Correlations between serum concentration of three bone-derived factors and obesity and visceral fat accumulation in a cohort of middle aged men and women

Background

The aim of this study was to investigate the interrelationships between three bone-derived factors [serum osteocalcin (OCN), fibroblast growth factor (FGF) 23, and neutrophil gelatinase-associated lipocalin (NGAL) levels] and body fat content and distribution, in order to reveal the potential endocrine function of bone in the development of obesity.

Methods

We recruited 1179 people (aged 59.5?±?6.2 years) from communities in Shanghai. Serum OCN levels were determined using an electrochemiluminescence immunoassay. Serum FGF23 and NGAL levels were determined using a sandwich enzyme-linked immunosorbent assay. The abdominal fat distribution, including visceral fat area (VFA), was assessed by magnetic resonance imaging. Visceral obesity was defined as a VFA?≥?80 cm².

Results

Serum OCN levels were inversely correlated with body fat parameters, while FGF23 and NGAL were positively correlated (P?<?0.05). After adjusting for confounders, waist circumference (W) and VFA had a closer relationship with serum OCN, FGF23, and NGAL levels than body mass index (BMI) and body fat percentage (fat%, all P?<?0.05). The risk of visceral obesity significantly increased with higher FGF23 and/or NGAL levels, as well as with reduced OCN levels (all P?<?0.05). In addition, serum OCN, FGF23, and NGAL levels were independently associated with visceral obesity (all P?<?0.01). The relationships persisted among subjects with normal glucose tolerance or subjects with hyperglycaemia (both P?<?0.05).

Conclusions

Compared to the indicators of overall adiposity such as BMI or fat%, visceral adiposity indicators (W or VFA) were more closely related to serum OCN, FGF23 and NGAL levels. There was no interaction among the relationship of three bone-derived factors with visceral obesity, which revealed the independent relationship of endocrine function of skeleton with body fat.

     

Bioinformatic prediction and analysis of glucolipid metabolic regulation by miR-34a in <Emphasis Type="Italic">Megalobrama amblycephala</Emphasis>

The objective of this study was to analyze the target genes and regulatory function of miR-34a in Megalobrama amblycephala using second-generation high-throughput sequencing and bioinformatic tools. Functional enrichment analysis was performed by gene ontology. MiR-34a and target gene expression levels were measured in M. amblycephala fed normal and high-carbohydrate diets. The results revealed that miR-34a was highly conserved in several species, and miR-34a of M. amblycephala has a close evolutionary relationship to that of zebrafish and common carp. miRanda, TargetScan, RNAhybrid predicted 5,185, 6,282 and 2,168 target genes, respectively, and 645 target genes were in common. According to annotation information, the target genes were enriched in phosphate metabolism, glycerophospholipid metabolism, Golgi vesicle transport, cell division, and other biological processes (P?<?0.05). Pathway enrichment analysis revealed that these target genes were mainly enriched in alpha-linolenic acid and linoleic acid metabolism, ether lipid metabolism, VEGF signaling pathway, Fc epsilon RI signaling pathway, GnRH signaling pathway, and MAPK signaling pathway (P?<?0.05). The regulatory role of miR-34a was more significant in the liver than in the brain of M. amblycephala. MiR-34a regulates glucose lipid homeostasis induced by high glucose diets by upregulating hepatic PI3K/Akt, FOXO, and TOR signaling pathways.     

Integrating CNVs into meta-QTL identified <Emphasis Type="Italic">GBP4</Emphasis> as positional candidate for adult cattle stature

