bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of an Olmesartan Medoxomil–Based Treatment Algorithm in Patients Stratified by Age, Race, or Sex
Authors: Oparil Suzanne , Pimenta Eduardo
Published: November 2009

J Clin Hypertens (Greenwich). 2010;12:3–13. ©2009 Wiley Periodicals, Inc.

Demographic factors are known to influence the prevalence of hypertension, and evidence suggests that they may also influence the response of patients with hypertension to blood pressure (BP)–lowering therapies. To determine the effect of demographic factors on the efficacy and safety of an olmesartan medoxomil (OM)–based treatment regimen, we performed a prespecified subgroup analysis of a 12‐week, randomized, placebo‐controlled, titrate‐to‐goal study in patients with hypertension, stratifying patients into treatment groups according to age, sex, or race. After 12 weeks, OM–based therapy significantly reduced BP from baseline in blacks, non‐blacks, men, women, and patients younger than 65 or 65 years and older compared with placebo, and enabled 51.9% to 79.5% of patients to achieve a BP goal of <140/90 mm Hg. The differences in BP‐lowering efficacy of OM–based therapy between subgroups were not clinically significant, and treatment was generally well tolerated in all groups. This study demonstrates that an OM‐based treatment algorithm is an effective and safe option for achieving recommended BP goal in patients with hypertension including blacks, non‐blacks, men, women, and patients younger than 65 or 65 years and older.
Compliance With Home Blood Pressure Monitoring Among Middle‐Aged Korean Americans With Hypertension
Authors: Kim Jiyun , Han Hae‐Ra , Song Heejung , Lee JongEun , Kim Kim B. , Kim Miyong T.
Published: November 2009

J Clin Hypertens (Greenwich).

The primary objective of this study was to investigate the factors affecting the level of compliance of home blood pressure monitoring (HBPM) and its relation to blood pressure (BP) control among hypertensive adults in a community setting. A total of 377 middle‐aged Korean Americans with high BP participated in this study. Along with structured behavioral education, the participants were instructed to measure their BP 3 times in a row upon waking and thrice again at bedtime, at least 2 or more times a week for 48 weeks. Using multivariate logistic regression, the authors examined the patterns and factors affecting HBPM and its relation to BP control status. The analyses revealed that older participants were more compliant with the HBPM instruction than were younger participants (adjusted odds ratio [OR], 5.29; 95% confidence interval [CI], 1.77–15.81) and those with more depressive symptoms were less compliant (OR, 0.19; 95% CI, 0.04–0.88). Participants who were more compliant to HBPM instruction were 4 times more likely than those who were noncompliant to have controlled their BP by the end of the intervention period (OR, 4.28; 95% CI, 1.79–10.23). These results suggest that the participants who checked their BP regularly at home had a stronger tendency to achieve BP control.
Health Care Services Provided During Physician Office Visits for Hypertension: Differences by Specialty
Authors: Fang Jing , Keenan Nora L. , Ayala Carma
Published: November 2009

J Clin Hypertens (Greenwich). 2010;12:89–95. ©2009 Wiley Periodicals, Inc.

The changing health care system has reduced patients’ access to specialty care. Often, patients with hypertension visit noncardiologists. The objective of this study is to compare differences by physician specialty in the provision of health care services during office visits for hypertension. The authors examined office visits for US physicians by using data from the National Ambulatory Medical Care Survey for 2003 to 2005. Of more than 274 million hypertension visits, 35.5%, 43.9%, 8.5%, and 12.1% visits were made to general practitioners/family physicians, internists, cardiologists, and other specialties, respectively. Visitors to cardiologists were more likely to have coronary heart disease and heart failure than visitors to other physicians. While prescriptions for antihypertensive drugs overall were similar by specialty, cardiologists were more likely to prescribe lipid‐lowering drugs (odds ratio [OR], 1.60; 95% confidence interval [CI], 1.14–2.24) and aspirin (OR, 2.76; 95% CI, 1.81–4.20), calcium channel blockers (OR, 1.48; 95% CI, 1.12–1.96), β‐blockers (OR, 1.83; 95% CI, 1.35–2.48), and α‐blockers (OR, 2.10; 95% CI, 1.46–2.95) than general practitioners/family physicians after adjusting for relevant risk factors. There was no difference by specialty in providing/making a referral for nutrition/exercise counseling among physicians. Among hypertension office visits in the United States, cardiologists were more likely to provide lipid‐lowering drugs, aspirin, calcium channel blocker, β‐blockers, and α‐blockers than other physicians.
Body, Gender and Transnationalism: Art and Cultural Criticism in a Changing Europe
Authors: Dekel Tal
Published: November 2009

The term transnationalism, dealing with all facets of immigration – refugees, foreign workers, illegal layovers and migrants from one country to another – has been one of the prominent topics on the public and political agenda of most Western countries in recent years. Through analysing several visual works, this article seeks to draw out the influence of economic, political and cultural changes upon a range of female artists in post‐communist countries today. These artists each react differently in their works to the globalisation processes and the major transitions to a capitalistic economy, from a critical and personal point of view. As a result, these artists create what I shall call ‘a polyphonic project’, which is a product of Central and Eastern European artists that set out, and indeed succeeded, to reclaim their voice and body as women, challenging questions of gender, nationality, politics and economy in a changing Europe.
Volk auf dem Weg: Transnational Migration of the Russian‐Germans from 1763 to the Present Day
Authors: Pohl J. Otto
Published: November 2009

