Miracle-dz/UniFAR-FTUs huggingface dataset:
Individual- and group-level sex ratios under local mate competition: consequences of infanticide and reproductive dominance

Abstract Extremely female-biased sex ratios of parasitoid wasps in multiple-foundress groups challenges evolutionary theory which predicts diminishing bias as foundress numbers increase. Recent theory based on foundress cooperation has achieved qualitative rather than quantitative success in explaining bias among parasitoids in the genus Sclerodermus. Here, we develop an explanation, expanding the theory of local mate competition, based on the observation that male production seems dominated by some foundresses within groups. Two sex ratio effects arise from such reproductive dominance: an immediate effect via suppression of male production, and a long-term evolutionary response to reproductive skew. We analyze the outcome of these effects at the individual and group level, the latter being more readily observable. Three model scenarios are analyzed: (1) random killing of developing sons in a group by all foundresses, without reproductive skew, (2) the development of reproductive dominance by some foundresses after sex allocation decisions by all foundresses have been implemented, and (3) reproductive dominance within foundress groups before sex allocation decisions are implemented. The 3 scenarios have subtly different implications for sex ratio evolution, with Models 2 and 3 being novel additions to theory, showing how reproductive dominance can alter the outcome of sex ratio evolution. All models match observations in their outcomes better than other recently proposed theory, but Models 2 and 3 are closest to observations in their underlying assumptions. Further, Model 2 shows that differential offspring mortality after parental investment can influence the primary sex ratio even when random with respect to parental and offspring characters, but targeted at entire clutches. The novel models are solved for both diploid and haplodiploid genetic systems, and confirmed with simulations. Overall, these models provide a feasible explanation for the extremely female-biased sex ratios produced by multi-foundress groups and expand the scope of local mate competition theory to consider reproductive dominance.
Growth produces coordination trade-offs in Trichoplax adhaerens, an animal lacking a central nervous system

Significance Coordination between cells is fundamental for multicellular life. The first multicellular animals were capable of growing to indeterminate sizes but lacked nervous systems that could facilitate coordination. We investigate how size variation affects coordination in such organisms by measuring the collective order in the locomotion of Trichoplax adhaerens, the simplest multicellular animal. We find that collective order decreases as such animals grow in size and use a simulation model to determine that this scaling phenomenon occurs at the phase transition between ordered and disordered movement, also known as criticality. Our findings therefore suggest a fundamental trade-off between increasing size and coordination in such a decentralized organism and provide evidence for the necessity of centralized control at larger sizes.
Sleep–wake patterns are altered with age, Prdm13 signaling in the DMH, and diet restriction in mice

This study found that age-associated sleep changes are ameliorated by DR in the presence of Prdm13 signaling in the DMH, suggesting Prdm13+ DMH neurons will be of great interest to explore a potential intervention on age-associated sleep changes. Old animals display significant alterations in sleep–wake patterns such as increases in sleep fragmentation and sleep propensity. Here, we demonstrated that PR-domain containing protein 13 (Prdm13)+ neurons in the dorsomedial hypothalamus (DMH) are activated during sleep deprivation (SD) in young mice but not in old mice. Chemogenetic inhibition of Prdm13+ neurons in the DMH in young mice promotes increase in sleep attempts during SD, suggesting its involvement in sleep control. Furthermore, DMH-specific Prdm13-knockout (DMH-Prdm13-KO) mice recapitulated age-associated sleep alterations such as sleep fragmentation and increased sleep attempts during SD. These phenotypes were further exacerbated during aging, with increased adiposity and decreased physical activity, resulting in shortened lifespan. Dietary restriction (DR), a well-known anti-aging intervention in diverse organisms, ameliorated age-associated sleep fragmentation and increased sleep attempts during SD, whereas these effects of DR were abrogated in DMH-Prdm13-KO mice. Moreover, overexpression of Prdm13 in the DMH ameliorated increased sleep attempts during SD in old mice. Therefore, maintaining Prdm13 signaling in the DMH might play an important role to control sleep–wake patterns during aging. Graphical Abstract
Cholesterol impacts the formation of huntingtin/lipid complexes and subsequent aggregation

