bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges and Benefits of Contact among Relatives: Morphological Copying
Authors: Mithun Marianne
Published: September 2013

Hierarchies of borrowability typically rank morphology as the most resistant to transfer of all aspects of language. Several explanations have been offered. One is that copying takes place primarily between typologically similar systems, and morphology is one of the ways languages can differ the most. Another is that more tightly integrated structures are more resistant to copying, and morphology is inherently tightly integrated. It has also been pointed out that copying depends on speakers establishing equivalence relations between elements of the languages in contact. Morphology may be less accessible to speaker consciousness than other aspects of language. Insight into contributing factors may come from contact situations involving related languages. Such languages are usually similar typologically. But they also present a major challenge: distinguishing contact effects from common inheritance and drift. Certain favorable circumstances can enhance their potential contributions. Most helpful are established genealogical relationships among the languages, a documented history of contact, morphological complexity, and sound changes diagnostic of copied forms. Examples here are drawn from Tuscarora, a Northern Iroquoian language. The Tuscarora separated from the other Northern Iroquoians early and spent perhaps two millennia in the American Southeast on their own. After they rejoined their relatives in the Northeast, there was close contact and intermarriage for two centuries. The languages share complex but similar morphologies. Extensive copying of forms can be discerned: not only whole words, but also bound stems, roots, and affixes. Functional features of bound forms were copied as well, including semantic extension.
Inherited similarity and contact-induced change in Mayan Languages
Authors: Law Danny
Published: September 2013

Similarity has been cited, generally anecdotally, as a significant factor shaping the outcomes of language contact. A detailed investigation of long-term contact among more than a dozen related Lowland Mayan languages has yielded specific examples of contact-induced language changes that, I argue, were facilitated by the systematic similarities shared by these languages because of genetic relatedness. Three factors that seem to have been particularly relevant in the Mayan case are 1) the high degree of overlap in linguistic structure, which would have allowed significant interlingual conflation, the collapsing of language boundaries at points of similarity between the languages, 2) the paradigmatic interchangeability of particular elements of related languages without the need for adaptation or accommodation, which facilitated the borrowing of various kinds of linguistic material, particularly bound morphemes, that in other contexts have been found to be highly resistant to borrowing, and 3) contact-induced drift, parallel secondary developments in more than one language that were triggered by contact-induced innovations but subsequently proceeded along similar paths of change after contact because of the preexisting structural similarities that the languages shared as a result of their common inheritance. I argue that these processes of change are much less likely, if not impossible, in situations of contact between unrelated languages, and suggest specific ways in which contact between genetically related languages can be qualitatively different from contact between unrelated languages.
Hittite and Hieroglyphic Luvian arha ‘away’: Common Inheritance or Borrowing?
Authors: Craig Melchert H.
Published: September 2013

Yakubovich (2010), in arguing convincingly that Hittite borrowed its enclitic reflexive particle from Luvian, emphasizes that this contact-induced change in the pronominal system was due not only to close and prolonged contact between speakers of the two languages, but also to the structural (in this case genetic) similarity of the respective systems (2010: 197ff.). Most discussion by Yakubovich and others has focused on Luvian influence on Hittite, prehistoric and in the Middle and New Hittite period. While a few lexical borrowings from Hittite into Luvian have been acknowledged, the question of Hittite-induced changes in Luvian grammatical morphemes has received little or no attention. I will argue that the likewise very similar systems of “local adverbs” and “preverbs” in the two languages led to a borrowing from Hittite into Luvian in this set of grammatical morphemes. While fine details assure a borrowing in this case, overall facts make borrowing far less likely in a second case to be considered. The very similarity of the respective systems makes it hard to determine whether the latter represents common inheritance or parallel independent developments possibly made more convergent by contact.
Contact or Inheritance? Criteria for distinguishing internal and external change in genetically related languages
Authors: Pat-El Na’ama
Published: September 2013

Several prominent scholars have recently doubted whether it is possible to differentiate borrowing from internal change, to the point that in some cases subgrouping is not feasible or is restricted (Dench, 2001; Dixon, 2001). Since a situation of prolonged and intense contact between closely related languages is very common, language contact and its results are a major problem if not a real hazard to historical linguistics. The main practical problem is how to differentiate internal changes, changes motivated by internal processes, from external changes, changes due to language contact, when the structure of the languages is so similar. In other words, how do we know which linguistic form is the source of the change: one of the attested languages, or the mother of both of them? In this paper, I suggest two preliminary criteria to isolate the source language in cases of contact: 1) the existence of intermediary stages, and 2) an even spread of the change across categories. I will show, using test cases from the Semitic language family that these criteria can help us distinguish between internal and external changes.
Aspects of Aramaic and Babylonian Linguistic Interaction in First Millennium BC Iraq
Authors: Beaulieu Paul-Alain
Published: September 2013