This article traces the migration patterns of the Russian‐Germans across international borders from their initial settlement in the Russian Empire starting in 1763 up to the present day. In particular it analyses the reasons behind these migration flows. Both push and pull factors motivated the immigration of ethnic Germans to the Russian Empire in the late eighteenth and nineteenth centuries. A similarly complex combination of such factors spurred the various waves of emigration by Russian‐Germans out of this territory during the late nineteenth and twentieth centuries. This article seeks to illuminate the primary causes of these migrant flows. It covers the main waves of German immigration into the Russian Empire including the initial settlement in the Volga region from 1763 to 1769, the establishment of the Mennonite colonies in Ukraine from 1789 to 1809 and the migration of German speakers to the Black Sea area from 1804 to 1856. It examines the various waves of emigration out of the territory of the former Russian Empire starting in the 1870s and continuing until today. The article goes on to analyse the immigration of Russian‐Germans to the Americas from Tsarist Russia from the 1870s until the First World War. Then it deals with the various waves of Russian‐German emigration under the Soviet regime starting in 1917–21 and reoccurring later in the 1920s, 1940s, 1970s and finally from 1987 to the collapse of the USSR. Finally, it examines the emigration of Russian‐Germans from Russia, Kazakhstan and Central Asia and their settlement in Germany until 2006. Special attention is given to the history of Stalinist repression and later discrimination against the Russian‐Germans as factors in their desire to emigrate.
Microbiologic Evaluation of Gallbladder Bile of Healthy Dogs and Dogs with Iatrogenic Hypercortisolism: A Pilot Study
Authors: Kook P.H. , Schellenberg S. , Grest P. , Reusch C.E. , Corboz L. , Glaus T.M.
Published: November 2009

Background:In people, hypercortisolism (HC) has been associated with acalculous cholecystitis and biliary dyskinesia, which may potentiate ascending biliary infections. In dogs, an association between HC and gallbladder disease recently has been documented, although the role of bacteria remains controversial. Furthermore, there is no information on the gallbladder bile microbial flora in healthy dogs.

Objectives:To investigate the microbial flora in gallbladder bile in healthy dogs, the relationship between iatrogenic hyperadrenocorticism and bactibilia and possible changes in biliary microbial flora after cortisol withdrawal in dogs.

Animals:Six control dogs and 6 dogs treated with hydrocortisone.

Methods:Gallbladder bile obtained by percutaneous ultrasound‐guided cholecystocentesis was cultured aerobically and anaerobically and examined cytologically before (d0), during (d28, d56, d84), and after (d28p, d56p, d84p) administration of hydrocortisone (8 mg/kg PO q12h).

Results:In the control group, 2/42 bile cultures yielded bacterial growth (Enterococcussp.;Escherichia colion d0) and 1/42 bile smears had cytological evidence of bacteria (d28). In the HC group, 2/42 bile cultures yielded bacterial growth (Enterococcussp. on d28;Bacillussp. on d28p) and 3/42 bile smears had cytological evidence of bacteria (d84, d84, d28p). All dogs remained healthy throughout the study period (168d).

Conclusions and Clinical Importance:Based on the results of conventional bacterial culture techniques, gallbladder bile of healthy dogs periodically may harbor bacteria, which do not appear to be clinically relevant. A 3‐month period of iatrogenic HC was not associated with bactibilia. A higher prevalence of bactibilia may be detected with micromolecular techniques.
Calcium and Phosphorus Homeostasis in Dogs with Spontaneous Chronic Kidney Disease at Different Stages of Severity
Authors: Cortadellas O. , Fernández del Palacio M.J. , Talavera J. , Bayón A.
Published: November 2009

Background:Studies in dogs with experimental chronic kidney disease (CKD) have demonstrated that abnormalities of calcium‐phosphorus (Ca‐P) homeostasis occur frequently and have a negative effect on kidney function and survival. However, the prevalence of these alterations in dogs with naturally occurring CKD at different stages of severity has not yet been investigated.

Hypothesis:Abnormalities of Ca‐P metabolism occur early in the course of CKD with an increased prevalence in more severe stages.

Animals:Fifty‐four dogs with CKD and 22 healthy dogs.

Methods:Blood and urine samples were obtained for a CBC, biochemistry, determination of parathyroid hormone (PTH), calcitriol, and ionized calcium concentrations and urinalysis. Based on urine protein/creatinine ratio and serum creatinine concentration, dogs were grouped according to the IRIS classification for CKD.

Results:Hyperparathyroidism (HPTH) (PTH ≥ 48 pg/mL) was diagnosed in 41 (75.9%) dogs with CKD. Its prevalence increased from 36.4% (stage 1) to 100% (stage 4). Hyperphosphatemia (P> 5.5 mg/dL) was present in 37 (68.5%) dogs; increasing in prevalence from 18% (stage 1) to 100% (stage 4). Receiver‐operating characteristic curve analysis showed that serum phosphorus concentration in the 4.5–5.5 mg/dL range correctly identified the presence of HPTH in most dogs. Calcitriol concentration progressively decreased in dogs with CKD and differences became statistically significant by stage 3.

Conclusion and Clinical Relevance:HPTH and hyperphosphatemia occur frequently in dogs with naturally occurring CKD, even at early stages of CKD in some dogs. These findings highlight the importance of monitoring these parameters early in the course of CKD.
Prevalence of Diarrhea and Enteropathogens in Racing Sled Dogs
Authors: McKenzie E. , Riehl J. , Banse H. , Kass P.H. , Nelson, Jr S. , Marks S.L.
Published: November 2009

Background:Diarrhea is highly prevalent in racing sled dogs, although the underlying causes are poorly understood.

