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1.
Cell ; 149(7): 1500-13, 2012 Jun 22.
Article in English | MEDLINE | ID: mdl-22726437

ABSTRACT

Mitosis is triggered by the activation of Cdk1-cyclin B1 and its translocation from the cytoplasm to the nucleus. Positive feedback loops regulate the activation of Cdk1-cyclin B1 and help make the process irreversible and all-or-none in character. Here we examine whether an analogous process, spatial positive feedback, regulates Cdk1-cyclin B1 redistribution. We used chemical biology approaches and live-cell microscopy to show that nuclear Cdk1-cyclin B1 promotes the translocation of Cdk1-cyclin B1 to the nucleus. Mechanistic studies suggest that cyclin B1 phosphorylation promotes nuclear translocation and, conversely, nuclear translocation promotes cyclin B1 phosphorylation, accounting for the feedback. Interfering with the abruptness of Cdk1-cyclin B1 translocation affects the timing and synchronicity of subsequent mitotic events, underscoring the functional importance of this feedback. We propose that spatial positive feedback ensures a rapid, complete, robust, and irreversible transition from interphase to mitosis and suggest that bistable spatiotemporal switches may be widespread in biological regulation.


Subject(s)
CDC2 Protein Kinase/metabolism , Cell Nucleus/metabolism , Cyclin B1/metabolism , Feedback , Mitosis , Active Transport, Cell Nucleus/drug effects , Cyclin B1/analysis , HeLa Cells , Humans , Models, Statistical , Phosphorylation , Sirolimus/analogs & derivatives
2.
Antimicrob Agents Chemother ; 68(7): e0011424, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38780260

ABSTRACT

Schistosomiasis, a widespread parasitic disease caused by the blood fluke of the genus Schistosoma, affects over 230 million people, primarily in developing countries. Praziquantel, the sole drug currently approved for schistosomiasis treatment, demonstrates effectiveness against patent infections. A recent study highlighted the antiparasitic properties of amiodarone, an anti-arrhythmic drug, exhibiting higher efficacy than praziquantel against prepatent infections. This study assessed the efficacy of amiodarone and praziquantel, both individually and in combination, against Schistosoma mansoni through comprehensive in vitro and in vivo experiments. In vitro experiments demonstrated synergistic activity (fractional inhibitory concentration index ≤0.5) for combinations of amiodarone with praziquantel. In a murine model of schistosomiasis featuring prepatent infections, treatments involving amiodarone (200 or 400 mg/kg) followed by praziquantel (200 or 400 mg/kg) yielded a substantial reduction in worm burden (60%-70%). Given the low efficacy of praziquantel in prepatent infections, combinations of amiodarone with praziquantel may offer clinical utility in the treatment of schistosomiasis.


Subject(s)
Amiodarone , Praziquantel , Schistosoma mansoni , Schistosomiasis mansoni , Amiodarone/pharmacology , Amiodarone/therapeutic use , Animals , Praziquantel/pharmacology , Praziquantel/therapeutic use , Schistosoma mansoni/drug effects , Mice , Schistosomiasis mansoni/drug therapy , Schistosomiasis mansoni/parasitology , Female , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , Drug Synergism , Drug Therapy, Combination , Male , Disease Models, Animal
3.
Mol Cell ; 64(2): 362-375, 2016 10 20.
Article in English | MEDLINE | ID: mdl-27768873

ABSTRACT

Cell division is characterized by a sequence of events by which a cell gives rise to two daughter cells. Quantitative measurements of cell-cycle dynamics in single cells showed that despite variability in G1-, S-, and G2 phases, duration of mitosis is short and remarkably constant. Surprisingly, there is no correlation between cell-cycle length and mitotic duration, suggesting that mitosis is temporally insulated from variability in earlier cell-cycle phases. By combining live cell imaging and computational modeling, we showed that positive feedback is the molecular mechanism underlying the temporal insulation of mitosis. Perturbing positive feedback gave rise to a sluggish, variable entry and progression through mitosis and uncoupled duration of mitosis from variability in cell cycle length. We show that positive feedback is important to keep mitosis short, constant, and temporally insulated and anticipate it might be a commonly used regulatory strategy to create modularity in other biological systems.


