the defense response and autophagy, and RPM1 INTERACTING PROTEIN 4 (RIN4), the best studied member of the NOI protein family and a known regulator of plant defense pathways. Interestingly, fragments of RIN4 mimicking the cleavage caused by the Pseudomonas syringae effector protease, AvrRpt2, fail to interact strongly with EXO70B1. We observed that transiently expressed RIN4, but not the plasma membrane (PM) protein aquaporin PIP2, recruits EXO70B1 to the PM. Unlike EXO70B1, RIN4 does not recruit the core exocyst subunit SEC6 to the PM under these conditions. Furthermore, the AvrRpt2 effector protease delivered by P. syringae is able to release both RIN4 and EXO70B1 to the cytoplasm. We present a model for how RIN4 might regulate the localization and putative function of EXO70B1 and speculate on the role the AvrRpt2 protease might have in the regulation of this defense response.

PMID: 28338727 [PubMed - as supplied by publisher]

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Neuronal Mitophagy in Neurodegenerative Diseases.

Neuronal Mitophagy in Neurodegenerative Diseases.

Front Mol Neurosci. 2017;10:64

Authors: Martinez-Vicente M

Abstract
Neuronal homeostasis depends on the proper functioning of different quality control systems. All intracellular components are subjected to continuous turnover through the coordinated synthesis, degradation and recycling of their constituent elements. Autophagy is the catabolic mechanism by which intracellular cytosolic components, including proteins, organelles, aggregates and any other intracellular materials, are delivered to lysosomes for degradation. Among the different types of selective autophagy described to date, the process of mitophagy involves the selective autophagic degradation of mitochondria. In this way, mitophagy is responsible for basal mitochondrial turnover, but can also be induced under certain physiological or pathogenic conditions to eliminate unwanted or damaged mitochondria. Dysfunctional cellular proteolytic systems have been linked extensively to neurodegenerative diseases (ND) like Alzheimer's disease (AD), Parkinson's disease (PD), or Huntington's disease (HD), with autophagic failure being one of the main factors contributing to neuronal cell death in these diseases. Neurons are particularly vulnerable to autophagic impairment as well as to mitochondrial dysfunction, due mostly to their particular high energy dependence and to their post-mitotic nature. The accurate and proper degradation of dysfunctional mitochondria by mitophagy is essential for maintaining control over mitochondrial quality and quantity in neurons. In this report, I will review the role of mitophagy in neuronal homeostasis and the consequences of its dysfunction in ND.

PMID: 28337125 [PubMed - in process]

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EGFR Family Members' Regulation of Autophagy Is at a Crossroads of Cell Survival and Death in Cancer.

EGFR Family Members' Regulation of Autophagy Is at a Crossroads of Cell Survival and Death in Cancer.

Cancers (Basel). 2017 Mar 24;9(4):

Authors: Henson E, Chen Y, Gibson S

Abstract
The epidermal growth factor receptor (EGFR) signaling pathways are altered in many cancers contributing to increased cell survival. These alterations are caused mainly through increased expression or mutation of EGFR family members EGFR, ErbB2, ErbB3, and ErbB4. These receptors have been successfully targeted for cancer therapy. Specifically, a monoclonal antibody against ErbB2, trastuzumab, and a tyrosine kinase inhibitor against EGFR, gefitinib, have improved the survival of breast and lung cancer patients. Unfortunately, cancer patients frequently become resistant to these inhibitors. This has led to investigating how EGFR can contribute to cell survival and how cancer cells can overcome inhibition of its signaling. Indeed, it is coming into focus that EGFR signaling goes beyond a single signal triggering cell proliferation and survival and is a sensor that regulates the cell's response to microenvironmental stresses such as hypoxia. It acts as a switch that modulates the ability of cancer cells to survive. Autophagy is a process of self-digestion that is inhibited by EGFR allowing cancer cells to survive under stresses that would normally cause death and become resistant to chemotherapy. Inhibiting EGFR signaling allows autophagy to contribute to cell death. This gives new opportunities to develop novel therapeutic strategies to treat cancers that rely on EGFR signaling networks and autophagy. In this review, we summarize the current understanding of EGFR family member regulation of autophagy in cancer cells and how new therapeutic strategies could be developed to overcome drug resistance.