Copy number variation (CNV) of DNA sequences, functionally significant but yet fully ascertained, is believed to confer considerable increments in unexplained heritability of quantitative traits. Identification of phenotype-associated CNVs (paCNVs) therefore is a pressing need in CNV studies to speed up their exploitation in cattle breeding programs. Here, we provided a new avenue to achieve this goal that is to project the published CNV data onto meta-quantitative trait loci (meta-QTL) map which connects causal genes with phenotypes. Any CNVs overlapping meta-QTL therefore will be potential paCNVs. This study reported potential paCNVs in Bos taurus autosome 3 (BTA3). Notably, overview indexes and CNVs both highlighted a narrower region (BTA3 54,500,000–55,000,000 bp, named BTA3_INQTL_6) within one constructed meta-QTL. Then, we ascertained guanylate-binding protein 4 (GBP4) among the nine positional candidate genes was significantly associated with adult cattle stature, including body weight (BW, P?<?0.05) and withers height (WHT, P?<?0.05), fitting GBP4 CNV either with three levels or with six levels in the model. Although higher copy number downregulated the mRNA levels of GBP2 (P?<?0.05) and GBP4 (P?<?0.05) in 1-Mb window (54.0–55.0 Mb) in muscle and adipose, additional analyses will be needed to clarify the causality behind the ascertained association.     

Characterization and prognosis of estrogen receptor-positive/progesterone receptor-negative male breast cancer: a population-based study

Background

The aim of this study was to explore the characteristics and prognostic information of estrogen receptor-positive/progesterone receptor-negative (ER+/PR?) male breast cancer.

Methods

Using the US National Cancer Institute’s Surveillance, Epidemiology, and End Results database, we compared the demographics, clinical characteristics, and outcome of estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) patients with ER+/PR? male breast cancer patients from 1990 to 2010. Two thousand three hundred twenty-two patients with ER+/PR+ tumors and 355 patients with ER+/PR? tumors were included in our study.

Results

ER+/PR? patients were younger (P?=?0.008) and more likely to be African American (P?<?0.001) while presented with higher histological grade (P?<?0.001), larger tumor size (P?=?0.010), and more invasion to the lymph nodes (P?=?0.034) and distant sites (P?<?0.001), thus later stage (P?=?0.001). Despite higher chance of receiving chemotherapy (51.0% vs 36.5%, P?<?0.001), ER+/PR? patients experienced significantly worse breast cancer-specific survival (BSCC) (P?<?0.001) and shorter overall survival (OS) (P?=?0.003). Multivariate Cox model confirmed that tumor size, lymph node invasion, metastasis, and surgery were independent prognostic factors of both BSCC and OS for ER+/PR? male breast cancer. Age at diagnosis and chemotherapy were significantly associated with OS but not with BSCC.

Conclusion

ER+/PR? male breast cancer was more aggressive and experienced shorter survival than ER+/PR+ patients. The prognosis was mainly associated with tumor size, lymph node invasion, metastasis, and surgery.

     

The efficacy and feasibility of total reconstruction versus nontotal reconstruction of the pelvic floor on short-term and long-term urinary continence rates after radical prostatectomy: a meta-analysis

Background

Recently, total pelvic floor reconstruction (TR) has been the treatment of choice for improving urinary incontinence (UI) after radical prostatectomy (RP). However, the superiority of TR with respect to urinary continence recovery following RP remains controversial. This study identified the effect of TR versus nonTR of the pelvic floor on short-term and long-term continence rates after RP.

Methods

A literature search was performed in November 2017 using the PubMed, Embase, and Web of Science databases. Only comparative research or clinical studies reporting urinary continence outcomes was included in the meta-analysis, and the quality of evidence was evaluated using the 2011 Level of Evidence for therapy research.

Results

We analyzed ten studies reporting urinary continence rates after RP at one or more postoperative time points (1, 2, 4, 12, 24, and 52 weeks). TR was associated with significantly better urinary continence outcomes at 1 week (OR 2.76, 95% CI 1.58–4.84, P?<?0.001), 2 weeks (OR 2.57, 95% CI 1.74–3.80, P?<?0.001), 4 weeks (OR 2.61, 95% CI 1.56–4.38, P?<?0.001), 12 weeks (OR 4.33, 95% CI 2.01–9.33, P?<?0.001), 24 weeks (OR 3.83, 95% CI 1.54–9.55, P?=?0.004), 52 weeks (OR 4.10, 95% CI 1.80–9.38, P?<?0.001) after RP. There was no difference in the rate of complications between the two arms (OR 0.54, 95% CI 0.19–1.54, P?=?0.25).

