Generating sequences and Poincar\'e series for a finite set of plane divisorial valuations

Let $V$ be a finite set of divisorial valuations centered at a 2-dimensional regular local ring $R$. In this paper we study its structure by means of the semigroup of values, $S_V$, and the multi-index graded algebra defined by $V$, \gr_V R. We prove that $S_V$ is finitely generated and we compute its minimal set of generators following the study of reduced curve singularities. Moreover, we prove a unique decomposition theorem for the elements of the semigroup. The comparison between valuations in $V$, the approximation of a reduced plane curve singularity $C$ by families of sets $V^{(k)}$ of divisorial valuations, and the relationship between the value semigroup of $C$ and the semigroups of the sets $V^{(k)}$, allow us to obtain the (finite) minimal generating sequences for $C$ as well as for $V$. We also analyze the structure of the homogeneous components of \gr_V R. The study of their dimensions allows us to relate the Poincar\'e series for $V$ and for a general curve $C$ of $V$. Since the last series coincides with the Alexander polynomial of the singularity, we can deduce a formula of A'Campo type for the Poincar\'e series of $V$. Moreover, the Poincar\'e series of $C$ could be seen as the limit of the series of $V^{(k)}$, $k\ge 0$

Motif affinity and mass spectrometry proteomic approach for the discovery of cellular AMPK targets: identification of mitochondrial fission factor as a new AMPK substrate

AMP-activated protein kinase (AMPK) is a key cellular energy sensor and regulator of metabolic homeostasis. Although it is best known for its effects on carbohydrate and lipid metabolism, AMPK is implicated in diverse cellular processes, including mitochondrial biogenesis, autophagy, and cell growth and proliferation. To further our understanding of energy homeostasis through AMPK-dependent processes, the design and application of approaches to identify and characterise novel AMPK substrates are invaluable. Here, we report an affinity proteomicstrategy for the discovery and validation of AMPK targets using an antibody to isolate proteins containing the phospho-AMPK substrate recognition motif from hepatocytes that had been treated with pharmacological AMPK activators. We identified 57 proteins that were uniquely enriched in the activator-treated hepatocytes, but were absent in hepatocytes lacking AMPK. We focused on two candidates, cingulin and mitochondrial fission factor (MFF), and further characterised/validated them as AMPK-dependent targets by immunoblotting with phosphorylation site-specific antibodies. A small-molecule AMPK activator caused transient phosphorylation of endogenous cingulin at S137 in intestinal Caco2 cells. Multiple splice-variants of MFF appear to express in hepatocytes and we identified a common AMPK-dependent phospho-site (S129) in all the 3 predominant variants spanning the mass range and a short variant-specific site (S146). Collectively, our proteomic-based approach using a phospho-AMPK substrate antibody in combination with genetic models and selective AMPK activators will provide a powerful and reliable platform for identifying novel AMPK-dependent cellular targets

Quantifying phase transformation during the manufacturing process of AISI 430 ferritic stainless steel

The effect of ferrite to austenite transformation phenomenon on microstructure and annealing performance of AISI 430 (EN 1.4016) ferritic stainless steel 16%Cr-0.04%C and 17%Cr-0.02%C was studied by electron backscatter diffraction and X-ray diffraction. Hot-rolled and annealed specimens of each ferritic stainless steel were collected from manufacturing route, where different states were analysed. Chemical composition shift of AISI 430 is correlated to microstructural behaviour of each material, while annealing temperature impact over grain growth phenomena is discussed

Plasma Proteomic Profiles of Cerebrospinal Fluid-Defined Alzheimer's Disease Pathology in Older Adults.

