In vivo measurement of surface pressures and retraction distances applied on abdominal organs during surgery

This study undertook the in vivo measurement of surface pressures applied by the fingers of the surgeon during typical representative retraction movements of key human abdominal organs during both open and hand-assisted laparoscopic surgery. Surface pressures were measured using a flexible thin-film pressure sensor for 35 typical liver retractions to access the gall bladder, 36 bowel retractions, 9 kidney retractions, 8 stomach retractions, and 5 spleen retractions across 12 patients undergoing open and laparoscopic abdominal surgery. The maximum and root mean square surface pressures were calculated for each organ retraction. The maximum surface pressures applied to these key abdominal organs are in the range 1 to 41 kPa, and the average maximum surface pressure for all organs and procedures was 14 ± 3 kPa. Surface pressure relaxation during the retraction hold period was observed. Generally, the surface pressures are higher, and the rate of surface pressure relaxation is lower, in the more confined hand-assisted laparoscopic procedures than in open surgery. Combined video footage and pressure sensor data for retraction of the liver in open surgery enabled correlation of organ retraction distance with surface pressure application. The data provide a platform to design strategies for the prevention of retraction injuries. They also form a basis for the design of next-generation organ retraction and space creation surgical devices with embedded sensors that can further quantify intraoperative retraction forces to reduce injury or trauma to organs and surrounding tissues

Identification of the factors associated with outcomes in a condition management programme

<p>Background: A requirement of the Government’s Pathways to Work (PtW) agenda was to introduce a Condition Management Programme (CMP). The aim of the present study was to identify the differences between those who engaged and made progress in this telephone-based biopsychosocial intervention, in terms of their health, and those who did not and to determine the client and practitioner characteristics and programme elements associated with success in a programme aimed at improving health.</p> <p>Methods: Data were obtained from the CMP electronic spreadsheets and clients paper-based case records. CMP standard practice was that questionnaires were administered during the pre- and post-assessment phases over the telephone. Each client’s record contains their socio-demographic data, their primary health condition, as well as the pre- and post-intervention scores of the health assessment tool administered. Univariate and multivariate statistical analysis was used to investigate the relationships between the database variables. Clients were included in the study if their records were available for analysis from July 2006 to December 2007.</p> <p> Results: On average there were 112 referrals per month, totalling 2016 referrals during the evaluation period. The majority (62.8%) of clients had a mental-health condition. Successful completion of the programme was 28.5% (575 “completers”; 144 “discharges”). Several factors, such as age, health condition, mode of contact, and practitioner characteristics, were significant determinants of participation and completion of the programme. The results showed that completion of the CMP was associated with a better mental-health status, by reducing the number of clients that were either anxious, depressed or both, before undertaking the programme, from 74% to 32.5%.</p> <p>Conclusions: Our findings showed that an individual's characteristics are associated with success in the programme, defined as completing the intervention and demonstrating an improved health status. This study provides some evidence that the systematic evaluation of such programmes and interventions could identify ways in which they could be improved.</p&gt

Cooperative Interaction of Transcription Termination Factors with the RNA Polymerase II C-terminal Domain

Phosphorylation of the C-terminal domain of RNA polymerase II controls the co-transcriptional assembly of RNA processing and transcription factors. Recruitment relies on conserved CTDinteracting domains that recognize different CTD phosphoisoforms during the transcription cycle, but the molecular basis for their specificity remains unclear. We show that the CTD-interacting domains of two transcription termination factors, Rtt103 and Pcf11, achieve high affinity and specificity both by specifically recognizing the phosphorylated CTD and by cooperatively binding to neighboring CTD repeats. Single amino acid mutations at the protein-protein interface abolish cooperativity and affect recruitment at the 3′-end processing site in vivo. We suggest that this cooperativity provides a signal-response mechanism to ensure that its action is confined only to proper polyadenylation sites where Serine 2 phosphorylation density is highest

Brief Report: Attenuated Emotional Suppression of the Attentional Blink in Autism Spectrum Disorder: Another Non-Social Abnormality?

