bluuebunny/crossref_metadata_2025 huggingface dataset:
Cold Hypersensitivity in the Hands and Feet May Be Associated with Functional Dyspepsia: Results of a Multicenter Survey Study
Authors: Bae Kwang-Ho , Lee Ju Ah , Park Ki-Hyun , Yoo Jong-Hyang , Lee Youngseop , Lee Siwoo
Published: March 2016

Aim. To investigate whether dyspepsia symptoms differ depending on the presence or absence of cold hypersensitivity in the hands and feet (CHHF). Methods. In all, 6044 patients were recruited and provided with a questionnaire about CHHF and dyspepsia. Based on their responses, subjects were divided into a CHHF group (persons who noted cold sensations; n = 1209) and a non‐CHHF group (persons who noted warm or intermediate sensations; n = 1744). The groups were compared in terms of their usual digestion status, using chi‐square tests and logistic regression analyses to calculate the propensity score and odds ratios (ORs). We analyzed the participants’ responses to questions on dyspepsia symptoms. Results. After matching, chi‐square tests indicated that the CHHF group had higher frequencies of the following symptoms: bad digestion, poor appetite, discomfort in the upper abdomen, motion sickness, epigastric burning, postprandial fullness, nausea, and bloating. Additionally, CHHF was associated with an increased OR for dyspepsia (bad digestion, vomiting, motion sickness, epigastric burning, postprandial fullness, nausea, epigastric pain, and bloating) compared with the non‐CHHF group. Conclusion. This study confirmed that CHHF patients have elevated frequencies of most dyspepsia symptoms.
Exenatide Is an Effective Antihyperglycaemic Agent in a Mouse Model of Wolfram Syndrome 1
Authors: Sedman Tuuli , Rünkorg Kertu , Krass Maarja , Luuk Hendrik , Plaas Mario , Vasar Eero , Volke Vallo
Published: March 2016

Wolfram syndrome 1 is a very rare monogenic disease resulting in a complex of disorders including diabetes mellitus. Up to now, insulin has been used to treat these patients. Some of the monogenic forms of diabetes respond preferentially to sulphonylurea preparations. The aim of the current study was to elucidate whether exenatide, a GLP-1 receptor agonist, and glipizide, a sulphonylurea, are effective in a mouse model of Wolfram syndrome 1. Wolframin-deficient mice were used to test the effect of insulin secretagogues. Wolframin-deficient mice had nearly normal fasting glucose levels but developed hyperglycaemia after glucose challenge. Exenatide in a dose of 10 μg/kg lowered the blood glucose level in both wild-type and wolframin-deficient mice when administered during a nonfasted state and during the intraperitoneal glucose tolerance test. Glipizide (0.6 or 2 mg/kg) was not able to reduce the glucose level in wolframin-deficient animals. In contrast to other groups, wolframin-deficient mice had a lower insulin-to-glucose ratio during the intraperitoneal glucose tolerance test, indicating impaired insulin secretion. Exenatide increased the insulin-to-glucose ratio irrespective of genotype, demonstrating the ability to correct the impaired insulin secretion caused by wolframin deficiency. We conclude that GLP-1 agonists may have potential in the treatment of Wolfram syndrome-related diabetes.
Reactive Pulmonary Capillary Hemangiomatosis and Pulmonary Veno-Occlusive Disease in a Patient with Repaired Scimitar Syndrome
Authors: Güttinger Eva , Vrugt Bart , Speich Rudolf , Ulrich Silvia , Schwitz Fabienne , Arrigo Mattia , Huber Lars C.
Published: March 2016

Pulmonary capillary hemangiomatosis (PCH) is a rare histological substrate within the spectrum of pulmonary arterial hypertension that possibly represents an unusual manifestation of pulmonary veno-occlusive disease (PVOD). One of the histological hallmarks of PCH is the proliferation of pulmonary capillaries in the alveolar septa that infiltrate adjacent structures such as bronchioles, vessels, and visceral pleura. The hyperplastic process involving the smallest vessels of the pulmonary vascular bed might reflect uncontrolled angiogenesis, but whether this vascular proliferation is idiopathic or, conversely, a reactive process remains to be elucidated. Here we discuss the pathogenesis of PCH exemplified by the first reported case of a young patient with repaired scimitar syndrome that developed unilateral PCH.
Molecular Characterization of a Novel Germline VHL Mutation by Extensive In Silico Analysis in an Indian Family with Von Hippel-Lindau Disease
Authors: Arunachal Gautham , Pachat Divya , Doss C. George Priya , Danda Sumita , Pai Rekha , Ebenazer Andrew
Published: March 2016

Von Hippel-Lindau [VHL] disease, an autosomal dominant hereditary cancer syndrome, is well known for its complex genotype-phenotype correlations. We looked for germline mutations in the VHL gene in an affected multiplex family with Type 1 VHL disease. Real-Time quantitative PCR for deletions and Sanger sequencing of coding regions along with flanking intronic regions were performed in two affected individuals and one related individual. Direct sequencing identified a novel heterozygous single nucleotide base substitution in both the affected members tested, segregating with VHL phenotype in this family. This variant in exon 3, c.473T>A, results in substitution of leucine, a highly conserved acid, to glutamine at position 158 [p.L158Q] and has not been reported thus far as a variant associated with disease causation. Further, this variant was not observed in 50 age and ethnicity matched healthy individuals. Extensive in silico prediction analysis along with molecular dynamics simulation revealed significant deleterious nature of the substitution L158Q on pVHL. The results of this study when collated support the view that the missense variation p.L158Q in the Elongin C binding domain of pVHL may be disease causing.
The EGF Receptor Promotes the Malignant Potential of Glioma by Regulating Amino Acid Transport System xc(—)
Authors: Tsuchihashi Kenji , Okazaki Shogo , Ohmura Mitsuyo , Ishikawa Miyuki , Sampetrean Oltea , Onishi Nobuyuki , Wakimoto Hiroaki , Yoshikawa Momoko , Seishima Ryo , Iwasaki Yoshimi , Morikawa Takayuki , Abe Shinya , Takao Ayumi , Shimizu Misato , Masuko Takashi , Nagane Motoo , Furnari Frank B. , Akiyama Tetsu , Suematsu Makoto , Baba Eishi , Akashi Koichi , Saya Hideyuki , Nagano Osamu
Published: March 2016

