Biofeedback in medicine: who,when, why and how?

Biofeedback is a mind-body technique in which individuals learn how to modify their physiology for the purpose of improving physical, mental, emotional and spiritual health. Much like physical therapy, biofeedback training requires active participation on the part of patients and often regular practice between training sessions. Clinical biofeedback may be used to manage disease symptoms as well as to improve overall health and wellness through stress management training. Research has shown that biofeedback interventions are efficacious in treating a variety of medical conditions, and many Americans are turning to biofeedback and other less traditional therapies for their routine healthcare.Clinical biofeedback training is growing increasingly popular in the USA, as many people are seeking out relatively new approaches to healthcare. This article provides an overview of clinical biofeedback training, outlines two models of training, details research which has established how effective biofeedback is in patients with a given disease, and describes who should be referred for biofeedback training.     

Apoptosis in the heart: when and why?

Since mammalian cardiac myocytes essentially rely on aerobic energy metabolism, it has been assumed that cardiocytes die in a catastrophic breakdown of cellular homeostasis (i.e. necrosis), if oxygen supply remains below a critical limit. Recent observations, however, indicate that a process of gene-directed cellular suicide (i.e. apoptosis) is activated in terminally differentiated cardiocytes of the adult mammalian heart by ischemia and reperfusion, and by cardiac overload as well. Apoptosis or programmed cell death is an actively regulated process of cellular self destruction, which requires energy and de novo gene expression, and which is directed by an inborn genetic program. The final result of this program is the fragmentation of nuclear DNA into typical nucleosomal ladders, while the functional integrity of the cell membrane and of other cellular organelles is still maintained. The critical step in this regulated apoptotic DNA fragmentation is the proteolytic inactivation of poly-[ADPribose]-polymerase (PARP) by a group of cysteine proteases with some structural homologies to interleukin-1-converting enzyme (ICE-related proteases [IRPs] such as apopain, yama and others). PARP catalyzes the ADP-ribosylation of nuclear proteins at the sites of spontaneous DNA strand breaks and thereby facilitates the repair of this DNA damage. IRP-mediated destruction of PARP, the supervisor of the genome, can be induced by activation of membrane receptors (e.g. FAS or APOI) and other signals, and is inhibited by activation of anti-death genes (e.g. bcl-2). Overload-triggered myocyte apoptosis appears to contribute to the transition to cardiac failure, which can be prevented by therapeutic hemodynamic unloading. In myocardial ischemia, the activation of the apoptotic program in cardiocytes does not exclude their final destiny to catastrophic necrosis with release of cytosolic enzymes, but might be considered as an adaptive process in hypoperfused ventricular zones, sacrificing some jeopardized myocytes to regulated apoptosis, which may by less arrhythmogenic than necrosis with the primary disturbance of membrane function.     

Alternative signaling pathways: when, where and why?

Alternative cell signal transduction pathways have been demonstrated in some experimental systems. The importance of their existence has not been completely appreciated. In this review we present the cases of alternative pathways resulted from a survey of the available experimental data. The alternative pathways could show different relationships, i.e., synergistic, redundant, additive, opposite and competitive effects. They could have distinct time courses and cell, organ, sex or species specification. Further, they could happen during physiological or pathological situations, and display differentiated sensitivity. These case studies together imply that alternative signal pathways could be involved in the regulation of cell functions at the pathway level. In-depth understanding of the importance of the alternative pathways will rely on building and exploration of mathematical models.     

Origin of sucrose metabolism in higher plants: when,how and why?

Since the discovery of sucrose biosynthesis, considerable advances have been made in understanding its regulation and crucial role in the functional biology of plants. However, important aspects of this metabolism are still an enigma. Studies in cyanobacteria and the publication of the sequences of several complete genomes have recently significantly increased our knowledge of the structures of proteins involved in sucrose metabolism and given us new insights into their origin and further evolution.     