Subject(s)
Cell Cycle Proteins/genetics , Chromatin/chemistry , Histones/genetics , Mitosis , Models, Statistical , Transcription Factors/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Chromatin/metabolism , Epithelial Cells/cytology , Epithelial Cells/metabolism , Feedback, Physiological , G2 Phase/genetics , HeLa Cells , Histones/metabolism , Humans , Kinetics , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Molecular Imaging , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Time Factors , Transcription Factors/metabolism , Transcription, Genetic , Red Fluorescent Protein
4.
Liver Transpl ; 29(1): 91-102, 2023 01 01.
Article in English | MEDLINE | ID: mdl-35643926

ABSTRACT

The liver plays a major role in drug metabolism. Liver transplantation impacts the intrinsic metabolic capability and extrahepatic mechanisms of drug disposition and elimination. Different levels of inflammation and oxidative stress during transplantation, the process of liver regeneration, and the characteristics of the graft alter the amount of functional hepatocytes and activity of liver enzymes. Binding of drugs to plasma proteins is affected by the hyperbilirubinemia status and abnormal synthesis of albumin and alpha-1-acid glycoproteins. Postoperative intensive care complications such as biliary, circulatory, and cardiac also impact drug distribution. Renally eliminated antimicrobials commonly present reduced clearance due to hepatorenal syndrome and the use of nephrotoxic immunosuppressants. In addition, liver transplantation recipients are particularly susceptible to multidrug-resistant infections due to frequent manipulation, multiple hospitalizations, invasive devices, and frequent use of empiric broad-spectrum therapy. The selection of appropriate anti-infective therapy must consider the pathophysiological changes after transplantation that impact the pharmacokinetics and pharmacodynamics of antibiotics and antifungal drugs.


Subject(s)
Antifungal Agents , Liver Transplantation , Humans , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Liver Transplantation/adverse effects , Liver
5.
Sex Transm Dis ; 50(9): 567-574, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37195274

ABSTRACT

BACKGROUND: Transgender women (TGW) are susceptible to the acquisition of sexually transmitted infections (STIs), including human papillomavirus (HPV). Nonetheless, the exact data for this population are scarce. We estimated HPV positivity at the anal, genital, and oral sites among TGW and also identified the related characteristics and behaviors that could be risk factors for HPV infection in a sample of TGW in Brazil. Furthermore, we characterized the site-specific HPV genotypes among those who were positive for HPV at these 3 sites. METHODS: A cross-sectional study was conducted on TGW in Goiânia City (Central-Midwest region), Brazil, between April 2018 and August 2019. Respondent-driven sampling was applied for recruitment. Next, self-collected anal, genital, and oral samples were examined for HPV DNA using polymerase chain reaction (SPF-10 primer). Human papillomavirus genotypes were identified in 12 TGW. RESULTS: In the TGW included in the study, the anal, genital, and oral HPV positivity values were 77.2% (95% confidence interval [CI], 67.3%-84.6%), 33.5% (95% CI, 26.1%-48.9%), and 10.9% (95% CI, 5.8%-17.0%), respectively. In addition, the majority of 12 participants who tested for HPV had multiple genotypes. HPV-52 was the most prevalent genotype identified at the anal (66.6%) and genital (40.0%) sites, whereas HPV-62 and HPV-66 were the most common at the oral site (25.0%). CONCLUSIONS: A high HPV positivity was observed among TGW. Therefore, additional epidemiological studies on HPV genotypes should generate health intervention information, including the prevention, diagnosis, and treatment of sexually transmitted infections.


