bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Buchwald Reaction as the Key Step for the Synthesis of Metabolically More Stable Analogues of Amodiaquine.
Authors: Le Fur Nicolas , Hochart Guillaume , Larchanche Paul‐Emmanuel , Melnyk Patricia
Published: September 2011

Target compounds (IX) are synthesized via key intermediates (VI) using a super‐electrophilic amidomethylation, cf.
ChemInform Abstract: Synthesis and Antibacterial Activity of Isochromene and Isoquinoline Derivative.
Authors: Dabholkar Vijay V. , Tripathi Dilip R.
Published: September 2011

Novel thiazolylisochromene derivative (VII) is synthesized by reaction of benzoic acid (V) with benzoin, and transformed into corresponding isoquinoline derivatives (IX).
ChemInform Abstract: Synthesis and Anticonvulsant Activity of 7‐Phenyl‐6,7‐dihydro‐[1,2,4]triazolo[1,5‐a]pyrimidin‐5(4H)‐ones and their Derivatives.
Authors: Deng Xian‐Qing , Quan Li‐Na , Song Ming‐Xia , Wei Cheng‐Xi , Quan Zhe‐Shan
Published: September 2011

Cyclization of methyl cinnamates (I) with triazolamine (II), pyrazolamine (VI), aminoimidazole (VIII), and benzoimidazolamine (X), affords the corresponding fused compounds in low to sufficient yields.
ChemInform Abstract: Synthesis and Structure of Novel (S)‐1,6‐Dialkylpiperazine‐2,5‐diones and (3S,6S)‐1,3,6‐Trialkylpiperazine‐2,5‐diones.
Authors: Malavasic Crt , Groselj Uros , Golobic Amalija , Bezensek Jure , Stanovnik Branko , Stare Katarina , Wagger Jernej , Svete Jurij
Published: September 2011

The dialkylpiperazines are prepared from α‐amino acid ester hydrochlorides in three steps.
ChemInform Abstract: Synthesis, Characterization, and Biological Activity of Some Aza‐Uracil Derivatives.
Authors: El‐Barbary Ahmed Ahmed , Hafiz Yehia Ahmed , Abdel‐Wahed Mohamed Shaker
Published: September 2011

The title compounds are screened for their in vitro antibacterial activities against Gram positive bacteria (B.
ChemInform Abstract: Highly Selective Methods for Synthesis of Internal (α‐) Vinylboronates Through Efficient NHC—Cu‐Catalyzed Hydroboration of Terminal Alkynes. Utility in Chemical Synthesis and Mechanistic Basis for Selectivity.
Authors: Jang Hwanjong , Zhugralin Adil R. , Lee Yunmi , Hoveyda Amir H.
Published: September 2011

Terminal aliphatic or aromatic alkynes can easily undergo hydroboration in the presence of NHC—Cu complexes.
ChemInform Abstract: Synthesis of Conformationally Modified Peptides Through Isonitrile Chemistry: Implications for Dealing with Polypeptide Aggregation.
Authors: Wu Xiangyang , Park Peter K. , Danishefsky Samuel J.
Published: September 2011

A method is presented for the introduction of a dimethyleneoxy bridge spanning the amide functionalities of two consecutive amino acids such as shown for (VII).
ChemInform Abstract: Synthetic Studies on Natural Products. Part 39. Total Synthesis of Racemic and (R)‐ and (S)‐4‐Methoxyalkanoic Acids and Their Antifungal Activity.
Authors: Das Biswanath , Shinde Digambar Balaji , Kanth Boddu Shashi , Kamle Avijeet , Kumar C. Ganesh
Published: September 2011

Methoxydecanoic acid (VIIa) and methoxyundecanoic acid (VIIb) are synthesized both in racemic and stereoselective form.
ChemInform Abstract: Synthesis and Evaluation of Monoamidoxime Derivatives: Toward New Antileishmanial Compounds.
Authors: Paloque Lucie , Bouhlel Ahlem , Curti Christophe , Dumetre Aurelien , Verhaeghe Pierre , Azas Nadine , Vanelle Patrice
Published: September 2011

