Dual Role for Hsc70 in the Biogenesis and Regulation of the Heme-Regulated Kinase of the α Subunit of Eukaryotic Translation Initiation Factor 2

The heme-regulated kinase of the alpha subunit of eukaryotic initiation factor 2 (HRI) is activated in rabbit reticulocyte lysate (RRL) in response to a number of environmental conditions, including heme deficiency, heat shock, and oxidative stress. Activation of HRI causes an arrest of initiation of protein synthesis. Recently, we have demonstrated that the heat shock cognate protein Hsc70 negatively modulates the activation of HRI in RRL in response to these environmental conditions. Hsc70 is also known to be a critical component of the Hsp90 chaperone machinery in RRL, which plays an obligatory role for HRI to acquire and maintain a conformation that is competent to activate. Using de novo-synthesized HRI in synchronized pulse-chase translations, we have examined the role of Hsc70 in the regulation of HRI biogenesis and activation. Like Hsp90, Hsc70 interacted with nascent HRI and HRI that was matured to a state which was competent to undergo stimulus-induced activation (mature-competent HRI). Interaction of HRI with Hsc70 was required for the transformation of HRI, as the Hsc70 antagonist clofibric acid inhibited the folding of HRI into a mature-competent conformation. Unlike Hsp90, Hsc70 also interacted with transformed HRI. Clofibric acid disrupted the interaction of Hsc70 with transformed HRI that had been matured and transformed in the absence of the drug. Disruption of Hsc70 interaction with transformed HRI in heme-deficient RRL resulted in its hyperactivation. Furthermore, activation of HRI in response to heat shock or denatured proteins also resulted in a similar blockage of Hsc70 interaction with transformed HRI. These results indicate that Hsc70 is required for the folding and transformation of HRI into an active kinase but is subsequently required to negatively attenuate the activation of transformed HRI.     

Body size and allometric variation in facial shape in children

Objectives

In group‐living primates, it has been reported that the alpha male exhibits high concentrations of cortisol and testosterone in the context of mating competition. We investigated how the presence of females affected salivary cortisol and testosterone levels in males from a small captive group of chimpanzees (Pan troglodytes). Specifically, we assessed whether the presence of females resulted in a rapid increase in salivary cortisol and testosterone levels in the alpha male.

Materials and methods

We compared the social behavior and salivary hormone concentrations of four males before and after the presentation of receptive females. Three times a day, we collected saliva samples, a useful matrix for investigating short‐term hormonal changes, and measured cortisol and testosterone concentration by liquid chromatography–tandem mass spectrometry (LC–MS/MS).

Results

The frequency of inter‐male aggression increased in the presence of females, indicating intense competition among males. Salivary cortisol levels increased in all males in the presence of females; however, the increase was significantly more pronounced in the alpha male. We found a complex three‐way interaction among the presence of females, sampling timings, and male dominance rank in the analysis of salivary testosterone. Contrary to our prediction, a post hoc analysis revealed that salivary testosterone levels decreased after female introduction and that the alpha male did not show a higher level of salivary testosterone.

Conclusions

Our study provides experimental evidence suggesting that the presence of females plays a significant role in the rank‐related variation in the cortisol levels in male chimpanzees. Furthermore, our findings demonstrate the usefulness of salivary hormones for detecting short‐term physiological changes in studies of socioendocrinology.

     

Do sister forks of bidirectionally growing replicons proceed at unequal rates?

DNA fibre autoradiography in different tissues of the rodents Bandicota bengalensis and Nesokia indica reveals a high frequency of such bidirectionally replicating replicons whose sister 'hot' tracks are of unequal size. These results suggest intrarepliconic difference in the rates of fork migration in the two directions.     

Ticks on snakes: The ecological correlates of ectoparasite infection in free‐ranging snakes in tropical Australia

Parasites profoundly influence the lives of their hosts, yet the dynamics of host–parasite interactions are poorly understood – especially in reptiles. We examined the ecological correlates of parasitism by ixodid ticks in an assemblage of 10 snake species in tropical Australia. In total, we recorded 3803 ticks on 1841 individual snakes of six species (no ticks were found on the other species). Molecular analyses confirmed the tropical reptile tick (Amblyomma fimbriatum: Ixodidae) to be the most common snake tick at our study site, with inter‐ and intraspecific variation in tick prevalence and intensity. Tick attachment sites were random on most snake species, but both male and female ticks congregated on the heads of the colubrid snake Boiga irregularis and the python Simalia amethistina. In these same species, tick loads were higher on snakes captured in woodland than in rainforest. Females of two python species (Aspidites melanocephalus and S. amethistina) had higher tick loads than did males. In B. irregularis, individuals captured in the dry season had higher tick loads than those captured in the wet season. In most parasitized snake species, larger individuals had greater tick loads. Data from snake recaptures confirmed individual tick burdens frequently varied, with little correlation between tick loads on the same snake at successive captures (except for B. irregularis). Finally, tick intensity was not correlated with (and thus, presumably did not influence) the body condition of any snake species in our study. Use of specific types of refuge sites may strongly influence tick loads on snakes in this system.     