Subject(s)
Papillomavirus Infections , Sexually Transmitted Diseases , Transgender Persons , Female , Humans , Male , Brazil/epidemiology , Cross-Sectional Studies , HIV Infections/epidemiology , Homosexuality, Male , Human Papillomavirus Viruses , Papillomaviridae/genetics , Papillomavirus Infections/epidemiology , Prevalence , Sexually Transmitted Diseases/epidemiology
6.
Immunology ; 165(2): 234-249, 2022 02.
Article in English | MEDLINE | ID: mdl-34775592

ABSTRACT

COVID-19 disease is the manifestation of syndrome coronavirus 2 (SARS-CoV-2) infection, which is causing a worldwide pandemic. This disease can lead to multiple and different symptoms, being lymphopenia associated with severity one of the most persistent. Natural killer cells (NK cells) are part of the innate immune system, being fighting against virus-infected cells one of their key roles. In this study, we determined the phenotype of NK cells after COVID-19 and the main characteristic of SARS-CoV-2-specific-like NK population in the blood of convalescent donors. CD57+ NKG2C+ phenotype in SARS-CoV-2 convalescent donors indicates the presence of 'memory'/activated NK cells as it has been shown for cytomegalovirus infections. Although the existence of this population is donor dependent, its expression may be crucial for the specific response against SARS-CoV-2, so that, it gives us a tool for selecting the best donors to produce off-the-shelf living drug for cell therapy to treat COVID-19 patients under the RELEASE clinical trial (NCT04578210).


Subject(s)
Adoptive Transfer , Blood Donors , COVID-19/immunology , Convalescence , Immunologic Memory , Killer Cells, Natural/immunology , SARS-CoV-2/immunology , Adult , Female , Humans , Male , Middle Aged
7.
Environ Res ; 214(Pt 1): 113758, 2022 11.
Article in English | MEDLINE | ID: mdl-35764127

ABSTRACT

Occupational exposures to hexavalent Chromium (Cr(VI)) can occur in welding, hot working stainless steel processing, chrome plating, spray painting and coating activities. Recently, within the human biomonitoring for Europe initiative (HBM4EU), a study was performed to assess the suitability of different biomarkers to assess the exposure to Cr(VI) in various job tasks. Blood-based biomarkers may prove useful when more specific information on systemic and intracellular bioavailability is necessary. To this aim, concentrations of Cr in red blood cells (RBC-Cr) and in plasma (P-Cr) were analyzed in 345 Cr(VI) exposed workers and 175 controls to understand how these biomarkers may be affected by variable levels of exposure and job procedures. Compared to controls, significantly higher RBC-Cr levels were observed in bath plating and paint application workers, but not in welders, while all the 3 groups had significantly greater P-Cr concentrations. RBC-Cr and P-Cr in chrome platers showed a high correlation with Cr(VI) in inhalable dust, outside respiratory protective equipment (RPE), while such correlation could not be determined in welders. In platers, the use of RPE had a significant impact on the relationship between blood biomarkers and Cr(VI) in inhalable and respirable dust. Low correlations between P-Cr and RBC-Cr may reflect a difference in kinetics. This study showed that Cr-blood-based biomarkers can provide information on how workplace exposure translates into systemic availability of Cr(III) (extracellular, P-Cr) and Cr(VI) (intracellular, RBC-Cr). Further studies are needed to fully appreciate their use in an occupational health and safety context.


Subject(s)
Air Pollutants, Occupational , Occupational Exposure , Biomarkers , Chromates , Chromium , Dust , Environmental Monitoring , Humans
8.
J Environ Manage ; 302(Pt B): 114100, 2022 Jan 15.
Article in English | MEDLINE | ID: mdl-34794053

ABSTRACT

Antimony is present in water by natural causes but is also mobilized in the environment by anthropogenic activities, particularly mining. Considering its toxicological behavior, antimony removal from contaminated groundwater and mine effluents is necessary. In this work, Sb(III) and Sb(V) removal from aqueous solution was studied using a resin prepared from pine bark tannins. Subsequent iron loading of the tannin resin was tested, but this chemical modification was shown not to improve adsorptive properties. Tannin resin (unmodified form) presented a good ability to uptake antimony, with maximum adsorption capacities, evaluated in batch mode, of 30-33 mg g-1 (Sb(III), pH 6) and 16-47 mg g-1 (Sb(V), pH 2), depending on the particle size. The performance of the adsorbent was not affected by high levels of sulfate, which characterize most mining-impacted waters, but depending on Sb-load of the water it could be moderately affected by metal cations coexisting in solution. The applicability of the tannin resin on Sb(III) uptake was confirmed in continuous fixed-bed experiments. Breakthrough curves were obtained for different inlet adsorbate concentrations, bed heights, flow rates and aqueous media (distilled water and a simulated mine effluent). The adsorptive capacity of the tannin resin was practically maintained and adsorbent usage rates as low as 0.11 kg m-3 were determined to treat efficiently (90% removal) 1 mg-Sb(III) L-1 contaminated water. Overall, tannin resin is a bio-derived sorbent that shows affinity for antimony in both redox states, being stable in pH conditions commonly found in Sb-contaminated waters.