This article investigates four areas where the influence of Aramaic on the Neo- and Late Babylonian dialects of Akkadian can be detected (8th-3rd centuries BC): the pronominal system, the verbal prefixes, the precative (i.e., jussive) conjugation, and cognate loanwords. In each case Babylonian appears to have replaced native forms with Aramaic equivalents that bore a close morphological, but not necessarily functional similarity to them. Aramaic and Babylonian both belonged to the Semitic family and were in intimate contact for centuries, being spoken and written side by side in the same society. While the changes that occurred in Babylonian can in each instance be analyzed as individual cases of interference and contamination, I propose to view them together as evidence that the close genetic relation between the two languages triggered a process that induced speakers of Babylonian to adopt Aramaic forms in specific cases where morphological similarity between the two languages was the strongest. These changes were highly selective, however, and do not provide evidence for a massive influx of Aramaic on Neo- and Late Babylonian, as has often been argued in the past.
Review of A. B. Nikolaev, Revoliutsiia i vlast’: How Has Nikolaev Changed the Interpretation of the February Revolution?
Authors: Hasegawa Tsuyoshi
Published: September 2013

A.B. Nikolaev’s book has not received much attention either in the West or in Russia, but it is an important book that has significantly changed our understanding the February Revolution of 1917. Nikolaev’s meticulously researched monograph, based on a wide array of new sources, challenges the previously dominant interpretation that the Provisional Committee of the State Duma (Duma Committee) was forced to seize power only to stem the tide of the insurgency from below. He argues that the Duma Committee was from its inception clear about its intention to overthrow the old regime and to create a new power to replace it even before the Petrograd Soviet was formed. The Duma Committee played a crucial role in prompting military units to take the side of the revolution, in steering the insurgents to the State Duma, in creating the Military Commission to organize insurgents to occupy strategic positions in the city, in taking over the food supply commission to feed the insurgents, in attacking and destroying the tsarist police, while preventing and suppressing potentially dangerous anarchical pogroms, and in taking control over the imperial bureaucracy. Nikolaev also raises an interesting question about the relationship between the Duma Committee, the State Duma and the Provisional Government by arguing that the Provisional Government made a hasty and cardinal mistake in cutting its relationship with the State Duma. This book is a landmark in the interpretation of the February Revolution, and especially of the role of the Duma liberals in the revolution.
Reflections on Tsuyoshi Hasegawa’s Review
Authors: Николаев Андрей Борисович
Published: September 2013

This article is a response to Tsuyoshi Hasegawa’s review of Nikolaev’s 2005 book, Revolution and Power: The IV State Duma, 27 February – 3 March 1917. It recounts the history of Nikolaev’s acquaintance with Hasegawa and underscores the importance of Hasegawa’s contributions to the understanding of the February Revolution. The response critically assesses Hasegawa’s interpretation of the February 1917 Revolution, especially his treatment of the role of Duma liberals and his emphasis on mass politics, but only in so far as the interpretation colors Hasegawa’s review of Nikolaev’s book. Nikolaev’s response adds new details to the history of the February Revolution, by showing how, on the evening of 27 February, the 1st Infantry Reserve Regiment joined the revolution. Nikolaev emphasizes that his main ambition is to persuade historians to take a new look at the role of the Duma liberals in February 1917.
From Historicism to Historical Sociology: An Examination of Nikolai Aleksandrovich Rozhkov’s Nomothetic Scheme of Historical Evolution
Authors: Gonzalez John
Published: September 2013

This article takes as its point of departure Thaden’s claim that the paradigm shift from historicism to historical sociology in Russian historiography at the turn of the nineteenth and twentieth century was an abortive one. It demonstrates that Nikolai Aleksandrovich Rozhkov (1868-1927) not only created the first post-Kliuchevskian historical sociology but that he did so using a Comtean nomothetic approach to social evolution. This is the first time that the theoretical underpinnings of Rozhkov’s interpretation of history as encapsulated in his laws of social statics have been explored in any detail. This article draws the conclusion that the positivist tradition created opportunities for cross-fertilization with other major currents of thought, including Marxism, and sheds new light on this relationship.
L. G. Zakharova’s Aleksandr II and the Abolition of Serfdom in Russia and P. A. Zaionchkovskii’s School of Historians
Authors: Hamburg G. M.
Published: September 2013

This essay examines the genesis of Larisa Georgievna Zakharova’s classic book, Aleksandr II and the Abolition of Serfdom in Russia, as a crucial moment in the development of Petr Andreevich Zaionchkovskii’s “school” of imperial Russian historians. The article analyzes the early years of the Zaionchkovskii school and Zakharova’s place in it, her search from 1970 to 1983 for a defensible doctoral dissertation, her book on the abolition of serfdom, and her 1983 doctoral dissertation defense. Using her book as a focal point, the essay identifies the common values that held members of Zaionchkovskii’s school together, but also explores the intellectual disagreements and personal tensions between Zaionchkovskii and Zakharova, his favorite student and hand-picked successor. The article demonstrates that, following Zaionchkovskii’s death in September 1983, Zakharova perpetuated his school by re-fashioning it after her own image and likeness.
ОПЫТ ИСТОРИОГАФИЧЕСКОГО ОСМЫСЛЕНИЯ ПОСЛЕДНИХ ДЕСЯТИЛЕТИЙ
Authors: Павловна Корзун Валентина , Пантелеймонович Мягков Герман
Published: September 2013

This article traces the turn in Russian historical scholarship from the “encounter” that occurred in the 1970s between historiography, the philosophy of science [naukovedenie] and class interest as an explanation for the appearance of scholarly communities of various types, to the creation of and transition to a new model of scholarship in the early twenty-first century oriented on the study of scholarly communities understood from an anthropological perspective. Analysis of various methods of studying schools of historiography in pre-revolutionary Russia enables the authors to identify the heuristic potential of a post-modern concept of a scientific or scholarly “school,” and to identify questions awaiting future research.
A new scoliid wasp in the Early Cretaceous Crato Formation in Brazil (Hymenoptera: Scoliidae)
Authors: NEL AndrÉ , ESCUILLIE François , GARROUSTE Romain
Published: September 2013

