Crystal structures of human immune protein FIBCD1 suggest an extended binding site compatible with recognition of pathogen-associated carbohydrate motifs.

Fibrinogen C domain-containing protein 1 (FIBCD1) is an immune protein proposed to be involved in host recognition of chitin on the surface of pathogens. As FIBCD1 readily binds acetylated molecules, we have determined the high-resolution crystal structures of a recombinant fragment of the FIBCD1 C-terminal domain complexed with small N-acetyl-containing ligands to determine the mode of recognition. All ligands bind at the conserved N-acetyl-binding site (S1) with galactose and glucose-derived ligands rotated 180° relative to each other.

Association of clinically-measured and dynamic ankle dorsiflexion assessed by markerless motion capture during the drop-jump task on landing biomechanics and risk of ankle injury in military personnel undergoing 10 weeks of physical training.

Objectives: Determine the influence of clinically-measured maximum dorsiflexion, dynamic peak dorsiflexion and percent of clinically-measured maximum dorsiflexion used during a drop-jump task on landing biomechanics and risk of ankle injury in military personnel.

Design: Prospective cohort study.

Methods: 672 participants (122 women) enrolled.

Fate Specification of GFAP-Negative Primitive Neural Stem Cells and Their Progeny at Clonal Resolution.

The mature brain contains an incredible number and diversity of cells that are produced and maintained by heterogeneous pools of neural stem cells (NSCs). Two distinct types of NSCs exist in the developing and adult mouse brain: Glial Fibrillary Acidic Protein (GFAP)-negative primitive (p)NSCs and downstream GFAP-positive definitive (d)NSCs. To better understand the embryonic functions of NSCs, we performed clonal lineage tracing within neurospheres grown from either pNSCs or dNSCs to enrich for their most immediate downstream neural progenitor cells (NPCs).

Sex differences in musculoskeletal injury epidemiology and subsequent loss of tactical readiness during Marine Corps Officer Candidates School.

Introduction: The US Marine Corps (USMC) Officer Candidates School (OCS) is a 10-week training course for Marine Officer Candidates (MOCs). OCS training is rigorous and demanding, which results in a high risk of musculoskeletal injuries (MSIs). The objective of this analysis was to describe MSIs among women and men during the USMC OCS at Quantico, Virginia, from September 2020 to November 2021.

Characterization of an RNA binding protein interactome reveals a context-specific post-transcriptional landscape of MYC-amplified medulloblastoma.

Pediatric medulloblastoma (MB) is the most common solid malignant brain neoplasm, with Group 3 (G3) MB representing the most aggressive subgroup. MYC amplification is an independent poor prognostic factor in G3 MB, however, therapeutic targeting of the MYC pathway remains limited and alternative therapies for G3 MB are urgently needed. Here we show that the RNA-binding protein, Musashi-1 (MSI1) is an essential mediator of G3 MB in both MYC-overexpressing mouse models and patient-derived xenografts.

Cancer-selective metabolic vulnerabilities in MYC-amplified medulloblastoma.

MYC-driven medulloblastoma (MB) is an aggressive pediatric brain tumor characterized by therapy resistance and disease recurrence. Here, we integrated data from unbiased genetic screening and metabolomic profiling to identify multiple cancer-selective metabolic vulnerabilities in MYC-driven MB tumor cells, which are amenable to therapeutic targeting. Among these targets, dihydroorotate dehydrogenase (DHODH), an enzyme that catalyzes de novo pyrimidine biosynthesis, emerged as a favorable candidate for therapeutic targeting.

Tyrosine kinase inhibitors and tumor lysis syndrome in hematologic malignancies: A systemic review.

Background: Effective treatments for hematologic malignancies include therapies that target tyrosine kinase (TK) signaling pathways. Tumor lysis syndrome (TLS) is an oncologic emergency that can occur due to rapid turnover following the initiation of treatments for hematologic malignancy. The incidence of TLS is under-reported and it is unclear as to whether TK inhibitors (TKIs) are associated with TLS.

The Road to CAR T-Cell Therapies for Pediatric CNS Tumors: Obstacles and New Avenues.

Pediatric central nervous system (CNS) tumors are the most common solid tumors diagnosed in children and are the leading cause of pediatric cancer-related death. Those who do survive are faced with the long-term adverse effects of the current standard of care treatments of chemotherapy, radiation, and surgery. There is a pressing need for novel therapeutic strategies to treat pediatric CNS tumors more effectively while reducing toxicity - one of these novel modalities is chimeric antigen receptor (CAR) T-cell therapy.

Childhood Medulloblastoma: An Overview.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor, representing 60% of childhood intracranial embryonal tumors. Despite multimodal advances in therapies over the last 20 years that have yielded a 5-year survival rate of 75%, high-risk patients (younger than 3 years, subtotal resection, metastatic lesions at diagnosis) still experience a 5-year overall survival of less than 70%. In this introductory chapter on pediatric MB, we describe the initial discrimination of MB based on histopathological examination and the more recent progress made in global gene expression profiling methods that have allowed scientists to more accurately subclassify and prognosticate on MB based on molecular characteristics.

Atomic-resolution crystal structures of the immune protein conglutinin from cow reveal specific interactions of its binding site with -acetylglucosamine.

Bovine conglutinin is an immune protein that is involved in host resistance to microbes and parasites and interacts with complement component iC3b, agglutinates erythrocytes, and neutralizes influenza A virus. Here, we determined the high-resolution (0.97-1.