Subject(s)
Antimony , Water Pollutants, Chemical , Adsorption , Anthropogenic Effects , Antimony/analysis , Plant Bark/chemistry , Tannins , Water , Water Pollutants, Chemical/analysis
9.
Microb Pathog ; 150: 104644, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33259886

ABSTRACT

The emergence of invasive Haemophilus influenzae infections in vaccinated patient is a public health concern. We have investigated the genomic basis of invasiveness and possible vaccine failure in H. influenzae causing invasive disease in vaccinated and unvaccinated children in Brazil. Three H. influenzae strains isolated from blood cultures of pediatric patients were sequenced. Serotype, MLST, resistome and virulome were predicted using bioinformatic tools, whereas single nucleotide polymorphisms (SNPs) analysis of cap loci and the presence of the putative virulence-enhancing IS1016-bexA partial deletion were predicted in silico. Infections were caused by H. influenzae type a (Hia), type b (Hib) and nontypeable (NTHi), belonging to international high-risk clones of sequence types ST23, ST6 and ST368, respectively, which have been identified in North American, European and Asian countries. Convergence of ampicillin resistance and virulence in Hib-ST6 was supported by blaTEM-1B and deletion in the bexA gene, whereas presence of SNPs in the cap-b locus was associated with antigenic modifications of the capsule structure. Hia-ST23 and NTHi-ST368 strains carried galU, lpsA, opsX, rfaF, iga1, lgtC and lic1/lic2 virulence genes, associated with colonization, adaptation and damage to the lung, or invasiveness. In summary, deletion in the bexA gene and presence of SNPs in the cap locus of Hib could be contributing to invasive disease and possible vaccine failure in pediatric patients, whereas serotype replacement of Hib with type "a" and NTHi strains denotes the ability of non-vaccine serotypes to re-colonize vaccinated patients. Finally, the dissemination of international high-risk clones of H. influenzae emphasizes the importance of monitoring changes in the molecular epidemiology of invasive H. influenzae disease.


Subject(s)
Haemophilus Infections , Haemophilus Vaccines , Asia , Brazil , Child , Clone Cells , Genomics , Haemophilus Infections/epidemiology , Haemophilus Infections/prevention & control , Haemophilus influenzae/genetics , Humans , Infant , Multilocus Sequence Typing , Serotyping
10.
BMC Cancer ; 20(1): 660, 2020 Jul 15.
Article in English | MEDLINE | ID: mdl-32669083

ABSTRACT

BACKGROUND: Expression of matrix metalloproteases 2, 9 and 14 (MMP-2, MMP-9, MMP-14), tissue inhibitors of metalloprotease 1 and 2 (TIMP-1, TIMP-2) and vascular endothelial growth factor A (VEGF-A) is involved in tumor invasion and metastasis via extracellular matrix degradation and angiogenesis. This study aimed to assess whether the expression of MMP-2, MMP-9, MMP-14, TIMP-1, and TIMP-2 in tumors and in the adjacent stroma is associated with cervical cancer prognosis. METHODS: This study analyzed a retrospective cohort of 64 patients. Protein expression was previously obtained by immunohistochemistry from biopsies containing both tumor and stroma. The expression and percentage of stained cells were categorized as high or low according to the cutoff points by using ROC curves. The follow-up data was collected from diagnosis to the last clinical visit. Clinical status categorized as alive without disease, alive with disease, death due to other causes, and death from the disease. The relative risk of death from the disease was evaluated according to the proteins expression using a cause-specific Cox regression model with a 95% confidence interval (95%CI). For the significant associations (p < 0.05), survival curves of patients with low and high expression were plotted for the competing risk survival curve analyses. RESULTS: High expression levels of stromal MMP-2 (RR; 95%CI: 3.91; 1.17-13.02) and stromal TIMP-2 (RR, 95%CI: 8.67; 1.15-65.27) were associated with a greater relative risk of death from the disease and with lower survival (p = 0.03; p = 0.04) than lower expression levels. Low expression levels of stromal MMP-9 (RR, 95%CI: 0.19; 0.05-0.65) and tumoral MMP-9 (HR, 95%CI: 0.19; 0.04-0.90) were protective factors against death from the disease and were associated with poorer survival. CONCLUSIONS: High expression levels of MMP-2 and TIMP-2 in the stroma were significantly associated with poor survival in cervical cancer patients. High expression of MMP-9 was associated with a favorable cervical cancer prognosis.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/mortality , Cervix Uteri/pathology , Uterine Cervical Dysplasia/mortality , Uterine Cervical Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Cervix Uteri/surgery , Female , Follow-Up Studies , Humans , Hysterectomy , Matrix Metalloproteinase 14/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment/methods , Survival Analysis , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-2/metabolism , Treatment Outcome , Tumor Microenvironment , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgery , Vascular Endothelial Growth Factor A/metabolism , Young Adult , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/surgery
11.
BMC Public Health ; 20(1): 517, 2020 Apr 17.
Article in English | MEDLINE | ID: mdl-32303204

