Computational investigation of the key factors affecting the second stage activation mechanisms of domain II m-calpain

The unique conformation of the active site in calpains along with the implication of their role in several diseases has prompted widespread research interest in the scientific community. Structural studies devoted to m- and μ-calpains have proposed a two-stage calcium-dependent activation mechanism for calpains. In this work, we performed conventional and targeted molecular dynamics simulations to investigate global and local changes in the structure of the protease core of m-calpain upon calcium binding. Simulations were performed on the protease core of calcium free (pdbid: 1kfu) and calcium bound (pdbid: 3df0) m-calpain with and without the presence of calcium ions. Our results indicate that the inactive, open conformation of the protease core does not transform into the active, closed conformation simply upon removal of constraints from the neighbor domains. The role of other factors, including calcium binding and the subsequent formation of an Arg94–Glu305 inter-domain salt bridge and the change in the orientation of Trp288 side chain, in the activation of the protease core is elicited.     

Signatures of Diversifying Selection in European Pig Breeds

Following domestication, livestock breeds have experienced intense selection pressures for the development of desirable traits. This has resulted in a large diversity of breeds that display variation in many phenotypic traits, such as coat colour, muscle composition, early maturity, growth rate, body size, reproduction, and behaviour. To better understand the relationship between genomic composition and phenotypic diversity arising from breed development, the genomes of 13 traditional and commercial European pig breeds were scanned for signatures of diversifying selection using the Porcine60K SNP chip, applying a between-population (differentiation) approach. Signatures of diversifying selection between breeds were found in genomic regions associated with traits related to breed standard criteria, such as coat colour and ear morphology. Amino acid differences in the EDNRB gene appear to be associated with one of these signatures, and variation in the KITLG gene may be associated with another. Other selection signals were found in genomic regions including QTLs and genes associated with production traits such as reproduction, growth, and fat deposition. Some selection signatures were associated with regions showing evidence of introgression from Asian breeds. When the European breeds were compared with wild boar, genomic regions with high levels of differentiation harboured genes related to bone formation, growth, and fat deposition.     

The C. elegans Male Exercises Directional Control during Mating through Cholinergic Regulation of Sex-Shared Command Interneurons

Background

Mating behaviors in simple invertebrate model organisms represent tractable paradigms for understanding the neural bases of sex-specific behaviors, decision-making and sensorimotor integration. However, there are few examples where such neural circuits have been defined at high resolution or interrogated.

Methodology/Principal Findings

Here we exploit the simplicity of the nematode Caenorhabditis elegans to define the neural circuits underlying the male’s decision to initiate mating in response to contact with a mate. Mate contact is sensed by male-specific sensilla of the tail, the rays, which subsequently induce and guide a contact-based search of the hermaphrodite’s surface for the vulva (the vulva search). Atypically, search locomotion has a backward directional bias so its implementation requires overcoming an intrinsic bias for forward movement, set by activity of the sex-shared locomotory system. Using optogenetics, cell-specific ablation- and mutant behavioral analyses, we show that the male makes this shift by manipulating the activity of command cells within this sex-shared locomotory system. The rays control the command interneurons through the male-specific, decision-making interneuron PVY and its auxiliary cell PVX. Unlike many sex-shared pathways, PVY/PVX regulate the command cells via cholinergic, rather than glutamatergic transmission, a feature that likely contributes to response specificity and coordinates directional movement with other cholinergic-dependent motor behaviors of the mating sequence. PVY/PVX preferentially activate the backward, and not forward, command cells because of a bias in synaptic inputs and the distribution of key cholinergic receptors (encoded by the genes acr-18, acr-16 and unc-29) in favor of the backward command cells.

Conclusion/Significance

Our interrogation of male neural circuits reveals that a sex-specific response to the opposite sex is conferred by a male-specific pathway that renders subordinate, sex-shared motor programs responsive to mate cues. Circuit modifications of these types may make prominent contributions to natural variations in behavior that ultimately bring about speciation.     

Cooperation in Health: Mapping Collaborative Networks on the Web

Objective

To map and investigate the relationships established on the web between leading health-research institutions around the world.

Methods

Sample selection was based on the World Health Organization (WHO) Collaborating Centres (CCs). Data on the 768 active CCs in 89 countries were retrieved from the WHO''s database. The final sample consisted of 190 institutions devoted to health sciences in 42 countries. Data on each institution''s website were retrieved using webometric techniques (interlinking), and an asymmetric matrix was generated for social network analysis.

