bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise and Osteoarthritis: Cause and Effects
Authors: Bennell Kim , Hinman Rana S. , Wrigley Tim V. , Creaby Mark W. , Hodges Paul 
Published: September 2011

AbstractOsteoarthritis (OA) is a common chronic joint condition predominantly affecting the knee, hip, and hand joints. Exercise plays a role in the development and treatment of OA but most of the literature in this area relates to knee OA. While studies indicate that exercise and physical activity have a generally positive effect on healthy cartilage metrics, depending upon the type of the activity and its intensity, the risk of OA development does appear to be moderately increased with sporting participation. In particular, joint injury associated with sports participation may be largely responsible for this increased risk of OA with sport. Various repetitive occupational tasks are also linked to greater likelihood of OA development. There are a number of physical impairments associated with OA including pain, muscle weakness and altered muscle function, reduced proprioception and postural control, joint instability, restricted range of motion, and lower aerobic fitness. These can result directly from the OA pathological process and/or indirectly as a result of factors such as pain, effusion, and reduced activity levels. These impairments and their underlying physiology are often targeted by exercise interventions and evidence generally shows that many of these can be modified by specific exercise. There is currently little clinical trial evidence to show that exercise can alter mechanical load and structural disease progression in those with established OA, although a number of impairments, that are amenable to change with exercise, appears to be associated with increased mechanical load and/or disease progression in longitudinal studies. © 2011 American Physiological Society.Compr Physiol1:1943‐2008, 2011.
Clinical and Molecular Genetic Features of Hereditary Pulmonary Arterial Hypertension
Authors: Brenner Laura , Chung Wendy K. 
Published: September 2011

AbstractPulmonary arterial hypertension (PAH) is a rare disorder that may be hereditary (HPAH), idiopathic (IPAH), or associated with either drug‐toxin exposures or other medical conditions. Familial cases have long been recognised and are usually due to mutations in the bone morphogenetic protein receptor type 2 gene (BMPR2), or, much less commonly, two other members of the transforming growth factor‐β superfamily, activin‐like kinase‐type 1 (ALK1), and endoglin (ENG), which are associated with hereditary hemorrhagic telangiectasia. In addition, approximately 20% of patients with IPAH carry mutations inBMPR2. Clinical testing forBMPR2mutations is available and may be offered to HPAH and IPAH patients but should be preceded by genetic counselling, since lifetime penetrance is only 10% to 20%, and there are currently no known effective preventative measures. Identification of a familial mutation can be valuable in reproductive planning and identifying family members who are not mutation carriers and thus will not require lifelong surveillance. With advances in genomic technology and with international collaborative efforts, genome‐wide association studies will be conducted to identify additional genes for HPAH, genetic modifiers forBMPR2penetrance, and genetic susceptibility to IPAH. In addition, collaborative studies ofBMPR2mutation carriers should enable identification of environmental modifiers, biomarkers for disease development and progression, and surrogate markers for efficacy end points in clinical drug development, thereby providing an invaluable resource for trials of PAH prevention. © 2011 American Physiological Society.Compr Physiol1:1721‐1728, 2011.
Exercise Physiology of Normal Development, Sex Differences, and Aging
Authors: Harms Craig A. , Cooper Dan , Tanaka Hirofumi 
Published: September 2011

AbstractThe scientific study of human development has evolved from studies of children to studies of the full lifespan. Many physiological changes occur throughout the lifespan and unique changes occur during normal development compared to healthy aging. An enlarging body of data supports the idea that there exist critical periods of development during which physiological perturbations to the internal milieu (e.g., disease or physical activity) can alter the overall programming of developmental processes. Although different physiological functions decline with age with widely varying rates, the aging changes accumulated throughout the physiological systems reduce the capacity to cope with the stress and maintain homeostasis. The understanding of this process of development and aging is complicated by important physiologic sex differences with regard to nearly all physiological systems. Regular physical activity can favorably modulate this developmental and aging process and can have important health benefits. However, a physically inactive lifestyle can markedly impair normal development and lead to numerous diseases. Life‐long physical activity is essential for preserving or delaying the onset of functional disability and chronic cardiovascular and metabolic diseases. © 2011 American Physiological Society.Compr Physiol1:1649‐1678, 2011.
Erythropoietin
Authors: Wenger Roland H. , Kurtz Armin 
Published: September 2011

