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High-energy breakfast based on whey protein reduces body weight, postprandial glycemia and HbA1C in Type 2 diabetes
Acute studies show that addition of whey protein at breakfast has a glucose-lowering effect through increased incretin and insulin secretion. However, whether this is a long-term effect in Type 2 diabetes is unknown. Fifty-six Type 2 diabetes participants aged 58.9±4.5 years, BMI 32.1±0.9 kg/m2 and HbA1C 7.8±0.1% (61.6±0.79 mmol/mol) were randomized to one of 3 isocaloric diets with similar lunch
Does next-generation sequencing of cyst fluid improve management of pancreatic cystic neoplasms?
Pancreatic cystic lesions represent a heterogeneous group of diseases ranging from benign to malignant lesions. They are increasingly being detected due to the widespread use of cross-sectional imaging. Their management is a challenge because it is often not possible to reliably discriminate between malignant and nonmalignant lesions using current imaging technology. Next-generation sequencing (NG
Quantification of l-carvone in toothpastes available on the Swedish market
Background: Toothpastes have widespread use in the population, and contain flavours to give a pleasant and often minty aroma. Flavours are prevalent allergens in toothpastes, and adverse reactions often present as perioral dermatitis or stomatitis. l-Carvone, a mint flavour found in spearmint oil, is one of these allergens. There are few studies on contact allergy to l-carvone, and some of them ha
Field data and simulations to estimate the role of standby energy use of lighting control systems in individual offices
This paper investigates the effectiveness of lighting control systems (LCSs) in 57 individual office rooms of an educational building located in Lund, Sweden. The study uses simulations based on actual occupancy data. The simulations, performed with Daysim via the Honeybee interface, focus on the portion of standby energy use on total lighting energy use considering different combinations of LCSs
Parmelia Ach. s. str. in the southern Baltic region
The distinguishing morphological and chemical characters of nine species of Parmelia Ach. s. str. occurring in the southern Baltic region, namely P. barrenoae Divakar et al., P. ernstiae Feuerer & A. Thell, P. fraudans (Nyl.) Nyl., P. omphalodes (L.) Ach. (including both subspecies P. omphalodes ssp. discordans (Nyl.) Skult and P. omphalodes ssp. omphalodes, P. pinnatifida Kurok., P. saxatilis
Transient HES5 Activity Instructs Mesodermal Cells toward a Cardiac Fate
Notch signaling plays a role in specifying a cardiac fate but the downstream effectors remain unknown. In this study we implicate the Notch downstream effector HES5 in cardiogenesis. We show transient Hes5 expression in early mesoderm of gastrulating embryos and demonstrate, by loss and gain-of-function experiments in mouse embryonic stem cells, that HES5 favors cardiac over primitive erythroid fa
Reprogramming mouse embryonic fibroblasts with transcription factors to induce a hemogenic program
This protocol details the induction of a hemogenic program in mouse embryonic fibroblasts (MEFs) via overexpression of transcription factors (TFs). We first designed a reporter screen using MEFs from human CD34-tTA/TetO-H2BGFP (34/H2BGFP) double transgenic mice. CD34+ cells from these mice label H2B histones with GFP, and cease labeling upon addition of doxycycline (DOX). MEFS were transduced with
Making a Hematopoietic Stem Cell
Previous attempts to either generate or expand hematopoietic stem cells (HSCs) in vitro have involved either ex vivo expansion of pre-existing patient or donor HSCs or de novo generation from pluripotent stem cells (PSCs), comprising both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). iPSCs alleviated ESC ethical issues but attempts to generate functional mature hematopoie
Hematopoietic Reprogramming In Vitro Informs In Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells
Definitive hematopoiesis emerges via an endothelial-to-hematopoietic transition in the embryo and placenta; however, the precursor cells to hemogenic endothelium are not defined phenotypically. We previously demonstrated that the induction of hematopoietic progenitors from fibroblasts progresses through hemogenic precursors that are Prom1+Sca1+CD34+CD45- (PS34CD45-). Guided by these studies, we an
Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm
Tbx3, a member of the T-box family, plays important roles in development, stem cells, nuclear reprogramming, and cancer. Loss of Tbx3 induces differentiation in mouse embryonic stem cells (mESCs). However, we show that mESCs exist in an alternate stable pluripotent state in the absence of Tbx3. In-depth transcriptome analysis of this mESC state reveals Dppa3 as a direct downstream target of Tbx3.
