bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-ethnic polygenic risk modifies the association between APOL1 high risk genotypes and chronic kidney disease
Authors: Vy Ha My T. , Gulamali Faris F. , Glicksberg Benjamin S , Gutierrez Orlando , Cooper Richard , Bottinger Erwin P , Cho Judy , Loos Ruth J.F. , Horowitz Carol R. , Do Ron , Nadkarni Girish N 
Published: November 2021

AbstractThe burden of advanced chronic kidney disease (CKD) falls disproportionately on minorities including African Americans (AAs) and Hispanic Americans (HAs) with admixed ancestry. Even though APOL1 high-risk genotypes increase risk of kidney disease, their penetrance is incomplete, indicating that the modification of APOL1 high risk may be polygenic. For this study, we used three multi-ethnic cohorts with APOL1 high risk genotypes and calculated a multi-ethnic PRS using publicly available summary statistics. We show that CKD risk is significantly modified by a multi-ethnic polygenic risk score. Standardizing population screening for CKD by including APOL1 high-risk genotypes and polygenic risk score may improve risk stratification and outcomes.
Repressing PTBP1 is incapable to convert reactive astrocytes to dopaminergic neurons in a mouse model of Parkinson’s disease
Authors: Chen Weizhao , Zheng Qiongping , Huang Qiaoying , Ma Shanshan , Li Mingtao 
Published: November 2021

AbstractLineage reprograming of resident glia cells to induced dopaminergic neurons (iDAns) holds attractive prospect for cell-replacement therapy of Parkinson’s disease (PD). Recently, whether repressing polypyrimidine tract binding protein 1 (PTBP1) could truly achieve efficient astrocyte-to-iDAn conversion in substantia nigra and striatum aroused widespread controversy. Although reporter positive iDAns were observed by two groups after delivering adeno-associated virus (AAV) expressing a reporter with shRNA or Crispr-CasRx to repress astroglial PTBP1, the possibility of AAV leaking into endogenous DAns could not be excluded without using a reliable lineage tracing method. By adopting stringent lineage tracing strategy, two other studies showed that neither knockdown nor genetic deletion of quiescent astroglial PTBP1 fails to obtain iDAns under physiological condition. However, the role of reactive astrocyte might be underestimated since upon brain injury, reactive astrocyte could acquire certain stem cell hallmarks which may facilitate the lineage conversion process. Therefore, whether reactive astrocytes could be genuinely converted to DAns after PTBP1 repression in a PD model needs further validation. In this study, we used Aldh1l1-CreERT2-mediated specific astrocyte-lineage tracing method to investigate whether reactive astrocytes could be converted to DAns in the 6-OHDA PD model. However, we found that no astrocyte-originated DAn was generated after effective knockdown of astroglial PTBP1 either in the substantia nigra or in the striatum, while AAV “leakage” to nearby neurons was observed. Our results further confirmed that repressing PTBP1 is unable to convert astrocytes to DAns no matter in physiological or PD-related pathological conditions.Graphic abstractHighlightsAAV-shPtbp1 rapidly and efficiently induces viral-reporter-labeled DAns in mouse brain under physiological conditionViral-reporter-positive DAns are not originated from PTBP1 repressed and lineage traced reactive astrocytes in a mouse PD model
Batch-Mask: An automated Mask R-CNN workflow to isolate non-standard biological specimens for color pattern analysis
Authors: Curlis John David , Renney Timothy , Davis Rabosky Alison R. , Moore Talia Y. 
Published: November 2021

