Microbe Profile: Typhimurium: the master of the art of adaptation.

Typhimurium is a major serovar that is found globally. It is responsible for outbreaks of self-limiting gastroenteritis that are broadly linked to the industrialization of food production. .

Quantitative imaging of loop extruders rebuilding interphase genome architecture after mitosis.

How cells establish the interphase genome organization after mitosis is incompletely understood. Using quantitative and super-resolution microscopy, we show that the transition from a Condensin to a Cohesin-based genome organization occurs dynamically over 2 h. While a significant fraction of Condensins remains chromatin-bound until early G1, Cohesin-STAG1 and its boundary factor CTCF are rapidly imported into daughter nuclei in telophase, immediately bind chromosomes as individual complexes, and are sufficient to build the first interphase TAD structures.

Predictive Methods and Probabilistic Mapping of Subcortical Brain Components in Fossil Carnivora.

Paleoneurology reconstructs the evolutionary history of nervous systems through direct observations from the fossil record and comparative data from extant species. Although this approach can provide direct evidence of phylogenetic links among species, it is constrained by the availability and quality of data that can be gleaned from the fossil record. Here, we sought to translate brain component relationships in a sample of extant Carnivora to make inferences about brain structure in fossil species.

Biomarkers.

Background: Growth/differentiation factor-15 (GDF15) has been associated with dementia risk, yet its predictive value across cohorts and sub-population, as well as its relationship with endophenotypes relevant to dementia, remains unknown.

Methods: Using the Atherosclerosis Risk in Communities (ARIC) study as the discovery cohort, we examined the relationship between plasma GDF15 levels (SomaScan) and risk for incident all-cause dementia (ACD) in late-life (N=4,287, 7-year follow-up, M=75±5) and in midlife (N=11,595, 20-year follow-up, M=57±6). Utilizing the UK Biobank (UKB; replication cohort), we related plasma GDF15 (Olink) to incident ACD (N=35,673, 14-year follow-up, M=61±5), vascular dementia (VaD) and Alzheimer's disease dementia (AD).

Biomarkers.

Background: With the approval of several anti-amyloid antibodies and a robust pipeline of new amyloid-based therapies, attention turns towards questions related to real-world clinical practice. Here we explore the impact of several biological pathways on the amyloid biomarker response of AD patients using a Quantitative Systems Pharmacology (QSP) approach with the ultimate objective to find measurable biomarkers for responder identification.

Method: Using a well-validated QSP biophysically realistic model of amyloid aggregation, we performed sensitivity analysis to identify key drivers of amyloid biomarkers both in a longitudinal observational context and after treatment with specific amyloid antibodies.

Biomarkers.

Background: Speech abnormalities are increasingly recognized as a manifestation of cognitive deficits in Alzheimer's disease (AD) and its preclinical and prodromal stages. Here, we investigated whether MRI measures of brain atrophy, specifically in the basal forebrain and cortical language areas, can predict cognitive decline and speech difficulties in older adults within the AD spectrum.

Method: The ongoing Prospect-AD study aims to develop an algorithm to automatically identify speech biomarkers in individuals with early signs of AD.

Biomarkers.

Background: The mitochondrial cascade hypothesis suggests that mitochondrial dysfunction plays an important role in the pathogenesis of Alzheimer's disease dementia. Recent data have shown that mitochondrial DNA copy number (mtDNAcn) in human blood is associated with dementia risk and cognitive function, but which specific cognitive measures or domains are associated with mitochondrial dysfunction and whether this relationship is affected by health deterioration such as physical frailty or mitochondrial somatic mutations is not clear.

Methods: We measured mtDNAcn and heteroplasmies using fastMitoCalc and MitoCaller, respectively, from UK Biobank Whole Genome Sequencing (WGS) data at study entry (2006-2010).

Biomarkers.

Background: Phase four of the Alzheimer's Disease Neuroimaging Initiative (ADNI4) began in 2023. This time-period corresponded to MRI vendors introducing product sequences with compressed sensing (CS), cross-vendor adoption of arterial spin-labelling (ASL) and multi-band slice excitation, and hardware improvements (head-coils, increased gradient amplitudes). These advances enabled the acquisition of new imaging measures and reduced scan times.

