Tumor necrosis factor-α impairs oligodendroglial differentiation through a mitochondria-dependent process

Mitochondrial defects, affecting parameters such as mitochondrial number and shape, levels of respiratory chain complex components and markers of oxidative stress, have been associated with the appearance and progression of multiple sclerosis. Nevertheless, mitochondrial physiology has never been monitored during oligodendrocyte progenitor cell (OPC) differentiation, especially in OPCs challenged with proinflammatory cytokines. Here, we show that tumor necrosis factor alpha (TNF-α) inhibits OPC differentiation, accompanied by altered mitochondrial calcium uptake, mitochondrial membrane potential, and respiratory complex I activity as well as increased reactive oxygen species production. Treatment with a mitochondrial uncoupler (FCCP) to mimic mitochondrial impairment also causes cells to accumulate at the progenitor stage. Interestingly, AMP-activated protein kinase (AMPK) levels increase during TNF-α exposure and inhibit OPC differentiation. Overall, our data indicate that TNF-α induces metabolic changes, driven by mitochondrial impairment and AMPK activation, leading to the inhibition of OPC differentiation.Multiple sclerosis (MS) is a neurological disorder of the central nervous system that is characterized by demyelination and neurodegeneration. Although the pathogenesis of MS is not completely understood, various findings suggest that immune-mediated loss of myelin and different types of mitochondrial dysfunction are associated with this disease.¹ Mitochondria are often described as cellular powerhouses that utilize oxygen to produce adenosine triphosphate (ATP), a molecule that is critical for most cellular functions.² In addition, mitochondria are the major sites of the intracellular production of highly reactive free radicals that, if not neutralized, alter cellular metabolism and damage cellular components.³In several studies, mitochondrial dysfunction has been reported to be frequently associated with demyelination, whereas proper function is required for correct oligodendrocyte differentiation and myelination.^{4, 5} Furthermore, there is in vitro evidence that cytokine-induced oligodendrocyte injury involves mitochondrial dysfunction.⁶ One cytokine that is of particular interest in MS is tumor necrosis factor alpha (TNF-α). Evidence implicating TNF-α in the underlying pathology of MS includes: (i) reports that MS patients have elevated TNF-α levels at the sites of active MS lesions at autopsy,⁷ (ii) reports that TNF-α levels are elevated in the cerebrospinal fluid and serum of individuals with MS compared with unaffected individuals and that these TNF-α levels correlate with the severity of the lesions.^{8, 9}Moreover, it has been widely reported that TNF-α is able to impair oligodendrocyte differentiation and that in leukemia cell lines, TNF-α-induced cell death requires impairments in the activity of mitochondrial respiratory chain complex I. Complex I is strategically important for regulating ATP synthesis and is one of the most important sources of reactive oxygen species (ROS) within cells.¹⁰ Despite this evidence, the relationships between mitochondrial physiology, TNF-α, and oligodendrocyte differentiation have not yet been examined. This study addressed the hypothesis that the impairment of oligodendrocyte differentiation caused by TNF-α exposure is causally linked to altered mitochondrial physiology.     

Pb-Induced Avoidance-Like Chloroplast Movements in Fronds of Lemna trisulca L.

Lead ions are particularly dangerous to the photosynthetic apparatus, but little is known about the effects of trace metals, including Pb, on regulation of chloroplast redistribution. In this study a new effect of lead on chloroplast distribution patterns and movements was demonstrated in mesophyll cells of a small-sized aquatic angiosperm Lemna trisulca L. (star duckweed). An analysis of confocal microscopy images of L. trisulca fronds treated with lead (15 μM Pb²⁺, 24 h) in darkness or in weak white light revealed an enhanced accumulation of chloroplasts in the profile position along the anticlinal cell walls, in comparison to untreated plants. The rearrangement of chloroplasts in their response to lead ions in darkness was similar to the avoidance response of chloroplasts in plants treated with strong white light. Transmission electron microscopy X-ray microanalysis showed that intracellular chloroplast arrangement was independent of the location of Pb deposits, suggesting that lead causes redistribution of chloroplasts, which looks like a light-induced avoidance response, but is not a real avoidance response to the metal. Furthermore, a similar redistribution of chloroplasts in L. trisulca cells in darkness was observed also under the influence of exogenously applied hydrogen peroxide (H₂O₂). In addition, we detected an enhanced accumulation of endogenous H₂O₂ after treatment of plants with lead. Interestingly, H₂O₂-specific scavenger catalase partly abolished the Pb-induced chloroplast response. These results suggest that H₂O₂ can be involved in the avoidance-like movement of chloroplasts induced by lead. Analysis of photometric measurements revealed also strong inhibition (but not complete) of blue-light-induced chloroplast movements by lead. This inhibition may result from disturbances in the actin cytoskeleton, as we observed fragmentation and disappearance of actin filaments around chloroplasts. Results of this study show that the mechanisms of the toxic effect of lead on chloroplasts can include disturbances in their movement and distribution pattern.     

Do we need species-specific guidelines for catch-and-release recreational angling to effectively conserve diverse fishery resources?

