A three dimensional model of the photosynthetic membranes of Ectothiorhodospira halochloris

The three dimensional organization of the complete photosynthetic apparatus of the extremely halophilic, bacteriochlorophyll b containing Ectothiorhodospira halochloris has been elaborated by several techniques of electron microscopy. Essentially all thylakoidal sacs are disc shaped and connected to the cytoplasmic membrane by small membraneous ldquobridgesrdquo. In sum, the lumina of all thylakoids (intrathylakoidal space) form one common periplasmic space. Thin sections confirm a paracrystalline arrangement of the photosynthetic complexes in situ. The ontogenic development of the photosynthetic apparatus is discussed based on a structural model derived from serial thin sections

Correction to Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission? [Journal of Neuroinflammation (2013) 10, 34] 10.1186/1742-2094-10-34

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[11C]acetate PET/CT Visualizes Skeletal Muscle Exercise Participation, Impaired Function, and Recovery after Hip Arthroplasty; First Results

Based on skeletal muscle acetate physiology we aimed studying muscle function after hip arthroplasty with [(11)C]acetate PET

Distinguishing patterns in the dynamics of long-term medication use by Markov analysis: beyond persistence

<p>Abstract</p> <p>Background</p> <p>In order to accurately distinguish gaps of varying length in drug treatment for chronic conditions from discontinuation without resuming therapy, short-term observation does not suffice. Thus, the use of inhalation corticosteroids (ICS) in the long-term, during a ten-year period is investigated. To describe medication use as a continuum, taking into account the timeliness and consistency of refilling, a Markov model is proposed.</p> <p>Methods</p> <p>Patients, that filled at least one prescription in 1993, were selected from the PHARMO medical record linkage system (RLS) containing >95% prescription dispensings per patient originating from community pharmacy records of 6 medium-sized cities in the Netherlands.</p> <p>The probabilities of continuous use, the refilling of at least one ICS prescription in each year of follow-up, and medication free periods were assessed by Markov analysis. Stratified analysis according to new use was performed.</p> <p>Results</p> <p>The transition probabilities of the refilling of at least one ICS prescription in the subsequent year of follow-up, were assessed for each year of follow-up and for the total study period.</p> <p>The change of transition probabilities in time was evaluated, e.g. the probability of continuing ICS use of starters in the first two years (51%) of follow-up increased to more than 70% in the following years. The probabilities of different patterns of medication use were assessed: continuous use (7.7%), cumulative medication gaps (1–8 years 69.1%) and discontinuing (23.2%) during ten-year follow-up for new users. New users had lower probability of continuous use (7.7%) and more variability in ICS refill patterns than previous users (56%).</p> <p>Conclusion</p> <p>In addition to well-established methods in epidemiology to ascertain compliance and persistence, a Markov model could be useful to further specify the variety of possible patterns of medication use within the continuum of adherence. This Markov model describes variation in behaviour and patterns of ICS use and could also be useful to investigate continuous use of other drugs applied in chronic diseases.</p

Surgical Techniques to Optimize Early Urinary Continence Recovery Post Robot Assisted Radical Prostatectomy for Prostate Cancer.

PURPOSE OF REVIEW: A variety of different surgical techniques are thought to impact on urinary continence (UC) recovery in patients undergoing robot assisted radical prostatectomy (RARP) for prostate cancer. Herein, we review current evidence and propose a composite evidence-based technique to optimize UC recovery after RARP. RECENT FINDINGS: A literature search on studies reporting on surgical techniques to improve early continence recovery post robotic prostatectomy was conducted on PubMed and EMBASE. The available data from studies ranging from randomized control trials to retrospective cohort studies suggest that minimizing damage to the internal and external urinary sphincters and their neural supply, maximal sparing of urethral length, creating a secure vesicourethral anastomosis, and providing anterior and posterior myo- fascio-ligamentous support to the anastomosis can improve early UC recovery post RARP. A composite evidence-based surgical technique incorporating the above principles could optimize early UC recovery post RARP. Evidence from randomized studies is required to prove benefit

