bluuebunny/crossref_metadata_2025 huggingface dataset:
Language at Three Timescales: The Role of Real‐Time Processes in Language Development and Evolution
Authors: McMurray Bob
Published: March 2016

Evolutionary developmental systems (evo‐devo) theory stresses that selection pressures operate on entire developmental systems rather than just genes. This study extends this approach to language evolution, arguing that selection pressure may operate on two quasi‐independent timescales. First, children clearly must acquire language successfully (as acknowledged in traditional evo‐devo accounts) and evolution must equip them with the tools to do so. Second, while this is developing, they must also communicate with others in the moment using partially developed knowledge. These pressures may require different solutions, and their combination may underlie the evolution of complex mechanisms for language development and processing. I present two case studies to illustrate how the demands of both real‐time communication and language acquisition may be subtly different (and interact). The first case study examines infant‐directed speech (IDS). A recent view is that IDS underwent cultural to statistical learning mechanisms that infants use to acquire the speech categories of their language. However, recent data suggest is it may not have evolved to enhance development, but rather to serve a more real‐time communicative function. The second case study examines the argument for seemingly specialized mechanisms for learning word meanings (e.g., fast‐mapping). Both behavioral and computational work suggest that learning may be much slower and served by general‐purpose mechanisms like associative learning. Fast‐mapping, then, may be a real‐time process meant to serve immediate communication, not learning, by augmenting incomplete vocabulary knowledge with constraints from the current context. Together, these studies suggest that evolutionary accounts consider selection pressure arising from both real‐time communicative demands and from the need for accurate language development.
Non‐specific phospholipase C1 affects silicon distribution and mechanical strength in stem nodes of rice
Authors: Cao Huasheng , Zhuo Lin , Su Yuan , Sun Linxiao , Wang Xuemin
Published: March 2016

Silicon, the second abundant element in the crust, is beneficial for plant growth, mechanical strength, and stress responses. Here we show that manipulation of the non‐specific phospholipase C1, NPC1, alters silicon content in nodes and husks of rice (Oryza sativa). Silicon content in NPC1‐overexpressing (OE) plants was decreased in nodes but increased in husks compared to wild‐type, whereas RNAi suppression of NPC1 resulted in the opposite changes to those of NPC1‐OE plants. NPC1 from rice hydrolyzed phospholipids and galactolipids to generate diacylglycerol that can be phosphorylated to phosphatidic acid. Phosphatidic acid interacts with Lsi6, a silicon transporter that is expressed at the highest level in nodes. In addition, the node cells of NPC1‐OE plants have lower contents of cellulose and hemicellulose, and thinner sclerenchyma and vascular bundle fibre cells than wild‐type plants; whereas NPC1‐RNAi plants displayed the opposite changes. These data indicate that NPC1 modulates silicon distribution and secondary cell wall deposition in nodes and grains, affecting mechanical strength and seed shattering.
Low‐molecular‐weight carbohydrate Pentaisomaltose may replace dimethyl sulfoxide as a safer cryoprotectant for cryopreservation of peripheral blood stem cells
Authors: Svalgaard Jesper Dyrendom , Haastrup Eva Kannik , Reckzeh Kristian , Holst Bjørn , Glovinski Peter Viktor , Gørløv Jette Sønderskov , Hansen Morten Bagge , Moench Kim Theilgaard , Clausen Christian , Fischer‐Nielsen Anne
Published: March 2016

BACKGROUND

Cryopreserved hematopoietic stem cell products are widely used for certain hematologic malignancies. Dimethyl sulfoxide (DMSO) is the most widely used cryoprotective agent (CPA) today, but due to indications of cellular toxicity, changes of the cellular epigenetic state, and patient‐related side effects, there is an increasing demand for DMSO‐free alternatives. We therefore investigated whether Pentaisomaltose (PIM), a low‐molecular‐weight carbohydrate (1 kDa), can be used for cryopreservation of peripheral blood stem cells, more specifically hematopoietic progenitor cell apheresis (HPC(A)) product.

STUDY DESIGN AND METHODS

We cryopreserved patient or donor HPC(A) products using 10% DMSO or 16% PIM and quantified the recovery of CD34+ cells and CD34+ subpopulations by multicolor flow cytometry. In addition, we compared the frequency of HPCs after DMSO and PIM cryopreservation using the colony‐forming cells (CFCs) assay.

RESULTS

The mean CD34+ cell recovery was 56.3 ± 23.7% (11.4%‐97.3%) and 58.2 ± 10.0% (45.7%‐76.9%) for 10% DMSO and 16% PIM, respectively. The distribution of CD34+ cell subpopulations was similar when comparing DMSO or PIM as CPA. CFC assay showed mean colony numbers of 70.7 ± 25.4 (range, 37.8‐115.5) and 67.7 ± 15.7 (range, 48‐86) for 10% DMSO and 16% PIM, respectively.

