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Papers by Zhangrui Cheng

Background: Previous studies of ageing have identified many pathways which are consistently alter... more Background: Previous studies of ageing have identified many pathways which are consistently altered in humans and model organisms. Dairy cows are often culled at quite young ages due to an inability to cope adequately with metabolic and infectious diseases, resulting in reduced milk production and infertility. Improved longevity is therefore a desirable trait which would benefit both farmers and their cows. This study analysed the transcriptome derived from RNA-seq data of leukocytes obtained from Holstein cows in early lactation with respect to lactation number. Results: Samples were divided into three age groups for analysis: i) primiparous (PP, n = 53), ii) multiparous in lactations 2-3 (MP 2-3, n = 121), and iii) MP in lactations 4-7 (MP>3, n = 55). Leukocyte expression was compared between PP vs MP>3 cows with MP 2-3 as background using DESeq2 followed by weighted gene co-expression network analysis (WGCNA). Seven modules were significantly correlated (r ≥ 0.25) to the tr...

Frontiers in Genetics

New Mendelian genetic conditions, which adversely affect livestock, arise all the time. To manage... more New Mendelian genetic conditions, which adversely affect livestock, arise all the time. To manage them effectively, some methods need to be devised that are quick and accurate. Until recently, finding the causal genomic site of a new autosomal recessive genetic disease has required a two-stage approach using single-nucleotide polymorphism (SNP) chip genotyping to locate the region containing the new variant. This region is then explored using fine-mapping methods to locate the actual site of the new variant. This study explores bioinformatic methods that can be used to identify the causative variants of recessive genetic disorders with full penetrance with just nine whole genome-sequenced animals to simplify and expedite the process to a one-step procedure. Using whole genome sequencing of only three cases and six carriers, the site of a novel variant causing perinatal mortality in Irish moiled calves was located. Four methods were used to interrogate the variant call format (VCF) d...

Additional file 1: Additional tables supporting the main text of the manuscript. Referred to as S... more Additional file 1: Additional tables supporting the main text of the manuscript. Referred to as Supplementary Tables 1–6. Supplementary Table 1. Milk yield data (kg/d) for the six dairy herds used in the study, organised by herd and parity. Supplementary Table 2. Mapping rate of all blood samples against the Bos taurus reference ARS-UCD1.2 and summary statistics. Supplementary Table 3. Gene ontology enrichment analysis of genes in significantly correlated modules. Supplementary Table 4. David functional cluster analysis of genes in significantly correlated modules. Supplementary Table 5A, 5B. (i) Top six most significant clusters; (ii) Number of genes highly expressed in the PP/MP3 cows per cluster. Supplementary Table 6. RNA concentration measured with Nanodrop, Bioanalyzer, and RIN values.

Journal of Dairy Science, 2021

Homeorhetic mechanisms assist dairy cows in the transition from pregnancy to lactation. Less succ... more Homeorhetic mechanisms assist dairy cows in the transition from pregnancy to lactation. Less successful cows develop severe negative energy balance (NEB), placing them at risk of metabolic and infectious diseases and reduced fertility. We have previously placed multiparous Holstein Friesian cows from 4 herds into metabolic clusters, using as biomarkers measurements of plasma nonesterified fatty acids, β-hydroxybutyrate, glucose and IGF-1 collected at 14 and 35 d in milk (DIM). This study characterized the global transcriptomic profiles of liver and circulating leukocytes from the same animals to determine underlying mechanisms associated with their metabolic and immune function. Liver biopsy and whole-blood samples were collected around 14 DIM for RNA sequencing. All cows with available RNA sequencing data were placed into balanced (BAL, n = 44), intermediate (n = 44), or imbalanced (IMBAL, n = 19) metabolic cluster groups. Differential gene expression was compared between the 3 groups using ANOVA, but only the comparison between BAL and IMBAL cows is reported. Pathway analysis was undertaken using DAVID Bioinformatic Resources (https: / / david .ncifcrf .gov/). Milk yields did not differ between BAL and IMBAL cows but dry matter intake was less in IMBAL cows and they were in greater energy deficit at 14 DIM (−4.48 v −11.70 MJ/d for BAL and IMBAL cows). Significantly differentially expressed pathways in hepatic tissue included AMPK signaling, glucagon signaling, adipocytokine signaling, and insulin resistance. Genes involved in lipid metabolism and cholesterol transport were more highly expressed in IMBAL cows but IGF1 and IG-FALS were downregulated. Leukocytes from BAL cows had greater expression of histones and genes involved in nucleosomes and cell division. Leukocyte expression of heat shock proteins increased in IMBAL cows, suggesting an unfolded protein response, and several key genes involved in immune responses to pathogens were upregulated (e.g., DEFB13, HP, OAS1Z, PTX3, and TLR4). Differentially expressed genes upregulated in IMBAL cows in both tissues included CD36, CPT1, KFL11, and PDK4, all central regulators of energy metabolism. The IMBAL cows therefore had greater difficulty maintaining glucose homeostasis and had dysregulated hepatic lipid metabolism. Their energy deficit was associated with a reduced capacity for cell division and greater evidence of stress responses in the leukocyte population, likely contributing to an increased risk of infectious disease.