Folylpoly-γ-glutamate synthesis by bacteria and mammalian cells

Summary The purification and properties of folylpolyglutamate synthetase fromCorynebacterium sp, and some properties of partially purified enzyme fromLactobacillus casei, Streptococcus faecalis, Neurospora crassa, pig liver, and Chinese hamster ovary cells, are described.TheCorynebacterium enzyme catalyzes a MgATP-dependent addition of glutamate to a variety of reduced pteroate and pteroylmono-, di-, and triglutamate substrates, with the concomitant production of MgADP and phosphate. Although glutamate moieties are added in a sequential fashion, the kinetic mechanism, which is Ordered Ter Ter, precludes the sequential addition of glutamate moieties to enzyme-bound folate. It is suggested that catalysis precedes via the formation of a pteroyl--glutamyl phosphate intermediate.Thein vivo distribution of folylpolyglutamates in bacteria and mammalian cells, which differ from source to source, appear to be a reflection of the ability of folylpolyglutamates to act as substrates for folylpolyglutamate synthetases from different sources.Only one enzyme appears to be involved in the conversion of pteroylmonoglutamates to polyglutamate forms in both bacteria and mammalian cells. Bacterial folylpolyglutamate synthetases use a variety of pteroylmonoglutamates as their preferred monoglutamate substrate, but use 5,10-methylenetetrahydropteroylpolyglutamates as their preferred, and sometimes only, polyglutamate substrate. Mono- and polyglutamyl forms of tetrahydrofolate are the preferred substrates of mammalian folylpolyglutamate synthetases.     

Plant species radiations: where,when, why?

The spatial and temporal patterns of plant species radiations are largely unknown. I used a nonlinear regression to estimate speciation and extinction rates from all relevant dated clades. Both are surprisingly high. A high species richness can be the result of either little extinction, thus preserving the diversity that dates from older radiations (a 'mature radiation'), or a 'recent and rapid radiation'. The analysis of radiations from different regions (Andes, New Zealand, Australia, southwest Africa, tropics and Eurasia) revealed that the diversity of Australia may be largely the result of mature radiations. This is in sharp contrast to New Zealand, where the flora appears to be largely the result of recent and rapid radiations. Mature radiations are characteristic of regions that have been climatically and geologically stable throughout the Neogene, whereas recent and rapid radiations are more typical of younger (Pliocene) environments. The hyperdiverse Cape and Neotropical floras are the result of the combinations of mature as well as recent and rapid radiations. Both the areas contain stable environments (the Amazon basin and the Cape Fold Mountains) as well as dynamic landscapes (the Andes and the South African west coast). The evolution of diversity can only be understood in the context of the local environment.     

Alien species in the Mediterranean Sea—which, when, where, why?

A critical evaluation of more than 2,200 publications, some dating back to the late 1800s, established the presence, and traced the spatio-temporal spread, of 558 alien metazoan species in the Mediterranean Sea. The majority of aliens in the eastern Mediterranean entered through the Suez Canal, whereas mariculture and shipping are powerful means of introduction in the northwestern Mediterranean and in the Adriatic Sea. Most aliens are thermophilic species. The possible causes for the epic scale of invasion in the Mediterranean Sea are discussed. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Guest editors: J. Davenport, G. Burnell, T. Cross, M. Emmerson, R. McAllen, R. Ramsay & E. Rogan Challenges to Marine Ecosystems     

Glucose-6-phosphate dehydrogenase laboratory assay: How, when, and why?

Glucose 6-phosphate dehydrogenase (G6PD) deficiency is the most common defect of red blood cells. Although some different laboratory techniques or methods are employed for the biochemical screening, a strict relationship between biochemists, clinicians, and molecular biologists is necessary for a definitive diagnosis. This article represents an overview on the current laboratory tests finalized to the screening or to the definitive diagnosis of G6PD-deficiency, underlying the problems regarding the biochemical and molecular identification of heterozygote females other than those regarding the standardization of the clinical and laboratory diagnostic procedures. Finally, this review is aimed to give a flow-chart for the complete diagnostic approach of G6PD-deficiency.     

