bluuebunny/crossref_metadata_2025_split huggingface dataset:
Schleiermacher and Otto on religion: a reappraisal
Authors: SMITH A. D. 
Published: August 2008

AbstractAn interpretation of the work of Schleiermacher and Otto recently offered by Andrew Dole, according to which these two thinkers differed over the extent to which religion can be explained naturalistically, and over the sense in which the supernatural can be admitted, is examined and refuted. It is argued that there is no difference between the two thinkers on this issue. It is shown that Schleiermacher's claim that a supernatural event is at the same time a natural event does not invite, but rather forecloses the possibility of, a naturalistic explanation of the event. It is further demonstrated that Otto, like Schleiermacher, denied the existence of supernatural events interpreted as events that infringe the laws of nature.
Role of bioregionalism in Bookmark Biosphere Reserve, Australia
Authors: PFUELLER SHARRON L. 
Published: August 2008

SUMMARYBioregionalism claims that interaction between the biophysical and human components of a region generates place-based environmental and social understanding and concern, which lead to locally shared power and responsibility in cooperative land management and governance. The Man and the Biosphere Programme's Seville Strategy calls for local community participation in a multi-stakeholder ecosystem-based approach to conservation, but it is unclear if tenets of bioregionalism play a role in its implementation. Bookmark Biosphere Reserve (BBR) in Australia has substantially succeeded in scientific research and monitoring, conservation, environmental education and sustainable land-use initiatives. Aspects of bioregionalism (for example recognition of the region's unique identity, local community sense of responsibility, integration of local knowledge, presence of motivated local leaders and cooperative community-based management through a network of groups) have contributed to success. Other crucial factors were funding, technical and scientific information and support from government agencies, leadership from members of state and federal government and from private philanthropic foundations, community capacity-building for sustainable land management and availability of volunteers from outside the region. Nevertheless, conflict arose in relation to governance, originating from the recognized difficulties of reconciling a diversity of allegiances, motivations, management styles and personalities, and resulted in division of BBR into two, one section being managed largely through the private sector and community volunteers, the other (renamed Riverland Biosphere Reserve) coordinated by a committee with more diverse affiliations. Bioregionalism can play a role in biosphere reserves but motivations and resources of external public and private organizations are also vital. Avoiding weaknesses of bioregional approaches requires greater attention to social aspects of environmental management. Governance structures and processes need to be inclusive, flexible and equitable in decision making and access to funds. They should support both agency and community-initiated activities and include conflict resolution mechanisms.
Overexpression of CART in the PVN Increases Food Intake and Weight Gain in Rats
Authors: Smith Kirsty L. , Gardiner James V. , Ward Helen L. , Kong Wing M. , Murphy Kevin G. , Martin Niamh M. , Ghatei Mohammad A. , Bloom Stephen R. 
Published: August 2008

Objective: Cocaine‐ and amphetamine‐regulated transcript (CART) codes for a hypothalamic neuropeptide, CART (55–102), which inhibits food intake. Intracerebroventricular injection of CART (55–102) reduces appetite, but also results in motor abnormalities. More recently, studies have demonstrated that administration of CART directly into the paraventricular nucleus (PVN) increases food intake. To investigate the role of CART in the regulation of energy balance in the PVN, we used recombinant adeno‐associated virus (rAAV) to overexpress CART in the PVN.Methods and Procedures: Male Wistar rats were injected with either rAAV‐encoding CART (rAAV‐CART) or rAAV‐encoding enhanced green fluorescent protein (rAAV‐EGFP) as a control. Food intake and body weight were measured regularly. Animals were fed on normal‐chow diet for the first 93 days of the study. After this point, they were fed on high‐fat diet. Animals were killed 138 days postinjection and blood and tissues were collected for analysis.Results: Overexpression of CART in the PVN resulted in increased cumulative food intake and body weight gain compared with rAAV‐EGFP controls when fed normal chow. These changes became significant at day 65 and 79, respectively and were accentuated on a high‐fat diet. A 4% increase in food intake was observed in rAAV‐CART animals on a normal‐chow diet and a 6% increase when fed a high‐fat diet. At the end of the study, rAAV‐CART‐treated animals had higher circulating leptin concentrations in accord with their higher body weight.Discussion: These data provide further evidence that hypothalamic CART plays an orexigenic role.
PGC-1α induces dynamic protein interactions on the ERRα gene multi-hormone response element nucleosome in kidney cells
Authors: Wang Liangli , Li Yin , Hu Peng , Teng Christina T. 
Published: August 2008

