bluuebunny/crossref_metadata_2025_split huggingface dataset:
H19 inhibition increases HDAC6 and regulates IRS1 levels and insulin signaling in the skeletal muscle during diabetes
Authors: Kumar Amit , Datta Malabika 
Published: July 2022

Abstract
Background
Histone deacetylases (HDACs) that catalyze removal of acetyl groups from histone proteins, are strongly associated with several diseases including diabetes, yet the precise regulatory events that control the levels and activity of the HDACs are not yet well elucidated.

Methods
Levels of H19 and HDACs were evaluated in skeletal muscles of normal and diabetic db/db mice by Western Blot analysis. C2C12 cells were differentiated and transfected with either the scramble or H19 siRNA and the levels of HDACs and Prkab2, Pfkfb3, Srebf1, Socs2, Irs1 and Ppp2r5b were assessed by Western Blot analysis and qRT-PCR, respectively. Levels of H9, HDAC6 and IRS1 were evaluated in skeletal muscles of scramble/ H19 siRNA injected mice and chow/HFD-fed mice.

Results
Our data show that the lncRNA H19 and HDAC6 exhibit inverse patterns of expression in the skeletal muscle of diabetic db/db mice and in C2C12 cells, H19 inhibition led to significant increase in HDAC activity and in the levels of HDAC6, both at the transcript and protein levels. This was associated with downregulation of IRS1 levels that were prevented in the presence of the HDAC inhibitor, SAHA, and HDAC6 siRNA suggesting the lncRNA H19-HDAC6 axis possibly regulates cellular IRS1 levels. Such patterns of H19, HDAC6 and IRS1 expression were also validated and confirmed in high fat diet-fed mice where as compared to normal chow-fed mice, H19 levels were significantly inhibited in the skeletal muscle of these mice and this was accompanied with elevated HDAC6 levels and decreased IRS1 levels. In-vivo inhibition of H19 led to significant increase in HDAC6 levels and this was associated with a decrease in IRS1 levels in the skeletal muscle.

Conclusions
Our results suggest a critical role for the lncRNA H19-HDAC6 axis in regulating IRS1 levels in the skeletal muscle during diabetes and therefore restoring normal H19 levels might hold a therapeutic potential for the management of aberrant skeletal muscle physiology during insulin resistance and type 2 diabetes.
Proteomic analysis of low- and high-grade human colon adenocarcinoma tissues and tissue-derived primary cell lines reveals unique biological functions of tumours and new protein biomarker candidates
Authors: Munro Matthew J. , Wickremesekera Susrutha K. , Tan Swee T. , Peng Lifeng 
Published: July 2022

Abstract
Background
Colon cancer is the third most common cancer and second highest cause of cancer deaths worldwide. The aim of the study was to find new biomarkers for diagnosis, prognosis and therapeutic drug targets for this disease.

Methods
Four low-grade and four high-grade human colon adenocarcinoma tumours with patient-matched normal colon tissues were analysed. Additionally, tissue-derived primary cell lines were established from each tumour tissue. The cell lines were validated using DNA sequencing to confirm that they are a suitable in vitro model for colon adenocarcinoma based on conserved gene mutations. Label-free quantitation proteomics was performed to compare the proteomes of colon adenocarcinoma samples to normal colon samples, and of colon adenocarcinoma tissues to tissue-derived cell lines to find significantly differentially abundant proteins. The functions enriched within the differentially expressed proteins were assessed using STRING. Proteomics data was validated by Western blotting.

Results
A total of 4767 proteins were identified across all tissues, and 4711 across primary tissue-derived cell lines. Of these, 3302 proteins were detected in both the tissues and the cell lines. On average, primary cell lines shared about 70% of proteins with their parent tissue, and they retained mutations to key colon adenocarcinoma-related genes and did not diverge far genetically from their parent tissues. Colon adenocarcinoma tissues displayed upregulation of RNA processing, steroid biosynthesis and detoxification, and downregulation of cytoskeletal organisation and loss of normal muscle function. Tissue-derived cell lines exhibited increased interferon-gamma signalling and aberrant ferroptosis. Overall, 318 proteins were significantly up-regulated and 362 proteins significantly down-regulated by comparisons of high-grade with low-grade tumours and low-grade tumour with normal colon tissues from both sample types.

