bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paraconexibacter algicola gen. nov., sp. nov., a novel actinobacterium isolated from a eutrophic lake during the end of cyanobacterial harmful algal blooms, and proposal of Paraconexibacteraceae fam. nov. in the order Solirubrobacterales
Authors: Chun Seong-Jun , Cui Yingshun , Jin Chunzhi , Cho A Ra , Wong Shu-Kuan , Lee Hyung-Gwan , Oh Hee-Mock , Ahn Chi-Yong 
Published: November 2019

A novel bacterium, strain Seoho-28T, was isolated from a shallow eutrophic lake during the end of cyanobacterial harmful algal blooms and was characterized taxonomically and phylogenetically. Strain Seoho-28T was a Gram-stain-negative, aerobic, rod-shaped and non-motile bacterium. The strain grew optimally with 0 % NaCl and at 25–30 °C on Reasoner's 2A medium. The phylogenetic analysis based on 16S rRNA gene sequences positioned the novel strain among the order

Solirubrobacterales

, but sequence similarities to known species were less than 94.7 %. The genomic DNA G+C content of the strain Seoho-28T was 74.2 mol%. Genomic comparisons of strain Seoho-28T with families in the order

Solirubrobacterales

were made using the Genome-to-Genome Distance Calculator, average nucleotide identity and average amino acid identity analyses (values indicated ≤14.9, ≤73.5 and ≤57.8 %, respectively). Strain Seoho-28T contained C16 : 0-iso, C18 : 1
ω9c and C16 : 0 as major fatty acids and MK-7 (H4) as the major quinone. Strain Seoho-28T contained diphosphatidylglycerol, phosphatidylinositol and an unidentified phospholipid as major polar lipids. Meso- and ll-diaminopimelic acids were the diagnostic diamino acids in the cell-wall peptidoglycan. Based on the genotypic, chemotaxonomic and phenotypic results, strain Seoho-28T represents a novel genus and species, Paraconexibacter algicola gen. nov., sp. nov., which belongs to a new family Paraconexibacteraceae in the order

Solirubrobacterales

and the class

Thermoleophilia

. The type strain is Seoho-28T (=KCTC 39791T=JCM 31881T).
Spatiotemporal tools for emerging and endemic disease hotspots in small areas – an analysis of dengue and chikungunya in Barbados, 2013 – 2016
Authors: Lippi Catherine A. , Stewart-Ibarra Anna M. , Romero Moory , Hinds Avery Q.J. , Lowe Rachel , Mahon Roché , Meerbeeck Cedric J. Van , Rollock Leslie , Hilaire Marquita Gittens-St. , Trotman Adrian R. , Holligan Dale , Kirton Shane , Borbor-Cordova Mercy J. , Ryan Sadie J. 
Published: November 2019

AbstractObjectiveTo detect potential hotspots of transmission of dengue and chikungunya in Barbados, and assess impact of input surveillance data and methodology on observed patterns of risk.MethodsUsing two methods of cluster detection, Moran’s I and spatial scan statistics, we analyzed the geospatial and temporal distribution of disease cases and rates across Barbados for dengue fever in 2013–2016, and a 2014 chikungunya outbreak.ResultsDuring years with high numbers of dengue cases, hotspots for cases were found with Moran’s I in south and central regions in 2013 and 2016, respectively. Using smoothed disease rates, clustering was detected every year for dengue. Hotspots were not detected via spatial scan statistics, but coldspots suggesting lower rates of disease activity were found in southwestern Barbados during high case years of dengue.ConclusionsSpatial analysis of surveillance data is useful in identifying outbreak hotspots, complementing existing early warning systems. We caution that these methods should be used in a manner appropriate to available data, and reflecting explicit public health goals – managing for overall case numbers, or targeting anomalous rates for further investigation.
Characterization of the prion protein binding properties of antisense oligonucleotides
Authors: Reidenbach Andrew G , Minikel Eric Vallabh , Zhao Hien T , Guzman Stacy G , Leed Alison J , Mesleh Michael F , Kordasiewicz Holly B , Schreiber Stuart L , Vallabh Sonia M 
Published: November 2019

