A totally laparoscopic associating liver partition and portal vein ligation for staged hepatectomy assisted with radiofrequency (radiofrequency assisted liver partition with portal vein ligation) for staged liver resection

In order to induce liver hypertrophy to enable liver resection in patients with a small future liver remnant, various methods have been proposed in addition to portal vein embolisation. Most recently, the ALPPS technique has gained significant international interest. This technique is limited by the high morbidity associated with an in-situ liver splitting and the patient undergoing two open operations. We present the case of a variant ALPPS technique performed entirely laparoscopically with no major morbidity or mortality. An increased liver volume of 57.9% was seen after 14 days. This technique is feasible to perform and compares favourably to other ALPPS methods whilst gaining the advantages of laparoscopic surgery

Sensitivity analysis of circadian entrainment in the space of phase response curves

Sensitivity analysis is a classical and fundamental tool to evaluate the role of a given parameter in a given system characteristic. Because the phase response curve is a fundamental input--output characteristic of oscillators, we developed a sensitivity analysis for oscillator models in the space of phase response curves. The proposed tool can be applied to high-dimensional oscillator models without facing the curse of dimensionality obstacle associated with numerical exploration of the parameter space. Application of this tool to a state-of-the-art model of circadian rhythms suggests that it can be useful and instrumental to biological investigations.Comment: 22 pages, 8 figures. Correction of a mistake in Definition 2.1. arXiv admin note: text overlap with arXiv:1206.414

Confluence of CHR Revisited:Invariants and Modulo Equivalence

Abstract simulation of one transition system by another is introduced as a means to simulate a potentially infinite class of similar transition sequences within a single transition sequence. This is useful for proving confluence under invariants of a given system, as it may reduce the number of proof cases to consider from infinity to a finite number. The classical confluence results for Constraint Handling Rules (CHR) can be explained in this way, using CHR as a simulation of itself. Using an abstract simulation based on a ground representation, we extend these results to include confluence under invariant and modulo equivalence, which have not been done in a satisfactory way before.Comment: Pre-proceedings paper presented at the 28th International Symposium on Logic-Based Program Synthesis and Transformation (LOPSTR 2018), Frankfurt am Main, Germany, 4-6 September 2018 (arXiv:1808.03326

The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed

Involvement of microbial mats in early fossilization by decay delay and formation of impressions and replicas of vertebrates and invertebrates

Microbial mats have been hypothesized to improve the persistence and the preservation of organic remains during fossilization processes. We test this hypothesis with long-term experiments (up to 5.5 years) using invertebrate and vertebrate corpses.Once placed on mats,the microbial community coats the corpses and forms a three-dimensional sarcophagus composed of microbial cells and exopolymeric substances (EPS). This coverage provides a template for i) moulding superficial features, resulting in negative impressions, and ii) generating replicas.The impressions of fly setulae, fish scales and frog skin verrucae are shaped mainly by small cells in an EPS matrix. Microbes also replicate delicate structures such as the three successive layers that compose a fish eye.The sarcophagus protects the body integrity, allowing the persistence of inner organs such as the ovaries and digestive apparatus in flies,the swim bladder and muscles in fish, and the bone marrow in frog legs.This study brings strong experimental evidence to the idea that mats favour metazoan fossilization by moulding, replicating and delaying decay. Rapid burial has classically been invoked as a mechanism to explain exceptional preservation. However, mats may play a similar role during early fossilization as they can preserve complex features for a long timeThis work, which is part of the research projects CGL2013-42643P and the research grant supporting M. Iniesto were funded by the Spanish Ministry of Economy and Competitiveness. The SEM facility at IMPMC was supported by Region Ile de France grant SESAME 2006 I-07-593/R, INSU-CNRS, INP-CNRS, and University Pierre et Marie Curie, Paris. SEM analyses performed for this study were supported by a grant from the Foundation Simone et Cino Del Duca (PI: K. Benzerara). Some SEM observations were also conducted at SIdI UAM (Madrid). Environmental SEM observations were performed at the MNCN (Madrid

