Neural Mechanisms of Exercise: Anti-Depression, Neurogenesis, and Serotonin Signaling

Depression is associated with decreased serotonin metabolism and functioning in the central nervous system, evidenced by both animal models of depression and clinical patient studies. Depression is also accompanied by decreased hippocampal neurogenesis in diverse animal models. Neurogenesis is mainly defined in dentate gyrus of hippocampus as well as subventricular zone. Moreover, hypothalamus, amygdala, olfactory tubercle, and piriform cortex are reported with evidences of adult neurogenesis. Physical exercise is found to modulate adult neurogenesis significantly, and results in mood improvement. The cellular mechanism such as adult neurogenesis upregulation was considered as one major mood regulator following exercise. The recent advances in molecular mechanisms underlying exercise-regulated neurogenesis have widen our understanding in brain plasticity in physiological and pathological conditions, and therefore better management of different psychiatric disorders.

Linfangiogénese no tecido adiposo em modelos de doença inflamatória crónica (asma e obesidade): uma abordagem por imunohistoquímica e lipidómica

O tecido adiposo é um órgão endócrino dinâmico, secretando factores importantes na regulação do metabolismo, fluxo vascular sanguíneo e linfático, e função imunológica, entre outros. Em caso de acumulação de tecido adiposo por ingestão de uma dieta gorda, ou por disfunção metabólica, os adipócitos podem desencadear uma reacção inflamatória por falha na drenagem linfática, acumulando-se mediadores inflamatórios, os quais potenciam a propagação da reacção. Assim, questiona-se uma potencial associação entre o aumento de tecido adiposo na obesidade, hipóxia adipocitária e estimulação da linfangiogénese. Além disso, a expressão de adipocinas varia de acordo com a distribuição do tecido adiposo (subcutâneo, TAS e visceral, TAV). Deste modo, pretende-se com este estudo contribuir para o aumento do conhecimento sobre os complexos mecanismos moleculares subjacentes à linfangiogénese. Ensaios com ratinhos da estirpe C57Bl/6J (modelo de obesidade) e BALB/c (modelo de asma e obesidade), divididos em grupos submetidos a dieta normal e dieta rica em gordura. Avaliação semi-quantitativa da expressão tecidular de LYVE-1 (marcador da linfangiogénese) por imunohistoquímica em material embebido em parafina, no TAS e TAV, e cromatografia líquida de ultra-performance acoplada de espectrometria de massa (UPLC-MS) para análise da expressão plasmática de ceramida e esfingosina-1-fosfato (S1P). No modelo de obesidade observou- -se diminuição do número de vasos linfáticos e expressão de LYVE-1 ao longo do tempo no TAV, e aumento de ambos os parâmetros e hipertrofia adipocitária no TAS. As concentrações de ceramida e S1P corroboram a existência de um processo inflamatório nos ratinhos em estudo, ainda que numa fase muito inicial. No modelo de asma e obesidade, após 17 semanas de tratamento, observou-se incremento da linfangiogénese no TAV, mas não no TAS. A resposta inflamatória avaliada através dos diferentes parâmetros permite afirmar que num estadio inicial de obesidade a proliferação linfática poderá estar a ser retardada pela hipertrofia adipocitária. A libertação de adipocinas será observada apenas numa fase posterior, desencadeando todo o processo inflamatório que incrementará a proliferação linfática. Adicionalmente, é possível sugerir que a maior pressão à qual o TAV se encontra sujeito não favorece a proliferação linfática, pelo menos num estadio incial.

Influence of Soil Chemistry and Plant Physiology in the Phytoremediation of Cu, Mn, and Zn

Different anthropogenic sources of metals can result from agricultural, industrial, military, mining and urban activities that contribute to environmental pollution. Plants can be grown for phytoremediation to remove or stabilize contaminants in water and soil. Copper (Cu), manganese (Mn) and zinc (Zn) are trace essential metals for plants, although their role in homeostasis in plants must be strictly regulated to avoid toxicity. In this review, we summarize the processes involved in the bioavailability, uptake, transport and storage of Cu, Mn and Zn in plants. The efficiency of phytoremediation depends on several factors including metal bioavailability and plant uptake, translocation and tolerance mechanisms. Soil parameters, such as clay fraction, organic matter content, oxidation state, pH, redox potential, aeration, and the presence of specific organisms, play fundamental roles in the uptake of trace essential metals. Key processes in the metal homeostasis network in plants have been identified. Membrane transporters involved in the acquisition, transport and storage of trace essential metals are reviewed. Recent advances in understanding the biochemical and molecular mechanisms of Cu, Mn and Zn hyperaccumulation are described. The use of plant-bacteria associations, plant-fungi associations and genetic engineering has opened a new range of opportunities to improve the efficiency of phytoremediation. The main directions for future research are proposed from the investigation of published results.