AbstractEfficient comparisons of biological color patterns are critical for understanding the mechanisms by which organisms evolve in ecosystems, including sexual selection, predator-prey interactions, and thermoregulation. However, elongate or spiral-shaped organisms do not conform to the standard orientation and photographic techniques required for automated analysis. Currently, large-scale color analysis of elongate animals requires time-consuming manual landmarking, which reduces their representation in coloration research despite their ecological importance.We present Batch-Mask: an automated and customizable workflow to facilitate the analysis of large photographic data sets of non-standard biological subjects. First, we present a user guide to run an open-source region-based convolutional neural network with fine-tuned weights for identifying and isolating a biological subject from a background (masking). Then, we demonstrate how to combine masking with existing manual visual analysis tools into a single streamlined, automated workflow for comparing color patterns across images.Batch-Mask was 60x faster than manual landmarking, produced masks that correctly identified 96% of all snake pixels, and produced pattern energy results that were not significantly different from the manually landmarked data set.The fine-tuned weights for the masking neural network, user guide, and automated workflow substantially decrease the amount of time and attention required to quantitatively analyze non-standard biological subjects. By using these tools, biologists will be able to compare color, pattern, and shape differences in large data sets that include significant morphological variation in elongate body forms. This advance will be especially valuable for comparative analyses of natural history collections, and through automation can greatly expand the scale of space, time, or taxonomic breadth across which color variation can be quantitatively examined.
Mapping of individual sensory nerve axons from digits to spinal cord with the Transparent Embedding Solvent System
Authors: Yi Yating , Men Yi , Zhang Shiwen , Wang Yuhong , Chen Zexi , Lachika Ed , Peng Hanchuan , Ge Woo-Ping , Zhao Hu 
Published: November 2021

SummaryUnderstanding the connections and projections of neurons has been a fundamental issue for neuroscience. Although strategies have been developed to map the projection of individual axons within the mouse brain, high resolution mapping of individual peripheral nerve axons in peripheral organs or spinal cord has never been achieved. Here, we designed the Transparent Embedding Solvent System (TESOS) method and developed a technical pipeline for imaging, reconstructing and analyzing large samples containing various tissue types at sub-micron resolution. The mouse whole body was reconstructed at micron-scale resolution. We were able to image, reconstruct and analyze the complete axonal projection of individual sensory neurons within an intact mouse paw or spinal cord at sub-micron resolution. Furtherly, we imaged and reconstructed the entire projection course of individual sensory neurons from adult mouse digits to the spinal cord. The TESOS method provides an efficient tool for micron-scale connectome mapping of the peripheral nervous system.
Multi-Branch-CNN: classification of ion channel interacting peptides using parallel convolutional neural networks
Authors: Yan Jielu , Zhang Bob , Zhou Mingliang , Kwok Hang Fai , Siu Shirley W. I. 
Published: November 2021

AbstractLigand peptides that have high affinity for ion channels are critical for regulating ion flux across the plasma membrane. These peptides are now being considered as potential drug candidates for many diseases, such as cardiovascular disease and cancers. There are several studies to identify ion channel interacting peptides computationally, but, to the best of our knowledge, none of them published available tools for prediction. To provide a solution, we present Multi-branch-CNN, a parallel convolutional neural networks (CNNs) method for identifying three types of ion channel peptide binders (sodium, potassium, and calcium). Our experiment shows that the Multi-Branch-CNN method performs comparably to thirteen traditional ML algorithms (TML13) on the test sets of three ion channels. To evaluate the predictive power of our method with respect to novel sequences, as is the case in real-world applications, we created an additional test set for each ion channel, called the novel-test set, which has little or no similarities to the sequences in either the sequences of the train set or the test set. In the novel-test experiment, Multi-Branch-CNN performs significantly better than TML13, showing an improvement in accuracy of 6%, 14%, and 15% for sodium, potassium, and calcium channels, respectively. We confirmed the effectiveness of Multi-Branch-CNN by comparing it to the standard CNN method with one input branch (Single-Branch-CNN) and an ensemble method (TML13-Stack). To facilitate applications, the data sets, script files to reproduce the experiments, and the final predictive models are freely available athttps://github.com/jieluyan/Multi-Branch-CNN.
Pathological characteristics of pulmonary toxicity in F344 rats exposed by inhalation to cross-linked water-soluble acrylic acid polymers
Authors: Yamano Shotaro , Takeda Tomoki , Goto Yuko , Hirai Shigeyuki , Furukawa Yusuke , Kikuchi Yoshinori , Misumi Kyohei , Suzuki Masaaki , Takanobu Kenji , Senoh Hideki , Saito Misae , Kondo Hitomi , Kobashi Yoichiro , Okamoto Kenzo , Kishimoto Takumi , Umeda Yumi 
Published: November 2021