Animal Health Research Reviews, 2019

Bovine viral diarrhea virus (BVDV) is an important infectious disease agent that causes significa... more Bovine viral diarrhea virus (BVDV) is an important infectious disease agent that causes significant reproductive and economic losses in the cattle industry worldwide. Although BVDV infection is known to cause poor fertility in cattle, a greater part of the underlying mechanisms particularly associated with early reproductive losses are not clearly understood. Previous studies reported viral compromise of reproductive function in infected bulls. In females, BVDV infection is thought to be capable of killing the oocyte, embryo or fetus directly, or to induce lesions that result in fetal abortion or malformation. BVDV infections may also induce immune dysfunction, and predispose cattle to other diseases that cause poor health and fertility. Other reports also suggested BVDV-induced disruption of the reproductive endocrine system, and a disruption of leukocyte and cytokine functions in the reproductive organs. More recent studies have provided evidence of viral-induced suppression of en...

Theriogenology, 2007

The peripartum period is of critical importance to subsequent health and fertility. Most cows ent... more The peripartum period is of critical importance to subsequent health and fertility. Most cows enter a state of negative energy balance (NEB) associated with many metabolic changes which have carry over effects on the resumption and normality of estrous cyclicity and the success of subsequent inseminations. A dataset on 500 lactations explored the relationships between metabolic traits measured before and after calving with fertility. Stepwise multiple regression analysis showed that longer calving to conception intervals were associated with altered profiles of IGF-I, urea and body condition score. These relationships between metabolic profiles and fertility differed between first lactation cows (which are still growing but produce less milk) and mature animals. Early postpartum the liver undergoes extensive biochemical and morphological modifications to adapt to NEB, the uterus is extensively remodeled and must clear bacterial infections, and the ovary must resume ovulatory cycles. RNA isolated from liver and uterine tissues harvested 2 weeks postpartum from cows in mild (MNEB) and severe (SNEB) energy balance was used to screen the Affymetrix 23K bovine microarray. In liver, SNEB resulted in differential expression of key genes involved in lipid catabolism, gluconeogenesis, and the synthesis and stability of IGF-I. This was accompanied by reduced systemic concentrations of IGF-I which is likely to impact on ovarian function and early embryo development. Within endometrium, cows in SNEB showed histological evidence for higher levels of inflammation and the microarray analysis identified groups of differentially expressed genes involved in tissue remodeling and immune response. This may delay uterine repair after calving, likely contributing to the observed reduction in fertility.

Veterinary Record, 2008

Lifetime records of 442 Holstein cows on one farm in North Queensland, Australia, were analysed t... more Lifetime records of 442 Holstein cows on one farm in North Queensland, Australia, were analysed to evaluate the effects of age at first calving (AFC) and first lactation milk yield on parities per lifetime, longevity, milk yield in subsequent lactations, lifetime milk production and the longevity index (LI), that is the proportion of a cow's life spent in active milk production. The mean daily yield in the first lactation was a reliable indicator of milk yield in subsequent lactations, estimated lifetime production, longevity and LI. The afc had no effect on lifetime days in milk. Neither the AFC nor the milk yield in the first lactation significantly affected the number of parities per lifetime. For the majority of cows, which produced less than 30 l/day in the first lactation, there was a significant positive relationship between longevity and AFC. However, none of the cows that produced more than 30 l/day in the first lactation survived for more than two lactations. The optimal AFC was thus two to two-and-a-half years, as these cows had the highest first lactation yield, estimated lifetime production and LI. The optimal mean daily yield in the first lactation was 20 to 30 l/day, as these cows lived longer and had a higher LI and lifetime production.