CONCLUSION

Our findings demonstrate that PIM cryopreservation of HPC(A) products provides recovery of CD34+ cells, CD34+ subpopulations, and CFCs similar to that of DMSO cryopreservation and therefore may have the potential to be used for cryopreservation of peripheral blood stem cells.
Caribbean Diversification and Development
Authors: Mohan Preeya
Published: March 2016

Small Island Developing States generally adopt diversification as their primary development strategy, often with little success. Nevertheless, there is no empirical study specifically focusing on the pattern of diversification of these countries in relation to their development. The objective of this paper was to study the export diversification pattern by the intensive (a more equally spread export basket) and extensive (an increase in new export lines) product margin of 21 Caribbean countries in relation to their level of development using panel data. The results show that despite their limited ability to diversify, Caribbean countries, as has been found for other parts of the world, first diversify and subsequently respecialise though at a substantially lower level of income than other countries and that the intensive margin plays a greater role in this process.
A three‐dimensional cell culture system as an in vitro canine mammary carcinoma model for the expression of connective tissue modulators
Authors: Cardoso T. C. , Sakamoto S. S. , Stockmann D. , Souza T. F. B. , Ferreira H. L. , Gameiro R. , Vieira F. V. , Louzada M. J. Q. , Andrade A. L. , Flores E. F.
Published: March 2016

In this study, derived complex carcinoma (CC) and simple carcinoma (SC) cell lines were established and cultured under two‐dimensional (2D) and three‐dimensional (3D) conditions. The 3D was performed in six‐well AlgiMatrix™ (LifeTechnologies®, Carlsbad, CA, USA) scaffolds, resulting in spheroids sized 50–125 µm for CC and 175–200 µm for SC. Cell viability was demonstrated up to 14 days for both models. Epidermal growth factor receptor (EGFR) was expressed in CC and SC in both systems. However, higher mRNA and protein levels were observed in SC 2D and 3D systems when compared with CC (P < 0.005). The connective tissue modulators, metalloproteinases‐1, ‐2, ‐9 and ‐13 (MMPs), relaxin receptors 1 and 2 (RXR1 and RXR2) and E‐cadherin (CDH1) were quantitated. All were upregulated similarly when canine mammary tumour (CMT)‐derived cell lines were cultured under 3D AlgiMatrix, except CDH1 that was downregulated (P < 0.005). These results are promising towards the used of 3D system to increase a high throughput in vitro canine tumour model.
Erythrocyte osmotic fragility and select hematologic variables in postparturient mares and their foals
Authors: Arfuso Francesca , Quartuccio Marco , Bazzano Marilena , Fazio Francesco , Piccione Giuseppe
Published: March 2016

Background

Knowledge of hematologic function in postparturient mares and foals is crucial for the monitoring of their health status and for the prompt diagnosis of pathologic conditions.

Objectives

The aim of this study was to evaluate erythrocyte osmotic fragility (EOF) and select hematologic variables in mares and their foals during the first month after foaling.

Methods

Blood samples were collected from each animal every 3 days from day 1 until day 30 after foaling, and tested for RBC count, HGB, HCT, MCV, and EOF. Two‐way repeated measures analysis of variance (ANOVA) and Bonferroni post hoc comparison test were applied to determine the effects of time and age (mares vs foals). Pearson correlation coefficients were computed for EOF and time or MCV values.

Results

There was a significant effect of time in RBC, HGB, HCT, and EOF (P < .001). Statistically significant differences were observed between mares and foals for RBC, MCV, and EOF (P < .05) throughout the experimental period. Significant correlations between EOF and both time and MCV (P < .05) were found in mares as well as in foals.

Conclusion

These results contribute to the understanding of perinatal changes in hematologic variables in mares and foals. In addition, the data support the relevance of specific reference intervals for postparturient mares and foals. The findings also provide useful information that could help clinicians to better interpret clinical data and diagnose equine disease.
Assessing the influence of component processing and donor characteristics on quality of red cell concentrates using quality control data
Authors: Jordan A. , Chen D. , Yi Q. ‐L. , Kanias T. , Gladwin M. T. , Acker J. P.
Published: March 2016

Background and Objectives

Quality control (QC) data collected by blood services are used to monitor production and to ensure compliance with regulatory standards. We demonstrate how analysis of quality control data can be used to highlight the sources of variability within red cell concentrates (RCCs).

Materials and Methods

We merged Canadian Blood Services QC data with manufacturing and donor records for 28 227 RCC between June 2011 and October 2014. Units were categorized based on processing method, bag manufacturer, donor age and donor sex, then assessed based on product characteristics: haemolysis and haemoglobin levels, unit volume, leucocyte count and haematocrit.

Results

Buffy‐coat method (top/bottom)‐processed units exhibited lower haemolysis than units processed using the whole‐blood filtration method (top/top). Units from female donors exhibited lower haemolysis than male donations. Processing method influenced unit volume and the ratio of additive solution to residual plasma.

Conclusions

Stored red blood cell characteristics are influenced by prestorage processing and donor factors. Understanding the relationship between processing, donors and RCC quality will help blood services to ensure the safety of transfused products.
Underdiagnosing of antibody‐mediated transfusion‐related acute lung injury: evaluation of cellular‐based versus bead‐based techniques
Authors: van Stein D. , Beckers E. A. M. , Peters A. L. , Porcelijn L. , Middelburg R. A. , Lardy N. M. , van Rhenen D. J. , Vlaar A. P. J.
Published: March 2016

Background and objectives

Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related mortality. To support the diagnosis of antibody‐mediated TRALI, HLA and HNA antibodies are tested in involved blood donors. Identification of antibody positive donors is important as exclusion of these donors is part of preventative strategies against TRALI. We compared cellular‐based versus bead‐based techniques for diagnosis of antibody‐mediated TRALI.

Materials and methods

All reported TRALI cases in the Netherlands during a 5‐year period were evaluated. Donors were screened for the presence of HLA class I and class II antibodies using both cellular‐based and bead‐based techniques.

