Sit4 Genetically Interacts with Vps27 to Regulate Mitochondrial Function and Lifespan in .

The Sit4 protein phosphatase plays a key role in orchestrating various cellular processes essential for maintaining cell viability during aging. We have previously shown that deletion promotes vacuolar acidification, mitochondrial derepression, and oxidative stress resistance, increasing yeast chronological lifespan. In this study, we performed a proteomic analysis of isolated vacuoles and yeast genetic interaction analysis to unravel how Sit4 influences vacuolar and mitochondrial function.

Beta-Adrenergic Blockade in Advanced Non-Small Cell Lung Cancer Patients Receiving Immunotherapy: A Multicentric Study.

Introduction The standard treatment of cancer has dramatically improved with immune checkpoint inhibitors (ICIs). Despite their proven advantage, many patients fail to exhibit a meaningful and lasting response. The beta-adrenergic signalling pathway may hold significant promise due to its role in promoting an immunosuppressive milieu within the tumour microenvironment.

Communication preferences and perceptions of cancer patient during their first medical oncology appointment.

Background: The first medical oncology appointment serves as a platform for patients to comprehend their diagnosis and prognostic implications of cancer. This study aimed to determine patients' communication preferences during their first medical oncology appointment and to assess the disparities between patients' preferences and perceptions.

Methods: A total of 169 cancer patients participated by completing the Communication in First Medical Oncology Appointment Questionnaire (C-FAQ), a two-section questionnaire designed to assess patients' preferences and perceptions regarding Content (information provided and its extent), Facilitation (timing and location of information delivery), and Support (emotional support) during their first medical oncology appointment.

Iron Limitation Restores Autophagy and Increases Lifespan in the Yeast Model of Niemann-Pick Type C1.

Niemann-Pick type C1 (NPC1) is an endolysosomal transmembrane protein involved in the export of cholesterol and sphingolipids to other cellular compartments such as the endoplasmic reticulum and plasma membrane. NPC1 loss of function is the major cause of NPC disease, a rare lysosomal storage disorder characterized by an abnormal accumulation of lipids in the late endosomal/lysosomal network, mitochondrial dysfunction, and impaired autophagy. NPC phenotypes are conserved in yeast lacking Ncr1, an orthologue of human NPC1, leading to premature aging.

Mitochondrial respiration promotes Cdc37-dependent stability of the Cdk1 homolog Cdc28.

Cdc28, the homolog of mammalian Cdk1, is a conserved key regulatory kinase for all major cell cycle transitions in yeast. We have found that defects in mitochondrial respiration (including deletion of ATP2, an ATP synthase subunit) inhibit growth of cells carrying a degron allele of Cdc28 (cdc28td) or Cdc28 temperature-sensitive mutations (cdc28-1 and cdc28-1N) at semi-permissive temperatures. Loss of cell proliferation in the atp2Δcdc28td double mutant is associated with aggravated cell cycle arrest and mitochondrial dysfunction, including mitochondrial hyperpolarization and fragmentation.

Phosphoregulation of the ATP synthase beta subunit stimulates mitochondrial activity for G2/M progression.

Mitochondrial ATP synthase is a multifunctional enzyme complex involved in ATP production. We previously reported that the ATP synthase catalytic beta subunit (Atp2p in yeast) is regulated by the 2A-like protein phosphatase Sit4p, which targets Atp2p at T124/T317 impacting on ATP synthase levels and mitochondrial respiration. Here we report that Atp2-T124/T317 is also potentially regulated by Cdc5p, a polo-like mitotic kinase.

Target of Rapamycin Complex 1 (TORC1), Protein Kinase A (PKA) and Cytosolic pH Regulate a Transcriptional Circuit for Lipid Droplet Formation.

Lipid droplets (LDs) are ubiquitous organelles that fulfill essential roles in response to metabolic cues. The identification of several neutral lipid synthesizing and regulatory protein complexes have propelled significant advance on the mechanisms of LD biogenesis in the endoplasmic reticulum (ER). However, our understanding of signaling networks, especially transcriptional mechanisms, regulating membrane biogenesis is very limited.

Production of IL-1β, IL-6 and CXCL8 by endometrium of crossbred heifers stimulated with various pathogen-associated molecular patterns.

