bluuebunny/crossref_metadata_2025_split huggingface dataset:
MetFinder: a neural network-based tool for automated quantitation of metastatic burden in histological sections from animal models
Authors: Karz Alcida , Coudray Nicolas , Bayraktar Erol , Galbraith Kristyn , Jour George , Shadaloey Arman Alberto Sorin , Eskow Nicole , Rubanov Andrey , Navarro Maya , Moubarak Rana , Baptiste Gillian , Levinson Grace , Mezzano Valeria , Alu Mark , Loomis Cynthia , Lima Daniel , Rubens Adam , Jilaveanu Lucia , Tsirigos Aristotelis , Hernando Eva 
Published: September 2023

AbstractDiagnosis of most diseases relies on expert histopathological evaluation of tissue sections by an experienced pathologist. By using standardized staining techniques and an expanding repertoire of markers, a trained eye is able to recognize disease-specific patterns with high accuracy and determine a diagnosis. As efforts to study mechanisms of metastasis and novel therapeutic approaches multiply, researchers need accurate, high-throughput methods to evaluate effects on tumor burden resulting from specific interventions. However, current methods of quantifying tumor burden are low in either resolution or throughput. Artificial neural networks, which can perform in-depth image analyses of tissue sections, provide an opportunity for automated recognition of consistent histopathological patterns. In order to increase the outflow of data collection from preclinical studies, we trained a deep neural network for quantitative analysis of melanoma tumor content on histopathological sections of murine models. This AI-based algorithm, made freely available to academic labs through a web-interface called MetFinder, promises to become an asset for researchers and pathologists interested in accurate, quantitative assessment of metastasis burden.
Resolution of ring chromosomes, Robertsonian translocations, and complex structural variants from long-read sequencing and telomere-to-telomere assembly
Authors: Mostovoy Yulia , Boone Philip M. , Huang Yongqing , Garimella Kiran V. , Tan Kar-Tong , Russell Bianca E. , Salani Monica , Curall Benjamin , Lucente Diane , Bowers Tera , DeSmet Tim , Gabriel Stacey , Morton Cynthia C. , Meyerson Matthew , Gusella James , Quintero-Rivera Fabiola , Brand Harrison , Talkowski Michael E. 
Published: September 2023

SummaryThe capacity to resolve structural variants (SVs) at sequence resolution in highly repetitive genomic regions has long been intractable. Consequently, the properties, origins, and functional effects of multiple classes of complex rearrangement are unknown. To resolve these challenges, we leveraged recent technical milestones: 1) Oxford-Nanopore (ONT) sequencing; 2) the gapless Telomere-to-Telomere (T2T) genome assembly; and 3) a novel tool to discover large-scale rearrangements from long-reads. We applied these technologies across 13 patients with ring chromosomes, Robertsonian translocations, and complex balanced SVs that were unresolved by short-read sequencing. We resolved 10 of 13 events, including ring chromosomes, the complex SVs, and a Robertsonian translocation. Multiple breakpoints were localized to highly repetitive regions inaccessible to short-read alignment, such as acrocentric p-arms, ribosomal DNA arrays, and telomeric repeats, and involved complex structures such as a deletion-inversion and interchromosomal dispersed duplications. We also leveraged ONT native methylation detection to discover phased differential methylation in a gene promoter proximal to a ring fusion site, suggesting a long-range positional effect with heterochromatin spreading. Breakpoint sequences were consistent with common mechanisms of SV formation, including microhomology-mediated mechanisms, non-homologous end-joining, and non-allelic homologous recombination. These methods provide some of the first glimpses into the sequence resolution of ring chromosomes and Robertsonian translocations and illuminate the structural diversity of chromosomal rearrangements with implications for molecular diagnosis and genome biology.HighlightsCryptic rearrangements revealed in repetitive and previously inaccessible regionsAligning long-reads to telomere-to-telomere assembly enabled breakpoint discoveryFirst sequence resolution of a Robertsonian translocation breakpointHaplotype-specific methylation changes associated with ring formationGraphical abstract
Partial Face Visibility and Facial Cognition: An Electroencephalography and Eye-Tracking Investigation
Authors: Chanpornpakdi Ingon , Wongsawat Yodchanan , Tanaka Toshihisa 
Published: September 2023