Conclusions

Compared with nonTR, TR is significantly and positively associated with a return to continence but not with complication rate in men following RP, suggesting that TR may be useful for decreasing the urinary incontinence rate after surgery.

     

Effect of short-chain fatty acids on the expression of genes involved in short-chain fatty acid transporters and inflammatory response in goat jejunum epithelial cells

Short-chain fatty acids (SCFAs) produced by microbial fermentation of dietary fibers are utilized by intestinal epithelial cells to provide an energy source for the ruminant. Although the regulation of mRNA expression and inflammatory response involved in SCFAs is established in other animals and tissues, the underlying mechanisms of the inflammatory response by SCFAs in goat jejunum epithelial cells (GJECs) have not been understood. Therefore, the objective of the study is to investigate the underlying mechanisms of the effects of SCFAs on SCFA transporters and inflammatory response in GJECs. These results showed that the acetate, butyrate, and SCFA concentration were markedly reduced in GJECs (p?<?0.01). In addition, the propionate concentration was significantly decreased in GJECs (p?<?0.05). The mRNA abundance of monocarboxylate transporter 1 (MCT1), MCT4, NHE1, and putative anion transporter 1 (PAT1) was elevated (p?<?0.05) by 20 mM SCFAs at pH 7.4 compared with exposure to the pH group. The anion exchanger 2 (AE2) was increased (p?<?0.05) by 20 mM SCFAs at pH 6.2. The mRNA abundance of vH⁺ ATPase B subunit (vH⁺ ATPase) was attenuated by SCFAs. For inflammatory responses, IL-1β and TNF-α were increased with SCFAs (p?<?0.05). In addition, IκBα involved in NF-κB signaling pathways was disrupted by SCFAs. Consistently, p-p65 signaling molecule was enhanced by adding SCFAs. However, IL-6 was attenuated by adding SCFAs (p?<?0.05). Furthermore, p-ErK1/2 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated by adding SCFAs. In conclusion, these novel findings demonstrated that mRNA abundance involved in SCFA absorption is probably associated to SCFAs and pH value, and mechanism of the inflammatory response by SCFAs may be involved in NF-κB and p-ErK1/2 MAPK signaling pathways in GJECs. These pathways may mediate protective inflammation response in GJECs.     

<Emphasis Type="Italic">Enterococcus faecalis</Emphasis> promotes osteoclast differentiation within an osteoblast/osteoclast co-culture system

Objective

To investigate the effects of heat-killed Enterococcus faecalis ATCC 29212 and P25RC clinical strain (derived from an obturated root canal with apical periodontitis) on osteoclast differentiation within an osteoblast/osteoclast co-culture system.

Results

Heat-killed E. faecalis significantly increased the proportion of multinucleated osteoclastic cells (MNCs) within the co-culture system. The IL-6 level was significantly increased upon exposure to heat-killed E. faecalis. Gene expression levels of NFATc1 and cathepsin K were significantly up-regulated compared to the untreated control. EphrinB2 and EphB4 expressions at both the mRNA and protein levels were also significantly upregulated compared to the untreated control.

Conclusions

Heat-killed E. faecalis can induce osteoclast differentiation within the osteoblast/osteoclast co-culture system in vitro, possibly through ephrinB2-EphB4 bidirectional signaling.

     

Role of perfusion parameters on DCE-MRI and ADC values on DWMRI for invasive ductal carcinoma at 3.0 Tesla

Background

The value of apparent diffusion coefficient (ADC) values and quantitative parameters (Ktrans, Kep, Ve) in detecting prognostic factor at 3.0 Tesla remains unclear, especially in predicting prognosis of breast cancer.

Methods

A total of 151 patients with IDC underwent breast DCE-MRI and DWI-MRI at 3.0 Tesla following surgery. The ADC values were acquired with b values of 0 and 1000?s/mm². The relationship between ADC values or DCE-MRI quantitative parameters and size, histologic grade (HG), lymph node metastasis (LNM), ER, PR, and Ki67 was evaluated. The predictive values of ADC, Ktrans, Kep, and Ve to prognosis of IDC were assessed.

