bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive Processing Speed and Loneliness in Stroke Survivors: Insights from a Large-Scale Cohort Study
Authors: Byrne Christopher , Coetzer Rudi , Ramsey Richard
Published: May 2024

Objective

Loneliness, when prolonged, is associated with many deleterious effects and has been shown to be highly prevalent in those with a history of stroke, yet the cognitive mechanisms underpinning this phenomenon remain unclear. Therefore, the current study aims to investigate the extent to which cognitive factors, with specific focus on processing speed, are associated with loneliness in those with a history of stroke.

Method

Utilizing data from the British Cohort Study, a nationally representative dataset, we conducted secondary data analysis. A total of 7,752 participants completed relevant questions related to health, social interactions, demographics, loneliness, and cognitive assessments. Among them, 47 had experienced a stroke (“stroke,” n = 47), 5,545 reported other health conditions (“ill,” n = 5,545), and 2,857 were deemed healthy (“healthy,” n = 2,857).

Results

Consistent with previous research, our findings confirmed a positive correlation between stroke history and heightened loneliness. However, inferential analysis revealed that processing speed, alongside other cognitive factors, had a minimal impact on loneliness, with correlations too small to draw definitive conclusions.

Conclusion

This study suggests that cognitive processing speed alone is not a robust predictor of loneliness in stroke survivors. Consequently, when developing interventions to combat loneliness in this population, it is crucial to consider a broader spectrum of factors, such as social engagement, emotional wellbeing, and interpersonal relationships. This underscores the imperative need for comprehensive assessments to better comprehend the multifaceted nature of loneliness and inform more effective intervention strategies.
Analysis on promotive effect of rocking culture on keratinocyte differentiation in 3-dimensional reconstitution human epidermis
Authors: Endo Mayuko , Teshima Hirofumi , Kitadani Kojin , Minoru Kobayashi , Tsuji Tokuji , Tatsukawa Hideki , Harada Hiroshi , Hitomi Kiyotaka
Published: May 2024

A 3-dimensional culture system of keratinocytes achieves cornification as a terminal differentiation that can mimic the formation of stratified epidermis. At the onset of keratinocyte differentiation, air-exposure treatment is essential for promotion. We have previously reported that the stimulation of differentiation is accompanied by downregulation of the transcriptional activity of the hypoxia-inducible factor (HIF) and also found that rocking treatment of cultured keratinocytes in the submerged condition restored their differentiation. A comparative study of cultured keratinocytes with and without rocking was then carried out to investigate the characteristics of the recovered differentiation by morphological and biochemical analyses. In addition, transcriptome analysis revealed the expected similar pattern between air-exposed and rocking cultures, including HIF-regulating transcripts. Furthermore, the promotive effect of rocking treatment was impaired under hypoxic culture conditions (1% O2). We showed that the restored promotion of differentiation by rocking culture is mainly due to the abrogation of transcriptional events by hypoxia.
Scn1a haploinsufficiency in the prefrontal cortex leads to cognitive impairment and depressive phenotype
Authors: Riga Maurizio S , Pérez-Fernández Mercedes , Miquel-Rio Lluis , Paz Verónica , Campa Leticia , Martínez-Losa Magdalena , Esteban Francisco J , Callado Luis F , Meana Javier , Artigas Francesc , Bortolozzi Analía , Álvarez-Dolado Manuel
Published: May 2024

Altered development and function of the prefrontal cortex (PFC) during adolescence is implicated in the origin of mental disorders. Deficits in the GABAergic system prominently contribute to these alterations. Nav1.1 is a voltage-gated Na+ channel critical for normal GABAergic activity. Here, we studied the role of Nav1.1 in PFC function and its potential relationship with the aetiology of mental disorders.

Dysfunction of Nav1.1 activity in the medial PFC (mPFC) of adolescent mice enhanced the local excitation/inhibition ratio, resulting in epileptic activity, cognitive deficits and depressive-like behaviour in adulthood, along with a gene expression profile linked to major depressive disorder (MDD). Additionally, it reduced extracellular serotonin concentration in the dorsal raphe nucleus and brain-derived neurotrophic factor expression in the hippocampus, two MDD-related brain areas beyond the PFC. We also observed alterations in oscillatory activity and impaired hippocampal-mPFC coherence during sleep. Finally, we found reduced expression levels of SCN1A, the gene encoding Nav1.1, in post-mortem PFC samples from human MDD subjects.