Performing manganese(III)‐ and microwave‐assisted reactions enable the synthesis of a new series of monoamidoximes.
ChemInform Abstract: Advanced Electron Microscopy of Metal‐Support Interactions in Supported Metal Catalysts
Authors: Liu Jingyue
Published: September 2011

Review: 219 refs.
ChemInform Abstract: Recent Advances in the Chemistry of Group 4 Metal Complexes Incorporating [OSSO]‐Type Bis(phenolato) Ligands as Post‐Metallocene Catalysts
Authors: Nakata Norio , Toda Tomoyuki , Ishii Akihiko
Published: September 2011

Review: 50 refs.
ChemInform Abstract: Development of Macrocyclic Polyoxazoles and Evaluation of Their G‐Quadruplex Stabilizing Activities
Authors: Tera Masayuki , Iida Keisuke , Shin‐ya Kazuo , Nagasawa Kazuo
Published: September 2011

Review: ca. 50 refs.
ChemInform Abstract: Synthesis of Annonaceous Acetogenins and Their Inhibitory Action with Mitochondrial Complex I
Authors: Hattori Yasunao , Konno Hiroyuki , Miyoshi Hideto , Makabe Hidefumi
Published: September 2011

Review: 55 refs.
ChemInform Abstract: Geometrical and Electronic Rules in Fullerene‐Based Compounds
Authors: Gan Li‐Hua , An Jie , Pan Fu‐Sheng , Chang Qing , Liu Zuo‐Hua , Tao Chang‐Yuan
Published: September 2011

Review: 77 refs.
ChemInform Abstract: Aza‐Michael Reaction: Achievements and Prospects
Authors: Rulev A. Yu.
Published: September 2011

Review: 269 refs.
ChemInform Abstract: Organic Nanoparticles
Authors: Utekhina A. Yu. , Sergeev G. B.
Published: September 2011

Review: 130 refs.
ChemInform Abstract: Rh‐Catalyzed Hydroacylation Reaction: Development from Intramolecular Reaction into Intermolecular Reaction
Authors: Imai Masanori , Suemune Hiroshi , Tanaka Masakazu
Published: September 2011

Review: about 50 refs.
ChemInform Abstract: Metathesis in Total Synthesis
Authors: Fuerstner Alois
Published: September 2011

Review: 58 refs.
ChemInform Abstract: Heterocycles from Gold Catalysis
Authors: Rudolph Matthias , Hashmi A. Stephen K.
Published: September 2011

Review: 41 refs.
ChemInform Abstract: Reactions of Anodic and Chemical Aromatic Substitution
Authors: Petrosyan Vladimir A.
Published: September 2011

Review: 53 refs.
ChemInform Abstract: The Importance of Developing Metal Complexes with Pronounced Catalase‐Like Activity.
Authors: Mahammed Atif , Gross Zeev
Published: September 2011

Review: 56 refs.
ChemInform Abstract: Search for Antidiabetic Constituents of Medicinal Food
Authors: Nakamura Seikuo , Matsuda Hisashi , Yoshikawa Masayuki
Published: September 2011

Review: 32 refs.
ChemInform Abstract: Sasa quelpaertensis Phenylpropanoid Derivative Suppresses Lipopolysaccharide‐Induced Nitric Oxide Synthase and Cyclo‐oxygenase‐2 Expressions in RAW 264.7 Cells
Authors: Moon Ji‐Young , Yang Eun‐Jin , Kim Sang Suk , Kang Ji‐Yong , Kim Gi‐Ok , Lee Nam Ho , Hyun Chang‐Gu
Published: September 2011

Review: 32 refs.
ChemInform Abstract: Solubility Enhancement Techniques
Authors: Vemula Varun Raj , Lagishetty Venkateshwarlu , Lingala Srikanth
Published: September 2011

Review: 100 refs.
ChemInform Abstract: Superparamagnetism and Monte Carlo Simulations
Authors: Serantes D. , Baldomir D.
Published: September 2011

Review: 41 refs.
ChemInform Abstract: Benzene and Heterocyclic Rings Formation in Cycloaddition Reactions Catalyzed by RuCp Derivatives: DFT Studies
Authors: Calhorda Maria Jose , Costa Paulo J. , Kirchner Karl A.
Published: September 2011

