Central Regulation of Brown Fat Thermogenesis in Response to Saturated or Unsaturated Long-Chain Fatty Acids.

Sensing of long-chain fatty acids (LCFA) in the hypothalamus modulates energy balance, and its disruption leads to obesity. To date, the effects of saturated or unsaturated LCFA on hypothalamic-brown adipose tissue (BAT) axis and the underlying mechanisms have remained largely unclear. Our aim was to characterize the main molecular pathways involved in the hypothalamic regulation of BAT thermogenesis in response to LCFA with different lengths and degrees of saturation.

Impact of c-di-GMP on the Extracellular Proteome of .

Extracellular matrix components of bacterial biofilms include biopolymers such as polysaccharides, nucleic acids and proteins. Similar to polysaccharides, the secretion of adhesins and other matrix proteins can be regulated by the second messenger cyclic diguanylate (cdG). We have performed quantitative proteomics to determine the extracellular protein contents of a strain expressing high cdG intracellular levels.

Iron complexes of bridging azo ligands in aqueous solution: changes in the thermal switching mechanism on coordination and oxidation state of metal centres.

Three azobenzenes CN(CH)-NN-(CHN) (py-iso), CN(CH)-NN-(CH)CN (cyano-iso) and CN(CH)-NN-(CH)NC (iso-iso) with good coordinating groups (pyridine, phenylcyano or phenylisocyano) at the ends of the diazenyl unit have been synthesized and fully characterised. These compounds have been used as ligands in the synthesis of water-soluble metallic species by coordination to {Fe(CN)} units, either in one or two of the anchoring groups of the derivatives. Both the azo derivatives and their complexes are photochemically active with respect to their -to- isomerisation process.

Luminescence, CPL and magnetic properties of 1D enantiopure Ln complexes with (-) and (-) α-methoxyphenylacetate ligand.

The reaction of Ln(NO)·6HO (Ln = Eu, Tb, Dy and Sm) with ()-(-)-α-methoxyphenylacetic acid (R-HMPA) and 1,10-phenanthroline (phen) in EtOH/HO allows the isolation of 1D chiral compounds of formula [Ln(μ--MPA)(-MPA)(phen)] in which Ln = Eu (R-Eu), Tb (R-Tb), Dy (R-Dy) and Sm (R-Sm). The same synthesis by using ()-(+)-α-methoxyphenylacetic acid (S-HMPA) instead of ()-(-)-α-methoxyphenylacetic acid allows the isolation of the enantiomeric compounds with formula [Ln(μ--MPA)(-MPA)(phen)] where Ln = Eu (S-Eu), Tb (S-Tb), Dy (S-Dy) and Sm (S-Sm). Single crystal X-Ray diffraction measurements were performed for compounds R/S-Eu, R/S-Tb, S-Dy and S-Sm.

Jacob-induced transcriptional inactivation of CREB promotes Aβ-induced synapse loss in Alzheimer's disease.

Synaptic dysfunction caused by soluble β-amyloid peptide (Aβ) is a hallmark of early-stage Alzheimer's disease (AD), and is tightly linked to cognitive decline. By yet unknown mechanisms, Aβ suppresses the transcriptional activity of cAMP-responsive element-binding protein (CREB), a master regulator of cell survival and plasticity-related gene expression. Here, we report that Aβ elicits nucleocytoplasmic trafficking of Jacob, a protein that connects a NMDA-receptor-derived signalosome to CREB, in AD patient brains and mouse hippocampal neurons.

Reduction of Obesity and Insulin Resistance through Dual Targeting of VAT and BAT by a Novel Combination of Metabolic Cofactors.

Obesity is an epidemic disease worldwide, characterized by excessive fat accumulation associated with several metabolic perturbations, such as metabolic syndrome, insulin resistance, hypertension, and dyslipidemia. To improve this situation, a specific combination of metabolic cofactors (MC) (betaine, N-acetylcysteine, L-carnitine, and nicotinamide riboside) was assessed as a promising treatment in a high-fat diet (HFD) mouse model. Obese animals were distributed into two groups, orally treated with the vehicle (obese + vehicle) or with the combination of metabolic cofactors (obese + MC) for 4 weeks.

