Craniomandibular System and Postural Balance after 3-Day Dry Immersion

The objective of the study was to determine the influence of simulated microgravity by exposure to dry immersion on the craniomandibular system. Twelve healthy male volunteers participated in a 3-day dry immersion study. Before and immediately after exposure we measured maximal bite force using piezoresistive sensors. The mechanical properties of the jaw and cervical muscles were evaluated before, during, and after dry immersion using MyotonPRO. Because recent studies reported the effects of jaw motor activity on the postural stability of humans, stabilometric measurements of center of pressure were performed before and after dry immersion in two mandibular positions: rest position without jaw clenching, and intercuspidal position during voluntary teeth clenching. Results revealed no significant changes of maximal bite force after dry immersion. All postural parameters were significantly altered by dry immersion. There were however no significant differences in stabilometric data according to mandibular position. Moreover the masseter tonicity increased immediately after the end of dry immersion period. Dry immersion could be used as a valid model for studying the effects of microgravity on human subjects. However, 3 days appear insufficient in duration to evaluate the effects of weightlessness on maximal bite force. Our research suggests a link between postural disturbance after dry immersion and masseter tonicity.     

Effect of pressure overload-induced hypertrophy on the expression and localization of p38 MAP kinase isoforms in the mouse heart

p38 mitogen-activated protein kinases (MAPKs) are serine/threonine specific protein kinases that respond to cellular stress and regulate a broad range of cellular activities. There are four major isoforms of p38 MAPK: α, β, γ, and δ. To date, the prominent isoform in heart has been thought to be p38α. We examined the expression of each p38 isoform at both the mRNA and protein level in murine heart. mRNA for all four p38 isoforms was detected. p38γ and p38δ were expressed at protein levels comparable to p38α and 38β, respectively. In the early phase of pressure-overload hypertrophy (1–7 days after constriction of the transverse aorta), the abundance of p38β, p38γ and p38δ mRNA increased; however, no corresponding changes were detected at the protein level. Confocal immunofluorescence studies revealed p38α and p38γ in both the cytoplasm and nucleus. In the established phase of hypertrophy induced by chronic pressure overload (7–28 days after constriction of the transverse aorta), p38γ immunoreactivity accumulated in the nucleus whereas the distribution of p38α remained unaffected. Hence, both p38α and p38γ are prominent p38 isoforms in heart and p38γ may play a role in mediating the changes in gene expression associated with cardiac remodeling during pressure-overload hypertrophy.     

Molecular Method for Detection of Total Coliforms in Drinking Water Samples

This work demonstrates the ability of a bacterial concentration and recovery procedure combined with three different PCR assays targeting the lacZ, wecG, and 16S rRNA genes, respectively, to detect the presence of total coliforms in 100-ml samples of potable water (presence/absence test). PCR assays were first compared to the culture-based Colilert and MI agar methods to determine their ability to detect 147 coliform strains representing 76 species of Enterobacteriaceae encountered in fecal and environmental settings. Results showed that 86 (58.5%) and 109 (74.1%) strains yielded a positive signal with Colilert and MI agar methods, respectively, whereas the lacZ, wecG, and 16S rRNA PCR assays detected 133 (90.5%), 111 (75.5%), and 146 (99.3%) of the 147 total coliform strains tested. These assays were then assessed by testing 122 well water samples collected in the Québec City region of Canada. Results showed that 97 (79.5%) of the samples tested by culture-based methods and 95 (77.9%), 82 (67.2%), and 98 (80.3%) of samples tested using PCR-based methods contained total coliforms, respectively. Consequently, despite the high genetic variability of the total coliform group, this study demonstrated that it is possible to use molecular assays to detect total coliforms in potable water: the 16S rRNA molecular assay was shown to be as efficient as recommended culture-based methods. This assay might be used in combination with an Escherichia coli molecular assay to assess drinking water quality.     

Successful Control of Ebola Virus Disease: Analysis of Service Based Data from Rural Sierra Leone

IntroductionThe scale and geographical distribution of the current outbreak in West Africa raised doubts as to the effectiveness of established methods of control. Ebola Virus Disease (EVD) was first detected in Sierra Leone in May 2014 in Kailahun district. Despite high case numbers elsewhere in the country, transmission was eliminated in the district by December 2014. We describe interventions underpinning successful EVD control in Kailahun and implications for EVD control in other areas.MethodsInternal service data and published reports from response agencies were analysed to describe the structure and type of response activities, EVD case numbers and epidemic characteristics. This included daily national situation reports and District-level data and reports of the Sierra Leone Ministry of Health and Sanitation, and Médecins Sans Frontières (MSF) patient data and internal epidemiological reports. We used EVD case definitions provided by the World Health Organisation over the course of the outbreak. Characteristics assessed included level of response activities and epidemiological features such as reported exposure (funeral-related or not), time interval between onset of illness and admission to the EVD Management Centre (EMC), work-related exposures (health worker or not) and mortality. We compared these characteristics between two time periods—June to July (the early period of response), and August to December (when coverage and quality of response had improved). A stochastic model was used to predict case numbers per generation with different numbers of beds and a varying percentage of community cases detected.ResultsThere were 652 probable/confirmed EVD cases from June-December 2014 in Kailahun. An EMC providing patient care opened in June. By August 2014 an integrated detection, treatment, and prevention strategy was in place across the district catchment zone. From June-July to August-December 2014 surveillance and contact tracing staff increased from 1.0 to 8.8 per confirmed EVD case, EMC capacity increased from 32 to 100 beds, the number of burial teams doubled, and health promotion activities increased in coverage. These improvements in response were associated with the following changes between the same periods: the proportion of confirmed/probable cases admitted to the EMC increased from 35% to 83% (χ² p-value<0·001), the proportion of confirmed patients admitted to the EMC <3 days of symptom onset increased from 19% to 37% (χ² p-value <0·001), and reported funeral contact in those admitted decreased from 33% to 16% (χ² p-value <0·001). Mathematical modelling confirmed the importance of both patient management capacity and surveillance and contact tracing for EVD control.DiscussionOur findings demonstrate that control of EVD can be achieved using established interventions based on identification and appropriate management of those who are at risk of and develop EVD, including in the context of ongoing transmission in surrounding regions. Key attributes in achieving control were sufficient patient care capacity (including admission to specialist facilities of suspect and probable cases for assessment), integrated with adequate staffing and resourcing of community-based case detection and prevention activities. The response structure and coverage targets we present are of value in informing effective control in current and future EVD outbreaks.     