Results

ADC value was positively related to size (P?=?0.04) and HER2 (P?=?0.046) expression and negatively related to ER (P?=?0.012) and PR (P?<?0.001) expression. Ktrans value has positive correlation with size (P?<?0.001), HG (P?<?0.001), LNM (P?<?0.001), HER2 (P?=?0.007), and Ki67 (P?<?0.001) expression and negative correlation with ER (P?<?0.001) and PR (P?<?0.001) expression. Kep value was positively related to size (P?<?0.001) and negatively related to ER (P?<?0.001) and PR (P?<?0.001) expression. Ve value was negatively related to HER2 expression (P?=?0.004). The Cox hazard ratio (HR) of ADC, Ktrans, Kep, and Ve values on survival was 5.26 (P?=?0.093), 1.081 (P?=?0.002), 1.006 (P?=?0.941), and 0.883 (P?=?0.926), respectively.

Conclusions

Ktrans value was a best predictive indicator of HG, LNM, ER, PR, and Ki67 expression, and ADC value was the best predictive indicator of HER2. Preoperative use of the 3.0 Tesla could provide important information to determine the optimal treatment plan.

     

Risk factors associated with 31-day unplanned readmission in 50,912 discharged patients after stroke in China

Background

Unplanned readmission within 31?days of discharge after stroke is a useful indicator for monitoring quality of hospital care. We evaluated the risk factors associated with 31-day unplanned readmission of stroke patients in China.

Methods

We identified 50,912 patients from 375 hospitals in 29 provinces, municipalities or autonomous districts across China who experienced an unplanned readmission after stroke between 2015 and 2016, and extracted data from the inpatients’ cover sheet data from the Medical Record Monitoring Database. Patients were grouped into readmission within 31?days or beyond for analysis. Chi-squared test was used to analyze demographic information, health system and clinical process-related factors according to the data type. Multilevel logistic modeling was used to examine the effects of patient (level 1) and hospital (level 2) characteristics on an unplanned readmission ≤31?days.

Results

Among 50,912 patients, 14,664 (28.8%) were readmitted within 31?days after discharge. The commonest cause of readmissions were recurrent stroke (34.8%), hypertension (22.94%), cardio/cerebrovascular disease (13.26%) and diabetes/diabetic complications (7.34%). Higher risks of unplanned readmissions were associated with diabetes (OR?=?1.089, P?=?0.001), use of clinical pathways (OR?=?1.174, P?<?0.001), and being discharged without doctor’s advice (OR?=?1.485, P?<?0.001). Lower risks were associated with basic medical insurances (OR ranging from 0.225 to 0.716, P?<?0.001) and commercial medical insurance (OR?=?0.636, P?=?0.021), compared to self-paying for medical services. And patients aged 50?years old and above (OR ranging from 0.650 to 0.985, P?<?0.05), with haemorrhagic stroke (OR?=?0.467, P?<?0.001), with length of stay more than 7?days in hospital (OR ranging from 0.082 to 0.566, P?<?0.001), also had lower risks.

Conclusions

Age, type of stroke, medical insurance status, type of discharge, use of clinical pathways, length of hospital stay and comorbidities were the most influential factors for readmission within 31?days.

     

Polymorphism of rs3737597 in DISC1 Gene on Chromosome 1q42.2 in sALS Patients: a Chinese Han Population Case-Control Study

Although lots of genes have been revealed to relate to sporadic amyotrophic lateral sclerosis (sALS), its genetic mechanisms still need to be further explored. We aimed to search the novel genetic factors of sALS and assess their contribution. We constructed an integrative dataset based on the 3227 subsignificant genes (P value?<?0.01) from two sALS-related genome-wide association studies (GWAS) (the US and Irish studies). A significant replication between both studies was confirmed by the gene set enrichment analysis in the integral level (P value?<?10^?4). Using the pathway overrepresentation analysis, we revealed the 34 shared Gene Ontology (GO) biological processes from the two independent studies (P value?<?0.01). Among these pathways, the nervous system developmental pathway (NSD function, GO:0007399) was further supported by the previously reported genes related to sALS (P value?=?3.28e?12). Importantly, four of 17 NSD-function-related target genes (disrupted-in-schizophrenia-1 (DISC1), CNTN4, NRXN3, and ERBB4) presented a considerable association with sALS in both studies. To further verify the association between the NSD function target genes and sALS, we preformed a two-stage case–control study based on 500 sALS patients and 500 controls of Chinese Han populations from mainland. A polymorphism of rs3737597 in DISC1 gene involved in the nervous system developmental pathway was closely associated with sALS. The nervous system developmental pathway is a potential pathogenesis of sALS, among them, the polymorphism of rs3737597 in DISC1 might play some roles.     