Herring gulls respond to human gaze direction.

Human-wildlife conflict is one of the greatest threats to species populations worldwide. One species facing national declines in the UK is the herring gull (Larus argentatus), despite an increase in numbers in urban areas. Gulls in urban areas are often considered a nuisance owing to behaviours such as food-snatching.

Modeling Urban Hydrology and Green Infrastructure Using the AGWA Urban Tool and the KINEROS2 Model.

Urban hydrology and green infrastructure (GI) can be modeled using the Automated Geospatial Watershed Assessment (AGWA) Urban tool and the Kinematic Runoff and Erosion (KINEROS2) model. The KINEROS2 model provides an urban modeling element with nine overland flow components that can be used to represent various land cover types commonly found in the built environment while treating runoff-runon and infiltration processes in a physically based manner. The AGWA Urban tool utilizes a Geographic Information System (GIS) framework to prepare parameters required for KINEROS2, executes the model, and imports results for visualization in the GIS.

Hope, optimism and survival in a randomised trial of chemotherapy for metastatic colorectal cancer.

Purpose: Psychological responses to cancer are widely believed to affect survival. We investigated associations between hope, optimism, anxiety, depression, health utility and survival in patients starting first-line chemotherapy for metastatic colorectal cancer.

Methods: Four hundred twenty-nine subjects with metastatic colorectal cancer in a randomised controlled trial of chemotherapy completed baseline questionnaires assessing the following: hopefulness, optimism, anxiety and depression and health utility.

Crystal structure of the tetrameric fibrinogen-like recognition domain of fibrinogen C domain containing 1 (FIBCD1) protein.

The high resolution crystal structures of a recombinant fragment of the C-terminal fibrinogen-like recognition domain of FIBCD1, a vertebrate receptor that binds chitin, have been determined. The overall tetrameric structure shows similarity in structure and aggregation to the horseshoe crab innate immune protein tachylectin 5A. The high affinity ligand N-acetylmannosamine (ManNAc) binds in the S1 site, predominantly via the acetyl group with the oxygen and acetamide nitrogen hydrogen-bonded to the protein and the methyl group inserted into a hydrophobic pocket.

Randomized phase 2 sequencing and pharmacokinetic study of gemcitabine and oxaliplatin in advanced non-small cell lung cancer.

Aim: This multicentre phase II trial examined the combination of gemcitabine and oxaliplatin in patients with advanced non-small cell lung cancer (NSCLC). The effect of sequence administration was randomized and pharmacokinetics (PK) assessed.

Methods: Eligible patients had stage IIIB or IV or recurrent NSCLC, no prior chemotherapy, World Health Organization performance status ≤2 and measurable disease.

Genotype and environment effects on nitrate accumulation in a diversity set of lettuce accessions at commercial maturity: the influence of nitrate uptake and assimilation, osmotic interactions and shoot weight and development.

Background: The causes of the natural variation in nitrate accumulation and associated traits are studied using a diverse population of 48 mature lettuce accessions grown hydroponically in winter and summer seasons. Information on the effects of genotype, environment and their interactions will inform future selection strategies for the production of low-nitrate varieties more suited to meeting EU requirements for harvested produce.

Results: The effects of genotype (G), environment (E) and G × E interactions were all significant, with nitrate concentrations lower but covering a wider range in summer.

A multicenter, randomized, open-label study to assess the steady-state pharmacokinetics of bevacizumab given with either XELOX or FOLFOX-4 in patients with metastatic colorectal cancer.

Purpose: To compare the pharmacokinetics (PK) of bevacizumab (BV) at steady-state under two different dosing regimens, 7.5 mg/kg q3w and 5.0 mg/kg q2w, concomitantly with a combination of capecitabine and oxaliplatin (XELOX) and FOLFOX-4 (oxaliplatin in combination with infusional 5-FU/LV), respectively, in patients with metastatic colorectal cancer (mCRC).

Screening for genotype and environment effects on nitrate accumulation in 24 species of young lettuce.

Background: Nitrate accumulates in plants in response to N supply, aerial environment (predominantly light), and genotype. This paper characterises the effects of genotype, environment, and their interactions on nitrate accumulation by 24 cultivated and wild lettuce accessions grown hydroponically in winter and summer. The results will inform future strategies for selecting for low-nitrate varieties.

Easing the transition: preparing nursing students for practice.

NHS Fife and the University of Dundee School of Nursing and Midwifery jointly offer final-year adult nursing students the opportunity to undertake an employment induction programme and apply for the nurse bank before they register with the Nursing and Midwifery Council. If successful, they are guaranteed places on a four-week paid induction programme on the nurse bank as soon as their registrations take effect. Early evaluation suggests that this opportunity helps participants to become more confident about making the transition from student to qualified practitioner.

Structural characterisation of ligand-binding determinants in human lung surfactant protein D: influence of Asp325.

The crystal structures of a biologically and therapeutically active recombinant homotrimeric fragment of human lung surfactant protein D with a series of bound ligands have been determined. While the structures reveal various different binding modes, all utilise a similarly positioned pair of mannose-type O3' and O4' hydroxyls with no direct interaction between any non-terminal sugar and protein. The orientation, position, and interactions of the bound terminal sugar depend on the sugar itself, the presence and form of glycosidic linkage, and the environment in the crystal, which, via Asp325, places stereochemical and electronic constraints, different for the three different subunits in the homotrimer, on the ligand-binding site.