ABSTRACT

BACKGROUND: Neglected tropical diseases (NTDs) comprise 20 communicable diseases that are prevalent in rural poor and remote communities with less access to the health system. For effective and efficient control, the WHO recommends that affected countries implement integrated control interventions that take into account the different co-endemic NTDs in the same community. However, implementing these integrated interventions involving several diseases with different etiologies, requiring different control approaches and driven by different vertical programs, remains a challenge. We report here the results and lessons learned from a pilot test of this integrated approach based on integrated screening of skin diseases in three co-endemic health districts of Côte d'Ivoire, a West African country endemic for Buruli ulcer, leprosy and yaw. METHOD: This cross-sectional study took place from April 2016 to March 2017 in 3 districts of Côte d'Ivoire co-endemic for BU, leprosy and yaws. The study was carried out in 6 stages: identification of potentially co-endemic communities; stakeholder training; social mobilization; mobile medical consultations; case detection and management; and a review meeting. RESULTS: We included in the study all patients with skin signs and symptoms at the screening stage who voluntarily accepted screening. In total, 2310 persons screened had skin lesions at the screening stage. Among them, 07 cases were diagnosed with Buruli ulcer. There were 30 leprosy cases and 15 yaws detected. Other types of ulcerations and skin conditions have been identified and represent the majority of cases detected. We learned from this pilot experience that integration can be successfully implemented in co-endemic communities in Côte d'Ivoire. Health workers are motivated and available to implement integrated interventions instead of interventions focused on a single disease. However, it is essential to provide capacity building, a minimum of drugs and consumables for the care of the patients identified, as well as follow-up of identified patients, including those with other skin conditions. CONCLUSIONS: The results of this study show that the integration of activities can be successfully implemented in co-endemic communities under the condition of staff capacity building and minimal care of identified patients.


Subject(s)
Buruli Ulcer/epidemiology , Leprosy/epidemiology , Mass Screening/methods , Mycobacterium leprae , Mycobacterium ulcerans , Neglected Diseases/epidemiology , Treponema pallidum/immunology , Yaws/epidemiology , Adolescent , Adult , Aged , Buruli Ulcer/diagnosis , Buruli Ulcer/microbiology , Child , Cote d'Ivoire/epidemiology , Cross-Sectional Studies , Endemic Diseases , Female , Humans , Leprosy/diagnosis , Leprosy/microbiology , Male , Middle Aged , Neglected Diseases/diagnosis , Neglected Diseases/microbiology , Pilot Projects , Prevalence , Rural Population , Yaws/diagnosis , Yaws/microbiology , Young Adult
12.
Cell Tissue Bank ; 21(4): 557-562, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33063150

