Gomesin, a peptide produced by the spider Acanthoscurria gomesiana, is a potent anticryptococcal agent that acts in synergism with fluconazole

Gomesin is an 18-residue cysteine-rich antimicrobial peptide produced by hemocytes of the spider Acanthoscurria gomesiana. in the present study, the antifungal properties of gomesin against Cryptococcus neoformans, the etiologic agent of cryptococcosis, were evaluated. Gomesin bound to the cell surface of cryptococci, which resulted in cell death associated with membrane permeabilization. Antifungal concentrations of gomesin were not toxic for human brain cells. Supplementation of cryptococcal cultures with the peptide (1 mu M) caused a decrease in capsule expression and rendered fungal cells more susceptible to killing by human brain phagocytes. the possible use of gomesin in combination with fluconazole, a standard antifungal drug, was also evaluated. in association with fluconazole, gomesin concentrations with low antimicrobial activity (0.1-1 mu M) inhibited fungal growth and enhanced the antimicrobial activity of brain phagocytes. These results reveal the potential of gomesin to promote inhibition of cryptococcal growth directly or by enhancing the effectiveness of host defenses.Univ Fed Rio de Janeiro, Inst Microbiol Prof Paulo Goes, Dept Microbiol Geral, Lab Estudos Integrados Bioquim Microbiana, BR-21941590 Rio de Janeiro, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508 São Paulo, BrazilUniv Texas, Dept Biol Sci, El Paso, TX 79968 USAUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilWeb of Scienc

Coherent optical phase transfer over a 32-km fiber with 1-s instability at 10−1710^{-17}

The phase coherence of an ultrastable optical frequency reference is fully maintained over actively stabilized fiber networks of lengths exceeding 30 km. For a 7-km link installed in an urban environment, the transfer instability is $6 \times 10^{-18}$ at 1-s. The excess phase noise of 0.15 rad, integrated from 8 mHz to 25 MHz, yields a total timing jitter of 0.085 fs. A 32-km link achieves similar performance. Using frequency combs at each end of the coherent-transfer fiber link, a heterodyne beat between two independent ultrastable lasers, separated by 3.5 km and 163 THz, achieves a 1-Hz linewidth.Comment: 4 pages, 4 figure

Chitin-Like Molecules Associate with Cryptococcus neoformans Glucuronoxylomannan To Form a Glycan Complex with Previously Unknown Properties

In prior studies, we demonstrated that glucuronoxylomannan (GXM), the major capsular polysaccharide of the fungal pathogen Cryptococcus neoformans, interacts with chitin oligomers at the cell wall-capsule interface. the structural determinants regulating these carbohydrate-carbohydrate interactions, as well as the functions of these structures, have remained unknown. in this study, we demonstrate that glycan complexes composed of chitooligomers and GXM are formed during fungal growth and macrophage infection by C. neoformans. To investigate the required determinants for the assembly of chitin-GXM complexes, we developed a quantitative scanning electron microscopy-based method using different polysaccharide samples as inhibitors of the interaction of chitin with GXM. This assay revealed that chitin-GXM association involves noncovalent bonds and large GXM fibers and depends on the N-acetyl amino group of chitin. Carboxyl and O-acetyl groups of GXM are not required for polysaccharide-polysaccharide interactions. Glycan complex structures composed of cryptococcal GXM and chitin-derived oligomers were tested for their ability to induce pulmonary cytokines in mice. They were significantly more efficient than either GXM or chitin oligomers alone in inducing the production of lung interleukin 10 (IL-10), IL-17, and tumor necrosis factor alpha (TNF-alpha). These results indicate that association of chitin-derived structures with GXM through their N-acetyl amino groups generates glycan complexes with previously unknown properties.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)NIHCenter for AIDS Research at EinsteinUniv Fed Rio de Janeiro, Inst Microbiol Prof Paulo de Goes, Rio de Janeiro, BrazilUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Ultraestrutura Celular Hertha Meyer, BR-21941 Rio de Janeiro, BrazilAlbert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USAAlbert Einstein Coll Med, Div Infect Dis, Dept Med, Bronx, NY 10467 USAUniversidade Federal de São Paulo, Disciplina Biol Celular, São Paulo, BrazilFiocruz MS, Fundacao Oswaldo Cruz, Ctr Desenvolvimento Tecnol, BR-21045900 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Disciplina Biol Celular, São Paulo, BrazilNIH: AI033142NIH: AI033774NIH: AI052733NIH: HL059842Web of Scienc

A Paracoccidioides brasiliensis glycan shares serologic and functional properties with cryptococcal glucuronoxylomannan