AbstractBackgroundRecently in Japan, six workers at a chemical plant that manufactures resins developed interstitial lung diseases after being involved in loading and packing cross-linked water-soluble acrylic acid polymers (CWAAPs). Since CWAAPs are not on the list of occupational diseases, the present study examined the lung damage potential of two CWAAPs (CWAAP-A and CWAAP-B) in rats, investigated pathological mechanisms, and established a method to rapidly evaluate the harmfulness of CWAAPs.MethodsUsing a whole-body inhalation exposure system, male F344 rats were exposed once to 40 or 100 mg/m3 of CWAAP-A for 4 hours or to 15 or 40 mg/m3 of CWAAP-A for 4 hours per day once per week for 2 months (a total of 9 exposures). In a separate set of experiments, male F344 rats were administered 1 mg/kg CWAAP-A or CWAAP-B by intratracheal instillation once every two weeks for 2 months (a total of five doses). Lung tissues, mediastinal lymph nodes, and bronchoalveolar lavage fluid were collected and subjected to biological and histopathological analyses.ResultsA single 4-hour exposure to CWAAP caused alveolar injury, and repeated exposures resulted in regenerative changes in the alveolar epithelium with activation of TGFβ signaling. During the recovery period after the last exposure, some alveolar lesions were partially healed, but other lesions developed into alveolitis with fibrous thickening of the alveolar septum. Rats administered CWAAP-A by intratracheal instillation developed qualitatively similar pulmonary pathology as rats exposed to CWAAP-A by inhalation. At 2 weeks after intratracheal instillation, rats administered CWAAP-B appeared to have a slightly higher degree of lung lesions compared to rats administered CWAAP-A, however, there was no difference in these lesions of CWAAP-A and CWAAP-B in rats examined 18 weeks after administration of these materials.ConclusionsThe present study provides evidence of rat lung pathogenesis after inhalation exposure to CWAAP-A. This study also demonstrates that the lung pathology of rats exposed to CWAAP-A by systemic inhalation was qualitatively similar to that of rats administered CWAAP-A by intratracheal instillation. The use of intratracheal instillation as an adjunct to systemic inhalation is expected to significantly accelerate the risk assessment for a variety of CWAAPs.
Polymer skulls with integrated transparent electrode arrays for cortex-wide opto-electrophysiological recordings
Authors: Donaldson Preston D. , Navabi Zahra S. , Carter Russell E. , Fausner Skylar M. L. , Ghanbari Leila , Ebner Timothy J. , Swisher Sarah L. , Kodandaramaiah Suhasa B. 
Published: November 2021

ABSTRACTElectrophysiological and optical imaging provide complementary neural sensing capabilities – electrophysiological recordings have the highest temporal resolution, while optical imaging allows recording the activities of genetically defined populations at high spatial resolution. Combining these complementary, yet orthogonal modalities to perform simultaneous large-scale, multimodal sensing of neural activity across multiple brain regions would be very powerful. Here we show that transparent, inkjet-printed electrocorticography (ECoG) electrode arrays can be seamlessly integrated with morphologically conformant transparent polymer skulls for multimodal recordings across the cortex. These ‘eSee-Shells’ were implanted on transgenic mice expressing the Ca2+indicator GCaMP6f in cortical excitatory cells and provided a robust opto-electrophysiological interface for over 100 days. eSee-Shells enable simultaneous mesoscale Ca2+imaging and ECoG acquisition under anesthesia as well as in awake animals presented with sensory stimuli. eSee-Shells further show sufficient clarity and transparency to observe single-cell Ca2+signals directly below the electrodes and interconnects. Simultaneous multimodal measurement of cortical dynamics reveals changes in both ECoG and Ca2+signals that depend on the behavioral state.
The impact of rare germline variants on human somatic mutation processes
Authors: Pour Mischan Vali , Lehner Ben , Supek Fran 
Published: November 2021

