bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning suggests polygenic contribution to cognitive dysfunction in amyotrophic lateral sclerosis
Authors: Placek Katerina , Benatar Michael , Wuu Joanne , Rampersaud Evadnie , Hennessy Laura , Van Deerlin Vivianna M. , Grossman Murray , Irwin David J. , Elman Lauren , McCluskey Leo , Quinn Colin , Granit Volkan , Statland Jeffrey M. , Burns Ted M. , Ravits John , Swenson Andrea , Katz Jon , Pioro Erik , Jackson Carlayne , Caress James , So Yuen , Maiser Samuel , Walk David , Lee Edward B. , Trojanowski John Q. , Cook Philip , Gee James , Sha Jin , Naj Adam C. , Rademakers Rosa ,   The CReATe Consortium, Chen Wenan , Wu Gang , Taylor J. Paul , McMillan Corey T. 
Published: December 2019

AbstractAmyotrophic lateral sclerosis (ALS) is a multi-system disease characterized primarily by progressive muscle weakness. Cognitive dysfunction is commonly observed in patients, however factors influencing risk for cognitive dysfunction remain elusive. Using sparse canonical correlation analysis (sCCA), an unsupervised machine-learning technique, we observed that single nucleotide polymorphisms collectively associate with baseline cognitive performance in a large ALS patient cohort (N=327) from the multicenter Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium. We demonstrate that a polygenic risk score derived using sCCA relates to longitudinal cognitive decline in the same cohort, and also to in vivo cortical thinning in the orbital frontal cortex, anterior cingulate cortex, lateral temporal cortex, premotor cortex, and hippocampus (N=90) as well as post mortem motor cortical neuronal loss (N=87) in independent ALS cohorts from the University of Pennsylvania Integrated Neurodegenerative Disease Biobank. Our findings suggest that common genetic polymorphisms may exert a polygenic contribution to the risk of cortical disease vulnerability and cognitive dysfunction in ALS.
Crystal structure of a human plasma membrane phospholipid flippase
Authors: Nakanishi Hanayo , Irie Katsumasa , Segawa Katsumori , Hasegawa Kazuya , Fujiyoshi Yoshinori , Nagata Shigekazu , Abe Kazuhiro 
Published: December 2019

AbstractATP11C, a member of P4-ATPase flippase, exclusively translocates phosphatidylserine from the outer to the inner leaflets of the plasma membrane, and maintains the asymmetric distribution of phosphatidylserine in the living cell. However, the mechanisms by which ATP11C translocates phosphatidylserine remain elusive. Here we show the crystal structures of a human plasma membrane flippase, ATP11C-CDC50A complex, in an outward-open E2P conformation. Two phosphatidylserine molecules are in a conduit that continues from the cell surface to the occlusion site in the middle of the membrane. Mutations in either of the phosphotidylserine binding sites or along the pathway between significantly impairs specific ATPase and transport activities. We propose a model for phosphatidylserine translocation from the outer to the inner leaflet of the plasma membrane.
The transcriptome dynamics of single cells during the cell cycle
Authors: Schwabe Daniel , Formichetti Sara , Junker Jan Philipp , Falcke Martin , Rajewsky Nikolaus 
Published: December 2019

AbstractDespite advances in single-cell data analysis, the dynamics and topology of the cell cycle in high-dimensional gene expression space remains largely unknown. Here, we use a linear analysis of transcriptome data to reveal that cells move along a circular trajectory in transcriptome space during the cell cycle. This movement occurs largely independently from other cellular processes. Non-cycling gene expression (changes in environment or epigenetic state) adds a third dimension and causes helical motion on a hollow cylinder. The circular trajectory shape indicates minimal acceleration of transcription, i.e. the cell cycle has evolved to minimize changes of transcriptional activity and its entailing regulatory effort. Thus, we uncover a general design principle of the cell cycle that may be of relevance to many other cellular differentiation processes.One Sentence SummaryCells traverse high-dimensional gene expression space in a 2D circular motion, thus minimizing changes of expression changes (“Acceleration”).
The mechanosensitive Piezo1 orchestrating angiogenesis is essential in bone fracture repair
Authors: Chen Peng , Zhang Gangyu , Jiang Shan , Ning Yile , Deng Bo , Pan Xianmei , Liu Silin , He Yu , Zhang Lei , Wan Rentao , Wu Zhiming , He Qi , Yin Jiang , Wang Haibin , Li Jing 
Published: December 2019