Viruses, 2019

In cattle, conceptus-derived interferon tau (IFNT) is the pregnancy recognition (PR) signal. Our ... more In cattle, conceptus-derived interferon tau (IFNT) is the pregnancy recognition (PR) signal. Our previous studies showed that non-cytopathic bovine viral diarrhoea virus (ncpBVDV) infection inhibited IFNT-induced interferon stimulated gene (ISG) expression, potentially causing early embryonic death. This study investigated the effect of bovine viral diarrhoea virus (BVDV) infection on upstream regulatory pathways of ISG production using an established PR model. Uterine endometrial cells from 10 apparently healthy and BVDV free cows were cultured and treated with 0 or 100 ng/mL IFNT for 24 h in the presence or absence of ncpBVDV infection. Microarray and pathway analysis were used to determine the IFNT-induced upstream regulators. Expression of the genes associated with the identified pathways were quantified with qPCR. IFNT challenge activated the signalling pathways associated with IFN receptors, JAK1/TYK2, IRFs and STATs and ncpBVDV infection inhibited the activation of IFNT on th...

Reproduction, 2010

Diets or supplements high in n-3 and n-6 polyunsaturated fatty acids (PUFAs) have been shown to i... more Diets or supplements high in n-3 and n-6 polyunsaturated fatty acids (PUFAs) have been shown to influence the timing of parturition. PUFAs are substrates for prostaglandin (PG) synthesis, and PGs play central roles in parturition. Hence, the effects of altering PUFA composition may be mediated through alterations in the type and relative quantities of PGs synthesised. Therefore, we have investigated the effects of a range of n-3 and n-6 PUFAs in vitro on PG synthesis by amnion cells of late gestation ewes. The n-6 PUFA, arachidonic acid (20:4, n-6), increased synthesis of two-series PGs. Degree of stimulation induced by the n-6 PUFAs was dependent on the position of the PUFA in the PG synthetic pathway, i.e. PG production of the two-series (principally prostaglandin E2:PGE2) increased progressively with longer chain PUFAs. Effects of n-3 PUFAs on output of PGE2 were more modest and variable. The two shorter chain n-3 PUFAs, α-linolenic acid (18:3, n-3) and stearidonic acid (18:4, n-...

Research in Veterinary Science, 2016

Bovine P-selectin (SELP) mediates leukocyte rolling and primes leukocyte adhesion to endothelium,... more Bovine P-selectin (SELP) mediates leukocyte rolling and primes leukocyte adhesion to endothelium, both essential for leukocyte recruitment to an infection site. We investigated SELP-mediated adhesion between bovine peripheral blood leukocytes (PBLs) and cultured bovine aortic endothelial cells pre-activated with lipopolysaccharide (LPS). We examined gene polymorphism for bovine selectins SELP, L-selectin (SELL) and E-selectin (SELE) and compared their SNP frequency between five dairy breeds (Holstein, Friesian, Jersey, Ayrshire and Brown Swiss). LPS treatment caused a rapid (10 min) and slower (4 h) enhancement of PBL adhesion (P<0.01). Antibody blocking of SELP inhibited LPS induced cell adhesion. SELP was highly polymorphic, with 9 of the 13 SNPs in its exons, whereas only three synonymous SNPs in SELL and one in SELE. The resulting amino acid changes for the three missense SELP SNP were located in the lectin domain and in two consensus repeat (CR) regions, CR2 and CR5. The Val475Met variant locus in the CR4 and CR5 linking region was very close to a predicted N-acetyl-D-glucosamine glycosylation site, which is likely to influence SELP function. The AA genotype was under-represented, only being found in 1% of 373 heifers genotyped from the 5 breeds (P=0.056), suggesting that AA homozygous animals carrying the Val475Met substitution for SELP may have compromised development. Our study thus confirmed that SELP mediates the attachment of PBL to endothelium and provides novel evidence that its high polymorphism is likely to affect biological function. This may potentially influence leukocyte migration and fertility, both key to successful performance in dairy cows.

Placenta, 2011

Objective: To use an in vitro model of the ovine placenta to determine effects of n-6 polyunsatur... more Objective: To use an in vitro model of the ovine placenta to determine effects of n-6 polyunsaturated fatty acid (PUFA) supplementation on prostaglandin (PG) production. PGs are key regulators of fetal maturation and parturition. Study design: Fetal allantochorion tissue (FC) was collected in late pregnancy (day 135). FC cells were isolated and cultured with 0e100 mM of linoleic acid (LA), g-linolenic acid (GLA) or arachidonic acid (AA) in serum free medium and challenged with control medium, lipopolysaccharide (LPS, 0.1 mg/ml), dexamethasone (DEX, 5 mM) or a combination of LPS (0.1 mg/ml) with DEX (5 mM). Spent medium was harvested at 2 h and 24 h post challenge for measuring PGs. Main outcome measures: To assess the effects of treatment on placental 1-and 2-series PGE production. Results: LA supplementation inhibited both PGE 1 and PGE 2 production. GLA predominantly stimulated PGE 1 generation, although it also increased PGE 2 production. AA supplementation predominantly increased PGE 2 production, but also stimulated PGE 1. DEX treatment with or without LPS inhibited PG production. Supplementation with n-6 PUFAs attenuated or neutralised the stimulatory effect of LPS challenge on FC cells for both PGE 1 and PGE 2 production. Conclusion: These data show that supplementation with n-6 PUFAs alters placental PG production, but their precise effects depend on their position in the biosynthetic pathway for PG synthesis. This study supports the possibility that GLA containing oils, widely promoted as dietary supplements, might reduce the risk of pre-term labour by inhibiting the responsiveness of PGE 2 production to LPS challenge in the placenta.