Extracellular free amino acids contribute to the interaction between a tumor and its microenvironment through effects on cellular metabolism and malignant behavior. System xc(–) is composed of xCT and CD98hc subunits and functions as a plasma membrane antiporter for the uptake of extracellular cystine in exchange for intracellular glutamate. Here, we show that the EGFR interacts with xCT and thereby promotes its cell surface expression and function in human glioma cells. EGFR-expressing glioma cells manifested both enhanced antioxidant capacity as a result of increased cystine uptake, as well as increased glutamate, which promotes matrix invasion. Imaging mass spectrometry also revealed that brain tumors formed in mice by human glioma cells stably overexpressing EGFR contained higher levels of reduced glutathione compared with those formed by parental cells. Targeted inhibition of xCT suppressed the EGFR-dependent enhancement of antioxidant capacity in glioma cells, as well as tumor growth and invasiveness. Our findings establish a new functional role for EGFR in promoting the malignant potential of glioma cells through interaction with xCT at the cell surface. Cancer Res; 76(10); 2954–63. ©2016 AACR.
Molecular Pathways: Immunosuppressive Roles of IRE1α-XBP1 Signaling in Dendritic Cells of the Tumor Microenvironment
Authors: Cubillos-Ruiz Juan R. , Bettigole Sarah E. , Glimcher Laurie H.
Published: March 2016

The endoplasmic reticulum (ER) is a massive cytoplasmic membrane network that functions primarily to ensure proper folding and posttranslational modification of newly synthesized secreted and transmembrane proteins. Abnormal accumulation of unfolded proteins in this organelle causes a state of "ER stress," which is a hallmark feature of various diseases, including cancer, neurodegeneration, and metabolic dysfunction. Cancer cells exploit the IRE1α-XBP1 arm of the ER stress response to efficiently adjust their protein-folding capacity and ensure survival under hostile tumor microenvironmental conditions. However, we recently found that dendritic cells (DC) residing in the ovarian cancer microenvironment also experience sustained ER stress and demonstrate persistent activation of the IRE1α-XBP1 pathway. This previously unrecognized process disrupts metabolic homeostasis and antigen-presenting capacity in DCs, thereby crippling their natural ability to support the protective functions of infiltrating antitumor T cells. In this review, we briefly discuss some of the mechanisms that fuel ER stress in tumor-associated DCs, the biologic processes altered by aberrant IRE1α-XBP1 signaling in these innate immune cells, and the unique immunotherapeutic potential of targeting this pathway in cancer hosts. Clin Cancer Res; 22(9); 2121–6. ©2016 AACR.
Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Antitumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies
Authors: Monjazeb Arta M. , Kent Michael S. , Grossenbacher Steven K. , Mall Christine , Zamora Anthony E. , Mirsoian Annie , Chen Mingyi , Kol Amir , Shiao Stephen L. , Reddy Abhinav , Perks Julian R. , T.N. Culp William , Sparger Ellen E. , Canter Robert J. , Sckisel Gail D. , Murphy William J.
Published: March 2016

Purpose: Previous studies demonstrate that intratumoral CpG immunotherapy in combination with radiotherapy acts as an in-situ vaccine inducing antitumor immune responses capable of eradicating systemic disease. Unfortunately, most patients fail to respond. We hypothesized that immunotherapy can paradoxically upregulate immunosuppressive pathways, a phenomenon we term “rebound immune suppression,” limiting clinical responses. We further hypothesized that the immunosuppressive enzyme indolamine-2,3-dioxygenase (IDO) is a mechanism of rebound immune suppression and that IDO blockade would improve immunotherapy efficacy.

Experimental Design: We examined the efficacy and immunologic effects of a novel triple therapy consisting of local radiotherapy, intratumoral CpG, and systemic IDO blockade in murine models and a pilot canine clinical trial.

Results: In murine models, we observed marked increase in intratumoral IDO expression after treatment with radiotherapy, CpG, or other immunotherapies. The addition of IDO blockade to radiotherapy + CpG decreased IDO activity, reduced tumor growth, and reduced immunosuppressive factors, such as regulatory T cells in the tumor microenvironment. This triple combination induced systemic antitumor effects, decreasing metastases, and improving survival in a CD8+ T-cell–dependent manner. We evaluated this novel triple therapy in a canine clinical trial, because spontaneous canine malignancies closely reflect human cancer. Mirroring our mouse studies, the therapy was well tolerated, reduced intratumoral immunosuppression, and induced robust systemic antitumor effects.

