Regulación de la producción mínima en las concesiones mineras del Perú

La minería a lo largo del tiempo ha sido pieza fundamental en el desarrollo de la economía del Perú, su importancia ha ido tomando mayor relevancia con su evolución. Al ser un país con una gran diversidad de recursos naturales, permite que su actividad genere grandes aportes para el erario del Estado, convirtiéndose en fuente vital para el dinamismo económico. Dicha actividad consiste en la extracción de minerales que se encuentran en los yacimientos del territorio. De tal modo, según lo indicado por la Constitución Política del Perú, el Estado es soberano en su aprovechamiento, siendo su mayor interés que los recursos naturales del territorio sean explotados y aprovechados de manera sostenible, teniendo como principal beneficiaria a la nación, generando réditos (producto del impuesto a la renta, regalía minera, pago de derecho de vigencia y otros) que serán distribuidos entre los gobiernos locales, regionales y central. De esta manera, al ser una actividad tan importante para el país amerita una adecuada regulación en todo su proceso, por tal motivo en el desarrollo del presente trabajo se expondrá la normativa adecuada para su aplicación. Posteriormente, se identificó una ambigüedad en la legislación encargada de regular la producción de los recursos minerales, que conlleva a consecuencias poco favorables para el Estado, desviando el fin esencial de su otorgamiento. En merito a lo indicado en el párrafo anterior, la presente investigación busca analizar las normas correspondientes y la incorrecta aplicación en dicha actividad, con el fin de viabilizar de acuerdo al concepto Constitucional el adecuado desarrollo productivo de la actividad minera en el Perú.Trabajo de suficiencia profesionalCampus Arequip

Upregulation of Trem2 expression occurs exclusively on microglial contact with plaques

Using spatial cell-type-enriched transcriptomics, we compare plaque-induced gene (PIG) expression in microglia touching plaques, neighboring plaques, and far from plaques in 18-month-old APPNLF/NLF knock-in mice with and without the Alzheimer’s disease risk mutation Trem2R47H/R47H. We report that, in AppNLF/NLF mice, expression of 35/55 PIGs, is exclusively upregulated in microglia that are touching plaques. In 7 PIGs including Trem2 this upregulation is prevented by the Trem2R47H/R47H mutation. Unlike in young mice, knockin of the Trem2R47H/R47H mutation does not significantly decrease the Trem2 expression but decreases protein levels by 20% in the absence of plaques. On plaques, despite the mutation preventing increased gene expression, TREM2 protein levels increased by 1.6-fold (compared to 3-fold with Trem2WT/WT) and microglial density increased 20-fold compared to 30-fold. Hence microglia must touch plaques before Trem2 gene expression is increased but small changes in protein expression can increase microglia density without a change in gene expression

Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology

Using spatial cell-type-enriched transcriptomics, we compare plaque-induced gene (PIG) expression in microglia-touching plaques, neighboring plaques, and far from plaques in an aged Alzheimer’s mouse model with late plaque development. In 18-month-old APPNL-F/NL-F knockin mice, with and without the Alzheimer’s disease risk mutation Trem2R47H/R47H, we report that expression of 38/55 PIGs have plaque-induced microglial upregulation, with a subset only upregulating in microglia directly contacting plaques. For seven PIGs, including Trem2, this upregulation is prevented in APPNL-F/NL-FTrem2R47H/R47H mice. These TREM2-dependent genes are all involved in phagocytic and degradative processes that we show correspond to a decrease in phagocytic markers and an increase in the density of small plaques in Trem2-mutated mice. Furthermore, despite the R47H mutation preventing increased Trem2 gene expression, TREM2 protein levels and microglial density are still marginally increased on plaques. Hence, both microglial contact with plaques and functioning TREM2 are necessary for microglia to respond appropriately to amyloid patholog

Anti-Inflammatory Activity and Changes in Antioxidant Properties of Leaf and Stem Extracts from Vitex mollis

Vitex mollis is used in traditional Mexican medicine for the treatment of some ailments. However, there are no studies on what happens to the anti-inflammatory activity or antioxidant properties and total phenolic content of leaves and stem extracts of Vitex mollis during the digestion process; hence, this is the aim of this work. Methanolic, acetonic, and hexanic extracts were obtained from both parts of the plant. Extract yields and anti-inflammatory activity (elastase inhibition) were measured. Additionally, changes in antioxidant activity (DPPH and ABTS) and total phenols content of plant extracts before and after in vitro digestion were determined. The highest elastase inhibition to prevent inflammation was presented by hexanic extracts (leaf = 94.63% and stem = 98.30%). On the other hand, the major extract yield (16.14%), antioxidant properties (ABTS = 98.51% and DPPH = 94.47% of inhibition), and total phenols (33.70 mg GAE/g of dried sample) were showed by leaf methanolic extract. Finally, leaf and stem methanolic extracts presented an antioxidant activity increase of 35.25% and 27.22%, respectively, in comparison to their initial values after in vitro digestion process. All samples showed a decrease in total phenols at the end of the digestion. These results could be the basis to search for new therapeutic agents from Vitex mollis

Need for tripeptidyl-peptidase II in major histocompatibility complex class I viral antigen processing when proteasomes are detrimental

