Is mPTP the gatekeeper for necrosis, apoptosis, or both?

Permeabilization of the mitochondrial membranes is a crucial step in apoptosis and necrosis. This phenomenon allows the release of mitochondrial death factors, which trigger or facilitate different signaling cascades ultimately causing the execution of the cell. The mitochondrial permeability transition pore (mPTP) has long been known as one of the main regulators of mitochondria during cell death. mPTP opening can lead to matrix swelling, subsequent rupture of the outer membrane, and a nonspecific release of intermembrane space proteins into the cytosol. While mPTP was purportedly associated with early apoptosis, recent observations suggest that mitochondrial permeabilization mediated by mPTP is generally more closely linked to events of late apoptosis and necrosis. Mechanisms of mitochondrial membrane permeabilization during cell death, involving three different mitochondrial channels, have been postulated. These include the mPTP in the inner membrane, and the mitochondrial apoptosis-induced channel (MAC) and voltage-dependent anion-selective channel (VDAC) in the outer membrane. New developments on mPTP structure and function, and the involvement of mPTP, MAC, and VDAC in permeabilization of mitochondrial membranes during cell death are explored. This article is part of a Special Issue entitled Mitochondria: the deadly organelle.     

β-aminoisobutyric Acid,l-BAIBA,Is a Muscle-Derived Osteocyte Survival Factor

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Glycation,glycolysis, and neurodegenerative diseases: Is there any connection?

This review considers the interrelation between different types of protein glycation, glycolysis, and the development of amyloid neurodegenerative diseases. The primary focus is on the role of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase in changing the concentration of carbonyl compounds – first and foremost, glyceraldehyde-3-phosphate and methylglyoxal. It has been suggested that various modifications of the enzyme – from the oxidation of the sulfhydryl groups of the active site to glycation with sugars – can lead to its inactivation, which causes a direct increase in glyceraldehyde-3-phosphate concentration and an indirect increase in the content of other aldehydes. This “primary inactivation” of glyceraldehyde-3-phosphate dehydrogenase promotes its glycation with aldehydes, including its own substrate, and a further irreversible decrease in its activity. Such a cycle can lead to numerous consequences – from the induction of apoptosis, which is activated by modified forms of the enzyme, to glycation of amyloidogenic proteins by glycolytic aldehydes. Of particular importance during the inhibition of glyceraldehyde-3-phosphate dehydrogenase is an increase in the content of the glycating compound methylglyoxal, which is much more active than reducing sugars (glucose, fructose, and others). In addition, methylglyoxal is formed by two pathways – in the cascade of reactions during glycation and from glycolytic aldehydes. The ability of methylglyoxal to glycate proteins makes it the main participant in this protein modification. We consider the effect of glycation on the pathological transformation of amyloidogenic proteins and peptides – β-amyloid peptide, α-synuclein, and prions. Our primary focus is on the glycation of monomeric forms of these proteins with methylglyoxal, although most works are dedicated to the analysis of the presence of “advanced glycation end products” in the already formed aggregates and fibrils of amyloid proteins. In our opinion, the modification of aggregates and fibrils is secondary in nature and does not play an important role in the development of neurodegenerative diseases. The glycation of amyloid proteins with carbonyl compounds can be one of the triggers of their transformation into toxic forms. The possible role of glycation of amyloidogenic proteins in the prevention of their modification by ubiquitin and the SUMO proteins due to a disruption of their degradation is separately considered.     

What Is Stochastic Resonance? Definitions, Misconceptions, Debates, and Its Relevance to Biology

Stochastic resonance is said to be observed when increases in levels of unpredictable fluctuations—e.g., random noise—cause an increase in a metric of the quality of signal transmission or detection performance, rather than a decrease. This counterintuitive effect relies on system nonlinearities and on some parameter ranges being “suboptimal”. Stochastic resonance has been observed, quantified, and described in a plethora of physical and biological systems, including neurons. Being a topic of widespread multidisciplinary interest, the definition of stochastic resonance has evolved significantly over the last decade or so, leading to a number of debates, misunderstandings, and controversies. Perhaps the most important debate is whether the brain has evolved to utilize random noise in vivo, as part of the “neural code”. Surprisingly, this debate has been for the most part ignored by neuroscientists, despite much indirect evidence of a positive role for noise in the brain. We explore some of the reasons for this and argue why it would be more surprising if the brain did not exploit randomness provided by noise—via stochastic resonance or otherwise—than if it did. We also challenge neuroscientists and biologists, both computational and experimental, to embrace a very broad definition of stochastic resonance in terms of signal-processing “noise benefits”, and to devise experiments aimed at verifying that random variability can play a functional role in the brain, nervous system, or other areas of biology.     

Is Lutzomyia serrana (Diptera, Psychodidae, Phlebotominae) present in Ecuador?

We describe a multivariate metric comparison of three sandfly species showing strong differences in size, which questions the geographical distribution of one of them. Two species are represented by a single population (L. robusta and L. guilvardae) and one by two populations (L. serrana). All of them belong to the series serrana (Diptera, Psychodidae, Phlebotominae). The morphometric data confirm that L. guilvardae is a distinct species. However, they suggest that L. robusta and L. serrana in Ecuador are the same taxon, and that it is distinguishable from the population of L. serrana in Bolivia. A multilocus enzyme electrophoresis analysis comparing L. serrana in Bolivia and L. robusta in Ecuador adds further evidence that these two populations are distinct species. Thus, our data seem to indicate that, in Ecuador, the population previously identified as L. serrana is actually the same species as the allopatric population previously identified as L. robusta. Accepting L. serrana in Ecuador as small-sized L. robusta, the resulting geographic distribution of this latter becomes in closer agreement with ecology and epidemiology.     

