Tellurite and Selenite: how can these two oxyanions be chemically different yet so similar in the way they are transformed to their metal forms by bacteria?

This opinion review explores the microbiology of tellurite, TeO32− and selenite, SeO32− oxyanions, two similar Group 16 chalcogen elements, but with slightly different physicochemical properties that lead to intriguing biological differences. Selenium, Se, is a required trace element compared to tellurium, Te, which is not. Here, the challenges around understanding the uptake transport mechanisms of these anions, as reflected in the model organisms used by different groups, are described. This leads to a discussion around how these oxyanions are subsequently reduced to nanomaterials, which mechanistically, has controversies between ideas around the molecule chemistry, chemical reactions involving reduced glutathione and reactive oxygen species (ROS) production along with the bioenergetics at the membrane versus the cytoplasm. Of particular interest is the linkage of glutathione and thioredoxin chemistry from the cytoplasm through the membrane electron transport chain (ETC) system/quinones to the periplasm. Throughout the opinion review we identify open and unanswered questions about the microbial physiology under selenite and tellurite exposure. Thus, demonstrating how far we have come, yet the exciting research directions that are still possible. The review is written in a conversational manner from three long-term researchers in the field, through which to play homage to the late Professor Claudio Vásquez.

Is the mitochondrion a promising drug target in trypanosomatids?

The trypanosomatids Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are etiological agents of important neglected tropical diseases, affecting millions of people worldwide, and the drugs available for these diseases present several limitations. Novel efficient and nontoxic drugs are necessary as an alternative to the current chemotherapy. The unique mitochondrion of trypanosomatids and its peculiar features turn this organelle a potential drug target. Several phenotypic studies describe the damage in the parasite mitochondrial ultrastructure, but the molecular target is unknown. Few reports demonstrated the electron transport system (ETS) as a target due to the high similarities to mammalian orthologues, hence ETS is not a good candidate for drug intervention. On the other hand, antioxidant enzymes, such as trypanothione reductase, and an alternative oxidase (AOX) seem to be interesting targets; however no high active inhibitors were developed up to now. Finally, due to the remarkable differences to mammalian machinery, together with the high biological importance for the parasite survival, the mitochondrial import system stands out as a very promising target in trypanosomatids. Archaic translocase of the outer membrane (ATOM) and translocase of the inner membrane (TIM) complexes, which mediate both protein and tRNA import, composed by specific subunits of these parasites, could be excellent candidates, deserving studies focused on the development of specific drugs.

Effects of myocardial infarction and an intensive exercise bout on kinetic of lactate, and LDH-B levels in spontaneously hypertensive rats

Aims: This study aimed to evaluate the kinetics of lactate and lactate dehydrogenase B (LDH-B) protein levels as well as the maximum effort capacity of spontaneously hypertensive rats (SHRs) with experimental acute myocardial infarction (AMI). Methods: thirty-two SHRs were divided into (n=8/group): S (sham), SE (sham+exercise), I (AMI), and IE (AMI+exercise). A maximum exercise test (treadmill) was evaluated before AMI or sham surgery. Echocardiography was performed 48h after the surgery. Lactacidemia was assessed at rest and during an intense exercise bout (48h after echocardiography). A two-way ANOVA followed by the post-hoc (Bonferroni) test was used, p<0.05. Results: In the end, the heart was removed for analysis of LDH-B. AMI resulted in lower cardiac output (S vs I: ∆51.3%, p<0.001), ejection fraction (S vs I: ∆60.5%, p<0.001) and shortening fraction (S vs I: ∆72.4%, p<0.001). The IE showed a reduction in exercise capacity when compared with pre-AMI values (1.50±0.1 vs 1.38±0.2 km/h; p=0.030) but not when compared with SE (1.41±0.3 vs 1.38±0.2 km/h; p=0.208). During the exhaustion exercise session, IE group showed lower lactacidemia at 12 min (∆9.7%, p=0.042) and 18 min (∆8.3%, p=0.038). No differences were observed in the protein level of LDH-B among the groups (p=0.573). However, when the AMI factor was considered alone, LDH-B expression was lower (sham vs AMI rats, p=0.040). Conclusion: LDH-B protein levels in cardiac tissue appear to be associated with AMI only. Furthermore, AMI induced a reduction in exercise capacity but did not affect lactacidemia during the intense exercise bout.(AU)