Fluorescently Labeled Ceramides and 1-Deoxyceramides: Synthesis, Characterization, and Cellular Distribution Studies.

Ceramides (Cer) are bioactive sphingolipids that have been proposed as potential disease biomarkers since they are involved in several cellular stress responses, including apoptosis and senescence. 1-Deoxyceramides (1-deoxyCer), a particular subtype of noncanonical sphingolipids, have been linked to the pathogenesis of type II diabetes. To investigate the metabolism of these bioactive lipids, as well as to have a better understanding of the signaling processes where they participate, it is essential to expand the toolbox of fluorescent sphingolipid probes exhibiting complementary subcellular localization.

Overlap between genetic variants associated with schizophrenia spectrum disorders and intelligence quotient: a systematic review.

Background: To study whether there is genetic overlap underlying the risk for schizophrenia spectrum disorders (SSDs) and low intelligence quotient (IQ), we reviewed and summarized the evidence on genetic variants associated with both traits.

Methods: We performed this review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and preregistered it in PROSPERO. We searched the Medline databases via PubMed, PsycInfo, Web of Science and Scopus.

The relevance of EGFR, ErbB receptors and neuregulins in human adipocytes and adipose tissue in obesity.

Objective: To investigate the potential role of EGFR, ErbBs receptors and neuregulins in human adipose tissue physiology in obesity.

Methods: Gene expression analysis in human subcutaneous (SAT) and visceral (VAT) adipose tissue in three independent cohorts [two cross-sectional (N = 150, N = 87) and one longitudinal (n = 25)], and in vitro gene knockdown and overexpression experiments were performed.

Results: While both SAT and VAT ERBB2 and ERBB4 mRNA increased in obesity, SAT EGFR mRNA was negatively correlated with insulin resistance, but did not change in obesity.

Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study.

Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients ( = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score.

The translational genetics of ADHD and related phenotypes in model organisms.

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder resulting from the interaction between genetic and environmental risk factors. It is well known that ADHD co-occurs frequently with other psychiatric disorders due, in part, to shared genetics factors. Although many studies have contributed to delineate the genetic landscape of psychiatric disorders, their specific molecular underpinnings are still not fully understood.

Elbow Extensor Muscles in Humans and Chimpanzees: Adaptations to Different Uses of the Upper Extremity in Hominoid Primates.

The anatomical and functional characteristics of the elbow extensor muscles (triceps brachii and anconeus) have not been widely studied in non-human hominoid primates, despite their great functional importance. In the present study, we have analyzed the muscle architecture and the expression of the myosin heavy chain (MHC) isoforms in the elbow extensors in humans and chimpanzees. Our main objective was to identify differences in these muscles that could be related to the different uses of the upper extremity in the two species.

Occurrence of slow relaxation of the magnetization in a family of copper(II)/manganese(II) quasi-isotropic complexes with different ground spin states.

A family of copper(II)/manganese(II) new clusters with the formulas [CuNa(L2)(MeOH)(ClO)] (1), [CuII2Mn(,-L3)(MeOH)](ClO) (2SS), [{CuMn(L1)(HO)(MeOH)}{Cu(L1)}](ClO) (3), [(μ-N){CuMn(L2)(HO)}{Cu(L2)](ClO)} (4) and [(μ-N){CuMn(L1)(N)}{CuNa(L1)(MeOH)}](ClO) (5) with L1 = ,'-ethylene-bis(3-methoxysalicylaldiimine), L2 = ,'-ethylene-bis(3-ethoxysalicylaldiimine) and L3 = ,'-cyclohexane-bis(3-ethoxysalicylaldiimine), has been synthesized, and structurally and magnetically characterized. Reduced magnetization studies demonstrate that the magnetic anisotropy of the systems is very small. However, dynamic magnetic studies and ultra-low-frequency Raman spectroscopy confirm the slow relaxation of these systems despite their quasi-isotropic nature, enlarging the range of non-anisotropic slow relaxing molecules.

