CD117+ Dendritic and Mast Cells Are Dependent on RasGRP4 to Function as Accessory Cells for Optimal Natural Killer Cell-Mediated Responses to Lipopolysaccharide.

Ras guanine nucleotide-releasing protein-4 (RasGRP4) is an evolutionarily conserved calcium-regulated, guanine nucleotide exchange factor and diacylglycerol/phorbol ester receptor. While an important intracellular signaling protein for CD117+ mast cells (MCs), its roles in other immune cells is less clear. In this study, we identified a subset of in vivo-differentiated splenic CD117+ dendritic cells (DCs) in wild-type (WT) C57BL/6 mice that unexpectedly contained RasGRP4 mRNA and protein.

Performance results for a workstation-integrated radiology peer review quality assurance program.

Objective: To assess review completion rates, RADPEER score distribution, and sources of disagreement when using a workstation-integrated radiology peer review program, and to evaluate radiologist perceptions of the program.

Design: Retrospective review of prospectively collected data.

Setting: Large private outpatient radiology practice.

Comparative Effectiveness of Conservative Interventions for Nonspecific Chronic Spinal Pain: Physical, Behavioral/Psychologically Informed, or Combined? A Systematic Review and Meta-Analysis.

Unlabelled: Nonspecific chronic spinal pain (NSCSP) is highly disabling. Current conservative rehabilitation commonly includes physical and behavioral interventions, or a combination of these approaches. Physical interventions aim to enhance physical capacity by using methods such as exercise, manual therapy, and ergonomics.

Unprecedented Topological Complexity in a Metal-Organic Framework Constructed from Simple Building Units.

A bismuth-based metal-organic framework (MOF), [Bi(BTC)(H2O)]·2H2O·MeOH denoted CAU-17, was synthesized and found to have an exceptionally complicated structure with helical Bi-O rods cross-linked by 1,3,5-benzenetricarboxylate (BTC(3-)) ligands. Five crystallographically independent 1D channels including two hexagonal channels, two rectangular channels, and one triangular channel have accessible diameters of 9.6, 9.

T Cell Help Amplifies Innate Signals in CD8(+) DCs for Optimal CD8(+) T Cell Priming.

DCs often require stimulation from CD4(+) T cells to propagate CD8(+) T cell responses, but precisely how T cell help optimizes the priming capacity of DCs and why this appears to differ between varying types of CD8(+) T cell immunity remains unclear. We show that CD8(+) T cell priming upon HSV-1 skin infection depended on DCs receiving stimulation from both IFN-α/β and CD4(+) T cells to provide IL-15. This was not an additive effect but resulted from CD4(+) T cells amplifying DC production of IL-15 in response to IFN-α/β.

A central role for hepatic conventional dendritic cells in supporting Th2 responses during helminth infection.

Dendritic cells (DCs) are the key initiators of T-helper (Th) 2 immune responses against the parasitic helminth Schistosoma mansoni. Although the liver is one of the main sites of antigen deposition during infection with this parasite, it is not yet clear how distinct DC subtypes in this tissue respond to S. mansoni antigens in vivo, or how the liver microenvironment might influence DC function during establishment of the Th2 response.

What Influences Patient-Therapist Interactions in Musculoskeletal Physical Therapy? Qualitative Systematic Review and Meta-Synthesis.

Background: Musculoskeletal physical therapy involves both specific and nonspecific effects. Nonspecific variables associated with the patient, therapist, and setting may influence clinical outcomes. Recent quantitative research has shown that nonspecific factors, including patient-therapist interactions, can influence treatment outcomes.

Human dendritic cell subsets and function in health and disease.

