Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts.

ObjectiveTo compare faecal microbial composition in patients with systemic sclerosis (SSc) from 2 independent cohorts with controls and to determine whether certain genera are associated with SSc-gastrointestinal tract (GIT) symptoms.DesignAdult patients with SSc from the University of California, Los Angeles (UCLA) and Oslo University Hospital (OUH) and healthy controls participated in this study (1:1:1). All participants provided stool specimens for 16S rRNA sequencing. Linear discriminant analysis effect size demonstrated genera with differential expression in SSc. Differential expression analysis for sequence count data identified specific genera associated with GIT symptoms as assessed by the GIT 2.0 questionnaire.ResultsThe UCLA-SSc and OUH-SSc cohorts were similar in age (52.1 and 60.5 years, respectively), disease duration (median (IQR): 6.6 (2.5-16.4) and 7.0 (1.0-19.2) years, respectively), gender distribution (88% and 71%, respectively), and GIT symptoms (mean (SD) total GIT 2.0 scores of 0.7 (0.6) and 0.6 (0.5), respectively). Principal coordinate analysis illustrated significant microbial community differences between SSc and controls (UCLA: p=0.001; OUH: p=0.002). Patients with SSc had significantly lower levels of commensal genera deemed to protect against inflammation, such as Bacteroides (UCLA and OUH), Faecalibacterium (UCLA), Clostridium (OUH); and significantly higher levels of pathobiont genera, such as Fusobacterium (UCLA), compared with controls. Increased abundance of Clostridium was associated with less severe GIT symptoms in both cohorts.ConclusionsThe present analysis detected specific aberrations in the lower GIT microbiota of patients with SSc from 2 geographically and ethnically distinct cohorts. These findings suggest that GIT dysbiosis may be a pathological feature of the SSc disease state

Cultivating compliance: governance of North Indian organic basmati smallholders in a global value chain

Focusing on a global value chain (GVC) for organic basmati rice, we study how farmers’ practices are governed through product and process standards, organic certification protocols, and contracts with buyer firms. We analyze how farmers’ entry into the GVC reconfigures their agencements (defined as heterogeneous arrangements of human and nonhuman agencies which are associated with each other). These reconfigurations entail the severance of some associations among procedural and material elements of the agencements and the formation of new associations, in order to produce cultivation practices that are accurately described by the GVC’s standards and protocols. Based on ethnography of two farmers in Uttarakhand, North India, we find that the same standards were enacted differently on the two farmers’ fields, producing variable degrees of (selective) compliance with the ‘official’ GVC standards. We argue that the disjuncture between the ‘official’ scripts of the standards and actual cultivation practices must be nurtured to allow farmers’ agencements to align their practices with local sociotechnical relations and farm ecology. Furthermore, we find that compliance and disjuncture were facilitated by many practices and associations that were officially ungoverned by the GVC

Kinetic model of II-VI(001) semiconductor surfaces: Growth rates in atomic layer epitaxy

We present a zinc-blende lattice gas model of II-VI(001) surfaces, which is investigated by means of Kinetic Monte Carlo (KMC) simulations. Anisotropic effective interactions between surface metal atoms allow for the description of, e.g., the sublimation of CdTe(001), including the reconstruction of Cd-terminated surfaces and its dependence on the substrate temperature T. Our model also includes Te-dimerization and the potential presence of excess Te in a reservoir of weakly bound atoms at the surface. We study the self-regulation of atomic layer epitaxy (ALE) and demonstrate how the interplay of the reservoir occupation with the surface kinetics results in two different regimes: at high T the growth rate is limited to 0.5 layers per ALE cycle, whereas at low enough T each cycle adds a complete layer of CdTe. The transition between the two regimes occurs at a characteristic temperature and its dependence on external parameters is studied. Comparing the temperature dependence of the ALE growth rate in our model with experimental results for CdTe we find qualitative agreement.Comment: 9 pages (REVTeX), 8 figures (EPS). Content revised, references added, typos correcte

Illusory perceptions of space and time preserve cross-saccadic perceptual continuity

When voluntary saccadic eye movements are made to a silently ticking clock, observers sometimes think that the second hand takes longer than normal to move to its next position. For a short period, the clock appears to have stopped (chronostasis). Here we show that the illusion occurs because the brain extends the percept of the saccadic target backwards in time to just before the onset of the saccade. This occurs every time we move the eyes but it is only perceived when an external time reference alerts us to the phenomenon. The illusion does not seem to depend on the shift of spatial attention that accompanies the saccade. However, if the target is moved unpredictably during the saccade, breaking perception of the target's spatial continuity, then the illusion disappears. We suggest that temporal extension of the target's percept is one of the mechanisms that 'fill in' the perceptual 'gap' during saccadic suppression. The effect is critically linked to perceptual mechanisms that identify a target's spatial stability

The R403Q Myosin Mutation Implicated in Familial Hypertrophic Cardiomyopathy Causes Disorder at the Actomyosin Interface

Mutations in virtually all of the proteins comprising the cardiac muscle sarcomere have been implicated in causing Familial Hypertrophic Cardiomyopathy (FHC). Mutations in the beta-myosin heavy chain (MHC) remain among the most common causes of FHC, with the widely studied R403Q mutation resulting in an especially severe clinical prognosis. In vitro functional studies of cardiac myosin containing the R403Q mutation have revealed significant changes in enzymatic and mechanical properties compared to wild-type myosin. It has been proposed that these molecular changes must trigger events that ultimately lead to the clinical phenotype.Here we examine the structural consequences of the R403Q mutation in a recombinant smooth muscle myosin subfragment (S1), whose kinetic features have much in common with slow beta-MHC. We obtained three-dimensional reconstructions of wild-type and R403Q smooth muscle S1 bound to actin filaments in the presence (ADP) and absence (apo) of nucleotide by electron cryomicroscopy and image analysis. We observed that the mutant S1 was attached to actin at highly variable angles compared to wild-type reconstructions, suggesting a severe disruption of the actin-myosin interaction at the interface.These results provide structural evidence that disarray at the molecular level may be linked to the histopathological myocyte disarray characteristic of the diseased state