Results

In total, 100 TRALI cases were reported of which 91 were fully tested. In 113 donors, HLA antibodies were detected of which 84 were only detected by bead‐based techniques, 12 only by cellular‐based tests and 17 by both assays. Antibody‐mediated TRALI was diagnosed in 44 of 91 reported cases. Twenty‐one (48%) of these cases would not have been identified using only cellular‐based assays.

Conclusion

Bead‐based techniques show a higher sensitivity for detecting incompatible donors in TRALI cases than cellular‐based assays. These results suggest that the use of bead‐based assays will result in a significant reduction of future TRALI reactions as more antibody positive donors will be excluded from future donations.
A sexually dimorphic effect of cholera toxin: rapid changes in colonic motility mediated via a 5‐HT3 receptor‐dependent pathway in female C57Bl/6 mice
Authors: Balasuriya Gayathri K. , Hill‐Yardin Elisa L. , Gershon Michael D. , Bornstein Joel C.
Published: March 2016

Key points

Cholera causes more than 100,000 deaths each year as a result of severe diarrhoea, vomiting and dehydration due to the actions of cholera toxin; more females than males are affected.

Cholera toxin induces hypersecretion via release of mucosal serotonin and over‐activation of enteric neurons, but its effects on gastrointestinal motility are not well characterized.

We found that cholera toxin rapidly and reversibly reduces colonic motility in female mice in oestrus, but not in males or females in prooestrus, an effect mediated by 5‐HT in the colonic mucosa and by 5‐HT3 receptors.

We show that the number of mucosal enterochromaffin cells containing 5‐HT changes with the oestrous cycle in mice.

These findings indicate that cholera toxin's effects on motility are rapid and depend on the oestrous cycle and therefore can help us better understand differences in responses in males and female patients.

Extensive studies of the mechanisms responsible for the hypersecretion produced by cholera toxin (CT) have shown that this toxin produces a massive over‐activation of enteric neural secretomotor circuits. The effects of CT on gastrointestinal motility, however, have not been adequately characterized. We investigated effects of luminal CT on neurally mediated motor activity in ex vivo male and female mouse full length colon preparations. We used video recording and spatiotemporal maps of contractile activity to quantify colonic migrating motor complexes (CMMCs) and resting colonic diameter. We compared effects of CT in female colon from wild‐type and mice lacking tryptophan hydroxylase (TPH1KO). We also compared CMMCs in colons of female mice in oestrus with those in prooestrus. In female (but not male) colon, CT rapidly, reversibly and concentration‐dependently inhibits CMMC frequency and induces a tonic constriction. These effects were blocked by granisetron (5‐HT3 antagonist) and were absent from TPH1KO females. CT effects were prominent at oestrus but absent at prooestrus. The number of EC cells containing immunohistochemically demonstrable serotonin (5‐HT) was 30% greater in female mice during oestrus than during prooestrus or in males. We conclude that CT inhibits CMMCs via release of mucosal 5‐HT, which activates an inhibitory pathway involving 5‐HT3 receptors. This effect is sex‐ and oestrous cycle‐dependent and is probably due to an oestrous cycle‐dependent change in the number of 5‐HT‐containing EC cells in the colonic mucosa.
Critical role of intercalated water for electrocatalytically active nitrogen-doped graphitic systems
Authors: Martinez Ulises , Dumont Joseph H. , Holby Edward F. , Artyushkova Kateryna , Purdy Geraldine M. , Singh Akhilesh , Mack Nathan H. , Atanassov Plamen , Cullen David A. , More Karren L. , Chhowalla Manish , Zelenay Piotr , Dattelbaum Andrew M. , Mohite Aditya D. , Gupta Gautam
Published: March 2016

Removal of intercalated water within graphitic sheets is critical to achieving high-performing oxygen reduction reaction catalysts.
Mutations in chromatin machinery and pediatric high-grade glioma
Authors: Lulla Rishi R. , Saratsis Amanda Muhs , Hashizume Rintaro
Published: March 2016

Mutations in chromatin machinery define pediatric high-grade gliomas; efforts to define and target their functions are under way.
FOXA1 defines cancer cell specificity
Authors: Zhang Gaihua , Zhao Yongbing , Liu Yi , Kao Li-Pin , Wang Xiao , Skerry Benjamin , Li Zhaoyu
Published: March 2016

Functional FOXA1 targeting is mostly unique to each of the four human cancer cell lines HepG2, LNCaP, MCF7, and T47D.
A Chemotaxis Receptor Modulates Nodulation during the Azorhizobium caulinodans-Sesbania rostrata Symbiosis
Authors: Jiang Nan , Liu Wei , Li Yan , Wu Hailong , Zhang Zhenhai , Alexandre Gladys , Elmerich Claudine , Xie Zhihong
Published: March 2016

Azorhizobium caulinodans
ORS571 is a free-living nitrogen-fixing bacterium which can induce nitrogen-fixing nodules both on the root and the stem of its legume host
Sesbania rostrata
. This bacterium, which is an obligate aerobe that moves by means of a polar flagellum, possesses a single chemotaxis signal transduction pathway. The objective of this work was to examine the role that chemotaxis and aerotaxis play in the lifestyle of the bacterium in free-living and symbiotic conditions. In bacterial chemotaxis, chemoreceptors sense environmental changes and transmit this information to the chemotactic machinery to guide motile bacteria to preferred niches. Here, we characterized a chemoreceptor of
A. caulinodans
containing an N-terminal PAS domain, named IcpB. IcpB is a soluble heme-binding protein that localized at the cell poles. An
icpB
mutant strain was impaired in sensing oxygen gradients and in chemotaxis response to organic acids. Compared to the wild-type strain, the
icpB
mutant strain was also affected in the production of extracellular polysaccharides and impaired in flocculation. When inoculated alone, the
icpB
mutant induced nodules on
S. rostrata
, but the nodules formed were smaller and had reduced N
2
-fixing activity. The
icpB
mutant failed to nodulate its host when inoculated competitively with the wild-type strain. Together, the results identify chemotaxis and sensing of oxygen by IcpB as key regulators of the
A. caulinodans
-
S. rostrata
symbiosis.

