bluuebunny/crossref_metadata_2025_split huggingface dataset:
A postnatal role for embryonic myosin revealed by MYH3 mutations that alter TGFβ signaling and cause autosomal dominant spondylocarpotarsal synostosis
Authors: Zieba Jennifer , Zhang Wenjuan , Chong Jessica X. , Forlenza Kimberly N. , Martin Jorge H. , Heard Kelly , Grange Dorothy K. , Butler Merlin G. , Kleefstra Tjitske , Lachman Ralph S. , Nickerson Deborah , Regnier Michael , Cohn Daniel H. , Bamshad Michael , Krakow Deborah 
Published: February 2017

AbstractSpondylocarpotarsal synostosis (SCT) is a skeletal disorder characterized by progressive vertebral, carpal and tarsal fusions, and mild short stature. The majority of affected individuals have an autosomal recessive form of SCT and are homozygous or compound heterozygous for nonsense mutations in the gene that encodes the cytoskeletal protein filamin B (FLNB), but a subset do not have FLNB mutations. Exome sequence analysis of three SCT patients negative for FLNB mutations identified an autosomal dominant form of the disease due to heterozygosity for missense or nonsense mutations in MYH3, which encodes embryonic myosin. Cells transfected with the MYH3 missense mutations had reduced TGFβ signaling, revealing a regulatory role for embryonic myosin in the TGFβ signaling pathway. In wild-type mice, there was persistent postnatal expression of embryonic myosin in the small muscles joining the neural arches of the spine suggesting that loss of myosin function in these muscles contribute to the disease. Our findings demonstrate that dominant mutations in MYH3 underlie autosomal dominant SCT, identify a postnatal role for embryonic myosin and suggest that altered regulation of signal transduction in the muscles within the spine may lead to the development of vertebral fusions.
The small molecule AUTEN-99 (autophagy enhancer-99) prevents the progression of neurodegenerative symptoms
Authors: Kovács Tibor , Billes Viktor , Komlós Marcell , Hotzi Bernadette , Manzéger Anna , Tarnóci Anna , Papp Diána , Szikszai Fanni , Szinyákovics Janka , Rácz Ákos , Noszál Béla , Veszelka Szilvia , Walter Fruzsina R. , Deli Mária A. , Hackler Laszlo , Alfoldi Robert , Huzian Orsolya , Puskas Laszlo G. , Liliom Hanna , Tárnok Krisztián , Schlett Katalin , Borsy Adrienn , Welker Ervin , Kovács Attila L. , Pádár Zsolt , Erdős Attila , Legradi Adam , Bjelik Annamaria , Gulya Károly , Gulyás Balázs , Vellai Tibor 
Published: February 2017

AbstractAutophagy functions as a main route for the degradation of superfluous and damaged constituents of the cytoplasm. Defects in autophagy are implicated in the development of various age-dependent degenerative disorders such as cancer, neurodegeneration and tissue atrophy, and in accelerated aging. To promote basal levels of the process in pathological settings, we previously screened a small molecule library for novel autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negative regulator of autophagic membrane formation. Here we identify AUTEN-99 (autophagy enhancer-99), which activates autophagy in cell cultures and animal models. AUTEN-99 appears to effectively penetrate through the blood-brain barrier, and impedes the progression of neurodegenerative symptoms in Drosophila models of Parkinson’s and Huntington’s diseases. Furthermore, the molecule increases the survival of isolated neurons under normal and oxidative stress-induced conditions. Thus, AUTEN-99 serves as a potent neuroprotective drug candidate for preventing and treating diverse neurodegenerative pathologies, and may promote healthy aging.
Epigenetic signatures of invasive status in populations of marine invertebrates
Authors: Ardura Alba , Zaiko Anastasija , Morán Paloma , Planes Serge , Garcia-Vazquez Eva 
Published: February 2017

