Secondary Modification of S100B Influences Anti Amyloid-ß Aggregation Activity and Alzheimer's Disease Pathology.

Proteinaceous aggregates accumulate in neurodegenerative diseases such as Alzheimer's Disease (AD), inducing cellular defense mechanisms and altering the redox status. S100 pro-inflammatory cytokines, particularly S100B, are activated during AD, but recent findings reveal an unconventional molecular chaperone role for S100B in hindering Aß aggregation and toxicity. This suggests a potential protective role for S100B at the onset of Aß proteotoxicity, occurring in a complex biochemical environment prone to oxidative damage. Herein, we report an investigation in which extracellular oxidative conditions are mimicked to test if the susceptibility of S100B to oxidation influences its protective activities. Resorting to mild oxidation of S100B, we observed methionine oxidation as inferred from mass spectrometry, but no cysteine-mediated crosslinking. Structural analysis showed that the folding, structure, and stability of oxidized S100B were not affected, and nor was its quaternary structure. However, studies on Aß aggregation kinetics indicated that oxidized S100B was more effective in preventing aggregation, potentially linked to the oxidation of Met residues within the S100:Aß binding cleft that favors interactions. Using a cell culture model to analyze the S100B functions in a highly oxidative milieu, as in AD, we observed that Aß toxicity is rescued by the co-administration of oxidized S100B to a greater extent than by S100B. Additionally, results suggest a disrupted positive feedback loop involving S100B which is caused by its oxidation, leading to the downstream regulation of IL-17 and IFN-α2 expression as mediated by S100B.

Genomic decoding of Theobroma grandiflorum (cupuassu) at chromosomal scale: evolutionary insights for horticultural innovation.

BACKGROUND: Theobroma grandiflorum (Malvaceae), known as cupuassu, is a tree indigenous to the Amazon basin, valued for its large fruits and seed pulp, contributing notably to the Amazonian bioeconomy. The seed pulp is utilized in desserts and beverages, and its seed butter is used in cosmetics. Here, we present the sequenced telomere-to-telomere genome of cupuassu, disclosing its genomic structure, evolutionary features, and phylogenetic relationships within the Malvaceae family. FINDINGS: The cupuassu genome spans 423 Mb, encodes 31,381 genes distributed in 10 chromosomes, and exhibits approximately 65% gene synteny with the Theobroma cacao genome, reflecting a conserved evolutionary history, albeit punctuated with unique genomic variations. The main changes are pronounced by bursts of long-terminal repeat retrotransposons at postspecies divergence, retrocopied and singleton genes, and gene families displaying distinctive patterns of expansion and contraction. Furthermore, positively selected genes are evident, particularly among retained and dispersed tandem and proximal duplicated genes associated with general fruit and seed traits and defense mechanisms, supporting the hypothesis of potential episodes of subfunctionalization and neofunctionalization following duplication, as well as impact from distinct domestication process. These genomic variations may underpin the differences observed in fruit and seed morphology, ripening, and disease resistance between cupuassu and the other Malvaceae species. CONCLUSIONS: The cupuassu genome offers a foundational resource for both breeding improvement and conservation biology, yielding insights into the evolution and diversity within the genus Theobroma.

Identification and functional characterization of the sugarcane (Saccharum spp.) AMT2-type ammonium transporter ScAMT3;3 revealed a presumed role in shoot ammonium remobilization.

