Chk2 sustains PLK1 activity in mitosis to ensure proper chromosome segregation.

Polo-like kinase 1 (PLK1) protects against genome instability by ensuring timely and accurate mitotic cell division, and its activity is tightly regulated throughout the cell cycle. Although the pathways that initially activate PLK1 in G2 are well-characterized, the factors that directly regulate mitotic PLK1 remain poorly understood. Here, we identify that human PLK1 activity is sustained by the DNA damage response kinase Checkpoint kinase 2 (Chk2) in mitosis.

Chk2 sustains PLK1 activity in mitosis to ensure proper chromosome segregation.

Polo-like kinase 1 (PLK1) protects against genome instability by ensuring timely and accurate mitotic cell division. PLK1 activity is tightly regulated throughout the cell cycle. Although the pathways that initially activate PLK1 in G2 are well-characterized, the factors that directly regulate PLK1 in mitosis remain poorly understood.

ATR promotes clearance of damaged DNA and damaged cells by rupturing micronuclei.

The human ataxia telangiectasia mutated and Rad3-related (ATR) kinase functions in the nucleus to protect genomic integrity. Micronuclei (MN) arise from genomic and chromosomal instability and cause aneuploidy and chromothripsis, but how MN are removed is poorly understood. Here, we show that ATR is active in MN and promotes their rupture in S phase by phosphorylating Lamin A/C at Ser395, which primes Ser392 for CDK1 phosphorylation and destabilizes the MN envelope.

Identifying barriers and utility of obtaining ambulatory blood pressure monitoring in a pediatric chronic kidney disease population.

Background: Hypertension is a prevalent complication of Chronic Kidney Disease (CKD) and Ambulatory Blood Pressure Monitoring (ABPM) is the gold standard for diagnosis. The aim of our study was to assess the usefulness of obtaining ABPM and to identify barriers to ABPM in this pediatric patient population.

Method: In this retrospective analysis of patients with CKD stage 3-5 who were seen in one academic medical center's outpatient Pediatric Nephrology clinics between 2018 and 2021, we performed logistic regression to evaluate for associations between demographic factors and odds of having an ABPM.

ATR protects centromere identity by promoting DAXX association with PML nuclear bodies.

Centromere protein A (CENP-A) defines centromere identity and nucleates kinetochore formation for mitotic chromosome segregation. Here, we show that ataxia telangiectasia and Rad3-related (ATR) kinase, a master regulator of the DNA damage response, protects CENP-A occupancy at interphase centromeres in a DNA damage-independent manner. In unperturbed cells, ATR localizes to promyelocytic leukemia nuclear bodies (PML NBs), which house the histone H3.

Retrospective study assessing outcomes in cardiac surgery after implementation of Quantra.

Background: The Quantra QPlus System is a cartridge-based device with a unique ultrasound technology that can measure the viscoelastic properties of whole blood during coagulation. These viscoelastic properties correlate directly with hemostatic function. The primary objective of this study was to assess blood product utilization in cardiac surgery patients before and after the implementation of the Quantra QPlus System.

Keeping RelApse in Chk: molecular mechanisms of Chk1 inhibitor resistance in lymphoma.

Chk1 is a member of the DNA damage response pathway, whose loss leads to replication stress and genome instability. Because of its protective role against lethal levels of DNA replication stress, Chk1 has been studied as a valuable and intriguing target for cancer therapy. However, one of the most prominent challenges with this strategy is development of resistance to Chk1 inhibitors, rendering the treatment ineffective.

Urinary Cannabis Metabolite Concentrations in Cannabis Hyperemesis Syndrome.

Objective: Cannabis Hyperemesis Syndrome (CHS) is characterized by recurrent episodes of intractable emesis associated with heavy use of cannabis. Recognition of CHS can be problematic due to the lack of specific biomarkers, which can point the clinician to the diagnosis. We present, retrospectively, a series of adolescent/young adult patients who presented to a pediatric gastroenterology (GI) service with acute on chronic nausea and vomiting, subsequently found to have CHS with associated elevated urinary cannabis metabolite concentrations.

