bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a rectal sexually transmitted infection – HIV coinfection model utilizing Chlamydia trachomatis and SHIVSF162p3
Authors: Henning Tara , Butler Katherine , Mitchell James , Ellis Shanon , Deyounks Frank , Farshy Carol , Phillips Christi , Papp John , Patton Dorothy , Caldwell Harlan , Sturdevant Gail , McNicholl Janet , Kersh Ellen 
Published: January 2014

AbstractBackgroundRectal sexually transmitted infections (STIs) may increase HIV susceptibility in men who have sex with men (MSM), and Chlamydia trachomatis is prevalent among HIV‐positive MSM. To study STIs and HIV infection in MSM, we first evaluated whether cynomolgus macaques can sustain both C. trachomatis and SHIVSF162p3 infections.MethodsFour SHIVSF162p3‐positive male cynomolgus macaques were used (n = 3 rectally inoculated with 106 IFU; n = 1 control). Systemic and rectal SHIV RNA levels and cytokines were measured by real‐time PCR and Luminex assays, respectively.ResultsMacaques were successfully Chlamydia infected. Rectal SHIV shedding (P = 0.02 χ2) and levels of G‐CSF, IL‐1ra, IL‐6, IL‐8, IFN‐γ, and TNF‐α (P ≤ 0.01, Mann–Whitney) in rectal secretions increased following infection.ConclusionsThese pilot data successfully demonstrate rectal C. trachomatis–SHIV coinfection in cynomolgus macaques and suggest the feasibility of a rectal C. trachomatis model for SHIV susceptibility and biomedical prevention studies in the context of rectal STIs.
The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism
Authors: Cisternas Pedro , Silva‐Alvarez Carmen , Martínez Fernando , Fernandez Emilio , Ferrada Luciano , Oyarce Karina , Salazar Katterine , Bolaños Juan P. , Nualart Francisco 
Published: January 2014

AbstractVitamin C is an essential factor for neuronal function and survival, existing in two redox states, ascorbic acid (AA), and its oxidized form, dehydroascorbic acid (DHA). Here, we show uptake of both AA and DHA by primary cultures of rat brain cortical neurons. Moreover, we show that most intracellular AA was rapidly oxidized to DHA. Intracellular DHA induced a rapid and dramatic decrease in reduced glutathione that was immediately followed by a spontaneous recovery. This transient decrease in glutathione oxidation was preceded by an increase in the rate of glucose oxidation through the pentose phosphate pathway (PPP), and a concomitant decrease in glucose oxidation through glycolysis. DHA stimulated the activity of glucose‐6‐phosphate dehydrogenase, the rate‐limiting enzyme of the PPP. Furthermore, we found that DHA stimulated the rate of lactate uptake by neurons in a time‐ and dose‐dependent manner. Thus, DHA is a novel modulator of neuronal energy metabolism by facilitating the utilization of glucose through the PPP for antioxidant purposes.
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We proposed that the ascorbic acid (AA) taken up by neurons is rapidly oxidized to dehydroascorbic acid (DHA), which inhibits glycolysis and activates the pentose phosphate pathway (PPP), consequently producing NADPH, a critical antioxidant in the recycling of oxidized glutathione (GSSG). In these metabolic conditions, neurons increase lactate uptake, probably using it as an energy source. This data supported the idea that DHA could play a critical role in the modulation of energy metabolism in neurons.
Characterisation of the cytokine milieu associated with the up‐regulation of IL‐6 and suppressor of cytokine 3 in chronic hepatitis C treatment non‐responders
Authors: Martinez Danica , Palmer Clovis , Simar David , Cameron Barbara A. , Nguyen Nam , Aggarwal Vipul , Lloyd Andrew R. , Zekry Amany 
Published: January 2014

