bluuebunny/crossref_metadata_2025 huggingface dataset:
Considering socio-political framings when analyzing coastal climate change effects can prevent maldevelopment on small islands
Authors: David C. Gabriel , Hennig Arne , Ratter Beate M. W. , Roeber Volker , Zahid  , Schlurmann Torsten
Published: October 2021

Adapting to climate change and sea level rise is challenging on small islands. False adaptation can lead to adverse impacts on natural and societal dynamics. Therefore, an interdisciplinary perspective on the interaction of natural dynamics, societal demands, and political decisions is crucial. In this sense, this study scrutinizes coastal processes and socio-political dimensions of erosion on the reef island Fuvahmulah, the Maldives. The national government and Fuvahmulah’s population have an opposed perception and attribution of the drivers and processes behind Fuvahmulah’s most pressing coastal issue – coastal erosion. To review these perceptions, natural dynamics are recreated with process-based methods and discussed regarding present and projected marine pressures. Population surveys and interviews with actors in coastal development complement the physical insights into erosion on Fuvahmulah and describe the socio-political dimension of climate change adaptation on small islands. This interdisciplinary approach demonstrates how small-islands’ adaptive capacities are typically impaired and disclose the potential of local knowledge to overcome maldevelopment.
RN7SK small nuclear RNA controls bidirectional transcription of highly expressed gene pairs in skin
Authors: Bandiera Roberto , Wagner Rebecca E. , Britto-Borges Thiago , Dieterich Christoph , Dietmann Sabine , Bornelöv Susanne , Frye Michaela
Published: October 2021

Pausing of RNA polymerase II (Pol II) close to promoters is a common regulatory step in RNA synthesis, and is coordinated by a ribonucleoprotein complex scaffolded by the noncoding RNA RN7SK. The function of RN7SK-regulated gene transcription in adult tissue homoeostasis is currently unknown. Here, we deplete RN7SK during mouse and human epidermal stem cell differentiation. Unexpectedly, loss of this small nuclear RNA specifically reduces transcription of numerous cell cycle regulators leading to cell cycle exit and differentiation. Mechanistically, we show that RN7SK is required for efficient transcription of highly expressed gene pairs with bidirectional promoters, which in the epidermis co-regulated cell cycle and chromosome organization. The reduction in transcription involves impaired splicing and RNA decay, but occurs in the absence of chromatin remodelling at promoters and putative enhancers. Thus, RN7SK is directly required for efficient Pol II transcription of highly transcribed bidirectional gene pairs, and thereby exerts tissue-specific functions, such as maintaining a cycling cell population in the epidermis.
Temporal evolution of master regulator Crp identifies pyrimidines as catabolite modulator factors
Authors: Lauritsen Ida , Frendorf Pernille Ott , Capucci Silvia , Heyde Sophia A. H. , Blomquist Sarah D. , Wendel Sofie , Fischer Emil C. , Sekowska Agnieszka , Danchin Antoine , Nørholm Morten H. H.
Published: October 2021

The evolution of microorganisms often involves changes of unclear relevance, such as transient phenotypes and sequential development of multiple adaptive mutations in hotspot genes. Previously, we showed that ageing colonies of an E. coli mutant unable to produce cAMP when grown on maltose, accumulated mutations in the crp gene (encoding a global transcription factor) and in genes involved in pyrimidine metabolism such as cmk; combined mutations in both crp and cmk enabled fermentation of maltose (which usually requires cAMP-mediated Crp activation for catabolic pathway expression). Here, we study the sequential generation of hotspot mutations in those genes, and uncover a regulatory role of pyrimidine nucleosides in carbon catabolism. Cytidine binds to the cytidine regulator CytR, modifies the expression of sigma factor 32 (RpoH), and thereby impacts global gene expression. In addition, cytidine binds and activates a Crp mutant directly, thus modulating catabolic pathway expression, and could be the catabolite modulating factor whose existence was suggested by Jacques Monod and colleagues in 1976. Therefore, transcription factor Crp appears to work in concert with CytR and RpoH, serving a dual role in sensing both carbon availability and metabolic flux towards DNA and RNA. Our findings show how certain alterations in metabolite concentrations (associated with colony ageing and/or due to mutations in metabolic or regulatory genes) can drive the evolution in non-growing cells.
Deglacial variability of South China hydroclimate heavily contributed by autumn rainfall
Authors: He Chengfei , Liu Zhengyu , Otto-Bliesner Bette L. , Brady Esther C. , Zhu Chenyu , Tomas Robert , Gu Sifan , Han Jing , Jin Yishuai
Published: October 2021

The deglacial hydroclimate in South China remains a long-standing topic of debate due to the lack of reliable moisture proxies and inconsistent model simulations. A recent hydroclimate proxy suggests that South China became wet in cold stadials during the last deglaciation, with the intensification proposed to be contributed mostly by the East Asian summer monsoon (EASM). Here, based on a deglacial simulation in a state-of-the-art climate model that well reproduces the evolution of EASM, winter monsoon (EAWM) and the associated water isotopes in East Asia, we propose that the intensified hydroclimate in South China is also contributed heavily by the rainfall in autumn, during the transition between EASM and EAWM. The excessive rainfall in autumn results from the convergence between anomalous northerly wind due to amplified land-sea thermal contrast and anomalous southerly wind associated with the anticyclone over Western North Pacific, both of which are, in turn, forced by the slowdown of the Atlantic thermohaline circulation. Regardless the rainfall change, however, the modeled δ18Op remains largely unchanged in autumn. Our results provide new insights to East Asia monsoon associated with climate change in the North Atlantic.
Structure and inhibition of Cryptococcus neoformans sterylglucosidase to develop antifungal agents
Authors: Pereira de Sa Nivea , Taouil Adam , Kim Jinwoo , Clement Timothy , Hoffmann Reece M. , Burke John E. , Rizzo Robert C. , Ojima Iwao , Del Poeta Maurizio , Airola Michael V.
Published: October 2021

