bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissociable Default Mode Network Connectivity Patterns Underlie Distinct Symptoms in Psychosis Risk
Authors: Ajunwa Chelsea C. , Zhang Jiahe , Collin Guusje , Keshavan Matcheri S. , Tang Yingying , Zhang Tianhong , Li Huijun , Shenton Martha E. , Stone William S. , Wang Jijun , Niznikiewicz Margaret , Whitfield-Gabrieli Susan 
Published: October 2024

AbstractThe Clinical High Risk (CHR) stage of psychosis is characterized by subthreshold symptoms of schizophrenia including negative symptoms, dysphoric mood, and functional deterioration. Hyperconnectivity of the default-mode network (DMN) has been observed in early schizophrenia, but the extent to which hyperconnectivity is present in CHR, and the extent to which such hyperconnectivity may underlie transdiagnostic symptoms, is not clear. As part of the Shanghai At-Risk for Psychosis (SHARP) program, resting-state fMRI data were collected from 251 young adults (158 CHR and 93 controls, M = 18.72, SD = 4.68, 129 male). We examined functional connectivity of the DMN by performing a whole-brain seed-to-voxel analysis with the MPFC as the seed. Symptom severity across a number of dimensions, including negative symptoms, positive symptoms, and affective symptoms were assessed. Compared to controls, CHRs exhibited significantly greater functional connectivity (p < 0.001 uncorrected) between the MPFC and 1) other DMN nodes including the posterior cingulate cortex (PCC), and 2) auditory cortices (superior and middle temporal gyri, STG/MTG). Furthermore, these two patterns of hyperconnectivity were differentially associated with distinct symptom clusters. Within CHR, MPFC-PCC connectivity was significantly correlated with anxiety (r= 0.23, p=0.006), while MPFC-STG/MTG connectivity was significantly correlated with negative symptom severity (r=0.26, p=0.001). Secondary analyses using item-level symptom scores confirmed a similar dissociation. These results demonstrate that two dissociable patterns of DMN hyperconnectivity found in the CHR stage may underlie distinct dimensions of symptomatology.
Brain-like learning with exponentiated gradients
Authors: Cornford Jonathan , Pogodin Roman , Ghosh Arna , Sheng Kaiwen , Bicknell Brendan A. , Codol Olivier , Clark Beverley A. , Lajoie Guillaume , Richards Blake A. 
Published: October 2024

AbstractComputational neuroscience relies on gradient descent (GD) for training artificial neural network (ANN) models of the brain. The advantage of GD is that it is effective at learning difficult tasks. However, it produces ANNs that are a poor phenomenological fit to biology, making them less relevant as models of the brain. Specifically, it violates Dale’s law, by allowing synapses to change from excitatory to inhibitory, and leads to synaptic weights that are not log-normally distributed, contradicting experimental data. Here, starting from first principles of optimisation theory, we present an alternative learning algorithm, exponentiated gradient (EG), that respects Dale’s Law and produces log-normal weights, without losing the power of learning with gradients. We also show that in biologically relevant settings EG outperforms GD, including learning from sparsely relevant signals and dealing with synaptic pruning. Altogether, our results show that EG is a superior learning algorithm for modelling the brain with ANNs.
Conserved gene content and unique phylogenetic history characterize the ‘bloopergene’ underlyingTriturus’balanced lethal system
Authors: de Visser Manon Chantal , France James , Paulouskaya Olga , Brown Thomas , Fahrbach Michael , van der Ploeg Chris , Wielstra Ben 
Published: October 2024

