bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating optimal β‐cell‐preserving treatment in latent autoimmune diabetes in adults: Results from a 21‐month randomized trial
Authors: Hals Ingrid K. , Fiskvik Fleiner Hanne , Reimers Nina , Astor Marianne C. , Filipsson Karin , Ma Zuheng , Grill Valdemar , Björklund Anneli 
Published: May 2019

AbstractAimsTo compare outcomes of glucagon‐stimulated C‐peptide tests (GSCTs) in people with latent autoimmune diabetes in adults (LADA) after a 21‐month intervention with either insulin or the dipeptidyl peptidase‐4 inhibitor sitagliptin.Research design and methodsWe included 64 glutamic acid decarboxylase (GAD) antibody‐positive individuals, who were diagnosed with diabetes <3 years before the study, aged 30 to 70 years, and without clinical need for insulin treatment. We stratified participants by age and body mass index (BMI) and evaluated β‐cell function by GSCT after a 48‐hour temporary withdrawal of study medication.ResultsAge at randomization (mean 53 years), BMI (mean 27 kg/m2) and metabolic markers were similar between treatment arms. Glycated haemoglobin concentrations during intervention did not differ between arms. Fasting C‐peptide concentrations after the intervention were similar, as were stimulated C‐peptide levels (0.82 ± 0.63 nmol/L after insulin, 0.82 ± 0.46 nmol/L after sitagliptin; nonsignificant). Autoimmunity in the study population (estimated from GAD antibody titres and positivity/no positivity for zinc transporter 8 and islet antigen 2 antibodies) affected the evolution of the GSCT results significantly, which deteriorated in participants with high but not in those with low autoimmunity. Adjustment using analysis of covariance for the degree of autoimmunity did not alter the findings of no difference between treatment arms.Conclusionsβ‐cell function after intervention was similar in patients with insulin‐ and sitagliptin‐treated LADA, regardless of the strength of autoimmunity. Further, participants with low levels of GAD antibodies did not experience progressive deterioration of β‐cell function over a 21‐month period. Taken together, these findings could be useful for clinicians' choices of treatment in people with LADA.
Asymmetric aortic valve is related to development of eccentric aortic regurgitation in patients with tricuspid aortic valve
Authors: Park Tae‐Ho , Kim Soo‐Jin , Cho Young‐Rak , Park Kyungil , Park Jong‐Sung , Kim Moo‐Hyun , Kim Young‐Dae 
Published: May 2019

AbstractBackgroundIt is unclear whether asymmetry itself plays a role in developing eccentric aortic regurgitation (AR) in patients with tricuspid aortic valve (TAV). The aim of this study was to determine whether an asymmetric aortic valve structure may have association with the development of eccentric AR in patients with TAV.MethodsOf the 164 410 patients who underwent echocardiography between January 2006 and January 2018 at Dong‐A University Hospital, 306 (mean age 69.9 ± 12.6 years; 62% men) eccentric AR were identified. After excluding patients with bicuspid and prolapsed AV, 104 patients who had eccentric AR with TAV were enrolled for the study. Comprehensive echocardiographic AV cusp measurements were compared to those of 104 age‐ and gender‐matched control patients with central AR.ResultsIn the eccentric and central AR groups, 66 (63.5%) and 48 patients (46.2%) had asymmetric AV, respectively. Mean cusp height was significantly larger in the eccentric AR group than in the central AR group (1.8 ± 0.3 cm vs 1.7 ± 0.2 cm, P = 0002). Furthermore, the mean cusp area and average asymmetry index of the cusp area were also significantly larger in the eccentric AR group than in the central AR group (2.6 ± 0.8 cm2 vs 2.3 ± 0.6 cm2, P = 0.001, and 7.1 ± 4.5% vs 4.9 ± 2.5%, P < 0.001, respectively).ConclusionAV asymmetry indices of eccentric AR were significantly larger than those of patients with central AR. These data suggest that the presence of asymmetric AV might have association with the development of eccentric AR in patients with TAV.
Occurrence of natural lectin with bacterial agglutination property in the serum of lepidopteran pest, Parasa lepida
Authors: Arumugam Ganesh , Karuppiah Hilda , Sreeramulu Bhuvaragavan , Paulchamy Ramaraj , Sundaram Janarthanan 
Published: May 2019

