bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the chemistry and bioavailability of dissolved organic matter from glaciers and rock glaciers
Authors: Fegel Timothy , Boot Claudia M. , Broeckling Corey D. , Hall Ed K. 
Published: March 2017

AbstractAs glaciers thaw in response to warming, they release dissolved organic matter (DOM) to alpine lakes and streams. The United States contains an abundance of both alpine glaciers and rock glaciers. Differences in DOM composition and bioavailability between glacier types, like rock and ice glaciers, remain undefined. To assess differences in glacier and rock glacier DOM we evaluated bioavailability and molecular composition of DOM from four alpine catchments each with a glacier and a rock glacier at their headwaters. We assessed bioavailability of DOM by incubating each DOM source with a common microbial community and evaluated chemical characteristics of DOM before and after incubation using untargeted gas chromatography mass spectrometry based metabolomics (GC-MS). Prior to incubations, ice glacier and rock glacier DOM had similar C:N ratios and chemical diversity, but differences in DOM composition. Incubations with a common microbial community showed DOM from ice glacier meltwaters contained a higher proportion of bioavailable DOM (BDOM) and resulted in greater bacterial growth efficiency (BGE). After incubation, DOM composition from each source was statistically indistinguishable. This study provides an example of how MS based metabolomics can be used to assess effects of DOM composition on differences in bioavailability of DOM. Furthermore, it illustrates the importance of microbial metabolism in structuring composition of DOM. Even though rock glaciers had significantly less BDOM than ice glaciers, both glacial types still have potential to be important sources of BDOM to alpine headwaters over the coming decades.Key PointsBioavailability of organic matter released from glaciers is greater than that of rock glaciers in the Rocky Mountains.The use of GC-MS for ecosystem metabolomics represents a novel approach for examining complex organic matter pools.Both glaciers and rock glaciers supply highly bioavailable sources of organic matter to alpine headwaters in Colorado.
Asymmetric evolution of the transcription profiles andcis-regulatory sites contributes to the retention of transcription factor duplicates
Authors: Panchy Nicholas L. , Azodi Christina B. , Winship Eamon F. , O’Malley Ronan C. , Shiu Shin-Han 
Published: March 2017

AbstractTranscription factors (TFs) play a key role in regulating plant development and response to environmental stimuli. While most genes revert to single copy after a duplication event, transcription factors are retained at a significantly higher rate. However, it is unclear why TF duplicates have higher rates of retention relative to other genes. In this study, we compared three types of features (expression, sequence, and conservation) of retained TFs following whole genome duplication (WGD) events to genes with other functions, usingArabidopsis thalianaas a model. We found that gene function groups with higher maximum expression but lower mean expression tended to have higher duplicate retention rate post WGD, though TFs in particular are retained more often than would be expected based on the features examined. Conversely, expression of individual genes was not associated with duplication, but sequence conservation was. Furthermore, we found that the evolution of TF expression patterns and cis-regulatory cites favors the partitioning of ancestral states among the resulting duplicates. In particular, we found that one duplicate retains the majority of ancestral expression and cis-regulatory sites, while the “non-ancestral” duplicate was enriched for novel regulatory sites. To investigate how this pattern of partitioning pattern evolved, we modeled the retention of ancestral states in duplicate pairs using a system of differential equations. Our findings indicate that duplicate pairs evolve to a partitioned state more often than away from it, which in combination with accumulation of new regulatory sites in non-ancestral duplicates, suggest that selection favors partitioning via neofunctionalization.Author SummaryGene expression is controlled by regulatory proteins known as transcription factors. These factors control how an organism develops and responds to its environment. The evolution of transcription factor functions also contributes to the emergence of new species and crop domestication. In plants, new transcription factors mainly arise due to polyploidy, multiplication of the genome. Although most duplicated copies are lost following a genome duplication event, transcription factors are exceptional because they are often kept. Furthermore, we found that transcription factor duplicates that tend to diverge in how they are expressed and regulated in an unusual way where one copy mirrors the original, pre-duplication functional states of the ancestral gene, while the other loses the ancestral status and instead accumulates novel regulatory sites. Our results suggest these duplicate transcription factors may have been kept because one copy preserve ancestral function while the other has evolved new ones.
Uncovering Robust Patterns of MicroRNA Co-Expression across Cancers Using Bayesian Relevance Networks
Authors: Ramachandran Parameswaran , Sánchez-Taltavull Daniel , Perkins Theodore J. 
Published: March 2017

