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1.
Ecology ; 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31840235

RESUMO

Tropical forests hold 30% of Earth's terrestrial carbon and at least 60% of its terrestrial biodiversity, but forest loss and degradation are jeopardizing these ecosystems. Although the regrowth of secondary forests has the potential to offset some of the losses of carbon and biodiversity, it remains unclear if secondary regeneration will be affected by climate changes such as higher temperatures and more frequent extreme droughts. We used a dataset of 10 repeated forest inventories spanning two decades (1999-2017) to investigate carbon and tree species recovery and how climate and landscape context influence carbon dynamics in an older secondary forest located in one of the oldest post-Columbian agricultural frontiers in the Brazilian Amazon. Carbon accumulation averaged 1.08 Mg ha-1  yr-1 , while species richness was effectively constant over the studied period. Moreover, we provide evidence that secondary forests are vulnerable to drought stress: carbon balance and growth rates were lower in drier periods. This contrasts with drought responses in primary forests, where changes in carbon dynamics are driven by increased stem mortality. These results highlight an important climate change-vegetation feedback, whereby the increasing dry-season lengths being observed across parts of Amazonia may reduce the effectiveness of secondary forests in sequestering carbon and mitigating climate change. In addition, the current rate of forest regrowth in this region was low compared with previous pan-tropical and Amazonian assessments - our secondary forests reached just 41.1% of the average carbon and 56% of the tree diversity in the nearest primary forests - suggesting that these areas are unlikely to return to their original levels on politically meaningful timescales.

2.
Phys Chem Chem Phys ; 21(48): 26466-26476, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31774419

RESUMO

Perylene bisimides (PBIs) can be functionalised to enable controlled aggregation into complex supramolecular structures and are promising materials for photovoltaic and solar fuel applications. Amino acid appended PBIs such as PBI-alanine (PBI-A) have been found to form photoconductive films containing worm-like structures that enable charge transport. However, despite being strong chromophores in the visible region, when PBI-A films are prepared by drying down solutions, activity only occurs under UV illumination. This limits potential applications. The requirement for UV illumination has previously been suggested to be due to the large ion-pair energy in the low dielectric environment of the dried samples. Hydrogel films, rehydrated xerogels and dry xerogels of PBI-A can also be prepared offering an ideal sample set to examine the influence of hydration on charge-separation. Using transient absorption (TA) spectroscopy, we demonstrate a correlation between water content and efficiency of generation of long-lived charge separated states within the PBI-A materials, highlighting their potential, particularly for light-driven water splitting.

3.
Haematologica ; 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537687

RESUMO

Cancer cells undergo massive alterations in their DNA methylation patterns which result in aberrant gene expression and malignant phenotypes. Abnormal DNA methylation is a prognostic marker in several malignancies, but its potential prognostic significance in adult T-cell acute lymphoblastic leukemia is poorly defined. Here, we performed methylated DNA immunoprecipitation to obtain a comprehensive genome-wide analysis of promoter methylation in adult T-cell Acute Lymphoblastic Leukemia (n=24) compared to normal thymi (n=3). We identified a CpG hypermethylator phenotype that distinguishes two T-cell acute lymphoblastic leukemia subgroups and further validate it in an independent series of 17 T-Lymphoblastic Lymphoma. Next, we identified a methylation classifier based on 9 promoters which accurately predict the methylation phenotype. This classifier was applied to an independent series of 168 primary adult T-cell Acute Lymphoblastic Leukemias treated accordingly to the GRAALL03/05 trial using methylation-specific multiplex ligation-dependent probe amplification. Importantly hypomethylation correlated with specific oncogenic subtypes of T-cell Acute Lymphoblastic Leukemias and identified patients associated with a poor clinical outcome. This methylation-specific multiplex ligation-dependent probe amplification based methylation profiling could be useful for therapeutic stratification of adult T-cell Acute Lymphoblastic Leukemias in routine practice. The GRAALL-2003 and -2005 studies were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively.