Collectively, our results provide a novel mechanistic framework linking adolescence-specific alterations in Nav1.1 function in the PFC to the pathogenesis of epilepsy and comorbidities such as cognitive impairment and depressive disorders.
Ultrastructural localization of calcium homeostasis modulator 1 in mouse taste buds
Authors: Ikuta Rio , Kakinohana Yuu , Hamada Shun
Published: May 2024

Taste receptor cells are morphologically classified as types II and III. Type II cells form a unique type of synapses referred to as channel synapses where calcium homeostasis modulator 1 (CALHM1) together with CALHM3 forms voltage-gated channels that release the neurotransmitter, adenosine triphosphate (ATP). To validate the proposed structural model of channel synapses, the ultrastructural localization of CALHM1 in type II cells of both fungiform and circumvallate taste buds was examined. A monoclonal antibody against CALHM1 was developed and its localization was evaluated via immunofluorescence and immunoelectron microscopy using the immunogold-silver labeling technique. CALHM1 was detected as puncta using immunofluorescence and along the presynaptic membrane of channel synapses facing atypical mitochondria, which provide ATP, by immunoelectron microscopy. In addition, it was detected along the plasma membrane lined by subsurface cisternae at sites apposed to afferent nerve fibers. Our results support the validity of a previously proposed structural model for channel synapses and provide insights into the function of subsurface cisternae whose function in taste receptor cells is unknown. We also examined the localization of CALHM1 in hybrid synapses of type III cells, which are conventional chemical synapses accompanied by mitochondria similar to atypical mitochondria of channel synapses. CALHM1 was not detected in the six hybrid synapses examined using immunoelectron microscopy. We further performed double immunolabeling for CALHM1 and Bassoon, which is detected as puncta corresponding to conventional vesicular synapses in type III cells. Our observations suggest that at least some, and probably most, hybrid synapses are not accompanied by CALHM1.
Integrating the Patient’s Voice into the Research Agenda for Treatment of Chemosensory Disorders
Authors: Murphy Claire , Dalton Pamela , Boateng Katie , Hunter Stephanie , Silberman Pamela , Trachtman Jenifer , Schrandt Suz , Naimi Bita , Garvey Emily , Joseph Paule V , Frank Conner , Albertazzi Abigail , Nyquist Gurston , Rawson Nancy E
Published: May 2024

World-wide some 658 million people were infected with COVID-19 and millions suffer from chemosensory impairment associated with long COVID. Current treatments for taste and smell disorders are limited. Involving patients has the potential to catalyze the dynamic exchange and development of new ideas and approaches to facilitate biomedical research and therapeutics. We assessed patients’ perceptions of the efficacy of treatments for chemosensory impairment using an online questionnaire completed by 5,815 people in the U.S. Logistic regression determined variables predictive of reported treatment efficacy for patients aged 18-24, 25-39, 40-60 and 60+ yrs. who were treated with nasal steroids, oral steroids, zinc, nasal rinse, smell training, theophylline, platelet rich plasma, and Omega 3. The most consistent predictor was age, with the majority of those 40-60 and 60+ reporting that nasal steroids, oral steroids, zinc, nasal rinse and smell training were only slightly effective or not effective at all. Many of these treatment strategies target regeneration and immune response, processes compromised by age. Only those under 40 reported more than slight efficacy of steroids or smell training. Findings emphasize the need to include patients of all ages in clinical trials. Older adults with olfactory impairment are at increased risk for Alzheimer’s disease (AD). We speculate that olfactory impairment associated with long COVID introduces the potential for a significant rise in AD. Long COVID-associated chemosensory impairment increases the urgency for translational and clinical research on novel treatment strategies. Suggestions for high priority areas for epidemiological, basic, and clinical research on chemosensory impairment follow.
“A Different Creature, Not So Human”: Globalgothic Shapeshifting and Weaponzed Rape in Nnedi Okorafor’s Who Fears Death
Authors: Stefanova Svetlana
Published: May 2024

This essay explores Nnedi Okorafor’s engagement with the traumatic consequences of a civil war in Africa through the shapeshifting motif in her novel Who Fears Death (2010). It argues that the interaction between Africanjujuism and globalgothic allows her to transcend the specificities of the conflict and address the transgenerational effects of ethnic violence as a global problem. Okorafor employs Africanjujuism to describe the protagonist’s shapeshifting as a means of healing, empowerment, and knowledge. In contrast, she uses Gothic tropes to depict extreme violence. Representing a girl born of wartime rape as the trickster god Eshu, who adds hope to a dark moment in history, constitutes a strong critique of a society in which women victims of war rape are often ignored and their children stigmatized.
The Disappearance of Leo Africanus: Rival Repertoires of Historical Scholarship in the Mid-Twentieth Century
Authors: Ossa-Richardson Anthony
Published: May 2024

This article is about two twentieth-century attempts to produce an edition of the famous Cosmography and Geography of Africa (1526) by Johannes Leo Africanus. One attempt was French, colonial, collaboratively authored, presentist and successful; the other was Italian, academic, single-authored, historicist and unsuccessful, in that it never appeared. Drawing primarily on unstudied archival material from several countries, I reconstruct the trajectories of each edition and its author(s), in an effort to understand more broadly the different ways in which scholarship was produced inside and outside universities in the period between the end of the First World War and the early 1960s. In other words, this is a comparative study of two ‘repertoires’, to borrow a term recently introduced by Rachel Ankeny and Sabina Leonelli: two institutional praxes embodying different understandings of the world, but also different material resources and codes of personal conduct. But this essay also attempts to say something about the Cosmography itself. One of Leo’s greatest achievements was to reach out beyond his own world to adopt the language, ideas and culture of his Italian readers; this could only be fully grasped after the rediscovery of an early manuscript in 1931, which showed that the supposedly foreign, Italian elements of the book were not added later by others. It was precisely this feature, I argue, that was better reflected by the successful French edition than by the unsuccessful Italian one.
Methods for studying microbial acid stress responses: from molecules to populations
Authors: Atasoy Merve , Bartkova Simona , Çetecioğlu-Gürol Zeynep , P Mira Nuno , O'Byrne Conor , Pérez-Rodríguez Fernando , Possas Aricia , Scheler Ott , Sedláková-Kaduková Jana , Sinčák Mirka , Steiger Matthias , Ziv Carmit , Lund Peter A
Published: May 2024