AbstractCo-expression networks have long been used as a tool for investigating the molecular circuitry governing biological systems. However, most algorithms for constructing co-expression networks were developed in the microarray era, before high-throughput sequencing—with its unique statistical properties—became the norm for expression measurement. Here we develop Bayesian Relevance Networks, an algorithm that uses Bayesian reasoning about expression levels to account for the differing levels of uncertainty in expression measurements between highly- and lowly-expressed entities, and between samples with different sequencing depths. It combines data from groups of samples (e.g., replicates) to estimate group expression levels and confidence ranges. It then computes uncertainty-moderated estimates of cross-group correlations between entities, and uses permutation testing to assess their statistical significance. Using large scale miRNA data from The Cancer Genome Atlas, we show that our Bayesian update of the classical Relevance Networks algorithm provides improved reproducibility in co-expression estimates and lower false discovery rates in the resulting co-expression networks. Software is available atwww.perkinslab.ca/Software.html.
Morphological Alternations of Intraepithelial and Stromal Telocytes in Response to Salinity Challenges
Authors: Abdel-latief Soliman Soha Mohamed , Ali Emeish Walaa Fathy 
Published: March 2017

Summary statementThe article represent an experimental study in which we investigated the effect of the ssalinty on the communicating cells (telocytes) and their target cells including chloride, stem, Rodlet cells, myoblastsAbstractTelocyte is a communicating cell established relations to various types of cells. Few experimental studies are performed on telocytes. The current study investigated responce of telocytes to salinity stress in relations to osmoregualtory, immune and stem cells. We exposed Common carp to salinity level 0.2, 6, 10, 14 ppt. Gill samples were fixed and processed for microscopic and TEM. Two types of telocytes were identified: intraepithelial and stromal telocytes. Intraepithelial telocytes comprised the cellular lining of the lymph spaces where they shed the secretory vesicles. Stromal telocytes shed their secretory vesicles in the secondary circulatory vessels. Telocyte enlarged and exhibited high secretory activities. They exert their effect either by direct contact or by paracrine mode. In sanity treated samples, chloride cells enlarged and the mitochondria became cigar-shaped. pavement cells enlarged and micro-ridges elongated. Stromal telocytes established contact with stem cell and skeletal myoblast. Macrophages and Rodlet cells increased in number. In conclusion, intraepithelial and stromal responded to salinity stress by activation of cellular signaling. They play a major role in osmoregulation, immunity, and regeneration.
Identification and characterization of m6A circular RNA epitranscriptomes
Authors: Zhou Chan , Molinie Benoit , Daneshvar Kaveh , Pondick Joshua V. , Wang Jinkai , Van Wittenberghe Nicholas O. , Xing Yi , Giallourakis Cosmas C. , Mullen Alan C. 
Published: March 2017

SummaryThis study brings together the expanding fields of RNA modifications and circular (circ) RNAs. We find that cells express thousands of m6A methylated circRNAs, with cell-type specificity observed between human embryonic stem cells and HeLa cells. m6A-circRNAs were identified by RNA sequencing of total RNA following ribosome depletion and m6A immunoprecipitation. The presence of m6A-circRNAs is corroborated by the identification of complexes between circRNAs and YTHDF1 and YTHDF2, proteins that “read” m6A sites in mRNAs.Furthermore, m6A modifications on non-linear RNAs depend on METTL3 and METTL14, the known m6A methyltransferase “writer” complex components, suggesting that circRNAs are methylated by the same complexes responsible for m6A modification of linear RNAs. Despite sharing m6A readers and writers, m6A-circRNAs are frequently derived from exons not methylated in mRNAs. Nevertheless, m6A-mRNAs that are methylated on the same exons as those composing m6A-circRNAs exhibit less stability than other m6A-mRNA, and this circRNA-mRNA cross-talk is regulated by YTHDF2. Thus, our results expand the m6A regulatory code through identification of the first circRNA epitranscriptome.
Presynaptic LRP4 Promotes Synapse Number and Function of Excitatory CNS Neurons
Authors: Mosca Timothy J. , Luginbuhl David J. , Wang Irving E. , Luo Liqun 
Published: March 2017

