A novel locus for split-hand/foot malformation associated with tibial hemimelia (SHFLD syndrome) maps to chromosome region 17p13.1-17p13.3

Split-hand/foot malformation (SHFM) associated with aplasia of long bones, SHFLD syndrome or Tibial hemimelia-ectrodactyly syndrome is a rare condition with autosomal dominant inheritance, reduced penetrance and an incidence estimated to be about 1 in 1,000,000 liveborns. To date, three chromosomal regions have been reported as strong candidates for harboring SHFLD syndrome genes: 1q42.2-q43, 6q14.1 and 2q14.2. We characterized the phenotype of nine affected individuals from a large family with the aim of mapping the causative gene. Among the nine affected patients, four had only SHFM of the hands and no tibial defects, three had both defects and two had only unilateral tibial hemimelia. In keeping with previous publications of this and other families, there was clear evidence of both variable expression and incomplete penetrance, the latter bearing hallmarks of anticipation. Segregation analysis and multipoint Lod scores calculations (maximum Lod score of 5.03 using the LINKMAP software) using all potentially informative family members, both affected and unaffected, identified the chromosomal region 17p13.1-17p13.3 as the best and only candidate for harboring a novel mutated gene responsible for the syndrome in this family. The candidate gene CRK located within this region was sequenced but no pathogenic mutation was detected.

Chromosome polymorphism in Astyanax fasciatus (Teleostei, Characidae). 2-Chromosomal location of a satellite DNA

Studies about composition of repetitive sequences and their chromosomal location have been helpful to evolutionary studies in many distinct organisms. In order to keep on assessing the possible relationships among different cytotypes of Astyanax fasciatus (Teleostei, Characiformes) in the Mogi-Guacu River (Sao Paulo State, Brazil), C-banding, chromomycin A 3 staining, and fluorescent in situ hybridization with a repetitive DNA sequence (As51) isolated from Astyanax scabripinnis were performed in the present work. The constitutive heterochromatin was distributed in terminal regions on long arms of submetacentric, subtelocentric, and acrocentric chromosomes and in the terminal region on short arms of a pair of submetacentric chromosomes in both standard cytotypes. This latter heterochromatic site was also GC-rich, as revealed by chromomycin A(3) staining, corresponding to the nucleolar organizer region (NOR), as shown by previous studies. The sites of the satellite As51 DNA were located in terminal regions on long arms of several chromosomes. Some variant karyotypic forms, which diverge from the two standard cytotypes, also presented distinctive chromosomes carrying As51 satellite DNA. It is possible that the standard 2n = 46 cytotype represents an invader population in the Mogi-Guacu River able to interbreed with the resident standard 2n = 48 cytotype. Therefore, the variant karyotypes would be related to a possible viable offspring, where complementary chromosomal rearrangements could favor new locations of the satellite DNA analyzed. Copyright (C) 2008 S. Karger AG, Basel

Genetic and Functional Evidence Implicating DLL1 as the Gene That Influences Susceptibility to Visceral Leishmaniasis at Chromosome 6q27