Water temperature, body mass and fasting heat production of pacu (Piaractus mesopotamicus)

ABSTRACT Knowledge on fasting heat production (HEf) of fish is key to develop bioenergetics models thus improving feeding management of farmed species. The core of knowledge on HEf of farmed, neotropical fish is scarce. This study assessed the effect of body mass and water temperature on standard metabolism and fasting heat production of pacu, Piaractus mesopotamicus, an omnivore, Neotropical fresh water characin important for farming and fisheries industries all through South American continent. An automated, intermittent flow respirometry system was used to measure standard metabolic rate (SMR) of pacu (17 - 1,050 g) at five water temperatures: 19, 23, 26, 29 and 33 °C. Mass specific SMR increased with increasing water temperature but decreased as function of body mass. The allometric exponent for scaling HEf was 0.788, and lied in the range recorded for all studied warm-water fish. The recorded van't Hoff factor (Q10) for pacu (2.06) shows the species low response to temperature increases. The model HEf = 0.04643×W0.7882×T1.837 allows to predict HEf (kJ d-1) from body mass (W, kg) and water temperature (T, °C), and can be used in bioenergetical models for the species.

Efecto de la temperatura en respuestas fisiológicas de la concha de abanico Argopecten purpuratus

Se determinó el efecto de la temperatura sobre la tasa de aclaramiento (TA), ingestión (TI) y consumo especifico de oxígeno (CEO) en individuos de Argopecten purpuratus (Lamarck, 1891) de distintos grupos de tallas. Las pruebas de TA y TI se realizaron a una concentración de Chaetoceros calcitrans de aproximadamente 1x10(6) cel.mL-1, se evaluaron dos temperaturas 17 y 22°C y se conformaron diferentes grupos de tallas promedio de 7.6 ± 0.265, 4.9 ± 0.058 y 3.7 ± 0.173 cm. En las pruebas de CEO los grupos de tallas promedio fueron 8.1 ± 0.351, 5.6 ± 0.058 y 4.3 ± 0.100 cm. Los resultados muestran un efecto significativo de la temperatura en la TA (L.h-1) y TI (cel.h-1 x 10(5)) sobre los individuos de mayor tamaño (7.6 ± 0.265 cm), observándose a 22°C un incremento promedio, respecto a 17°C, de hasta 250% para TA y 48% para TI. Además, se observó una relación directa del tamaño corporal con las TA y TI en ambas temperaturas. Se registró el efecto de la temperatura de 22°C sobre CEO en todos los grupos evaluados, con un incremento de 239.8, 165.3 y 183.4% para individuos de tallas de 8.1 ± 0.351, 5.6 ± 0.058 y 4.3 ± 0.100 respectivamente. Asimismo, los resultados muestran una relación indirecta del tamaño corporal con la CEO, en ambas temperaturas evaluadas.

The effect of temperature on the clearance rate (CR), ingestion rate (IR) and specific oxygen consumption (SOC) in individuals of Argopecten purpuratus at different size groups were determined. The CR and IR tests were performed at a concentration of approximately 1x10(6) cel.mlL-1 of Chaetoceros calcitrans, two temperatures 17 and 22 °C were evaluated and different groups of average size were formed of 7.6 ± 0.265, and 0.058 ± 4.9 3.7 ± 0.173 cm. In SOC test the average size groups were 8.1 ± 0.351, 0.058 ± 5.6 and 4.3 ± 0.100 cm. The results show a significant effect of temperature in CR (Lh-1) and IR (cel.h-1 x 10(5)) on the larger individuals (7.6 ± 0.265 cm), it was observed at 22 °C an average increase, about 17 °C, up to 250% to CR and 48% to IR. In addition, a direct relationship of body size with CR and IR in both temperatures was observed. The effect of temperature at 22 ° C on SOC in all groups was evaluated, with an increase of 239.8, 165.3 and 183.4% for size individuals of 8.1 ± 0.351, 0.058 ± 5.6 and 4.3 ± 0.100 respectively. Furthermore, in both evaluated temperatures, the results show an indirect relationship of body size with the SOC.