AbstractIn a balanced lethal system, half the reproductive output succumbs.Triturusnewts are the best-known example. Their chromosome 1 comes in two distinct versions and embryos carrying the same version twice experience developmental arrest. Those possessing two different versions survive, suggesting that each version carries something uniquely vital. With target capture we obtain over 7,000 nuclear DNA markers across the genusTriturusand all main lineages of Salamandridae (the family to whichTriturusbelongs) to investigate the evolutionary history ofTriturus’chromosome 1 versus other chromosomes. Dozens of genes are completely missing from either one or the other version of chromosome 1 inTriturus. Furthermore, the unique gene content of 1A versus 1B is remarkably similar acrossTriturusspecies, suggesting that the balanced lethal system evolved beforeTriturusradiated. The tree topology of chromosome 1 differs from the rest of the genome, presumably due to pervasive, ancient hybridization betweenTriturus’ancestor and other newt lineages. Our findings accentuate the complex nature ofTriturus’chromosome 1 – the ‘bloopergene’ driving the evolutionarily enigmatic balanced lethal system.
Long-term Immunity of a Microneedle Array Patch of SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice
Authors: Kim Eun , Khan Muhammad S. , Shin Juyeop , Huang Shaohua , Ferrari Alessandro , Han Donghoon , An Eunjin , Kenniston Thomas W. , Cassaniti Irene , Baldanti Fausto , Jeong Dohyeon , Gambotto Andrea 
Published: October 2024

AbstractCOVID-19 vaccines effectively prevent symptomatic infection and severe disease, including hospitalization and death. However, unequal vaccine distribution during the pandemic, especially in low- and middle-income countries, has led to the emergence of vaccine-resistant strains. This underscores the need for alternative, safe, and thermostable vaccine platforms, such as dissolved microneedle array patches (MAP) delivering a subunit vaccine, which eliminate the need for cold chain and trained healthcare personnel. This study demonstrates that the SARS-CoV-2 S1 monomer with RS09, a TLR-4 agonist peptide, serves as an optimal protein subunit immunogen. This combination stimulates a stronger S1-specific immune response, resulting in binding to the membrane-bound spike on the cell surface and ACE2-binding inhibition, compared to the monomer S1 alone or trimer S1, regardless of RS09. MAP delivery of the rS1RS09 subunit vaccine elicited higher and longer-lasting immunity compared to conventional intramuscular injection. S1-specific IgG levels remained significantly elevated for up to 70 weeks post-administration. Additionally, different doses of 5, 15, and 45μg of MAP vaccines induced robust and sustained Th2-prevalent immune responses, suggesting a dose-sparing effect and inducing significantly high neutralizing antibodies against the Wuhan, Delta, and Omicron variants at 15 and 45μg dose. Moreover, gamma irradiation as a terminal sterilization method did not significantly affect immunogenicity, with irradiated vaccines maintaining comparable efficacy to non-irradiated ones. The stability of MAP vaccines was evaluated after long-term storage at room temperature and refrigeration for 19 months, showing minimal protein degradation. Further, after an additional one-month of storage at elevated temperature (42°C), rS1RS09 in both non-irradiated and irradiated MAP degraded less than 3%, while the liquid subunit vaccine degraded over 23%. Overall, these results indicate that gamma irradiation sterilized MAP-rS1RS09 vaccines maintain stability during extended storage without refrigeration, supporting their potential for mass production and widespread use in global vaccination efforts.
Experimental field trials model how the climate crisis will alter the phyllosphere and carposphere fungal communities ofVitissp. L’Acadie Blanc
Authors: Blakney Andrew J.C. , Carisse Odile , Van Der Heyden Hervé , Pitre Frederic E. , Pedneault Karine 
Published: October 2024