Pathogenic fungi exhibit a heavy burden on medical care and new therapies are needed. Here, we develop the fungal specific enzyme sterylglucosidase 1 (Sgl1) as a therapeutic target. Sgl1 converts the immunomodulatory glycolipid ergosterol 3β-D-glucoside to ergosterol and glucose. Previously, we found that genetic deletion of Sgl1 in the pathogenic fungus Cryptococcus neoformans (Cn) results in ergosterol 3β-D-glucoside accumulation, renders Cn non-pathogenic, and immunizes mice against secondary infections by wild-type Cn, even in condition of CD4+ T cell deficiency. Here, we disclose two distinct chemical classes that inhibit Sgl1 function in vitro and in Cn cells. Pharmacological inhibition of Sgl1 phenocopies a growth defect of the Cn Δsgl1 mutant and prevents dissemination of wild-type Cn to the brain in a mouse model of infection. Crystal structures of Sgl1 alone and with inhibitors explain Sgl1’s substrate specificity and enable the rational design of antifungal agents targeting Sgl1.
Mapping epigenetic divergence in the massive radiation of Lake Malawi cichlid fishes
Authors: Vernaz Grégoire , Malinsky Milan , Svardal Hannes , Du Mingliu , Tyers Alexandra M. , Santos M. Emília , Durbin Richard , Genner Martin J. , Turner George F. , Miska Eric A.
Published: October 2021

Epigenetic variation modulates gene expression and can be heritable. However, knowledge of the contribution of epigenetic divergence to adaptive diversification in nature remains limited. The massive evolutionary radiation of Lake Malawi cichlid fishes displaying extensive phenotypic diversity despite extremely low sequence divergence is an excellent system to study the epigenomic contribution to adaptation. Here, we present a comparative genome-wide methylome and transcriptome study, focussing on liver and muscle tissues in phenotypically divergent cichlid species. In both tissues we find substantial methylome divergence among species. Differentially methylated regions (DMR), enriched in evolutionary young transposons, are associated with transcription changes of ecologically-relevant genes related to energy expenditure and lipid metabolism, pointing to a link between dietary ecology and methylome divergence. Unexpectedly, half of all species-specific DMRs are shared across tissues and are enriched in developmental genes, likely reflecting distinct epigenetic developmental programmes. Our study reveals substantial methylome divergence in closely-related cichlid fishes and represents a resource to study the role of epigenetics in species diversification.
Self-assembled multifunctional neural probes for precise integration of optogenetics and electrophysiology
Authors: Zou Liang , Tian Huihui , Guan Shouliang , Ding Jianfei , Gao Lei , Wang Jinfen , Fang Ying
Published: October 2021

Optogenetics combined with electrical recording has emerged as a powerful tool for investigating causal relationships between neural circuit activity and function. However, the size of optogenetically manipulated tissue is typically 1-2 orders of magnitude larger than that can be electrically recorded, rendering difficulty for assigning functional roles of recorded neurons. Here we report a viral vector-delivery optrode (VVD-optrode) system for precise integration of optogenetics and electrophysiology in the brain. Our system consists of flexible microelectrode filaments and fiber optics that are simultaneously self-assembled in a nanoliter-scale, viral vector-delivery polymer carrier. The highly localized delivery and neuronal expression of opsin genes at microelectrode-tissue interfaces ensure high spatial congruence between optogenetically manipulated and electrically recorded neuronal populations. We demonstrate that this multifunctional system is capable of optogenetic manipulation and electrical recording of spatially defined neuronal populations for three months, allowing precise and long-term studies of neural circuit functions.
DHHC9-mediated GLUT1 S-palmitoylation promotes glioblastoma glycolysis and tumorigenesis
Authors: Zhang Zhenxing , Li Xin , Yang Fan , Chen Chao , Liu Ping , Ren Yi , Sun Pengkai , Wang Zixiong , You Yongping , Zeng Yi-Xin , Li Xinjian
Published: October 2021

Glucose transporter GLUT1 is a transmembrane protein responsible for the uptake of glucose into the cells of many tissues through facilitative diffusion. Plasma membrane (PM) localization is essential for glucose uptake by GLUT1. However, the mechanism underlying GLUT1 PM localization remains enigmatic. We find that GLUT1 is palmitoylated at Cys207, and S-palmitoylation is required for maintaining GLUT1 PM localization. Furthermore, we identify DHHC9 as the palmitoyl transferase responsible for this critical posttranslational modification. Knockout of DHHC9 or mutation of GLUT1 Cys207 to serine abrogates palmitoylation and PM distribution of GLUT1, and impairs glycolysis, cell proliferation, and glioblastoma (GBM) tumorigenesis. In addition, DHHC9 expression positively correlates with GLUT1 PM localization in GBM specimens and indicates a poor prognosis in GBM patients. These findings underscore that DHHC9-mediated GLUT1 S-palmitoylation is critical for glucose supply during GBM tumorigenesis.
Ni-catalyzed hydroalkylation of olefins with N-sulfonyl amines
Authors: Yan Xiao-Biao , Li Lun , Wu Wen-Qiang , Xu Lun , Li Ke , Liu Yu-Cheng , Shi Hang
Published: October 2021

