Significance of IL-34 and SDC-1 in the pathogenesis of RA cells and preclinical models.

IL-34 shares a common receptor with M-CSF, while it can bind to other distinct receptors including protein-tyrosine phosphatase zeta (PTPζ), and syndecan1 (SDC-1). In physiological conditions, IL-34 has a critical role in the maintenance and development of Langerhans and microglial cells in part through PTPζ ligation. Conversely, in autoimmune diseases such as rheumatoid arthritis (RA), SDC-1-induced phosphorylation of M-CSFR was responsible for the pathological effect of IL-34 in patient cells and/or preclinical models. Intriguingly, enrichment of IL-34 is strongly linked to rheumatoid factor (RF), disease activity score (DAS)28, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and radiographic progression. In parallel, IL-34-induced naïve cell reprogramming into glycolytic RA CD14+CD86+GLUT1+ macrophage was dysregulated via M-CSFR or SDC-1 antibody therapy. Moreover, the inflammatory and erosive imprints of IL-34 arthritic mice were mitigated by glucose uptake inhibition and SDC-1, or RAG deficiency through nullifying macrophage metabolic rewiring and their ability to advance Th1/Th17 cell polarization. Consistently, IL-34-/- and SDC-1-/- mice could effectively impair CIA joint inflammation, osteoclast formation, and neovascularization by restraining monocyte infiltration as well as suppressing the inflammatory macrophage and T effector cell reconfiguration via metabolic deactivation. In conclusion, targeting IL-34/SDC-1 signaling, or its interconnected metabolites can uniquely intercept the crosstalk between glycolytic RA myeloid and lymphoid cells and their ability to trigger arthritis.

In vivo alterations in calcium buffering capacity in transgenic mouse model of synucleinopathy.

Abnormal accumulation of α-synuclein is centrally involved in the pathogenesis of many disorders with Parkinsonism and dementia. Previous in vitro studies suggest that α-synuclein dysregulates intracellular calcium. However, it is unclear whether these alterations occur in vivo. For this reason, we investigated calcium dynamics in transgenic mice expressing human WT α-synuclein using two-photon microscopy. We imaged spontaneous and stimulus-induced neuronal activity in the barrel cortex. Transgenic mice exhibited augmented, long-lasting calcium transients characterized by considerable deviation from the exponential decay. The most evident pathology was observed in response to a repetitive stimulation in which subsequent stimuli were presented before relaxation of calcium signal to the baseline. These alterations were detected in the absence of significant increase in neuronal spiking response compared with age-matched controls, supporting the possibility that α-synuclein promoted alterations in calcium dynamics via interference with intracellular buffering mechanisms. The characteristic shape of calcium decay and augmented response during repetitive stimulation can serve as in vivo imaging biomarkers in this model of neurodegeneration, to monitor progression of the disease and screen candidate treatment strategies.

Richmond Latino needs assessment: a community-university partnership to identify health concerns and service needs for Latino youth.

The presence of Latinos in Virginia is a new phenomenon and as a result, less is known about the health needs of these newest community members. We formed a community-university partnership to identify health concerns and service needs as they relate to Latino youth living in Richmond, Virginia and the surrounding area. Using a mixed-method approach, survey data was obtained from 212 Latino adults, qualitative interviews were conducted with 15 community leaders and focus groups with 23 Latino parents (16 mothers, 7 fathers) and 6 Latino boys. Participants expressed concern about sexually transmitted infections/pregnancy among youth (76%), youth behavior problems at home/school (75%), and mental health problems (75%). Participants also expressed worry that youth would lose their connection to their Latin culture (83%). Qualitative data provided more information regarding these concerns by linking them with inter-ethnic tensions, and immigration and acculturation-related stressors. Survey participants also indicated a need for bilingual mental health services (88%) and after-school programs for youth (94%). This study provided the local community with information on the health concerns and service needs of a new group of community youth-Latino youth. Findings were presented to local community and City organizations that used the information to respond to the identified needs and/or concerns. The process in which the data was obtained may prove useful to other individuals interested in obtaining local level health information in emerging communities.