The cell wall of the yeast form of the dimorphic fungus Paracoccidioides brasiliensis is enriched with alpha 1,3-glucans. in Cryptococcus neoformans, alpha 1,3-glucans interact with glucuronoxylomannan (GXM), a hetero-polysaccharide that is essential for fungal virulence. in this study, we investigated the occurrence of P. brasiliensis glycans sharing properties with cryptococcal GXM. Protein database searches in P. brasiliensis revealed the presence of sequences homologous to those coding for enzymes involved in the synthesis of GXM and capsular architecture in C. neoformans. in addition, monoclonal antibodies (mAbs) raised to cryptococcal GXM bound to P. brasiliensis cells. Using protocols that were previously established for extraction and analysis of C neoformans GXM, we recovered a P. brasiliensis glycan fraction composed of mannose and galactose, in addition to small amounts of glucose, xylose and rhamnose. in comparison with the C. neoformans GXM, the P. brasiliensis glycan fraction components had smaller molecular dimensions. the P. brasiliensis components, nevertheless, reacted with different GXM-binding mAbs. Extracellular vesicle fractions of P. brasiliensis also reacted with a GXM-binding mAb, suggesting that the polysaccharide-like molecule is exported to the extracellular space in secretory vesicles. An acapsular mutant of C. neoformans incorporated molecules from the P. brasiliensis extract onto the cell wall, resulting in the formation of surface networks that resembled the cryptococcal capsule. Coating the C. neoformans acapsular mutant with the P. brasiliensis glycan fraction resulted in protection against phagocytosis by murine macrophages. These results suggest that P. brasiliensis and C. neoformans share metabolic pathways required for the synthesis of similar polysaccharides and that P. brasiliensis yeast cell walls have molecules that mimic certain aspects of C. neoformans GXM. These findings are important because they provide additional evidence for the sharing of antigenically similar components across phylogenetically distant fungal species. Since GXM has been shown to be important for the pathogenesis of C neoformans and to elicit protective antibodies, the finding of similar molecules in P. brasiliensis raises the possibility that these glycans play similar functions in paracoccidiomycosis. (C) 2012 Elsevier Inc. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)NIHCenter for AIDS Research at EinsteinInterhemispheric Research Training Grant in Infectious Diseases, Fogarty International CenterDepartment of EnergyFiocruz MS, CDTS, BR-21040360 Rio de Janeiro, BrazilUniv Fed Rio de Janeiro, Inst Microbiol Prof Paulo de Goes, BR-21941902 Rio de Janeiro, BrazilAlbert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USAUniversidade Federal de São Paulo, Disciplina Biol Celular, BR-04023062 São Paulo, BrazilUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Ultraestrutura Celular Hertha Meyer, BR-21941903 Rio de Janeiro, BrazilAlbert Einstein Coll Med, Div Infect Dis, Dept Med, Bronx, NY 10461 USAUniversidade Federal de São Paulo, Disciplina Biol Celular, BR-04023062 São Paulo, BrazilNIH: AI033142NIH: AI033774NIH: AI052733NIH: HL059842Interhemispheric Research Training Grant in Infectious Diseases, Fogarty International Center: NIH D43-TW007129Department of Energy: DE-FG-9-93ER-20097Web of Scienc

Incidence of WHO stage 3 and 4 conditions following initiation of Anti-Retroviral Therapy in resource limited settings

To determine the incidence of WHO clinical stage 3 and 4 conditions during early anti-retroviral therapy (ART) in resource limited settings (RLS)

Complex network analysis of arboviruses in the same geographic domain: Differences and similarities.

Arbovirus can cause diseases with a broad spectrum from mild to severe and long-lasting symptoms, affecting humans worldwide and therefore considered a public health problem with global and diverse socio-economic impacts. Understanding how they spread within and across different regions is necessary to devise strategies to control and prevent new outbreaks. Complex network approaches have widespread use to get important insights on several phenomena, as the spread of these viruses within a given region. This work uses the motif-synchronization methodology to build time varying complex networks based on data of registered infections caused by Zika, chikungunya, and dengue virus from 2014 to 2020, in 417 cities of the state of Bahia, Brazil. The resulting network sets capture new information on the spread of the diseases that are related to the time delay in the synchronization of the time series among different municipalities. Thus the work adds new and important network-based insights to previous results based on dengue dataset in the period 2001-2016. The most frequent synchronization delay time between time series in different cities, which control the insertion of edges in the networks, ranges 7 to 14 days, a period that is compatible with the time of the individual-mosquito-individual transmission cycle of these diseases. As the used data covers the initial periods of the first Zika and chikungunya outbreaks, our analyses reveal an increasing monotonic dependence between distance among cities and the time delay for synchronization between the corresponding time series. The same behavior was not observed for dengue, first reported in the region back in 1986, either in the previously 2001-2016 based results or in the current work. These results show that, as the number of outbreaks accumulates, different strategies must be adopted to combat the dissemination of arbovirus infections

Life expectancy and mortality in 363 cities of Latin America

The concept of a so-called urban advantage in health ignores the possibility of heterogeneity in health outcomes across cities. Using a harmonized dataset from the SALURBAL project, we describe variability and predictors of life expectancy and proportionate mortality in 363 cities across nine Latin American countries. Life expectancy differed substantially across cities within the same country. Cause-specific mortality also varied across cities, with some causes of death (unintentional and violent injuries and deaths) showing large variation within countries, whereas other causes of death (communicable, maternal, neonatal and nutritional, cancer, cardiovascular disease and other noncommunicable diseases) varied substantially between countries. In multivariable mixed models, higher levels of education, water access and sanitation and less overcrowding were associated with longer life expectancy, a relatively lower proportion of communicable, maternal, neonatal and nutritional deaths and a higher proportion of deaths from cancer, cardiovascular disease and other noncommunicable diseases. These results highlight considerable heterogeneity in life expectancy and causes of death across cities of Latin America, revealing modifiable factors that could be amenable to urban policies aimed toward improving urban health in Latin America and more generally in other urban environments

Building a Data Platform for Cross-Country Urban Health Studies: the SALURBAL Study.