IMPORTANCE
Bacterial chemotaxis has been implicated in the establishment of various plant-microbe associations, including that of rhizobial symbionts with their legume host. The exact signal(s) detected by the motile bacteria that guide them to their plant hosts remain poorly characterized.
Azorhizobium caulinodans
ORS571 is a diazotroph that is a motile and chemotactic rhizobial symbiont of
Sesbania rostrata
, where it forms nitrogen-fixing nodules on both the roots and the stems of the legume host. We identify here a chemotaxis receptor sensing oxygen in
A. caulinodans
that is critical for nodulation and nitrogen fixation on the stems and roots of
S. rostrata
. These results identify oxygen sensing and chemotaxis as key regulators of the
A. caulinodans-S. rostrata
symbiosis.
Ecophysiological Distinctions of Haloarchaea from a Hypersaline Antarctic Lake as Determined by Metaproteomics
Authors: Tschitschko Bernhard , Williams Timothy J. , Allen Michelle A. , Zhong Ling , Raftery Mark J. , Cavicchioli Ricardo
Published: March 2016

Deep Lake in the Vestfold Hills is hypersaline and the coldest system in Antarctica known to support microbial growth (temperatures as low as −20°C). It represents a strong experimental model because the lake supports a low-complexity community of haloarchaea, with the three most abundant species totaling ∼72%. Moreover, the dominant haloarchaea are cultivatable, and their genomes are sequenced. Here we use metaproteomics linked to metagenome data and the genome sequences of the isolates to characterize the main pathways, trophic strategies, and interactions associated with resource utilization. The dominance of the most abundant member,
Halohasta litchfieldiae
, appears to be predicated on competitive utilization of substrates (e.g., starch, glycerol, and dihydroxyacetone) produced by
Dunaliella
, the lake's primary producer, while also possessing diverse mechanisms for acquiring nitrogen and phosphorus. The second most abundant member, strain DL31, is proficient in degrading complex proteinaceous matter.
Hht. litchfieldiae
and DL31 are inferred to release labile substrates that are utilized by
Halorubrum lacusprofundi
, the third most abundant haloarchaeon in Deep Lake. The study also linked genome variation to specific protein variants or distinct genetic capacities, thereby identifying strain-level variation indicative of specialization. Overall, metaproteomics revealed that rather than functional differences occurring at different lake depths or through size partitioning, the main lake genera possess major trophic distinctions, and phylotypes (e.g., strains of
Hht. litchfieldiae
) exhibit a more subtle level of specialization. This study highlights the extent to which the lake supports a relatively uniform distribution of taxa that collectively possess the genetic capacity to effectively exploit available nutrients throughout the lake.

IMPORTANCE
Life on Earth has evolved to colonize a broad range of temperatures, but most of the biosphere (∼85%) exists at low temperatures (≤5°C). By performing unique roles in biogeochemical cycles, environmental microorganisms perform functions that are critical for the rest of life on Earth to survive. Cold environments therefore make a particularly important contribution to maintaining healthy, stable ecosystems. Here we describe the main physiological traits of the dominant microorganisms that inhabit Deep Lake in Antarctica, the coldest aquatic environment known to support life. The hypersaline system enables the growth of halophilic members of the
Archaea
: haloarchaea. By analyzing proteins of samples collected from the water column, we determined the functions that the haloarchaea were likely to perform. This study showed that the dominant haloarchaea possessed distinct lifestyles yet formed a uniform community throughout the lake that was collectively adept at using available light energy and diverse organic substrates for growth.
Silica-Induced Protein (Sip) in Thermophilic Bacterium Thermus thermophilus Responds to Low Iron Availability
Authors: Fujino Yasuhiro , Nagayoshi Yuko , Iwase Makoto , Yokoyama Takushi , Ohshima Toshihisa , Doi Katsumi
Published: March 2016

Thermus thermophilus
HB8 expresses silica-induced protein (Sip) when cultured in medium containing supersaturated silicic acids. Using genomic information, Sip was identified as a Fe
3+
-binding ABC transporter. Detection of a 1-kb hybridized band in Northern analysis revealed that
sip
transcription is monocistronic and that
sip
has its own terminator and promoter. The sequence of the
sip
promoter showed homology with that of the σ
A
-dependent promoter, which is known as a housekeeping promoter in HB8. Considering that
sip
is transcribed when supersaturated silicic acids are added, the existence of a repressor is presumed. DNA microarray analysis suggested that supersaturated silicic acids and iron deficiency affect
Thermus
cells similarly, and enhanced
sip
transcription was detected under both conditions. This suggested that
sip
transcription was initiated by iron deficiency and that the ferric uptake regulator (Fur) controlled the transcription. Three Fur gene homologues (TTHA0255, TTHA0344, and TTHA1292) have been annotated in the HB8 genome, and electrophoretic mobility shift assays revealed that the TTHA0344 product interacts with the
sip
promoter region. In medium containing supersaturated silicic acids, free Fe
3+
levels were decreased due to Fe
3+
immobilization on colloidal silica. This suggests that, because Fe
3+
ions are captured by colloidal silica in geothermal water,
Thermus
cells are continuously exposed to the risk of iron deficiency. Considering that Sip is involved in iron acquisition, Sip production may be a strategy to survive under conditions of low iron availability in geothermal water.