SUMMARYPrecise coordination of synaptic connections ensures proper information flow within circuits. The activity of presynaptic organizing molecules signaling to downstream pathways is essential for such coordination, though such entities remain incompletely known. We show that LRP4, a conserved transmembrane protein known for its postsynaptic roles, functions presynaptically as an organizing molecule. In theDrosophilabrain, LRP4 preferentially localizes to excitatory neuron terminals at or near active zones. Loss of presynaptic LRP4 reduces excitatory (not inhibitory) synapse number, impairs active zone architecture, and abolishes olfactory attraction - the latter of which can be suppressed by reducing presynaptic GABABreceptors. LRP4 overexpression increases synapse number in excitatory and inhibitory neurons, suggesting an instructive role and a common downstream synapse addition pathway. Mechanistically, LRP4 functions via the conserved kinase SRPK79D to ensure normal synapse number and behavior. This highlights a presynaptic function for LRP4, enabling deeper understanding of how synapse organization is coordinated.
Developing Gene-Specific Meta-Predictor of Variant Pathogenicity
Authors: Rychkova Anna , Buu MyMy C. , Scharfe Curt , Lefterova Martina I. , Odegaard Justin I. , Schrijver Iris , Milla Carlos , Bustamante Carlos D. 
Published: March 2017

AbstractRapid, accurate, and inexpensive genome sequencing promises to transform medical care. However, a critical hurdle to enabling personalized genomic medicine is predicting the functional impact of novel genomic variation. Various methods of missense variants pathogenicity prediction have been developed by now. Here we present a new strategy for developing a pathogenicity predictor of improved accuracy by applying and training a supervised machine learning model in a gene-specific manner. Our meta-predictor combines outputs of various existing predictors, supplements them with an extended set of stability and structural features of the protein, as well as its physicochemical properties, and adds information about allele frequency from various datasets. We used such a supervised gene-specific meta-predictor approach to train the model on theCFTRgene, and to predict pathogenicity of about 1,000 variants of unknown significance that we collected from various publicly available and internal resources. OurCFTR-specific meta-predictor based on the Random Forest model performs better than other machine learning algorithms that we tested, and also outperforms other available tools, such as CADD, MutPred, SIFT, and PolyPhen-2. Our predicted pathogenicity probability correlates well with clinical measures of Cystic Fibrosis patients and experimental functional measures of mutated CFTR proteins. Training the model on one gene, in contrast to taking a genome wide approach, allows taking into account structural features specific for a particular protein, thus increasing the overall accuracy of the predictor. Collecting data from several separate resources, on the other hand, allows to accumulate allele frequency information, estimated as the most important feature by our approach, for a larger set of variants. Finally, our predictor will be hosted on the ClinGen Consortium database to make it available to CF researchers and to serve as a feasibility pilot study for other Mendelian diseases.
CaMK (CMK-1) and O-GlcNAc transferase (OGT-1) modulate mechanosensory responding and habituation in an interstimulus interval-dependent manner inCaenorhabditis elegans
Authors: Ardiel Evan L. , McDiarmid Troy A. , Timbers Tiffany A. , Lee Kirsten C. Y. , Safaei Javad , Pelech Steven L. , Rankin Catharine H. 
Published: March 2017

AbstractThe ability to learn is an evolutionarily conserved adaptation that remains incompletely understood. Genetically tractable model organisms facilitate mechanistic explanations of learning that span genetic, neural circuit, and behavioural levels. Many aspects of neural physiology, including processes that underlie learning (e.g.neurotransmitter release and long-lasting changes in synaptic strength), are regulated by brief and local changes in [μm] levels of free intracellular Ca2+. On this scale, changes in [Ca2+] activate many Ca2+-sensors, including the Ca2+/calmodulin-dependent kinases (CaMKs). Here we reveal that theCaenorhabditis elegansortholog of CaMK1/4, CMK-1, functions in primary sensory neurons to regulate responses to mechanical stimuli and behavioral plasticity, specifically habituation, a conserved form of non-associative learning. The habituation phenotypes ofcmk-1mutants were dependent on interstimulus interval (ISI), such that CMK-1 slows habituation at short ISIs, but promotes it at long ISIs. We predicted potential CaMK phosphorylation targets from catalytic site analysis of the human andC. elegansCaMKs and mutant analysis of these candidates implicated O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, in mechanosensitivity and learning. Cell specific rescue and knockdown experiments showed that both CMK-1 and OGT-1 function cell autonomously in mechanosensory neurons to modulate learning. Interestingly, despite their similar mutant phenotypes, detailed behavioral analysis of double mutants demonstrated that CMK-1 and OGT-1 act in parallel genetic pathways. Our research identifies CMK-1 and OGT-1 as co-expressed yet independent regulators of mechanosensitivity and learning.
Serum soluble interleukin‐2 receptor level is more sensitive than angiotensin‐converting enzyme or lysozyme for diagnosis of sarcoidosis and may be a marker of multiple organ involvement
Authors: Thi Hong Nguyen Chuyen , Kambe Naotomo , Kishimoto Izumi , Ueda‐Hayakawa Ikuko , Okamoto Hiroyuki 
Published: March 2017

