Força de uma casca esférica em um corpo acelerado: independência da posição

Em um trabalho anterior [Physicae Organum \textbf{2} (2), 1 (2016)], foi mostrado que uma força gravitacional do tipo Weber, a qual, além do termo newtoniano, inclui termos que contemplam o movimento relativo entre os corpos que interagem, é \emph{não-nula} quando um corpúsculo em repouso no centro de uma casca esférica homogênea é acelerado em relação a ela. Nesta nota, mostramos matematicamente que a mesma força é obtida qualquer que seja a posição do corpúsculo no interior da casca

Prostatic carcinomas with neuroendocrine differentiation diagnosed in needle biopsies, a morphologic study of 7 cases among 465 sequential biopsies in a tertiary cancer center

Purpose: Neuroendocrine carcinomas (NEC) of the prostate are rare, with only a few series hitherto reported. the objective of this study was to assess in a single institution the clinical and morphologic characteristics of neuroendocrine carcinomas diagnosed in needle core biopsies.Materials and Methods: the current study analyses seven cases diagnosed in needle biopsies at a large tertiary regional cancer center from Northeastern Brazil. Two pathologists reviewed specimens retrospectively, and demographic and morphologic characteristics were compared to 458 acinar tumors diagnosed in the same period.Results: There were five small cell carcinomas and two low-grade neuroendocrine carcinomas (carcinoid). NEC were associated with an acinar component in 5/7 cases and the Gleason score of the acinar component was always > 6. the number of cores involved in prostates with NEC was greater (65% compared to 24% of acinar tumors, p < 0.05). the mean PSA at diagnosis was 417.7 (range 5.7-1593, SD 218.3), compared to 100.5 (p = 0.1) of acinar tumors (range 0.3-8545, SD 22.7). Prostates harboring NEC were bigger (p < 0.001, mean volume 240 mL vs. 53 mL of acinar tumors). Treatment of NEC included palliative surgery, chemotherapy, and hormonal therapy.Conclusions: NEC of the prostate is rare and often associated with a high-grade acinar component. Prostates with NEC tend to be larger and involve a greater number of cores than acinar tumors. PSA at diagnosis does not seem to predict the presence of NE tumors in needle biopsy.Hosp Canc, Inst Canc Ceara, BR-60430230 Fortaleza, Ceara, BrazilEscola Paulista Med, BR-04023 São Paulo, BrazilEscola Paulista Med, BR-04023 São Paulo, BrazilWeb of Scienc

Electrochemical study of simple coumarin and its determination in aqueous infusion of Mikania glomerata

The present study aims the development and application of an electrochemical method for simple coumarin determination in aqueous media by using a boron-doped diamond electrode (BDDE). The studies were carried out at pH 8.0 by cyclic voltammetry (CV) and registered an irreversible reduction process controlled by diffusion with the peak potential recorded around -1.6 V. The square wave voltammetry analysis (SWV) showed the reversible behavior of the electrochemical reduction of coumarin at the same pH. Additionally, the reversibility of the process was improved by increasing the solution pH. The chronoamperometry study showed that the coumarin reduction process involves two electrons. From the optimized SWV parameters, the analytical curve was constructed in a linear range between 0.5 × 10-5 and 10.0 × 10-5 mol L-1. The limits of detection and quantification were 1.5 × 10-6 mol L-1 and 4.5 × 10-6 mol L-1, respectively. The coumarin was determined in an aqueous infusion of Mikania glomerata, showing recovery values between 92 and 104%.O presente estudo teve por objetivos o desenvolvimento e a aplicação de um método eletroquímico para a determinação da cumarina simples em meio aquoso utilizando o eletrodo de diamante dopado com boro (BDDE). Os estudos foram realizados em pH 8,0 utilizando a voltametria cíclica (CV) e observou-se um processo de redução irreversível controlado por difusão com um pico de redução em torno de -1,6 V. Entretanto, foi possível observar por voltametria de onda quadrada (SWV) que no mesmo pH a redução da cumarina possui um caráter reversível. Além disso, esta reversibilidade se tornou mais evidente com o aumento do pH da solução. Um estudo cronoamperométrico mostrou que o processo de redução da cumarina envolve dois elétrons. A partir dos parâmetros otimizados da SWV uma curva analítica foi construída no intervalo linear de 0,5 × 10-5 a 10,0 × 10-5 mol L-1. Os limites de detecção e de quantificação foram 1,5 × 10-6 mol L-1 e 4,5 × 10-6 mol L-1, respectivamente. A cumarina foi determinada em amostras de Mikania glomerata (infusão aquosa) com valores de recuperação entre 92 e 104%.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo (UNIFESP) Instituto de Ciências Ambientais, Químicas e Farmacêuticas Departamento de Ciências Exatas e da TerraUniversidade Federal do ABC Centro de Ciências Naturais e HumanasUNIFESP, Instituto de Ciências Ambientais, Químicas e Farmacêuticas Depto. de Ciências Exatas e da Terra2008/50588-6SciEL