IMPORTANCE
The thermophilic bacterium
Thermus thermophilus
HB8 produces silica-induced protein (Sip) in the presence of supersaturated silicic acids. Sip has homology with iron-binding ABC transporter; however, the mechanism by which Sip expression is induced by silicic acids remains unexplained. We demonstrate that Sip captures iron and its transcription is regulated by the repressor ferric uptake regulator (Fur). This implies that Sip is expressed with iron deficiency. In addition, it is suggested that negatively charged colloidal silica in supersaturated solution absorbs Fe
3+
ions and decreases iron availability. Considering that geothermal water contains ample silicic acids, it is suggested that thermophilic bacteria are always facing iron starvation. Sip production may be a strategy for surviving under conditions of low iron availability in geothermal water.
Novel Cupriavidus Strains Isolated from Root Nodules of Native Uruguayan Mimosa Species
Authors: Platero Raúl , James Euan K. , Rios Cecilia , Iriarte Andrés , Sandes Laura , Zabaleta María , Battistoni Federico , Fabiano Elena
Published: March 2016

The large legume genusMimosais known to be associated with both alphaproteobacterial and betaproteobacterial symbionts, depending on environment and plant taxonomy, e.g., Brazilian species are preferentially nodulated byBurkholderia, whereas those in Mexico are associated with alphaproteobacterial symbionts. Little is known, however, about the symbiotic preferences ofMimosaspp. at the southern subtropical limits of the genus. In the present study, rhizobia were isolated from field-collected nodules fromMimosaspecies that are native to a region in southern Uruguay. Phylogenetic analyses of sequences of the 16S rRNA,recA, andgyrBcore genome and thenifHandnodAsymbiosis-essential loci confirmed that all the isolates belonged to the genusCupriavidus. However, none were in the well-described symbiotic speciesC. taiwanensis, but instead they were closely related to other species, such asC. necator, and to species not previously known to be symbiotic (or diazotrophic), such asC. basilensisandC. pinatubonensis. Selection of these novelCupriavidussymbionts by UruguayanMimosaspp. is most likely due to their geographical separation from their Brazilian cousins and to the characteristics of the soils in which they were found.

IMPORTANCEWith the aim of exploring the diversity of rhizobia associated with nativeMimosaspecies, symbionts were isolated from root nodules on fiveMimosaspecies that are native to a region in southern Uruguay, Sierra del Abra de Zabaleta. In contrast to data obtained in the major centers of diversification of the genusMimosa, Brazil and Mexico, where it is mainly associated withBurkholderiaandRhizobium/Ensifer, respectively, the present study has shown that all the isolated symbiotic bacteria belonged to the genusCupriavidus. Interestingly, none of nodules contained bacteria belonging to the well-described symbiotic speciesC. taiwanensis, but instead they were related to otherCupriavidusspecies such asC. necatorandC. pinatubonensis. These data suggest the existence of a higher diversity within beta-rhizobialCupriavidusthan was previously suspected, and thatMimosaspp. from Sierra del Abra de Zabaleta, may be natural reservoirs for novel rhizobia.
Indirect measure of visceral adiposity ‘A Body Shape Index’ (ABSI) is associated with arterial stiffness in patients with type 2 diabetes
Authors: Bouchi Ryotaro , Asakawa Masahiro , Ohara Norihiko , Nakano Yujiro , Takeuchi Takato , Murakami Masanori , Sasahara Yuriko , Numasawa Mitsuyuki , Minami Isao , Izumiyama Hajime , Hashimoto Koshi , Yoshimoto Takanobu , Ogawa Yoshihiro
Published: March 2016

Objective

Among indirect measures of visceral adiposity, A Body Shape Index (ABSI), which is defined as waist circumference (WC)/(body mass index (BMI)2/3×height1/2), is unique in that ABSI is positively correlated with visceral adiposity and is supposed to be independent of BMI. ABSI has been also shown to be linearly and positively associated with visceral fat mass and all-cause and cardiovascular disease (CVD) in the general population. It is, however, uncertain whether ABSI could be associated with arterial stiffness in patients with diabetes.

Methods

This is a cross-sectional study of 607 patients with type 2 diabetes (mean age 64±12 years; 40.0% female). Visceral fat area (VFA, cm2) and subcutaneous fat area (SFA, cm2) were assessed with a dual-impedance analyzer. In order to estimate the risk for CVD, brachial-ankle pulse wave velocity (baPWV, cm) was used for the assessment of arterial stiffness.

Results

ABSI was significantly and positively correlated with VFA (r=0.138, p=0.001) and negatively associated with BMI (r=−0.085, p=0.037). The correlation of z-score for ABSI with VFA remained significant (r=0.170, p<0.001) but not with BMI (r=0.009, p=0.820). ABSI (standardized β 0.095, p=0.043) but not WC (standardized β −0.060, p=0.200) was significantly and positively correlated with baPWV in the multivariate model including BMI as a covariate.