Conclusions: These results suggest that IDO maintains immune suppression in the tumor after therapy, and IDO blockade promotes a local antitumor immune response with systemic consequences. The efficacy and limited toxicity of this strategy are attractive for clinical translation. Clin Cancer Res; 22(17); 4328–40. ©2016 AACR.
Consumption of Drugs and Nonpharmacological Therapies in Caregivers of Patients with Alzheimer's Disease: A Case-Control Study in Madrid
Authors: Martín-García Raquel , Martín-Avila Guillermo , De la Rubia-Marcos María , Maroto-Rodríguez Raquel , Ortega-Angulo Celia , Carreras Rodriguez María Teresa , Abad Santos Francisco , Gago Veiga Ana Beatriz
Published: March 2016

Background: Dementia is a neurodegenerative disease whose prevalence is rising, and the need for assistance to patients becomes indispensable. The different types of dementia and their treatments have been widely studied; however, the health status of caregivers also requires our attention. Objective: The aim of our research was to evaluate whether caregivers of patients with dementia consume more medications than the general population, indicating underlying pathologies. Methods: A total of 91 caregivers of dementia patients were interviewed and their answers were compared with those from a control group of 48 people, taking into account demographic data, characteristics of patients and caregivers, pharmacological and nonpharmacological treatments and burden. Results: Caregivers showed a significantly higher consumption of anxiolytics, antidepressants and antiplatelets (22.3, 13.2 and 11%, respectively) than the control group (14.6, 0 and 0%, respectively). Moreover, 45.1% of the caregivers used nonpharmacological therapies compared with 6.2% of the control group. There was a tendency to take more medications in those caregivers suffering from burden and those who had to take care of patients with behavioral changes. Conclusion: Caregivers of dementia patients need more pharmacological and nonpharmacological therapies. They are a risk group that needs better care from the health system.
Diffusion Tensor Imaging Abnormalities in the Cerebral White Matter Correlate with Sex-Dependent Neurobehavioral Deficits in Adult Mice with Neonatal Ischemia
Authors: Breu Markus , Zhang Jiangyang , Porambo Michael , Pletnikov Mikhail V. , Goeral Katharina , Kakara Mihir , Johnston Michael V. , Fatemi Ali
Published: March 2016

Background: Neonatal white matter injury (NWMI) is the leading cause of cerebral palsy in prematurely born children. In order to develop a test bed for therapeutics, we recently reported a mouse model of NWMI by using a modified Rice-Vannucci model of neonatal ischemia on postnatal day 5 (P5) in CD-1 mice. We have previously shown that these mice illustrate initial neuroinflammation and oligodendroglial differentiation arrest followed by long-term dysmyelination, periventricular astrogliosis and axonal injury, resembling human NWMI. The objective of this study was to determine the sex-dependent long-term effects of neonatal brain injury on neurobehavioral and advanced in vivo neuroimaging indices in this mouse model, and to correlate these variables with histopathology. Methods: After right common artery ligation on P5, in vivo T2-weighted imaging and diffusion tensor imaging (DTI) were performed on ligated and control animals at 4 and 8 weeks. Common sets of regions of interest were used to compare fractional anisotropy (FA) values between ischemic and control mice. Behavioral testing (open field, startle response and grip strength) was performed at adult age. Finally, the animals were sacrificed for immunohistochemical (IHC) assessment of major white matter tracts. Results: DTI revealed significant sex-dependent changes in FA values ipsi- and contralateral to the ligation. Behavioral testing showed decreased reaction to acoustic stimuli in males but not females. Similarly, increased number of rearings and lack of novelty-induced habituation in the open field were encountered only in the male subgroup. Several regional correlations were found between FA values and these behavioral alterations. IHC studies revealed degeneration of mature oligodendrocytes and damage of white matter tracts in ligated animals, as previously reported in this model, and showed regional correlation with in vivo FA values and behavioral alterations. Conclusions: Our findings suggest structural sex-dependent long-term abnormalities after neonatal ischemia. These changes lead to behavioral deficits resembling common problems of patients with cerebral palsy.
FP-CIT- and IBZM-SPECT in Corticobasal Syndrome: Results from a Clinical Follow-Up Study
Authors: Hammesfahr Sven , Antke Christina , Mamlins Eduards , Beu Markus , Wojtecki Lars , Ferrea Stefano , Dinkelbach Lars , Moldovan Alexia-Sabine , Schnitzler Alfons , Müller Hans Wilhelm , Südmeyer Martin
Published: March 2016

Objective: To evaluate the striatal presynaptic dopamine transporter (FP-CIT-SPECT) and postsynaptic D2 receptor (IBZM-SPECT) binding in patients with corticobasal syndrome (CBS). Background: FP-CIT and IBZM are commercially available and approved SPECT tracers for in vivo molecular imaging of pre- and postsynaptic nigrostriatal neuronal degeneration, but only few data for CBS are available. Methods: 23 patients meeting clinical criteria for early- to mid-stage CBS (disease duration ≤4 years) were examined with SPECT radiotracers FP-CIT and IBZM. All suspected CBS patients underwent a clinical follow-up examination and were re-evaluated after 19.7 ± 15.2 months (mean ± SD). Postmortem diagnosis was available for 2 patients. In patients who met research criteria for probable CBS at the final follow-up visit (n = 19; disease duration: 1.95 ± 0.91 years), SPECT binding values were compared to those of age- and gender-matched Parkinson's disease (PD) patients (n = 18, disease duration: 1.92 ± 0.91 years; clinical follow-up: 32 ± 29.6 months) and neurologically normal control subjects (n = 19). Results: In comparison to the healthy control subjects, both patient groups showed significant and asymmetric reduction of the striatal presynaptic dopamine transporter binding, but PD patients had significantly lower FP-CIT binding ratios than probable-CBS patients. FP-CIT binding values of probable-CBS patients and healthy controls demonstrated marked overlaps, and in 7 patients (39%) scans revealed no dopaminergic deficit. IBZM uptake did not show significant between-group differences. Conclusion: Our data indicate that in the early- to mid-stage CBS the degree of nigrostriatal impairment is only mild with a significant proportion of preserved dopamine transporter binding.
Apolipoprotein E Genotype and Sex Influence Glucose Tolerance in Older Adults: A Cross-Sectional Study
Authors: Hanson Angela J. , Banks William A. , Hernandez Saucedo Hector , Craft Suzanne
Published: March 2016