Sugarcane (Saccharum spp.) is an important crop for sugar and bioethanol production worldwide. To maintain and increase sugarcane yields in marginal areas, the use of nitrogen (N) fertilizers is essential, but N overuse may result in the leaching of reactive N to the natural environment. Despite the importance of N in sugarcane production, little is known about the molecular mechanisms involved in N homeostasis in this crop, particularly regarding ammonium (NH4 +), the sugarcane's preferred source of N. Here, using a sugarcane bacterial artificial chromosome (BAC) library and a series of in silico analyses, we identified an AMMONIUM TRANSPORTER (AMT) from the AMT2 subfamily, sugarcane AMMONIUM TRANSPORTER 3;3 (ScAMT3;3), which is constitutively and highly expressed in young and mature leaves. To characterize its biochemical function, we ectopically expressed ScAMT3;3 in heterologous systems (Saccharomyces cerevisiae and Arabidopsis thaliana). The complementation of triple mep mutant yeast demonstrated that ScAMT3;3 is functional for NH3/H+ cotransport at high availability of NH4 + and under physiological pH conditions. The ectopic expression of ScAMT3;3 in the Arabidopsis quadruple AMT knockout mutant restored the transport capacity of 15N-NH4 + in roots and plant growth under specific N availability conditions, confirming the role of ScAMT3;3 in NH4 + transport in planta. Our results indicate that ScAMT3;3 belongs to the low-affinity transport system (Km 270.9 µM; Vmax 209.3 µmol g-1 root DW h-1). We were able to infer that ScAMT3;3 plays a presumed role in NH4 + source-sink remobilization in the shoots via phloem loading. These findings help to shed light on the functionality of a novel AMT2-type protein and provide bases for future research focusing on the improvement of sugarcane yield and N use efficiency.

An integrated analysis of mRNA and sRNA transcriptional profiles in Coffea arabica L. roots: insights on nitrogen starvation responses

Coffea arabica L. is an important agricultural commodity, accounting for 60% of traded coffee worldwide. Nitrogen (N) is a macronutrient that is usually limiting to plant yield; however, molecular mechanisms of plant acclimation to N limitation remain largely unknown in tropical woody crops. In this study, we investigated the transcriptome of coffee roots under N starvation, analyzing poly-A+ libraries and small RNAs. We also evaluated the concentration of selected amino acids and N-source preferences in roots. Ammonium was preferentially taken up over nitrate, and asparagine and glutamate were the most abundant amino acids observed in coffee roots. We obtained 34,654 assembled contigs by mRNA sequencing, and validated the transcriptional profile of 12 genes by RT-qPCR. Illumina small RNA sequencing yielded 8,524,332 non-redundant reads, resulting in the identification of 86 microRNA families targeting 253 genes. The transcriptional pattern of eight miRNA families was also validated. To our knowledge, this is the first catalog of differentially regulated amino acids, N sources, mRNAs, and sRNAs in Arabica coffee roots.

An integrated analysis of mRNA and sRNA transcriptional profiles in Coffea arabica L. roots: insights on nitrogen starvation responses

Coffea arabica L. is an important agricultural commodity, accounting for 60% of traded coffee worldwide. Nitrogen (N) is a macronutrient that is usually limiting to plant yield; however, molecular mechanisms of plant acclimation to N limitation remain largely unknown in tropical woody crops. In this study, we investigated the transcriptome of coffee roots under N starvation, analyzing poly-A+ libraries and small RNAs. We also evaluated the concentration of selected amino acids and N-source preferences in roots. Ammonium was preferentially taken up over nitrate, and asparagine and glutamate were the most abundant amino acids observed in coffee roots. We obtained 34,654 assembled contigs by mRNA sequencing, and validated the transcriptional profile of 12 genes by RT-qPCR. Illumina small RNA sequencing yielded 8,524,332 non-redundant reads, resulting in the identification of 86 microRNA families targeting 253 genes. The transcriptional pattern of eight miRNA families was also validated. To our knowledge, this is the first catalog of differentially regulated amino acids, N sources, mRNAs, and sRNAs in Arabica coffee roots.

