The effect of dendritic cell mobilization on CD8+ T cell responses to influenza A virus

Influenza A viruses (IAV) cause respiratory infections with potentially catastrophic consequences. Neutralizing antibodies towards surface proteins of IAV prevent reinfection. However, mutations in these proteins allow the virus to evade these antibodies. Enhancing cytotoxic T cell-mediated immunity has been proposed as an attractive strategy to combat flu. Recombinant human FMS-like tyrosine kinase 3 ligand (FL) is known to mobilize dendritic cells (DCs) in mice. Given that DCs are the most potent antigen-presenting cells, I hypothesized that their mobilization by FL will improve the CD8+ T cell response to IAV. Quantification of CD8+ T cell responses to IAV epitopes by intracellular cytokine staining revealed that FL treatment can indeed increase the frequencies and absolute numbers of mouse T cells specific for select IAV epitopes. Additionally, FL treatment increased the killing function of IAV-specific T cells. My results suggest that FL may exert a therapeutic benefit in the context of flu infection

Examining the profound effects of COVID19 on mental health: A comprehensive systematic review on anxiety and depression

The COVID-19 pandemic has presented challenges to humanity, economically and in health and wellbeing. The associated limited social isolation and lifestyle changes has increased the risk for mental health services, especially among vulnerable people. This highlights the need for mental health services, burden that already stretch the health systems. This review presents an exposition on COVID-19 and mental health, and ways to minimise, and possibly prevent, their effect on the psychological well-being of those people. We searched four databases (Academic Search Complete, CINAHL Plus, PsycINFO and PsycARTICLES) using specific search terms and eligibility criteria. Of the 33 included studies, 31 were quantitative, and one qualitative and mixed method each. The studies were analysed using thematic narrative synthesis that resulted in three main themes: (a) the internal and external influences on COVID-19 behaviour, (b) the impact of COVID-19 on health and well-being and (c) the coping strategies used. Since COVID-19 will exist for the foreseeable future, understanding its impact on health and mental well-being and the coping techniques to be adopted are important now than ever. This study contributes to such an understanding along with suggestions regarding ways to minimise the impact of COVID-19 on mental health using context-appropriate strategies

Individual aggregates of amyloid beta induce temporary calcium influx through the cell membrane of neuronal cells.

Local delivery of amyloid beta oligomers from the tip of a nanopipette, controlled over the cell surface, has been used to deliver physiological picomolar oligomer concentrations to primary astrocytes or neurons. Calcium influx was observed when as few as 2000 oligomers were delivered to the cell surface. When the dosing of oligomers was stopped the intracellular calcium returned to basal levels or below. Calcium influx was prevented by the presence in the pipette of the extracellular chaperone clusterin, which is known to selectively bind oligomers, and by the presence a specific nanobody to amyloid beta. These data are consistent with individual oligomers larger than trimers inducing calcium entry as they cross the cell membrane, a result supported by imaging experiments in bilayers, and suggest that the initial molecular event that leads to neuronal damage does not involve any cellular receptors, in contrast to work performed at much higher oligomer concentrations.Herchel Smith (Postdoctoral Fellowship), Engineering and Physical Sciences Research Council (studentship), European Research Council (Advanced Grant (669237)), Augustus Newman Foundatio

A Streamlined DNA Tool for Global Identification of Heavily Exploited Coastal Shark Species (Genus Rhizoprionodon)

Obtaining accurate species-specific landings data is an essential step toward achieving sustainable shark fisheries. Globally distributed sharpnose sharks (genus Rhizoprionodon) exhibit life-history characteristics (rapid growth, early maturity, annual reproduction) that suggests that they could be fished in a sustainable manner assuming an investment in monitoring, assessment and careful management. However, obtaining species-specific landings data for sharpnose sharks is problematic because they are morphologically very similar to one another. Moreover, sharpnose sharks may also be confused with other small sharks (either small species or juveniles of large species) once they are processed (i.e., the head and fins are removed). Here we present a highly streamlined molecular genetics approach based on seven species-specific PCR primers in a multiplex format that can simultaneously discriminate body parts from the seven described sharpnose shark species commonly occurring in coastal fisheries worldwide. The species-specific primers are based on nucleotide sequence differences among species in the nuclear ribosomal internal transcribed spacer 2 locus (ITS2). This approach also distinguishes sharpnose sharks from a wide range of other sharks (52 species) and can therefore assist in the regulation of coastal shark fisheries around the world

Repeated, long-distance migrations by a philopatric predator targeting highly contrasting ecosystems