AbstractThe hormone erythropoietin (Epo) is the main humoral regulator of erythropoiesis. It binds to specific receptors belonging to the cytokine receptor superfamily. Epo stimulates proliferation and differentiation of erythroid precursor cells, but may also bind to and exert some additional effects in nonhemopoietic tissues. It is mainly produced in the kidneys and to minor extents also in the liver and in the brain. The plasma concentration of erthyropoietin is inversely related to the oxygen content of the blood. The secretion of Epo into the circulation and hence its plasma concentrations are mainly determined by the transcription rate of the Epo gene, which itself is essentially under control of the cellular oxygen concentration. Sinks of the oxygen concentrations increase the activity of the hypoxia‐inducible transcription factor (HIF), which in turn triggers Epo gene transcription. Disorders of kidney function lead to inappropriate Epo production, what may result in anemia or polycythemia. © 2011 American Physiological Society.Compr Physiol1:1759‐1794, 2011.
Insights into Biomedicine from Animal Adaptations
Authors: Singer Michael A. 
Published: September 2011

AbstractEvolution represents a natural experimental process for testing animal design features. Driven by environmental pressures, animals have evolved adaptations which can give valuable insights into human biomedical conditions. The giraffe by virtue of its extremely long neck has a mean arterial pressure much higher than other mammals. However, the giraffe does not develop vascular damage or heart failure despite its high mean arterial pressure. The giraffe's cardiovascular physiology challenges a number of current concepts concerning the genesis of hypertensive vascular damage in the human. All animals senesce, and, in general, the manifestations of this senescence are similar to the aging features observed in humans. The characteristics of aging in natural animals strongly suggest that the so‐called chronic degenerative diseases of humans are not really diseases but actually manifestations of the aging phenotype. Glucose regulation in birds and the naked mole rat has features which mimic the characteristics of the diabetic state, yet these animals do not develop the complications occurring in humans with diabetes. Disruptions in the functioning of the circadian molecular clock are thought to underlie certain neuropsychiatric disorders. The honeybee and the zebrafish have emerged as natural animal models for studying the regulation of molecular clocks and the mechanisms underlying plasticity of circadian rhythms. These examples underscore the valuable insights that natural animals can furnish with respect to biomedical disorders. Yet, this information data base remains a largely untapped resource. © 2011 American Physiological Society.Compr Physiol1:2063‐2081, 2011.
Renal Transport of Organic Anions and Cations
Authors: Pelis Ryan M. , Wright Stephen H. 
Published: September 2011

AbstractOrganic anions and cations (OAs and OCs, respectively) comprise an extraordinarily diverse array of compounds of physiological, pharmacological, and toxicological importance. The kidney, primarily the renal proximal tubule, plays a critical role in regulating the plasma concentrations of these organic electrolytes and in clearing the body of potentially toxic xenobiotics agents, a process that involves active, transepithelial secretion. This transepithelial transport involves separate entry and exit steps at the basolateral and luminal aspects of renal tubular cells. Basolateral and luminal OA and OC transport reflects the concerted activity of a suite of separate proteins arranged in parallel in each pole of proximal tubule cells. The cloning of multiple members of several distinct transport families, the subsequent characterization of their activity, and their subcellular localization within distinct regions of the kidney, now allows the development of models describing the molecular basis of the renal secretion of OAs and OCs. New information on naturally occurring genetic variation of many of these processes provides insight into the basis of observed variability of drug efficacy and unwanted drug‐drug interactions in human populations. The present review examines recent work on these issues. © 2011 American Physiological Society.Compr Physiol1:1795‐1835, 2011.
Mechanisms of Muscle Injury, Repair, and Regeneration
Authors: Tidball James G. 
Published: September 2011

