bluuebunny/crossref_metadata_2025 huggingface dataset:
Income Impact of Micro-enterprise Finance: An Empirical Study on Government Initiatives in Rural India
Authors: Tripathy K.K. , Jain Sudhir K.
Published: October 2012

This paper assesses the distributional implications of the world’s largest-ever government operated micro-finance programme and examines the suitability of the Self Help Group (SHG)–micro-enterprise framework towards effective income generation and poverty alleviation. The statistical analysis indicates that while internal savings and group corpus have a positive and significant effect on the income growth of beneficiaries, bank credit does not have any such impact. The results also highlight that the socially and economically forward regions are more likely to benefit from this programme. This has policy implications towards effective governance of government operated micro-finance initiatives in developing nations.
Growth, Employment, Exports and Wagner’s Law: Evidence from Pakistan’s Agriculture Sector (1960–2009)
Authors: Zaman Khalid , Khan Muhammad Mushtaq , Ahmad Mehboob , Khilji Bashir Ahmad
Published: October 2012

The objective of this study is to empirically examine the relationship between growth, employment, exports and their impact on gross national expenditure (as a percentage of agriculture GDP), specifically in the context of Pakistan’s agriculture sector by using the Bound Testing approach. Data sets from 1960–2009 are taken for time series analysis. The analysis demonstrates that, in the long-run, Wagner’s Law does not hold in Pakistan’s agriculture sector, as agriculture growth is negatively correlated with the share of agriculture expenditure; while, in the short-run, Wagner’s law does hold, as it supports the hypothesis. Agricultural employment tends to be a significant negative correlation with the agricultural expenditure in the long-run. However, these results disappear in the short-run. Agricultural raw material exports have a significant and positive impact on agriculture expenditures both in the short- and long-run.
Sport and exercise medicine’s professional project: The impact of formal qualifications on the organization of British Olympic medical services
Authors: Scott Andrea
Published: October 2012

This article documents the intended and unintended outcomes of recent organizational change in UK elite sport. Drawing on semi-structured interviews with 14 doctors and 14 physiotherapists who are current members of the British Olympic Association medical and physiotherapy committees, it argues that attempts by managers in sports medicine to create a highly specialized area of practice have created more immediate tensions within and between both professional groups. The first half of the article argues that on the one hand, the introduction of formal qualifications in sports medicine has created opportunities for clinicians to work full-time in sport, created a clearer distinction between specialized and non-specialized practitioners, provided greater access to and involvement in supportive networks and created more formal pathways for those wishing to enter or progress within the field. At the same time, however, an examination of the working relations between current members of the British Olympic Association’s medical and physiotherapy committees highlights, in microcosm, the social organization of sports medicine post organizational change. Thus, this article highlights that attempts by higher managerial sports medicine clinicians to achieve professional status have created a fragmented and internally divided sports medicine speciality made up of a diverse set of practitioners at different stages of sports medicine’s professional project.
A Crossover Randomized Prospective Pilot Study Evaluating a Central Venous Catheter Team in Reducing Catheter-Related Bloodstream Infections in Pediatric Oncology Patients
Authors: Secola Rita , Azen Colleen , Lewis Mary Ann , Pike Nancy , Needleman Jack , Sposto Richard , Doering Lynn
Published: October 2012

Background: Treatment for most children with cancer includes the use of a central venous catheter (CVC). CVCs provide reliable venous access for delivery of chemotherapy and supportive care. This advantage is mitigated by an increased risk of bloodstream infections (BSIs). Despite the ubiquitous use of CVCs, few prospective studies have been conducted to address infection prevention strategies in pediatric oncology patients. Design: Prospective, crossover pilot study of a CVC team intervention versus standard care. Setting: Two inpatient oncology units in a metropolitan children’s hospital. Patients: A total of 41 patients/135 admissions for the experimental unit (EU) and 41/129 admissions for the control unit (CU). Methods: Patients received a CVC blood draw bundle procedure by a CVC registered nurse (RN) team member (experimental intervention: EU) for 6 months and by the assigned bedside RN (standard care: CU) for 6 months. Feasibility of implementing a CVC RN team; a significant difference in CVC-related BSIs between the team intervention versus standard care and risk factors associated in the development of CVC-related BSIs were determined. Results: There were 7 CVC-related BSIs/1238 catheter days in the EU group (5.7/1000 catheter days) versus 3 CVC-related BSIs/1419 catheter days in the CU group (2.1/1000 catheter days; P = .97). Selected risk factors were not significantly associated with the development of a CVC-related BSI. Conclusions: A CVC team in the care of pediatric oncology patients is feasible; however, a larger cohort will be required to adequately determine the effectiveness of the team reducing CVC-related BSIs.
Crystalloid Granulomas of the Parotid Gland Mimicking Tumor
Authors: Ho Caleb , Sasaki Clarence T. , Prasad Manju L.
Published: October 2012

