Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passage.

Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passage.

Elife. 2018 Mar 29;7:

Authors: Wendorff TJ, Berger JM

Abstract
Type II topoisomerases manage DNA supercoiling and aid chromosome segregation using a complex, ATP-dependent duplex strand passage mechanism. Type IIB topoisomerases and their homologs support both archaeal/plant viability and meiotic recombination. Topo VI, a prototypical type IIB topoisomerase, comprises two Top6A and two Top6B protomers; how these subunits cooperate to engage two DNA segments and link ATP turnover to DNA transport is poorly understood. Using multiple biochemical approaches, we show that Top6B, which harbors the ATPase activity of topo VI, recognizes and exploits the DNA crossings present in supercoiled DNA to stimulate subunit dimerization by ATP. Top6B self-association in turn induces extensive DNA bending, which is needed to support duplex cleavage by Top6A. Our observations explain how topo VI tightly coordinates DNA crossover recognition and ATP binding with strand scission, providing useful insights into the operation of type IIB topoisomerases and related meiotic recombination and GHKL ATPase machineries.

PMID: 29595473 [PubMed - as supplied by publisher]

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Polysulfide-triggered fluorescent indicator suitable for super-resolution microscopy and application in imaging.

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Polysulfide-triggered fluorescent indicator suitable for super-resolution microscopy and application in imaging.

Chem Commun (Camb). 2018 Mar 28;:

Authors: A AH, Sreedharan S, Ali F, Smythe CG, Thomas JA, Das A

Abstract
A new physiologically benign and cell membrane permeable BODIPY based molecular probe, MB-Sn, specifically senses intracellular hydrogen polysulfides (H2Sn, n > 1) localized in the endoplasmic reticulum. This reagent is suitable for mapping the intracellular distribution of H2Sn by wide-field as well as super-resolution Structured Illumination Microscopy (SIM).

PMID: 29589001 [PubMed - as supplied by publisher]

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Evolution of dietary preferences and the innate urge to heal: Drug discovery lessons from Ayurveda.

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Evolution of dietary preferences and the innate urge to heal: Drug discovery lessons from Ayurveda.

J Ayurveda Integr Med. 2018 Mar 22;:

Authors: Shrungeswara AH, Unnikrishnan MK

Abstract
Highly specialized and functionally integrated cognitive systems facilitate hedonistic and healthy food preferences. Guided by survival needs, flavor preferences not only select safe, nutritious dietary components, but also those with negligible calorific value but significant health benefits, for example, spices. Feeding behavior, both innate and acquired, is guided not only by taste receptors on the tongue but also visceral organs. The gustatory cortex receives information from all senses, not just taste, suggesting multiple checkpoints in predicting and evaluating healthy foods. Ayurvedic interpretation of 'rasa' as chemistry is compatible with medicinal value of diets because, taste and odor are chemosensory perceptions. As flavor and taste are linked to the chemical structure of compounds, taste might offer clues about pharmacological activity. Ayurvedic idea of vipaka, or post digestive perception of taste, recognizes the extended role of taste receptors beyond the tongue and stretching into the viscera. Ayurvedic wisdom is consistent with evolutionary guideposts that suggest three successive stages of nutritional appraisal: before, during, and after ingesting food. While olfaction induces affinity or revulsion even before ingestion, gustatory receptors on the tongue evaluates nutritional value upon contact, and the chemoreceptors in the deeper metabolic systems probably pronounce the final verdict on the nutritive and health benefits of ingested substances. Alliesthesia, neophobia, and the extreme variation in human T2R genes (coding for bitterness receptors) illustrate the importance of adaptive learning of dietary preferences. These evolutionary clues are compatible with the Ayurvedic principle of 'rasa', in facilitating the process of drug discovery.

PMID: 29576440 [PubMed - as supplied by publisher]

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Parasite Tolerance and Host Competence in Avian Host Defense to West Nile Virus.

Parasite Tolerance and Host Competence in Avian Host Defense to West Nile Virus.

