Classic life-history theory predicts that menopause should not occur because there should be no selection for survival after the cessation of reproduction 1. Yet, human females routinely live 30 ...years after they have stopped reproducing 2. Only two other species-killer whales (Orcinus orca) and short-finned pilot whales (Globicephala macrorhynchus) 3, 4-have comparable postreproductive lifespans. In theory, menopause can evolve via inclusive fitness benefits 5, 6, but the mechanisms by which postreproductive females help their kin remain enigmatic. One hypothesis is that postreproductive females act as repositories of ecological knowledge and thereby buffer kin against environmental hardships 7, 8. We provide the first test of this hypothesis using a unique long-term dataset on wild resident killer whales. We show three key results. First, postreproductively aged females lead groups during collective movement in salmon foraging grounds. Second, leadership by postreproductively aged females is especially prominent in difficult years when salmon abundance is low. This finding is critical because salmon abundance drives both mortality and reproductive success in resident killer whales 9, 10. Third, females are more likely to lead their sons than they are to lead their daughters, supporting predictions of recent models 5 of the evolution of menopause based on kinship dynamics. Our results show that postreproductive females may boost the fitness of kin through the transfer of ecological knowledge. The value gained from the wisdom of elders can help explain why female resident killer whales and humans continue to live long after they have stopped reproducing.
Epilepsy diagnosis is often delayed or inaccurate, exposing people to ongoing seizures and their substantial consequences until effective treatment is initiated. Important factors contributing to ...this problem include delayed recognition of seizure symptoms by patients and eyewitnesses; cultural, geographical, and financial barriers to seeking health care; and missed or delayed diagnosis by health-care providers. Epilepsy diagnosis involves several steps. The first step is recognition of epileptic seizures; next is classification of epilepsy type and whether an epilepsy syndrome is present; finally, the underlying epilepsy-associated comorbidities and potential causes must be identified, which differ across the lifespan. Clinical history, elicited from patients and eyewitnesses, is a fundamental component of the diagnostic pathway. Recent technological advances, including smartphone videography and genetic testing, are increasingly used in routine practice. Innovations in technology, such as artificial intelligence, could provide new possibilities for directly and indirectly detecting epilepsy and might make valuable contributions to diagnostic algorithms in the future.
Prolonged life after reproduction is difficult to explain evolutionarily unless it arises as a physiological side effect of increased longevity or it benefits related individuals (i.e., increases ...inclusive fitness). There is little evidence that postreproductive life spans are adaptive in nonhuman animals. By using multigenerational records for two killer whale (Orcinus orca) populations in which females can live for decades after their final parturition, we show that postreproductive mothers increase the survival of offspring, particularly their older male offspring. This finding may explain why female killer whales have evolved the longest postreproductive life span of all nonhuman animals.
Children born to mothers, with or at risk, of human immunodeficiency virus type-1 (HIV-1) infection are on the rise due to affordable access of antiretroviral therapy (ART) to pregnant women or those ...of childbearing age. Each year, up to 1.3 million HIV-1-infected women on ART have given birth with recorded mother-to-child HIV-1 transmission rates of less than 1%. Despite this benefit, the outcomes of children exposed to antiretroviral drugs during pregnancy, especially pre- and post- natal neurodevelopment remain incompletely understood. This is due, in part, to the fact that pregnant women are underrepresented in clinical trials. This is underscored by any potential risks of neural tube defects (NTDs) linked, in measure, to periconceptional usage of dolutegravir (DTG). A potential association between DTG and NTDs was first described in Botswana in 2018. Incidence studies of neurodevelopmental outcomes associated with DTG, and other integrase strand transfer inhibitors (INSTIs) are limited as widespread use of INSTIs has begun only recently in pregnant women. Therefore, any associations between INSTI use during pregnancy, and neurodevelopmental abnormalities remain to be explored. Herein, United States Food and Drug Administration approved ARVs and their use during pregnancy are discussed. We provide updates on INSTI pharmacokinetics and adverse events during pregnancy together with underlying mechanisms which could affect fetal neurodevelopment. Overall, this review seeks to educate both clinical and basic scientists on potential consequences of INSTIs on fetal outcomes as a foundation for future scientific investigations.
A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the cause of the COVID-19 pandemic that originated in China in December 2019. Although extensive ...research has been performed on SARS-CoV-2, the binding behavior of spike (S) protein and receptor binding domain (RBD) of SARS-CoV-2 at different environmental conditions have yet to be studied. The objective of this study is to investigate the effect of temperature, fatty acids, ions, and protein concentration on the binding behavior and rates of association and dissociation between the S protein and RBD of SARS-CoV-2 and the hydrophobic aminopropylsilane (APS) biosensors using biolayer interferometry (BLI) validated with molecular dynamics simulation. Our results suggest three conditions-high ionic concentration, presence of hydrophobic fatty acids, and low temperature-favor the attachment of S protein and RBD to hydrophobic surfaces. Increasing the temperature within an hour from 0 to 25 °C results in S protein detachment, suggesting that freezing can cause structural changes in the S protein, affecting its binding kinetics at higher temperature. At all the conditions, RBD exhibits lower dissociation capabilities than the full-length S trimer protein, indicating that the separated RBD formed stronger attachment to hydrophobic surfaces compared to when it was included in the S protein.
•Active thioredoxin of 90% purity and 95% recovery was purified by HEA HyperCel chromatography.•HEA HyperCel had salt-tolerant and more selective binding than Capto adhere and Toyopearl NH2-750F ...mixed-mode resins.•Process optimization by high-throughput screening and scale-up performance was evaluated.•Molecular dynamics simulations provide protein-ligand interactions aiding process development.
