Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma.

Multiple Myeloma (MM) is a haematological neoplasm characterised by the clonal proliferation of malignant plasma cells in the bone marrow. The success of proteasome inhibitors in the treatment of MM has highlighted the importance of the ubiquitin proteasome system (UPS) in the pathogenesis of this disease. In this study, we analysed gene expression of UPS components to identify novel therapeutic targets within this pathway in MM.

The role of the CCN family of proteins in blood cancers.

Haematopoiesis is the term used to describe the production of blood cells. This is a tightly regulated hierarchical system in which mature circulating blood cells develop from a small population of haematopoietic stem (HSC) and progenitor cells within the microenvironment of the bone marrow. Molecular and genetic abnormalities arising in these stem cells lead to a block in the normal programme of proliferation and differentiation and result in the development of the blood cancers known as the leukaemias and lymphomas.

GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity.

Breast cancers possess fundamentally altered metabolism that fuels their pathogenicity. While many metabolic drivers of breast cancers have been identified, the metabolic pathways that mediate breast cancer malignancy and poor prognosis are less well understood. Here, we used a reactivity-based chemoproteomic platform to profile metabolic enzymes that are enriched in breast cancer cell types linked to poor prognosis, including triple-negative breast cancer (TNBC) cells and breast cancer cells that have undergone an epithelial-mesenchymal transition-like state of heightened malignancy.

A tyrosine-reactive irreversible inhibitor for glutathione S-transferase Pi (GSTP1).

Glutathione S-transferase Pi (GSTP1) mediates cellular defense against reactive electrophiles. Here, we report LAS17, a dichlorotriazine-containing compound that irreversibly inhibits GSTP1 and is selective for GSTP1 within cellular proteomes. Mass spectrometry and mutational studies identified Y108 as the site of modification, providing a unique mode of GSTP1 inhibition.

Posterior sternoclavicular Salter-Harris fracture-dislocation in a patient with unossified medial clavicle epiphysis.

Sternoclavicular injuries are relatively rare, composing less than 1 % of all musculoskeletal fractures or dislocations. When sternoclavicular injuries do occur, they typically present as an isolated dislocation of the sternoclavicular joint without associated fracture of the clavicle or manubrium. However, in patients with unfused medial clavicle physis, sternoclavicular joint injuries can present as a fracture-dislocation through the unfused physis.

Working memory and spatial judgments: Cognitive load increases the central tendency bias.

Previous work demonstrates that memory for simple stimuli can be biased by information about the distribution of which the stimulus is a member. Specifically, people underestimate values greater than the distribution's average and overestimate values smaller than the average. This is referred to as the central tendency bias.

RANAVIRUS EPIZOOTIC IN CAPTIVE EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) WITH CONCURRENT HERPESVIRUS AND MYCOPLASMA INFECTION: MANAGEMENT AND MONITORING.

Frog virus 3 (FV3) and FV3-like viruses are members of the genus Ranavirus (family Iridoviridae) and are becoming recognized as significant pathogens of eastern box turtles (Terrapene carolina carolina) in North America. In July 2011, 5 turtles from a group of 27 in Maryland, USA, presented dead or lethargic with what was later diagnosed as fibrinonecrotic stomatitis and cloacitis. The presence of FV3-like virus and herpesvirus was detected by polymerase chain reaction (PCR) in the tested index cases.

Complex Interplay of the UL136 Isoforms Balances Cytomegalovirus Replication and Latency.

Unlabelled: Human cytomegalovirus (HCMV), a betaherpesvirus, persists indefinitely in the human host through poorly understood mechanisms. The UL136 gene is carried within a genetic locus important to HCMV latency termed the UL133/8 locus, which also carries UL133, UL135, and UL138. Previously, we demonstrated that UL136 is expressed as five protein isoforms ranging from 33-kDa to 19-kDa, arising from alternative transcription and, likely, translation initiation mechanisms.

Spatial working memory capacity predicts bias in estimates of location.

Spatial memory research has attributed systematic bias in location estimates to a combination of a noisy memory trace with a prior structure that people impose on the space. Little is known about intraindividual stability and interindividual variation in these patterns of bias. In the current work, we align recent empirical and theoretical work on working memory capacity limits and spatial memory bias to generate the prediction that those with lower working memory capacity will show greater bias in memory of the location of a single item.

Pet-1 Switches Transcriptional Targets Postnatally to Regulate Maturation of Serotonin Neuron Excitability.

Unlabelled: Newborn neurons enter an extended maturation stage, during which they acquire excitability characteristics crucial for development of presynaptic and postsynaptic connectivity. In contrast to earlier specification programs, little is known about the regulatory mechanisms that control neuronal maturation. The Pet-1 ETS (E26 transformation-specific) factor is continuously expressed in serotonin (5-HT) neurons and initially acts in postmitotic precursors to control acquisition of 5-HT transmitter identity.

Insights into structure and redox potential of lignin peroxidase from QM/MM calculations.

Redox potentials are computed for the active form (compound I) of lignin peroxidase (LiP) using a suitable QM/MM methodology (B3LYP/SDD/6-311G**//BP86/SVP:CHARMM). Allowing for dynamic conformational averaging, a potential of 0.67(33) V relative to ferrocenium/ferrocene is obtained for the active form with its oxoiron(iv) core.

Moral Legitimacy: The Struggle Of Homeopathy in the NHS.

This article deploys a well-established theoretical model from the accountability literature to the domain of bioethics. Specifically, homeopathy is identified as a controversial industry and the strategic action of advocates to secure moral legitimacy and attract public funding is explored. The Glasgow Homeopathic Hospital (GHH) is used as the location to examine legitimizing strategies, from gaining legitimacy as a National Health Service (NHS) hospital in 1948, followed by maintaining and repairing legitimacy in response to government enquires in 2000 and 2010.