Background. Visceral leishmaniasis (VL) is caused by Leishmania donovani and Leishmania infantum chagasi. Genome-wide linkage studies from Sudan and Brazil identified a putative susceptibility locus on chromosome 6q27. Methods. Twenty-two single-nucleotide polymorphisms (SNPs) at genes PHF10, C6orf70, DLL1, FAM120B, PSMB1, and TBP were genotyped in 193 VL cases from 85 Sudanese families, and 8 SNPs at genes PHF10, C6orf70, DLL1, PSMB1, and TBP were genotyped in 194 VL cases from 80 Brazilian families. Family-based association, haplotype, and linkage disequilibrium analyses were performed. Multispecies comparative sequence analysis was used to identify conserved noncoding sequences carrying putative regulatory elements. Quantitative reverse-transcription polymerase chain reaction measured expression of candidate genes in splenic aspirates from Indian patients with VL compared with that in the control spleen sample. Results. Positive associations were observed at PHF10, C6orf70, DLL1, PSMB1, and TBP in Sudan, but only at DLL1 in Brazil (combined P = 3 x 10(-4) at DLL1 across Sudan and Brazil). No functional coding region variants were observed in resequencing of 22 Sudanese VL cases. DLL1 expression was significantly (P = 2 x 10(-7)) reduced (mean fold change, 3.5 [SEM, 0.7]) in splenic aspirates from patients with VL, whereas other 6q27 genes showed higher levels (1.27 x 10(-6) < P < .01) than did the control spleen sample. A cluster of conserved noncoding sequences with putative regulatory variants was identified in the distal promoter of DLL1. Conclusions. DLL1, which encodes Delta-like 1, the ligand for Notch3, is strongly implicated as the chromosome 6q27 VL susceptibility gene.

High-frequency extensions of magnetorotational instability in astrophysical plasmas

High-frequency extensions of magnetorotational instability driven by the Velikhov effect beyond the standard magnetohydrodynamic (MHD) regime are studied. The existence of the well-known Hall regime and a new electron inertia regime is demonstrated. The electron inertia regime is realized for a lesser plasma magnetization of rotating plasma than that in the Hall regime. It includes the subregime of nonmagnetized electrons. It is shown that, in contrast to the standard MHD regime and the Hall regime, magnetorotational instability in this subregime can be driven only at positive values of dln Omega/dlnr, where Omega is the plasma rotation frequency and r is the radial coordinate. The permittivity of rotating plasma beyond the standard MHD regime, including both the Hall regime and the electron inertia regime, is calculated.

Contributions to the theory of magnetorotational instability and waves in a rotating plasma

The one-fluid magnetohydrodynamic (MHD) theory of magnetorotational instability (MRI) in an ideal plasma is presented. The theory predicts the possibility of MRI for arbitrary 0, where 0 is the ratio of the plasma pressure to the magnetic field pressure. The kinetic theory of MRI in a collisionless plasma is developed. It is demonstrated that as in the ideal MHD, MRI can occur in such a plasma for arbitrary P. The mechanism of MRI is discussed; it is shown that the instability appears because of a perturbed parallel electric field. The electrodynamic description of MRI is formulated under the assumption that the dispersion relation is expressed in terms of the permittivity tensor; general properties of this tensor are analyzed. It is shown to be separated into the nonrotational and rotational parts. With this in mind, the first step for incorporation of MRI into the general theory of plasma instabilities is taken. The rotation effects on Alfven waves are considered.

Instability of equilibrium points of some Lagrangian systems

In this work we show that, if L is a natural Lagrangian system such that the k-jet of the potential energy ensures it does not have a minimum at the equilibrium and such that its Hessian has rank at least n - 2, then there is an asymptotic trajectory to the associated equilibrium point and so the equilibrium is unstable. This applies, in particular, to analytic potentials with a saddle point and a Hessian with at most 2 null eigenvalues. The result is proven for Lagrangians in a specific form, and we show that the class of Lagrangians we are interested can be taken into this specific form by a subtle change of spatial coordinates. We also consider the extension of this results to systems subjected to gyroscopic forces. (C) 2008 Elsevier Inc. All rights reserved.

Superoxide Dismutase 1-mediated Production of Ethanol- and DNA-derived Radicals in Yeasts Challenged with Hydrogen Peroxide MOLECULAR INSIGHTS INTO THE GENOME INSTABILITY OF PEROXIREDOXIN-NULL STRAINS