Hypothesis:Clostridium perfringensenterotoxin (CPE) andClostridium difficileToxin A and B are associated with diarrhea in racing sled dogs.

Animals:One hundred and thirty‐five sled dogs.

Methods:Freshly voided feces were obtained from 55 dogs before racing and from 80 dogs after 400 miles of racing. Samples were visually scored for diarrhea, mucus, blood, and melena. CPE andC. difficileToxin A and B were detected by ELISA. Samples were cultured forC. perfringens, C. difficile, Campylobacter, Salmonella, andEscherichia coli0157;GiardiaandCryptosporidiumspp. were detected via immunofluorescence.

Results:Diarrhea occurred in 36% of dogs during racing, and hematochezia, fecal mucus or melena, or all 3 occurred in 57.5% of dogs.Salmonellawas isolated from 78.2% of dogs before racing, and from 71.3% of dogs during racing.C. perfringensandC. difficilewere isolated from 100 and 58.2% of dogs before racing, and from 95 and 36.3% of dogs during racing. Dogs were more likely to test positive for CPE during than before racing (18.8 versus 5.5%,P= .021); however, no enteropathogens or their respective toxins were significantly associated with hematochezia or diarrhea.

Conclusions and Clinical Importance:Sled dogs participating in long distance racing have a high prevalence of diarrhea and hematochezia that is not associated with common enteropathogens. It is possible that diarrhea and hematochezia represent the effect of prolonged exercise on the gastrointestinal tract.
Prospective Evaluation of Laparoscopic Pancreatic Biopsies in 11 Healthy Cats
Authors: Cosford K.L. , Shmon C.L. , Myers S.L. , Taylor S.M. , Carr A.P. , Steiner J.M. , Suchodolski J.S. , Mantovani F.
Published: November 2009

Background: Definitive diagnosis of feline pancreatic disease is dependent on histologic examination of biopsies.

Hypothesis: Laparoscopic punch biopsy of the pancreas does not significantly affect pancreatic health or clinical status of healthy cats, and provides an adequate biopsy sample for histopathology.

Animals: Eleven healthy female domestic shorthair cats.

Methods: Effects of laparoscopic pancreatic visualization alone in 5 cats compared with laparoscopic pancreatic visualization and punch biopsy in 6 cats were studied. Temperature, pulse, and respiratory rate, physical examination, and daily caloric intake were evaluated for 1 week before and 1 week after the procedure. Pain scores (simple descriptive score and dynamic interactive visual assessment score) were evaluated hourly during the 1st 6 hours postprocedure. Complete blood cell counts, serum biochemical profiles, serum feline pancreatic lipase immunoreactivity, and urine specific gravity were evaluated before the procedure and at 6, 24, and 72 hours postprocedure. One month postprocedure, during sterilization, the pancreas was reassessed visually in all cats, and microscopically in the biopsy group.

Results: For all variables evaluated, there were no significant differences between biopsy and control cats. Re‐evaluation of the pancreatic biopsy site 1 month later documented a normal tissue response to biopsy. The laparoscopic punch biopsy forceps provided high‐quality pancreatic biopsy samples with an average size of 5 mm × 4 mm on 2‐dimensional cut section.

Conclusions and Clinical Importance: Laparoscopic pancreatic biopsy is a useful and safe technique in healthy cats.
China, Russia, and the Challenge to the Global Commons
Authors: Weitz Richard
Published: November 2009

During the second half of the twentieth century, the USA enjoyed unfettered freedom to use the global commons – those domains that remain outside the territory of any single nation state but provide the means for connecting much of the world. The most prominent of these realms are the world's oceans (still the main thoroughfare for trading goods between countries), outer space (the domain used by most long‐distance communications and broadcast media), and the Internet (increasingly the most effective media for storing and moving large quantities of information great distances at low cost). Billions of people access these domains each day, but they are especially important for commercial and military actors.

China and Russia have launched major campaigns to contest the American presence in the global commons. These initiatives include challenging US surveillance operations in international waters, trying to constrain American military access to outer space, and enhancing their capacity to disrupt US use of the Internet. Overcoming Chinese and Russian anti‐access efforts are essential for preserving the security of the USA and its allies. In particular, as the US military has reduced its forward bases in Japan, South Korea, and other Asia–Pacific countries, it has become increasingly dependent on the global commons to rapidly deploy forces based in the USA to potential conflict regions. A failure to overcome anti‐access threats could lead Asia–Pacific countries to call into question US security guarantees.
Why Does China Reassure South‐East Asia?*
Authors: Sun Xuefeng
Published: November 2009

This article addresses the following provocative puzzle: why has China chosen to reassure South‐East Asian states during the past decade? The author develops a dual pressure model to explain China's reassurance policy. This dual pressure model maintains that US dominance and China's domestic priorities have combined to compel China to reassure its South‐East Asian neighbors. In the shadow of US dominance, a rising China has no other choice but to reassure its neighbors in order to alleviate strategic pressures against it. The reassurance policy not only sends benign signals to the USA, but also neutralizes China's neighbors in the case of US containment of China. At the domestic level, China's top priorities lie in maintaining social stability in the process of economic development and preventing Taiwan's declaration of de jure independence. These tremendous tasks require the cooperation of China's South‐East Asian neighbors. Therefore, it is in line with China's domestic priorities to reassure the South‐East Asia states. Based on the dual pressure model, the author takes an optimistic view that China will continue to follow the reassurance policy towards its South‐East Asian neighbors in order to foster a peaceful and prosperous neighborhood in the decade to come.
Framing Anti‐Americanism and the Media in South Korea: TV vs Newspaper*
Authors: Kim Yongho , Hur Jaeyoung
Published: November 2009