AbstractBackground & AimsIn chronic hepatitis C virus infection (CHC), expression of suppressor of cytokine signalling‐3 (SOCS3) has been shown to be associated with obesity and non‐response to antiviral therapy. In this study, we aimed to determine the effect of SOCS3 induction on the cytokine response in patients receiving Pegylated interferon (PegIFN) and ribavirin (RBV) therapy.MethodsPeripheral blood mononuclear cells (PBMC) collected at baseline and at 12 weeks from CHC patients receiving PegIFN/RBV therapy were examined for mRNA and protein SOCS3 expression. Immunological assays were employed to examine cytokine production.ResultsThere was increased expression of SOCS3 in PBMC of non‐responders at week 12 of therapy, when compared to treatment responders (P = 0.0001). The expression of SOCS3 correlated with body mass index (BMI) (r = 0.54; P = 0.01). Patients with low SOCS3 expression at week 12 of therapy had lower HCV‐specific IFN‐γ production in enzyme‐linked immunosorbent spot (ELISpot) assays (P = 0.01), and reduced ex‐vivo production of the anti‐HCV effector cytokines interleukin (IL)‐2 and tumour necrosis factor (TNF)‐α(P = 0.01 and P = 0.04 respectively). Analysis of serum cytokine levels revealed higher levels of IL‐6 at week 12 in the high SOCS3 expression group (P = 0.02) while IL‐6 levels correlated with SOCS3 expression in the entire cohort (P = 0.04). Ex‐vivo studies confirmed that IL‐6 induced SOCS3, and neutralisation of IL‐6 reduced levels of SOCS3.ConclusionIn subjects with increased BMI and non‐response to antiviral therapy, the IL‐6/SOCS3 axis appears to play a crucial role in altering the anti‐HCV‐cytokine response associated with antiviral therapy.
Treatments to slow progression of autosomal dominant polycystic kidney disease: systematic review and meta‐analysis of randomized trials
Authors: Myint Thida M , Rangan Gopi K , Webster Angela C 
Published: January 2014

AbstractAimAutosomal dominant polycystic kidney disease (ADPKD) is a monogenetic disorder that leads to kidney failure. Our aim was to undertake a meta‐analysis of randomized trials of interventions that have been hypothesized to reduce the progression of total kidney volume (TKV) and renal function in ADPKD.MethodsRelevant trials were identified, and outcomes were: change in TKV, total cyst volume (TCV), renal function and adverse events. Meta‐analysis used random effects, with results expressed as mean difference and risk ratio both with 95% confidence intervals (CI).ResultsEleven trials (2262 patients) were included. Compared with placebo, Target of Rapamycin complex 1 (TORC1) inhibitors (5 trials, n = 619), showed no significant change in TKV (P = 0.21), TCV (P = 0.06) or eGFR (P = 0.22). Somatostatin analogues (3 trials, n = 157) reduced TKV by 9% (95% CI −10.33 to −7.58%) but did not alter eGFR. The vasopressin receptor antagonist (n = 1455) attenuated TKV increase to 3%/year (95% CI −3.48 to −2.52) and slowed kidney function decline over a 3‐year period. A single trial (n = 41) of eicosapentaenoic acid did not alter the progression of either TKV (P = 0.9) or renal dysfunction (P = 0.78). Adverse events were significant for interventions in all trials compared with placebo.ConclusionThese data suggest that somatostatin analogues and vasopressin receptor antagonists attenuate TKV increase. The neutral effects of TORC1 inhibitors on TKV could be true, or due to heterogeneity in study population, drug efficacy and follow‐up duration. In the future, further well‐designed and powered trials of longer duration using new biomarkers or therapeutic agents with better tolerance are required.
Strategic patent analysis in plant biotechnology: terpenoid indole alkaloid metabolic engineering as a case study
Authors: Miralpeix Bruna , Sabalza Maite , Twyman Richard M. , Capell Teresa , Christou Paul 
Published: January 2014

SummaryThe do‐it‐yourself patent search is a useful alternative to professional patent analysis particularly in the context of publicly funded projects where funds for IP activities may be limited. As a case study, we analysed patents related to the engineering of terpenoid indole alkaloid (TIA) metabolism in plants. We developed a focused search strategy to remove redundancy and reduce the workload without missing important and relevant patents. This resulted in the identification of approximately 50 key patents associated with TIA metabolic engineering in plants, which could form the basis of a more detailed freedom‐to‐operate analysis. The structural elements of this search strategy could easily be transferred to other contexts, making it a useful generic model for publicly funded research projects.
Regulatory options for genetically modified crops in India
Authors: Choudhary Bhagirath , Gheysen Godelieve , Buysse Jeroen , van der Meer Piet , Burssens Sylvia 
Published: January 2014