AbstractEpigenetics, as a DNA signature that affects gene expression and enables rapid reaction of an organism to environmental changes, is likely involved in the process of biological invasions. DNA methylation is an epigenetic mechanism common to plants and animals for regulating gene expression. In this study we show, for the first time in any marine species, significant reduction of global methylation levels during the expansive phase of a pygmy mussel (Xenostrobus securis) recent invasion in Europe (two-year old), while in older introductions such epigenetic signature of invasion was progressively reduced. Decreased methylation was interpreted as a rapid way of increasing phenotypic plasticity that would help invasive populations to thrive. This epigenetic signature of early invasion was stronger than the expected environmental signature of environmental stress in younger populations sampled from ports, otherwise detected in a much older population (>90 year old) of the also invasive tubewormFicopomatus enigmaticusestablished in similar locations. Higher epigenetic than genetic diversity found inX. securiswas confirmed fromF. enigmaticussamples. As reported for introduced plants and vertebrates, epigenetic variation could compensate for relatively lower genetic variation caused by founder effects. These phenomena were compared with epigenetic mechanisms involved in metastasis, as parallel processes of community (biological invasion) and organism (cancer) invasions.
Genome editing reveals dmrt1 as an essential male sex-determining gene in Chinese tongue sole (Cynoglossus semilaevis)
Authors: Cui Zhongkai , Liu Yun , Wang Wenwen , Wang Qian , Zhang Ning , Lin Fan , Wang Na , Shao Changwei , Dong Zhongdian , Li Yangzhen , Yang Yingming , Hu Mengzhu , Li Hailong , Gao Fengtao , Wei Zhanfei , Meng Liang , Liu Yang , Wei Min , Zhu Ying , Guo Hua , Cheng Christopher H. K. , Schartl Manfred , Chen Songlin 
Published: February 2017

AbstractChinese tongue sole is a marine fish with ZW sex determination. Genome sequencing suggested that the Z-linked dmrt1 is a putative male determination gene, but direct genetic evidence is still lacking. Here we show that TALEN of dmrt1 efficiently induced mutations of this gene. The ZZ dmrt1 mutant fish developed ovary-like testis, and the spermatogenesis was disrupted. The female-related genes foxl2 and cyp19a1a were significantly increased in the gonad of the ZZ dmrt1 mutant. Conversely, the male-related genes Sox9a and Amh were significantly decreased. The dmrt1 deficient ZZ fish grew much faster than ZZ male control. Notably, we obtained an intersex ZW fish with a testis on one side and an ovary on the other side. This fish was chimeric for a dmrt1 mutation in the ovary, and wild-type dmrt1 in the testis. Our data provide the first functional evidence that dmrt1 is a male determining gene in tongue sole.
Hypoxia-induced angiotensin II by the lactate-chymase-dependent mechanism mediates radioresistance of hypoxic tumor cells
Authors: Xie Guozhu , Liu Ying , Yao Qiwei , Zheng Rong , Zhang Lanfang , Lin Jie , Guo Zhaoze , Du Shasha , Ren Chen , Yuan Quan , Yuan Yawei 
Published: February 2017

AbstractThe renin-angiotensin system (RAS) is a principal determinant of arterial blood pressure and fluid and electrolyte balance. RAS component dysregulation was recently found in some malignancies and correlated with poor patient outcomes. However, the exact mechanism of local RAS activation in tumors is still unclear. Here, we find that the local angiotensin II predominantly exists in the hypoxic regions of tumor formed by nasopharyngeal carcinoma CNE2 cells and breast cancer MDA-MB-231 cells, where these tumor cells autocrinely produce angiotensin II by a chymase-dependent rather than an angiotensin converting enzyme-dependent mechanism. We further demonstrate in nasopharyngeal carcinoma CNE2 and 5–8F cells that this chymase-dependent effect is mediated by increased levels of lactate, a by-product of glycolytic metabolism. Finally, we show that the enhanced angiotensin II plays an important role in the intracellular accumulation of HIF-1α of hypoxic nasopharyngeal carcinoma cells and mediates the radiation-resistant phenotype of these nasopharyngeal carcinoma cells. Thus, our findings reveal the critical role of hypoxia in producing local angiotensin II by a lactate-chymase-dependent mechanism and highlight the importance of local angiotensin II in regulating radioresistance of hypoxic tumor cells.
Genomic structure and insertion sites of Helicobacter pylori prophages from various geographical origins
Authors: Vale Filipa F. , Nunes Alexandra , Oleastro Mónica , Gomes João P. , Sampaio Daniel A. , Rocha Raquel , Vítor Jorge M. B. , Engstrand Lars , Pascoe Ben , Berthenet Elvire , Sheppard Samuel K. , Hitchings Matthew D. , Mégraud Francis , Vadivelu Jamuna , Lehours Philippe 
Published: February 2017