The method of choice for the development of new vaccines is to target distinct dendritic cell subsets with antigen in vivo and to harness their function in situ to enhance cell-mediated immunity or induce tolerance to specific antigens. The innate functions of dendritic cells themselves may also be targeted by inhibitors or activators that would target a specific function such as interferon production, potentially important in autoimmune disease and chronic viral infections. Importantly targeting dendritic cells requires detailed knowledge of both the surface phenotype and function of each dendritic cell subset, including how they may respond to different types of vaccine adjuvants, their ability to produce soluble mediators and to process and present antigens and induce priming of naïve T cells.

Pentagonal helices in a periodic metal-organic framework. Crystals as computers for discovering structures of minimal transitivity.

The structure of a recently-published metal-organic framework is deconstructed into its underlying net which is found to be of exceptional complexity. It is shown that this is because of local pentagonal symmetry and the structure is in fact the simplest possible (minimal transitivity) given that local symmetry.

Peptide identification and angiotensin converting enzyme (ACE) inhibitory activity in prolyl endoproteinase digests of bovine α(s)-casein.

Incubation of sodium caseinate (NaCN) and purified α-casein (αs-CN) with an Aspergillus niger derived prolyl endoproteinase (An-PEP) for 1, 2, 3, 4, 8 and 24 h resulted in the generation of potent angiotensin converting enzyme (ACE) inhibitory hydrolysates. An ACE IC50 of 21.1±5.

Individualised cognitive functional therapy compared with a combined exercise and pain education class for patients with non-specific chronic low back pain: study protocol for a multicentre randomised controlled trial.

Introduction: Non-specific chronic low back pain (NSCLBP) is a very common and costly musculoskeletal disorder associated with a complex interplay of biopsychosocial factors. Cognitive functional therapy (CFT) represents a novel, patient-centred intervention which directly challenges pain-related behaviours in a cognitively integrated, functionally specific and graduated manner. CFT aims to target all biopsychosocial factors that are deemed to be barriers to recovery for an individual patient with NSCLBP.

The cell surface receptor Slamf6 modulates innate immune responses during Citrobacter rodentium-induced colitis.

The homophilic cell surface receptors CD150 (Slamf1) and CD352 (Slamf6) are known to modulate adaptive immune responses. Although the Th17 response was enhanced in Slamf6(-/-) C57BL/6 mice upon oral infection with Citrobacter rodentium, the pathologic consequences are indistinguishable from an infection of wild-type C57BL/6 mice. Using a reporter-based binding assay, we show that Slamf6 can engage structures on the outer cell membrane of several Gram(-) bacteria.

Negative Regulation of Humoral Immunity Due to Interplay between the SLAMF1, SLAMF5, and SLAMF6 Receptors.

Whereas the SLAMF-associated protein (SAP) is involved in differentiation of T follicular helper (Tfh) cells and antibody responses, the precise requirements of SLAMF receptors in humoral immune responses are incompletely understood. By analyzing mice with targeted disruptions of the Slamf1, Slamf5, and Slamf6 genes, we found that both T-dependent and T-independent antibody responses were twofold higher compared to those in single knockout mice. These data suggest a suppressive synergy of SLAMF1, SLAMF5, and SLAMF6 in humoral immunity, which contrasts the decreased antibody responses resulting from a defective GC reaction in the absence of the adapter SAP.

Identification of short peptide sequences in complex milk protein hydrolysates.

Numerous low molecular mass bioactive peptides (BAPs) can be generated during the hydrolysis of bovine milk proteins. Low molecular mass BAP sequences are less likely to be broken down by digestive enzymes and are thus more likely to be active in vivo. However, the identification of short peptides remains a challenge during mass spectrometry (MS) analysis due to issues with the transfer and over-fragmentation of low molecular mass ions.

Physiotherapists may stigmatise or feel unprepared to treat people with low back pain and psychosocial factors that influence recovery: a systematic review.

Question: What are physiotherapists' perceptions about identifying and managing the cognitive, psychological and social factors that may act as barriers to recovery for people with low back pain (LBP)?