Crystals and crystalloids may be seen in salivary glands in association with tumors and cysts. Rarely, crystalloids may lead to granulomatous reaction mimicking neoplasm and infectious diseases. We present the case of an 81-year-old man with right parotid gland swelling and a clinical and radiological diagnosis of tumor. A granulomatous inflammation was seen on intraoperative pathology. On final pathology, the parotid gland showed multiple granulomas with central cavitation and palisading histiocytes with eosinophilic intracytoplasmic and extracellular crystalloids. The crystalloids were variably shaped, needle-like, polyhedral, rhomboid, rectangular and irregular, nonpolarizable, nonbirefringent, and nonrefractile and were orange-red with trichrome and bluish-purple with Brown and Brenn stain. Remnants of a duct lining within the lesion suggested a granulomatous response to ruptured cyst contents releasing secretions supersaturated in proteins and their precipitates.
Activity Restriction Increases Deoxypyridinoline Excretion in Hospitalized High-Risk Pregnant Women
Authors: Vanderspank Dana , Bernier Suzanne M. , Sopper Maggie M. , Watson Patricia , Mottola Michelle F.
Published: October 2012

Purpose:

Activity restriction (AR), one of the most common interventions used in high-risk pregnancies, may exacerbate loss of bone mass. The purpose of this study was to determine changes over time in bone resorption in hospitalized AR women during late pregnancy.

Methods:

This was a short-term prospective study conducted in two tertiary-care obstetric hospitals. We measured urinary deoxypyridinoline (Dpd) excretion, a marker of bone resorption, once per week in a convenience sample of 14 hospitalized AR women in the third trimester and compared values at 28–31 and 34–36 weeks’ gestation to those of 11 ambulatory control women. Both groups completed a bone-loading questionnaire, 3-day food intake record, and pedometer step counts at the same gestational age.

Results:

Urinary Dpd excretion increased from Days 1–7 (2.60 ± 0.32 nmol/mmol creatinine) to Days 22–28 (5.36 ± 0.83 nmol/mmol creatinine; p ≤ .05). Dpd excretion was higher in AR women (4.51 ± 0.31 nmol/mmol creatinine) than ambulatory women (2.72 ± 0.39 nmol/mmol creatinine) at 34–36 weeks’ gestation ( p ≤ .05). Energy intake between ambulatory and AR women was not different ( p ≥ .05). All women met the daily requirements for calcium and vitamin D intake during pregnancy. Average daily pedometer steps for the AR women were significantly less compared to controls (1,329 ± 936 and 8,024 ± 1,890 steps/day, respectively; p ≤ .05).

Conclusions:

AR leads to increased bone resorption in hospitalized pregnant women, which may impact future risk of developing osteopenia and osteoporosis.
How salient is Europe? An analysis of European election manifestos, 1979–2004
Authors: Spoon Jae-Jae
Published: October 2012

What determines how ‘European’ a party’s manifesto is? This article examines the salience of European issues in national parties’ Euromanifestos during the 1979–2004 period. I argue that domestic politics, including voter, party, and party system factors, influence the European content of a party’s Euromanifesto. Using data from the Euromanifestos Project for 14 member states, I find that the differential emphasis on European issues in the national party system, intra-party dissent on European integration, voter ambivalence on membership of the European Union, and party type all influence the salience of European issues in a party’s manifesto. These findings have important implications for understanding both how parties use manifestos to manipulate the political agenda and the dimensions of contestation in elections to the European Parliament.
In Ireland ‘Latin Americans are kind of cool’: Evaluating a national context of reception with a transnational lens
Authors: Marrow Helen B
Published: October 2012

In this article, I analyze how government policies and social reception shaped Latin Americans’ patterns of incorporation and identity formation in Ireland, a new immigrant destination country in Europe where Latin American migrants lack both historical presence and (neo)colonial linkages, in the early 2000s. I show that Latin Americans in Ireland perceived a weaker form of racialization, not only than several other immigrant, refugee and racial groups there, but also than Latin Americans going to the USA, Spain, and (for Brazilians) Portugal. I then argue that these results illustrate how many Latin American migrants are now embedded within a transnational social field that connects flows of people and ideas across several different receiving countries – both traditional and new – which in turn shapes their relative evaluations of individual national receiving ‘contexts of reception’. I conclude by examining the implications of these results for immigration and Latino Studies scholarship.
Engaging with money in a northern periphery of early modern Europe
Authors: Herva Vesa-Pekka , Nurmi Risto , Symonds James
Published: October 2012

While contextual and interpretive approaches to money have recently emerged in archaeology, coins have attracted little serious attention in the post-medieval archaeology of the western world. The relative neglect of coins as archaeological finds probably derives from an (implicit) assumption that the function and meaning of coins is readily apparent.

A close study of coin finds, however, combined with various sources of contextual data, can provide new views on how people understood and engaged with coinage even in the comparatively recent past, as this article seeks to illustrate by considering money and coin finds from a northern periphery of early modern Sweden. Economic factors are important for appreciating the significance of coinage and the patterning of the studied coin finds, but this article proposes that non-monetary uses of coins were more important to the local understanding of money than has previously been recognized.
When science alone is not enough: Radiocarbon timescales, history, ethnography and elite settlements in southern Africa
Authors: Chirikure Shadreck , Manyanga Munyaradzi , Pollard A. Mark
Published: October 2012

