On the evocability of a positive oestrogen feedback action on LH secretion in transsexual men and women.

In transsexual men with homosexual behaviour and intact testicular function, as well as in homosexual men with normal gender identity, following a negative oestrogen feedback effect a delayed positive oestrogen feedback action on LH secretion was evoked. By contrast, in transsexual men with hypo- or asexuality and intact testes or hypergonadotrophic hypo- or agonadism, as well as in heterosexual men with normal gender identity, a negative oestrogen feedback effect was not followed by a positive feedback action on LH release. In transsexual women with homosexual behaviour and oligo- and/or hypomenorrhoea, only a weak or at best moderate positive oestrogen feedback action on LH release was evocable, similarly as in castrated and oestrogen-primed heterosexual men. By contrast, in a transsexual woman with bisexual behaviour and eumenorrhoea, a strong positive oestrogen feedback action on LH secretion was evocable, as well as in heterosexual women with normal gender identity.     

Changes in prostacyclin and thromboxane biosynthesis and their catabolic enzyme activity in kidneys of aging rats

The effects of aging on the prostacyclin and thromboxane biosynthesis and prostaglandin catabolic enzyme activity in rat kidney were investigated. The prostacyclin biosynthesis, using arachidonic acid as substrate, was the greatest in young kidneys (2 months old) and then progressively decreased in mature (12 months old) and old (24 months old) kidneys, while thromboxane biosynthetic activity showed no significant change as a function of age. When prostaglandin H2 was used as substrate, the prostacyclin and thromboxane biosynthesis showed similar results as when arachidonic acid was used as substrate; the prostacyclin biosynthesis progressively decreased and thromboxane biosynthesis showed no significant change as a function of age. The fatty acid cyclooxygenase in kidney was measured by a specific radioimmunoassay. No significant change in renal fatty acid cyclooxygenase as a function of age was found. Thus, we concluded that the progressive decrease in renal prostacyclin biosynthesis as a function of age is due to a defect in prostacyclin synthetase in aged kidneys. The prostaglandin catabolic enzyme, NAD+-dependent 15-hydroxyprostaglandin dehydrogenase, in kidneys was also investigated. The enzyme activity progressively decreased as a function of age, which suggested a decrease in the metabolism of thromboxane A2 in aged kidneys. The present results, indicating a decrease in renal prostacyclin biosynthesis and renal 15-hydroxyprostaglandin dehydrogenase activity with aging, might contribute to a plausible explanation of the progressive decrease in renal functions in the elderly.     

Biotechnological uses of cyanobacteria

Cyanobacteria (blue-green algae) are 0₂-evolving photosynthesizing prokaryotes that have an extensive history of use as a human food source and as a fertilizer in rice fields. They have also been recognized as an excellent source of vitamins and proteins and as such are found in health food stores in North America and elsewhere. Cyanobacteria have a great deal of potential as a source of fine chemicals, as a biofertilizer and as a source of renewable fuel. This potential is being realized as data from research in the areas of the physiology and chemistry of these organisms are gathered and as the knowledge of cyanobacterial genetics and genetic engineering increases. We review, here, the present (and possible future) uses of cyanobacteria and assess the state of the art with respect to the genetic manipulation of cyanobacteria.     

Transforming growth factor beta1 and prostaglandin E2 concentrations are associated with bone formation markers in ulcerative colitis patients

Osteoporosis is a significant complication of a multifactoral etiology associated with inflammatory bowel disease. The aim of study was to evaluate the relationships between bone mineral density as well as bone turnover markers and inflammatory activity modulators (i.e., PGE2 and TGFbeta1) in ulcerative colitis (UC). Twenty-one active ulcerative colitis subjects and 14 healthy individuals were included into the study. We observed no significant differences in serum concentrations of osteoprotegerin and osteocalcin, as well as bone mineral density between UC patients and healthy individuals. Plasma concentrations of PGE2, TGFbeta1 and TNF-alpha were significantly higher in UC patients than in controls. Serum osteocalcin demonstrated a positive correlation with both serum PGE2 and plasma TGFbeta1. Moreover there was significant correlation between osteoprotegerin and TGFbeta1 as well as serum TNF-alpha concentrations. In conclusion a positive association between PGE2 and TGFbeta1 and bone formation markers-osteoprotegerin and osteocalcin, as well as a comparable BMD in UC patients and healthy individuals was shown. Our results may indicate that increase of PGE2 as well as TGFbeta1 concentrations may play a protective role against bone loss in ulcerative colitis patients.     

