Potato virus A genome-linked protein VPg is an intrinsically disordered molten globule-like protein with a hydrophobic core

Genome-linked protein VPg of Potato virus A (PVA; genus Potyvirus) has essential functions in all critical steps of PVA infection, i.e. replication, movement, and virulence. Structural features of the recombinant PVA VPg were investigated with the aim to create an outline for structure-function relationships. Circular dichroism data of PVA VPg revealed a distinct near-UV spectrum indicating that the environment around its aromatic residues is structured but rather flexible, and a far-UV spectrum that was characterized by features typical for intrinsically disordered proteins. Temperature-induced denaturation followed a typical all-or-none transition whereas urea- and GdmHCl-induced denaturation proceeded via a route best described by a three-state-model. The conclusion drawn was that the overall structure of PVA VPg is significantly unstable even in the absence of denaturants. Acrylamide fluorescence quenching and 1-anilino-8-naphthalene sulfonate binding experiments together with 1D and 2D NMR data further verified that PVA VPg behaves as a partially folded species that contains a hydrophobic core domain. Regions predicted to be disordered in PVA VPg were the ones that were cut the fastest by trypsin whereas regions predicted to be structured and to contain the most conserved amino acids among potyvirus VPgs were trypsin-resistant. Amino acid composition analysis of potyvirus VPgs revealed a clear enrichment of disorder and depletion of structure-promoting residues. Taken together it seems that the native structure of PVA VPg, and probably that of potyviral VPg in general, resembles a partially disordered molten globule. Further experimentation is required to understand the functional regulation achieved via this property.     

The role of genetic breast cancer susceptibility variants as prognostic factors

Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 (8q24), rs3817198 (LSP1), rs889312 (MAP3K1), rs3803662 (TOX3), rs13387042 (2q35), rs4973768 (SLC4A7), rs6504950 (COX11) and rs10941679 (5p12) were genotyped for 25 853 BC patients with the available follow-up; 62 other SNPs, which have been suggested as BC risk SNPs by a GWAS or as candidate SNPs from individual studies, were genotyped for replication purposes in subsets of these patients. Cox proportional hazard models were used to test the association of these SNPs with overall survival (OS) and BC-specific survival (BCS). For the confirmed loci, we performed an accessory analysis of publicly available gene expression data and the prognosis in a different patient group. One of the 11 SNPs, rs3803662 (TOX3) and none of the 62 candidate/GWAS SNPs were associated with OS and/or BCS at P<0.01. The genotypic-specific survival for rs3803662 suggested a recessive mode of action [hazard ratio (HR) of rare homozygous carriers=1.21; 95% CI: 1.09-1.35, P=0.0002 and HR=1.29; 95% CI: 1.12-1.47, P=0.0003 for OS and BCS, respectively]. This association was seen similarly in all analyzed tumor subgroups defined by nodal status, tumor size, grade and estrogen receptor. Breast tumor expression of these genes was not associated with prognosis. With the exception of rs3803662 (TOX3), there was no evidence that any of the SNPs associated with BC susceptibility were associated with the BC survival. Survival may be influenced by a distinct set of germline variants from those influencing susceptibility.     

Does clinical supervision promote medical–surgical nurses’ well-being at work? A quasi-experimental 4-year follow-up study

koivu a., saarinen pi. & hyrkas k. (2012) Journal of Nursing Management 20, 401–413 Does clinical supervision promote medical–surgical nurses’ well-being at work? A quasi-experimental 4-year follow-up study Aim The aim of the present paper is to report results of a quasi-experimental study exploring the effects of clinical supervision (CS) on the development of medical–surgical nurses’ well-being at work over a 4-year period. Background Effective workplace interventions are needed to prevent stress and burnout. More robust scientific evidence is needed to confirm the restorative effects of CS in nursing. Methods A questionnaire survey on the perceptions of work and health was conducted in 2003 and 2007 on 14 units of a Finnish university hospital where 19 CS group processes had been completed between 2004 and 2007. Results Improvement in job resources as well as reduction in professional inefficacy and psychological distress were found among nurses who received effective CS (n = 41), but were not present among the nurses who found their CS less effective (n = 43) or who did not attend CS (n = 82). Conclusions The results provide robust evidence for the positive effects of CS on medical–surgical nurses’ well-being at work. Implications for nursing management Stress is a developmental challenge in the professional growth of individual nurses. One option for management to sustain nurses’ well-being at work is to develop a learning organization in the workplace making use of CS.     