CT Permeability Imaging Predicts Clinical Outcomes in Acute Ischemic Stroke Patients Treated with Intra-arterial Thrombolytic Therapy

In this study, we determined whether a prediction of final infarct volume (FIV) and clinical outcomes in patients with an acute stroke is improved by using a contrast transfer coefficient (K ^trans) as a biomarker for blood–brain barrier (BBB) dysfunction. Here, consecutive patients admitted with signs and symptoms suggesting acute hemispheric stroke were included in this study. Ninety-eight participants with intra-arterial therapy were assessed (46 female). Definition of predicted FIV was performed using conventional perfusion CT (PCT-PIV) parameters alone and in combination with K ^trans (K ^trans-PIV). Multiple logistic regression analyses and linear regression modeling were conducted to determine independent predictors of the 90-day modified Rankin score (mRS) and FIV, respectively. We found that patients with favorable outcomes were younger and had lower National Institutes of Health Stroke Scale (NIHSS) score, smaller PCT-PIV, K ^trans-PIV, and smaller FIV (P?<?0.001). K ^trans-PIV showed good correlation with FIV (P?<?00.001, R ²?=?0.6997). In the regression analyses, K ^trans-PIV was the best predictor of clinical outcomes (P?=?0.009, odds ratio (OR)?=?1.960) and also the best predictor for FIV (F?=?75.590, P?<?0.0001). In conclusion, combining PCT and K ^trans maps derived from first-pass PCT can identify at-risk cerebral ischemic tissue more precisely than perfusion parameters alone. This provides improved accuracy in predicting FIV and clinical outcomes.     

High IKZF1/3 protein expression is a favorable prognostic factor for survival of relapsed/refractory multiple myeloma patients treated with lenalidomide

The aim of this study is to assess nucleoprotein expression of IKZF1/3 in patients with relapsed/refractory multiple myeloma (MM) who received lenalidomide-based therapy and correlated them with their clinical outcomes. A total of 50 patients diagnosed with MM were entered in the study with the median follow-up of 86.4 months. By immunohistochemistry (IHC), IKZF1 and IKZF3 were expressed in 72 and 58% of the cases, respectively. IKZF1 and IKZF3 expressions were associated with longer median progression free survival (P?=?0.0029 and P?<?0.0001) and overall survival (P?=?0.0014 and P?<?0.0001). IKZF3 expression also appears predicted a favorable response to the lenalidomide-based therapy.     

Experimental research into the potential therapeutic effect of GYY4137 on Ovariectomy-induced osteoporosis

Background

Evidence has shown that endogenous H₂S plays an important role in the physiological and pathophysiological processes of many organs. The study aimed to explore whether exogenous H₂S has a potential therapeutic effect on a rat ovariectomy-induced model of osteoporosis.

Methods

The OVX osteoporosis model was established in female Sprague-Dawley rats by full bilateral ovariectomy. The rats were randomly divided into four groups, with the two experimental groups receiving an intraperitoneal injection of GYY4137 or sodium alendronate. The level of H₂S in the plasma was determined and common laboratory indicators to diagnose osteoporosis, such as alkaline phosphatase (ALP) activity and the levels of osteocalcin (OCN), calcitonin, parathyroid hormone and leptin were measured. The bone mineral density (BMD) of the 4th and 5th lumbar vertebrae was measured using dual-energy X-ray absorptiometry. The maximum stress of femoral fracture was obtained through a three-point bending test of the femur.