Background: Glucose intolerance and apolipoprotein ε4 allele (E4+) are risk factors for Alzheimer's disease (AD). Insulin sensitizers show promise for treating AD, but are less effective in E4+ individuals. Little is known about how the APOE genotype influences glucose metabolism. Methods: Cross-sectional analysis of 319 older adults who underwent oral glucose tolerance tests; a subset had insulin, amyloid beta (Aβ42), and Mini Mental Status Examination. Glucose and insulin patterns with respect to cognitive diagnosis, E4 status, and sex were examined with analysis of covariance and Pearson correlation. Results: People with cognitive impairment had higher fasting insulin levels. E4 status did not affect fasting glucose values, whereas men had higher fasting glucose levels than women. E4+ men had the lowest and E4+ women had the highest glucose levels, compared to E4- groups; insulin did not differ by sex or E4 group. E4 status and sex moderated correlations between metabolic measures and AD risk factors including age and Aβ. Conclusions: Insulin resistance was associated with cognitive impairment, and sex, E4 status, and glucose values are interrelated in older adults at risk of AD. Understanding glucose metabolism for different APOE and sex groups may help elucidate differences in therapeutic responses.
Genetic Association between Presenilin 2 Polymorphisms and Alzheimer's Disease and Dementia of Lewy Body Type in a Japanese Population
Authors: Suzuki Ayako , Shibata Nobuto , Kasanuki Koji , Nagata Tomoyuki , Shinagawa Shunichiro , Kobayashi Nobuyuki , Ohnuma Tohru , Takeshita Yoshihide , Kawai Eri , Takayama Toshiki , Nishioka Kenya , Motoi Yumiko , Hattori Nobutaka , Nakayama Kazuhiko , Yamada Hisashi , Arai Heii
Published: March 2016

Background/Aims: Mutations in the presenilin 2 (PSEN2) gene cause familial Alzheimer's disease (AD). Common polymorphisms affect gene activity and increase the risk of AD. Nonsynonymous polymorphisms in the PSEN2 gene showed Lewy body dementia (LBD) phenotypes clinically. Therefore, we aimed to investigate whether PSEN2 gene polymorphisms were associated with AD or LBD. Methods: Seven single nucleotide polymorphisms (SNPs) of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBD patients, and 105 age-matched controls. Results: Linkage disequilibrium (LD) examination showed strong LD from rs1295645 to rs8383 on the gene in our cases from Japan. There were no associations between the SNPs studied here and AD onset, and haplotypic analyses did not detect genetic associations between AD and the PSEN2 gene. Although the number of the cases was small, the SNPs studied did not modify the risk of developing LBD in a Japanese population. Conclusion: The common SNPs of the PSEN2 gene did not affect the risk of AD or LBD in a Japanese population. Because genetic variability of the PSEN2 gene is associated with behavioral and psychological symptoms of dementia (BPSD) in AD and LBD, further detailed analyses considering BPSD of both diseases would be required.
Interstitial Chromosome 3p14.1 Deletion due to a Maternal Insertion: Phenotype and Association with Balanced Parental Rearrangement
Authors: Hajek Catherine , Wang Jia-Chi , Mahon Loretta W. , Martinez Ariadna , Saitta Sulagna C.
Published: March 2016

Interstitial deletions of 3p14p12 are rare chromosome abnormalities. We present a patient with multiple congenital anomalies and a 15.4-Mb interstitial loss of chromosome 3p14p12 detected by chromosomal microarray (CMA). Our patient shared many phenotypic features with other reported cases involving the same region including prominent forehead, short palpebral fissures, hand and foot anomalies, genital abnormalities, and bilateral hearing loss. Given the clinical similarity of these cases with significant overlap of the deleted regions, it is likely that the phenotype is related to the deletion of specific genes within the region. Further molecular cytogenetic investigation revealed that our patient's rearrangement was derived from a cryptic insertion of a segment of chromosome 3p into chromosome 18q in the mother, which was balanced and therefore not visible on the mother's CMA. To our knowledge, this finding has not been previously reported. This case illustrates the importance of using molecular cytogenetics for structural analysis and parental studies. CMA is commonly the first-line study in patients with multiple congenital anomalies; however, it is not the appropriate modality to define a structural rearrangement that may be the cause of a deletion. The use of adjunct studies to define the mechanism of an identified copy number aberration has direct clinical application: to identify the underlying cause of the chromosomal abnormality and to define the recurrence risk. Additionally, this case adds to the current body of work regarding a recurrent phenotype that can be attributed to interstitial chromosome 3p deletions, which may help define the phenotypic implications of deletions in this region and support early clinical management.
Empreendimentos e ações públicas e privadas em Maceió/AL no início do milênio
Authors: Cavalcanti Verônica Robalinho , Faria Geraldo Majela Gaudêncio , Costa Viviane Regina , Silva Luiz Gustavo Oliveira da , Moura Luan Rubens Dias de
Published: March 2016