Huntington's disease (HD) is a neurodegenerative disease resulting from an expansion of the polyglutamine (polyQ) domain within the huntingtin protein (htt). PolyQ expansion triggers toxic aggregation and alters htt/lipid interactions. The first 17 amino acids at the N‐terminus of htt (Nt17) have a propensity to form an amphipathic α‐helix crucial to aggregation and membrane binding. Htt interacts closely with a variety of membrane systems including those of the endoplasmic reticulum, mitochondria, nuclear envelope, and plasma membrane. Membrane composition heavily influences both htt aggregation and lipid interactions, and cholesterol is a crucial membrane component that modulates properties such as fluidity, permeability, and organization. In HD, cholesterol homeostasis is disrupted, and likely plays a role in toxicity. The objective of these studies was to identify the impact of cholesterol on htt aggregation and lipid interactions in various lipid systems. Lipid systems of POPC, DOPC, and POPG with varied levels of exogenously added cholesterol were exposed to htt, and the influences on aggregation, lipid binding, and htt/lipid complexation were evaluated using thioflavin‐T aggregation assays, atomic force microscopy, colorimetric lipid binding assays, and mass spectrometry. The addition of cholesterol to DOPC vesicles enhanced htt aggregation. In the presence of vesicles of either POPC or POPG, the addition of cholesterol reduced htt aggregation. Htt/lipid binding decreased for POPC and increased for both DOPC and POPG with increasing cholesterol content, with observed differences in htt/lipid complexation. Altered cholesterol content influences htt aggregation, lipid binding, and complexation differently depending on overall lipid composition.
Ecohydrological Footprints: Quantitative Response of Ecosystems to Changes in their Hydrological Drivers

Ecohydrological footprints are defined as the response of ecosystem functions or services to changes in their hydrologic drivers. In this thesis, several diverse footprints are addressed: noise-driven effects on storage-discharge relations and catchment streamflow distributions, that are important drivers of biodiversity; soil salinization and its ecohydrological implications; topological effects of the ecological interaction networks on living communities (e.g. on their species persistence); and form and function of the global virtual water trade network. The coherence of the conceptual framework is provided by the study of drivers and controls of ecohydrological variability using methodological approaches based on statistical mechanics. In fact, this thesis work outlines a significant portion of environmental statistical mechanics, an overarching discipline that is emerging in recent years, which applies mathematical tools from statistical mechanics to model several ecohydrological processes. The proposed relevance of this thesis lies in the major effects of hydrologic drivers on ecological process. The view that emerges from current research in ecohydrology, that this thesis supports, is that there exists a definite need for an integrated understanding of ecological and hydrological processes. Because stochasticity is intrinsic to environmental and ecohydrological variability, noise plays an important and constructive role in ecohydrological processes. In this thesis, a stochastic approach is applied to analyze different ecohydrological processes, ranging from green and blue water flows in river basins (part I), ecosystem dynamics affected by the directional dispersal provided by river networks (part II) to water footprints of human society (part III). Methods range from novel exact solutions to stochastic differential equations to random graph theory applications, and imply the analysis of suitable field data. An analytical framework for quantitative analysis is laid out to tackle complex problems and to estimate the effects of environmental change on the interaction of the hydrologic processes with the biota. The main results of this thesis are: i) the achievement of exact solutions for the probability distribution of catchment streamflow, that takes in account stochastic fluctuations in the storage-discharge relation and for the condition of a noise induced phenomena to the streamflows regimes; ii) the stationary solutions of soil salinity under stochastic hydrologic forcing; iii) a novel solution of the Ito−Stratonovich problem in multiplicative Poisson processes; iv) the proper framework for species’ persistence time distributions, as a function of topological constraints on the ecosystem, and its connection with other important macroeco-
Randomized controlled pilot study assessing fructose tolerance during fructose reintroduction in non‐constipated irritable bowel syndrome patients successfully treated with a low FODMAP diet

