An model to study immune activation, epithelial disruption and stromal remodelling in inflammatory bowel disease and fistulising Crohn's disease.

At present, preclinical models of inflammatory bowel disease (IBD) are insufficient, limiting translation between research and new therapeutics. This is especially true for fistulising Crohn's disease (CD), as the severe lack of relevant models hinders research progression. To address this, we present human IBD mucosal models that recapitulate multiple pathological hallmarks of IBD simultaneously in one model system - immune cell infiltration, stromal remodelling and epithelial disruption.

SDF-1 Bound Heparin Nanoparticles Recruit Progenitor Cells for Their Differentiation and Promotion of Angiogenesis after Stroke.

Angiogenesis after stroke is correlated with enhanced tissue repair and functional outcomes. The existing body of research in biomaterials for stroke focuses on hydrogels for the delivery of stem cells, growth factors, or small molecules or drugs. Despite the ability of hydrogels to enhance all these delivery methods, no material has significantly regrown vasculature within the translatable timeline of days to weeks after stroke.

SDF-1 Bound Heparin Nanoparticles Recruit Progenitor Cells for Their Differentiation and Promotion of Angiogenesis After Stroke.

Angiogenesis after stroke is correlated with enhanced tissue repair and functional outcomes. The existing body of research in biomaterials for stroke focuses on hydrogels for the delivery of stem cells, growth factors, or small molecules or drugs. Despite the ability of hydrogels to enhance all these delivery methods, no material has significantly regrown vasculature within the translatable timeline of days to weeks after stroke.

Development of a mammalian neurosensory full-thickness skin equivalent and its application to screen sensitizing stimuli.

Human skin equivalents (HSEs) are an increasingly popular research tool due to limitations associated with animal testing for dermatological research. They recapitulate many aspects of skin structure and function, however, many only contain two basic cell types to model dermal and epidermal compartments, which limits their application. We describe advances in the field skin tissue modeling to produce a construct containing sensory-like neurons that is responsive to known noxious stimuli.

Salt-inducible kinase 2 regulates fibrosis during bleomycin-induced lung injury.

Idiopathic pulmonary fibrosis is a progressive and normally fatal disease with limited treatment options. The tyrosine kinase inhibitor nintedanib has recently been approved for the treatment of idiopathic pulmonary fibrosis, and its effectiveness has been linked to its ability to inhibit a number of receptor tyrosine kinases including the platelet-derived growth factor, vascular endothelial growth factor, and fibroblast growth factor receptors. We show here that nintedanib also inhibits salt-inducible kinase 2 (SIK2), with a similar IC to its reported tyrosine kinase targets.

Salt inducible kinases 2 and 3 are required for thymic T cell development.

Salt Inducible Kinases (SIKs), of which there are 3 isoforms, are established to play roles in innate immunity, metabolic control and neuronal function, but their role in adaptive immunity is unknown. To address this gap, we used a combination of SIK knockout and kinase-inactive knock-in mice. The combined loss of SIK1 and SIK2 activity did not block T cell development.

Monitoring, Scaffolding, Intervening, and Overriding: Adult Children's Perspectives on Supporting Older Parents.

When older parents experience age-related functional limitations, adult children may begin to monitor and try to control their parents' behavior. This shift can lead to tension due to differences in values both generations share, with parents prioritizing autonomy and self-sufficiency and adult children prioritizing safety and convention. Although a great deal of research on the transition from adolescence to adulthood focuses on governance transfer and changing boundaries of autonomy, monitoring, and control, less is known about how this happens in later life.

A Complete Survey of RhoGDI Targets Reveals Novel Interactions with Atypical Small GTPases.

There are three RhoGDIs in mammalian cells, which were initially defined as negative regulators of Rho family small GTPases. However, it is now accepted that RhoGDIs not only maintain small GTPases in their inactive GDP-bound form but also act as chaperones for small GTPases, targeting them to specific intracellular membranes and protecting them from degradation. Studies to date with RhoGDIs have usually focused on the interactions between the "typical" or "classical" small GTPases, such as the Rho, Rac, and Cdc42 subfamily members, and either the widely expressed RhoGDI-1 or the hematopoietic-specific RhoGDI-2.

Nuts and bolts of the salt-inducible kinases (SIKs).

The salt-inducible kinases, SIK1, SIK2 and SIK3, most closely resemble the AMP-activated protein kinase (AMPK) and other AMPK-related kinases, and like these family members they require phosphorylation by LKB1 to be catalytically active. However, unlike other AMPK-related kinases they are phosphorylated by cyclic AMP-dependent protein kinase (PKA), which promotes their binding to 14-3-3 proteins and inactivation. The most well-established substrates of the SIKs are the CREB-regulated transcriptional co-activators (CRTCs), and the Class 2a histone deacetylases (HDAC4/5/7/9).

Use of Porous Polystyrene Scaffolds to Bioengineer Human Epithelial Tissues In Vitro.

In vitro epithelial models are valuable tools for both academic and industrial laboratories to investigate tissue physiology and disease. Epithelial tissues comprise the surface epithelium, basement membrane, and underlying supporting stromal cells. There are various types of epithelial tissue and they have a diverse and intricate architecture in vivo, which cannot be successfully recapitulated using two-dimensional (2D) cell culture.

Salt-inducible kinases are required for the IL-33-dependent secretion of cytokines and chemokines in mast cells.