'From blood to blood' : De-differentiation of hematopoietic progenitors to stem cells
Recent studies have reported that fibroblasts or differentiated pluripotent cells can be reprogrammed with transcription factors (TFs) into cells with hematopoietic potential. A study published in Cell now suggests that committed blood precursors may provide a source for blood stem cell transplantation after reprogramming (Riddell et al, 2014). The authors report that a combination of eight TFs re
"There will be blood" from fibroblasts
Reprogramming cell fates : Insights from combinatorial approaches
Epigenetic reprogramming can be achieved in different ways, including nuclear transfer, cell fusion, or the expression of transcription factors (TFs). Combinatorial overexpression provides an opportunity to define the minimal core network of TFs that instructs specific cell fates. This approach has been employed to induce mouse and human pluripotency and differentiated cell types from cells that c
Induction of a hemogenic program in mouse fibroblasts
Definitive hematopoiesis emerges during embryogenesis via an endothelial-to-hematopoietic transition. We attempted to induce this process in mouse fibroblasts by screening a panel of factors for hemogenic activity. We identified a combination of four transcription factors, Gata2, Gfi1b, cFos, and Etv6, that efficiently induces endothelial-like precursor cells, with the subsequent appearance of hem
Regulation of embryonic and induced pluripotency by aurora kinase-p53 signaling
Many signals must be integrated to maintain self-renewal and pluripotency in embryonic stem cells (ESCs) and to enable induced pluripotent stem cell (iPSC) reprogramming. However, the exact molecular regulatory mechanisms remain elusive. To unravel the essential internal and external signals required for sustaining the ESC state, we conducted a short hairpin (sh) RNA screen of 104 ESC-associated p
Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming
The homeodomain transcription factor Nanog plays an important role in embryonic stem cell (ESC) self-renewal and is essential for acquiring ground-state pluripotency during reprogramming. Understanding how Nanog is transcriptionally regulated is important for further dissecting mechanisms of ESC pluripotency and somatic cell reprogramming. Here, we report that Nanog is subjected to a negative auto
Using heterokaryons to understand pluripotency and reprogramming
Reprogramming differentiated cells towards pluripotency can be achieved by different experimental strategies including the forced expression of specific 'inducers' and nuclear transfer. While these offer unparalleled opportunities to generate stem cells and advance disease modelling, the relatively low levels of successful reprogramming achieved (1-2%) makes a direct analysis of the molecular even
Short RNAs Are Transcribed from Repressed Polycomb Target Genes and Interact with Polycomb Repressive Complex-2
Polycomb proteins maintain cell identity by repressing the expression of developmental regulators specific for other cell types. Polycomb repressive complex-2 (PRC2) catalyzes trimethylation of histone H3 lysine-27 (H3K27me3). Although repressed, PRC2 targets are generally associated with the transcriptional initiation marker H3K4me3, but the significance of this remains unclear. Here, we identify
CHD7 targets active gene enhancer elements to modulate ES cell-specific gene expression.
CHD7 is one of nine members of the chromodomain helicase DNA-binding domain family of ATP-dependent chromatin remodeling enzymes found in mammalian cells. De novo mutation of CHD7 is a major cause of CHARGE syndrome, a genetic condition characterized by multiple congenital anomalies. To gain insights to the function of CHD7, we used the technique of chromatin immunoprecipitation followed by massiv