Citotoxicity of Fipronil on Hepatocytes Isolated from Rat and Effects of Its Biotransformation

ABSTRACT The aim of this study was to characterize the mechanism of toxicity of fipronil on hepatocytes isolated from the rat and the effect of its biotransformation on the toxicological potential. The toxicity of fipronil was assessed by monitoring the oxygen consumption and mitochondrial membrane potential, intracellular ATP concentration, Ca2+ homeostasis and cell viability. The cell viability was evaluated by trypan blue exclusion in hepatocytes that were isolated from the normal rats and by the release of the enzymes alanine transaminase and aspartate transaminase in hepatocytes that were isolated from the normal rats or proadifen-pretreated rats. Fipronil reduced mitochondrial respiration in the cells that were energized with glutamate plus malate in a dose-dependent manner and dissipated the mitochondrial membrane potential that was accompanied by a reduction in ATP concentration and a disruption of intracellular Ca2+ homeostasis. The cell viability was affected by fipronil with higher potency in hepatocytes that were isolated from the normal rats, which indicated that the metabolism of this insecticide increased its toxicological potential. The results of this study indicated that the toxicity of fipronil to the hepatocytes was related to the inhibition of mitochondrial activity, which led to decreased ATP synthesis and a consequent alteration in intracellular Ca2+ homeostasis and ultimately resulted in cell death.

Biogenêse mitocondrial e exercício físico: hipótese do acoplamento elétrico-transcripcional / Mitochondrial biogenesis and physical exercise: electric-transcriptional coupling hypothesis

Resumo Uma das principais modificações ocorridas no organismo em decorrência do treinamento físico-esportivo envolvendo exercícios físicos de longa duração é o aumento na quantidade e qualidade funcional de mitocôndrias do tecido muscular esquelético. Não existe até o momento um mecanismo causal explicativo para esse fenômeno. A proposta a ser discutida neste ensaio é denominada por "hipótese do acoplamento elétrico-transcripcional". Segundo a mesma, modificações na atividade elétrica celular, principalmente de despolarização membranar, constituem-se em método de controle e regulação dos processos de biossíntese no organismo multicelular. Por exemplo, estudos que provocaram hiperpolarização artificial em células somáticas induziram diferenciação celular e supressão da proliferação, sendo que o contrário ocorreu com a despolarização. Ou seja, a despolarização celular durante o exercício físico devido a contração muscular intensa e constante pode ativar processos responsáveis por biossínteses e, possivelmente, duplicação de mitocôndria.

Abstract One of the main changes happened in skeletal muscle tissue as a result of physical and sport training with prolonged exercise is the increase in the quantity and functional quality of mitochondria. There is not yet an explanatory causal mechanism for this phenomenon. The suggestion to be discussed in this assay is called "electric-transcriptional coupling hypothesis". In this hypothesis, changes in electrical activity, mainly membrane depolarization, are considered methods used for the control of biosynthesis in multicellular organisms. For example, studies that resulted in somatic cell hyperpolarization induced suppression of differentiation and proliferation, and the opposite happened with depolarization. That is, cell depolarization that occur during the exercise as a consequence of intense and prolonged muscle contraction could activate processes responsible for biosynthesis and, possibly, mitochondrial replication.

Bioenergetics of Human Cancer Cells and Normal Cells during Proliferation and Differentiation.

