bluuebunny/crossref_metadata_2025_split huggingface dataset:
Negative frequency dependent selection contributes to the maintenance of a global polymorphism in mitochondrial DNA
Authors: Kurbalija Novičić Zorana , Sayadi Ahmed , Jelić Mihailo , Arnqvist Göran 
Published: February 2020

AbstractBackgroundUnderstanding the forces that maintain diversity across a range of scales is at the very heart of biology. Frequency-dependent processes are generally recognized as the most central process for the maintenance of ecological diversity. The same is, however, not generally true for genetic diversity. Negative frequency dependent selection, where rare genotypes have an advantage, is often regarded as a relatively weak force in maintaining genetic variation in life history traits because recombination disassociates alleles across many genes. Yet, many regions of the genome show low rates of recombination and genetic variation in such regions (i.e., supergenes) may in theory be upheld by frequency dependent selection.ResultsWe studied what is essentially a ubiquitous life history supergene (i.e., mitochondrial DNA) in the fruit flyDrosophila subobscura, showing sympatric polymorphism with two main mtDNA genotypes co-occurring in populations world-wide. Using an experimental evolution approach involving manipulations of genotype starting frequencies, we show that negative frequency dependent selection indeed acts to maintain genetic variation in this region. Moreover, the strength of selection was affected by food resource conditions.ConclusionsOur work provides novel experimental support for the view that balancing selection through negative frequency dependency acts to maintain genetic variation in life history genes. We suggest that the emergence of negative frequency dependent selection on mtDNA is symptomatic of the fundamental link between ecological processes related to resource use and the maintenance of genetic variation.
Comparative transcriptome analysis indicates conversion of stamens into pistil-like structures in male sterile wheat (Triticum aestivum L.) with Aegilops crassa cytoplasm
Authors: Liu Qi , Liu Zihan , Li Wei , Song Xiyue 
Published: February 2020

AbstractBackgroundAegilops crassacytoplasm is an important source for investigating cytoplasmic male sterility (CMS). Moreover, the stamens of line C303A exhibit a high degree of pistillody, turning almost white. However, the molecular mechanism that underlies pistillody in C303A remains unclear. Therefore, to obtain a better understanding of pistillody in C303A, the phenotypic and cytological features of C303A were observed to identify the key stage for the homeotic transformation of stamens into pistil-like structures. Transcriptome profiles were determined for stamens using Illumina RNA sequencing.ResultsMorphological observations of the CMS wheat line withAegilops crassacytoplasm C303A showed that the pistils developed normally, but the stamens were ultimately aborted and they released no pollen when mature. According to paraffin section observations, the stamens began to transform into pistils or pistil-like structures in the binucleate stage (BNS). Therefore, the stamens were collected from line C303A and its maintainer 303B in the BNS for transcriptome sequencing. In total, 20,444 wheat genes were determined as differentially expressed in C303A and 303B stamens, with 10,283 upregulated and 10,161 downregulated genes. Gene Ontology enrichment analyses showed that most of the differentially expressed genes (DEGs) were annotated with GO terms comprising metabolic process, cell, cellular process, catalytic activity, and cell part. Analysis based on the Kyoto Encyclopedia of Genes and Genomes database showed that the enriched DEGs were mainly associated with energy metabolism. We also found several essential genes that may contribute to pistillody in C303A. These findings suggest that disrupted energy metabolism and reactive oxygen metabolism induce pistillody and eventually lead to abortion in C303A.ConclusionWe determined the complex transcriptome profiles for C303A stamens and demonstrated that disrupted energy metabolism and class B MADS-box genes are related to pistillody. These findings may facilitate future studies of the mechanistic response of the wheat stamen and pollen development in CMS.
Immune-related miRNA-mRNA regulation network in the livers of DHAV-3-infected ducklings
Authors: Wu Fengyao , Lu Fengying , Fan Xin , Chao Jin , Liu Chuanmin , Pan Qunxing , Sun Huawei , Zhang Xiaofei 
Published: February 2020