Review: 77 refs.
ChemInform Abstract: The Use of Molecularly Imprinted Polymers for Sampling and Sample Preparation
Authors: Sellergren Boerje , Esteban Antonio Martin
Published: September 2011

Review: 238 refs.
ChemInform Abstract: Chromatographic NMR
Authors: Caldarelli Stefano
Published: September 2011

Review: 52 refs.
Analysis of energy dissipation in stirred suspension polymerisation reactors using computational fluid dynamics
Authors: Nogueira E. S. , Pinto J. C. , Vianna A. S.
Published: September 2011

This work evaluates the spatial distribution of normalised rates of droplet breakage and droplet coalescence in liquid–liquid dispersions maintained in agitated tanks at operation conditions normally used to perform suspension polymerisation reactions. Particularly, simulations are performed with multiphase computational fluid dynamics (CFD) models to represent the flow field in liquid–liquid styrene suspension polymerisation reactors for the first time. CFD tools are used first to compute the spatial distribution of the turbulent energy dissipation rates (ε) inside the reaction vessel; afterwards, normalised rates of droplet breakage and particle coalescence are computed as functions of ε. Surprisingly, multiphase simulations showed that the rates of energy dissipation can be very high near the free vortex surfaces, which has been completely neglected in previous works. The obtained results indicate the existence of extremely large energy dissipation gradients inside the vessel, so that particle breakage occurs primarily in very small regions that surround the impeller and the free vortex surface, while particle coalescence takes place in the liquid bulk. As a consequence, particle breakage should be regarded as an independent source term or a boundary phenomenon. Based on the obtained results, it can be very difficult to justify the use of isotropic assumptions to formulate particle population balances in similar systems, even when multiple compartment models are used to describe the fluid dynamic behaviour of the agitated vessel. © 2011 Canadian Society for Chemical Engineering
Impact of residual normal metaphases in core binding factor acute myeloid leukemia
Authors: Medeiros Bruno C. , Othus Megan , Fang Min , Appelbaum Frederick R. , Estey Elihu H.
Published: September 2011

BACKGROUND:

Karyotype allows for stratification of outcomes in acute myeloid leukemia (AML) patients. Previous data suggested that the presence of residual normal cells improved the prognosis in patients with monosomy 7. The Southwest Oncology Group (SWOG) reported the impact of residual normal metaphases in AML patients with monosomal karyotype (MK) and found a similar relationship. We determined the influence of residual normal metaphases in patients with core binding factor (CBF) AML.

METHODS:

The presence and total number of normal and abnormal metaphases were tallied for patients with CBF AML treated in 10 consecutive SWOG trials and used as a variable to determine the effect on complete remission, refractory disease, and overall survival (OS) rates.

RESULTS:

Among 113 CBF AML patients, median age of diagnosis was 45 years (range, 18‐77 years), and median OS was 4 years (CI—2 years—not reached). Patients with inv(16) and no normal metaphases had improved OS compared with those with 1+ normal metaphases (P = .00005), whereas no difference was noted for patients with t(8;21). Multivariate analysis demonstrated that having cells with a normal karyotype had a negative impact on survival (HR, 2.11; 95% CI, 1.09‐4.08; P = .026). This shorter survival was a consequence of a higher rate of refractory disease in older patients (OR, 1.03; 95% CI, 0.9998‐1.06; P = .05) and in those with normal metaphases (HR, 1.26 95% CI, 1.04‐1.51; P = .02).

CONCLUSIONS:

In patients with CBF AML, the presence of cells with normal metaphases and increasing age negatively affect the prognosis, especially in patients with inv(16). Cancer 2012;. © 2011 American Cancer Society.
Metabolism, Temperature, and Ventilation
Authors: Mortola Jacopo P. , Maskrey Michael
Published: September 2011