AbstractMechanical ion channel proteinPiezo1play vital roles in angiogenesis which has been proved to be high importance in varieties of biological processes. Bone formation in the fracture repair requires oxygen and nutrients from new blood vessels generated from fractured lesion. Understanding the underlying mechanisms linking angiogenesis and bone formation must be of great value for improved fracture healing. Here we employed mice with genetically modified endothelial specific depletion ofPiezo1channels to explore the hypothesis thatPiezo1is vital to the initiation of fracture healing. In this study, we demonstrated thatPiezo1expression and wide distribution along the bone and impaired endothelialPiezo1channels result in derangements in bone fracture repair. Intriguingly, the calcium activated proteolytic caplain activity severely disrupted during vascularization, precluded osteoblast maturation and mineralization and subsequently the phosphorylatedPI3K-AKTreduction. Furthermore,Piezo1endothelial disruption impairedNotchsignaling in bone union. These data collectively suggest thatPiezo1channels serve as a basis for clinical strategies to improve bone regeneration and treat delayed or nonunion in bone fracture.
Zebrafishdazlregulates cystogenesis upstream of the meiotic transition and germline stem cell specification and independent of meiotic checkpoints
Authors: Bertho Sylvain , Clapp Mara , Banisch Torsten U. , Bandemer Jan , Raz Erez , Marlow Florence L. 
Published: December 2019

AbstractFertility and gamete reserves are maintained by asymmetric divisions of the germline stem cells to produce new stem cells or daughters that differentiate as gametes. Before entering meiosis, differentiating germ cells (GCs) of sexual animals typically undergo cystogenesis. This evolutionary conserved process involves synchronous and incomplete mitotic divisions of a germ cell daughter (cystoblast) to generate sister cells connected by stable intercellular bridges that facilitate exchange of materials to support a large synchronous population of gamete progenitors. Here we investigate cystogenesis in zebrafish and identified Deleted in azoospermia (Dazl), a conserved vertebrate RNA binding protein as a regulator of this process. Analysis ofdazlmutants revealed an essential role for Dazl in regulating incomplete cytokinesis and germline cyst formation before the meiotic transition. Accordingly,dazlmutant GCs form defective ring canals, and ultimately remain as individual cells that fail to differentiate as meiocytes. In addition to promoting cystoblast divisions and meiotic entry,dazlfunction is required upstream of germline stem cell establishment and fertility.Summary StatementWe show that zebrafishdazlis required for incomplete cytokinesis to generate germline cysts during cystogenesis, acts upstream of germline stem cell establishment, and is required for meiosis, and fertility.
KCNQ channels enable reliable presynaptic spiking and synaptic transmission at high-frequency
Authors: Zhang Yihui , Li Dainan , Darwish Youad , Trussell Laurence O. , Huang Hai 
Published: December 2019

SUMMARYThe presynaptic action potential (AP) results in calcium influx which triggers neurotransmitter release. For this reason, the AP waveform is crucial in determining the timing and strength of synaptic transmission. The calyx of Held nerve terminals of rat show minimum changes in AP waveform during high-frequency AP firing. We found that the stability of the calyceal AP waveform requires KCNQ K+channel activated during high-frequency spiking activity. High-frequency presynaptic spikes gradually led to accumulation of KCNQ channels in open states which kept interspike membrane potential sufficiently negative to maintain Na+channel availability. Accordingly, blocking KCNQ channels during stimulus trains led to inactivation of presynaptic Na+, and to a lesser extent KV1 channels, thereby reducing the AP height and broadening AP duration. Thus, while KCNQ channels are generally thought to prevent hyperactivity of neurons, we find that in axon terminals these channels function to facilitate high-frequency firing needed for sensory coding.HIGHLIGHTSKCNQ channels are activated during high-frequency firingThe activity of KCNQ channels helps the recovery of Na+and KV1 channels from inactivation and maintains action potential waveformReliable presynaptic action potential waveform preserves stable Ca2+influx and reliable synaptic signaling
ETHYLENE RESPONSE FACTOR 115integrates jasmonate and cytokinin signaling machineries to repress adventitious rooting inArabidopsis
Authors: Lakehal Abdellah , Dob Asma , Rahneshan Zahra , Novák Ondřej , Escamez Sacha , Alallaq Sanaria , Strnad Miroslav , Tuominen Hannele , Bellini Catherine 
Published: December 2019