4.
Cancer Lett ; 465: 45-58, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31473251

RESUMO

Therapeutic strategies aiming to leverage anti-tumor immunity are being intensively investigated as they show promising results in cancer therapy. The PD-1/PD-L1 pathway constitutes an important target to restore functional anti-tumor immune response. Here, we report that BET protein inhibition suppresses PD-1/PD-L1 in triple-negative breast cancer. BET proteins control PD-1 expression in T cells, and PD-L1 in breast cancer cell models. BET protein targeting reduces T cell-derived interferon-γ production and signaling, thereby suppressing PD-L1 induction in breast cancer cells. Moreover, BET protein inhibition improves tumor cell-specific T cell cytotoxic function. Overall, we demonstrate that BET protein targeting represents a promising strategy to overcome tumor-reactive T cell exhaustion and improve anti-tumor immune responses, by reducing the PD-1/PD-L1 axis in triple-negative breast cancer.

5.
Future Healthc J ; 6(Suppl 1): 47, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31363571
6.
Proc Natl Acad Sci U S A ; 116(27): 13490-13497, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31213547

RESUMO

Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases.

7.
Sci Rep ; 9(1): 6801, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043634

RESUMO

Heart failure (HF) is characterized by poor survival, a loss of catecholamine reserve and cellular structural remodeling in the form of disorganization and loss of the transverse tubule network. Indeed, survival rates for HF are worse than many common cancers and have not improved over time. Tadalafil is a clinically relevant drug that blocks phosphodiesterase 5 with high specificity and is used to treat erectile dysfunction. Using a sheep model of advanced HF, we show that tadalafil treatment improves contractile function, reverses transverse tubule loss, restores calcium transient amplitude and the heart's response to catecholamines. Accompanying these effects, tadalafil treatment normalized BNP mRNA and prevented development of subjective signs of HF. These effects were independent of changes in myocardial cGMP content and were associated with upregulation of both monomeric and dimerized forms of protein kinase G and of the cGMP hydrolyzing phosphodiesterases 2 and 3. We propose that the molecular switch for the loss of transverse tubules in HF and their restoration following tadalafil treatment involves the BAR domain protein Amphiphysin II (BIN1) and the restoration of catecholamine sensitivity is through reductions in G-protein receptor kinase 2, protein phosphatase 1 and protein phosphatase 2 A abundance following phosphodiesterase 5 inhibition.

8.
Plant Dis ; 103(6): 1075-1083, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31009362

RESUMO

Soybean (Glycine max) has become an important crop in Manitoba, Canada, with a 10-fold increase in dedicated acreage over the past decade. Given the rapid increase in production, scarce information about foliar diseases present in the province has been recorded. In order to describe the foliar pathogens affecting this legume, we harnessed next-generation sequencing (NGS) to carry out a comprehensive survey across Manitoba in 2016. Fields were sampled during the V2/3 (33 fields) and R6 (70 fields) growth stages, with at least three symptomatic leaves per field collected and subjected to RNA sequencing. We successfully detected several bacteria, fungi, and viruses known to infect soybean, including Pseudomonas savastanoi pv. glycinea, Septoria glycines, and Peronospora manshurica, as well as pathogens not previously identified in the province (e.g., Pseudomonas syringae pv. tabaci, Cercospora sojina, and Bean yellow mosaic virus). For some microorganisms, we were able to disentangle the different pathovars present and/or assemble their genome sequence. Since NGS generates data on the entire flora and fauna occupying a leaf sample, we also identified residual pathogens (i.e., pathogens of crops other than soybean) and multiple species of arthropod pests. Finally, the sequence information produced by NGS allowed for the development of polymerase chain reaction-based diagnostics for some of the most widespread and important pathogens. Although there are many benefits of using NGS for large-scale plant pathogen diagnoses, we also discuss some of the limitations of this technology.