Consentimento e proteção de adultos e crianças: dilemas comuns e peculiares em países em desenvolvimento / Consent and protection of adults and children: common and peculiar dilemmas in developing countries

O presente trabalho faz revisão dos artigos recentemente publicados em revistas médicas de circulação nacional e internacional sobre o tema do consentimento informado. Apresenta, em sua introdução, os aspectos históricos e a dimensão global das questões jurídicas e legais, discorrendo sobre a importância ética do assunto. A seguir, pontua algumas das peculiaridades da prática do uso do consentimento informado na pediatria, arguindo sobre a necessidade do respeito à autonomia da criança e do adolescente. Desenvolve uma linha de análise bioética desta prática em unidades de terapia intensiva neonatal em países emdesenvolvimento, nas quais além da vulnerabilidade dos pacientes, na maioria bebês prematuros, somam-se outros aspectos técnicos, culturais, religiosos, educacionais, econômicos, sociais etc. Conclui ressaltando a complexidade deste procedimento e alerta que apenas seu uso não garante efetivamente o respeito e a proteção dos pacientes, quer envolvidos ou não em protocolos de pesquisas.

O papel das Secretarias Estaduais de Saúde na Construção da Hemorrede Pública: uma reflexão sobreo compartilhamento de responsabilidades em face aodesafio do fornecimento de plasma à Hemobrás / The role of State Health Departments in the construction of Hemorrede: a reflection on sharing responsibilities in meeting the challenge of providing plasma to Hemobrás

O Brasil vem implantando sua hemorrede nacional, levando assistência hemoterápica aos serviços de saúde. A implantação das hemorredes estaduais estabeleceu a participação dos Estados no esforço de consolidar a Política Nacional de Sangue, Componentese Hemoderivados, implementada pelo Sistema Nacional do Sangue – SINASAN. Garantir atendimento hemoterápico é responsabilidade das hemorredes estaduais, que agora passam o fornecimento de plasma à Hemobrás, com qualidade e em quantidade suficiente. A hemorrede tem dificuldades para obter sangue de doadores voluntários. Ações integradase mais investimentos para a melhoria da sua qualificação técnica e gerencial são necessários. Nessa perspectiva, este trabalho apresenta uma reflexão das relações intergovernamentais na gestão da hemoterapia, das dificuldades das hemorredes e o esforço da gestãocompartilhada para o fornecimento do plasma qualificado à Hemobrás.

Brazil has been implementing its National Hemorrede, taking hemotherapy care to health services. The deployment of regional Hemorredes established the participation of statesin efforts to consolidate the National Policy on Blood, Blood Components and Blood Products, implemented by the National Blood System – SINASAN. Ensuring hemotherapeutic complianceis the responsibility of regional Hemorredes, who now supply plasma to Hemobrás, with quality and in sufficient quantity. The Hemorrede have trouble getting blood from volunteer donors.Integrated actions and investments are needed to improve their technical and managerial. In this perspective, it presents a reflection of the intergovernmental relations in the management of hemotherapeudic, the difficulties of Hemorredes and the effort of shared management to supply of plasma qualified to Hemobrás.

Citrus plastid-related gene profiling based on expressed sequence tag analyses

Plastid-related sequences, derived from putative nuclear or plastome genes, were searched in a large collection of expressed sequence tags (ESTs) and genomic sequences from the Citrus Biotechnology initiative in Brazil. The identified putative Citrus chloroplast gene sequences were compared to those from Arabidopsis, Eucalyptus and Pinus. Differential expression profiling for plastid-directed nuclear-encoded proteins and photosynthesis-related gene expression variation between Citrus sinensis and Citrus reticulata, when inoculated or not with Xylella fastidiosa, were also analyzed. Presumed Citrus plastome regions were more similar to Eucalyptus. Some putative genes appeared to be preferentially expressed in vegetative tissues (leaves and bark) or in reproductive organs (flowers and fruits). Genes preferentially expressed in fruit and flower may be associated with hypothetical physiological functions. Expression pattern clustering analysis suggested that photosynthesis- and carbon fixation-related genes appeared to be up- or down-regulated in a resistant or susceptible Citrus species after Xylella inoculation in comparison to non-infected controls, generating novel information which may be helpful to develop novel genetic manipulation strategies to control Citrus variegated chlorosis (CVC).