Limited data exist to guide FODMAP (fermentable oligo‐, di‐, monosaccharides, and polyols) reintroduction to assess tolerance following a low FODMAP diet (LFD). Fructose reintroduction is often stepwise up to 7.5 g fructose (e.g., three tsp of honey). We aimed to determine the fructose tolerance threshold in non‐constipated, LFD‐responsive patients with irritable bowel syndrome (IBS) and assess whether stool microbiome predicted LFD response or fructose tolerance.
Double‐Edged Effects of Venglustat on Behavior and Pathology in Mice Overexpressing α‐Synuclein

Venglustat is a brain‐penetrant, small molecule inhibitor of glucosylceramide synthase used in clinical testing for treatment of Parkinson's disease (PD). Despite beneficial effects in certain cellular and rodent models, patients with PD with mutations in GBA, the gene for lysosomal glucocerebrosidase, experienced worsening of their motor function under venglustat treatment (NCT02906020, MOVES‐PD, phase 2 trial).
The relationship between resting‐state amplitude fluctuations and memory‐related deactivations of the default mode network in young and older adults

The default mode network (DMN) typically exhibits deactivations during demanding tasks compared to periods of relative rest. In functional magnetic resonance imaging (fMRI) studies of episodic memory encoding, increased activity in DMN regions even predicts later forgetting in young healthy adults. This association is attenuated in older adults and, in some instances, increased DMN activity even predicts remembering rather than forgetting. It is yet unclear whether this phenomenon is due to a compensatory mechanism, such as self‐referential or schema‐dependent encoding, or whether it reflects overall reduced DMN activity modulation in older age. We approached this question by systematically comparing DMN activity during successful encoding and tonic, task‐independent, DMN activity at rest in a sample of 106 young (18–35 years) and 111 older (60–80 years) healthy participants. Using voxel‐wise multimodal analyses, we assessed the age‐dependent relationship between DMN resting‐state amplitude (mean percent amplitude of fluctuation, mPerAF) and DMN fMRI signals related to successful memory encoding, as well as their modulation by age‐related hippocampal volume loss, while controlling for regional grey matter volume. Older adults showed lower resting‐state DMN amplitudes and lower task‐related deactivations. However, a negative relationship between resting‐state mPerAF and subsequent memory effect within the precuneus was observed only in young, but not older adults. Hippocampal volumes showed no relationship with the DMN subsequent memory effect or mPerAF. Lastly, older adults with higher mPerAF in the DMN at rest tend to show higher memory performance, pointing towards the importance of a maintained ability to modulate DMN activity in old age.
Extracting relevant predictive variables for COVID-19 severity prognosis: An exhaustive comparison of feature selection techniques

With the COVID-19 pandemic having caused unprecedented numbers of infections and deaths, large research efforts have been undertaken to increase our understanding of the disease and the factors which determine diverse clinical evolutions. Here we focused on a fully data-driven exploration regarding which factors (clinical or otherwise) were most informative for SARS-CoV-2 pneumonia severity prediction via machine learning (ML). In particular, feature selection techniques (FS), designed to reduce the dimensionality of data, allowed us to characterize which of our variables were the most useful for ML prognosis. We conducted a multi-centre clinical study, enrolling n = 1548 patients hospitalized due to SARS-CoV-2 pneumonia: where 792, 238, and 598 patients experienced low, medium and high-severity evolutions, respectively. Up to 106 patient-specific clinical variables were collected at admission, although 14 of them had to be discarded for containing ⩾60% missing values. Alongside 7 socioeconomic attributes and 32 exposures to air pollution (chronic and acute), these became d = 148 features after variable encoding. We addressed this ordinal classification problem both as a ML classification and regression task. Two imputation techniques for missing data were explored, along with a total of 166 unique FS algorithm configurations: 46 filters, 100 wrappers and 20 embeddeds. Of these, 21 setups achieved satisfactory bootstrap stability (⩾0.70) with reasonable computation times: 16 filters, 2 wrappers, and 3 embeddeds. The subsets of features selected by each technique showed modest Jaccard similarities across them. However, they consistently pointed out the importance of certain explanatory variables. Namely: patient’s C-reactive protein (CRP), pneumonia severity index (PSI), respiratory rate (RR) and oxygen levels –saturation Sp O2, quotients Sp O2/RR and arterial Sat O2/Fi O2–, the neutrophil-to-lymphocyte ratio (NLR) –to certain extent, also neutrophil and lymphocyte counts separately–, lactate dehydrogenase (LDH), and procalcitonin (PCT) levels in blood. A remarkable agreement has been found a posteriori between our strategy and independent clinical research works investigating risk factors for COVID-19 severity. Hence, these findings stress the suitability of this type of fully data-driven approaches for knowledge extraction, as a complementary to clinical perspectives.
Adolescents’ neural reactivity to parental criticism is associated with diminished happiness during daily interpersonal situations