SummaryThe introduction of semi‐dwarfing, high‐yielding and nutrients‐responsive crop varieties in the 1960s and 1970s alleviated the suffering of low crop yield, food shortages and epidemics of famine in India and other parts of the Asian continent. Two semi‐dwarfing genes, Rht in wheat and Sd‐1 in rice heralded the green revolution for which Dr. Norman Borlaug was awarded the Nobel Peace Prize in 1970. In contrast, the revolutionary new genetics of crop improvement shamble over formidable obstacles of regulatory delays, political interferences and public misconceptions. India benefited immensely from the green revolution and is now grappling to deal with the nuances of GM crops. The development of GM mustard discontinued prematurely in 2001 and insect‐resistant Bt cotton varieties were successfully approved for commercial cultivation in 2002 in an evolving nature of regulatory system. However, the moratorium on Bt brinjal by MOEF in 2010 meant a considerable detour from an objective, science‐based, rigorous institutional process of regulatory approval to a more subjective, nonscience‐driven, political decision‐making process. This study examines what ails the regulatory system of GM crops in India and the steps that led to the regulatory logjam. Responding to the growing challenges and impediments of existing biosafety regulation, it suggests options that are critical for GM crops to take roots for a multiplier harvest.
Photodecomposition of Chloroform Catalyzed by Unmodified MCM‐41 Mesoporous Silica
Authors: Peña Laura A. , Chan Alissa M. , Cohen Larissa R. , Hou Karen , Harvey Brent M. , Hoggard Patrick E. 
Published: January 2014

AbstractUnactivated MCM‐41 mesoporous silica catalyzes the photodecomposition of chloroform to phosgene and hydrogen chloride under near‐UV (λ > 360 nm) irradiation. The rate of photodecomposition increases toward an asymptotic limit as the O2 partial pressure is increased. Deuterochloroform does not decompose under the same experimental conditions. Low concentrations of both cyclohexane and ethanol quench the photodecomposition, whereas water, up to its solubility limit, does not. Dissolved tetraalkylammonium salts suppress photodecomposition. The data are consistent with a mechanism in which light absorption by an SiO2 defect yields an electron‐deficient oxygen atom, which then abstracts hydrogen from chloroform. The resulting CCl3 radicals react with oxygen to form a peroxy radical that decomposes, eventually yielding phosgene and hydrogen chloride.
miR444a has multiple functions in the rice nitrate‐signaling pathway
Authors: Yan Yongsheng , Wang Huacai , Hamera Sadia , Chen Xiaoying , Fang Rongxiang 
Published: January 2014

SummaryNitrate () is a key signaling molecule in plant metabolism and development, in addition to its role as a nutrient. It has been shown previously in Arabidopsis that ANR1, a MADS‐box transcription factor, is a major component in the ‐signaling pathway that triggers lateral root growth and that miR444, which is specific to monocots, targets four genes that are homologous to ANR1 in rice. Here, we show that miR444a plays multiple roles in the rice ‐signaling pathway – not only in root development, but also involving nitrate accumulation and even Pi‐starvation responses. miR444a overexpression resulted in reduced rice lateral root elongation, but promoted rice primary and adventitious root growth, in a nitrate‐dependent manner. In addition, overexpression of miR444a improved nitrate accumulation and expression of nitrate transporter genes under high nitrate concentration conditions, but reduced the remobilization of nitrate from old leaves to young leaves thus affecting the plant's ability to adapt to nitrogen‐limitating conditions. Intriguingly, we found that Pi starvation strongly induced miR444 accumulation in rice roots and that overexpression of miR444a altered Pi‐starvation‐induced root architecture and enhanced Pi accumulation and expression of three Pi transporter genes. We further provide evidence that miR444a is involved in the interaction between the ‐signaling and Pi‐signaling pathways in rice. Taken together, our observations demonstrated that miR444a plays multiple roles in the rice ‐signaling pathway in nitrate‐dependent root growth, nitrate accumulation and phosphate‐starvation responses.
Auxin biosynthetic gene TAR2 is involved in low nitrogen‐mediated reprogramming of root architecture in Arabidopsis
Authors: Ma Wenying , Li Jingjuan , Qu Baoyuan , He Xue , Zhao Xueqiang , Li Bin , Fu Xiangdong , Tong Yiping 
Published: January 2014