The dsbA-dsbB disulfide bond formation system of Burkholderia cepacia is involved in the production of protease and alkaline phosphatase, motility, metal resistance, and multi-drug resistance

In a previous study, we isolated a dsbB mutant of Burkholderia cepacia KF1 and showed that phenotypes of protease production and motility are dependent on DsbB, a membrane-bound disulfide bond oxidoreductase. We have now isolated a dsbA mutant by transposon mutagenesis, cloned the dsbA gene encoding a periplasmic disulfide bond oxidoreductase, and characterized the function of the DsbA-DsbB disulfide bond formation system in B. cepacia. The complementing DNA fragment had an open reading frame for a 212-amino acid polypeptide with a potential redox-active site sequence of Cys-Pro-His-Cys that is homologous to Escherichia coli DsbA. The dsbA mutant, as well as the previously isolated dsbB mutant, was defective in the production of extracellular protease and alkaline phosphatase, as well as in motility. In addition, mutation in the DsbA-DsbB system resulted in an increase in sensitivity to Cd2+ and Zn2+ as well as a variety of antibiotics including beta-lactams, kanamycin, erythromycin, novobiocin, ofloxacin and sodium dodecyl sulfate. These results suggested that the DsbA-DsbB system might be involved in the formation of a metal efflux system as well as a multi-drug resistance system.     

The specific targeting of immune regulation: T-cell responses against Indoleamine 2,3-dioxygenase

Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in many settings including cancer. In recent years, we have described spontaneous CD8(+) as well as CD4(+) T-cell reactivity against IDO in the tumor microenvironment of different cancer patients as well as in the peripheral blood of both cancer patients and to a lesser extent in healthy donors. We have demonstrated that IDO-reactive CD8(+) T cells were peptide-specific, cytotoxic effector cells, which are able to recognize and kill IDO-expressing cells including tumor cells as well as dendritic cells. Consequently, IDO may serve as a widely applicable target for immunotherapeutic strategies with a completely different function as well as expression pattern compared to previously described antigens. IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals, and IDO-based immunotherapy may consequently be synergistic with additional immunotherapy. In this regard, we have shown that the presence of IDO-specific T cells boosted immunity against CMV and tumor antigens by eliminating IDO(+) suppressive cells and changing the regulatory microenvironment. The current review summarizes current knowledge of IDO as a T-cell antigen, reports the initial results that are suggesting a general function of IDO-specific T cells in immunoregulation, and discusses future opportunities.     

Age dependent changes in enzymes involved in macromolecular synthesis in Turbatrix aceti.

The specific activities of elongation factor 1, RNA and DNA polymerase, as well as fructose-1,6-diphosphate aldolase were determined as a function of age in the nematode Turbatrix aceti. It was found that the specific activities of both DNA polymerase and aldolase declined constantly as the animal aged. In contrast, both elongation factor 1 and RNA polymerase showed sharp increases in their specific activities at 5 and 15 days, respectively, before ultimately declining. It was also shown that elongation factor 1, which exists mainly as a high molecular weight species in the young animal, undergoes a conversion to a lower molecular weight species as the organism ages. In addition there is a progressive accumulation of inactive or partially active elongation factor 1 molecules in older animals. The addition of α-tocopherol to the growth medium of these nematodes resulted in an increased life-span as well as alterations in the patterns of the enzyme activities.     

Governing Dementia: A Historical Investigation of the Power of States and Professionals in the Conceptualization of Dementia in China

This study intends to understand how Chinese states and healthcare professionals interact with each other in adopting biomedical concepts within the context of globalization of mental health. The conceptualization of dementia as a stigmatized mental disorder in China serves as a salient case to examine interactions between states and professionals as well as the interrelationships between different healthcare professionals in producing knowledge. By engaging the biopolitical approach, this project explores the historically-contingent conceptualizations of dementia, namely dementia as a vague and stigmatized condition in imperial China, dementia as biosocial deviance in Republican China, dementia as a product of capitalism during Mao-era China, and dementia as a stigmatized mental illness in contemporary China. These dynamics indicate that Chinese professionals have been largely influenced by state ideologies in assimilating biomedical concepts. Through the historical analysis of state-professional interactions in conceptualizing dementia, this study provides an avenue to understand how biomedical concepts transfer within the global context can be read as a site of power struggle between ethnomedicine and biomedicine, between various competing forms of healthcare professionals, and between indigenous sovereignty and governmentality. Moreover, the study of conceptualizing dementia in China sheds light on the larger sociopolitical processes of governmentality in China.     

p62: a versatile multitasker takes on cancer

Since its initial discovery as an atypical protein kinase C (PKC)-interacting protein, p62 has emerged as a crucial molecule in a myriad of cellular functions. This multifunctional role of p62 is explained by its ability to interact with several key components of various signaling mechanisms. Not surprisingly, p62 is required for tumor transformation owing to its roles as a key molecule in nutrient sensing, as a regulator and substrate of autophagy, as an inducer of oxidative detoxifying proteins, and as a modulator of mitotic transit and genomic stability; all crucial events in the control of cell growth and cancer.     

