The opsonizing ligand on Salmonella typhimurium influences incorporation of specific, but not azurophil, granule constituents into neutrophil phagosomes.

Phagosomes were purified from human neutrophils ingesting Salmonella typhimurium opsonized with adsorbed normal human serum or with rabbit IgG. Constituents within the phagosome were endogenously labeled by supplying the cells with 125INa during phagocytosis. Lactoferrin and vitamin B12 binding protein (TC1 and TC3), markers for specific granules, were present in the phagosomes from neutrophils ingesting S. typhimurium opsonized with IgG but were 3.5- to 5-fold less prominent in phagosomes from cells phagocytosing Salmonella bearing C3 fragments only. In contrast, iodinated azurophilic granule components, most prominently defensins, were the major constituents in phagosomes prepared under both opsonization conditions. Furthermore, labeled complement (CR1 and CR3) and immunoglobulin (Fc gamma RIII) receptors were incorporated in the phagosome regardless of the ligand mediating phagocytosis. These results suggest that the ligand-receptor interactions mediating phagocytosis influence incorporation of neutrophil-specific granule contents into phagosomes

A regulatory code for neurogenic gene expression in the Drosophila embryo

Bioinformatics methods have identified enhancers that mediate restricted expression in the Drosophila embryo. However, only a small fraction of the predicted enhancers actually work when tested in vivo. In the present study, co-regulated neurogenic enhancers that are activated by intermediate levels of the Dorsal regulatory gradient are shown to contain several shared sequence motifs. These motifs permitted the identification of new neurogenic enhancers with high precision: five out of seven predicted enhancers direct restricted expression within ventral regions of the neurogenic ectoderm. Mutations in some of the shared motifs disrupt enhancer function, and evidence is presented that the Twist and Su(H) regulatory proteins are essential for the specification of the ventral neurogenic ectoderm prior to gastrulation. The regulatory model of neurogenic gene expression defined in this study permitted the identification of a neurogenic enhancer in the distant Anopheles genome. We discuss the prospects for deciphering regulatory codes that link primary DNA sequence information with predicted patterns of gene expression

Computational fluid dynamics modeling of symptomatic intracranial atherosclerosis may predict risk of stroke recurrence.

BackgroundPatients with symptomatic intracranial atherosclerosis (ICAS) of ≥ 70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset.MethodsPatients with a symptomatic ICAS lesion of 70-99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year.ResultsOverall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (-2.46-0.79), 4.5 (2.2-20.6), and 7.4 (5.2-12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004-1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002-1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594-0.903; P = 0.014) and 0.776 (95% CI, 0.594-0.903; P = 0.002) in receiver operating characteristic analysis.ConclusionsHemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70-99% luminal stenosis

Network Physiology reveals relations between network topology and physiological function

The human organism is an integrated network where complex physiologic systems, each with its own regulatory mechanisms, continuously interact, and where failure of one system can trigger a breakdown of the entire network. Identifying and quantifying dynamical networks of diverse systems with different types of interactions is a challenge. Here, we develop a framework to probe interactions among diverse systems, and we identify a physiologic network. We find that each physiologic state is characterized by a specific network structure, demonstrating a robust interplay between network topology and function. Across physiologic states the network undergoes topological transitions associated with fast reorganization of physiologic interactions on time scales of a few minutes, indicating high network flexibility in response to perturbations. The proposed system-wide integrative approach may facilitate the development of a new field, Network Physiology.Comment: 12 pages, 9 figure

Predator-Induced Vertical Behavior of a Ctenophore

Although many studies have focused on Mnemiopsis leidyi predation, little is known about the role of this ctenophore as prey when abundant in native and invaded pelagic systems. We examined the response of the ctenophore M. leidyi to the predatory ctenophore Beroe ovata in an experiment in which the two species could potentially sense each other while being physically separated. On average, M. leidyi responded to the predator’s presence by increasing variability in swimming speeds and by lowering their vertical distribution. Such behavior may help explain field records of vertical migration, as well as stratified and near-bottom distributions of M. leidyi

Are we there yet?:An update on transitional care in rheumatology

Abstract Significant progress has been made in the understanding of transitional care in rheumatology over the last few decades, yet universal implementation has not been realised and unmet needs continue to be reported. Possible explanations for this include lack of evidence as to which model is most effective; lack of attention to the multiple dimensions, stakeholders and systems involved in health transitions; and lack of consideration of the developmental appropriateness of transition interventions and the services/organisations/systems where such interventions are delivered. Successful transition has major implications to both the young people with juvenile-onset rheumatic disease and their families. Future research in this area will need to reflect both the multidimensional (biopsychosocial) and the multisystemic (multiple systems and stakeholders across personal/social/family support networks and health/social care/education systems). Only then will we be able to determine which aspects of transition readiness and service components influence which dimension. It is therefore imperative we continue to research and develop this area, involving both paediatric and adult rheumatology clinicians and researchers, remembering to look beyond both the condition and our discipline. Neither should we forget to tap into the exciting potential associated with digital technology to ensure further advances in transitional care are brought about in and beyond rheumatology