Conclusions
The differences exhibited between tissues and cell lines highlight the additional information that can be obtained from patient-derived primary cell lines. DNA sequencing and proteomics confirmed that these cell lines can be considered suitable in vitro models of the parent tumours. Various potential biomarkers for colon adenocarcinoma initiation and progression and drug targets were identified and discussed, including seven novel markers: ACSL4, ANK2, AMER3, EXOSC1, EXOSC6, GCLM, and TFRC.
Proteomics-based diagnostic peptide discovery for severe fever with thrombocytopenia syndrome virus in patients
Authors: Lee Sang-Yeop , Lee Hayoung , Yun Sung Ho , Park Edmond Changkyun , Seo Giwan , Kim Hye-Yeon , Jun Sangmi , Kim Nam Hoon , Tark Dongseob , Lee Ju Yeon , Lee Chang-Seop , Kim Seung Il 
Published: July 2022

Abstract
Background
Severe fever with thrombocytopenia syndrome (SFTS) virus is an emerging infectious virus which causes severe hemorrhage, thrombocytopenia, and leukopenia, with a high fatality rate. Since there is no approved therapeutics or vaccines for SFTS, early diagnosis is essential to manage this infectious disease.

Methods
Here, we tried to detect SFTS virus in serum samples from SFTS patients by proteomic analysis. Firstly, in order to obtain the reference MS/MS spectral data of SFTS virus, medium from infected Vero cell culture was used for shotgun proteomic analysis. Then, tryptic peptides in sera from SFTS patients were confirmed by comparative analysis with the reference MS/MS spectral data of SFTS virus.

Results
Proteomic analysis of culture medium successfully discovered tryptic peptides from all the five antigen proteins of SFTS virus. The comparative spectral analysis of sera of SFTS patients revealed that the N-terminal tryptic peptide of the nucleocapsid (N) protein is the major epitope of SFTS virus detected in the patient samples. The prevalence of the peptides was strongly correlated with the viral load in the clinical samples.

Conclusions
Proteomic analysis of SFTS patient samples revealed that nucleocapsid (N) protein is the major antigen proteins in sera of SFTS patients and N-terminal tryptic peptide of the N protein might be a useful proteomic target for direct detection of SFTS virus. These findings suggest that proteomic analysis could be an alternative tool for detection of pathogens in clinical samples and diagnosis of infectious diseases.
Vitamin C attenuates predisposition to high-fat diet-induced metabolic dysregulation in GLUT10-deficient mouse model
Authors: Jiang Chung-Lin , Tsao Chang-Yu , Lee Yi-Ching 
Published: July 2022

Abstract
Background
The development of type 2 diabetes mellitus (T2DM) is highly influenced by complex interactions between genetic and environmental (dietary and lifestyle) factors. While vitamin C (ascorbic acid, AA) has been suggested as a complementary nutritional treatment for T2DM, evidence for the significance and beneficial effects of AA in T2DM is thus far inconclusive. We suspect that clinical studies on the topic might need to account for combination of genetic and dietary factors that could influence AA effects on metabolism. In this study, we tested this general idea using a mouse model with genetic predisposition to diet-induced metabolic dysfunction. In particular, we utilized mice carrying a human orthologous GLUT10G128E variant (GLUT10G128E mice), which are highly sensitive to high-fat diet (HFD)-induced metabolic dysregulation. The genetic variant has high relevance to human populations, as genetic polymorphisms in glucose transporter 10 (GLUT10) are associated with a T2DM intermediate phenotype in nondiabetic population.

Results
We investigated the impacts of AA supplementation on metabolism in wild-type (WT) mice and GLUT10G128E mice fed with a normal diet or HFD. Overall, the beneficial effects of AA on metabolism were greater in HFD-fed GLUT10G128E mice than in HFD-fed WT mice. At early postnatal stages, AA improved the development of compromised epididymal white adipose tissue (eWAT) in GLUT10G128E mice. In adult animals, AA supplementation attenuated the predisposition of GLUT10G128E mice to HFD-triggered eWAT inflammation, adipokine dysregulation, ectopic fatty acid accumulation, metabolic dysregulation, and body weight gain, as compared with WT mice.

