bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin‐induced mitochondrial function and ABCD2 up‐regulation in X‐linked adrenoleukodystrophy involves AMP‐activated protein kinase
Authors: Singh Jaspreet , Olle Brittany , Suhail Hamid , Felicella Michelle M. , Giri Shailendra 
Published: February 2016

AbstractX‐linked adrenoleukodystrophy (X‐ALD) is a progressive neurometabolic disease caused by mutations/deletions in the Abcd1 gene. Similar mutations/deletions in the Abcd1 gene often result in diagonally opposing phenotypes of mild adrenomyeloneuropathy and severe neuroinflammatory cerebral adrenoleukodystrophy (ALD), which suggests involvement of downstream modifier genes. We recently documented the first evidence of loss of AMP‐activated protein kinase α1 (AMPKα1) in ALD patient‐derived cells. Here, we report the novel loss of AMPKα1 in postmortem brain white matter of patients with ALD phenotype. Pharmacological activation of AMPK can rescue the mitochondrial dysfunction and inhibit the pro‐inflammatory response. The FDA approved anti‐diabetic drug Metformin, a well‐known AMPK activator, induces mitochondrial biogenesis and is documented for its anti‐inflammatory role. We observed a dose‐dependent activation of AMPKα1 in metformin‐treated X‐ALD patient‐derived fibroblasts. Metformin also induced mitochondrial oxidative phosphorylation and ATP levels in X‐ALD patient‐derived fibroblasts. Metformin treatment decreased very long chain fatty acid levels and pro‐inflammatory cytokine gene expressions in X‐ALD patient‐derived cells. Abcd2 [adrenoleukodystrophy protein‐related protein] levels were increased in metformin‐treated X‐ALD patient‐derived fibroblasts and Abcd1‐KO mice primary mixed glial cells. Abcd2 induction was AMPKα1‐dependent since metformin failed to induce Abcd2 levels in AMPKα1‐KO mice‐derived primary mixed glial cells. In vivo metformin (100 mg/Kg) in drinking water for 60 days induced Abcd2 levels and mitochondrial oxidative phosphorylation protein levels in the brain and spinal cord of Abcd1‐KO mice. Taken together, these results provide proof‐of‐principle for therapeutic potential of metformin as a useful strategy for correcting the metabolic and inflammatory derangements in X‐ALD by targeting AMPK.
imageThere is no effective therapy for inherited peroxisomal disorder X‐linked adrenoleukodystrophy (X‐ALD). We document the therapeutic potential of FDA approved drug, Metformin, for X‐ALD by targeting AMPK. Metformin induced peroxisomal Abcd2 levels in vitro and in vivo. Metformin lowered VLCFA levels, improved mitochondrial function and ameliorated inflammatory gene expression in X‐ALD patient‐derived cells. Metformin‐induced Abcd2 levels were dependent on AMPKα1, a metabolic and anti‐inflammatory gene, recently documented by our laboratory to play a putative role in X‐ALD pathology.Read the Editorial Highlight for this article on page 10.
Pulmonary hypertension and right ventricular failure in broiler chickens reared at high altitude is affected by dietary source of n‐6 and n‐3 fatty acids
Authors: Rostami A. , Zamani Moghaddam A. K. , Hassanpour H. , Khajali F. 
Published: February 2016

SummaryThe present study evaluated the development of pulmonary hypertension and right ventricular failure in broiler chickens reared at high altitude (2100 m) as affected by dietary intake of n‐3 and n‐6 fatty acid sources. Flax oil and soy oil were used as sources of n‐3 and n‐6 fatty acids, respectively, either with or without α‐tocopheryl acetate. A total of 192 day‐old broiler chicks (Ross 308) were used in a completely randomized design using isoenergetic and isonitrogenous experimental diets. Results showed that dietary flax oil significantly (p < 0.05) improved feed conversion ratio during 21–42 days of age. However, body weight gain did not significantly differ among the experimental groups in entire trial. Birds received flax oil had significantly higher serum concentration of nitric oxide (NO) but they had lower serum concentration of malondialdehyde when compared with their counterparts fed with soy oil. Liver and abdominal fat weights were significantly (p < 0.05) reduced by substitution of soy oil for flax oil. The right‐to‐total ventricle weight ratio (RV/TV) and mortality from pulmonary arterial hypertension (PAH) were significantly (p < 0.05) decreased in birds that received flax oil. In conclusion, n‐3 fatty acids could significantly reduce RV:TV and PAH mortality in birds by increasing circulatory level of NO and suppressing hepatic lipogenesis.
Effects of selenium supplementation on the oxidative state of acute heat stress‐exposed quails
Authors: Del Vesco A. P. , Gasparino E. , Zancanela V. , Grieser D. O. , Stanquevis C. E. , Pozza P. C. , Oliveira Neto A. R. 
Published: February 2016

