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Concurrent stem- and lineage-affiliated chromatin programs precede hematopoietic lineage restriction

The emerging notion of hematopoietic stem and progenitor cells (HSPCs) as a low-primed cloud without sharply demarcated gene expression programs raises the question on how cellular-fate options emerge and at which stem-like stage lineage priming is initiated. Here, we investigate single-cell chromatin accessibility of Lineage-, cKit+, and Sca1+ (LSK) HSPCs spanning the early differentiation landsc

Recommendations for addressing the translational gap between experimental and clinical research on amyloid diseases

This paper is a report of recommendations for addressing translational challenges in amyloid disease research. They were developed during and following an international online workshop organized by the LINXS Institute of Advanced Neutron and X-Ray Science in March 2021. Key suggestions include improving cross-cultural communication between basic science and clinical research, increasing the influe

Quantitative imaging by automated bone scan index (BSI) as a response biomarker in standard clinical care of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide

Background: Enzalutamide (ENZ), an androgen receptor antagonist therapy, was approved for patients (pts) with mCRPC. However, in standard of care for mCRPC pts, change in prostate specific antigen (PSA) is not accepted as an efficacy response measurement and the radiological change is inadequately measured in an interpreter-dependent subjective analysis of bone scan. Therefore, an objective effica

Dietary Fat Intake and Development of Specific Breast Cancer Subtypes.

We prospectively evaluated fat intake as predictor of developing breast cancer (BC) subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2), in a large (n = 337327) heterogeneous cohort of women, with 10062 BC case patients after 11.5 years, estimating BC hazard ratios (HRs) by Cox proportional hazard modeling. High total and satu

A New Look at Drugs Targeting Malignant Melanoma – An Application for Mass Spectrometry Imaging

Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors (PKI) has been highly effective for certain subsets of MM patients. Vemurafenib, a PKI targeting BR

Gene therapy cures the anemia and lethal bone marrow failure in mouse model for RPS19-deficient Diamond-Blackfan anemia.

Diamond-Blackfan anemia is a congenital erythroid hypoplasia caused by functional haploinsufficiency of genes encoding ribosomal proteins. Mutations involving the ribosomal protein S19 gene are detected in 25 % of patients. Enforced expression of ribosomal protein S19 improves the overall proliferative capacity, erythroid colony-forming potential and erythroid differentiation of hematopoietic prog

High prevalence of type 2 diabetes in Iraqi and Swedish residents in a deprived Swedish neighbourhood - a population based study

Background: Immigrants from the Middle-East are at high risk of developing type 2 diabetes (T2D). The aim of the present survey was to measure, in a single deprived neighbourhood, the prevalence rates of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and T2D in residents originating from Iraq and to compare them to those in residents born in Sweden. An additional aim was to ident

Modeling chronic myeloid leukemia in immunodeficient mice reveals expansion of aberrant mast cells and accumulation of pre-B cells.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that, if not treated, will progress into blast crisis (BC) of either myeloid or B lymphoid phenotype. The BCR-ABL1 fusion gene, encoding a constitutively active tyrosine kinase, is thought to be sufficient to cause chronic phase (CP) CML, whereas additional genetic lesions are needed for progression into CML BC. To generate a humanize

Habitat geometry in artificial microstructure affects bacterial and fungal growth, interactions, and substrate degradation

Microhabitat conditions determine the magnitude and speed of microbial processes but have been challenging to investigate. In this study we used microfluidic devices to determine the effect of the spatial distortion of a pore space on fungal and bacterial growth, interactions, and substrate degradation. The devices contained channels differing in bending angles and order. Sharper angles reduced fu

Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer’s Disease

Alzheimer’s disease affects millions of lives worldwide. This terminal disease is characterized by the formation of amyloid aggregates, so-called amyloid oligomers. These oligomers are composed of β-sheet structures, which are believed to be neurotoxic. However, the actual secondary structure that contributes most to neurotoxicity remains unknown. This lack of knowledge is due to the challenging n

Absence of Epstein-Barr and Cytomegalovirus Infection in Neuroblastoma Cells by Standard Detection Methodologies.

Indications exist in the scientific literature that infection with human herpes family viruses may contribute to the pathogenesis of neuroblastoma (NB). However, systematic investigations regarding viral presence in NB cells have been scarcely reported. Here, the presence of DNA from Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) was assessed by PCR in 12 NBs, supplemented with RNA in s

Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

Background:Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC

Glucocorticoid-resistant B cell acute lymphoblastic leukemia displays receptor tyrosine kinase activation

The response of childhood acute lymphoblastic leukemia (ALL) to dexamethasone predicts the long-term remission outcome. To explore the mechanisms of dexamethasone resistance in B cell ALL (B-ALL), we generated dexamethasone-resistant clones by prolonged treatment with dexamethasone. Using RNA-sequencing and high-throughput screening, we found that dexamethasone-resistant cells are dependent on rec

The retinoblastoma gene undergoes rearrangements in BRCA1-deficient basal-like breast cancer.

Breast tumors from BRCA1 germ line mutation carriers typically exhibit features of the basal-like molecular subtype. However, the specific genes recurrently mutated as a consequence of BRCA1 dysfunction have not been fully elucidated. In this study, we utilized gene expression profiling to molecularly subtype 577 breast tumors, including 72 breast tumors from BRCA1/2 mutation carriers. Focusing on

On the effectiveness of aerosol extinguishing agents for battery vent gases and hydrogen

It is well known that Lithium-ion batteries in thermal runaway can emit gases with high hydrogen concentrations which, in case of delayed ignition, can cause a gas explosion. Aerosol suppression agents are sometimes used to suppress fires and/or prevent ignition of released gases in such situations. The agent has been studied for suppression of fires (diffusion flames), but less is known about the

Concomitant use of warfarin and ticagrelor as an alternative to triple antithrombotic therapy after an acute coronary syndrome.

Treatment with warfarin in combination with clopidogrel has been shown to reduce the incidence of major bleeding as compared to triple antithrombotic therapy (TT; warfarin, clopidogrel and aspirin). However, there are uncertainties regarding the risk for thrombosis since poor-responsiveness to clopidogrel is common. Ticagrelor is a more potent platelet inhibitor, but data supporting concurrent use

Ockuperad film - Kurosawas filmproduktion under de amerikanska ockupationsåren, 1945-52

Syftet med denna uppsats är att undersöka hur den amerikanska ockupationen påverkade den japanska filmen i allmänhet, och Akira Kurosawas (1910-1998) produktion under denna tidsperiod i synnerhet. För att uppnå detta skisserar jag en översiktlig och lättillgänglig bild av den japanska filmhistorien, från dess tidigaste skede fram till 1952, vilken jag hoppas kan fungera som en historisk fond. Vad