Conclusions

ABSI appears to reflect visceral adiposity independently of BMI and to be a substantial marker of arterial stiffening in patients with type 2 diabetes.
Association between subjective social status and cardiovascular disease and cardiovascular risk factors: a systematic review and meta-analysis
Authors: Tang Karen L , Rashid Ruksana , Godley Jenny , Ghali William A
Published: March 2016

Objective

To determine the association between subjective social status (SSS), or the individual's perception of his or her position in the social hierarchy, and the odds of coronary artery disease (CAD), hypertension, diabetes, obesity and dyslipidaemia.

Study Design

Systematic review and meta-analysis.

Methods

We searched PubMed, MEDLINE, EMBASE, CINAHL, PsycINFO, SocINDEX, Web of Science and reference lists of all included studies up to October 2014, with a verification search in July 2015. Inclusion criteria were original studies in adults that reported odds, risk or hazard ratios of at least one outcome of interest (CAD, hypertension, diabetes, obesity or dyslipidaemia), comparing ‘lower’ versus ‘higher’ SSS groups, where SSS is measured on a self-anchoring ladder. ORs were pooled using a random-effects model.

Results

10 studies were included in the systematic review; 9 of these were included in the meta-analysis. In analyses unadjusted for objective socioeconomic status (SES) measures such as income, education or occupation, the pooled OR comparing the bottom versus the top of the SSS ladder was 1.82 (95% CI 1.10 to 2.99) for CAD, 1.88 (95% CI 1.27 to 2.79) for hypertension, 1.90 (95% CI 1.25 to 2.87) for diabetes, 3.68 (95% CI 2.03 to 6.64) for dyslipidaemia and 1.57 (95% CI 0.95 to 2.59) for obesity. These associations were attenuated when adjusting for objective SES measures, with the only statistically significant association remaining for dyslipidaemia (OR 2.10, 95% CI 1.09 to 4.06), though all ORs remained greater than 1.

Conclusions

Lower SSS is associated with significantly increased odds of CAD, hypertension, diabetes and dyslipidaemia, with a trend towards increased odds of obesity. These trends are consistently present, though the effects attenuated when adjusting for SES, suggesting that perception of one's own status on a social hierarchy has health effects above and beyond one's actual income, occupation and education.
TOP2Acopy number and TOP2A expression in uterine benign smooth muscle tumours and leiomyosarcoma
Authors: Baiocchi Glauco , Poliseli Fernando Luís Visoni , De Brot Louise , Mantoan Henrique , Schiavon Beatriz Nunes , Faloppa Carlos Chaves , Vassallo Jose , Soares Fernando Augusto , Cunha Isabela Werneck
Published: March 2016

Aims

To examineTOP2Acopy number, TOP2A expression, and its prognostic value in uterine leiomyosarcoma (LMS) and other benign smooth muscle tumours.

Methods

We analysed 37 patients treated for uterine LMS with immunohistochemistry for protein expression and fluorescence in situ hybridisation (FISH) for copy number. Twelve cases of leiomyoma variants (LMVs), 4 smooth muscle tumours of uncertain malignant potential (STUMP) and 23 leiomyomas (LMs) were also included.

Results

Eighteen patients with LMS (48.6%) were International Federation of Gynecology and Obstetrics (FIGO) stage I, six (16.2%) were stage II, four (10.8%) were stage III, and nine (24.3%) were stage IV. Twenty-one (56.8%) patients with LMS showed high expression of TOP2A. Greater TOP2A levels were found in patients with stage ≥II disease compared with stage I and also in high mitotic index tumours (>20/10 HPF (high power field)). Eleven (36.7%) cases had abnormalTOP2Acopy numbers. There was no link betweenTOP2Acopy number and TOP2A expression. All patients with benign smooth muscle tumours had low TOP2A immunohistochemical expression and one (7.7%) patient hadTOP2Aamplification. TOP2A expression andTOP2Acopy number had no impact on disease outcomes. Only the presence of disease outside of the uterus negatively impacted survival compared with early disease (53.4 vs 15.8 months; p<0.001).

Conclusions

TOP2A is highly expressed in advanced LMS but not in non-malignant diseases. TOP2A expression does not correlate with FISH results and does not predict outcome. TOP2A levels are higher in high-mitotic index tumours and in more advanced stages of disease.
Pathophysiological effects of different risk factors for heart failure
Authors: Yang Hong , Wang Ying , Negishi Kazuaki , Nolan Mark , Marwick Thomas H
Published: March 2016

Background

Hypertension and type 2 diabetes mellitus (T2DM) are important causes of non-ischaemic heart failure (HF). Understanding the pathophysiology of early HF may guide screening. We hypothesised that the underlying physiology differed according to aetiology.

Methods

In this cross-sectional study of 521 asymptomatic community-based subjects ≥65 years with ≥1 HF risk factors, 187 participants (36%) had T2DM and hypertension (T2DM+/HTN+), 109 (21%) had T2DM with no hypertension (T2DM+/HTN−) and 72 (14%) had neither T2DM nor hypertension (T2DM−/HTN−). In 153 patients (29%), clinic blood pressure was ≥140/90 mm Hg, defined as active hypertension (T2DM−/HTN+). All underwent a comprehensive echocardiogram, including conventional parameters for systolic and diastolic function as well as global longitudinal strain (GLS), diastolic strain (DS) and DS rate (DSR). A 6 min walk (6MW) test was used to assess functional capacity.

