Biology subjects

Klein, L.

Publications and source records attributed to Klein, L..

4 recordsLinked to original sources

bioRxiv2018

Peripartum cardiomyopathy and hypertensive disorders of pregnancy and cardiovascular events among 1.6 million California pregnancies

BackgroundCardiovascular complications during and soon after pregnancy present an opportunity to assess risk for subsequent cardiovascular disease. We sought to determine whether peripartum cardiomyopathy and hypertensive disorder of pregnancy subtypes predict future myocardial infarction, heart failure, or stroke independent of one another and independent of other risks like gestational diabetes, preterm birth, and intrauterine growth restriction.\n\nMethods and ResultsThe California Healthcare Cost and Utilization Project database was used to identify all hospitalized pregnancies from 2005-2009, with follow-up through 2011, for a retrospective cohort study. Pregnancies, exposures, covariates and outcomes were defined by ICD-9 codes. Among 1.6 million pregnancies (mean age 28y; median follow-up time to event 2.7y), 558 cases of peripartum cardiomyopathy, 123,603 cases of hypertensive disorders of pregnancy, 107,636 cases of gestational diabetes, 116,768 preterm births, and 23,504 cases of intrauterine growth restriction were observed. Using multivariable Cox proportional hazards models, peripartum cardiomyopathy was independently associated with a 13.0-fold increase in myocardial infarction [95%CI, 4.1-40.9], a 39.2-fold increase in heart failure [95%CI, 30.0-51.9], and a 7.7-fold increase in stroke [95%CI, 2.4-24.0]. Hypertensive disorders of pregnancy were associated with a 1.4 [95%CI, 1.0-2.0] to 7.6 [95%CI, 5.4-10.7] fold higher risk of myocardial infarction, heart failure, and stroke. Gestational diabetes, preterm birth, and intrauterine growth restriction had more modest associations with CVD.\n\nConclusionsThese findings support close monitoring of women with cardiovascular pregnancy complications for prevention of early subsequent cardiovascular events and further study of mechanisms underlying their development.

epidemiology↗

bioRxiv2017

Stimulus content shapes cortical response statistics

Spike count correlations (SCCs) are ubiquitous in sensory cortices, are characterized by rich structure and arise from structured internal interactions. Yet, most theories of visual perception focus exclusively on the mean responses of individual neurons. Here, we argue that feedback interactions in primary visual cortex (V1) establish the context in which individual neurons process complex stimuli and that changes in visual context give rise to stimulus-dependent SCCs. Measuring V1 population responses to natural scenes in behaving macaques, we show that the fine structure of SCCs is stimulus-specific and variations in response correlations across-stimuli are independent of variations in response means. Moreover, we demonstrate that stimulus-specificity of SCCs in V1 can be directly manipulated by controlling the high-order structure of synthetic stimuli. We propose that stimulus-specificity of SCCs is a natural consequence of hierarchical inference where inferences on the presence of high-level image features modulate inferences on the presence of low-level features.

neuroscience↗

bioRxiv2017

Persistent homology demarcates a leaf morphospace

Current morphometric methods that comprehensively measure shape cannot compare the disparate leaf shapes found in seed plants and are sensitive to processing artifacts. We explore the use of persistent homology, a topological method applied across the scales of a function, to overcome these limitations. The described method isolates subsets of shape features and measures the spatial relationship of neighboring pixel densities in a shape. We apply the method to the analysis of 182,707 leaves, both published and unpublished, representing 141 plant families collected from 75 sites throughout the world. By measuring leaves from throughout the seed plants using persistent homology, a defined morphospace comparing all leaves is demarcated. Clear differences in shape between major phylogenetic groups are detected and estimates of leaf shape diversity within plant families are made. This approach does not only predict plant family, but also the collection site, confirming phylogenetically invariant morphological features that characterize leaves from specific locations. The application of a persistent homology method to measure leaf shape allows for a unified morphometric framework to measure plant form, including shape and branching architectures.

plant biology↗

bioRxiv2017

ADAM17 Is The Main Sheddase For The Generation Of Human Triggering Receptor Expressed In Myeloid Cells (hTREM2) Ectodomain And Cleaves TREM2 After Histidine 157

Triggering receptor expressed in myeloid cells (TREM2) is a member of the immunoglobulin superfamily and is expressed in macrophages, dendritic cells, microglia, and osteoclasts. TREM2 plays a role in phagocytosis, regulates release of cytokine, contributes to microglia maintenance, and its ectodomain is shed from the cell surface. Using both pharmacological and genetic approaches we report here that the main protease contributing to the release of TREM2 ectodomain is ADAM17, (a disintegrin and metalloproteinase domain containing protein, also called TACE, TNF converting enzyme) while ADAM10 plays a minor role. Using mutational analysis, we demonstrate that the main cleavage site of the sheddases is located within the stalk region of TREM2 proximal to the plasma membrane. Complementary biochemical experiments reveal that cleavage occurs between histidine 157 and serine 158. Shedding is not altered for the R47H-mutated TREM2 protein that confers an increased risk for the development of Alzheimers disease. O-glycosylation is detected within the stalk region, but distant to the cleavage site. These findings reveal a link between shedding of TREM2 and its regulation during inflammatory conditions or chronic neurodegenerative disease like AD in which activity or expression of sheddases might be altered.

cell biology↗