The genotype–phenotype distinction: from Mendelian genetics to 21st century biology

Genetica - The Genotype-Phenotype (G-P) distinction was proposed in the context of Mendelian genetics, in the wake of late nineteenth century studies about heredity. In this paper, we provide a...     

Is there a link between vitamin D status,SARS‐CoV‐2 infection risk and COVID‐19 severity?

The outbreak of COVID‐19 emerged in December 2019 rapidly spread across the globe and has become pandemic. Little is known about the protective factors of this infection, which is equally distributed between genders and different ages while severe and poor prognosis cases are strongly associated to old males and the presence of comorbidities. Thus, preventive measures aiming at reducing the number of infection and/or their severity are strongly needed. Vitamin D has got great attention and has been claimed as potentially protective against the infection since it may be associated with immunocompetence, inflammation, aging, and those diseases involved in determining the outcomes of COVID‐19. This narrative review aims at collecting the literature available on the involvement of the vitamin D status in the pathogenesis of COVID‐19 and the putative utility of vitamin D supplementation in the therapeutics. It emerges that a poor vitamin D status seems to associate with an increased risk of infection whereas age, gender and comorbidities seem to play a more important role in COVID‐19 severity and mortality. While randomized control trials are needed to better inquire into this topic, vitamin D supplementation may be useful beside its potential effects on SARS‐CoV‐2 infection and COVID‐19.     

Estimating the cumulative incidence of COVID-19 in the United States using influenza surveillance,virologic testing,and mortality data: Four complementary approaches

Effectively designing and evaluating public health responses to the ongoing COVID-19 pandemic requires accurate estimation of the prevalence of COVID-19 across the United States (US). Equipment shortages and varying testing capabilities have however hindered the usefulness of the official reported positive COVID-19 case counts. We introduce four complementary approaches to estimate the cumulative incidence of symptomatic COVID-19 in each state in the US as well as Puerto Rico and the District of Columbia, using a combination of excess influenza-like illness reports, COVID-19 test statistics, COVID-19 mortality reports, and a spatially structured epidemic model. Instead of relying on the estimate from a single data source or method that may be biased, we provide multiple estimates, each relying on different assumptions and data sources. Across our four approaches emerges the consistent conclusion that on April 4, 2020, the estimated case count was 5 to 50 times higher than the official positive test counts across the different states. Nationally, our estimates of COVID-19 symptomatic cases as of April 4 have a likely range of 2.3 to 4.8 million, with possibly as many as 7.6 million cases, up to 25 times greater than the cumulative confirmed cases of about 311,000. Extending our methods to May 16, 2020, we estimate that cumulative symptomatic incidence ranges from 4.9 to 10.1 million, as opposed to 1.5 million positive test counts. The proposed combination of approaches may prove useful in assessing the burden of COVID-19 during resurgences in the US and other countries with comparable surveillance systems.     

Parameters and determinants of responses to selection in antibody libraries

The sequences of antibodies from a given repertoire are highly diverse at few sites located on the surface of a genome-encoded larger scaffold. The scaffold is often considered to play a lesser role than highly diverse, non-genome-encoded sites in controlling binding affinity and specificity. To gauge the impact of the scaffold, we carried out quantitative phage display experiments where we compare the response to selection for binding to four different targets of three different antibody libraries based on distinct scaffolds but harboring the same diversity at randomized sites. We first show that the response to selection of an antibody library may be captured by two measurable parameters. Second, we provide evidence that one of these parameters is determined by the degree of affinity maturation of the scaffold, affinity maturation being the process by which antibodies accumulate somatic mutations to evolve towards higher affinities during the natural immune response. In all cases, we find that libraries of antibodies built around maturated scaffolds have a lower response to selection to other arbitrary targets than libraries built around germline-based scaffolds. We thus propose that germline-encoded scaffolds have a higher selective potential than maturated ones as a consequence of a selection for this potential over the long-term evolution of germline antibody genes. Our results are a first step towards quantifying the evolutionary potential of biomolecules.     

