Natural Indoles,Indole-3-Carbinol (I3C) and 3,3’-Diindolylmethane (DIM), Attenuate Staphylococcal Enterotoxin B-Mediated Liver Injury by Downregulating miR-31 Expression and Promoting Caspase-2-Mediated Apoptosis

Staphylococcal enterotoxin B (SEB) is a potent superantigen capable of inducing inflammation characterized by robust immune cell activation and proinflammatory cytokine release. Exposure to SEB can result in food poisoning as well as fatal conditions such as toxic shock syndrome. In the current study, we investigated the effect of natural indoles including indole-3-carbinol (I3C) and 3,3’-diindolylmethane (DIM) on SEB-mediated liver injury. Injection of SEB into D-galactosamine-sensitized female C57BL/6 mice resulted in liver injury as indicated by an increase in enzyme aspartate transaminase (AST) levels, induction of inflammatory cytokines, and massive infiltration of immune cells into the liver. Administration of I3C and DIM (40mg/kg), by intraperitonal injection, attenuated SEB-induced acute liver injury, as evidenced by decrease in AST levels, inflammatory cytokines and cellular infiltration in the liver. I3C and DIM triggered apoptosis in SEB-activated T cells primarily through activation of the intrinsic mitochondrial pathway. In addition, inhibitor studies involving caspases revealed that I3C and DIM-mediated apoptosis in these activated cells was dependent on caspase-2 but independent of caspase-8, 9 and 3. In addition, I3C and DIM caused a decrease in Bcl-2 expression. Both compounds also down-regulated miR-31, which directly targets caspase-2 and influences apoptosis in SEB-activated cells. Our data demonstrate for the first time that indoles can effectively suppress acute hepatic inflammation caused by SEB and that this may be mediated by decreased expression of miR-31 and consequent caspase-2-dependent apoptosis in T cells.     

Reef Fishes in Biodiversity Hotspots Are at Greatest Risk from Loss of Coral Species

Coral reef ecosystems are under a variety of threats from global change and anthropogenic disturbances that are reducing the number and type of coral species on reefs. Coral reefs support upwards of one third of all marine species of fish, so the loss of coral habitat may have substantial consequences to local fish diversity. We posit that the effects of habitat degradation will be most severe in coral regions with highest biodiversity of fishes due to greater specialization by fishes for particular coral habitats. Our novel approach to this important but untested hypothesis was to conduct the same field experiment at three geographic locations across the Indo-Pacific biodiversity gradient (Papua New Guinea; Great Barrier Reef, Australia; French Polynesia). Specifically, we experimentally explored whether the response of local fish communities to identical changes in diversity of habitat-providing corals was independent of the size of the regional species pool of fishes. We found that the proportional reduction (sensitivity) in fish biodiversity to loss of coral diversity was greater for regions with larger background species pools, reflecting variation in the degree of habitat specialization of fishes across the Indo-Pacific diversity gradient. This result implies that habitat-associated fish in diversity hotspots are at greater risk of local extinction to a given loss of habitat diversity compared to regions with lower species richness. This mechanism, related to the positive relationship between habitat specialization and regional biodiversity, and the elevated extinction risk this poses for biodiversity hotspots, may apply to species in other types of ecosystems.     

A Multi-Area Stochastic Model for a Covert Visual Search Task

Decisions typically comprise several elements. For example, attention must be directed towards specific objects, their identities recognized, and a choice made among alternatives. Pairs of competing accumulators and drift-diffusion processes provide good models of evidence integration in two-alternative perceptual choices, but more complex tasks requiring the coordination of attention and decision making involve multistage processing and multiple brain areas. Here we consider a task in which a target is located among distractors and its identity reported by lever release. The data comprise reaction times, accuracies, and single unit recordings from two monkeys’ lateral interparietal area (LIP) neurons. LIP firing rates distinguish between targets and distractors, exhibit stimulus set size effects, and show response-hemifield congruence effects. These data motivate our model, which uses coupled sets of leaky competing accumulators to represent processes hypothesized to occur in feature-selective areas and limb motor and pre-motor areas, together with the visual selection process occurring in LIP. Model simulations capture the electrophysiological and behavioral data, and fitted parameters suggest that different connection weights between LIP and the other cortical areas may account for the observed behavioral differences between the animals.     

