bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased frontotemporal connectivity in patients with parkinson’s disease experiencing face pareidolia
Authors: Kajiyama Yuta , Hattori Noriaki , Nakano Tomohito , Revankar Gajanan S. , Otomune Hironori , Hashimoto Ryota , Mori Etsuro , Ikeda Manabu , Mihara Masahito , Mochizuki Hideki 
Published: October 2021

AbstractThe precise neural underpinnings of face pareidolia in patients with Parkinson’s disease (PD) remain unclear. We aimed to clarify face recognition network abnormalities associated with face pareidolia in such patients. Eighty-three patients with PD and 40 healthy controls were recruited in this study. Patients with PD were classified into pareidolia and nonpareidolia groups. Volumetric analyses revealed no significant differences between the pareidolia (n = 39) and nonpareidolia (n = 44) patient groups. We further observed decreased functional connectivity among regions of interest in the bilateral frontotemporal lobes in patients with pareidolia. Seed-based analysis using bilateral temporal fusiform cortices as seeds revealed significantly decreased connectivity with the bilateral inferior medial prefrontal cortices in the pareidolia group. Post hoc regression analysis further demonstrated that the severity of face pareidolia was negatively correlated with functional connectivity between the bilateral temporal fusiform and medial prefrontal cortices. Our findings suggest that top-down modulation of the face recognition network is impaired in patients with PD experiencing face pareidolia.
DNA methylation atlas of the mouse brain at single-cell resolution
Authors: Liu Hanqing , Zhou Jingtian , Tian Wei , Luo Chongyuan , Bartlett Anna , Aldridge Andrew , Lucero Jacinta , Osteen Julia K. , Nery Joseph R. , Chen Huaming , Rivkin Angeline , Castanon Rosa G. , Clock Ben , Li Yang Eric , Hou Xiaomeng , Poirion Olivier B. , Preissl Sebastian , Pinto-Duarte Antonio , O’Connor Carolyn , Boggeman Lara , Fitzpatrick Conor , Nunn Michael , Mukamel Eran A. , Zhang Zhuzhu , Callaway Edward M. , Ren Bing , Dixon Jesse R. , Behrens M. Margarita , Ecker Joseph R. 
Published: October 2021

AbstractMammalian brain cells show remarkable diversity in gene expression, anatomy and function, yet the regulatory DNA landscape underlying this extensive heterogeneity is poorly understood. Here we carry out a comprehensive assessment of the epigenomes of mouse brain cell types by applying single-nucleus DNA methylation sequencing1,2 to profile 103,982 nuclei (including 95,815 neurons and 8,167 non-neuronal cells) from 45 regions of the mouse cortex, hippocampus, striatum, pallidum and olfactory areas. We identified 161 cell clusters with distinct spatial locations and projection targets. We constructed taxonomies of these epigenetic types, annotated with signature genes, regulatory elements and transcription factors. These features indicate the potential regulatory landscape supporting the assignment of putative cell types and reveal repetitive usage of regulators in excitatory and inhibitory cells for determining subtypes. The DNA methylation landscape of excitatory neurons in the cortex and hippocampus varied continuously along spatial gradients. Using this deep dataset, we constructed an artificial neural network model that precisely predicts single neuron cell-type identity and brain area spatial location. Integration of high-resolution DNA methylomes with single-nucleus chromatin accessibility data3 enabled prediction of high-confidence enhancer–gene interactions for all identified cell types, which were subsequently validated by cell-type-specific chromatin conformation capture experiments4. By combining multi-omic datasets (DNA methylation, chromatin contacts, and open chromatin) from single nuclei and annotating the regulatory genome of hundreds of cell types in the mouse brain, our DNA methylation atlas establishes the epigenetic basis for neuronal diversity and spatial organization throughout the mouse cerebrum.
An atlas of cortical arealization identifies dynamic molecular signatures
Authors: Bhaduri Aparna , Sandoval-Espinosa Carmen , Otero-Garcia Marcos , Oh Irene , Yin Raymund , Eze Ugomma C. , Nowakowski Tomasz J. , Kriegstein Arnold R. 
Published: October 2021