The new genus and species of scoliid wasp Araripescolia magnifica Nel, Escuillie & Garrouste, gen. et sp. nov. is described from the Early Cretaceous Crato formation in Brazil. It seems to be more closely related to the modern Campsomerinae than to the other Cretaceous Scoliidae: Archaeoscoliinae and Proscoliinae.
Archeterokrohnia docrickettsae (Chaetognatha: Phragmophora: Heterokrohniidae), a new species of deep-sea arrow worm from the Gulf of California
Authors: THUESEN ERIK V. , HADDOCK STEVEN H.D.
Published: September 2013

A new species of deep-sea chaetognath, Archeterokrohnia docrickettsae n. sp. is described from a single specimen captured by the ROV Doc Ricketts ~2 m above the sea floor at 3245 m depth in the Pescadero Basin of the Gulf of California, Mexico. This is the first record of a living specimen of Archeterokrohnia and the second known occurrence of Archeterokrohnia in the Pacific Ocean. In life, the head and trunk sections were orange, while the tail section was translucent, a unique colour pattern not before seen in chaetognaths. Observations of its swimming behaviour in situ are given. Comparisons are made with the three other species of Archeterokrohnia. At 28.5 mm in length, this is the largest known species of the genus. An artificial key to the four species of Archeterokrohnia is presented.
Dasytes plumbeus (Müller) (Coleoptera: Melyridae: Dasytinae), a Palearctic soft-winged flower beetle new to North America
Authors: HOEBEKE E. RICHARD , WHEELER ALFRED G. JR.
Published: September 2013

Dasytes plumbeus (Müller), a dasytine melyrid beetle native to the Palearctic Region, is newly reported from North America. In 2010 and 2011, specimens from three locations were swept from vegetation and flowers in the greater Vancouver area of British Columbia, Canada. This is the first confirmed record of the species in the New World. Our collections, coupled with Internet images of D. plumbeus found in the Vancouver area, suggest the beetle is established in British Columbia.
Authorship of some polychaete (Annelida) names derived from the works of Renier and Savigny
Authors: MUIR ALEXANDER I. , PETERSEN MARY E.
Published: September 2013

Full citations of animal specific or generic names ultimately derived from unpublished manuscripts should commemorate the work of the person who described the new species as well as the person who eventually validly published the name. We suggest that biologists should use the following authorships when citing these names: Terebella infundibulum Renier in Meneghini, 1847 (now used in the genus Myxicola); Nereis coccinea Renier in Meneghini, 1847 (now used in the genus Lumbrineris); Thalassema scutatum Renier in Ranzani, 1817 (now known as Sternaspis scutata); Polynoe Savigny in Lamarck, 1818. The case of Myxicola infundibulum is further complicated by a possible homonymy, and to avoid confusion we suggest that the name is used for the Myxicola species found in the Adriatic.
Prediction of Seasonal Atlantic Basin Accumulated Cyclone Energy from 1 July
Authors: Klotzbach Philip J.
Published: October 2013

The Tropical Meteorology Project at Colorado State University currently issues seasonal forecasts for Atlantic basin hurricane activity in early April, June, and August. This paper examines the potential for issuing an additional seasonal forecast on 1 July, using a two-predictor forecast model. The two predictors are selected from the ECMWF Interim Re-Analysis (ERA-Interim) and explain over 60% of the cross-validated variance in post–30 June accumulated cyclone energy over the hindcast period from 1979 to 2012. The two predictors selected are May–June-averaged 2-m temperatures in the eastern tropical and subtropical Atlantic along with May–June 200-mb zonal winds in the tropical Indian Ocean. The May–June-averaged 2-m temperatures are shown to strongly correlate with August–October 2-m temperatures in the main development region, while the 200-mb zonal wind flow over the tropical Indian Ocean is shown to strongly correlate with El Niño–Southern Oscillation. In addition, each predictor is shown to correlate significantly with accumulated cyclone energy, both during the hindcast period of 1979–2012 and with an independent period from 1948 to 1978.
Urban Forms and Civic Space in Nineteenth- to Early Twentieth-Century Bangkok and Rangoon
Authors: Moore Elizabeth Howard , Osiri Navanath
Published: September 2013

Buddhist spaces in Bangkok and Rangoon both had long common traditions prior to nineteenth- and early twentieth-century colonial incursions. Top–down central city planning with European designs transformed both cities. While Siamese kings personally initiated civic change that began to widen economic and social interaction of different classes, British models segregated European, Burmese, Indian, and Chinese populations to exacerbate social differences. In addition, the Siamese rulers maintained and enhanced civic spaces of religious compounds while the British occupied the Shwedagon pagoda for military purposes and created spacious gardens for their own use. The article underlines the disparity in the provision of urban forms in central city planning between the royal vision of nation-building developed by King Chulalongkorn and his successor King Vajiravudh and the new capital of Rangoon laid out by colonial engineers where the traditional ritual spaces became the staging ground for nationalist movements. In both cities, urban forms and civic spaces were essential in legitimizing political authority. The article demonstrates the manner in which spatial and visual systems colored the production of civic space to initiate social integration in Bangkok and preamble disintegration in colonial Rangoon.
The death of the Right to Information Bill in Botswana
Authors: Botlhale Emmanuel Kopang , Molefhe Kaelo
Published: October 2013

