Resumo O objetivo desse estudo foi avaliar os efeitos sazonais dos meses do ano sobre as respostas fisiológicas e produtivas de vacas leiteiras mestiças criadas em clima amazônico. Foram avaliadas 20 vacas lactantes, alimentadas com pasto de Brachiaria decumbens, com acesso livre a água e suplementação mineral. Foram registrados dados das variáveis climáticas temperatura do ar (TA), umidade relativa do ar (UR), precipitação pluviométrica (PP) e índice de temperatura e Umidade (ITU) durante os meses de janeiro a abril de 2019. Os dados fisiológicos coletados foram: frequência respiratória (FR, mov/min), frequência cardíaca (FC, bat./min), temperatura retal (TR, ºC), temperatura superficial do úbere (TSU, ºC), temperatura superfície corporal (TSC, ºC), temperatura superficial do dorso (TSD, ºC), temperatura superficial da fronte (TSF, ºC) e temperatura superficial da canela (TSCA, °C). Também foi mensurada a produção de leite (PL, kg). Houve diferença significativa (P<0,05) da TSCA e FR com valores variando de 34,8 a 35,5°C e 32,0 a 36,2 mov/min, respectivamente. Não houve diferença significativa (P>0,05) para TSC e os valores observados para PL e ITU foram 3,8; 3,8; 4,6; 4,1 kg e 77,7; 79,7; 80,6; 80,1, respectivamente. Houve efeito sazonal dos meses avaliados sobre a taxa respiratória dos animais, no entanto, isso não alterou a PL nem o ITU. O ambiente amazônico é propício a causar estresse térmico em vacas lactantes mantidas a pasto, sendo necessário o uso de sombreamento para facilitar a capacidade de dissipação de calor corporal desses animais. 2 decumbens mineral TA, TA , (TA) UR, UR (UR) PP (PP (ITU 2019 FR, (FR movmin mov/min mov min mov/min) FC, FC (FC bat./min, batmin bat./min bat bat./min) TR, TR (TR ºC, ºC TSU, TSU (TSU TSC, (TSC TSD, TSD (TSD TSF, TSF (TSF TSCA, (TSCA °C. C °C . °C) PL, (PL kg. kg) P<0,05 P005 P 0 05 (P<0,05 348 34 8 34, 355C 35 5 320 32 32, 362 36 36, respectivamente P>0,05 (P>0,05 3,8 38 3 4,6 46 4 6 41 1 4, 77,7 777 77 7 79,7 797 79 80,6 806 80 801 80,1 animais entanto (TA (UR 201 P<0,0 P00 (P<0,0 P>0,0 (P>0,0 3, 77, 79, 80, P<0, P0 (P<0, P>0, (P>0, P<0 (P<0 P>0 (P>0 P< (P< P> (P> (P

Abstract The objective of this study was to evaluate the seasonal effect of months of the year upon the physiological and productive responses of crossbred dairy cows raised in an Amazonian climate. Twenty lactating cows were evaluated, fed on Brachiaria decumbens pasture, with free access to water and mineral supplementation. Data from climate variables air temperature (AT), relative humidity (RH), rainfall (RA) and temperature and humidity index (THI) were recorded dur ing the months of January to April 2019. The physiological data collected were: respiratory rate (RR, mov/min), heart rate (HR, beats/min), rectal temperature (RT, ºC), udder surface temperature (UST, ºC), body surface temperature (BST, ºC), dorsum surface temperature (DST, ºC), front surface temperature (FST, ºC) and rear shin temperature (RST). Milk production (MP) was also measured. There was a significant difference (P<0.05) of RST and RR with values ranging from 34.8 to 35.5°C and 32.0 to 36.2 mov/min, respectively. There were no significant difference (P>0.05) for BST, and the values for MP and THI were 3.8; 3.8; 4.6; 4.1 kg and 77.7; 79.7; 80.6; 80.1, respectively. It was concluded that there was a seasonal effect of the months of the year evaluated on the respiratory rate of animals, however, it did not change the MP and the THI. The Amazon environment is conducive to causing thermal stress in lactating cows raised on pasture, requiring the use of shading to facilitate the ability of these animals to dissipate heat. pasture supplementation AT, AT , (AT) RH, RH (RH) RA (RA (THI 2019 RR, (RR movmin mov/min mov min mov/min) HR, HR (HR beats/min, beatsmin beats/min beats beats/min) RT, RT (RT ºC, ºC UST, UST (UST BST (BST DST, DST (DST FST, FST (FST RST. . (RST) (MP measured P<0.05 P005 P 0 05 (P<0.05 348 34 8 34. 355C C 35 5 320 32 32. 362 36 2 36. respectively P>0.05 (P>0.05 3.8 38 3 4.6 46 4 6 41 1 4. 77.7 777 77 7 79.7 797 79 80.6 806 80 801 80.1 however heat (AT (RH 201 (RST P<0.0 P00 (P<0.0 P>0.0 (P>0.0 3. 77. 79. 80. 20 P<0. P0 (P<0. P>0. (P>0. P<0 (P<0 P>0 (P>0 P< (P< P> (P> (P