The study of how micro-organisms detect and respond to different stresses has a long history of producing fundamental biological insights while being simultaneously of significance in many applied microbiological fields including infection, food and drink manufacture, and industrial and environmental biotechnology. This is well-illustrated by the large body of work on acid stress. Numerous different methods have been used to understand the impacts of low pH on growth and survival of micro-organisms, ranging from studies of single cells to large and heterogeneous populations, from the molecular or biophysical to the computational, and from well-understood model organisms to poorly defined and complex microbial consortia. Much is to be gained from an increased general awareness of these methods, and so the present review looks at examples of the different methods that have been used to study acid resistance, acid tolerance, and acid stress responses, and the insights they can lead to, as well as some of the problems involved in using them. We hope this will be of interest both within and well beyond the acid stress research community.
Regulation of copper uptake by the SWI/SNF chromatin remodeling complex in Candida albicans affects susceptibility to antifungal and oxidative stresses under hypoxia
Authors: Khemiri Inès , Tebbji Faiza , Burgain Anaïs , Sellam Adnane
Published: May 2024

Candida albicans is a human colonizer and also an opportunistic yeast occupying different niches that are mostly hypoxic. While hypoxia is the prevalent condition within the host, the machinery that integrates oxygen status to tune the fitness of fungal pathogens remains poorly characterized. Here, we uncovered that Snf5, a subunit of the chromatin remodeling complex SWI/SNF, is required to tolerate antifungal stress particularly under hypoxia. RNA-seq profiling of snf5 mutant exposed to amphotericin B and fluconazole under hypoxic conditions uncovered a signature that is reminiscent of copper (Cu) starvation. We found that under hypoxic and Cu-starved environments, Snf5 is critical for preserving Cu homeostasis and the transcriptional modulation of the Cu regulon. Furthermore, snf5 exhibits elevated levels of reactive oxygen species and an increased sensitivity to oxidative stress principally under hypoxia. Supplementing growth medium with Cu or increasing gene dosage of the Cu transporter CTR1 alleviated snf5 growth defect and attenuated reactive oxygen species levels in response to antifungal challenge. Genetic interaction analysis suggests that Snf5 and the bona fide Cu homeostasis regulator Mac1 function in separate pathways. Together, our data underlined a unique role of SWI/SNF complex as a potent regulator of Cu metabolism and antifungal stress under hypoxia.
Support for Family Caregivers: Implications of Work Strain and Its Intersections With Formal and Informal Help
Authors: Svec Joseph , Nemmers Natasha , Lee Jeong Eun
Published: May 2024

Objectives

This study seeks to assess whether and to what extent caregiver work strain is ameliorated by the presence of additional family caregivers and formal service use. Building on the stress process model and stress-appraisal moderation, we examine how formal and informal support varies in associations with caregiver distress for men and women.

Methods

This study utilizes data provided by the National Study of Caregiving, which is linked with care-recipient information from the National Health and Aging Trends Study. Using panel methods for the pooled waves, we estimated caregiver outcomes of emotional well-being on the intersection of experiences of work strain and (a) the number of additional caregivers and (b) utilization of 6 different types of formal support.

Results

Additional informal caregivers for each respective care recipient are associated with lower levels of distress, although utilization of formal services (paid help and Medicaid funding) is positively associated with caregiver distress. Informal support can offset the impact of work strain, but interactions are only evident for women caregivers.

Discussion

The findings suggest that informal support, exemplified by the number of additional caregivers, corresponds with reduced emotional distress among employed caregivers and can mitigate the negative impacts of work strain. However, positive associations between formal support and male and female caregiver distress suggest that the context of formal services may offer limited or untimely support. This study is expected to broaden our understanding of informal caregiving in later life and provide practical implications on how to sustain informal care.
Intersectional Inequalities in the Transition to Grandparenthood and Cognitive Functioning: A Longitudinal Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy
Authors: Alonso-Perez Enrique , Heisig Jan Paul , Kreyenfeld Michaela , Gellert Paul , O’Sullivan Julie Lorraine
Published: May 2024

Objectives

In aging societies, more people become vulnerable to experiencing cognitive decline. Simultaneously, the role of grandparenthood is central for older adults and their families. Our study investigates inequalities in the level and trajectories of cognitive functioning among older adults, focusing on possible intersectional effects of social determinants and grandparenthood as a life course transition that may contribute to delaying cognitive decline.

Methods

Using longitudinal data from the Survey of Health, Aging, and Retirement in Europe, we analyzed a sample of 19,953 individuals aged 50–85 without grandchildren at baseline. We applied multilevel analysis of individual heterogeneity and discriminatory accuracy to investigate variation in cognitive functioning across 48 intersectional strata, defined by sex/gender, migration, education, and occupation. We allowed the impact of becoming a grandparent on cognitive functioning trajectories to vary across strata by including random slopes.

