bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambulatory physiological measures obtained under naturalistic urban mobility conditions have acceptable reliability
Authors: Korkmaz Dilber , Knauth Kilian , Brands Angela , Schmeck Marie , Büning Pia , Peters Jan
Published: April 2024

Ambulatory assessment methods in psychology and clinical neuroscience are powerful research tools for collecting data outside of the laboratory. These methods encompass physiological, behavioral, and self-report measures obtained while individuals navigate in real-world environments, thereby increasing the ecological validity of experimental approaches. Despite the recent increase in applications of ambulatory physiology, data on the reliability of these measures is still limited. To address this issue, twenty-six healthy participants (N= 15 female, 18-34 years) completed an urban walking route (2.1 km, 30 min walking duration, temperatureM= 19.8° degree Celsius,Range= 12°-37° degrees Celsius) on two separate testing days, while GPS-location and ambulatory physiological measures (cardiovascular and electrodermal activity) were continuously recorded. Bootstrapped test-retest reliabilities of single measures and aggregate scores derived via principal component analysis (PCA) were computed. The first principal component (PC#1) accounted for 39% to 45% of variance across measures. PC#1 scores demonstrated an acceptable test-retest reliability (r= .60) across testing days, exceeding the reliabilities of most individual measures (heart rate:r= .53, heart rate variability:r= .50, skin conductance level:r= .53, no. of skin conductance responses:r= .28, skin conductance response amplitude:r= .60). Results confirm that ambulatory physiological measures recorded during naturalistic navigation in urban environments exhibit acceptable test-retest reliability, in particular when compound scores across physiological measures are analyzed, a prerequisite for applications in (clinical) psychology and digital health.

Author summary

Psychophysiological assessments have been predominantly limited to controlled laboratory settings, leaving the reliability of field measurements unclear. In this study, we conducted a proof-of-concept investigation inN=26 healthy participants navigating the same urban route on two separate days. Cardiovascular and electrodermal activity were continuously recorded and combined with GPS-based location tracking. Psychophysiological measurements obtained under naturalistic urban mobility conditions showed acceptable test-retest reliability, in particular when multiple measures where combined into a compound score via principal component analysis. Shedding light on the reliability of ambulatory assessments in urban environments emphasizes the potential for psychophysiological measurements to contribute valuable insights beyond the constraints of traditional laboratory settings.
A Computational Model of Deep Brain Stimulation for Parkinson’s Disease Tremor
Authors: Nair Sandeep Sathyanandan , Chakravarthy V. Srinivasa
Published: April 2024

Parkinson’s Disease (PD) is a progressive neurological disorder that is typically characterized by a range of motor dysfunctions and its impact extends beyond physical abnormalities into emotional well-being and cognitive symptoms. The loss of dopaminergic neurons in the Substantia nigra pars compacta (SNc) leads to an array of dysfunctions in the functioning of Basal Ganglia (BG) circuitry that manifests into PD. While active research is being carried out in finding the root cause of SNc cell deaths, various therapeutic techniques are prevalent to manage the symptoms of PD. The most common approach in managing the symptoms is replenishing the lost dopamine in the form of taking dopaminergic medications such as Levodopa amidst its long-term complications. Another commonly used intervention for PD is deep brain stimulation (DBS), which is a invasive technique where an electrode is surgically inserted into the skull and a high frequency current of appropriate characteristics is delivered to the brain region. DBS is most commonly used when levodopa medication efficacy reduces and also in combination with levodopa medication that will help reducing the required dosage of medication prolonging the therapeutic effect. DBS is also a go to option when motor complications such as dyskinesias emerge as a side effect of medication. Several studies have also reported that though DBS is found to be effective in suppressing severe motor symptoms such as tremor and rigidity, it has adverse effect on cognitive capabilities. Henceforth it is important to understand the exact mechanism of DBS in alleviating the motor symptoms. A computational model of DBS stimulation for motor symptoms will offer great insights in understanding the mechanisms underlying the DBS and in this line in our current study we model a cortico-basal ganglia circuitry of arm reaching where we simulate healthy controls (HC) and PD symptoms as well as the DBS effect on the PD tremor. With DBS current characteristics of 220 pA, 130 Hz and 100 microseconds pulse-width we were able to see maximum therapeutic effect using our model. This model can be extended to accommodate cognitive dynamics in future so as to study the impact of DBS on cognitive symptoms and optimizing the parameters to get optimal performance effect across modalities.
Gene pseudogenization in fertility-associated genes in cheetah (Acinonyx jubatus), a species with long-term low effective population size
Authors: Peers Jessica A. , Nash Will J. , Haerty Wilfried
Published: April 2024

The ongoing global biodiversity crisis is placing an increasing number of mammalian populations at risk of decline. Species that have survived severe historic bottlenecks, such as the cheetah (Acinonyx jubatus) exhibit symptoms of inbreeding depression including reproductive and developmental defects. Although it has long been suggested that such defects stem from an accumulation of weakly deleterious mutations, the implications of such mutations leading to pseudogenization has not been assessed.