AbstractInsects depend on lectins for non‐self recognition and clearance of invading pathogens. Naturally occurring lectin showing specificity for galactose was purified from the serum of lepidopteran pest Parasa lepida by affinity chromatography using Sepharose 6B coupled with galactose as a gel matrix. Preliminary studies on crude serum agglutinin revealed that the agglutinin molecule showed varying degrees of specificity to avian and mammalian red blood cells tested. Among them, the highest titer of 128 was recorded against rabbit red blood cell type. The agglutinin molecule in the crude serum was stable up to 60°C and at pH between 6 and 9. Also, the hemagglutinating activity was neither dependent on divalent cations nor sensitive to ethylenediaminetetraacetic acid treatment. Galactose inhibited the hemagglutinating activity at minimum inhibitory concentration of 12.5 mM and hence it was used as a ligand for affinity chromatography. Native polyacrylamide gel electrophoresis analysis revealed a single band and the molecular weight of the lectin was found to be approximately 90 kDa. Bacterial agglutination activity of the purified lectin with two significant toxin bacteria, namely Salmonella typhi and Bacillus thuringiensis, was observed.
Evolution, not transgenerational plasticity, explains the adaptive divergence of acorn ant thermal tolerance across an urban–rural temperature cline
Authors: Martin Ryan A. , Chick Lacy D. , Yilmaz Aaron R. , Diamond Sarah E. 
Published: May 2019

AbstractAlthough studies increasingly disentangle phenotypic plasticity from evolutionary responses to environmental change, few test for transgenerational plasticity in this context. Here, we evaluate whether phenotypic divergence of acorn ants in response to urbanization is driven by transgenerational plasticity rather than evolution. F2 generation worker ants (offspring of laboratory‐born queens) exhibited similar divergence among urban and rural populations as field‐born worker ants, suggesting that evolutionary divergence rather than transgenerational plasticity was primarily responsible for shifts toward higher heat tolerance and diminished cold tolerance in urban acorn ants. Hybrid offspring from matings between urban and rural populations also indicated that evolutionary divergence was likely the primary mechanism underlying population differences in thermal tolerance. Specifically, thermal tolerance traits were not inherited either maternally or paternally in the hybrid pairings as would be expected for strong parental or grandparental effects mediated through a single sex. Urban–rural hybrid offspring provided further insight into the genetic architecture of thermal adaptation. Heat tolerance of hybrids more resembled the urban–urban pure type, whereas cold tolerance of hybrids more resembled the rural–rural pure type. As a consequence, thermal tolerance traits in this system appear to be influenced by dominance rather than being purely additive traits, and heat and cold tolerance might be determined by separate genes. Though transgenerational plasticity does not appear to explain divergence of acorn ant thermal tolerance, its role in divergence of other traits and across other urbanization gradients merits further study.
Experimental warming alters the community composition, diversity, and N2 fixation activity of peat moss (Sphagnum fallax) microbiomes
Authors: Carrell Alyssa A. , Kolton Max , Glass Jennifer B. , Pelletier Dale A. , Warren Melissa J. , Kostka Joel E. , Iversen Colleen M. , Hanson Paul J. , Weston David J. 
Published: May 2019

AbstractSphagnum‐dominated peatlands comprise a globally important pool of soil carbon (C) and are vulnerable to climate change. While peat mosses of the genus Sphagnum are known to harbor diverse microbial communities that mediate C and nitrogen (N) cycling in peatlands, the effects of climate change on Sphagnum microbiome composition and functioning are largely unknown. We investigated the impacts of experimental whole‐ecosystem warming on the Sphagnum moss microbiome, focusing on N2 fixing microorganisms (diazotrophs). To characterize the microbiome response to warming, we performed next‐generation sequencing of small subunit (SSU) rRNA and nitrogenase (nifH) gene amplicons and quantified rates of N2 fixation activity in Sphagnum fallax individuals sampled from experimental enclosures over 2 years in a northern Minnesota, USA bog. The taxonomic diversity of overall microbial communities and diazotroph communities, as well as N2 fixation rates, decreased with warming (p < 0.05). Following warming, diazotrophs shifted from a mixed community of Nostocales (Cyanobacteria) and Rhizobiales (Alphaproteobacteria) to predominance of Nostocales. Microbiome community composition differed between years, with some diazotroph populations persisting while others declined in relative abundance in warmed plots in the second year. Our results demonstrate that warming substantially alters the community composition, diversity, and N2 fixation activity of peat moss microbiomes, which may ultimately impact host fitness, ecosystem productivity, and C storage potential in peatlands.
Disentangling how climate change can affect an aquatic food web by combining multiple experimental approaches
Authors: Amundrud Sarah L. , Srivastava Diane S. 
Published: May 2019