Peroxiredoxins are receiving increasing attention as defenders against oxidative damage and sensors of hydrogen peroxide-mediated signaling events. In the yeast Saccharomyces cerevisiae, deletion of one or more isoforms of the peroxiredoxins is not lethal but compromises genome stability by mechanisms that remain under scrutiny. Here, we show that cytosolic peroxiredoxin-null cells (tsa1 Delta tsa2 Delta) are more resistant to hydrogen peroxide than wildtype (WT) cells and consume it faster under fermentative conditions. Also, tsa1 Delta tsa2 Delta cells produced higher yields of the 1-hydroxyethyl radical from oxidation of the glucose metabolite ethanol, as proved by spin-trapping experiments. A major role for Fenton chemistry in radical formation was excluded by comparing WT and tsa1 Delta tsa2 Delta cells with respect to their levels of total and chelatable metal ions and of radical produced in the presence of chelators. The main route for 1-hydroxyethyl radical formation was ascribed to the peroxidase activity of Cu, Zn-superoxide dismutase (Sod1), whose expression and activity increased similar to 5- and 2-fold, respectively, in tsa1 Delta tsa2 Delta compared with WT cells. Accordingly, overexpression of human Sod1 in WT yeasts led to increased 1-hydroxyethyl radical production. Relevantly, tsa1 Delta tsa2 Delta cells challenged with hydrogen peroxide contained higher levels of DNA-derived radicals and adducts as monitored by immuno-spin trapping and incorporation of (14)C from glucose into DNA, respectively. The results indicate that part of hydrogen peroxide consumption by tsa1 Delta tsa2 Delta cells is mediated by induced Sod1, which oxidizes ethanol to the 1-hydroxyethyl radical, which, in turn, leads to increased DNA damage. Overall, our studies provide a pathway to account for the hypermutability of peroxiredoxin-null strains.

Haemodynamic instability after cardiac surgery: nurses` perceptions of clinical decision-making

Background. Cardiac surgical patients are distinguished by their potential for instability in the early postoperative period, highly invasive haemodynamic monitoring technologies and unique clinical presentations as a result of undergoing cardiopulmonary bypass. Little is known about nurses’ perceptions of assuming responsibility for such patients. An nderstanding of nurses’ perceptions may identify areas of practice that can be improved and assist in determining the adequacy of current decision supports.

Aim. The aim of this study was to describe critical care nurses’ perceptions of assuming responsibility for the nursing management of cardiac patients in the initial two-hour postoperative period. Design. An exploratory descriptive study based on naturalistic decision-making.

Methods. Thirty-eight nurses were interviewed immediately following a two-hour observation of their clinical practice. Content analysis and a systematic thematic analysis process called ‘Framework’ were used to analyse the interview transcripts.

Results. Nurses described their perceptions of managing patients in terms of how they felt about making decisions for complex cardiac surgical patients and in terms of how clinical processes unique to the admission phase impacted their decision-making. Nurses felt either daunted or stimulated and challenged when making decisions. Nurses identified handover from anaesthetists, settling in procedures and forms of
collegial assistance as important processes that impacted their decision-making.

Conclusion. Nurses’ previous experiences with similar patients influenced how they felt about making decisions during the initial two-hour postoperative period, but did not alter their views about processes important for patient safety during this time. Relevance to clinical practice. Feelings expressed by nurses in this study highlight the need for clinical supervision and appropriate allocation of resources during the immediate recovery period after cardiac surgery. Nurses identified ways to improve clinical processes that impacted their decision-making during the immediate recovery of cardiac surgical patients.

Effect of six weeks of dura disc and mini-trampoline balance training on postural sway in athletes with functional ankle instability