Here, we use comparative analysis of eight felid genomes to better understand the impacts of deleterious mutations in the cheetah. We find novel pseudogenization events specific to the cheetah. Through careful curation, we identify 89 genes with previously unreported premature termination codons that likely affect gene function, 65 of which are caused by point mutations. With the addition of population data, we find 22 PTCs fixed in wild populations, four of which (DEFB116, ARL13A, CFAP119 and NC5TD4) are also found in a more recent reference genome. Mutations within three of these genes are linked with sterility, including azoospermia, which is common in cheetahs. Our results highlight the power of comparative genomic approaches for the discovery of novel causative variants in declining species.
Generalizing the response and satisfaction threshold models for multiple task types: A maximal entropy approach
Authors: Lynch C.M. , Pavlic T.P.
Published: April 2024

Response threshold models are often used to test hypotheses about division of labor in social-insect colonies. Each worker’s probability to engage in a task rapidly increases when a cue associated with task demand crosses some “response threshold.” Threshold variability across workers generates an emergent division of labor that is consistent over time and flexibly adaptive to increasing demands, which allows for testable predictions about the shape of hypothetical response-threshold distributions. Although there are myriad different task types in a social-insect colony, the classical response-threshold model is built to understand variability in response to a single type of task. As such, it does not immediately allow for testing predictions about how different workers prioritize different task types or how demand for some tasks interferes with responding to demand for others. To rectify this, we propose a multi-task generalization that degenerates into the standard model for a single task. We replace the classical Hill response probability with a model that draws worker choices from a Boltzmann distribution, which is an approach inspired by multi-class machine learning.
Tap into non-symbiotic carbon? Exogenous myristate fuels the growth of symbiotic arbuscular mycorrhizal fungi but disrupts their carbon-phosphorus exchange with host plants
Authors: Chen Hanwen , Xiong Tian , Guan Baoxing , Huang Jiaqi , Zhao Danrui , Chen Yao , Liang Haoran , Li Yingwei , Wu Jingwen , Ye Shaoping , Li Ting , Shu Wensheng , Li Jin-tian , Wang Yutao
Published: April 2024

Arbuscular mycorrhizal fungi (AMF) form symbiotic relationships with the roots of most land plants. In this association, known as arbuscular mycorrhiza (AM), the obligate biotrophic fungi acquire host-derived (symbiotic) carbohydrates and, in return, facilitate plant uptake of mineral nutrients such as phosphate. However, the capacity of symbiotic AMF to access external non-symbiotic carbon sources remains unclear, complicating our understanding of the nutritional exchanges in AM and their ecosystem functions. In this study, we explored the direct uptake of exogenous13C1-labeled myristate by symbiotic AMF (Rhizophagus irregularis) and their growth responses using a two-compartment and a single-compartment AMF-carrot hairy root co-culture system, respectively. Additionally, we assessed the impact of exogenous myristate on the carbon-phosphorus exchange between AMF and two host species in a greenhouse experiment, using13C-neutral lipid fatty acid-isotope ratio mass spectrometry technology, alongside physiological and transcriptome analyses. Our findings reveal that symbiotic AMF can absorb external nonsymbiotic myristate, at least under the conditions tested, as evidenced by13C enrichment and transcriptional activation of putative fatty acid transport and metabolism genes in extraradical hyphae. Exogenous myristate increased both intraradical and extraradical fungal biomass, potentially due to suppressed mycorrhizal defense responses in host roots. Intriguingly, exogenous myristate reduced the mycorrhizal phosphorus benefits for both Medicago sativa and Oryza sativa and decreased their carbon allocation to symbiotic AMF, although these effects were influenced by host identity and soil phosphorus conditions. These findings advance our understanding of the nutritional interactions in AM, which are essential for comprehending and manipulating this symbiotic relationship.
Meta-analysis of the pathogenLeishmania donovani’s transcriptome reveals multiple modes of regulation including two reciprocally regulated gene modules
Authors: Paranjape Pradyumna , Vinod P K , Vaidya Tushar
Published: April 2024

Leishmania donovanicauses a neglected tropical disease called visceral leishmaniasis. Additionally, leishmaniasis also manifests opportunistically, under conditions of immune compromise. The continued non-availability of effectively curative interventions (drugs or vaccines) against this disease necessitates a deeper knowledge ofLeishmaniabiology in order to evolve novel strategies against the disease. We have used a meta-analysis approach to analyseLeishmania’s composite genetic network rather than investigating individual candidate genes. We performed Weighted Gene Co-expression Network Analysis (WGCNA) on publicly availableLeishmania donovanitranscriptome data to identify co-regulatory genetic modules. This clustering ofLeishmania donovanitranscriptomes revealed that genes fall in 30 distinct co-regulated modules with 32 to 3012 genes. In order to analyse the distribution of genes inLeishmaniagene modules, we queried the enrichment or depletion of various annotation-qualifiers in the modules. We observed that several modules are specifically and individually enriched or depleted for annotation qualifiers derived from GO-annotation and KEGG-pathways and are differentially associated with life-phases and experimental conditions. Additionally, modules are also enriched or depleted for sequence based genetic features such as chromosomal location, location on co-transcriptional segment, rank of transcript from initiation of transcription, skewed usage of known RNA Binding Protein motifs. Classification of uncharacterized transcripts into co-regulatory modules provides insights in their probable characteristics, aiding future empirical investigation. Strikingly, two of the modules have reciprocal features including individual associations with logarithmic or stationary growth phases ofLeishmania, two important life-phases that simulate the vector-dwelling pro-cyclic and the pre-infective meta-cyclic forms. Collectively, our analyses ofLeishmaniaco-regulated gene modules is suggestive of additional regulatory modes over the mere differential mRNA stabilization.
Stem cell homeostasis in the root ofArabidopsisinvolves cell type specific complex formation of key transcription factors
Authors: Strotmann Vivien I. , García-Gómez Monica L. , Stahl Yvonne
Published: April 2024