This study indicates a stark contrast between the frames by TV news and that of the major newspapers in the coverage of the two candlelight demonstrations in 2002 and 2008 in South Korea. The contrast implies that the frames used by TV news and major newspapers were constructed by two different thematic frames that competed for dominance in public concern: national interest on the one hand, and national prestige and human interests on the other. The TV news framed stories on the 2002 Yangju county accident and the import of American beef in ways to trigger anti‐Americanism, which was contrasted with major newspapers' consistent emphasis on national interest. Difference in ownership, target audience and the degree of dependence on advertising sponsors offered plausible explanations for the difference in frames. In addition, the number of journalists going into politics also offered insights into why TV news and newspapers framed the 2002 Yangju county accident and the import of US beef in very unique ways, either by triggering anti‐demonstrations or by tranquilizing protests through emphasizing national interests. Overall, difference in frames between major TV news and major newspaper stories represents ideological difference in the public opinion over conservatives versus progressives.
The Dokdo/Takeshima Dispute between Korea and Japan: Understanding the Whole Picture*
Authors: Cho Jinman , Kim HeeMin , Choi Jun Young
Published: November 2009

In the past, most studies on territorial disputes have been in the discipline of history and international law. In this paper, we expand the debate by adopting a utility‐theory approach to the issue of Dokdo/Takeshima. We introduce two different types of utility functions over the disputed islet, and show how moving from one to the other can alter the outcome of the dispute.

We conclude that: (i) utilizing historical and/or legal argument alone will not resolve the Dokdo/Takeshima dispute; (ii) the different mixture of two different types of utilities changes the outcome of the debate; and (iii) the current configuration of preferences/utilities among Koreans and Japanese over the issue of Dokdo/Takeshima will never allow mutually satisfactory negotiated solutions to the dispute. Overall our diagnosis and predictions are pessimistic.
Financial Regionalism in East Asia: Regional Surveillance Cooperation and Enforcement Problem*
Authors: Jung Heon Joo
Published: November 2009

Since the Asian financial crisis in 1997, many financial cooperative arrangements among the ASEAN+3 countries have been formed to facilitate policy coordination and to prevent another crisis from adversely affecting East Asia. This paper focuses on regional surveillance cooperation, which has been regarded as a pre‐requisite for deeper financial cooperation including bilateral swap arrangements under Chiang Mai Initiatives. Although East Asian states have acknowledged the significance of the regional surveillance mechanism in the midst of the crisis, which could facilitate information sharing and frank discussion of potential risks in the region, it showed little progress until very recently. What explains this unsuccessful regional surveillance cooperation given the initial enthusiasm and widely‐acknowledged need for it? This article takes seriously domestic implementation capacities and enforcement problems on a regional level. It argues that member states are discouraged from exchanging frank views on other states' financial conditions because they expect that even non‐intrusive policies would not necessarily be successfully implemented in those countries where sufficient domestic regulatory and supervisory capacities are lacking. Moreover, regional surveillance cooperation had troubles in enforcement: the norm of non‐interventionism, lack of independent regional agencies and staff that could monitor and enforce compliance, and lack of transparency. In these circumstances, current surveillance mechanisms are likely to become a stumbling block for deeper financial integration in East Asia until serious efforts are made to tackle problems with enforcement.
State‐Business Relations and Investment in Egypt
Authors: Abdel‐Latif Abla , Schmitz Hubert
Published: November 2009

Summary

This study shows that informal relationships between key policymakers and investors have played an important role in raising levels of investment and fostering economic growth. Comparative observations show that common social roots and common professional background facilitate the emergence of an effective public‐private growth alliance but the only necessary conditions are common interest and common understanding of the problems to be solved.

The comparative research on two old and two new sectors shows in detail how informal relationships have emerged and how they have made an impact but it warns against overstating their investment‐enhancing role. Effective relationships between policymakers and investors – abbreviated to CIPI – are not the direct cause of increases in investment but can play a critical role in unleashing the profit potential of specific sectors. Research on the food industry shows how CIPI helped to overcome supply constraints and political obstacles in decision‐making. Research on the communications industry shows how CIPI helped Egypt to overcome initial barriers to entry and establish a new industry virtually from scratch. While the gains were sometimes appropriated by a few actors, the research shows that exclusive relationships can have inclusive effects, depending on how the private sector is organised.

Quantitative examination of whether CIPI had an enduring investment‐enhancing effect was inconclusive. There is no doubt however that the CIPI was an effective transitional arrangement. It helped investors to overcome barriers to economic growth, it helped policymakers to overcome deficiencies in their own government agencies and it helped both sides to work together in establishing new sector‐specific rules and improving the general regulatory framework. The general lesson from this research is that such transitional arrangements deserve more attention, both to gain a better understanding of the political economy of investment and growth and to make research more relevant for policy.

