• Henry Nyholm posted an update 6 months, 3 weeks ago

    The marked overexpression of cyclin-dependent kinase 5 (CDK5) or Notch1 receptor, which plays critical roles in pancreatic ductal adenocarcinoma (PDAC) development, has been detected in numerous PDAC cell lines and tissues. Although, a previous study has demonstrated that CDK5 inhibition disrupts Notch1 functions in human umbilical vein endothelial cells, the mechanism underlying Notch1 activation regulated by CDK5 remains unclear. Herein, we identified a physical interaction between CDK5 and Notch1 in PDAC cells, with the Notch1 peptide phosphorylated by CDK5/p25 kinase. CDK5 blockade resulted in the profound inhibition of Notch signaling. Accordingly, CDK5 inhibition sensitized PDAC cell proliferation and migration following Notch inhibition. In conclusion, CDK5 positively regulates Notch1 function via phosphorylation, which in turn promotes cell proliferation and migration. The combinational inhibition of CDK5 and Notch signaling may be an effective strategy in the treatment of PDAC.Infants born preterm, low birthweight or with other perinatal complications require frequent and accurate growth monitoring for optimal nutrition and growth. We implemented an mHealth tool to improve growth monitoring and nutritional status assessment of high risk infants. We conducted a pre-post quasi-experimental study with a concurrent control group among infants enrolled in paediatric development clinics in two rural Rwandan districts. During the pre-intervention period (August 2017-January 2018), all clinics used standard paper-based World Health Organization (WHO) growth charts. During the intervention period (August 2018-January 2019), Kirehe district adopted an mHealth tool for child growth monitoring and nutritional status assessment. Data on length/height; weight; length/height-for-age (L/HFA), weight-for-length/height (WFL/H) and weight-for-age (WFA) z-scores; and interval growth were tracked at each visit. We conducted a ‘difference-in-difference’ analysis to assess whether the mHealth tool was associated with greater improvements in completion and accuracy of nutritional assessments and nutritional status at 2 and 6 months of age. We observed 3529 visits. find more mHealth intervention clinics showed significantly greater improvements on completeness for corrected age (endline 65% vs. 55%; p = 0.036), L/HFA (endline 82% vs. 57%; p ≤ 0.001), WFA (endline 93% vs. 67%; p ≤ 0.001) and WFL/H (endline 90% vs. 59%; p ≤ 0.001) z-scores compared with control sites. Accuracy of growth monitoring did not improve. Prevalence of stunting, underweight and inadequate interval growth at 6-months corrected age decreased significantly more in the intervention clinics than in control clinics. Results suggest that integrating mHealth nutrition interventions is feasible and can improve child nutrition outcomes. Improved tool design may better promote accuracy.Powdery mildews are major diseases for a range of crops. The loss of function of specific Mildew Locus O (MLO) genes has long been associated with pre-haustorial plant resistance to powdery mildew and has proven to be durable in several species. Erysiphe pisi is the major causal agent of powdery mildew in pea (Pisum sativum L.) and in the closely related Lathyrus sativus L. and Lathyrus cicera L. PsMLO1 has been extensively studied in pea. However, no MLO gene family members have been isolated and characterized in Lathyrus species so far. In this study, MLO1 genes were isolated and characterized in L. sativus and L. cicera genotypes with varied levels of partial resistance against powdery mildew. Phylogenetic analyses confirmed that Lathyrus MLO1 belongs to Clade V, like all dicot MLO proteins associated with powdery mildew susceptibility. A L. sativus recombinant inbred line population (RIL) was genotyped by sequencing to develop a high-density L. sativus genetic linkage map. DNA sequence polymorphisms between the analyzed genotypes allowed the location of MLO1 in the newly developed L. sativus RIL genetic linkage map. Subsequent comparative mapping between L. sativus and L. cicera genetic maps and P. sativum, Lens culinaris Medik., and Medicago truncatula Gaertn. reference genomes revealed important aspects of the conservation of the MLO1 locus position and of the overall chromosomal rearrangements occurring during legume evolution, with relevance to legume disease resistance breeding programs.

    Low branched-chain amino acid (BCAA) to tyrosine ratio (BTR) is known as an indicator of amino acid imbalance. We elucidated usefulness of newly developed albumin-bilirubin (ALBI) score as alternative methods of BTR in patients with naïve hepatocellular carcinoma (HCC) retrospectively.

    In 842 patients with HCC and without BCAA supplementation (71years, male 614, Child-Pugh ABC=68911637), relationships among BTR and clinical features were evaluated. Of those, 438 patients, with Milan criteria HCC, treated curatively were divided into the high-BTR (>4.4) (n=293) and low-BTR (≤4.4) (n=145) groups. The prognostic value of BTR was evaluated using inverse probability weighting (IPW) with propensity score.

    The low-BTR group showed worse prognosis than the other (3-, 5-, 10-year overall survival rates 88.9% vs. 86.3%/70.5% vs. 78.1%/38.1% vs. 52.3%, respectively; p<0.001). Multivariate Cox-hazard analysis adjusted for IPW showed elderly (≥65 years) HR 2.314, p=0.001), female gender (HR 0.422, p<0.001), ECOG PS ≥2 (HR 3.032, p=0.002), low platelet count (HR 1.757, p=0.010), and low BTR (≤4.4) (HR 1.852, p=0.005) to be significant prognostic factors. Both serum albumin level (r=0.370, p<0.001) and ALBI score (r=-0.389, p<0.001) showed a significant relationship with BTR. Child-Pugh class B, modified ALBI grade (mALBI) 2a, and mALBI 2b predictive values for BTR were 3.589, 4.509, and 4.155 (AUC range 0.735-0.770), respectively, while the predictive value of ALBI score for low-BTR (≤4.4) was -2.588 (AUC 0.790).

    ALBI score -2.588 was a predictor for low-BTR (≤4.4), which was prognostic factors for early HCC patients, and at least patients with mALBI 2b might have an amino acid imbalance.

    ALBI score -2.588 was a predictor for low-BTR (≤4.4), which was prognostic factors for early HCC patients, and at least patients with mALBI 2b might have an amino acid imbalance.

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