Hydroalkylation, the direct addition of a C(sp3)–H bond across an olefin, is a desirable strategy to produce valuable, complex structural motifs in functional materials, pharmaceuticals, and natural products. Herein, we report a reliable method for accessing α-branched amines via nickel-catalyzed hydroalkylation reactions. Specifically, by using bis(cyclooctadiene)nickel (Ni(cod)2) together with a phosphine ligand, we achieved a formal C(sp3)–H bond insertion reaction between olefins and N-sulfonyl amines without the need for an external hydride source. The amine not only provides the alkyl motif but also delivers hydride to the olefin by means of a nickel-engaged β–hydride elimination/reductive elimination process. This method provides a platform for constructing chiral α-branched amines by using a P-chiral ligand, demonstrating its potential utility in organic synthesis. Notably, a sulfonamidyl boronate complex formed in situ under basic conditions promotes ring-opening of the azanickellacycle reaction intermediate, leading to a significant improvement of the catalytic efficiency.
A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex
Authors: Yao Zizhen , Liu Hanqing , Xie Fangming , Fischer Stephan , Adkins Ricky S. , Aldridge Andrew I. , Ament Seth A. , Bartlett Anna , Behrens M. Margarita , Van den Berge Koen , Bertagnolli Darren , de Bézieux Hector Roux , Biancalani Tommaso , Booeshaghi A. Sina , Bravo Héctor Corrada , Casper Tamara , Colantuoni Carlo , Crabtree Jonathan , Creasy Heather , Crichton Kirsten , Crow Megan , Dee Nick , Dougherty Elizabeth L. , Doyle Wayne I. , Dudoit Sandrine , Fang Rongxin , Felix Victor , Fong Olivia , Giglio Michelle , Goldy Jeff , Hawrylycz Mike , Herb Brian R. , Hertzano Ronna , Hou Xiaomeng , Hu Qiwen , Kancherla Jayaram , Kroll Matthew , Lathia Kanan , Li Yang Eric , Lucero Jacinta D. , Luo Chongyuan , Mahurkar Anup , McMillen Delissa , Nadaf Naeem M. , Nery Joseph R. , Nguyen Thuc Nghi , Niu Sheng-Yong , Ntranos Vasilis , Orvis Joshua , Osteen Julia K. , Pham Thanh , Pinto-Duarte Antonio , Poirion Olivier , Preissl Sebastian , Purdom Elizabeth , Rimorin Christine , Risso Davide , Rivkin Angeline C. , Smith Kimberly , Street Kelly , Sulc Josef , Svensson Valentine , Tieu Michael , Torkelson Amy , Tung Herman , Vaishnav Eeshit Dhaval , Vanderburg Charles R. , van Velthoven Cindy , Wang Xinxin , White Owen R. , Huang Z. Josh , Kharchenko Peter V. , Pachter Lior , Ngai John , Regev Aviv , Tasic Bosiljka , Welch Joshua D. , Gillis Jesse , Macosko Evan Z. , Ren Bing , Ecker Joseph R. , Zeng Hongkui , Mukamel Eran A.
Published: October 2021

Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain1–3. With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the mouse primary motor cortex, a structure that has an evolutionarily conserved role in locomotion. We developed computational and statistical methods to integrate multimodal data and quantitatively validate cell-type reproducibility. The resulting reference atlas—containing over 56 neuronal cell types that are highly replicable across analysis methods, sequencing technologies and modalities—is a comprehensive molecular and genomic account of the diverse neuronal and non-neuronal cell types in the mouse primary motor cortex. The atlas includes a population of excitatory neurons that resemble pyramidal cells in layer 4 in other cortical regions4. We further discovered thousands of concordant marker genes and gene regulatory elements for these cell types. Our results highlight the complex molecular regulation of cell types in the brain and will directly enable the design of reagents to target specific cell types in the mouse primary motor cortex for functional analysis.
An atlas of gene regulatory elements in adult mouse cerebrum
Authors: Li Yang Eric , Preissl Sebastian , Hou Xiaomeng , Zhang Ziyang , Zhang Kai , Qiu Yunjiang , Poirion Olivier B. , Li Bin , Chiou Joshua , Liu Hanqing , Pinto-Duarte Antonio , Kubo Naoki , Yang Xiaoyu , Fang Rongxin , Wang Xinxin , Han Jee Yun , Lucero Jacinta , Yan Yiming , Miller Michael , Kuan Samantha , Gorkin David , Gaulton Kyle J. , Shen Yin , Nunn Michael , Mukamel Eran A. , Behrens M. Margarita , Ecker Joseph R. , Ren Bing
Published: October 2021