SummaryThis study aimed to evaluate the effect of heat stress (HS) and selenium supplementation on markers of stress, meat quality and gene expression. For this, meat quails of 42 days of age were fed a diet that either met [0.33 mg/kg, nutritional demand for selenium (SS)] or did not meet [0.11 mg/kg, selenium deficient (SD)] the nutritional demands for selenium during the 7 days of evaluation. In addition, the animals were kept at either a thermal comfort temperature (25 °C) or exposed to HS (38 °C for 24 h). Glutathione synthetase (GSS), glutathione reductase (GSR) and uncoupling protein (UCP) gene expression were influenced by the interaction between temperature and diet. Animals subjected to HS and fed the SS diet exhibited the highest GSS and GSR gene expression. In terms of UCP gene expression, the lowest values were observed in HS animals on the SD diet. Glutathione peroxidase 7 (GPX7) gene expression, body temperature (BT) and creatine kinase (CK) activity were influenced by both selenium supplementation and HS. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) activity and creatinine content all were influenced by the diet/environment interaction. The highest AST activity, ALT activity and creatinine levels were observed in animals that were both on the SD diet and exposed to HS. HS animals also exhibited an increased heterophil/lymphocyte ratio and lower triiodothyronine (T3) hormone levels than birds that remained at the comfortable temperature. Animals subjected to HS and fed with selenium supplemented diet showed better results regarding gene expression and, thus, better results for the activities of enzymes used as stress markers, which could be due to the higher antioxidant capacity provided by the action of the studied genes.
Pseudo‐nitzschia arctica sp. nov., a new cold‐water cryptic Pseudo‐nitzschia species within the P. pseudodelicatissima complex
Authors: Percopo Isabella , Ruggiero Maria Valeria , Balzano Sergio , Gourvil Priscillia , Lundholm Nina , Siano Raffaele , Tammilehto Anna , Vaulot Daniel , Sarno Diana 
Published: February 2016

A new nontoxic Pseudo‐nitzschia species belonging to the P. pseudodelicatissima complex, P. arctica, was isolated from different areas of the Arctic. The erection of P. arctica is mainly supported by molecular data, since the species shares identical ultrastructure with another species in the complex, P. fryxelliana, and represents a new case of crypticity within the genus. Despite their morphological similarity, the two species are not closely related in phylogenies based on LSU, ITS and rbcL. Interestingly, P. arctica is phylogenetically most closely related to P. granii and P. subcurvata, from which the species is, however, morphologically different. P. granii and P. subcurvata lack the central larger interspace which is one of the defining features of the P. pseudodelicatissima complex. The close genetic relationship between P. arctica and the two species P. granii and P. subcurvata is demonstrated by analysis of the secondary structure of ITS2 which revealed no compensatory base changes, two hemi‐compensatory base changes, and two deletions in P. arctica with respect to the other two species. These findings emphasize that rates of morphological differentiation, molecular evolution and speciation are often incongruent for Pseudo‐nitzschia species, resulting in a restricted phylogenetic value for taxonomic characters used to discriminate species. The description of a new cryptic species, widely distributed in the Arctic and potentially representing an endemic component of the Arctic diatom flora, reinforces the idea of the existence of noncosmopolitan Pseudo‐nitzschia species and highlights the need for combined morphological and molecular analyses to assess the distributional patterns of phytoplankton species.
Taxonomic revision of Chlamydomonas subg. Amphichloris (Volvocales, Chlorophyceae), with resurrection of the genus Dangeardinia and descriptions of Ixipapillifera gen. nov. and Rhysamphichloris gen. nov.
Authors: Nakada Takashi , Tomita Masaru , Wu Jiunn‐Tzong , Nozaki Hisayoshi 
Published: February 2016

