Breadth of the Wild: Global Patterns in Elasmobranch Dietary Niche Breadth

A widely recognized pattern in ecology is the latitudinal diversity gradient: increasing biodiversity with decreasing latitude. The latitude niche-breadth hypothesis states that the stable climate of the tropics allows for increased specialization (smaller niche), promoting greater biodiversity in the available niche space. The highly dynamic climate of the poles drives the evolution of generalists (larger niche), limiting biodiversity. While the fundamental question of “what drives species richness?” on land remains debated, it is even less understood in the marine environment. Elasmobranchs (sharks, skates, and rays) are a data-rich, globally distributed group that occupy an array of functional roles, inhabiting coastal to open ocean habitats from the poles to the tropics. In this thesis, I use a global-scale stomach contents dataset to calculate standardized Levin’s niche breadth for 237 populations of 85 elasmobranch species in order to examine spatial patterns in niche breadth. I find that niche breadth varies widely across all functional, taxonomic, and regional groups, highlighting the diversity and potential resiliency of this clade. Niche breadth of elasmobranchs does not follow a latitudinal gradient. Instead, niche varies with depth, with niche breadth generally increasing with increasing depth. This depth gradient is strongest in bottom-dwelling elasmobranchs with smaller range sizes and weakest in wide-ranging pelagic elasmobranchs. This pattern suggests that for species with limited mobility, specialization may mediate coexistence in highly biodiverse areas with elevated competition. Why this pattern applies in a depth, but not latitudinal, gradient remains unclear

Reconstructed Russian Fisheries Catches in the Barents Sea: 1950-2014

The management of marine living resources that straddle country borders has historically been a challenge, particularly in cases where political tensions are high. The jointly managed fisheries resources in the Barents Sea are a notable exception, wherein the Russian Federation (formerly Soviet Union) and Norway have relatively successfully managed fish stocks together since the 1950s, including during the high tensions of the Cold War and the dissolution of the Soviet Union. Using ICES statistics as reported baseline landings, the total catch of the region by the Russian fisheries was reconstructed for the period 1950-2014. Total catch was divided into reported landings, unreported landings, and discards, and assigned to four sectors: industrial, artisanal, recreational, and subsistence. Unreported landings and discards between 1950 and 2014 accounted for ~12 and 55% of the total catch, respectively, with discards being substantial in the early decades. A majority of the catch was caught using pelagic and bottom trawls, contributing to the high rate of discards. Both discards and landings reached their peak in the 1970s, after which overexploitation contributed to numerous stock declines. Stocks recovered in the 1990s following adoption of legislation and gear regulations limiting discards as part of a joint effort by Norway and Russia to more sustainably manage stocks. The trend of declining Russian Barents Sea catches after the 1980s matches global trends of declining catch, although the present case appears to be mainly due to more successful management interventions. It is assumed that small-scale fisheries removals are minor in the region, but further research to refine estimates of small-scale fishing can improve upon the present study. While this study highlights historical declines in catch due to overexploitation, it does not explore fluctuations in catch caused by environmental variation. In the rapidly warming Arctic region it is of vital importance to understand how stocks may be further affected by climate change in addition to fishing pressure

Time Course of Brain Network Reconfiguration Supporting Inhibitory Control

Hemodynamic research has recently clarified key nodes and links in brain networks implementing inhibitory control. Although fMRI methods are optimized for identifying the structure of brain networks, the relatively slow temporal course of fMRI limits the ability to characterize network operation. The latter is crucial for developing a mechanistic understanding of how brain networks shift dynamically to support inhibitory control. To address this critical gap, we applied spectrally resolved Granger causality (GC) and random forest machine learning tools to human EEG data in two large samples of adults (test sample n = 96, replication sample n = 237, total N = 333, both sexes) who performed a color–word Stroop task. Time–frequency analysis confirmed that recruitment of inhibitory control accompanied by slower behavioral responses was related to changes in theta and alpha/beta power. GC analyses revealed directionally asymmetric exchanges within frontal and between frontal and parietal brain areas: top-down influence of superior frontal gyrus (SFG) over both dorsal ACC (dACC) and inferior frontal gyrus (IFG), dACC control over middle frontal gyrus (MFG), and frontal–parietal exchanges (IFG, precuneus, MFG). Predictive analytics confirmed a combination of behavioral and brain-derived variables as the best set of predictors of inhibitory control demands, with SFG theta bearing higher classification importance than dACC theta and posterior beta tracking the onset of behavioral response. The present results provide mechanistic insight into the biological implementation of a psychological phenomenon: inhibitory control is implemented by dynamic routing processes during which the target response is upregulated via theta-mediated effective connectivity within key PFC nodes and via beta-mediated motor preparation

Molecular mechanism of biased signaling at the kappa opioid receptor

The κ-opioid receptor (KOR) has emerged as an attractive drug target for pain management without addiction, and biased signaling through particular pathways of KOR may be key to maintaining this benefit while minimizing side-effect liabilities. As for most G protein-coupled receptors (GPCRs), however, the molecular mechanisms of ligand-specific signaling at KOR have remained unclear. To better understand the molecular determinants of KOR signaling bias, we apply structure determination, atomic-level molecular dynamics (MD) simulations, and functional assays. We determine a crystal structure of KOR bound to the G protein-biased agonist nalfurafine, the first approved KOR-targeting drug. We also identify an arrestin-biased KOR agonist, WMS-X600. Using MD simulations of KOR bound to nalfurafine, WMS-X600, and a balanced agonist U50,488, we identify three active-state receptor conformations, including one that appears to favor arrestin signaling over G protein signaling and another that appears to favor G protein signaling over arrestin signaling. These results, combined with mutagenesis validation, provide a molecular explanation of how agonists achieve biased signaling at KOR