The mammalian cerebrum performs high-level sensory perception, motor control and cognitive functions through highly specialized cortical and subcortical structures1. Recent surveys of mouse and human brains with single-cell transcriptomics2–6and high-throughput imaging technologies7,8have uncovered hundreds of neural cell types distributed in different brain regions, but the transcriptional regulatory programs that are responsible for the unique identity and function of each cell type remain unknown. Here we probe the accessible chromatin in more than 800,000 individual nuclei from 45 regions that span the adult mouse isocortex, olfactory bulb, hippocampus and cerebral nuclei, and use the resulting data to map the state of 491,818 candidatecis-regulatory DNA elements in 160 distinct cell types. We find high specificity of spatial distribution for not only excitatory neurons, but also most classes of inhibitory neurons and a subset of glial cell types. We characterize the gene regulatory sequences associated with the regional specificity within these cell types. We further link a considerable fraction of thecis-regulatory elements to putative target genes expressed in diverse cerebral cell types and predict transcriptional regulators that are involved in a broad spectrum of molecular and cellular pathways in different neuronal and glial cell populations. Our results provide a foundation for comprehensive analysis of gene regulatory programs of the mammalian brain and assist in the interpretation of noncoding risk variants associated with various neurological diseases and traits in humans.
Morphological diversity of single neurons in molecularly defined cell types
Authors: Peng Hanchuan , Xie Peng , Liu Lijuan , Kuang Xiuli , Wang Yimin , Qu Lei , Gong Hui , Jiang Shengdian , Li Anan , Ruan Zongcai , Ding Liya , Yao Zizhen , Chen Chao , Chen Mengya , Daigle Tanya L. , Dalley Rachel , Ding Zhangcan , Duan Yanjun , Feiner Aaron , He Ping , Hill Chris , Hirokawa Karla E. , Hong Guodong , Huang Lei , Kebede Sara , Kuo Hsien-Chi , Larsen Rachael , Lesnar Phil , Li Longfei , Li Qi , Li Xiangning , Li Yaoyao , Li Yuanyuan , Liu An , Lu Donghuan , Mok Stephanie , Ng Lydia , Nguyen Thuc Nghi , Ouyang Qiang , Pan Jintao , Shen Elise , Song Yuanyuan , Sunkin Susan M. , Tasic Bosiljka , Veldman Matthew B. , Wakeman Wayne , Wan Wan , Wang Peng , Wang Quanxin , Wang Tao , Wang Yaping , Xiong Feng , Xiong Wei , Xu Wenjie , Ye Min , Yin Lulu , Yu Yang , Yuan Jia , Yuan Jing , Yun Zhixi , Zeng Shaoqun , Zhang Shichen , Zhao Sujun , Zhao Zijun , Zhou Zhi , Huang Z. Josh , Esposito Luke , Hawrylycz Michael J. , Sorensen Staci A. , Yang X. William , Zheng Yefeng , Gu Zhongze , Xie Wei , Koch Christof , Luo Qingming , Harris Julie A. , Wang Yun , Zeng Hongkui
Published: October 2021

Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits.
Isoform cell-type specificity in the mouse primary motor cortex
Authors: Booeshaghi A. Sina , Yao Zizhen , van Velthoven Cindy , Smith Kimberly , Tasic Bosiljka , Zeng Hongkui , Pachter Lior
Published: October 2021

Full-length SMART-seq1 single-cell RNA sequencing can be used to measure gene expression at isoform resolution, making possible the identification of specific isoform markers for different cell types. Used in conjunction with spatial RNA capture and gene-tagging methods, this enables the inference of spatially resolved isoform expression for different cell types. Here, in a comprehensive analysis of 6,160 mouse primary motor cortex cells assayed with SMART-seq, 280,327 cells assayed with MERFISH2 and 94,162 cells assayed with 10x Genomics sequencing3, we find examples of isoform specificity in cell types—including isoform shifts between cell types that are masked in gene-level analysis—as well as examples of transcriptional regulation. Additionally, we show that isoform specificity helps to refine cell types, and that a multi-platform analysis of single-cell transcriptomic data leveraging multiple measurements provides a comprehensive atlas of transcription in the mouse primary motor cortex that improves on the possibilities offered by any single technology.
Thalamic circuits for independent control of prefrontal signal and noise
Authors: Mukherjee Arghya , Lam Norman H. , Wimmer Ralf D. , Halassa Michael M.
Published: October 2021

Interactions between the mediodorsal thalamus and the prefrontal cortex are critical for cognition. Studies in humans indicate that these interactions may resolve uncertainty in decision-making1, but the precise mechanisms are unknown. Here we identify two distinct mediodorsal projections to the prefrontal cortex that have complementary mechanistic roles in decision-making under uncertainty. Specifically, we found that a dopamine receptor (D2)-expressing projection amplifies prefrontal signals when task inputs are sparse and a kainate receptor (GRIK4) expressing-projection suppresses prefrontal noise when task inputs are dense but conflicting. Collectively, our data suggest that there are distinct brain mechanisms for handling uncertainty due to low signals versus uncertainty due to high noise, and provide a mechanistic entry point for correcting decision-making abnormalities in disorders that have a prominent prefrontal component2–6.
Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial
Authors: Stephenson Kathryn E. , Julg Boris , Tan C. Sabrina , Zash Rebecca , Walsh Stephen R. , Rolle Charlotte-Paige , Monczor Ana N. , Lupo Sofia , Gelderblom Huub C. , Ansel Jessica L. , Kanjilal Diane G. , Maxfield Lori F. , Nkolola Joseph , Borducchi Erica N. , Abbink Peter , Liu Jinyan , Peter Lauren , Chandrashekar Abishek , Nityanandam Ramya , Lin Zijin , Setaro Alessandra , Sapiente Joseph , Chen Zhilin , Sunner Lisa , Cassidy Tyler , Bennett Chelsey , Sato Alicia , Mayer Bryan , Perelson Alan S. , deCamp Allan , Priddy Frances H. , Wagh Kshitij , Giorgi Elena E. , Yates Nicole L. , Arduino Roberto C. , DeJesus Edwin , Tomaras Georgia D. , Seaman Michael S. , Korber Bette , Barouch Dan H.
Published: October 2021