AbstractThe human brain is subdivided into distinct anatomical structures, including the neocortex, which in turn encompasses dozens of distinct specialized cortical areas. Early morphogenetic gradients are known to establish early brain regions and cortical areas, but how early patterns result in finer and more discrete spatial differences remains poorly understood1. Here we use single-cell RNA sequencing to profile ten major brain structures and six neocortical areas during peak neurogenesis and early gliogenesis. Within the neocortex, we find that early in the second trimester, a large number of genes are differentially expressed across distinct cortical areas in all cell types, including radial glia, the neural progenitors of the cortex. However, the abundance of areal transcriptomic signatures increases as radial glia differentiate into intermediate progenitor cells and ultimately give rise to excitatory neurons. Using an automated, multiplexed single-molecule fluorescent in situ hybridization approach, we find that laminar gene-expression patterns are highly dynamic across cortical regions. Together, our data suggest that early cortical areal patterning is defined by strong, mutually exclusive frontal and occipital gene-expression signatures, with resulting gradients giving rise to the specification of areas between these two poles throughout successive developmental timepoints.
The mouse cortico–basal ganglia–thalamic network
Authors: Foster Nicholas N. , Barry Joshua , Korobkova Laura , Garcia Luis , Gao Lei , Becerra Marlene , Sherafat Yasmine , Peng Bo , Li Xiangning , Choi Jun-Hyeok , Gou Lin , Zingg Brian , Azam Sana , Lo Darrick , Khanjani Neda , Zhang Bin , Stanis Jim , Bowman Ian , Cotter Kaelan , Cao Chunru , Yamashita Seita , Tugangui Amanda , Li Anan , Jiang Tao , Jia Xueyan , Feng Zhao , Aquino Sarvia , Mun Hyun-Seung , Zhu Muye , Santarelli Anthony , Benavidez Nora L. , Song Monica , Dan Gordon , Fayzullina Marina , Ustrell Sarah , Boesen Tyler , Johnson David L. , Xu Hanpeng , Bienkowski Michael S. , Yang X. William , Gong Hui , Levine Michael S. , Wickersham Ian , Luo Qingming , Hahn Joel D. , Lim Byung Kook , Zhang Li I. , Cepeda Carlos , Hintiryan Houri , Dong Hong-Wei 
Published: October 2021

AbstractThe cortico–basal ganglia–thalamo–cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1–4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico–basal ganglia–thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico–﻿basal ganglia–thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.
Transposon-associated TnpB is a programmable RNA-guided DNA endonuclease
Authors: Karvelis Tautvydas , Druteika Gytis , Bigelyte Greta , Budre Karolina , Zedaveinyte Rimante , Silanskas Arunas , Kazlauskas Darius , Venclovas Česlovas , Siksnys Virginijus 
Published: October 2021

AbstractTransposition has a key role in reshaping genomes of all living organisms1. Insertion sequences of IS200/IS605 and IS607 families2 are among the simplest mobile genetic elements and contain only the genes that are required for their transposition and its regulation. These elements encode tnpA transposase, which is essential for mobilization, and often carry an accessory tnpB gene, which is dispensable for transposition. Although the role of TnpA in transposon mobilization of IS200/IS605 is well documented, the function of TnpB has remained largely unknown. It had been suggested that TnpB has a role in the regulation of transposition, although no mechanism for this has been established3–5. A bioinformatic analysis indicated that TnpB might be a predecessor of the CRISPR–Cas9/Cas12 nucleases6–8. However, no biochemical activities have been ascribed to TnpB. Here we show that TnpB of Deinococcus radiodurans ISDra2 is an RNA-directed nuclease that is guided by an RNA, derived from the right-end element of a transposon, to cleave DNA next to the 5′-TTGAT transposon-associated motif. We also show that TnpB could be reprogrammed to cleave DNA target sites in human cells. Together, this study expands our understanding of transposition mechanisms by highlighting the role of TnpB in transposition, experimentally confirms that TnpB is a functional progenitor of CRISPR–Cas nucleases and establishes TnpB as a prototype of a new system for genome editing.
Wild meat consumption in tropical forests spares a significant carbon footprint from the livestock production sector
Authors: Nunes André Valle , Peres Carlos A. , Constantino Pedro de Araujo Lima , Fischer Erich , Nielsen Martin Reinhardt 
Published: October 2021