Experimental increase in fecundity causes upregulation of fecundity and body maintenance genes in the fat body of ant queens

In most organisms, fecundity and longevity are negatively associated and the molecular regulation of these two life-history traits is highly interconnected. In addition, nutrient intake often has opposing effects on lifespan and reproduction. In contrast to solitary insects, the main reproductive individual of social hymenopterans, the queen, is also the most long-lived. During development, queen larvae are well-nourished, but we are only beginning to understand the impact of nutrition on the queens'' adult life and the molecular regulation and connectivity of fecundity and longevity. Here, we used two experimental manipulations to alter queen fecundity in the ant Temnothorax rugatulus and investigated associated changes in fat body gene expression. Egg removal triggered a fecundity increase, leading to expression changes in genes with functions in fecundity such as oogenesis and body maintenance. Dietary restriction lowered the egg production of queens and altered the expression of genes linked to autophagy, Toll signalling, cellular homeostasis and immunity. Our study reveals that an experimental increase in fecundity causes the co-activation of reproduction and body maintenance mechanisms, shedding light on the molecular regulation of the link between longevity and fecundity in social insects.     

Salinity-induced limits to mangrove canopy height

Aim

Mangrove canopy height is a key metric to assess tidal forests' resilience in the face of climate change. In terrestrial forests, tree height is primarily determined by water availability, plant hydraulic design, and disturbance regime. However, the role of water stress remains elusive in tidal environments, where saturated soils are prevalent, and salinity can substantially affect the soil water potential.

Location

Global.

Time Period

The canopy height dataset provides a global snapshot of the maximum mangrove height geographical distribution for the year 2000. Climate and environmental variables extend over the period 1970–2018.

Major Taxa Studied

Mangroves.

Methods

We use global observations of maximum canopy height, species richness, air temperature, and seawater salinity—a proxy of soil water salt concentration—to explore the causal link between salinity and mangrove stature.

Results

Our findings suggest that salt stress limits mangrove height. High salinity favours more salt-tolerant species, narrowing the spectrum of viable traits. Highly salt-tolerant mangroves have evolved to cope with high salt concentrations in the soil, but this adaptation comes at a cost. They typically have lower rates of photosynthesis and growth, resulting in reduced productivity and smaller stature compared to more salt-sensitive mangrove species. This suggests a causal link between salinity, biodiversity, and tree height, where high salinity selects for more salt-tolerant species that tend to be less productive and shorter.

Conclusions

We hypothesize that the salinity-induced limit to mangrove canopy height is the direct result of a reduction of primary productivity, an increment in the risk of xylem cavitation, and an indirect consequence of the decrease in biodiversity. As sea-level rise enhances coastal salinisation, failure to account for these effects can lead to incorrect estimates of future carbon stocks in Tropical coastal ecosystems and endanger preservation efforts.     

FTIR spectra of algal species can be used as physiological fingerprints to assess their actual growth potential

Fourier transform infrared (FTIR) spectra were measured from cells of Microcystis aeruginosa and Protoceratium reticulatum, whose growth rates were manipulated by the availability of nutrients or light. As expected, the macromolecular composition changed in response to the treatments. These changes were species‐specific and depended on the type of perturbation applied to the growth regime. Microcystis aeruginosa showed an increase in the carbohydrate‐to‐protein ratio with decreased growth rates, under nutrient limitation, whereas light limitation induced a decrease of the carbohydrate‐to‐protein ratio with decreasing proliferation rates. The macromolecular pools of P. reticulatum showed a higher degree of compositional homeostasis. Only when the lowest light irradiance and nutrient availability were supplied, an increase of the carbohydrate‐to‐protein FTIR absorbance ratio was observed. A species‐specific partial least squares (PLS) model was developed using the whole FTIR spectra. This model afforded a very high correlation between the predicted and the measured growth rates, regardless of the growth conditions. On the contrary, the prediction based on absorption band ratios generally used in FTIR studies would strongly depend on growth conditions. This new computational method could constitute a substantial improvement in the early warning systems of algal blooms and, in general, for the study of algal growth, e.g. in biotechnology. Furthermore, these results confirm the suitability of FTIR spectroscopy as a tool to map complex biological processes like growth under different environmental conditions.     

Discovery,synthesis, selectivity modulation and DMPK characterization of 5-azaspiro[2.4]heptanes as potent orexin receptor antagonists

Starting from a orexin 1 receptor selective antagonist 4,4-disubstituted piperidine series a novel potent 5-azaspiro[2.4]heptane dual orexin 1 and orexin 2 receptor antagonist class has been discovered. SAR and Pharmacokinetic optimization of this series is herein disclosed. Lead compound 15 exhibits potent activity against orexin 1 and orexin 2 receptors along with low cytochrome P450 inhibition potential, good brain penetration and oral bioavailability in rats.