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Hemogenic Reprogramming of Human Fibroblasts by Enforced Expression of Transcription Factors

The cellular and molecular mechanisms underlying specification of human hematopoietic stem cells (HSCs) remain elusive. Strategies to recapitulate human HSC emergence in vitro are required to overcome limitations in studying this complex developmental process. Here, we describe a protocol to generate hematopoietic stem and progenitor-like cells from human dermal fibroblasts employing a direct cell

Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming

During development, hematopoietic stem and progenitor cells (HSPCs) arise from specialized endothelial cells by a process termed endothelial-to-hematopoietic transition (EHT). The genetic program driving human HSPC emergence remains largely unknown. We previously reported that the generation of hemogenic precursor cells from mouse fibroblasts recapitulates developmental hematopoiesis. Here, we dem

Intake of different types of red meat, poultry, and fish and incident colorectal cancer in women and men: results from the Malmö Diet and Cancer Study.

Background : Colorectal cancer (CRC) is considered one of the most common forms of cancer in the Western world. High intake of red and processed meat is considered to increase CRC development. Objective : This study examined associations between intake of red meats, poultry, and fish and incident CRC, and if weight status modifies the associations. Design : In the Malmö Diet and Cancer Study, diet

Male infertility and prostate cancer risk: a nested case-control study.

The pathogenesis of prostate cancer is unclear, although experimental evidence implicates androgens as playing an important role. Infertile men frequently suffer from some degree of hypogonadism and may hence be hypothesized to be at lower risk of developing prostate cancer than fertile men. To test this hypothesis, we conducted a case-control study nested within "the Malmö Diet and Cancer Study"

SMAD4 binds HOXA9 in the cytoplasm and protects primitive hematopoietic cells against nuclear activation by HOXA9 and leukemia transformation.

We studied leukemic stem cells (LSCs) in a Smad4(-/-) mouse model of acute myelogenous leukemia (AML) induced either by the HOXA9 gene or by the fusion oncogene NUP98-HOXA9. While HOXA9-SMAD4 complexes accumulate in the cytoplasm of normal hematopoietic stem- and progenitor cells (HSPCs) transduced with these oncogenes, there is no cytoplasmic accumulation of HOXA9 in Smad4(-/-) HSPCs and as a con

A candidate CpG SNP approach identifies a breast cancer associated ESR1-SNP.

Altered DNA methylation is often seen in malignant cells, potentially contributing to carcinogenesis by suppressing gene expression. We hypothesized that heritable methylation potential might be a risk factor for breast cancer and evaluated possible association with breast cancer for single nucleotide polymorphisms (SNPs) either involving CpG sequences in extended 5'- regulatory regions of candida

Understanding and Modulating Immunity With Cell Reprogramming

Cell reprogramming concepts have been classically developed in the fields of developmental and stem cell biology and are currently being explored for regenerative medicine, given its potential to generate desired cell types for replacement therapy. Cell fate can be experimentally reversed or modified by enforced expression of lineage specific transcription factors leading to pluripotency or attain

Electrostatic interactions control the adsorption of extracellular vesicles onto supported lipid bilayers

Communication between cells located in different parts of an organism is often mediated by membrane-enveloped nanoparticles, such as extracellular vesicles (EVs). EV binding and cell uptake mechanisms depend on the heterogeneous composition of the EV membrane. From a colloidal perspective, the EV membrane interacts with other biological interfaces via both specific and non-specific interactions, w

Design of an AI Support for Diagnosis of Dyspneic Adults at Time of Triage in the Emergency Department

We created an AI support for diagnosis in dyspneic adults at time of triage in the emergency department.Complete data from an entire regional health care system was analyzed, to find AI-derived, unknown, important diagnostic predictors. Most important were prior diagnoses of heart failure or COPD, daily smoking, atrial fibrillation/flutter, life difficulties and maternal care.Sensitivity for AHF,

Solar heating may explain extreme diel flight altitude changes in migrating birds

Great reed warblers, Acrocephalus arundinaceus,1 and great snipes, Gallinago media,2 exhibit a diel cycle in flight altitudes—flying much higher during the day than the night—when performing migratory flights covering both night and day. One hypothesis proposed to explain this behavior is that the birds face additional heating by solar radiation during daytime and hence must climb to very high, an

Nasal polyposis is a risk factor for nonadherence to CPAP treatment in sleep apnea : the population-based DISCOVERY study

STUDY OBJECTIVES: The aim was to evaluate nasal polyposis as a risk factor for nonadherence to continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). METHODS: This was a population-based, longitudinal analysis of patients starting CPAP treatment for OSA in the Swedish quality registry Swedevox between 2010 and 2018. Data were cross-linked with national

Type 2 diabetes, adiposity and cancer morbidity and mortality risk taking into account competing risk of noncancer deaths in a prospective cohort setting

Type 2 diabetes (T2D) and adiposity associate with increased risk of several cancers, but the impact of competing risk of noncancer deaths on these associations is not known. We prospectively examined participants in the Malmö Diet and Cancer Study aged 44–73 years with no history of cancer at baseline (n = 26,953, 43% men). T2D was ascertained at baseline and during follow-up, and body mass index

Cytohesin 1 regulates homing and engraftment of human hematopoietic stem and progenitor cells

Adhesion is a key component of hematopoietic stem cell regulation mediating homing and retention to the niche in the bone marrow. Here, using an RNA interference screen, we identify cytohesin 1 (CYTH1) as a critical mediator of adhesive properties in primary human cord blood-derived hematopoietic stem and progenitor cells (HSPCs). Knockdown of CYTH1 disrupted adhesion of HSPCs to primary human mes

Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) dat

Evaluation of reproducibility in MRI quantitative volumetric assessment and its role in the prediction of overall survival and progression-free survival in glioblastoma

Background: Residual tumor volume (RTV) and extent of resection (EOR) have previously been shown to affect survival in glioblastoma (GB) patients. Quantitative radiological assessment (QRA) of these factors could potentially affect clinical decision-making in the postoperative period. Purpose: The first aim was to evaluate the reproducibility of different volume estimation methods of RTV and EOR b

Modelling human rostro-caudal neural patterning with a microfluidic morphogenic gradient

The study of biological mechanisms involved in human fetal brain development requires suitable models. To date, most findings have been acquired from animal models that fail to account for human-specific developmental traits. To counteract this limitation, a novel in vitro model is proposed where human pluripotent stem cells are differentiated into a coherent fetal brain tissue in a gradient formi

Aerosolization and recovery of viable murine norovirus in an experimental setup

Noroviruses are the major cause for viral acute gastroenteritis in the world. Despite the existing infection prevention strategies in hospitals, the disease continues to spread and causes extensive and numerous outbreaks. Hence, there is a need to investigate the possibility of airborne transmission of norovirus. In this study, we developed an experimental setup for studies on the infectivity of a