AbstractWhether sustainable or not, wild meat consumption is a reality for millions of tropical forest dwellers. Yet estimates of spared greenhouse gas (GHG) emissions from consuming wild meat, rather than protein from the livestock sector, have not been quantified. We show that a mean per capita wild meat consumption of 41.7 kg yr−1 for a population of ~ 150,000 residents at 49 Amazonian and Afrotropical forest sites can spare ~ 71 MtCO2-eq annually under a bovine beef substitution scenario, but only ~ 3 MtCO2-eq yr−1 if this demand is replaced by poultry. Wild meat offtake by these communities could generate US$3M or US$185K in carbon credit revenues under an optimistic scenario (full compliance with the Paris Agreement by 2030; based on a carbon price of US$50/tCO2-eq) and US$1M or US$77K under a conservative scenario (conservative carbon price of US$20.81/tCO2-eq), representing considerable incentives for forest conservation and potential revenues for local communities. However, the wild animal protein consumption of ~ 43% of all consumers in our sample was below the annual minimum per capita rate required to prevent human malnutrition. We argue that managing wild meat consumption can serve the interests of climate change mitigation efforts in REDD + accords through avoided GHG emissions from the livestock sector, but this requires wildlife management that can be defined as verifiably sustainable.
Impact of children born with low birth weight on stunting and wasting in Sindh province of Pakistan: a propensity score matching approach
Authors: Abbas Faisal , Kumar Ramesh , Mahmood Tahir , Somrongthong Ratana 
Published: October 2021

AbstractLow Birth Weight (LBW) is considered as a major public health issue and leading cause of neonatal death. Almost one in four newborns are reported as underweight in Pakistan. Children born with low birth weight are highly vulnerable to develop diseases and death and/or remain undernourished (i.e., stunted and wasted). This study determines the LBW newborns are more prone to develop stunting and wasting in province of Sindh, Pakistan. Moreover, regression-based estimation of the impact of LBW on the child health outcomes of under five years of age, may be prone to selection bias because of the nature of non-experimental data set, thus, propensity score matching methods are used in this study. Data for this study was used from Multiple Indicators Cluster Survey (MICS-2014). MICS is a two-stage, stratified cluster sampling household level data covering urban and rural areas and consists of 19,500 households from five administrative divisions and 28 districts of Sindh province of Pakistan. The total sample size of children less than five years of age after cleaning the data are 7781, of which 2095 are LBW having birth weight categorized as “smaller than average and very small” and 5686 are normal birth weight (NBW) having birth weight very large, larger than average, and average. This study employed propensity score matching (PSM) regression methods to understand whether the children born as low birth weight are more prone to stunting and wasting and/or both. In province of Sindh, moderate wasting children under five years were 21%, severe wasting 6% and both wasting and stunting 10%. The propensity score results are shown significant in all groups. Specifically, all four types of PSM methods confirm a significant difference in the potential outcome variables—meaning that a child born with LBW has a significant adverse effect on the potential child health outcome variables (stunting, wasting and both). Thus, the propensity score matching findings confirm a significant and adverse effect of LBW on potential health outcomes of under five children. Similarly, low birth weight children are significantly more likely to be moderately wasted (OR = 1.5, CI = 1.3–1.6) and severely wasted (OR = 1.6, CI = 1.3–2.0) and both (stunted and wasted, OR = 2.0, CI = 1.7–2.3) as compared to children with normal birth weight. Male children, if born with low birth weight, are significantly more likely to be moderately wasted (OR = 1.3, CI = 1.1–1.5) and both (wasted and stunted, OR = 1.3, CI = 1.1–1.5) than girls. This large data analysis finding proved that the LBW newborns are on higher risk to develop wasting and stunting in Pakistan.
Cytokine response in cerebrospinal fluid of meningitis patients and outcome associated with pneumococcal serotype
Authors: Müller Annelies , Schramm Diana B. , Kleynhans Jackie , de Gouveia Linda , Meiring Susan , Ramette Alban , von Gottberg Anne , Hathaway Lucy Jane 
Published: October 2021