Human immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial of a single administration of the HIV-1 V3-glycan-specific antibody PGT121 at 3, 10 and 30 mg kg–1 in HIV-uninfected adults and HIV-infected adults on antiretroviral therapy (ART), as well as a multicenter, open-label trial of one infusion of PGT121 at 30 mg kg–1 in viremic HIV-infected adults not on ART (no. NCT02960581). The primary endpoints were safety and tolerability, pharmacokinetics (PK) and antiviral activity in viremic HIV-infected adults not on ART. The secondary endpoints were changes in anti-PGT121 antibody titers and CD4+ T-cell count, and development of HIV-1 sequence variations associated with PGT121 resistance. Among 48 participants enrolled, no treatment-related serious adverse events, potential immune-mediated diseases or Grade 3 or higher adverse events were reported. The most common reactions among PGT121 recipients were intravenous/injection site tenderness, pain and headache. Absolute and relative CD4+ T-cell counts did not change following PGT121 infusion in HIV-infected participants. Neutralizing anti-drug antibodies were not elicited. PGT121 reduced plasma HIV RNA levels by a median of 1.77 log in viremic participants, with a viral load nadir at a median of 8.5 days. Two individuals with low baseline viral loads experienced ART-free viral suppression for ≥168 days following antibody infusion, and rebound viruses in these individuals demonstrated full or partial PGT121 sensitivity. The trial met the prespecified endpoints. These data suggest that further investigation of the potential of antibody-based therapeutic strategies for long-term suppression of HIV is warranted, including in individuals off ART and with low viral load.
Identifying hidden coalitions in the US House of Representatives by optimally partitioning signed networks based on generalized balance
Authors: Aref Samin , Neal Zachary P.
Published: October 2021

In network science, identifying optimal partitions of a signed network into internally cohesive and mutually divisive clusters based on generalized balance theory is computationally challenging. We reformulate and generalize two binary linear programming models that tackle this challenge, demonstrating their practicality by applying them to partition signed networks of collaboration and opposition in the US House of Representatives. These models guarantee a globally optimal network partition and can be practically applied to signed networks containing up to 30,000 edges. In the US House context, we find that a three-cluster partition is better than a conventional two-cluster partition, where the otherwise hidden third coalition is composed of highly effective legislators who are ideologically aligned with the majority party.
Electricity-consumption data reveals the economic impact and industry recovery during the pandemic
Authors: Wang Xinlei , Si Caomingzhe , Gu Jinjin , Liu Guolong , Liu Wenxuan , Qiu Jing , Zhao Junhua
Published: October 2021

Coping with the outbreak of Coronavirus disease 2019 (COVID-19), many countries have implemented public-health measures and movement restrictions to prevent the spread of the virus. However, the strict mobility control also brought about production stagnation and market disruption, resulting in a severe worldwide economic crisis. Quantifying the economic stagnation and predicting post-pandemic recovery are imperative issues. Besides, it is significant to examine how the impact of COVID-19 on economic activities varied with industries. As a reflection of enterprises’ production output, high-frequency electricity-consumption data is an intuitive and effective tool for evaluating the economic impact of COVID-19 on different industries. In this paper, we quantify and compare economic impacts on the electricity consumption of different industries in eastern China. In order to address this problem, we conduct causal analysis using a difference-in-difference (DID) estimation model to analyze the effects of multi-phase public-health measures. Our model employs the electricity-consumption data ranging from 2019 to 2020 of 96 counties in the Eastern China region, which covers three main economic sectors and their 53 sub-sectors. The results indicate that electricity demand of all industries (other than information transfer industry) rebounded after the initial shock, and is back to pre-pandemic trends after easing the control measures at the end of May 2020. Emergency response, the combination of all countermeasures to COVID-19 in a certain period, affected all industries, and the higher level of emergency response with stricter movement control resulted in a greater decrease in electricity consumption and production. The pandemic outbreak has a negative-lag effect on industries, and there is greater resilience in industries that are less dependent on human mobility for economic production and activities.
Hepatobiliary phenotype of individuals with chronic intestinal disorders
Authors: Voss Jessica , Schneider Carolin V. , Kleinjans Moritz , Bruns Tony , Trautwein Christian , Strnad Pavel
Published: October 2021

