Identifying Vessel Branching from Fluid Stresses on Microscopic Robots

Objects moving in fluids experience patterns of stress on their surfaces determined by the geometry of nearby boundaries. Flows at low Reynolds number, as occur in microscopic vessels such as capillaries in biological tissues, have relatively simple relations between stresses and nearby vessel geometry. Using these relations, this paper shows how a microscopic robot moving with such flows can use changes in stress on its surface to identify when it encounters vessel branches.Comment: Version 2 has minor clarification

Adaptation or constraint? Reference-dependent scatter in honey bee dances

The waggle dance of the honey bee is used to recruit nest mates to a resource. Dancer bees, however, may indicate many directions within a single dance bout; we show that this scatter in honey bee dances is strongly dependent on the sensory modality used to determine a reference angle in the dance. Dances with a visual reference are more precise than those with a gravity reference. This finding undermines the idea that scatter is introduced into dances, which the bees could perform more precisely, in order to spread recruits out over resource patches. It also calls into question reported interspecific differences that had been interpreted as adaptations of the dance to different habitats. Our results support a non-adaptive hypothesis: that dance scatter results from sensory and performance constraints, rather than modulation of the scatter by the dancing bee. However, an alternative adaptive hypothesis cannot be ruled out

X4 Human Immunodeficiency Virus Type 1 gp120 Promotes Human Hepatic Stellate Cell Activation and Collagen I Expression through Interactions with CXCR4

<div><h3>Background & Aims</h3><p>Patients coinfected with HIV-1 and HCV develop more rapid liver fibrosis than patients monoinfected with HCV. HIV RNA levels correlate with fibrosis progression implicating HIV directly in the fibrotic process. While activated hepatic stellate cells (HSCs) express the 2 major HIV chemokine coreceptors, CXCR4 and CCR5, little is known about the pro-fibrogenic effects of the HIV-1 envelope protein, gp120, on HSCs. We therefore examined the <em>in vitro</em> impact of X4 gp120 on HSC activation, collagen I expression, and underlying signaling pathways and examined the <em>in vivo</em> expression of gp120 in HIV/HCV coinfected livers.</p> <h3>Methods</h3><p>Primary human HSCs and LX-2 cells, a human HSC line, were challenged with X4 gp120 and expression of fibrogenic markers assessed by qRT-PCR and Western blot +/− either CXCR4-targeted shRNA or anti-CXCR4 neutralizing antibody. Downstream intracellular signaling pathways were evaluated with Western blot and pre-treatment with specific pathway inhibitors. Gp120 immunostaining was performed on HIV/HCV coinfected liver biopsies.</p> <h3>Results</h3><p>X4 gp 120 significantly increased expression of alpha-smooth muscle actin (a-SMA) and collagen I in HSCs which was blocked by pre-incubation with either CXCR4-targeted shRNA or anti-CXCR4 neutralizing antibody. Furthermore, X4 gp120 promoted Extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and pretreatment with an ERK inhibitor attenuated HSC activation and collagen I expression. Sinusoidal staining for gp120 was evident in HIV/HCV coinfected livers.</p> <h3>Conclusions</h3><p>X4 HIV-1 gp120 is pro-fibrogenic through its interactions with CXCR4 on activated HSCs. The availability of small molecule inhibitors to CXCR4 make this a potential anti-fibrotic target in HIV/HCV coinfected patients.</p> </div

Therapeutic issues in HIV/HCV-coinfected patients

The importance of treating hepatitis C virus (HCV)-associated morbidities in a growing population of patients coinfected with human immunodeficiency virus (HIV) has increased since the introduction of highly active antiretroviral therapy. As a result, investigative attention is turning to HCV-related liver disease and treatment-associated issues in coinfection. HIV/HCV-coinfected patients have higher HCV RNA loads and show more rapid progression of fibrosis than do monoinfected patients. Combination therapy with pegylated interferon plus ribavirin (RBV) is the standard of care for HCV in coinfected patients. Therapy slows fibrosis progression, but toxicity prevents identification of the most effective RBV dose. Coinfected patients have about a threefold greater risk of antiretroviral therapy-associated hepatotoxicity than patients with HIV only. Other challenges include anaemia, mitochondrial toxicity, drug–drug interactions and leucopenia. Thus, chronic hepatitis C should be treated in HIV/HCV-coinfected patients, but steps must be taken to prevent and treat potential toxicities. The first European Consensus Conference on the Treatment of Chronic Hepatitis B and C in HIV Co-infected Patients was held March 2005 in Paris to address these issues. This article reviews the peer-reviewed literature and expert opinion published from 1990 to 2005, and compares results with presentations and recommendations from the Consensus Conference to best present current issues in coinfection