Biomarkers.

Background: Alzheimer's disease (AD) impacts over 50 million individuals and imposes a substantial burden on patients, caregivers, and society at large. Recent research suggests that AD is a continuum comprising preclinical, prodromal, and dementia stages, with underlying pathology manifesting well before symptoms appear. Early and accurate diagnosis is therefore crucial for optimal clinical outcomes; yet current diagnostic methods, such as neuroimaging and cerebrospinal fluid lumbar puncture, are expensive and invasive.

Biomarkers.

Background: The Centiloid method (CL) was introduced as a tracer-independent measure for cortical amyloid load and is now commonly used in Alzheimer's disease (AD) clinical trials. To facilitate its implementation into clinical settings, the AMYPAD consortium set out to integrate existing literature and recent work from the consortium to provide clinical context-of-use recommendations of the Centiloid scale, which has been submitted to the European Medicine Agency for endorsement as a Biomarker Qualification Opinion.

Method: Screening of the literature was performed on the 7/11/23 on PubMed to identify articles mentioning "Centiloid".

Biomarkers.

Background: Recent advances in automatic face recognition have increased the risk that de-identified research imaging data could be re-identified from face imagery in brain scans.

Method: An ADNI committee of independent imaging experts evaluated 11 published techniques for face-deidentification ("de-facing") and selected four algorithms (FSL-UK Biobank, HCP/XNAT, mri_reface, and BIC) for formal testing using 183 longitudinal scans of 61 racially and ethnically diverse ADNI participants, evaluated by their facial feature removal on 3D rendered surfaces (confirming sufficient privacy protection) and by comparing measurements from ADNI routine image analyses on unmodified vs. de-faced images (confirming negligible side effects on analyses).

Biomarkers.

Background: Mild cognitive impairment (MCI) is currently a clinical diagnosis characterized by decline in memory and daily cognitive function from baseline. Exploratory studies using optical coherence tomography angiography have reported alterations in the retinal capillary plexus vessel density and attenuation of the retinal nerve fiber layer, but these results appear to be mixed. We used ultra-widefield (UWF) imaging to evaluate retinal and choroidal vasculature and structure in individuals with mild cognitive impairment (MCI) compared to controls with normal cognition.

Biomarkers.

Background: There is a strong link between tau and progression of Alzheimer's disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial heterogeneity of tau in typical AD, validating this connectivity-based tau spreading model in AD variants with distinct tau deposition patterns is crucial.

Biomarkers.

Background: Several studies have investigated the link between sleep disturbances and allostatic load (AL), but the results are varied, and less is known about the associations in clinical samples. The goal of this study is to assess the associations between sleep disturbances and AL among memory clinic participants, and to examine differences according to sex, beta-amyloid status and history of burnout status.

Method: The study was based on 146 memory clinic participants diagnosed with either Mild Cognitive Impairment (MCI) or Subjective Cognitive Impairment (SCI) in the Cortisol and Stress in Alzheimer's Disease Study (Co-STAR) (Sweden).

Biomarkers.

Background: Chronic exposition to stressor factors has been postulated as a cause of structural changes in the brain in the context of dementia. One of these changes can be the fiber integrity loss, that can be measured by diffusion tensor imaging (DTI). We obtained DTI whole brain metrics to relate them with allostatic load in subjects of a chilean cohort of cognitive complaint subjects.

Biomarkers.

Background: Subjective cognitive decline (SCD), in the absence of objective cognitive impairment, may be the first symptomatic manifestation of Alzheimer's disease (AD). Previous studies have suggested that its combination with amyloid-positivity (Aβ+) may represent stage 2 AD, and is associated with a higher risk of future cognitive decline. Here, we aim to (1) confirm this using the plasma Aβ42/40 ratio, and (2) test whether the addition of plasma phospho-tau181 (ptau, a marker of Aβ and tau pathology) could help refine the prediction of future cognitive decline in SCD patients.

Biomarkers.