Findings

The results showed that American and European institutions, such as the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH) and the National Institute of Health and Medical Research (INSERM), are the most highly connected on the web and have a higher capacity to attract hyperlinks. The Karolinska Institute (KI-SE) in Sweden is well placed as an articulation point between several integrants of the network and the component''s core but lacks general recognition on the web by hyperlinks. Regarding the north-south divide, Mexico and Brazil appear to be key southern players on the web. The results showed that the hyperlinks exchanged between northern and southern countries present an abysmal gap: 99.49% of the hyperlinks provided by the North are directed toward the North itself, in contrast to 0.51% that are directed toward the South. Regarding the South, its institutions are more connected to its northern partners, with 98.46% of its hyperlinks directed toward the North, and mainly toward the United States, compared with 1.54% toward southern neighbors.

Conclusion

It is advisable to strengthen integration policies on the web and to increase web networking through hyperlink exchange. In this way, the web could actually reflect international cooperation in health and help to legitimize and enhance the visibility of the many existing south-south collaboration networks.     

Phylogeographic Pattern and Extensive Mitochondrial DNA Divergence Disclose a Species Complex within the Chagas Disease Vector Triatoma dimidiata

Background

Triatoma dimidiata is among the main vectors of Chagas disease in Latin America. However, and despite important advances, there is no consensus about the taxonomic status of phenotypically divergent T. dimidiata populations, which in most recent papers are regarded as subspecies.

Methodology and Findings

A total of 126 cyt b sequences (621 bp long) were produced for specimens from across the species range. Forty-seven selected specimens representing the main cyt b clades observed (after a preliminary phylogenetic analysis) were also sequenced for an ND4 fragment (554 bp long) and concatenated with their respective cyt b sequences to produce a combined data set totalling 1175 bp/individual. Bayesian and Maximum-Likelihood phylogenetic analyses of both data sets (cyt b, and cyt b+ND4) disclosed four strongly divergent (all pairwise Kimura 2-parameter distances >0.08), monophyletic groups: Group I occurs from Southern Mexico through Central America into Colombia, with Ecuadorian specimens resembling Nicaraguan material; Group II includes samples from Western-Southwestern Mexico; Group III comprises specimens from the Yucatán peninsula; and Group IV consists of sylvatic samples from Belize. The closely-related, yet formally recognized species T. hegneri from the island of Cozumel falls within the divergence range of the T. dimidiata populations studied.

Conclusions

We propose that Groups I–IV, as well as T. hegneri, should be regarded as separate species. In the Petén of Guatemala, representatives of Groups I, II, and III occur in sympatry; the absence of haplotypes with intermediate genetic distances, as shown by multimodal mismatch distribution plots, clearly indicates that reproductive barriers actively promote within-group cohesion. Some sylvatic specimens from Belize belong to a different species – likely the basal lineage of the T. dimidiata complex, originated ∼8.25 Mya. The evidence presented here strongly supports the proposition that T. dimidiata is a complex of five cryptic species (Groups I–IV plus T. hegneri) that play different roles as vectors of Chagas disease in the region.     

Racial Discrimination & Cardiovascular Disease Risk: My Body My Story Study of 1005 US-Born Black and White Community Health Center Participants (US)

Objectives

To date, limited and inconsistent evidence exists regarding racial discrimination and risk of cardiovascular disease (CVD).

Methods

Cross-sectional observational study of 1005 US-born non-Hispanic black (n = 504) and white (n = 501) participants age 35–64 randomly selected from community health centers in Boston, MA (2008–2010; 82.4% response rate), using 3 racial discrimination measures: explicit self-report; implicit association test (IAT, a time reaction test for self and group as target vs. perpetrator of discrimination); and structural (Jim Crow status of state of birth, i.e. legal racial discrimination prior 1964).

Results

Black and white participants both had adverse cardiovascular and socioeconomic profiles, with black participants most highly exposed to racial discrimination. Positive crude associations among black participants occurred for Jim Crow birthplace and hypertension (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.28, 2.89) and for explicit self-report and the Framingham 10 year CVD risk score (beta  = 0.04; 95% CI 0.01, 0.07); among white participants, only negative crude associations existed (for IAT for self, for lower systolic blood pressure (SBP; beta  = −4.86; 95% CI −9.08, −0.64) and lower Framingham CVD score (beta  = −0.36, 95% CI −0.63, −0.08)). All of these associations were attenuated and all but the white IAT-Framingham risk score association were rendered null in analyses that controlled for lifetime socioeconomic position and additional covariates. Controlling for racial discrimination, socioeconomic position, and other covariates did not attenuate the crude black excess risk for SBP and hypertension and left unaffected the null excess risk for the Framingham CVD score.