Results

GLS in T2DM−/HTN+ group (−18.9±2.7%) was similar to that in T2DM−/HTN− group (−19.4±2.4%) and greater than T2DM+/HTN− (−18.0±2.8%, p=0.005). DS in T2DM−/HTN− (0.47±0.15%) exceeded that in T2DM−/HTN+ (0.43±0.14%) and T2DM+/HTN− (0.43±0.13%). 6MW distance was preserved in T2DM−/HTN+ (482±85 m) and reduced in T2DM+/HTN− (469±93, p<0.001). Those with T2DM and active hypertension had worst GLS, DS, DSR and shortest 6MW distance (p<0.002). In multivariable analysis, GLS was associated with T2DM but neither active hypertension nor a history of hypertension. Diastolic markers and left ventricular (LV) mass were associated with hypertension and T2DM. Thus, patients with HF risk factors show different functional disturbances according to aetiology.

Conclusions

Patients with hypertension had relatively less impaired GLS and preserved 6MW distance but more impaired diastolic function.
Hydrogen sulfide depletion contributes to microvascular remodeling in obesity
Authors: Candela Joseph , Velmurugan Gopal V. , White Carl
Published: March 2016

Structural remodeling of the microvasculature occurs during obesity. Based on observations that impaired H2S signaling is associated with cardiovascular pathologies, the current study was designed to test the hypothesis that altered H2S homeostasis is involved in driving the remodeling process in a diet-induced mouse model of obesity. The structural and passive mechanical properties of mesenteric resistance arterioles isolated from 30-wk-old lean and obese mice were assessed using pressure myography, and vessel H2S levels were quantified using the H2S indicator sulfidefluor 7-AM. Remodeling gene expression was assessed using quantitative RT-PCR, and histological staining was used to quantify vessel collagen and elastin. Obesity was found to be associated with decreased vessel H2S concentration, inward hypertrophic remodeling, altered collagen-to-elastin ratio, and reduced vessel stiffness. In addition, mRNA levels of fibronectin, collagen types I and III, matrix metalloproteinases 2 and 9, and tissue inhibitor of metalloproteinase 1 were increased and elastin was decreased by obesity. Evidence that decreased H2S was responsible for the genetic changes was provided by experiments in which H2S levels were manipulated, either by inhibition of the H2S-generating enzyme cystathionine γ-lyase with dl-propargylglycine or by incubation with the H2S donor GYY4137. These data suggest that, during obesity, depletion of H2S is involved in orchestrating the genetic changes underpinning inward hypertrophic remodeling in the microvasculature.
Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig
Authors: Beaumont Eric , Wright Gary L. , Southerland Elizabeth M. , Li Ying , Chui Ray , KenKnight Bruce H. , Armour J. Andrew , Ardell Jeffrey L.
Published: March 2016

Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs ( n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15–20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls ( n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO ( P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling.
Murine models of cardiovascular comorbidity in chronic obstructive pulmonary disease
Authors: Khedoe P. Padmini S.J. , Rensen Patrick C.N. , Berbée Jimmy F.P. , Hiemstra Pieter S.
Published: March 2016

Patients with chronic obstructive pulmonary disease (COPD) have an increased risk for cardiovascular disease (CVD). Currently, COPD patients with atherosclerosis (i.e., the most important underlying cause of CVD) receive COPD therapy complemented with standard CVD therapy. This may, however, not be the most optimal treatment. To investigate the link between COPD and atherosclerosis and to develop specific therapeutic strategies for COPD patients with atherosclerosis, a substantial number of preclinical studies using murine models have been performed. In this review, we summarize the currently used murine models of COPD and atherosclerosis, both individually and combined, and discuss the relevance of these models for studying the pathogenesis and development of new treatments for COPD patients with atherosclerosis. Murine and clinical studies have provided complementary information showing a prominent role for systemic inflammation and oxidative stress in the link between COPD and atherosclerosis. These and other studies showed that murine models for COPD and atherosclerosis are useful tools and can provide important insights relevant to understanding the link between COPD and CVD. More importantly, murine studies provide good platforms for studying the potential of promising (new) therapeutic strategies for COPD patients with CVD.
TheBDKRB2 +9/-9 Polymorphisms Influence Pro-Inflammatory Cytokine Levels in Knee Osteoarthritis by Altering TLR-2 Expression: Clinical and in Vitro Studies
Authors: Chen Shuo , Zhang Lei , Xu Ruonan , Ti Yunfan , Zhao Yunlong , Zhou Liwu , Zhao Jianning
Published: March 2016

Background/Aims: The bradykinin B2 receptor (BDKRB2) +9/-9 gene polymorphisms have been shown to be associated with the susceptibility and severity of osteoarthritis (OA); however, the underlying mechanisms are unclear. In this study, we investigated the correlation between the BDKRB2 +9/-9 polymorphisms and pro-inflammatory cytokine levels in OA and the molecular mechanisms involved. Methods: A total of 156 patients with primary knee OA and 121 healthy controls were enrolled. The BDKRB2 +9/-9 polymorphisms were genotyped. The tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 levels were determined using Enzyme-linked immunosorbent assay (ELISA). The toll-like receptor (TLR)-2 and TLR-4 mRNA levels were determined by quantitative real-time PCR. The basal and bradykinin-stimulated pro-inflammatory cytokine secretion in human OA synoviocytes and the involvement of TLR-2 and mitogen-activated protein kinases (MAPKs) were investigated. Results: The presence of -9 bp genotype is associated with higher TNF-α, IL-6, and IL-8 levels and higher TLR-2 expression in OA patients. The basal and bradykinin-induced TLR-2 expressions in human OA synoviocytes were significantly reduced by specific inhibitors of p38, JNK1/2, and ERK1/2. Both the B2 receptor antagonist MEN16132 and TLR-2 silencing inhibited IL-6 and IL-8 secretion in human OA synoviocytes. Conclusion: The data suggested that the BDKRB2 +9/-9 polymorphisms influence pro-inflammatory cytokine levels in knee osteoarthritis by altering TLR-2 expression.
Elevated B Cell Activation is Associated with Type 2 Diabetes Development in Obese Subjects
Authors: Zhai Xiao , Qian Guangfang , Wang Yiran , Chen Xiao , Lu Jiancan , Zhang Yaping , Huang Qin , Wang Qijin
Published: March 2016