Despite the known functional relationship between the gut and the liver, the clinical consequences of this circuit remain unclear. We assessed the hepatobiliary phenotype of cohorts with celiac disease (CeD), Crohn´s disease (CD) and ulcerative colitis (UC). Baseline liver function tests and the frequency of hepatobiliary diseases were analyzed in 2377 CeD, 1738 CD, 3684 UC subjects and 488,941 controls from the population-based UK Biobank cohort. In this cohort study associations were adjusted for age, sex, BMI, diabetes, and alcohol consumption. Compared to controls, cohorts with CeD, but not CD/UC displayed higher AST/ALT values. Subjects with CD/UC but not CeD had increased GGT levels. Elevated ALP and cholelithiasis were significantly more common in all intestinal disorders. Non-alcoholic steatohepatitis and hepatocellular carcinoma (HCC) were enriched in CeD and CD (NASH: taOR = 4.9 [2.2–11.0] in CeD, aOR = 4.2 [1.7–10.3] in CD, HCC: aOR = 4.8 [1.8–13.0] in CeD, aOR = 5.9 [2.2–16.1] in CD), while cholangitis was more common in the CD/UC cohorts (aOR = 11.7 [9.1–15.0] in UC, aOR = 3.5 [1.8–6.8] in CD). Chronic hepatitis, autoimmune hepatitis (AIH) and cirrhosis were more prevalent in all intestinal disorders. In UC/CD, a history of intestinal surgery was associated with elevated liver enzymes and increased occurrence of gallstones (UC: aOR = 2.9 [2.1–4.1], CD: 1.7 [1.2–2.3]). Our data demonstrate that different intestinal disorders predispose to distinct hepatobiliary phenotypes. An increased occurrence of liver cirrhosis, NASH, AIH and HCC and the impact of surgery warrant further exploration.
Total synthesis of (±)-decursivine via BINOL-phosphoric acid catalyzed tandem oxidative cyclization
Authors: Parvatkar Prakash T. , Smotkin Eugene S. , Manetsch Roman
Published: October 2021

The synthesis of tetracyclic indole alkaloid (±)-decursivine was accomplished using BINOL-phosphoric acid catalyzed tandem oxidative cyclization as a key step with (bis(trifluoroacetoxy)iodo)benzene (PIFA) as an oxidizing agent. This represents one of the shortest and highest yielding routes for the synthesis of (±)-decursivine from readily available starting materials.
Mechanisms and management considerations of parent-chosen feeding approaches to infants with swallowing difficulties: an observational study
Authors: Jadcherla Sudarshan R. , Hasenstab Kathryn A. , Osborn Erika K. , Levy Deborah S. , Ipek Haluk , Helmick Roseanna , Sultana Zakia , Logue Nicole , Yildiz Vedat O. , Blosser Hailey , Shah Summit H. , Wei Lai
Published: October 2021

Videofluoroscopy swallow studies (VFSS) and high-resolution manometry (HRM) methods complement to ascertain mechanisms of infant feeding difficulties. We hypothesized that: (a) an integrated approach (study: parent-preferred feeding therapy based on VFSS and HRM) is superior to the standard-of-care (control: provider-prescribed feeding therapy based on VFSS), and (b) motility characteristics are distinct in infants with penetration or aspiration defined as penetration-aspiration scale (PAS) score ≥ 2. Feeding therapies were nipple flow, fluid thickness, or no modification. Clinical outcomes were oral-feeding success (primary), length of hospital stay and growth velocity. Basal and adaptive HRM motility characteristics were analyzed for study infants. Oral feeding success was 85% [76–94%] in study (N = 60) vs. 63% [50–77%] in control (N = 49),p = 0.008. Hospital-stay and growth velocity did not differ between approaches or PAS ≥ 2 (allP > 0.05). In study infants with PAS ≥ 2, motility metrics differed for increased deglutition apnea during interphase (p = 0.02), symptoms with pharyngeal stimulation (p = 0.02) and decreased distal esophageal contractility (p = 0.004) with barium. In conclusion, an integrated approach with parent-preferred therapy based on mechanistic understanding of VFSS and HRM metrics improves oral feeding outcomes despite the evidence of penetration or aspiration. Implementation of new knowledge of physiology of swallowing and airway protection may be contributory to our findings.
Modular fluorescent nanoparticle DNA probes for detection of peptides and proteins
Authors: Stawicki Cassandra M. , Rinker Torri E. , Burns Markus , Tonapi Sonal S. , Galimidi Rachel P. , Anumala Deepthi , Robinson Julia K. , Klein Joshua S. , Mallick Parag
Published: October 2021

Fluorescently labeled antibody and aptamer probes are used in biological studies to characterize binding interactions, measure concentrations of analytes, and sort cells. Fluorescent nanoparticle labels offer an excellent alternative to standard fluorescent labeling strategies due to their enhanced brightness, stability and multivalency; however, challenges in functionalization and characterization have impeded their use. This work introduces a straightforward approach for preparation of fluorescent nanoparticle probes using commercially available reagents and common laboratory equipment. Fluorescent polystyrene nanoparticles, Thermo Fisher Scientific FluoSpheres, were used in these proof-of-principle studies. Particle passivation was achieved by covalent attachment of amine-PEG-azide to carboxylated particles, neutralizing the surface charge from − 43 to − 15 mV. A conjugation-annealing handle and DNA aptamer probe were attached to the azide-PEG nanoparticle surface either through reaction of pre-annealed handle and probe or through a stepwise reaction of the nanoparticles with the handle followed by aptamer annealing. Nanoparticles functionalized with DNA aptamers targeting histidine tags and VEGF protein had high affinity (EC50s ranging from 3 to 12 nM) and specificity, and were more stable than conventional labels. This protocol for preparation of nanoparticle probes relies solely on commercially available reagents and common equipment, breaking down the barriers to use nanoparticles in biological experiments.
Population viability analysis of the endangered Dupont’s Lark Chersophilus duponti in Spain
Authors: García-Antón Alexander , Traba Juan
Published: October 2021