Collecting large-scale population data on dietary intake is challenging, particularly when resources and funding are constrained. Technology offers the potential to develop novel ways of collecting ...large amounts of dietary information while making it easier, more convenient, intuitive, and engaging for users. INTAKE24 is an online multiple pass 24 h dietary recall tool developed for use in national food and nutrition surveys. The development of INTAKE24 was a four-stage iterative process of user interaction and evaluation with the intended end users, 11-24 years old. A total of 80 11-24 years old took part in the evaluation, 20 at each stage. Several methods were used to elicit feedback from the users including, 'think aloud', 'eye tracking', semi-structured interviews, and a system usability scale. Each participant completed an interviewer led recall post system completion. Key system developments generated from the user feedback included a 'flat' interface, which uses only a single interface screen shared between all of the various activities (e.g., free text entry, looking up foods in the database, portion size estimation). Improvements to the text entry, search functionality, and navigation around the system were also influenced through feedback from users at each stage. The time to complete a recall using INTAKE24 almost halved from the initial prototype to the end system, while the agreement with an interviewer led recall improved. Further developments include testing the use of INTAKE24 with older adults and translation into other languages for international use. Our future aim is to validate the system with recovery biomarkers.
Regulatory T cells (Tregs) maintain immune tolerance. While Treg-mediated neuroprotective activities are now well-accepted, the lack of defined antigen specificity limits their therapeutic potential. ...This is notable for neurodegenerative diseases where cell access to injured brain regions is required for disease-specific therapeutic targeting and improved outcomes. To address this need, amyloid-beta (Aβ) antigen specificity was conferred to Treg responses by engineering the T cell receptor (TCR) specific for Aβ (TCR
). The TCR
were developed from disease-specific T cell effector (Teff) clones. The ability of Tregs expressing a transgenic TCR
(TCR
-Tregs) to reduce Aβ burden, transform effector to regulatory cells, and reverse disease-associated neurotoxicity proved beneficial in an animal model of Alzheimer's disease.
TCR
-Tregs were generated by CRISPR-Cas9 knockout of endogenous TCR and consequent incorporation of the transgenic TCR
identified from Aβ reactive Teff monoclones. Antigen specificity was confirmed by MHC-Aβ-tetramer staining. Adoptive transfer of TCR
-Tregs to mice expressing a chimeric mouse-human amyloid precursor protein and a mutant human presenilin-1 followed measured behavior, immune, and immunohistochemical outcomes.
TCR
-Tregs expressed an Aβ-specific TCR. Adoptive transfer of TCR
-Tregs led to sustained immune suppression, reduced microglial reaction, and amyloid loads.
F-fluorodeoxyglucose radiolabeled TCR
-Treg homed to the brain facilitating antigen specificity. Reduction in amyloid load was associated with improved cognitive functions.
TCR
-Tregs reduced amyloid burden, restored brain homeostasis, and improved learning and memory, supporting the increased therapeutic benefit of antigen specific Treg immunotherapy for AD.
For the majority of social species, group composition is dynamic, and individuals are interconnected in a heterogeneous social network. Social network structure has far-reaching implications for the ...ecology of individuals and populations. However, we have little understanding of how ecological variables shape this structure. We used a long-term data set (1984–2007) to examine the relationship between food availability and social network structure in the endangered southern resident killer whales. During the summer months individuals in this population feed primarily on chinook salmon, Oncorhynchus tshawytscha, which show annual variation in abundance. We tested the hypothesis that temporal variation in chinook salmon will correlate with variation in social network structure. Using a null model that controlled for population demography, group size and sampling effort, we found a significant relationship between the connectivity of the social network and salmon abundance, with a more interconnected social network in years of high salmon abundance. Our results demonstrate that resource availability may be an important determinant of social network structure. Given the central importance of the social network for population processes such as the maintenance of cooperation and the transmission of information and disease, a change in social network structure caused by a change in food availability may have significant ecological and evolutionary consequences.
► Significant correlation between salmon abundance and social structure in resident killer whales. ► In years of high chinook salmon abundance the social structure is more interconnected. ► This may have implications for information or disease transfer, gene flow and mating dynamics. ► These effects occur independent of group size.
Objective
Anxiety and depression are common comorbidities in people living with epilepsy. Emerging research suggests that these conditions may even predate epilepsy onset. This review aimed to ...summarize the prevalence of clinically significant anxiety and depressive symptoms in people with first seizures and newly diagnosed epilepsy, as well as clinicodemographic factors associated with these symptoms.
Methods
A scoping literature review was performed. OVID Medline and Embase were searched from January 1, 2000, through May 1, 2022. Articles of interest were selected based on predetermined inclusion and exclusion criteria.
Results
From 1836 studies identified on screening, 16 met eligibility criteria and were included in the review. Clinically significant anxiety and depressive symptoms, as determined by validated cutoff scores for anxiety and depression screening instruments, were common in people with first seizures (range 13–28%) and newly diagnosed epilepsy (range 11–45%). They were associated with a range of clinicodemographic factors including past psychiatric history and trauma, personality traits, self‐esteem, and stigma profiles.
Significance
There is substantial evidence that clinically significant anxiety and depressive symptoms are often present at the time and shortly following the first seizure or epilepsy diagnosis. Future research is needed to better understand the complex interactions between these common psychiatric comorbidities, new‐onset seizure disorders, and certain clinicodemographic characteristics. This knowledge may inform targeted and holistic treatment approaches.
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