Assuntos
Agricultura/métodos , Bactérias/genética , Fungos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Vírus de Plantas/genética , Soja , Sequenciamento de Nucleotídeos em Larga Escala/normas , Manitoba , Soja/microbiologia , Soja/virologia
9.
Faraday Discuss ; 215(0): 84-97, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-30972395

RESUMO

Conjugated ladder polymers (cLaPs) are introduced as organic semiconductors for photocatalytic hydrogen evolution from water under sacrificial conditions. Starting from a linear conjugated polymer (cLiP1), two ladder polymers are synthesized via post-polymerization annulation and oxidation techniques to generate rigidified, planarized materials bearing dibenzo[b,d]thiophene (cLaP1) and dibenzo[b,d]thiophene sulfone subunits (cLaP2). The high photocatalytic activity of cLaP1 (1307 µmol h-1 g-1) in comparison to that of cLaP2 (18 µmol h-1 g-1) under broadband illumination (λ > 295 nm) in the presence of a hole-scavenger is attributed to a higher yield of long-lived charges (µs to ms timescale), as evidenced by transient absorption spectroscopy. Additionally, cLaP1 has a larger overpotential for proton reduction and thus an increased driving force for the evolution of hydrogen under sacrificial conditions.

10.
BMJ Open ; 9(3): e026642, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30872554

RESUMO

OBJECTIVES: Smokers who use e-cigarettes (EC) do so mostly to stop smoking, but many continue to use both products. It is not known whether these 'dual users' are interested in stop-smoking medications and whether they can benefit from them. SETTING, PARTICIPANTS AND MEASURES: Dual users were recruited over social media and posted study questionnaire and saliva kits at baseline, 3 and 6 months. Those interested in varenicline were posted the medication and received weekly calls over the first 6 weeks, followed by three calls at fortnightly intervals. RESULTS: Of 204 participants, 124 (61%, CI=54% to 68%) expressed interest in receiving varenicline and 80 (39%, CI=32% to 45%) started varenicline (varenicline users, VU). VU were more dependent smokers (F=6.2, p=0.01) with higher cigarette consumption (F=8.7, p<0.01) who were using stronger nicotine e-liquids (F=13.9, p<0.001) than dual users not opting for varenicline (varenicline non-users, VN). In terms of abstinence for at least 3 months at the 6-month follow-up, VU were more likely than VN to report abstinence from smoking (17.5% vs 4.8%, p=0.006, RR=3.6, CI:1.4 to 9.0), vaping (12.5% vs 1.6%, p=0.007, RR=7.8, CI:1.7 to 34.5) and both smoking and vaping (8.8% vs 0.8%, p=0.02, RR=10.9, CI:1.4 to 86.6). The differences were significant across sensitivity analyses (RRs=4.9 to 14.0; p=0.02 to p<0.001 at 3 months; RRs=3.0 to 14.0; p=0.01 to p<0.001 at 6 months). VU reported a greater reduction in enjoyment of vaping by the end of the varenicline use period (F=4.1, p=0.04) and recorded a significantly greater reduction in nicotine intake than VN at 3 months (F=13.9, p<0.001) and 6 months (F=26.5, p<0.001). CONCLUSION: Varenicline offered to dual users is likely to promote successful abstinence from both smoking and vaping, although a randomised trial is needed to confirm this. Among dual users who want to stop smoking, there seems to be a high level of interest in smoking-cessation treatments.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30691217

RESUMO

Drinking water monitoring is essential for identifying health-related risks, as well as for building foundations for management of safe drinking water supplies. However, statistical analyses of drinking water quality monitoring data are challenging because of non-normal (skewed distributions) and missing values. Therefore, a new method combining a water quality index (WQI) with spatial analysis is introduced in this paper to fill the gap between data collection and data analysis. Water constituent concentrations in different seasons and from different water sources were compared based on WQIs. To generate a WQI map covering all of the study areas, predicted WQI values were created for locations in the study area based on spatial interpolation from nearby observed values. The accuracy value of predicted and measured values of our method was 0.99, indicating good predication performance. Overall, the results of this study indicate that this method will help fill the gap between the collection of large amounts of drinking water data and data analysis for drinking water monitoring and process control.


