Chronic Traumatic Encephalopathy in a Routine Neuropathology Service in Australia.

Chronic traumatic encephalopathy (CTE) is a neuropathological diagnosis defined by a unique pattern of hyperphosphorylated tau (p-tau) accumulation that begins in neocortical regions of the brain. It is associated with a range of neuropsychological symptoms, but a definitive diagnosis can only be made by postmortem brain examination. In 2018, we instituted CTE screening for all autopsy brains as part of our routine departmental protocol by performing p-tau immunohistochemistry on a restricted set of 3 neocortical blocks (frontal, temporal, and parietal).

Molecular Analysis of pSK1 par: A Novel Plasmid Partitioning System Encoded by Staphylococcal Multiresistance Plasmids.

The segregation of prokaryotic plasmids typically requires a centromere-like site and two proteins, a centromere-binding protein (CBP) and an NTPase. By contrast, a single 245 residue Par protein mediates partition of the prototypical staphylococcal multiresistance plasmid pSK1 in the absence of an identifiable NTPase component. To gain insight into centromere binding by pSK1 Par and its segregation function we performed structural, biochemical and in vivo studies.

Cross-skilling training to support medical redeployment in the COVID-19 pandemic.

During the response to the COVID-19 pandemic, doctors will be redeployed into roles with which they are unfamiliar. Adequate training must be provided to reacquaint doctors with medical ward practice, supporting psychological wellbeing and patient safety. Here we describe a cross-skilling programme in North Bristol NHS Trust designed to address colleague anxiety and support wellbeing during redeployment.

Distribution of tau hyperphosphorylation in canine dementia resembles early Alzheimer's disease and other tauopathies.

Some aged community dogs acquire a degenerative syndrome termed Canine Cognitive Dysfunction (CCD) that resembles human dementia because of Alzheimer's Disease (AD), with comparable cognitive and behavioral deficits. Dogs also have similar neuroanatomy, share our domestic environment and develop amyloid-β plaques, making them likely a valuable ecological model of AD. However, prior investigations have demonstrated a lack of neurofibrillary tau pathology in aged dogs, an important hallmark of AD, though elevated phosphorylated tau (p-tau) at the Serine 396 (S396) epitope has been reported in CCD.

Clustering of activated microglia occurs before the formation of dystrophic neurites in the evolution of Aβ plaques in Alzheimer's disease.

Alzheimer's disease (AD) is a late-onset disease that has proved difficult to model. Microglia are implicated in AD, but reports vary on precisely when and how in the sequence of pathological changes they become involved. Here, post-mortem human tissue from two differentially affected regions of the AD brain and from non-demented individuals with a high load of AD-type pathology (high pathology controls) was used to model the disease time course in order to determine how microglial activation relates temporally to the deposition of hallmark amyloid-β (Aβ) and hyperphosphorylated microtubule associated protein tau pathology.

The relationship between the morphological subtypes of microglia and Alzheimer's disease neuropathology.

Microglial associations with both the major Alzheimer's disease (AD) pathognomonic entities, β-amyloid-positive plaques and tau-positive neurofibrillary tangles, have been noted in previous investigations of both human tissue and mouse models. However, the precise nature of their role in the pathogenesis of AD is debated; the major working hypothesis is that pro-inflammatory activities of activated microglia contribute to disease progression. In contrast, others have proposed that microglial dystrophy with a loss of physiological and neuroprotective activities promotes neurodegeneration.

Diagnosis and Management of Anorectal Disorders in the Primary Care Setting.

Anorectal disorders are very common among a wide population of patients. Because patients may be embarrassed about the anatomic location of their symptoms, they may present to care late in the course of their illness. Care should be taken to validate patient concerns and normalize fears.

Microglia show altered morphology and reduced arborization in human brain during aging and Alzheimer's disease.

Changes in microglia function are involved in Alzheimer's disease (AD) for which ageing is the major risk factor. We evaluated microglial cell process morphologies and their gray matter coverage (arborized area) during ageing and in the presence and absence of AD pathology in autopsied human neocortex. Microglial cell processes were reduced in length, showed less branching and reduced arborized area with aging (case range 52-98 years).

STED imaging of tau filaments in Alzheimer's disease cortical grey matter.

Alzheimer's disease (AD) involves the propagation of filaments of tau protein throughout the cerebral cortex. Imaging tau filaments and oligomers in human brain at high resolution would help contribute insight into the mechanism and progression of tauopathic diseases. STED microscopy is a nano-scale imaging technique and we aimed to test the abilities of this method for resolving tau structures within human brain.