Abstract The goal of this study was to examine the relation between real-world socio-emotional measures and neural activation to parental criticism, a salient form of social threat for adolescents. This work could help us understand why heightened neural reactivity to social threat consistently emerges as a risk factor for internalizing psychopathology in youth. We predicted that youth with higher reactivity to parental criticism (vs neutral comments) in the subgenual anterior cingulate cortex (sgACC), amygdala and anterior insula would experience (i) less happiness in daily positive interpersonal situations and (ii) more sadness and anger in daily negative interpersonal situations. Participants (44 youth aged 11–16 years with a history of anxiety) completed a 10-day ecological momentary assessment protocol and a neuroimaging task in which they listened to audio clips of their parents’ criticism and neutral comments. Mixed-effects models tested associations between neural activation to critical (vs neutral) feedback and emotions in interpersonal situations. Youth who exhibited higher activation in the sgACC to parental criticism reported less happiness during daily positive interpersonal situations. No significant neural predictors of negative emotions (e.g. sadness and anger) emerged. These findings provide evidence of real-world correlates of neural reactivity to social threat that may have important clinical implications.
Preference-Based Human-in-the-Loop Optimization for Perceived Realism of Haptic Rendering

The fidelity of haptic rendering is characterized by the perceived realism capturing the level of similarity to a corresponding tangible object. Perceived realism depends on the musculoskeletal, mental, and perceptual properties of the individuals that manipulate the system. Human-in-the-loop (HiL) studies provide a feasible means for the concurrent optimization of the performance of the overall haptic rendering process, as the physical limitations of the hardware, the factors affecting the fidelity of the rendering algorithm, and the limitations of human action and perception can all be considered simultaneously. In this study, we propose the use of preference-based HiL optimization techniques based on sample-efficient Bayesian optimization algorithms and qualitative pairwise comparisons to maximize the perceived realism of haptic rendering tasks. We present two HiL optimization studies that maximize the perceived realism of spring and friction rendering and validate our results by comparing the HiL-optimized rendering models with expert-tuned nominal models. We show that the system parameters can effectively be optimized within a reasonable amount of time using a preference-based HiL optimization approach. Furthermore, we demonstrate that the approach provides an efficient means of studying the effect of haptic rendering parameters on perceived realism by capturing the interactions among the parameters, even for relatively high dimensional parameter spaces.
Meningococcal disease within the Gulf Cooperation Council Countries

ABSTRACT This review reports on the recent epidemiology of invasive meningococcal disease (IMD) within the Gulf Cooperation Council (GCC) Countries (focusing from 2012 onwards), the existing immunization strategies and the potential for IMD resurgence. MenACWY vaccination is now established in infant or adolescent immunization programs in Saudi Arabia, Bahrain, Kuwait, and the United Arab Emirates. At present, GCC Countries do not include MenB immunization. National health surveillance reports indicate a total of 156 IMD cases reported across the GCC Countries between 2012 and 2021; between 30% and 80% of cases were reported in individuals aged ≥15 years. Lack of serogroup data hinders the assessment of vaccine impact and decision-making on additional vaccine introductions (e.g. MenB immunization). Hajj/Umrah pilgrimage and the increasing number of large-scale commercial and social events held in the GCC Countries pose a potential risk for future IMD outbreaks. Immunization policies for such events could be strengthened. Graphical abstract
Exploration of anti‐leukemic effect of soft coral‐derived 13‐acetoxysarcocrassolide: Induction of apoptosis via oxidative stress as a potent inhibitor of heat shock protein 90 and topoisomerase II