Lateral ankle sprain (LAS) is one of the most common injuries incurred during sporting activities, and effective rehabilitation programs for this condition are challenging to develop. The purpose of this research was to compare the effect of 6 weeks of balance training on either a mini-trampoline or a dura disc on postural sway and to determine if the mini-trampoline or the dura disc is more effective in improving postural sway. Twenty subjects (11 men, 9 women) with a mean age of 25.4 ± 4.2 years were randomly allocated into a control group, a dura disc training (DT) group, or a mini-trampoline (MT) group. Subjects completed 6 weeks of balance training. Postural sway was measured by subjects performing a single limb stance on a force plate. The disbursement of the center of pressure was obtained from the force plate in the medial-lateral and the anterior-posterior sway path and was subsequently used for pretest and posttest analysis. After the 6-week training intervention, there was a significant (p < 0.05) difference in postural sway between pre- and posttesting for both the MT (pretest = 56.8 ± 20.5 mm, posttest = 33.3 ± 8.5 mm) and DT (pretest = 41.3 ± 2.6 mm, posttest = 27.2 ± 4.8 mm) groups. There was no significant (p > 0.05) difference detected for improvements between the MT and DT groups. These results indicate that not only is the mini-trampoline an effective tool for improving balance after LAS, but it is equally as effective as the dura disc.

GAD2 on chromosome 10p12 is a candidate gene for human obesity

The gene GAD2 encoding the glutamic acid decarboxylase enzyme (GAD65) is a positional candidate gene for obesity on Chromosome 10p11–12, a susceptibility locus for morbid obesity in four independent ethnic populations. GAD65 catalyzes the formation of γ-aminobutyric acid (GABA), which interacts with neuropeptide Y in the paraventricular nucleus to contribute to stimulate food intake. A case-control study (575 morbidly obese and 646 control subjects) analyzing GAD2 variants identified both a protective haplotype, including the most frequent alleles of single nucleotide polymorphisms (SNPs) +61450 C>A and +83897 T>A (OR = 0.81, 95% CI [0.681–0.972], p = 0.0049) and an at-risk SNP (−243 A>G) for morbid obesity (OR = 1.3, 95% CI [1.053–1.585], p = 0.014). Furthermore, familial-based analyses confirmed the association with the obesity of SNP +61450 C>A and +83897 T>A haplotype (χ2 = 7.637, p = 0.02). In the murine insulinoma cell line βTC3, the G at-risk allele of SNP −243 A>G increased six times GAD2 promoter activity (p < 0.0001) and induced a 6-fold higher affinity for nuclear extracts. The −243 A>G SNP was associated with higher hunger scores (p = 0.007) and disinhibition scores (p = 0.028), as assessed by the Stunkard Three-Factor Eating Questionnaire. As GAD2 is highly expressed in pancreatic β cells, we analyzed GAD65 antibody level as a marker of β-cell activity and of insulin secretion. In the control group, −243 A>G, +61450 C>A, and +83897 T>A SNPs were associated with lower GAD65 autoantibody levels (p values of 0.003, 0.047, and 0.006, respectively). SNP +83897 T>A was associated with lower fasting insulin and insulin secretion, as assessed by the HOMA-B% homeostasis model of β-cell function (p = 0.009 and 0.01, respectively). These data support the hypothesis of the orexigenic effect of GABA in humans and of a contribution of genes involved in GABA metabolism in the modulation of food intake and in the development of morbid obesity.

Interest, nations, and the state in development: Instability in archipelic Southeast Asia

The Southeast Asian archipelago has become marked by divisions
within existing states, placing significant local constraints upon
the process of ‘development’. These divisions include ‘vertical’
challenges to the state, i.e. they have the capacity to split the state
into geographic divisions based on proto-nationalist identity, and
‘horizontal’ challenges to the state, defined by ethnic and
communal rivalry and conflict. This brief paper will canvas some
issues in such divisions.

Leading educational re-design to sustain socially just schools under conditions of instability

There is now significant evidence that school and leadership redesign is necessary in order to achieve more socially just educational futures for all students and a productive and professionally rewarding environment for teachers. Redesign requires some fundamental shifts in how schools work; engagement with and through learning communities based on systematic critical inquiry; and inclusive leadership practices that address the complexities of the relationships between diversity, culture, gender and race in schooling. I argue that democratic leadership is most conducive to initiating and sustaining equitable outcomes. The article concludes with consideration of principles that could sustain leadership for social justice.