InArabidopsis thaliana, the stem cell niche (SCN) within the root apical meristem (RAM) is maintained by an intricate regulatory network that ensures optimal growth and high developmental plasticity. Yet, many aspects of this regulatory network of stem cell quiescence and replenishment are still not fully understood. Here, we investigate the interplay of the key transcription factors (TFs) BRASSINOSTEROID AT VASCULAR AND ORGANIZING CENTRE (BRAVO), PLETHORA 3 (PLT3) and WUSCHEL-RELATED HOMEOBOX 5 (WOX5) involved in SCN maintenance. Phenotypical analysis of mutants involving these TFs uncover their combinatorial regulation of cell fates and divisions in the SCN. Moreover, interaction studies employing fluorescence resonance energy transfer fluorescence lifetime imaging microscopy (FRET-FLIM) in combination with novel analysis methods, allowed us to quantify protein-protein interaction (PPI) affinities as well as higher-order complex formation of these TFs. We integrated our experimental results into a computational model, suggesting that cell type specific profiles of protein complexes and characteristic complex formation, that is also dependent on prion-like domains in PLT3, contribute to the intricate regulation of the SCN. We propose that these unique protein complex ‘signatures’ could serve as a read-out for cell specificity thereby adding another layer to the sophisticated regulatory network that balances stem cell maintenance and replenishment in theArabidopsisroot.
Similarity of drug targets to human microbiome metaproteome promotes pharmacological promiscuity
Authors: Beaudoin Christopher A. , Norget Shannon , Hala Sharif , van Tonder Andries J.
Published: April 2024

Similarity between candidate drug targets and human proteins is commonly assessed to minimize the occurrence of side effects. Although numerous drugs have been found to disrupt the health of the human microbiome, no comprehensive comparison between established drug targets and the human microbiome metaproteome has yet been conducted. Therefore, herein, sequence and structure alignments between human and pathogen drug targets and representative human gut, oral, and vaginal microbiome metaproteomes were performed. Both human and pathogen drug targets were found to be similar in sequence, function, structure, and drug binding capacity to proteins in diverse pathogenic and non-pathogenic bacteria from all three microbiomes. The gut metaproteome was identified as particularly susceptible overall to off-target effects. Certain symptoms, such as infections and immune disorders, may be more common among drugs that non-selectively target host microbiota. These findings suggest that similarities between human microbiome metaproteomes and drug target candidates should be routinely checked.
Interplay between a polerovirus and a closterovirus decreases aphid transmission of the polerovirus
Authors: Khechmar Souheyla , Chesnais Quentin , Villeroy Claire , Brault Véronique , Drucker Martin
Published: April 2024

Multi-infection of plant by viruses is very common and can change drastically infection parameters such as virus accumulation, distribution and vector transmission. Sugar beet is an important crop that is frequently co-infected by the polerovirus beet chlorosis virus (BChV) and the closterovirus beet yellows virus (BYV), both vectored by the green peach aphid (Myzus persicae). These phloem-limited viruses are acquired while aphids ingest phloem sap from infected plants. Here we found that co-infection decreased transmission of BChV by ∼50%, but had no impact on BYV transmission. The drastic reduction of BChV transmission was not due to lower accumulation of BChV in co-infected plants, nor to reduced phloem sap ingestion by aphids from these plants. Using the SABER-FISHin situhybridization technique on plants, we observed that 40% of the infected phloem cells were co-infected and that co-infection caused redistribution of BYV in these cells. The BYV accumulation pattern changed from distinct intracellular spherical inclusions in mono-infected cells to a diffuse form in co-infected cells. There, BYV co-localized with BChV throughout the cytoplasm, indicative of virus-virus interactions. We propose that BYV-BChV interactions could restrict BChV access to the sieve tubes and reduce its accessibility for aphids and present a model of how co-infection could alter BChV intracellular movement and/or phloem loading and reduce BChV transmission.