The southern African recent past is replete with examples of elite settlements, some of which were occupied sequentially, and by different rulers. Shona, Venda and Tswana traditions identify the many dry stone walled capitals with former kings who ruled during different reigns. This historical reality is often not factored when considering the issues of political centres and urbanism in the Iron Age. The resolution of radiocarbon dating produces an aggregate time that conflates the chronology of capitals or elite centres when they may not have been contemporary – ‘the suck in and smear’ phenomenon described by Baillie (1991) . This article combines historical and archaeological information to develop an alternative explanation for the existence of hundreds of elite Zimbabwe settlements, some of which were synchronous according to the radiocarbon chronology. The main indication is that rather than suffering from a glut of elites, southern African urban and political centres are associated with individual leaders of competing polities which may not have been part of unified hierarchical and sequential structures. The archaeology of the region stands to benefit from understanding the dynamics of politics, power and leadership in this way.
Growing up in rural Galilee, Palestine: memories of childhood geographies
Authors: Falah Ghazi-Walid
Published: October 2012

This paper reconstructs the author’s geographies of childhood growing up as a Palestinian in a small village in the Galilee in the early 1950s. It seeks to narrate his experience as a ‘shepherd boy and a schoolboy’ at a certain phase of his life. This type of duality in performance of tasks in everyday life – being a schoolboy but also a shepherd/goatherd contributing to the family’s work, and the maintenance of the household and home from a young age – is presented as a revealing experiential autoethnographic window. It becomes a prism for exploring spatial memory and attachment, and for reading a place and understanding what such places mean to their indigenous inhabitants and occupiers (i.e. people are not ‘thrown’ into places but they make them). The paper further demonstrates that indigenous attachment by individuals to their home place can be a catalyst for political resistance and directly challenge forces emanating from state ideology, as illustrated here in the case of Palestine. Today, as 60 years ago, Palestinian ‘homes’ are seen by Palestinians who are challenging Israeli policies of uprooting on a daily basis as sites impregnated with distinctive existential qualities and a high level of resistance. Such places and spaces acquire substantial new meaning for their indigenous owners who are compelled to dare to protect and guard them.
Hyperglycaemia in acute lacunar stroke: A Chinese hospital-based study
Authors: Fang Yuan , Zhang Shihong , Wu Bo , Liu Ming
Published: October 2012

Admission hyperglycaemia is very common in acute ischaemic stroke (IS) patients and is associated with worse outcome in non-lacunar infarction, but its association with lacunar infarction remains controversial. We investigated the association between hyperglycaemia and clinical outcome in patients with acute lacunar stroke in a hospitalised Chinese population. Consecutive patients with acute IS were enrolled and classified into lacunar and non-lacunar stroke groups based on clinical criteria according to the Oxfordshire Community Stroke Project (OCSP) and findings on brain computed tomography (CT) or magnetic resonance imaging (MRI) scan. Hyperglycaemia was defined as blood glucose > 6.1 mmol/L. Univariate and multivariate analyses were used to examine the association between hyperglycaemia and outcomes in diabetic and non-diabetic groups. The main outcome measure was a poor outcome [defined as modified Rankin Scale (mRS) score ≥ 3] at 12 months after stroke. Of the 2020 acute ISs, 689 (34.1%) were acute lacunar strokes, of which 159 (23%) were diabetic and the other 530 (77%) were non-diabetic. In non-lacunar stroke, admission hyperglycaemia was independently associated with increased risk of poor outcome at 1 year (odds ratio (OR) = 1.782; 95% confidence interval (CI) = 1.340–2.370, p = 0.0005). In lacunar stroke, hyperglycaemia was not associated with functional outcome (OR = 1.337; 95% CI = 0.939–1.093, p = 0.086) irrespective of the diabetic status.
Systems Theory and Thinking as a Foundational Theory in Human Resource Development—A Myth or Reality?
Authors: Yawson Robert M.
Published: October 2012

This study reviews systems theory and thinking (ST&T) as a foundational discipline or theory in human resource development (HRD) research and practice. Using systematic evidence review (SER) of the literature and mapping analysis of HRD curricula across some leading U.S. universities, disconnect between theory and practice of ST&T is discussed. The use of SER of the literature in HRD research is an important aspect of this study. The study recommended the incorporation of more ST&T courses into the HRD undergraduate and graduate curricula. Recommendations of how systems thinking can become more relevant to HRD research and practice are offered.
Traumatic Nonanastomotic Pseudoaneurysm of Axillofemoral Bypass Graft
Authors: Mousa Albeir Y. , Nanjundappa Aravinda , Abu-Halimah Shadi , AbuRahma Ali F.
Published: October 2012

Traumatic nonanastomtic disruption of an axillofemoral bypass graft (AFBG) is a relatively rare entity. However, we are reporting on an 82-year-old female who presented with a pulsating mass on her left side, which was noticed about 2 weeks after she fell on her side. The patient had undergone an ABFG about 15 years earlier for limb revascularization, and she had an occluded aortobifemoral bypass graft. A diagnosis of localized rupture with pseudoaneurysm (PSA) was confirmed with arterial duplex ultrasound and computed tomograph (CT) angiogram scans. A 7-cm PSA with partial disruption of the polytetrafluoroethylene (PTFE) graft at the level of the fifth thoracic vertebrae was noted. An initial work-up to eliminate the possibility of sepsis and localized mycotic seeding was negative. The patient was taken to the hybrid angiogram room, and a percutaneous cut down of the AFBG was performed with local dissection below the site of rupture. A limited angiogram showed a focal PSA of the AFBG. An intravascular ultrasound (IVUS) was performed to calibrate the diameter of the AFBG, and a covered stent was deployed across the area of the disrupted graft. A completion angiogram showed complete exclusion of the PSA with good runoff throughout the graft. The authors will review the management of the traumatic PSA with an endovascular approach.
A Mycobacterium bovis Mycotic Abdominal Aortic Aneurysm Resulting From Bladder Cancer Treatment, Resection, and Reconstruction With a Cryopreserved Aortic Graft
Authors: Psoinos Charles M. , Simons Jessica P. , Baril Donald T , Robinson William P. , Schanzer Andres
Published: October 2012