AbstractSkeletal muscle continuously adapts to changes in its mechanical environment through modifications in gene expression and protein stability that affect its physiological function and mass. However, mechanical stresses commonly exceed the parameters that induce adaptations, producing instead acute injury. Furthermore, the relatively superficial location of many muscles in the body leaves them further vulnerable to acute injuries by exposure to extreme temperatures, contusions, lacerations or toxins. In this article, the molecular, cellular, and mechanical factors that underlie muscle injury and the capacity of muscle to repair and regenerate are presented. Evidence shows that muscle injuries that are caused by eccentric contractions result from direct mechanical damage to myofibrils. However, muscle pathology following other acute injuries is largely attributable to damage to the muscle cell membrane. Many feaures in the injury‐repair‐regeneration cascade relate to the unregulated influx of calcium through membrane lesions, including: (i) activation of proteases and hydrolases that contribute muscle damage, (ii) activation of enzymes that drive the production of mitogens and motogens for muscle and immune cells involved in injury and repair, and (iii) enabling protein‐protein interactions that promote membrane repair. Evidence is also presented to show that the myogenic program that is activated by acute muscle injury and the inflammatory process that follows are highly coordinated, with myeloid cells playing a central role in modulating repair and regeneration. The early‐invading, proinflammatory M1 macrophages remove debris caused by injury and express Th1 cytokines that play key roles in regulating the proliferation, migration, and differentiation of satellite cells. The subsequent invasion by anti‐inflammatory, M2 macrophages promotes tissue repair and attenuates inflammation. Although this system provides an effective mechanism for muscle repair and regeneration following acute injury, it is dysregulated in chronic injuries. In this article, the process of muscle injury, repair and regeneration that occurs in muscular dystrophy is used as an example of chronic muscle injury, to highlight similarities and differences between the injury and repair processes that occur in acutely and chronically injured muscle. © 2011 American Physiological Society.Compr Physiol1:2029‐2062, 2011.
Ca2+‐Activated Cl−Channels
Authors: Ferrera Loretta , Zegarra‐Moran Olga , Galietta Luis J.V. 
Published: September 2011

AbstractCa2+‐activated Cl−channels (CaCCs) are plasma membrane proteins involved in various important physiological processes. In epithelial cells, CaCC activity mediates the secretion of Cl−and of other anions, such as bicarbonate and thiocyanate. In smooth muscle and excitable cells of the nervous system, CaCCs have an excitatory role coupling intracellular Ca2+elevation to membrane depolarization. Recent studies indicate that TMEM16A (transmembrane protein 16 A or anoctamin 1) and TMEM16B (transmembrane protein 16 B or anoctamin 2) are CaCC‐forming proteins. Induced expression of TMEM16A and B in null cells by transfection causes the appearance of Ca2+‐activated Cl−currents similar to those described in native tissues. Furthermore, silencing of TMEM16A by RNAi causes disappearance of CaCC activity in cells from airway epithelium, biliary ducts, salivary glands, and blood vessel smooth muscle. Mice devoid of TMEM16A expression have impaired Ca2+‐dependent Cl−secretion in the epithelial cells of the airways, intestine, and salivary glands. These animals also show a loss of gastrointestinal motility, a finding consistent with an important function of TMEM16A in the electrical activity of gut pacemaker cells, that is, the interstitial cells of Cajal. Identification of TMEM16 proteins will help to elucidate the molecular basis of Cl−transport. © 2011 American Physiological Society.Compr Physiol1:2155‐2174, 2011.
Women Entering Clinical Psychology: Q‐Sort Narratives of Career Attraction of Female Clinical Psychology Trainees in the UK
Authors: Baker Martyn , Nash Jen 
Published: September 2011

The great majority of the UK clinical psychology workforce are women, and this fact prompted an examination of the various ways clinical psychology might be seen as attractive to women—a neglected research topic. Female clinical psychology trainees from a variety of training programmes Q‐sorted statements of potential job attractors. The process of analysis is outlined before most of the article is devoted to explicating the five narratives of attraction generated: making a difference, waiting for what I want, idealising challenge, identifying with distress and acknowledging power and privilege. Two super‐ordinate ‘stories’ spanning the narratives are suggested—an over‐riding attraction to the profession and a rebuttal of the suggestion that this attraction may be based on any overtly gendered grounds. In the absence of previous empirical data of women's attraction to clinical psychology, the small but significant contribution to understanding the profession made by the analysis is acknowledged—as is the need for further research to confirm and develop the findings. Copyright © 2011 John Wiley & Sons, Ltd.Key Practitioner MessageAppreciating how female trainee psychologists rate job incentives is a further step towards greater knowledge of workforce attractors.There is a general narrative of job attraction to clinical psychology and other more specific ones, where clear attractors for some trainees are equally clear disincentives for others.Although data from broader samples of colleagues are required, the findings have implications for more targeted clinical psychology recruitment, at both pre‐qualification and post‐qualification levels.The findings also have agency as a stimulus for self‐reflection.
Epidemiological investigation of the UGT2B17 polymorphism in doping control urine samples and its correlation to T/E ratios
Authors: Anielski Patricia , Simmchen Juliane , Wassill Lars , Ganghofner Dirk , Thieme Detlef 
Published: September 2011