AbstractFace masks became a part of everyday life in the SARS-CoV-2 pandemic. Previous studies showed that the face cognition mechanism involves holistic face processing, and the absence of face features could lower cognition ability. This is opposed to the experience during the pandemic, when people were able to correctly recognize faces, although the mask covered a part of the face. This paper shows a strong correlation in face cognition based on the EEG and eye-tracking data between the full and partial faces. We observed two event-related potentials, P3a in the frontal lobe and P3b in the parietal lobe, as subcomponents of P300. Both P3a and P3b were lowered when the eyes were invisible, and P3a evoked by the nose covered was larger than the full face. The eye-tracking data showed that 16 out of 18 participants focused on the eyes associated with the EEG results. Our results demonstrate that the eyes are the most crucial feature of facial cognition. Moreover, the face with the nose covered might enhance cognition ability due to the visual working memory capacity. Our experiment shows the possibility of people recognizing faces using both holistic face processing and structural face processing. Furthermore, people can recognize the masked face as well as the full face in similar cognition patterns due to the high correlation in the cognition mechanism.
Developmental stage shapes the realized energy landscape for a flight specialist
Authors: Nourani Elham , Faure Louise , Brønnvik Hester , Scacco Martina , Bassi Enrico , Fiedler Wolfgang , Grüebler Martin U. , Hatzl Julia S. , Jenny David , Roverselli Andrea , Sumasgutner Petra , Tschumi Matthias , Wikelski Martin , Safi Kamran 
Published: September 2023

AbstractThe heterogeneity of the physical environment determines the cost of transport for animals, shaping their energy landscape. Animals respond to this energy landscape by adjusting their distribution and movement to maximize gains and reduce costs. Much of our knowledge about energy landscape dynamics focuses on factors external to the animal, particularly the spatio-temporal variations of the environment. However, an animal’s internal state can significantly impact its ability to perceive and utilize available energy, creating a distinction between the “fundamental” and the “realized” energy landscapes. Here we show that the realized energy landscape varies along the ontogenetic axis. Locomotor and cognitive capabilities of individuals change over time, especially during the early life stages. We investigate the development of the realized energy landscape in the Central European Alpine population of the golden eagleAquila chrysaetos, a large predator that requires negotiating the atmospheric environment to achieve energy-efficient soaring flight. We quantified weekly energy landscapes using environmental features for 55 juvenile golden eagles, demonstrating that energetic costs of traversing the landscape decreased with age. Consequently, the potentially flyable area within the Alpine region increased 2,170-fold during their first three years of independence. Our work contributes to a predictive understanding of animal movement by presenting ontogeny as a mechanism shaping the realized energy landscape.
Ketogenic diet administration later in life improves memory and regulates the synaptic cortical proteome through the cAMP/PKA signaling pathway in aging mice
Authors: Acuña-Catalán Diego , Shah Samah , Wehrfritz Cameron , Nomura Mitsunori , Acevedo Alejandro , Olmos Cristina , Quiroz Gabriel , Huerta Hernán , Bons Joanna , Ampuero Estibaliz , Wyneken Ursula , Sanhueza Magdalena , Arancibia Felipe , Contreras Darwin , Cárdenas Julio César , Morales Bernardo , Schilling Birgit , Newman John C. , González-Billault Christian 
Published: September 2023