Results

The OVX osteoporosis model was successfully established. GYY4137 was injected to increase the level of H₂S in the plasma in one group, designated OVX-GYY during the observation period (p?<?0.05). At 12 weeks, the BMD value of the fourth lumbar vertebra in the OVX-GYY group had increased (p?<?0.05). The BMD femur value in the OVX-vehicle group had decreased (p?<?0.05). Bilateral ovariectomy leads to biochemical disorders related to bone metabolism and hormone levels in rat plasma (all p?<?0.05). Ovariectomy also reduced blood calcium, blood phosphate and calcitonin, and increased parathyroid hormone and leptin. The opposite results were obtained for the groups with alendronate sodium or GYY4137 treatment (all p?<?0.05).

Conclusions

Through the slow release of H₂S, GYY4137 did an excellent job of simulating endogenous neuroendocrine gaseous signaling molecules. Exogenous H₂S had a regulatory effect on osteoporosis in ovariectomized rats, showing potential value for the treatment of human postmenopausal osteoporosis.

     

Effect of ATP and Bax on the apoptosis of <Emphasis Type="Italic">Eimeria tenella</Emphasis> host cells

Background

Eimeria tenella (E. tenella) is a species of Eimeria that causes haemorrhagic caecal coccidiosis, resulting in major economic losses in the global poultry industry. After E. tenella infection, the amount of ATP and Bax in host cells showed highly significant changes. Therefore, it is necessary to investigate the effects of ATP and Bax on the apoptosis of E. tenella host cells.

Results

The ATP-treated group and the V5-treated group had higher E. tenella infection rates than the untreated group at 24, 48, 72, 96, and 120 h after infection with E. tenella. The results of flow cytometry showed that compared with the control group, the mitochondrial permeability transition pore (MPTP) opening in the untreated group was highly significantly increased (P?<?0.01) at 4, 24, 48, 72, 96, and 120 h. Moreover, results from Hoechst-Annexin V-PI staining and flow cytometry showed that the rates of early apoptosis, late apoptosis, and necrosis in the untreated group were significantly lower (P?<?0.05) or highly significantly lower (P?<?0.01) than those of the control group at 4 h, while the rates of early apoptosis, late apoptosis, and necrosis in the untreated group were higher at varying degrees than those in the control group at 24–120 h (P?<?0.05 or P?<?0.01). After treatment with ATP and Bax inhibitors, the rates of early apoptosis, late apoptosis, and necrosis, in addition to the MPTP opening in both the ATP-treated and V5-treated groups, were significantly lower (P?<?0.05) or highly significantly lower (P?<?0.01) than those in the untreated group.

Conclusions

ATP and Bax play important roles in regulating the apoptosis of E. tenella host cells.

     

Novel 1q22-q23.1 duplication in a patient with lambdoid and metopic craniosynostosis,muscular hypotonia,and psychomotor retardation

Craniosynostosis (CS) refers to the group of craniofacial malformations characterized by the premature closure of one or more cranial sutures. The disorder is clinically and genetically heterogeneous and occurs usually as an isolated trait, but can also be syndromic. In 30–60% of patients, CS is caused by known genetic factors; however, in the rest of the cases, causative molecular lesions remain unknown. In this paper, we report on a sporadic male patient affected by complex CS (metopic and unilateral lambdoid synostosis), muscular hypotonia, psychomotor retardation, and facial dysmorphism. Since a subset of CS results from submicroscopic chromosomal aberrations, we performed array comparative genomic hybridization (array CGH) in order to identify possibly causative copy-number variation. Array CGH followed by breakpoint sequencing revealed a previously unreported de novo 1.26 Mb duplication at chromosome 1q22-q23.1 that encompassed two genes involved in osteoblast differentiation: BGLAP, encoding osteocalcin (OCN), and LMNA, encoding lamin A/C. OCN is a major component of bone extracellular matrix and a marker of osteogenesis, whereas mutations in LMNA cause several genetic disorders called laminopathies, including mandibuloacral dysostosis (MAD) that manifests with low bone mass, severe bone deformities, and delayed closure of the cranial sutures. Since LMNA and BGLAP overexpression promote osteoblast differentiation and calcification, phenotype of our patient may result from misexpression of the genes. Based on our findings, we hypothesize that both LMNA and BGLAP may be implicated in the pathogenesis of CS in humans. However, further studies are needed to establish the exact pathomechanism underlying development of this defect.     