Mechanisms associated with winter intraseasonal extreme sea ice extent in the Weddell Sea

Previous studies have shown evidence of atmospheric extratropical wave trains modulating sea ice area in the Weddell and Amundsen/Bellingshausen seas on intraseasonal time-scales (20–100 d). Here we investigate mechanisms relating intraseasonal extreme sea ice extent and Ekman layer dynamics with emphasis on the Weddell Sea. This study extends from 1989 to 2013 and focuses on the winter season. Wind stress τ is calculated with winds from the Climate Forecast System reanalysis (CFSR) to evaluate momentum transfer between the atmosphere and the Ekman layer. Lag-composites of the anomalies of Ekman transport and the Ekman pumping indicate that divergence of mass in the Ekman layer and upwelling lead the occurrence of extreme sea ice contraction on intraseasonal time-scales in the Weddell Sea. Opposite conditions (i.e., convergence of the mass and downwelling) lead extreme sea ice expansion on intraseasonal time-scales. This study suggests that the Ekman pumping resulting from the anomalous wind stress on intraseasonal time-scales can transport these warmer waters to the surface contributing to sea ice melting. Additionally, high resolution sea ice fraction and ocean currents obtained from satellite and in situ data are used to investigate in detail mechanisms associated with persistent extreme sea ice expansion and contraction on intraseasonal time-scales. These case studies reveal that atmospheric circumpolar waves on intraseasonal time-scales can induce contrasting anomalies of about ±20% in sea ice concentration at the Weddell and western Antarctica Peninsula margins within less than 30 d. This study shows that extreme anomalies in sea ice may lag between 5–25 d (1–5 pentads) the ocean-atmospheric forcing on intraseasonal time-scales

Hidden patterns of codon usage bias across kingdoms

The genetic code encodes 20 amino acids using 64 nucleotide triplets or codons. 18 of the 20 amino acids are encoded by multiple synonymous codons which are used in organismal genomes in a biased fashion. Codon bias arises because evolutionary selection favours particular nucleotide sequences over others encoding the same amino acid sequence. Despite many existing hypotheses, there is no current consensus on what the evolutionary drivers are. Using ideas from stochastic thermodynamics we derive from first principles a mathematical model describing the statistics of codon usage bias and apply it to extensive genomic data. Our main conclusions include the following findings: (1) Codon usage cannot be explained solely by selection pressures that act on the genome-wide frequency of codons, but also includes pressures that act at the level of individual genes. (2) Codon usage is not only biased in the usage frequency of nucleotide triplets but also in how they are distributed across mRNAs. (3) A new model-based measure of codon usage bias that extends existing measures by taking into account both codon frequency and codon distribution reveals distinct, amino acid specific patterns of selection in distinct branches of the tree of life

tackling malaria

Malaria is an infectious disease that affects over 216 million people worldwide, killing over 445,000 patients annually. Due to the constant emergence of parasitic resistance to the current antimalarial drugs, the discovery of new drug candidates is a major global health priority. Aiming to make the drug discovery processes faster and less expensive, we developed binary and continuous Quantitative Structure-Activity Relationships (QSAR) models implementing deep learning for predicting antiplasmodial activity and cytotoxicity of untested compounds. Then, we applied the best models for a virtual screening of a large database of chemical compounds. The top computational predictions were evaluated experimentally against asexual blood stages of both sensitive and multi-drug-resistant Plasmodium falciparum strains. Among them, two compounds, LabMol-149 and LabMol-152, showed potent antiplasmodial activity at low nanomolar concentrations (EC50 <500 nM) and low cytotoxicity in mammalian cells. Therefore, the computational approach employing deep learning developed here allowed us to discover two new families of potential next generation antimalarial agents, which are in compliance with the guidelines and criteria for antimalarial target candidates.publishersversionpublishe

The Repetitive Cytoskeletal Protein H49 of Trypanosoma cruzi Is a Calpain-Like Protein Located at the Flagellum Attachment Zone