The effects of DHEA, 3β-hydroxy-5α-androstane-6,17-dione, and 7-amino-DHEA analogues on short term and long term memory in the mouse

Neurosteroids have been reported to modulate memory processes in rodents. Three analogues of dehydroepiandrosterone (DHEA), two of them previously described (7β-aminoDHEA and 7β-amino-17-ethylenedioxy-DHEA), and a new one (3β-hydroxy-5α-androstane-6,17-dione) were synthesized, and their effects were evaluated on memory. This study examined their effects on long term and short term memory in male (6 weeks old) NMRI mice in comparison with the reference drug. Long term memory was assessed using the passive avoidance task and short term memory (spatial working memory) using the spontaneous alternation task in a Y maze. Moreover, the effects of DHEA and its analogues on spontaneous locomotion were measured. In all tests, DHEA and analogues were injected at three equimolar doses (0.300–1.350–6.075 μM/kg). DHEA and its three analogues administered immediately post-training at the highest doses (6.075 μM/kg, s.c.) improved retention in passive avoidance test. Without effect per se in the spatial working memory task, the four compounds failed to reverse scopolamine (1 mg/kg, i.p.)-induced deficit in spontaneous alternation. These data suggested an action of DHEA and analogues in consolidation of long term memory particularly when emotional components are implied. Moreover, data indicated that pharmacological modulation of DHEA as performed in this study provides derivatives giving the same mnemonic profile than reference molecule.     

New lithocholic and chenodeoxycholic piperazinylcarboxamides with antiproliferative and pro-apoptotic effects on human cancer cell lines

Six new synthetic bile acid derivatives were synthesized and tested in vitro against various human cancer cells (glioblastoma multiforme (GBM), multiple myeloma (KMS-11), and colonic carcinoma (HCT-116) cell lines. The best activity was obtained with compound IIIb on multiple myeloma cells (LD(50): 8.5+/-0.5 microM). This activity was associated with Mcl-1 and PARP-1 cleavage, inhibition of NFkappaB signaling, and DNA fragmentation, demonstrating an apoptotic cell death signaling pathway.     

Sex hormone control of left ventricular structure/function: mechanistic insights using echocardiography, expression, and DNA methylation analyses in adult mice

Calcium flux into and out of the sarco(endo)plasmic reticulum is vitally important to cardiac function because the cycle of calcium entry and exit controls contraction and relaxation. Putative estrogen and androgen consensus binding sites near to a CpG island are present in the cardiac calsequestrin 2 (CSQ2) promoter. Cardiomyocytes express sex hormone receptors and respond to sex hormones. We hypothesized that sex hormones control CSQ2 expression in cardiomyocytes and so affect cardiac structure/function. Echocardiographic analysis of male and female C57bl6n mice identified thinner walled and lighter hearts in females and significant concentric remodeling after long-term gonadectomy. CSQ2 and sodium-calcium exchanger-1 (NCX1) expression was significantly increased in female compared with male hearts and decreased postovariectomy. NCX1, but not CSQ2, expression was increased postcastration. CSQ2 expression was reduced when H9c2 cells were cultured in hormone-deficient media; increased when estrogen receptor-α (ERα), estrogen receptor-β (ERβ), or androgen agonists were added; and increased in hearts from ERβ-deficient mice. CSQ2 expression was reduced in mice fed a diet low in the methyl donor folic acid and in cells treated with 5-azadeoxycytidine suggesting an involvement of DNA methylation. DNA methylation in CpG in the CSQ2 CpG island was significantly different in males and females and was additionally changed postgonadectomy. Expression of DNA methyltransferases 1, 3a, and 3b was unchanged. These studies strongly link sex hormone-directed changes in CSQ2 expression to DNA methylation with changed expression correlated with altered left ventricular structure and function.     

Collective ERK/Akt activity waves orchestrate epithelial homeostasis by driving apoptosis-induced survival

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FBXW7/hCDC4 controls glioma cell proliferation in vitro and is a prognostic marker for survival in glioblastoma patients

Ubiquitin is a highly versatile post-translational modification that controls virtually all types of cellular events. Over the past ten years we have learned that diverse forms of ubiquitin modifications and of ubiquitin binding modules co-exist in the cell, giving rise to complex networks of protein:protein interactions. A central problem that continues to puzzle ubiquitinologists is how cells translate this myriad of stimuli into highly specific responses. This is a classical signalling problem. Here, we draw parallels with the phosphorylation signalling pathway and we discuss the expanding repertoire of ubiquitin signals, signal tranducers and signalling-regulated E3 enzymes. We examine recent advances in the field, including a new mechanism of regulation of E3 ligases that relies on ubiquitination.