Discordances between pediatric and adult thresholds in the diagnosis of hypertension in adolescents with CKD.

Background: Adolescents with chronic kidney disease (CKD) are a unique population with a high prevalence of hypertension. Management of hypertension during the transition from adolescence to adulthood can be challenging given differences in normative blood pressure values in adolescents compared with adults.

Methods: In this retrospective analysis of the Chronic Kidney Disease in Children Cohort Study, we compared pediatric versus adult definitions of ambulatory- and clinic-diagnosed hypertension in their ability to discriminate risk for left ventricular hypertrophy (LVH) and kidney failure using logistic and Cox models, respectively.

Sympathomimetic-Induced Hyperthermia and Hyponatremia: A Simulation Case for Emergency Medicine Residents.

Introduction: MDMA (3,4-methylenedioxymethamphetamine) is a popular drug of abuse associated with a variety of clinical manifestations. There are a number of life-threatening sequelae, including, but not limited to, agitated delirium, cardiac dysrhythmias, and hyperthermia. Similar to other substances that cause sympathomimetic toxidromes, MDMA also induces a syndrome of inappropriate antidiuretic hormone secretion-like state resulting in hyponatremia.

Metabolic reduction after long-duration flight is not related to fat-free mass loss or flight duration in a migratory passerine.

Migratory birds catabolize large quantities of protein during long flights, resulting in dramatic reductions in organ and muscle mass. One of the many hypotheses to explain this phenomenon is that decrease in lean mass is associated with reduced resting metabolism, saving energy after flight during refueling. However, the relationship between lean body mass and resting metabolic rate remains unclear.

Trends in Living Donation by Race and Ethnicity Among Children With End-stage Renal Disease in the United States, 1995-2015.

Background: Living donor kidney transplants have declined among adults with end-stage renal disease (ESRD), with increases in racial/ethnic disparities over time. Secular trends in racial/ethnic disparities in living donor kidney transplantation have not been well studied in children.

Methods: Using multivariable Cox modeling, we examined changes in living donor kidney transplant rates over time and probability of receiving living donor kidney transplantation within 2 years of incident ESRD by race/ethnicity among 19 772 children in the US Renal Data System, 1995-2015.

Repetitive Fragile Sites: Centromere Satellite DNA As a Source of Genome Instability in Human Diseases.

Maintenance of an intact genome is essential for cellular and organismal homeostasis. The centromere is a specialized chromosomal locus required for faithful genome inheritance at each round of cell division. Human centromeres are composed of large tandem arrays of repetitive alpha-satellite DNA, which are often sites of aberrant rearrangements that may lead to chromosome fusions and genetic abnormalities.

Emotion-focused treatments for anorexia nervosa: a systematic review of the literature.

Purpose: The present review explores emotion-focused treatments for anorexia nervosa (AN).

Methods: We conducted a systematic literature search across key databases (PsychINFO, PubMed/Medline, and Web of Science) prior to September 2015. Twenty studies were selected for systematic review.

Phosphorylation at serine 331 is required for Aurora B activation.

Aurora B kinase activity is required for successful cell division. In this paper, we show that Aurora B is phosphorylated at serine 331 (Ser331) during mitosis and that phosphorylated Aurora B localizes to kinetochores in prometaphase cells. Chk1 kinase is essential for Ser331 phosphorylation during unperturbed prometaphase or during spindle disruption by taxol but not nocodazole.

Akt/PKB suppresses DNA damage processing and checkpoint activation in late G2.