γ-glutamyltransferase in human diploid fibroblasts and other mammalian cells

Summary γ-Glutamyltransferase was determined in WI-38 human diploid fibroblasts and compared to enzyme levels determined in several other mammalian cell lines including: fibroblast-like cells from human skin, tibia and foreskin; epithelial-like cells from human, bovine and monkey kidney; and transformed cells (Chinese hamster ovary, HeLa S₃ and SV-40 transformed WI-38). Transformed cells had the lowest activity found followed in increasing order by fibroblasts, human and bovine epithelial cells and monkey kidney epithelial cells. The enzyme isolated from the plasma membrane of WI-38 cells, like the enzyme from kidney and brain, was found to be irreversibly inhibited by iodoacetamide, reversibly by serine-borate, and had a strong specificity for certain amino acids. The possibility exists that γ-glutamyltransferase could be involved in transport of amino acids into cells in culture; and glutamine, used in media, is an excellent substrate for the enzyme. Preliminary reports of some of this work were presented at meetings of The American Society of Biological Chemists in Minneapolis (Abstracts Fed. Proc. 33: 957, 1974) and at Atlantic City (Abstracts Fed. Proc. 34: 2243, 1975). This work was supported by Grant NIH 1 P01 HD 07173. The WI-38 starter cultures and cell pack used in these studies were obtained through Contract M01 HD 42828 to Stanford University from the National Institute of Aging.     

Rabbit relinquishment through online classified advertisements in the United Kingdom: when,why, and how many?

To identify implicit causes of companion rabbit relinquishment, this study investigated whether there was annual and seasonal variation in the number of advertisements and ages of rabbits posted as free or for sale on classified websites in the United Kingdom. The number of advertisements posted decreased from 2014 to 2016. There was an increase in the number of advertisements for free rabbits in winter compared with other seasons, which could be a result of caregivers’ reduced willingness to interact with their rabbits and carry out husbandry during periods of inclement weather. Rabbits advertised as free were older than rabbits advertised for sale, and rabbits relinquished due to human-related reasons were older than those relinquished because of rabbit-related factors. It is recommended that further research is undertaken to elucidate whether providing education to prospective rabbit caregivers regarding the life span of rabbits and their substantial husbandry requirements, especially in winter, would deter the purchase of rabbits by caregivers unable or unwilling to care for them in the long term.     

Open questions: why should we care about ER-phagy and ER remodelling?

The endoplasmic reticulum (ER) is one of the most complex organelles in the eukaryotic cell. Recent findings suggest that a process called ER-phagy plays a major role in maintaining the ER’s shape and function.     

Multiple aggregates and aggresomes of C-terminal truncated human αA-crystallins in mammalian cells and protection by αB-crystallin

Background

Cleavage of 11 (αA162), 5 (αA168) and 1 (αA172) residues from the C-terminus of αA-crystallin creates structurally and functionally different proteins. The formation of these post-translationally modified αA-crystallins is enhanced in diabetes. In the present study, the fate of the truncated αA-crystallins expressed in living mammalian cells in the presence and absence of native αA- or αB-crystallin has been studied by laser scanning confocal microscopy (LSM).

Methodology/Principal Findings

YFP tagged αAwt, αA162, αA168 and αA172, were individually transfected or co-transfected with CFP tagged αAwt or αBwt, expressed in HeLa cells and studied by LSM. Difference in protein aggregation was not caused by different level of α-crystallin expression because Western blotting results showed nearly same level of expression of the various α-crystallins. The FRET-acceptor photo-bleaching protocol was followed to study in situ protein-protein interaction. αA172 interacted with αAwt and αBwt better than αA168 and αA162, interaction of αBwt being two-fold stronger than that of αAwt. Furthermore, aggresomes were detected in cells individually expressing αA162 and αA168 constructs and co-expression with αBwt significantly sequestered the aggresomes. There was no sequestration of aggresomes with αAwt co-expression with the truncated constructs, αA162 and αA168. Double immunocytochemistry technique was used for co-localization of γ-tubulin with αA-crystallin to demonstrate the perinuclear aggregates were aggresomes.