ABSTRACTJasmonate (JA), an oxylipin-derived phytohormone, plays crucial roles not only in plant immunity and defense against herbivorous insects but also in plant growth and developmental processes, including regeneration and organogenesis. However, the mechanistic basis of its mode of action and precise role in integrating other signaling cues are poorly understood. Here we provide genetic evidences that JA signaling acts in both NINJA-dependent and -independent modulation of the transcriptional activity of MYC transcription factors involved in the inhibition of adventitious root initiation (ARI). Our data show that NINJA-dependent JA signaling in pericycle cells blocks early events of ARI. Moreover, transcriptomic comparison ofninja-1myc2-322Bdouble mutant (which produce extremely few ARs) and wild type seedlings identified a novel molecular network governed by the APETALA2/ETHYLENE RESPONSE FACTOR 115 (ERF115) transcription factor. We demonstrate that JA-inducedERF115activates the cytokinin signaling machinery and thereby represses ARI. Altogether, our results reveal a molecular network involving cooperative crosstalk between JA and CK machineries that inhibits ARI.
Dreaming saints: exploratory authority and Islamic praxes of history in Central Java
Authors: Alatas Ismail Fajrie 
Published: December 2019

AbstractThis article examines dreaming as an Islamic practice of historical inquiry among traditionalist Muslims of Central Java, Indonesia. Combining insights from the anthropologies of Islam and history, it looks at alternative praxes of history, how they are interpreted through Islamic frameworks, and how they generate forms of religious authority. The article follows the work of a Sufi master, Habib Luthfi bin Yahya, in identifying old unmarked graves as saintly tombs through dreams. Successful history‐making projects have resulted in the increasing – albeit contested – recognition of Habib Luthfi's role as a dreaming saint, a form of Islamic authority premised on his perceived ability to oneirically explore the past on behalf of others and arbitrate history. By observing the connection between praxes of history and the formation of religious authority, the article calls for the broadening of anthropological studies of Islam beyond their current preoccupation with the religion's prescriptive dimension.
Uneasy translations: vernacularizing demography for post‐Soviet statecraft
Authors: Leykin Inna 
Published: December 2019

AbstractThe article explores a series of professional development seminars for state bureaucrats in the context of the moral panic over Russia's ‘demographic crisis’. It follows the vernacularization of social knowledge for state bureaucrats – a central practice that marks these pedagogical engagements. The article explores this practice's potentialities and limitations for effectively communicating social knowledge to administrative audiences. It grounds itself in the theoretical discussions of expertise and demonstrates how vernacularizing social knowledge for post‐Soviet statecraft shapes the social and political meanings of Russia's demographic crisis, investing state policies and discourses with authority.
Successful societies: Decision‐making and the quality of attentiveness
Authors: Stones Rob , Turner Bryan S. 
Published: December 2019

AbstractCombining moral philosophy with sociological theory to build on themes introduced in Hall and Lamont’s Successful Societies (2009), the paper outlines a distinctive perspective. It holds that a necessary condition of successful societies is that decision‐makers base their decisions on a high level of attentiveness (concern and comprehension) towards subjectively valued and morally legitimate forms of life. Late modern societies consist of a plurality of forms of life, each providing grounds for what Alasdair MacIntyre has called internal goods—valued and morally valuable practices. The status of such goods is examined, and distinctions are drawn between their manifest and latent, and transposable and situationally specific, characteristics. We integrate this refined idea of internal goods into a developed conception of habitus that is both morally informed and situationally embedded. The sociological approach of strong structuration theory (SST) is employed to demonstrate how this conception of habitus can guide the critique of decision‐making that damages internal goods. We identify the most pervasive and invidious forms of damaging decision‐making in contemporary societies as those involving excessive forms of instrumental reasoning. We argue that our developed conception of habitus, anchored in the collectively valued practices of specific worlds, can be a powerful focus for resistance. Accounts of scholarship in higher education and of the white working class in America illustrate the specificities of singular, particular, social worlds and illuminate critical challenges raised by the perspective we advocate.
Progress and challenges in engineering cyanobacteria as chassis for light‐driven biotechnology
Authors: Hitchcock Andrew , Hunter C. Neil , Canniffe Daniel P. 
Published: December 2019