Augmented versus Virtual Reality Laparoscopic Simulation: What Is the Difference?: A Comparison of the ProMIS Augmented Reality Laparoscopic Simulator versus LapSim Virtual Reality Laparoscopic Simulator

BACKGROUND: Virtual reality (VR) is an emerging new modality for laparoscopic skills training; however, most simulators lack realistic haptic feedback. Augmented reality (AR) is a new laparoscopic simulation system offering a combination of physical objects and VR simulation. Laparoscopic instruments are used within an hybrid mannequin on tissue or objects while using video tracking. This study was designed to assess the difference in realism, haptic feedback, and didactic value between AR and VR laparoscopic simulation. METHODS: The ProMIS AR and LapSim VR simulators were used in this study. The participants performed a basic skills task and a suturing task on both simulators, after which they filled out a questionnaire about their demographics and their opinion of both simulators scored on a 5-point Likert scale. The participants were allotted to 3 groups depending on their experience: experts, intermediates and novices. Significant differences were calculated with the paired t-test. RESULTS: There was general consensus in all groups that the ProMIS AR laparoscopic simulator is more realistic than the LapSim VR laparoscopic simulator in both the basic skills task (mean 4.22 resp. 2.18, P <0.000) as well as the suturing task (mean 4.15 resp. 1.85, P <0.000). The ProMIS is regarded as having better haptic feedback (mean 3.92 resp. 1.92, P <0.000) and as being more useful for training surgical residents (mean 4.51 resp. 2.94, P <0.000). CONCLUSIONS: In comparison with the VR simulator, the AR laparoscopic simulator was regarded by all participants as a better simulator for laparoscopic skills training on all tested feature

Coffee bean extracts rich and poor in kahweol both give rise to elevation of liver enzymes in healthy volunteers

BACKGROUND: Coffee oil potently raises serum cholesterol levels in humans. The diterpenes cafestol and kahweol are responsible for this elevation. Coffee oil also causes elevation of liver enzyme levels in serum. It has been suggested that cafestol is mainly responsible for the effect on serum cholesterol levels and that kahweol is mainly responsible for the effect on liver enzyme levels. The objective of this study was to investigate whether coffee oil that only contains a minute amount of kahweol indeed does not cause elevation of liver enzyme levels. METHODS: The response of serum alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) to Robusta coffee oil (62 mg/day cafestol, 1.6 mg/day kahweol) was measured in 18 healthy volunteers. RESULTS: After nine days one subject was taken off Robusta oil treatment due to an ALAT level of 3.6 times the upper limit of normal (ULN). Another two subjects stopped treatment due to other reasons. After 16 days another two subjects were taken off Robusta oil treatment. One of those subjects had levels of 5.8 ULN for ALAT and 2.0 ULN for ASAT; the other subject had an ALAT level of 12.4 ULN and an ASAT level of 4.7 ULN. It was then decided to terminate the study. The median response of subjects to Robusta oil after 16 days was 0.27 ULN (n = 15, 25(th),75(th )percentile: 0.09;0.53) for ALAT and 0.06 ULN (25(th),75(th )percentile -0.06;0.22) for ASAT. CONCLUSIONS: We conclude that the effect on liver enzyme levels of coffee oil containing hardly any kahweol is similar to that of coffee oil containing high amounts of kahweol. Therefore it is unlikely that kahweol is the component of coffee oil that is responsible for the effect. Furthermore, we conclude that otherwise unexplained elevation of liver enzyme levels observed in patients might be caused by a switch from consumption of filtered coffee to unfiltered coffee