Indistinguishable Landscapes of Meiotic DNA Breaks in rad50+ and rad50S Strains of Fission Yeast Revealed by a Novel rad50+ Recombination Intermediate

The fission yeast Schizosaccharomyces pombe Rec12 protein, the homolog of Spo11 in other organisms, initiates meiotic recombination by creating DNA double-strand breaks (DSBs) and becoming covalently linked to the DNA ends of the break. This protein–DNA linkage has previously been detected only in mutants such as rad50S in which break repair is impeded and DSBs accumulate. In the budding yeast Saccharomyces cerevisiae, the DSB distribution in a rad50S mutant is markedly different from that in wild-type (RAD50) meiosis, and it was suggested that this might also be true for other organisms. Here, we show that we can detect Rec12-DNA linkages in Sc. pombe rad50+ cells, which are proficient for DSB repair. In contrast to the results from Sa. cerevisiae, genome-wide microarray analysis of Rec12-DNA reveals indistinguishable meiotic DSB distributions in rad50+ and rad50S strains of Sc. pombe. These results confirm our earlier findings describing the occurrence of widely spaced DSBs primarily in large intergenic regions of DNA and demonstrate the relevance and usefulness of fission yeast studies employing rad50S. We propose that the differential behavior of rad50S strains reflects a major difference in DSB regulation between the two species—specifically, the requirement for the Rad50-containing complex for DSB formation in budding yeast but not in fission yeast. Use of rad50S and related mutations may be a useful method for DSB analysis in other species

Presenilin/γ-Secretase Regulates Neurexin Processing at Synapses

Neurexins are a large family of neuronal plasma membrane proteins, which function as trans-synaptic receptors during synaptic differentiation. The binding of presynaptic neurexins to postsynaptic partners, such as neuroligins, has been proposed to participate in a signaling pathway that regulates synapse formation/stabilization. The identification of mutations in neurexin genes associated with autism and mental retardation suggests that dysfunction of neurexins may underlie synaptic defects associated with brain disorders. However, the mechanisms that regulate neurexin function at synapses are still unclear. Here, we show that neurexins are proteolytically processed by presenilins (PS), the catalytic components of the γ-secretase complex that mediates the intramembraneous cleavage of several type I membrane proteins. Inhibition of PS/γ-secretase by using pharmacological and genetic approaches induces a drastic accumulation of neurexin C-terminal fragments (CTFs) in cultured rat hippocampal neurons and mouse brain. Neurexin-CTFs accumulate mainly at the presynaptic terminals of PS conditional double knockout (PS cDKO) mice lacking both PS genes in glutamatergic neurons of the forebrain. The fact that loss of PS function enhances neurexin accumulation at glutamatergic terminals mediated by neuroligin-1 suggests that PS regulate the processing of neurexins at glutamatergic synapses. Interestingly, presenilin 1 (PS1) is recruited to glutamatergic terminals mediated by neuroligin-1, thus concentrating PS1 at terminals containing β-neurexins. Furthermore, familial Alzheimer's disease (FAD)-linked PS1 mutations differentially affect β-neurexin-1 processing. Expression of PS1 M146L and PS1 H163R mutants in PS−/− cells rescues the processing of β-neurexin-1, whereas PS1 C410Y and PS1 ΔE9 fail to rescue the processing defect. These results suggest that PS regulate the synaptic function and processing of neurexins at glutamatergic synapses, and that impaired neurexin processing by PS may play a role in FAD

Differences in Walking Pattern during 6-Min Walk Test between Patients with COPD and Healthy Subjects