Is research into ethnicity and health racist,unsound, or important science?

Much historical research on race, intelligence, and health was racist, unethical, and ineffective. The concepts of race and ethnicity are difficult to define but continue to be applied to the study of the health of immigrant and ethnic minority groups in the hope of advancing understanding of causes of disease. While a morass of associations has been generated, race and ethnicity in health research have seldom given fundamental new understanding of disease. Most such research is "black box epidemiology." Researchers have not overcome the many conceptual and technical problems of research into ethnicity and health. By emphasising the negative aspects of the health of ethnic minority groups, research may have damaged their social standing and deflected attention from their health priorities. Unless researchers recognise the difficulties with research into ethnicity and health and correct its weaknesses, 20th century research in this subject may suffer the same ignominious fate as that of race science in the 19th century.     

Is there a relationship between hypoxia,contact resistance,and intercellular communication?

Summary This investigation addresses the shape of radiation survival curves of cells cultured as multicell spheroids. It is shown that spheroids of cells capable of intercellular communication by gap-junctions display survival curves lacking a radioresistant fraction of hypoxic cells. Compared to the corresponding monolayers, these spheroid survival curves exhibit a uniform increase in radioresistance due to the contact effect. In contrast, biphasic survival curves indicative of hypoxic cells are obtained with non-communicating spheroids, however, without indication of a contact effect. Evidence is presented that this relationship between intercellular communication, hypoxia, and contact effect may possibly also hold for survival curves of solid tumors.     

Trisomy 8, a Cytogenetic Abnormality in Myelodysplastic Syndromes,Is Constitutional or Not?

Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS) in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8) can be found as a constitutional mosaicism (cT8M). We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional cytogenetics (CC) and on granulocytes, CD3+ lymphocytes and oral mucosa cells by fluorescence in situ hybridization (FISH). In peripheral blood CC, +8 was seen in 4/32 patients. By FISH, only one patient with chronic myelomonocytic leukemia showed +8 in all cell samples and was interpreted as a cT8M. In our series +8 was acquired in all MDS. Probably, once discarded cT8M by FISH from CD3+ lymphocytes and non-hematological cells, +8 should be considered with enough evidence to MDS.     

Human hips,breasts and buttocks: Is fat deceptive?

In humans, reproductive-age females, unlike other ages and classes of individuals, deposit fat preferentially on the breasts, hips, and buttocks. This suggests that such fat deposition is a deceptive sexual signal, mimicking other signals of high reproductive value and potential.     

How Abnormal Is the Behaviour of Captive,Zoo-Living Chimpanzees?

BACKGROUND: Many captive chimpanzees (Pan troglodytes) show a variety of serious behavioural abnormalities, some of which have been considered as possible signs of compromised mental health. The provision of environmental enrichments aimed at reducing the performance of abnormal behaviours is increasing the norm, with the housing of individuals in (semi-)natural social groups thought to be the most successful of these. Only a few quantitative studies of abnormal behaviour have been conducted, however, particularly for the captive population held in zoological collections. Consequently, a clear picture of the level of abnormal behaviour in zoo-living chimpanzees is lacking. METHODS: We present preliminary findings from a detailed observational study of the behaviour of 40 socially-housed zoo-living chimpanzees from six collections in the United States of America and the United Kingdom. We determined the prevalence, diversity, frequency, and duration of abnormal behaviour from 1200 hours of continuous behavioural data collected by focal animal sampling. RESULTS, CONCLUSION AND SIGNIFICANCE: Our overall finding was that abnormal behaviour was present in all sampled individuals across six independent groups of zoo-living chimpanzees, despite the differences between these groups in size, composition, housing, etc. We found substantial variation between individuals in the frequency and duration of abnormal behaviour, but all individuals engaged in at least some abnormal behaviour and variation across individuals could not be explained by sex, age, rearing history or background (defined as prior housing conditions). Our data support a conclusion that, while most behaviour of zoo-living chimpanzees is 'normal' in that it is typical of their wild counterparts, abnormal behaviour is endemic in this population despite enrichment efforts. We suggest there is an urgent need to understand how the chimpanzee mind copes with captivity, an issue with both scientific and welfare implications.     

The Leeuwenhoek Lecture, 1980. Is it a virus?

It was shown many years ago that viruses can cause common cold but it is often forgotten that there were prolonged investigations and disagreements before this was agreed. It wa difficult to detect or propagate any virus in the laboratory and it has taken more than two decades of research to arrive at a reasonably complete list of the viruses that cause colds and related diseases. To do so, new techniques were developed by which these very specialized viruses can be grown and studied. Nevertheless unanswered questions remain on the relation between them and the diseases. This research has required finding answers to several different questions about the viruses and the diseases. The questions cannot all be answered in the same way for all virus infections, and recent research has shown that we can learn a great deal about certain viruses and diseases without answering all of the questions; for instance, the role of rotaviruses in diarrhoea was established though the viruses could not be effectively grown in the laboratory. In the light of these ideas I shall refer to the evidence that mental diseases may be due to virus infections and the recent finding that cerebrospinal fluid from such patients produced a cytopathic effect in tissue cultures that was apparently due to a virus-like agent.