AbstractSkin lesions in sarcoidosis are often the initial symptoms that enable the dermatologist to be the first to diagnose this granulomatosis. However, diagnosis is sometimes very problematic. In 2015, the diagnostic criteria for sarcoidosis were updated in Japan, with elevated serum soluble interleukin‐2 receptor (sIL‐2R) replacing negative tuberculin reaction. Therefore, we assessed the clinical utility of sIL‐2R compared with two other common markers, angiotensin‐converting enzyme (ACE) and lysozyme, in patients who visited the dermatology clinic. Data from 72 patients showed that sIL‐2R was more sensitive than both ACE and lysozyme in supporting a diagnosis of sarcoidosis (52.8%) compared with ACE (29%) and lysozyme (26.4%). Additionally, the sIL‐2R level was significantly higher in patients with multiple organ involvement and parenchymal infiltration. Patients with elevated sIL‐2R levels had higher serum ACE and lysozyme levels, a higher incidence of pulmonary involvement, more severe chest radiographic stage and a high incidence of expression‐specific signs by imaging analysis. Receiver–operator curve analysis showed that sIL‐2R was a better marker at the threshold cut‐off point compared with ACE and lysozyme for identifying patients with multiple organ involvement, detecting patients with pulmonary disease and parenchymal infiltration as well as predicting the presence of specific signs in the diagnosis of sarcoidosis. Moreover, the kinetics of sIL‐2R levels correlated closely with clinical manifestations, in contrast to the modest changes of ACE and lysozyme levels during the follow‐up period. In conclusion, sIL‐2R may be considered a good marker for diagnosis and a potential indicator of disease activity.
Concomitant confluent and reticulated papillomatosis and acanthosis nigricans in an obese girl with insulin resistance successfully treated with oral minocycline: Case report and published work review
Authors: Fukumoto Takeshi , Kozaru Takeshi , Sakaguchi Masanobu , Oka Masahiro 
Published: March 2017

AbstractConcomitant confluent and reticulated papillomatosis (CRP) and acanthosis nigricans (AN) is rare. We present a case of concomitant CRP and obesity‐associated AN in a 12‐year‐old obese Japanese girl. Curiously, oral minocycline therapy, which has been shown to be effective for CRP, was effective against both CRP and AN. Possible mechanisms by which minocycline could have improved skin lesions of CRP and obesity‐associated AN are discussed. In addition, reports of concomitant CRP and obesity‐associated AN are reviewed. CRP and obesity‐associated AN share common clinicopathological features and some reports have described concomitant CRP and obesity‐associated AN. Together with the observation that skin lesions of CRP and obesity‐associated AN in the present case responded to oral minocycline therapy, these facts suggest a tight relationship or a common pathogenetic pathway between these pathologies.
Two cases of melanomas paradoxically metastasizing to the intestinal tract during nivolumab therapy
Authors: Miyazawa Hajime , Yanagi Teruki , Yamaguchi Yasuyuki , Imafuku Keisuke , Kitamura Shinya , Hata Hiroo , Uehara Jiro , Ichikawa Nobuki , Ohno Yosuke , Yoshida Tadashi , Homma Shigenori , Kawamura Hideki , Taketomi Akinobu , Shimizu Hiroshi 
Published: March 2017