JEL classification: P16, 010.
Ca2+‐dependent components of inactivation of unitary cardiac L‐type Ca2+ channels
Authors: Josephson Ira R. , Guia Antonio , Lakatta Edward G. , Lederer W. Jonathan , Stern Michael D.
Published: November 2009

A Ca2+ ion‐dependent inactivation (CDI) of L‐type Ca2+ channels (LCC) is vital in limiting and shaping local Ca2+ ion signalling in a variety of excitable cell types. However, under physiological conditions the unitary LCC properties that underlie macroscopic inactivation are unclear. Towards this end, we have probed the gating kinetics of individual cardiac LCCs recorded with a physiological Ca2+ ion concentration (2 mm) permeating the channel, and in the absence of channel agonists. Upon depolarization the ensemble‐averaged LCC current decayed with a fast and a slow exponential component. We analysed the unitary behaviour responsible for this biphasic decay by means of a novel kinetic dissection of LCC gating parameters. We found that inactivation was caused by a rapid decrease in the frequency of LCC reopening, and a slower decline in mean open time of the LCC. In contrast, with barium ions permeating the channel ensemble‐averaged currents displayed only a single, slow exponential decay and little time dependence of the LCC open time. Our results demonstrate that the fast and slow phases of macroscopic inactivation reflect the distinct time courses for the decline in the frequency of LCC reopening and the open dwell time, both of which are modulated by Ca2+ influx. Analysis of the evolution of CDI in individual LCC episodes was employed to examine the stochastic nature of the underlying molecular switch, and revealed that influx on the order of a thousand Ca2+ ions may be sufficient to trigger CDI. This is the first study to characterize both the unitary kinetics and the stoichiometry of CDI of LCCs with a physiological Ca2+ concentration. These novel findings may provide a basis for understanding the mechanisms regulating unitary LCC gating, which is a pivotal element in the local control of Ca2+‐dependent signalling processes.
Homeostasis of intrinsic excitability in hippocampal neurones: dynamics and mechanism of the response to chronic depolarization
Authors: O’Leary Timothy , van Rossum Mark C. W. , Wyllie David J. A.
Published: November 2009

In order to maintain stable functionality in the face of continually changing input, neurones in the CNS must dynamically modulate their electrical characteristics. It has been hypothesized that in order to retain stable network function, neurones possess homeostatic mechanisms which integrate activity levels and alter network and cellular properties in such a way as to counter long‐term perturbations. Here we describe a simple model system where we investigate the effects of sustained neuronal depolarization, lasting up to several days, by exposing cultures of primary hippocampal pyramidal neurones to elevated concentrations (10–30 mm) of KCl. Following exposure to KCl, neurones exhibit lower input resistances and resting potentials, and require more current to be injected to evoke action potentials. This results in a rightward shift in the frequency‐input current (FI) curve which is explained by a simple linear model of the subthresholdI–Vrelationship. No changes are observed in action potential profiles, nor in the membrane potential at which action potentials are evoked. Furthermore, following depolarization, an increase in subthreshold potassium conductance is observed which is accounted for within a biophysical model of the subthresholdI–Vcharacteristics of neuronal membranes. The FI curve shift was blocked by the presence of the L‐type Ca2+channel blocker nifedipine, whilst antagonism of NMDA receptors did not interfere with the effect. Finally, changes in the intrinsic properties of neurones are reversible following removal of the depolarizing stimulus. We suggest that this experimental system provides a convenient model of homeostatic regulation of intrinsic excitability, and permits the study of temporal characteristics of homeostasis and its dependence on stimulus magnitude.
Amiloride‐sensitive channels are a major contributor to mechanotransduction in mammalian muscle spindles
Authors: Simon Anna , Shenton Fiona , Hunter Irene , Banks Robert W. , Bewick Guy S.
Published: November 2009

We investigated whether channels of the epithelial sodium/amiloride‐sensitive degenerin (ENaC/DEG) family are a major contributor to mechanosensory transduction in primary mechanosensory afferents, using adult rat muscle spindles as a model system. Stretch‐evoked afferent discharge was reduced in a dose‐dependent manner by amiloride and three analogues – benzamil, 5‐(N‐ethyl‐N‐isopropyl) amiloride (EIPA) and hexamethyleneamiloride (HMA), reaching ≥85% inhibition at 1 mm. Moreover, firing was slightly but significantly increased by ENaC δ subunit agonists (icilin and capsazepine). HMA's profile of effects was distinct from that of the other drugs. Amiloride, benzamil and EIPA significantly decreased firing (P < 0.01 each) at 1 μm, while 10 μm HMA was required for highly significant inhibition (P < 0.0001). Conversely, amiloride, benzamil and EIPA rarely blocked firing entirely at 1 mm, whereas 1 mm HMA blocked 12 of 16 preparations. This pharmacology suggests low‐affinity ENaCs are the important spindle mechanotransducer. In agreement with this, immunoreactivity to ENaC α, β and γ subunits was detected both by Western blot and immunocytochemistry. Immunofluorescence intensity ratios for ENaC α, β or γ relative to the vesicle marker synaptophysin in the same spindle all significantly exceeded controls (P < 0.001). Ratios for the related brain sodium channel ASIC2 (BNaC1α) were also highly significantly greater (P < 0.005). Analysis of confocal images showed strong colocalisation within the terminal of ENaC/ASIC2 subunits and synaptophysin. This study implicates ENaC and ASIC2 in mammalian mechanotransduction. Moreover, within the terminals they colocalise with synaptophysin, a marker for the synaptic‐like vesicles which regulate afferent excitability in these mechanosensitive endings.
Trypanosoma cruzi
Targets Akt in Host Cells as an Intracellular Antiapoptotic Strategy
Authors: Chuenkova Marina V. , PereiraPerrin Mercio
Published: November 2009