Design: Systematic review and qualitative metasynthesis of qualitative studies in which physiotherapists were questioned, using focus groups or semi-structured interviews, about identifying and managing cognitive, psychological and social factors in people with LBP.

Participants: Qualified physiotherapists with experience in treating patients with LBP.

Outcome Measures: Studies were synthesised in narrative format and thematic analysis was used to provide a collective insight into the physiotherapists' perceptions.

Migration of myeloid cells during inflammation is differentially regulated by the cell surface receptors Slamf1 and Slamf8.

Previous studies have demonstrated that the cell surface receptor Slamf1 (CD150) is requisite for optimal NADPH-oxidase (Nox2) dependent reactive oxygen species (ROS) production by phagocytes in response to Gram- bacteria. By contrast, Slamf8 (CD353) is a negative regulator of ROS in response to Gram+ and Gram- bacteria. Employing in vivo migration after skin sensitization, induction of peritonitis, and repopulation of the small intestine demonstrates that in vivo migration of Slamf1-/- dendritic cells and macrophages is reduced, as compared to wt mice.

SLAMF4 Is a Negative Regulator of Expansion of Cytotoxic Intraepithelial CD8+ T Cells That Maintains Homeostasis in the Small Intestine.

Background & Aims: Intraepithelial T lymphocyte cells (IEL) are the first immune cells to respond to pathogens; they help maintain the integrity of the epithelial barrier. We studied the function of the mouse glycoprotein Signaling Lymphocyte Activation Molecule Family receptor (SLAMF) 4 (encoded by Slamf4) on the surface of CD8αβ αβ T-cell receptor (TCR)(+) IELs, and the roles of these cells in homeostasis of the small intestine in mice.

Methods: SLAMF4(-) CD8(+) αβTCR(+) cells isolated from spleens of OT-I Rag1(-/-) mice were induced to express gut-homing receptors and transferred to C57BL/6J mice; levels of SLAMF4(+) cells were measured in small intestine tissues.

Extraction of antioxidant and ACE inhibitory peptides from Thai traditional fermented shrimp pastes.

Antioxidant and angiotensin converting enzyme (ACE) inhibitory peptides were extracted and isolated from two different types of Thai traditional fermented shrimp pastes, Kapi Ta Dam (Kp-B6) and Kapi Ta Deang (Kp-R6). Compounds with masses less than 500Da were found to be predominantly presented in both extracts. Following fractionation with sequential anion exchange chromatography and solid phase extraction (C18 matrix), three dipeptides were identified.

Generation and identification of angiotensin converting enzyme (ACE) inhibitory peptides from a brewers' spent grain protein isolate.

An alkaline extracted brewers' spent grain protein-enriched isolate (BSG-PI) was hydrolysed using Alcalase, Corolase PP, Flavourzyme and Promod 144MG, yielding Alc hydrolysate (H), CorH, FlavH and ProH, respectively. The degree of hydrolysis (DH) of the protein hydrolysates varied from 4.45% for ProH to 16.

High-symmetry embeddings of interpenetrating periodic nets. Essential rings and patterns of catenation.

Symmetrical embeddings are given for multiply intergrown sets of some commonly occurring nets such as dia (diamond), qtz (quartz), pcu (net of primitive cubic lattice) and srs (labyrinth net of the G minimal surface). Data are also given for all known pairs of nets which have edge-transitive self-dual tilings. Examples are given for symmetrical polycatenation of the 2-periodic nets sql (square lattice) and hcb (honeycomb).

Formation of a new archetypal Metal-Organic Framework from a simple monatomic liquid.

We report a molecular-dynamics simulation of a single-component system of particles interacting via a spherically symmetric potential that is found to form, upon cooling from a liquid state, a low-density porous crystalline phase. Its structure analysis demonstrates that the crystal can be described by a net with a topology that belongs to the class of topologies characteristic of the Metal-Organic Frameworks (MOFs). The observed net is new, and it is now included in the Reticular Chemistry Structure Resource database.