Conclusions/Significance

αA172 showed the strongest interaction with both αAwt and αBwt. Native αB-crystallin provided protection to partially unfolded truncated αA-crystallins whereas native αA-crystallin did not. Aggresomes were detected in cells expressing αA162 and αA168 and αBwt co-expression with these constructs diminished the aggresome formation. Co-localization of γ-tubulin in perinuclear aggregates validates for aggresomes.     

Induction of T → G and T → A transversions by 5-formyluracil in mammalian cells

Oxidatively damaged thymine, 5-formyluracil (5-fU), was incorporated into a predetermined site of double-stranded shuttle vectors. The nucleotide sequences in which the modified base was incorporated were 5′-CFTAAG-3′ and 5′-CTFAAG-3′ (F represents 5-fU), the recognition site for the restriction enzyme AflII (5′-CTTAAG-3′). The 5-fU was incorporated into a template strand of either the leading or lagging strand of DNA replication. The modified DNAs were transfected into simian COS-7 cells, and the DNAs replicated in the cells were recovered and were analyzed after the second transfection into Escherichia coli. The 5-fU did not block DNA replication in mammalian cells. The 5-fU residues were weakly mutagenic, and their mutation frequencies in double-stranded vectors were 0.01–0.04%. The T → G and T → A transversions were the mutations found most frequently, suggesting the formation of 5-fU·C and 5-fU·T base pairs, respectively. This is the first report that clearly shows the induction of transversion mutations by an oxidized pyrimidine base in DNA in mammalian cells.     

Quantitative comparative mutagenesis in bacteria, mammalian cells, and animal-mediated assays A convenient way of estimating genotoxic activity in vivo?

The accumulation of environmental compounds which exhibit genotoxic properties in short-term assays and the increasing lag of time for obtaining confirmation or not in long-term animal mutagenicity and carcinogenicity tests, makes it necessary to develop alternative, rapid methodologies for estimating genotoxic activity in vivo. In the experimental approach used here, it was assumed that the genotoxic activity of foreign compounds in animals, and ultimately humans, is determined among others by exposure level, organ distribution of (DNA) dose, and genotoxic potency per unit of dose, and that knowledge about these 3 parameters may allow to rapidly determine the expected degree of genotoxicity in various organs of exposed animals. In view of the high degree of qualitative correlation between mutagenic activity of chemicals in bacteria and in cultured mammalian cells, and their mutagenic and carcinogenic properties in animals, and in order to be able to distinguish whether mutagenic potency differences were due to differences in (DNA) dose rather than other physiological factors, the results of mutagenicity tests obtained in the present experiments using bacteria and mammalian cells were compared on the basis of DNA dose rather than exposure concentrations, with the following questions in mind: Is there an absolute or a relative correlation between the mutagenic potencies of various ethylating agents in bacteria (E. coli K12) and in mammalian cells (V79 Chinese hamster) after treatment in standardized experiments, and can specific DNA adducts be made responsible for mutagenicity? Is the order of mutagenic potency of various ethylating agents observed in bacteria in vitro representative of the ranking of mutagenic potency found in vivo? Since the answer to this last question was negative, a further question addressed to was whether short-term in vivo assays could be developed for a rapid determination of the presence (and persistence) of genotoxic factors in various organs of mice treated with chemicals. In quantitative comparative mutagenesis experiments using E. coli K12 and Chinese hamster cells treated under standardized conditions in vitro with 5 ethylating agents, there was no indication of an absolute correlation between the number of induced mutants per unit of dose in the bacteria and the mammalian cells. The ranking of mutagenic potency was, however, identical in bacteria and mammalian cells, namely, ENNG greater than ENU greater than or equal to DES greater than DEN congruent to EMS, the mutagenic activity of DEN being dependent on the presence of mammalian liver preparations.(ABSTRACT TRUNCATED AT 400 WORDS)