A surface protein of the intracellular parasite
Trypanosoma cruzi
acts both intracellularly and extracellularly to keep infected cells alive.
Tyrosine Phosphorylation Inhibits PKM2 to Promote the Warburg Effect and Tumor Growth
Authors: Hitosugi Taro , Kang Sumin , Vander Heiden Matthew G. , Chung Tae-Wook , Elf Shannon , Lythgoe Katherine , Dong Shaozhong , Lonial Sagar , Wang Xu , Chen Georgia Z. , Xie Jianxin , Gu Ting-Lei , Polakiewicz Roberto D. , Roesel Johannes L. , Boggon Titus J. , Khuri Fadlo R. , Gilliland D. Gary , Cantley Lewis C. , Kaufman Jonathan , Chen Jing
Published: November 2009

Tyrosine phosphorylation of pyruvate kinase M2 gives tumor cells a metabolic advantage.
Differential Treatment in the ER
Authors: Wong Wei
Published: November 2009

Components of the endoplasmic reticulum quality control are involved in immune responses mediated by the plant pattern recognition receptor EFR.
Arrested Development
Authors: VanHook Annalisa M.
Published: November 2009

An adult-phase diapause protects the germ line of starved nematodes, and pheromone receptors required for a nematode larval-phase diapause are identified.
Sleep and Alzheimer’s Disease
Authors: Hurtley Stella M.
Published: November 2009

Sleep patterns can influence amyloid plaque formation in a mouse model of Alzheimer’s disease.
The Other Path to Cancer
Authors: Ray L. Bryan
Published: November 2009

Activation of an epigenetic switch causes stable cell transformation.
Acetylation Goes Global: The Emergence of Acetylation Biology
Authors: Norris Kristi L. , Lee Joo-Yong , Yao Tso-Pang
Published: November 2009

Proteomic analysis shows protein acetylation to be more prevalent than previously appreciated.
Gallium Disrupts Iron Uptake by Intracellular and ExtracellularFrancisellaStrains and Exhibits Therapeutic Efficacy in a Murine Pulmonary Infection Model
Authors: Olakanmi Oyebode , Gunn John S. , Su Shengchang , Soni Shilpa , Hassett Daniel J. , Britigan Bradley E.
Published: November 2009

Francisella tularensisrequires iron (Fe) for growth, but the biologic sources of Fe for this organism are largely unknown. We found thatFrancisellasp. growing in broth culture or within human macrophages can acquire Fe from the two major host Fe-binding proteins, lactoferrin (Lf) and transferrin (Tf). Fe acquisition is a potential target for novel therapies. Gallium (Ga) is a transition metal that interferes with cellular Fe metabolism by competing with Fe for uptake/utilization. Growth of eitherF. tularensislive vaccine strain (LVS) orFrancisella novicidawas inhibited by ≥2 μM Ga chelated to Tf or Lf, with GaLf being somewhat more potent.Francisellaspp. express two Fe-containing antioxidant enzymes, catalase (KatG) and Fe cofactored superoxide dismutase (FeSOD). Growth of LVS with 10 μM GaTf or GaLf led to a dramatic decrease in bacterial catalase activity and in FeSOD activity that was associated with an increased susceptibility to H2O2. Ga also protected mice from intranasal challenge withF. novicida. Whereas 100% of theF. novicida-infected mice died by day 9, 75% of the mice receiving Ga continued to survive to at least day 15. Thus, a single intranasal dose of Ga followed by daily intraperitoneal Ga at a dose tolerated by the animals resulted in prolonged survival. These data support the potential utility of Ga as a therapy forF. tularensisinfection of the lung.
Structure-Microbicidal Activity Relationship of Synthetic Fragments Derived from the Antibacterial α-Helix of Human Lactoferrin
Authors: Håversen L. , Kondori N. , Baltzer L. , Hanson L. Å. , Dolphin G. T. , Dunér K. , Mattsby-Baltzer I.
Published: November 2009

There is a need for new microbicidal agents with therapeutic potential due to antibiotic resistance in bacteria and fungi. In this study, the structure-microbicidal activity relationship of amino acid residues 14 to 31 (sequence 14-31) from the N-terminal end, corresponding to the antibacterial α-helix of human lactoferrin (LF), was investigated by downsizing, alanine scanning, and substitution of amino acids. Microbicidal analysis (99% killing) was performed by a microplate assay using
Escherichia coli
,
Staphylococcus aureus
, and
Candida albicans
as test organisms. Starting from the N-terminal end, downsizing of peptide sequence 14-31 showed that the peptide sequence 19-31 (KCFQWQRNMRKVR, HL9) was the optimal length for antimicrobial activity. Furthermore, HL9 bound to lipid A/lipopolysaccharide, as shown by neutralizing endotoxic activity in a
Limulus
assay. Alanine scanning of peptide sequence 20-31 showed that Cys20, Trp23, Arg28, Lys29, or Arg31 was important for expressing full killing activity, particularly against
C. albicans
. Substituting the neutral hydrophilic amino acids Gln24 and Asn26 for Lys and Ala (HLopt2), respectively, enhanced microbicidal activity significantly against all test organisms compared to the amino acids natural counterpart, also, in comparison with HL9, HLopt2 had more than 10-fold-stronger fungicidal activity. Furthermore, HLopt2 was less affected by metallic salts than HL9. The microbicidal activity of HLopt2 was slightly reduced only at pH 7.0, as tested in the pH range of 4.5 to 7.5. The results showed that the microbicidal activity of synthetic peptide sequences, based on the antimicrobial α-helix region of LF, can be significantly enhanced by optimizing the length and substitution of neutral amino acids at specific positions, thus suggesting a sequence lead with therapeutic potential.
Efficacy Profiles of Daptomycin for Treatment of Invasive and Noninvasive Pulmonary Infections with
Streptococcus pneumoniae
Authors: Henken Stefanie , Bohling Jennifer , Martens-Lobenhoffer Jens , Paton James C. , Ogunniyi A. David , Briles David E. , Salisbury Vyvyan C. , Wedekind Dirk , Bode-Böger Stefanie M. , Welsh Thomas , Bange Franz C. , Welte Tobias , Maus Ulrich A.
Published: November 2009