AbstractHelicobacter pylorigenetic diversity is known to be influenced by mobile genomic elements. Here we focused on prophages, the least characterized mobile elements ofH. pylori. We present the full genomic sequences, insertion sites and phylogenetic analysis of 28 prophages found inH. pyloriisolates from patients of distinct disease types, ranging from gastritis to gastric cancer, and geographic origins, covering most continents. The genome sizes of these prophages range from 22.6–33.0 Kbp, consisting of 27–39 open reading frames. A 36.6% GC was found in prophages in contrast to 39% inH. pylorigenome. Remarkably a conserved integration site was found in over 50% of the cases. Nearly 40% of the prophages harbored insertion sequences (IS) previously described inH. pylori. Tandem repeats were frequently found in the intergenic region between the prophage at the 3′ end and the bacterial gene. Furthermore, prophage genomes present a robust phylogeographic pattern, revealing four distinct clusters: one African, one Asian and two European prophage populations. Evidence of recombination was detected within the genome of some prophages, resulting in genome mosaics composed by different populations, which may yield additionalH. pyloriphenotypes.
A data-driven approach for evaluating multi-modal therapy in traumatic brain injury
Authors: Haefeli Jenny , Ferguson Adam R. , Bingham Deborah , Orr Adrienne , Won Seok Joon , Lam Tina I. , Shi Jian , Hawley Sarah , Liu Jialing , Swanson Raymond A. , Massa Stephen M. 
Published: February 2017

AbstractCombination therapies targeting multiple recovery mechanisms have the potential for additive or synergistic effects, but experimental design and analyses of multimodal therapeutic trials are challenging. To address this problem, we developed a data-driven approach to integrate and analyze raw source data from separate pre-clinical studies and evaluated interactions between four treatments following traumatic brain injury. Histologic and behavioral outcomes were measured in 202 rats treated with combinations of an anti-inflammatory agent (minocycline), a neurotrophic agent (LM11A-31), and physical therapy consisting of assisted exercise with or without botulinum toxin-induced limb constraint. Data was curated and analyzed in a linked workflow involving non-linear principal component analysis followed by hypothesis testing with a linear mixed model. Results revealed significant benefits of the neurotrophic agent LM11A-31 on learning and memory outcomes after traumatic brain injury. In addition, modulations of LM11A-31 effects by co-administration of minocycline and by the type of physical therapy applied reached statistical significance. These results suggest a combinatorial effect of drug and physical therapy interventions that was not evident by univariate analysis. The study designs and analytic techniques applied here form a structured, unbiased, internally validated workflow that may be applied to other combinatorial studies, both in animals and humans.
Retinal Structure and Function in Eyes with Optic Nerve Hypoplasia
Authors: Katagiri Satoshi , Nishina Sachiko , Yokoi Tadashi , Mikami Masashi , Nakayama Yuri , Tanaka Michiko , Azuma Noriyuki 
Published: February 2017

AbstractWe investigated retinal structure and function in eyes with optic nerve hypoplasia (ONH). Twenty-nine eyes of 18 patients with ONH and 21 eyes of 21 control patients were analyzed. Spectral-domain optical coherence tomography (SD-OCT), full-field electroretinography (FF-ERG), and focal macular ERG (FM-ERG) were performed. SD-OCT analysis of the macular region showed significant ganglion cells complex (GCC) thinning nasally and temporally (P < 0.05), but the thickness from the inner nuclear layer (INL) to the retinal pigment epithelium (RPE) became thinner only nasally (P < 0.05). SD-OCT analysis of the circumpapillary region showed significant thinning in the retinal nerve fiber layer and from the INL to the RPE (P < 0.05). The horizontal SD-OCT images showed variable foveal abnormalities. FF-ERG analysis showed significantly reduced amplitudes (P < 0.05) and preserved implicit time in the photopic negative response. The amplitudes and implicit times of the other FF-ERG components did not differ significantly. FM-ERG analysis showed significantly reduced amplitudes (P < 0.05) but preserved implicit times in all components. The current study showed the change of retinal structure and function in eyes with ONH compared with those with control, representing by decreased retinal ganglion cells (RGCs) and their axons, foveal abnormalities, and preserved peripheral retina except for the RGCs and their axons.
Wnt5a is a crucial regulator of neurogenesis during cerebellum development
Authors: Subashini Chandramohan , Dhanesh Sivadasan Bindu , Chen Chih-Ming , Riya Paul Ann , Meera Vadakkath , Divya Thulasi Sheela , Kuruvilla Rejji , Buttler Kerstin , James Jackson 
Published: February 2017