Differentiating Biological Colours with Few and Many Sensors: Spectral Reconstruction with RGB and Hyperspectral Cameras

Background

The ability to discriminate between two similar or progressively dissimilar colours is important for many animals as it allows for accurately interpreting visual signals produced by key target stimuli or distractor information. Spectrophotometry objectively measures the spectral characteristics of these signals, but is often limited to point samples that could underestimate spectral variability within a single sample. Algorithms for RGB images and digital imaging devices with many more than three channels, hyperspectral cameras, have been recently developed to produce image spectrophotometers to recover reflectance spectra at individual pixel locations. We compare a linearised RGB and a hyperspectral camera in terms of their individual capacities to discriminate between colour targets of varying perceptual similarity for a human observer.

Main Findings

(1) The colour discrimination power of the RGB device is dependent on colour similarity between the samples whilst the hyperspectral device enables the reconstruction of a unique spectrum for each sampled pixel location independently from their chromatic appearance. (2) Uncertainty associated with spectral reconstruction from RGB responses results from the joint effect of metamerism and spectral variability within a single sample.

Conclusion

(1) RGB devices give a valuable insight into the limitations of colour discrimination with a low number of photoreceptors, as the principles involved in the interpretation of photoreceptor signals in trichromatic animals also apply to RGB camera responses. (2) The hyperspectral camera architecture provides means to explore other important aspects of colour vision like the perception of certain types of camouflage and colour constancy where multiple, narrow-band sensors increase resolution.     

Cell competition: Winning out by losing notch

Cell competition where ‘loser’ cells are eliminated by neighbors with higher fitness is a widespread phenomenon in development. However, a growing body of evidence argues cells with somatic mutations compete with their wild type counterparts in the earliest stages of cancer development. Recent studies have begun to shed light on the molecular and cellular mechanisms that alter the competitiveness of cells carrying somatic mutations in adult tissues. Cells with a ‘winner’ phenotype create clones which may expand into extensive fields of mutant cells within normal appearing epithelium, favoring the accumulation of further genetic alterations and the evolution of cancer. Here we focus on how mutations which disrupt the Notch signaling pathway confer a ‘super competitor’ status on cells in squamous epithelia and consider the broader implications for cancer evolution.     

Evaluation of a Minimally Invasive Cell Sampling Device Coupled with Assessment of Trefoil Factor 3 Expression for Diagnosing Barrett's Esophagus: A Multi-Center Case–Control Study

BackgroundBarrett''s esophagus (BE) is a commonly undiagnosed condition that predisposes to esophageal adenocarcinoma. Routine endoscopic screening for BE is not recommended because of the burden this would impose on the health care system. The objective of this study was to determine whether a novel approach using a minimally invasive cell sampling device, the Cytosponge, coupled with immunohistochemical staining for the biomarker Trefoil Factor 3 (TFF3), could be used to identify patients who warrant endoscopy to diagnose BE.ConclusionsThe Cytosponge-TFF3 test is safe and acceptable, and has accuracy comparable to other screening tests. This test may be a simple and inexpensive approach to identify patients with reflux symptoms who warrant endoscopy to diagnose BE.     

Speeding Up Ecological and Evolutionary Computations in R; Essentials of High Performance Computing for Biologists

Computation has become a critical component of research in biology. A risk has emerged that computational and programming challenges may limit research scope, depth, and quality. We review various solutions to common computational efficiency problems in ecological and evolutionary research. Our review pulls together material that is currently scattered across many sources and emphasizes those techniques that are especially effective for typical ecological and environmental problems. We demonstrate how straightforward it can be to write efficient code and implement techniques such as profiling or parallel computing. We supply a newly developed R package (aprof) that helps to identify computational bottlenecks in R code and determine whether optimization can be effective. Our review is complemented by a practical set of examples and detailed Supporting Information material (S1–S3 Texts) that demonstrate large improvements in computational speed (ranging from 10.5 times to 14,000 times faster). By improving computational efficiency, biologists can feasibly solve more complex tasks, ask more ambitious questions, and include more sophisticated analyses in their research.