SummaryAging is a complex biological process that compromises brain function and neuronal network activity, leading to cognitive decline and synaptic dysregulation. In recent years, a cyclic Ketogenic Diet (KD) has emerged as a potential treatment to ameliorate cognitive decline by improving memory in aged mice after long-term administration. However, the molecular mechanisms that govern such changes remains unclear. Additionally, whether short-term cyclic KD administration later in life preserves memory has not been addressed in detail. Accordingly, here we investigated how a short-term cyclic KD starting at 20-23 months-old regulates brain function of aged mice. Behavioral testing and long-term potentiation (LTP) recordings revealed that a cyclic KD improves working memory and hippocampal LTP in 24-27 months-old mice after 16 weeks of treatment. Moreover, the diet also promotes higher dendritic arborization complexity and dendritic spine density in the prefrontal cortex. Furthermore, to elucidate the molecular mechanisms underlying the memory improvements elicited by a cyclic KD, cortical synaptosomes of aged mice fed with this diet for 1 year were analyzed by mass spectrometry. Bioinformatics analysis revealed that long-term cyclic KD administration predominantly modulates the presynaptic compartment by inducing changes in the cAMP/PKA signaling pathway, the synaptic vesicle cycle, and the actin/microtubule cytoskeleton. To test these findingsin vivo, synaptic proteins from cortices of 24–27-month-old mice fed with control or cyclic KD for 16 weeks were analyzed by western blot. Interestingly, increased Brain Derived Neurotrophic Factor abundance, MAP2 phosphorylation and PKA activity were observed. Overall, we show that a cyclic KD regulates brain function and memory even when it is administered at late mid-life and significantly triggers several molecular features of long-term administration, including the PKA signaling pathway and cytoskeleton dynamics, thus promoting synaptic plasticity at advanced age.
Nurturing care practices for children with developmental disabilities in sub-Saharan Africa: A scoping review protocol
Authors: Onyango Silas , Nampijja Margaret , Otwate Paul , Langat Nelson , Oloo Linda , Okelo Kenneth , Kitsao-Wekulo Patricia 
Published: September 2023

AbstractBackgroundThe majority of children with neurodevelopmental disorders(NDDs) reside in low- and middle-income countries (LMICs). NDDs is a public health concern in countries in sub-Saharan Africa (SSA). Nurturing care has been recommended as a pathway for addressing the developmental needs and unlocking the full potential of children, including those with NDDs. However, little information exists on the strategies to support children with NDDs using the Nurturing Care Framework in many SSA Countries. The proposed scoping review aims to identify, explore, and map the literature on nurturing care practices for children with NDDs in SSA. The review will also determine gaps in the provision of nurturing care for children with NDD. Further, the review will highlight the drivers of care as well as the experiences of the caregivers in relation to the care provided.MethodsThe review will be implemented in six steps: identification of the research question; identification of relevant studies, selection of studies to be included, charting the data and collating, summarizing, reporting the results, and stakeholder consultation. The selection of the articles will be completed in two parts: a database search followed by a manual search. We will search the following electronic databases: PubMed, ScienceDirect, Scopus, Open Grey and AJOL. All studies published after May 2018 to May 2023 that include relevant terms will be identified and included. The research team will develop a data extraction form for use in capturing relevant information from each of the included studies. A patterning chat that will summarize and analyze the key findings of each article will be created.DiscussionWe anticipate the study will provide evidence on the existing nurturing care practices for children with NDDs and unearth gaps in the provision of nurturing care for children with NDD. Key determinants of care and the experiences of the parents/caregivers of children will also be identified. The study will provide key recommendations on interventions to improve the quality of care for children with NDDs. Through this study, awareness of the unmet nurturing care needs of these children will be increased. The evidence generated may assist policymakers and stakeholders in addressing the needs of children with NDDs.
A dynamic bias in chromatin protein deposition at G-quadruplex sites
Authors: Lobo Thamar Jessurun , Chen Deng , Zwinderman Martijn R. H. , Lansdorp Peter M , Dekker Frank J. , Guryev Victor 
Published: September 2023