Adopting a rights-based approach, this paper argues that the right to information is a fundamental human right. Hence, governments are obligated to make information available to citizens by signing Right to Information (RTI) covenants and acts to facilitate the availability of information. The developing world lags behind in this regard and, similarly, Botswana does not have a RTI Act. Efforts to correct this were killed in April 2012 when the RTI bill was rejected. This was a regressive step; hence, Botswana failed the democracy test. Hence, reason must triumph over partisan politics for the bill to be passed. Finally three general lessons emerge from this case; (i) in dominant party systems, legislation reflects the interests of the ruling party; (ii) the need to strengthen parliaments in dominant party systems to entrench democracy; and (iii) the need for non-state actors to lobby and advocate for democracy-enhancing legislation such the RTI act.
Establishment of the Election Commission Library in Nepal
Authors: Prajuli Ramesh , Garner Susan
Published: October 2013

The story of the development of democracy in Nepal, and the probability of the first election under a new constitution, has seen the inauguration of a unique library under the auspices of the Election Commission Nepal (ECN) in Kathmandu. With the assistance of the United Nations Development Programme (UNDP), Australian AID (AusAID), the Australian Electoral Commission (AEC) and USAID through the International Foundation for Electoral Systems (IFES), this library has developed from the foundation up. It has centralized old archives into a new building, developed policies hitherto unfamiliar, trained staff and is actively seeking to broaden its clientele to reaches beyond the city boundary. It is primarily a reference library, but in promoting the ideology of democratic processes in this previous monarchy, it seeks to broaden its influence to outer enclaves.
Group cognitive behavioural therapy and group recreational activity for adults with autism spectrum disorders: A preliminary randomized controlled trial
Authors: Hesselmark Eva , Plenty Stephanie , Bejerot Susanne
Published: October 2013

Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This preliminary randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive behavioural therapy and recreational activity. Both interventions comprised 36 weekly 3-h sessions led by two therapists in groups of 6–8 patients. A total of 68 psychiatric patients with autism spectrum disorders participated in the study. Outcome measures were Quality of Life Inventory, Sense of Coherence Scale, Rosenberg Self-Esteem Scale and an exploratory analysis on measures of psychiatric health. Participants in both treatment conditions reported an increased quality of life at post-treatment ( d = 0.39, p < 0.001), with no difference between interventions. No amelioration of psychiatric symptoms was observed. The dropout rate was lower with cognitive behavioural therapy than with recreational activity, and participants in cognitive behavioural therapy rated themselves as more generally improved, as well as more improved regarding expression of needs and understanding of difficulties. Both interventions appear to be promising treatment options for adults with autism spectrum disorder. The interventions’ similar efficacy may be due to the common elements, structure and group setting. Cognitive behavioural therapy may be additionally beneficial in terms of increasing specific skills and minimizing dropout.
Pioneers in the hills: Early Mesolithic foragers at Šebrn Abri (Istria, Croatia)
Authors: Miracle Preston , Galanidou Nena , Forenbaher Stašo
Published: October 2013

In this paper, we examine the strategies used by early Mesolithic people as they moved into the karstic uplands of north-eastern Istria, Croatia. These strategies are inferred from detailed analyses of the lithic and faunal assemblages from Šebrn, a small upland rock-shelter occupied for a relatively short period of time in the early Holocene. We conclude that Šebrn's lithic assemblages are in technology and typology relatively homogeneous and can be treated as a single unit (related to the Sauveterrian and Epigravettian, sensu lato). The faunal remains, in contrast, reveal a dynamic situation of temporal changes in the scope and focus of activities on site. Drawing on several lines of evidence from the lithic and faunal assemblages, we suggest that the initial use of the site was intermittent and people who pursued a generalized subsistence strategy visited it. With the passage of time and as people learned about upland environments, they turned to a specialized procurement of red deer. Šebrn became part of a settlement system that related lowlands to uplands and the site gained significance in the cultural landscape as people brought to it expectations about what they would do and how long they would stay.
Functional examination of MLH1, MSH2, and MSH6 intronic mutations identified in Danish colorectal cancer patients
Authors: Petersen Sanne M , Dandanell Mette , Rasmussen Lene J , Gerdes Anne-Marie , Krogh Lotte N , Bernstein Inge , Okkels Henrik , Wikman Friedrik , Nielsen Finn C , Hansen Thomas v O
Published: October 2013

Background

Germ-line mutations in the DNA mismatch repair genes MLH1, MSH2, and MSH6 predispose to the development of colorectal cancer (Lynch syndrome or hereditary nonpolyposis colorectal cancer). These mutations include disease-causing frame-shift, nonsense, and splicing mutations as well as large genomic rearrangements. However, a large number of mutations, including missense, silent, and intronic variants, are classified as variants of unknown clinical significance.

Methods

Intronic MLH1, MSH2, or MSH6 variants were investigated using in silico prediction tools and mini-gene assay to asses the effect on splicing.

