Development and evaluation of a risk algorithm predicting alcohol dependence after early onset of regular alcohol use.

Aims: Likelihood of alcohol dependence (AD) is increased among people who transition to greater levels of alcohol involvement at a younger age. Indicated interventions delivered early may be effective in reducing risk, but could be costly. One way to increase cost-effectiveness would be to develop a prediction model that targeted interventions to the subset of youth with early alcohol use who are at highest risk of subsequent AD.

Dementia Risk Score for a Population in Southern Europe Calculated Using Competing Risk Models.

Background: Dementia prevention can be addressed if the intervention is applied early.

Objective: The objective of this study was to develop and validate competing risk models to predict the late risk of dementia based on variables assessed in middle age in a southern European population.

Methods: We conducted a prospective observational study of the EPIC-Spain cohort that included 25,015 participants.

Concentrations of bisphenol-A in adults from the general population: A systematic review and meta-analysis.

Background: Human bisphenol-A (BPA) exposure has been linked to adverse health effects even at low doses, which may be of potential public health concern.

Objective: To summarize BPA concentrations in general human population and their variability according to sex, geographic area, and analytical method.

Methods: Systematic review and meta-analysis of studies reporting BPA concentrations in adult human populations.

Mediterranean Diet and Risk of Dementia and Alzheimer's Disease in the EPIC-Spain Dementia Cohort Study.

The Mediterranean diet (MD) has shown to reduce the occurrence of several chronic diseases. To evaluate its potential protective role on dementia incidence we studied 16,160 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain Dementia Cohort study recruited between 1992-1996 and followed up for a mean (±SD) of 21.6 (±3.

Quail-chick grafting experiments corroborate that Tbr1-positive eminential prethalamic neurons migrate along three streams into hypothalamus, subpallium and septocommissural areas.

The prethalamic eminence (PThE), a diencephalic caudal neighbor of the telencephalon and alar hypothalamus, is frequently described in mammals and birds as a transient embryonic structure, undetectable in the adult brain. Based on descriptive developmental analysis of Tbr1 gene brain expression in chick embryos, we previously reported that three migratory cellular streams exit the PThE rostralward, targeting multiple sites in the hypothalamus, subpallium and septocommissural area, where eminential cells form distinct nuclei or disperse populations. These conclusions needed experimental corroboration.

Incidence of Dementia and Associated Factors in the EPIC-Spain Dementia Cohort.

Background: Dementia has become a public health priority as the number of cases continues to grow worldwide.

Objective: To assess dementia incidence and determinants in the EPIC-Spain Dementia Cohort.

Methods: 25,015 participants (57% women) were recruited from three Spanish regions between 1992-1996 and followed-up for over 20 years.

Dystonia genes functionally converge in specific neurons and share neurobiology with psychiatric disorders.

Dystonia is a neurological disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and postures, often occurring in absence of any structural brain abnormality. Psychiatric comorbidities, including anxiety, depression, obsessive-compulsive disorder and schizophrenia, are frequent in patients with dystonia. While mutations in a fast-growing number of genes have been linked to Mendelian forms of dystonia, the cellular, anatomical, and molecular basis remains unknown for most genetic forms of dystonia, as does its genetic and biological relationship to neuropsychiatric disorders.

The first comprehensive phylogenetic and biochemical analysis of NADH diphosphatases reveals that the enzyme from Tuber melanosporum is highly active towards NAD.

Nudix (for nucleoside diphosphatases linked to other moieties, X) hydrolases are a diverse family of proteins capable of cleaving an enormous variety of substrates, ranging from nucleotide sugars to NAD-capped RNAs. Although all the members of this superfamily share a common conserved catalytic motif, the Nudix box, their substrate specificity lies in specific sequence traits, which give rise to different subfamilies. Among them, NADH pyrophosphatases or diphosphatases (NADDs) are poorly studied and nothing is known about their distribution.

An uncharacterized FMAG_01619 protein from Fusobacterium mortiferum ATCC 9817 demonstrates that some bacterial macrodomains can also act as poly-ADP-ribosylhydrolases.

Macrodomains constitute a conserved fold widely distributed that is not only able to bind ADP-ribose in its free and protein-linked forms but also can catalyse the hydrolysis of the latter. They are involved in the regulation of important cellular processes, such as signalling, differentiation, proliferation and apoptosis, and in host-virus response, and for this, they are considered as promising therapeutic targets to slow tumour progression and viral pathogenesis. Although extensive work has been carried out with them, including their classification into six distinct phylogenetically clades, little is known on bacterial macrodomains, especially if these latter are able to remove poly(ADP-ribose) polymer (PAR) from PARylated proteins, activity that only has been confirmed in human TARG1 (C6orf130) protein.

Comparative inhibitory profile and distribution of bacterial PARPs, using Clostridioides difficile CD160 PARP as a model.

Poly-ADP-ribose polymerases (PARPs) are involved in the regulation of important cellular processes, such as DNA repair, aging and apoptosis, among others. They have been considered as promising therapeutic targets, since human cancer cells carrying BRCA1 and BRCA2 mutations are highly sensitive to human PARP-1 inhibitors. Although extensive work has been carried out with the latter enzyme, little is known on bacterial PARPs, of which only one has been demonstrated to be active.

Structural and functional analysis of macrodomain reveals a network of waters involved in substrate binding and catalysis.

Macrodomains are ubiquitous conserved domains that bind or transform ADP-ribose (ADPr) metabolites. In humans, they are involved in transcription, X-chromosome inactivation, neurodegeneration and modulating PARP1 signalling, making them potential targets for therapeutic agents. Unfortunately, some aspects related to the substrate binding and catalysis of MacroD-like macrodomains still remain unclear, since mutation of the proposed catalytic aspartate does not completely abolish enzyme activity.

Measuring NLR Oligomerization III: Detection of NLRP3 Complex by Bioluminescence Resonance Energy Transfer.

Bioluminescent resonance energy transfer (BRET) is a natural phenomenon resulting from a non-radiative energy transfer between a bioluminescent donor (Renilla luciferase) and a fluorescent protein acceptor. BRET signal is dependent on the distance and the orientation between the donor and the acceptor and could be used to study protein-protein interactions and conformational changes within proteins in real time in living cells. This protocol describes the use of BRET technique to study NLRP3 oligomerization in living cells before and during NLRP3 inflammasome activation.

Measuring IL-1β Processing by Bioluminescence Sensors I: Using a Bioluminescence Resonance Energy Transfer Biosensor.

IL-1β processing is one of the hallmarks of inflammasome activation and drives the initiation of the inflammatory response. For decades, Western blot or ELISA have been extensively used to study this inflammatory event. Here, we describe the use of a bioluminescence resonance energy transfer (BRET) biosensor to monitor IL-1β processing in real time and in living macrophages either using a plate reader or a microscope.

New Insights into the Phylogeny and Gene Context Analysis of Binder of Sperm Proteins (BSPs).

Seminal plasma (SP) proteins support the survival of spermatozoa acting not only at the plasma membrane but also by inhibition of capacitation, resulting in higher fertilizing ability. Among SP proteins, BSP (binder of sperm) proteins are the most studied, since they may be useful for the improvement of semen diluents, storage and subsequent fertilization results. However, an updated and detailed phylogenetic analysis of the BSP protein superfamily has not been carried out with all the sequences described in the main databases.

Molecular characterization of a new N-acetylneuraminate synthase (NeuB1) from Idiomarina loihiensis.

N-Acetylneuraminate lyase synthase (NeuB; E.C. 2.