Results

Intersectional strata accounted for 17.43% of the overall variance in cognitive functioning, with most of the stratum-level variation explained by additive effects of the stratum-defining characteristics. Transition to grandparenthood was associated with higher cognitive functioning, showing a stronger effect for women. Stratum-level variation in the grandparenthood effect was modest, especially after accounting for interactions between grandparenthood and the stratum-defining variables.

Discussion

This study highlights the importance of social determinants for understanding heterogeneities in older adults’ level of cognitive functioning and its association with the transition to grandparenthood. Cumulative disadvantages negatively affect cognitive functioning, hence adopting an intersectional lens is useful to decompose inequalities and derive tailored interventions to promote equal healthy aging.
Validation of the Perceived Community Support Questionnaire for Older Chinese
Authors: Che Run-Ping , Cheung Mei-Chun , Herrero Juan
Published: May 2024

Background and Objectives

Community support has a profound positive impact on older people’s health and plays a crucial role in facilitating aging in place. This impact is particularly significant in the Chinese context, where community support can alleviate the pressure on traditional family caregiving. This study translated, adapted, and validated the perceived community support questionnaire (PCSQ) for use with older Chinese.

Research Design and Methods

Data for this validation study were collected from a cross-sectional survey of 1,064 Chinese aged 65 years and above. Following the cultural adaptation of the PCSQ-14, confirmatory factor analysis (CFA) was conducted to examine its factor structure. Criterion validity, convergent and discriminant validity, internal consistency reliability, and test–retest reliability of the scale were also assessed.

Results

Based on the CFA results, the adapted PCSQ-14 was found to have a 3-factor solution for community integration, community participation, and community organizations. The criterion-related validity was supported by its significant correlation with depression. Convergent and discriminant validity were established, with the internal consistency of the scale being 0.90. The test–retest reliability intraclass correlation coefficient for the scale was 0.78.

Discussion and Implications

The adapted version of the PCSQ-14 demonstrated promising psychometric properties in assessing perceived community support in older Chinese. The adapted PCSQ-14 could assist researchers in determining older Chinese adults’ perceptions of community support, and could also assist practitioners and policymakers in developing targeted services for older people and allocating resources more effectively.
A generalized curvilinear solver for spherical shell Rayleigh–Bénard convection
Authors: Naskar Souvik , Chongsiripinyo Karu , Mishra Siddhant , Pal Anikesh , Jananan Akshay
Published: May 2024

A 3-D finite-difference solver has been developed and implemented for Boussinesq convection in a spherical shell. The solver transforms any complex curvilinear domain into an equivalent Cartesian domain using Jacobi transformation and solves the governing equations in the latter. This feature enables the solver to account for the effects of the non-spherical shape of the convective regions of planets and stars. Apart from parallelization using MPI, implicit treatment of the viscous terms using a pipeline alternating direction implicit scheme and HYPRE multigrid accelerator for pressure correction makes the solver efficient for high-fidelity direct numerical simulations. We have performed simulations of Rayleigh–Bénard convection at two Rayleigh numbers Ra = 105 and 107 while keeping the Prandtl number fixed at unity (Pr = 1). The average radial temperature profile and the Nusselt number match very well, both qualitatively and quantitatively, with the existing literature. Closure of the turbulent kinetic energy budget, apart from the relative magnitude of the grid spacing compared to the local Kolmogorov scales, ensures sufficient spatial resolution.
Inhibitors of dermatan sulfate epimerase 1 decreased accumulation of glycosaminoglycans in mucopolysaccharidosis type I fibroblasts
Authors: Maccarana Marco , Li Binjie , Li Honglian , Fang Jianping , Yu Mingjia , Li Jin-ping
Published: May 2024

Genetic deficiency of alpha-L-iduronidase causes mucopolysaccharidosis type I (MPS-I) disease, due to accumulation of glycosaminoglycans (GAGs) including chondroitin/dermatan sulfate (CS/DS) and heparan sulfate (HS) in cells. Currently, patients are treated by infusion of recombinant iduronidase or by hematopoietic stem cell transplantation. An alternative approach is to reduce the L-iduronidase substrate, through limiting the biosynthesis of iduronic acid. Our earlier study demonstrated that ebselen attenuated GAGs accumulation in MPS-I cells, through inhibiting iduronic acid producing enzymes. However, ebselen has multiple pharmacological effects, which prevents its application for MPS-I. Thus, we continued the study by looking for novel inhibitors of dermatan sulfate epimerase 1 (DS-epi1), the main responsible enzyme for production of iduronic acid in CS/DS chains. Based on virtual screening of chemicals towards chondroitinase AC, we constructed a library with 1,064 compounds that were tested for DS-epi1 inhibition. Seventeen compounds were identified to be able to inhibit 27%–86% of DS-epi1 activity at 10 μM. Two compounds were selected for further investigation based on the structure properties. The results show that both inhibitors had a comparable level in inhibition of DS-epi1while they had negligible effect on HS epimerase. The two inhibitors were able to reduce iduronic acid biosynthesis in CS/DS and GAG accumulation in WT and MPS-I fibroblasts. Docking of the inhibitors into DS-epi1 structure shows high affinity binding of both compounds to the active site. The collected data indicate that these hit compounds may be further elaborated to a potential lead drug used for attenuation of GAGs accumulation in MPS-I patients.
Combining Computational Fluid Dynamics and Experimental Data to Understand Fish Schooling Behavior
Authors: Pan Yu , Lauder George V
Published: May 2024