AbstractBackgroundDuck hepatitis A virus type 3 (DHAV-3) is one of the most harmful pathogens in the duck industry. However, the molecular mechanism underlying DHAV-3 infection in ducklings remains poorly understood. To study the genetic regulatory network for miRNA-mRNA and the signaling pathways involved in DHAV-3 infection in ducklings, we conducted global miRNA and mRNA expression profiling of duckling liver tissues infected with lethal DHAV-3 by high-throughput sequencing.ResultsWe found 156 differentially expressed miRNAs (DEMs) and 7717 differentially expressed genes (DEGs) in livers of mock-infected and DHAV-3-infected duckling. A total of 19,606 miRNA-mRNA pairs with negatively correlated expression patterns were identified in miRNA-mRNA networks constructed on the basis of these DEMs and DEGs. Moreover, immune-related pathways, including the cytokine-cytokine receptor interaction, apoptosis, Toll-like receptor, Jak-STAT, and RIG-I-like receptor signaling pathway, were significantly enriched through analyzing functions of mRNAs in the network in response to DHAV-3 infection. Furthermore, apl-miR-32-5p, apl-miR-125-5p, apl-miR-128-3p, apl-miR-460-5p, and novel-m0012-3p were identified as potential regulators in the immune-related signaling pathways during DHAV-3 infection. And some host miRNAs were predicted to target the DHAV-3 genome.ConclusionsThis is the first integrated analysis of miRNA and mRNA in DHAV-3-infected ducklings. The results indicated the important roles of miRNAs in regulating immune response genes and revealed the immune related miRNA-mRNA regulation network in the DHAV-3-infected duckling liver. These findings increase our knowledge of the roles of miRNAs and their target genes in DHAV-3 replication and pathogenesis. They also aid in the understanding of host-virus interactions.
Proximity ligation assay reveals both pre- and postsynaptic localization of the APP-processing enzymes ADAM10 and BACE1 in rat and human adult brain
Authors: Lundgren Jolanta L. , Vandermeulen Lina , Sandebring-Matton Anna , Ahmed Saheeb , Winblad Bengt , Di Luca Monica , Tjernberg Lars O. , Marcello Elena , Frykman Susanne 
Published: February 2020

Abstract
Background
Synaptic degeneration and accumulation of amyloid β-peptides (Aβ) are hallmarks of the Alzheimer diseased brain. Aβ is synaptotoxic and produced by sequential cleavage of the amyloid precursor protein (APP) by the β-secretase BACE1 and by γ-secretase. If APP is instead cleaved by the α-secretase ADAM10, Aβ will not be generated. Although BACE1 is considered to be a presynaptic protein and ADAM10 has been reported to mainly localize to the postsynaptic density, we have previously shown that both ADAM10 and BACE1 are highly enriched in synaptic vesicles of rat brain and mouse primary hippocampal neurons.

Results
Here, using brightfield proximity ligation assay, we expanded our previous result in primary neurons and investigated the in situ synaptic localization of ADAM10 and BACE1 in rat and human adult brain using both pre- and postsynaptic markers. We found that ADAM10 and BACE1 were in close proximity with both the presynaptic marker synaptophysin and the postsynaptic marker PSD-95. The substrate APP was also detected both pre- and postsynaptically. Subcellular fractionation confirmed that ADAM10 and BACE1 are enriched to a similar degree in synaptic vesicles and as well as in the postsynaptic density.

Conclusions
We show that the α-secretase ADAM10 and the β-secretase BACE1 are located in both the pre- and postsynaptic compartments in intact brain sections. These findings increase our understanding of the regulation of APP processing, thereby facilitating development of more specific treatment strategies.
A comparative gene co-expression analysis using self-organizing maps on two congener filmy ferns identifies specific desiccation tolerance mechanisms associated to their microhabitat preference
Authors: Ostria-Gallardo Enrique , Larama Giovanni , Berríos Graciela , Fallard Ana , Gutiérrez-Moraga Ana , Ensminger Ingo , Bravo León A. 
Published: February 2020

Abstract
Background
Filmy-ferns (Hymenophyllaceae) are poikilohydric, homoiochlorophyllous desiccation-tolerant (DT) epiphytes. They can colonize lower and upper canopy environments of humid forest. Filmy-ferns desiccate rapidly (hours), contrasting with DT angiosperms (days/weeks). It has been proposed that desiccation tolerance in filmy-ferns would be associated mainly with constitutive features rather than induced responses during dehydration. However, we hypothesize that the inter-specific differences in vertical distribution would be associated with different dynamics of gene expression within the dehydration or rehydration phases. A comparative transcriptomic analysis with an artificial neural network was done on Hymenophyllum caudiculatum (restricted to lower canopy) and Hymenophyllum dentatum (reach upper canopy) during a desiccation/rehydration cycle.