Ecohealth. 2018 Mar 22;:

Authors: Burgan SC, Gervasi SS, Martin LB

Abstract
Competence, or the propensity of a host to transmit parasites, is partly underlain by host strategies to cope with infection (e.g., resistance and tolerance). Resistance represents the ability of hosts to prevent or clear infections, whereas tolerance captures the ability of individuals to cope with a given parasite burden. Here, we investigated (1) whether one easy-to-measure form of tolerance described well the dynamic relationships between host health and parasite burden, and (2) whether individual resistance and tolerance to West Nile virus (WNV) were predictable from single cytokine measures. We exposed house sparrows (HOSP) to WNV and measured subsequent changes in host performance, viral burden, and cytokine expression. We then used two novel approaches (one complex, one simpler) to estimate tolerance within-individual HOSP using four separate host performance traits. We lastly investigated changes in the expression of pro-inflammatory cytokine interferon-γ (IFN-γ) and anti-inflammatory cytokine interleukin-10 (IL-10). Both approaches to estimating tolerance were equivalent among WNV-infected HOSP; thus, an easy-to-measure tolerance estimation may be successfully applied in field studies. Constitutive expression of IFN-γ and IL-10 were predictive of resistance and tolerance to WNV, implicating these cytokines as viable biomarkers of host competence to WNV.

PMID: 29569179 [PubMed - as supplied by publisher]

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The Role of the Sucrose-Responsive IR60b Neuron for Drosophila melanogaster: A Hypothesis.

The Role of the Sucrose-Responsive IR60b Neuron for Drosophila melanogaster: A Hypothesis.

Chem Senses. 2018 Mar 13;:

Authors: Szyszka P, Galizia CG

Abstract
In a recent paper, Joseph and colleagues (Joseph et al., 2017) have characterized an IR60b receptor-expressing neuron in Drosophila. They showed that it responds to sucrose and serves to limit sucrose consumption, and proposed that it may thereby act to prevent overfeeding. Here, we propose an alternative hypothesis for the functional role of sucrose feeding control, and for how this limitation of sucrose uptake is accomplished. Adult fruit flies feed by excreting saliva onto the food, and imbibing the predigested liquefied food, or by filling the crop, where the food is predigested. Enzymes in the saliva hydrolyze starch and disaccharides into absorbable monosaccharides. Premature ingestion into the midgut would not give the enzymes in the saliva enough time to predigest the food. Thus, IR60b neurons might serve as a sensor to monitor the digestive state of external food or crop content: when disaccharides (sucrose) concentration is high, ingestion to the gut is inhibited, keeping a low concentration of starch and disaccharides in the midgut.

PMID: 29546407 [PubMed - as supplied by publisher]

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Re-test reliability of gustatory testing and introduction of the sensitive Taste-Drop-Test.

Re-test reliability of gustatory testing and introduction of the sensitive Taste-Drop-Test.

Chem Senses. 2018 Mar 12;:

Authors: Fjaeldstad A, Niklassen A, Fernandes H

Abstract
The sense of taste holds a key integrate role in assessing the flavour of food before swallowing is initiated. If the expectations for taste are not met, palatability and pleasure of the food can decrease. In patients suffering from taste disorders, this may impair appetite and nutritional state. Testing gustatory function can be important for diagnostics and assessment of treatment effects. However, the gustatory tests applied are required to be both sensitive and reliable.In this study, we investigate the re-test validity of popular Taste Strips gustatory test for gustatory screening. Furthermore, we introduce a new sensitive Taste-Drop-Test, which was found to be superior for detecting a more accurate measure of tastant sensitivity.

PMID: 29538619 [PubMed - as supplied by publisher]

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Visual-olfactory Interactions: Bimodal Facilitation and Impact on the Subjective Experience.

Visual-olfactory Interactions: Bimodal Facilitation and Impact on the Subjective Experience.

Chem Senses. 2018 Mar 08;:

Authors: Amsellem S, Höchenberger R, Ohla K

Abstract
Odors are inherently ambiguous and therefore susceptible to redundant sensory as well as context information. The identification of an odor object relies largely on visual input. Thus far, it is unclear whether visual and olfactory stimuli are indeed integrated at an early perceptual stage and which role the congruence between the visual and olfactory inputs plays. Previous studies on visual-olfactory interaction used either congruent or incongruent information, leaving it open whether nuances of visual-olfactory congruence shape perception differently. We aimed to answer 1) whether visual-olfactory information is integrated at early stages of processing, 2) whether visual-olfactory congruence is a gradual or dichotomous phenomenon, and 3) whether visual information influences bimodal stimulus evaluation and odor identity. We found a bimodal RT speedup that is consistent with parallel processing according to race models. Subjectively, pleasantness of bimodal stimuli increased with increasing congruence, and orange images biased odor composition toward orange. Visual-olfactory congruence was perceived in gradual and distinct categories, consistent with the notion that congruence is a gradual phenomenon. Together, the data provide evidence for bimodal facilitation consistent with parallel processing of the visual and olfactory stimuli, and that visual-olfactory interactions influence various levels of the subjective experience.

PMID: 29528380 [PubMed - as supplied by publisher]

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