Ending a decade of deception: a valiant failure, a not-so-valiant failure, and a success story

Prior studies involving two methods, Brooks Parsimony Analysis (BPA) and TreeMap, have found BPA to be the more reliable method. Recent criticisms leveled at these studies argue that the tests were unfairly created and biased in favor of BPA. The authors of a recent critique offered new exemplars to demonstrate flaws in BPA, plus a simple fix to correct the flaws found in TreeMap. A re‐evaluation of their exemplars clearly shows that the authors' calculations are incorrect, their understanding of the methods is lacking, and that their simple fix does not work. Additional analyses using TreeMap 2.02 are run to show that TreeMap 2.02, like TreeMap 1.0, cannot adequately deal with widespread parasites, contrary to the claims of its supporters. Furthermore, the exemplars corroborate previous findings that BPA, when calculated correctly, is more reliable than TreeMap1.0 and TreeMap 2.02 and therefore the method of choice in coevolutionary and biogeographic studies.     

Diabetes,oxidative stress,and antioxidants: a review

Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Free radicals are formed disproportionately in diabetes by glucose oxidation, nonenzymatic glycation of proteins, and the subsequent oxidative degradation of glycated proteins. Abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes, increased lipid peroxidation, and development of insulin resistance. These consequences of oxidative stress can promote the development of complications of diabetes mellitus. Changes in oxidative stress biomarkers, including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione levels, vitamins, lipid peroxidation, nitrite concentration, nonenzymatic glycosylated proteins, and hyperglycemia in diabetes, and their consequences, are discussed in this review. In vivo studies of the effects of various conventional and alternative drugs on these biomarkers are surveyed. There is a need to continue to explore the relationship between free radicals, diabetes, and its complications, and to elucidate the mechanisms by which increased oxidative stress accelerates the development of diabetic complications, in an effort to expand treatment options.     

Carnitine: a nutritional, biosynthetic, and functional perspective

Carnitine status in humans is reported to vary according to body composition, gender, and diet. Plasma carnitine concentration positively correlates with the dietary intake of carnitine. The content of carnitine in foodstuff is based on old and inadequate methodology. Nevertheless, dietary carnitine is important. The molecular biology of the enzymes of carnitine biosynthesis has recently been accomplished. Carnitine biosynthesis requires pathways in different tissues and is an efficient system. Overall biosynthesis is determined by the availability of trimethyllysine from tissue proteins. Carnitine deficiency resulting from a defect in biosynthesis has yet to be reported.

The role of carnitine in long-chain fatty acid oxidation is well defined. Recent evidence supports a role for the voltage-dependent anion channel in the transport of acyl-CoAs through the mitochondrial outer membrane. The mitochondrial outer membrane carnitine palmitoyltransferase-I in liver can be phosphorylated and when phosphorylated the sensitivity to malonyl-CoA is greatly decreased. This may explain the change in sensitivity of liver carnitine palmitoyltransferase-I observed during fasting and diabetes. Recently reported data clarify the role of carnitine and the carnitine transport system in the interplay between peroxisomes and mitochondrial fatty acid oxidation. Lastly, the buffering of the acyl-CoA/CoA coupled by carnitine reflects intracellular metabolism. This mass action effect underlies the use of carnitine as a therapeutic agent. In summary, these new observations help to further our understanding of the molecular aspects of carnitine in medicine.     