ABSTRACT

On March 19 World Health Organization declare the pandemic situation by outbreak coronavirus disease 2019 in the world. The pressure on the health care system has been very high in several countries. Spanish National Transplant Organization (ONT) have made many efforts in maintaining transplantation activity. Although the impact of the pandemic on organ activity has been analysed, to date, less data exist regarding the impact on tissue activity. The aim of this study has been the evaluation of the possible impact on the procurement, processing and distribution of tissues during the peak period of the pandemic COVID-19 in Spain. For this study, a multicentre analysis has been made with a survey of the tissue banks in Spain, during the period March 1 to April 30, 2020. Our data suggest that the impact of coronavirus in Spain has affected dramatically tissue donation but with a moderate effect on stored tissues such as bone, valves, vessels or skin. Tissue banks should prepare if future next pandemic waves surges so that tissue provision is guaranteed both in urgent and elective surgeries.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Tissue Banks/statistics & numerical data , Tissue and Organ Procurement/statistics & numerical data , Transplantation/statistics & numerical data , Betacoronavirus , COVID-19 , Humans , Pandemics , SARS-CoV-2 , Spain/epidemiology , Surveys and Questionnaires
13.
Mol Syst Biol ; 12(12): 888, 2016 Dec 01.
Article in English | MEDLINE | ID: mdl-27909043

ABSTRACT

The coordinated regulation of protein kinases is a rapid mechanism that integrates diverse cues and swiftly determines appropriate cellular responses. However, our understanding of cellular decision-making has been limited by the small number of simultaneously monitored phospho-regulatory events. Here, we have estimated changes in activity in 215 human kinases in 399 conditions derived from a large compilation of phosphopeptide quantifications. This atlas identifies commonly regulated kinases as those that are central in the signaling network and defines the logic relationships between kinase pairs. Co-regulation along the conditions predicts kinase-complex and kinase-substrate associations. Additionally, the kinase regulation profile acts as a molecular fingerprint to identify related and opposing signaling states. Using this atlas, we identified essential mediators of stem cell differentiation, modulators of Salmonella infection, and new targets of AKT1. This provides a global view of human phosphorylation-based signaling and the necessary context to better understand kinase-driven decision-making.


Subject(s)
Human Embryonic Stem Cells/cytology , Protein Kinases/metabolism , Systems Biology/methods , Cell Differentiation , Databases, Protein , Gene Expression Regulation, Enzymologic , HeLa Cells , Human Embryonic Stem Cells/enzymology , Humans , Phosphorylation , Proteomics/methods , Signal Transduction
14.
J Environ Manage ; 192: 224-233, 2017 May 01.
Article in English | MEDLINE | ID: mdl-28171834

ABSTRACT

Arsenic is a semi-metal element that can enter in water bodies and drinking water supplies from natural deposits and from mining, industrial and agricultural practices. The aim of the present work was to propose an alternative process for removing As from water, based on adsorption on a brown seaweed (Sargassum muticum), after a simple and inexpensive treatment: coating with iron-oxy (hydroxides). Adsorption equilibrium and kinetics were studied and modeled in terms of As oxidation state (III and V), pH and initial adsorbate concentration. Maximum adsorption capacities of 4.2 mg/g and 7.3 mg/g were obtained at pH 7 and 20 °C for arsenite and arsenate, respectively. When arsenite was used as adsorbate, experimental evidences pointed to the occurrence of redox reactions involving As(III) oxidation to As(V) and Fe(III) reduction to Fe(II), with As(V) uptake by the adsorbent. The proposed adsorption mechanism was then based on the assumption that arsenate was the adsorbed arsenic species. The most relevant drawback found in the present work was the considerable leaching of iron to the solution. Arsenite removal from a mining-influenced water by adsorption plus precipitation was studied and compared to a traditional process of coagulation/flocculation. Both kinds of treatment provided practically 100% of arsenite removal from the contaminated water, leading at best in 12.9 µg/L As after the adsorption and precipitation assays and 14.2 µg/L after the coagulation/flocculation process.