CD8(+) T lymphocytes recognize infected cells that display virus-derived antigenic peptides complexed with major histocompatibility complex class I molecules. Peptides are mainly byproducts of cellular protein turnover by cytosolic proteasomes. Cytosolic tripeptidyl-peptidase II (TPPII) also participates in protein degradation. Several peptidic epitopes unexpectedly do not require proteasomes, but it is unclear which proteases generate them. We studied antigen processing of influenza virus nucleoprotein epitope NP(147-155), an archetype epitope that is even destroyed by a proteasome-mediated mechanism. TPPII, with the assistance of endoplasmic reticulum trimming metallo-aminopeptidases, probably ERAAP (endoplasmic reticulum aminopeptidase associated with antigen processing), was crucial for nucleoprotein epitope generation both in the presence of functional proteasomes and when blocked by lactacystin, as shown with specific chemical inhibitors and gene silencing. Different protein contexts and subcellular targeting all allowed epitope processing by TPPII as well as trimming. The results show the plasticity of the cell's assortment of proteases for providing ligands for recognition by antiviral CD8(+) T cells. Our observations identify for the first time a set of proteases competent for antigen processing of an epitope that is susceptible to destruction by proteasomes.This work was supported in part by grants from Spanish Ministerio de Educación y Ciencia and from Instituto de Salud Carlos III (to M. D. V.), by a grant from Spanish Ministerio de Educación y Ciencia (to L. C. A.), by an institutional grant from the Fundación Ramón Areces to the Centro de Biología Molecular Severo Ochoa, and by a grant from Comunidad de Madrid (to M. D. V. and L. C. A.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.S

Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder

Studies of the major psychoses, schizophrenia (SZ) and bipolar disorder (BD), have traditionally focused on genetic and environmental risk factors, although more recent work has highlighted an additional role for epigenetic processes in mediating susceptibility. Since monozygotic (MZ) twins share a common DNA sequence, their study represents an ideal design for investigating the contribution of epigenetic factors to disease etiology. We performed a genome-wide analysis of DNA methylation on peripheral blood DNA samples obtained from a unique sample of MZ twin pairs discordant for major psychosis. Numerous loci demonstrated disease-associated DNA methylation differences between twins discordant for SZ and BD individually, and together as a combined major psychosis group. Pathway analysis of our top loci highlighted a significant enrichment of epigenetic changes in biological networks and pathways directly relevant to psychiatric disorder and neurodevelopment. The top psychosis-associated, differentially methylated region, significantly hypomethylated in affected twins, was located in the promoter of ST6GALNAC1 overlapping a previously reported rare genomic duplication observed in SZ. The mean DNA methylation difference at this locus was 6%, but there was considerable heterogeneity between families, with some twin pairs showing a 20% difference in methylation. We subsequently assessed this region in an independent sample of postmortem brain tissue from affected individuals and controls, finding marked hypomethylation (>25%) in a subset of psychosis patients. Overall, our data provide further evidence to support a role for DNA methylation differences in mediating phenotypic differences between MZ twins and in the etiology of both SZ and BD

State Control and the Effects of Foreign Relations on Bilateral Trade

Do states use trade to reward and punish partners? WTO rules and the pressures of globalization restrict states’ capacity to manipulate trade policies, but we argue that governments can link political goals with economic outcomes using less direct avenues of influence over firm behavior. Where governments intervene in markets, politicization of trade is likely to occur. In this paper, we examine one important form of government control: state ownership of firms. Taking China and India as examples, we use bilateral trade data by firm ownership type, as well as measures of bilateral political relations based on diplomatic events and UN voting to estimate the effect of political relations on import and export flows. Our results support the hypothesis that imports controlled by state-owned enterprises (SOEs) exhibit stronger responsiveness to political relations than imports controlled by private enterprises. A more nuanced picture emerges for exports; while India’s exports through SOEs are more responsive to political tensions than its flows through private entities, the opposite is true for China. This research holds broader implications for how we should think about the relationship between political and economic relations going forward, especially as a number of countries with partially state-controlled economies gain strength in the global economy

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants

International Nosocomial Infection Control Consortium (INICC) report, data summary for 2003-2008, issued June 2009

Q3Artículo original95-106We report the results of the International Infection Control Consortium (INICC) surveillance study from January 2003 throughDecember 2008 in 173 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study, using Centersfor Disease Control and Prevention (CDC) US National Healthcare Safety Network (NHSN; formerly the National Nosocomial Infec-tion Surveillance system [NNIS]) definitions for device-associated health care-associated infection, we collected prospective datafrom 155,358 patients hospitalized in the consortium’s hospital ICUs for an aggregate of 923,624 days. Although device utilizationin the developing countries’ ICUs was remarkably similar to that reported from US ICUs in the CDC’s NHSN, rates of device-asso-ciated nosocomial infection were markedly higher in the ICUs of the INICC hospitals: the pooled rate of central venous catheter(CVC)-associated bloodstream infections (BSI) in the INICC ICUs, 7.6 per 1000 CVC-days, is nearly 3-fold higher than the 2.0 per1000 CVC-days reported from comparable US ICUs, and the overall rate of ventilator-associated pneumonia (VAP) was also farhigher, 13.6 versus 3.3 per 1000 ventilator-days, respectively, as was the rate of catheter-associated urinary tract infection (CAUTI),6.3 versus 3.3 per 1000 catheter-days, respectively. Most strikingly, the frequencies of resistance ofStaphylococcus aureusisolatesto methicillin (MRSA) (84.1% vs 56.8%, respectively),Klebsiella pneumoniaeto ceftazidime or ceftriaxone (76.1% vs 27.1%, respec-tively),Acinetobacter baumanniito imipenem (46.3% vs 29.2%, respectively), andPseudomonas aeruginosato piperacillin (78.0%vs 20.2%, respectively) were also far higher in the consortium’s ICUs, and the crude unadjusted excess mortalities of device-relatedinfections ranged from 23.6% (CVC-associated bloodstream infections) to 29.3% (VAP)