Twenty-five individuals with Autism Spectrum Disorder and 25 typically developed individuals participated in an Attentional Blink paradigm to determine whether emotional words would capture attention similarly in the two groups. Whilst the emotionality of words facilitated attention in typical comparison participants, this effect was attenuated in the ASD group. The magnitude of the emotional modulation of attention in ASD also correlated significantly with participants’ VIQ, which was not observed for the comparison group. Together these observations replicate and extend the findings of Corden et al. (J Autism Develop Disord 38:1072–1080, 2008) and implicate abnormalities in emotional processes outside the broader context of social cognition in ASD. We discuss our findings in relation to possible abnormalities in amygdala function that may underlie the disorder

The Non-Canonical CTD of RNAP-II Is Essential for Productive RNA Synthesis in Trypanosoma brucei

The carboxy-terminal domain (CTD) of the largest subunit (RPB1) of RNA polymerase II (RNAP-II) is essential for gene expression in metazoa and yeast. The canonical CTD is characterized by heptapeptide repeats. Differential phosphorylation of canonical CTD orchestrates transcriptional and co-transcriptional maturation of mRNA and snRNA. Many organisms, including trypanosomes, lack a canonical CTD. In these organisms, the CTD is called a non-canonical CTD or pseudo-CTD (ΨCTD. In the African trypanosome, Trypanosoma brucei, the ΨCTD is ∼285 amino acids long, rich in serines and prolines, and phosphorylated. We report that T. brucei RNAP-II lacking the entire ΨCTD or containing only a 95-amino-acid-long ΨCTD failed to support cell viability. In contrast, RNAP-II with a 186-amino-acid-long ΨCTD maintained cellular growth. RNAP-II with ΨCTD truncations resulted in abortive initiation of transcription. These data establish that non-canonical CTDs play an important role in gene expression

An Investigation of a Role for U2 snRNP Spliceosomal Components in Regulating Transcription

There is mounting evidence to suggest that the synthesis of pre-mRNA transcripts and their subsequent splicing are coordinated events. Previous studies have implicated the mammalian spliceosomal U2 snRNP as having a novel role in stimulating transcriptional elongation in vitro through interactions with the elongation factors P-TEFb and Tat-SF1; however, the mechanism remains unknown [1]. These factors are conserved in Saccharomyces cerevisiae, a fact that suggests that a similar interaction may occur in yeast to stimulate transcriptional elongation in vivo. To address this possibility we have looked for evidence of a role for the yeast Tat-SF1 homolog, Cus2, and the U2 snRNA in regulating transcription. Specifically, we have performed a genetic analysis to look for functional interactions between Cus2 or U2 snRNA and the P-TEFb yeast homologs, the Bur1/2 and Ctk1/2/3 complexes. In addition, we have analyzed Cus2-deleted or -overexpressing cells and U2 snRNA mutant cells to determine if they show transcription-related phenotypes similar to those displayed by the P-TEFb homolog mutants. In no case have we been able to observe phenotypes consistent with a role for either spliceosomal factor in transcription elongation. Furthermore, we did not find evidence for physical interactions between the yeast U2 snRNP factors and the P-TEFb homologs. These results suggest that in vivo, S. cerevisiae do not exhibit functional or physical interactions similar to those exhibited by their mammalian counterparts in vitro. The significance of the difference between our in vivo findings and the previously published in vitro results remains unclear; however, we discuss the potential importance of other factors, including viral proteins, in mediating the mammalian interactions

Transcriptional activity of Hyacinthus orientalis L. female gametophyte cells before and after fertilization

We characterized three phases of Hyacinthus orientalis L. embryo sac development, in which the transcriptional activity of the cells differed using immunolocalization of incorporated 5′-bromouracil, the total RNA polymerase II pool and the hypo- (initiation) and hyperphosphorylated (elongation) forms of RNA Pol II. The first stage, which lasts from the multinuclear stage to cellularization, is a period of high transcriptional activity, probably related to the maturation of female gametophyte cells. The second stage, encompassing the period of embryo sac maturity and the progamic phase, involves the transcriptional silencing of cells that will soon undergo fusion with male gametes. During this period in the hyacinth egg cell, there are almost no newly formed transcripts, and only a small pool of RNA Pol II is present in the nucleus. The transcriptional activity of the central cell is only slightly higher than that observed in the egg cell. The post-fertilization stage is related to the transcriptional activation of the zygote and the primary endosperm cell. The rapid increase in the pool of newly formed transcripts in these cells is accompanied by an increase in the pool of RNA Pol II, and the pattern of enzyme distribution in the zygote nucleus is similar to that observed in the somatic cells of the ovule. Our data, together with the earlier results of Pięciński et al. (2008), indicate post-fertilization synthesis and the maturation of numerous mRNA transcripts, suggesting that fertilization in H. orientalis induces the activation of the zygote and endosperm genomes