Sex, status, and criminality: a theoretical nexus

This article offers a theoretical explanation for relationships between social status and involvement in serious and persistent criminal behavior from an evolutionary perspective. The theory's central premise is that natural selection has produced females who bias their mating choices toward males who strive for status. This bias has resulted in males devoting greater time and energy to status striving (relative to females). To account for why nearly all "victimizing" forms of criminality are more common among males than among females, the theory asserts that status striving exists along a continuum of competitive/victimizing behavior. One end of this continuum is epitomized by crude (criminal) forms of the behavior that societies generally discourage and even punish. The other end consists of sophisticated (commercial) forms that societies tolerate and even encourage. According to the theory, most males begin to exhibit non-playful forms of competitive/victimizing behavior around the onset of puberty as they start their reproductive careers. Adolescent males with the greatest abilities to learn will transition quickly from crude forms of competitive/victimizing behavior to more sophisticated forms, while males who have the greatest difficulties learning will transition more slowly. A major deduction from the theory is that genes on the Y-chromosome must be affecting the brain in ways that promote status-striving behavior. This deduction needs empirical scrutiny, although it is consistent with evidence (a) that the Y-chromosome transforms would-be ovaries into testes, the latter being specialized organs for the production of testosterone, and (b) that testosterone alters brain functioning in ways that contribute to both status striving and criminality.     

Individualization,inequality, and labor: a qualitative approach

In this paper, we show how we came to explore Beck’s theory of individualization in the light of a qualitative study of livelihood strategies in post-2008 Spain and Cyprus. We observed that experiences of downward social mobility in contexts of welfare retreat and precarious labor conditions were compelling people to build marketed individualities and to create individual biographies with recourse to a highly individualized rhetoric. However, analysis of a very diverse sample of subjects from different socio-economic backgrounds showed us that individualization theory must be conceptualized within a framework of social structures, and that Beck’s individualization theory fails to recognize its persistence in contemporary societies. We therefore propose looking at individualization as a contemporary process through which class differences are expressed. Only in this way can it serve as a useful theoretical tool with which to understand the workings of contemporary capitalism and the ways in which new values and moral frameworks are being formed.     

Diabetes, metallothionein, and zinc interactions: a review

Epidemiological evidence, associating diabetes with zinc (Zn) deficiencies, has resulted in numerous research studies describing the effects of Zn and associated metallothionein (MT), on reducing diabetic complications associated with oxidative stress. MT has been found to have a profound effect on the reduction of oxidative stress induced by the diabetic condition. Over expression of MT in various metabolic organs has also been shown to reduce hyperglycaemia-induced oxidative stress, organ specific diabetic complications, and DNA damage in diabetic experimental animals, which have been further substantiated by the results from MT-knockout mice. Additionally, supplementation with Zn has been shown to induce in vivo MT synthesis in experimental animals and to reduce diabetes related complications in both humans and animal models. Although the results are promising, some caution regarding this topic is however necessary, due to the fact that the majority of the studies done have been animal based. Hence more human intervention trials are needed regarding the positive effects of MT and Zn before firm conclusions can be made regarding their use in the treatment of diabetes.     

Evolution of a colour pattern: history,development, and selection

Patterns of melanin pigmentation in birds are extremely varied. Nevertheless it is easy to think of many patterns that are never observed, and others that frequently recur in diverse and distantly related species. Using as our model the avian genus Phylloscopus we ask how the restricted range of observed patterns might be attributable to a restricted range of variants produced by developmental perturbations. The patterns we consider consist of unmelanized patches on the wings, crown and rump on otherwise pigmented upperparts. We use reaction-diffusion models to show that gross features of the pattern can be simply predicted from considerations of embryo shape. We suggest that birds are expected to have more patterned heads, because the head region is relatively larger than other regions in the developing embryo. A comparative analysis across many species of birds and a phylogenetic analysis within the genus Phylloscopus show that the component elements of the pattern have repeatedly been lost and gained during evolution. A shift in a threshold reading could explain the appearance and disappearance of the unmelanized patches, perhaps through changes in the sensitivity of melanocytes to epidermal signals. Such threshold shifts would make the transition between patterned and unpatterned forms particularly easy once the patterns have been exposed to selection in some distant ancestor. This partitioning of the roles of selection and development implies that many features of the patterns reflect developmental mechanisms in both immediate and more distant ancestors.     