Results

We describe in silico and in vitro characterization of nine intronic MLH1, MSH2, or MSH6 mutations identified in Danish colorectal cancer patients, of which four mutations are novel. The analysis revealed aberrant splicing of five mutations (MLH1 c.588 + 5G > A, MLH1 c.677 + 3A > T, MLH1 c.1732-2A > T, MSH2 c.1276 + 1G > T, and MSH2 c.1662-2A > C), while four mutations had no effect on splicing compared to wild type (MLH1 c.117-34A > T, MLH1 c.1039-8 T > A, MSH2 c.2459-18delT, and MSH6 c.3439-16C > T).

Conclusions

In conclusion, we classify five MLH1/MSH2 mutations as pathogenic, whereas four MLH1/MSH2/MSH6 mutations are classified as neutral. This study supports the notion that in silico prediction tools and mini-gene assays are important for the classification of intronic variants, and thereby crucial for the genetic counseling of patients and their family members.
Antioxidant and pro-oxidant effects of oil palm (Elaeis guineensis) leaves extract in experimental diabetic nephropathy: a duration-dependent outcome
Authors: Varatharajan Rajavel , Sattar Munavvar Zubaid Abdul , Chung Ivy , Abdulla Mahmood Ameen , Kassim Normadiah M , Abdullah Nor Azizan
Published: September 2013

Background

Catechins-rich oil palm (Elaeis guineensis) leaves extract (OPLE) is known to have antioxidant activity. Several polyphenolic compounds reported as antioxidants such as quercetin, catechins and gallic acid have been highlighted to have pro-oxidant activity at high doses. Therefore, the present study was conducted to investigate the antioxidant and pro-oxidant effects of chronically administering high dose of OPLE (1000 mg kg-1) in an animal model of diabetic nephropathy (DN).

Methods

Animal body weight, indexes of glycaemia, renal function and morphology were assessed in diabetic animals with and without OPLE (1000 mg kg-1) for 4 and 12 weeks respectively. Oxidative stress was quantified by measuring levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG), lipid peroxides (LPO) and reduced glutathione (GSH). Transforming growth factor-beta1 (TGF-β1), a key mediator of extracellular matrix accumulation, was analysed in plasma. The mechanisms of OPLE action were evaluated by assessing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits (p22phox and p67phox) expression.

Results

Oral administration with high dose of catechins-rich OPLE (1000 mg kg-1) to STZ-induced diabetic rats for 4 weeks attenuated renal dysfunction (hyperfiltration, proteinuria) and development of glomerulosclerosis and tubulointerstitial fibrosis, features that are associated with DN. Suppression of increases in oxidative stress markers (8-OHdG, LPO) and the fibrotic cytokine, TGF-β1 was observed. OPLE also reduced renal expression of NADPH oxidase subunits p22phox and p67phox. In contrast and surprisingly, identical dose of OPLE when administered to diabetic animals for 12 weeks caused worsening of renal dysfunction, histopathology in addition to further elevation of oxidative stress marker (LPO) and TGF-β1. These unfavourable effects of prolonged treatment with 1000 mg kg-1OPLE were accompanied by increase expression of one of the NADPH oxidase subunits, p22phox.

Conclusion

Our study indicates that chronic administration of 1000 mg kg-1OPLE exerts both antioxidant and pro-oxidant effects in DN depending on the duration of treatment. The present study also reveals that the antioxidant/pro-oxidant effects of OPLE are in part, due to modulation of NADPH activity.
Entada africana fraction CH2Cl2/MEOH 5% inhibits inducible nitric oxide synthase and pro-inflammatory cytokines gene expression induced by lipopolysaccharide in microglia
Authors: Owona Brice Ayissi , Njayou Nico Frederic , Laufer Stefan A , Schluesener Hermann J , Moundipa Paul Fewou
Published: October 2013

Background

Inflammatory response in the CNS mediated by microglia cells play an important role in host defense and is implicated in the pathology of neurodegenerative diseases. We investigated the capacity of Entada africana to protect microglia from inflammatory insults by exploring the effect of the CH2Cl2/MEOH 5% fraction (Ea5) on pro-inflammatory cytokines mRNA expression. Finally, we studied the effect of Ea5 on the inhibition of p38 MAPK Kinase. The results were compared to those obtained with Baicalin, a well reported anti-inflammatory flavonoid.

Methods

Barks from E. africana were harvested in 2010, in the west region of Cameroon. A crude extract was prepared using CH2Cl2/MEOH 1:1 V/V. The crude extract obtained was further fractionated by flash chromatography. A mouse microglia cell line (N9) was stimulated by LPS with or without different concentrations of Baicalin and Ea5. The release of NO was evaluated using the Griess method. The expression of pro-inflammatory cytokines mRNA (TNFα, IL-1β, IL-6) and iNOS/NO were measured by RT- PCR. The inhibition of p38 MAPK Kinase was assessed using ELISA.

Results

We found that Ea5, as well as Baicalin inhibited LPS-induced NO production in a dose dependent manner. Ea5 was most active in term of NO inhibition (87.07%), in comparison to Baicalin (70.85%). The expression of TNFα, IL-1β, IL-6 and iNOS was strongly suppressed by Ea5 in microglia. Ea5 also inhibited the activity of p38MAPK Kinase, up to 30% for the concentrations tested, whereas a prominent inhibition was obtained with Baicalin.