Cancer cells are known to have different metabolic properties than normal cells, particularly their tendency to undergo glycolysis even under aerobic favoring conditions. This has created interest in how mitochondrial function in tumor cells may differ from that in normal cells. Using human malignant cells (SW-620, PC-3, HT-1080, SK-MEL, HL-60, K-562 and MOLT-3), human fibroblast (CCL-153) and human T Cells, we investigated three key parameters that have been typically to describe mitochondrial function: cellular ATP production, mitochondrial potential and cellular cardiolipin levels. On average, tumor cancer cells had more ATP production and greater mitochondrial potentials. For example, ATP levels in malignant cells ranged from 20 to 69 μmole/106 cells, with a cancer cell average of 40±18 μmole/106 cells. For normal cells, the ATP level range went from 9 to 24 μmole/106 cells, for an average of 15±11 μmole/106 cells. Mitochondrial potentials tended to be three times higher in cancer cells, perhaps because overall mitochondrial mass (as measured by relative cardiolipin levels) were twice as high in cancer cells. Higher mitochondrial masses are consistent with proliferation. Proliferating cells in general showed higher mitochondrial function compared to quiescent cells (confluent monolayers), and HL-60 cells showed reductions in all three mitochondrial parameters measured here when the cells were exposed to the differentiating agent TPA. The effects of ATP production inhibitors CCCP and oligomycin on mitochondrial function in normal and cancer cells were also compared. In general, in these experiments, cancer cell mitochondrial inhibition with these agents produced a decrease ATP levels by 30-40% while in normal cells ATP production was reduced by 60%. These results provide evidence of a mitochondrial dysfunction in cancer cells. Cancer cells appear to better withstand interference with ATP synthesis in mitochondria since they rely mainly on glycolysis as an energy producing mechanism.

Mechanisms involved in reproductive damage caused by gossypol in rats and protective effects of vitamin E

BACKGROUND: Gossypol is a chemical present in the seeds of cotton plants (Gossypium sp.) that reduces fertility in farm animals. Vitamin E is an antioxidant and may help to protect cells and tissues against the deleterious effects of free radicals. The aim of this study was to evaluate the mechanisms of reproductive toxicity of gossypol in rats and the protective effects of vitamin E. Forty Wistar rats were used, divided into four experimental groups (n = 10): DMSO/ saline + corn oil; DMSO/saline + vitamin E; gossypol + corn oil; and gossypol + vitamin E. RESULTS: Fertility was significantly reduced in male rats treated with gossypol in that a significant decrease in epididy-mal sperm count was observed (P < 0.05) and the number of offspring was significantly reduced in females mated with them (P < 0.05). This dysfunction was prevented by vitamin E. Gossypol caused a significant increase in the activity of the enzymes glutathione peroxidase (P < 0.01) and glutathione reductase (P < 0.01), but vitamin E did not reduce the enzyme activities (P > 0.05). The levels of reduced glutathione and pyridine nucleotides in testis homogen-ate were significantly reduced by gossypol (P < 0.05 and P < 0.01, respectively) and this reduction was accompanied by increased levels of oxidized glutathione (P < 0.05). Vitamin E showed a preventive effect on the changes in the levels of these substances. Gossypol significantly increased the levels of malondialdehyde (P < 0.01), a lipid peroxida-tion indicator, whereas treatment with vitamin E inhibited the action of the gossypol. Vitamin E prevented a decrease in mitochondrial ATP induced by gossypol (P < 0.05). CONCLUSIONS: This study suggests that the reproductive dysfunction caused by gossypol may be related to oxidative stress and mitochondrial bioenergetic damage and that treatment with vitamin E can prevent the infertility caused by the toxin.

Determinação dos metabolismos lático e alático da capacidade anaeróbia por meio do consumo de oxigênio / Determination of lactic and alactic metabolisms of the anaerobic capacity using oxygen uptake