ERR (oestrogen-related receptor)-α modulates the oestrogen signalling pathway and regulates genes participating in the physiological energy balance programme. Oestrogen and PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1α), the master regulator of the energy homoeostasis programme, both regulate the expression of ERRα through the MHRE (multi-hormone response element) of the ERRα gene. Although the molecular mechanism of oestrogen action on ERRα regulation is well characterized, the mechanism of PGC-1α induction is unclear. In this study, we examine chromatin structural changes and protein interactions at the MHRE nucleosome in response to PGC-1α expression in HK2 human kidney cells. We mapped the nucleosome positions of the ERRα gene promoter and examined the changes of histone acetylation in response to PGC-1α expression. The interactions of DNA-binding proteins, ERRα and ERRγ, co-activators {CBP [CREB (cAMP-response-element-binding protein)-binding protein], p300, PCAF (p300/CBP-associated factor)}, co-repressor [RIP140 (receptor-interacting protein of 140 kDa)] and RNA polymerase II at the MHRE nucleosome region were investigated over time before and after PGC-1α expression in the HK2 cells. We found a dynamic cyclic interaction of these proteins shortly after PGC-1α expression and a slower cycling interaction, with fewer proteins involved, 20 h later. By using the siRNA (small interfering RNA) knockdown approach, we discovered that ERRγ was involved in the initial phase, but not in the later phase, of PGC-1α-induced ERRα expression.
An RPE cell line as a useful in vitro model for studying retinoic acid receptor β: expression and affinity
Authors: Pavan Barbara , Dalpiaz Alessandro , Biondi Carla , Nieddu Marzia , De Luca Antonella , Prasad Puttur D. , Paganetto Guglielmo , Favaloro Bartolo 
Published: August 2008

Retinoids mediate their biological effect by interacting with specific nuclear receptors. Of the several known RAR (retinoic acid receptor) subtypes, RAR-β is of particular interest, since its expression is silenced in many cancers and it is believed to be a tumour suppressor. Specific ligands of RAR-β can potentially be used in anti-cancer therapy. In the present study, we have investigated the feasibility of using HRPE cells (human retinal pigment epithelial cells) as an experimental model for characterizing RAR-β–ligand interaction. RT–PCR (reverse transcription–PCR) and Western blot analyses show that HRPE cells specifically express only RAR-β and none of the other receptor subtypes. In addition, we show that the expression of RAR-β increases with increasing passage number of the cells. Interestingly, the increase in RAR-β expression is not associated with telomere shortening, a typical biomarker of cellular senescence. In the present study, we also describe a protocol for characterizing RAR-β–ligand interactions using nuclear extract from late passage HRPE cells as a source of endogenous RAR-β. Using [3H]CD367 as the ligand, RAR-β in HRPE cells showed an affinity of 9.6±0.6 nM and a Bmax of 780±14 fmol/mg of protein. We have confirmed the feasibility of using this assay to detect the interaction of ligands with RAR-β by investigating the ability of certain flavonoids to inhibit the binding of [3H]CD367 to nuclear extracts from HRPE cells. The inhibition constant of the flavonoids for RAR-β was between approx. 1–30 μM, showing that the flavonoids interact with RAR-β with low affinity.
Aerobic interval training reduces cardiovascular risk factors more than a multitreatment approach in overweight adolescents
Authors: Tjønna Arnt E. , Stølen Tomas O. , Bye Anja , Volden Marte , Slørdahl Stig A. , Ødegård Rønnaug , Skogvoll Eirik , Wisløff Ulrik 
Published: August 2008