AbstractPredicting the biological effects of climate change presents major challenges due to the interplay of potential biotic and abiotic mechanisms. Climate change can create unexpected outcomes by altering species interactions, and uncertainty over the ability of species to develop in situ tolerance or track environmental change further hampers meaningful predictions. As multiple climatic variables shift in concert, their potential interactions further complicate ecosystem responses. Despite awareness of these complexities, we still lack controlled experiments that manipulate multiple climatic stressors, species interactions, and prior exposure of species to future climatic conditions. Particularly studies that address how changes in water availability interact with other climatic stressors to affect aquatic ecosystems are still rare. Using aquatic insect communities of Neotropical tank bromeliads, we combined controlled manipulations of drought length and species interactions with a space‐for‐time transplant (lower elevations represent future climate) and a common garden approach. Manipulating drought length and experiment elevation revealed that adverse effects of drought were amplified at the warmer location, highlighting the potential of climatic stressors to synergistically affect communities. Manipulating the presence of omnivorous tipulid larvae showed that negative interactions from tipulids, presumably from predation, arose under drought, and were stronger at the warmer location, stressing the importance of species interactions in mediating community responses to climate change. The common garden treatments revealed that prior community exposure to potential future climatic conditions did not affect the outcome. In this powerful experiment, we demonstrated how complexities arise from the interplay of biotic and abiotic mechanisms of climate change. We stress that single species can steer ecological outcomes, and suggest that focusing on such disproportionately influential species may improve attempts at making meaningful predictions of climate change impacts on food webs.
Treatment responses in patients with vitiligo to very potent topical corticosteroids combined with vitaminotherapy in Madagascar
Authors: Sendrasoa Fandresena A. , Ranaivo Irina M. , Sata Moril , Andrianarison Malalaniaina , Raharolahy Onivola , Rakotoarisaona Mendrika F. , Razanakoto Naina H. , Ramarozatovo Lala S. , Rapelanoro Rabenja Fahafahantsoa 
Published: May 2019

AbstractIntroductionVitiligo is a refractory disease in which treatment modalities are not yet established. We aim to assess results obtained 10 years after the initiation of a therapeutic protocol which combines very potent topical corticosteroids (TCS), vitaminotherapy (B12 and C), and suppression of microtraumas in the management of nonsegmental vitiligo in Madagascar.MethodsIt was a prospective and descriptive study over a period of 6 years (2011–2016) in the Department of Dermatology, Joseph Raseta Befelatanana, Antananarivo, Madagascar. The diagnosis of vitiligo was based on clinical data. Patients who agreed to follow the treatment protocol, which combined very potent TCS (two applications/day for 10 days, and then one application/day for the following 10 days), oral vitamin C 500 mg/day for 20 days, and oral vitamin B12 100 mg/day for 20 days, were included in the study. Two successive courses of treatment were made 10 days apart.ResultsThe details of 308 vitiligo patients were analyzed. The mean age of patients was 33.3 years. There was a female preponderance (sex ratio: 0.6). The duration of treatment in our patients varied from 3 to 18 months. Two hundred and thirty‐nine patients had good therapeutic compliance and attended regular follow‐up. Excellent repigmentation (more than 76% area repigmented) was noted in 50 patients (65.7%) less than 14 years of age. Lesions evolving in less than 1 year in 31 patients (36.9%) had excellent response to treatment. Localized lesions responded favorably to treatment with excellent repigmentation in 108 patients.ConclusionThese results show that therapeutic response is better in young people, lesions less than 1 year of evolution, and for localization of vitiligo in the face and neck.
Polymorphisms in MAPK9 (rs4147385) and CSF1R (rs17725712) are associated with the development of inhibitors in patients with haemophilia A in North China
Authors: Zhao Mingming , Zhang Yujing , Liu Yanyan , Sun Guoxun , Tian Hong , Hong Luojia 
Published: May 2019

