Suppression of the JAK/STAT pathway inhibits neuroinflammation in the line 61-PFF mouse model of Parkinson's disease.

Parkinson's disease (PD) is characterized by neuroinflammation, progressive loss of dopaminergic neurons, and accumulation of α-synuclein (α-Syn) into insoluble aggregates called Lewy pathology. The Line 61 α-Syn mouse is an established preclinical model of PD; Thy-1 is used to promote human α-Syn expression, and features of sporadic PD develop at 9-18 months of age. To accelerate the PD phenotypes, we injected sonicated human α-Syn preformed fibrils (PFFs) into the striatum, which produced phospho-Syn (p-α-Syn) inclusions in the substantia nigra pars compacta and significantly increased MHC Class II-positive immune cells.

Concomitant septic and crystal arthropathy: a single-centre 10-year retrospective observational study in New Zealand.

Aim: To quantify and characterise patients with coexistent septic arthritis (SA) and crystal arthritis (CA) (SACA) in an emergency department (ED) setting.

Methods: A single-centre, retrospective, 10-year observational study was conducted at a major referral centre. Patients with a positive joint aspirate for CA or SA carried out in ED, were included.

Suppression of the JAK/STAT Pathway Inhibits Neuroinflammation in the Line 61-PFF Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is characterized by neuroinflammation, progressive loss of dopaminergic neurons, and accumulation of a-synuclein (a-Syn) into insoluble aggregates called Lewy pathology. The Line 61 a-Syn mouse is an established preclinical model of PD; Thy-1 is used to promote human a-Syn expression, and features of sporadic PD develop at 9-18 months of age. To accelerate the PD phenotypes, we injected sonicated human a-Syn preformed fibrils (PFFs) into the striatum, which produced phospho-Syn (p-a-Syn) inclusions in the substantia nigra pars compacta and significantly increased MHC Class II-positive immune cells.

A framework for graduate leadership education for sustainability guided by the SDGs.

In this article, we outline the work of using the Sustainable Development Goals (SDGs) in graduate leadership education for sustainability (GLES). We identify how the SDGs can serve as an effective operationalization of the concept of sustainability, propose a framework of GLES, provide specific examples of the use of the SDGs in graduate education, and share recommendations for fostering GLES.

expression in myeloid cells modulates the pathogenesis of dextran sulfate sodium (DSS)-induced colitis.

Introduction: Myeloid cells play a critical role in the pathogenesis of Inflammatory Bowel Diseases (IBDs), including Ulcerative Colitis (UC) and Crohn's Disease (CD). Dysregulation of the JAK/STAT pathway is associated with many pathological conditions, including IBD. Suppressors Of Cytokine Signaling (SOCS) are a family of proteins that negatively regulate the JAK/STAT pathway.

Protein Kinase CK2 Controls CD8 T Cell Effector and Memory Function during Infection.

Protein kinase CK2 is a serine/threonine kinase composed of two catalytic subunits (CK2α and/or CK2α') and two regulatory subunits (CK2β). CK2 promotes cancer progression by activating the NF-κB, PI3K/AKT/mTOR, and JAK/STAT pathways, and also is critical for immune cell development and function. The potential involvement of CK2 in CD8 T cell function has not been explored.

Sociocultural Conversations: Examining the Influence of Difficult Dialogues on Leadership Development.

In this chapter, the authors review the factors that contribute to sociocultural conversations, their outcomes, and potential new directions for research and practice. They also provide ways to incorporate sociocultural conversations in practice.

Teaching students with autism spectrum disorder to tolerate haircutting.

We describe intervention with 2 adolescent male students who had autism spectrum disorder (ASD) and resisted haircutting performed by care providers at a residential school. The students were exposed to a graduated hierarchy of steps including the presence of hair clippers, and increased duration of hair clippers against their scalp and hair. Edible reinforcement was presented contingent on completion of a step without interfering behavior.

Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases.

The Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway is utilized by numerous cytokines and interferons, and is essential for the development and function of both innate and adaptive immunity. Aberrant activation of the JAK/STAT pathway is evident in neuroinflammatory diseases such as Multiple Sclerosis and Parkinson's Disease. Innate immunity is the front line defender of the immune system and is composed of various cell types, including microglia, macrophages and neutrophils.

Inhibition of the JAK/STAT Pathway Protects Against α-Synuclein-Induced Neuroinflammation and Dopaminergic Neurodegeneration.

Unlabelled: Parkinson's Disease (PD) is an age-related, chronic neurodegenerative disorder. At present, there are no disease-modifying therapies to prevent PD progression. Activated microglia and neuroinflammation are associated with the pathogenesis and progression of PD.