BACKGROUND: To date, detailed analyses of walking patterns using accelerometers during the 6-min walk test (6MWT) have not been performed in patients with chronic obstructive pulmonary disease (COPD). Therefore, it remains unclear whether and to what extent COPD patients have an altered walking pattern during the 6MWT compared to healthy elderly subjects. METHODOLOGY/PRINCIPAL FINDINGS: 79 COPD patients and 24 healthy elderly subjects performed the 6MWT wearing an accelerometer attached to the trunk. The accelerometer features (walking intensity, cadence, and walking variability) and subject characteristics were assessed and compared between groups. Moreover, associations were sought with 6-min walk distance (6MWD) using multiple ordinary least squares (OLS) regression models. COPD patients walked with a significantly lower walking intensity, lower cadence and increased walking variability compared to healthy subjects. Walking intensity and height were the only two significant determinants of 6MWD in healthy subjects, explaining 85% of the variance in 6MWD. In COPD patients also age, cadence, walking variability measures and their interactions were included were significant determinants of 6MWD (total variance in 6MWD explained: 88%). CONCLUSIONS/SIGNIFICANCE: COPD patients have an altered walking pattern during 6MWT compared to healthy subjects. These differences in walking pattern partially explain the lower 6MWD in patients with COPD

Cognitive and affective perspective-taking in conduct-disordered children high and low on callous-unemotional traits

<p>Abstract</p> <p>Background</p> <p>Deficits in cognitive and/or affective perspective-taking have been implicated in Conduct-Disorder (CD), but empirical investigations produced equivocal results. Two factors may be implicated: (a) distinct deficits underlying the antisocial conduct of CD subgroups, (b) plausible disjunction between cognitive and affective perspective-taking with subgroups presenting either cognitive or affective-specific deficits.</p> <p>Method</p> <p>This study employed a second-order false-belief paradigm in which the cognitive perspective-taking questions tapped the character's thoughts and the affective perspective-taking questions tapped the emotions generated by these thoughts. Affective and cognitive perspective-taking was compared across three groups of children: (a) CD elevated on Callous-Unemotional traits (<it>CD-high-CU</it>, <it>n </it>= 30), (b) CD low on CU traits (<it>CD-low-CU</it>, <it>n </it>= 42), and (c) a 'typically-developing' comparison group (<it>n </it>= 50), matched in age (7.5 – 10.8), gender and socioeconomic background.</p> <p>Results</p> <p>The results revealed deficits in <it>CD-low-CU </it>children for both affective and cognitive perspective-taking. In contrast <it>CD-high-CU </it>children showed relative competency in cognitive, but deficits in affective-perspective taking, a finding that suggests an affective-specific defect and a plausible dissociation of affective and cognitive perspective-taking in <it>CD-high-CU </it>children.</p> <p>Conclusion</p> <p>Present findings indicate that deficits in cognitive perspective-taking that have long been implicated in CD appear to be characteristic of a subset of CD children. In contrast affective perspective-taking deficits characterise both CD subgroups, but these defects seem to be following diverse developmental paths that warrant further investigation.</p

Meiotic Recombination Hotspots of Fission Yeast Are Directed to Loci that Express Non-Coding RNA

Polyadenylated, mRNA-like transcripts with no coding potential are abundant in eukaryotes, but the functions of these long non-coding RNAs (ncRNAs) are enigmatic. In meiosis, Rec12 (Spo11) catalyzes the formation of dsDNA breaks (DSBs) that initiate homologous recombination. Most meiotic recombination is positioned at hotspots, but knowledge of the mechanisms is nebulous. In the fission yeast genome DSBs are located within 194 prominent peaks separated on average by 65-kbp intervals of DNA that are largely free of DSBs.). Furthermore, we tested and rejected the hypothesis that the ncRNA loci and DSB peaks localize preferentially, but independently, to a third entity on the chromosomes.Meiotic DSB hotspots are directed to loci that express polyadenylated ncRNAs. This reveals an unexpected, possibly unitary mechanism for what directs meiotic recombination to hotspots. It also reveals a likely biological function for enigmatic ncRNAs. We propose specific mechanisms by which ncRNA molecules, or some aspect of RNA metabolism associated with ncRNA loci, help to position recombination protein complexes at DSB hotspots within chromosomes