Association mapping to discover significant marker-trait associations for resistance against fusarium wilt variant 2 in pigeonpea [<Emphasis Type="Italic">Cajanus cajan</Emphasis> (L.) Millspaugh] using SSR markers

Pigeonpea production is severely constrained by wilt disease caused by Fusarium udum. In the current study, we discover the putative genomic regions that control resistance response to variant 2 of fusarium wilt using association mapping approach. The association panel comprised of 89 diverse pigeonpea genotypes including seven varieties, three landraces and 79 germplasm lines. The panel was screened rigorously for 3 consecutive years (2013–14, 2014–15 and 2015–2016) against variant 2 in a wilt-sick field. A total of 65 pigeonpea specific hypervariable SSR markers (HASSRs) were screened representing seven linkage groups and 29 scaffolds of the pigeonpea genome. A total of 181 alleles were detected, with average values of gene diversity and polymorphism information content (PIC) of 0.55 and 0.47, respectively. Further analysis using model based (STRUCTURE) and distance based (clustering) approaches separated the entire pigeonpea collection into two distinct subgroups (K = 2). The marker trait associations (MTAs) were established based on three-year wilt incidence data and SSR dataset using a unified mixed linear model. Consequently, six SSR markers were identified, which were significantly associated with wilt resistance and explained up to 6% phenotypic variance (PV) across the years. Among these SSRs, HASSR18 was found to be the most stable and significant, accounting for 5–6% PV across the years. To the best of our knowledge, this is the first report of identification of favourable alleles for resistance to variant 2 of Fusarium udum in pigeonpea using association mapping. The SSR markers identified here will greatly facilitate marker assisted resistance breeding against fusarium wilt in pigeonpea.     

Drought and child vaccination coverage in 22 countries in sub-Saharan Africa: A retrospective analysis of national survey data from 2011 to 2019

BackgroundExtreme weather events, including droughts, are expected to increase in parts of sub-Saharan Africa and are associated with a number of poor health outcomes; however, to the best of our knowledge, the link between drought and childhood vaccination remains unknown. The objective of this study was to evaluate the relationship between drought and vaccination coverage.Methods and findingsWe investigated the association between drought and vaccination coverage using a retrospective analysis of Demographic and Health Surveys data in 22 sub-Saharan African countries among 137,379 children (50.4% male) born from 2011 to 2019. Drought was defined as an established binary variable of annual rainfall less than or equal to the 15th percentile relative to the 29 previous years, using data from Climate Hazards Group InfraRed Precipitation with Station (CHIRPS) data. We evaluated the association between drought at the date of birth and receipt of bacillus Calmette–Guérin (BCG), diphtheria–pertussis–tetanus (DPT), and polio vaccinations, and the association between drought at 12 months of age and receipt of measles vaccination. We specified logistic regression models with survey fixed effects and standard errors clustered at the enumeration area level, adjusting for child-, mother-, and household-level covariates and estimated marginal risk differences (RDs). The prevalence of drought at date of birth in the sample was 11.8%. Vaccination rates for each vaccination ranged from 70.6% (for 3 doses of the polio vaccine) to 86.0% (for BCG vaccination); however, only 57.6% of children 12 months and older received all recommended doses of BCG, DPT, polio, and measles vaccinations. In adjusted models, drought at date of birth was negatively associated with BCG vaccination (marginal RD = −1.5; 95% CI −2.2, −0.9), DPT vaccination (marginal RD = −1.4; 95% CI −2.2, −0.5), and polio vaccination (marginal RD = −1.3; 95% CI −2.3, −0.3). Drought at 12 months was negatively associated with measles vaccination (marginal RD = −1.9; 95% CI −2.8, −0.9). We found a dose–response relationship between drought and DPT and polio vaccinations, with the strongest associations closest to the timing of drought. Limitations include some heterogeneity in findings across countries.ConclusionsIn this study, we observed that drought was associated with lower odds of completion of childhood BCG, DPT, and polio vaccinations. These findings indicate that drought may hinder vaccination coverage, one of the most important interventions to prevent infections among children. This work adds to a growing body of literature suggesting that health programs should consider impacts of severe weather in their programming.

Jason M. Nagata and colleagues investigate the association between drought and child vaccination coverage in 22 countries in sub-Saharan Africa, using Demographic and Health Survey data from 2011 to 2019.     

The pursuit of happiness: A reinforcement learning perspective on habituation and comparisons

In evaluating our choices, we often suffer from two tragic relativities. First, when our lives change for the better, we rapidly habituate to the higher standard of living. Second, we cannot escape comparing ourselves to various relative standards. Habituation and comparisons can be very disruptive to decision-making and happiness, and till date, it remains a puzzle why they have come to be a part of cognition in the first place. Here, we present computational evidence that suggests that these features might play an important role in promoting adaptive behavior. Using the framework of reinforcement learning, we explore the benefit of employing a reward function that, in addition to the reward provided by the underlying task, also depends on prior expectations and relative comparisons. We find that while agents equipped with this reward function are less happy, they learn faster and significantly outperform standard reward-based agents in a wide range of environments. Specifically, we find that relative comparisons speed up learning by providing an exploration incentive to the agents, and prior expectations serve as a useful aid to comparisons, especially in sparsely-rewarded and non-stationary environments. Our simulations also reveal potential drawbacks of this reward function and show that agents perform sub-optimally when comparisons are left unchecked and when there are too many similar options. Together, our results help explain why we are prone to becoming trapped in a cycle of never-ending wants and desires, and may shed light on psychopathologies such as depression, materialism, and overconsumption.