Background: Psychotic symptoms may manifest in Alzheimer's disease (AD), especially in advanced disease stages and in patients with higher polygenic risk scores for schizophrenia (SCZ-PRS). Such genetic risk seems also to influence grey matter volume (GMV) alterations in patients with psychosis. Since multiple neurotransmitter systems, namely dopamine (DA) and serotonin (5-HT), have been implicated in psychosis, the aim of this study was to investigate whether a SCZ-PRS may explain variance in the association between GMV and the cerebral distribution of DA and 5-HT.

Association between socioeconomic status and patient-reported outcome at 1 year after shoulder arthroplasty for osteoarthritis or cuff-tear arthropathy: a nationwide cohort study of 2,292 arthroplasties.

Purpose:  We aimed to evaluate the association between socioeconomic factors and patient-reported Western Ontario Osteoarthritis of the Shoulder (WOOS) index at 1 year after hemiarthroplasty, reverse, or anatomical total shoulder arthroplasty for osteoarthritis or cuff-tear arthropathy.

Methods:  Eligible patients were identified using linked national data from the Danish Shoulder Arthroplasty Registry and Statistics Denmark between April 2012 and April 2019. Univariable and multivariable linear regression was used to identify the association between socioeconomic factors and the WOOS index at 1 year following primary shoulder arthroplasty adjusted for age, sex, underlying diagnosis, implant design, and comorbidities.

Biomarkers.

Background: Alzheimer's disease (AD) is a complex disorder with a strong genetic component, yet many genetic risk factors remain unknown. Integrating genome-wide association studies (GWAS) and high-throughput proteomic platforms is a useful strategy to evaluate protein quantitative trait loci (pQTLs) and to detect candidate genes and pathways involved in AD. Due to the novelty of these techniques, the identification of reliable protein measures through a comprehensive quality control is mandatory.

Biomarkers.

Background: Use of the supratentorial white matter (sWM) as a reference region for amyloid PET, alone or in a composite, can facilitate the detection of subtle changes in amyloid load (Wong et al., 2010; Landau et al., 2015).

Biomarkers.

Background: Chronic exposure to stress, quantified by allostatic load (AL), has been postulated as a cause of structural brain changes in the context of dementia. White matter hyperintensities (WMH), detected in MRI FLAIR, are a common brain abnormality representing small vessel disease or degenerative changes in the brain. Here, we studied differences in tract-specific WMH volume across three risk levels of AL in Chilean subjects with cognitive complaint, to explore links between chronic stress exposure and prodromal steps of dementia.

Biomarkers.

Background: Cerebral small vessel disease (cSVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although risk factors for cSVD have been identified, little is known about the biological processes and molecular mediators that influence cSVD development and progression.

Methods: Within the Atherosclerosis Risk in Communities (ARIC) study, we used SomaScan Multiplexed Proteomic technology to relate 4,877 plasma proteins to concurrently measured MRI-defined cSVD characteristics, including WMHs, CMHs, and lacunar infarcts, in late-life (n=1508; mean age: 76).

Socioeconomic Deprivation and Risk of Operative Mortality After Emergency Laparotomy: A Systematic Review and Meta-Analysis.

Aims: The aim was to determine the effect of socioeconomic deprivation on operative mortality after emergency laparotomy.

Methods: A PRISMA-compliant systematic review and meta-analysis (random-effects modeling) was performed searching for studies comparing operative mortality between the least and the most socioeconomically deprived patients undergoing emergency laparotomy. Both unadjusted and adjusted odds ratio (OR) were calculated as summary measure.

Biomarkers.

Background: Changes in Amyloid-β (A) and hyperphosphorylated Tau (T) in the brain and cerebrospinal fluid (CSF) precedes AD symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies.

Method: We used the Somascan assay for measuring the protein levels of 7,029 analytes in CSF of 2,286 participants from four different cohorts. We employed a three-stage analytical approach (discovery, replication, and meta-analysis).

Comparative transcriptomics pinpoints conserved and specific transcriptional responses to phosphorus limitation.

Translating biological knowledge from Arabidopsis to crop species is important to advance agriculture and secure food production in the face of dwindling fertilizer resources and biotic and abiotic stresses. However, it is often not trivial to identify functional homologs (orthologs) of Arabidopsis genes in crops. Combining sequence and expression data can improve the correct prediction of orthologs.