Abstract Despite highly variable efficacy, BCG (Bacillus Calmette-Guérin) is the only vaccine available to prevent the tuberculosis (TB). Genomic heterogeneity between attenuated BCG strains and virulent Mycobacterium tuberculosis might help to explain this vaccine’s impaired capacity to induce long-term protection. Here, we investigate the lipid-related genes absent in attenuated BCG strains in order to correlate changes in both lipid metabolism and cell-wall lipid content to vaccine impairment. Whole genome sequences of M. tuberculosis H37Rv and the six most used BCG strains worldwide were aligned and the absent regions functionally categorized. Genomes of the BCG strains showed a total of 14 non-homologous lipid-related genes, including those belonging to mce3 operon, as well as the gene echaA1, which encodes an enoyl-CoA hydratase, and the genes encoding phospholipases PlcA, PlcB and PlcC. Taken together, the depletion of these M. tuberculosis H37Rv genomic regions were associated with marked alterations in lipid-related genes of BCG strains. Such alterations may indicate a dormant-like state and can be determining factors to the vaccine’s inability to induce long-term protection. These lipids can be further evaluated as an adjuvant to boost the current BCG-based vaccine.

RESUMO Introdução: Novos estudos de regulação gênica do exercício físico por meio de técnicas pós-genômicas em ensaios de resistência (endurance) e força caracterizam a transcriptômica do exercício físico. Entre os genes afetados, destacamos a via da proteína quinase ativada por AMP (AMPK), cuja ativação ocorre durante o exercício como resultado das alterações dos níveis de fosfato energético da fibra muscular. Objetivo: Avaliar a via de sinalização da AMPK por revisão sistemática da expressão de genes e análise in silico. Método: Foi efetuada uma revisão sistemática para avaliar a regulação gênica da via de sinalização AMPK, caracterizando os genes estudados na literatura, as variações de regulação obtidas, na forma de fold change e tipos de exercício usados. Resultados: A via de sinalização AMPK mostrou 133 genes no repositório KEGG (Kyoto Encyclopedia of Genes and Genomes), os quais foram confrontados com a revisão sistemática da literatura, totalizando 65 genes. Dezessete genes apresentaram UR e 24 mostraram DR com relação ao seu respectivo controle. Além destes, 20 genes estavam presentes nos trabalhos, apresentando tanto UR e DR e quatro genes não apresentaram dados de regulação. Verificou-se regulação específica em função do tipo de exercício efetuado. Discussão: Dos 133 genes da via AMPK, 48,8% foram amostrados nos trabalhos revisados, indicando que uma parte significativa da via é regulada pelo exercício. O estudo apresentou a regulação gênica básica de dois mecanismos para a recuperação energética, a biogênese mitocondrial e o bloqueio da gliconeogênese. Conclusão: Este trabalho mostrou que o exercício atua ativamente na via de sinalização da AMPK, na importância da regulação via PGC-1α e no papel de outros genes, regulando a expressão de mais da metade dos genes amostrados.

ABSTRACT Introduction: New studies of gene regulation by physical exercise through post-genomic techniques in endurance and strength tests characterize the physical exercise transcriptomics. Among the affected genes, we highlight the AMP-activated protein kinase (AMPK) pathway, the activation of which occurs during exercise because of changes in muscle fiber energetic phosphate levels. Objective: To evaluate the AMPK signaling pathway by systematic review of gene expression and in silico analysis. Method: A systematic review was performed in order to assess the gene regulation of AMPK signaling pathway, characterizing the genes studied in the literature, regulation variations obtained in the form of fold change, and types of exercise performed. Results: The AMPK signaling pathway showed 133 genes in the KEGG repository (Kyoto Encyclopedia of Genes and Genomes), which were compared with the systematic review of the literature, totaling 65 genes. Seventeen genes presented UR and 24 showed DR in relation to their respective control. In addition to these, 20 genes were present in the literature, presenting both UR and DR and four genes showed no regulatory data. Specific regulation was verified according to the type of exercises performed. Discussion: Of the 133 genes of the AMPK pathway, 48.8% were sampled in the revised studies indicating that a significant part of the pathway is regulated by exercise. The study presented the basic gene regulation of two mechanisms for energy recovery, mitochondrial biogenesis, and gluconeogenesis blockade. Conclusion: This work showed that the exercise actively works in the AMPK signaling pathway, in the importance of regulation via PGC-1α and in the role of other genes, regulating the expression of more than half of the genes sampled.