AbstractPrevious studies indicate that genomic loci harboring G-quadruplexes (G4s)—stacked structures that can form in single-stranded DNA—can be linked to epigenetic instability. However, the role of chromatin redistribution and the genome-wide nature of this process need further investigation. Here, we provide experimental evidence that connects G4s to alterations in the deposition of chromatin proteins. We have used metabolic labelling and immunoprecipitation of new and parental proteins in hRPE-1 cells to investigate global chromatin deposition dynamics.We identify a reciprocal, local bias in chromatin protein deposition at G4 sites favoring the association of parental proteins with the G4 and new proteins with the C4 DNA strand. The deposition bias at G4 sites does not depend on replication directionality and is strengthened by G4 stabilization. Slowing down replication forks upon hydroxyurea treatment reverses the bias, supposedly affected by decoupling between helicase and polymerase. Interestingly, upon combined G4 stabilization and slowing of the replication forks, new proteins exhibit a redistribution pattern similar to G4 stabilization alone, while parental protein redistribution more resembles one after hydroxyurea treatment, hinting at mechanistic differences between parental and new histone distribution. We also report that the genomic distribution of putative quadruplexes is not random and depends on loop size, where G4s with shorter loops have a preference for the DNA strand replicated by leading and G4s with longer loops by lagging strand replication. These findings provide insight into the mechanisms behind G4 occurrence and its role in epigenetic instability and help to improve our understanding of the factors influencing biases in global chromatin protein redeposition.
Evolution of a large periplasmic disk inCampylobacterotaflagella facilitated efficient motility alongside autoagglutination
Authors: Cohen Eli J. , Drobnič Tina , Ribardo Deborah A. , Yoshioka Aoba , Umrekar Trishant , Guo Xuefei , Fernandez Jose-Jesus , Brock Emma , Wilson Laurence , Nakane Daisuke , Hendrixson David R. , Beeby Morgan 
Published: September 2023

SummaryAlthough the bacterial flagella ofEscherichia coliandSalmonella entericaare distributed around the cell body, many bacteria instead place their flagella at their poles. This widespread form of flagellar motility is relatively poorly understood, but these polar flagellar motors invariably feature periplasmic disk structures of unknown function. The flagellar motor ofCampylobacter jejunifeatures a 100 nm-wide periplasmic disk associated with scaffolding a wider ring of motor proteins to increase torque, but the size of this disk is excessive for a role solely in scaffolding motor proteins. Here we show that the basal disk inC. jejuniis a flange that braces the motor during disentanglement of the flagellar filament from interactions with the cell body and other filaments, interactions that are otherwise important for host colonization. Our results reveal an entanglement of co-dependencies in the evolution of flagellar motor structure and cell plan in the Campylobacterota (previously epsilonproteobacteria). Note that this manuscript has a sibling manuscript titled’Molecular model of a bacterial flagellar motor in situ reveals a “parts-list” of protein adaptations to increase torque’that describes a molecular model of theCampylobacter jejuniflagellar motor discussed here.
Post-ejaculatory Inhibition of Female Sexual Drive via Heterogeneous Neuronal Ensembles in the Medial Preoptic Area
Authors: Ishii Kentaro K , Hashikawa Koichi , Chea Jane , Yin Shihan , Fox Rebecca Erin , Kan Suyang , Shah Meha , Zhou Charles , Navarrete Jovana , Murry Alexandria D. , Szelenyi Eric R , Golden Sam A. , Stuber Garret D. 
Published: September 2023

SUMMARYMale ejaculation acutely suppresses sexual motivation in male mice. In contrast, relatively little is known about how male ejaculation affects sexual motivation and sexual behavior in female mice. How the brain responds to completion of mating is also unclear. Here, by using self-paced mating assay, we first demonstrate that female mice show decreased sexual motivation acutely after experiencing male ejaculation. By using brain-wide analysis of activity-dependent labeling, we next pinpointed the medial preoptic area as a brain region strongly activated during the post-ejaculatory period. Furthermore, using freely movingin vivocalcium imaging to compare neural activity of inhibitory and excitatory neurons in the medial preoptic area, we revealed that a subset of the neurons in this region respond significantly and specifically to male ejaculation but not to female-to-male sniffing or to male mounting. While there were excitatory and inhibitory neurons that showed increased response to male ejaculation, the response magnitude as well as the proportion of neurons responding to the event was significantly larger in the inhibitory neuron population. Next, by unbiased classification of their responses, we also found a subpopulation of neurons that increase their activity late after the onset of male ejaculation. These neurons were all inhibitory indicating that male ejaculation induces a prolonged inhibitory activity in the medial preoptic area. Lastly, we found that chemogenetic activation of medial preoptic area neurons that were active during post-ejaculatory period, but not during appetitive or consummatory periods, were sufficient to suppress female sexual motivation. Together, our data illuminate the importance of medial preoptic area as a brain node which encodes a negative signal that sustains low sexual motivation state after the female mice experience ejaculation.HighlightsFemale mice show decreased sexual motivation in the post-ejaculatory period.A subset of MPOA neurons in female respond specifically to male ejaculation.Male-ejaculation evokes persistent activity in MPOA inhibitory neurons in females.Activation of a subset of MPOA neurons is sufficient to suppress female sexual motivation.
SARS-CoV-2 ORF8 modulates lung inflammation and clinical disease progression
Authors: McGrath Marisa E. , Xue Yong , Taylor Louis , Dillen Carly , Ardanuy Jeremy , Gonzalez-Juarbe Norberto , Baracco Lauren , Kim Raymond , Hart Rebecca , Assad-Garcia Nacyra , Vashee Sanjay , Frieman Matthew B. 
Published: September 2023