IMPORTANCE

Mixed viral infections in plants are understudied yet can have significant influences on disease dynamics and virus transmission. We investigated how co-infection with two unrelated viruses, beet chlorosis virus (BChV) and beet yellows virus (BYV), affects aphid transmission of the viruses in sugar beet plants. We show that co-infection reduced BChV transmission by about 50% without affecting BYV transmission, despite similar virus accumulation rates in co-infected and mono-infected plants. Follow-up experiments examined the localization and intra-cellular distribution of the viruses, leading to the discovery that co-infection caused a redistribution of BYV in the phloem vessels and altered its repartition pattern within plant cells, suggesting virus-virus interactions. In conclusion, the interplay between BChV and BYV affects the transmission of BChV but not BYV, possibly through direct or indirect virus-virus interactions at the cellular level. Understanding these interactions could be crucial for managing virus propagation in crops and preventing yield losses.
The process that the evolution from C3towards C4photosynthesis is driven
Authors: Zhao Yong-Yao , Zhang Yao Xin , Yu Xin Qi , Zhu Xin-Guang
Published: April 2024

Compared to the plants with C3photosynthesis, the plants with C4photosynthesis have higher light, water, and nitrogen use efficiencies. Though only 3% of higher plants have C4photosynthesis, C4photosynthesis contribute about 23% of terrestrial gross primary productivity. Currently, it remains elusive how the procedure of the evolution from C3towards C4photosynthesis is driven. Here,Flaveriagenus, the chief model for C4evolutionary researches, was used to study this driving through a combined analysis of ecological, physiological and biochemical data. From proto-Kranz to C4-like, results showed that precipitation was negatively associated with the activity of C4metabolic core enzyme and C4flux, respectively. With increased vein density, an increased temperature and precipitation were observed during the earlier evolutionary stage. Our study indicated that decreasing precipitation and increasing temperature accompanied the transition from C3to C2photosynthesis and further transition from C2to developing C4photosynthesis. There was a positive relationship between CO2compensation point, stomatal density and precipitation, supporting the notion that decreasing precipitation enhances photorespiration through reducing stomatal conductance during the evolution. As the driving force from proto-Kranz to C4-like, our study highlights that drought dominated rather than heat during C4evolution. This study suggests that the driving force between certain stages during the evolution towards C4photosynthesis are different and increased water availability should be needed in the initial phase.
A new method for detecting mixedMycobacterium tuberculosisinfection and reconstructing constituent strains provides insights into transmission
Authors: Sobkowiak Benjamin , Cudahy Patrick , Chitwood Melanie H. , Clark Taane G. , Colijn Caroline , Grandjean Louis , Walter Katharine S. , Crudu Valeriu , Cohen Ted
Published: April 2024

Background

Mixed infection with multiple strains of the same pathogen in a single host can present clinical and analytical challenges. Whole genome sequence (WGS) data can identify signals of multiple strains in samples, though the precision of previous methods can be improved. Here, we presentMixInfect2,a new tool to accurately detect mixed samples fromMycobacterium tuberculosisWGS data. We then evaluate three approaches for reconstructing the underlying mixed constituent strain sequences. This allows these samples to be included in downstream analysis to gain insights into the epidemiology and transmission of mixed infections.

Methods

We employed a Gaussian mixture model to cluster allele frequencies at mixed sites (hSNPs) in each sample to identify signals of multiple strains. Building upon our previous tool, MixInfect, we increased the accuracy of classifyingin vitromixed samples through multiple improvements to the bioinformatic pipeline. Major and minor proportion constituent strains were reconstructed using three approaches and assessed by comparing the estimated sequence to the known constituent strain sequence. Lastly, mixed infections in a real-worldMycobacterium tuberculosispopulation from Moldova were detected with MixInfect2 and clusters of recent transmission that included major and minor constituent strains were built.

Results

All 36/36in vitromixed and 12/12 non-mixed samples were correctly classified with MixInfect2, and major strain proportions estimated with high accuracy, outperforming previous tools. Reconstructed major strain sequences closely matched the true constituent sequence by taking the allele at the highest frequency at hSNPs, while the best performing approach to reconstruct the minor proportion strain sequence was identifying the closest non-mixed isolate in the same population, though no approach was effective when the minor strain proportion was at 5%. Finally, fewer mixed infections were identified in Moldova than previous estimates (6.6% vs 17.4%) and we found multiple instances where the constituent strains of mixed samples were present in transmission clusters.

Conclusions

MixInfect2 accurately detects samples with evidence of mixed infection from WGS data and provides an excellent estimate of the mixture proportions. While there are limitations in reconstructing the constituent strain sequences of mixed samples, we present recommendations for the best approach to include these isolates in further analyses.
Brain-wide arousal signals are segregated from movement planning in the superior colliculus
Authors: Johnston Richard , Smith Matthew A.
Published: April 2024