An Indocyanine Green-Based Nanoprobe for In Vivo Detection of Cellular Senescence

There is an urgent need to improve conventional cancer-treatments by preventing detrimental side effects, cancer recurrence and metastases. Recent studies have shown that presence of senescent cells in tissues treated with chemo- or radiotherapy can be used to predict the effectiveness of cancer treatment. However, although the accumulation of senescent cells is one of the hallmarks of cancer, surprisingly little progress has been made in development of strategies for their detection in vivo. To address a lack of detection tools, we developed a biocompatible, injectable organic nanoprobe (NanoJagg), which is selectively taken up by senescent cells and accumulates in the lysosomes. The NanoJagg probe is obtained by self-assembly of indocyanine green (ICG) dimers using a scalable manufacturing process and characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. In vitro, ex vivo and in vivo studies all indicate that NanoJaggs are a clinically translatable probe for detection of senescence and their PAT signal makes them suitable for longitudinal monitoring of the senescence burden in solid tumors after chemotherapy or radiotherapy.</p

An Indocyanine Green-Based Nanoprobe for In Vivo Detection of Cellular Senescence

There is an urgent need to improve conventional cancer-treatments by preventing detrimental side effects, cancer recurrence and metastases. Recent studies have shown that presence of senescent cells in tissues treated with chemo- or radiotherapy can be used to predict the effectiveness of cancer treatment. However, although the accumulation of senescent cells is one of the hallmarks of cancer, surprisingly little progress has been made in development of strategies for their detection in vivo. To address a lack of detection tools, we developed a biocompatible, injectable organic nanoprobe (NanoJagg), which is selectively taken up by senescent cells and accumulates in the lysosomes. The NanoJagg probe is obtained by self-assembly of indocyanine green (ICG) dimers using a scalable manufacturing process and characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. In vitro, ex vivo and in vivo studies all indicate that NanoJaggs are a clinically translatable probe for detection of senescence and their PAT signal makes them suitable for longitudinal monitoring of the senescence burden in solid tumors after chemotherapy or radiotherapy.</p

Transmission Electron Microscopy Reveals Distinct Macrophage- and Tick Cell-Specific Morphological Stages of Ehrlichia chaffeensis

Background: Ehrlichia chaffeensis is an emerging tick-borne rickettsial pathogen responsible for human monocytic ehrlichiosis. Despite the induction of an active host immune response, the pathogen has evolved to persist in its vertebrate and tick hosts. Understanding how the organism progresses in tick and vertebrate host cells is critical in identifying effective strategies to block the pathogen transmission. Our recent molecular and proteomic studies revealed differences in numerous expressed proteins of the organism during its growth in different host environments. Methodology/Principal Findings: Transmission electron microscopy analysis was performed to assess morphological changes in the bacterium within macrophages and tick cells. The stages of pathogen progression observed included the attachment of the organism to the host cells, its engulfment and replication within a morulae by binary fission and release of the organisms from infected host cells by complete host cell lysis or by exocytosis. E. chaffeensis grown in tick cells was highly pleomorphic and appears to replicate by both binary fission and filamentous type cell divisions. The presence of Ehrlichia-like inclusions was also observed within the nucleus of both macrophages and tick cells. This observation was confirmed by confocal microscopy and immunoblot analysis. Conclusions/Significance: Morphological differences in the pathogen’s progression, replication, and processing within macrophages and tick cells provide further evidence that E. chaffeensis employs unique host-cell specific strategies in support of adaptation to vertebrate and tick cell environments

Real-life biomarker response to anti-IL5 and anti-IgE therapies in severe asthma patients

Funding: This study was conducted by the Observational and Pragmatic Research Institute (OPRI) Pte Ltd and was partially funded by Optimum Patient Care Global and AstraZeneca Ltd. No funding was received by OPRI for its contribution.Peer reviewedPostprin

Development of a Novel ex vivo Nasal Epithelial Cell Model Supporting Colonization With Human Nasal Microbiota

The nasal mucosa provides first line defense against inhaled pathogens while creating a unique microenvironment for bacterial communities. Studying the impact of microbiota in the nasal cavity has been difficult due to limitations with current models including explant cultures, primary cells, or neoplastic cell lines. Most notably, none have been shown to support reproducible colonization by bacterial communities from human donors. Therefore, to conduct controlled studies of the human nasal ecosystem, we have developed a novel ex vivo mucosal model that supports bacterial colonization of a cultured host mucosa created by immortalized human nasal epithelial cells (NEC). For this model, immortalized NEC established from 5 male and 5 female donors were cultured with an air-interfaced, apical surface on a porous transwell membrane. NEC were grown from nasal turbinate tissues harvested from willed bodies or from discarded tissue collected during sinonasal procedures. Immortalized cells were evaluated through molecular verification of cell type, histological confirmation of tissue differentiation including formation of tight junctions, NEC multilayer viability, metabolism, physiology and imaging of the luminal surface by scanning electron microscopy. Results showed proper differentiation and multilayer formation at seven to 10 days after air interface that was maintained for up to 3 weeks. The optimized mucosal cultures created an environment necessary to sustain colonization by nasal microbiomes (NMBs) that were collected from healthy volunteers, cryogenically preserved and characterized with customized quantitative polymerase chain reaction (qPCR) arrays. Polymicrobial communities of nasal bacteria associated with healthy and inflamed states were consistently reproduced in matured NEC co-cultures by transplant of NMBs from multiple community types. The cultured NMBs were stable after an initial period of bacterial replication and equilibration. This novel ex vivo culture system is the first model that supports controlled cultivation of NMBs, allowing for lab-based causation studies and further experimentation to explore the complexities of host-microbe and microbe-microbe interactions