The aim of the present study was to compare the effects of a multidisciplinary approach (MTG) and aerobic interval training (AIT) on cardiovascular risk factors in overweight adolescents. A total of 62 overweight and obese adolescents from Trøndelag County in Norway, referred to medical treatment at St Olav's Hospital, Trondheim, Norway, were invited to participate. Of these, 54 adolescents (age, 14.0±0.3 years) were randomized to either AIT (4×4 min intervals at 90% of maximal heart rate, each interval separated by 3 min at 70%, twice a week for 3 months) or to MTG (exercise, dietary and psychological advice, twice a month for 12 months). Follow-up testing occurred at 3 and 12 months. V̇O2max (maximal oxygen uptake) increased more after AIT compared with MTG, both at 3 months (11 compared with 0%; P&lt;0.01) and 12 months (12 compared with −1%; P&lt;0.01). AIT enhanced endothelial function compared with MTG at both 3 months (absolute change, 5.1 compared with 3.9%; P&lt;0.01) and 12 months (absolute change, 6.3 compared with 1.0%; P&lt;0.01). AIT was favourable compared with MTG in reducing BMI (body mass index), percentage of fat, MAP (mean arterial blood pressure) and increasing peak oxygen pulse. In addition, AIT induced a more favourable regulation of blood glucose and insulin compared with MTG. In conclusion, the novel findings of the present proof-of-concept study was that 3 months of twice weekly high-intensity exercise sessions reduced several known cardiovascular risk factors in obese adolescents more than that observed after a multitreatment strategy, which was initiated as hospital treatment. Follow-up at 12 months confirmed that AIT improved or maintained these risk factors to a better degree than MTG.
A multicentre phase II clinical experience with the novel aza‐epothilone Ixabepilone (BMS247550) in patients with relapsed or refractory indolent non‐Hodgkin lymphoma and mantle cell lymphoma
Authors: O’Connor Owen A. , Portlock Carol , Moskowitz Craig , Straus David , Hamlin Paul , Stubblefield Michael , Dumetrescu Otila , Colevas A. Dimitrios , Grant Barbara , Zelenetz Andrew 
Published: August 2008

SummaryThe epothilones represent a novel group of microtubule stabilization agents that appear to retain activity even in chemotherapy‐resistant cell lines and animal models. Because of their ability to overcome chemotherapy resistance, we conducted a phase II study of Ixabepilone in patients with indolent non‐Hodgkin lymphoma and mantle cell lymphoma (MCL). Ixabepilone was given at a dose of 25 mg/m2 weekly for three of four consecutive weeks. Patients were required to have received ≤4 prior chemotherapy regimens, with an interval of at least one month since the last treatment, 3 months from prior rituximab, and 7 d from prior steroids, an absolute neutrophil count >1 × 109/l and a platelet count >50 × 109/l. Dose reductions were allowed. The overall response rate in assessable patients was 27% in this otherwise heavily treated population. One patient with chemotherapy‐refractory follicular lymphoma attained a complete remission that lasted approximately 8 months. Three responses were also seen in refractory MCL and one in small lymphocytic lymphoma. The duration of response ranged from 2 to 8 months. Major toxicities included fatigue, myelosuppression and neuropathy. These data suggest that Ixabepilone has activity in chemotherapy‐refractory lymphoma.
Treating TTP/HUS with plasma exchange: a single centre’s 25‐year experience
Authors: Forzley Brian R. , Sontrop Jessica M. , Macnab Jennifer J. , Chen Salina , Clark William F. 
Published: August 2008

SummaryThrombotic thrombocytopenic purpura/Haemolytic uremic syndrome (TTP/HUS) is a thrombotic microangiopathy with a 6‐month mortality rate of 16–29%. The present study described the clinical features, treatment regime and 6‐month all‐cause mortality rate of TTP/HUS patients at the London Health Sciences Centre (LHSC), Canada. Data for this retrospective cohort study were obtained from inpatient and outpatient records for all patients referred for plasma exchange therapy at LHSC, Canada between 1981 and 2006. Patients (n = 110) were categorized as: idiopathic primary (38%) or relapsed (16%), and secondary responsive (30%) or non‐responsive (16%). Mortality data were available for all but three patients. The all‐cause 6‐month mortality rate was 19% overall and was 12% and 26% among idiopathic and secondary TTP/HUS patients, respectively. No mortality events occurred among the 17 idiopathic patients who relapsed. Relapsed patients had the least severe presenting characteristics, the fastest response time, and experienced significant improvement in the severity of clinical features between the first and final presentation. These findings suggest an excellent outcome for relapsed TTP/HUS patients. Patient education, surveillance, and aggressive plasma exchange therapy are hypothesized to improve the likelihood of survival: these hypotheses should be tested in a randomized controlled trial.
Hb Southern Italy: coexistence of two missence mutations (the Hb Sun Prairie α2 130 Ala → Pro and Hb Caserta α2 26 Ala → Thr) in a single HBA2 gene
Authors: Passarello Cristina , Giambona Antonino , Prossomariti Luciano , Ammirabile Massimiliano , Pucci Piero , Renda Disma , Pagano Leonilde , Maggio Aurelio 
Published: August 2008