SummaryCyanobacteria are prokaryotic phototrophs that, in addition to being excellent model organisms for studying photosynthesis, have tremendous potential for light‐driven synthetic biology and biotechnology. These versatile and resilient microorganisms harness the energy of sunlight to oxidise water, generating chemical energy (ATP) and reductant (NADPH) that can be used to drive sustainable synthesis of high‐value natural products in genetically modified strains. In this commentary article for the Synthetic Microbiology Caucus we discuss the great progress that has been made in engineering cyanobacterial hosts as microbial cell factories for solar‐powered biosynthesis. We focus on some of the main areas where the synthetic biology and metabolic engineering tools in cyanobacteria are not as advanced as those in more widely used heterotrophic chassis, and go on to highlight key improvements that we feel are required to unlock the full power of cyanobacteria for future green biotechnology.
The embryonic development of the bovine stomach revisited
Authors: Kalenberg Christina Alexandra , Stoffel Michael Hubert 
Published: December 2019

AbstractThe adult anatomy and physiology of the bovine (Bos taurus) stomach have been investigated extensively. Despite the many studies, however, the early development of the stomach has not yet been fully elucidated. The goal of the present study, therefore, was to review the available literature, to visualize the embryonic and early foetal development of the bovine stomach and to shed light on unresolved issues. The stomachs of fifteen bovine embryos and eleven foetuses from 26 to 80 days of gestation were photographed both in situ and after exenteration and critical point drying. A series of photographs was obtained that yielded a contiguous and comprehensive view of all the developmental changes that occurred until the virtually final configuration of the stomach was attained. In addition, the serosal surface was studied by electron microscopy, thus revealing subtle regional differences in the lining of the peritoneal cavity. Our observations corroborate the contention that all the compartments evolve from the fusiform primordium and that no outgrowth at the level of the oesophagus occurs. The greater curvature as well as the attachment line of the dorsal mesogastrium shift to the left, which is similar to the process in monogastrians. The rumen and reticulum develop from separate protrusions, and further compartmentalization results from constrictions and bulges and not from folding. Between 55 and 60 days of gestation, the entire bovine stomach except for the abomasum eventually relocates to its final position. In summary, previously debated key issues were addressed and integrated with current findings.
Long‐term trends of Chlamydia trachomatis in a clinic population at the Royal Women's Hospital, Melbourne
Authors: Garland Suzanne Marie , Subasinghe Asvini Kokila , Ahmed Navera , Jayasinghe Yasmin , Marceglia Alex 
Published: December 2019

BackgroundChlamydia trachomatis (C. trachomatis) prevalence has been reported to be increasing. Whether this is a true increase over time or confounded by increases in testing and/or use of more sensitive assays is to be determined.Materials and MethodsOne laboratory service has been detecting C. trachomatis for the past 30 years within the Royal Women's Hospital Melbourne. We conducted a retrospective audit of records over the period 1986–2016 from a clinic population routinely offered chlamydia screening. These were women presenting for family planning advice (termination of pregnancy, intrauterine device insertion or considered at high risk), who underwent chlamydia testing in the context of various diagnostic assays used over this time period. Assays utilised included culture, enzyme immunoassay (EIA), DNA probe, and nucleic acid amplification testing (NAAT). Non‐parametric test for trend was used to determine significant differences between prevalence estimates across ordered groups. Least squares regression was conducted to describe a linear trend matching known data points.ResultsOverall, there was no significant change for chlamydia prevalence which was 2.2%, in the 30‐year study period (P = 0.7). Over time diagnostic assays changed from culture, to EIA, DNA probe, to the more sensitive NAAT. The bulk of the positives were in women under 25 years of age (57%).ConclusionChlamydia prevalence has been stable over 30 years, remaining a problem in young women. Screening for those at risk needs underscoring in a national sexual health program.
Letter: is tenofovir superior to entecavir for hepatocellular carcinoma prevention in chronic hepatitis B? Authors’ reply
Authors: Yip Terry C.‐F. , Wong Grace L.‐H. 
Published: December 2019