Reproducibility of the serum lipid response to coffee oil in healthy volunteers

BACKGROUND: Humans and animals show a certain consistency in the response of their serum lipids to fat-modified diets. This may indicate a genetic basis underlying this response. Coffee oil might be used as a model substance to investigate which genes determine differences in the serum lipid response. Before carrying out such studies our objective was to investigate to what extent the effect of coffee oil on serum lipid concentrations is reproducible within subjects. METHODS: The serum lipid response of 32 healthy volunteers was measured twice in separate five-week periods in which coffee oil was administered (69 mg cafestol / day). RESULTS: Total cholesterol levels increased by 24% in period 1 (range:0;52%) and 18% in period 2 (1;48%), LDL cholesterol by 29 % (-9;71%) and 20% (-12;57%), triglycerides by 66% (16;175%) and 58% (-13;202%), and HDL cholesterol did not change significantly: The range of the HDL response was -19;25% in period 1 and -20;33% in period 2. The correlation between the two responses was 0.20 (95%CI -0.16, 0.51) for total cholesterol, 0.16 (95%CI -0.20, 0.48) for LDL, 0.67 (95%CI 0.42, 0.83) for HDL, and 0.77 (95%CI 0.56, 0.88) for triglycerides. CONCLUSIONS: The responses of total and LDL cholesterol to coffee oil were poorly reproducible within subjects. The responses of HDL and triglycerides, however, appeared to be highly reproducible. Therefore, investigating the genetic sources of the variation in the serum-lipid response to coffee oil is more promising for HDL and triglycerides

Dissecting the multifunctional role of the N-terminal disordered domain of a plant virus coat protein in RNA packaging, viral movement and interference with antiviral plant defense

[EN] The coat protein (CP) of Melon necrotic spot virus (MNSV) is structurally composed of three major domains. The middle S-domain builds a robust protein shell around the viral genome, whereas the C-terminal protruding domain, or P-domain, is involved in the attachment of virions to the transmission vector. Here, we have shown that the N-terminal domain, or R-domain, and the arm region, which connects the R-domain and S-domain, are involved in different key steps of the viral cycle, such as cell-to-cell movement and the suppression of RNA silencing and pathogenesis through their RNA-binding capabilities. Deletion mutants revealed that the CP RNA-binding ability was abolished only after complete, but not partial, deletion of the R-domain and the arm region. However, a comparison of the apparent dissociation constants for the CP RNA-binding reaction of several partial deletion mutants showed that the arm region played a more relevant role than the R-domain in in vitro RNA binding. Similar results were obtained in in vivo assays, although, in this case, full-length CPs were required to encapsidate full-length genomes. We also found that the R-domain carboxyl portion and the arm region were essential for efficient cell-to-cell movement, for enhancement of Potato virus X pathogenicity, for suppression of systemic RNA silencing and for binding of small RNAs. Therefore, unlike other carmovirus CPs, the R-domain and the arm region of MNSV CP have acquired, in addition to other essential functions such as genome binding and encapsidation functions, the ability to suppress RNA silencing by preventing systemic small RNA transport.This work was funded by grant BIO2014-54862-R from the Spanish Ministry of Science and Innovation and the Prometeo Program GV2014/010 from the Generalitat Valenciana. J.A.N. and M.S.-S. are the recipients of a postdoctoral contract and a PhD fellowship, respectively, from the Ministerio de Educacion y Ciencia of Spain. We thank L. Corachan for technical assistance. The authors have no conflicts of interest to declare.Serra Soriano, M.; Navarro Bohigues, JA.; Pallás Benet, V. (2017). Dissecting the multifunctional role of the N-terminal disordered domain of a plant virus coat protein in RNA packaging, viral movement and interference with antiviral plant defense. Molecular Plant Pathology. 18(6):837-849. https://doi.org/10.1111/mpp.12448S83784918

New Insights into Human Nondisjunction of Chromosome 21 in Oocytes

Nondisjunction of chromosome 21 is the leading cause of Down syndrome. Two risk factors for maternal nondisjunction of chromosome 21 are increased maternal age and altered recombination. In order to provide further insight on mechanisms underlying nondisjunction, we examined the association between these two well established risk factors for chromosome 21 nondisjunction. In our approach, short tandem repeat markers along chromosome 21 were genotyped in DNA collected from individuals with free trisomy 21 and their parents. This information was used to determine the origin of the nondisjunction error and the maternal recombination profile. We analyzed 615 maternal meiosis I and 253 maternal meiosis II cases stratified by maternal age. The examination of meiosis II errors, the first of its type, suggests that the presence of a single exchange within the pericentromeric region of 21q interacts with maternal age-related risk factors. This observation could be explained in two general ways: 1) a pericentromeric exchange initiates or exacerbates the susceptibility to maternal age risk factors or 2) a pericentromeric exchange protects the bivalent against age-related risk factors allowing proper segregation of homologues at meiosis I, but not segregation of sisters at meiosis II. In contrast, analysis of maternal meiosis I errors indicates that a single telomeric exchange imposes the same risk for nondisjunction, irrespective of the age of the oocyte. Our results emphasize the fact that human nondisjunction is a multifactorial trait that must be dissected into its component parts to identify specific associated risk factors