AbstractThe climate crisis is changing temperature regimes worldwide, threatening global viticulture and wine production, as temperature is a primary driver of grape development. In Atlantic Canada, temperatures are projected to increase, inducing premature grape ripening, which can impact their biochemical profiles and, consequently, the quality of the vines and wines produced. Temperature is also a key factor in determining the composition and structure of resident fungal communities on the leaves (phyllosphere) and fruits (carposphere) of grape vines. Therefore, to better understand how these communities might change under potential future temperature regimes, we experimentally manipulated grapevines (Vitissp. cv. L’Acadie blanc) in the field. We used on-the-row mini-greenhouses to increase the temperature at different developmental, or phenological, stages of the fruits, and across the whole season. Phyllosphere and carposphere were sampled at four developmental stages, their DNA was extracted, and the fungal communities were identified via ITS metabarcoding. We found that phyllosphere and carposphere had significantly different community composition, which remained relatively stable throughout plant development. Increased temperature treatments had the most significant effect on fungal phyllosphere communities; we observed that phyllosphere samples exposed to higher temperatures before the onset of ripening maintained more diverse fungal communities throughout development. Our analysis showed that the increase in fungal diversity among phyllopshere communities corresponds to enrichments in potential phytopathogenic fungal taxa. However, this increase in phyllosphere fungal diversity was not conserved at other growth stages when the leaves developed at higher temperatures for the whole season. The results of this study will contribute to better understanding the impact of the climate crisis on grapevine phyllosphere and carposphere fungal community composition and assembly. This will allow producers to better adapt to climate variability and to better understand the role that these communities could play on grapevine health.
Structure of AcMNPV nucleocapsid reveals DNA portal organization and packaging apparatus of circular dsDNA baculovirus
Authors: Effantin Gregory , Kandiah Eaazhisai , Pelosse Martin 
Published: October 2024

AbstractBaculoviruses are large DNA viruses found in nature propagating amongst insects and lepidoptera in particular. Their viral cycle has been studied and characterized over decades and they are nowadays considered as invaluable biotechnology tools widely used as biopesticides, recombinant expression systems or delivery vehicle for gene therapy. However, very little is known about the baculovirus nucleocapsid assembly at a molecular level. Here, we solved the whole structure of the nucleocapsid ofAutographa californicamultiple nucleopolyhedrovirus (AcMNPV) by applying cryo-electron microscopy (CryoEM) combined tode novomodelling and Alphafold2 predictions. Our structure completes prior observations from the helical sheath and the basal structure and elucidate the intricate architecture of the apical cap, unravelling for the first time the organization of a baculoviral DNA portal featuring intriguing symmetry mismatches between its core and vertex. The core, closing the capsid at the apex, holds two antiparallel DNA helices of the covalently closed circular (ccc) DNA genome tethered to Ac54 proteins. Different symmetry components at the apical cap and basal structure are constituted of the same building block, made of Ac101/Ac144, proving the versatility of this modular pair. The crown forming the portal vertex displays a C21 symmetry and contains, amongst others, the motor-like protein Ac66. Our findings support the viral portal to be involved in DNA packaging, most probably in conjunction with other parts of a larger DNA packaging apparatus that are not bound to mature virions and await further elucidation.
Artificial intelligence networks combining histopathology and machine learning can extract axon pathology in autism spectrum disorder
Authors: Yazdanbakhsh Arash , Dang Kim , Kuang Kelvin , Lian Tingru , Liu Xuefeng , Xie Songlin , Zikopoulos Basilis 
Published: October 2024

AbstractAxon features that underlie the structural and functional organization of cortical pathways have distinct patterns in the brains of neurotypical controls (CTR) compared to individuals with Autism Spectrum Disorder (ASD). However, detailed axon study demands labor-intensive surveys and time-consuming analysis of microscopic sections from post-mortem human brain tissue, making it challenging to systematically examine large regions of the brain. To address these challenges, we developed an approach that uses machine learning to automatically classify microscopic sections from ASD and CTR brains, while also considering different white matter regions: superficial white matter (SWM), which contains a majority of axons that connect nearby cortical areas, and deep white matter (DWM), which is comprised exclusively by axons that participate in long-range pathways. The result was a deep neural network that can successfully classify the white matter below the anterior cingulate cortex (ACC) of ASD and CTR groups with 98% accuracy, while also distinguishing between DWM and SWM pathway composition with high average accuracy, up to 80%. Multidimensional scaling analysis and sensitivity maps further underscored the reliability of ASD vs CTR classification, based on the consistency of axon pathology, while highlighting the important role of white matter location that constrains pathway dysfunction, based on several shared anatomical markers. Large datasets that can be used to expand training, validation, and testing of this network have the potential to automate high-resolution microscopic analysis of post-mortem brain tissue, so that it can be used to systematically study white matter across brain regions in health and disease.One Sentence StatementHistopathology-trained AI can identify ASD network disruptions and guide development of diagnostics and targeted therapeutics.
F-BAR proteins CIP4 and FBP17 function in cortical neuron radial migration and process outgrowth
Authors: English Lauren A. , Taylor Russell J. , Cameron Connor J. , Broker Emily A. , Dent Erik W. 
Published: October 2024