PMID: 28338617 [PubMed]

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Role of autophagy in the progression of osteoarthritis: The autophagy inhibitor, 3-methyladenine, aggravates the severity of experimental osteoarthritis.

Role of autophagy in the progression of osteoarthritis: The autophagy inhibitor, 3-methyladenine, aggravates the severity of experimental osteoarthritis.

Int J Mol Med. 2017 Mar 23;:

Authors: Cheng NT, Meng H, Ma LF, Zhang L, Yu HM, Wang ZZ, Guo A

Abstract
Accumulating evidence suggests that autophagy is closely related to the pathogenesis of osteoarthritis (OA). The aim of this study was to determine the changes in autophagy during the progression of OA and to elucidate the specific role of autophagy in OA. For this purpose, a cellular model of OA was generated by stimulating SW1353 cells with interleukin (IL)-1β and a rabbit model of OA was also established by an intra-articular injection of collagenase, followed by treatment with the autophagy specific inhibitor, 3-methyladenine (3-MA). Cell viability was analyzed by MTS assay, and the mRNA expression levels of matrix metalloproteinases (MMP)-13 and tissue inhibitor of metalloproteinase (TIMP)-1 were determined by RT-qPCR. Cartilage degeneration was examined under a light microscope, and autophagosome and chondrocyte degeneration was observed by transmission electron microscopy. The protein expression of Beclin-1 and light chain 3 (LC3)B was evaluated by western blot analysis and immunofluorescence staining. We found that the autophagy was enhanced during the early stages and was weakened during the late stages of experimental OA. The inhibition of autophagy by 3-MA significantly aggravated the degeneration of chondrocytes and cartilage in experimental OA. Our results thus determine the changes in autophagy during different stages of OA, as well as the role of impaired autophagy in the development of OA. Our data suggest that the regulation of autophagy may be a potential therapeutic strategy with which to attenuate OA.

PMID: 28339018 [PubMed - as supplied by publisher]

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Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling.

Apigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling.

Sci Rep. 2017 Mar 23;7(1):372

Authors: Lin CM, Chen HH, Lin CA, Wu HC, Sheu JJ, Chen HJ

Abstract
The bioflavonoid apigenin has been shown to possess cancer-preventive and anti-cancer activities. In a drug screening, we found that apigenin can inhibit Wnt/β-catenin signaling, a pathway that participates in pivotal biological functions, which dis-regulation results in various human diseases including cancers. However, the underlying mechanism of apigenin in this pathway and its link to anti-cancer activities remain largely unknown. Here we showed that apigenin reduced the amount of total, cytoplasmic, and nuclear β-catenin, leading to the suppression in the β-catenin/TCF-mediated transcriptional activity, the expression of Wnt target genes, and cell proliferation of Wnt-stimulated P19 cells and Wnt-driven colorectal cancer cells. Western blotting and immunofluorescent staining analyses further revealed that apigenin could induce autophagy-mediated down-regulation of β-catenin in treated cells. Treatment with autophagy inhibitors wortmannin and chloroquine compromised this effect, substantiating the involvement of autophagy-lysosomal system on the degradation of β-catenin during Wnt signaling through inhibition of the AKT/mTOR signaling pathway. Our data not only pointed out a route for the inhibition of canonical Wnt signaling through the induction of autophagy-lysosomal degradation of key player β-catenin, but also suggested that apigenin or other treatments which can initiate this degradation event are potentially used for the therapy of Wnt-related diseases including cancers.

PMID: 28337019 [PubMed - in process]

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Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway.

Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway.

Int J Mol Med. 2017 Mar 21;:

Authors: Li WD, Li NP, Song DD, Rong JJ, Qian AM, Li XQ

Abstract
The aim of the present study was to investigate the effect of metformin on endothelial progenitor cell (EPC) migration and to explore the possible mechanisms. EPCs were treated with metformin, and the migration of EPCs was evaluated by wound healing and Matrigel invasion assays. We also examined the expression levels of of MMP-2 and MMP-9 in EPCs with or without metformin treatment via RT-PCR and western blot analysis, and activities of MMP-2 and MMP-9 in EPCs under different conditions was examined by zymography. Moreover, we also assessed the AMPK/mTOR/autophagy pathway to explore the possible mechanisms. Metformin treatment significantly downregulated matrix metalloproteinase-2 (MMP-2) and MMP-9 expression, and subsequently decreased the migration of EPCs. Increased levels of phosphorylated (p)-AMPK and LC3II expression, as well as decreased levels of p-mTOR and p62 contributed to this phenomenon. The AMPK inhibitor compound C reversed the effect exerted by metformin. In conclusion, our results showed that metformin inhibited the migration of EPCs by decreasing MMP-2 and MMP-9. The AMPK/mTOR/autophagy pathway was demonstrated to be involved in the regulatory mechanisms.