In mammals and birds, all oxygen used (o2) must pass through the lungs; hence, some degree of coupling betweeno2and pulmonary ventilation (e) is highly predictable. Nevertheless,eis also involved with CO2elimination, a task that is often in conflict with the convection of O2. In hot or cold conditions, the relationship betweeneando2includes the participation of the respiratory apparatus to the control of body temperature and water balance. Some compromise among these tasks is achieved through changes in breathing pattern, uncoupling changes in alveolar ventilation frome. This article examines primarily the relationship betweeneando2under thermal stimuli. In the process, it considers how the relationship is influenced by hypoxia, hypercapnia or changes in metabolic level. The shuffling of tasks in emergency situations illustrates that the constraints one‐o2for the protection of blood gases have ample room for flexibility. However, when other priorities do not interfere with the primary goal of gas exchange,efollows metabolic rate quite closely. The fact that arterial CO2remains stable when metabolism is changed by the most diverse circumstances (moderate exercise, cold, cold and exercise combined, variations in body size, caloric intake, age, time of the day, hormones, drugs, etc.) makes it unlikely thateand metabolism are controlled in parallel by the condition responsible for the metabolic change. Rather, some observations support the view that the gaseous component of metabolic rate, probably CO2, may provide the link between the metabolic level ande. © 2011 American Physiological Society.Compr Physiol1:1679‐1709, 2011.
Expiratory Flow Limitation
Authors: Pedersen Ole F. , Butler James P.
Published: September 2011

Expiratory flow limitation occurs when flow ceases to increase with increasing expiratory effort. The equal pressure point concept has been largely successful in providing intuitive understanding of the phenomenon, wherein maximal flows are determined by lung recoil and resistance upstream of the site where bronchial transmural pressure is zero (the EPP). Subsequent work on the fluid dynamical foundations led to the wave‐speed theory of flow limitation, where flow is limited at a site when the local gas velocity is equal to speed of propagation of pressure waves. Each is a local theory; full predictions require knowledge of both density‐dependent Bernoulli pressure drops and viscosity‐dependent pressure losses due to dissipation. The former is dominant at mid to high lung volumes, whereas the latter is more important at low lung volumes as the flow‐limiting site moves peripherally. The observation of relative effort independence of the maximal flow versus volume curves is important clinically insofar as such maneuvers, when carefully performed, offer a unique window into the mechanics of the lung itself, with little confounding effects. In particular, the important contributions of lung recoil and airways resistance can often be assessed, with implications and applications to diagnosis and management of pulmonary disease. © 2011 American Physiological Society.Compr Physiol1:1861‐1882, 2011.
Neuronal Control of Breathing: Sex and Stress Hormones
Authors: Behan Mary , Kinkead Richard
Published: September 2011

There is a growing public awareness that hormones can have a significant impact on most biological systems, including the control of breathing. This review will focus on the actions of two broad classes of hormones on the neuronal control of breathing: sex hormones and stress hormones. The majority of these hormones are steroids; a striking feature is that both groups are derived from cholesterol. Stress hormones also include many peptides which are produced primarily within the paraventricular nucleus of the hypothalamus (PVN) and secreted into the brain or into the circulatory system. In this article we will first review and discuss the role of sex hormones in respiratory control throughout life, emphasizing how natural fluctuations in hormones are reflected in ventilatory metrics and how disruption of their endogenous cycle can predispose to respiratory disease. These effects may be mediated directly by sex hormone receptors or indirectly by neurotransmitter systems. Next, we will discuss the origins of hypothalamic stress hormones and their relationship with the respiratory control system. This relationship is 2‐fold: (i)viadirect anatomical connections to brainstem respiratory control centers, and (ii)viasteroid hormones released from the adrenal gland in response to signals from the pituitary gland. Finally, the impact of stress on the development of neural circuits involved in breathing is evaluated in animal models, and the consequences of early stress on respiratory health and disease is discussed. © 2011 American Physiological Society.Compr Physiol1:2101‐2139, 2011.
Inflammatory Mechanisms in the Pathogenesis of Pulmonary Arterial Hypertension
Authors: Chami Hala El , Hassoun Paul M.
Published: September 2011