Mycotic abdominal aortic aneurysms (AAAs) are a clinical challenge for vascular surgeons due to their critical location, surrounding inflammation, risk of rupture, and danger of reinfection following treatment. We present a case of Mycobacterium bovis AAA in a 69-year-old male after treatment with intravesicular bacillus Calmette-Guérin (BCG) therapy for bladder carcinoma. The classical approach for mycotic AAA entails extra-anatomic reconstruction followed by resection with oversewing of the proximal and distal aortic stumps. Alternative in-line reconstruction options have also been advocated. This case illustrates a technically straightforward, durable, in-line repair within an infected field utilizing cryopreserved aortic allograft.
Testing Psychometric Properties and the Cross-Ethnic Construct Validity of the Risk and Resiliency Checkup
Authors: Lee Sei-Young
Published: October 2012

The psychometric properties of the risk and resiliency checkup (RRC) were examined in a sample of 2,835 youth offenders. Solid evidence for internal consistency and convergent validity were demonstrated by correlations between the RRC subscales and the total scores. Three hypothetical factor models for the RRC were explored: a second-order factor model, a first-order 2-factor model without covariance, and a first-order 2-factor model with covariance. The first-order 2-factor model with covariance of the RRC was selected for further analyses. Recognizing that measurement invariance was rarely tested with risk assessments, this study examined the measurement invariance of the RRC model across three ethnic groups. The data supported configural invariance as well as partial metric invariance. This study presents substantial empirical evidence for the construct validity of the RRC across three ethnic groups. However, the first-order 2-factor model for the RRC indicates that risk and protective factors appear to be different dimensions.
Identification of key regulatory pathways of myeloid differentiation using an mESC-based karyotypically normal cell model
Authors: Li Dong , Yang Hong , Nan Hong , Liu Peng , Pang Sulei , Zhao Qian , Karni Rotem , Kamps Mark P. , Xu Yuanfu , Zhou Jiaxi , Wiedmer Therese , Sims Peter J. , Wang Fei
Published: October 2012

Understanding the process of myeloid differentiation offers important insights into both normal and abnormal developmental processes but is limited by the dearth of experimental models. Here we show that myeloid progenitors can be derived from embryonic stem cells, immortalized, and applied to the study of the mechanisms underlying myeloid differentiation. The embryonic stem cell–derived myeloid progenitors, when immortalized with estrogen-regulated Hoxb8 protein, demonstrate normal karyotyping, are genetically tractable, and can be differentiated into functional neutrophils. Using this model, we identified mammalian target of rapamycin complex 1 as a critical regulator of myeloid differentiation. Together, our studies led to a convenient, karyotypically normal, and genetically manipulatable cellular system, which can be used to shed new light on the mechanisms for myeloid differentiation.
Ganjam virus/Nairobi sheep disease virus induces a pro-inflammatory response in infected sheep
Authors: bin Tarif Abid , Lasecka Lidia , Holzer Barbara , Baron Michael D
Published: October 2012

Partly due to climate change, and partly due to changes of human habitat occupation, the impact of tick-borne viruses is increasing. Nairobi sheep disease virus (NSDV) and Ganjam virus (GV) are two names for the same virus, which causes disease in sheep and goats and is currently known to be circulating in India and East Africa. The virus is transmitted by ixodid ticks and causes a severe hemorrhagic disease. We have developed a real-time PCR assay for the virus genome and validated it in a pilot study of the pathogenicity induced by two different isolates of NSDV/GV. One isolate was highly adapted to tissue culture, grew in most cell lines tested, and was essentially apathogenic in sheep. The second isolate appeared to be poorly adapted to cell culture and retained pathogenicity in sheep. The real-time PCR assay for virus easily detected 4 copies or less of the viral genome, and allowed a quantitative measure of the virus in whole blood. Measurement of the changes in cytokine mRNAs showed similar changes to those observed in humans infected by the closely related virus Crimean Congo hemorrhagic fever virus.
dsPIG: a tool to predict imprinted genes from the deep sequencing of whole transcriptomes
Authors: Li Hua , Su Xiao , Gallegos Juan , Lu Yue , Ji Yuan , Molldrem Jeffrey J , Liang Shoudan
Published: October 2012

Background

Dysregulation of imprinted genes, which are expressed in a parent-of-origin-specific manner, plays an important role in various human diseases, such as cancer and behavioral disorder. To date, however, fewer than 100 imprinted genes have been identified in the human genome. The recent availability of high-throughput technology makes it possible to have large-scale prediction of imprinted genes. Here we propose a Bayesian model (dsPIG) to predict imprinted genes on the basis of allelic expression observed in mRNA-Seq data of independent human tissues.