The superior colliculus (SC) is traditionally considered a brain region that functions as an interface between processing visual inputs and generating eye movement outputs. Although its role as a primary reflex center is thought to be conserved across vertebrate species, evidence suggests that the SC has evolved to support higher-order cognitive functions including spatial attention. When it comes to oculomotor areas such as the SC, it is critical that high precision fixation and eye movements are maintained even in the presence of signals related to ongoing changes in cognition and brain state, both of which have the potential to interfere with eye position encoding and movement generation. In this study, we recorded spiking responses of neuronal populations in the SC while monkeys performed a memory-guided saccade task and found that the activity of some of the neurons fluctuated over tens of minutes. By leveraging the statistical power afforded by high-dimensional neuronal recordings, we were able to identify a low-dimensional pattern of activity that was correlated with the subjects’ arousal levels. Importantly, we found that the spiking responses of deep-layer SC neurons were less correlated with this brain-wide arousal signal, and that neural activity associated with changes in pupil size and saccade tuning did not overlap in population activity space with movement initiation signals. Taken together, these findings provide a framework for understanding how signals related to cognition and arousal can be embedded in the population activity of oculomotor structures without compromising the fidelity of the motor output.
Somatosensory-evoked response induces extensive diffusivity and kurtosis changes associated with neural activity in rodents
Authors: Hertanu Andreea , Pavan Tommaso , Jelescu Ileana O.
Published: April 2024

Neural tissue microstructure is dynamic during brain activity, presenting changes in cellular morphology and membrane permeability. The sensitivity of diffusion MRI (dMRI) to restrictions and hindrances in the form of cell membranes or subcellular structures enables the exploration of brain activity under a new paradigm, offering a more direct functional contrast than its BOLD counterpart. The current work aims at probing Mean Diffusivity (MD) and Mean Kurtosis (MK) changes and their time-dependence signature across various regions in the rat brain during somatosensory processing and integration, upon unilateral forepaw stimulation. We report adecreasein MD in the contralateral primary somatosensory cortex, forelimb region (S1FL), previously ascribed to cellular swelling and increased tortuosity in the extracellular space, paralleled by a positive BOLD response. For the first time, we also report a paireddecreasein MK during stimulation in S1FL, suggesting increased membrane permeability. This observation was further supported by the reduction in exchange time estimated from the kurtosis time-dependence analyses. Conversely, the secondary somatosensory cortex and subcortical areas, formerly reported as responsive to sensory stimulation in rodents (thalamus, striatum, hippocampal subfields), displayed a marked MD and MKincrease,paralleled by a weak-to-absent BOLD response. Overall, MD and MK uncovered functional-induced changes with higher sensitivity than BOLD. Although the exact origin of the MD and MK increase is yet to be unraveled, the potential of dMRI to provide complementary functional insights, even below the BOLD detection threshold, has been showcased.
Florigen-producing cells express FPF1-LIKE PROTEIN 1 that accelerates flowering and stem growth in long days with sunlight red/far-red ratio inArabidopsis
Authors: Takagi Hiroshi , Lee Nayoung , Hempton Andrew K. , Purushwani Savita , Notaguchi Michitaka , Yamauchi Kota , Shirai Kazumasa , Kawakatsu Yaichi , Uehara Susumu , Albers William G. , Downing Benjamin L. R. , Ito Shogo , Suzuki Takamasa , Matsuura Takakazu , Mori Izumi C. , Mitsuda Nobutaka , Kurihara Daisuke , Matsushita Tomonao , Song Young Hun , Sato Yoshikatsu , Nomoto Mika , Tada Yasuomi , Hanada Kousuke , Cuperus Josh T. , Queitsch Christine , Imaizumi Takato
Published: April 2024

Seasonal changes in spring induce flowering by expressing the florigen, FLOWERING LOCUS T (FT), inArabidopsis.FTis expressed in unique phloem companion cells with unknown characteristics. The question of which genes are co-expressed withFTand whether they have roles in flowering remains elusive. Through tissue-specific translatome analysis, we discovered that under long-day conditions with the natural sunlight red/far-red ratio, theFT-producing cells express a gene encoding FPF1-LIKE PROTEIN 1 (FLP1). The masterFTregulator, CONSTANS (CO), controlsFLP1expression, suggestingFLP1’s involvement in the photoperiod pathway. FLP1 promotes early flowering independently ofFT,is active in the shoot apical meristem, and induces the expression ofSEPALLATA 3(SEP3), a key E-class homeotic gene. Unlike FT, FLP1 facilitates inflorescence stem elongation. Our cumulative evidence indicates that FLP1 may act as a mobile signal. Thus, FLP1 orchestrates floral initiation together with FT and promotes inflorescence stem elongation during reproductive transitions.
Variation in the Distribution of Large-scale Spatiotemporal Patterns of Activity Across Brain States
Authors: Meyer-Baese Lisa , Anumba Nmachi , Bolt T , Daley L , LaGrow TJ , Zhang Xiaodi , Xu Nan , Pan Wen-Ju , Schumacher E , Keilholz Shella
Published: April 2024