Assuntos
Água Potável/análise , Monitoramento Ambiental/métodos , Análise Espacial , Qualidade da Água/normas , Estações do Ano , Abastecimento de Água
12.
Clin Cancer Res ; 25(8): 2483-2493, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30659025

RESUMO

PURPOSE: Biological explanation for discrepancies in patient-related response to chemotherapy depending on the underlying oncogenic events is a promising research area. TLX1- or TLX3-deregulated T-cell acute lymphoblastic leukemias (T-ALL; TLX1/3+) share an immature cortical phenotype and similar transcriptional signatures. However, their prognostic impacts differ, and inconsistent clinical outcome has been reported for TLX3. We therefore hypothesized that the overlapping transcriptional profiles of TLX1+ and TLX3+ T-ALLs would allow identification of candidate genes, which might determine their distinct clinical outcomes. EXPERIMENTAL DESIGN: We compared TLX1+ and TLX3+ adult T-ALL outcome in the successive French national LALA-94 and GRAALL-2003/2005 multicentric trials and analyzed transcriptomic data to identify differentially expressed genes. Epigenetic regulation of asparagine synthetase (ASNS) and in vitro l-asparaginase sensitivity were evaluated for T-ALL cell lines and primary samples. RESULTS: We show that TLX1+ patients expressed low levels of ASNS when compared with TLX3+ and TLX-negative patients, due to epigenetic silencing of ASNS by both DNA methylation and a decrease of active histone marks. Promoter methylation of the ASNS gene correlated with l-asparaginase sensitivity in both T-ALL cell lines and patient-derived xenografts. Finally, ASNS promoter methylation was an independent prognostic factor for both event-free survival [HR, 0.42; 95% confidence interval (CI), 0.24-0.71; P = 0.001] and overall survival (HR, 0.40; 95% CI, 0.23-0.70; P = 0.02) in 160 GRAALL-2003/2005 T-ALL patients and also in an independent series of 47 LL03-treated T lymphoblastic lymphomas (P = 0.012). CONCLUSIONS: We conclude that ASNS methylation status at diagnosis may allow individual adaptation of l-asparaginase dose.

13.
Ticks Tick Borne Dis ; 10(3): 515-522, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30612950

RESUMO

For more than 50 years DEET (N,N-Diethyl-m-toluamide) has been considered the gold standard of repellents. It is applied to the skin or clothing to deter mosquitoes and other blood-sucking invertebrate pests from approaching and/or settling, and ultimately it provides temporary protection from bites. Despite rampant global use, surprisingly little is understood about DEET's mode of action and the molecular targets of the active ingredient. Furthermore, the theories into its mechanism for repellency are largely based off fruit fly and mosquito research. Since ticks possess a unique sensory structure, the Haller's organ, the specific genes and pathways associated with DEET avoidance may differ from insects. In these studies, we collected American dog ticks (Dermacentor variabilis) from four natural populations within Manitoba, Canada. We first carried out behavior assays, which showed DEET effectively repelled the ticks. RNA sequencing revealed that DEET caused a rapid and substantial reduction in the abundance of transcripts encoding cytochrome P450 and acetylcholinesterase genes, which gradually recovered over the 24 h time course. Finally, enzymatic kinetics provided functional support for DEET's role as an effective inhibitor of P450 s. While many facets of its mode of action remain to be worked out, our study provides valuable insights into the molecular underpinnings of DEET's repellence in ticks.