Platelet and cardiovascular activity of the hydantoin BW245C, a potent prostaglandin analogue

The platelet anti-aggregating, cardiovascular and gastro-intestinal actions of a hydantoin prostaglandin analogue, BW245C have been compared with prostacyclin and PGD2 in several species. In human plasma in vitro, BW245C was 0.2 times as active as prostacyclin and 8 times as active as PGD2 in inhibiting platelet aggregation. In rat and rabbit plasma, BW245C was only weakly active but was more potent in sheep and horse plasma. Since the activity of PGD2 varied in a parallel fashion, BW245C may interact with PGD2 binding sites on platelets. The potency of BW245C as a vasodepressor also varied between species, being 0.5, 0.1, 0.06 and less than 0.02 times as active as prostacyclin in the anaesthetised dog, monkey, rat and rabbit respectively. The relative activity of BW245C as an inhibitor of platelet aggregation ex vivo was more comparable, being 0.08, 0.04 and 0.05 times as active as prostacyclin following intravenous infusion in the rabbit dog and monkey respectively. In the rabbit, BW245C was a highly selective platelet inhibitor with minimal cardiovascular actions, whereas in the dog and monkey, BW245C lowered BP in anti-aggregating doses. The potent platelet anti-aggregating actions of BW245C following parenteral or oral administration makes this hydantoin a potentially-useful anti-thrombotic prostaglandin analogue.     

Enantioselective synthesis of amines via reductive amination with a dehydrogenase mutant from Exigobacterium sibiricum: Substrate scope,co-solvent tolerance and biocatalyst immobilization

In recent years, the reductive amination of ketones in the presence of amine dehydrogenases emerged as an attractive synthetic strategy for the enantioselective preparation of amines starting from ketones, an ammonia source, a reducing reagent and a cofactor, which is recycled in situ by means of a second enzyme. Current challenges in this field consists of providing a broad synthetic platform as well as process development including enzyme immobilization. In this contribution these issues are addressed. Utilizing the amine dehydrogenase EsLeuDH-DM as a mutant of the leucine dehydrogenase from Exigobacterium sibiricum, a range of aryl-substituted ketones were tested as substrates revealing a broad substrate tolerance. Kinetics as well as inhibition effects were also studied and the suitability of this method for synthetic purpose was demonstrated with acetophenone as a model substrate. Even at an elevated substrate concentration of 50?mM, excellent conversion was achieved. In addition, the impact of water-miscible co-solvents was examined, and good activities were found when using DMSO of up to 30% (v/v). Furthermore, a successful immobilization of the EsLeuDH-DM was demonstrated utilizing a hydrophobic support and a support for covalent binding, respectively, as a carrier.     

How stem cells age and why this makes us grow old

Recent data suggest that we age, in part, because our self-renewing stem cells grow old as a result of heritable intrinsic events, such as DNA damage, as well as extrinsic forces, such as changes in their supporting niches. Mechanisms that suppress the development of cancer, such as senescence and apoptosis, which rely on telomere shortening and the activities of p53 and p16(INK4a), may also induce an unwanted consequence: a decline in the replicative function of certain stem-cell types with advancing age. This decreased regenerative capacity appears to contribute to some aspects of mammalian ageing, with new findings pointing to a 'stem-cell hypothesis' for human age-associated conditions such as frailty, atherosclerosis and type 2 diabetes.     

Pyrroloquinoline-quinone and its versatile roles in biological processes

Pyrroloquinoline-quinine (PQQ) was initially characterized as a redox cofactor for membrane-bound dehydrogenases in the bacterial system. Subsequently, PQQ was shown to be an antioxidant protecting the living cells from oxidative damage in vivo and the biomolecules from artificially produced reaction oxygen species in vitro. The presence of PQQ has been documented from different biological samples. It functions as a nutrient and vitamin for supporting the growth and protection of living cells under stress. Recently, the role of PQQ has also been shown as a bio-control agent for plant fungal pathogens, an inducer for proteins kinases involved in cellular differentiation of mammalian cells and as a redox sensor leading to development of biosensor. Recent reviews published on PQQ and enzymes requiring this cofactor have brought forth the case specific roles of PQQ. This review covers the comprehensive information on various aspects of PQQ known till date. These include the roles of PQQ in the regulation of cellular growth and differentiation in mammalian system, as a nutrient and vitamin in stress tolerance, in crop productivity through increasing the availability of insoluble phosphate and as a bio-control agent, and as a redox agent leading to the biosensor development. Most recent findings correlating the exceptionally high redox recycling ability of PQQ to its potential as anti-neurodegenerative, anticancer and pharmacological agents, and as a signalling molecule have been distinctly brought out. This review discusses different findings suggesting the versatility in PQQ functions and provides the most plausible intellectual basis to the ubiquitous roles of this compound in a large number of biological processes, as a nutrient and a perspective vitamin.     