Use of and attitudes toward current care guidelines among primary and secondary care nurses in Finland

Attitudes toward, familiarity with, and use of clinical guidelines in general and the national Hypertension Guideline were studied. A questionnaire study was conducted before and after an educational program (VALTIT) among primary and secondary care nurses in P?ij?t-H?me, Finland. The program included centralized training sessions and interactive local workshops. Prior to the program, a majority of nurses had a positive attitude toward guidelines but used guidelines seldom. Primary care nurses were better aware of the Hypertension Guideline than secondary care nurses, but the guideline was poorly used by both groups. At the follow-up, familiarity with the Hypertension Guideline and use of guidelines increased among primary care nurses. In future, primary care nurses will have a more autonomous role in patient care and should participate in clinical guideline development and related research. Our study has shown they are a potential target of such interventions.     

A critical re-examination of sexual dimorphism in the corpus callosum microstructure

Recent diffusion-tensor imaging (DTI) studies suggest sexual dimorphism in the micro-structural architecture of the corpus callosum. However, the corpus callosum is also found to be larger in males than in females, a fact that might introduce a systematic bias to the analysis of DTI parameters. Diffusion parameters obtained in the larger male corpus callosum could be less affected by partial-volume averaging with surrounding non-callosal tissue than respective parameters obtained in the smaller female corpus callosum, i.e. the sex of the subject and partial-volume effects would be confounded. The objective of the present DTI study was to re-examine microstructural sex differences in the corpus callosum, while controlling for corpus callosum size differences between sexes. We compared 41 female and 34 male participants using regional tract-based spatial statistics (TBSS) analysis. Clusters of significantly higher fractional anisotropy (FA) and lower diffusion strength in males compared to females were detected in the genu and truncus of the corpus callosum. However, only the sex difference located in the anterior genu subregions could be unequivocally interpreted. This was the only cluster where the diffusion parameters did not correlate with regional callosal size. The present results indicate a stronger inter-hemispheric connectivity between the frontal lobes in males than females, which might be related to sex differences in hemispheric asymmetry and brain size.     

Auditory verbal hallucinations in schizophrenia as aberrant lateralized speech perception: evidence from dichotic listening

We report evidence that auditory verbal hallucinations (AVH) in schizophrenia patients are perceptual distortions lateralized to the left hemisphere. We used a dichotic listening task with repeated presentations of consonant-vowel syllables, a different syllable in the right and left ear. This task produces more correct reports for the right ear syllable in healthy individuals, indicative of left hemisphere speech processing focus. If AVHs are lateralized to the left hemisphere language receptive areas, then this should interfere with correct right ear reports in the dichotic task, which would result in significant negative correlations with severity of AVHs. We correlated the right and left ear correct reports with the PANSS hallucination symptom, and a randomly selected negative symptom, in addition to the sum total of the positive and negative symptoms, in 160 patients with schizophrenia. The results confirmed the predictions with significant negative correlations for the right ear scores with the PANSS hallucination item, and for the sum total of positive symptoms, while all other correlations were close to zero. The results are unambiguous evidence for AVHs as aberrant speech perceptions originating in the left hemisphere.     

Arm movement improves performance in clinical balance and mobility tests

Previous studies have suggested that arm movements can contribute to preventing the loss of balance or falls, and that aging affects the functions of arm movements. Clinical balance and mobility tests may be able to detect such aging effects. As the first step to approaching this question, the purpose of this pilot study was to investigate the effects of arm movements on the performance of clinical balance and mobility tests. Ten participants were evaluated in four clinical tests: (1) Maximal Step Length Test (MST), (2) Step Test (ST), (3) Timed Up and Go Test (TUG), and (4) Walk along an Elliptical Line (WEL). Each test was performed with free and limited arm movement and the outcomes were compared. Statistical analysis indicated a significant improvement in test performance when arms were used freely for three out of four tests (MST, ST and TUG), with inconclusive results on WEL. This pilot study showed improved performance on the clinical balance and mobility tests, suggesting that the contribution of arm movements is sufficiently large to be detected. This implies a feasibility for novel usage of clinical balance and mobility tests, i.e., to test the effectiveness of arm usage in balance and mobility.