Chlamydomonas (Cd.) is one of the largest but most polyphyletic genera of freshwater unicellular green algae. It consists of 400–600 morphological species and requires taxonomic revision. Toward reclassification, each morphologically defined classical subgenus (or subgroup) should be examined using culture strains. Chlamydomonas subg. Amphichloris is characterized by a central nucleus between two axial pyrenoids, however, the phylogenetic structure of this subgenus has yet to be examined using molecular data. Here, we examined 12 strains including six newly isolated strains, morphologically identified as Chlamydomonas subg. Amphichloris, using 18S rRNA gene phylogeny, light microscopy, and mitochondria fluorescent microscopy. Molecular phylogenetic analyses revealed three independent lineages of the subgenus, separated from the type species of Chlamydomonas, Cd. reinhardtii. These three lineages were further distinguished from each other by light and fluorescent microscopy—in particular by the morphology of the papillae, chloroplast surface, stigmata, and mitochondria—and are here assigned to three genera: Dangeardinia emend., Ixipapillifera gen. nov., and Rhysamphichloris gen. nov. Based on the molecular and morphological data, two to three species were recognized in each genus, including one new species, I. pauromitos. In addition, Cd. deasonii, which was previously assigned to subgroup “Pleiochloris,” was included in the genus Ixipapillifera as I. deasonii comb. nov.
Characterization of an Inherited Neurologic Syndrome in Toyger Cats with Forebrain Commissural Malformations, Ventriculomegaly and Interhemispheric Cysts
Authors: Keating M.K. , Sturges B.K. , Sisó S. , Wisner E.R. , Creighton E.K. , Lyons L.A. 
Published: February 2016

BackgroundIn children, frequent congenital malformations with concomitant agenesis of the corpus callosum are diagnosed by neuroimaging in association with other cerebral malformations, including interhemispheric cysts and ventriculomegaly. Similar studies providing full characterization of brain defects by in vivo magnetic resonance imaging (MRI), and correlations with the pertinent anatomic pathologic examinations are absent in veterinary medicine.Hypothesis/ObjectivesCongenital brain defects underlie the neurologic signs observed in Toyger cats selectively bred for a short ear phenotype.AnimalsUsing proper pedigree analysis and genetic evaluations, 20 related Oriental‐derived crossbred Toyger cats were evaluated. Seven clinically healthy (carrier) cats and 13 clinically affected cats that had neurologic signs, short ear phenotype and concomitant complex brain anomalies were studied.MethodsComplete physical and neurologic examinations and MRI were performed in all clinically healthy and affected cats. Postmortem and histopathologic examinations were performed in 8 affected cats and 5 healthy cats.ResultsNeurologic and MRI investigations confirmed 13 clinically affected cats with structural brain abnormalities. Ventriculomegaly with frequent concomitant supratentorial interhemispheric, communicating ventricular type‐1b cysts and multiple midline and callosal malformations were detected in all cats displaying neurologic signs. Genetic analysis confirmed autosomal recessive mode of inheritance with no chromosomal abnormalities.Conclusions and Clinical ImportanceNeuroanatomic dissections and histopathology were helpful for evaluation of abnormalities in midline brain structures, and for the full characterization of cysts. However, MRI was more sensitive for detection of small cysts. In this feline model, MRI diagnosis had extremely good correlation with pathologic abnormalities noted in the subset of animals that were examined by both modalities.
Applying the Verifiability Approach to insurance claims settings: Exploring the effect of the information protocol
Authors: Harvey Adam C. , Vrij Aldert , Nahari Galit , Ludwig Katharina 
Published: February 2016