AbstractAntisense oligonucleotides (ASOs) designed to lower prion protein (PrP) expression in the brain through RNAse H1-mediated degradation of PrP RNA are in development as prion disease therapeutics. ASOs were previously reported to sequence-independently interact with PrP and inhibit prion accumulation in cell culture, yetin vivostudies using a new generation of ASOs found that only PrP-lowering sequences were effective at extending survival. Cerebrospinal fluid (CSF) PrP has been proposed as a pharmacodynamic biomarker for trials of such ASOs, but is only interpretable if PrP lowering is indeed the relevant mechanism of actionin vivoand if measurement of PrP is unconfounded by any PrP-ASO interaction. Here we examine the PrP-binding and antiprion properties of ASOsin vitroand in cell culture. Binding parameters determined by isothermal titration calorimetry were similar across all ASOs tested, indicating that ASOs of various chemistries bind full-length recombinant PrP with low- to mid-nanomolar affinity in a sequence-independent manner. Nuclear magnetic resonance, dynamic light scattering, and visual inspection of ASO-PrP mixtures suggested, however, that this interaction is characterized by the formation of large aggregates, a conclusion further supported by the salt dependence of the affinity measured by isothermal titration calorimetry. Sequence-independent inhibition of prion accumulation in cell culture was observed. The inefficacy of non-PrP-lowering ASOs against prion diseasein vivomay be because their apparent activityin vitrois an artifact of aggregation, or because the concentration of ASOs in relevant compartments within the central nervous system (CNS) quickly drops below the effective concentration for sequence-independent antiprion activity after bolus dosing into CSF. ELISA-based measurements of PrP concentration in human CSF were not impacted by the addition of ASO. These findings support the further development of PrP-lowering ASOs and of CSF PrP as a pharmacodynamic biomarker.
Human URAT1/SLC22A12gene promoter is regulated by 27-hydroxycholesterol through estrogen response elements
Authors: Matsubayashi Masaya , Sakaguchi Yoshihiko M. , Sahara Yoshiki , Nanaura Hitoki , Kikuchi Sotaro , Ashari Arvand , Bui Linh , Kobashigawa Shinko , Nakanishi Mari , Nagata Riko , Matsui Takeshi K. , Kashino Genro , Hasegawa Masatoshi , Takasawa Shin , Eriguchi Masahiro , Tsuruya Kazuhiko , Nagamori Shushi , Sugie Kazuma , Nakagawa Takahiko , Takasato Minoru , Umetani Michihisa , Mori Eiichiro 
Published: November 2019

AbstractElevated levels of uric acid, a metabolite of purine in humans, is related to various diseases, such as gout, atherosclerosis and renal dysfunction. The excretion and reabsorption of uric acid to/from urine is tightly regulated by uric acid transporters. The amino acid sequences of uric acid reabsorption transporters, URAT1/SLC22A12, OAT4/SLC22A11, and OAT10/SLC22A13, share closer phylogenic relationship, whereas the gene promoter sequences are distant phylogenic relationship. Through the single-cell RNA-sequencing analysis of an adult human kidney, we found that only a small number of cells express these transporters, despite their role in the regulation of serum uric acid levels. Transcriptional motif analysis on these transporter genes, revealed that the URAT1/SLC22A12gene promoter displayed the most conserved estrogen response elements (EREs) among the three transporters. The endogenous selective estrogen receptor modulator (SERM) 27-hydroxycholesterol (27HC) had positive effects on the transcriptional activity of URAT1/SLC22A12. We also found that 27HC increased the protein and gene expression of URAT1/SLC22A12in mouse kidneys and human kidney organoids, respectively. These results strongly suggest the role of 27HC for URAT1/SLC22A12expression in renal proximal tubules and upregulation of serum uric acid levels and also show the relationship between cholesterol metabolism and serum uric acid regulation.Significance StatementThe elevated levels of serum uric acid cause various diseases, and the excretion/reabsorption of uric acid to/from urine is tightly regulated by the uric acid transporters. We found that despite the role in serum uric acid regulation, only a small number of cells express URAT1/SLC22A12. We also found that URAT1/SLC22A12gene promoter region has effective estrogen response elements, and endogenous selective estrogen receptor (ER) modulator 27-hydroxycholesterol (27HC) increased URAT1/SLC22A12expression in the mice kidneys and human kidney organoids. These suggest that 27HC increases URAT1/SLC22A12expression and upregulate serum uric acid levels. Since 27HC connects cholesterol metabolism, our study indicates the important link between cholesterol metabolism and serum uric acid regulation, and also provides a novel therapeutic approach to hyperuricemia.
Induced pluripotent stem cell-derived primary proprioceptive neurons as Friedreich ataxia cell model
Authors: Dionisi Chiara , Rai Myriam , Chazalon Marine , Schiffmann Serge N. , Pandolfo Massimo 
Published: November 2019