The outcome of prenatal identification of sex chromosome abnormalities.

Objective: The outcome of a pregnancy following identification of a sex chromosome abnormality (SCA) is unclear. The aims of this study were to ascertain the prevalence of SCA detected prenatally in Scotland and to determine the outcomes for these cases.

Design: Following retrospective identification of all prenatal karyotypes performed in Scotland between 2000 and 2012, data linkage was performed to obtain information regarding maternal characteristics and pregnancy outcomes.

Prescribing Patterns of Metformin in High-risk Patients with Prediabetes.

Aims: The primary objective of this study is to examine the rates of metformin prescribing in patients with prediabetes who are either less than 60 years of age, have a BMI greater than 35 kg/m2, or women with a history of gestational diabetes mellitus (GDM). Secondary objectives include: 1) examination of the time from diagnosis of prediabetes to the initiation of metformin and 2) if metformin initiation status and length of time correlates to the patient having any other additional diabetes mellitus (DM) risk factors.

Methods: This was a single center, retrospective cohort study.

Concepts, technologies, and practices for drug delivery past the blood-brain barrier to the central nervous system.

While neurodegenerative diseases and cancers are on the rise, treatments for diseases of the central nervous system (CNS) remain limited. The blood brain barrier (BBB) poses the greatest challenge to CNS drug delivery and has therefore been a primary focus in the development of novel CNS drug delivery techniques. Limitations set by the BBB include molecule size, polarity, substrate specificity, and active efflux mechanisms.

Association of American Veterinary Medical Colleges (AAVMC): 50 Years of History and Service.

The mission of the Association of American Veterinary Medical Colleges (AAVMC) is to advance the quality of academic veterinary medicine. Founded in 1966 by the 18 US colleges of veterinary medicine and 3 Canadian colleges of veterinary medicine then in existence, the AAVMC is celebrating 50 years of public service. Initially, the AAVMC comprised the Council of Deans, the Council of Educators, and the Council of Chairs.

The Fate of the Neuromuscular Hip After Spinal Fusion.

Background: The goals of treatment of neuromuscular scoliosis are to achieve a balanced spine and level pelvis with most constructs including pelvic fixation. However, the pelvis can become a stiff "end vertebra" that prevents compensatory mechanisms to adjust to hip deformities in this patient population. The purpose of this study is to determine the frequency of hip pathology and surgery after spinal fusion in this patient population.

Creating and using real-world evidence to answer questions about clinical effectiveness.

New forms of evidence are needed to complement evidence generated from randomised controlled trials (RCTs). Real-World Evidence (RWE) is a potential new form of evidence, but remains undefined. This paper sets to fill that gap by defining RWE as the output from a rigorous research process which: (1) includes a clear a priori statement of a hypothesis to be tested or research question to be answered; (2) defines the data sources that will be used and critically appraises their strengths and weaknesses; and (3) applies appropriate methods, including advanced analytics.

A Simple and Sensitive Method to Quantify Biodegradable Nanoparticle Biodistribution using Europium Chelates.

The biodistribution of biodegradable nanoparticles can be difficult to quantify. We report a method using time resolved fluorescence (TRF) from a lanthanide chelate to minimize background autofluorescence and maximize the signal to noise ratio to detect biodegradable nanoparticle distribution in mice. Specifically, antenna chelates containing europium were entrapped within nanoparticles composed of polylactic acid-polyethylene glycol diblock copolymers.

Cohort Study of Carbon Black Exposure and Risk of Malignant and Nonmalignant Respiratory Disease Mortality in the US Carbon Black Industry.

Objective: To evaluate lung cancer and respiratory disease mortality associations with cumulative inhalable carbon black exposure among 6634 US carbon black workers.

Methods: This analysis was performed using standardized mortality ratio (SMRs) and Cox regression analyses.

Results: Lung cancer mortality was decreased overall (SMR = 0.

Formaldehyde Exposure and Mortality Risks From Acute Myeloid Leukemia and Other Lymphohematopoietic Malignancies in the US National Cancer Institute Cohort Study of Workers in Formaldehyde Industries.

Objectives: To evaluate associations between cumulative and peak formaldehyde exposure and mortality from acute myeloid leukemia (AML) and other lymphohematopoietic malignancies.

Methods: Cox proportional hazards analyses.

Results: Acute myeloid leukemia was unrelated to cumulative exposure.

Dosimetric Consequences of 3D Versus 4D PET/CT for Target Delineation of Lung Stereotactic Radiotherapy.

Introduction: Lung tumor delineation is frequently performed using 3D positron emission tomography (PET)/computed tomography (CT), particularly in the radiotherapy treatment planning position, by generating an internal target volume (ITV) from the slow acquisition PET. We investigate the dosimetric consequences of stereotactic ablative body radiotherapy (SABR) planning on 3D PET/CT in comparison with gated (4D) PET/CT.

Methods: In a prospective clinical trial, patients with lung metastases were prescribed 26 Gy single-fraction SABR to the covering isodose.

Humanized mouse models of human cytomegalovirus infection.

The generation of humanized mouse models in which immune deficient mice are engrafted with human tissues allows for the direct in vivo investigation of human-restricted viruses. These humanized mouse models have been developed and improved over the past 30 years. It is now possible to achieve high levels of human cell engraftment producing human myeloid and lymphoid lineage cells.

The gold(i)-catalysed protodecarboxylation mechanism.

A mechanistic study of the gold-catalysed protodecarboxylation is described. Each reaction step has been investigated experimentally and computationally. More specifically, the activation parameters for the decarboxylation step have been determined through kinetic studies.