Synopsis

Understanding the flow physics behind fish schooling poses significant challenges due to the difficulties in directly measuring hydrodynamic performance and the three-dimensional, chaotic, and complex flow structures generated by collective moving organisms. Numerous previous simulations and experiments have utilized computational, mechanical, or robotic models to represent live fish. And existing studies of live fish schools have contributed significantly to dissecting the complexities of fish schooling. But the scarcity of combined approaches that include both computational and experimental studies, ideally of the same fish schools, has limited our ability to understand the physical factors that are involved in fish collective behavior. This underscores the necessity of developing new approaches to working directly with live fish schools. An integrated method that combines experiments on live fish schools with computational fluid dynamics (CFD) simulations represents an innovative method of studying the hydrodynamics of fish schooling. CFD techniques can deliver accurate performance measurements and high-fidelity flow characteristics for comprehensive analysis. Concurrently, experimental approaches can capture the precise locomotor kinematics of fish and offer additional flow information through particle image velocimetry (PIV) measurements, potentially enhancing the accuracy and efficiency of CFD studies via advanced data assimilation techniques. The flow patterns observed in PIV experiments with fish schools and the complex hydrodynamic interactions revealed by integrated analyses highlight the complexity of fish schooling, prompting a reevaluation of the classic Weihs model of school dynamics. The synergy between CFD models and experimental data grants us comprehensive insights into the flow dynamics of fish schools, facilitating the evaluation of their functional significance and enabling comparative studies of schooling behavior. In addition, we consider the challenges in developing integrated analytical methods and suggest promising directions for future research.
Synthetic antimicrobial peptides: activity against vancomycin-resistant Enterococcus faecalis and modulation of chloramphenicol antibacterial activity
Authors: Gomes Lima Patrícia , Filho Noronha Souza Pedro , Pantoja Mesquita Felipe , Larré Oliveira Thaís , Drawanz Hartwig Daiane
Published: May 2024

Aims

Enterococcus faecalis (E. faecalis) is a leading cause of nosocomial infection and presents a wide spectrum of antibiotic resistance, being vancomycin-resistant Enterococcus (VRE) one of the most relevant. Synthetic antimicrobial peptides (SAMPs) are currently a promising option to overcome antimicrobial resistance. Thus, the purpose of this study was to assess the effect of eight SAMPs against vancomycin-resistant E. faecalis, as well as to investigate their mechanism of action and synergy with conventional antibiotics.

Methods and results

Here, eight SAMPs, Mo-CBP3-PepI, Mo-CBP3-PepII, Mo-CBP3-PepIII, RcAlb-PepI, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA, were tested for antibacterial activity in vitro against E. faecalis (ATCC® 51299) through broth microdilution. A maximum of 48% of E. faecalis growth inhibition was achieved by treatment with SAMPs alone. However, when these peptides were combined with the antibiotic chloramphenicol, assessed by checkerboard method, the inhibition increased to 55%–76% of inhibition, two to three-folds of increase if compared to the effects of the compounds alone. Microscopic analysis showed that E. faecalis cells treated with a combination of SAMPs and chloramphenicol resulted in bacterial membrane damage. The biofilm inhibition maximum was 22% for SAMPs alone, when combined with chloramphenicol, the maximum increased to 33%.

Conclusions

SAMPs and their combination with chloramphenicol demonstrate antibacterial activity against E. faecalis, possibly by inducing bacterial membrane damage.
Genetic response of a perennial grass to warm and wet environments interacts and is associated with trait means as well as plasticity
Authors: Münzbergová Zuzana , Šurinová Maria , Biscarini Filippo , Níčová Eva
Published: May 2024

The potential for rapid evolution is an important mechanism allowing species to adapt to changing climatic conditions. Although such potential has been largely studied in various short-lived organisms, to what extent we can observe similar patterns in long-lived plant species, which often dominate natural systems, is largely unexplored. We explored the potential for rapid evolution in Festuca rubra, a long-lived grass with extensive clonal growth dominating in alpine grasslands. We used a field sowing experiment simulating expected climate change in our model region. Specifically, we exposed seeds from five independent seed sources to novel climatic conditions by shifting them along a natural climatic grid and explored the genetic profiles of established seedlings after 3 years. Data on genetic profiles of plants selected under different novel conditions indicate that different climate shifts select significantly different pools of genotypes from common seed pools. Increasing soil moisture was more important than increasing temperature or the interaction of the two climatic factors in selecting pressure. This can indicate negative genetic interaction in response to the combined effects or that the effects of different climates are interactive rather than additive. The selected alleles were found in genomic regions, likely affecting the function of specific genes or their expression. Many of these were also linked to morphological traits (mainly to trait plasticity), suggesting these changes may have a consequence on plant performance. Overall, these data indicate that even long-lived plant species may experience strong selection by climate, and their populations thus have the potential to rapidly adapt to these novel conditions.
Range of trait variation in prey determines evolutionary contributions to predator growth rates
Authors: Hermann Ruben J , Pantel Jelena H , Réveillon Tom , Becks Lutz
Published: May 2024