AbstractHuman induced pluripotent stem cells (iPSCs) are used to generate models of human diseases that recapitulate the pathogenic process as it occurs in affected cells. Many differentiated cell types can currently be obtained from iPSCs, but no validated protocol is yet available to specifically generate primary proprioceptive neurons. Proprioceptors are affected in a number of genetic and acquired diseases, including Friedreich ataxia (FRDA).FRDA is a recessive neurodegenerative and systemic disease due to epigenetic suppression of frataxin (FXN) expression caused by the presence of expanded GAA repeats at the FXN locus. The most characteristic early neuropathologic finding in FRDA is the loss of large primary proprioceptive neurons in the dorsal root ganglia (DRGs), with associated loss of large myelinated fibers in the dorsal roots and in the posterior columns of the spinal cord. Both a developmental deficit and progressive neurodegeneration are thought to underlie the loss of proprioceptors in FRDA, though the relative contribution of these two components is unclear. The basis of the high specific vulnerability of proprioceptors in FRDA is also unknown. In order to address these open questions about FRDA pathogenesis and at the same time develop a cell model that can be applied to other conditions primarily affecting proprioceptors, we set up a protocol to differentiate iPSCs into primary proprioceptive neurons. We modified the dual-SMAD inhibition/WNT activation protocol, previously used to generate nociceptor-enriched cultures of primary sensory neurons from iPSCs, to favor instead the generation of proprioceptors. We succeeded in substantially enriching iPSC-derived primary sensory neuron cultures in proprioceptors, largely exceeding the proportion normally represented by these cells in dorsal root ganglia. We also showed that almost pure populations of proprioceptors can be purified from these cultures by fluorescence-activated cell sorting. Finally, we demonstrated that iPSCs from a FRDA patient can generate normal appearing proprioceptors but have subtle differentiation deficits and more limited survival.
Tailor: non-parametric and rapid score calibration method for database search-based peptide identification in shotgun proteomics
Authors: Sulimov Pavel , Kertész-Farkas Attila 
Published: November 2019

AbstractPeptide-spectrum-match (PSM) scores used in database searching are calibrated to spectrum- or spectrum-peptide-specific null distributions. Some calibration methods rely on specific assumptions and use analytical models (e.g. binomial distributions), whereas other methods utilize exact empirical null distributions. The former may be inaccurate because of unjustified assumptions, while the latter are accurate, albeit computationally exhaustive. Here, we introduce a novel, non-parametric, heuristic PSM score calibration method, called Tailor, which calibrates PSM scores by dividing it with the top 100-quantile of the empirical, spectrum-specific null distributions (i.e. the score with an associated p-value of 0.01 at the tail, hence the name) observed during database searching. Tailor does not require any optimization steps or long calculations; it does not rely on any assumptions on the form of the score distribution, it works with any score functions with high- and low-resolution information. In our benchmark, we re-calibrated the match scores of XCorr from Crux, HyperScore scores from X!Tandem, and the p-values from OMSSA with Tailor method, and obtained more spectrum annotation than with raw scores at any false discovery rate level. Moreover, Tailor provided slightly more annotations than E-values of X!Tandem and OMSSA and approached the performance of the computationally exhaustive exact p-value method for XCorr on spectrum datasets containing low-resolution fragmentation information (MS2) around 20-150 times faster. On high-resolution MS2 datasets, the Tailor method with XCorr achieved state-of-the-art performance, and produced more annotations than the well-calibrated Res-ev score around 50-80 times faster.Graphical TOC Entry
Allosteric coupling between α-rings of the 20S proteasome
Authors: Yu Zanlin , Yu Yadong , Wang Feng , Myasnikov Alexander G. , Coffino Philip , Cheng Yifan 
Published: November 2019