SummaryIn plants, the plasticity of root architecture in response to nitrogen availability largely determines nitrogen acquisition efficiency. One poorly understood root growth response to low nitrogen availability is an observed increase in the number and length of lateral roots (LRs). Here, we show that low nitrogen‐induced Arabidopsis LR growth depends on the function of the auxin biosynthesis gene TAR2 (tryptophan aminotransferase related 2). TAR2 was expressed in the pericycle and the vasculature of the mature root zone near the root tip, and was induced under low nitrogen conditions. In wild type plants, low nitrogen stimulated auxin accumulation in the non‐emerged LR primordia with more than three cell layers and LR emergence. Conversely, these low nitrogen‐mediated auxin accumulation and root growth responses were impaired in the tar2‐c null mutant. Overexpression of TAR2 increased LR numbers under both high and low nitrogen conditions. Our results suggested that TAR2 is required for reprogramming root architecture in response to low nitrogen conditions. This finding suggests a new strategy for improving nitrogen use efficiency through the engineering of TAR2 expression in roots.
Cutaneous involvement in canine leishmaniosis due to Leishmania infantum (syn. L.chagasi)
Authors: Saridomichelakis Manolis N. , Koutinas Alexander F. 
Published: January 2014

BackgroundCanine leishmaniosis, a zoonotic infectious disease caused by Leishmania infantum (syn. L. chagasi), is fairly common in endemic areas, and skin lesions are the most frequent clinical manifestation. Despite the large volume of relevant scientific information, there is a relative paucity of up‐to‐date review articles on the cutaneous manifestations of the disease.Hypothesis/ObjectivesThis review provides current information on the macroscopic and histological skin lesions of dogs with leishmaniosis and comments on their pathogenesis and definitive diagnosis.MethodsPublished articles have been thoroughly reviewed and the retrieved information has been used and supplemented as appropriate with the authors' clinical experience.ResultsThe main clinicopathological presentations of canine leishmaniosis are exfoliative, ulcerative, nodular, sterile pustular and papular dermatitis and nodules at the site of parasite inoculation. Histopathology is usually dominated by mononuclear inflammatory infiltrates; immunohistochemical findings are variable, and Leishmania amastigotes are present in both diseased and normal‐looking skin of dogs with leishmaniosis. Definitive diagnosis of the skin lesions in a dog with leishmaniosis is based on their macroscopic appearance, exclusion of main differentials, histopathology, demonstration of the parasite in the skin and complete response to antileishmanial treatment.Conclusions and clinical importanceCanine leishmaniosis due to L. infantum is characterized by diverse cutaneous manifestations that may reflect different host–parasite relationships. Furthermore, different types of skin lesions may occur, in various combinations, in the same dog. The definitive diagnosis of these lesions is based on clinical and laboratory examinations and on the response to antileishmanial treatment.
Validation of the Canine Atopic Dermatitis Extent and Severity Index (CADESI)‐4, a simplified severity scale for assessing skin lesions of atopic dermatitis in dogs
Authors: Olivry Thierry , Saridomichelakis Manolis , Nuttall Tim , Bensignor Emmanuel , Griffin Craig E. , Hill Peter B. 
Published: January 2014

BackgroundSeverity scales are used to grade skin lesions in clinical trials for treatment of dogs with atopic dermatitis (AD). At this time, only two scales have been validated, namely the Canine Atopic Dermatitis Extent and Severity Index (CADESI)‐3 and the Canine Atopic Dermatitis Lesion Index (CADLI). However, the high number of assessed sites makes the CADESI‐3 impractical.Hypothesis/ObjectivesThe aim of this study was to develop and validate a fourth version of the CADESI that is simpler and quicker to administer.MethodsBody sites, lesions and severity grades were revised by members of the International Committee on Allergic Diseases of Animals (ICADA). The newly designed CADESI‐4 was tested for its validity (i.e. content, construct and criterion), reliability (i.e. inter‐ and intra‐observer reliability and internal consistency), responsiveness (i.e. sensitivity to change) and time to administer. Disease severity benchmarks were chosen using receiver operating characteristic methodology.ResultsThe CADESI‐4 was simplified in comparison to its previous version to comprise 20 body sites typically affected in atopic dogs. Three lesions (erythema, lichenification and alopecia/excoriation) were scored from 0 to 3 at each site. The CADESI‐4 had satisfactory validity, reliability and sensitivity to change. On average, the time to administer a CADESI‐4 was one‐third that of a CADESI‐3. Proposed benchmarks for mild, moderate and severe AD skin lesions are 10, 35 and 60, respectively.Conclusions and clinical importanceThe CADESI‐4 is simpler to use and quicker to administer than its previous version. The ICADA recommends the CADESI‐4 instead of the CADESI‐3 to score skin lesions of AD in dogs enrolled in clinical trials.
Ophraella communa, the ragweed leaf beetle, has successfully landed in Europe: fortunate coincidence or threat?
Authors: Müller‐Schärer H , Lommen S T E , Rossinelli M , Bonini M , Boriani M , Bosio G , Schaffner U 
Published: January 2014