Results
Raw reads were assembled into 69,599 transcripts for H. dentatum and 34,726 transcripts for H. caudiculatum. Few transcripts showed significant changes in differential expression (DE). H. caudiculatum had ca. twice DE genes than H. dentatum and higher proportion of increased-and-decreased abundance of genes occurs during dehydration. In contrast, the abundance of genes in H. dentatum decreased significantly when transitioning from dehydration to rehydration. According to the artificial neural network results, H. caudiculatum enhanced osmotic responses and phenylpropanoid related pathways, whilst H. dentatum enhanced its defense system responses and protection against high light stress.

Conclusions
Our findings provide a deeper understanding of the mechanisms underlying the desiccation tolerance responses of two filmy ferns and the relationship between the species-specific response and the microhabitats these ferns occupy in nature.
Modulation of volatile compound metabolome and transcriptome in grape berries exposed to sunlight under dry-hot climate
Authors: He Lei , Xu Xiao-Qing , Wang Yu , Chen Wei-Kai , Sun Run-Ze , Cheng Guo , Liu Bin , Chen Wu , Duan Chang-Qing , Wang Jun , Pan Qiu-Hong 
Published: February 2020

AbstractBackgroundBasal leaf removal is widely practiced to increase grape cluster sunlight exposure that controls berry rot and improves quality. Studies on its influence on volatile compounds in grape berries have been performed mostly in Mediterranean or marine climate regions. It is uncertain whether similar efficiency can be achieved when grape berries are grown under continental climate. This study aimed to dissect the variation in volatile compound production and transcriptome in sunlight-exposed grape berries in a dry-hot climate region and to propose the key genes related to the variation.ResultsFour cluster sunlight exposure strategies, including basal leaf removal at pepper-corn size stage, leaf removal at véraison (LR-V), leaf moving at véraison (LM-V), and half-leaf removal at véraison, were implemented at the north foot of the Mt. Tianshan region of northwestern China. Various cluster exposure treatments resulted in a decline in the concentrations of norisoprenoids and monoterpenes in ripening grape berries. Bothβ-carotene and lutein, the substrates of norisoprenoid biosynthesis, were reduced by cluster sunlight exposure. K-means cluster analysis showed that some genes involved in biosynthesis such asVviTPS55,VviTPS60,VviTPS66,VviCCD4aandVviCCD4bexhibited lower expression levels in exposed berries at least at one of the tested stages. Two C6-derived esters with fruity attributes, ethyl hexanoate and hexyl acetate, were reduced markedly. In contrast, main C6 alcohol compound levels were elevated in the LR-V- and LM-V-treated grape berries, which corresponded to the up-regulated expression ofVviLOXA,VviLOXOandVviADH1in the oxylipin pathway. Most of the differentially expressed genes in the exposed and control berries were enriched to the “stress response” processes, and this transcriptome difference was accumulated as the berries matured. Besides, LR-V treatment stimulated a significant up-regulation in photosynthesis-related genes in the grape berries, which did not happen with LM-V treatment.ConclusionsCluster sunlight exposure in dry-hot climate viticulture resulted in different volatile-targeted transcriptomic and metabolic responses from those obtained in the temperate Mediterranean or marine climate region. Therefore, a modified canopy management should be adopted to improve the aroma of grape berries.
Persistent unexplained chest pain and dyspnea in a patient with coronary artery disease: a case report
Authors: Mobarek Sameh K. 
Published: February 2020

Abstract
Background
Neurogenic orthostatic hypotension, a sustained decrease in blood pressure upon standing, is caused by autonomic nervous system failure and characterized by an insufficient increase in heart rate needed to maintain blood pressure upon standing. In this case, neurogenic orthostatic hypotension symptoms preceded a diagnosis of Parkinson disease. A diagnosis of underlying neurogenic orthostatic hypotension significantly changed the course of treatment for this patient.

