Essential amino acid ratios and mTOR affect lipogenic gene networks and miRNA expression in bovine mammary epithelial cells

Background： The objective of this study was to study how changing the ratio of Lys to Thr, Lys to His, and Lys to Val affects the expression of lipogenic genes and microRNA （miRNA） in bovine mammary epithelial cells. Results： Triplicate cultures with the respective ＂optimal＂ amino acid （AA） ratio （OPAA = Lys：Met 2.9：1; Thr：Phe 1.05：1; Lys：Thr 1.8：1; Lys：His 2.38：1; Lys：Val 1.23：1） plus rapamycin （OPAARMC; positive control）, OPAA, Lys：Thr 2.1：1 （LT2.1）, Lys：Thr 1.3：1 （LT1.3）, Lys：His 3.05：1 （LH3.0）, or Lys：Val 1.62：1 （LV1.6） were incubated in lactogenic medium for 12 h. The expression of 15 lipogenic genes and 7 miRNA were evaluated. Responses to LT2.1, LT1.3, LH3.0, and LV1.6 relative to the control （OPAARMC） included up-regulated expression ofACSS2, FABP3, ACACA, FASN, SCD, LPIN1, INSIG1, SREBF1, PPARD, and NR1H3 （commonly known as LXR-a）. Furthermore, LV1.6 up-regulated expression of ACSL1, DGAT1, and RXRA and down-regulated PPARG expression. Although no effect of OPAA on expression of PPARG was observed, compared with the control, OPAA up-regulated expression of the PPAR targets ACSS2, FABP3, ACACA, FASN, SCD, LPIN1, INSIG1, and SREBF1. Compared with the control, the expression of the anti-lipogenic MIR27AB was down-regulated by OPAA, LT2.1, LT1.3 and LH3.0. In contrast, compared with the control, the expression of the pro-lipogenic MIR21 was up-regulated by LT2.1, LT1.3, LH3.0, and LV1.6. Conclusions： The observed up-regulation of lipogenic gene networks and the changes in expression of key miRNA involved in the control of lipogenic balance are indicative of a potentially important role of EAA ratios and mTOR signaling in the regulation of milk fat synthesis.

Novel TINF2 gene mutation in dyskeratosis congenita with extremely short telomeres:A case report

BACKGROUND Dyskeratosis congenita is a rare disease characterized by bone marrow failure and a clinical triad of oral leukoplakia,nail dystrophy,and abnormal skin pigmentation.The genetics of dyskeratosis congenita include mutations in genes involved in telomere maintenance,including TINF2.CASE SUMMARY Here,we report a female patient who presented thrombocytopenia,anemia,reticulate hyperpigmentation,dystrophy in fingernails and toenails,and leukoplakia on the tongue.A histopathological study of the skin showed dyskeratocytes;however,a bone marrow biopsy revealed normal cell morphology.The patient was diagnosed with dyskeratosis congenita,but her family history did not reveal significant antecedents.Whole-exome sequencing showed a novel heterozygous punctual mutation in exon 6 from the TINF2 gene,namely,NM_001099274.1:-c.854delp.(Val285-Alafs*32).An analysis of telomere length showed short telomeres relative to the patient’s age.CONCLUSION The disease in this patient was caused by a germline novel mutation of TINF2 in one of her parents.

SARS-CoV-2:Air pollution highly correlated to the increase in mortality.The case of Guadalajara,Jalisco,Mexico

Objectives:To determine whether air pollution or changes in SARS-CoV-2 lineages lead to an increase in mortality.Methods:Descriptive statistics were used to calculate rates of infection(2020-2021).RT ePCR was used to compare viral loads from October 2020 to February 2021.Nextgeneration sequencing(NGS)(n=92)was used to examine and phylogenetically map SARS-CoV-2 lineages.A correlative“air pollution/temperature”index(I)was developed using regression analysis.PM_(2.5),PM_(10),O_(3),NO_(2),SO_(2),and CO concentrations were analyzed and compared to the mortality.Results:The mortality rate during the last year was~32%.Relative SARS-CoV-2 viral loads increased in December 2020 and January 2021.NGS revealed that approximately 80%of SARS-CoV-2 linages were B.1.243(33.7%),B1.1.222(11.2%),B.1.1(9%),B.1(7%),B.1.1.159(7%),and B.1.2(7%).Two periods were analyzed,the prehigh-and high-mortality periods and no significant lineage differences or new lineages were found.Positive correlations of air pollution/temperature index values with mortality were found for IPM_(2.5) and IPM_(10).INO_(2).ISO_(2),and ICO but not for O_(3).Using ICO,we developed a model to predict mortality with an estimated variation of~±5 deaths per day.