Preferential Recruitment of Neutrophils into the Cerebellum and Brainstem Contributes to the Atypical Experimental Autoimmune Encephalomyelitis Phenotype.

The JAK/STAT pathway is critical for development, regulation, and termination of immune responses, and dysregulation of the JAK/STAT pathway, that is, hyperactivation, has pathological implications in autoimmune and neuroinflammatory diseases. Suppressor of cytokine signaling 3 (SOCS3) regulates STAT3 activation in response to cytokines that play important roles in the pathogenesis of neuroinflammatory diseases, including IL-6 and IL-23. We previously demonstrated that myeloid lineage-specific deletion of SOCS3 resulted in a severe, nonresolving atypical form of experimental autoimmune encephalomyelitis (EAE), characterized by lesions, inflammatory infiltrates, elevated STAT activation, and elevated cytokine and chemokine expression in the cerebellum.

Early CNS neurodegeneration in radiologically isolated syndrome.

Objective: Increasing evidence indicates that the thalamus may be a location of early neurodegeneration in multiple sclerosis (MS). Our objective was to identify the presence of gray matter volume loss and thinning in patients with radiologically isolated syndrome (RIS).

Methods: Sixty-three participants were included in this case-control study.

Rimonabant's reductive effects on high densities of food reinforcement, but not palatability, in lean and obese Zucker rats.

Rationale: Cannabinoid antagonists purportedly have greater effects in reducing the intake of highly palatable food compared to less palatable food. However, this assertion is based on free-feeding studies in which the amount of palatable food eaten under baseline conditions is often confounded with other variables, such as unequal access to both food options and differences in qualitative features of the foods.

Objective: We attempted to reduce these confounds by using a model of choice that programmed the delivery rates of sucrose and carrot-flavored pellets.

Obese and lean Zucker rats demonstrate differential sensitivity to rates of food reinforcement in a choice procedure.

The obese Zucker rat carries two recessive fa alleles that result in the expression of an obese phenotype. Obese Zuckers have higher food intake than lean controls in free-feed studies in which rats have ready access to a large amount of one type of food. The present study examined differences in obese and lean Zucker rats using concurrent schedules of reinforcement, which more ecologically models food selection using two food choices that have limited, but generally predictable availability.

Identification of eRF1 residues that play critical and complementary roles in stop codon recognition.

The initiation and elongation stages of translation are directed by codon-anticodon interactions. In contrast, a release factor protein mediates stop codon recognition prior to polypeptide chain release. Previous studies have identified specific regions of eukaryotic release factor one (eRF1) that are important for decoding each stop codon.

Rimonabant reduces the essential value of food in the genetically obese Zucker rat: an exponential demand analysis.

Research on free-food intake suggests that cannabinoids are implicated in the regulation of feeding. Few studies, however, have characterized how environmental factors that affect food procurement interact with cannabinoid drugs that reduce food intake. Demand analysis provides a framework to understand how cannabinoid blockers, such as rimonabant, interact with effort in reducing demand for food.

Outcome of Escherichia coli and/or Klebsiella bloodstream infection in children with central venous catheters.

We conducted a retrospective cohort study of children with catheter-associated bloodstream infections (BSIs) due to Escherichia coli and/or Klebsiella. Risk factors for poor outcome (ie, death or recurrence of infection) were receipt of mechanical ventilation (adjusted odds ratio [aOR], 4.6 [95% confidence interval {CI}, 1.

A naturalistic comparison of the effectiveness of trainee and qualified clinical psychologists.

Objective: To compare the effect of clinician type on the outcome for adult mental health clients treated by trainee and qualified clinical psychologists.

Design: Naturalistic, non-random between-participants group design: a group of 60 adult mental health out-patients treated by trainees and a matched group of 60 patients treated by qualified clinical psychologists.

Method: Participants completed a range of established measures at assessment and outcome of their treatment during routine clinical practice.

SB 242784, a selective inhibitor of the osteoclastic V-H+ATPase, inhibits arterial calcification in the rat.

The present experiments were carried out to further test the hypothesis that arterial calcification is linked to bone resorption by determining whether the selective inhibition of bone resorption with SB 242784, a specific inhibitor of the osteoclastic V-H+-ATPase, will inhibit arterial calcification. Treatment for 96 hours with toxic doses of vitamin D caused widespread calcification in the aorta and in the femoral, mesenteric, hepatic, renal, and carotid arteries, and treatment with SB 242784 completely prevented the vitamin D-induced calcification of each of these arteries at a dose of 40 mg/kg per day and significantly reduced calcification at a dose of 10 mg/kg per day. Treatment with vitamin D also caused extensive calcification in the lungs, tracheal cartilage, and kidneys, and treatment with SB 242784 prevented or reduced calcification at each of these sites.