SummaryThis study describes a new molecular condition in the α2‐globin gene (HBA2) found in six unrelated families from Southern Italy (Campania and Sicily). This new double mutant form of haemoglobin is called Hb Southern Italy and originated from the coexistence of two known mutations occurring in the same globin gene, HBA2 26 G→A (Hb Caserta) and HBA2 130 G→C (Hb Sun Prairie). Hb Sun Prairie was originally observed in Indian patients in either the homozygous state, with severe hemolytic anemia, and in the heterozygous state with microcytosis, or in asymptomatic cases as an α‐thalassemia carrier phenotype. Hb Caserta was observed for the first time in a Casertian family (South Italy) that displayed a slowmigrating haemoglobin upon investigation. We report the clinical phenotype and molecular study of this new double mutant form of haemoglobin in heterozygous and homozygous subjects, as well as in association with α° delectional thalassemia.
Predictors of survival in patients with systemic light‐chain amyloidosis and cardiac involvement initially ineligible for stem cell transplantation and treated with oral melphalan and dexamethasone
Authors: Lebovic D. , Hoffman J. , Levine B. M. , Hassoun H. , Landau H. , Goldsmith Y. , Maurer M. S. , Steingart R. M. , Cohen A. D. , Comenzo R. L. 
Published: August 2008

SummaryThe treatment of systemic light‐chain (AL) amyloidosis with symptomatic cardiac involvement at diagnosis remains a challenge. We report the results of 40 consecutive newly diagnosed AL cardiac patients who were not candidates for stem cell transplant and therefore received monthly oral melphalan and dexamethasone. Median survival was 10·5 months and baseline predictors of survival included gender, troponin I and interventricular septal thickness. The most significant predictor of survival was response to therapy. The haematological response rate was 58% (23/40) with 13% (5/40) complete responses; most responses were noted in <3 cycles. Achievement of a rapid response to therapy extends survival.
Depletion of CD4+CD25+CD127lo regulatory T cells does not increase allergen‐driven T cell activation
Authors: Skrindo I. , Farkas L. , Kvale E. O. , Johansen F.‐E. , Jahnsen F. L. 
Published: August 2008

SummaryBackground
It has been suggested that allergic diseases are caused by defective suppression of allergen‐specific Th2 cells by CD4+CD25+ regulatory T cells. However, such studies have been hampered by the difficulty in distinguishing regulatory T cells from CD25‐expressing activated T cells. Recently, it was shown that conventional T cells expressed high levels of CD127, whereas regulatory T cells were CD127lo, allowing discrimination between these distinct T cell subpopulations.Objective
The aim of this study was to study whether the putative regulatory subset defined as CD4+CD25+CD127lo was involved in grass pollen‐reactive T cell responses.Methods
Peripheral blood mononuclear cells (PBMCs) were obtained from allergic donors and non‐atopic controls out of season. Grass pollen‐induced cytokine production and proliferation were compared in cultures of undepleted cells and cells depleted of CD4+CD25+, CD4+CD25+CD127hi or CD4+CD25+CD127lo T cells.Results
Undepleted cell cultures from allergic patients showed significantly increased proliferation and Th2 cytokine production compared with non‐atopic controls. Depletion of all CD25+ T cells did not increase cytokine production or proliferation, and more importantly, no increase in Th2 cytokine production or proliferation was observed in cell cultures depleted of CD4+CD25+CD127lo cells (putative regulatory T cells) compared with undepleted PBMCs in both the allergic and the non‐atopic group.Conclusion
Our study showed that T cells from grass pollen‐allergic patients and non‐atopic controls responded very differently to grass pollen extract, but this difference could not be explained by differences in regulatory T cell function. Further studies are needed to understand the importance of regulatory T cells in allergy.
Thyroid function and the natural history of depression: findings from the Caerphilly Prospective Study (CaPS) and a meta‐analysis
Authors: Williams M. D. , Harris R. , Dayan C. M. , Evans J. , Gallacher J , Ben‐Shlomo Y. 
Published: August 2008