Uterine bacterial infections are common during the post-partum period of dairy herds and, apparently, incidences in crossbred cattle are less than in Holsteins. The aims of this study were (I) to evaluate production of interleukin 1-β (IL-1β), interleukin-6 (IL-6) and chemokine CXCL8 using endometrial explants from Bos indicus crossbred heifers at diestrous, stimulated by various pathogen-associated molecular patterns (PAMP), and (II) assess production of these cytokines by lipopolysaccharide-stimulated endometrial explants from heifers when samples were collected at different stages of estrous cycle. In the first experiment, endometrial explants from heifers at diestrous were stimulated by ten-fold serial dilutions of lipopolysaccharide (LPS), triacylated lipopeptide (PAM3) or peptidoglycan (PGN).

Signaling pathways governing iron homeostasis in budding yeast.

Iron is an essential element for eukaryotes as it participates as a redox-active co-factor in many biological processes. Since iron is also potentially toxic, iron levels are carefully regulated. In the yeast Saccharomyces cerevisiae, iron homeostasis is maintained by the transcriptional control of the iron acquisition systems (iron regulon), mainly by the iron-responsive transcriptional factors Aft1p and Yap5p.

Incentives and barriers to HIV testing among female sex workers in Ceará.

Objective: Estimating HIV prevalence and describing the incentives and barriers for HIV testing among female sex workers.

Methods: This cross-sectional study recruited 402 women aged 18 years or older, residing in Fortaleza, state of Ceará, Brazil, who reported having had sexual intercourse in exchange for money in last four months. The sample was recruited using Respondent Driven Sampling, between August and November 2010.

The ceramide activated protein phosphatase Sit4 impairs sphingolipid dynamics, mitochondrial function and lifespan in a yeast model of Niemann-Pick type C1.

The Niemann-Pick type C is a rare neurodegenerative disease that results from loss-of-function point mutations in NPC1 or NPC2, which affect the homeostasis of sphingolipids and sterols in human cells. We have previously shown that yeast lacking Ncr1, the orthologue of human NPC1 protein, display a premature ageing phenotype and higher sensitivity to oxidative stress associated with mitochondrial dysfunctions and accumulation of long chain bases. In this study, a lipidomic analysis revealed specific changes in the levels of ceramide species in ncr1Δ cells, including decreases in dihydroceramides and increases in phytoceramides.

[Evaluation of implementation of the protocol for managing tuberculosis/ human immunodeficiency virus coinfection in specialized care services in ceará state].

Objectives: Identify barriers and strategies for implementation of the protocol for managing tuberculosis/ human immunodeficiency virus (TB/HIV) coinfection in specialized care services in Ceará state, through evaluation research.

Methods: The study followed iPIER methodology, a new initiative to help improve the implementation of health programs through the use of research that is conducted as a part of the implementation process. Data were collected on the structure and processes of 22 services and barriers were explored in four focus groups with 28 participants, from the standpoint of the health team, administrators, and users.

Hazardous alcohol use among transwomen in a Brazilian city.

There is a lack of information about alcohol use by transgender women. We estimated the prevalence of dangerous alcohol use in the last 12 months by transgender women, who are known as travestis in Brazil, and we identified the associated risk factors. Three hundred travestis were recruited using Respondent Driving Sampling (RDS).

Changes in endometrial transcription of TLR2, TLR4, and CD14 during the first-week postpartum in dairy cows with retained placenta.

Changes in the endometrial transcription of pattern recognition receptors may increase the susceptibility to postpartum uterine infections in Holstein cows with retained placenta. To test this hypothesis, nine cows with retained placenta and ten cows without retained placenta were submitted to endometrial biopsies at the first and seventh days postpartum. Cows were monitored weekly with clinical and gynecological examinations until 42 days postpartum.

Comparative proteomic analyses of urine from rat urothelial carcinoma chemically induced by exposure to N-butyl-N-(4-hydroxybutyl)-nitrosamine.

Bladder cancer is estimated to be the ninth most common malignancy with a high rate of recurrence and progression despite therapy, early diagnosis being crucial for timely intervention. Using a well-established animal model of urothelial carcinoma, we performed a comprehensive analysis of urine proteome profile from healthy animals and animals with urothelial carcinoma at two time-points of disease pathogenesis. GeLC-MS/MS, followed by bioinformatics analysis of unique proteins and the ones present in significantly distinct levels among groups, highlighted the biological processes involved in disease pathogenesis such as, for instance, response to selenium and to drugs, neutral lipid metabolism at earlier stages of disease, and inflammation, immune response and wound healing at advanced stages.