AbstractSomatic mutations are an inevitable component of ageing and the most important cause of cancer. The rates and types of somatic mutation vary across individuals, but relatively few inherited influences on mutation processes are known. We performed a comprehensive gene-based rare variant association study with diverse mutational processes, using human cancer genomes from over 11,000 individuals of European ancestry. By combining burden and variance tests, we identify 207 associations involving 15 somatic mutational phenotypes and 42 genes that replicated in an independent data set at a FDR of 1%. We associated rare inherited deleterious variants in novel genes such asMSH3,EXO1,SETD2, andMTORwith two different forms of DNA mismatch repair deficiency, and variants in genes such asEXO1,PAXIP1, andWRNwith deficiency in homologous recombination repair. In addition, we identified associations with other mutational processes, such asAPEX1with APOBEC-signature mutagenesis. Many of the novel genes interact with each other and with known mutator genes within cellular sub-networks. Considered collectively, damaging variants in the newly-identified genes are prevalent in the population. We suggest that rare germline variation in diverse genes commonly impacts mutational processes in somatic cells.
CXCR4+ Treg cells control serum IgM levels and natural IgM autoantibody production by B1 cells in the bone marrow
Authors: Elias Shlomo , Sharma Rahul , Schizas Michael , Valdez Izabella , Park Sun-Mi , Gonzalez-Figueroa Paula , Li Quan-Zhen , Hoyos Beatrice , Rudensky Alexander Y. 
Published: November 2021

AbstractRegulatory T (Treg) cells represent a specialized lineage of suppressive CD4+ T cells, whose functionality is critically dependent on their ability to migrate to, and dwell in the proximity of cells they control. Here we show that continuous expression of the chemokine receptor CXCR4 in Treg cells is required for their ability to accumulate in the bone marrow (BM). Induced CXCR4 ablation in Treg cells led to their rapid depletion and consequent increase in mature B cells, foremost B-1 subset, observed exclusively in the BM without detectable changes in plasma cells or hematopoietic stem cells or any signs of systemic or local immune activation elsewhere. Dysregulation of BM B-1 B cells was associated with a highly specific increase in IgM autoantibodies and the total serum IgM levels. Thus, Treg cells control autoreactive B-1 B cells in a CXCR4-dependent manner. These findings have significant implications for understanding of regulation of B cell autoreactivity and malignancies.
Chromosome 1q amplification perturbs a ceRNA network to promote melanoma metastasis
Authors: Xu Xiaonan , Wang Kaizhen , Vera Olga , Verma Akanksha , Elemento Olivier , Yu Xiaoqing , Karreth Florian A. 
Published: November 2021

SUMMARYSomatic copy number alterations (CNAs) promote cancer, but the underlying driver genes are often not obvious when only the functions of the encoded proteins are considered. mRNAs can act as competitive endogenous miRNA sponges (ceRNAs) to post-transcriptionally regulate gene expression in a protein coding-independent manner. However, whether ceRNAs contribute to the oncogenic effects of CNAs is unknown. We report that chromosome 1q gains promote melanoma progression and metastasis at least in part through overexpression of three mRNAs with ceRNA activity: CEP170, NUCKS1, and ZC3H11A. Genetic studies reveal that these ceRNAs enhance melanoma metastasis by sequestering tumor suppressor miRNAs, thereby alleviating the repression of several pro-metastatic target genes. This regulatory RNA network is evident in other cancer types, suggesting that chromosome 1q ceRNA deregulation is a common driver of cancer progression. Taken together, our work demonstrates that ceRNAs mediate the oncogenicity of somatic CNAs.
Rapid reconstruction of neural circuits using tissue expansion and lattice light sheet microscopy
Authors: Lillvis Joshua L. , Otsuna Hideo , Ding Xiaoyu , Pisarev Igor , Kawase Takashi , Colonell Jennifer , Rokicki Konrad , Goina Cristian , Gao Ruixuan , Hu Amy , Wang Kaiyu , Bogovic John , Milkie Daniel E. , Meienberg Linus , Boyden Edward S. , Saalfeld Stephan , Tillberg Paul W. , Dickson Barry J. 
Published: November 2021

AbstractElectron microscopy (EM) allows for the reconstruction of dense neuronal connectomes but suffers from low throughput, limiting its application to small numbers of reference specimens. We developed a protocol and analysis pipeline using tissue expansion and lattice light-sheet microscopy (ExLLSM) to rapidly reconstruct selected circuits across many samples with single synapse resolution and molecular contrast. We validate this approach in Drosophila, demonstrating that it yields synaptic counts similar to those obtained by EM, can be used to compare counts across sex and experience, and to correlate structural connectivity with functional connectivity. This approach fills a critical methodological gap in studying variability in the structure and function of neural circuits across individuals within and between species.
Multiplexed Cell-Based Diagnostic Devices for Detection of Renal Biomarkers Using Genetic Circuits
Authors: Köse Sıla , Ahan Recep Erdem , Köksaldı İlkay Çisil , Olgaç Muazzez Asburçe Bike , Kasapkara Çiğdem Seher , Şeker Urartu Özgür Şafak 
Published: November 2021