Tem sido sugerido que a participação do metabolismo anaeróbio alático (MAA) pode ser estimada a partir do cálculo da fase rápida do excesso do consumo de oxigênio após o exercício (EPOC RÁPIDO). Considerando que o Déficit Máximo Acumulado de Oxigênio (MAOD) representa a quantidade total de energia transferida pelos metabolismos anaeróbios, o objetivo desse estudo foi analisar se o método de subtrair o EPOC RÁPIDO do MAOD (MAOD LA-1) proporciona uma estimativa satisfatória do metabolismo anaeróbio lático (MAL). Para esse fim, o MAOD LA-1 foi comparado ao método capaz de expressar em equivalente de oxigênio a energia oriunda do acúmulo de lactato no sangue (MAOD LA-2). Nove homens adultos ativos foram submetidos a quatro sessões experimentais: 1) um teste progressivo até a exaustão em um cicloergômetro para a mensuração do consumo máximo de oxigênio (VO2max) e da potência externa correspondente ao VO2max (WVO2max); 2 e 3) seis testes de cargas constantes (3 testes por sessão) com intensidades abaixo da WVO2max; 4) um teste de carga constante com a intensidade equivalente a 110% da WVO2max. O principal achado foi que os dois métodos (MAOD LA-1 e MAOD LA-2) empregados na estimativa da contribuição do MAL no MAOD geraram valores estatisticamente similares (p > 0,05). Além disso, os valores percentuais do MAOD LA-1 (representando o MAL) e do EPOC RÁPIDO (representando o MAA) foram de aproximadamente 78% e 22%, respectivamente. Logo, os procedimentos propostos na presente investigação podem auxiliar futuros trabalhos que porventura objetivem fragmentar as contribuições dos componentes anaeróbio do MAOD.

It has been suggested that the participation of alactic anaerobic metabolism (AAM) in physical activity can be estimated by calculating the fast component of excess post-exercise oxygen consumption (EPOC FAST). Considering that maximal accumulated oxygen deficit (MAOD) represents the total amount of energy transferred by anaerobic metabolisms, this study aimed to analyze whether subtracting EPOC FAST from MAOD (MAOD LA-1) provides a satisfactory estimate of lactic anaerobic metabolism (LAM). For this purpose, MAOD LA-1 was compared with the method by which the energy derived from blood lactate accumulation (MAOD LA-2) is expressed as oxygen equivalent. Nine active adult men were submitted to four experimental sessions: 1) a maximal incremental exercise test until exhaustion on a cycle ergometer to measure the maximal oxygen consumption (VO2max) and the external power corresponding to VO2max (WVO2max); 2) and 3) six constant-workload tests (3 per session) at intensities below WVO2max; 4) one constant-workload test at an intensity corresponding to 110% of WVO2max. The main finding was that both methods (MAOD LA-1 e MAOD LA-2) that were used to estimate the contribution of LAM in MAOD resulted in similar statistical values (p > 0.05). In addition, percentage values of MAOD LA-1 (representing MAL) and EPOC FAST (representing AAM) were approximately 78 and 22%, respectively. Thus, the procedure proposed in this paper may be of interest to future studies on the.

A influência do tempo de detenção celular e decaimento endógeno na estequiometria de reações em processos biológicos de tratamento de águas residuárias: I - Crescimento quimioheterotrófico / The influence of cell detention time and endogenous decay on the stoichiometry reactions of biological processes in wastewater treatment: I - Chemoheterotrophic growth

No metabolismo quimioheterotrófico, um mesmo substrato orgânico é utilizado como fonte de energia e síntese celular. Este artigo apresenta uma metodologia que pode ser usada para calcular a estequiometria do metabolismo quimioheterotrófico considerando o tempo de detenção celular e o decaimento endógeno. O método se baseia em princípios da bioenergética e é útil para o desenvolvimento de balanços de massa em processos biológicos de tratamento de águas residuárias. Também serve para se estimar as necessidades de nutrientes, alcalinidade e aceptores de elétrons para as reações desejadas, assim como a biomassa formada e gases produzidos.

In chemohetrotrophic metabolism, an organic substrate is used as energy and cell synthesis sources. This article presents a methodology that can be used to calculate the stoichiometry of chemoheterotrophic metabolism, considering solids detention time and endogenous decay. The method is based on bioenergetic principles, and is useful for mass balance calculations for biological processes used in wastewater treatment. It is also applied to estimate nutrients, alkalinity and electron acceptor requirements for the intended reactions, as well as biomass and gas production.