ABSTRACTNeurite initiation from newly born neurons is a critical step in neuronal differentiation and migration. Neuronal migration in the developing cortex is accompanied by dynamic extension and retraction of neurites as neurons progress through bipolar and multipolar states. However, there is a relative lack of understanding regarding how the dynamic extension and retraction of neurites is regulated during neuronal migration. In recent work we have shown that CIP4, a member of the F-BAR family of membrane bending proteins, inhibits cortical neurite formation in culture, while family member FBP17 induces premature neurite outgrowth. These results beg the question of how CIP4 and FBP17 function in radial neuron migration and differentiationin vivo, including the timing and manner of neurite extension and retraction. Indeed, the regulation of neurite outgrowth is essential for the transitions between bipolar and multipolar states during radial migration. To examine the effects of modulating expression of CIP4 and FBP17in vivo, we usedin uteroelectroporation, in combination with our published Double UP technique, to compare knockdown or overexpression cells with control cells within the same mouse tissue of either sex. We show that either knockdown or overexpression of CIP4 and FBP17 results in the marked disruption of radial neuron migration by modulating neuronal morphology and neurite outgrowth, consistent with our findings in culture. Our results demonstrate that the F-BAR proteins CIP4 and FBP17 are essential for proper radial migration in the developing cortex and thus play a key role in cortical development.SIGNIFICANCE STATEMENTDuring embryonic development, radial migration of newly born cortical neurons is a complex process that underlies the proper formation of the neocortex, the outermost layers of neurons in the brain. Disruptions in radial migration results in profound effects on cognitive function and can lead to devastating developmental disabilities. To better understand this critical process in brain development we examined two members of the F-BAR family of membrane bending proteins, CIP4 and FBP17, which are present in the developing brain. We demonstrate that intracellular concentrations of these proteins must be tightly regulated. Increasing or decreasing levels of either protein has profound effects on neuronal morphology and proper radial migration, suggesting they are key players in cortical development.
Palmitoylated Importin α Regulates Mitotic Spindle Orientation Through Interaction with NuMA
Authors: Sutton Patrick James , Mosqueda Natalie , Brownlee Christopher W. 
Published: October 2024

AbstractRegulation of cell division orientation is a fundamental process critical to differentiation and tissue homeostasis. Microtubules emanating from the mitotic spindle pole bind a conserved complex of proteins at the cell cortex which orients the spindle and ultimately the cell division plane. Control of spindle orientation is of particular importance in developing tissues, such as the developing brain. Misorientation of the mitotic spindle and thus subsequent division plane misalignment can contribute to improper segregation of cell fate determinants in developing neuroblasts, leading to a rare neurological disorder known as microcephaly. We demonstrate that the nuclear transport protein importin α, when palmitoylated, plays a critical role in mitotic spindle orientation through localizing factors, such as NuMA, to the cell cortex. We also observe craniofacial developmental defects inXenopus laeviswhen importin α palmitoylation is abrogated, including smaller head and brains, a hallmark of spindle misorientation and microcephaly. These findings characterize not only a role for importin α in spindle orientation, but also a broader role for importin α palmitoylation which has significance for many cellular processes.
Proximity labeling reveals differential interaction partners of the human mitochondrial import receptor proteins TOMM20 and TOMM70
Authors: Akram Saira , Zittlau Katharina I. , Maček Boris , Jansen Ralf-Peter 
Published: October 2024