AbstractWe report two cases of melanomas in patients who developed intestinal metastasis despite other metastatic sites responding to nivolumab and despite the patients having favorable findings such as vitiligo and normal lactate dehydrogenase. The first case is an 85‐year‐old man who had been administrated nivolumab for lung/cutaneous metastases. After 22 courses of nivolumab therapy, fever and anorexia had appeared and his bodyweight had decreased. An intussusception on the ileocecal valve was revealed by computed tomography, and emergency surgery revealed metastatic lesions on the colon. The second case is an 87‐year‐old woman treated with nivolumab for lymph node metastases. After 10 courses, laboratory tests had revealed anemia and positive fecal occult blood. Her bodyweight had decreased. Capsule endoscopy showed scattered tumors and clots, indicating metastases of melanoma. The frequency of symptomatic intestinal metastasis of melanoma is very low. Further, intestinal metastasis of melanoma is difficult to detect through routine examinations. Our cases suggest that fecal occult blood test and decreased bodyweight are indications of intestinal metastases.
Evaluation of positron emission tomography imaging to detect lymph node metastases in patients with extramammary Paget's disease
Authors: Fujiwara Masao , Suzuki Takahiro , Senoo Ayumi , Fukamizu Hidekazu , Tokura Yoshiki 
Published: March 2017

AbstractPatients with extramammary Paget's disease (EMPD) have a relatively good prognosis, when spread of the tumor cells is limited to the epidermis. However, invasive EMPD has a poor prognosis, when the patients have regional lymph node metastasis. Detection of nodal metastasis is thus mandatory to manage EMPD. To evaluate the 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) imaging to assess lymph node metastasis, 15 patients with histologically proven primary EMPD were enrolled in this study. All patients underwent whole‐body PET prior to sentinel lymph node biopsy (SLNB). The maximum standardized uptake value (SUVmax) of more than 2.5 was evaluated as positive PET indicative of malignancy. Among 14 cases with the primary genital lesions, 11 cases underwent bilateral SLNB of the inguinal nodal basin and the remaining three cases unilateral SLNB. One case with a primary axillary lesion underwent unilateral SLNB of the axillary nodal basin. Therefore, a total of 26 regional basins were investigated. In general, nodal basins can be categorized into four groups: (i) histologically negative and PET negative (true negative); (ii) histologically positive and PET negative (false negative); (iii) histologically positive and PET positive (true positive); and (iv) histologically negative and PET positive (false positive) groups. In the 26 nodal basins, there were 19 true negative and seven true positive cases, and neither false negative nor false positive cases were observed. The mean SUVmax was significantly higher in the true positive basins (8.03 ± 3.34) than in the true negative basins (0.26 ± 0.56). The SUVmax value may be useful for detection of nodal metastasis.
Peripartum type B aortic dissection in patients with Marfan syndrome who underwent aortic root replacement: a case series study
Authors: Sayama S , Takeda N , Iriyama T , Inuzuka R , Maemura S , Fujita D , Yamauchi H , Nawata K , Bougaki M , Hyodo H , Shitara R , Nakayama T , Komatsu A , Nagamatsu T , Osuga Y , Fujii T 
Published: March 2017

ObjectiveTo investigate pregnancy outcomes, especially the risk of pregnancy‐related aortic dissection (AD), in patients with Marfan syndrome (MFS) after prophylactic aortic root replacement (ARR).DesignRetrospective case series study.SettingTertiary perinatal care centre at a university hospital.PopulationPregnant women fulfilling the revised Ghent nosology (2010) criteria for MFS who were managed at our institute.MethodsThe pregnancy outcomes of all patients with MFS managed at our institute between 1982 and September 2016 were reviewed retrospectively based on medical records.Main outcome measuresObstetrical management and complication including the incidence of AD throughout the peripartum period.ResultsAmong 22 patients (28 pregnancies) who had been managed as potential MFS or related disorders, 14 (17 pregnancies) fulfilled the revised Ghent nosology (2010) criteria for MFS and were enrolled in this study. Five patients (five pregnancies) had received ARR before conception: three (60%) developed type B aortic dissection [AD(B)] during the peripartum period, compared with only one of 10 patients (12 pregnancies) without ARR (P < 0.05, Chi‐square test).ConclusionsOur study results suggest that MFS patients after prophylactic ARR are still at high risk of AD(B) during the peripartum period. Careful pre‐pregnancy counselling and multidisciplinary care throughout the peripartum period are essential for the management of MFS, even after surgical repair of an ascending aortic aneurysm.Tweetable abstractMFS patients after prophylactic ARR are still at high risk of type B aortic dissection during the peripartum period.