Cerebrospinal fluid (CSF) biomarkers of the beta-amyloid and microtubule associated protein tau metabolism have proven the capacity to improve classification of subjects developing Alzheimer's disease (AD). The blood plasma proteome was characterized to further elaborate upon the mechanisms involved and identify proteins that may improve classification of older adults developing an AD dementia. Identify and describe plasma protein expressions that best classify subjects with CSF-defined presence of AD pathology and cerebral amyloidosis. We performed a cross-sectional analysis of samples collected from community-dwelling elderly with (n = 72) or without (n = 48) cognitive impairment. CSF Aβ1-42, tau, and phosphorylated tau (P-tau181) were measured using ELISA, and mass spectrometry quantified the plasma proteomes. Presence of AD pathology was defined as CSF P-tau181/Aβ1-42 > 0.0779, and presence of amyloidosis was defined as CSF Aβ1-42 < 724 pg/mL. Two hundred and forty-eight plasma proteins were quantified. Plasma proteins did not improve classification of the AD CSF biomarker profile in the whole sample. When the analysis was separately performed in the cognitively impaired individuals, the diagnosis accuracy of AD CSF profile was 88.9% with 19 plasma proteins included. Within the full cohort, there were 16 plasma proteins that improved diagnostic accuracy of cerebral amyloidosis to 92.4%. Plasma proteins improved classification accuracy of AD pathology in cognitively-impaired older adults and appeared representative of amyloid pathology. If confirmed, those candidates could serve as valuable blood biomarkers of the preclinical stages of AD or risk of developing AD

Alzheimer disease pathology and the cerebrospinal fluid proteome.

Altered proteome profiles have been reported in both postmortem brain tissues and body fluids of subjects with Alzheimer disease (AD), but their broad relationships with AD pathology, amyloid pathology, and tau-related neurodegeneration have not yet been fully explored. Using a robust automated MS-based proteomic biomarker discovery workflow, we measured cerebrospinal fluid (CSF) proteomes to explore their association with well-established markers of core AD pathology. Cross-sectional analysis was performed on CSF collected from 120 older community-dwelling adults with normal (n = 48) or impaired cognition (n = 72). LC-MS quantified hundreds of proteins in the CSF. CSF concentrations of β-amyloid 1-42 (Aβ <sub>1-42</sub> ), tau, and tau phosphorylated at threonine 181 (P-tau181) were determined with immunoassays. First, we explored proteins relevant to biomarker-defined AD. Then, correlation analysis of CSF proteins with CSF markers of amyloid pathology, neuronal injury, and tau hyperphosphorylation (i.e., Aβ <sub>1-42</sub> , tau, P-tau181) was performed using Pearson's correlation coefficient and Bonferroni correction for multiple comparisons. We quantified 790 proteins in CSF samples with MS. Four CSF proteins showed an association with CSF Aβ <sub>1-42</sub> levels (p value ≤ 0.05 with correlation coefficient (R) ≥ 0.38). We identified 50 additional CSF proteins associated with CSF tau and 46 proteins associated with CSF P-tau181 (p value ≤ 0.05 with R ≥ 0.37). The majority of those proteins that showed such associations were brain-enriched proteins. Gene Ontology annotation revealed an enrichment for synaptic proteins and proteins originating from reelin-producing cells and the myelin sheath. We used an MS-based proteomic workflow to profile the CSF proteome in relation to cerebral AD pathology. We report strong evidence of previously reported CSF proteins and several novel CSF proteins specifically associated with amyloid pathology or neuronal injury and tau hyperphosphorylation

Circadian and Feeding Rhythms Orchestrate the Diurnal Liver Acetylome.

Lysine acetylation is involved in various biological processes and is considered a key reversible post-translational modification in the regulation of gene expression, enzyme activity, and subcellular localization. This post-translational modification is therefore highly relevant in the context of circadian biology, but its characterization on the proteome-wide scale and its circadian clock dependence are still poorly described. Here, we provide a comprehensive and rhythmic acetylome map of the mouse liver. Rhythmic acetylated proteins showed subcellular localization-specific phases that correlated with the related metabolites in the regulated pathways. Mitochondrial proteins were over-represented among the rhythmically acetylated proteins and were highly correlated with SIRT3-dependent deacetylation. SIRT3 activity being nicotinamide adenine dinucleotide (NAD) <sup>+</sup> level-dependent, we show that NAD <sup>+</sup> is orchestrated by both feeding rhythms and the circadian clock through the NAD <sup>+</sup> salvage pathway but also via the nicotinamide riboside pathway. Hence, the diurnal acetylome relies on a functional circadian clock and affects important diurnal metabolic pathways in the mouse liver

Indigencia, un abordaje multidisciplinar y una propuesta de intervención en la Zona Centro de Guadalajara

El trabajo se propone hacer un abordaje multidisciplinario de tipo exploratorio en el que se estudien aspectos legales, económicos, sociales, asistenciales, culturales y de difusión del fenómeno de la indigencia y de los actores que la viven y conviven con ella pensando en que este tema podría dar pie a abordajes más profundos desde la academia y otras instancias