AbstractThe role of Wnt5a has been extensively explored in various aspects of development but its role in cerebellar development remains elusive. Here, for the first time we unravel the expression pattern and functional significance of Wnt5a in cerebellar development using Wnt5a−/− and Nestin-Cre mediated conditional knockout mouse models. We demonstrate that loss of Wnt5a results in cerebellar hypoplasia and depletion of GABAergic and glutamatergic neurons. Besides, Purkinje cells of the mutants displayed stunted, poorly branched dendritic arbors. Furthermore, we show that the overall reduction is due to decreased radial glial and granule neuron progenitor cell proliferation. At molecular level we provide evidence for non-canonical mode of action of Wnt5a and its regulation over genes associated with progenitor proliferation. Altogether our findings imply that Wnt5a signaling is a crucial regulator of cerebellar development and would aid in better understanding of cerebellar disease pathogenesis caused due to deregulation of Wnt signaling.
Biological motion distorts size perception
Authors: Veto Peter , Einhäuser Wolfgang , Troje Nikolaus F. 
Published: February 2017

AbstractVisual illusions explore the limits of sensory processing and provide an ideal testbed to study perception. Size illusions – stimuli whose size is consistently misperceived – do not only result from sensory cues, but can also be induced by cognitive factors, such as social status. Here we investigate, whether the ecological relevance of biological motion can also distort perceived size. We asked observers to judge the size of point-light walkers (PLWs), configurations of dots whose movements induce the perception of human movement, and visually matched control stimuli (inverted PLWs). We find that upright PLWs are consistently judged as larger than inverted PLWs, while static point-light figures do not elicit the same effect. We also show the phenomenon using an indirect paradigm: observers judged the relative size of a disc that followed an inverted PLW larger than a disc following an upright PLW. We interpret this as a contrast effect: The upright PLW is perceived larger and thus the subsequent disc is judged smaller. Together, these results demonstrate that ecologically relevant biological-motion stimuli are perceived larger than visually matched control stimuli. Our findings present a novel case of illusory size perception, where ecological importance leads to a distorted perception of size.
Non-reliance of metazoans on stromatolite-forming microbial mats as a food resource
Authors: Rishworth Gavin M. , Perissinotto Renzo , Bird Matthew S. , Strydom Nadine A. , Peer Nasreen , Miranda Nelson A. F. , Raw Jacqueline L. 
Published: February 2017

AbstractGrazing and burrowing organisms usually homogenise microalgal mats that form on benthic sediments of many aquatic ecosystems. In the absence of this disruption, microalgal mats can accrete laminated deposits (stromatolites). Stromatolites are rare in modern coastal ecosystems, but persist at locations where metazoans are largely excluded. This study aimed to assess the trophic structure at stromatolite locations where metazoans co-occur, to determine the grazing influence exerted by the metazoans on the stromatolite-forming microalgae (cyanobacteria and diatoms). Stable isotope signatures (δ13C and δ15N) were used as food-web tracers and dietary composition of consumers was calculated using source mixing models. Results clearly demonstrate that the dominant macrofaunal grazers do not utilise stromatolite material as a food resource, but rather subsist on autochthonous macroalgae. For instance, the mean (±SD) dietary composition of two of the most abundant grazers, Melita zeylanica (Amphipoda) and Composetia cf. keiskama (Polychaeta), consisted of 80 ± 11% and 91 ± 7% macroalgae, respectively. This suggests that the stromatolite-forming benthic microalgae are not disrupted significantly by grazing pressures, allowing for the layered mineralisation process to perpetuate. Additionally, grazers likely have a restrictive influence on pool macroalgae, maintaining the competitive balance between micro- and macroalgal groups.
DNA analysis of a 30,000-year-old Urocitellus glacialis from northeastern Siberia reveals phylogenetic relationships between ancient and present-day arctic ground squirrels
Authors: Faerman Marina , Bar-Gal Gila Kahila , Boaretto Elisabetta , Boeskorov Gennady G. , Dokuchaev Nikolai E. , Ermakov Oleg A. , Golenishchev Fedor N. , Gubin Stanislav V. , Mintz Eugenia , Simonov Evgeniy , Surin Vadim L. , Titov Sergei V. , Zanina Oksana G. , Formozov Nikolai A. 
Published: February 2017