As intervenções públicas e privadas na cidade de Maceió (AL) revelam o modo como o espaço da cidade tem sido produzido, os impactos gerados na conformação urbana e as tendências geradas para a expansão ou consolidação da forma urbana. As ações do poder público têm, sobretudo, focalizado a mobilidade urbana com a abertura ou reforma de vias estruturantes na cidade, consolidando a hegemonia do transporte individual privado sobre o transporte público de massa. Por sua vez, as ações do capital privado dirigem suas atenções para os espaços livres e vazios da cidade que apresentam maior potencial de retorno financeiro, procurando, primeiro, incorporar novas áreas de expansão imobiliária com a abertura de novas vias e, depois, ofertar produtos destinados, em geral, à população de poder aquisitivo mais elevado. Uma terceira frente são as ações consorciadas entre agentes públicos e privados no âmbito de programas nacionais de habitação popular. Essas têm resultado na construção de grandes empreendimentos localizados na periferia urbana distante e mesmo em terras ainda de uso rural, cabendo ao Estado o ônus da ampliação e qualificação de infraestrutura e serviços. A análise do conjunto das ações públicas e privadas sobre o espaço da cidade permitiu constatar forte protagonismo do setor imobiliário nos processos de gestão e desenho da cidade.
Avaliação do caráter da paisagem: abordagens européias
Authors: Luca Virginia De , Santiago Alina Golçalves
Published: March 2016

O caráter da paisagem resulta da combinação particular dos atributos definidores do padrão de paisagem por meio dos elementos que distinguem uma paisagem da outra, cujo arranjo é modelado pelas ações culturais e naturais de cada local. A abordagem de cunho teórico perpassa por alguns autores e algumas organizações internacionais europeias, principalmente do Reino Unido e da Espanha. O presente estudo tem como objetivo apresentar uma breve proposta para o estudo da paisagem a partir do enfoque da Convenção Europeia da Paisagem (CEP). A CEP, aprovada em 2000 em Florença, compreende a relação entre os aspectos naturais e culturais da paisagem com foco no desenvolvimento sustentável e na relação equilibrada e harmoniosa entre as necessidades sociais, econômicas e ambientais de cada comunidade, e tem como objetivo promover a proteção, a gestão e o ordenamento da paisagem. Sendo assim, é possível proteger a paisagem por meio de ações de conservação e manutenção dos traços significativos ou característicos de uma paisagem, justificadas pelo seu valor patrimonial resultante da configuração natural ou da intervenção humana. Como as paisagens sempre mudaram e continuarão a mudar, seja por processos naturais ou pela ação humana, faz-se necessário o acompanhamento das mudanças no sentido de enriquecer a diversidade e a qualidade de cada uma delas.
Alterations in Multi‐Scale Cardiac Architecture in Association With Phosphorylation of Myosin Binding Protein‐C
Authors: Taylor Erik N. , Hoffman Matthew P. , Barefield David Y. , Aninwene George E. , Abrishamchi Aurash D. , Lynch Thomas L. , Govindan Suresh , Osinska Hanna , Robbins Jeffrey , Sadayappan Sakthivel , Gilbert Richard J.
Published: March 2016

Background

The geometric organization of myocytes in the ventricular wall comprises the structural underpinnings of cardiac mechanical function. Cardiac myosin binding protein‐C (
MYBPC
3) is a sarcomeric protein, for which phosphorylation modulates myofilament binding, sarcomere morphology, and myocyte alignment in the ventricular wall. To elucidate the mechanisms by which
MYBPC
3 phospho‐regulation affects cardiac tissue organization, we studied ventricular myoarchitecture using generalized Q‐space imaging (
GQI
).
GQI
assessed geometric phenotype in excised hearts that had undergone transgenic (
TG
) modification of phospho‐regulatory serine sites to nonphosphorylatable alanines (
MYBPC
3
AllP−/(t/t)
) or phospho‐mimetic aspartic acids (
MYBPC
3
AllP+/(t/t)
).

Methods and Results

Myoarchitecture in the wild‐type (
MYBPC
3

WT

) left‐ventricle (
LV
) varied with transmural position, with helix angles ranging from −90/+90 degrees and contiguous circular orientation from the
LV
mid‐myocardium to the right ventricle (
RV
). Whereas
MYBPC
3
AllP+/(t/t)
hearts were not architecturally distinct from
MYBPC
3

WT

,
MYBPC
3
AllP−/(t/t)
hearts demonstrated a significant reduction in
LV
transmural helicity. Null
MYBPC
3
(t/t)
hearts, as constituted by a truncated
MYBPC
3 protein, demonstrated global architectural disarray and loss in helicity. Electron microscopy was performed to correlate the observed macroscopic architectural changes with sarcomere ultrastructure and demonstrated that impaired phosphorylation of
MYBPC
3 resulted in modifications of the sarcomere aspect ratio and shear angle. The mechanical effect of helicity loss was assessed through a geometric model relating cardiac work to ejection fraction, confirming the mechanical impairments observed with echocardiography.

Conclusions

We conclude that phosphorylation of
MYBPC
3 contributes to the genesis of ventricular wall geometry, linking myofilament biology with multiscale cardiac mechanics and myoarchitecture.
Early Fiber Number Ratio Is a Surrogate of Corticospinal Tract Integrity and Predicts Motor Recovery After Stroke
Authors: Bigourdan Antoine , Munsch Fanny , Coupé Pierrick , Guttmann Charles R.G. , Sagnier Sharmila , Renou Pauline , Debruxelles Sabrina , Poli Mathilde , Dousset Vincent , Sibon Igor , Tourdias Thomas
Published: March 2016

Background and Purpose—

The contribution of imaging metrics to predict poststroke motor recovery needs to be clarified. We tested the added value of early diffusion tensor imaging (DTI) of the corticospinal tract toward predicting long-term motor recovery.