Conclusions
Taken together, our findings suggest that AA has greater beneficial effects on metabolism in HFD-fed GLUT10G128E mice than HFD-fed WT mice. As such, AA plays an important role in supporting eWAT development and attenuating HFD-induced metabolic dysregulation in GLUT10G128E mice. Our results suggest that proper WAT development is essential for metabolic regulation later in life. Furthermore, when considering the usage of AA as a complementary nutrition for prevention and treatment of T2DM, individual differences in genetics and dietary patterns should be taken into account.
Whole-Genome Sequencing of Rice Mutant Library Members Induced by N-Methyl-N-Nitrosourea Mutagenesis of Fertilized Egg Cells
Authors: Kubo Takahiko , Yamagata Yoshiyuki , Matsusaka Hiroaki , Toyoda Atsushi , Sato Yutaka , Kumamaru Toshihiro 
Published: July 2022

AbstractAlthough targeted genome editing technology has become a powerful reverse genetic approach for accelerating functional genomics, conventional mutant libraries induced by chemical mutagens remain valuable for plant studies. Plants containing chemically induced mutations are simple yet effective genetic tools that can be grown without regard for biosafety issues. Whole-genome sequencing of mutant individuals reduces the effort required for mutant screening, thereby increasing their utility. In this study, we sequenced members of a mutant library of Oryza sativa cv. Nipponbare derived from treating single fertilized egg cells with N-methyl-N-nitrosourea (MNU). By whole-genome sequencing 266 M1 plants in this mutant library, we identified a total of 0.66 million induced point mutations. This result represented one mutation in every 146-kb of genome sequence in the 373 Mb assembled rice genome. These point mutations were uniformly distributed throughout the rice genome, and over 70,000 point mutations were located within coding sequences. Although this mutant library was a small population, nonsynonymous mutations were found in nearly 61% of all annotated rice genes, and 8.6% (3248 genes) had point mutations with large effects on gene function, such as gaining a stop codon or losing a start codon. WGS showed MNU-mutagenesis using rice fertilized egg cells induces mutations efficiently and is suitable for constructing mutant libraries for an in silico mutant screening system. Expanding this mutant library and its database will provide a useful in silico screening tool that facilitates functional genomics studies with a special emphasis on rice.
A meta-analysis on the susceptibility to the development of bladder cancer in the presence of DNMT3A, DNMT3B, and MTHFR gene polymorphisms
Authors: Touala-Chaila Zohra , Abderrahmane Rym-Khadidja , Benseddik Khedidja , Meroufel Djebaria Naima 
Published: July 2022

Abstract
Background
The etiology of bladder cancer is not yet well known. In this study, we want to evaluate the effect of polymorphisms of genes that have an epigenetic effect (MTHFR, DNMT3A/B) on the susceptibility to develop bladder cancer (BC).

Methods
A systematic review was performed for MTHFR, DNMT3A, and DNMT3B, followed by a meta-analysis conducted for rs1801131, rs1801133, rs2274976, rs1550117, and rs1569686 SNPs. A sensitivity and a subgroup analysis were then used.

Results
20 studies were included, where no statistically significant association between any of the analyzed SNPs and the occurrence of BC was detected. Subgroup analysis revealed a statistically significant association in North African population with rs1801133: TT vs. TC + CC (P = 0.013; OR 95% CI = 0.52 [0.311–0.872]); TT vs.TC (P = 0.003; OR 95% CI = 0.448 [0.261–0.769]) and in North American population with rs1801131: CC vs. CA (P = 0.039; OR 95% CI = 0.71 [0.523–0.984]). A sensitivity analysis revealed that there is a statistically significant association between rs1801131 and the occurrence of BC (OR = 0.79, 95%CI [0.65–0.97]), (OR = 0.80, 95%CI [0.65–0.98]) and (OR = 0.78, 95%CI [0.63–0.96]) which correspond to CC vs. CA + AA; CC vs. CA; and CC vs. AA genetic models.