Assuntos
Inibidores da Colinesterase/farmacologia , Inibidores das Enzimas do Citocromo P-450/farmacologia , DEET/farmacologia , Dermacentor/efeitos dos fármacos , Repelentes de Insetos/farmacologia , Animais , Colinesterases/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Dermacentor/enzimologia , Expressão Gênica , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala
14.
Theriogenology ; 125: 249-258, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30476758

RESUMO

In cattle breeding, the development of genomic selection strategies based on single nucleotide polymorphism (SNP) interrogation has led to improved rates of genetic gain. Additionally, the application of genomic selection to in-vitro produced (IVP) embryos is expected to bring further benefits thanks to the ability to test a greater number of individuals before establishing a pregnancy and to ensure only carriers of desirable traits are born. However, aneuploidy, a leading cause of developmental arrest, is known to be common in IVP embryos. Karyomapping is a comprehensive screening test based on SNP typing that can be used for simultaneous genomic selection and aneuploidy detection, offering the potential to maximize pregnancy rates. Moreover, Karyomapping can be used to characterize the frequency and parental origin of aneuploidy in bovine IVP embryos, which have remained underexplored to date. Here, we report the use of Karyomapping to characterize the frequency and parental origin of aneuploidy in IVP bovine embryos in order to establish an estimate of total aneuploidy rates in each parental germline. We report an estimate of genome wide recombination rate in cattle and demonstrate, for the first time, a proof of principle for the application of Karyomapping to cattle breeding, with the birth of five calves after screening. This combined genomic selection and aneuploidy screening approach was highly reliable, with calves showing 98% concordance with their respective embryo biopsies for SNP typing and 100% concordance with their respective biopsies for aneuploidy screening. This approach has the potential to simultaneously improve pregnancy rates following embryo transfer and the rate of genetic gain in cattle breeding, and is applicable to basic research to investigate meiosis and aneuploidy.


Assuntos
Aneuploidia , Blastocisto/fisiologia , Bovinos/embriologia , Mapeamento Cromossômico/veterinária , Cariotipagem/veterinária , Diagnóstico Pré-Implantação/veterinária , Animais , Bovinos/genética , Mapeamento Cromossômico/métodos , Transferência Embrionária/veterinária , Embrião de Mamíferos , Feminino , Fertilização In Vitro/veterinária , Cariotipagem/métodos , Nascimento Vivo , Polimorfismo de Nucleotídeo Único , Gravidez , Diagnóstico Pré-Implantação/métodos
15.
J Health Psychol ; 24(8): 1011-1022, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28810431

RESUMO

Despite a medical discourse of the 'normalisation' of HIV, it remains a highly stigmatising condition and makes the issue of disclosing one's HIV status particularly complex. This article reports on the experience of 18 people living with HIV in the United Kingdom of disclosing their HIV+ status in arguably their most important relationship, their intimate partnership. Five main themes arose: disclosure as the battlefield, preparing psychologically to disclose, disclosure as a test of the partner's love, disclosure as an opportunity for the partner to know them more deeply and the renegotiation of the relationship narrative.