Catch-and-release recreational angling has become very popular as a conservation strategy and as a fisheries management tool for a diverse array of fishes. Implicit in catch-and-release angling strategies is the assumption that fish experience low mortality and minimal sub-lethal effects. Despite the importance of this premise, research on this topic has focused on several popular North American sportfish, with negligible efforts directed towards understanding catch-and-release angling effects on alternative fish species. Here, we summarise the existing literature to develop five general trends that could be adopted for species for which no data are currently available: (1) minimise angling duration, (2) minimise air exposure, (3) avoid angling during extremes in water temperature, (4) use barbless hooks and artificial lures/flies, and (5) refrain from angling fish during the reproductive period. These generalities provide some level of protection to all species, but do have limitations. Therefore, we argue that a goal of conservation science and fisheries management should be the creation of species-specific guidelines for catch-and-release. These guidelines would take into account the inter-specific diversity of fishes and variation in fishing techniques. As recreational angling continues to grow in popularity, expanding to many developing countries, and targeting alternative species, it is important that reasonable data appropriate for specific fish and fisheries are available. The sustainable use and conservation of recreational fishery resources will depend upon the development and dissemination of effective catch-and-release angling strategies based upon sound science to stakeholders around the world.     

Obesity and aging affects skeletal muscle renin–angiotensin system and myosin heavy chain proportions in pre-diabetic Zucker rats

Journal of Physiology and Biochemistry - There is a gap in the knowledge regarding regulation of local renin–angiotensin system (RAS) in skeletal muscle during development of obesity and...     

Effect of weight and frontal area of external telemetry packages on the kinematics,activity levels and swimming performance of small‐bodied sharks

This study sought to observe the effects of submerged weight and frontal cross‐sectional area of external telemetry packages on the kinematics, activity levels and swimming performance of small‐bodied juvenile sharks, using lemon sharks Negaprion brevirostris (60–80 cm total length, L_T) as a model species. Juveniles were observed free‐swimming in a mesocosm untagged and with small and large external accelerometer packages that increased frontal cross‐sectional area of the animals and their submerged weight. Despite adhering to widely used standards for tag mass, the presence of an external telemetry package altered swimming kinematics, activity levels and swimming performance of juvenile N. brevirostris relative to untagged individuals, suggesting that tag mass is not a suitable standalone metric of device suitability. Changes in swimming performance could not be detected from tail‐beat frequency, which suggests that tail‐beat frequency is an unsuitable standalone metric of swimming performance for small N. brevirostris. Lastly, sharks experienced treatment‐specific changes in activity level and swimming kinematics from morning to afternoon observation. Therefore, the presence of external telemetry packages altered the kinematics, activity levels and swimming performance of small young‐of‐the‐year N. brevirostris and these data may therefore be relevant to other similar‐sized juveniles of other shark species.     

Morphological correlates of swimming activity in wild largemouth bass (Micropterus salmoides) in their natural environment

Individual variation in morphology has been linked to organismal performance in numerous taxa. Recently, the relationship between functional morphology and swimming performance in teleost fishes has been studied in laboratory experiments. In this study, we evaluate the relationship between morphology and swimming activity of wild largemouth bass (Micropterus salmoides) during the reproductive period, providing the first data derived on free-swimming fish not exposed to forced swim trials in the laboratory. Sixteen male largemouth bass were angled from their nests, telemetered, and subsequently monitored by a whole-lake acoustic hydrophone array with sub-meter accuracy. Additionally, eleven morphological measurements were taken from digital images of each fish. A principal components analysis of the morphological measurements described 79.8% of the variance. PC1 was characterized by measures of overall body stoutness, PC2 was characterized by measures of the length and depth of the caudal region, and PC3 characterized individuals with relatively large anterior portions of the body and relatively small caudal areas. Of these variables, only PC3 showed significant relationships to swimming activity throughout the parental care period. PC3 was negatively correlated with multiple measures of swimming activity across the parental care period. Furthermore, swimming performance of individual male bass was noted to be repeatable across the parental care period indicating that this phenomenon extends beyond the laboratory.     

Seasonal pattern of depth selection in smallmouth bass

The current study used a stationary acoustic telemetry array to monitor the depth selection of adult smallmouth bass Micropterus dolomieu in a large, oligotrophic lake in Ontario, Canada. At an annual scale, smallmouth bass demonstrated regular, seasonal changes in inhabited depths: fish occupied shallow water during the summer (2–5 m depth) and descended to deeper water (12–15 m depth) during winter under ice. Smallmouth bass remained above the thermocline in the summer, seasonal depth patterns did not vary across fish size and movements to and from seasonal depths were closely linked to the development and degradation of the thermocline. At finer time scales, smallmouth bass exhibited diel vertical migrations in summer, with fish moving to <2 m at night, and then descending to 3–5 m during the day. This pattern remained constant during the summer period examined, and varied with size such that larger fish remained deeper than smaller fish. During winter, depth did not vary across the 3-month monitoring period ( c . 14 m), but small (<2 m) changes in depth were observed periodically, suggesting limited movements were occurring. Results are further discussed in the context of climate change and reproductive success for this species.     

Proper functioning of the GINS complex is important for the fidelity of DNA replication in yeast

The role of replicative DNA polymerases in ensuring genome stability is intensively studied, but the role of other components of the replisome is still not fully understood. One of such component is the GINS complex (comprising the Psf1, Psf2, Psf3 and Sld5 subunits), which participates in both initiation and elongation of DNA replication. Until now, the understanding of the physiological role of GINS mostly originated from biochemical studies. In this article, we present genetic evidence for an essential role of GINS in the maintenance of replication fidelity in Saccharomyces cerevisiae. In our studies we employed the psf1‐1 allele (Takayama et al., 2003) and a novel psf1‐100 allele isolated in our laboratory. Analysis of the levels and specificity of mutations in the psf1 strains indicates that the destabilization of the GINS complex or its impaired interaction with DNA polymerase epsilon increases the level of spontaneous mutagenesis and the participation of the error‐prone DNA polymerase zeta. Additionally, a synergistic mutator effect was found for the defects in Psf1p and in the proofreading activity of Pol epsilon, suggesting that proper functioning of GINS is crucial for facilitating error‐free processing of terminal mismatches created by Pol epsilon.