Long-distance movements of animals are an important driver of population spatial dynamics and determine the extent of overlap with area-focused human activities, such as fishing. Despite global concerns of declining shark populations, a major limitation in assessments of population trends or spatial management options is the lack of information on their long-term migratory behaviour. For a large marine predator, the tiger shark Galeocerdo cuvier, we show from individuals satellite-tracked for multiple years (up to 1101 days) that adult males undertake annually repeated, round-trip migrations of over 7,500 km in the northwest Atlantic. Notably, these migrations occurred between the highly disparate ecosystems of Caribbean coral reef regions in winter and high latitude oceanic areas in summer, with strong, repeated philopatry to specific overwintering insular habitat. Partial migration also occurred, with smaller, immature individuals displaying reduced migration propensity. Foraging may be a putative motivation for these oceanic migrations, with summer behaviour showing higher path tortuosity at the oceanic range extremes. The predictable migratory patterns and use of highly divergent ecosystems shown by male tiger sharks appear broadly similar to migrations seen in birds, reptiles and mammals, and highlight opportunities for dynamic spatial management and conservation measures of highly mobile sharks

A mitotic function for the high-mobility group protein HMG20b regulated by its interaction with the BRC repeats of the BRCA2 tumor suppressor.

The inactivation of BRCA2, a suppressor of breast, ovarian and other epithelial cancers, triggers instability in chromosome structure and number, which are thought to arise from defects in DNA recombination and mitotic cell division, respectively. Human BRCA2 controls DNA recombination via eight BRC repeats, evolutionarily conserved motifs of ∼35 residues, that interact directly with the recombinase RAD51. How BRCA2 controls mitotic cell division is debated. Several studies by different groups report that BRCA2 deficiency affects cytokinesis. Moreover, its interaction with HMG20b, a protein of uncertain function containing a promiscuous DNA-binding domain and kinesin-like coiled coils, has been implicated in the G2-M transition. We show here that HMG20b depletion by RNA interference disturbs the completion of cell division, suggesting a novel function for HMG20b. In vitro, HMG20b binds directly to the BRC repeats of BRCA2, and exhibits the highest affinity for BRC5, a motif that binds poorly to RAD51. Conversely, the BRC4 repeat binds strongly to RAD51, but not to HMG20b. In vivo, BRC5 overexpression inhibits the BRCA2-HMG20b interaction, recapitulating defects in the completion of cell division provoked by HMG20b depletion. In contrast, BRC4 inhibits the BRCA2-RAD51 interaction and the assembly of RAD51 at sites of DNA damage, but not the completion of cell division. Our findings suggest that a novel function for HMG20b in cytokinesis is regulated by its interaction with the BRC repeats of BRCA2, and separate this unexpected function for the BRC repeats from their known activity in DNA recombination. We propose that divergent tumor-suppressive pathways regulating chromosome segregation as well as chromosome structure may be governed by the conserved BRC motifs in BRCA2

First insights into the vertical habitat use of the whitespotted eagle ray Aetobatus narinari revealed by pop‐up satellite archival tags

The whitespotted eagle ray Aetobatus narinari is a tropical to warm‐temperate benthopelagic batoid that ranges widely throughout the western Atlantic Ocean. Despite conservation concerns for the species, its vertical habitat use and diving behaviour remain unknown. Patterns and drivers in the depth distribution of A. narinari were investigated at two separate locations, the western North Atlantic (Islands of Bermuda) and the eastern Gulf of Mexico (Sarasota, Florida, U.S.A.). Between 2010 and 2014, seven pop‐up satellite archival tags were attached to A. narinari using three methods: a through‐tail suture, an external tail‐band and through‐wing attachment. Retention time ranged from 0 to 180 days, with tags attached via the through‐tail method retained longest. Tagged rays spent the majority of time (82.85 ± 12.17% S.D.) within the upper 10 m of the water column and, with one exception, no rays travelled deeper than ~26 m. One Bermuda ray recorded a maximum depth of 50.5 m, suggesting that these animals make excursions off the fore‐reef slope of the Bermuda Platform. Individuals occupied deeper depths (7.42 ± 3.99 m S.D.) during the day versus night (4.90 ± 2.89 m S.D.), which may be explained by foraging and/or predator avoidance. Each individual experienced a significant difference in depth and temperature distributions over the diel cycle. There was evidence that mean hourly depth was best described by location and individual variation using a generalized additive mixed model approach. This is the first study to compare depth distributions of A. narinari from different locations and describe the thermal habitat for this species. Our study highlights the importance of region in describing A. narinari depth use, which may be relevant when developing management plans, whilst demonstrating that diel patterns appear to hold across individuals