Gene Expression and Alternative Splicing Analysis in a Large-Scale Multiple Sclerosis Study.

Multiple Sclerosis (MS) is an autoimmune neurodegenerative disease affecting approximately 3 million people globally. Despite rigorous research on MS, aspects of its development and progression remain unclear. We utilized a publicly available RNA-seq dataset (GSE138614) consisting of the post-mortem white matter tissues of five donors without any neurological disorders and ten MS patient donors.

Gene expression and alternative splicing analysis in a large-scale Multiple Sclerosis study.

Background: Multiple Sclerosis (MS) is an autoimmune neurodegenerative disease affecting approximately 3 million people globally. Despite rigorous research on MS, aspects of its development and progression remain unclear. Understanding molecular mechanisms underlying MS is crucial to providing insights into disease pathways, identifying potential biomarkers for early diagnosis, and revealing novel therapeutic targets for improved patient outcomes.

Catalysis of an S2 pathway by geometric preorganization.

Bimolecular nucleophilic substitution (S2) mechanisms occupy a central place in the historical development and teaching of the field of organic chemistry. Despite the importance of S2 pathways in synthesis, catalytic control of ionic S2 pathways is rare and notably uncommon even in biocatalysis, reflecting the fact that any electrostatic interaction between a catalyst and the reacting ion pair necessarily stabilizes its charge and, by extension, reduces polar reactivity. Nucleophilic halogenase enzymes navigate this tradeoff by desolvating and positioning the halide nucleophile precisely on the S2 trajectory, using geometric preorganization to compensate for the attenuation of nucleophilicity.

Malignant melanotic nerve sheath tumor with PRKAR1A, KMT2C, and GNAQ mutations.

Malignant melanotic nerve sheath tumor (MMNST) is a rare and potentially aggressive lesion defined in the 2021 WHO Classification of Tumors of the Central Nervous System. MMNST demonstrate overlapping histologic and clinical features of schwannoma and melanoma. MMNST often harbor mutations, especially within the Carney Complex.

Catastrophic antiphospholipid syndrome accompanied by complement regulatory gene mutation.

Background: Antiphospholipid syndrome (APS), particularly the catastrophic antiphospholipid syndrome (CAPS), is one of the rare causes of thrombotic microangiopathy (TMA). CAPS is the most severe form of APS, especially when accompanied by complement dysregulation, causes progressive microvascular thrombosis and failure in multiple organs. In this report, a case of CAPS with TMA accompanied by a genetic defect in the complement system is presented.

Phenotypic and genotypic characteristics of children with Bartter syndrome.

Introduction: Bartter syndrome (BS) is a group of autosomal-recessive tubular disorders and it is classified into five genetic subtypes. BS can also be classified by phenotype (antenatal, classic). Patients with mutations in the same gene can present different phenotypes.

Novel Organoselenium Redox Modulators with Potential Anticancer, Antimicrobial, and Antioxidant Activities.

Novel organic selenides were developed in good yields (up to 91%), and their chemical entities were confirmed by IR, MS, and H- and C-NMR spectroscopy. Their anticancer and antimicrobial properties were estimated against different human cancer (MCF-7 and HepG2) and healthy (WI-38) cell lines, as well as several microbial strains (, , and ). Furthermore, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) bioassays were used for the estimation of the antioxidant activities.

Molecular Aspects of Distal Kidney Tubular Acidosis in Children, Its Long-Term Outcome, and Relationship with Hyperammonemia.

Objective: We aimed to present the characteristics, genetic analysis results, long-term progno- sis of our patients with distal kidney tubular acidosis, and the relationship between hyperam- monemia and distal kidney tubular acidosis.

Materials And Methods: Biochemical, clinical, and imaging findings were collected at presen- tation and the last clinic visit, and results of the genetic analysis were recorded.

Results: Our study included 9 patients (3 female, 33%).

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes.

Astroblastomas (ABs) are rare brain tumors of unknown origin. We performed an integrative genetic and epigenetic analysis of AB-like tumors. Here, we show that tumors traceable to neural stem/progenitor cells (radial glia) that emerge during early to later brain development occur in children and young adults, respectively.

Rapid Reductions in Breast Density following Tamoxifen Therapy as Evaluated by Whole-Breast Ultrasound Tomography.

Purpose: Women whose mammographic breast density declines within 12-18 months of initiating tamoxifen for chemoprevention or adjuvant treatment show improved therapeutic responses compared with those whose density is unchanged. We tested whether measuring changes in sound speed (a surrogate of breast density) using ultrasound tomography (UST) could enable rapid identification of favorable responses to tamoxifen.