Ecophysiological responses to the effect of annual management on an endemic viviparous fish in central plateau of México

Studies on the biological aspects of fish typically focus on species that currently have commercial value, causing species that lack such market value to be ignored. This is the case of several freshwater fish, specifically of several members of the Goodeidae family. In the State of Querétaro there are several species of this family characterized for being viviparous and having distinctive sexual dimorphism that may have commercial potential. The subject of this study is Girardinichthys multiradiatus, a viviparous fish endemic to the upper-half of the Lerma River basin. The lack of knowledge regarding its biology and ecology has prevented the development of guidelines to manage its habitat and to preserve its population. The objective was to determine the ecophysiological responses of G. multiradiatus to its environmental management. From the sampling (24 hours every two months) population structure and dynamics were analyzed throughout a hydrological cycle using meristic data (standard length). Trophic and ecophysiological responses to fluctuations in environmental factors were also identified. Although the mexcalpique is a polytrophic species, results show that it prefers feeding on Diptera or Cladocera, while detritus is the third substance frequently found in their stomachs. Environmentally, the water regime is responsible for fluctuations in the population dynamics of the species, while temperature changes are the most influence its energy balance. These results can guide efforts to conserve this species and its habitat.

Los estudios sobre aspectos biológicos de los peces se centran, generalmente, en especies que actualmente tienen interés comercial, lo que ocasiona que las especies que carecen de tal valor en el mercado estén prácticamente olvidadas; tal es el caso de varios peces de agua dulce y más específicamente de algunos integrantes de la familia Godeidae. En el estado de Querétaro se encuentran varias especies pertenecientes a esta familia que se caracterizan por ser vivíparas y presentar un marcado dimorfismo sexual, aspectos que pudieran definir un potencial comercial. El pez objeto de este estudio es Girardinichthys multiradiatus, especie endémica de la parte alta-media de la cuenca del río Lerma; los lugares donde habita presentan procesos de degradación, fragmentación del hábitat y extracción de agua, que ponen en riesgo su existencia. Además, la falta de conocimiento sobre su biología y ecología, no permiten que se elaboren pautas de gestión de sus poblaciones o hábitats con fines de conservación y preservación de la especie o de los procesos ecológicos que mantienen la estabilidad del ecosistema que ocupa. En el presente trabajo se estudió la población de G. multiradiatus localizada en el bordo de San Martín, Amealco. El objetivo del presente trabajo fue determinar las respuestas ecofisológicas de G. multiradiatus debido al manejo de su ambiente. Se hicieron ciclos de 24 horas en muestreos bimensuales a lo largo de un ciclo hidrológico en el que se analizaron la estructura y dinámica de la población; asimismo, se determinaron las respuestas tróficas y ecofisiológicas de la población ante las fluctuaciones de los factores ambientales de su entorno. Los resultados muestran que aunque el mexcalpique es polítrofo, prefiere dípteros, cladóceros y detritus, habiendo diferencias alimentarias entre las clases de edades. G. multiradiatus presenta 12 clases de talla que van de 8 a 48 mm de longitud patrón. En el medio ambiente, el régimen de agua es responsable de las fluctuaciones en la dinámica poblacional de las especies, mientras que el cambio de temperatura es el factor de mayor influencia sobre su balance energético. Estos resultados pueden guiar los esfuerzos para conservar esta especie y su hábitat.

La acupuntura y su aplicación en estomatología / The acupuncture and its application in Stomatology

Con la finalidad de realizar una actualización de los conocimientos sobre la aplicación de la acupuntura en estomatología, se realiza una revisión bibliográfica sobre este tema basado en la información obtenida de textos y revistas consultadas en centros de referencia y a través de localizadores electrónicos como Pubmed, Medline y Google de los últimos años. Según se pudo constatar esta temática tiene vigencia y su aplicación resulta de gran utilidad en el tratamiento de las afecciones estomatológicas(AU)

To carry out an updating of knowledges on implementation of Acupuncture in Stomatology, a bibliographic review was conducted on this subject on the base of information gathered from texts and journals consulted in reference center and through electronic localization devices like Pubmed, Medline and Google of the past years. It was confirmed that this subject matter has validity and its implementation is very useful in the treatment of stomatologic affections(AU)

Sub-lethal impact of carbaryl on food utilization in the freshwater prawn Macrobrachium malcolmsonii.