Case presentation
An 84-year-old woman was referred to a cardiologist by her primary care practitioner for evaluation of exertional dyspnea and chest pain upon walking a few feet. Her medical history included hypertension, hypothyroidism, and osteoarthritis. Based on her continued symptoms, the patient underwent 2 cardiac catheterizations for coronary artery stenosis. After the catheterizations, exertional dyspnea and chest pain continued, and subsequently, dysphagia to solid foods and episodic dizziness developed. Orthostatic evaluation showed a supine blood pressure of 150/80 mmHg with a heart rate of 70 beats per min. Upon standing for 3 min, the patient’s blood pressure decreased to 110/74 mmHg with a heart rate of 76 beats per min. The diagnostic criteria for orthostatic hypotension were met, and the lack of an adequate compensatory heart rate increase upon standing was consistent with a neurogenic cause (ie, neurogenic orthostatic hypotension), which was supported by tilt-table testing results. Although nonpharmacologic treatments were initially successful, episodes of lightheadedness, chest pain, and dyspnea upon standing became more frequent, and the patient was prescribed droxidopa (200 mg; 3 times daily). Droxidopa significantly improved her symptoms, with the patient reporting resolution of her chest pain and significant improvement of dyspnea and dizziness. She was diagnosed with Parkinson disease approximately 6 months later.

Conclusions
This case highlights the importance of evaluating and identifying potential causes of symptoms of cardiovascular disease when persistent symptoms do not improve after cardiac interventions. This case complements findings demonstrating that signs of autonomic failure, such as neurogenic orthostatic hypotension, may precede the motor symptoms of Parkinson disease. Importantly, this case provides real-world evidence for the efficacy of droxidopa to treat the symptoms of neurogenic orthostatic hypotension, after an appropriate diagnosis.
Dietary quality indices modifies the effects of melanocortin-4 receptor (MC4R) rs17782313 polymorphism on cardio-metabolic risk factors and hypothalamic hormones in obese adults
Authors: Khodarahmi Mahdieh , Kahroba Houman , Jafarabadi Mohammad Asghari , Mesgari-Abbasi Mehran , Farhangi Mahdieh Abbasalizad 
Published: February 2020

Abstract
Background
Although the Melanocortin-4 Receptor (MC4R) gene rs17782313 C/T has been consistently related to obesity risk, the interaction between MC4R polymorphism and diet quality indices on cardio-metabolic risk factors has not yet investigated. Therefore we aimed to test this hypothesis.

Methods
This cross-sectional study recruited 188 (96 males and 92 females) healthy obese adults aged 20–50 years. Diet quality indices including Healthy Eating Index-2015 (HEI-2015) and Diet Quality Index-International (DQI-I) were constructed using data from a validated food frequency questionnaire. MC4R s17782313 were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The interaction between MC4R polymorphism and diet quality indices was tested by Analysis of covariance (ANCOVA) multivariate interaction model.

Results
There were significant gene-diet interactions between rs17782313 and HEI-2015 (P Interaction < 0.05) in modulating low-density lipoprotein cholesterol (LDL-C) levels among female group; rare allele heterozygotes of rs17782313 had highest mean of LDL-C concentration when placed in second tertile of HEI (P < 0.05). Moreover, rs17782313 and both indices (HEI and DQI-I) had significant interaction on serum glucose concentrations, systolic and diastolic blood pressure (SBP, DBP) in males (P Interaction < 0.05); when adherence to these indices was low, the obesity risk allele was associated with serum glucose concentrations, SBP and DBP. These gene-diet interactions remained significant even after adjustment for potential confounders.

Conclusion
Our study showed that MC4R rs17782313 interacts with adherence to the dietary quality indices (HEI and DQI-I) to influence several cardio-metabolic risk factors in obese male and females. Further large prospective studies are warranted to confirm our findings.
18F- FDG PET/CT-derived parameters predict clinical stage and prognosis of esophageal cancer
Authors: Mantziari Styliani , Pomoni Anastasia , Prior John O. , Winiker Michael , Allemann Pierre , Demartines Nicolas , Schäfer Markus 
Published: February 2020

Abstract
Background
Although 18F- FDG PET/CT is validated in baseline workup of esophageal cancer to detect distant metastases, it remains underused in assessing local staging and biology of the primary tumor. This study aimed to evaluate the association between 18F- FDG PET/CT-derived parameters of esophageal cancer, and its clinico-pathological features and prognosis.

Methods
All patients (n = 86) with esophageal adenocarcinoma or squamous cell cancer operated between 2005 and 2014 were analyzed. Linear regression was used to identify clinico-pathologic features of esophageal cancer associated with the tumor’s maximal Standardized Uptake Value (SUVmax), Total Lesion Glycolysis (TLG) and Metabolic Tumor Volume (MTV). ROC curve analysis was performed to precise the optimal cutoff of each variable associated with a locally advanced (cT3/4) status, long-term survival and recurrence. Kaplan Meier curves and Cox regression were used for survival analyses.