Background: Trypanosoma cruzi has a single flagellum attached to the cell body by a network of specialized cytoskeletal and membranous connections called the flagellum attachment zone. Previously, we isolated a DNA fragment (clone H49) which encodes tandemly arranged repeats of 68 amino acids associated with a high molecular weight cytoskeletal protein. in the current study, the genomic complexity of H49 and its relationships to the T. cruzi calpain-like cysteine peptidase family, comprising active calpains and calpain-like proteins, is addressed. Immunofluorescence analysis and biochemical fractionation were used to demonstrate the cellular location of H49 proteins.Methods and Findings: All of H49 repeats are associated with calpain-like sequences. Sequence analysis demonstrated that this protein, now termed H49/calpain, consists of an amino-terminal catalytic cysteine protease domain II, followed by a large region of 68-amino acid repeats tandemly arranged and a carboxy-terminal segment carrying the protease domains II and III. the H49/calpains can be classified as calpain-like proteins as the cysteine protease catalytic triad has been partially conserved in these proteins. the H49/calpains repeats share less than 60% identity with other calpain-like proteins in Leishmania and T. brucei, and there is no immunological cross reaction among them. It is suggested that the expansion of H49/calpain repeats only occurred in T. cruzi after separation of a T. cruzi ancestor from other trypanosomatid lineages. Immunofluorescence and immunoblotting experiments demonstrated that H49/calpain is located along the flagellum attachment zone adjacent to the cell body.Conclusions: H49/calpain contains large central region composed of 68-amino acid repeats tandemly arranged. They can be classified as calpain-like proteins as the cysteine protease catalytic triad is partially conserved in these proteins. H49/calpains could have a structural role, namely that of ensuring that the cell body remains attached to the flagellum by connecting the subpellicular microtubule array to it.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Beca Presidente de la Republica-ChileUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, São Paulo, BrazilUniv Antofagasta, Lab Bioquim, Dept Biomed, Antofagasta, ChileUniv Bandeirante São Paulo, São Paulo, BrazilUniv Brasilia, Dept Biol Celular, Inst Biol, Brasilia, DF, BrazilFiocruz MS, Ctr Pesquisa Rene Rachou CPqRR, Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, São Paulo, BrazilWeb of Scienc

Intrauterine Blood Plasma Platelet-Therapy Mitigates Persistent Breeding-Induced Endometritis, Reduces Uterine Infections, and Improves Embryo Recovery in Mares

Microorganisms, including pathogenic or opportunistic bacteria and fungi, may gain access to the uterus during breeding, and infectious endometritis plays a major role in equine subfertility. This study aimed to assess the post-breeding inflammatory response, endometrial culture, and embryo recovery of mares susceptible to persistent breeding-induced endometritis (PBIE) treated with plasma-rich (PRP) or -poor (PPP) plasma. Mares (n = 12) susceptible to PBIE had three cycles randomly assigned to receive intrauterine infusions of lactate ringer solution (LRS, control), or autologous PRP or PPP pre- (−48 and −24 h) and post-breeding (6 and 24 h). Mares were bred with fresh semen from one stallion. Intrauterine fluid accumulation (IUF) and endometrial neutrophils were assessed every 24 h up to 96 h post-breeding. Uterine cytokines (Ilβ, IL6, CXCL8, and IL10) were evaluated before (0 h), 6, and 24 h post-breeding, and endometrial culture three and nine days after breed. Embryo flushing was performed 8 days post-ovulation. Data were analyzed with mixed model, Tukey’s post-hoc test, and multivariate regression. PRP treatment reduced endometrial neutrophils, post-breeding IUF, and pro-inflammatory cytokines when compared to control-assigned cycles, but not significantly different than PPP. Controls had a significantly higher percentage of positive bacterial cultures (33%) in comparison to PRP-assigned cycles (0%), whereas cycles treated with PPP were not significantly different from the other groups (25%). The PRP-assigned cycles had significantly greater embryo recovery rates (83%) than the control (33%), though not significantly different than PPP (60%). Plasma infusion reduced the duration and intensity of the post-breeding inflammatory response and improved embryo recovery in mares susceptible to PBIE. Platelets incrementally downregulate PBIE and appear to have a dose-dependent antimicrobial property

C7orf59/LAMTOR4 phosphorylation and structural flexibility modulate ragulator assembly

Ragulator is a pentamer composed of p18, MP1, p14, C7orf59, and hepatitis B virus X-interacting protein (HBXIP; LAMTOR 1-5) which acts as a lysosomal scaffold of the Rag GTPases in the amino acid sensitive branch of TORC1 signaling. Here, we present the crystal structure of human HBXIP-C7orf59 dimer (LAMTOR 4/5) at 2.9 angstrom and identify a phosphorylation site on C7orf59 which modulates its interaction with p18. Additionally, we demonstrate the requirement of HBXIP-C7orf59 to stabilize p18 and allow further binding of MP1-p14. The structure of the dimer revealed an unfolded N terminus in C7orf59 (residues 1-15) which was shown to be essential for p18 binding. Full-length p18 does not interact stably with MP1-p14 in the absence of HBXIP-C7orf59, but deletion of p18 residues 108-161 rescues MP1-p14 binding. C7orf59 was phosphorylated by protein kinase A (PKA) in vitro and mutation of the conserved Ser67 residue to aspartate prevented phosphorylation and negatively affected the C7orf59 interaction with p18 both in cell culture and in vitro. C7orf59 Ser67 was phosphorylated in human embryonic kidney 293T cells. PKA activation with forskolin induced dissociation of p18 from C7orf59, which was prevented by the PKA inhibitor H-89. Our results highlight the essential role of HBXIP-C7orf59 dimer as a nucleator of pentameric Ragulator and support a sequential model of Ragulator assembly in which HBXIP-C7orf59 binds and stabilizes p18 which allows subsequent binding of MP1-p149915891602CNPQ - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo2014/12445-0; 2017/21455-7; 2014/17264-3190174/2012-