Dynamic Filament Formation by a Divergent Bacterial Actin-Like ParM Protein.

Actin-like proteins (Alps) are a diverse family of proteins whose genes are abundant in the chromosomes and mobile genetic elements of many bacteria. The low-copy-number staphylococcal multiresistance plasmid pSK41 encodes ParM, an Alp involved in efficient plasmid partitioning. pSK41 ParM has previously been shown to form filaments in vitro that are structurally dissimilar to those formed by other bacterial Alps.

A paralogue of the phosphomutase-like gene family in Candida glabrata, CgPmu2, gained broad-range phosphatase activity due to a small number of clustered substitutions.

Inorganic phosphate is required for a range of cellular processes, such as DNA/RNA synthesis and intracellular signalling. The phosphate starvation-inducible phosphatase activity of Candida glabrata is encoded by the gene CgPMU2 (C. glabrata phosphomutase-like protein).

Cofilin rods and aggregates concur with tau pathology and the development of Alzheimer's disease.

Background: Imaging of human brain as well as cellular and animal models has highlighted a role for the actin cytoskeleton in the development of cell pathology in Alzheimer's disease (AD). Rods and aggregates of the actin-associated protein cofilin are abundant in grey matter of postmortem AD brain and rods are found inside neurites in animal and cell models of AD.

Objective: We sought further understanding of the significance of cofilin rods/aggregates to the disease process: Do rods/aggregates correlate with AD progression and the development of hallmark neurofibrillary tangles and neuropil threads? Are cofilin rods/aggregates found in the same neurites as hyperphosphorylated tau?

Methods: The specificity of rods/aggregates to AD compared with general aging and their spatial relationship to tau protein was examined in postmortem human hippocampus, inferior temporal cortex, and anterior cingulate cortex.

Novel acid phosphatase in Candida glabrata suggests selective pressure and niche specialization in the phosphate signal transduction pathway.

Evolution through natural selection suggests unnecessary genes are lost. We observed that the yeast Candida glabrata lost the gene encoding a phosphate-repressible acid phosphatase (PHO5) present in many yeasts including Saccharomyces cerevisiae. However, C.

The functional outcome of the fractured clavicle.

Background: The severity of symptoms, rate and completeness of recovery after closed treatment of the fractured clavicle has not been fully explored.

Methods: The severity and duration of pain, analgesic requirements, ability to perform daily activities, return to work, driving and sport along with appearance of the shoulder were recorded in 56 patients between 1 and 2 years after fracture. Radiographs were assessed by Robinson's classification [8].

Spitzenkörper, vacuoles, ring-like structures, and mitochondria of Phanerochaete velutina hyphal tips visualized with carboxy-DFFDA, CMAC and DiOC6(3).

Growth and organelle morphology in the wood rotting basidiomycete fungus Phanerochaete velutina were examined in Petri dishes, on agar-coated slides, and in submerged cultures, using DIC, fluorescence and four-dimensional (4-D; x,y,z,t) confocal microscopy, with several fluorescent probes. Phanerochaete is ideal for this work because of its fast growth, robustness, and use in a wide range of other studies. The probe carboxy-DFFDA, widely used for labelling vacuoles, has no effect either on hyphal tip extension or colony growth at the concentrations usually applied in labelling experiments.

Changes in vacuolar and mitochondrial motility and tubularity in response to zinc in a Paxillus involutus isolate from a zinc-rich soil.

Short-term effects of zinc on organelles were investigated in Paxillus involutus from a zinc-rich soil. Vacuoles were labelled with Oregon Green 488 carboxylic acid and mitochondria with DiOC(6)(3). Hyphae were treated with ZnSO(4) in the range 1-100 mM and examined by fluorescence microscopy.

Regulators of GTP-binding proteins cause morphological changes in the vacuole system of the filamentous fungus, Pisolithus tinctorius.

Tubule formation is a widespread feature of the endomembrane system of eukaryotic cells, serving as an alternative to the better-known transport process of vesicular shuttling. In filamentous fungi, tubule formation by vacuoles is particularly pronounced, but little is known of its regulation. Using the hyphae of the basidiomycete Pisolithus tinctorius as our test system, we have investigated the effects of four drugs whose modulation, in animal cells, of the tubule/vesicle equilibrium is believed to be due to the altered activity of a GTP-binding protein (GTP gamma S, GDP beta S, aluminium fluoride, and Brefeldin A).