bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissociable neurofunctional and molecular characterizations of reward and punishment sensitivity
Authors: Xu Ting , Zhu Chunhong , Zhou Xinqi , Chen Zhiyi , Gan Xianyang , Cui Xiaobing , Zhou Feng , Zhang Ran , Zhao Weihua , Zhang Xiaodong , Chen Hong , He Qinghua , Lei Xu , Qiu Jiang , Feng Tingyong 
Published: January 2025

AbstractWhile the hyper-and hypo-reward or punishment sensitivities (RS, PS) have received considerable attention as prominent transdiagnostic features of psychopathology, the lack of an overarching neurobiological characterization currently limits their early identifications and neuromodulations. Here we combined microarray data from the Allen Human Brain Atlas with a multimodal fMRI approach to uncover the neurobiological signatures of RS and PS in a discovery-replication design (N=655 participants). Both RS and PS were mapped separately in the brain, with the intrinsic functional connectome in the fronto-striatal network encoding reward responsiveness, while the fronto-insular system was particularly engaged in punishment sensitivity. This dissociable functional connectome patterns related to RS and PS were also specific in differentiating decisions driven by social or monetary reward and punishment motivations. Further imaging transcriptomic analyses revealed that functional connectome variations for RS and PS were associated with topography of specific gene sets enriched in ontological pathways, including synaptic transmission, dopaminergic metabolism, immune response and stress adaptation. On the neurotransmitter level, the serotonin neuromodulator was identified as a pivotal hub regulating the intrinsic functional connectome patterns of RS and PS, with this process critically dependent on its interactions with dopaminergic, opioid and GABAergic systems. Overall, these findings indicate dissociable neural connectome mapping of RS and PS and highlight their linkage with transcriptomic profiles, which may offer valuable insights into the treatment evaluation for symptomatology relevant to reward/punishment processing deficits.
Widespread 3D genome reorganization precedes programmed DNA rearrangement inOxytricha trifallax
Authors: Villano Danylo J. , Prahlad Manasa , Singhal Ankush , Sanbonmatsu Karissa Y. , Landweber Laura F. 
Published: January 2025

AbstractGenome organization recapitulates function, yet ciliates likeOxytricha trifallaxpossess highly-specialized germline genomes, which are largely transcriptionally silent. During post-zygotic development,Oxytricha’s germline undergoes large-scale genome editing, rearranging precursor genome elements into a transcriptionally-active genome with thousands of gene-sized nanochromosomes. Transgenerationally-inherited RNAs, derived from the parental somatic genome, program the retention and reordering of germline fragments. Retained and eliminated DNA must be distinguished and processed separately, but the role of chromatin organization in this process is unknown. We developed tools for studyingOxytrichanuclei and apply them to map the 3D organization of precursor and developmental states using Hi-C. We find that the precursor conformation primes the germline for development, while a massive spatial reorganization during development differentiates retained from eliminated regions before DNA rearrangement. Further experiments suggest a role for RNA-DNA interactions and chromatin remodeling in this process, implying a critical role for 3D architecture in programmed genome rearrangement.
A multipurpose microhaplotype panel for genetic analysis of California Chinook salmon
Authors: Anderson Eric C. , Clemento Anthony J. , Campell Matthew A. , Pearse Devon E. , Beulke Anne K. , Columbus Cassie , Campbell Ellen , Thompson Neil F. , Garza John Carlos 
Published: January 2025

AbstractGenetic methods have become an essential component of ecological investigation and conservation planning for fish and wildlife. Among these methods is the use of genetic marker data to identify individuals to populations, or stocks, of origin. More recently, methods that involve genetic pedigree reconstruction to identify relationships between individuals within populations have also become common. We present, here, a novel set of multi-allelic microhaplotype genetic markers for Chinook salmon which provide unprecedented resolution for population discrimination and relationship identification from a rapidly and economically assayed panel of markers. We show how this set of microhaplotypes provides definitive power to identify all known lineages of Chinook salmon in California. The inclusion of genetic loci that have known associations with phenotype and that were identified as outliers in examination of whole genome sequence data, allows resolution of stocks that are not highly genetically differentiated but are phenotypically distinct and managed as such. This same set of multiallelic genetic markers have ample variation to accurately identify parent-offspring and full-sibling pairs in all California populations, including the genetically depauperate winter-run lineage. Validation of this marker panel in coastal salmon populations not previously studied with modern genetic methods, also reveals novel biological insights, including the presence of a single copy of a haplotype for a phenotype that has not been documented in that part of the species range, and a clear signal of mixed ancestry for a salmon population that is on the geographic margins of the primary evolutionary lineages present in California.
Balancing doses of EL222 and light improves optogenetic induction of protein production inKomagataella phaffii
Authors: Hoffman Shannon M. , Espinel-Ríos Sebastián , Lalwani Makoto A. , Kwartler Sarah K. , Avalos José L. 
Published: January 2025

