Sino-Canadian Collaborations in Stem Cell Research: A Scientometric Analysis

Background

International collaboration (IC) is essential for the advance of stem cell research, a field characterized by marked asymmetries in knowledge and capacity between nations. China is emerging as a global leader in the stem cell field. However, knowledge on the extent and characteristics of IC in stem cell science, particularly China’s collaboration with developed economies, is lacking.

Methods and Findings

We provide a scientometric analysis of the China–Canada collaboration in stem cell research, placing this in the context of other leading producers in the field. We analyze stem cell research published from 2006 to 2010 from the Scopus database, using co-authored papers as a proxy for collaboration. We examine IC levels, collaboration preferences, scientific impact, the collaborating institutions in China and Canada, areas of mutual interest, and funding sources. Our analysis shows rapid global expansion of the field with 48% increase in papers from 2006 to 2010. China now ranks second globally after the United States. China has the lowest IC rate of countries examined, while Canada has one of the highest. China–Canada collaboration is rising steadily, more than doubling during 2006–2010. China–Canada collaboration enhances impact compared to papers authored solely by China-based researchers This difference remained significant even when comparing only papers published in English.

Conclusions

While China is increasingly courted in IC by developed countries as a partner in stem cell research, it is clear that it has reached its status in the field largely through domestic publications. Nevertheless, IC enhances the impact of stem cell research in China, and in the field in general. This study establishes an objective baseline for comparison with future studies, setting the stage for in-depth exploration of the dynamics and genesis of IC in stem cell research.     

Multiple Ca(2+)-dependent modulators mediate alkalosis-induced vasodilation in newborn piglet lungs

We previously found that alkalosis-induced vasodilation was mediated by endothelium-derived nitric oxide (EDNO) in newborn piglet pulmonary artery and vein rings precontracted with the thromboxane mimetic U-46619. In contrast, prostacyclin or K(+) channel activation contributed to the response in other preparations. This study was undertaken to determine whether EDNO alone also mediates alkalosis-induced pulmonary vasodilation in piglet lungs vasoconstricted with hypoxia and, if not, to identify the mediator(s) involved. Responses to alkalosis were measured during hypoxia under control conditions after blocking nitric oxide synthase (N(omega)-nitro-L-arginine), cyclooxygenase (meclofenamate), or both endothelium-derived modulators (Dual); after blocking voltage-dependent (4-aminopyridine), ATP- dependent (glibenclamide), or Ca(2+)-dependent K(+) (K(Ca); tetraethylammonium) K(+) channels; and after blocking both endothelium-derived modulators and K(Ca) channels (Triple). Vasodilator responses measured after 20 min of alkalosis were blunted in Dual and tetraethylammonium lungs and abolished in Triple lungs. Thus alkalosis-induced vasodilation in hypoxic lungs appeared to be mediated by three Ca(2+)-dependent modulators: EDNO, prostacyclin, and K(Ca) channels. In addition, a transient, unidentified modulator contributed to the nadir of the vasodilator response measured at 10 min of alkalosis. Future studies are needed to identify factors that contribute to the discordance between isolated vessels and whole lungs.     

Mediators of alkalosis-induced relaxation of piglet pulmonary veins

Pulmonary venous constriction leads to significant pulmonary hypertension and increased edema formation in several models using newborns. Although alkalosis is widely used in treating neonatal and pediatric pulmonary hypertension, its effects on pulmonary venous tone have not previously been directly measured. This study sought to determine whether alkalosis caused pulmonary venous relaxation and, if so, to identify the mediator(s) involved. Pulmonary venous rings (500-microm external diameter) were isolated from 1-wk-old piglets and precontracted with the thromboxane mimetic U-46619. Responses to hypocapnic alkalosis were then measured under control conditions after inhibition of endothelium-derived modulator activity or K(+) channels. In control rings, alkalosis caused a 34.4 +/- 4.8% decrease in the U-46619-induced contraction. This relaxation was significantly blunted in rings without functional endothelium and in rings treated with nitric oxide synthase or guanylate cyclase inhibitors. However, neither cyclooxygenase inhibition nor voltage-dependent, calcium-dependent, or ATP-dependent K(+)-channel inhibitors altered alkalosis-induced relaxation. These data suggest that alkalosis caused significant dilation of piglet pulmonary veins that was mediated by the nitric oxide-cGMP pathway.     

Association of Variants at UMOD with Chronic Kidney Disease and Kidney Stones—Role of Age and Comorbid Diseases

Chronic kidney disease (CKD) is a worldwide public health problem that is associated with substantial morbidity and mortality. To search for sequence variants that associate with CKD, we conducted a genome-wide association study (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We observed an association between CKD and a variant with 80% population frequency, rs4293393-T, positioned next to the UMOD gene (GeneID: 7369) on chromosome 16p12 (OR = 1.25, P = 4.1×10⁻¹⁰). This gene encodes uromodulin (Tamm-Horsfall protein), the most abundant protein in mammalian urine. The variant also associates significantly with serum creatinine concentration (SCr) in Icelandic subjects (N = 24,635, P = 1.3×10⁻²³) but not in a smaller set of healthy Dutch controls (N = 1,819, P = 0.39). Our findings validate the association between the UMOD variant and both CKD and SCr recently discovered in a large GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases substantially with both age (P = 3.0×10⁻¹⁷) and number of comorbid diseases (P = 0.008). The association with CKD is also stronger in the older age groups. These results suggest that the UMOD variant may influence the adaptation of the kidney to age-related risk factors of kidney disease such as hypertension and diabetes. The variant also associates with serum urea (P = 1.0×10⁻⁶), uric acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7×10⁻⁵).     