Methods—

One hundred seventeen patients were prospectively assessed at 24 to 72 hours and 1 year after ischemic stroke with diffusion tensor imaging and motor scores (Fugl-Meyer). The initial fiber number ratio (iFNr) and final fiber number ratio were computed as the number of streamlines along the affected corticospinal tract normalized to the unaffected side and were compared with each other. The prediction of motor recovery (ΔFugl-Meyer) was first modeled using initial Fugl-Meyer and iFNr. Multivariate ordinal logistic regression models were also used to study the association of iFNr, initial Fugl-Meyer, age, and stroke volume with Fugl-Meyer at 1 year.

Results—

The iFNr correlated with the final fiber number ratio at 1 year (
r
=0.70;
P
<0.0001). The initial Fugl-Meyer strongly predicted motor recovery (≈73% of initial impairment) for all patients except those with initial severe stroke (Fugl-Meyer<50). For these severe patients (n=26), initial Fugl-Meyer was not correlated with motor recovery (
R
2
=0.13; p=ns), whereas iFNr showed strong correlation (
R
2
=0.56;
P
<0.0001). In multivariate analysis, the iFNr was an independent predictor of motor outcome (β=2.601; 95% confidence interval=0.304–5.110;
P
=0.031), improving prediction compared with using only initial Fugl-Meyer, age, and stroke volume (
P
=0.026).

Conclusions—

Early measurement of FNr at 24 to 72 hours poststroke is a surrogate marker of corticospinal tract integrity and provides independent prediction of motor outcome at 1 year especially for patients with severe initial impairment.
Paracetamol, Ibuprofen, and Recurrent Major Cardiovascular and Major Bleeding Events in 19 120 Patients With Recent Ischemic Stroke
Authors: Gonzalez-Valcarcel Jaime , Sissani Leila , Labreuche Julien , Bousser Marie-Germaine , Chamorro Angel , Fisher Marc , Ford Ian , Fox Kim M. , Hennerici Michael G. , Mattle Heinrich P. , Rothwell Peter M. , Steg Philippe Gabriel , Vicaut Eric , Amarenco Pierre ,   for the PERFORM Investigators
Published: March 2016

Background and Purpose—

The presumed safety of paracetamol in high–cardiovascular risk patients has been questioned. We determined whether paracetamol or ibuprofen use is associated with major cardiovascular events (MACE) or major bleeding in 19 120 patients with recent ischemic stroke or transient ischemic attack of mainly atherothrombotic origin included in the Prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) trial.

Methods—

We performed 2 nested case–control analysis (2153 cases with MACE during trial follow-up and 4306 controls matched on Essen stroke risk score; 809 cases with major bleeding matched with 1616 controls) and a separate time-varying analysis.

Results—

12.3% were prescribed paracetamol and 2.5% ibuprofen. Median duration of treatment was 14 (interquartile range 5–145) days for paracetamol and 9 (5–30) days for ibuprofen. Paracetamol, but not ibuprofen, was associated with increased risk of MACE (odds ratio 1.21, 95% confidence interval [CI] 1.04–1.42) or a major bleeding (odds ratio 1.60, 95% CI 1.26–2.03), with no impact of daily dose and duration of paracetamol treatment. Time-varying analysis found an increased risk of MACE with both paracetamol (hazard ratio 1.22, 95% CI 1.05–1.43) and ibuprofen (hazard ratio 1.47, 95% CI 1.06–2.03) and of major bleeding with paracetamol (hazard ratio 1.95, 95% CI 1.45–2.62).

Conclusions—

There was a weak and inconsistent signal for association between paracetamol or ibuprofen and MACE or major bleeding, which may be related to either a genuine but modest effect of these drugs or to residual confounding.

Clinical Trial Registration—

http://www.isrctn.com
. Unique identifier: ISRCTN66157730.
Directional escape strategy by the striped plateau lizard (Sceloporus virgatus): turning to direct escape away from predators at variable escape angles
Authors: Cooper William E.
Published: March 2016

A prey’s orientation to a predator’s approach path affects risk of fleeing straight ahead. By turning to flee closer to straight away from the predator before fleeing, prey can reduce risk. Laboratory studies suggest that escape angles should lead away from predators and be unpredictable. I studied orientation, turn, and escape angles and in a study of striped plateau lizards,Sceloporus virgatus. Lizards fled away from a predator, but often not straight away. Escape angles were variable and bimodally distributed: one mode was straight away for distancing prey from predator and one was near 90°, which maintains ability to monitor the predator or requires turning by the predator. Turn angles increased as orientation shifted toward the predator. Escape angle was closer to straight away when turn angle was larger, but turning did not fully compensate for degree of orientation toward the predator. Directional escape strategies of diverse prey are compared.
SUBCLASSIFICATION OF ADJECTIVES IN THE PEKING DIALECT
Authors: Mingyang Hu
Published: March 2016

Dans le parler de Pékin, les adjectifs ne constituent pas un ensemble homogène. Ils peuvent être subdivisés selon des critères morphologiques et syntaxiques.

Les adjectifs peuvent être redoublés. Le schéma de redoublement est AA ou AAr pour les adjectifs dissyllabiques. Cependant, tous les adjectifs ne sont pas susceptibles de redoublement. Lesquels le sont et lesquels ne le sont pas ?

Certains adjectifs peuvent avoir des suffixes modaux (au sens de "modulation"). Quels suffixes de ce type y a t-il dans le dialecte de Pékin ? Quels sont les adjectifs avec lesquels ils sont compatibles ?

D'autre part, il est admis que les adjectifs peuvent être employés aussi bien en fonction attributive qu'en fonction prédicative, alors qu'en réalité tous les adjectifs n'ont pas cette double aptitude : certains ne s'emploient qu'en fonction predicative et d'autres seulement en fonction attributive.

Enfin, certains adjectifs peuvent être employés adverbialement, d'autres pas.