This is part of the PLOS Computational Biology Education collection.

     

Large-Scale Analysis of Kinase Signaling in Yeast Pseudohyphal Development Identifies Regulation of Ribonucleoprotein Granules

Yeast pseudohyphal filamentation is a stress-responsive growth transition relevant to processes required for virulence in pathogenic fungi. Pseudohyphal growth is controlled through a regulatory network encompassing conserved MAPK (Ste20p, Ste11p, Ste7p, Kss1p, and Fus3p), protein kinase A (Tpk2p), Elm1p, and Snf1p kinase pathways; however, the scope of these pathways is not fully understood. Here, we implemented quantitative phosphoproteomics to identify each of these signaling networks, generating a kinase-dead mutant in filamentous S. cerevisiae and surveying for differential phosphorylation. By this approach, we identified 439 phosphoproteins dependent upon pseudohyphal growth kinases. We report novel phosphorylation sites in 543 peptides, including phosphorylated residues in Ras2p and Flo8p required for wild-type filamentous growth. Phosphoproteins in these kinase signaling networks were enriched for ribonucleoprotein (RNP) granule components, and we observe co-localization of Kss1p, Fus3p, Ste20p, and Tpk2p with the RNP component Igo1p. These kinases localize in puncta with GFP-visualized mRNA, and KSS1 is required for wild-type levels of mRNA localization in RNPs. Kss1p pathway activity is reduced in lsm1Δ/Δ and pat1Δ/Δ strains, and these genes encoding P-body proteins are epistatic to STE7. The P-body protein Dhh1p is also required for hyphal development in Candida albicans. Collectively, this study presents a wealth of data identifying the yeast phosphoproteome in pseudohyphal growth and regulatory interrelationships between pseudohyphal growth kinases and RNPs.     

“They Know,They Agree,but They Don’t Do”- The Paradox of Tuberculosis Case Notification by Private Practitioners in Alappuzha District,Kerala, India

Background

Despite being a recognized standard of tuberculosis (TB) care internationally, mandatory TB case notification brings forth challenges from the private sector. Only three TB cases were notified in 2013 by private practitioners compared to 2000 TB cases notified yearly from the public sector in Alappuzha district. The study objective was to explore the knowledge, opinion and barriers regarding TB Notification among private practitioners offering TB services in Alappuzha, Kerala state, India.

Methods & Findings

This was a mixed-methods study with quantitative (survey) and qualitative components conducted between December 2013 and July 2014. The survey, using a structured questionnaire, among 169 private practitioners revealed that 88% were aware of mandatory notification. All patient-related details requested in the notification form (except government-issued identification number) were perceived to be important and easy to provide by more than 80% of practitioners. While more than 95% felt that notification should be mandatory, punitive action in case of failure to notify was considered unnecessary by almost two third. General practitioners (98%) were more likely to be aware of notification than specialists (84 %). (P<0.01). Qualitative purposive personal interviews (n=34) were carried out among private practitioners and public health providers. On thematic framework analysis of the responses, barriers to TB notification were grouped into three themes: ‘private provider misconceptions about notification’, ‘patient confidentiality, and stigma and discrimination ’and ‘lack of cohesion and coordination between public and private sector’. Private practitioners did not consider it necessary to notify TB cases treated with daily regimen.

Conclusion

Communication strategies like training, timely dissemination of information of policy changes and one-to-one dialogue with private practitioners to dispel misconceptions may enhance TB notification. Trust building strategies like providing feedback about referred cases from private sector, health personnel visit or a liaison private doctor may ensure compliance to public health activities.