Apo structure of Mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase DXPS: Dynamics and implications for inhibitor design.

The enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXPS) catalyses the first step of the MEP pathway, a key process for isoprenoid biosynthesis in bacteria that is absent in humans, making it a promising drug target. We present the structure of Mycobacterium tuberculosis DXPS in its apo form, obtained through a soaking method that removes thiamine diphosphate (ThDP) and metals from pre-formed crystals. The apo structure had three regions with absence of electron density near the active site that are unique to the apo form of the enzyme.

C-H Bond Activation by Sulfated Zirconium Oxide is Mediated by a Sulfur-Centered Lewis Superacid.

Sulfated zirconium oxide (SZO) catalyzes the hydrogenolysis of isotactic polypropylene (iPP, M=13.3 kDa, Đ=2.4, =94 %) or high-density polyethylene (HDPE, M=2.

Detection of human brain cancers using genomic and immune cell characterization of cerebrospinal fluid through CSF-BAM.

Unlabelled: Patients who have radiographically detectable lesions in their brain or other symptoms compatible with brain tumors pose challenges for diagnosis. The only definitive way to diagnose such patients is through brain biopsy, an obviously invasive and dangerous procedure. Here we present a new workflow termed "CSF-BAM" that simultaneously identifies cell or T cell receptor rearrangements, neuploidy, and using PCR-mediated amplification of both strands of the DNA from CSF samples.

The Management of Symptomatic Moyamoya Disease in Pediatric Patients: A Systematic Review and Meta-Analysis.

Background And Objectives: The optimal management strategy for pediatric patients with symptomatic moyamoya disease (MMD) is not well established. This systematic review and meta-analysis compares surgical vs conservative management and direct/combined bypass (DB/CB) vs indirect bypass (IB) for pediatric patients with symptomatic MMD.

Methods: MEDLINE and PubMed were searched from inception to March 17, 2024.

Molecular Tumor Board of the University Medical Center Groningen (UMCG-MTB): outcome of patients with rare or complex mutational profiles receiving MTB-advised targeted therapy.

Purpose: Molecular tumor boards (MTBs) are considered beneficial for treatment decision making for patients with cancer with uncommon, rare, or complex mutational profiles. The lack of international MTB guidelines results in significant variation in practices and recommendations. Therefore, periodic follow-up is necessary to assess and govern MTB functioning.

The prediction of treatment outcome in NSCLC patients harboring an EGFR exon 20 mutation using molecular modeling.

Introduction: The structural effect of uncommon heterogenous in-frame deletion and/or insertion mutations within exon 20 (EGFRex20+) in relation to therapy response is poorly understood. This study aims to elucidate the structural alterations caused by EGFRex20+ mutations and correlate these changes with patient responses.

Material And Method: We selected EGFRex20+ mutations from advanced NSCLC patients in the Position20 and AFACET studies for computational analysis.

MEDI1814 selectively reduces free Aβ42 in cerebrospinal fluid of non-clinical species and Alzheimer's disease patients.

Introduction: Small molecules and antibodies are being developed to lower amyloid beta (Aβ) peptides.

Methods: We describe MEDI1814, a fully human high-affinity monoclonal antibody selective for Aβ, the pathogenic self-aggregating species of Aβ.

Results: MEDI1814 reduces free Aβ without impacting Aβ in the cerebrospinal fluid of rats and cynomolgus monkeys after systemic administration.

Effects of Gender and Country of Training on Perceived Access to Opportunities for Neurosurgical Research and Gender-Concordant Mentorship.

Background: The current neurosurgical workforce is not large enough to address the significant burden of neurosurgical disease worldwide, and women are under-represented in this surgical specialty. However, trainee opportunities are particularly scarce in lower- and middle-income countries, where the burden of neurosurgical disease is high. Thus, the primary aim of this study was to assess the effects of gender and country on perceived access to neurosurgical research and mentorship opportunities.

Tuning Reinforcement Learning Parameters for Cluster Selection to Enhance Evolutionary Algorithms.

The ability to find optimal molecular structures with desired properties is a popular challenge, with applications in areas such as drug discovery. Genetic algorithms are a common approach to global minima molecular searches due to their ability to search large regions of the energy landscape and decrease computational time via parallelization. In order to decrease the amount of unstable intermediate structures being produced and increase the overall efficiency of an evolutionary algorithm, clustering was introduced in multiple instances.

First-principles investigation of oxidized Si- and Ge-terminated diamond (100) surfaces.