L'auteur, qui a examiné, selon les critères énumérés cidessus, un ensemble de quatre cents adjectifs usuels du parler de Pékin, présente les résultats complets de son enquête : liste des formes, statistiques et conclusions.
WU, MIN AND A LITTLE HAKKA LEXICAL TONE SANDHI: RIGHT AND LEFT
Authors: Ballard William L.
Published: March 2016

An initial assay of Wu and Min lexical tone sandhi opens inquiry into a possible source : Austronesian pitch accent, and into a sandhi origin for the "third" tone ( qu/departing ). One important element in such an assay is the feature Right/Left : focus = preservation, stress, retention, etc, towards the Right or towards the Left. Northern Wu appears to be focus Left, and destressing seems to be spreading in the area. Southern Wu and Min are focus Right. Southern Wu focus does not prevent some Right mergers, and often it is the last two syllables acting together that is the focus. Northern Min shows similarities to Southern Wu, but Southern Min can be said to have no tone sandhi at all : The Amoy et al tone circles appear to be artifacts of changes in isolation values, since they are virtual reconstructions of the probable prototone values. The one Hakka dialect examined appears to be like Northern Min/Southern Wu. On the basis of this assay, I would hazard the guess that in the study of the origin of lexical tone sandhi, Southern Min should be classified with the Cantonese/Thai type, Northern Wu as a separate type heavily influenced by Mandarin, and Southern Wu/Northern Min as the preservation of the oldest, most Austronesianoid type of sandhi. Further speculation would be foolhardly until more information is available and more detailed comparisons and histories are drawn up.
A CONTRASTIVE STUDY OF THE DOLAKHALI AND KATHMANDU NEWARI DIALECTS
Authors: Genetti Carol
Published: March 2016

Dans cet article sont décrits plusieurs aspects de la morphologie et syntaxe du dialecte newari de Dolakha, en particulier la déclinaison casuelle du nom, la conjugaison, les catégories thématiques du verbe, et la formation des propositions relatives. Quelques remarques sont faites sur la phonologie, la négation, et l'ordre des mots dans la proposition. C'est la première notice du dialecte dolakhali à paraitre dans une langue européenne. A partir de la comparaison entre dolakhali et un des dialectes newari les mieux connus, celui de Katmandou l'auteur tente de reconstruire certains aspects de la morphologie verbale du Proto-Newari.
SANDHI TONAL DES SYNTAGMES DISSYLLABIQUES DU MIN-NAN PARLE A TAIWAN
Authors: Yueh-Chin Chang
Published: March 2016

This study examines the realization of modified tones (the tones that a syllable carries in a non final position) in Min-nan by means of instrumental and statistical analyses. Previous studies reported that the modified tons 1'() and 2' () 4' () and 6' ( ended with a glottal stop), 5' () and 7' ( ended with a glottal stop) are the same tones respectively. Such fact was observable only at Fo level and duration level in the present study. Significant differences in intensity were observed, especially between modified tones 4' and 6'b.
LE SYLLABAIRE DES YI DES MONTS FRAIS (LIANGSHAN, SICHUAN)
Authors: Coyaud Maurice
Published: March 2016

Starting from 8.000 characters, a group of Sichuan Yi linguists created in 1978 a syllabary of 819 characters for the syllables of their language including three (out of four ) tones : 55, 33, 21. The difficulties entailed by the indirect (by the use of a diacritic semi-circle) representation of the tone 34 are examined together with a series of problems arising from the classification of the dictionary in 26 keys : allotaxy is frequent. The consistency of the graphemic system is evaluated as well as the seldom formal relations with the Sani-Yi writing system. The Appendix contains the list (classified by keys) of the syllabic characters of Sichuan Yi with one or two words translated in French.
PIG, TONE SANDHI AND WUMIN
Authors: Ballard William L.
Published: March 2016

Several scholars have made various remarks about the language history of the Wu and Min areas. Some of these remarks concern non-Chinese languages that may have been spoken in the area(s) and that may have left some traces in the forms of Chinese spoken there now (substrata). Other remarks concern the possible prehistory of what appear now to be transitional or mixed forms, or features that may be present due to some ancient influence or borrowing. In considering such matters it is important to keep in mind the basic principles (and biases) of historical linguistics, and of the potential role of philological materials in the discussion. My fieldwork in China this spring, as well as my research in the past, point to some special historical relationship between southern Wu and northern Min. This appears to mean that the boundaries between the northern and southern types of each of the two dialect groups are stronger than they have been portrayed in the past, and that the traditional boundary between Wu and Min is considerably weaker than has been supposed. The total sum of dialect facts cannot be ignored in trying to ascertain the language history of this area; it would appear that various elements of the traditional view of the history of the southern dialects are in error in various ways. In particular, it is at least possible that Wu and Min, in some sense, share a common ancestor not common to any other Chinese dialects.
Palpada panorama sp. n. (Diptera: Syrphidae), a big-eyed hoverfly from Peru and Suriname
Authors: REEMER MENNO , MORALES MIRIAN N.
Published: March 2016

The hoverfly species Palpada panorama sp. n. (Diptera: Syrphidae) is described based on specimens from Peru and Suriname. It belongs to the scutellaris species group and it is most similar to P. erratica (Curran, 1930), from which it differs most notably by the strongly enlarged ommatidia in the upper half of the eye. Additional differences between these two species and an adjustment for the latest identification key for the species of the scutellaris group are given.
Redescription of Protanura papillata Cassagnau & Delamare Deboutteville, 1955 (Collembola, Neanuridae, Neanurinae), with new records from Middle East, and with supplemented diagnosis and key to the genus
Authors: SMOLIS ADRIAN , SKARŻYŃSKI DARIUSZ , KAHRARIAN MORTEZA , KAPRUS IGHOR J.
Published: March 2016