Daptomycin is a novel lipopeptide antibiotic with excellent activity against Gram-positive bacterial pathogens, but its therapeutic value for the treatment of invasive pneumococcal disease compared to that for the treatment of pneumococcal pneumonia is incompletely defined. We investigated the efficacy of daptomycin in two models of
Streptococcus pneumoniae
-induced lung infection, i.e., pneumococcal pneumonia and septic pneumococcal disease. Mice were infected with a bioluminescent, invasive serotype 2
S. pneumoniae
strain or a less virulent serotype 19
S. pneumoniae
strain and were then given semitherapeutic or therapeutic daptomycin or ceftriaxone. Readouts included survival; bacterial loads; and septic disease progression, as determined by biophotonic imaging. Semitherapeutic daptomycin treatment fully protected the mice against the progression of septic disease induced by serotype 2
S. pneumoniae
, while therapeutic treatment of the mice with daptomycin or ceftriaxone led to ∼70% or ∼60% survival, respectively. In contrast, mice infected with serotype 19
S. pneumoniae
developed severe pneumonia and lung leakage even in the presence of increased intra-alveolar daptomycin levels, resulting in only 40% survival, whereas the ceftriaxone-treated mice had 100% survival. Together, although daptomycin demonstrates little efficacy in the treatment of pneumococcal pneumonia, daptomycin is highly effective in preventing
S. pneumoniae
-induced septic death, thus possibly offering a therapeutic option for patients with life-threatening septic pneumococcal disease.
Interaction of Ceftobiprole with the Low-Affinity PBP 5 of
Enterococcus faecium
Authors: Henry Xavier , Amoroso Ana , Coyette Jacques , Joris Bernard
Published: November 2009

Ceftobiprole is a new cephalosporin that exhibits a high level of affinity for methicillin-resistant
Staphylococcus aureus
PBP 2a. It was reported that ceftobiprole did not interact with a mutated form of the low-affinity protein
Enterococcus faecium
PBP 5 (PBP 5fm) that, when overexpressed, confers a β-lactam resistance phenotype to the bacterium. Our results show that ceftobiprole binds to unmutated PBP 5fm to form a stable acyl-enzyme and that ceftobiprole is able to efficiently kill a penicillin-resistant
Enterococcus faecium
strain that produces this protein.
Escherichia coli
Sequence Type ST131 as an Emerging Fluoroquinolone-Resistant Uropathogen among Renal Transplant Recipients
Authors: Johnson James R. , Johnston Brian , Clabots Connie , Kuskowski Michael A. , Pendyala Swaroop , DebRoy Chitrita , Nowicki Bogdan , Rice James
Published: November 2009

Among 40
Escherichia coli
urine isolates from renal transplant recipients (Galveston, TX, 2003 to 2005), sequence type ST131 (O25:H4) was highly prevalent (representing 35% of isolates overall and 60% of fluoroquinolone-resistant isolates), virulent appearing, antimicrobial resistant (but extended-spectrum-cephalosporin susceptible), and associated with black race. Pulsotypes were diverse; some were linked to other locales. ST131 emerged significantly during the study period. These findings suggest that
E. coli
ST131 may constitute an important new multidrug-resistant threat to renal transplant recipients.
In Vitro
and
In Vivo
Efficacies of Teicoplanin-Loaded Calcium Sulfate for Treatment of Chronic Methicillin-Resistant
Staphylococcus aureus
Osteomyelitis
Authors: Jia Wei-Tao , Luo Shi-Hua , Zhang Chang-Qing , Wang Jian-Qiang
Published: November 2009

The
i
n vitro
and
in vivo
therapeutic efficacies of teicoplanin-loaded calcium sulfate (TCS; 10% [wt] teicoplanin) were investigated in a rabbit model of chronic methicillin-resistant
Staphylococcus aureus
(MRSA) osteomyelitis. The
in vitro
elution characteristics of teicoplanin from TCS pellets were realized by carrying out an evaluation of the release kinetics, recovery rate, and antibacterial activity of the released teicoplanin. Chronic osteomyelitis was induced by inoculating 10
7
CFU of a MRSA strain into the tibial cavity of rabbits. After 3 weeks, the animals were treated by debridement followed by implantation of TCS pellets in group 1, calcium sulfate (CS) pellets alone in group 2, and intravenous (i.v.) teicoplanin (6 mg/kg of body weight every 12 h for three doses and then every 24 h up to 4 weeks) in group 3. Animals in group 4 were left untreated. After 6 weeks, the efficacy of the osteomyelitis treatment was evaluated by hematological, radiological, microbiological, and histological examinations.
In vitro
elution studies showed sustained release of teicoplanin at a therapeutic level over a time period of 3 weeks. The released teicoplanin maintained its antibacterial activity.
In vivo
, the best therapeutic effect was observed in animals treated with TCS pellets, resulting in significantly lower radiological and histological scores, lower positive rates of MRSA culture and bacterial load, and excellent bone regeneration compared with those treated by CS alone or i.v. teicoplanin, without any local or systemic adverse effects. TCS pellets are an effective alternative to i.v. teicoplanin for the treatment of chronic MRSA osteomyelitis, particularly because teicoplanin is delivered locally while the TCS pellets simultaneously promote bone defect repair.
Panel of Prototypical Raltegravir-Resistant Infectious Molecular Clones in a Novel Integrase-Deleted Cloning Vector
Authors: Reuman Elizabeth C. , Bachmann Michael H. , Varghese Vici , Fessel W. Jeffrey , Shafer Robert W.
Published: November 2009