Inflammation is a prominent feature of human and experimental pulmonary hypertension (PH) as suggested by infiltration of various inflammatory cells and increased expression of certain cytokines in remodeled pulmonary vessels. Macrophages, T and B lymphocytes, and dendritic cells are found in the vascular lesions of idiopathic pulmonary arterial hypertension (PAH) as well as in PAH associated with connective tissue diseases or infectious etiologies such as HIV. In addition, PAH is often characterized by the presence of circulating chemokines and cytokines, increased expression of growth (such as VEGF and PDGF) and transcriptional (e.g., nuclear factor of activated T cells or NFAT) factors, and viral protein components (e.g., HIV‐1Nef), which directly contribute to further recruitment of inflammatory cells and the pulmonary vascular remodeling process. These inflammatory pathways may thus serve as potential specific therapeutic targets. This article provides an overview of inflammatory pathways involving chemokines and cytokines as well as growth factors, highlighting their potential role in pulmonary vascular remodeling and the possibility of future targeted therapy. © 2011 American Physiological Society.Compr Physiol1:1929‐1941, 2011.
Exercise and Osteoarthritis: Cause and Effects
Authors: Bennell Kim , Hinman Rana S. , Wrigley Tim V. , Creaby Mark W. , Hodges Paul
Published: September 2011

Osteoarthritis (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

Pulmonary 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

The 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

The 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

Evolution 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

Organic 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

Skeletal 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

Ca2+‐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 Message

Appreciating 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

The 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

The 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

Survival 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

DCs 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

The 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.
HMGB1 blockade attenuates experimental autoimmune myocarditis and suppresses Th17‐cell expansion
Authors: Su Zhaoliang , Sun Caixia , Zhou Chenglin , Liu Yanfang , Zhu Haitao , Sandoghchian Siamak , Zheng Dong , Peng Tianqing , Zhang Yu , Jiao Zhijun , Wang Shengjun , Xu Huaxi
Published: September 2011

High‐mobility group box 1 (HMGB1), a non‐histone nuclear protein, has been implicated in cardiovascular diseases. Dilated cardiomyopathy (DCM), one of the leading causes of heart failure, is often caused by coxsackievirus B3‐triggered myocarditis and promoted by the post‐infectious autoimmune process. Th17 cells, a novel CD4+ T subset, may be important in the pathogenesis of autoimmune myocarditis. In the present study, we attempted to block HMGB1 function with a monoclonal antibody specific for HMGB1 B box and investigated the effects of the blockade on Th17 cells and experimental autoimmune myocarditis (EAM). After induction of EAM, HMGB1 protein levels were significantly elevated both in the heart and blood. Administration of an anti‐HMGB1 B box mAb attenuated cardiac pathological changes and reduced the number of infiltrating inflammatory cells in the heart during EAM. These protective effects of HMGB1 blockade correlated with a reduced number of Th17 cells in local tissues and lower levels of IL‐17 in the serum. Furthermore, in vitro, studies demonstrated that HMGB1 promoted Th17‐cell expansion. Therefore, we speculate that HMGB1 blockade ameliorates cardiac pathological changes in EAM by suppressing Th17 cells.
Regioselective Deprotection of Peracetylated Disaccharides at the Primary Position Catalyzed by Immobilized Acetyl Xylan Esterase from Bacillus pumilus
Authors: Bavaro Teodora , Filice Marco , Bonomi Paolo , Abu alassal Qais , Speranza Giovanna , Guisan Jose M. , Terreni Marco
Published: September 2011

In this work peracetylated lactose and related compounds have been tested as advanced intermediate substrates in enzymatic deprotections catalyzed by acetyl xylan esterase (AXE) from Bacillus pumilus. In particular, we present a simple and efficient enzymatic procedure to obtain products bearing only one free primary hydroxy group in the C6′ position of the galactoside moiety of “lacto” carbohydrates. In particular, good yields (60–70 %) have been achieved in the hydrolysis of 1‐O‐methyl lactosamine and hexaacetyl lactal. The products obtained are of great interest as advanced building blocks for the synthesis of very important oligosaccharides of biological relevance.
Hepatitis E
Authors: Aggarwal Rakesh , Jameel Shahid
Published: September 2011