LINKED CONTENTThis article is linked to Brancaccio et al and Yuan et al papers. To view these articles, visit https://doi.org/10.1111/apt.15188 and https://doi.org/10.1111/apt.15603.
The effect of artificial insemination prior to transfer of a limited number of vitrified and warmed porcine embryos by open pulled straw (OPS) method on their survival ability for farrowing
Authors: Tajima Shigeyuki , Uchikura Kenzo , Kurita Takayuki , Kikuchi Kazuhiro 
Published: December 2019

AbstractEmbryo transfer (ET) of 20 porcine expanded blastocysts (ExBs) vitrified and warmed (VW) by open pulled straw (OPS) to a recipient allows stable piglet production. The efficiency of artificial insemination (AI) prior to ET of 10 VW ExBs for piglet production was investigated. For one trial, 10–15 VW ExBs from single donor were assigned, 10 were used for ET and the remains were assessed for their in vitro viability. In the non‐AI/ET group, 10 were transferred to each of five recipients. As AI/ET group, 10 were transferred to each of five recipients after AI. In AI/non‐ET group, only AI was performed to seven gilts. In the non‐AI/ET group, the pregnancy rate was 40%, but none of them farrowed. In the AI/ET group, all recipients produced piglets. Four (80.0%) delivered piglets from transferred VW ExBs. The survival rate of VW ExBs to term was 20.0% (10/50). In the AI/non‐ET group, six of the seven gilts farrowed. There was no difference in in vitro viability between the non‐AI/ET and AI/ ET groups (62.5% and 68.3%, respectively). AI prior to ET can be an appropriate way to maintain pregnancy and assist the development of a low number of VW ExBs to term.
The role of anti‐complement factor H antibodies in the development of atypical haemolytic uremic syndrome: a possible contribution to abnormality of platelet function
Authors: Fujisawa Madoka , Yasumoto Atsushi , Kato Hideki , Sugawara Yuka , Yoshida Yoko , Yatomi Yutaka , Nangaku Masaomi 
Published: December 2019

SummaryAtypical haemolytic uremic syndrome (aHUS) is associated with complement system abnormality, such as production of complement factor H (CFH) autoantibodies. The growing evidence indicates complement overactivation on platelets is intimately involved in aHUS pathogenesis, besides endothelial injury. We here showed plasma from patients with anti‐CFH antibodies induced aggregation of washed platelets, while purified anti‐CFH antibodies suppressed aggregation. This suggested anti‐CFH antibody itself suppressed thrombosis, while other plasma factor including complement factors could overactivate the platelets, leading to aggregation, which augmented the notion the state of complement activation influenced by anti‐CFH antibodies is important in the aggregation of platelets in aHUS.
Negative allosteric modulators of the human calcium‐sensing receptor bind to overlapping and distinct sites within the 7‐transmembrane domain
Authors: Josephs Tracy M. , Keller Andrew N. , Khajehali Elham , DeBono Aaron , Langmead Christopher J. , Conigrave Arthur D. , Capuano Ben , Kufareva Irina , Gregory Karen J. , Leach Katie 
Published: December 2019

Background and PurposeNegative allosteric modulators (NAMs) that target the calcium‐sensing receptor (CaS receptor) were originally developed for the treatment of osteoporosis by stimulating the release of endogenous parathyroid hormone, but failed in human clinical trials. Several chemically and structurally distinct NAM scaffolds have been described, but it is not known how these different scaffolds interact with the CaS receptor to inhibit receptor signalling in response to agonists.Experimental ApproachIn the present study, we used a mutagenesis approach combined with analytical pharmacology and computational modelling to probe the binding sites of four distinct NAM scaffolds.Key ResultsAlthough all four scaffolds bind to the 7‐transmembrane and/or extracellular or intracellular loops, they occupy distinct regions, as previously shown for positive allosteric modulators of the CaS receptor. Furthermore, different NAM scaffolds mediate negative allosteric modulation via distinct amino acid networks.Conclusion and ImplicationsThese findings aid our understanding of how different NAMs bind to and inhibit the CaS receptor. Elucidation of allosteric binding sites in the CaS receptor has implications for the discovery of novel allosteric modulators.