AbstractStreptococcus pneumoniae causes life-threatening meningitis. Its capsular polysaccharide determines the serotype and influences disease severity but the mechanism is largely unknown. Due to evidence of elevated cytokines levels in the meningeal inflammatory response, we measured 41 cytokines/chemokines and growth factors in cerebrospinal fluid (CSF) samples from 57 South African meningitis patients (collected in the period 2018–2019), with confirmed S. pneumoniae serotypes, using a multiplexed bead-based immunoassay. Based on multivariable Bayesian regression, using serotype 10A as a reference and after adjusting for HIV and age, we found IL-6 concentrations significantly lower in patients infected with serotypes 6D (undetectable) and 23A (1601 pg/ml), IL-8 concentrations significantly higher in those infected with 22A (40,459 pg/ml), 7F (32,400 pg/ml) and 15B/C (6845 pg/ml), and TNFα concentration significantly higher in those infected with serotype 18A (33,097 pg/ml). Although a relatively small number of clinical samples were available for this study and 28% of samples could not be assigned to a definitive serotype, our data suggests 15B/C worthy of monitoring during surveillance as it is associated with in-hospital case fatality and not included in the 13-valent polysaccharide conjugate vaccine, PCV13. Our data provides average CSF concentrations of a range of cytokines and growth factors for 18 different serotypes (14, 19F, 3, 6A, 7F, 19A, 8, 9N, 10A, 12F, 15B/C, 22F, 16F, 23A, 31, 18A, 6D, 22A) to serve as a basis for future studies investigating host–pathogen interaction during pneumococcal meningitis. We note that differences in induction of IL-8 between serotypes may be particularly worthy of future study.
Evaluation of head posture using an inertial measurement unit
Authors: Al-Yassary Mustafa , Billiaert Kelly , Antonarakis Gregory S. , Kiliaridis Stavros 
Published: October 2021

AbstractAn inertial measurement unit (IMU) is an electronic device that measures and track the orientation of a body. We conducted this study in accordance with the STARD guidelines to evaluate the accuracy of IMU (index test) for measuring head posture compared to the current gold standard using a cervical range of motion (CROM) device. The reproducibility of the hunter and mirror-guided head posture was also evaluated. In vitro and in vivo tests were carried out to assess the validity of the IMU. To assess reproducibility, thirty healthy young adults were asked to look at four different locations in two different sessions while the head posture was recorded. Excellent correlation (r = 0.99; p < 0.001) was found between the IMU and CROM device with an absolute mean difference of 0.45° ± 0.58° (p = 0.85) for the in vitro test and 0.88° ± 1.20° (p = 0.99) for the in vivo test. For the reproducibility test, moderate to good correlation coefficients were found (r = 0.55 to 0.89; all p < 0.05) between the two sessions. The intraclass correlation coefficient ranged from moderate to excellent reliability (ICC from 0.74 to 0.96). These results suggest that the IMU sensors, when calibrated correctly, can be adequate to analyze head posture.
Functional characterization of a bioengineered liver after heterotopic implantation in pigs
Authors: Anderson Brett D. , Nelson Erek D. , Joo DongJin , Amiot Bruce P. , Katane Aleksandr A. , Mendenhall Alyssa , Steiner Benjamin G. , Stumbras Aron R. , Nelson Victoria L. , Palumbo R. Noelle , Gilbert Thomas W. , Davidow Dominique S. , Ross Jeffrey J. , Nyberg Scott L. 
Published: October 2021

AbstractOrgan bioengineering offers a promising solution to the persistent shortage of donor organs. However, the progression of this technology toward clinical use has been hindered by the challenges of reconstituting a functional vascular network, directing the engraftment of specific functional cell types, and defining appropriate culture conditions to concurrently support the health and phenotypic stability of diverse cell lineages. We previously demonstrated the ability to functionally reendothelialize the vasculature of a clinically scaled decellularized liver scaffold with human umbilical vein endothelial cells (HUVECs) and to sustain continuous perfusion in a large animal recovery model. We now report a method for seeding and engrafting primary porcine hepatocytes into a bioengineered liver (BEL) scaffold previously reendothelialized with HUVECs. The resulting BELs were competent for albumin production, ammonia detoxification and urea synthesis, indicating the presence of a functional hepatocyte compartment. BELs additionally slowed ammonia accumulation during in vivo perfusion in a porcine model of surgically induced acute liver failure. Following explant of the graft, BEL parenchyma showed maintenance of canonical endothelial and hepatocyte markers. Taken together, these results support the feasibility of engineering a clinically scaled functional BEL and establish a platform for optimizing the seeding and engraftment of additional liver specific cells.
The enpp4 ectonucleotidase regulates kidney patterning signalling networks in Xenopus embryos
Authors: Massé Karine , Bhamra Surinder , Paroissin Christian , Maneta-Peyret Lilly , Boué-Grabot Eric , Jones Elizabeth A. 
Published: October 2021

