Anatomy of a hotspot: Cisplatin hotspots in the tdk gene of Escherichia coli.

We previously reported that certain sub-regions of the thyA gene of Escherichia coli are more mutable than others when many different mutagens and mutators are analyzed (Mashiach et al., Mutation Research Fundamental Molecular Mechansims of Mutagenesis, 821: 111702, 2021). In this study, we focus on a single mutagen, cisplatin and verify that mutations occur preferentially at specific 3 bp sequences, but only when they appear in certain subregions of the gene.

Sexual and Reproductive Health Protective Factors among Adolescents with Child Welfare Involvement.

Youth with child welfare involvement experience disproportionate rates of sexual and reproductive health (SRH) risks and adverse outcomes. However, little is known about SRH protective factors among youth with child welfare involvement. This study examined whether birth control knowledge or SRH agency, norms, and expectancies differed by gender, age, race/ethnicity, or out-of-home care status among 245 youth, ages 12-15, with open child welfare cases due to maltreatment.

TNFR2 Depletion Reduces Psoriatic Inflammation in Mice by Downregulating Specific Dendritic Cell Populations in Lymph Nodes and Inhibiting IL-23/IL-17 Pathways.

TNF-α, a proinflammatory cytokine, is a crucial mediator of psoriasis pathogenesis. TNF-α functions by activating TNFR1 and TNFR2. Anti-TNF drugs that neutralize TNF-α, thus blocking the activation of TNFR1 and TNFR2, have been proven highly therapeutic in psoriatic diseases.

Severe maternal morbidity associated with cerclage use in pregnancy.

Objective: To quantify the frequency of serious maternal complications associated with cerclage use during pregnancy.

Study Design: We performed a retrospective population-based cohort study of all live births in Ohio from 2006 to 2015. Maternal sociodemographic, medical, and obstetric characteristics were compared for births in which cerclage was utilized during the pregnancy versus those without cerclage.

Regional Contribution of Previable Infant Deaths to Infant Mortality Rates in the United States.

Objective: Lack of standardization of infant mortality rate (IMR) calculation between regions in the United States makes comparisons potentially biased. This study aimed to quantify differences in the contribution of early previable live births (<20 weeks) to U.S.

Contribution of previable births to infant mortality rate racial disparity in the United States.

Objective: To quantify racial differences in contribution of previable live births (<20 weeks gestational age (GA)) to United States (US) Infant Mortality Rates (IMR).

Methods: Population-based retrospective cohort of US live births (2007-14) using CDC WONDER database stratified by maternal race/ethnicity. We compared the contribution of previable births to IMR and calculated modified IMRs (≥20 weeks GA) excluding previable live births in each group.

Coordinated regulation of hepatic FoxO1, PGC-1α and SREBP-1c facilitates insulin action and resistance.

Unlabelled: Type 2 diabetes is characterized by insulin resistance, hyperinsulinemia and hepatic overproduction of glucose and lipids. Insulin increases lipogenic enzyme expression by activating Akt and aPKC which activate SREBP-1c; this pathway is hyperactivated in insulin-resistant states. Insulin suppresses gluconeogenic enzyme expression by Akt-dependent phosphorylation/inactivation of FoxO1 and PGC-1α; this pathway is impaired in insulin-resistant states by aPKC excess, which displaces Akt from scaffolding-protein WD40/ProF, where Akt phosphorylates/inhibits FoxO1.

Towards the complete small RNome of .

In recent years, the Gram-negative bacterium has garnered considerable attention for its unprecedented capacity to rapidly develop resistance to antibacterial therapeutics. This is coupled with the seemingly epidemic emergence of new hyper-virulent strains. Although strain-specific differences for isolates have been well described, these studies have primarily focused on proteinaceous factors.

Classification of footwear outsole patterns using Fourier transform and local interest points.

Successful classification of questioned footwear has tremendous evidentiary value; the result can minimize the potential suspect pool and link a suspect to a victim, a crime scene, or even multiple crime scenes to each other. With this in mind, several different automated and semi-automated classification models have been applied to the forensic footwear recognition problem, with superior performance commonly associated with two different approaches: correlation of image power (magnitude) or phase, and the use of local interest points transformed using the Scale Invariant Feature Transform (SIFT) and compared using Random Sample Consensus (RANSAC). Despite the distinction associated with each of these methods, all three have not been cross-compared using a single dataset, of limited quality (i.