Results

Our model (dsPIG) was capable of identifying imprinted genes with high sensitivity and specificity and a low false discovery rate when the number of sequenced tissue samples was fairly large, according to simulations. By applying dsPIG to the mRNA-Seq data, we predicted 94 imprinted genes in 20 cerebellum samples and 57 imprinted genes in 9 diverse tissue samples with expected low false discovery rates. We also assessed dsPIG using previously validated imprinted and non-imprinted genes. With simulations, we further analyzed how imbalanced allelic expression of non-imprinted genes or different minor allele frequencies affected the predictions of dsPIG. Interestingly, we found that, among biallelically expressed genes, at least 18 genes expressed significantly more transcripts from one allele than the other among different individuals and tissues.

Conclusion

With the prevalence of the mRNA-Seq technology, dsPIG has become a useful tool for analysis of allelic expression and large-scale prediction of imprinted genes. For ease of use, we have set up a web service and also provided an R package for dsPIG athttp://www.shoudanliang.com/dsPIG/.
Balancing selection and genetic drift at major histocompatibility complex class II genes in isolated populations of golden snub-nosed monkey (Rhinopithecus roxellana)
Authors: Luo Mao-Fang , Pan Hui-Juan , Liu Zhi-Jin , Li Ming
Published: October 2012

Background

Small, isolated populations often experience loss of genetic variation due to random genetic drift. Unlike neutral or nearly neutral markers (such as mitochondrial genes or microsatellites), major histocompatibility complex (MHC) genes in these populations may retain high levels of polymorphism due to balancing selection. The relative roles of balancing selection and genetic drift in either small isolated or bottlenecked populations remain controversial. In this study, we examined the mechanisms maintaining polymorphisms of MHC genes in small isolated populations of the endangered golden snub-nosed monkey (Rhinopithecus roxellana) by comparing genetic variation found in MHC and microsatellite loci. There are few studies of this kind conducted on highly endangered primate species.

Results

Two MHC genes were sequenced and sixteen microsatellite loci were genotyped from samples representing three isolated populations. We isolated nineDQA1alleles and sixteenDQB1alleles and validated expression of the alleles. Lowest genetic variation for both MHC and microsatellites was found in the Shennongjia (SNJ) population. Historical balancing selection was revealed at both theDQA1andDQB1loci, as revealed by excess non-synonymous substitutions at antigen binding sites (ABS) and maximum-likelihood-based random-site models. Patterns of microsatellite variation revealed population structure.FSToutlier analysis showed that population differentiation at the two MHC loci was similar to the microsatellite loci.

Conclusions

MHC genes and microsatellite loci showed the same allelic richness pattern with the lowest genetic variation occurring in SNJ, suggesting that genetic drift played a prominent role in these isolated populations. As MHC genes are subject to selective pressures, the maintenance of genetic variation is of particular interest in small, long-isolated populations. The results of this study may contribute to captive breeding and translocation programs for endangered species.
Oocyte-somatic cells interactions, lessons from evolution
Authors: Charlier Cathy , Montfort Jérôme , Chabrol Olivier , Brisard Daphné , Nguyen Thaovi , Le Cam Aurélie , Richard-Parpaillon Laurent , Moreews François , Pontarotti Pierre , Uzbekova Svetlana , Chesnel Franck , Bobe Julien
Published: October 2012

Background

Despite the known importance of somatic cells for oocyte developmental competence acquisition, the overall mechanisms underlying the acquisition of full developmental competence are far from being understood, especially in non-mammalian species. The present work aimed at identifying key molecular signals from somatic origin that would be shared by vertebrates.

Results

Using a parallel transcriptomic analysis in 4 vertebrate species - a teleost fish, an amphibian, and two mammals - at similar key steps of developmental competence acquisition, we identified a large number of species-specific differentially expressed genes and a surprisingly high number of orthologous genes exhibiting similar expression profiles in the 3 tetrapods and in the 4 vertebrates. Among the evolutionary conserved players participating in developmental competence acquisition are genes involved in key processes such as cellular energy metabolism, cell-to-cell communications, and meiosis control. In addition, we report many novel molecular actors from somatic origin that have never been studied in the vertebrate ovary. Interestingly, a significant number of these new players actively participate in Drosophila oogenesis.

Conclusions

Our study provides a comprehensive overview of evolutionary-conserved mechanisms from somatic origin participating in oocyte developmental competence acquisition in 4 vertebrates. Together our results indicate that despite major differences in ovarian follicular structure, some of the key players from somatic origin involved in oocyte developmental competence acquisition would be shared, not only by vertebrates, but also by metazoans. The conservation of these mechanisms during vertebrate evolution further emphasizes the important contribution of the somatic compartment to oocyte quality and paves the way for future investigations aiming at better understanding what makes a good egg.
FK506 biosynthesis is regulated by two positive regulatory elements in Streptomyces tsukubaensis
Authors: Goranovič Dušan , Blažič Marko , Magdevska Vasilka , Horvat Jaka , Kuščer Enej , Polak Tomaž , Santos-Aberturas Javier , Martínez-Castro Miriam , Barreiro Carlos , Mrak Peter , Kopitar Gregor , Kosec Gregor , Fujs Štefan , Martín Juan F , Petković Hrvoje
Published: October 2012

Background

FK506 (Tacrolimus) is an important immunosuppressant, produced by industrial biosynthetic processes using various Streptomyces species. Considering the complex structure of FK506, it is reasonable to expect complex regulatory networks controlling its biosynthesis. Regulatory elements, present in gene clusters can have a profound influence on the final yield of target product and can play an important role in development of industrial bioprocesses.