AbstractIntroductionThe formation of neutralizing antibodies (FVIII inhibitors) in haemophilia A patients is an immune response to the deficient factor. This process is multifactorial and includes environmental and genetic factors. Some genetic markers that play a decisive role in the immune response have been identified as risk factors for inhibitor development.ObjectiveOur aim was to investigate the association between polymorphisms in several genes involved in the regulation of the immune response and inhibitor development in patients with haemophilia A in North China.MethodsWe analysed eight SNPs (MAPK9 rs4147385, CSF1R rs17725712, CD44 rs927335, STAT4 rs7574865, IKZF1 rs4917014, ETS1 rs6590330, BANK1 rs17266594 and rs10516487) by Snapshot SNP genotyping assays in 100 haemophilia A patients, including 29 with inhibitors and 71 without inhibitors.ResultsOur results demonstrated that the rs17725712 A allele and the AA homozygous genotype of CSF1R were more frequent in patients with inhibitors. The rs4147385 G allele in MAPK9 was also more frequent in the inhibitor cohort.ConclusionWe confirmed an association of CSF1R rs17725712 and MAPK9 rs4147385 with inhibitor development in haemophilia A patients in North China.
Social Welfare and Remittances to Older Adults in Two Caribbean Cities
Authors: Quashie Nekehia T. 
Published: May 2019

AbstractThis study explores the correlates of financial and material remittances to older adults in Havana and Bridgetown. These cities, both within countries at a very advanced stage of population ageing, have different institutional contexts for older adults. Data come from the 2000 Survey on Health, Well‐Being and Aging in Latin America and the Caribbean (SABE) of adults 60 years and older with children overseas, Havana (n = 461) and Bridgetown (n = 1,003), representing 342 and 531 families, respectively. Multivariate logistic regression analyses indicate that remittances to Havana were significantly associated with parents' and children's socio‐economic resources. Remittances to Bridgetown were associated with parents' sociodemographic characteristics and sibling's coresidence with parents. In both cities, remittances were positively associated with parents' support of their children. The findings suggest remittances are both a household survival strategy, which can reinforce socioeconomic inequality, and symbolic of social norms of family relations.
Cirsium japonicum var. maackii and apigenin block Hif‐2α‐induced osteoarthritic cartilage destruction
Authors: Cho Chanmi , Kang Li‐Jung , Jang Dain , Jeon Jimin , Lee Hyemi , Choi Sangil , Han Seong Jae , Oh Eunjeong , Nam Jiho , Kim Chun Sung , Park Eunkuk , Jeong Seon‐Yong , Park Chan Hum , Shin Yu Su , Eyun Seong‐il , Yang Siyoung 
Published: May 2019

AbstractAlthough Hif‐2α is a master regulator of catabolic factor expression in osteoarthritis development, Hif‐2α inhibitors remain undeveloped. The aim of this study was to determine whether Cirsium japonicum var. maackii (CJM) extract and one of its constituents, apigenin, could attenuate the Hif‐2α‐induced cartilage destruction implicated in osteoarthritis progression. In vitro and in vivo studies demonstrated that CJM reduced the IL‐1β‐, IL‐6, IL‐17‐ and TNF‐α‐induced up‐regulation of MMP3, MMP13, ADAMTS4, ADAMTS5 and COX‐2 and blocked osteoarthritis development in a destabilization of the medial meniscus mouse model. Activation of Hif‐2α, which directly up‐regulates MMP3, MMP13, ADAMTS4, IL‐6 and COX‐2 expression, is inhibited by CJM extract. Although cirsimarin, cirsimaritin and apigenin are components of CJM and can reduce inflammation, only apigenin effectively reduced Hif‐2α expression and inhibited Hif‐2α‐induced MMP3, MMP13, ADAMTS4, IL‐6 and COX‐2 expression in articular chondrocytes. IL‐1β induction of JNK phosphorylation and IκB degradation, representing a critical pathway for Hif‐2α expression, was completely blocked by apigenin in a concentration‐dependent manner. Collectively, these effects indicate that CJM and one of its most potent constituents, apigenin, can lead to the development of therapeutic agents for blocking osteoarthritis development as novel Hif‐2α inhibitors.
Emotion versus cognition: differential pathways to theory of mind for children with high versus low callous‐unemotional traits
Authors: Satlof‐Bedrick Emma , Waller Rebecca , Olson Sheryl L. 
Published: May 2019