This study determines the toxic effect of carbaryl (Sevin® 50% W.P) on the food utilization parameters in intermoult juveniles of the prawn, Macrobrachium malcolmsonii. The prawns (4.5-5.0 cm in length and 1.0- 1.25 g wet wt.) were exposed to three sub-lethal concentrations of carbaryl (5.15, 7.73 and 15.47 μg l-1) for duration of 40 days. The toxic medium was renewed daily. The prawns were fed ad libitum with known energy quantity of boiled goat liver on daily basis. The overall wet weight gain was calculated. The energy lost through unconsumed food (15-60%), faeces (15-109%), ammonia excretion (9-27%) and moults (13-26%) of the prawns were calculated. The feeding rate, the rate and efficiency of absorption, the metabolic and food conversion rates and the gross and net food conversions efficiencies were found to be significantly declined (p<0.05) in test prawns when compared to that of the control. The energy lost through faeces, ammonia excretion and exuvia was found to be significantly elevated (p<0.05) in test prawns than that of the control. The effect of carbaryl on the bioenergetics parameters was severe in the highest sub-lethal concentration, less in the intermediate concentration and least in the lowest sub-lethal concentration. The results indicated that decrease in feeding, absorption, metabolism and food conversion are interdependent and toxicity of carbaryl diverting energy from production to maintenance pathways, which ultimately resulting in declined growth of M. malcolmsonii.

New paradigm for ATP synthesis and consumption.

A central postulate of the chemiosmotic theory of ATP synthesis (Mitchell 1966) in mitochondria is the presence of a delocalized electrical potential of about 200 mV (Δφ) across the energy-transducing membrane between two bulk aqueous compartments. This Δφ forms the major component of the driving force for ATP synthesis, according to this theory. Experimental techniques to measure this electrical potential difference can be classified into two categories. The first method is to use ions that are permeant to the inner mitochondrial membrane or to introduce non-physiological substances that are charged and membrane-permeant. By achieving transmembrane diffusion of these ions or substances, Δφ can be calculated using the assumption of equilibrium and the Nernst equation (Mitchell 1966). The second method is to employ microelectrodes to penetrate the inner mitochondrial membrane and make direct measurements of the potential across it (Tedeschi 1980). Each method has its own protagonists. The long-standing paradox in bioenergetics is that while the former method produces results favouring the chemiosmotic theory, the latter method finds results, such as a zero Δφ, which cannot be reconciled with the chemiosmotic theory. A large amount of experimental and analytical research and scientific debate has taken place over several decades in an attempt to resolve the paradox. However, this has led to a polarization of scientific opinion, with each group claiming the correctness of their experimental technique. Even after such a large body of work, the paradox could not be resolved. Accordingly, all previous mechanisms, including the chemiosmotic theory, are also polarized and explain only data recorded from one set of experimental techniques. However, no one considered that both sets of experimental data could be correct and reflect some important aspect of the overall process of oxidative phosphorylation and could evolve a mechanism that could explain both poles. In view of these facts, the emergence of Nath’s torsional mechanism of energy transduction and ATP synthesis can be considered to be a milestone in the understanding of the process. The mechanism had its 10th anniversary recently (Nath 2010a, b). One key aspect of the mechanism is its ability to explain both the sets of experimental data on a rational basis. The following is a brief description of the mechanism in the membrane as per the understanding of this author. Consider a sequence of movement of ions through the energy-transducing membrane. Assuming that there are specific access channels for themovement of anions and protons, only one type of access channel is open at a given time (or both may be closed). Now, let us assume that an anion has moved through an open access channel through the membrane. This movement closes the open anion access channel and opens an adjacent proton access channel. The local electrical potential (Δψ) thus created is used or stored by themolecular motor. Then, the proton moves through its open access channel along its electrochemical gradient and a reciprocal process takes place. In each movement half the energy is transferred to the molecular motor. The process is akin to the principle of alternating current motors. The torque produced by the molecular motor is finally used in the synthesis of ATP. It should be noted that the time average charge in the transport cycle is zero. How can this mechanism explain the two poles of experimental data? In the first method, an external charged agent is introduced. This dissipates the Δψ created in the access channel during the first half-cycle and the same (that is the local potential created by the primary translocation) is measured. In the second method of measurement, the microelectrode measures an average potential after completion of a cycle, which is zero. The proposed torsional mechanism thus explains both experimental data sets without any ambiguity. Thus, the long-standing paradox of the contradictory but correct experimental results is resolved. This is an important achievement of the torsional mechanism (Nath 2010b).