SummaryObjective   Low thyroid function has been associated with depression in clinical populations. We have examined whether thyroid function in the normal range is associated with minor psychiatric morbidity.Design   Prospective cohort study of 2269 middle aged men (45–59 years) with thyroid function (total T4 only, TSH unavailable) measured between 1979 and 1983 and with repeat measures of minor psychiatric morbidity (GHQ‐30) over a mean of 12·3 years follow‐up. We also undertook a systematic review and meta‐analysis of population‐based studies examining thyroid function and mood.Results   There was a positive association between total T4 and chronic psychiatric morbidity (odds ratio 1·21, 95% CI 1·02–1·43, P= 0·03), but this was consistent with chance after adjusting for social class, alcohol and smoking behaviours. The association with incident and recovery from psychiatric morbidity was weaker and consistent with chance.We identified seven eligible studies, from our systematic review and included six studies, including our own, in a meta‐analysis. The pooled estimate showed a positive association (odds ratio 1·12, 95% CI 1·02–1·22, P‐value = 0·01) between depression and T4 and an inverse association with TSH (odds ratio 0·92, 95% CI 0·88–0·97, P= 0·0007) with no evidence of heterogeneity or publication bias.Conclusion   The results from CaPS and our meta‐analysis are consistent and suggest that, if anything, higher levels of thyroxine in the normal range are associated with increased risk of depression. The effects of thyroid hormone on mood may differ in normal populations and patients with clinical thyroid dysfunction.
Polymorphisms of the SHBG gene contribute to the interindividual variation of sex steroid hormone blood levels in young, middle‐aged and elderly men
Authors: Vanbillemont Griet , Bogaert Veerle , De Bacquer Dirk , Lapauw Bruno , Goemaere Stefan , Toye Kaatje , Van Steen Kristel , Taes Youri , Kaufman Jean‐Marc 
Published: August 2008

Summary
Objective  In men there is a large interindividual variation of SHBG levels and consequently of testosterone (T) and E2 levels. Family and twin studies suggested a strong genetic contribution, besides metabolic and hormonal influences. The aim of this study was to examine the influence of a missense mutation in exon 8 (Asp327Asn) and a (TAAAA)n‐repeat in the promoter region of the SHBG gene, on SHBG and sex steroid serum concentrations in a population of healthy men.
Design  SHBG and hormone levels were measured in 1485 men, contributed by three independent cohort studies and representing three different age groups (young, middle‐aged and elderly men). The number of TAAAA‐repeats was determined by fragment‐analysis; carriers of the Asn327‐allele were identified using restriction fragment length polymorphism analysis.
Results  In the different age groups, carriers of six TAAAA‐repeats presented with higher SHBG (young 19%, middle‐aged 20% and elderly 26%; P < 0·001) and T (young 9%, middle‐aged 22% and elderly 21%; P < 0·05) levels compared to non‐carriers. For free T, a modest increase was found for carriers in the middle‐aged group, but not for the young and elderly group. E2 and free E2 did not differ between carriers and non‐carriers in the different age‐groups. The Asn327‐allele was associated with higher mean SHBG (14·20%, P < 0·001) and T levels (7·33%; P = 0·01) in the middle‐aged group only.
Conclusions  Our findings show that and the (TAAAA)n‐repeat and the Asp327Asn polymorphism contribute to the genetically determined interindividual variation in total serum T levels in healthy men through variation in SHBG concentrations.
Expanding clinical spectrum of non‐autoimmune hyperthyroidism due to an activating germline mutation, p.M453T, in the thyrotropin receptor gene
Authors: Supornsilchai Vichit , Sahakitrungruang Taninee , Wongjitrat Nattakarn , Wacharasindhu Suttipong , Suphapeetiporn Kanya , Shotelersuk Vorasuk 
Published: August 2008

SummaryObjective  To describe clinical and genetic features of a Thai family with non‐autoimmune hyperthyroidism (NAH) caused by an activating germline mutation in the thyrotropin receptor (TSHR) gene.Patients  Three affected individuals from the same family (a father and his two children) were studied. Clinical and imaging findings were reviewed and compared.Genetic analysis  Genomic DNA was extracted from peripheral blood leukocytes and mutation analysis of the entire coding sequence of the TSHR gene was performed in both children and their parents by direct DNA sequencing.Results  A heterozygous germline T to C transition in exon 10 of the TSHR gene (c.1358T→C) resulting in the substitution of methionine (ATG) by threonine (ACG) at codon 453 (p.M453T) was identified in the father and his two children. They presented with different clinical severity and variable age of onset. In addition to hyperthyroidism, ventriculomegaly and bilateral shortening of the fifth metacarpal bones and the middle phalanges of the fifth fingers were consistently found in all affected individuals.Conclusions  Ventriculomegaly and bilateral shortening of the fifth metacarpal bones and the middle phalanges of the fifth fingers might be characteristic features of NAH because of an activating TSHR germline mutation. In addition, the shortening of the middle phalanges of the fifth fingers has never been previously described, expanding the phenotypic spectrum of the disease.