Conclusion

Despite worse exposures among the black participants, racial discrimination and socioeconomic position were not associated, in multivariable analyses, with risk of CVD. We interpret results in relation to constrained variability of exposures and outcomes and discuss implications for valid research on social determinants of health.     

Evidence of a landlocked reproducing population of the marine pejerrey Odontesthes argentinensis (Actinopterygii; Atherinopsidae)

In South America, the order Atheriniformes includes the monophyletic genus Odontesthes with 20 species that inhabit freshwater, estuarine and coastal environments. Pejerrey Odontesthes argentinensis is widely distributed in coastal and estuarine areas of the Atlantic Ocean and is known to foray into estuaries of river systems, particularly in conditions of elevated salinity. However, to our knowledge, a landlocked self-sustaining population has never been recorded. In this study, we examined the pejerrey population of Salada de Pedro Luro Lake (south-east of Buenos Aires Province, Argentina) to clarify its taxonomic identity. An integrative taxonomic analysis based on traditional meristic, landmark-based morphometrics and genetic techniques suggests that the Salada de Pedro Luro pejerrey population represents a novel case of physiological and morphological adaptation of a marine pejerrey species to a landlocked environment and emphasises the environmental plasticity of this group of fishes.     

Noise does not equal bias in assessing the evolutionary history of the angiosperm flora of China: A response to Qian (2019)

In response to our paper on the evolutionary history of the Chinese flora, Qian suggests that certain features of the divergence time estimation employed might have led to biased conclusions in Lu et al (2018). Here, we consider Qian's specific criticisms, explore the extent of uncertainty in the data and demonstrate that (i) no systematic bias toward dates that are too young or too old is detected in Lu et al.; (ii) constraint of the crown age of angiosperms does not bias the generic ages estimated by Lu et al.; and (iii) ages derived from the Chinese regional phylogeny do not bias the conclusions reported by Lu et al. All these analyses confirm that the conclusions reported previously are robust. We argue that, like many large-scale biodiversity analyses, sources of noise in divergence time estimation are to be expected, but these should not be confused with bias.     

Cave-adapted evolution in the North American amblyopsid fishes inferred using phylogenomics and geometric morphometrics

Cave adaptation has evolved repeatedly across the Tree of Life, famously leading to pigmentation and eye degeneration and loss, yet its macroevolutionary implications remain poorly understood. We use the North American amblyopsid fishes, a family spanning a wide degree of cave adaptation, to examine the impact of cave specialization on the modes and tempo of evolution. We reconstruct evolutionary relationships using ultraconserved element loci, estimate the ancestral histories of eye-state, and examine the impact of cave adaptation on body shape evolution. Our phylogenomic analyses provide a well-supported hypothesis for amblyopsid evolutionary relationships. The obligate blind cavefishes form a clade and the cave-facultative eyed spring cavefishes are nested within the obligate cavefishes. Using ancestral state reconstruction, we find support for at least two independent subterranean colonization events within the Amblyopsidae. Eyed and blind fishes have different body shapes, but not different rates of body shape evolution. North American amblyopsids highlight the complex nature of cave-adaptive evolution and the necessity to include multiple lines of evidence to uncover the underlying processes involved in the loss of complex traits.     

Why do animals hybridize?

Animal hybridization is increasingly recognized as common and evolutionarily important, but the role of behavior in promoting hybridization events is not well understood. Understanding the behavioral causes of hybridization requires understanding the ecological, demographic, and phenotypic influences on mate choice in hybridizing taxa. Here, I review how these influences on mate choice can contribute to hybridization by (1) circumventing (female) choice, (2) bringing formerly isolated species into sympatry, (3) masking cues important for mate recognition, (4) altering the traits or preferences involved in mate recognition, or (5) altering the costs and benefits of mate choice. In particular, hybridization in response to either high direct costs of mate choice or high direct benefits of heterospecific mating may be widespread, a possibility that awaits further testing. Adopting a mate choice perspective to the study of hybridization challenges the assumption of hybrids as reproductive “mistakes” and allows for functional explanations regarding the occurrence and maintenance of hybridization. As evidence of the prevalence and evolutionary importance of animal hybridization accumulates, investigations into the role of behavior will be increasingly important for our understanding of diversification and for conservation applications.