Subject(s)
Arsenic , Iron , Adsorption , Hydrogen-Ion Concentration , Seaweed , Water , Water Pollutants, Chemical , Water Purification
15.
Antimicrob Agents Chemother ; 60(8): 5044-6, 2016 08.
Article in English | MEDLINE | ID: mdl-27216068

ABSTRACT

BKC-1 is a new class A serine carbapenemase that was recently identified in Klebsiella pneumoniae clinical isolates. The principal objective of this study was to evaluate the frequency of blaBKC-1 by testing a collection of Klebsiella isolates. Only 2 of 635 Klebsiella isolates (0.3%) carried blaBKC-1 The two BKC-1-producing isolates belonged to clonal complex 442 and possessed identical pulsed-field gel electrophoresis patterns. The blaBKC-1 gene was inserted into a 10-kb plasmid that was identical to the previously reported plasmid, p60136. The BKC-producing K. pneumoniae isolates presented also possessed other mechanisms for beta-lactam resistance, such as genes encoding extended-spectrum beta-lactamases and mutations in the genes ompK35 and ompK36, encoding the major porins.


Subject(s)
Bacterial Proteins/metabolism , Klebsiella/drug effects , Klebsiella/enzymology , beta-Lactamases/metabolism , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Electrophoresis, Gel, Pulsed-Field , Klebsiella/genetics , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/enzymology , Klebsiella pneumoniae/genetics , Microbial Sensitivity Tests , Mutation/genetics , Plasmids/genetics , beta-Lactamases/genetics
16.
Am J Obstet Gynecol ; 215(6): 753.e1-753.e9, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27402054

ABSTRACT

BACKGROUND: Human papillomavirus and Chlamydia trachomatis share the same route of sexual transmission and possess similar risk factors, indicating that coinfection may act synergistically in the induction of epithelial cell abnormalities. OBJECTIVE: This study aimed to determine the prevalence of human papillomavirus and Chlamydia trachomatis in adolescents and young women and identify factors associated with coinfection. STUDY DESIGN: This cross-sectional study included 276 female participants, aged 15-24 years, who were sexually active. Interviews were conducted and cervical specimens were collected for cervical smears and molecular tests. All cervical specimens were tested for 27 human papillomavirus genotypes by polymerase chain reaction amplification and hybridization to a human papillomavirus linear array. Detection of Chlamydia trachomatis was performed by polymerase chain reaction using primers directed to the region encoding the cryptic plasmid. Bivariate and multivariate analyses were performed to evaluate the factors associated with coinfection with human papillomavirus and Chlamydia trachomatis. The odds ratio, the adjusted odds ratio, and the 95% confidence interval were calculated. RESULTS: The prevalence of infection by Chlamydia trachomatis and human papillomavirus was 9.1% (95% confidence interval, 5.61-12.4) and 47.1% (95% confidence interval, 41.0-53.2), respectively. The prevalence of coinfection with human papillomavirus and Chlamydia trachomatis was 5.8% (95% confidence interval, 3.3-9.2); coinfection with 1 human papillomavirus type was 3.3% (95% confidence interval, 1.5-6.1) and with multiple types was 2.5% (95% confidence interval, 1.0-5.2). The prevalence of cytological abnormalities was 12.3% (95% confidence interval, 8.6-16.79). Human papillomavirus infections of high oncogenic risk were more prevalent (85.4%). Factors independently associated with coinfection of human papillomavirus/Chlamydia trachomatis obtained by multivariate analysis were the initiation of sexual activity under 16 years of age with an an odds ratio of 4.9 (95% confidence interval, 1.0-23.63; P = .05) and cytological abnormalities with an odds ratio of 10.7 (95% confidence interval, 1.9-59.5; P = .01), which indicates there is risk for the detection of cytological abnormalities in adolescents and young women coinfected with human papillomavirus/Chlamydia trachomatis. CONCLUSION: The prevalence of coinfection among our study population was of a magnitude that warrants attention by public health services. Adolescents and young women should be monitored for Chlamydia trachomatis infection and vaccinated against human papillomavirus. The association between cytological abnormalities and coinfection with human papillomavirus and Chlamydia trachomatis indicates the potential synergistic role of these infections in carcinogenesis of the cervix.