P53 and Cancer-Associated Sialylated Glycans Are Surrogate Markers of Cancerization of the Bladder Associated with Schistosoma haematobium Infection

BACKGROUND: Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers. METHODOLOGY/PRINCIPAL FINDINGS: Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder cancer biomarkers. These included the oncoprotein p53, the tumour proliferation rate (Ki-67>17%), cell-surface cancer-associated glycan sialyl-Tn (sTn) and sialyl-Lewisa/x (sLea/sLex), involved in immune escape and metastasis. Bladder tumours of non-S. haematobium etiology and normal urothelium were used as controls. S. haematobium-associated benign/pre-malignant lesions present alterations in p53 and sLex that were also found in bladder tumors. Similar results were observed in non-S. haematobium associated tumours, irrespectively of their histological nature, denoting some common molecular pathways. In addition, most benign/pre-malignant lesions also expressed sLea. However, proliferative phenotypes were more prevalent in lesions adjacent to bladder tumors while sLea was characteristic of sole benign/pre-malignant lesions, suggesting it may be a biomarker of early carcionogenesis associated with the parasite. A correlation was observed between the frequency of the biomarkers in the tumor and adjacent mucosa, with the exception of Ki-67. Most S. haematobium eggs embedded in the urothelium were also positive for sLea and sLex. Reinforcing the pathologic nature of the studied biomarkers, none was observed in the healthy urothelium. CONCLUSION/SIGNIFICANCE: This preliminary study suggests that p53 and sialylated glycans are surrogate biomarkers of bladder cancerization associated with S. haematobium, highlighting a missing link between infection and cancer development. Eggs of S. haematobium express sLea and sLex antigens in mimicry of human leukocytes glycosylation, which may play a role in the colonization and disease dissemination. These observations may help the early identification of infected patients at a higher risk of developing bladder cancer and guide the future development of non-invasive diagnostic tests.

Lettuce (Lactuca sativa L.) leaf-proteome profiles after exposure to cylindrospermopsin and a microcystin-LR/cylindrospermopsin mixture: A concentration-dependent response

The intensification of agricultural productivity is an important challenge worldwide. However, environmental stressors can provide challenges to this intensification. The progressive occurrence of the cyanotoxins cylindrospermopsin (CYN) and microcystin-LR (MC-LR) as a potential consequence of eutrophication and climate change is of increasing concern in the agricultural sector because it has been reported that these cyanotoxins exert harmful effects in crop plants. A proteomic-based approach has been shown to be a suitable tool for the detection and identification of the primary responses of organisms exposed to cyanotoxins. The aim of this study was to compare the leaf-proteome profiles of lettuce plants exposed to environmentally relevant concentrations of CYN and a MC-LR/CYN mixture. Lettuce plants were exposed to 1, 10, and 100 lg/l CYN and a MC-LR/CYN mixture for five days. The proteins of lettuce leaves were separated by twodimensional electrophoresis (2-DE), and those that were differentially abundant were then identified by matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF/TOF MS). The biological functions of the proteins that were most represented in both experiments were photosynthesis and carbon metabolism and stress/defense response. Proteins involved in protein synthesis and signal transduction were also highly observed in the MC-LR/CYN experiment. Although distinct protein abundance patterns were observed in both experiments, the effects appear to be concentration-dependent, and the effects of the mixture were clearly stronger than those of CYN alone. The obtained results highlight the putative tolerance of lettuce to CYN at concentrations up to 100 lg/l. Furthermore, the combination of CYN with MC-LR at low concentrations (1 lg/l) stimulated a significant increase in the fresh weight (fr. wt) of lettuce leaves and at the proteomic level resulted in the increase in abundance of a high number of proteins. In contrast, many proteins exhibited a decrease in abundance or were absent in the gels of the simultaneous exposure to 10 and 100 lg/l MC-LR/CYN. In the latter, also a significant decrease in the fr. wt of lettuce leaves was obtained. These findings provide important insights into the molecular mechanisms of the lettuce response to CYN and MC-LR/CYN and may contribute to the identification of potential protein markers of exposure and proteins that may confer tolerance to CYN and MC-LR/CYN. Furthermore, because lettuce is an important crop worldwide, this study may improve our understanding of the potential impact of these cyanotoxins on its quality traits (e.g., presence of allergenic proteins).

Cation transporters/channels in plants: Tools for nutrient biofortification

Cation transporters/channels are key players in a wide range of physiological functions in plants, including cell signaling, osmoregulation, plant nutrition and metal tolerance. The recent identification of genes encoding some of these transport systems has allowed new studies toward further understanding of their integrated roles in plant. This review summarizes recent discoveries regarding the function and regulation of the multiple systems involved in cation transport in plant cells. The role of membrane transport in the uptake, distribution and accumulation of cations in plant tissues, cell types and subcellular compartments is described. We also discuss how the knowledge of inter- and intra-species variation in cation uptake, transport and accumulation as well as the molecular mechanisms responsible for these processes can be used to increase nutrient phytoavailability and nutrients accumulation in the edible tissues of plants. The main trends for future research in the field of biofortification are proposed.