Production,purification, characterization,immobilization, and application of Serrapeptase: a review

Background

Serrapeptase is a proteolytic enzyme with many favorable biological properties like anti-inflammatory, analgesic, anti-bacterial, fibrinolytic properties and hence, is widely used in clinical practice for the treatment of many diseases. Although Serrapeptase is widely used, there are very few published papers and the information available about the enzyme is very meagre. Hence this review article compiles all the information about this important enzyme Serrapeptase.

Methods

A literature search against various databases and search engines like PubMed, SpringerLink, Scopus etc. was performed.

Results

We gathered and highlight all the published information regarding the molecular aspects, properties, sources, production, purification, detection, optimizing yield, immobilization, clinical studies, pharmacology, interaction studies, formulation, dosage and safety of the enzyme Serrapeptase.

Conclusion

Serrapeptase is used in many clinical studies against various diseases for its anti-inflammatory, fibrinolytic and analgesic effects. There is insufficient data regarding the safety of the enzyme as a health supplement. Data about the antiatherosclerotic activity, safety, tolerability, efficacy and mechanism of action of the Serrapeptase are still required.

     

Oxygen, oxysterols, ouabain, and ozone: a cautionary tale

The recent account of the oxidation of tissue cholesterol by ozone created in human arterial plaques by the oxidation of water by electronically excited (singlet) dioxygen depends on the identification of the oxysterols formed and on the presumption that they are formed uniquely by ozone action. The chief oxysterols found, 3beta-hydroxy-5-oxo-5,6-secocholestan-6-al and 3beta,5-dihydroxy-5beta-B-norcholestane-6beta-carboxaldehyde, were identified as their 2,4-dinitrophenylhydrazones by chromatographic properties and a single mass spectral ion m/z 597 interpreted as [M-H](-). Conventional identification procedures for oxysterols were not conducted. Accordingly, absent other evidence, error may exist; such errors are known in the literature. Moreover, the assertion that ozone be the only oxidant that could form the 5,6-secosterol aldehyde from cholesterol is unproven. Other equally novel unproven processes can be posed. The account of biological ozone mimics prior 30-year-old reports of singlet oxygen itself in biological systems. Lest a similar history develop for biological ozone three topics of steroid oxidation are here reviewed to aid in understanding the current matter. Caution in evaluating the account of biological ozone is warranted.     

AMPK: An odyssey of a metabolic regulator,a tumor suppressor,and now a contextual oncogene

Metabolic reprogramming is a unique but complex biochemical adaptation that allows solid tumors to tolerate various stresses that challenge cancer cells for survival. Under conditions of metabolic stress, mammalian cells employ adenosine monophosphate (AMP)-activated protein kinase (AMPK) to regulate energy homeostasis by controlling cellular metabolism. AMPK has been described as a cellular energy sensor that communicates with various metabolic pathways and networks to maintain energy balance. Earlier studies characterized AMPK as a tumor suppressor in the context of cancer. Later, a paradigm shift occurred in support of the oncogenic nature of AMPK, considering it a contextual oncogene. In support of this, various cellular and mouse models of tumorigenesis and clinicopathological studies demonstrated increased AMPK activity in various cancers. This review will describe AMPK's pro-tumorigenic activity in various malignancies and explain the rationale and context for using AMPK inhibitors in combination with anti-metabolite drugs to treat AMPK-driven cancers.     

Threading a peptide through a peptide: protein loops, rotaxanes, and knots

Proteins adopt complex folds in nature that typically avoid conformations that are knotted or “threaded” through closed loops. Is this the result of fundamental barriers to folding, or have proteins simply evolved to avoid threaded conformations? Organic synthesis has been used in supramolecular chemistry to install topological links in small molecules. By following these principles, we now show that it is possible to assemble a topologically linked protein complex by threading a linear protein through a cyclic protein to form a [2]pseudo‐rotaxane. Subsequent ring closure using native chemical ligation cyclizes the linear protein, forming a [2]heterocatenane. Although the kinetics of protein threading are slower than the folding kinetics of the native protein, threading appears to be a highly efficient process.