Steppe lands in Europe are critically affected by habitat loss and fragmentation, and hold over 50% of IUCN Red List bird species in Europe. Dupont’s Lark is a threatened steppe-specialist passerine whose European geographic range is restricted to Spain, with less than 2000 pairs and an annual population decline of − 3.9%. Its strongly fragmented habitat leads to a metapopulation structure in the Iberian Peninsula that includes 24 populations and 100 subpopulations. We present an updated Population Viability Analysis based on the latest scientific knowledge regarding distribution, population trends, breeding biology and connectivity. Our results predict metapopulation extinction in 2–3 decades, through a centripetal contraction process from the periphery to the core. The probability of extinction in 20 years was 84.2%, which supports its relisting to Endangered in Spain following IUCN criteria. We carried out a sensitivity analysis showing that some parameters, especially productivity and survival of adults and juveniles, help to increase metapopulation viability. Simulation of management scenarios showed that habitat restoration in a subset of key subpopulations had a positive effect on the overall metapopulation persistence. Translocations of a limited number of individuals from source to recipient locations may help to rescue the most endangered subpopulations without reducing the global time to extinction of the metapopulation. In addition, we identified the most critical areas for action, where local populations of the species are prone to extinction. This work suggests that the viability of the Dupont’s Lark metapopulation could be improved and its risk of extinction reduced if urgent and localized conservation measures are applied. In the short-term, habitat loss and fragmentation due to ploughing, reforestation and infrastructures implementation in Dupont’s Lark habitat must be avoided. Habitat restoration and translocations could help to avoid imminent extinction of critical subpopulations. Restoration of extensive grazing is recommended as the most effective way to achieve the long-term conservation of Dupont’s Lark in Spain.
Using machine learning methods for supporting GR2M model in runoff estimation in an ungauged basin
Authors: Ditthakit Pakorn , Pinthong Sirimon , Salaeh Nureehan , Binnui Fadilah , Khwanchum Laksanara , Pham Quoc Bao
Published: October 2021

Estimating monthly runoff variation, especially in ungauged basins, is inevitable for water resource planning and management. The present study aimed to evaluate the regionalization methods for determining regional parameters of the rainfall-runoff model (i.e., GR2M model). Two regionalization methods (i.e., regression-based methods and distance-based methods) were investigated in this study. Three regression-based methods were selected including Multiple Linear Regression (MLR), Random Forest (RF), and M5 Model Tree (M5), and two distance-based methods included Spatial Proximity Approach and Physical Similarity Approach (PSA). Hydrological data and the basin's physical attributes were analyzed from 37 runoff stations in Thailand's southern basin. The results showed that using hydrological data for estimating the GR2M model parameters is better than using the basin's physical attributes. RF had the most accuracy in estimating regional GR2M model’s parameters by giving the lowest error, followed by M5, MLR, SPA, and PSA. Such regional parameters were then applied in estimating monthly runoff using the GR2M model. Then, their performance was evaluated using three performance criteria, i.e., Nash–Sutcliffe Efficiency (NSE), Correlation Coefficient (r), and Overall Index (OI). The regionalized monthly runoff with RF performed the best, followed by SPA, M5, MLR, and PSA. The Taylor diagram was also used to graphically evaluate the obtained results, which indicated that RF provided the products closest to GR2M's results, followed by SPA, M5, PSA, and MLR. Our finding revealed the applicability of machine learning for estimating monthly runoff in the ungauged basins. However, the SPA would be recommended in areas where lacking the basin's physical attributes and hydrological information.
Higher hemoglobin levels are an independent risk factor for adverse metabolism and higher mortality in a 20-year follow-up
Authors: Tapio Joona , Vähänikkilä Hannu , Kesäniemi Y. Antero , Ukkola Olavi , Koivunen Peppi
Published: October 2021

The aim of this study was to cross-sectionally and longitudinally examine whether higher hemoglobin (Hb) levels within the normal variation associate with key components of metabolic syndrome and total and cardiovascular mortality. The study included 967 Finnish subjects (age 40–59 years) followed for ≥ 20 years. The focus was on Hb levels, cardiovascular diseases (CVDs) and mortality rates. Higher Hb levels associated positively with key anthropometric and metabolic parameters at baseline. At the follow-up similar associations were seen in men. The highest Hb quartile showed higher leptin levels and lower adiponectin levels at baseline and follow-up (p < 0.05) and lower plasma ghrelin levels at baseline (p < 0.05). Higher baseline Hb levels associated independently with prevalence of type 2 diabetes at follow-up (p < 0.01). The highest Hb quartile associated with higher serum alanine aminotransferase levels (p < 0.001) and independently with increased risk for liver fat accumulation (OR 1.63 [1.03; 2.57]) at baseline. The highest Hb quartile showed increased risk for total (HR = 1.48 [1.01; 2.16]) and CVD-related mortality (HR = 2.08 [1.01; 4.29]). Higher Hb levels associated with an adverse metabolic profile, increased prevalence of key components of metabolic syndrome and higher risk for CVD-related and total mortality.
Dual solution for double-diffusive mixed convection opposing flow through a vertical cylinder saturated in a Darcy porous media containing gyrotactic microorganisms
Authors: Alsenafi Abdulaziz , Ferdows M.
Published: October 2021