PMID: 28339020 [PubMed - as supplied by publisher]

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β-Elemene: Mechanistic Studies on Cancer Cell Interaction and Its Chemosensitization Effect.

β-Elemene: Mechanistic Studies on Cancer Cell Interaction and Its Chemosensitization Effect.

Front Pharmacol. 2017;8:105

Authors: Jiang Z, Jacob JA, Loganathachetti DS, Nainangu P, Chen B

Abstract
Over the past decade, screening and identifying novel compounds for their biomedical applications has become an upcoming area of research. Identifying the molecular mechanisms of these compounds has become an integral part of anticancer research. β-elemene, a sesquiterpene, is renowned for its anticancer activity against a variety of cell lines. Recent studies on β-elemene have elucidated that it possesses anti-proliferative effect on cancer cells by creating an apoptotic trigger. Interestingly, it also induces protective autophagy in some cancerous cell lines and is less cytotoxic compared to other widely accepted chemotherapeutic agents. This provides an edge with the perception of limited toxicity to normal cells. This mini-review precisely focuses on the studies performed to identify the mechanism of anticancer activity of β-elemene against cancer cells of multiple origin. In accordance to the evaluation made by the studies mentioned, apoptosis has been identified to be most possible reason behind anticancer activity exerted by β-elemene against a variety of cancer cell lines. Cell cycle arrest and necrosis have been credited to be possible alternate mechanisms for the anticancer effect of β-elemene.

PMID: 28337141 [PubMed - in process]

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α-Synuclein binds to the ER-mitochondria tethering protein VAPB to disrupt Ca(2+) homeostasis and mitochondrial ATP production.

α-Synuclein binds to the ER-mitochondria tethering protein VAPB to disrupt Ca(2+) homeostasis and mitochondrial ATP production.

Acta Neuropathol. 2017 Mar 23;:

Authors: Paillusson S, Gomez-Suaga P, Stoica R, Little D, Gissen P, Devine MJ, Noble W, Hanger DP, Miller CC

Abstract
α-Synuclein is strongly linked to Parkinson's disease but the molecular targets for its toxicity are not fully clear. However, many neuronal functions damaged in Parkinson's disease are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. This signalling involves close physical associations between the two organelles that are mediated by binding of the integral ER protein vesicle-associated membrane protein-associated protein B (VAPB) to the outer mitochondrial membrane protein, protein tyrosine phosphatase-interacting protein 51 (PTPIP51). VAPB and PTPIP51 thus act as a scaffold to tether the two organelles. Here we show that α-synuclein binds to VAPB and that overexpression of wild-type and familial Parkinson's disease mutant α-synuclein disrupt the VAPB-PTPIP51 tethers to loosen ER-mitochondria associations. This disruption to the VAPB-PTPIP51 tethers is also seen in neurons derived from induced pluripotent stem cells from familial Parkinson's disease patients harbouring pathogenic triplication of the α-synuclein gene. We also show that the α-synuclein induced loosening of ER-mitochondria contacts is accompanied by disruption to Ca(2+) exchange between the two organelles and mitochondrial ATP production. Such disruptions are likely to be particularly damaging to neurons that are heavily dependent on correct Ca(2+) signaling and ATP.

PMID: 28337542 [PubMed - as supplied by publisher]

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Effects of autophagy and endocytosis on the activity of matrix metalloproteinase‑2 in human renal proximal tubular cells under hypoxia.

Effects of autophagy and endocytosis on the activity of matrix metalloproteinase‑2 in human renal proximal tubular cells under hypoxia.