Methods: We evaluated serial density measures at baseline and at 1 to 3, 4 to 6, and 12+ months among 74 women (aged 30-70 years) following initiation of tamoxifen for clinical indications, including an elevated risk of breast cancer (20%) and diagnoses of in situ (39%) or invasive (40%) breast carcinoma, enrolled at Karmanos Cancer Institute and Henry Ford Health System (Detroit, MI, USA).

The Potential Role of the Fat-Glandular Interface (FGI) in Breast Carcinogenesis: Results from an Ultrasound Tomography (UST) Study.

This study explored the relationship between the extent of the fat-glandular interface (FGI) and the presence of malignant vs. benign lesions. Two hundred and eight patients were scanned with ultrasound tomography (UST) as part of a Health Insurance Portability and Accountability Act (HIPAA)-compliant study.

Multicenter Study of Whole Breast Stiffness Imaging by Ultrasound Tomography (SoftVue) for Characterization of Breast Tissues and Masses.

We evaluated whole breast stiffness imaging by SoftVue ultrasound tomography (UST), extracted from the bulk modulus, to volumetrically map differences in breast tissues and masses. A total 206 women with either palpable or mammographically/sonographically visible masses underwent UST scanning prior to biopsy as part of a prospective, HIPAA-compliant multicenter cohort study. The volumetric data sets comprised 298 masses (78 cancers, 105 fibroadenomas, 91 cysts and 24 other benign) in 239 breasts.

Aurora-A kinase is differentially expressed in the nucleus and cytoplasm in normal Müllerian epithelium and benign, borderline and malignant serous ovarian neoplasms.

Background: Aurora-A kinase is important for cellular proliferation and is implicated in the tumorigenesis of several malignancies, including of the ovary. Information regarding the expression patterns of Aurora-A in normal Müllerian epithelium as well as benign, borderline and malignant epithelial ovarian neoplasms is limited.

Methods: We investigated Aurora-A expression by immunohistochemistry in 15 benign, 19 borderline and 17 malignant ovarian serous tumors, and 16 benign, 8 borderline, and 2 malignant ovarian mucinous tumors.

Kinetic Analysis of a Cysteine-Derived Thiyl-Catalyzed Asymmetric Vinylcyclopropane Cycloaddition Reflects Numerous Attractive Noncovalent Interactions.

Kinetic studies of a vinylcyclopropane (VCP) cycloaddition, catalyzed by peptide-based thiyl radicals, are described. Reactions were analyzed by using reaction progress kinetic analysis, revealing that ring-opening of the VCP is both rate- and enantio-determining. These conclusions are further corroborated by studies involving racemic and enantiopure VCP starting material.

Tunable and Cooperative Catalysis for Enantioselective Pictet-Spengler Reaction with Varied Nitrogen-Containing Heterocyclic Carboxaldehydes.

Herein we report an organocatalytic enantioselective functionalization of heterocyclic carboxaldehydes via the Pictet-Spengler reaction. Through careful pairing of novel squaramide and Brønsted acid catalysts, our method tolerates a breadth of heterocycles, enabling preparation of a series of heterocycle conjugated β-(tetrahydro)carbolines in good yield and enantioselectivity. Careful selection of carboxylic acid co-catalyst is essential for toleration of a variety of regioisomeric heterocycles.

The Fat-glandular Interface and Breast Tumor Locations: Appearances on Ultrasound Tomography Are Supported by Quantitative Peritumoral Analyses.

Objective: To analyze the preferred tissue locations of common breast masses in relation to anatomic quadrants and the fat-glandular interface (FGI) using ultrasound tomography (UST).

Methods: Ultrasound tomography scanning was performed in 206 consecutive women with 298 mammographically and/or sonographically visible, benign and malignant breast masses following written informed consent to participate in an 8-site multicenter, Institutional Review Board-approved cohort study. Mass locations were categorized by their anatomic breast quadrant and the FGI, which was defined by UST as the high-contrast circumferential junction of fat and fibroglandular tissue on coronal sound speed imaging.

Biotic and Abiotic Elicitors of Stilbenes Production in L. Cell Culture.

The in vitro cell cultures derived from the grapevine ( L.) have been used for the production of stilbenes treated with different biotic and abiotic elicitors. The red-grape cultivar Váh has been elicited by natural cellulose from , the cell wall homogenate from and synthetic jasmonates.

A Novel Marker, Based on Ultrasound Tomography, for Monitoring Early Response to Neoadjuvant Chemotherapy.

Objective: To evaluate the combination of tumor volume and sound speed as a potential imaging marker for assessing neoadjuvant chemotherapy (NAC) response.

Methods: This study was carried out under an IRB-approved protocol (written consent required). Fourteen patients undergoing NAC for invasive breast cancer were examined with ultrasound tomography (UST) throughout their treatment.