Anticipatory synergy adjustments in preparation to self-triggered perturbations in elderly individuals

We tested the ability of healthy elderly persons to use anticipatory synergy adjustments (ASAs) prior to a self-triggered perturbation of one of the fingers during a multifinger force production task. An index of a force-stabilizing synergy was computed reflecting covariation of commands to fingers. The subjects produced constant force by pressing with the four fingers of the dominant hand on force sensors against constant upwardly directed forces. The middle finger could be unloaded either by the subject pressing the trigger or unexpectedly by the experimenter. In the former condition, the synergy index showed a drop (interpreted as ASA) prior to the time of unloading. This drop started later and was smaller in magnitude as compared with ASAs reported in an earlier study of younger subjects. At the new steady state, a new sharing pattern of the force was reached. We conclude that aging is associated with a preserved ability to explore the flexibility of the mechanically redundant multifinger system but a decreased ability to use feedforward adjustments to self-triggered perturbations. These changes may contribute to the documented drop in manual dexterity with age.     

Microbial transformations in a cyclodextrin medium. Part 2. Reduction of androstenedione to testosterone by Saccharomyces cerevisiae

Summary An intensive and systematic investigation of the reductive transformation of androstenedione (AD) to testosterone by Saccharomyces cerevisiae was undertaken in the presence of natural and chemically modified cyclodextrins (CD). The bioconversion was significantly larger in the presence of - and -CD and hydroxypropyl--CD b but only slight in the presence of -CD and dimethyl- and trimethyl--CD. The performance of the various cyclodextrin media was interpreted in the light of the measured phase solubility diagrams of AD. Further investigation focused on biotransformation of the -CD-androstenedione complex, the formation of which was studied by differential scanning calorimetry and X-ray powder diffractometry and stoichiometry determined by ¹H-nuclear magnetic resonance. A mechanism whereby CDs reduce the effective inhibitory concentrations of substrate and product as well as facilitate transport of the complexed substrate through the yeast cell wall has been suggested for the CD-promoted biotransformation. Offprint requests to: R. Bar     

Effects of bacterial treatment at early stages of Atlantic cod (Gadus morhua L.) on larval survival and development

Aims: To assess the effects of bacterial treatment at the earliest stages of cod rearing on the microbial load, larval development and performance, testing three bacterial strains (Carnobacterium divergens V41, Arthrobacter sp. and Enterococcus sp.) in vivo that were previously shown to have inhibitory potential towards fish pathogens in vitro. Methods and Results: A bacterial mixture was added eight times to the rearing water from the prehatch to the mid‐larval stage (a 38‐day period). Microbiological analysis of ova, larvae and rearing water was performed regularly. Larval performance and development were evaluated by survival rate, hypersalinity tolerance and physiological measurements. Different larval survival rates were observed within and between treatments, and possibly explained by variations in larval microflora and established probionts. Larvae from one silo, which had been bathed in the bacterial suspension, showed the highest survival rate (42·1%), lowest Vibrio levels, and were significantly heavier (19·3%) and more stress tolerant than control larvae (P < 0·01). This coincided with the intestinal establishment of two of the tested bacteria. Conclusions: Arthrobacter and Enterococcus strains added regularly to the rearing water from the postfertilized egg stage can become established in larval gastrointestinal tract. The Enterococcus strain was associated with increased larval growth, performance and microflora control, indicating its probiotic nature. Significance and Impact of the Study: Regular application of autochthonous probionts may promote larval welfare, development and stress tolerance at early stages, hence increasing production yield in intensive cod larviculture.     

Radiographic closure time of appendicular growth plates in the Icelandic horse

Background  

The Icelandic horse is a pristine breed of horse which has a pure gene pool established more than a thousand years ago, and is approximately the same size as living and extinct wild breeds of horses. This study was performed to compare the length of the skeletal growth period of the "primitive" Icelandic horse relative to that reported for large horse breeds developed over the recent centuries. This information would provide practical guidance to owners and veterinarians as to when the skeleton is mature enough to commence training, and would be potentially interesting to those scientists investigating the pathogenesis of osteochondrosis. Interestingly, osteochondrosis has not been documented in the Icelandic horse.     

Establishment of a gene transfer system for Rhodothermus marinus

Genetic manipulation of Rhodothermus marinus has been hampered by the lack of a selection system for gene transfer. We report construction of a Rhodothermus/Escherichia coli shuttle plasmid, containing the R. marinus trpB gene, based on pUC18 and the cryptic R. marinus plasmid pRM21. A plasmid-less R. marinus recipient strain was selected on the basis of growth characteristics and absence of restriction activity. The shuttle plasmid, pRM100, was successfully introduced into a TrpB^– mutant of the recipient strain using electroporation and was found to transform it to prototrophy. No loss or rearrangement of pRM100 was observed after growth for 80 generations in non-selective medium. The relative copy numbers of pRM100 and of the parental plasmid, pRM21, were determined as 7±1 and 42±4, respectively. The shuttle plasmid was used to optimize an electroporation protocol, and the maximal number of transformants obtained was 4.3±0.7×10⁶ cfu/g DNA at 22.5 kV/cm, 200 and 25 F. Transformation failed, however, after chemical preparation of cells according to several protocols. This is the first report of genetic transformation in the genus Rhodothermus.