Role of Cajal Bodies and Nucleolus in the Maturation of the U1 snRNP in Arabidopsis

Background: The biogenesis of spliceosomal snRNPs takes place in both the cytoplasm where Sm core proteins are added and snRNAs are modified at the 59 and 39 termini and in the nucleus where snRNP-specific proteins associate. U1 snRNP consists of U1 snRNA, seven Sm proteins and three snRNP-specific proteins, U1-70K, U1A, and U1C. It has been shown previously that after import to the nucleus U2 and U4/U6 snRNP-specific proteins first appear in Cajal bodies (CB) and then in splicing speckles. In addition, in cells grown under normal conditions U2, U4, U5, and U6 snRNAs/snRNPs are abundant in CBs. Therefore, it has been proposed that the final assembly of these spliceosomal snRNPs takes place in this nuclear compartment. In contrast, U1 snRNA in both animal and plant cells has rarely been found in this nuclear compartment. Methodology/Principal Findings: Here, we analysed the subnuclear distribution of Arabidopsis U1 snRNP-specific proteins fused to GFP or mRFP in transiently transformed Arabidopsis protoplasts. Irrespective of the tag used, U1-70K was exclusively found in the nucleus, whereas U1A and U1C were equally distributed between the nucleus and the cytoplasm. In the nucleus all three proteins localised to CBs and nucleoli although to different extent. Interestingly, we also found that the appearance of the three proteins in nuclear speckles differ significantly. U1-70K was mostly found in speckles whereas U1A and U1C in,90 % of cells showed diffuse nucleoplasmic in combination with CBs and nucleolar localisation. Conclusions/Significance: Our data indicate that CBs and nucleolus are involved in the maturation of U1 snRNP. Difference

Role of Cajal Bodies and Nucleolus in the Maturation of the U1 snRNP in Arabidopsis

Background: The biogenesis of spliceosomal snRNPs takes place in both the cytoplasm where Sm core proteins are added and snRNAs are modified at the 59 and 39 termini and in the nucleus where snRNP-specific proteins associate. U1 snRNP consists of U1 snRNA, seven Sm proteins and three snRNP-specific proteins, U1-70K, U1A, and U1C. It has been shown previously that after import to the nucleus U2 and U4/U6 snRNP-specific proteins first appear in Cajal bodies (CB) and then in splicing speckles. In addition, in cells grown under normal conditions U2, U4, U5, and U6 snRNAs/snRNPs are abundant in CBs. Therefore, it has been proposed that the final assembly of these spliceosomal snRNPs takes place in this nuclear compartment. In contrast, U1 snRNA in both animal and plant cells has rarely been found in this nuclear compartment. Methodology/Principal Findings: Here, we analysed the subnuclear distribution of Arabidopsis U1 snRNP-specific proteins fused to GFP or mRFP in transiently transformed Arabidopsis protoplasts. Irrespective of the tag used, U1-70K was exclusively found in the nucleus, whereas U1A and U1C were equally distributed between the nucleus and the cytoplasm. In the nucleus all three proteins localised to CBs and nucleoli although to different extent. Interestingly, we also found that the appearance of the three proteins in nuclear speckles differ significantly. U1-70K was mostly found in speckles whereas U1A and U1C in,90 % of cells showed diffuse nucleoplasmic in combination with CBs and nucleolar localisation. Conclusions/Significance: Our data indicate that CBs and nucleolus are involved in the maturation of U1 snRNP. Difference

The importance of waist circumference and body mass index in cross-sectional relationships with risk of cardiovascular disease in Vietnam

