Evaluation of energy balance of Friesian x Bunaji dairy cows using milk composition based indicator traits

The potentials of using milk composition as indicators of energy balance (EB) in dairy cows were evaluated. Milk composition traits (milk protein, fat and lactose percentages) from thirteen (13) primiparous and 47 multiparous (F1) Friesian x Bunaji cows were studied. The milk composition was analyzed weekly from 4 to 300 days postpartum. The analyzed percentage milk fat, protein and lactose were used to calculate the other milk composition parameters. The mean estimates of EB based on milk measures for all the 3 stages of lactation were positive. However, the magnitude of the average estimates of the EB increased with stages of lactation; 21.99, 46.514 and 59.097MJ/d for stages 1, 2 and 3 respectively. The magnitude and direction of the correlations between EB and milk composition traits varied across stages of lactation; the correlation coefficient was relatively stronger in the 3rd stage than the 1st and 2nd stages of lactation. The potential indicators of EB identified from this study were the protein contained variables, such as milk protein content (MPC), fat-protein ratio (FPR), change in milk protein content (dmPc), change in fat-protein ratio (dFPR) and change in protein-lactose ratio (dPLR). These variables had strong relationship with EB both within and across lactation stages. However, dmPc seems to be the variable most common to all of these potential milk production variables. It had very strong and positive relationship with EB both within and across lactation stages. This suggested that high milk protein is associated with positive EB, while the decrease in milk protein content is associated with negative energy balance (NEB). Therefore, the dynamics of changes in milk composition measures during lactation could be used to monitor the EB status of dairy cows.Keywords: Crossbred cows, Friesian x Bunaji cows, Dairy, Lactation stages, Milk protein content, Energy balance, Indicators, Fat-protein ratio, Protein-lactose rati

Effect of post-partum body condition score on milk yield and composition of Friesian x Bunaji dairy cows

The study determines the effect of dam body condition on milk yield and milk composition of dairy cows. The milk production records of 60 Friesian x Bunaji dairy cows were used for the study. The body condition score (BCS) was recorded on scale 1 to 5 with an increment of 0.25 points. The mean initial milk yield (IMY), daily milk yield (DMY) and total milk yield (TMY) was 6.54, 6.51 and 1872kg, respectively, while the mean peak yield (PY), peak day (PD), peak week (PWK) and lactation length (LL) were 10.61kg, 26.94 days, 4.33 weeks and 283.87 days, respectively. The mean fat, protein and lactose content of the milk was 4.22, 4.15 and 4.00 %, respectively, while the mean fat, protein and lactose yield was 0.269, 0.272 and 0.261 kg/day. The ratios of the milk composition were FPR (1.02), FLR (1.03) and PLR (104). There was relatively high variability in the population of the experimental animals with regard to their milk yield characteristics (CV = 15.38 – 67.13%) compared to the milk composition variables (CV = 4.36 – 26.09%). The effect of dam body condition score was significant (p<0.05) on all the milk yield  characteristics except IMY, PY and ADY. Dams with moderate BCS of between 2.5 to 3.5 during the lactation period takes longer days to peak yield (PD = 27.41 ± 3.27 days) and peak week (PWK = 4.43 ± 0.49 weeks) with longer lactation length (LL = 301 ± 31.17 days) and consequently higher TMY (1995.25 kg/lactation). However, those with higher BCS (>3.5) had higher IY (7.00 ± 1.86 kg) and shorter days to peak yield (PD = 20.50 ± 13.12 days), PWK (3.0 ± 1.95 weeks) and shorter LL (275.33 ± 25.44 days), which invariably resulted in relatively lower TMY (1819.83 ± 335.80 kg/lactation). The dam BCS had significant effect (p<0.05) on the percentage milk fat (MFC), milk lactose (MLC), fat protein ratio (FPR) and fat lactose ratio (FLR). Dams with higher (>3.5) BCS had higher MFC, MLC, FPR and FLR. It is obvious that BCS is an important factor that reflects the metabolic stability of dairy cows.Keywords: Post-partum, Body condition score, Milk yield, Milk composition, Friesian X Bunaji dairy cow

Acquired resistance to DZNep-mediated apoptosis is associated with copy number gains of AHCY in a B-cell lymphoma model

BackgroundEnhancer of zeste homolog 2 (EZH2) is considered an important driver of tumor development and progression by its histone modifying capabilities. Inhibition of EZH2 activity is thought to be a potent treatment option for eligible cancer patients with an aberrant EZH2 expression profile, thus the indirect EZH2 inhibitor 3-Deazaneplanocin A (DZNep) is currently under evaluation for its clinical utility. Although DZNep blocks proliferation and induces apoptosis in different tumor types including lymphomas, acquired resistance to DZNep may limit its clinical application.MethodsTo investigate possible mechanisms of acquired DZNep resistance in B-cell lymphomas, we generated a DZNep-resistant clone from a previously DZNep-sensitive B-cell lymphoma cell line by long-term treatment with increasing concentrations of DZNep (ranging from 200 to 2000nM) and compared the molecular profiles of resistant and wild-type clones. This comparison was done using molecular techniques such as flow cytometry, copy number variation assay (OncoScan and TaqMan assays), fluorescence in situ hybridization, Western blot, immunohistochemistry and metabolomics analysis.ResultsWhole exome sequencing did not indicate the acquisition of biologically meaningful single nucleotide variants. Analysis of copy number alterations, however, demonstrated among other acquired imbalances an amplification (about 30 times) of the S-adenosyl-L-homocysteine hydrolase (AHCY) gene in the resistant clone. AHCY is a direct target of DZNep and is critically involved in the biological methylation process, where it catalyzes the reversible hydrolysis of S-adenosyl-L-homocysteine to L-homocysteine and adenosine. The amplification of the AHCY gene is paralleled by strong overexpression of AHCY at both the transcriptional and protein level, and persists upon culturing the resistant clone in a DZNep-free medium.ConclusionsThis study reveals one possible molecular mechanism how B-cell lymphomas can acquire resistance to DZNep, and proposes AHCY as a potential biomarker for investigation during the administration of EZH2-targeted therapy with DZNep