AbstractThe proteasomal machinery performs essential regulated protein degradation in eukaryotes. Classic proteasomes are symmetric, with a regulatory ATPase docked at each end of the cylindrical 20S. Asymmetric complexes are also present in cells, either with a single ATPase or with an ATPase and non-ATPase at two opposite ends. The mechanism that populates these different proteasomal complexes is unknown. Using archaea homologs, we constructed asymmetric forms of proteasomes. We demonstrate that the gate conformation of two opposite ends of 20S are coupled: binding one ATPase opens a gate locally, and also the remote opposite gate allosterically. Such allosteric coupling leads to cooperative binding of proteasomal ATPases to 20S, and promotes formation of proteasomes symmetrically configured with two identical ATPases. It may also promote formation of asymmetric complexes with an ATPase and a non-ATPase at opposite ends. We propose that in eukaryotes a similar mechanism regulates the composition of the proteasomal population.
Adaptations to Oral and Pharyngeal Swallowing Function Induced by Injury to the Mylohyoid Muscle
Authors: King Suzanne N. , Fletcher Brittany , Kimbel Bradley , Bonomo Nicholas , Pitts Teresa 
Published: November 2019

AbstractMuscle injury is a frequent side effect of radiation treatment for head and neck cancer. To understand the pathophysiology of injury-related dysfunction, we investigated the effects of a single muscle injury to the mylohyoid on oropharyngeal swallowing function in the rat. The mylohyoid protects the airway from food/liquid via hyolaryngeal elevation and plays an active role during both oral and pharyngeal swallowing. We hypothesized (1) that fibrosis to the mylohyoid alters swallowing bolus flow and licking patterns; (2) that injury to the mylohyoid changes normal activity of submental, laryngeal, and pharyngeal muscles during swallowing. A chilled cryoprobe was applied to the rat mylohyoid muscle to create a localized injury. After 1- and 2-weeks post-injury, swallowing bolus transit was assessed via videofluoroscopy and licking behavior via an electrical lick sensor. The motor activity of five swallow-related muscles were analyzed immediately after injury using electromyography (EMG). Comparisons were made pre- and post-injury. Fibrosis was confirmed in the mylohyoid at 2-weeks post-injury by measuring collagen content. One-week after injury, bolus size decreased, swallowing rate reduced, and licking patterns were altered. Immediately post-injury, there was a significant depression in mylohyoid and thyropharyngeus EMG amplitudes during swallowing. Our results demonstrated that injury to the mylohyoid is sufficient to cause changes in deglutition. These disruptions in oral and pharyngeal swallowing were detected prior to long-term fibrotic changes, including delays in tongue movement, alterations in bolus flow, and changes in sensorimotor function. Therefore, injuring a single important swallowing muscle can have dramatic clinical effects.
Development and validation of a deep learning framework for Alzheimer’s disease classification
Authors: Kolachalama Vijaya B. , Qiu Shangran , Joshi Prajakta S. , Miller Matthew I. , Xue Chonghua , Karjadi Cody , Chang Gary H. , Joshi Anant S. , Dwyer Brigid , Zhu Shuhan , Kaku Michelle , Zhou Yan , Alderazi Yazan J. , Swaminathan Arun , Kedar Sachin , Saint-Hilaire Marie-Helene , Auerbach Sanford H. , Yuan Jing , Sartor E. Alton , Au Rhoda 
Published: November 2019

AbstractAlzheimer’s disease (AD) is the primary cause of dementia worldwide (1), with an increasing morbidity burden that may outstrip diagnosis and management capacity as the population ages. Current methods integrate patient history, neuropsychological testing and magnetic resonance imaging (MRI) to identify likely cases, yet effective practices remain variably-applied and lacking in sensitivity and specificity (2). Here we report an explainable deep learning strategy that delineates unique AD signatures from multimodal inputs of MRI, age, gender, and mini-mental state examination (MMSE) score. Our framework linked a fully convolutional network (FCN) to a multilayer perceptron (MLP) to construct high resolution maps of disease probability from local brain structure. This enabled precise, intuitive visualization of individual AD risk en route to accurate diagnosis. The model was trained using clinically-diagnosed AD and cognitively normal (NC) subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset (n=417) (3), and validated on three independent cohorts: the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL, n=382) (4), the Framingham Heart Study (FHS, n=102) (5), and the National Alzheimer’s Coordinating Center (NACC, n=582) (6). Model performance was consistent across datasets, with mean accuracy values of 0.966, 0.948, 0.815, and 0.916 for ADNI, AIBL, FHS and NACC, respectively. Moreover, our approach exceeded the diagnostic performance of a multi-institutional team of practicing neurologists (n=11), and high-risk cerebral regions predicted by the model closely tracked postmortem histopathological findings. This framework provides a clinically-adaptable strategy for using routinely available imaging techniques such as MRI to generate nuanced neuroimaging signatures for AD diagnosis, as well as a generalizable approach for linking deep learning to pathophysiological processes in human disease.
Blocks in tricarboxylic acid cycle ofSalmonella entericacause global perturbation of carbon storage, motility and host-pathogen-interaction
Authors: Noster Janina , Hansmeier Nicole , Persicke Marcus , Chao Tzu-Chiao , Kurre Rainer , Popp Jasmin , Liss Viktoria , Reuter Tatjana , Hensel Michael 
Published: November 2019