Conclusion

These results suggest that E. africana may contain promising compounds useful for the treatment of diseases cause by over-activation of microglia such as Alzheimer disease and other neurological diseases.
Preference-based Health status in a German outpatient cohort with multiple sclerosis
Authors: Reese Jens Peter , Wienemann Gabriele , John Axel , Linnemann Alexandra , Balzer-Geldsetzer Monika , Mueller Ulrich Otto , Eienbröker Christian , Tackenberg Björn , Dodel Richard
Published: October 2013

Background

To prospectively determine health status and health utility and its predictors in patients with multiple sclerosis (MS).

Methods

A total of 144 MS patients (mean age: 41.0 ±11.3y) with different subtypes (patterns of progression) and severities of MS were recruited in an outpatient university clinic in Germany. Patients completed a questionnaire at baseline (n = 144), 6 months (n = 65) and 12 months (n = 55). Health utilities were assessed using the EuroQol instrument (EQ-5D, EQ VAS). Health status was assessed by several scales (Expanded Disability Severity Scale (EDSS), Modified Fatigue Impact Scale (M-FIS), Functional Assessment of MS (FAMS), Beck Depression Inventory (BDI-II) and Multiple Sclerosis Functional Composite (MSFC)). Additionally, demographic and socioeconomic parameters were assessed. Multivariate linear and logistic regressions were applied to reveal independent predictors of health status.

Results

Health status is substantially diminished in MS patients and the EQ VAS was considerably lower than that of the general German population. No significant change in health-status parameters was observed over a 12-months period. Multivariate analyses revealed M-FIS, BDI-II, MSFC, and EDSS to be significant predictors of reduced health status. Socioeconomic and socio-demographic parameters such as working status, family status, number of household inhabitants, age, and gender did not prove significant in multivariate analyses.

Conclusion

MS considerably impairs patients’ health status. Guidelines aiming to improve self-reported health status should include treatment options for depression and fatigue. Physicians should be aware of depression and fatigue as co-morbidities. Future studies should consider the minimal clinical difference when health status is a primary outcome.
Aromatase inhibitor treatment with an intravaginal device and its effect on pre-ovulatory ovarian follicles in a bovine model
Authors: Yapura Jimena , Mapletoft Reuben J , Pierson Roger A , Singh Jaswant , Adams Gregg P
Published: October 2013

Background

Letrozole, a non-steroidal aromatase inhibitor, prevents the body from producing its own estrogen. The objectives of the present study were to test the hypotheses that letrozole treatment, initiated prior to selection of the preovulatory dominant follicle, will induce the growth of more than one follicle to a pre-ovulatory size, and will delay ovulation.

Methods

Post-pubertal beef heifers were given two luteolytic doses of PGF (12 h apart) and monitored by ultrasonography for ovulation. Five to eight days later, ovarian follicular wave emergence was synchronized by ultrasound-guided transvaginal follicular ablation (Day 0=wave emergence) and a luteolytic dose of PGF was given 60 and 72 h later. On Day 1, heifers were divided randomly into two groups (n=15/group) and an intravaginal device containing 1 g of letrozole or a blank device (control) was inserted. The intravaginal devices were removed on Day 7, or at the time of ovulation, whichever occurred first. Transrectal ultrasonography and blood sample collection were performed daily from the day of ablation to 12 days after subsequent ovulation.

Results

The mean (+/-SEM) interval from device placement to ovulation was longer in letrozole-treated animals compared to controls (6.1+/-0.25 vs 5.1+/-0.26 days, respectively; P<0.01). Single dominant follicles were present in both groups. The day-to-day diameter profiles of the dominant follicles of the ovulatory wave were larger (P<0.05) and the maximum diameters greater in letrozole-treated heifers (14.6+/-0.51 vs 12.4+/-0.53 mm, respectively; P<0.01). The diameter profile of the corpus luteum (CL) that formed after treatment did not differ between groups; however, plasma progesterone concentrations were higher (P<0.01) in heifers treated with letrozole. Estradiol concentrations were reduced following letrozole treatment (P<0.05), although a preovulatory rise of estradiol occurred in both groups.

Conclusions

Administration of letrozole with an intravaginal device during growth of the ovulatory follicle delayed ovulation by 24 h and resulted in the formation of a CL that secreted higher levels of progesterone. A sustained-release intravaginal device may be useful for the development of an aromatase inhibitor-based protocol to control ovulation for herd synchronization and to enhance fertility by increasing circulating progesterone concentrations during the first 7 days post-ovulation in cattle.
The proteases HtrA2/Omi and UCH-L1 regulate TNF-induced necroptosis
Authors: Sosna Justyna , Voigt Susann , Mathieu Sabine , Kabelitz Dieter , Trad Ahmad , Janssen Ottmar , Meyer-Schwesinger Catherine , Schütze Stefan , Adam Dieter
Published: October 2013

Background

In apoptosis, proteolysis by caspases is the primary mechanism for both initiation and execution of programmed cell death (PCD). In contrast, the impact of proteolysis on the regulation and execution of caspase-independent forms of PCD (programmed necrosis, necroptosis) is only marginally understood. Likewise, the identity of the involved proteases has remained largely obscure. Here, we have investigated the impact of proteases in TNF-induced necroptosis.