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Long-term cellular immunity of vaccines for Zaire Ebola Virus Diseases

Recent Ebola outbreaks underscore the importance of continuous prevention and disease control efforts. Authorized vaccines include Merck’s Ervebo (rVSV-ZEBOV) and Johnson & Johnson’s two-dose combination (Ad26.ZEBOV/MVA-BN-Filo). Here, in a five-year follow-up of the PREVAC randomized trial (NCT02876328), we report the results of the immunology ancillary study of the trial. The primary endpoint is to evaluate long-term memory T-cell responses induced by three vaccine regimens: Ad26–MVA, rVSV, and rVSV–booster. Polyfunctional EBOV-specific CD4+ T-cell responses increase after Ad26 priming and are further boosted by MVA, whereas minimal responses are observed in the rVSV groups, declining after one year. In-vitro expansion for eight days show sustained EBOV-specific T-cell responses for up to 60 months post-prime vaccination with both Ad26-MVA and rVSV, with no decline. Cytokine production analysis identify shared biomarkers between the Ad26-MVA and rVSV groups. In secondary endpoint, we observed an elevation of pro-inflammatory cytokines at Day 7 in the rVSV group. Finally, we establish a correlation between EBOV-specific T-cell responses and anti-EBOV IgG responses. Our findings can guide booster vaccination recommendations and help identify populations likely to benefit from revaccination

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Nutritional profile of toasted canavalia ensiformis seed and its potetial as partially replacement for soybean in the diet of clarias gariepinus

The nutritional value of Jack bean (Canavalia ensiformis) in animal feeds have been limited by the presence of antinutritional factors. This study investigates the efficacy of toasting as a processing method in improving the nutritional value and the utilization of C. ensiformis seeds in the diet of Clarias gariepinus. Result obtained reveals that the proximate composition of toasted C. ensiformis seed was not significant affected when compared to the raw seed. However, many essential amino acids were significantly reduced by toasting. Of all phytonutrient isolated in the seed, lectin and canavaline were not markedly reduced with toasting. Fingerlings of C. gariepinus fed diets (35%CP) formulate by substituting soybeans (inclusion at 38.19%) with C. ensiformis at 0, 5, 10, 15 and 20% revealed significant reduction in growth as the substitution levels increased. It was concluded that toasting alone is not an effective method for improving utilization of C. ensiformis in the diet of African catfish. Research on other processing methods or are recommende

Nanotheranostics: Platforms, Current Applications, and Mechanisms of Targeting in Breast and Prostate Cancers

Globally, cancer is one of the deadliest diseases, needing a meticulous diagnosis and targeted treatment plan to achieve an initial prognosis, followed by precision and optimization in treatment. Nonselective targeting, difficulty in accurately monitoring treatment end-results, serious drug side-effects, and severity of disease resulting in metastasis are the key flaws of traditional techniques. Nanotechnology and nanoparticles possess special features to completely transform the field of diagnosis and treatment of cancer. A holistic strategy that employs a dual function of diagnosis and therapy while utilizing a nanocarrier is referred to as a nanotheranostic. The nanotheranostic framework was created to surmount a variety of biological and physiological obstacles, effectively delivering the cargo to the intended target location, while simultaneously facilitating therapeutic intervention, surveillance, and validation to demonstrate improved treatment effectiveness. As a result, a nanotheranostic platform can be useful for targeted drug delivery, release, and distribution assessment, in addition to patient classification and survival. Nanotheranostic techniques also lead to reduced drug side-effects compared with conventional therapies. In this review, we outline current studies on nanotheranostics and their advantages over conventional treatment strategies, the applications and challenges/limitations of nanotheranostics, and the mechanisms of targeting in breast and prostate cancers

Scientific considerations for global drug development.

Requiring regional or in-country confirmatory clinical trials before approval of drugs already approved elsewhere delays access to medicines in low- and middle-income countries and raises drug costs. Here, we discuss the scientific and technological advances that may reduce the need for in-country or in-region clinical trials for drugs approved in other countries and limitations of these advances that could necessitate in-region clinical studies

A virus-based biocatalyst

Contains fulltext : 35236.pdf (publisher's version ) (Closed access)Virus particles are probably the most precisely defined nanometre-sized objects that can be formed by protein self-assembly. Although their natural function is the storage and transport of genetic material, they have more recently been applied as scaffolds for mineralization and as containers for the encapsulation of inorganic compounds(1,2). The reproductive power of viruses has been used to develop versatile analytical methods, such as phage display, for the selection and identification of (bio) active compounds(3). To date, the combined use of self-assembly and reproduction has not been used for the construction of catalytic systems. Here we describe a self-assembled system based on a plant virus that has its coat protein genetically modified to provide it with a lipase enzyme. Using single-object and bulk catalytic studies, we prove that the virus-anchored lipase molecules are catalytically active. This anchored biocatalyst, unlike man-made supported catalysts, has the capability to reproduce itself in vivo, generating many independent catalytically active copies