AbstractKomagataella phaffii, also known asPichia pastoris, is a powerful host for recombinant protein production, in part due to its exceptionally strong and tightly controlled PAOX1promoter. MostK. phaffiibioprocesses for recombinant protein production rely on PAOX1to achieve dynamic control in two-phase processes. Cells are first grown under conditions that repress PAOX1(growth phase), followed by methanol-induced recombinant protein expression (production phase). In this study, we propose a methanol-free approach for dynamic metabolic control inK. phaffiiusing optogenetics, which can help enhance input tunability and flexibility in process optimization and control. The light-responsive transcription factor EL222 fromErythrobacter litoralisis used to regulate protein production from the PC120promoter inK. phaffiiwith blue light. We used two system designs to explore the advantages and disadvantages of coupling or decoupling EL222 integration with that of the gene of interest. We investigate the relationship between EL222 gene copy number and light dosage to improve production efficiency for intracellular and secreted proteins. Experiments in lab-scale bioreactors demonstrate the feasibility of the outlined optogenetic systems as potential alternatives to conventional methanol-inducible bioprocesses usingK. phaffii.
Scaly-Tail Organ Enhances Static Stability during Pel’s Scaly-tailed Flying Squirrels’ Arboreal Locomotion
Authors: Schulz Andrew K. , Chellapurath Mrudul , Khandelwal Pranav C. , Rezaei SeyedReza , Merker Stefan , Jusufi Ardian 
Published: January 2025

AbstractScaly-tailed squirrels (Anomaluridae) are one of the least studied mammalian families. Their namesake is due to a peculiar and unique scaly-tail organ extruding from the caudal vertebrate that has been predicted to help reduce skidding. This study investigates the function of the scaly-tail organ found inAnomalurus pelii, investigating its potential role in enhancing arboreal locomotion. As these animals glide from tree to tree in a habitat abundant with smooth-bark trees, we hypothesize that the scaly-tail organ assists with friction enhancement in their native smooth-bark habitat. Through a combination of analyses using mathematical and physical models for experimental validation, we explore whether the scaly-tail organ could improve the sliding and overturning stability during perching. Our experimental results showed that the scaly-tail organ can act as a skid-reduction mechanism by enhancing substrate engagement on intermediate roughness substrates by 58%. Mathematical models showed the scaly-tail organ enhances overturning stability by acting as an additional support point. Our model showed that the scaly-tailed squirrel can reach up to 82.5◦inclination without claw force; however, without scales, it reduces to 79.6◦. Overall, this research highlights the functional significance of scaly-tail organs in adaptations in scaly-tailed flying squirrels and contributes to our understanding of their locomotion strategies and environmental stresses. Our study also provides insights into innovative perching mechanisms for robots operating in arboreal environments.
Unexpected D-tour Ahead: Why the D-Statistic, applied to Humans, Measures Mutation Rate Variation not Neanderthal Introgression
Authors: Amos William , Elhaik Eran 
Published: January 2025