16.
Ann Rheum Dis ; 78(2): 249-260, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30472652

RESUMO

BACKGROUND: The phosphatidylinositol 3-kinase delta isoform (PI3Kδ) belongs to an intracellular lipid kinase family that regulate lymphocyte metabolism, survival, proliferation, apoptosis and migration and has been successfully targeted in B-cell malignancies. Primary Sjögren's syndrome (pSS) is a chronic immune-mediated inflammatory disease characterised by exocrine gland lymphocytic infiltration and B-cell hyperactivation which results in systemic manifestations, autoantibody production and loss of glandular function. Given the central role of B cells in pSS pathogenesis, we investigated PI3Kδ pathway activation in pSS and the functional consequences of blocking PI3Kδ in a murine model of focal sialoadenitis that mimics some features of pSS. METHODS AND RESULTS: Target validation assays showed significant expression of phosphorylated ribosomal protein S6 (pS6), a downstream mediator of the phosphatidylinositol 3-kinase delta (PI3Kδ) pathway, within pSS salivary glands. pS6 distribution was found to co-localise with T/B cell markers within pSS aggregates and the CD138+ plasma cells infiltrating the glands. In vivo blockade of PI3Kδ activity with seletalisib, a PI3Kδ-selective inhibitor, in a murine model of focal sialoadenitis decreased accumulation of lymphocytes and plasma cells within the glands of treated mice in the prophylactic and therapeutic regimes. Additionally, production of lymphoid chemokines and cytokines associated with ectopic lymphoneogenesis and, remarkably, saliva flow and autoantibody production, were significantly affected by treatment with seletalisib. CONCLUSION: These data demonstrate activation of PI3Kδ pathway within the glands of patients with pSS and its contribution to disease pathogenesis in a model of disease, supporting the exploration of the therapeutic potential of PI3Kδ pathway inhibition in this condition.


Assuntos
Fosfatidilinositol 3-Quinase/metabolismo , Piridinas/farmacologia , Quinolinas/farmacologia , Sialadenite/enzimologia , Transdução de Sinais/efeitos dos fármacos , Síndrome de Sjogren/enzimologia , Animais , Autoanticorpos/biossíntese , Linfócitos B/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Camundongos , Fosfatidilinositol 3-Quinase/efeitos dos fármacos , Plasmócitos/metabolismo , Proteína S6 Ribossômica/metabolismo , Glândulas Salivares/metabolismo , Sialadenite/tratamento farmacológico , Síndrome de Sjogren/tratamento farmacológico
17.
J Am Heart Assoc ; 7(23): e009972, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30520673

RESUMO

Background Atrial fibrillation ( AF ) is common in the elderly, but rare in the young; however, the changes that occur with age that promote AF are not fully understood. Action potential ( AP ) alternans may be involved in the initiation of AF . Using a translationally relevant model, we investigated whether age-associated atrial vulnerability to AF was associated with susceptibility to AP alternans. Methods and Results AF was induced in conscious young and old sheep using 50 Hz burst pacing. Old sheep were more vulnerable to AF . Monophasic and cellular AP s were recorded from the right atrium in vivo and from myocytes isolated from the left and right atrial appendages. AP alternans occurred at lower stimulation frequencies in old sheep than young in vivo (old, 3.0±0.1 Hz; young, 3.3±0.1 Hz; P<0.05) and in isolated myocytes (old, 1.6±0.1 Hz; young, 2.0±0.1 Hz; P<0.05). Simultaneous recordings of [Ca2+]i and membrane potential in myocytes showed that alternans of AP s and [Ca2+]i often occurred together. However, at low stimulation rates [Ca2+]i alternans could occur without AP alternans, whereas at high stimulation rates AP alternans could still be observed despite disabling Ca2+ cycling using thapsigargin. Conclusions We have shown, for the first time in a large mammalian model, that aging is associated with increased duration of AF and susceptibility to AP alternans. We suggest that instabilities in Ca2+ handling initiate alternans at low stimulation rates, but that AP restitution alone can sustain alternans at higher rates.


Assuntos
Potenciais de Ação/fisiologia , Fibrilação Atrial/etiologia , Fatores Etários , Animais , Fibrilação Atrial/fisiopatologia , Função Atrial/fisiologia , Cálcio/fisiologia , Suscetibilidade a Doenças/etiologia , Feminino , Átrios do Coração/fisiopatologia , Potenciais da Membrana/fisiologia , Células Musculares/fisiologia , Ovinos
18.
Artigo em Inglês | MEDLINE | ID: mdl-30591690