13‐Acetoxysarcocrassolide (13‐AC) is a marine cembranoid derived from the aquaculture soft coral of Lobophytum crassum. The cytotoxic effect of 13‐AC against leukemia cells was previously reported but its mechanism of action is still unexplored. In the current study, we showed that 13‐AC induced apoptosis of human acute lymphoblastic leukemia Molt4 cells, as evidenced by the cleavage of PARP and caspases, phosphatidylserine externalization, as well as the disruption of mitochondrial membrane potential. The use of N‐acetylcysteine (NAC), a reactive oxygen species (ROS) scavenger, attenuated the cytotoxic effect induced by 13‐AC. Molecular docking and thermal shift assay indicated that the cytotoxic mechanism of action of 13‐AC involved the inhibition of heat shock protein 90 (Hsp 90) activity by eliciting the level of Hsp 70 and topoisomerase IIα in Molt4 cells. 13‐AC also exhibited potent antitumor activity by reducing the tumor volume (48.3%) and weight (72.5%) in the in vivo Molt4 xenograft mice model. Our findings suggested that the marine cembranoid, 13‐AC, acted as a dual inhibitor of Hsp 90 and topoisomerase IIα, exerting more potent apoptotic activity via the enhancement of ROS generation.
Electric and magnetic tuning of Gilbert damping constant in LSMO/PMN-PT(011) heterostructure

Electric field control of magnetodynamics in magnetoelectric (ME) heterostructures has been the subject of recent interest due to its fundamental complexity and promising applications in room temperature (RT) devices. The present work focuses on the tuning of magnetodynamic parameters of epitaxially grown ferromagnetic (FM) La0.7Sr0. 3MnO3 (LSMO) on a ferro(piezo)electric (FE) Pb(Mg0.33Nb0.67)O3-PbTiO3 (PMN-PT) single crystal substrate. The uniaxial magnetic anisotropy of LSMO on PMN-PT confirms the ME coupling at the FM/FE heterointerface. The magnitude of the Gilbert damping constant (α) of this uniaxial LSMO film measured along the hard magnetic axis is significantly small compared to the easy axis. Furthermore, a marked decrease in the α values of LSMO at positive and negative electrical remanence of PMN-PT is observed, which is interpreted in the framework of strain induced spin dependent electronic structure. The present results clearly encourage the prospects of electric field controlled magnetodynamics, thereby realising the RT spin-wave based device applications with ultra-low power consumption.
Molecular insights into the role of electronic cigarettes in oral carcinogenesis

Abstract Electronic cigarette (EC) usage or vaping has seen a significant rise in recent years across various parts of the world. They have been publicized as a safe alternative to smoking; however, this is not supported strongly by robust research evidence. Toxicological analysis of EC liquid and aerosol has revealed presence of several toxicants with known carcinogenicity. Oral cavity is the primary site of exposure of both cigarette smoke and EC aerosol. Role of EC in oral cancer is not as well-researched as that of traditional smoking. However, several recent studies have shown that it can lead to a wide range of potentially carcinogenic molecular events in oral cells. This review delineates the oral carcinogenesis potential of ECs at the molecular level, providing a summary of the effects of EC usage on cancer therapy resistance, cancer stem cells (CSCs), immune evasion, and microbiome dysbiosis, all of which may lead to increased tumor malignancy and poorer patient prognosis. This review of literature indicates that ECs may not be as safe as they are perceived to be, however further research is needed to definitively determine their oncogenic potential.