Background/Aims: Despite strong association between obesity and the pathogenesis of type 2 diabetes (T2D), only a subset of obese individuals eventually develops T2D. We sought to determine the immunological factors behind this heterogeneity. Methods: Peripheral blood of obese non-diabetic subjects and obese diabetic subjects were collected and the B cell responses in these subjects were analyzed. Results: We found that the B cells from obese diabetic subjects had similar B cell subtype composition and secreted similar levels of low-grade pro-inflammatory cytokines to obese non-diabetic subjects, characteristic to the background chronic immune activation frequently observed in obese subjects. When examining adaptive B cell antibody responses, however, obese diabetic subjects presented much higher levels of polyclonal activation and antibody secretion, with impaired ability to response to new antigens such as seasonal influenza vaccination. Conclusions: These data demonstrated that in obese diabetic subjects, B cell adaptive response is impaired and potentially contribute to overall higher inflammation.
Very Early versus Delayed Rehabilitation for Acute Ischemic Stroke Patients with Intravenous Recombinant Tissue Plasminogen Activator: A Nationwide Retrospective Cohort Study
Authors: Momosaki Ryo , Yasunaga Hideo , Kakuda Wataru , Matsui Hiroki , Fushimi Kiyohide , Abo Masahiro
Published: March 2016

Background: Although the safety and feasibility of very early rehabilitation for stroke are well recognized, the initiation of rehabilitation is sometimes delayed after thrombolysis. The purpose of this study was to clarify the association between very early rehabilitation and outcomes in acute ischemic stroke patients who received tissue plasminogen activator, using a national inpatient database in Japan. Methods: We identified patients who were admitted to acute-care hospitals with ischemic stroke and were treated with intravenous recombinant tissue plasminogen activator on the same day of stroke onset and received rehabilitation within 3 days from admission. The primary outcome was functional independence on discharge. We compared the outcomes of a very early rehabilitation group with a comparison group. Results: We identified 6,153 eligible patients, of whom 4,266 received very early rehabilitation. The proportion of functional independence on discharge was 41.2 and 36.6% in the very early rehabilitation group and the comparison group, respectively. Multivariable logistic regression analysis showed that the very early rehabilitation was significantly associated with a higher proportion of functional independence after adjustment for confounding factors. There was no significant difference in 7-, 30-, 90-day mortality or incidence of intracerebral hemorrhage between the groups after adjusting for baseline characteristics. Instrumental variable analysis confirmed a higher proportion of functionally independent patients in the very early rehabilitation group. Conclusion: Patients with acute ischemic stroke undergoing very early rehabilitation after thrombolysis were more likely to achieve functional independence without an increase in adverse outcomes.
Blood Brain Barrier Disruption in Diabetic Stroke Related to Unfavorable Outcome
Authors: Yu Xinfeng , Xu Xiaojun , Jackson Alan , Sun Jianzhong , Huang Peiyu , Mao Yingying , Chen Zhicai , Lou Min , Jiang Quan , Zhang Minming
Published: March 2016

Background: Diabetes mellitus (DM) is associated with a wide range of microvascular abnormalities in the brain. These include the dysfunction of the blood brain barrier (BBB). In this study, we test the hypotheses that disruption of the BBB in patients presenting with acute stroke is common in patients with DM and is related to outcome. Methods: Sixty-two consecutive patients with ischemic stroke in the middle cerebral artery territory were enrolled within 3-7 days after onset. In ischemic lesion, BBB disruption was detected by parenchymal enhancement (PE) on 5 min delayed post-contrast T1 weighted imaging. National Institute of Health Stroke Score (NIHSS) assessed neurologic impairment on admission. Clinical outcome at 3 months was classified as unfavorable if the modified Rankin scale was >1. The independent factors associated with clinical outcome were analyzed using multivariate logistic regression analysis and OR with its 95% CIs were estimated. Results: An unfavorable stroke outcome was found in 19 diabetic patients and 21 non-diabetic patients. Diabetic patients had a significantly higher frequency of PE than non-diabetic patients (58.6 vs. 27.3%, p = 0.013) and DM was independently associated with PE (OR 4.40; 95% CI 1.22-15.83; p = 0.023). PE was significantly more common in diabetic patients with unfavorable stroke outcome (73.7%) than in other 3 subgroups: diabetic patients with favorable stroke outcome (30.0%), non-diabetic patients with favorable stroke outcome (38.1%) and unfavorable stroke outcome (8.3%; p = 0.002). PE was independently associated with unfavorable outcome (UO) in diabetic stroke (DS; OR 7.04; 95% CI 1.20-41.52; p = 0.031). Admission NIHSS score was associated with UO in non-DS (NDS) (OR 1.71; 95% CI 1.10-2.66; p = 0.017). Conclusions: Compared with NDS, DS had increased BBB disruption defined by the presence of PE. A different form of the relationship between admission NIHSS and UO in NDS, BBB disruption was related with UO in diabetic patients after stroke.