RESUMO

In many regions where drinking water supply is intermittent and unreliable, households adapt by storing water in cisterns or rooftop tanks. Both intermittent supply and stored water can be vulnerable to contamination by microorganisms with deleterious health effects. The Metropolitan Zone of Guadalajara is a rapidly growing urban center with over five million residents where household storage is nearly ubiquitous. This pilot study was conducted in July 2018 to examine the microbiological quality of drinking water in Guadalajara. Samples were tested for free available chlorine residual, total coliform bacteria, and Escherichia coli. A survey on access to water and public perspectives was also conducted. Water exiting rooftop tanks exceeded regulatory limits for total coliform levels in half of the homes studied. Piped water arriving at two homes had total coliform levels that far exceeded regulatory limits. No E. coli were detected in any of the samples. Only 35% of homes had a chlorine residual between the recommended 0.2 and 1.5 mg/L. Many homes reported unpleasant odors and colors. Only 7% of residents drank the piped water. Future studies are needed, especially during April and May when many homes reported a higher disruption to water service.


Assuntos
Água Potável/microbiologia , Abastecimento de Água , Cloro/análise , Água Potável/análise , Humanos , México , Projetos Piloto , Purificação da Água/métodos , Qualidade da Água
19.
Front Immunol ; 9: 1952, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30258435

RESUMO

Tertiary lymphoid structures (TLS) are frequently observed in target organs of autoimmune diseases. TLS present features of secondary lymphoid organs such as segregated T and B cell zones, presence of follicular dendritic cell networks, high endothelial venules and specialized lymphoid fibroblasts and display the mechanisms to support local adaptive immune responses toward locally displayed antigens. TLS detection in the tissue is often associated with poor prognosis of disease, auto-antibody production and malignancy development. This review focuses on the contribution of TLS toward the persistence of the inflammatory drive, the survival of autoreactive lymphocyte clones and post-translational modifications, responsible for the pathogenicity of locally formed autoantibodies, during autoimmune disease development.


Assuntos
Autoanticorpos/imunologia , Linfócitos B/imunologia , Células Dendríticas Foliculares/imunologia , Imunidade Humoral , Neoplasias/imunologia , Estruturas Linfoides Terciárias/imunologia , Animais , Autoimunidade , Linfócitos B/patologia , Células Dendríticas Foliculares/patologia , Humanos , Neoplasias/patologia , Estruturas Linfoides Terciárias/patologia
20.
Mol Cell ; 71(6): 923-939.e10, 2018 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-30174292

RESUMO

The approximately thirty core subunits of kinetochores assemble on centromeric chromatin containing the histone H3 variant CENP-A and connect chromosomes with spindle microtubules. The chromatin proximal 16-subunit CCAN (constitutive centromere associated network) creates a mechanically stable bridge between CENP-A and the kinetochore's microtubule-binding machinery, the 10-subunit KMN assembly. Here, we reconstituted a stoichiometric 11-subunit human CCAN core that forms when the CENP-OPQUR complex binds to a joint interface on the CENP-HIKM and CENP-LN complexes. The resulting CCAN particle is globular and connects KMN and CENP-A in a 26-subunit recombinant particle. The disordered, basic N-terminal tail of CENP-Q binds microtubules and promotes accurate chromosome alignment, cooperating with KMN in microtubule binding. The N-terminal basic tail of the NDC80 complex, the microtubule-binding subunit of KMN, can functionally replace the CENP-Q tail. Our work dissects the connectivity and architecture of CCAN and reveals unexpected functional similarities between CENP-OPQUR and the NDC80 complex.


Assuntos
Proteínas Cromossômicas não Histona/ultraestrutura , Cinetocoros/fisiologia , Cinetocoros/ultraestrutura , Centrômero/fisiologia , Proteína Centromérica A/metabolismo , Proteína Centromérica A/ultraestrutura , Proteínas Cromossômicas não Histona/metabolismo , Proteínas do Citoesqueleto , Células HeLa , Humanos , Cinetocoros/metabolismo , Microtúbulos/metabolismo , Microtúbulos/fisiologia , Proteínas Nucleares/metabolismo
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