AbstractImport of most mitochondrial proteins requires that their precursor proteins are bound by the (peripheral) receptor proteins TOM20, TOM22, and TOM70. For budding yeast TOM20 and TOM70, there is evidence of specific yet overlapping substrate recognition, but no such data is available for metazoan cells. Using APEX2-based proximity labeling, we thus created association profiles for human TOMM20 and TOMM70 in HeLa cells. We particularly focused on their interaction with RNA-binding proteins (RBPs) since there is evidence for RNA association with the mitochondrial outer membrane (MOM) and local translation at the mitochondrial surface, but these processes are poorly understood. Our results show a preferred association of several RBPs and translation factors with TOMM20 over TOMM70. These include SYNJBP2, a previously identified membrane-bound RBP that binds and protects mRNAs encoding mitochondrial proteins. Translational inhibition by puromycin resulted in an even increased association of these RBPs with TOMM20 compared to TOMM70, suggesting that TOMM20 but not TOMM70 might play a role in preserving cellular hemostasis during translation stress by retaining protective RBPs and translation-related proteins at the MOM.
Plant species vary in nectar peroxide, an antimicrobial defense tolerated by some bacteria and yeasts
Authors: Landucci Leta , Vannette Rachel L. 
Published: October 2024

SummaryFloral nectar attracts pollinators but can also harbor microbes including plant pathogens. Nectar contains antimicrobial constituents including hydrogen peroxide, yet it is unclear how widespread nectar hydrogen peroxide might be among plant species or how effective against common nectar microbes. Here, we surveyed 45 flowering plant species distributed across 23 families and reviewed the literature for measurements of 13 other species to assess the field-realistic range of nectar hydrogen peroxide (Aim 1) and explored whether plant defense hormones induce nectar hydrogen peroxide upregulation (Aim 2). Further, we tested the hypotheses that variation in microbial tolerance to peroxide is predicted by microbe isolation environment (Aim 3), that increasing hydrogen peroxide in flowers alters microbial abundance and community assembly (Aim 4), and that microbial community context affects microbial tolerance to peroxide (Aim 5). We found that sampled plants contained nectar hydrogen peroxide ranging from 0 to 2940 µM, although half of the sampled species concentrations were less than 100 µM. While plant defensive hormones did not change the concentration of hydrogen peroxide in floral nectar, enzymatically upregulated concentrations in living flowers significantly reduced microbial growth. Together, our results suggest that nectar peroxide is a common but not pervasive antimicrobial defense among nectar-producing plants. In addition, nectar microbes vary in tolerance and detoxification ability, and co-growth can facilitate the survival and growth of less tolerant species, suggesting a key role for community dynamics in microbial colonization of nectar.
Reward invigorates isometric gripping actions
Authors: Marbaker Rachel M. , Schmad Ryan C. , Al-Ghamdi Razan A. , Sukumar Shruthi , Ahmed Alaa A. 
Published: October 2024

ABSTRACTIndividuals exhibit a propensity to move faster toward more rewarding stimuli. While this phenomenon has been observed in movements, the effect of reward on implicit control of isometric actions, like gripping or grasping, is relatively unknown. How reward-related invigoration generalizes to other effortful actions is an important question. Reward invigorates reaching movements and saccades, supporting the idea that reward pays the additional effort cost of moving faster. Effort in isometric force generation is less understood, so here we ask whether and how reward-related invigoration generalizes to isometric force gripping. And if so, what implicit characteristics of gripping change when there is a prospect of reward? Participants (N=19) gripped a force transducer and the force applied was mapped to radial position of an onscreen cursor. Each trial, a target appeared in one of four locations; increasing grip force moved the cursor toward the target. The gripping action was interchangeable for all target positions. In each block of 100 trials, one target was consistently rewarded, while the other targets were not. When gripping to acquire the rewarded target, participants reacted faster, generated force more rapidly and to a greater extent, while intriguingly maintaining the same accuracy and integral of force over time. These findings support the generalization of reward-related invigoration in isometric force tasks, and that the brain exquisitely trades-off reward and effort costs to obtain reward more rapidly without compromising accuracy or more effort costs than necessary.NEW & NOTEWORTHYGripping actions are important for day-to-day tasks, for medical diagnostics like strength and force control, and for choice selection in decision-making experiments. Comparing isometric gripping responses to reward and nonreward cues, we observed reward-based invigoration mediated by selective increases in effort. These findings can be leveraged to provide additional insight into the decision making process, and better understand the effect of reward on movement vigor and the implicit control of accuracy.