Conclusion
This is the first study to assess the effect of DNMTs on bladder cancer risk. No statistically significant association was found between polymorphisms of MTHFR, DNMT3A/B genes and bladder cancer development, except for the North African and the North American populations with rs1801133 and rs1801131, respectively, with a protective effect of rs1801131 based on a sensitivity analysis.
On the equivalence between marker effect models and breeding value models and direct genomic values with the Algorithm for Proven and Young
Authors: Bermann Matias , Lourenco Daniela , Forneris Natalia S. , Legarra Andres , Misztal Ignacy 
Published: July 2022

Abstract
Background
Single-step genomic predictions obtained from a breeding value model require calculating the inverse of the genomic relationship matrix $$({\mathbf{G}}^{-1})$$

(

G

-
1

)

. The Algorithm for Proven and Young (APY) creates a sparse representation of $${\mathbf{G}}^{-1}$$

G

-
1

with a low computational cost. APY consists of selecting a group of core animals and expressing the breeding values of the remaining animals as a linear combination of those from the core animals plus an error term. The objectives of this study were to: (1) extend APY to marker effects models; (2) derive equations for marker effect estimates when APY is used for breeding value models, and (3) show the implication of selecting a specific group of core animals in terms of a marker effects model.

Results
We derived a family of marker effects models called APY-SNP-BLUP. It differs from the classic marker effects model in that the row space of the genotype matrix is reduced and an error term is fitted for non-core animals. We derived formulas for marker effect estimates that take this error term in account. The prediction error variance (PEV) of the marker effect estimates depends on the PEV for core animals but not directly on the PEV of the non-core animals. We extended the APY-SNP-BLUP to include a residual polygenic effect and accommodate non-genotyped animals. We show that selecting a specific group of core animals is equivalent to select a subspace of the row space of the genotype matrix. As the number of core animals increases, subspaces corresponding to different sets of core animals tend to overlap, showing that random selection of core animals is algebraically justified.

Conclusions
The APY-(ss)GBLUP models can be expressed in terms of marker effect models. When the number of core animals is equal to the rank of the genotype matrix, APY-SNP-BLUP is identical to the classic marker effects model. If the number of core animals is less than the rank of the genotype matrix, genotypes for non-core animals are imputed as a linear combination of the genotypes of the core animals. For estimating SNP effects, only relationships and estimated breeding values for core animals are needed.
Computational analysis of potential candidate genes involved in the cold stress response of ten Rosaceae members
Authors: Shafi K. Mohamed , Sowdhamini Ramanathan 
Published: July 2022

Abstract
Background
Plant species from Rosaceae family are economically important. One of the major environmental factors impacting those species is cold stress. Although several Rosaceae plant genomes have recently been sequenced, there have been very few research conducted on cold upregulated genes and their promoter binding sites. In this study, we used computational approaches to identify and analyse potential cold stress response genes across ten Rosaceae family members.

Results
Cold stress upregulated gene data from apple and strawberry were used to identify syntelogs in other Rosaceae species. Gene duplication analysis was carried out to better understand the distribution of these syntelog genes in different Rosaceae members. A total of 11,145 popular abiotic stress transcription factor-binding sites were identified in the upstream region of these potential cold-responsive genes, which were subsequently categorised into distinct transcription factor (TF) classes. MYB classes of transcription factor binding site (TFBS) were abundant, followed by bHLH, WRKY, and AP2/ERF. TFBS patterns in the promoter regions were compared among these species and gene families, found to be quite different even amongst functionally related syntelogs. A case study on important cold stress responsive transcription factor family, AP2/ERF showed less conservation in TFBS patterns in the promoter regions. This indicates that syntelogs from the same group may be comparable at the gene level but not at the level of cis-regulatory elements. Therefore, for such genes from the same family, different repertoire of TFs could be recruited for regulation and expression. Duplication events must have played a significant role in the similarity of TFBS patterns amongst few syntelogs of closely related species.