Results
High baseline SUVmax was associated with cT3/4 status and middle-third tumor location, TLG with a cT3/4 and cN+ status, whereas MTV only with active smoking. A cT3/4 status was significantly predicted by a SUVmax > 8.25 g/mL (p < 0.001), TLG > 41.7 (p < 0.001) and MTV > 10.70 cm3 (p < 0.01) whereas a SUVmax > 12.7 g/mL was associated with an early tumor recurrence and a poor disease-free survival (median 13 versus 56 months, p = 0.030), particularly in squamous cell cancer.

Conclusions
Baseline 18F- FDG PET/CT has a high predictive value of preoperative cT stage, as its parameters SUVmax, TLG and MTV can predict a locally advanced tumor with high accuracy. A SUVmax > 12.7 g/mL may herald early tumor recurrence and poor disease-free survival.
Abnormal blood pressure circadian rhythms are relevant to cerebral infarction and Leukoaraiosis in hypertensive patients
Authors: Yang Kang , Zhu Xiaodong , Feng Yulan , Shen Fanxia , Chen Jie , Fu Ningzhen , Sun Jialan , Fu Yi 
Published: February 2020

Abstract
Background
To investigate the relationships between blood pressure (BP) circadian rhythms and acute cerebral infarction (ACI), silent cerebral infarction (SCI) and the severity of leukoaraiosis in hypertensive patients.

Methods
A retrospective case-control study was performed among hypertensive patients with 24-h ambulatory blood pressure monitoring (ABPM) and cranial magnetic resonance imaging (MRI).

Results
A total of 1267 patients were enrolled. Lower nocturnal blood pressure (BP) decreases were observed in ACI patients than in controls (3.3% vs 8.2%, P<0.001). Reverse-dipper pattern (RD) and non-dipper pattern (ND) were found to be independent risk factors for ACI. In ACI patients, both RD and ND BP circadian rhythms were revealed to be independent risk factors for moderate-severe leukoaraiosis. In addition, in SCI patients, RD (OR = 1.7, 95% CI, 0.9–3.0; P = 0.047) or extreme-dipper pattern (ED) (OR = 2.9, 95% CI, 1.2–7.0; P = 0.015) were found to be independent risk factors for moderate-severe leukoaraiosis. Moreover, the greater the severity of leukoaraiosis was, the higher the ratio of abnormal BP circadian rhythms.

Conclusion
RD and ND BP circadian rhythms might not only be relevant to the onset of ACI but also correlate with the severity of leukoaraiosis. Thus, when modulating BP with antihypertensive drugs, the BP circadian rhythms, and not merely the BP level, should warrant more attention.
Development and validation of a preoperative nomogram for predicting survival of patients with locally advanced prostate cancer after radical prostatectomy
Authors: Zhou Xianghong , Ning Qingyang , Jin Kun , Zhang Tao , Ma Xuelei 
Published: February 2020

Abstract
Background
For selected locally advanced prostate cancer (PCa) patients, radical prostatectomy (RP) is one of the first-line treatments. We aimed to develop a preoperative nomogram to identify what kinds of patients can get the most survival benefits after RP.

Methods
We conducted analyses with data from the Surveillance, Epidemiology, and End Results (SEER) database. Covariates used for analyses included age at diagnosis, marital status, race, American Joint Committee on Cancer (AJCC) 7th TNM stage, Prostate specific antigen, Gleason biopsy score (GS), percent of positive cores. We estimated the cumulative incidence function for cause-specific death. The Fine and Gray’s proportional subdistribution hazard approach was used to perform multivariable competing risk analyses and reveal prognostic factors. A nomogram was built by these factors (including GS, percent of positive cores and N stage) and validated by concordance index and calibration curves. Risk stratification was established based on the nomogram.

Results
We studied 14,185 patients. N stage, GS, and percent of positive cores were the independent prognostic factors used to construct the nomogram. For validating, in the training cohort, the C-index was 0.779 (95% CI 0.736–0.822), and in the validation cohort, the C-index was 0.773 (95% CI 0.710–0.836). Calibration curves showed that the predicted survival and actual survival were very close. The nomogram performed better over the AJCC staging system (C-index 0.779 versus 0.764 for training cohort, and 0.773 versus 0.744 for validation cohort). The new stratification of risk groups based on the nomogram also showed better discrimination than the AJCC staging system.

Conclusions
The preoperative nomogram can provide favorable prognosis stratification ability to help clinicians identify patients who are suitable for surgery.