Hepatic insulin resistance in ob/ob mice involves increases in ceramide, aPKC activity, and selective impairment of Akt-dependent FoxO1 phosphorylation.

Pathogenesis of insulin resistance in leptin-deficient ob/ob mice is obscure. In another form of diet-dependent obesity, high-fat-fed mice, hepatic insulin resistance involves ceramide-induced activation of atypical protein kinase C (aPKC), which selectively impairs protein kinase B (Akt)-dependent forkhead box O1 protein (FoxO1) phosphorylation on scaffolding protein, 40 kDa WD(tryp-x-x-asp)-repeat propeller/FYVE protein (WD40/ProF), thereby increasing gluconeogenesis. Resultant hyperinsulinemia activates hepatic Akt and mammalian target of rapamycin C1, and further activates aPKC; consequently, lipogenic enzyme expression increases, and insulin signaling in muscle is secondarily impaired.

Atypical PKC: a target for treating insulin-resistant disorders of obesity, the metabolic syndrome and type 2 diabetes mellitus.

Introduction: The prevalence of obesity, the metabolic syndrome and type 2 diabetes mellitus have reached pandemic levels. Present therapies do not directly target the key factor responsible for the insulin resistance that underlies the development of these syndromes.

Areas Covered: This review focuses on hepatic atypical PKC (aPKC) as a key target for treating these disorders.

PKCλ haploinsufficiency prevents diabetes by a mechanism involving alterations in hepatic enzymes.

Tissue-specific knockout (KO) of atypical protein kinase C (aPKC), PKC-λ, yields contrasting phenotypes, depending on the tissue. Thus, whereas muscle KO of PKC-λ impairs glucose transport and causes glucose intolerance, insulin resistance, and liver-dependent lipid abnormalities, liver KO and adipocyte KO of PKC-λ increase insulin sensitivity through salutary alterations in hepatic enzymes. Also note that, although total-body (TB) homozygous KO of PKC-λ is embryonic lethal, TB heterozygous (Het) KO (TBHetλKO) is well-tolerated.

Akt-dependent phosphorylation of hepatic FoxO1 is compartmentalized on a WD40/ProF scaffold and is selectively inhibited by aPKC in early phases of diet-induced obesity.

Initiating mechanisms that impair gluconeogenic enzymes and spare lipogenic enzymes in diet-induced obesity (DIO) are obscure. Here, we examined insulin signaling to Akt and atypical protein kinase C (aPKC) in liver and muscle and hepatic enzyme expression in mice consuming a moderate high-fat (HF) diet. In HF diet-fed mice, resting/basal and insulin-stimulated Akt and aPKC activities were diminished in muscle, but in liver, these activities were elevated basally and were increased by insulin to normal levels.

Hepatic Atypical Protein Kinase C: An Inherited Survival-Longevity Gene that Now Fuels Insulin-Resistant Syndromes of Obesity, the Metabolic Syndrome and Type 2 Diabetes Mellitus.

This review focuses on how insulin signals to metabolic processes in health, why this signaling is frequently deranged in Western/Westernized societies, how these derangements lead to, or abet development of, insulin-resistant states of obesity, the metabolic syndrome and type 2 diabetes mellitus, and what our options are for restoring insulin signaling, and glucose/lipid homeostasis. A central theme in this review is that excessive hepatic activity of an archetypal protein kinase enzyme, "atypical" protein kinase C (aPKC), plays a critically important role in the development of impaired glucose metabolism, systemic insulin resistance, and excessive hepatic production of glucose, lipids and proinflammatory factors that underlie clinical problems of glucose intolerance, obesity, hepatosteatosis, hyperlipidemia, and, ultimately, type 2 diabetes. The review suggests that normally inherited genes, in particular, the aPKC isoforms, that were important for survival and longevity in times of food scarcity are now liabilities in times of over-nutrition.