Estimates of Heritabilities of Milk Fat and Milk Protein and Their Correlations with Milk Yield in Sahiwal Cattle of Punjab Pakistan

This study aimed to estimate the genetic parameters for lactation milk yield (LMY), lactation fat yield (LFY), and lactation protein yield (LPY) in the Sahiwal cattle breed of Pakistan. Performance data of 3364 purebred Sahiwal cattle with 9964 herd test records were collected from the public and/or private herds. Various edits were applied, such as herd test day records < 3, unknown calving and drying dates, etc., which reduced the data set to 1039 animals with 4489 herd test records. Lactation yields for milk, fat, and protein were calculated using the test interval method. Preliminary data analysis was performed using PROC MIXED in SAS. The animal model under the REML method was used to estimate the genetic parameters of the milk yield, milk fat, and milk protein. A multivariate model (3-traits) was fitted, which included the fixed effects of parity besides random effects of herd-year-season of calving (HYS), animal and residuals for all three traits. Mean ± SD (kg) of LMY, LFY, and LPY were 1444.07±554.51, 60.48±25.18, and 48.26±19.39, respectively. Parity and HYS significantly varied (p<0.05) among cows for all investigated production traits. The estimates of heritabilities with their standard errors for LMY, LFY, and LPY were 0.164±0.065, 0.124±0.061, and 0.181±0.067, respectively. The phenotypic and genetic correlations were high among all three production traits, which ranged between 0.879 to 0.975 and 0.990 to 0.999, respectively, with standard errors ranging from 0.002 to 0.03. Low to moderate heritability estimates for milk component traits obtained in the present study suggest that these traits could be improved through genetic selection

Nivolumab in the Treatment of Recurrent or Refractory Pediatric Brain Tumors: A Single Institutional Experience.

Successful use of immune checkpoint inhibitors in a variety of cancers has generated interest in using this approach in pediatric brain tumors. We performed a retrospective review of 10 consecutive children (6 boys, 4 girls; ages, 2 to 17 y), with recurrent or refractory pediatric brain tumors (5 high-grade glioma, 1 low-grade glioma, pineoblastoma, medulloblastoma, ependymoma, and CNS embryonal tumor, NOS) treated at Rady Children's Hospital San Diego from 2015 to 2017 with the immune checkpoint inhibitor nivolumab (3 mg/kg every 2 wk). Eight of 10 patients received prior chemotherapy and 9 radiation therapy. Nine patients had radiographic disease progression (median, 2.5 doses). Median time to progression was 5.5 weeks (1.6 to 24 wk). Three patients (2 with high-grade glioma, 1 with CNS embryonal tumor NOS) showed a partial response to treatment at the primary tumor site and 2 of 3 had progression of metastatic disease. Grade 2 toxicities were observed without dose limiting side effects. Tumor mutation burden (TMB) was low to intermediate (median, 1.3; range, 0 to 6.3). Median survival for PD-L1 positive patients was 13.7 weeks versus 4.2 weeks for PD-L1 negative patients (ρ=0.08) nivolumab was well tolerated in our series of pediatric recurrent brain tumors with some transient partial responses in patients with positive PD-L1 expression and higher TMB. Our findings suggest that the use of immune checkpoint inhibitors in pediatric brain tumor patients should be limited to those with elevated PD-L1 expression and TMB

A dominant negative ADIPOQ mutation in a diabetic family with renal disease, hypoadiponectinemia, and hyperceramidemia

Abstract Adiponectin, encoded by ADIPOQ, is an insulin-sensitizing, anti-inflammatory, and renoprotective adipokine that activates receptors with intrinsic ceramidase activity. We identified a family harboring a 10-nucleotide deletion mutation in ADIPOQ that cosegregates with diabetes and end-stage renal disease. This mutation introduces a frameshift in exon 3, resulting in a premature termination codon that disrupts translation of adiponectin’s globular domain. Subjects with the mutation had dramatically reduced circulating adiponectin and increased long-chain ceramides levels. Functional studies suggest that the mutated protein acts as a dominant negative through its interaction with non-mutated adiponectin, decreasing circulating adiponectin levels, and correlating with metabolic disease