Evolutionary and ecological dynamics can occur on similar timescales and thus influence each other. While it has been shown that the relative contribution of ecological and evolutionary change to population dynamics can vary, it still remains unknown what influences these differences. Here, we test whether prey populations with increased variation in their defence and competitiveness traits will have a stronger impact on evolution for predator growth rates. We controlled trait variation by pairing distinct clonal lineages of the green alga Chlamydomonas reinhardtii with known traits as prey with the rotifer Brachionus calyciforus as predator and compared those results with a mechanistic model matching the empirical system. We measured the impact of evolution (shift in prey clonal frequency) and ecology (shift in prey population density) for predator growth rate and its dependency on trait variation using an approach based on a 2-way ANOVA. Our experimental results indicated that higher trait variation, i.e., a greater distance in trait space, increased the relative contribution of prey evolution to predator growth rate over 3–4 predator generations, which was also observed in model simulations spanning longer time periods. In our model, we also observed clone-specific results, where a more competitive undefended prey resulted in a higher evolutionary contribution, independent of the trait distance. Our results suggest that trait combinations and total prey trait variation combine to influence the contribution of evolution to predator population dynamics, and that trait variation can be used to identify and better predict the role of eco-evolutionary dynamics in predator–prey systems.
Utilization of Telemedicine for Evaluation of Patients and Distribution of a Scarce Resource During the COVID-19 Pandemic
Authors: Weakley Kathryn , Bryant Kristina
Published: May 2024

Telemedicine can be utilized to safely evaluate patients, equitably distribute a scarce resource, and generate wRVUs during pandemics.
Plant protein–lipid interfaces studied by molecular dynamics simulations
Authors: Neubergerová Michaela , Pleskot Roman
Published: May 2024

The delineation of protein–lipid interfaces is essential for understanding the mechanisms of various membrane-associated processes crucial to plant development and growth, including signalling, trafficking, and membrane transport. Due to their highly dynamic nature, the precise characterization of lipid–protein interactions by experimental techniques is challenging. Molecular dynamics simulations provide a powerful computational alternative with a spatial–temporal resolution allowing the atomistic-level description. In this review, we aim to introduce plant scientists to molecular dynamics simulations. We describe different steps of performing molecular dynamics simulations and provide a broad survey of molecular dynamics studies investigating plant protein–lipid interfaces. Our aim is also to illustrate that combining molecular dynamics simulations with artificial intelligence-based protein structure determination opens up unprecedented possibilities for future investigations of dynamic plant protein–lipid interfaces.
Decoding the functionality of plant transcription factors
Authors: Dhatterwal Pinky , Sharma Namisha , Prasad Manoj
Published: May 2024

Transcription factors (TFs) intricately govern cellular processes and responses to external stimuli by modulating gene expression. TFs help plants to balance the trade-off between stress tolerance and growth, thus ensuring their long-term survival in challenging environments. Understanding the factors and mechanisms that define the functionality of plant TFs is of paramount importance for unravelling the intricate regulatory networks governing development, growth, and responses to environmental stimuli in plants. This review provides a comprehensive understanding of these factors and mechanisms defining the activity of TFs. Understanding the dynamic nature of TFs has practical implications for modern molecular breeding programmes, as it provides insights into how to manipulate gene expression to optimize desired traits in crops. Moreover, recent studies also report the functional duality of TFs, highlighting their ability to switch between activation and repression modes; this represents an important mechanism for attuning gene expression. Here we discuss what the possible reasons for the dual nature of TFs are and how this duality instructs the cell fate decision during development, and fine-tunes stress responses in plants, enabling them to adapt to various environmental challenges.
Insight–HXMT observations of thermonuclear X-ray bursts from 4U 1608–52 in the low/hard state: the energy-dependent hard X-ray deficit and cooling saturation of the corona
Authors: Chen Y P , Zhang S , Ji L , Zhang S N , Peng J Q , Kong L D , Chang Z , Shui Q C , Tao L , Qu J L , Ge M Y , Li J
Published: May 2024

