Oncogenic H-Ras V12 promotes anchorage-independent cytokinesis in human fibroblasts

Cell anchorage is required for cell proliferation of untransformed cells, whereas anchorage-independent growth can be induced by oncogenes and is a hallmark of transformation. Whereas anchorage-dependent control of the progression of the G(1) phase of the cell cycle has been extensively studied, it is less clear whether and how anchorage may control other cell cycle phases and whether oncogenes may affect such controls. Here, we found that lack of cell anchorage did not influence progression through the cell cycle S phase, G(2) phase, or most of mitosis of primary human fibroblasts. However, unanchored fibroblasts could not complete cytokinesis. The cleavage furrow and central spindle were still formed in the absence of anchorage, but cells were unable to complete ingression, causing binucleation. Importantly, V12 H-Ras-transformed fibroblasts and two cancer cell lines progressed through the entire cell cycle without anchorage, including through cytokinesis. This indicates that oncogenic signaling may contribute to anchorage-independent growth and tumorigenesis by promoting the final cleavage furrow ingression during cytokinesis.     

The Stockholm Neonatal Family-Centered Care Study: effects on salivary cortisol in infants and their mothers

Background

Parental involvement in the care of preterm infants in neonatal intensive care units (NICUs) is common, but little is known about the effect on stress responses in mothers and infants.

Aims

The aim of this study is to evaluate the effect of family-centered care on salivary cortisol reactivity in mothers and preterm infants and the correlation between the mothers' and the preterm infants' salivary cortisol levels.

Methods

This study is part of a randomized controlled trial conducted at two level-II NICUs, including Family Care (FC), where parents were able to stay 24 h/day from admission to discharge, and Standard Care (SC). To investigate the cortisol response, saliva was collected from 289 preterm infants and their mothers before and after a diaper change at the time of discharge.

Results

No significant differences were found between the two groups in salivary cortisol reactivity, either in mothers or in infants. The results revealed a correlation between preterm infants' and their mothers' baseline and response cortisol in the FC group: r = 0.31 (p = 0.001) and r = 0.24 (p = 0.01), respectively. Such correlation was not observed in the SC group: r = 0.14 (p = 0.14) and r = 0.18 (p = 0.07), respectively.

Conclusions

Family-centered care had no effect on salivary cortisol reactivity during diaper change. However, sharing the same environment may increase the concordance between preterm infants' and their mothers' salivary cortisol levels.     

Hfq-dependent regulation of OmpA synthesis is mediated by an antisense RNA

This paper shows that the small RNA MicA (previously SraD) is an antisense regulator of ompA in Escherichia coli. MicA accumulates upon entry into stationary phase and down-regulates the level of ompA mRNA. Regulation of ompA (outer membrane protein A), previously attributed to Hfq/mRNA binding, is lost upon deletion of the micA gene, whereas overexpression of MicA inhibits the synthesis of OmpA. In vitro, MicA binds to the ompA mRNA leader. Enzymatic and chemical probing was used to map the structures of MicA, the ompA mRNA leader, and the complex formed upon binding. MicA binding generates a footprint across the ompA Shine-Dalgarno sequence, consistent with a 12 + 4 base-pair interaction, which is additionally supported by the effect of mutations in vivo and by bioinformatics analysis of enterobacterial micA/ompA homolog sequences. MicA is conserved in many enterobacteria, as is its ompA target site. In vitro toeprinting confirmed that binding of MicA specifically interferes with ribosome binding. We propose that MicA, when present at high levels, blocks ribosome binding at the ompA translation start site, which-in line with previous work-secondarily facilitates RNase E cleavage and subsequent mRNA decay. MicA requires the presence of the Hfq protein, although the mechanistic basis for this remains unclear.     

Colon heat and colon cancer

Epidemiological findings on the relation between foods and colon cancer are inconsistent. Many, but far from all, found positive associations for meat and fat and negative ones for vegetables and fruits. Explanations so far have focused on direct biochemical conversions in the colon or transit time, but they remain unable to explain the contradictory observations. One aspect grossly ignored has been bacterially produced heat which is beyond somatic control. A present day affluent lifestyle includes a more sedentary life, the strongest of all risk factors for colon cancer, with more sitting and less diffusion of bacterial heat, more fat and sugar, rich in energy and less of energy poor foods like cereals. A temperature higher by less than 1 degrees C in the colon over decades may promote tumour growth to a distinguishable extent.     