Genetic machinery for RNA silencing and defense against viruses in Citrus

RNA silencing mechanisms are conserved throughout eukaryotic evolution, possibly due to their importance in viral resistance and other aspects of cell biology. Here, we explored the Citrus EST (CitEST) database in search of sequences related to the most important known genes involved in RNA silencing. Transcripts strongly matching Argonaute (AGO), Dicer-like (DCL), Hua enhancer (HEN), and RNA-dependent RNA Polymerase (RdRP) were found in many of the citrus libraries. The reads were clustered and quantified. This shows that post-transcriptional gene silencing apparatus is active in citrus. It seems plausible that a better understanding of the players of RNA silencing in Citrus spp. and related genera may help create new tools to defeat the viral diseases that affect the citrus industry. Functional analyses of these citrus genes would enable the pursuit of this hypothesis.

Expression profile of oxidative and antioxidative stress enzymes based on ESTs approach of citrus

Plants not only evolve but also reduce oxygen in photosynthesis. An inevitable consequence of this normal process is the production of reactive oxygen species (ROS). Plants are adequately protected by the presence of multiple antioxidative enzymes in the cytosol and also in the different cell organelles such as chloroplasts, mitochondria, and peroxisomes. Traditionally, ROS were considered to be only a toxic byproduct of aerobic metabolism. However, recently it has become apparent that plants actively produce these molecules which may control many different physiological processes such as abiotic and biotic stress response, pathogen defense and systemic signaling. The search results using the Citrus Genome Program in Brazil (CitEST) for oxidative stress and the antioxidant enzyme system in Citrus Sinensis variety ‘Pera IAC’ indicated that the multiple ROS-scavenging enzymes were expressed throughout all citrus tissues. The analyses demonstrated the ubiquitous expression of metallothioneins, probably indicating a constitutive expression pattern. Oxalate oxidase has been identified as the most abundant expressed gene in developing fruits, which suggests a specific function in the ripening of citrus fruit. Moreover, infected leaves with Xylella fastidiosa and Leprosis citri showed a massive change in their ROS gene expression profile which may indicate that the suppression of ROS detoxifying mechanisms may be involved in the induction of the diseases.

In silico analysis of phytohormone metabolism and communication pathways in citrus transcriptome

Plant hormones play a crucial role in integrating endogenous and exogenous signals and in determining developmental responses to form the plant body throughout its life cycle. In citrus species, several economically important processes are controlled by phytohormones, including seed germination, secondary growth, fruit abscission and ripening. Integrative genomics is a powerful tool for linking newly researched organisms, such as tropical woody species, to functional studies already carried out on established model organisms. Based on gene orthology analyses and expression patterns, we searched the Citrus Genome Sequencing Consortium (CitEST) database for Expressed Sequence Tags (EST) consensus sequences sharing similarity to known components of hormone metabolism and signaling pathways in model species. More than 600 homologs of functionally characterized hormone metabolism and signal transduction members from model species were identified in citrus, allowing us to propose a framework for phytohormone signaling mechanisms in citrus. A number of components from hormone-related metabolic pathways were absent in citrus, suggesting the presence of distinct metabolic pathways. Our results demonstrated the power of comparative genomics between model systems and economically important crop species to elucidate several aspects of plant physiology and metabolism.