Diamond is a semiconductor material with remarkable structural, thermal, and electronic properties that has garnered significant interest in the field of electronics. Although hydrogen (H) and oxygen (O) terminations are conventionally favored in transistor designs, alternative options, such as silicon (Si) and germanium (Ge), are being explored because of their resilience to harsh processing conditions during fabrication. Density-functional theory was used to examine the non-oxidized and oxidized group-IV (Si and Ge)-terminated diamond (100) surfaces.

Cryo-EM structure of 1-deoxy-D-xylulose 5-phosphate synthase DXPS from Plasmodium falciparum reveals a distinct N-terminal domain.

Plasmodium falciparum is the main causative agent of malaria, a deadly disease that mainly affects children under five years old. Artemisinin-based combination therapies have been pivotal in controlling the disease, but resistance has arisen in various regions, increasing the risk of treatment failure. The non-mevalonate pathway is essential for the isoprenoid synthesis in Plasmodium and provides several under-explored targets to be used in the discovery of new antimalarials.

Overcoming Treatment Resistance in Medulloblastoma: Underlying Mechanisms and Potential Strategies.

Medulloblastoma is the most frequently encountered malignant brain tumor in the pediatric population. The standard of care currently consists of surgical resection, craniospinal irradiation, and multi-agent chemotherapy. However, despite this combination of multiple aggressive modalities, recurrence of the disease remains a substantial concern, and treatment resistance is a rising issue.

Carcinogenic formaldehyde in U.S. residential buildings: Mass inventories, human health impacts, and associated healthcare costs.

Formaldehyde, a human carcinogen, is formulated into building materials in the U.S. and worldwide.

Evaluation of cervical spine clearance scores in children younger than 3 years with blunt trauma.

Objective: The PEDSPINE I and PEDSPINE II scores were developed to determine when patients require advanced imaging to rule out cervical spine injury (CSI) in children younger than 3 years of age with blunt trauma. This study aimed to evaluate these scores in an institutional cohort.

Methods: The authors identified patients younger than 3 years with blunt trauma who received cervical spine MRI from their institution's prospective database from 2012 to 2015.

Perceived Barriers to Pursuing a Career in Neurosurgery in Nigeria: A Cross-Sectional Survey of Nigerian Medical Students and Unspecialized Physicians.

Background: Nigeria has an inadequate number of neurosurgeons to meet the population's demand for neurosurgical care. Furthermore, few Nigerian neurosurgeons are female. This study sought to evaluate perceived barriers to pursuing neurosurgery among Nigerian trainees.

Small-Molecule Allosteric Inhibitors of Human Aspartate Transcarbamoylase Suppress Proliferation of Bone Osteosarcoma Epithelial Cells.

Aspartate transcarbamoylase (ATC) is the first committed step in de novo pyrimidine biosynthesis in eukaryotes and plants. A potent transition state analog of human ATCase (PALA) has previously been assessed in clinical trials for the treatment of cancer, but was ultimately unsuccessful. Additionally, inhibition of this pathway has been proposed to be a target to suppress cell proliferation in E.

Otolaryngology Applicant Perspectives on In-person and Virtual Residency Interviews.

Objective: The objective of this study was to understand applicant perspectives on in-person and virtual otolaryngology residency interviews.

Study Design: Survey study.

Setting: Otolaryngology residency applicants who were interviewed during 2022-2023.

Socioeconomic characteristics and postoperative outcomes of patients undergoing prenatal vs. postnatal repair of myelomeningoceles.

Purpose: To investigate differences in sociodemographic characteristics and short-term outcomes between patients undergoing prenatal versus postnatal myelomeningocele repair.

Methods: Patients who underwent myelomeningocele repair at our institution were stratified based on prenatal or postnatal timing of repair. Baseline characteristics and outcomes were compared.

Engineering a Plant Polyketide Synthase for the Biosynthesis of Methylated Flavonoids.

Homoeriodictyol and hesperetin are naturally occurring O-methylated flavonoids with many health-promoting properties. They are produced in plants in low abundance and as complex mixtures of similar compounds that are difficult to separate. Synthetic biology offers the opportunity to produce various flavonoids in a targeted, bottom-up approach in engineered microbes with high product titers.

Thiosulfate sulfurtransferase deficiency promotes oxidative distress and aberrant NRF2 function in the brain.

Thiosulfate sulfurtransferase (TST, EC 2.8.1.