ABSTRACTThe deletion polymorphism of the enzyme UGT2B17 is known to correlate with the level of the testosterone to epitestosterone (T/E) ratio in urine specimen. Due to the importance of the T/E ratio to detect testosterone abuse in doping analysis, a PCR‐ELISA system (Genotype® UGT test, AmplexDiagnostics) was established to identify the UGT2B17 phenotype in urine samples. Epidemiological investigations in a set of 674 routine doping controls (in‐ and out‐of‐competition) resulted in 22.8% homozygote gene‐deleted and 74.5% UGT2B17‐positive athletes. The validated test system has shown to be robust and sensitive: in only 18 cases (2.7%) isolation of cell material from urine failed.Following hydrolysis of glucuronidated conjugates, steroids were analyzed as bis‐TMS derivatives by gas chromatography‐mass spectrometry (GC‐MS), for example, testosterone (T) and epitestosterone (E). Additionally, isotope ration mass spectrometry (IRMS) analysis and luteinizing hormone (LH) measurement were applied. Mean T/E ratios significantly correlated with the UGT2B17 phenotype (del: T/E 0.9; pos: 1.7), however the values did not differ as distinctive as reported in previous studies. Additionally, the T/E ratios in the gene‐deleted group did not show a normal curve of distribution (median of T/E 0.5). Obviously, beside the UGT2B17 deletion further influences have to be taken into account, for example, polymorphisms or induction of other metabolizing enzymes. Our results indicate that the UGT2B17 polymorphism might be insufficient when utilized solely as a crucial parameter for individual interpretation of T/E in urine. Nevertheless, the detection of the UGT2B17‐gene deletion in urine samples would provide additional information important for gathering evidence in analysis of steroids in doping control. Copyright © 2011 John Wiley & Sons, Ltd.
Spatial‐genetic structuring in a red‐breasted merganser (Mergus serrator) colony in the Canadian Maritimes
Authors: Fishman David J. , Craik Shawn R. , Zadworny David , Titman Rodger D. 
Published: September 2011

AbstractThe clustering of kin is widespread across the animal kingdom and two of the primary mechanisms underlying the formation of these patterns in adult kin are (1) philopatric tendencies and (2) actively maintained kin associations. Using polymorphic microsatellites, we had set out to characterize the level of genetic‐spatial organization within a colony of female red‐breasted mergansers (Mergus serrator) breeding on a series of small barrier islands in Kouchibouguac National Park, NB, Canada. Additionally, using nesting data from this colony, we explored possibilities for the existence of kin associations and/or cooperative interactions between these individuals; specifically in the form of the synchronization of breeding activities (i.e., incubation initiation). Our results include: (1) the detection of broad‐scale genetic structuring over the entire colony, as females nesting on separate islands were to some extent genetically distinct; (2) the detection of weak, yet significant, positive spatial autocorrelation of kin at the fine scale, but only in the more densely‐populated areas of this colony; and (3) the synchrony of breeding activities among proximally nesting females, apart from any factors of relatedness. While these results confirm the existence of genetic‐spatial organization within this colony, the underlying mechanisms producing such a signal are inconclusive.
Lack of IL‐7 and IL‐15 signaling affects interferon‐γ production by, more than survival of, small intestinal intraepithelial memory CD8+ T cells
Authors: Isakov Dmitry , Dzutsev Amiran , Berzofsky Jay A. , Belyakov Igor M. 
Published: September 2011