Studies examining urban health and the environment must ensure comparability of measures across cities and countries. We describe a data platform and process that integrates health outcomes together with physical and social environment data to examine multilevel aspects of health across cities in 11 Latin American countries. We used two complementary sources to identify cities with ≥ 100,000 inhabitants as of 2010 in Argentina, Brazil, Chile, Colombia, Costa Rica, El Salvador, Guatemala, Mexico, Nicaragua, Panama, and Peru. We defined cities in three ways: administratively, quantitatively from satellite imagery, and based on country-defined metropolitan areas. In addition to "cities," we identified sub-city units and smaller neighborhoods within them using census hierarchies. Selected physical environment (e.g., urban form, air pollution and transport) and social environment (e.g., income, education, safety) data were compiled for cities, sub-city units, and neighborhoods whenever possible using a range of sources. Harmonized mortality and health survey data were linked to city and sub-city units. Finer georeferencing is underway. We identified 371 cities and 1436 sub-city units in the 11 countries. The median city population was 234,553 inhabitants (IQR 141,942; 500,398). The systematic organization of cities, the initial task of this platform, was accomplished and further ongoing developments include the harmonization of mortality and survey measures using available sources for between country comparisons. A range of physical and social environment indicators can be created using available data. The flexible multilevel data structure accommodates heterogeneity in the data available and allows for varied multilevel research questions related to the associations of physical and social environment variables with variability in health outcomes within and across cities. The creation of such data platforms holds great promise to support researching with greater granularity the field of urban health in Latin America as well as serving as a resource for the evaluation of policies oriented to improve the health and environmental sustainability of cities

Critical swimming speed of matrinxã (Brycon amazonicus) exposed to hypoxia

Escape is the first response of fish to stress, that depends on the swimming performance and the physiological adjustments. This study has investigated the critical swimming speed (Ucrit) of matrinxã after exposure to hypoxia. To achieve that, the fishes were exposed to hypoxia and analyzed before and after forced swimming, using Ucrit. The hypoxia caused an increase of lactate, glucose, cortisol and hematocrit. No changes of plasma sodium and potassium levels, as well as the Ucrit, were observed. We suggest that matrinxã is sensitive to hypoxia, but the physiological adjustments are sufficient to keep its swimming performance.A primeira resposta ao estresse é a fuga, que depende do desempenho natatório e de ajustes fisiológicos. Este estudo investigou a velocidade crítica de natação (Ucrit) de matrinxã após exposição à hipoxia. Para isso, os peixes foram expostos à hipoxia, sendo uma parte do grupo analisada antes e outra após natação forçada, por meio da Ucrit. A hipoxia resultou no aumento de lactato, glicose, cortisol e hematócrito. Mudanças nos níveis de sódio e potássio, bem como os valores de Ucrit não foram observadas. Sugere-se que o matrinxã seja sensível à hipoxia, mas os ajustes fisiológicos são suficientes para manter seu desempenho natatório

Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progression-free survival in multiple myeloma

Despite the good response of stem cell transplant (SCT) in the treatment of multiple myeloma (MM), most patients relapse or do not achieve complete remission, suggesting that additional treatment is needed. We assessed the impact of thalidomide in maintenance after SCT in untreated patients with MM. A hundred and eight patients (<70 years old) were randomized to receive maintenance with dexamethasone (arm A; n = 52) or dexamethasone with thalidomide (arm B; n = 56; 200 mg daily) for 12 months or until disease progression. After a median follow-up of 27 months, an intention to treat analysis showed a 2-year progression-free survival (PFS) of 30% in arm A (95% CI 2238) and 64% in arm B (95% CI 5771; P = 0.002), with median PFS of 19 months and 36 months, respectively. In patients who did not achieve at least a very good partial response, the PFS at 2 years was significantly higher when in use of thalidomide (19 vs. 59%; P = 0.002). Overall survival at 2 years was not significantly improved (70 vs. 85% in arm A and arm B, respectively; P = 0.27). The addition of thalidomide to dexamethasone as maintenance improved the PFS mainly in patients who did not respond to treatment after SCT. Am. J. Hematol. (c) 2012 Wiley Periodicals, Inc.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)CNPq (Conselho Nacional do Desenvolvimento Cientifico e Tecnologico)Conselho Nacional do Desenvolvimento Cientifico e Tecnologico (CNPq)FAPERJ (Fundacao de Apoio a Pesquisa do Estado do Rio de Janeiro)FAPERJ (Fundacao de Apoio a Pesquisa do Estado do Rio de Janeiro