RESUMEN Introducción: Nuevos estudios de regulación génica del ejercicio físico por medio de técnicas pos-genómicas en ensayos de resistencia (endurance) y fuerza caracterizan la transcriptómica del ejercicio físico. Entre los genes afectados, destacamos la vía de la proteína quinasa activada por AMP (AMPK), cuya activación ocurre durante el ejercicio como resultado de las alteraciones de los niveles de fosfato energético de la fibra muscular. Objetivo: Evaluar la vía de señalización AMPK por revisión sistemática de la expresión de genes y análisis in silico. Método: Se ha efectuado una revisión para evaluar la regulación génica de la vía de señalización AMPK, caracterizando los genes estudiados en la literatura, las variaciones de regulación obtenidas en forma de fold change y tipos de ejercicios utilizados. Resultados: La vía de señalización AMPK mostró 133 genes en el repositorio KEGG (Kyoto Encyclopedia of Genes and Genomes), los cuales fueran confrontados con la revisión sistemática de la literatura, totalizando 65 genes. Diecisiete genes presentaron UR y 24 mostraron DR con respecto a su respectivo control. Además de estos, 20 genes estaban presentes en los trabajos, presentando tanto UR y DR y cuatro genes no presentaron dados de regulación. Se observó una regulación específica en función del tipo de ejercicio efectuado. Discusión: De los 133 genes de la vía AMPK, 48,8% fueron muestreados en los trabajos revisados, indicando que una parte significativa de la vía es regulada por el ejercicio. El estudio presentó la regulación génica básica de dos mecanismos para la recuperación energética, la biogénesis mitocondrial y el bloqueo de la gluconeogénesis. Conclusión: Este trabajo mostró que el ejercicio actúa activamente en la vía de señalización AMPK, en la importancia de la regulación vía factor PGC-1a y en el papel de otros genes, regulando la expresión de más de la mitad de los genes muestreados.

Abstract: The lipid-rich cell wall of Mycobacterium tuberculosis is a dynamic structure that is involved in the regulation of the transport of nutrients, toxic host-cell effector molecules, and anti-tuberculosis drugs. It is therefore postulated to contribute to the long-term bacterial survival in an infected human host. Accumulating evidence suggests that M. tuberculosis remodels the lipid composition of the cell wall as an adaptive mechanism against host-imposed stress. Some of these lipid species (trehalose dimycolate, diacylated sulphoglycolipid, and mannan-based lipoglycans) trigger an immunopathologic response, whereas others (phthiocerol dimycocerosate, mycolic acids, sulpholipid-1, and di-and polyacyltrehalose) appear to dampen the immune responses. These lipids appear to be coordinately expressed in the cell wall of M. tuberculosis during different phases of infection, ultimately determining the clinical fate of the infection. This review summarizes the current state of knowledge on the metabolism, transport, and homeostatic or immunostatic regulation of the cell wall lipids, and their orchestrated interaction with host immune responses that results in bacterial clearance, persistence, or tuberculosis.

Cutaneous leishmaniasis (CL) is the most frequent clinical form of tegumentary leishmaniasis and is characterised by a single or a few ulcerated skin lesions that may disseminate into multiple ulcers and papules, which characterise disseminated leishmaniasis (DL). In this study, cells were quantified using immunohistochemistry and haematoxylin and eosin staining (CD4+, CD68+, CD20+, plasma cells and neutrophils) and histopathology was used to determine the level of inflammation in biopsies from patients with early CL, late CL and DL (ulcers and papules). The histopathology showed differences in the epidermis between the papules and ulcers from DL. An analysis of the cells present in the tissues showed similarities between the ulcers from localised CL (LCL) and DL. The papules had fewer CD4+ T cells than the DL ulcers. Although both CD4+ cells and macrophages contribute to inflammation in early CL, macrophages are the primary cell type associated with inflammation intensity in late ulcers. The higher frequency of CD20+ cells and plasma cells in lesions demonstrates the importance of B cells in the pathogenesis of leishmaniasis. The number of neutrophils was the same in all of the analysed groups. A comparison between the ulcers from LCL and DL and the early ulcers and papules shows that few differences between these two clinical forms can be distinguished by observing only the tissue.

Introduction Leishmania braziliensis infection induces a large spectrum of lesions that clinically manifest as nodules or papules that progress to ulcers. Although it is already known that T helper cells predominate in the lesions, cytotoxic T cells have also been reported to be present, and their role in leishmaniasis immunopathogenesis is not well known. This study investigated the amounts of CD8+ and granzyme B+ cells in different clinical forms of human cutaneous leishmaniasis (CL). Methods Forty tissue fragments from early (E-CL) and late CL (L-CL) lesions and from disseminated leishmaniasis (DL) - papules and ulcers - were characterized. The inflamed area per fragment was calculated, and the CD8 and granzyme B expression levels in the infiltrates were quantified by counting positive cells in 15 fields. The localization of CD8 and granzyme B was graded subjectively. Results Inflammation was higher in L-CL and DL ulcers. CD8 expression was increased in late ulcerated lesions compared to recent lesions. The increase in CD8+ cells also correlated with the duration of the lesion. Papules had a higher frequency of granzyme B+ cells than E-CL lesions, although the frequency was similar to those for late and DL ulcers. CD8+ cells were mostly found in the papillary dermis. Conclusions CD8+ T and granzyme B+ cells are present in the inflammatory infiltrates of CL and DL and may participate in the immunopathogenesis of Leishmania infection.