BackgroundTheory of mind (ToM) serves as a foundation for developing social cognition. Developmental theory suggests that early emotion understanding supports the development of ToM, but few studies have tested this question within longitudinal designs. Additionally, children with callous‐unemotional (CU) traits directly challenge this theory as they appear to develop intact ToM despite deficits in emotion understanding. Inhibitory control is proposed as one possible compensatory mechanism for ToM development in children with high CU traits.MethodsWe examined emotion understanding and inhibitory control at age 3 as predictors of ToM at age 6 and tested whether these pathways were different in children with high versus low levels of CU traits. Multimethod data included observations of child emotion understanding and inhibitory control and parent reports of CU traits drawn from a prospective, longitudinal study (N = 240, 48% female).ResultsConsistent with our hypothesis, emotion understanding at age 3 significantly predicted ToM at age 6 only for children with low CU traits. Although there was a significant interaction between inhibitory control and CU traits in relation to later ToM, the simple slopes were not significant.ConclusionsWe find prospective longitudinal evidence that emotion understanding is a developmental precursor of ToM. However, this pathway was not evident in children with high CU traits. Future research is needed to further explore potential mechanisms by which children with CU traits develop ToM with a potential focus on higher‐order cognitive skills.
Leucine‐rich repeat kinase 2 phosphorylation on synapsin I regulates glutamate release at pre‐synaptic sites
Authors: Marte Antonella , Russo Isabella , Rebosio Claudia , Valente Pierluigi , Belluzzi Elisa , Pischedda Francesca , Montani Caterina , Lavarello Chiara , Petretto Andrea , Fedele Ernesto , Baldelli Pietro , Benfenati Fabio , Piccoli Giovanni , Greggio Elisa , Onofri Franco 
Published: May 2019

AbstractLeucine‐rich repeat kinase 2 (LRRK2) is a large multidomain scaffolding protein with kinase and GTPase activities involved in synaptic vesicle (SV) dynamics. While its role in Parkinson’s disease has been largely investigated, little is known about LRRK2 physiological role and until now few proteins have been described as substrates. We have previously demonstrated that LRRK2 through its WD40 domain interacts with synapsin I, an important SV‐associated phosphoprotein involved in neuronal development and in the regulation of neurotransmitter release. To test whether synapsin I is substrate for LRRK2 and characterize the properties of its phosphorylation, we used in vitro kinase and binding assays as well as cellular model and site‐direct mutagenesis. Using synaptosomes in superfusion, patch‐clamp recordings in autaptic WT and synapsin I KO cortical neurons and SypHy assay on primary cortical culture from wild‐type and BAC human LRRK2 G2019S mice we characterized the role of LRRK2 kinase activity on glutamate release and SV trafficking. Here we reported that synapsin I is phosphorylated by LRRK2 and demonstrated that the interaction between LRRK2 WD40 domain and synapsin I is crucial for this phosphorylation. Moreover, we showed that LRRK2 phosphorylation of synapsin I at threonine 337 and 339 significantly reduces synapsin I‐SV/actin interactions. Using complementary experimental approaches, we demonstrated that LRRK2 controls glutamate release and SV dynamics in a kinase activity and synapsin I‐dependent manner. Our findings show that synapsin I is a LRRK2 substrate and describe a novel mechanisms of regulation of glutamate release by LRRK2 kinase activity.
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A digital dissection of two teleost fishes: comparative functional anatomy of the cranial musculoskeletal system in pike (Esox lucius) and eel (Anguilla anguilla)
Authors: Brocklehurst Robert , Porro Laura , Herrel Anthony , Adriaens Dominique , Rayfield Emily 
Published: May 2019

AbstractAdvances in X‐ray computed tomography (CT) have led to a rise in the use of non‐destructive imaging methods in comparative anatomy. Among these is contrast‐enhanced CT scanning, which employs chemical stains to visualize soft tissues. Specimens may then be ‘digitally dissected’, producing detailed, three‐dimensional digital reconstructions of the soft‐ and hard‐tissue anatomy, allowing examination of anatomical structures in situ and making accurate measurements (lengths, volumes, etc.). Here, we apply this technique to two species of teleost fish, providing one of the first comprehensive three‐dimensional (3D) descriptions of teleost cranial soft tissue and quantifying differences in muscle anatomy that may be related to differences in feeding ecology. Two species with different feeding ecologies were stained, scanned and imaged to create digital 3D musculoskeletal reconstructions: Esox lucius (Northern Pike), predominantly a suction feeder; and Anguilla anguilla (European eel), which captures prey predominantly by biting. Muscle cross‐sectional areas were calculated and compared between taxa, focusing on muscles that serve important roles in feeding. The adductor mandibulae complex – used in biting – was larger in Esox than Anguilla relative to head size. However, the overall architecture of the adductor mandibulae was also very different between the two species, with that of Anguilla better optimized for delivering forceful bites. Levator arcus palatini and sternohyoideus – which are used in suction feeding – are larger in Esox, whereas the levator operculi is larger in Anguilla. Therefore, differences in the size of functionally important muscles do not necessarily correlate neatly with presumed differences in feeding mode.