Journal of Endocrinology, 2004

We investigated the effect of n-6 polyunsaturated fatty acids (PUFAs) on prostaglandin (PG) produ... more We investigated the effect of n-6 polyunsaturated fatty acids (PUFAs) on prostaglandin (PG) production by the uterus. A mixed population of endometrial cells (epthelium and stroma) from late-gestation ewes were cultured in defined medium containing linoleic acid (LA, 18:2, n-6), gamma-linolenic acid (GLA, 18:3, n-6) or arachidonic acid (AA, 20:4, n-6) in concentrations of 0 (control), 20 or 100 microM. After 45 h in test medium with or without added PUFAs, cells were challenged with control medium (CM), oxytocin (OT, 250 nM), lipopolysaccharide (LPS, 0.1 micro g/ml) or dexamethasone (DEX, 5 microM) for 22 h in the continued presence of the same concentration of PUFA and the medium was collected for measurement of PGF(2alpha) and PGE(2). Supplementation with LA inhibited the production of PGF(2alpha) but did not alter PGE(2), whereas GLA and AA increased production of both PGs. All PUFA supplements thus increased the ratio of PGE(2) to PGF(2alpha) (E:F ratio) two- to threefold. In co...

Journal of Endocrinology, 2005

Polyunsaturated fatty acids derived from the diet are incorporated into cell membranes where they... more Polyunsaturated fatty acids derived from the diet are incorporated into cell membranes where they act as precursors for prostaglandin (PG) synthesis. Linoleic acid (LA; 18:2 n-6) is a major constituent of plant oils and its consumption in Westernized populations is increasing. This study investigated the influence of LA on PG production by the uterus and placenta. Pregnant ewes were fed a control or an LA-enriched diet. Oxytocin (OT) was injected on day 45 (early) or day 133 (late) of gestation to measure the release of 13,14-dihydro-15-keto PGF2α (PGFM). Ewes were killed on day 46 or day 138 for collection of uterine intercaruncular endometrium and fetal allantochorion. Basal and stimulated PG release from explant cultures was assessed before and after in vitro treatment with OT, lipopolysaccharide (LPS), dexamethasone (DEX) or calcium ionophore (CaI). Expression of cyclooxygenase (COX)-1 and COX-2 was determined by Western blot in endometrium of late-gestation ewes. Circulating PG...

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2004

Additional file 2: Supplementary Fig. 1. Additional figures supporting the main text of the manus... more Additional file 2: Supplementary Fig. 1. Additional figures supporting the main text of the manuscript. Referred to as Supplementary Figs. 1–3. Supplementary Fig. 1. Volcano plot of differentially expressed genes (padj 1). Supplementary Fig. 2. Outliers detected by sample clustering (WGCNA). Supplementary Fig. 3. Principal component analysis of herd effect. A) with herd effect, B) herd effect removed.

Bovine Viral Diarrhea virus (BVDV) is a pestivirus with a single-stranded, positive sense RNA gen... more Bovine Viral Diarrhea virus (BVDV) is a pestivirus with a single-stranded, positive sense RNA genome. It is endemic in many cattle populations, causing major economic losses in part due to reduced fertility. BVDV exhibits great genetic diversity and is classified as type 1 or 2 (BVDV-1, BVDV-2) with either non-cytopathogenic (ncp) or cytopathogenic (cp) biotypes. Differing strains of ncpBVDV differ in virulence, affecting clinical outcome. BVDV replicates in the reproductive tract, affecting host immunity and embryo survival. This study used an in vitro model of primary bovine endometrial cell cultures to compare the effects of two BVDV ncp type 1a strains of differing virulence (termed HO and KY) on endometrial transcription of candidate interferon stimulated genes (ISG) using qPCR. Half the cultures were stimulated with interferon tau (IFNT, the conceptus produced pregnancy recognition factor) in the presence or absence of viral infection. Cultures were replicated on cells from 10...