Regional hyperperfusion in older adults with objectively-defined subtle cognitive decline

Although cerebral blood flow (CBF) alterations are associated with Alzheimer’s disease (AD), CBF patterns across prodromal stages of AD remain unclear. Therefore, we investigated patterns of regional CBF in 162 Alzheimer’s Disease Neuroimaging Initiative participants characterized as cognitively unimpaired (CU; n = 80), objectively-defined subtle cognitive decline (Obj-SCD; n = 31), or mild cognitive impairment (MCI; n = 51). Arterial spin labeling MRI quantified regional CBF in a priori regions of interest: hippocampus, inferior temporal gyrus, inferior parietal lobe, medial orbitofrontal cortex, and rostral middle frontal gyrus. Obj-SCD participants had increased hippocampal and inferior parietal CBF relative to CU and MCI participants and increased inferior temporal CBF relative to MCI participants. CU and MCI groups did not differ in hippocampal or inferior parietal CBF, but CU participants had increased inferior temporal CBF relative to MCI participants. There were no CBF group differences in the two frontal regions. Thus, we found an inverted-U pattern of CBF signal across prodromal AD stages in regions susceptible to early AD pathology. Hippocampal and inferior parietal hyperperfusion in Obj-SCD may reflect early neurovascular dysregulation, whereby higher CBF is needed to maintain cognitive functioning relative to MCI participants, yet is also reflective of early cognitive inefficiencies that distinguish Obj-SCD from CU participants.     

Contrast-enhanced thoracic 3D-MR angiography in infants and children

Purpose: To optimise breath-hold contrast-enhanced MR angiography (MRA) in infants and children with suspected congenital heart or thoracic vessel malformation.Material and Methods: Thirty-nine children (median age 1 year) were examined, using five different ultrafast MRA sequences with a TR between 3.2 and 5.0 ms and the contrast agent meglumine gadoterate. A test injection was used to determine contrast travel time. Different parameters for contrast injection were evaluated. Signal-to-noise ratio (SNR) measurements were performed and image quality and injection timing were evaluated.Results: MRA was successful in all patients and image quality was considered very good in 52%. Adequate SNR was achieved with no significant differences between the MR sequences. SNR decreased only 25-30% between subsequent scans. The mean contrast dose was 0.23 mmol/kg. The mean scan time was 12.5±3.8 s; the shorter scan times made dynamic examinations possible with high temporal resolution. Highest spatial resolution was obtained with TR 4.6/5.0 sequences.Conclusion: A contrast dose of 0.2 mmol/kg b.w. is recommended with an injection rate of 0.5 to 1.2 ml/s, depending on patient size and scan time. The scan delay time should equal the contrast travel time for optimal vessel enhancement. In the future, contrast-enhanced MRA may be a potential alternative to angiocardiography in infants and children.     

Longitudinal variations and predictors of increased perceived impact of multiple sclerosis, a two-year study

OBJECTIVE: To explore variations and the capacity of selected factors - contextual factors, disease-related characteristics, cognition, fatigue, mood and time - to predict an increase in the perceived physical and psychological impact of multiple sclerosis (MS) over a two-year period. METHODS: At an MS specialist clinic, 219 outpatients were included in the study and data were collected every 6 months. The Multiple Sclerosis Impact Scale was used for assessment of the perceived physical and psychological impact of MS. For statistical analysis of changes in impact during the study period, Friedman ANOVA was used and predictors of increased impact were explored with Generalized Estimating Equations employing proportional odds models. RESULTS: The majority had changes in perceived physical impact of established important magnitude and the psychological impact varied significantly. A period of more than 10 years since diagnosis, cognitive disability, fatigue and signs of depression were independent predictors of increase in physical impact. Weak or moderate sense of coherence, absence of immunomodulatory treatment, fatigue and signs of depression were independent predictors of increase in psychological impact. CONCLUSION: The fluctuation in perceived impact should be taken into account in clinical decision-making and when designing studies and interpreting the results. This study identifies the predictors of increased perceived physical and psychological impact that health-related services should pay special attention to, in order to provide interventions aimed at minimizing the perceived impact of MS.     

Randomized controlled trial of rehabilitation at home after stroke: one-year follow-up of patient outcome, resource use and cost

BACKGROUND AND PURPOSE: This study sought to evaluate early supported discharge and continued rehabilitation at home after stroke, at a minimum of 6 months after the intervention, in terms of patient outcome, resource use and health care cost. METHODS: Eighty-three patients, moderately impaired 5-7 days after acute stroke, were included in a randomized controlled trial, 42 being allocated to the intervention and 41 to routine rehabilitation. One-year follow-up of patient outcome included mortality, motor capacity, dysphasia, activities of daily living, social activities, perceived dysfunction, and self-reported falls. Resource use over 12 months included inpatient hospital care, outpatient health care, use of health-related services, informal care, and cost of health care. RESULTS: On univariate analysis there was no difference in patient outcome. Multivariate regression analysis showed that intervention had a significant effect on independence in activities of daily living. A significant difference in inpatient hospital care, initial and recurrent, was observed, with a mean of 18 (intervention) versus 33 days (control) (p = 0.002). Further significant differences were that the control group registered more outpatient visits to hospital occupational therapists (p = 0.02), private physical therapists (p = 0.03) and day-hospital attendance (p = <0.001), while the intervention group registered more visits to nurses in primary care (p = 0.03) and home rehabilitation (p = <0.001). Other differences in outcomes or resource utilization were nonsignificant. CONCLUSION: In Sweden, early supported discharge with continued rehabilitation at home proved no less beneficial as a rehabilitation service, and provided care and rehabilitation for 5 moderately disabled stroke patients over 12 months after stroke onset for the cost of 4 in routine rehabilitation.