Results

Three putative regulatory elements, namely fkbR, belonging to the LysR-type family, fkbN, a large ATP-binding regulator of the LuxR family (LAL-type) and allN, a homologue of AsnC family regulatory proteins, were identified in the FK506 gene cluster from Streptomyces tsukubaensis NRRL 18488, a progenitor of industrial strains used for production of FK506. Inactivation of fkbN caused a complete disruption of FK506 biosynthesis, while inactivation of fkbR resulted in about 80% reduction of FK506 yield. No functional role in the regulation of the FK506 gene cluster has been observed for the allN gene. Using RT-PCR and a reporter system based on a chalcone synthase rppA, we demonstrated, that in the wild type as well as in fkbN- and fkbR-inactivated strains, fkbR is transcribed in all stages of cultivation, even before the onset of FK506 production, whereas fkbN expression is initiated approximately with the initiation of FK506 production. Surprisingly, inactivation of fkbN (or fkbR) does not abolish the transcription of the genes in the FK506 gene cluster in general, but may reduce expression of some of the tested biosynthetic genes. Finally, introduction of a second copy of the fkbR or fkbN genes under the control of the strong ermE* promoter into the wild type strain resulted in 30% and 55% of yield improvement, respectively.

Conclusions

Our results clearly demonstrate the positive regulatory role of fkbR and fkbN genes in FK506 biosynthesis in S. tsukubaensis NRRL 18488. We have shown that regulatory mechanisms can differ substantially from other, even apparently closely similar FK506-producing strains, reported in literature. Finally, we have demonstrated the potential of these genetically modified strains of S. tsukubaensis for improving the yield of fermentative processes for production of FK506.
Keratin 8 variants are infrequent in patients with alcohol-related liver cirrhosis and do not associate with development of hepatocellular carcinoma
Authors: Usachov Valentyn , Nahon Pierre , Lunova Mariia , Ziol Marianne , Rufat Pierre , Sutton Angela , Beaugrand Michel , Strnad Pavel
Published: October 2012

Background

Keratins 8/18 (K8/K18) are established hepatoprotective proteins and K8/K18 variants predispose to development and adverse outcome of multiple liver disorders. The importance of K8/K18 in alcoholic liver disease as well as in established cirrhosis remains unknown.

Methods

We analyzed the K8 mutational hot-spots in 261 prospectively followed-up patients with alcoholic cirrhosis (mean follow-up 65 months). PCR-amplified samples were pre-screened by denaturing high-performance liquid chromatography and conspicuous samples were sequenced.

Results

67 patients developed hepatocellular carcinoma (HCC) and 133 died. Fourteen patients harbored amino-acid-altering K8 variants (5xG62C, 8xR341H). The presence of K8 variants did not associate with development of HCC (log-rank=0.5) or death (log-rank=0.7) and no significant associations were obtained for the single K8 variants after a correction for multiple testing was performed.

Conclusions

Keratin variants are expressed in a low percentage of patients with alcoholic cirrhosis and do not influence HCC development. Further studies conducted in larger prospective cohorts are needed to find out whether presence of K8 R341H variant predispose to non-HCC-related liver mortality.
Carotid intima-media thickness is associated with cognitive deficiency in hypertensive patients with elevated central systolic blood pressure
Authors: Dias Eros da Mota , Giollo Luiz Tadeu , Martinelli Débora Dada , Mazeti Camila , Júnior Heitor Moreno , Vilela-Martin José Fernando , Yugar-Toledo Juan Carlos
Published: October 2012

Background

The role of hypertension in the loss of cognitive function is controversial. Relationships between hypertension and increases in cerebral vascular resistance, diffused lesions and multiple lacunar infarcts of the white matter are well known. Thus, the objectives of this study were: to evaluate the relationship between hypertension and cognitive dysfunction (CD), identify risk factors and determine the association between early markers of vascular disease and CD in hypertensive individuals.

Methods

Two hundred individuals aged between 40 and 80 years old were evaluated in this cross-sectional prospective study. Fifty participants were controls (CT). The remaining 150 hypertensive patients were subdivided into two groups, those with CD (HCD) and those without CD (HNCD). All participants underwent clinical evaluations and biochemical blood tests were performed. CD was investigated using the Mini Mental State Examination (MMSE) following the guidelines for its use in Brazil. The impact of hypertension on the arterial bed was assessed by identifying and measuring changes in the intima-media thickness (IMT) by vascular ultrasonography of the carotid arteries and analyses of the central blood pressure and Augmentation Index by applanation tonometry of the radial artery.

Results

There were no significant differences in the total cholesterol, high-density lipoprotein cholesterol and triglycerides plasma concentrations between the three groups. The serum creatinine and estimated glomerular filtration rate were within normal ranges for all three groups. A significantly lower MMSE score was recorded for the HCD Group compared to the HNCD and CT Groups (p-value < 0.05).