Dissection of Pol II Trigger Loop Function and Pol II Activity–Dependent Control of Start Site Selection In Vivo

Structural and biochemical studies have revealed the importance of a conserved, mobile domain of RNA Polymerase II (Pol II), the Trigger Loop (TL), in substrate selection and catalysis. The relative contributions of different residues within the TL to Pol II function and how Pol II activity defects correlate with gene expression alteration in vivo are unknown. Using Saccharomyces cerevisiae Pol II as a model, we uncover complex genetic relationships between mutated TL residues by combinatorial analysis of multiply substituted TL variants. We show that in vitro biochemical activity is highly predictive of in vivo transcription phenotypes, suggesting direct relationships between phenotypes and Pol II activity. Interestingly, while multiple TL residues function together to promote proper transcription, individual residues can be separated into distinct functional classes likely relevant to the TL mechanism. In vivo, Pol II activity defects disrupt regulation of the GTP-sensitive IMD2 gene, explaining sensitivities to GTP-production inhibitors, but contrasting with commonly cited models for this sensitivity in the literature. Our data provide support for an existing model whereby Pol II transcriptional activity provides a proxy for direct sensing of NTP levels in vivo leading to IMD2 activation. Finally, we connect Pol II activity to transcription start site selection in vivo, implicating the Pol II active site and transcription itself as a driver for start site scanning, contravening current models for this process

Mixed emotions: The contribution of alexithymia to the emotional symptoms of autism

It is widely accepted that autism is associated with disordered emotion processing, and in particular, with deficits of emotional reciprocity such as impaired emotion recognition and reduced empathy. However, a close examination of the literature reveals wide heterogeneity within the autistic population with respect to emotional competence. Here we argue that, where observed, emotional impairments are due to alexithymia - a condition that frequently co-occurs with autism - rather than a feature of autism per se. Alexithymia is a condition characterized by a reduced ability to identify and describe one’s own emotion, but which results in reduced empathy and an impaired ability to recognize the emotions of others. We briefly review studies of emotion processing in alexithymia, and in autism, before describing a recent series of studies directly testing this ‘alexithymia hypothesis’. If found to be correct, the alexithymia hypothesis has wide-reaching implications for the study of autism, and how we might best support sub-groups of autistic individuals with, and without, accompanying alexithymia. Finally, we note the presence of elevated rates of alexithymia, and inconsistent reports of emotional impairments, in eating disorders, schizophrenia, substance abuse, Parkinson’s Disease, Multiple Sclerosis, and anxiety disorders. We speculate that examining the contribution of alexithymia to the emotional symptoms of these disorders may bear fruit in the same way that it is starting to do in autism

Determination of sin2 θeff w using jet charge measurements in hadronic Z decays

The electroweak mixing angle is determined with high precision from measurements of the mean difference between forward and backward hemisphere charges in hadronic decays of the Z. A data sample of 2.5 million hadronic Z decays recorded over the period 1990 to 1994 in the ALEPH detector at LEP is used. The mean charge separation between event hemispheres containing the original quark and antiquark is measured for bb̄ and cc̄ events in subsamples selected by their long lifetimes or using fast D*'s. The corresponding average charge separation for light quarks is measured in an inclusive sample from the anticorrelation between charges of opposite hemispheres and agrees with predictions of hadronisation models with a precision of 2%. It is shown that differences between light quark charge separations and the measured average can be determined using hadronisation models, with systematic uncertainties constrained by measurements of inclusive production of kaons, protons and A's. The separations are used to measure the electroweak mixing angle precisely as sin2 θeff w = 0.2322 ± 0.0008(exp. stat.) ±0.0007(exp. syst.) ± 0.0008(sep.). The first two errors are due to purely experimental sources whereas the third stems from uncertainties in the quark charge separations