AbstractIt is widely accepted that humans interbred with Neanderthals and other extinct hominins, leaving a lasting genetic legacy. However, much of the supporting evidence was developed using the statistic D, which assumes, without testing, both that mutation rate is constant and that recurrent mutations are vanishingly rare. These assumptions together preclude an alternative explanation based on variation in mutation rates across human populations. Here we critically evaluate the assumptions underlying D and confirm that neither is valid. Over 40% of SNPs in dbSNP carry recurrent mutations. Theory indicates that D does not vary with mutation rate as long as the mutation rate does not vary between populations. In practice, D calculated separately for different sequence motifs varies greatly, implying strongly that mutation rates do vary between populations. We show that most, if not all, D-informative sites result from two mutations rather than the one mutation expected under the introgression hypothesis. Moreover, individual non-Africans carry a signal in more than five times as many genomic windows as can be accounted for by the 2% legacy they are thought to carry, indicating a signal that is radically more diffuse than expected. Remarkably, partitioning the data by whether the chimpanzee or Neanderthal allele is the major allele in humans reveals that the overall reported D-value of ∼5% actually comprises two opposing components: one with D ∼ 30% and another with D ∼ -25%. Tellingly, the positive component is produced by sites where the Neanderthal allele is themajorallele, the exact opposite of what should be the case under introgression, where introgressed alleles should be rare. We show further that the entire D signal can be accounted for by sites where the Neanderthal allele is fixed outside Africa and the chimpanzee allele is rare inside Africa. Investigating potential mechanisms, we extend the published observation that the mutability of three-base combinations across human populations is influenced by flanking sequence heterozygosity to reveal how genomic regions that lost more heterozygosity out of Africa exhibit higher D-values. This correlation supports a model where loss of heterozygosity slowed the mutation rate, thereby reducing the divergence between Neanderthals and non-Africans. Across independent tests, our findings consistently indicate that the mutation rate variation hypothesis provides a more compelling explanation for the observed patterns in human-Neanderthal genetic relationships than the introgression hypothesis. We argue that the mutation rate variation hypothesis would help settle a number of conflicting patterns in the literature and, hence, that the concept of archaic introgression into humans and its implications for hominin-derived traits warrants reconsideration.
The bully phage: A Shiga toxin-encoding prophage interferes with the induction of co-hosted prophages
Authors: Hashuel Rachel , Wellins Tamara , Rachimi Maayan , Gutman Eran , Melki Reut , Taktuk Linoy , Wasserzug Pe’era Pash , Avissar Rinat , Roitman Karina , Litvak Yael 
Published: January 2025

AbstractShiga toxin (Stx) prophages lysogenize various bacterial species, converting them into dangerous pathogens and driving the ongoing emergence of new outbreaks globally. These pathogens are polylysogens, harboring multiple prophages within their genomes. Yet, the impact of Stx prophage acquisition on resident prophages remains largely unknown. Usingin vivotransmission studies with the murine pathogenCitrobacter rodentiumthat carries an Stx prophage, we demonstrate that the Stx prophage readily lysogenizes commensalEscherichia colistrains within the intestine. Markedly, this lysogenization altered the induction activity of prophages encoded within each new toxigenic host strain. Moreover, the Stx prophage abolished the induction of ϕNP, the most active native prophage ofC. rodentium. We further show that ϕNP inhibition is mediated by the Stx Cro repressor, which exhibits dual functionality, promoting its own lytic cycle while repressing the expression of ϕNP lytic genes. Our findings reveal a novel competition strategy among prophages, and suggest that interfering with the induction of co-hosted prophages likely plays a role in the emergence and evolution of new Stx-producing pathogens.
Modelling symplasmic transport: from biophysical basics to steeper root gradients
Authors: Deinum Eva E. , Marée Athanasius F. M. , Benitez-Alfonso Yoselin , Grieneisen Verônica A. 
Published: January 2025