Results

The serine protease inhibitor TPKC protected from TNF-induced necroptosis in multiple murine and human cells systems whereas inhibitors of metalloproteinases or calpain/cysteine and cathepsin proteases had no effect. A screen for proteins labeled by a fluorescent TPCK derivative in necroptotic cells identified HtrA2/Omi (a serine protease previously implicated in PCD) as a promising candidate. Demonstrating its functional impact, pharmacological inhibition or genetic deletion of HtrA2/Omi protected from TNF-induced necroptosis. Unlike in apoptosis, HtrA2/Omi did not cleave another protease, ubiquitin C-terminal hydrolase (UCH-L1) during TNF-induced necroptosis, but rather induced monoubiquitination indicative for UCH-L1 activation. Correspondingly, pharmacologic or RNA interference-mediated inhibition of UCH-L1 protected from TNF-induced necroptosis. We found that UCH-L1 is a mediator of caspase-independent, non-apoptotic cell death also in diseased kidney podocytes by measuring cleavage of the protein PARP-1, caspase activity, cell death and cell morphology. Indicating a role of TNF in this process, podocytes with stably downregulated UCH-L1 proved resistant to TNF-induced necroptosis.

Conclusions

The proteases HtrA2/Omi and UCH-L1 represent two key components of TNF-induced necroptosis, validating the relevance of proteolysis not only for apoptosis, but also for caspase-independent PCD. Since UCH-L1 clearly contributes to the non-apoptotic death of podocytes, interference with the necroptotic properties of HtrA2/Omi and UCH-L1 may prove beneficial for the treatment of patients, e.g. in kidney failure.
Expression changes of ionic channels in early phase of cultured rat atrial myocytes induced by rapid pacing
Authors: Ji Qiang , Liu Hua , Mei Yunqing , Wang Xisheng , Feng Jing , Ding Wenjun
Published: September 2013

Background

Recent studies have demonstrated that atrial electrical remodeling was an important contributing factor for the occurrence, persistence and maintenance of atrial fibrillation. The expression changes of ionic channels, especially L-type calcium channel and potassium channel Kv4.3, were the important molecular mechanism of atrial electrical remodeling. This study aimed to observe the expression changes of ionic channels in a rapid paced cell model with primary cultured atrial myocytes.

Methods

The primary rat atrial myocytes were cultured, characteristics of the cultured myocytes were observed with light microscope and the cell phenotype was harvested by immunocytochemical stain to detect α-actin. The cellular model of rapid pacing was established with primary cultured atrial myocytes. The expressions of L-type calcium channel α1c and potassium channel Kv4.3 in cultured atrial myocytes were detected by immunocytochemistry, reverse transcription polymerase chain reaction and Western blot after rapid pacing.

Results

The primary rat atrial myocytes were isolated and cultured successfully, and used for following experiment by identification of activity and purity. Cellular model of rapid electrical field pacing was established successfully. There is no significant difference in cell activity after pacing compared to that before pacing by 3-[4, 5-dimethylthiazol-2-y1]-2, 5-diphenytetrazolium bromide assay, and cell degeneration can be observed by transmission electron microscope. The mRNA expression of L-type calcium channel α1c started to reduce after 6 h of rapid pacing and continued to decline as pacing continued. Protein expression changes were paralleled with decreased mRNA expression of the L-type calcium channel α1c. The mRNA expressions of potassium channel Kv4.3 were not altered within the first 6 h, but after 12 h, mRNA expressions were reduced. Longer pacing periods did not further decrease mRNA expression of potassium channel Kv4.3. Protein expression changes were paralleled with decreased mRNA expression of potassium channel Kv4.3.

Conclusions

Rapid paced cultured atrial myocyte model was established utilized primary cultured atrial myocytes and this model can be used for studying the early electrical remodeling in atrial fibrillation. Expressions of L-type calcium channel α1c and potassium channel Kv4.3 were both reduced at different levels in early phase of rapid pacing atrial myocytes. It implicates the occurrence of ionic channel remodeling of atrial myocytes.
Clinical significance of cytogenetic aberrations in bone marrow of patients with diffuse large B-cell lymphoma: prognostic significance and relevance to histologic involvement
Authors: Kim Seon Young , Kim Hyo Jung , Kang Hye Jin , Kim Jin Seok , Eom Hyeon Seok , Kim Tae Min , Yoon Sung-Soo , Suh Cheolwon , Lee Dong Soon ,   Korean Society of Hematology Lymphoma Working Party
Published: October 2013

Background

Although knowledge of the genetics of diffuse large B-cell lymphoma (DLBCL) has been increasing, little is known about the characteristics and prognostic significance of cytogenetic abnormalities and the clinical utility of cytogenetic studies performed on bone marrow (BM) specimens. To investigate the significance of isolated cytogenetic aberrations in the absence of histologic BM involvement, we assessed the implication of cytogenetic staging and prognostic stratification by a retrospective multicenter analysis of newly diagnosed DLBCL patients.

Methods

We analyzed cytogenetic and clinical data from 1585 DLBCL patients whose BM aspirates had been subjected to conventional karyotyping for staging. If available, interphase fluorescence in situ hybridization (FISH) data were also collected from patients.