Conclusions
Our study overall suggests that, despite being from the same gene family, different combinations of TFs may play a role in their regulation and expression. The findings of this study will provide information about potential genes involved in the cold stress response, which will aid future functional research of these gene families involved in many important biological processes.
Coordination of leaf hydraulic and economic traits in Cinnamomum camphora under impervious pavement
Authors: Zhang Cheng , Liu Huihui , Huang Nuo , Zhang Fengyu , Meng Yanqiong , Wang Jianan , Li Yiyong 
Published: July 2022

Abstract
Background
Paved urban environments can pose great threats to the physiological functioning and ecological services of street trees. In this context, assessment of leaf phenotypic plasticity is crucial for understanding the ecological strategy of tree species under impervious pavements.

Results
In this study, we measured a set of leaf economic traits, hydraulic traits of Cinnamomum camphora, and surrounding environmental factors in a street site (the soil was covered by the impervious pavement) and a park site (the soil was covered by grass) in Hefei, eastern China. Compared with the park site, trees in the street site had higher stomatal length (SL), leaf thickness (LT), maximum photochemical quantum yield of photosystem II (Y(II)), and lower stomatal density (SD), specific leaf area (SLA), the leaf water potential at 50% loss of hydraulic conductance (P50), and leaf turgor loss point (TLP). Redundancy analysis showed that air relative humidity and volumetric soil water content caused these traits to be altered.

Conclusions
Our results showed that C. camphora adapted to the street pavement environment through the coordination of leaf economic and leaf hydraulic traits, and adopted the slow investment return type in the leaf economic spectrum and high drought resistance to meet its actual physiological needs. This finding provides a new perspective for understanding the physiological strategies of street trees to adapt to urban pavement environments.
Effects of ultrasound-guided erector spinae plane block with dexmedetomidine combined with ropivacaine of the same dose and different concentrations on analgesic effect and rehabilitation quality of patients undergoing thoracoscopic wedge resection of the lung: a prospective, randomized, controlled trial
Authors: Jian Chunfang , Shen Yi , Fu Hangxiang , Yu Lizhen 
Published: July 2022

AbstractObjectiveTo investigate the analgesic effect and rehabilitation quality of patients undergoing thoracoscopic wedge resection of the lung under erector spinae plane (ESP) block with dexmedetomidine combined with the same dose and different concentrations of ropivacaine.MethodsSeventy patients undergoing thoracoscopic wedge resection were randomly divided into groups A (n = 35) and B (n = 35). To perform ESP block, the groups were administered dexmedetomidine (0.5 μg/kg) combined with 30 mL of 0.33% ropivacaine or 20 mL of 0.5% ropivacaine, respectively, half an hour before general anesthesia induction. We compared the onset time of anesthesia, the block level, and the duration of the block between the two groups. The number of compressions of the analgesic pump within 24 h and 48 h postoperatively and the time of the first compression were noted. The visual analog scale (VAS) scores of static and cough at 0.5 h, 6 h, 12 h, 24 h, and 48 h postoperatively were noted. Furthermore, the 40-item quality of recovery questionnaire (QoR-40) score was recorded at 24 h postoperatively. In addition, we noted the time taken to get out of the bed for the first time, the length of hospital stay, analgesia satisfaction, and the occurrence of related adverse reactions and complications within 48 h postoperatively.ResultsThe range of ESP block was wider in Group A than in Group B (P < 0.05). Group B had a significantly shorter onset time (P < 0.05) and lower static and cough VAS scores at 6 h and 12 h postoperatively (P < 0.05); this was associated with significantly fewer compressions of the analgesic pump within 24 h and 48 h postoperatively and significantly more time until the first compression of the analgesic pump was required (P < 0.05). Group B was associated with significantly superior QoR-40 scores 24 h postoperatively and significantly shorter time to get out of the bed for the first time than Group A (P < 0.05).ConclusionDexmedetomidine combined with 0.5% ropivacaine for ESP block is better than 0.33% ropivacaine for overall analgesia and postoperative rehabilitation of patients undergoing thoracoscopic wedge resection.Trial registrationChiCTR2200058114, Date of registration: 30/03/2022.