Mol Med Rep. 2017 Mar 22;:

Authors: Yu W, Wang Z, Li Y, Liu L, Liu J, Ding F, Zhang X, Cheng Z, Chen P

Abstract
Tubulointerstitial fibrosis is characterized by tubular atrophy with basement membrane thickening and accumulation of interstitial extracellular matrix (ECM). A decrease in the activity of matrix metalloproteinase‑2 (MMP‑2) may promote this process. Although proximal tubular cells are sensitive to oxygen deprivation, whether cellular autophagy or endocytosis induced by hypoxia can alter the activity of MMP‑2 remains to be elucidated. The aim of the present study was to investigate whether autophagy and endocytosis induced by hypoxia can have an effect on the activity of MMP‑2 in HK‑2 cells. The investigations involved exposing the HK‑2 cell line to an autophagy inhibitor, 3‑MA, or an endocytotic inhibitor, filipin. The mRNA expression of MMP‑2 was elevated in the hypoxic milieu. Furthermore, it was found that filipin increased the activity of MMP‑2 under hypoxia. These results suggested that autophagy and endocytosis were potential mediators for the altered expression of MMP‑2, and endocytosis was a potential target for regulating the activity of MMP‑2. These data suggested that hypoxia may be an important pro‑fibrogenic stimulus, which acts in part via endocytosis.

PMID: 28339082 [PubMed - as supplied by publisher]

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The small heat shock proteins αB-crystallin (HSPB5) and Hsp27 (HSPB1) inhibit the intracellular aggregation of α-synuclein.

The small heat shock proteins αB-crystallin (HSPB5) and Hsp27 (HSPB1) inhibit the intracellular aggregation of α-synuclein.

Cell Stress Chaperones. 2017 Mar 23;:

Authors: Cox D, Ecroyd H

Abstract
Protein homeostasis, or proteostasis, is the process of maintaining the conformational and functional integrity of the proteome. Proteostasis is preserved in the face of stress by a complex network of cellular machinery, including the small heat shock molecular chaperone proteins (sHsps), which act to inhibit the aggregation and deposition of misfolded protein intermediates. Despite this, the pathogenesis of several neurodegenerative diseases has been inextricably linked with the amyloid fibrillar aggregation and deposition of α-synuclein (α-syn). The sHsps are potent inhibitors of α-syn aggregation in vitro. However, the limited availability of a robust, cell-based model of α-syn aggregation has, thus far, restricted evaluation of sHsp efficacy in the cellular context. As such, this work sought to establish a robust model of intracellular α-syn aggregation using Neuro-2a cells. Aggregation of α-syn was found to be sensitive to inhibition of autophagy and the proteasome, resulting in a significant increase in the proportion of cells containing α-syn inclusions. This model was then used to evaluate the capacity of the sHsps, αB-c and Hsp27, to prevent α-syn aggregation in cells. To do so, we used bicistronic expression plasmids to express the sHsps. Unlike traditional fluorescent fusion constructs, these bicistronic expression plasmids enable only individual transfected cells expressing the sHsps (via expression of the fluorescent reporter) to be analysed, but without the need to tag the sHsp, which can affect its oligomeric structure and chaperone activity. Overexpression of both αB-c and Hsp27 significantly reduced the intracellular aggregation of α-syn. Thus, these findings suggest that overexpressing or boosting the activity of sHsps may be a way of preventing amyloid fibrillar aggregation of α-syn in the context of neurodegenerative disease.

PMID: 28337642 [PubMed - as supplied by publisher]

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Regulatory effects of autophagy on spermatogenesis.

Regulatory effects of autophagy on spermatogenesis.

Biol Reprod. 2017 Feb 25;:

Authors: Yin J, Ni B, Tian ZQ, Yang F, Liao WG, Gao YQ

Abstract
Abnormal spermatogenesis is an important pathophysiological process underlying male infertility. Apoptosis of spermatogenic cells and disruption of ectoplasmic specialization (ES) have been characterized as the key biological events of this disorder. Under physiological and pathophysiological conditions (such as exposure to starvation, environmental chemicals, radiation), autophagy is activated in spermatogenic or Sertoli cells in order to maintain survival of the spermatogenic cells by inhibiting spermatogenic cell apoptosis and stabilizing the integrity of ES via degradation of PDZ and LIM domain 1 (PDLIM1), a negative regulator of cytoskeletal organization. Here, we review the most recent research progress towards understanding the pivotal effects of autophagy on spermatogenesis.

PMID: 28339784 [PubMed - as supplied by publisher]

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Πληροφορίες

Τρίτη 28 Μαρτίου 2017

Κυριακή 26 Μαρτίου 2017

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Δημοφιλείς αναρτήσεις

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