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Interacting morphogens produce periodic patterns in developing tissues. read more Such patterning can be modelled as reaction-diffusion (RD) processes (as originally formulated by Alan Turing), and although these models have been developed and refined over the years, they often tend to oversimplify biological complexity by restricting the number of interacting morphogens. A new paper in Development reports how perturbation analysis can guide multi-morphogen modelling of the striped patterning the roof of the mouse mouth. To hear more about the story, we caught up with first author Andrew Economou and his former supervisor Jeremy Green, Professor of Developmental Biology at King's College, London.
Although diabetic kidney disease is the leading cause of ESKD in the United States, identifying those patients who progress to ESKD is difficult. Efforts are under way to determine if plasma biomarkers can help identify these high-risk individuals.
In our case-cohort study of 894 Chronic Renal Insufficiency Cohort Study participants with diabetes and an eGFR of <60 ml/min per 1.73 m
at baseline, participants were randomly selected for the subcohort; cases were those patients who developed progressive diabetic kidney disease (ESKD or 40% eGFR decline). Using a multiplex system, we assayed plasma biomarkers related to tubular injury, inflammation, and fibrosis (KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40). Weighted Cox regression models related biomarkers to progression of diabetic kidney disease, and mixed-effects models estimated biomarker relationships with rate of eGFR change.
Median follow-up was 8.7 years. Higher concentrations of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were each as the highest risk after accounting for the other biomarkers. These findings validate previous literature on TNFR-1, TNFR-2, and KIM-1 in patients with prevalent CKD and provide new insights into the influence of suPAR and YKL-40 as plasma biomarkers that require validation.
Cultured cell lines are widely used for research in the physiology, pathophysiology, toxicology, and pharmacology of the renal proximal tubule. The lines that are most appropriate for a given use depend upon the genes expressed. New tools for transcriptomic profiling using RNA sequencing (RNA-Seq) make it possible to catalog expressed genes in each cell line.
Fourteen different proximal tubule cell lines, representing six species, were grown on permeable supports under conditions specific for the respective lines. RNA-Seq followed standard procedures.
Transcripts expressed in cell lines variably matched transcripts selectively expressed in native proximal tubule. Opossum kidney (OK) cells displayed the highest percentage match (45% of proximal marker genes [TPM threshold =15]), with pig kidney cells (LLC-PK1) close behind (39%). Lower-percentage matches were seen for various human lines, including HK-2 (26%), and lines from rodent kidneys, such as NRK-52E (23%). Nominally, identical OK cells from different sources differed substantially in expression of proximal tubule markers. Mapping cell line transcriptomes to gene sets for various proximal tubule functions (sodium and water transport, protein transport, metabolic functions, endocrine functions) showed that different lines may be optimal for experimentally modeling each function. An online resource (https//esbl.nhlbi.nih.gov/JBrowse/KCT/) has been created to interrogate cell line transcriptome data. Proteomic analysis of NRK-52E cells confirmed low expression of many proximal tubule marker proteins.
No cell line fully matched the transcriptome of native proximal tubule cells. However, some of the lines tested are suitable for the study of particular metabolic and transport processes seen in the proximal tubule.
No cell line fully matched the transcriptome of native proximal tubule cells. However, some of the lines tested are suitable for the study of particular metabolic and transport processes seen in the proximal tubule.This study investigated parental factors and beliefs supporting aggression as predictors of physical aggression by adolescents. The participants were 2,443 junior high school students from Ankara, Turkey, who completed measures of parental support for aggression, family conflict, parental monitoring, beliefs supporting aggression, and physical aggression. The findings showed both direct and indirect effects of parental factors on physical aggression through beliefs supporting aggression. Furthermore, a multigroup model comparison indicated invariance of the structural relationships among variables in the model across gender and that the hypothesized structural model was a close fit for both the girl and the boy data. The findings suggest that it might be beneficial to consider beliefs supporting aggression and parental factors as risk factors when designing interventions to target physical aggression among adolescents.Unarousable child with short bowelA 4-year-old boy was admitted with progressive lethargy of a few hours' duration and no other symptoms. His medical history was relevant for short bowel syndrome (SBS), following neonatal volvulus, with residual bowel length of 23 cm and intact ileocecal valve. He had similar self-limiting episodes in the past, after weaning parenteral nutrition, especially after eating large meals. The day before, he had consumed a large amount of apples.Arterial blood gas (ABG) analysis showed metabolic acidosis with normal lactacidaemia (pH 7.09, pCO2 19 mm Hg, pO2 101 mm Hg, HCO3 5.8 mmol/L, BE -24, anion gap 29.4, chloride 116 mmol/L, L-lactate level 4 mmol/L).On admission, the child could be awakened, but he was confused with slurred speech (Glasgow Coma Scale 14), with a body temperature of 37 C°, a heart rate of 125 beats/min and a respiratory rate of 38 breaths/min. The abdomen was distended, without guarding and with normal bowel sounds. Blood glucose levels were normal, as well as white blood cell count, liver and kidney function test and C reactive protein. An abdominal ultrasound ruled out an intussusception. An abdominal X-ray was performed too (see figure 1).edpract;archdischild-2020-318826v1/F1F1F1Figure 1Abdominal distension with gas and bloating. QUESTIONS Which is the most likely diagnosis?EncephalitisD-lactic acidosisDehydration with third space fluid collection and acidosisHereditary fructose intolerance.How is this diagnosis confirmed?D lactic dosageBreath test for bacterial overgrowthUrine organic acid dosageSearch for reductive substances in the stools.How should this patient be managed?Intravenous fluids to facilitate D-lactic excretionRestrict carbohydrates in the dietIntravenous bicarbonatesAntibiotic treatment to reduce bowel bacterial overgrowth. Answers can be found on page 2.
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