Identifying sugarcane expressed sequences associated with nutrient transporters and peptide metal chelators

A absorçäo de nutrientes pelas plantas é um processo ativo, requerendo energia para o acúmulo de nutrientes essenciais em níveis mais elevados nos tecidos vegetais do que na soluçäo do solo, enquanto que a presença de metais tóxicos ou excesso de nutrientes requererem mecanismos para modular o acúmulo de íons. Genes que codificam transportadores de íons, isolados de plantas e de leveduras, foram usados para identificar homólogos presumíveis no banco de dados de seqüências expressas de cana-de-açúcar (SUCEST). Cinco consensos de grupos de seqüências com homologia a genes de transportadores de fosfato de alta afinidade foram identificados. O consenso de um dos grupos permitiu a prediçäo da proteína completa, com 541 amino ácidos e 81 por cento de identidade com o gene NtPT1 de Nicotiana tabacum, consistindo de 12 domínios transmembrana divididos por uma grande regiäo hidrofílica. Homólogos presumíveis a genes transportadores de micronutrientes de Arabidopsis thaliana também foram detectados em algumas bibliotecas do SUCEST. A absorçäo de ferro em gramíneas envolve a liberaçäo de um composto fito-sideróforo, ácido mugenêico (MA), que complexa com FeÝ+, sendo entäo absorvido por um transportador específico. Seqüências expressas (EST, expressed sequence tag) de cana-de-açúcar homólogas aos genes que codificam as três enzimas da via de biossíntese do ácido mugenêico (nicotianamina sintase; nicotianamina transferase; e a sintetase presumível do ácido mugenêico ids3), além de um transportador presumível de FeÝ+-fito-sideróforo foram também detectados. Sete grupos de seqüências de cana-de-açúcar foram identificados com grande homologia com os membros da família de genes ZIP (ZIP1, ZIP3, ZIP4, IRT1 e ZNT1), enquanto que quatro grupos apresentaram homologia com ZIP2 e três com ZAT. Seqüências homólogas aos membros de uma outra família de genes, Nramp, que codificam transportadores de metais de ampla espectro, foram também detectados com expressäo constitutiva. Transcritos parciais homólogos aos genes que codificam y-glutamilcisteína sintetase, glutationa sintetase e fitoquelatina sintase (responsáveis pela biossíntese da proteína quelante de metais, fitoquelatina) e todos os quatro tipos do outro principal peptídeo quelante de metais em plantas, metalotioneína (MT), foram identificados: MT do tipo I sendo a mais abundante, seguido pela MT do tipo II, com padräo de expressäo similar àquele descrito para MT de Arabidopsis.

Mating system in a natural population of Theobroma grandiflorum (Willd. ex Spreng.) Schum., by microsatellite markers

The aim of this research was to study the mating system of a natural population of Theobroma grandiflorum (cupuassu) from Nova Ipixuna, Pará state, using microsatellite markers. ...

Trombose mesentérica como complicação da colecistectomia videolaparoscópica / Intestinal ischaemia after laparoscopic cholecystectomy

Intestinal complications after laparoscopic cholecystectomy are rare and usually caused by direct injury sustained on trocar insertion. However, intestinal ischaemia has been reported as an unusual complication of the pneumoperitoneum. We describe a 55-years-old patient who underwent an uneventful laparoscopic cholecystectomy after an episode of acute cholecystitis. Initial recovery was complicated by development of increasing abdominal pain which led to open laparotomy on day 2. Gangrene of the distal ileum and right-sided colon was detected and small bowel resection with right colectomy and primary anastomosis was performed. Histological examination of the resected ileum showed features of venous hemorragic infarction and trombosis. In view of the proximity of the operation it is assumed that ileal ischaemia was precipitated by carbon dioxide pneumoperitoneum. Some studies have been demonstrated that, within 30 minutes of establishing a pneumoperitoneum at an intraabdominal pressure of 16mmHg, cardiac output, blood flow in the superior mesenteric artery and portal vein decrease progressively. Carbon dioxide pneumoperitoneum may lead to mechanical compression of the splanchnic veins and mesenteric vasoconstriction as a result of carbon dioxide absortion. The distribution of the ischaemic segment of intestine is also unusual as the most precarious blood supply is traditionally at the splenic flexure of the colon. It has been suggested that intermittent decompression of the abdomen reduces the risk of mesenteric ischaemia during pneumoperitoneum especially in patients with predisposing clinical features for arteriosclerosis intestinal. In present patient was observed intestinal venous infarction what remains unclear but we think the carbon dioxide pneumoperitoneum have been related to it