AbstractSurvival of antigen‐specific CD8+ T cells in peripheral lymphoid organs during viral infection is known to be dependent predominantly on IL‐7 and IL‐15. However, little is known about a possible influence of tissue environmental factors on this process. To address this question, we studied survival of memory antigen‐specific CD8+ T cells in the small intestine. Here, we show that 2 months after vaccinia virus infection, B8R20–27/H2‐Kb tetramer+ CD8+ T cells in the small intestinal intraepithelial (SI‐IEL) layer are found in mice deficient in IL‐15 expression. Moreover, SI‐IEL and lamina propria lymphocytes do not express the receptor for IL‐7 (IL‐7Rα/CD127). In addition, after in vitro stimulation with B8R20–27 peptide, SI‐IEL cells do not produce high amounts of IFN‐γ neither at 5 days nor at 2 months postinfection (p.i.). Importantly, the lack of IL‐15 was found to shape the functional activity of antigen‐specific CD8+ T cells, by narrowing the CTL avidity repertoire. Taken together, these results reveal that survival factors, as well as the functional activity, of antigen‐specific CD8+ T cells in the SI‐IEL compartments may markedly differ from their counterparts in peripheral lymphoid tissues.
Similar inflammatory DC maturation signatures induced by TNF or Trypanosoma brucei antigens instruct default Th2‐cell responses
Authors: Pletinckx Katrien , Stijlemans Benoit , Pavlovic Vladimir , Laube Regina , Brandl Carolin , Kneitz Susanne , Beschin Alain , De Baetselier Patrick , Lutz Manfred B. 
Published: September 2011

AbstractDCs represent the major cell type leading to polarized T‐helper (Th) cell responses in vivo. Here, we asked whether the instruction of murine Th2 responses by DCs matured with the proinflammatory cytokine TNF is qualitatively different from maturation by different types of TLR4/MyD88‐dependent variant‐specific surface glycoproteins (VSGs) of Trypanosoma brucei (T. brucei). The results obtained by analyzing DC surface markers, Notch ligand mRNA, cytokines, asthma, and experimental autoimmune encephalomyelitis (EAE) models as well as performing microarrays indicate that both types of stimuli induce similar inflammatory, semi‐mature DC profiles. DCs matured by TNF or VSG treatment expressed a common inflammatory signature of 24 genes correlating with their Th2‐polarization capacity. However, the same 24 genes and 4498 additional genes were expressed by DCs treated with LPS that went on to induce Th1 cells. These findings support the concept of a default pathway for Th2‐cell induction in DCs matured under suboptimal or inflammatory conditions, independent of the surface receptors and signaling pathways involved. Our data also indicate that quantitative differences in DC maturation might direct Th2‐ vs Th1‐cell responses, since suboptimally matured inflammatory DCs induce default Th2‐cell maturation, whereas fully mature DCs induce Th1‐cell maturation.
Elevated BCR signaling and decreased survival of Lyn‐deficient transitional and follicular B cells
Authors: Gross Andrew J. , Proekt Irina , DeFranco Anthony L. 
Published: September 2011

AbstractThe Src‐family tyrosine kinase Lyn negatively regulates BCR signaling and also myeloid cell activity. Mice deficient in Lyn have substantially decreased numbers of peripheral B cells, despite spontaneously producing IgG anti‐DNA antibodies. Here, we examine the mechanism underlying the B‐cell depletion in these mice. Lyn‐deficient B cells were out‐competed by WT B cells in mixed BM chimeras at two steps, at the T1 to T2 transitional maturation stage in the spleen and again between the T2 or T3 stage and the mature follicular B‐cell population. Lyn‐deficient T2 and follicular B cells expressed elevated levels of the pro‐apoptotic factor Bim and deletion of Bim restored splenic B cells of Lyn‐deficient mice to close to WT numbers. Lyn‐deficient T2 and later stage B cells also had changes in cell surface phenotype consistent with increased in vivo BCR signaling. Similarly, an increased proportion of T2 and follicular B cells had elevated basal intracellular free calcium levels. Overall, these observations suggest that increased BCR signaling is responsible for increased death of weakly self‐reactive Lyn‐deficient B cells both at the T2 stage and additionally as these cells mature to follicular B cells.