During thermonuclear bursts, it is suspected that cooling of the corona by the burst emission may be the cause of hard X-ray deficits. Although such a deficit has been observed in nine sources, it has not been observed from 4U 1608–52, a nearby prolific burster. Therefore, the authenticity and universality of the hard X-ray deficit may be in question. To investigate this suspicion, Insight–HXMT performed cadence observations during the low/hard state of 4U 1608–52 in 2022 September and detected 10 thermonuclear X-ray bursts. Two of these bursts show a double-peaked structure in the soft X-ray band, which could be caused by the high temperature of the burst emission and a marginal photospheric radius expansion (PRE) around the burst peak time. This is indicated by their peak fluxes being up to the Eddington limit and having a large colour factor at the peak of the bursts. A hard X-ray deficit is observed at a significant level during bursts at > 30 keV. Furthermore, the fraction of this deficit shows saturation at 50 per cent for the first eight bursts. This saturation may indicate that the corona is layered and only part of the corona is cooled by the bursts: for example, the part close to the neutron star surface is cooled while the rest remains intact during bursts. This result provides a clue to the geometry of the corona. For example, a possible scenario is that the corona has two forms: a quasi-spheric corona between the neutron star and the disc and a disc corona on both surfaces of the disc.
Analysis of galaxies at the extremes: a kinematic analysis of the Virgo cluster dwarfs VCC 9 and VCC 1448 using the Keck cosmic web imager
Authors: Gannon Jonah S , Forbes Duncan A , Romanowsky Aaron J , Brodie Jean P , Haacke Lydia , Ferré-Mateu Anna , Danieli Shany , van Dokkum Pieter , Buzzo Maria Luisa , Couch Warrick J , Shen Zili
Published: May 2024

We present spatially resolved Keck Cosmic Web Imager stellar spectroscopy of the Virgo cluster dwarf galaxies VCC 9 and VCC 1448. These galaxies have similar stellar masses and large half-light radii but very different globular cluster (GC) system richness (∼25 versus ∼99 GCs). Using the KCWI data, we spectroscopically confirm 10 GCs associated with VCC 1448 and one GC associated with VCC 9. We make two measurements of dynamical mass for VCC 1448 based on the stellar and GC velocities, respectively. VCC 1448’s mass measurements suggest that it resides in a halo in better agreement with the expectation of the stellar mass–halo mass relationship than the expectation from its large GC counts. For VCC 9, the dynamical mass we measure agrees with the expected halo mass from both relationships. We compare VCC 1448 and VCC 9 to the GC-rich galaxy Dragonfly 44 (∼74 GCs), which is similar in size but has ∼1 dex less stellar mass than either Virgo galaxy. In dynamical mass – GC number space, Dragonfly 44 and VCC 1448 exhibit richer GC systems given their dynamical mass than that of VCC 9 and other ‘normal’ galaxies. We also place the galaxies in kinematics–ellipticity space finding evidence of an anticorrelation between rotational support and the fraction of a galaxy’s stellar mass in its GC system, that is, VCC 9 is more rotationally supported than VCC 1448, which is more rotationally supported than Dragonfly 44. This trend may be expected if a galaxy’s GC content depends on its natal gas properties at formation.
Dynamical coupling of Keplerian orbits in a hierarchical four-body system: from the Galactic Centre to compact planetary systems
Authors: Singhal M , Šubr L , Haas J
Published: May 2024

This study focuses on the long-term evolution of two bodies in nearby initially coplanar orbits around a central dominant body perturbed by a fourth body on a distant Keplerian orbit. Our previous works that considered this setup enforced circular orbits by adding a spherical potential of extended mass, which dampens Kozai–Lidov oscillations; it led to two qualitatively different modes of the evolution of the nearby orbits. In one scenario, their mutual interaction exceeds the effect of differential precession caused by a perturbing body. This results in a long-term coherent evolution, with nearly coplanar orbits experiencing only small oscillations of inclination. We extend the previous work by (i) considering post-Newtonian corrections to the gravity of the central body, either instead of or in addition to the potential of extended mass, (ii) relaxing the requirement of strictly circular orbits, and (iii) removing the strict requirement of complete Kozai–Lidov damping. Thus, we identify the modes of interorbital interaction described for the zero eccentricity case in the more general situation, which allows for its applicability to a much broader range of astrophysical systems than considered initially. In this work, we scale the systems to the orbits of S-stars; we consider the clockwise disc to represent the perturbing body, with post-Newtonian corrections to the gravity of Sagittarius A* playing the role of damping potential. Considering post-Newtonian corrections, even stellar-mass central bodies in compact planetary systems can allow for the coupled evolution of Keplerian orbits.
A stochastic gravitational wave background in LISA from unresolved white dwarf binaries in the Large Magellanic Cloud
Authors: Rieck Steven , Criswell Alexander W , Korol Valeriya , Keim Michael A , Bloom Malachy , Mandic Vuk
Published: May 2024

The Laser Interferometer Space Antenna (LISA) is expected to detect a wide variety of gravitational wave sources in the mHz band. Some of these signals will elude individual detection, instead contributing as confusion noise to one of several stochastic gravitational-wave backgrounds (SGWBs) – notably including the ‘Galactic foreground’, a loud signal resulting from the superposition of millions of unresolved double white dwarf binaries (DWDs) in the Milky Way. It is possible that similar, weaker SGWBs will be detectable from other DWD populations in the local Universe, including the Large Magellanic Cloud (LMC). We use the Bayesian LISA Inference Package (blip) to investigate the possibility of an anisotropic SGWB generated by unresolved DWDs in the LMC. To do so, we compute the LMC SGWB from a realistic DWD population generated via binary population synthesis, simulate 4 years of time-domain data with blip comprised of stochastic contributions from the LMC SGWB and the LISA detector noise, and analyse this data with blip’s spherical harmonic anisotropic SGWB search. We also consider the case of spectral separation from the Galactic foreground. We present the results of these analyses and show, for the first time, that the unresolved DWDs in the LMC will comprise a significant SGWB for LISA.
Correcting for the overabundance of low-mass quiescent galaxies in semi-analytic models
Authors: Harrold Jimi E , Almaini Omar , Pearce Frazer R , Yates Robert M
Published: May 2024