AbstractThe number of synthetic biology based solutions employed in the medical industry is growing every year. The whole cell biosensors being one of them, have been proven valuable tools for developing low-cost, portable, personalized medicine alternatives to conventional techniques. Based on this concept, we targeted one of the major health problems in the world, Chronic Kidney Disease (CKD). To do so, we developed two novel biosensors for the detection of two important renal biomarkers; urea and uric acid. Using advanced gene expression control strategies we improved the operational range and the response profiles of each biosensor to meet clinical specifications. We further engineered these systems to enable multiplexed detection as well as an AND-logic gate operating system. Finally, we tested the applicability of these systems and optimized their working dynamics inside complex medium human blood serum. This study could help the efforts to transition from labor-intensive and expensive laboratory techniques to widely available, portable, low cost diagnostic options.
Elevated Plasma Matrix Metalloproteinase-8 associates with Sputum Culture Positivity in Pulmonary Tuberculosis
Authors: Walker N.F. , Karim F. , Moosa M.Y.S. , Moodley S. , Mazibuko M. , Khan K. , Sterling T.R. , van der Heijden Y.F. , Grant A.D. , Elkington P.T. , Pym A. , Leslie A. 
Published: November 2021

AbstractCurrent methods for tuberculosis (TB) treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during TB treatment as biomarkers. Plasma MMP-1, -8 and -10 significantly decreased during treatment. Plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture positive relative to culture negative participants, prior to (median 4609 pg/ml, IQR 2353-9048 vs 775 pg/ml, IQR 551-4920, p=0.019) and after 6 months (median 3650, IQR 1214-3888 vs 720, IQR 551-1321, p=0.008) of TB treatment. Consequently, plasma MMP-8 is a potential biomarker to enhance TB treatment monitoring and screen for possible culture positivity.
Comparative analysis of antibody production by mRNA 1273, AZD 1222 and BBIBP-CorV on elderly people suffering from different co-morbidity in Bangladesh
Authors: Hoque Ashraful , Rahman Md Marufur , Parvez Shahnewaz , Imam Hossain , Nahar Nurun , Hasan Chowdhury Forhad Uddin 
Published: November 2021

AbstractBackgroundAs the pandemic spread so quickly all over the world, the scientist did not get the right time to cover all age group populations for a vaccine trial. The elderly population is usually vulnerable for COVID-19 which was proven by different research work and focus was to save this group of people was the prime concern for every country of the world. Though vaccines that got emergency use authorization have proven their efficacy which one is better for elderly people suffering from different co-morbid conditions is still not established. In this study, we want to evaluate the antibody production by mRNA 1273, AZD 1222, and BBIBP-CorV in elderly people with different comorbidity.MethodWe include 40 people in each group who have at least one comorbid condition and the total sample size was 120. The sample was taken from them before vaccination and 14 days after the second dose. Adverse event following immunization was recorded if any. Antibody measurement was done by ELISA method by using DiaSino SARS-CoV-2 S1 RBD IgG Quant.ResultAmong 120 participants with an equal number of participants in each of the vaccine groups all of them were aged between 60-72 years, of whom 65% were males and 35 % were females. Anti S1 RBD IgG was detected among all the participants from each vaccine group after 14 days of taking their 2nd dose. A non-parametric multiple comparison test (Kruskal-Wallis test) of Anti S1 RBD IgG levels among three vaccine groups revealed significant differences (P-value <0.05) between groups. The IgG level was almost twice in the mRNA-1273 group (mean 577.1± 44.33 AU/ml) compared to AZD1222(mean 308.5 ±37.91 AU/ml) and BBIBP-CorV group.ConclusionFrom this small sample size, we predicate that mRNA 1273 produce much higher anti-S1 RBD IgG than the other two vaccines. Every vaccine is safe and effective whose is approved by WHO. Calculative use of the vaccine may produce an outcome for the future as we are still way behind in the proper amount of vaccine production.