Chufa (Cyperus esculentus L. var. sativus boeck.): An unconventional crop. studies related to applications and cultivation

Tubers ofCyperus esculentuswere an important food in ancient Egypt. In Spain the tubers are used to make a beverage named horchata, and are also consumed as fresh after soaking. In other countries tubers are used in sweetmeats or uncooked as a side dish. New products obtained can enhance the interest in this crop: as a source of dietary fiber in food technology; as a high quality cooking/salad oil or as biodiesel fuel; as caramel to add body, flavor or color to other products; as a source of starch; as an antioxidant-containing food, etc. The results of a twenty-year research program on nutrition, fertilization, lodging control, planting date, soil texture and use of herbicides are shown. Three cultivars (‘Ametlla Bonrepos’, ‘Gegant Africana’, and ‘Llargueta Alboraia’) are selected and characterized using horticultural and morphological traits, the chemical composition of tubers and horchatas, and the RAPD technique.     

Lanthanum as an electron microscopic stain

Applications of lanthanum as an electron microscopic tracer have been reviewed. This electron-dense trivalent cation, which binds avidly to calcium binding sites, can be used as tracer for delineating extracellular spaces and intercellular junctions. It has served as a basis for classification of junctional structures. It can also be used as a calcium probe, a tracer in studying the permeability of barriers, as an intracellular marker and as an electron microscopic stain for such membrane components as surface glycoprotein. Each of these applications may require a different methodology. Thus methodological considerations in the use of this tracer have also been reviewed. The recent recognition that lanthanum is more than a passive tracer and that by reacting with different cell components may serve as a true stain, will extend the use of lanthanum in electron microscope histochemistry.     

FSI analysis of a human trachea before and after prosthesis implantation

In this work we analyzed the response of a stenotic trachea after a stent implantation. An endotracheal stent is the common treatment for tracheal diseases such as stenosis, chronic cough, or dispnoea episodes. Medical treatment and surgical techniques are still challenging due to the difficulties in overcoming potential complications after prosthesis implantation. A finite element model of a diseased and stented trachea was developed starting from a patient specific computerized tomography (CT) scan. The tracheal wall was modeled as a fiber reinforced hyperelastic material in which we modeled the anisotropy due to the orientation of the collagen fibers. Deformations of the tracheal cartilage rings and of the muscular membrane, as well as the maximum principal stresses, are analyzed using a fluid solid interaction (FSI) approach. For this reason, as boundary conditions, impedance-based pressure waveforms were computed modeling the nonreconstructed vessels as a binary fractal network. The results showed that the presence of the stent prevents tracheal muscle deflections and indicated a local recirculatory flow on the stent top surface which may play a role in the process of mucous accumulation. The present work gives new insight into clinical procedures, predicting their mechanical consequences. This tool could be used in the future as preoperative planning software to help the thoracic surgeons in deciding the optimal prosthesis type as well as its size and positioning.     

Immunocytochemical localization of serotonin in embryos, larvae and adults of the lancelet, Branchiostoma floridae

Serotonin (5-hydroxytryptamine) is a biogenic amine distributed throughout the metazoans and has an old evolutionary history. It is involved as a developmental signal in the early morphogenesis of both invertebrates and vertebrates, whereas in adults it acts mainly as a neurotransmitter and gastrointestinal hormone. In vertebrates, serotonin regulates the morphogenesis of the central nervous system and the specification of serotonergic as well as dopaminergic neurons. The present study uses, as an experimental model, an invertebrate chordate, the lancelet Branchiostoma floridae, characterized by its remarkable homologies with vertebrates that allows the 'bauplan' of the probable ancestor of vertebrates to be outlined. In particular, the involvement of serotonin as a developmental signal in embryos and larvae, as well as a neurotransmitter and gastrointestinal hormone in adult specimens of Branchiostoma floridae, gives further support to a common origin of cephalocordates and vertebrates.