A few large-scale spatiotemporal patterns of brain activity (quasiperiodic patterns or QPPs) account for most of the spatial structure observed in resting state functional magnetic resonance imaging (rs-fMRI). The QPPs capture well-known features such as the evolution of the global signal and the alternating dominance of the default mode and task positive networks. These widespread patterns of activity have plausible ties to neuromodulatory input that mediates changes in nonlocalized processes, including arousal and attention. To determine whether QPPs exhibit variations across brain conditions, the relative magnitude and distribution of the three strongest QPPs were examined in two scenarios. First, in data from the Human Connectome Project, the relative incidence and magnitude of the QPPs was examined over the course of the scan, under the hypothesis that increasing drowsiness would shift the expression of the QPPs over time. Second, using rs-fMRI in rats obtained with a novel approach that minimizes noise, the relative incidence and magnitude of the QPPs was examined under three different anesthetic conditions expected to create distinct types of brain activity. The results indicate that both the distribution of QPPs and their magnitude changes with brain state, evidence of the sensitivity of these large-scale patterns to widespread changes linked to alterations in brain conditions.
Site saturation mutagenesis of 500 human protein domains reveals the contribution of protein destabilization to genetic disease
Authors: Beltran Antoni , Jiang Xiang’er , Shen Yue , Lehner Ben
Published: April 2024

Missense variants that change the amino acid sequences of proteins cause one third of human genetic diseases1. Tens of millions of missense variants exist in the current human population, with the vast majority having unknown functional consequences. Here we present the first large-scale experimental analysis of human missense variants across many different proteins. Using DNA synthesis and cellular selection experiments we quantify the impact of >500,000 variants on the abundance of >500 human protein domains. This dataset, Human Domainome 1, reveals that >60% of pathogenic missense variants reduce protein stability. The contribution of stability to protein fitness varies across proteins and diseases, and is particularly important in recessive disorders. Combining stability measurements with protein language models annotates functional sites across proteins. Mutational effects on stability are largely conserved in homologous domains, allowing accurate stability prediction across entire protein families using energy models. Domainome 1 demonstrates the feasibility of assaying human protein variants at scale and provides a large consistent reference dataset for clinical variant interpretation and the training and benchmarking of computational methods.
Peaks and Distributions of White Matter Tract-related Strains in Bicycle Helmeted Impacts: Implication for Helmet Ranking and Optimization
Authors: Zhou Zhou , Fahlstedt Madelen , Li Xiaogai , Kleiven Svein
Published: April 2024

Traumatic brain injury (TBI) in cyclists is a growing public health problem, with helmets being the major protection gear. Finite element head models have been increasingly used to engineer safer helmets often by mitigating brain strain peaks. However, how different helmets alter the spatial distribution of brain strain remains largely unknown. Besides, existing research primarily used maximum principal strain (MPS) as the injury parameter, while white matter fiber tract-related strains, increasingly recognized as effective predictors for TBI, have rarely been used for helmet evaluation. To address these research gaps, we used an anatomically detailed head model with embedded fiber tracts to simulate fifty-one helmeted impacts, encompassing seventeen bicycle helmets under three impact locations. We assessed the helmet performance based on four tract-related strains characterizing the normal and shear strain oriented along and perpendicular to the fiber tract, as well as the prevalently used MPS. Our results showed that both the helmet model and impact location affected the strain peaks. Interestingly, we noted that helmets did not alter strain distribution, except for one helmet under one specific impact location. Moreover, our analyses revealed that helmet ranking outcome based on strain peaks was affected by the choice of injury metrics (Kendall’s tau coefficient: 0.58 ∼ 0.93). Significant correlations were noted between tract-related strains and angular motion-based injury metrics. This study provided new insights into computational brain biomechanics and highlighted the helmet ranking outcome was dependent on the choice of injury metrics. Our results also hinted that the performance of helmets could be augmented by mitigating the strain peak and optimizing the strain distribution with accounting the selective vulnerability of brain subregions, although more research was needed to develop region-specific injury criteria.
Temporal dynamics and biogeography of sympagic and planktonic autotrophic microbial eukaryotes during the under-ice Arctic bloom
Authors: Sim Clarence Wei Hung , Ribeiro Catherine Gerikas , Le Gall Florence , Probert Ian , Gourvil Priscillia , Lovejoy Connie , Vaulot Daniel , Lopes dos Santos Adriana
Published: April 2024

Photosynthetic microbial eukaryotes play a pivotal role as primary producers in the Arctic Ocean, where seasonal blooms within and below the ice are crucial phenomena, contributing significantly to global primary production and biogeochemical cycling. In this study, we investigated the taxonomic composition of sympagic algae and phytoplankton communities during the Arctic under-ice spring bloom using metabarcoding of the 18S rRNA gene. Samples were obtained from three size fractions over a period of nearly three months at an ice camp deployed on landfast ice off the coast of Baffin Island as part of the Green Edge project. We classified the major sympagic and phytoplankton taxa found in this study into biogeographical categories using publicly available metabarcoding data from more than 2,800 oceanic and coastal marine samples. This study demonstrated the temporal succession of taxonomic groups during the development of the under-ice bloom, illustrated by an overall transition from polar to polar-temperate taxa, in particular in the smallest size fraction. Overlooked classes such as Pelagophyceae (undescribed Pelagomonadales clade A1 and the genus Ankylochrysis), Bolidophyceae (Parmales environmental clade 2), and Cryptophyceae (Baffinella frigidus) might play a greater role than anticipated within the pico-sized communities in and under the ice pack during the pre-bloom period. Finally, we emphasize the importance of microdiversity, taking the example of B. frigidus for which a new strain isolated during Green Edge represents an ice ecotype while the type strain is clearly linked to marine waters.
The impact of social complexity on the efficacy of natural selection in termites
Authors: Roux Camille , Ha Alice , Weyna Arthur , Lode Morgan , Romiguier Jonathan
Published: April 2024