SummaryWe report the occurrence of the North American ragweed leaf beetle Ophraella communa in Europe. During our surveys to monitor populations of the invasive alien plant Ambrosia artemisiifolia in Europe, we found the beetle south of the Alps, in more than 130 sites in southern Switzerland (Ticino) and northern Italy (Lombardia, Piemonte and Emilia‐Romagna). At sites where O. communa was present, up to 100% of the plants were attacked with damage levels high enough to completely defoliate and prevent flowering and seed set of most ragweed plants. That in its first year of discovery, O. communa was already found over a large area of c. 20 000 km2 and in all habitat types occupied by A. artemisiifolia reflects its great dispersal potential and wide habitat suitability. This oligophagous beetle is a successful biological control agent against A. artemisiifolia in China, but despite extensive host specificity tests, the risk of attack and the level of damage of sunflower under field conditions remain unclear. The recently launched COST Action on ‘Sustainable management of Ambrosia artemisiifolia in Europe (SMARTER)’ offers an ideal framework to respond quickly to the recent establishment of O. communa in Europe and to collect data that can help determine whether this event should be considered a troublesome introduction or whether it is likely to become the first case of a successful biological control of an invasive weed in continental Europe.
The combined influence of fat consumption and repeated mental stress on brachial artery flow‐mediated dilatation: a preliminary study
Authors: Poitras Veronica J. , Slattery David J. , Levac Brendan M. , Fergus Stevenson , Gurd Brendon J. , Pyke Kyra E. 
Published: January 2014

New Findings
What is the central question of this study?
Both a high‐fat meal and acute mental stress can impair conduit artery endothelial function. The objective of this study was to determine whether the combination of a high‐fat meal and repeated postprandial stressful tasks would exacerbate dysfunction versus either stimulus alone.
What is the main finding and its importance?
Endothelial function was modestly greater when the postprandial state was accompanied by mental stress. Thus, in healthy subjects acute stress may confer protection from a negative impact of food consumption, possibly due in part to a stress‐induced reduction in plasma phosphorus levels. These findings challenge the position of acute mental stress as universally detrimental to endothelial function.
Experienced separately, both acute mental stress and high‐fat meal consumption can transiently impair endothelial function, and the purpose of the present study was to investigate their combined impact. On four separate days, 10 healthy men (23 years old) underwent brachial artery flow‐mediated dilatation (FMD) tests, before and hourly for 4 h post‐consumption of a high‐fat (HFM; 54 g fat) or low‐fat meal (LFM; 0 g fat; each meal ∼1000 calories), with hourly mental stress (mental arithmetic, speech) or control (counting) tasks (conditions HFM+S, LFM+S, HFM and LFM). Data are presented as means ± SD. Plasma triglycerides increased and remained elevated after the high‐fat but not the low‐fat meal (P = 0.004) and were not affected by mental stress (P = 0.329). Indices of stress reactivity increased during mental stress tasks (mean arterial pressure, ∼∆20 mmHg; heart rate, ∼∆22 beats min−1; salivary cortisol, ∼∆2.37 nmol l−1; and plasma noradrenaline, ∼∆0.17 ng ml−1) and were not influenced by meal (P > 0.05). There was no effect of the type of meal on FMD (P = 0.562); however, FMD was 4.5 ± 0.5% in the control conditions and 5.8 ± 0.6% in the mental stress conditions (P = 0.087), and this difference was significant when normalized for the shear stress stimulus (FMD/area under the curve of shear stress, P = 0.045). Overall, these preliminary data suggest that postprandial FMD was augmented with mental stress irrespective of meal type. These results are contrary to previous reports of impaired endothelial function after mental stress or fat consumption independently and highlight the need to further investigate the mechanisms underlying the interactions between these factors.