The steady mixed convection flow towards an isothermal permeable vertical cylinder nested in a fluid-saturated porous medium is studied. The Darcy model is applied to observe bioconvection through porous media. The suspension of gyrotactic microorganisms is considered for various applications in bioconvection. Appropriate similarity variables are opted to attain the dimensionless form of governing equations. The resulting momentum, energy, concentration, and motile microorganism density equations are then solved numerically. The resulting dual solutions are graphically visualized and physically analyzed. The results indicate that depending on the systems' parameters, dual solutions exist in opposing flow beyond a critical point where both solutions are connected. Our results were also compared with existing literature.
Age estimation using methylation-sensitive high-resolution melting (MS-HRM) in both healthy felines and those with chronic kidney disease
Authors: Qi Huiyuan , Kinoshita Kodzue , Mori Takashi , Matsumoto Kaori , Matsui Yukiko , Inoue-Murayama Miho
Published: October 2021

Age is an important ecological tool in wildlife conservation. However, it is difficult to estimate in most animals, including felines—most of whom are endangered. Here, we developed the first DNA methylation-based age-estimation technique—as an alternative to current age-estimation methods—for two feline species that share a relatively long genetic distance with each other: domestic cat (Felis catus; 79 blood samples) and an endangered Panthera, the snow leopard (Panthera uncia; 11 blood samples). We measured the methylation rates of two gene regions using methylation-sensitive high-resolution melting (MS-HRM). Domestic cat age was estimated with a mean absolute deviation (MAD) of 3.83 years. Health conditions influenced accuracy of the model. Specifically, the models built on cats with chronic kidney disease (CKD) had lower accuracy than those built on healthy cats. The snow leopard-specific model (i.e. the model that resets the model settings for snow leopards) had a better accuracy (MAD = 2.10 years) than that obtained on using the domestic cat model directly. This implies that our markers could be utilised across species, although changing the model settings when targeting different species could lead to better estimation accuracy. The snow leopard-specific model also successfully distinguished between sexually immature and mature individuals.
IoT device fabrication using roll-to-roll printing process
Authors: Phung Thanh Huy , Gafurov Anton Nailevich , Kim Inyoung , Kim Sung Yong , Kim Kyoung Min , Lee Taik-Min
Published: October 2021

With the development of technology, wireless and IoT devices are increasingly used from daily life to industry, placing demands on rapid and efficient manufacturing processes. This study demonstrates the fabrication of an IoT device using a roll-to-roll printing process, which could shorten the device fabrication time and reduce the cost of mass production. Here, the fabricated IoT device is designed to acquire data through the sensor, process the data, and communicate with end-user devices via Bluetooth communication. For fabrication, a four-layer circuit platform consisting of two conductive layers, an insulating layer including through holes, and a solder resist layer is directly printed using a roll-to-roll screen printing method. After the printing of the circuit platform, an additional layer of solder paste is printed to assemble the electrical components into the device, inspiring the fully roll-to-roll process for device fabrication. Successful IoT device deployment opens the chance to broaden the roll-to-roll fabrication process to other flexible and multilayer electronic applications.
A case study on TBM cutterhead temperature monitoring and mud cake formation discrimination method
Authors: Fu Jie , Xia Yimin , Lan Hao , Wu Dun , Lin Laikuang
Published: October 2021

The mud cake is easily formed during the tunnel boring machine (TBM) excavation in clay soils or rocks containing clay minerals. Mud cake will lead to soil disturbance of tunnel face, clogging cutterhead and even affect the construction efficiency and personnel safety. In this study, a discrimination method of mud cake formation based on cutterhead temperature was proposed. An online monitoring system was designed and installed on the slurry balance TBM. The results show that: (a) the cutterhead temperature data can be reliably detected and transmitted by the system; (b) in a tunneling cycle, the temperature at some positions of the cutterhead will increase first and then decrease; (c) during the field test, the temperature variation is around 2.5 °C under the normal condition, but the temperature variation will increase more than 50 °C due to the mud cake or geological change; (d) compared with the cooling rate, mud cake formation can be accurately discriminated.
Segmental contribution to whole-body angular momentum during stepping in healthy young and old adults
Authors: Begue Jérémie , Peyrot Nicolas , Lesport Angélique , Turpin Nicolas A. , Watier Bruno , Dalleau Georges , Caderby Teddy
Published: October 2021

Recent evidence suggests that during volitional stepping older adults control whole-body angular momentum (H) less effectively than younger adults, which may impose a greater challenge for balance control during this task in the elderly. This study investigated the influence of aging on the segment angular momenta and their contributions to H during stepping. Eighteen old and 15 young healthy adults were instructed to perform a series of stepping at two speed conditions: preferred and as fast as possible. Full-body kinematics were recorded to compute angular momenta of the trunk, arms and legs and their contributions to total absolute H on the entire stepping movement. Results indicated that older adults exhibited larger angular momenta of the trunk and legs in the sagittal plane, which contributed to a higher sagittal plane H range during stepping compared to young adults. Results also revealed that older adults had a greater trunk contribution and lower leg contribution to total absolute H in the sagittal plane compared to young adults, even though there was no difference in the other two planes. These results stress that age-related changes in H control during stepping arise as a result of changes in trunk and leg rotational dynamics.