In eusocial species, reproduction is monopolized by a few reproductive individuals. From the perspective of population genetics, this implies that the effective population size (Ne) of these organisms is likely to be smaller compared to solitary species, as has been proposed in the literature for eusocial Hymenoptera. In this study, we investigate the genomic consequences of eusociality in termites (Isoptera) across two different timescales. First, by analyzing transcriptome data from 66 Blattodea species, we focus on the ratio of nonsynonymous to synonymous mutations (dN/dS) as a marker of natural selection efficiency and effective population size. Our results demonstrate an elevated dN/dS ratio in termites compared to other Blattodea members, which further generalizes the idea that convergent evolution toward eusociality strongly reduces effective population size and genome-wide efficiency of natural selection. Then, by comparing 68 termite transcriptomes, we show that this decrease in natural selection efficiency is even more pronounced in termites displaying high levels of social complexity. This study contributes to understanding the complex interplay between social structures and natural selection patterns, highlighting the genetic footprint of eusociality in shaping termite evolution.
Effects of social position on subsequent courtship and mating activity in an African cichlid
Authors: Martashvili Anastasia , Jedwab Sara , Vij Lakshita , Kuighadush Avraham Zion , Alvarado S.G.
Published: April 2024

Within social hierarchies, rank can be dynamic and modulated by changes in molecular and/or physiological substrates. Here, we sought to better understand how social environment and rank shape male spawning behaviors and outcomes in African cichlid fishAstatotilapia burtoni. First, using a social dyad paradigm, we generated territorial (T)/ Non-territorial (NT) male pairs. After establishing a stable social hierarchy, the behaviors of the Ts and NTs were recorded and scored. Afterward, pairs were separated and individually moved into a spawning phase, which consisted of a new tank with novel females and no other males where their behaviors were scored. While previous studies have shown how territorial and non-territorial males have unique behavioral profiles, we sought to deepen this interpretation with a focus on the latency of decision-making, and on transition matrices representing enriched sequences of behavior. We found that while the courtship behaviors are shared between stably territorial and ascending males in the spawning phase, only the animals that were territorial in the dyad phase were the ones that were reproductively successful in the subsequent 16 hour spawning phase.
Advancing cooperative breeding research with a peer-reviewed and “live” Cooperative-Breeding Database (Co-BreeD)
Authors: Mocha Yitzchak Ben , Woith Maike , Drobniak Szymon M. , Markman Shai , Frisoni Francesca , Baglione Vittorio , Boersma Jordan , Cousseau Laurence , Covas Rita , Braga de Miranda Guilherme Henrique , Dey Cody J. , Doutrelant Claire , Gula Roman , Heinsohn Robert , Kingma Sjouke A. , Li Jianqiang , Middleton Kyle-Mark , Radford Andrew N. , Restrepo Carla , Rubenstein Dustin R. , Schradin Carsten , Theuerkauf Jörn , Warrington Miyako H. , Williams Dean A. , Woxvold Iain A. , Griesser Michael
Published: April 2024

Research on cooperative breeding (a system with the core characteristic of individuals providing care for the offspring of others) is important for understanding sociality and cooperation. However, large-scale comparative analyses on the drivers and consequences of cooperation frequently use considerably inaccurate datasets (e.g. due to inconsistent definitions and outdated information). To advance comparative research on cooperative breeding, we introduce theCooperative-BreedingDatabase (Co-BreeD), a growing database of key socio-biological parameters of birds and mammals. First, we describe Co-BreeD’s structure as a (i) sample-based (i.e. multiple samples per species linked to an exact sampling location and period), (ii) peer-reviewed and (iii) updatable resource. Respectively, these curating principles allow for (i) investigating intra- and inter-species variation and linking between fine-scale social and environmental parameters, (ii) accuracy and (iii) continuous correction and expansion with the publication of new data. Second, we present the first Co-BreeD dataset, which estimates the prevalence of breeding events with potential alloparents in 265 samples from 233 populations of 150 species, including 2 human societies (N = 26,366 breeding events). We conclude by demonstrating (i) how Co-BreeD facilitates more accurate comparative research (e.g. increased explanatory power by enabling the study of cooperative breeding as a continuous trait, and statistically accounting for the sampling error probabilities), and (ii) that cooperative breeding in birds and mammals is more prevalent than currently estimated.
Flotillin-2 dampens T cell antigen-sensitivity and functionality
Authors: Moon Sookjin , Zhao Fei , Uddin Mohammad N. , Tucker Charles J. , Karmaus Peer W. F. , Fessler Michael B.
Published: April 2024