The poorly known Neanurini genus Protanura is rediagnosed and briefly compared with Lathriopyga. Protanura papillata Cassagnau & Delamare Deboutteville, 1955, known to date only from Lebanon, is redescribed based on the lectotype and new extensive material from Middle East.
Two new species of Xosopsaltria Kirkaldy, 1904, with a key to the species of South African pygmy bladder cicadas (Hemiptera: Cicadidae: Cicadettinae: Tettigomyiini)
Authors: Sanborn Allen F. , Villet Martin H.
Published: March 2016

Two species, Xosopsaltria brachyptera n. sp. and Xosopsaltria vitripennis n. sp., are described as new. Notes on their biology and a key to the South African pygmy bladder cicadas are also provided.
Three new species of oribatid mites of the family Punctoribatidae (Acari, Oribatida) from alpine bogs of New Zealand
Authors: ERMILOV SERGEY G. , MINOR MARIA A.
Published: March 2016

Three new species of oribatid mites of the family Punctoribatidae (Acari, Oribatida) are described from alpine bogs of the Central Otago region in the South Island of New Zealand. Macrogena hexasetosa sp. nov. is morphologically most similar to M. brevisensilla Ermilov & Minor, 2015, however, it differs from the latter by larger body size, the presence of six pairs of genital setae, notogastral and ano-adanal setae of medium size, setiform rostral setae, narrower tutorial cusps, the absence of antero-ventral teeth on genua I, II and femora II, and by the absence of striae on the subcapitular mentum. Porallozetes badamdorji sp. nov. differs from the type species—P. dispar (Hammer, 1973)—by larger body length, the presence of interlamellar setae, short and clavate bothridial setae, anterior notogastral margin, notogastral setae of medium size, semi-oval dorsophragmata, and by the position of notogastral porose areas A2 posteriorly to A1. Safrobates gerdi sp. nov. differs from the type species—S. miniporus Mahunka, 1989—by larger body size, the presence of setiform rostral setae, and by notogastral setae of medium length. Porallozetes and Safrobates are recorded in New Zealand for the first time. Generic diagnoses for Macrogena, Porallozetes and Safrobates are given.
Three new species and new distributional data for five rare species of Aphelinus (Hymenoptera: Aphelinidae) from China
Authors: CHEN YE , LI CHENG-DE
Published: March 2016

Eight species of Aphelinus Dalman (Hymenoptera, Aphelinidae) from China are reviewed. Three species, A. pseudonepalensis sp. nov., A. truncaticlavus sp. nov. and A. maculigaster sp. nov. are newly described, four species, A. meghalayanus Hayat, A. huberi Hayat, A. sharpae Hayat, and A. maculatus Yasnosh are reported as new to China, and A. asychis Walker is newly reported from Tibet, China. A key to the Chinese species of Aphelinus based on females is given.
Interethnic conflict and the potential dangers of cross-group ties
Authors: Larson Jennifer M
Published: March 2016

Bridging social ties is thought to reduce the likelihood of interethnic violence. This logic has motivated countless development projects and international programs seeking to forge cross-group ties between groups with a conflictual history. However, this article identifies an important mechanism by which certain cross-group ties can make interethnic peace strictly less likely. The results stem from a game-theoretic model which formalizes civil society as a network and relates intergroup cooperation to the particular networks that transmit information from person to person in each group. The model reveals that, first, groups are capable of enforcing cross-group cooperation, even when no cross-group ties are present and the networks within each group are missing links, using peer-enforcement strategies, and their ability to do so depends on the structure of these networks. Second, when attempting to enforce intergroup cooperation, groups with sparse networks may be at risk of a long-lasting series of back-and-forth retaliation that groups with denser networks would avoid. Finally, there exists a mechanism by which some cross-group ties make intergroup cooperation strictly less likely. When interethnic cooperation is enforced by threatening coordinated retaliation for any misbehavior, success depends on expectations about how quickly retaliation can be coordinated and how many will participate in it. Some individuals in a network are in a position to send news to many others quickly; others are not. The latter therefore coordinate retaliation more slowly and would be relatively vulnerable to cross-group defections if they could be identified. Cross-group ties expose the vulnerability and generate incentives to disrupt interethnic peace; cross-group ties between the least embedded individuals in each ethnic group are the most dangerous. Programs seeking to impose ties should avoid exposing this vulnerability without taking steps to mitigate its danger.
Darwin and Deep Time: Temporal Scales and the Naturalist’s Imagination
Authors: Dear Peter
Published: March 2016

Charles Darwin built a world around an implied metaphysics of time that treated deep time as something qualitatively different from ordinary, experienced time. He did not simply require a vast amount of time within which his primary evolutionary mechanism of natural selection could operate; in practice, he required a deep time that functioned according to different rules from those of ordinary, “shallow” time. The experience of the naturalist occupied shallow time, but it was from that experience that Darwin necessarily had to build his arguments concerning a transformism that took place on an entirely different temporal scale. Much of his reconstruction of what took place in deep time relied on inferences drawn from taxonomic classification, and those inferences in turn depended to a large degree on conclusions reached through the already-established practices of his fellow non-transformist naturalists. By bootstrapping his transformist arguments, focused on both natural and sexual selection, with non-transformist classificatory judgments, Darwin attempted to convince his fellow naturalists of the truth of evolution in deep time. In other words, while Darwin argued for the existence of selectionist processes themselves in contemporary shallow time, their transformist consequences could only be traced out in deep time, being evidenced by both contemporary and paleontological slices, or laminae, of shallow time. This served to protect transformism from the dangers of unorthodoxy by preserving uniformity within shallow time.