The IMT was significantly different between the HNCD and HCD Groups (p-value = 0.0124). A significant difference in the IMT was also observed between hypertensive patients and the CT Group (p-value < 0.0001). Age, low-density cholesterol, high-density cholesterol, triglycerides and IMT increased the Odds Ratio for cognitive dysfunction.

The central systolic pressure was significantly higher in the HCD and HNCD Groups compared to CT Group (p-value < 0.0001).

Conclusions

Hypertensive patients with CD have changes in the vascular morphology characterized by an increased carotid IMT, enhanced atherosclerotic lipid profile and impaired hemodynamic functional manifested by elevated central systolic blood pressure.
Association of anemia with worsened activities of daily living and health-related quality of life scores derived from the Minimum Data Set in long-term care residents
Authors: Bailey Robert A , Reardon Gregory , Wasserman Michael R , McKenzie R Scott , Hord R Steve
Published: October 2012

Background

Among long-term care (LTC) residents, we explored the association between anemia status and hemoglobin (Hb) level with Activities of Daily Living (ADL) functioning and health-related quality of life (HRQOL).

Methods

Data were derived from the AnalytiCare database, containing laboratory and Minimum Data Set (MDS) reports for 27 LTC facilities in Colorado. Study timeframe was 1/1/07-9/15/08. Patients were selected based on: residence in LTC >90 days, Hb and serum creatinine value within 90 days of the earliest non-admission (index) MDS. From the index MDS, the method of 1) Carpenter et al. [BMC Geriatrics 6:7(2006)] was used to derive a summary measure of ADL performance (the MDS-ADL score) and 2) Wodchis et al. [IJTAHC 19:3(2003)] was used to assign HRQOL scores (MDS items were mapped to the Health Utilities Index Mark 2 (HUI2) scoring function to create the MDS-HSI score). Anemia was defined as Hb <12 g/dL females and <13 g/dL males. Adjusted linear regression was used to evaluate the independent association of anemia and hemoglobin level on MDS-ADL and MDS-HSI scores.

Results

838 residents met all inclusion criteria; 46% of residents were anemic. Mean (SD) MDS-ADL score was 14.9 (7.5) [0–28 scale, where higher score indicates worse functioning]. In the adjusted model, anemia was associated with a significantly worse MDS-ADL score (+1.62 points, P=.001). Residents with Hb levels 10 to <11 g/dL had significantly worse ADL score (+2.06 points, P=.005) than the >13 g/dL reference. The mean MDS-HSI score was 0.431 (0.169) [range, where 0=dead to 1=perfect health]. Compared with non-anemic residents, in this adjusted model, residents with anemia had significantly worse MDS-HSI scores (−0.034 points, P=.005). Residents with hemoglobin levels <10 g/dL had significantly worse MDS-HSI scores (−0.058 points, P=.016) than the >13 g/dL reference.

Conclusions

After adjusting for several covariates, LTC residents with anemia, and many of those with moderate to severe declines in Hb level, had significantly poorer outcomes in both ADL functioning and HRQOL. The association between Hb level and the HRQOL measure of MDS-HSI appears to be largely explained by the mobility domain of the HRQOL measure.
Pool boiling of nanoparticle-modified surface with interlaced wettability
Authors: Hsu Chin-Chi , Su Tsung-Wen , Chen Ping-Hei
Published: October 2012

This study investigated the pool boiling heat transfer under heating surfaces with various interlaced wettability. Nano-silica particles were used as the coating element to vary the interlaced wettability of the surface. The experimental results revealed that when the wettability of a surface is uniform, the critical heat flux increases with the more wettable surface; however, when the wettability of a surface is modified interlacedly, regardless of whether the modified region becomes more hydrophilic or hydrophobic, the critical heat flux is consistently higher than that of the isotropic surface. In addition, this study observed that critical heat flux was higher when the contact angle difference between the plain surface and the modified region was smaller.
Programming of neurotoxic cofactor CXCL-10 in HIV-1-associated dementia: abrogation of CXCL-10-induced neuro-glial toxicity in vitro by PKC activator
Authors: Mehla Rajeev , Bivalkar-Mehla Shalmali , Nagarkatti Mitzi , Chauhan Ashok
Published: October 2012

Background

More than 50% of patients undergoing lifelong suppressive antiviral treatment for HIV-1 infection develop minor HIV-1-associated neurocognitive disorders. Neurological complications during HIV-1 infection are the result of direct neuronal damage by proinflammatory products released from HIV-1-infected or -uninfected activated lymphocytes, monocytes, macrophages, microglia and astrocytes. The specific pro-inflammatory products and their roles in neurotoxicity are far from clear. We investigated proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF) of HIV-demented (HIV-D) and HIV-nondemented (HIV-ND) patients and studied their affect on neuroglial toxicity.

