Semi-Quantitative MALDI Measurements of Blood-Based Samples for Molecular Diagnostics.

Accurate and precise measurement of the relative protein content of blood-based samples using mass spectrometry is challenging due to the large number of circulating proteins and the dynamic range of their abundances. Traditional spectral processing methods often struggle with accurately detecting overlapping peaks that are observed in these samples. In this work, we develop a novel spectral processing algorithm that effectively detects over 1650 peaks with over 3.

Predicting prognosis in COVID-19 patients using machine learning and readily available clinical data.

Rationale: Prognostic tools for aiding in the treatment of hospitalized COVID-19 patients could help improve outcome by identifying patients at higher or lower risk of severe disease. The study objective was to develop models to stratify patients by risk of severe outcomes during COVID-19 hospitalization using readily available information at hospital admission.

Methods: Hierarchical ensemble classification models were trained on a set of 229 patients hospitalized with COVID-19 to predict severe outcomes, including ICU admission, development of acute respiratory distress syndrome, or intubation, using easily attainable attributes including basic patient characteristics, vital signs at admission, and basic lab results collected at time of presentation.

A Genetic Variant in the BCL2 Gene Associates with Adalimumab Response in Hidradenitis Suppurativa Clinical Trials and Regulates Expression of BCL2.

Hidradenitis suppurativa is a chronic skin disease with a significant genetic component and prevalence from 0.5% to 4%. Adalimumab is the only treatment approved by either the European Medicines Agency or the U.

Inhibition of myogenic microRNAs 1, 133, and 206 by inflammatory cytokines links inflammation and muscle degeneration in adult inflammatory myopathies.

Objective: The molecular basis of inflammatory myopathies such as dermatomyositis (DM), polymyositis, and inclusion body myositis, which share the characteristics of chronic muscle inflammation and skeletal muscle wasting, are poorly understood. As such, effective targeted treatments for these diseases are lacking, resulting in critical unmet medical needs for these devastating diseases. The purpose of this study was to identify possible new targets for drug development by exploring the mechanism by which inflammation may play a role in the pathology of the inflammatory myopathies.

MicroRNA-206 induces G1 arrest in melanoma by inhibition of CDK4 and Cyclin D.

Expression profiling of microRNAs in melanoma lesional skin biopsies compared with normal donor skin biopsies, as well as melanoma cell lines compared with normal melanocytes, revealed that hsa-miR-206 was down-regulated in melanoma (-75.4-fold, P = 1.7 × 10(-4)).

Tumor recognition and self-recognition induce distinct transcriptional profiles in antigen-specific CD4 T cells.

Tumors express a wide variety of both mutated and nonmutated Ags. Whether these tumor Ags are broadly recognized as self or foreign by the immune system is currently unclear. Using an autochthonous prostate cancer model in which hemagglutinin (HA) is specifically expressed in the tumor (ProHA x TRAMP mice), as well as an analogous model wherein HA is expressed in normal tissues as a model self-Ag (C3HA(high)), we examined the transcriptional profile of CD4 T cells undergoing Ag-specific division.

Kruppel-like factor 4 is essential for inflammatory monocyte differentiation in vivo.

Several members of the Kruppel-like factor (KLF) family of transcription factors play important roles in differentiation, survival, and trafficking of blood and immune cell types. We demonstrate in this study that hematopoietic cells from KLF4(-/-) fetal livers (FL) contained normal numbers of functional hematopoietic progenitor cells, were radioprotective, and performed as well as KLF4(+/+) cells in competitive repopulation assays. However, hematopoietic "KLF4(-/-) chimeras" generated by transplantation of KLF4(-/-) fetal livers cells into lethally irradiated wild-type mice completely lacked circulating inflammatory (CD115(+)Gr1(+)) monocytes, and had reduced numbers of resident (CD115(+)Gr1(-)) monocytes.

CD34+ hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control.

MicroRNAs (miRNAs) are a recently identified class of epigenetic elements consisting of small noncoding RNAs that bind to the 3' untranslated region of mRNAs and down-regulate their translation to protein. miRNAs play critical roles in many different cellular processes including metabolism, apoptosis, differentiation, and development. We found 33 miRNAs expressed in CD34+ hematopoietic stem-progenitor cells (HSPCs) from normal human bone marrow and mobilized human peripheral blood stem cell harvests.

Ex vivo soluble fas ligand treatment of donor cells to selectively reduce murine acute graft versus host disease.

Background: Allogeneic bone marrow transplantation (BMT) and donor lymphocyte infusion (DLI) provide valuable treatments for a range of diseases. However, the therapeutic utility of BMT and DLI is reduced by the high incidence of graft-versus-host disease (GvHD) mediated by activated donor T lymphocytes directed against recipient alloantigens.

Methods: Using mouse models, we developed and evaluated a strategy to selectively enhance activation-induced cell death (AICD) of anti-recipient T cells within transplant donor cell populations, with the goal of reducing GvHD.

TAGmapper: a web-based tool for mapping SAGE tags.

Serial Analysis of Gene Expression (SAGE) is an important means of obtaining quantitative information about expression of genes in different samples. Short SAGE tags are 10 nucleotides long and often contain enough information to uniquely identify the gene(s) corresponding to the tag. We have observed, however, that the currently available resources are not adequate for accurate mapping of all SAGE tags to genes.

Microarray and serial analysis of gene expression analyses identify known and novel transcripts overexpressed in hematopoietic stem cells.

The human CD34(+)/CD38(-)/Lin(-) cell subset, comprising approximately 1-10% of the CD34(+) cell population, contains few of the less primitive hematopoietic (lineage-committed) progenitor cells (HPCs) but most of the primitive in vivo engrafting (lympho-)hematopoietic stem cells (HSCs). We analyzed gene expression in CD34(+)/CD38(-)/Lin(-) cell populations isolated from normal human adult donor bone marrow, neonatal placental/umbilical cord blood, and mobilized adult donor peripheral blood stem-progenitor cells. As measured by Affymetrix microarrays, 4746 genes were expressed in CD34(+)/CD38(-)/Lin(-) cells from all three tissues.

Kinetics of CCR7 expression differ between primary activation and effector memory states of T(H)1 and T(H)2 cells.

We explored the kinetics of CCR7 expression on T(H)1 and T(H)2 polarized cells as well as on antigen-specific T cell lines at various stages of differentiation. A striking pattern of early (days 7-14) inducible CCR7 expression was seen preferentially on primary T(H)1 cell lines, as compared to T(H)2 cells, and was dependent on the strength and duration of the T cell receptor signal. Upon repeated restimulation (days 21-28) and differentiation, a switch occurred in which T(H)2 cells had high CCR7 expression, whereas T(H)1 cells lost CCR7 expression.

Human CD34+ hematopoietic stem/progenitor cells express high levels of FLIP and are resistant to Fas-mediated apoptosis.

We sought to determine whether lympho-hematopoietic stem-progenitor cells (HSC) from human placental/umbilical cord blood (CB) or adult mobilized blood (PBSC) are sensitive to Fas-induced apoptosis. Human CD34+ cells from CB or PBSC were cultured in serum-free medium, with or without hematopoietic growth factors (FKT: FLT-3 ligand [FL], KIT ligand [KL], and thrombopoietin [TPO]), and with or without soluble Fas ligand (sFasL) or agonistic anti-Fas antibody. After 5-48 hours of culture, cells were assessed for viability and stained with Annexin V and 7-Aminoactinomycin D for apoptosis analysis by fluorescence-activated cell sorting.