Subject(s)
Chlamydia Infections/epidemiology , Coinfection/epidemiology , Papillomavirus Infections/epidemiology , Uterine Cervical Diseases/epidemiology , Vaginal Diseases/epidemiology , Adolescent , Brazil/epidemiology , Cross-Sectional Studies , Female , Humans , Multivariate Analysis , Odds Ratio , Polymerase Chain Reaction , Prevalence , Risk Factors , Vaginal Smears , Young Adult
17.
PLoS Comput Biol ; 11(8): e1004362, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26312481

ABSTRACT

The African clawed frog Xenopus laevis is an important model organism for studies in developmental and cell biology, including cell-signaling. However, our knowledge of X. laevis protein post-translational modifications remains scarce. Here, we used a mass spectrometry-based approach to survey the phosphoproteome of this species, compiling a list of 2636 phosphosites. We used structural information and phosphoproteomic data for 13 other species in order to predict functionally important phospho-regulatory events. We found that the degree of conservation of phosphosites across species is predictive of sites with known molecular function. In addition, we predicted kinase-protein interactions for a set of cell-cycle kinases across all species. The degree of conservation of kinase-protein interactions was found to be predictive of functionally relevant regulatory interactions. Finally, using comparative protein structure models, we find that phosphosites within structured domains tend to be located at positions with high conformational flexibility. Our analysis suggests that a small class of phosphosites occurs in positions that have the potential to regulate protein conformation.


Subject(s)
Oocytes/metabolism , Phosphoproteins/analysis , Phosphoproteins/chemistry , Animals , Female , Mass Spectrometry , Models, Molecular , Phosphoproteins/metabolism , Phosphorylation , Protein Interaction Maps , Proteomics , Xenopus laevis
18.
Rev Esc Enferm USP ; 50(1): 167-79, 2016 Feb.
Article in Portuguese | MEDLINE | ID: mdl-27007434

ABSTRACT

OBJECTIVE: To identify knowledge produced about drug utilization by the elderly in the primary health care context from 2006 to 2014. METHOD: An integrative review of the PubMed, LILACS, BDENF, and SCOPUS databases, including qualitative research papers in Portuguese, English, and Spanish. It excluded papers with insufficient information regarding the methodological description. RESULTS: Search found 633 papers that, after being subjected to the inclusion and exclusion criteria, made up a corpusof 76 publications, mostly in English and produced in the United States, England, and Brazil. Results were pooled in eight thematic categories showing the current trend of drug use in the elderly, notably the use of psychotropics, polypharmacy, the prevention of adverse events, and adoption of technologies to facilitate drug management by the elderly. Studies point out the risks posed to the elderly as a consequence of changes in metabolism and simultaneous use of several drugs. CONCLUSION: There is strong concern about improving communications between professionals and the elderly in order to promote an exchange of information about therapy, and in this way prevent major health complications in this population.


Subject(s)
Drug Utilization/statistics & numerical data , Primary Health Care , Aged , Humans
19.
Mol Syst Biol ; 15(4): e8864, 2019 04 05.
Article in English | MEDLINE | ID: mdl-30952682
20.
J Environ Manage ; 151: 326-42, 2015 Mar 15.
Article in English | MEDLINE | ID: mdl-25585146

ABSTRACT

Arsenic and antimony are metalloids, naturally present in the environment but also introduced by human activities. Both elements are toxic and carcinogenic, and their removal from water is of unquestionable importance. The present article begins with an overview of As and Sb chemistry, distribution and toxicity, which are relevant aspects to understand and develop remediation techniques. A brief review of the recent results in analytical methods for speciation and quantification was also provided. The most common As and Sb removal techniques (coagulation/flocculation, oxidation, membrane processes, electrochemical methods and phyto and bioremediation) are presented with discussion of their advantages, drawbacks and the main recent achievements. Literature review on adsorption and biosorption were focused in detail. Considering especially the case of developing countries or rural communities, but also the finite energy resources that over the world are still dependent, recent research have focused especially readily available low-cost adsorbents, as minerals, wastes and biosorbents. Many of these alternative sorbents have been presenting promising results and can be even superior when compared to the commercial ones. Sorption capacities were accurately compiled for As(III,V) and Sb(III,V) species in order to provide to the reader an easy but detailed comparison. Some aspects related to experimental conditions, comparison criteria, lack of research studies, economic aspects and adsorption mechanisms were critically discussed.


Subject(s)
Antimony/chemistry , Arsenic/chemistry , Wastewater/chemistry , Water Pollutants, Chemical/chemistry , Water/chemistry , Adsorption
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