PurposeLie detection in insurance claim settings is difficult as liars can easily incorporate deceptive statements within descriptions of otherwise truthful events. We examined whether the Verifiability Approach (VA) could be used effectively in insurance settings. According to the VA, liars avoid disclosing details that they think can be easily checked, whereas truth tellers are forthcoming with verifiable details.MethodThe study experimentally manipulated notifying claimants about the interviewer's intention to check their statements for verifiable details (the ‘Information Protocol’). It was hypothesized that such an instruction would (1) encourage truth tellers to provide more verifiable details than liars and to report identifiable witnesses who had witnessed the event within their statements, and (2) would enhance the diagnostic accuracy of the VA. Participants reported 40 genuine and 40 fabricated insurance claim statements, in which half the liars and truth tellers were notified about the interviewer's intention to check their statements for verifiable details.ResultsBoth hypotheses were supported. In terms of accuracy, notifying claimants about the interviewer's intention to check their statements for verifiable details increased accuracy rates from around chance level to around 80%.ConclusionThe VA, including the information protocol, can be used in insurance settings.
Effect of prior drought and pathogen stress onArabidopsistranscriptome changes to caterpillar herbivory
Authors: Davila Olivas Nelson H. , Coolen Silvia , Huang Pingping , Severing Edouard , van Verk Marcel C. , Hickman Richard , Wittenberg Alexander H. J. , de Vos Martin , Prins Marcel , van Loon Joop J. A. , Aarts Mark G. M. , van Wees Saskia C. M. , Pieterse Corné M. J. , Dicke Marcel 
Published: February 2016

SummaryIn nature, plants are exposed to biotic and abiotic stresses that often occur simultaneously. Therefore, plant responses to combinations of stresses are most representative of how plants respond to stresses.We usedRNAseq to assess temporal changes in the transcriptome ofArabidopsis thalianato herbivory byPieris rapaecaterpillars, either alone or in combination with prior exposure to drought or infection with the necrotrophic fungusBotrytis cinerea.Pre‐exposure to drought stress orBotrytisinfection resulted in a significantly different timing of the caterpillar‐induced transcriptional changes. Additionally, the combination of drought andP. rapaeinduced an extensive downregulation ofA. thalianagenes involved in defence against pathogens. Despite a more substantial growth reduction observed for plants exposed to drought plusP. rapaefeeding compared withP. rapaefeeding alone, this did not affect weight increase of this specialist caterpillar.Plants respond to combined stresses with phenotypic and transcriptional changes that differ from the single stress situation. The effect of a previous exposure to drought orB. cinereainfection on transcriptional changes to caterpillars is largely overridden by the stress imposed by caterpillars, indicating that plants shift their response to the most recent stress applied.
Integration of decoy domains derived from protein targets of pathogen effectors into plant immune receptors is widespread
Authors: Kroj Thomas , Chanclud Emilie , Michel‐Romiti Corinne , Grand Xavier , Morel Jean‐Benoit 
Published: February 2016

Summary

Plant immune receptors of the class of nucleotide‐binding and leucine‐rich repeat domain (NLR) proteins can contain additional domains besides canonical NB‐ARC (nucleotide‐binding adaptor shared by APAF‐1, R proteins, and CED‐4 (NB‐ARC)) and leucine‐rich repeat (LRR) domains. Recent research suggests that these additional domains act as integrated decoys recognizing effectors from pathogens. Proteins homologous to integrated decoys are suspected to be effector targets and involved in disease or resistance.

Here, we scrutinized 31 entire plant genomes to identify putative integrated decoy domains in NLR proteins using the Interpro search. The involvement of the Zinc Finger–BED type (ZBED) protein containing a putative decoy domain, called BED, in rice (Oryza sativa) resistance was investigated by evaluating susceptibility to the blast fungus Magnaporthe oryzae in rice over‐expression and knock‐out mutants.

This analysis showed that all plants tested had integrated various atypical protein domains into their NLR proteins (on average 3.5% of all NLR proteins). We also demonstrated that modifying the expression of the ZBED gene modified disease susceptibility.