Hepatitis E refers to liver disease caused by the hepatitis E virus (HEV), a small, nonenveloped virus with a single-stranded RNA genome. The virus has four genotypes, but only one serotype. Genotypes 1 and 2 exclusively infect humans, whereas genotypes 3 and 4 also infect pigs and several other mammalian species. Though HEV does not grow well in cell culture, several aspects of its biology and pathogenesis have been worked out using animal models and cell transfection studies, and by analogy with other related viruses. HEV itself appears noncytopathic, and the liver injury during hepatitis E may be mediated by the host immune response. In areas with poor sanitation, HEV infection is common and presents as outbreaks and also as sporadic cases with acute self-limited hepatitis. The transmission is feco-oral, usually through contaminated drinking water. The disease often affects young adults and is particularly severe among pregnant women and persons with preexisting liver cirrhosis. In the developed world, the disease is being increasingly recognized. It occurs as occasional sporadic cases, most often among elderly men with coexisting illnesses. These appear to be related to zoonotic transmission. Chronic infection is known among immunosuppressed persons in these regions and may progress to liver cirrhosis. Serological tests for diagnosis of HEV exposure and recent infection, namely immunoglobulin (Ig)G and IgM anti-HEV, respectively, need further improvement in sensitivity and specificity, particularly when used in developed countries. Two recombinant protein vaccines have undergone successful human trials, but are not yet commercially available. Recent development of cell-culture methods for HEV should allow a better understanding of this enigmatic agent. (Hepatology 2011)
Magnetic resonance imaging of focal liver lesions: Approach to imaging diagnosis
Authors: Fowler Kathryn J. , Brown Jeffrey J. , Narra Vamsi R.
Published: September 2011

This article is a review of magnetic resonance imaging (MRI) of incidental focal liver lesions. This review provides an overview of liver MRI protocol, diffusion-weighted imaging, and contrast agents. Additionally, the most commonly encountered benign and malignant lesions are discussed with emphasis on imaging appearance and the diagnostic performance of MRI based on a review of the literature. (Hepatology 2011)
Interleukin 28B Polymorphism Predicts Pegylated Interferon Plus Ribavirin Treatment Outcome in Chronic Hepatitis C Genotype 4
Authors: De Nicola Stella , Aghemo Alessio , Grazia Rumi Maria , Galmozzi Enrico , Valenti Luca , Soffredini Roberta , De Francesco Raffaele , Prati Gian Maria , D'Ambrosio Roberta , Cheroni Cristina , Donato Maria Francesca , Colombo Massimo
Published: September 2011

Single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) region are the strongest baseline predictors of a sustained virologic response (SVR) to peg-interferon (PegIFN) and ribavirin (Rbv) in patients with hepatitis C virus (HCV) genotype 1 infection. Whether this holds true for HCV-4 patients too is unknown. The aim was to investigate the predictive power of the rs12979860 IL28B SNP for a response to Peg-IFN and Rbv in HCV-4 patients. All HCV-4 patients consecutively treated between September 2004 and June 2010 with PegIFN and Rbv at two liver centers at the Maggiore Hospital Milan (Italy) underwent TaqMan SNP Genotyping assays for testing rs12979860 genotype. Of 112 treated patients (98 males, 75 of Egyptian descent, 26 with cirrhosis) 103 were included in the final analysis; five discontinued treatment for nonvirologic reasons and four did not consent to genetic testing. Twenty-four (23%) were genotype CC, 65 (63%) CT, and 14 (14%) TT. Overall, 50 (49%) achieved an SVR: 21 (88%) CC patients versus 29 (37%) CT/TT (

P

< 0.0001). CC patients more often had a rapid virologic response (RVR) than CT/TT patients (12, 50% versus 23, 29%;

P

= 0.08), while also showing lower relapse rates (0% [0/21] versus 36% [16/45]

P

= 0.0013). In non-RVR patients, SVR rates were higher in CC than CT/TT patients (9 [75%] versus 13 [23%]

P

= 0.001). By logistic regression, the IL28B rs12979860 CC genotype was an independent predictor of SVR with an odds ratio of 8.0 (95% confidence interval 2.00-32.01;

P

= 0.003).

Conclusion :

The IL28B rs12979860 SNP may have an added value in the treatment algorithm of HCV-4 patients because it is the strongest predictor of an SVR to PegIFN/Rbv therapy. (Hepatology 2012)