AbstractThe enpp ectonucleotidases regulate lipidic and purinergic signalling pathways by controlling the extracellular concentrations of purines and bioactive lipids. Although both pathways are key regulators of kidney physiology and linked to human renal pathologies, their roles during nephrogenesis remain poorly understood. We previously showed that the pronephros was a major site of enpp expression and now demonstrate an unsuspected role for the conserved vertebrate enpp4 protein during kidney formation in Xenopus. Enpp4 over-expression results in ectopic renal tissues and, on rare occasion, complete mini-duplication of the entire kidney. Enpp4 is required and sufficient for pronephric markers expression and regulates the expression of RA, Notch and Wnt pathway members. Enpp4 is a membrane protein that binds, without hydrolyzing, phosphatidylserine and its effects are mediated by the receptor s1pr5, although not via the generation of S1P. Finally, we propose a novel and non-catalytic mechanism by which lipidic signalling regulates nephrogenesis.
ssDNA recombineering boosts in vivo evolution of nanobodies displayed on bacterial surfaces
Authors: Al-ramahi Yamal , Nyerges Akos , Margolles Yago , Cerdán Lidia , Ferenc Gyorgyi , Pál Csaba , Fernández Luis Ángel , de Lorenzo Víctor 
Published: October 2021

AbstractssDNA recombineering has been exploited to hyperdiversify genomically-encoded nanobodies displayed on the surface of Escherichia coli for originating new binding properties. As a proof-of-principle a nanobody recognizing the antigen TirM from enterohaemorrhagic E. coli (EHEC) was evolved towards the otherwise not recognized TirM antigen from enteropathogenic E. coli (EPEC). To this end, E. coli cells displaying this nanobody fused to the intimin outer membrane-bound domain were subjected to multiple rounds of mutagenic oligonucleotide recombineering targeting the complementarity determining regions (CDRs) of the cognate VHH gene sequence. Binders to the EPEC-TirM were selected upon immunomagnetic capture of bacteria bearing active variants and nanobodies identified with a new ability to strongly bind the new antigen. The results highlight the power of combining evolutionary properties of bacteria in vivo with oligonucleotide synthesis in vitro for the sake of focusing diversification to specific segments of a gene (or protein thereof) of interest.
Adipose gene expression profiles reveal insights into the adaptation of northern Eurasian semi-domestic reindeer (Rangifer tarandus)
Authors: Weldenegodguad Melak , Pokharel Kisun , Niiranen Laura , Soppela Päivi , Ammosov Innokentyi , Honkatukia Mervi , Lindeberg Heli , Peippo Jaana , Reilas Tiina , Mazzullo Nuccio , Mäkelä Kari A. , Nyman Tommi , Tervahauta Arja , Herzig Karl-Heinz , Stammler Florian , Kantanen Juha 
Published: October 2021

AbstractReindeer (Rangifer tarandus) are semi-domesticated animals adapted to the challenging conditions of northern Eurasia. Adipose tissues play a crucial role in northern animals by altering gene expression in their tissues to regulate energy homoeostasis and thermogenic activity. Here, we perform transcriptome profiling by RNA sequencing of adipose tissues from three different anatomical depots: metacarpal (bone marrow), perirenal, and prescapular fat in Finnish and Even reindeer (in Sakha) during spring and winter. A total of 16,212 genes are expressed in our data. Gene expression profiles in metacarpal tissue are distinct from perirenal and prescapular adipose tissues. Notably, metacarpal adipose tissue appears to have a significant role in the regulation of the energy metabolism of reindeer in spring when their nutritional condition is poor after winter. During spring, genes associated with the immune system are upregulated in the perirenal and prescapular adipose tissue. Blood and tissue parameters reflecting general physiological and metabolic status show less seasonal variation in Even reindeer than in Finnish reindeer. This study identifies candidate genes potentially involved in immune response, fat deposition, and energy metabolism and provides new information on the mechanisms by which reindeer adapt to harsh arctic conditions.