AbstractIn contrast to the abundant fossil record of arctic ground squirrels, Urocitellus parryii, from eastern Beringia, only a limited number of fossils is known from its western part. In 1946, unnamed GULAG prisoners discovered a nest with three mummified carcasses of arctic ground squirrels in the permafrost sediments of the El’ga river, Yakutia, Russia, that were later attributed to a new species, Citellus (Urocitellus) glacialis Vinogr. To verify this assignment and to explore phylogenetic relationships between ancient and present-day arctic ground squirrels, we performed 14C dating and ancient DNA analyses of one of the El’ga mummies and four contemporaneous fossils from Duvanny Yar, northeastern Yakutia. Phylogenetic reconstructions, based on complete cytochrome b gene sequences of five Late Pleistocene arctic ground squirrels and those of modern U. parryii from 21 locations across western Beringia, provided no support for earlier proposals that ancient arctic ground squirrels from Siberia constitute a distinct species. In fact, we observed genetic continuity of the glacialis mitochondrial DNA lineage in modern U. parryii of the Kamchatka peninsula. When viewed in a broader geographic perspective, our findings provide new insights into the genetic history of U. parryii in Late Pleistocene Beringia.
Genome-wide DNA-(de)methylation is associated with Noninfectious Bud-failure exhibition in Almond (Prunus dulcis [Mill.] D.A.Webb)
Authors: Fresnedo-Ramírez Jonathan , Chan Helen M. , Parfitt Dan E. , Crisosto Carlos H. , Gradziel Thomas M. 
Published: February 2017

AbstractNoninfectious bud-failure (BF) remains a major threat to almond production in California, particularly with the recent rapid expansion of acreage and as more intensive cultural practices and modern cultivars are adopted. BF has been shown to be inherited in both vegetative and sexual progeny, with exhibition related to the age and propagation history of scion clonal sources. These characteristics suggest an epigenetic influence, such as the loss of juvenility mediated by DNA-(de)methylation. Various degrees of BF have been reported among cultivars as well as within sources of clonal propagation of the same cultivar. Genome-wide methylation profiles for different clones within almond genotypes were developed to examine their association with BF levels and association with the chronological time from initial propagation. The degree of BF exhibition was found to be associated with DNA-(de)methylation and clonal age, which suggests that epigenetic changes associated with ageing may be involved in the differential exhibition of BF within and among almond clones. Research is needed to investigate the potential of DNA-(de)methylation status as a predictor for BF as well as for effective strategies to improve clonal selection against age related deterioration. This is the first report of an epigenetic-related disorder threatening a major tree crop.
Identification of a substrate domain that determines system specificity in mycobacterial type VII secretion systems
Authors: Phan Trang H. , Ummels Roy , Bitter Wilbert , Houben Edith N. G. 
Published: February 2017

AbstractType VII secretion (T7S) systems are specialized machineries used by mycobacterial pathogens to transport important virulence factors across their highly hydrophobic cell envelope. There are up to five mycobacterial T7S systems, named ESX-1 to ESX-5, at least three of which specifically secrete a different subset of substrates. The T7S substrates or substrate complexes are defined by the general secretion motif YxxxD/E. However this motif does not determine system specificity. Here, we show that the substrate domain recognized by the EspG chaperone is the determinant factor for this specificity. We first show that the introduction of point mutations into the EspG1-binding domain of the ESX-1 substrate pair PE35/PPE68_1 affects their secretion. Subsequently, we demonstrate that replacing this domain by the EspG5-binding domain of the ESX-5 substrate PPE18 resulted in EspG5 dependence and exclusive rerouting to the ESX-5 system. This rerouting of PE35/PPE68_1 to the ESX-5 system had a negative effect on the secretion of endogenous ESX-5 substrates.
Complement component 5 promotes lethal thrombosis
Authors: Mizuno Tomohiro , Yoshioka Kengo , Mizuno Masashi , Shimizu Mie , Nagano Fumihiko , Okuda Tomoyuki , Tsuboi Naotake , Maruyama Shoichi , Nagamatsu Tadashi , Imai Masaki 
Published: February 2017

AbstractExtracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, the pathological mechanism underlying liver injury has remained unclear. Here, we investigated whether C5 promotes liver injury associated with histone-induced lethal thrombosis. C5-sufficient and C5-deficient mice received single tail vein injections of purified, unfractionated histones obtained from calf thymus (45–75 μg/g). Subsequently, the mice were monitored for survival for up to 72 h. Based on the survival data, the 45 μg/g dose was used for analysis of blood cell count, liver function, blood coagulation ability, and promotion of platelet aggregation and platelet/leukocyte aggregate (PLA) production by extracellular histones. C5-deficient mice were protected from lethal thrombosis and had milder thrombocytopenia, consumptive coagulopathy, and liver injury with embolism and lower PLA production than C5-sufficient mice. These results indicate that C5 is associated with coagulation disorders, PLA production, and embolism-induced liver injury. In conclusion, C5 promotes liver injury associated with histone-induced lethal thrombosis.