Insulinomas do pâncreas: diagnóstico e tratamento / Pancreatic insulinomas: diagnosis and treatment

RACIONAL: O insulinoma é uma neoplasia que pertence ao grupo de tumores neuroendócrinos do pâncreas; embora raro, é o mais freqüente entre eles. OBJETIVO: Avaliar os resultados clínico e imunohistoquímico de doentes com insulinoma de pâncreas submetidos a tratamento cirúrgico. PACIENTES E MÉTODOS: Foram detalhados o quadro clínico, exames laboratoriais e de imagem, dando ênfase aos aspectos cirúrgicos, complicações e acompanhamento, a médio e longo prazos, de 12 doentes portadores de insulinoma. A cirurgia foi indicada para todos, com base nas evidências clínicas e laboratoriais de hipoglicemia e hiperinsulinemia. RESULTADOS: Em sete doentes conseguiu-se a localizaçäo prévia da lesäo; em cinco, sua localizaçäo foi identificada durante a cirurgia mediante palpaçäo e através do ultra-som intra-operatório. O procedimento mais freqüentemente utilizado foi a ressecçäo pancreática em oito doentes. A complicaçäo cirúrgica mais freqüente foi a fístula pancreática, observada em sete doentes. Dois apresentaram tardiamente diabetes mellitus. Näo houve mortes na presente casuística. CONCLUSÄO: Na totalidade dos doentes obteve-se a reversäo clínica dos sintomas, caracterizada pelo desaparecimento da tríade de Whipple, além de normalizaçäo ou aumento dos níveis de glicemia, quando comparados aos valores do pré-operatório

Bases científicas da alimentação da criança: suas consequências sociais (carta aberta ao Sr. M. R. G. P.) / Scientific basis of chid nutrition: its social consequences (open letter to Mr. M. R. G. P.)

Nesta casa, Fernandes Figueira informa sobre a proposta de oferecimento de leite de vaca, e talvez de cabra, às crianças pobres cujas mães são forçadas a trabalhar. A partir, ele questiona as consequências que ocasionariam esta atitude. (AU)

Observaçöes diagnósticas da gastropatia congestiva da hipertesäo portal por cirrose alcoólica e por esquistossomose / Diagnosis observations of congestive gastropathy of portal hypertension by alcoholic cirrhosis and schistosomiasis

A gastropatia observada em doentes com hipertensão portal de etiologia cirrótica constitui entidade controversa notadamente quanto à relação entre os achados endoscópicos e histológicos. Sua importância clínica fundamenta-se no fato de ser responsabilizada por aproximadamente 30 a 50 por cento das hemorragias digestivas observadas nesses doentes. A observação dessa entidade em doentes esquistossomóticos com hipertensão portal e com reserva funcional hepática preservada é incomum. Macroscopicamente, o endocospista observa edema da mucosa gástrica, e pequenas manchas avermelhadas com aspecto em mosaico. As biópsias revelam ectasia vascular com ou sem inflamação crônica dos vasos da mucosa e submucosa do estômago. Neste estudo comparou-se prospectivamente 10 doentes com cirrose alcoólica e 10 doentes com hipertensão portal de etiologia esquitossomótica. O grupo controle foi representado por 12 doentes sem doenças hepática. Os achados endoscópicos e histológicos da mucosa do estômago não diferiram significantemente entre os doentes cirróticos esquistossomóticos, e o grupo controle. Os autores concluem que há uma efetiva dificuldade na correlação diagnostica endoscópica e histopatológica da gastropatia congestiva da hipertensão portal que poderá ser melhor definida em casuística mais numerosa e com técnica endoscópica de colheita de amostras mais profundas da mucosa do estômago.