Genome-wide association study of <Emphasis Type="Italic">Mycobacterium avium</Emphasis> subspecies <Emphasis Type="Italic">Paratuberculosis</Emphasis> infection in Chinese Holstein

Background

Paratuberculosis is a contagious, chronic and enteric disease in ruminants, which is caused by Mycobacterium avium subspecies paratuberculosis (MAP) infection, resulting in enormous economic losses worldwide. There is currently no effective cure for MAP infection or a vaccine, it is thus important to explore the genetic variants that contribute to host susceptibility to infection by MAP, which may provide a better understanding of the mechanisms of paratuberculosis and benefit animal genetic improvement. Herein we performed a genome-wide association study (GWAS) to identify genomic regions and candidate genes associated with susceptibility to MAP infection in dairy cattle.

Results

Using Illumina Bovine 50?K (54,609 SNPs) and GeneSeek HD (138,893 SNPs) chips, two analytical approaches were performed, GRAMMAR-GC and ROADTRIPS in 937 Chinese Holstein cows, among which individuals genotyped by the 50?K chip were imputed to HD SNPs with Beagle software. Consequently, 15 and 11 significant SNPs (P?<?5?×?10^??5) were identified with GRAMMAR-GC and ROADTDRIPS, respectively. A total of 10 functional genes were in proximity to (i.e., within 1?Mb) these SNPs, including IL4, IL5, IL13, IRF1, MyD88, PACSIN1, DEF6, TDP2, ZAP70 and CSF2. Functional enrichment analysis showed that these genes were involved in immune related pathways, such as interleukin, T cell receptor signaling pathways and inflammatory bowel disease (IBD), implying their potential associations with susceptibility to MAP infection. In addition, by examining the publicly available cattle QTLdb, a previous QTL for MAP was found to be overlapped with one of regions detected currently at 32.5?Mb on BTA23, where the TDP2 gene was anchored.

Conclusions

In conclusion, we identified 26 SNPs located on 15 chromosomes in the Chinese Holstein population using two GWAS strategies with high density SNPs. Integrated analysis of GWAS, biological functions and the reported QTL information helps to detect positional candidate genes and the identification of regions associated with susceptibility to MAP traits in dairy cattle.

     

Hair Mineral and Trace Element Contents as Reliable Markers of Nutritional Status Compared to Serum Levels of These Elements in Children Newly Diagnosed with Inflammatory Bowel Disease

Patients with inflammatory bowel disease (IBD) are at high risk for nutritional deficiencies because of long-term inflammation in the gut mucosa and decreased oral intake. Because inflammation responses affect serum micronutrient concentrations, serum levels are limited in reflecting body nutrient status in acute and chronic illness. We investigated the usefulness of measuring trace elements in hair as reliable markers of nutritional status compared to serum levels in children with IBD. We retrospectively analyzed pediatric patients newly diagnosed with Crohn’s disease (n?=?49) and ulcerative colitis (n?=?16) and controls (n?=?29) from 2012 to 2016. Serum micronutrient levels, inflammatory markers, and hair trace element content were evaluated and compared at the time of diagnosis and before initiating treatment. Serum calcium (p?<?0.001), iron (p?<?0.001), zinc (p?=?0.013), selenium (p?=?0.008), albumin (p?<?0.001), prealbumin (p?<?0.001), hemoglobin and hematocrit (p?<?0.001), and WBC (p?=?0.001) and lymphocytes (p?<?0.001) differed significantly between the groups. After adjustment for the erythrocyte sedimentation rate, serum zinc and selenium levels were no longer significantly different between the groups (p?<?0.062 and p?<?0.057, respectively). Following hair analysis for mineral and trace elements, iron (p?=?0.033), selenium (p?=?0.017), and manganese (p?=?0.009) differed significantly between the groups. Serum micronutrient levels need cautious interpretation in conjunction with inflammatory markers. Hair mineral and trace element measurement may support understanding micronutrient status in children with IBD.