AbstractThe virus severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, is the causative agent of the current COVID-19 pandemic. It possesses a large 30 kilobase (kb) genome that encodes structural, non-structural, and accessory proteins. Although not necessary to cause disease, these accessory proteins are known to influence viral replication and pathogenesis. Through the synthesis of novel infectious clones of SARS-CoV-2 that lack one or more of the accessory proteins of the virus, we have found that one of these accessory proteins, ORF8, is critical for the modulation of the host inflammatory response. Mice infected with a SARS-CoV-2 virus lacking ORF8 exhibit increased weight loss and exacerbated macrophage infiltration into the lungs. Additionally, infection of mice with recombinant SARS-CoV-2 viruses encoding ORF8 mutations found in variants of concern reveal that naturally occurring mutations in this protein influence disease severity. Our studies with a virus lacking this ORF8 protein and viruses possessing naturally occurring point mutations in this protein demonstrate that this protein impacts pathogenesis.SignificanceSince its emergence in 2019, SARS-CoV-2 has accrued mutations throughout its 30kb genome. Of particular interest are the mutations present in the ORF8 protein, which occur in every major variant. The precise function and impact of this protein on disease severity and pathogenesis remains understudies. Our studies reveal that the ORF8 protein modulates the immune response by impacting macrophage infiltration into the lungs. Additionally, we have shown that the ORF8 protein of SARS-CoV-2 has accrued mutations throughout its evolution that lead to a loss of function phenotype in this protein. Our work reveals that the ORF8 protein of SARS-CoV-2 contributes significantly to disease progression through modulation of the inflammatory response.
Proteome-scale prediction of molecular mechanisms underlying dominant genetic diseases
Authors: Badonyi Mihaly , Marsh Joseph A 
Published: September 2023

AbstractMany dominant genetic disorders result from protein-altering mutations, acting primarily through dominant-negative (DN), gain-of-function (GOF), and loss-of-function (LOF) mechanisms. Deciphering the mechanisms by which dominant diseases exert their effects is often experimentally challenging and resource intensive, but is essential for developing appropriate therapeutic approaches. Diseases that arise via a LOF mechanism are more amenable to be treated by conventional gene therapy, whereas DN and GOF mechanisms may require gene editing or targeting by small molecules. Moreover, pathogenic missense mutations that act via DN and GOF mechanisms are more difficult to identify than those that act via LOF using nearly all currently available variant effect predictors. Here, we introduce a tripartite statistical model made up of support vector machine binary classifiers trained to predict whether human protein-coding genes are likely to be associated with DN, GOF, or LOF molecular disease mechanisms. We test the utility of the predictions by examining biologically and clinically meaningful properties known to be associated with the mechanisms. Our results strongly support that the models are able to generalise on unseen data and offer insight into the functional attributes of proteins associated with different mechanisms. We hope that our predictions will serve as a springboard for researchers studying novel variants and those of uncertain clinical significance, guiding variant interpretation strategies and experimental characterisation. Predictions for the human UniProt reference proteome are available athttps://osf.io/z4dcp/.