We created an HIV-1 cloning vector, pNL4.3ΔIN, to generate recombinant infectious molecular clones for analysis of patient-derived HIV-1 integrase coding regions. Using this vector, we constructed a panel of clinically derived viruses with the canonical patterns of raltegravir resistance mutations and submitted the panel to the NIH AIDS Research and Reference Reagent Program. Investigational integrase inhibitors with activity against these clones are likely to retain activity against the most clinically relevant raltegravir-resistant variants.
Waging War against UropathogenicEscherichia coli: Winning Back the Urinary Tract
Authors: Sivick Kelsey E. , Mobley Harry L. T.
Published: November 2009

Urinary tract infection (UTI) caused by uropathogenicEscherichia coli(UPEC) is a substantial economic and societal burden—a formidable public health issue. Symptomatic UTI causes significant discomfort in infected patients, results in lost productivity, predisposes individuals to more serious infections, and usually necessitates antibiotic therapy. There is no licensed vaccine available for prevention of UTI in humans in the United States, likely due to the challenge of targeting a relatively heterogeneous group of pathogenic strains in a unique physiological niche. Despite significant advances in the understanding of UPEC biology, mechanistic details regarding the host response to UTI and full comprehension of genetic loci that influence susceptibility require additional work. Currently, there is an appreciation for the role of classic innate immune responses—from pattern receptor recognition to recruitment of phagocytic cells—that occur during UPEC-mediated UTI. There is, however, a clear disconnect regarding how factors involved in the innate immune response to UPEC stimulate acquired immunity that facilitates enhanced clearance upon reinfection. Unraveling the molecular details of this process is vital in the development of a successful vaccine for prevention of human UTI. Here, we survey the current understanding of host responses to UPEC-mediated UTI with an eye on molecular and cellular factors whose activity may be harnessed by a vaccine that stimulates lasting and sterilizing immunity.
BUILDING CUSTOMER MODELS FROM BUSINESS DATA: AN AUTOMATIC APPROACH BASED ON FUZZY CLUSTERING AND MACHINE LEARNING
Authors: ROMDHANE LOTFI BEN , FADHEL NADIA , AYEB BECHIR
Published: November 2009

Data mining (DM) is a new emerging discipline that aims to extract knowledge from data using several techniques. DM turned out to be useful in business where the data describing the customers and their transactions is in the order of terabytes. In this paper, we propose an approach for building customer models (said also profiles in the literature) from business data. Our approach is three-step. In the first step, we use fuzzy clustering to categorize customers, i.e., determine groups of customers. A key feature is that the number of groups (or clusters) is computed automatically from data using the partition entropy as a validity criteria. In the second step, we proceed to a dimensionality reduction which aims at keeping for each group of customers only the most informative attributes. For this, we define the information loss to quantify the information degree of an attribute. Hence, and as a result to this second step, we obtain groups of customers each described by a distinct set of attributes. In the third and final step, we use backpropagation neural networks to extract useful knowledge from these groups. Experimental results on real-world data sets reveal a good performance of our approach and should simulate future research.
A COMPOSITIONAL METHOD USING AN EVOLUTIONARY ALGORITHM FOR FINDING FUZZY RULES IN 3-LAYERED HIERARCHICAL FUZZY STRUCTURE
Authors: ZAJACZKOWSKI J. , VERMA B.
Published: November 2009

This paper presents a novel compositional method for finding fuzzy rules in a three-layered hierarchical fuzzy structure. The proposed method incorporates a multi-objective evolutionary algorithm and a large set of initial conditions, including dynamical conditions of the system under investigation. The proposed method is focused on handling the large set of initial conditions by a multi-objective evolutionary algorithm and it can be applied to a wide range of dynamical control systems in robotics. The method has been evaluated on a dynamical system such as the inverted pendulum. The experimental results and analysis showed that the proposed method is much better than the existing methods such as amalgamation and single objective evolutionary algorithm based methods.
Genetic and Epigenetic Mechanisms Underlying Cell-Surface Variability in Protozoa and Fungi
Authors: Verstrepen Kevin J. , Fink Gerald R.
Published: November 2009

Eukaryotic microorganisms have evolved ingenious mechanisms to generate variability at their cell surface, permitting differential adherence, rapid adaptation to changing environments, and evasion of immune surveillance. Fungi such as Saccharomyces cerevisiae and the pathogen Candida albicans carry a family of mucin and adhesin genes that allow adhesion to various surfaces and tissues. Trypanosoma cruzi, T. brucei, and Plasmodium falciparum likewise contain large arsenals of different cell surface adhesion genes. In both yeasts and protozoa, silencing and differential expression of the gene family results in surface variability. Here, we discuss unexpected similarities in the structure and genomic location of the cell surface genes, the role of repeated DNA sequences, and the genetic and epigenetic mechanisms—all of which contribute to the remarkable cell surface variability in these highly divergent microbes.