Methods and results

Bioplex array showed elevated levels of signatory chemokines or cytokines (IL-6, IFN-γ, CXCL10, MCP-1 and PDGF) in the CSF of HIV-D patients (n = 7) but not in that of HIV-ND patients (n = 7). Among the signatory cytokines and chemokines, CXCL10 was distinctly upregulated in-vitro in HIV-1 (NLENG1)-activated human fetal astrocytes, HIV-1 (Ba-L)-infected macrophages, and HIV-1 (NLENG1)-infected lymphocytes. Virus-infected macrophages also had increased levels of TNF-α. Consistently, human fetal astrocytes treated with HIV-1 and TNF-α induced the signatory molecules. CXCL10 in combination with HIV-1 synergistically enhanced neuronal toxicity and showed chemotactic activity (~ 40 fold) for activated peripheral blood mononuclear cells (PBMC), suggesting the intersection of signaling events imparted by HIV-1 and CXCL10 after binding to their respective surface receptors, CXCR4 and CXCR3, on neurons. Blocking CXCR3 and its downstream MAP kinase (MAPK) signaling pathway suppressed combined CXCL10 and HIV-1-induced neurotoxicity. Bryostatin, a PKC modulator and suppressor of CXCR4, conferred neuroprotection against combined insult with HIV-1 and CXCL10. Bryostatin also suppressed HIV-1 and CXCL10-induced PBMC chemotaxis. Although, therapeutic targeting of chemokines in brain may have adverse consequences on the host, current findings and earlier evidence suggest that CXCL10 could strongly impede neuroinflammation.

Conclusion

We have demonstrated induction of CXCL10 and other chemokines/cytokines during HIV-1 infection in the brain, as well as synergism of CXCL10 with HIV-1 in neuronal toxicity, which was dampened by bryostatin.
Reduction of porcine circovirus type 2 (PCV2) viremia by a reformulated inactivated chimeric PCV1-2 vaccine-induced humoral and cellular immunity after experimental PCV2 challenge
Authors: Seo Hwi Won , Oh Yeonsu , Han Kiwon , Park Changhoon , Chae Chanhee
Published: October 2012

Background

The objective of the present study was to elucidate the humoral and cellular immune response mechanisms by which a reformulated inactivated chimeric PCV1-2 vaccine reduces the PCV2 viremia. Forty PCV2 seronegative 3-week-old pigs were randomly divided into the following four groups: vaccinated challenged (T01), vaccinated non-challenged (T02), non-vaccinated challenged (T03), and non-vaccinated non-challenged (T04) animals. The pigs in groups T01 and T02 were immunized with a reformulated inactivated chimeric PCV1-2 vaccine (Fostera™ PCV; Pfizer Animal Health) administered as a 2.0 ml dose at 21 days of age. At 35 days of age (0 days post-challenge), the pigs in groups T01 and T03 were inoculated intranasally with 2 ml each of PCV2b.

Results

A reduction of PCV2 viremia coincided with the appearance of both PCV2-specific neutralizing antibodies (NA) and interferon-γ-secreting cells (IFN-γ-SCs) in the vaccinated animals. However, the presence of anti-PCV2 IgG antibodies did not correlate with the reduction of PCV2 viremia. Lymphocyte subset analysis indicated that the numbers of CD3+ and CD4+ cells increased in vaccinated animals but the numbers of CD4+ cells decreased transiently in non-vaccinated animals. The observation of a delayed type hypersensitivity response in only the vaccinated animals also supports a CD4+ cell-associated protective cellular immune response induced by the reformulated inactivated chimeric PCV1-2 vaccine.

Conclusions

The induction of PCV2-specific NA and IFN-γ-SCs, and CD4+ cells by the reformulated inactivated chimeric PCV1-2 vaccine is the important protective immune response leading to reduction of the PCV2 viremia and control of the PCV2 infection. To our knowledge this is the first demonstration of protective humoral and cellular immunity induced by the reformulated inactivated chimeric PCV1-2 vaccine and its effect on reduction of PCV2 viremia by vaccination.
Effects of ionizing radiation in combination with Erufosine on T98G glioblastoma xenograft tumours: a study in NMRI nu/nu mice
Authors: Henke Guido , Meier Verena , Lindner Lars H , Eibl Hansjörg , Bamberg Michael , Belka Claus , Budach Wilfried , Jendrossek Verena
Published: October 2012

Background

Erufosine is a promising anticancer drug that increases the efficacy of radiotherapy in glioblastoma cell lines in vitro. Moreover, treatment of nude mice with repeated intraperitoneal or subcutaneous injections of Erufosine is well tolerated and yields drug concentrations in the brain tissue that are higher than the concentrations required for cytotoxic drug effects on glioblastoma cell lines in vitro.

Methods

In the present study we aimed to evaluate the effects of a combined treatment with radiotherapy and Erufosine on growth and local control of T98G subcutaneous glioblastoma xenograft- tumours in NMRI nu/nu mice.

Results

We show that repeated intraperitoneal injections of Erufosine resulted in a significant drug accumulation in T98G xenograft tumours on NMRI nu/nu mice. Moreover, short-term treatment with 5 intraperitoneal Erufosine injections caused a transient decrease in the growth of T98G tumours without radiotherapy. Furthermore, an increased radiation-induced growth delay of T98G xenograft tumours was observed when fractionated irradiation was combined with short-term Erufosine-treatment. However, no beneficial drug effects on fractionated radiotherapy in terms of local tumour control were observed.

Conclusions

We conclude that short-term treatment with Erufosine is not sufficient to significantly improve local control in combination with radiotherapy in T98G glioblastoma xenograft tumours. Further studies are needed to evaluate efficacy of extended drug treatment schedules.