Molecular detection of haemotropic Mycoplasma species in urban and rural cats from Portugal.

Objectives: The aim of the present study was to evaluate the prevalence of haemoplasma infection in cats in Portugal and to assess risk factors for infection.

Methods: Real-time polymerase chain reaction techniques were used to assess 236 urban and rural cats from central and southern Portugal.

Results: The overall prevalence of haemoplasma in the target population was 27.

Biomarkers for cardiac cachexia: reality or utopia.

Cardiac cachexia is a serious complication of chronic heart failure, characterized by significant weight loss and body wasting. Chronic heart failure-related muscle wasting results from a chronic imbalance in the activation of anabolic or catabolic pathways, caused by a series of immunological, metabolic, and neurohormonal processes. In spite of the high morbidity and mortality associated to this condition, there is no universally accepted definition or specific biomarkers for cardiac cachexia, which makes its diagnosis and treatment difficult.

Recent insights on the molecular mechanisms and therapeutic approaches for cardiac cachexia.

Cardiac cachexia (CC) affects a large proportion of patients with chronic heart failure, a major public health issue in western countries. The pathophysiology of CC is complex and multifactorial, resulting from several factors interacting in a complex system with metabolic, immune and neurohormonal consequences, triggered to protect the heart and the circulation from damage. Despite the adverse clinical effects, CC diagnosis is not straightforward and has not specifically been targeted, with therapeutic strategies only comprising interventions with appetite stimulants, and anti-inflammatory substances.

Travestis, an unexplored population at risk of HIV in a large metropolis of northeast Brazil: a respondent-driven sampling survey.

Travestis are highly vulnerable to HIV infection in Brazil. We conducted a survey among 304 travestis using Respondent-Driven Sampling from August to December 2008. Travestis are young (49% <24 years), poorly educated (55% just elementary school), low social class (62% Class C-E), reside with families (49%) or friends/madam (22%), are victims of homophobia (91%) and violence (61%).

Blood pressure control in hypertensive patients within Family Health Program versus at Primary Healthcare Units: analytical cross-sectional study.

Context And Objective: Hypertension is a public health problem due to its high prevalence and long-term cardiovascular complications. In Brazil in 2005, cardiovascular diseases were responsible for 28% of all deaths. Efforts are being made within primary care to achieve adequate hypertension control.

Transcription of pattern recognition receptors and abortive agents induced chemokines in the bovine pregnant uterus.

Pattern recognition receptors (PRRs) are important components of the innate immune system whose ligands are specific pathogen associated molecular patterns (PAMPs). Considering the scarcity of studies on transcription of PRRs in the pregnant uterus of cows, and its response to PAMPs and microorganisms that cause abortion in cattle, this study aimed to characterize the transcription of TLR1-10, NOD1, NOD2 and MD2 in bovine uterus throughout gestation and to investigate the sensitivity of different uterine tissues at third trimester of pregnancy to purified TLR ligands or heat-killed Brucella abortus, Salmonella enterica serotype Dublin (S. Dublin), Listeria monocytogenes, and Aspergillus fumigatus, by assessing chemokine transcription.

Postpartum toll-like receptors and β-defensin 5 mRNA levels in the endometrium of Holstein cows.

Toll-like receptors (TLRs) and β-defensins are important components of the innate immune system. This study aimed to evaluate endometrial mRNA levels of TLRs (1/6, 2, 4, and 5) and β-defensin 5 in Holstein cows by quantitative real time RT-PCR. Uterine biopsies were performed from 6 to 12 h after parturition, and cows were divided into two groups: (i) cows with placental retention and clinical signs of uterine infection until 45 days postpartum (n=10) or (ii) cows with normal puerperium (n=10).

[Characteristics of the patients seen in 1999 by referral centres for sexually transmitted diseases in Ceará (Northeast Brazil)].

Since 1995, in the State of Ceará, in Northeast Brazil, there is a public health project focusing on training and continuing education of health reference teams taking care of patients with sexually transmitted diseases (STD). An information system including a patient's form was worked out and established. The characteristics of the patients seen at consultation in 1999 are described.