This study suggests that integration of decoy domains in NLR immune receptors is widespread and frequent in plants. The integrated decoy model is therefore a powerful concept to identify new proteins involved in disease resistance. Further in‐depth examination of additional domains in NLR proteins promises to unravel many new proteins of the plant immune system.
Failed fiberoptic intubation in a child with epidermolysis bullosa, rescued with combined use of the Glidescope®
Authors: Fitzmaurice Bethany C. , Lambert Barry G. 
Published: February 2016

SummaryWe present the case of a 13‐year‐old male with epidermolysis bullosa having an elective syndactyly release. These patients present significant challenges to the anaesthetist; extreme care in patient handling is required. Recurrent and pronounced scarring of intra‐oral, pharyngeal and laryngeal tissues is a feature, resulting in a difficult airway. Following a failed intubation using a fibreoptic bronchoscope, we describe a combined technique by adding in the Glidescope®. This proved immediately successful. Its utilisation has been reported in adults. We wish to present our experience in the paediatric population, and this is the first report in a child with epidermiolysis bullosa.
Life hassles and delusional ideation: Scoping the potential role of cognitive and affective mediators
Authors: Kingston Cara , Schuurmans‐Stekhoven James 
Published: February 2016

ObjectivesAn intertemporal association between major psychological stress and subsequent delusion formation has been established by others. The current study explores (1) whether the stress from life hassles predicts delusional ideation and (2) if so, do self‐criticism, self‐reassurance, and positive and negative affectivity (PA and NA, respectively) mediate this link. This paper thus aimed to scope‐out viable psychological processes involved in the formation of stress‐induced delusions.DesignA cross‐sectional survey using a non‐clinical community sample.MethodsResponses (N = 251) to an online community survey were tested via a nonparametric bootstrap sampling approach to examine the effects of multiple mediators.ResultsSelf‐criticism and NA appear to mediate a connection found between life hassles and delusions. A second mediation analysis found that life hassles positively predicts NA directly and indirectly (via self‐criticism). NA in turn predicted delusional tendencies. Life events had direct statistical effects on delusions in all models. Neither PA nor self‐reassurance mediated the stress‐delusion link.ConclusionsSelf‐criticism and NA seem to be viable mediators worth contemplating when elaborating upon the connection between life hassles and delusions. Compared to self‐criticism, NA appears to be the intervening variable most proximal to delusions and explains more variance. Even if these cross‐sectional results were interpreted as causative, life hassles and delusions remained directly interconnected in all mediation models (suggesting much of the association remains unexplained). Although the results are theory‐consistent, investigations using longitudinal, known‐group, and experimental methods are now warranted to establish causation and possible feedback loops – especially from delusion to life hassles.Practitioner points

Self‐criticism and negative affectivity (NA) mediate the link between stressful life events and delusions suggesting they might actively elicit delusional ideation, whereas self‐reassurance and PA (although negatively associated with life hassles) have no unique predictive link to delusions.

This study offers initial evidence that NA and self‐criticism may be viable clinical intervention targets for early psychosis‐sufferers under stress – especially for medically non‐compliant and marginal (where drug treatment is not clinically indicated) cases.

The clinical efficacy of alleviating self‐criticism and/or negative emotional processes in those displaying early psychosis or at high risk appear worthy of exploration using both practice‐based case studies and formal experimental research methods.
Functional analysis of alternative transcripts of the soybean Rj2 gene that restricts nodulation with specific rhizobial strains
Authors: Tang F. , Yang S. , Zhu H. 
Published: February 2016

AbstractThe Rj2 gene is a TIR‐NBS‐LRR‐type resistance gene in soybean (Glycine max) that restricts root nodule symbiosis with a group of Bradyrhizobium japonicum strains including USDA122. Rj2 generates two distinct transcript variants in its expression profile through alternative splicing. Alternative splicing of Rj2 is caused by the retention of the 86‐bp intron 4. Inclusion of intron 4 in mature mRNA introduces an in‐frame stop codon; as such, the alternative transcript is predicted to encode a truncated protein consisting of the entire portion of the TIR, NBS and LRR domains but missing the C‐terminal domain of the full‐length Rj2 protein encoded by the regular transcript. Since alternative splicing has been shown to be essential for full activity of several plant R genes, we attempted to test whether the alternative splicing is required for Rj2‐mediated nodulation restriction. Here we demonstrated that the Rj2‐mediated nodulation restriction does not require the combined presence of the regular and alternative transcripts, and the expression of the regular transcript alone is sufficient to confer nodulation restriction.