Cytokines and chemokines are important regulators of airway hyper-responsiveness, immune cell infiltration, and inflammation and are produced when mast cells are stimulated with interleukin-33 (IL-33). Here, we establish that the salt-inducible kinases (SIKs) are required for the IL-33-stimulated transcription of il13, gm-csf and tnf and hence the production of these cytokines. The IL-33-stimulated secretion of IL-13, granulocyte-macrophage colony stimulating factor, and tumor necrosis factor was strongly reduced in fetal liver-derived mast cells from mice expressing a kinase-inactive mutant of SIK3 and abolished in cells expressing kinase-inactive mutants of SIK2 and SIK3.

Bioengineering Novel Co-culture Models That Represent the Human Intestinal Mucosa With Improved Caco-2 Structure and Barrier Function.

The Caco-2 monolayer is the most widely used model of the human intestinal mucosa to study absorption. However, models lack communication from other cells present in the native intestine, such as signals from fibroblasts in the lamina propria. In this study, we have investigated the effects of fibroblasts upon the Caco-2 epithelium through two mechanisms: indirect signaling from fibroblasts and direct contact with fibroblasts.

Conditional and biased regeneration of cone photoreceptor types in the zebrafish retina.

A major challenge in regenerative medicine is replacing cells lost through injury or disease. While significant progress has been made, much remains unknown about the accuracy of native regenerative programs in cell replacement. Here, we capitalized on the regenerative capacity and stereotypic retinal organization of zebrafish to determine the specificity with which retinal Müller glial cells replace lost neuronal cell types.

Click by Click Microporous Annealed Particle (MAP) Scaffolds.

Macroporous scaffolds are being increasingly used in regenerative medicine and tissue repair. While the recently developed microporous annealed particle (MAP) scaffolds have overcome issues with injectability and in situ hydrogel formation, limitations with respect to tunability to be able to manipulate hydrogel strength and rigidity for broad applications still exist. To address these key issues, here hydrogel microparticles (HMPs) of hyaluronic acid (HA) are synthesized using the thiol-norbornene click reaction and then HMPs are subsequently annealed into a porous scaffold using the tetrazine-norbornene click reaction.

Salt-inducible kinases (SIKs) regulate TGFβ-mediated transcriptional and apoptotic responses.

The signalling pathways initiated by members of the transforming growth factor-β (TGFβ) family of cytokines control many metazoan cellular processes, including proliferation and differentiation, epithelial-mesenchymal transition (EMT) and apoptosis. TGFβ signalling is therefore strictly regulated to ensure appropriate context-dependent physiological responses. In an attempt to identify novel regulatory components of the TGFβ signalling pathway, we performed a pharmacological screen by using a cell line engineered to report the endogenous transcription of the TGFβ-responsive target gene PAI-1.

The family context as a foundation for romantic relationships: A person-centered multi-informant longitudinal study.

This 8-wave person-centered multi-informant study tested whether the quality of parent-adolescent relationships predicted the romantic experiences of young adults and their partners ( = 374; 54.8% girls; = 13.08 years, = 0.

Bioengineering the microanatomy of human skin.

Recreating the structure of human tissues in the laboratory is valuable for fundamental research, testing interventions, and reducing the use of animals. Critical to the use of such technology is the ability to produce tissue models that accurately reproduce the microanatomy of the native tissue. Current artificial cell-based skin systems lack thorough characterisation, are not representative of human skin, and can show variation.

Injectable and Spatially Patterned Microporous Annealed Particle (MAP) Hydrogels for Tissue Repair Applications.

Spatially patterned hydrogels are becoming increasingly popular in the field of regenerative medicine and tissue repair because of their ability to guide cell infiltration and migration. However, postfabrication technologies are usually required to spatially pattern a hydrogel, making these hydrogels difficult to translate into the clinic. Here, an injectable spatially patterned hydrogel is reported using hyaluronic acid (HA)-based particle hydrogels.

All in the family: Within-family differences in parental monitoring and adolescent information management.

This article used a sample of 2 adolescents per family to (a) examine the extent to which parental monitoring and adolescent information management are characteristics of families or of dyads and (b) replicate past research on parental monitoring and adolescent information management using models that distinguish differences between families from differences within them. Within- and between-family differences were examined as a function of parents (positive and negative parenting, immigration status), individual and peer-reported problem behavior, and adolescent characteristics (age, gender) in a sample of 300 Swedish families with 2 siblings each (aged 10 to 19). Parents' self-reports of their monitoring of siblings and of their adolescents' information management were consistently more similar than adolescents' self-reports or reports on parents.

Preventing and Responding to Sexual Misconduct: Preliminary Efficacy of a Peer-Led Bystander Training Program for Preventing Sexual Misconduct and Reducing Heavy Drinking Among Collegiate Athletes.

Sexual misconduct occurs with disproportionate frequency on college campuses, and alcohol is involved in most sexual assaults. Importantly, collegiate athletes are at risk for both heavy drinking and sexual misconduct. Thus, the current study evaluated the efficacy of a novel, 2.

In situ forming injectable hydrogels for drug delivery and wound repair.

Hydrogels have been utilized in regenerative applications for many decades because of their biocompatibility and similarity in structure to the native extracellular matrix. Initially, these materials were formed outside of the patient and implanted using invasive surgical techniques. However, advances in synthetic chemistry and materials science have now provided researchers with a library of techniques whereby hydrogel formation can occur in situ upon delivery through standard needles.

Outbreak of influenza and rhinovirus co-circulation among unvaccinated recruits, U.S. Coast Guard Training Center Cape May, NJ, 24 July-21 August 2016.

Military and Coast Guard recruits are particularly susceptible to respiratory infections. Although seasonal influenza vaccinations are mandatory for recruits, the vaccine expires annually in June. On 29 July 2016, the U.