We compare the l-galaxies semi-analytic model to deep observational data from the UKIDSS Ultra Deep Survey (UDS) across the redshift range 0.5 < z < 3. We find that the overabundance of low-mass, passive galaxies at high redshifts in the model can be attributed solely to the properties of ‘orphan’ galaxies, i.e. satellite galaxies where the simulation has lost track of the host dark matter sub-halo. We implement a simple model that boosts the star formation rates in orphan galaxies by matching them to non-orphaned satellite galaxies at a similar evolutionary stage. This straightforward change largely addresses the discrepancy in the low-mass passive fraction across all redshifts. We find that the orphan problem is somewhat alleviated by higher resolution simulations, but the preservation of a larger gas reservoir in orphans is still required to produce a better fit to the observed space density of low-mass passive galaxies. Our findings are also robust to the precise definition of the passive galaxy population. In general, considering the vastly different prescriptions used for orphans in semi-analytic models, we recommend that they are analysed separately from the resolved satellite galaxy population, particularly with JWST observations reigniting interest in the low-mass regime in which they dominate.
The value of virtual molecular tumor boards for informed clinical decision-making
Authors: Angel Martín , Demiray Mutlu , Dişel Umut , Passos João
Published: May 2024

Genomic profiling and other new technologies have increased the volume and complexity of information available for guiding clinical decision-making in precision oncology. Consequently, there is a need for multidisciplinary expert teams, in the form of molecular tumor boards (MTBs), who can translate this information into a therapeutic plan, including matching patients to suitable clinical trials. Virtual MTBs (vMTBs) can help to overcome many of the challenges associated with in-person MTBs, such as limited time availability, access to appropriate experts or datasets, or interactions between institutions. However, real-world experience from vMTBs is lacking. Here, we describe oncologists’ vMTB experiences and the value of working with multicenter and/or multinational vMTBs. We also address knowledge gaps and barriers that could affect the implementation of vMTBs in routine clinical practice. Case studies from Argentina, Turkey, and Portugal illustrate the value of informed clinical decision-making by vMTBs, including expansion of therapeutic options for patients, faster time to treatment, and the resulting improvement in patient outcomes or impact of vMTB discussions on patients. With the uptake of comprehensive genomic profiling and the evolution of some cancers now being conceptualized as a collection of rare diseases with small patient populations based on molecular profiling, the importance of MTBs has increased in modern cancer management. However, an adjustment in clinical decision-making by healthcare professionals is required and evidence of the added value of vMTBs is lacking. Existing vMTBs and recommendations from participating oncologists could point toward a structured evaluation and analysis of this new platform.
Molecularly matched targeted therapy: a promising approach for refractory metastatic melanoma
Authors: Connell Emily , Gerard Émilie , Oules Bénédicte , Brunet-Possenti Florence , Lamoureux Anouck , Bonnefille Hugo , Mary-Prey Sorilla , Carrasquilla Ana , Mouret Stéphane , Kramkimel Nora , Lesage Candice , Stoebner Pierre-Emmanuel , Bartoli Axel , Monestier Sandrine , Correard Florian , Gros Audrey , Jeanson Arnaud , Ouafik L’Houcine , Gaudy-Marqueste Caroline , Tomasini Pascale , Charles Julie , Amini-Adle Mona , Malissen Nausicaa
Published: May 2024

Background

Only a fraction of patients with metastatic melanoma derive durable benefit from approved treatments. The clinical impact of personalized medicine strategies for melanoma, apart from BRAF, NRAS, or CKIT targeting, has rarely been reported.

Materials and Methods

By means of the Group of Cutaneous Oncology of the French Society of Dermatology, we retrospectively included all patients with advanced melanoma aged 18 years and older for whom molecular testing identified one or more actionable molecular alterations and who accordingly received molecularly matched therapy. We excluded patients with only BRAF, NRAS, or CKIT alterations and patients who received molecularly matched therapy for less than 15 days.

Results

We included 26 patients with a median follow-up of 8 months (1-54), a median age of 63 years (24-89), and a sex ratio of 2.7. These patients had been heavily pretreated, and 64% had elevated LDH levels. The disease control rate was 38%, with 4 cases of partial response (overall response rate: 15%) and 6 of stable disease for at least 6 months. The median duration of treatment was 3.1 months (0.9-13.5). Among patients with disease control, the median duration of control was 6.6 months (2.6-13.5) and 3 cases were ongoing at the end of the study. Patients with controlled disease had GNA11, MAP2K1, FYCO1-RAF1, HRAS, ATM, CCND1, MDM2/CDK4, and CDKN2A/NRAS alterations.

Conclusions

High-throughput sequencing followed by matched targeted therapy is a promising approach for patients with advanced melanoma refractory to approved treatments.