BackgroundWaist circumference (WC) is an indicator of intra-abdominal adipose tissue, high levels of which confer an increased risk of cardiometabolic disease. Population data on WC should be more informative than data on body mass index (BMI), which is a general indicator of body size. This study aimed to evaluate the importance of WC relative to BMI in cross-sectional relationships with blood pressure (BP), glucose, and total cholesterol (TC) in the adult population of Vietnam.MethodsThe data were collected in a population-based survey conducted during 2009-10 using the "WHO STEPwise approach to surveillance of risk factors for non-communicable disease" (STEPS) methodology. The survey participants (n = 14 706 aged 25 to 64 years) were selected by multi-stage stratified cluster sampling from eight provinces representative of the eight geographical regions of Vietnam. All measurements were performed in accordance with the STEPS protocols. All analyses were performed using complex survey methods.ResultsThe measurements of WC and BMI were highly correlated (men r = 0.80, women r = 0.77). For men, the strongest and predominant associations with BP, glucose, and TC were for WC or an index based on WC. For women, this was true for glucose but BMI was more important for BP and TC. WC or an index based on WC provided better discrimination than BMI of hypertension and elevated glucose, and of raised TC for men. Information on four new anthropometric indices did not improve model fit or subject discrimination.ConclusionFor BP/hypertension, glucose/elevated glucose, and TC/raised TC, WC was more informative than BMI for Vietnamese men, but both WC and BMI were important for Vietnamese women. Both WC and BMI need to be assessed for estimation of CVD risk in Vietnam

A comparative study of four intensive care outcome prediction models in cardiac surgery patients

<p>Abstract</p> <p>Background</p> <p>Outcome prediction scoring systems are increasingly used in intensive care medicine, but most were not developed for use in cardiac surgery patients. We compared the performance of four intensive care outcome prediction scoring systems (Acute Physiology and Chronic Health Evaluation II [APACHE II], Simplified Acute Physiology Score II [SAPS II], Sequential Organ Failure Assessment [SOFA], and Cardiac Surgery Score [CASUS]) in patients after open heart surgery.</p> <p>Methods</p> <p>We prospectively included all consecutive adult patients who underwent open heart surgery and were admitted to the intensive care unit (ICU) between January 1^st2007 and December 31^st2008. Scores were calculated daily from ICU admission until discharge. The outcome measure was ICU mortality. The performance of the four scores was assessed by calibration and discrimination statistics. Derived variables (Mean- and Max- scores) were also evaluated.</p> <p>Results</p> <p>During the study period, 2801 patients (29.6% female) were included. Mean age was 66.9 ± 10.7 years and the ICU mortality rate was 5.2%. Calibration tests for SOFA and CASUS were reliable throughout (p-value not < 0.05), but there were significant differences between predicted and observed outcome for SAPS II (days 1, 2, 3 and 5) and APACHE II (days 2 and 3). CASUS, and its mean- and maximum-derivatives, discriminated better between survivors and non-survivors than the other scores throughout the study (area under curve ≥ 0.90). In order of best discrimination, CASUS was followed by SOFA, then SAPS II, and finally APACHE II. SAPS II and APACHE II derivatives had discrimination results that were superior to those of the SOFA derivatives.</p> <p>Conclusions</p> <p>CASUS and SOFA are reliable ICU mortality risk stratification models for cardiac surgery patients. SAPS II and APACHE II did not perform well in terms of calibration and discrimination statistics.</p

Antibodies for Assessing Circadian Clock Proteins in the Rodent Suprachiasmatic Nucleus

Research on the mechanisms underlying circadian rhythmicity and the response of brain and body clocks to environmental and physiological challenges requires assessing levels of circadian clock proteins. Too often, however, it is difficult to acquire antibodies that specifically and reliably label these proteins. Many of these antibodies also lack appropriate validation. The goal of this project was to generate and characterize antibodies against several circadian clock proteins. We examined mice and hamsters at peak and trough times of clock protein expression in the suprachiasmatic nucleus (SCN). In addition, we confirmed specificity by testing the antibodies on mice with targeted disruption of the relevant genes. Our results identify antibodies against PER1, PER2, BMAL1 and CLOCK that are useful for assessing circadian clock proteins in the SCN by immunocytochemistry