3,4-Methylenedioxy methamphetamine, synthetic cathinones and psychedelics: From recreational to novel psychotherapeutic drugs.

The utility of classical drugs used to treat psychiatric disorders (e.g., antidepressants, anxiolytics) is often limited by issues of lack of efficacy, delayed onset of action or side effects.

Assessing the digenic model in rare disorders using population sequencing data.

An important fraction of patients with rare disorders remains with no clear genetic diagnostic, even after whole-exome or whole-genome sequencing, posing a difficulty in giving adequate treatment and genetic counseling. The analysis of genomic data in rare disorders mostly considers the presence of single gene variants in coding regions that follow a concrete monogenic mode of inheritance. A digenic inheritance, with variants in two functionally-related genes in the same individual, is a plausible alternative that might explain the genetic basis of the disease in some cases.

Serum neuregulin 4 is negatively correlated with insulin sensitivity in humans and impairs mitochondrial respiration in HepG2 cells.

Neuregulin 4 (NRG4) has been described to improve metabolic disturbances linked to obesity status in rodent models. The findings in humans are controversial. We aimed to investigate circulating NRG4 in association with insulin action in humans and the possible mechanisms involved.

Optimized Asymmetric Synthesis of Umuravumbolide.

Herein, the asymmetric synthesis of umuravumbolide () is described. The new approach features highly stereoselective transformations (dr ≥ 95:5) to install both stereocenters and the olefin, which involve a new radical alkylation, an Ando olefination, and a Krische allylation on a allylic alcohol, not reported before. The application of such successful reactions, together with the limited use of protecting groups and concession steps, makes it possible to complete the synthesis in 10 steps, resulting in a 39% overall yield from chiral -acyl oxazolidinone .

Oxidative Stress Is Associated with Overgrowth in Drosophila Mutant Imaginal Discs.

The loss-of-function conditions for an () in larvae reared at 29 °C results in malignant brain tumours and hyperplastic imaginal discs. Unlike the former that have been extensively characterised, little is known about the latter. Here we report the results of a study of the hyperplastic mutant wing imaginal discs.

Differential expression of miR-1249-3p and miR-34b-5p between vulnerable and resilient phenotypes of cocaine addiction.

Cocaine addiction is a complex brain disorder involving long-term alterations that lead to loss of control over drug seeking. The transition from recreational use to pathological consumption is different in each individual, depending on the interaction between environmental and genetic factors. Epigenetic mechanisms are ideal candidates to study psychiatric disorders triggered by these interactions, maintaining persistent malfunctions in specific brain regions.

Amide-Driven Secondary Building Unit Structural Transformations between Zn(II) Coordination Polymers.

The behavior of coordination polymers (CPs) against external stimuli has witnessed remarkable attention, especially when the resulting CPs present reversible molecular arrays. Accordingly, CPs with these characteristics can lead to differences in their properties owing to these structural differences, being promising for their use as potential molecular switches with diverse applications. Herein, we have synthesized four Zn(II) CPs bearing α-acetamidocinnamic acid (HACA) and 4,4'-bipyridine (4,4'-bipy).

Inborn Errors of Nucleoside Transporter (NT)-Encoding Genes ( and ).

The proper regulation of nucleotide pools is essential for all types of cellular functions and depends on de novo nucleotide biosynthesis, salvage, and degradation pathways. Despite the apparent essentiality of these processes, a significant number of rare diseases associated with mutations in genes encoding various enzymes of these pathways have been already identified, and others are likely yet to come. However, knowledge on genetic alterations impacting on nucleoside and nucleobase transporters is still limited.