Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.

Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here, we compare combined CRISPR-Cas9 editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. Dual targeting of the BCL11A +58 and +55 enhancers with 3xNLS-SpCas9 and two single guide RNAs (sgRNAs) resulted in superior HbF induction, including in sickle cell disease (SCD) patient xenografts, attributable to simultaneous disruption of core half E-box/GATA motifs at both enhancers.

BCL11A +58/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody-drug conjugate.

Editing the +58 region of the BCL11A erythroid enhancer has shown promise in treating β-globin disorders. To address variations in fetal hemoglobin (HbF) response, we investigated editing both +58 and +55 enhancers. Rhesus macaques transplanted with edited hematopoietic stem/progenitor cells (HSPCs) following busulfan conditioning exhibited durable, high-level (∼90%) editing frequencies post transplantation with sustained HbF reactivation over 4 years, without hematological perturbations.

Scalable assessment of genome editing off-targets associated with genetic variants.

Genome editing with RNA-guided DNA binding factors carries risk of off-target editing at homologous sequences. Genetic variants may introduce sequence changes that increase homology to a genome editing target, thereby increasing risk of off-target editing. Conventional methods to verify candidate off-targets rely on access to cells with genomic DNA carrying these sequences.

Metabolomic Profiling of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy for Predicting Disease-Free and Overall Survival.

Breast cancer (BC) remains a significant global health concern, with neoadjuvant chemotherapy (NACT) offering preoperative benefits like tumor downstaging and treatment response assessment. However, identifying factors influencing post-NACT treatment response and survival outcomes is challenging. Metabolomic approaches offer promising insights into understanding these outcomes.

Environmental impact assessment due to the intake of uranium contained in surface waters in a semi-arid region in Brazil.

In Santa Quitéria City, part of the population uses surface water for potation. These waters do not undergo any treatment before consumption. As the region has a deposit of uranium, assessing water quality becomes important.

Internal dose rate due to intake of uranium and thorium by fish from a dam reservoir associated with a uranium mine in Brazil.

Uranium mining can cause environmental impacts on non-human biota around mine sites. Because of this, the reduction in non-human biota exposure becomes an important issue. Environmental radioprotection results from the evolution of human radioprotection; it is based on dose rate to non-human biota and uses, as a biological target, and has harmful effects on populations.

An evaluation of relational and NoSQL distributed databases on a low-power cluster.

The constant growth of social media, unconventional web technologies, mobile applications, and Internet of Things (IoT) devices create challenges for cloud data systems in order to support huge datasets and very high request rates. NoSQL databases, such as Cassandra and HBase, and relational SQL databases with replication, such as Citus/PostgreSQL, have been used to increase horizontal scalability and high availability of data store systems. In this paper, we evaluated three distributed databases on a low-power low-cost cluster of commodity Single-Board Computers (SBC): relational Citus/PostgreSQL and NoSQL databases Cassandra and HBase.

Zinc-dithiocarbimates for the control of Hemileia vastatrix: a versatile alternative.

Background: The purpose of this work was to investigate the potential use of zinc-dithiocarbimate salts to control Hemileia vastatrix, the causal agent of the coffee leaf rust disease, and to evaluate their toxicity towards Apis mellifera, one of the most important coffee plant pollinators.

Results: Zinc-dithiocarbimate salts were prepared and fully characterized by infrared, proton ( H) and carbon-13 ( C) nuclear magnetic resonance and elemental analyses of carbon (C), hydrogen (H), nitrogen (N) and zinc (Zn). X-ray diffraction technique studies confirmed the proposed structures.

Antioxidant Activities of (Mart.) J. B. Gillett) (Burseraceae) Leaf Extracts Using and Assays.

is widely used in folk medicine without any scientific basis. Considering this, the aim of this study was to evaluate the chemical profile and the antioxidant activity of leaf extracts using and assays. Six extracts were obtained from fresh leaves using a serial extraction (nonpolar to polar solvents).

Leaf Extract as a Potential Antioxidant Molecule Using In Vitro and In Vivo Assays.

The genus is widely used in traditional folk medicine, but few scientific data exist for this genus. The goal of this study was to characterise the chemical composition and antioxidant activities of leaf extracts using and assays. Six extracts were obtained: hexane (HE), chloroform (CE), ethanol (EE), methanol (ME), water end extract (WEE), and water extract (WE).

Draft Genome Sequence of Vancomycin-Resistant Enterococcus faecium UEL170 (Sequence Type 412), Isolated from a Patient with Urinary Tract Infection in a Tertiary Hospital in Southern Brazil.

Enterococcus faecium is a leading cause of health care-associated infections, with specific lineages circulating in hospital settings worldwide. Here, we report the draft genome sequence of the multidrug-resistant and biofilm-producing E. faecium UEL170, sequence type 412 (ST412), isolated from an inpatient with a urinary tract infection.

Schistosoma mansoni Egg, Adult Male and Female Comparative Gene Expression Analysis and Identification of Novel Genes by RNA-Seq.

Background: Schistosomiasis is one of the most prevalent parasitic diseases worldwide and is a public health problem. Schistosoma mansoni is the most widespread species responsible for schistosomiasis in the Americas, Middle East and Africa. Adult female worms (mated to males) release eggs in the hepatic portal vasculature and are the principal cause of morbidity.

High hydrostatic pressure activates transcription factors involved in Saccharomyces cerevisiae stress tolerance.

A number of transcriptional control elements are activated when Saccharomyces cerevisiae cells are submitted to various stress conditions, including high hydrostatic pressure (HHP). Exposure of Saccharomyces cerevisiae cells to HHP results in global transcriptional reprogramming, similar to that observed under other industrial stresses, such as temperature, ethanol and oxidative stresses. Moreover, treatment with a mild hydrostatic pressure renders yeast cells multistress tolerant.

High hydrostatic pressure activates gene expression that leads to ethanol production enhancement in a Saccharomyces cerevisiae distillery strain.

High hydrostatic pressure (HHP) is a stress that exerts broad effects on microorganisms with characteristics similar to those of common environmental stresses. In this study, we aimed to identify genetic mechanisms that can enhance alcoholic fermentation of wild Saccharomyces cerevisiae isolated from Brazilian spirit fermentation vats. Accordingly, we performed a time course microarray analysis on a S.