AbstractDevelopment and spatial pattern formation are inherently linked. The coordinated determination of cell fates is crucial in any developmental process and requires extensive intercellular communication. Plants cells exchange many molecular signals via the symplasmic pathway, i.e., via plasmodesmata: narrow channels connecting the cytoplasm of neighbouring cells. Regulation of symplasmic transport is vital for normal plant development, and mutations that disrupt this regulation are often embryo or seedling lethal. In many tissues, symplasmic transport of small molecules is diffusion driven, resulting in a non-selective and bidirectional transport, although net directionality could arise from gradients. This has led to the (dogmatic) belief that symplasmic transport can only be detrimental to pattern formation, because signalling molecules cannot be confined, and gradients would fade. Here, we develop a detailed biophysical description of symplasmic transport to explore how plasmodesmata affect gradients in a linear tissue. We then apply the model in more complex tissue contexts, observing and explaining, e.g., that symplasmic transport may result insteepergradients in the root apical meristem. In conclusion, our model provides a reference framework for estimating the consequences of symplasmic transport and explains how symplasmic transport can contribute to more robust developmental patterning.
Molecular basis for shifted receptor recognition by an encephalitic arbovirus
Authors: Fan Xiaoyi , Li Wanyu , Oros Jessica , Plung Jesse S. , Plante Jessica A. , Basu Himanish , Nagappan-Chettiar Sivapratha , Boeckers Joshua M. , Tjang Laurentia V. , Mann Colin J. , Brusic Vesna , Buck Tierra K. , Varnum Haley , Yang Pan , Malcolm Linzy M. , Choi So Yoen , de Souza William M. , Chiu Isaac M. , Umemori Hisashi , Weaver Scott C. , Plante Kenneth S. , Abraham Jonathan 
Published: January 2025

AbstractAfter decades of inactivity throughout the Americas, western equine encephalitis virus (WEEV) recently re-emerged in South America, causing a large-scale outbreak in humans and horses. WEEV binds protocadherin 10 (PCDH10) as a receptor; however, nonpathogenic strains no longer bind human or equine PCDH10 but retain the ability to bind avian receptors. Highly virulent WEEV strains can also bind the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as alternative receptors. Here, by determining cryo-electron microscopy structures of WEEV strains isolated from 1941–2005 bound to mammalian receptors, we identify polymorphisms in the WEEV spike protein that explain shifts in receptor dependencies and that can allow nonpathogenic strains to infect primary cortical neurons. We predict the receptor dependencies of additional strains and of a related North American alphavirus. Our findings have implications for outbreak preparedness and enhance understanding of arbovirus neurovirulence through virus receptor binding patterns.
The sex-specific effects of RAGE signaling and Type 2 Diabetes on mouse cortical bone mechanics, structure, and material properties
Authors: Hung Timothy , Broz Kaitlyn S , Walk Remy E , Tang Simon Y 
Published: January 2025

AbstractIndividuals with type 2 diabetes (T2D) are prone to fracture at numerous skeletal sites despite presenting with a higher bone mineral density (BMD). The accumulation of Advanced Glycation End-products (AGEs) in the bone tissues of patients with T2D could be contributing to this paradox, of increased skeletal fragility with higher BMD. AGEs can impair bone cell homeostasis via the receptor for AGEs (RAGE). To investigate the effects of diabetes, AGE accumulation, and RAGE signaling on mouse cortical bone, we utilized male and female leptin receptor-deficient (db/db) mice from three age groups ranging from 3-14 months of age, which were crossed with animals carrying constitutively RAGE-deficient alleles (RAGE−/−). The morphological, mechanical and material outcomes were measured using microCT, 3-pt bending, and an AGE assay. We observed significant impairments dependent on age and sex to the bone matrix and whole-bone mechanical behavior due to diabetes with some impairments alleviated with the ablation of RAGE. In older female diabetic mice, the removal of RAGE signaling prevented the deficits in bone mechanics, morphology and tissue mineral density (TMD). Male diabetic mice without RAGE signaling exhibited improved material properties. The study demonstrated that some bone impairments associated with T2D are prevented with RAGE ablation and may be partially reversible with the inhibition of RAGE signaling.Graphical Abstract
Nuclear basket proteins Mlp1 and Nup2 drive heat shock-induced 3D genome restructuring
Authors: Mohajan Suman , Rubio Linda S. , Gross David S. 
Published: January 2025

ABSTRACTThe nuclear pore complex (NPC), a multisubunit complex located within the nuclear envelope, regulates RNA export and the import and export of proteins. Here we address the role of the NPC in driving thermal stress-induced 3D genome repositioning ofHeat Shock Responsive(HSR) genes in yeast. We found that two nuclear basket proteins, Mlp1 and Nup2, although dispensable for NPC integrity, are required for drivingHSRgenes into coalesced chromatin clusters, consistent with their strong, heat shock-dependent recruitment toHSRgene regulatory and coding regions.HSRgene clustering occurs predominantly within the nucleoplasm and is independent of the essential scaffold-associated proteins Nup1 and Nup145. Notably, double depletion of Mlp1 and Nup2 has little effect on the formation of Heat Shock Factor 1 (Hsf1)-containing transcriptional condensates, Hsf1 and Pol II recruitment toHSRgenes, orHSRmRNA abundance. Our results define a 3D genome restructuring role for nuclear basket proteins extrinsic to the NPC and downstream ofHSRgene activation.
Hydrodynamic cues enhance algal lipid production while sustaining biomass in motile species
Authors: Kakavand Narges , Sengupta Anupam 
Published: January 2025