T cell receptor (TCR) engagement triggers T cell responses, yet how TCR-mediated activation is regulated at the plasma membrane remains unclear. Here, we report that deleting the membrane scaffolding protein Flotillin-2 (Flot2) increases T cell antigen sensitivity, resulting in enhanced TCR signaling and effector function to weak TCR stimulation. T cell-specific Flot2-deficient mice exhibited reduced tumor growth and enhanced immunity to infection. Flot2-null CD4+T cells exhibited increased T helper 1 polarization, proliferation, Nur77 induction, and phosphorylation of ZAP70 and LCK upon weak TCR stimulation, indicating a sensitized TCR-triggering threshold. Single cell-RNA sequencing suggested that Flot2-null CD4+T cells follow a similar route of activation as wild-type CD4+T cells but exhibit higher occupancy of a discrete activation state under weak TCR stimulation. Given prior reports that TCR clustering influences sensitivity of T cells to stimuli, we evaluated TCR distribution with super-resolution microscopy. Flot2 ablation increased the number of surface TCR nanoclusters on naïve CD4+T cells. Collectively, we posit that Flot2 modulates T cell functionality to weak TCR stimulation, at least in part, by regulating surface TCR clustering. Our findings have implications for improving T cell reactivity in diseases with poor antigenicity, such as cancer and chronic infections.
5-HT Neurons Integrate GABA and Dopamine Inputs to Regulate Meal Initiation
Authors: Conde Kristine M. , Wong HueyZhong , Fang Shuzheng , Li Yongxiang , Yu Meng , Deng Yue , Liu Qingzhuo , Fang Xing , Wang Mengjie , Shi Yuhan , Ginnard Olivia Z. , Yang Yuxue , Tu Longlong , Liu Hesong , Liu Hailan , Yin Na , Bean Jonathan C. , Han Junying , Burt Megan E. , Jossy Sanika V. , Yang Yongjie , Tong Qingchun , Arenkiel Benjamin R. , Wang Chunmei , He Yang , Xu Yong
Published: April 2024

Obesity is a growing global health epidemic with limited effective therapeutics. Serotonin (5-HT) is one major neurotransmitter which remains an excellent target for new weight-loss therapies, but there remains a gap in knowledge on the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using a closed-loop optogenetic feeding paradigm, we showed that the 5-HTDRN◊arcuate nucleus (ARH) circuit plays an important role in regulating meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HTDRNneurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response to GABAergic inputs can be enhanced by hunger. Additionally, deletion of the GABAAreceptor subunit in 5-HT neurons inhibits meal initiation with no effect on the satiation process. Finally, we identified the instrumental role of dopaminergic inputs via dopamine receptor D2 in 5-HTDRNneurons in enhancing the response to GABA-induced feeding. Thus, our results indicate that 5-HTDRNneurons are inhibited by synergistic inhibitory actions of GABA and dopamine, which allows for the initiation of a meal.
Evaluating the breeding potential of cultivated lentils for increasing protein and amino acid concentration in the Northern Great Plains
Authors: Wright Derek M. , Hang Jiayi , House James D. , Bett Kirstin E.
Published: April 2024

The rising demand for plant-based proteins has intensified interest in pulse crops due to their high protein concentration. However, few studies have evaluated protein and amino acid composition/variability in cultivated lentil (Lens culinarisMedik.). We evaluated protein and amino acid composition using near-infrared reflectance spectroscopy (NIRS) in a diversity panel grown in four site-years in Saskatchewan, Canada, followed by genome-wide association analyses with phenology-related traits as covariates. We found little correlation between days from sowing to flowering, region of origin, cotyledon color, or seed size, and protein concentration. Reproductive period was correlated with protein concentration. We also observed large variability between environments and more variability within market classes than among them. Our results demonstrate the potential for breeders to identify germplasm and select for increased protein and amino acid concentration and quality using a high-throughput NIRS method. We were able to identify numerous molecular markers for use in marker-assisted breeding. Our approach could be replicated by breeders from other regions or with other pulse crops to help meet the demand for plant-based protein and improvements in protein quality.
Towards EEG-to-Text: Handwritten Character Classification via Continuous Kinematic Decoding
Authors: Crell Markus R. , Müller-Putz Gernot R.
Published: April 2024

The classification of handwritten letters from invasive neural signals has lately been subject of research to restore communication abilities in people with limited movement capacities. This study explores the classification of ten letters (a,d,e,f,j,n,o,s,t,v) from non-invasive neural signals of 20 participants using two methods: the direct classification from low-frequency and broadband electroencephalogram (EEG) and a two-step approach comprising the continuous decoding of hand kinematics and the application of those in subsequent classification. When using low-frequency EEG, results show moderate accuracies of 23.1 % for ten letters and 39.0 % for a subset of five letters with highest discriminability of the trajectories. The two-step approach yielded significantly higher performances of 26.2 % for ten letters and 46.7 % for the subset of five letters. Hand kinematics could be reconstructed with a correlation of 0.10 to 0.57 (average chance level: 0.04) between the decoded and original kinematic. The study shows the general feasibility of extracting handwritten letters from non-invasively recorded neural signals and indicates that the proposed two-step approach can improve performances. As an exploratory investigation of the neural mechanisms of handwriting in EEG, results suggest movement speed as the most informative kinematic for the decoding of short hand movements.