Perspective beyond Cancer Genomics: Bioenergetics of Cancer Stem Cells

Although the notion that cancer is a disease caused by genetic and epigenetic alterations is now widely accepted, perhaps more emphasis has been given to the fact that cancer is a genetic disease. It should be noted that in the post-genome sequencing project period of the 21st century, the underlined phenomenon nevertheless could not be discarded towards the complete control of cancer disaster as the whole strategy, and in depth investigation of the factors associated with tumorigenesis is required for achieving it. Otto Warburg has won a Nobel Prize in 1931 for the discovery of tumor bioenergetics, which is now commonly used as the basis of positron emission tomography (PET), a highly sensitive noninvasive technique used in cancer diagnosis. Furthermore, the importance of the cancer stem cell (CSC) hypothesis in therapy-related resistance and metastasis has been recognized during the past 2 decades. Accumulating evidence suggests that tumor bioenergetics plays a critical role in CSC regulation; this finding has opened up a new era of cancer medicine, which goes beyond cancer genomics.

Bases neurais e metabólicas da fadiga durante o exercício / Neural and metabolic bases of the fatigue during the exercise

A proposta deste estudo foi realizar uma revisão de literatura sobre as possíveis causas da fadiga durante o exercício e seus principais locais de manifestação. A fadiga tem etiologia multifatorial, porém é um fator limitante do desempenho físico e sua origem depende do tipo, intensidade e duração do exercício; tipo de fibra recrutada; grau de aptidão individual e pode ser dividida em central e periférica. Os principais locais de manifestação analisados foram o Sistema Nervoso Central, unidade motora, sarcolema, túbulos T, retículo sarcoplasmático e as pontes cruzadas. Sendo que as principais causas pesquisadas foram a hipoglicemia; o aumento na razão triptofano livre/ aminoácidos neutros; nível de amônia cerebral; depleção parcial do ATP-CP; falhas na bomba de sódio e Potássio, junção neuromuscular, sarcolema, túbulos T e retículo sarcoplasmático; acúmulo de metabólitos; atividade enzimática; e não menos importante o estresse oxidativo. Estes mecanismos são caracterizados por alteração na produção de força requerida em conseqüência da deterioração de um ou de vários processos responsáveis pela excitação-contração-relaxamento muscular.

The aim of this study was to review the literature on the possible causes of the fatigue during theexercise and its main places of manifestation. The fatigue has multifatorial etiology, however it is a limit factor of thephysical performance and its origin depends on the type, intensity and duration of exercise; type of enlisted fiber; degree ofindividual aptitude and can be dived in central and peripheral. The main analyzed place of manifestation had been theCentral Nervous System, motor unit, sarcolema, T-tuble, sarcoplasmatic reticulum and the crossed bridges. Being that themain searched causes had been the hypoglycemia; the increase in the reason free triptofano / neural amino acids; cerebralammonia level; partial depletion of the ATP-CP; imperfections in the bomb of Sodium and Potassium, neuromuscularjunction, sarcolema, T-tubles and sarcoplasmatic reticulum; metabolites accumulation of enzymatic activity and did not less important the oxidative stress. These mechanisms are characterized by alteration in force production required inconsequence of the deterioration of one or some responsible processes for the muscular excitement-contraction-relaxation.