Using chemical genetics to reversibly inhibit Cdk1, we find that cells arrested in late G2 are unable to delay mitotic entry after irradiation. Late G2 cells detect DNA damage lesions and form gamma-H2AX foci but fail to activate Chk1. This reflects a lack of DNA double-strand break processing because late G2 cells fail to recruit RPA (replication protein A), ATR (ataxia telangiectasia and Rad3 related), Rad51, or CtIP (C-terminal interacting protein) to sites of radiation-induced damage, events essential for both checkpoint activation and initiation of DNA repair by homologous recombination.

Vertebrate cells genetically deficient for Cdc14A or Cdc14B retain DNA damage checkpoint proficiency but are impaired in DNA repair.

A recent study suggested that human Cdc14B phosphatase has a central function in the G2 DNA damage checkpoint. In this study, we show that chicken DT40, human HCT116, and human telomerase reverse transcription-immortalized retinal pigment epithelial cells deleted for the Cdc14A or Cdc14B gene are DNA damage checkpoint proficient and arrest efficiently in G2 in response to irradiation. Cdc14A knockout (KO) or Cdc14B-KO cells also maintain normal levels of Chk1 and Chk2 activation after irradiation.

Adipose tissue distribution after weight restoration and weight maintenance in women with anorexia nervosa.

Background: Body image distortions are a core feature of anorexia nervosa (AN). We, and others, previously reported abnormalities in adipose tissue distribution after acute weight restoration in adult women with AN compared with body mass index-matched healthy control women. Whether these abnormalities persist over time remains unknown.

From guidelines to careflows: modelling and supporting complex clinical processes.

Research on computer interpretable clinical guidelines has largely focused on individual points of care rather than processes of care. Whether we consider simple aids like clinical alerts and reminders or more sophisticated data interpretation and decision-making, guideline developers tend to focus on specific tasks rather than processes like care plans and pathways which are extended in time. In contrast, research on business process modelling has demonstrated notations and tools which deal directly with process modelling, but has not been concerned with problems like data interpretation and decision making.

c-Jun supports ribosomal RNA processing and nucleolar localization of RNA helicase DDX21.

The molecular mechanisms by which the AP-1 transcription factor c-Jun exerts its biological functions are not clearly understood. In addition to its well established role in transcriptional regulation of gene expression, several reports have suggested that c-Jun may also regulate cell behavior by non-transcriptional mechanisms. Here, we report that small interfering RNA-mediated depletion of c-Jun from mammalian cells results in inhibition of 28 S and 18 S rRNA accumulation.

The impact of a genetics education program on physicians' knowledge and genetic counseling referral patterns.

Background: Gaps in the knowledge of general practitioners (GPs) in medical genetics prevent the effective utilization of genetic services and increase the risk of liability. Educators recommend that genetics should be integrated into existing teaching programs but the effectiveness of these types of programs is unknown.

Aim: The objective of this study was to provide a 2-year educational program for GPs untrained in genetics and to document its impact on genetic knowledge and referrals to a genetic counselor (GC).

DNA mismatch repair and Chk1-dependent centrosome amplification in response to DNA alkylation damage.

Centrosome amplification is frequently observed in tumor cells exposed to genotoxic stress, however the underlying mechanisms and biological consequences are poorly understood. Here, we show that the anti-metabolite and alkylating agent 6-thioguanine (6-TG) induces centrosome amplification resulting in the formation of multi-polar spindles when damaged cells subsequently enter mitosis. These aberrant, multi-polar mitoses are frequently resolved by asymmetric cell divisions causing unequal segregation of genetic material and cell death in one or both daughter products.

Chk1 is required for spindle checkpoint function.

The spindle checkpoint delays anaphase onset in cells with mitotic spindle defects. Here, we show that Chk1, a component of the DNA damage and replication checkpoints, protects vertebrate cells against spontaneous chromosome missegregation and is required to sustain anaphase delay when spindle function is disrupted by taxol, but not when microtubules are completely depolymerized by nocodazole. Spindle checkpoint failure in Chk1-deficient cells correlates with decreased Aurora-B kinase activity and impaired phosphorylation and kinetochore localization of BubR1.