AbstractAchieving enhanced lipid yield without compromising biomass is one of the long-standing challenges in our quest to produce algal biofuel sustainably. Multiple factors, including temperature, nutrients and light conditions impact lipid production, however such lipid-enhancing strategies often lead to reduced biomass, thereby offsetting the total volume of lipid recovered. Hydrodynamic cues remain poorly studied, specifically in the context of lipid production in motile algae, concurrently with biomass generation and photo-physiology, a key fitness parameter. By imposing hydrodynamic cues to biophysically stress distinct strains of raphidophyteHeterosigma akashiwoat specific time points along the growth stages (indicating different nutritional states), we quantify the lipid production, alongside algal biomass and photo-physiology. Early induction (hydrodynamic cues implemented during the lag phase) and delayed induction (hydrodynamic cues implemented during the exponential phase) were studied. Delayed induction of hydrodynamic cues suppressed growth and photo-physiology without significant enhancement of lipid production, however, early induction allowed to significantly increase lipid content, up to 300%, without observable changes in biomass and photo-physiology. Based on this, we propose a hydrodynamic strategy for enhanced lipid production with sustained biomass and physiological fitness. This work presents hydrodynamic perturbation and its onset timing as tunable parameters to advance lipid production technologies across diverse motile species.
Solriamfetol enhances alertness and cognitive performance in mice
Authors: Haddar Meriem , Tzanoulinou Stamatina , Chen Li Yuan , Tafti Mehdi , Vassalli Anne 
Published: January 2025

AbstractSolriamfetol [(R)-2-amino-3-phenylpropylcarbamate hydrochloride], a phenylalanine derivative initially developed as potential antidepressant, was shown by our group in 2009 to have potent, dose-dependent wake-promoting activity in mice. Solriamfetol (Sunosi®) is used since 2019 to counteract excessive daytime sleepiness (EDS) in patients with narcolepsy and obstructive sleep apnea (OSA). It has several advantages over other stimulants, notably that it is not associated with strong psychomotor activity, does not induce behavioral stereotypies and anxiety-related behaviors, in contrast to amphetamines and modafinil. Its mode-of-action remains incompletely solved. It was reported to act as dual dopamine-and-noradrenaline-reuptake-inhibitor (DNRI), and more recently, to have TAAR1 agonist activity. In our early mouse study, we showed that, at 150 mg/kg, Solriamfetol induces a state of wakefulness featuring a dramatic upregulation of EEG gamma activity, a cognitive biomarker, and the expression of genes implicated in neural plasticity, learning and memory. Besides being prescribed to treat EDS, central nervous system stimulants are commonly used as ‘smart drugs’ to enhance cognition in normal individuals. Therefore, based on Solriamfetol’s ability to potently induce wakefulness, EEG and molecular markers of learning and memory, we aimed to determine whether it could improve the cognitive performance of wild-type mice. Because at doses of 50-150 mg/kg, Solriamfetol induced an alert waking state associated with low mobility, thus precluding behavioral testing, we used lower doses (1-3 mg/kg) to assess cognition in a battery of tests evaluating short- or long-term memory and spatial navigation. We found that compared to saline, Solriamfetol 3 mg/kg consistently improves sustained attention for a novel object, as well as spatial memory. Next, to determine the brain activity correlates of enhanced cognition, we performed EEG/EMG recording while the mice performed the novel object recognition (NOR) task. Power spectral density (PSD) analysis revealed that 3 mg/kg Solriamfetol reduced EEG delta (an index of sleepiness) during exposure to a novel context, and enhanced EEG fast-gamma (an index of mental concentration) during execution of the NOR task. Taken together, our data demonstrate that low-dose Solriamfetol improves memory and attentional performance in wild-type mice.