Results

Histologic BM involvement were found in 259/1585 (16.3%) patients and chromosomal abnormalities were detected in 192 (12.1%) patients (54 patients with single abnormalities and 138 patients with 2 or more abnormalities). Isolated cytogenetic aberrations (2 or more abnormalities) without histologic involvement were found in 21 patients (1.3%). Two or more cytogenetic abnormalities were associated with inferior overall survival (OS) compared with a normal karyotype or single abnormality in both patients with histologic BM involvement (5-year OS, 22.0% vs. 52.7%; P < 0.001) and those without BM involvement (31.8% vs. 66.5%; P < 0.001). This result demonstrated that BM cytogenetic results have a significant prognostic impact that is independent of BM histology. The following abnormalities were most frequently observed: rearrangements involving 14q32, 19q13, 19p13, 1p, 3q27, and 8q24; del(6q); dup(1q); and trisomy 18. In univariate analysis, several specific abnormalities including abnormalities at 16q22-q24, 6p21-p25, 12q22-q24, and -17 were associated with poor prognosis. Multivariate analyses performed for patients who had either chromosomal abnormalities or histologic BM involvement, revealed IPI high risk, ≥ 2 cytogenetic abnormalities, and several specific chromosomal abnormalities, including abnormalities at 19p13, 12q22-q24, 8q24, and 19q13 were significantly associated with a worse prognosis.

Conclusions

We suggest that isolated cytogenetic aberrations can be regarded as BM involvement and cytogenetic evaluation of BM improves staging accuracy along with prognostic information for DLBCL patients.
Long-term survival after intensive care unit discharge in Thailand: a retrospective study
Authors: Luangasanatip Nantasit , Hongsuwan Maliwan , Lubell Yoel , Limmathurotsakul Direk , Teparrukkul Prapit , Chaowarat Sirirat , Day NicholasPJ , Graves Nicholas , Cooper Ben S
Published: October 2013

Introduction

Economic evaluations of interventions in the hospital setting often rely on the estimated long-term impact on patient survival. Estimates of mortality rates and long-term outcomes among patients discharged alive from the intensive care unit (ICU) are lacking from lower- and middle-income countries. This study aimed to assess the long-term survival and life expectancy (LE) amongst post-ICU patients in Thailand, a middle-income country.

Methods

In this retrospective cohort study, data from a regional tertiary hospital in northeast Thailand and the regional death registry were linked and used to assess patient survival time after ICU discharge. Adult ICU patients aged at least 15 years who had been discharged alive from an ICU between 1 January 2004 and 31 December 2005 were included in the study, and the death registry was used to determine deaths occurring in this cohort up to 31st December 2010. These data were used in conjunction with standard mortality life tables to estimate annual mortality and life expectancy.

Results

This analysis included 10,321 ICU patients. During ICU admission, 3,251 patients (31.5%) died. Of 7,070 patients discharged alive, 2,527 (35.7%) were known to have died within the five-year follow-up period, a mortality rate 2.5 times higher than that in the Thai general population (age and sex matched). The mean LE was estimated as 18.3 years compared with 25.2 years in the general population.

Conclusions

Post-ICU patients experienced much higher rates of mortality than members of the general population over the five-year follow-up period, particularly in the first year after discharge. Further work assessing Health Related Quality of Life (HRQOL) in both post-ICU patients and in the general population in developing countries is needed.
Pulse propagation by a capacitive mechanism drives embryonic blood flow
Authors: Anton Halina , Harlepp Sebastien , Ramspacher Caroline , Wu Dave , Monduc Fabien , Bhat Sandeep , Liebling Michael , Paoletti Camille , Charvin Gilles , Freund Jonathan B. , Vermot Julien
Published: October 2013

Pulsatile flow is a universal feature of the blood circulatory system in vertebrates and can lead to diseases when abnormal. In the embryo, blood flow forces stimulate vessel remodeling and stem cell proliferation. At these early stages, when vessels lack muscle cells, the heart is valveless and the Reynolds number (Re) is low, few details are available regarding the mechanisms controlling pulses propagation in the developing vascular network. Making use of the recent advances in optical-tweezing flow probing approaches, fast imaging and elastic-network viscous flow modeling, we investigated the blood-flow mechanics in the zebrafish main artery and show how it modifies the heart pumping input to the network. The movement of blood cells in the embryonic artery suggests that elasticity of the network is an essential factor mediating the flow. Based on these observations, we propose a model for embryonic blood flow where arteries act like a capacitor in a way that reduces heart effort. These results demonstrate that biomechanics is key in controlling early flow propagation and argue that intravascular elasticity has a role in determining embryonic vascular function.
The G protein-coupled receptor GPRC5B contributes to neurogenesis in the developing mouse neocortex
Authors: Kurabayashi Nobuhiro , Nguyen Minh Dang , Sanada Kamon
Published: October 2013

Neural progenitor cells in the developing brain give rise to neurons and glia. Multiple extrinsic signalling molecules and their cognate membrane receptors have been identified to control neural progenitor fate. However, a role for G protein-coupled receptors in cell fate decisions in the brain remains largely putative. Here we show that GPRC5B, which encodes an orphan G protein-coupled receptor, is present in the ventricular surface of cortical progenitors in the mouse developing neocortex and is required for their neuronal differentiation. GPRC5B-depleted progenitors fail to adopt a neuronal fate and ultimately become astrocytes. Furthermore, GPRC5B-mediated signalling is associated with the proper regulation of β-catenin signalling, a pathway crucial for progenitor fate decision. Our study uncovers G protein-coupled receptor signalling in the neuronal fate determination of cortical progenitors.