AbstractThe tricarboxylic acid cycle is a central metabolic hub in most cells. Virulence functions of bacterial pathogens such as facultative intracellularSalmonella entericaserovar Typhimurium (STM) are closely connected to cellular metabolism. During systematic analyses of mutant strains with defects in TCA cycle, a strain deficient in all fumarase isoforms (ΔfumABC) elicited a unique metabolic profile. Alongside fumarate STM ΔfumABCaccumulates intermediates of glycolysis and pentose phosphate pathway. Analyses by metabolomics and proteomics revealed that fumarate accumulation redirects carbon fluxes towards glycogen synthesis due to high (p)ppGpp levels. In addition, we observed reduced abundance of CheY, leading to altered motility and increased phagocytosis of STM by macrophages. Deletion of glycogen synthase restored normal carbon fluxes and phagocytosis, and partially levels of CheY. We propose that utilization of accumulated fumarate as carbon source induces a status similar to exponential to stationary growth phase transition by switching from preferred carbon sources to fumarate, which increases (p)ppGpp levels and thereby glycogen synthesis. Thus, we observed a new form of interplay between metabolism of STM, and cellular functions and virulence.ImportanceWe performed perturbation analyses of the tricarboxylic acid cycle of the gastrointestinal pathogenSalmonella entericaserovar Typhimurium. The defect of fumarase activity led to accumulation of fumarate, but also resulted in a global alteration of carbon fluxes, leading to increased storage of glycogen. Gross alterations were observed in proteome and metabolome compositions of fumarase-deficientSalmonella. In turn, these changes were linked to aberrant motility patterns of the mutant strain, and resulted in highly increased phagocytic uptake by macrophages. Our findings indicate that basic cellular functions and specific virulence functions inSalmonellacritically depend on the proper function of the primary metabolism.
Species delimitation in the grey zone: introgression obfuscates phylogenetic inference and species boundaries in a cryptic frog complex (Ranidae: Pulchrana picturata)
Authors: Chan Kin Onn , Hutter Carl R. , Wood Perry L. , Lee Grismer L. , Brown Rafe M. 
Published: November 2019

ABSTRACTAs molecular methods continue to elucidate genetic structure at increasingly finer resolutions, delimiting species in the grey zone of the speciation continuum is becoming more relevant in biodiversity research, especially in under-studied biodiversity hotspots such as Southeast Asia where new species are being described at an unprecedented rate. Obvious species at both ends of the speciation continuum have mostly been described and attention is now turning towards the “grey zone:” an intermediate stage in which species criteria are in conflict and boundaries between populations and species are less clear. This study demonstrates that widely-used criteria (phylogenetic placement, genetic divergence, phylogeny- and distance-based species delimitation methods) can overestimate species diversity/boundaries when introgression is present. However, a comprehensive species delimitation framework that considers spatial and genetic population structure, introgression, and the use of species delimitation methods based on parameter estimation, can provide a more accurate characterization of species boundaries in this grey zone. We applied this approach to a group of Southeast Asian frogs from the Pulchrana picturata Complex that exhibits continuous morphological variation and high genetic divergences. Results showed that introgression was rampant among Bornean populations, which led to phylogenetic discordance and an overestimation of species. We suspect that our results do not form an isolated case; and that introgression among cryptic populations, occurring continuously across a wide geographic area (e.g., the topographically complex island of Borneo, and Earth’s major continents), may be more common than previously thought.