Interferon-γ Inducible Protein (IP-10) Expression Is Mediated by CD8+ T Cells and Is Regulated by CD4+ T Cells During the Elicitation of Contact Hypersensitivity

To investigate the potential roles of CD4+ and CD8+ T cells during contact hypersensitivity, we examined the T-cell-dependent expression of proinflammatory cytokine genes in the responses to dinitrofluorobenzene and oxazolone. Whole cell RNA was isolated from challenged ear tissue and analyzed for level of cytokine gene expression by Northern blot and densitometry analysis. Expression of interleukin 1β and the three chemokine genes (IP-10, JE, and KC) examined was dependent on the hapten dose used for sensitization and correlated with the immune response, i.e., ear swelling, elicited. Antibody-mediated depletion of CD8+ T cells before sensitization resulted in the absence of IP-10 expression following hapten challenge, indicating the ability of immune CD8+ T cells to mediate IP-10 expression. Depletion of CD4+ T cells resulted in higher levels of IP-10 and KC expression during elicitation of contact sensitivity, suggesting CD4+ T cells inhibit the expression of these proinflammatory genes. Depletion of CD4+ T cells resulted in contact hypersensitivity responses of higher magnitude and depletion of CD8+ T cells resulted in responses of lower magnitude. Transfer of CD8+ T-cell-depleted immune cells resulted in low, but detectable levels of IP-10 expression, indicating the ability of some oxazolone-immune CD4+ T cells to mediate IP-10 expression. These results indicate the differential induction of proinflammatory cytokine gene expression during elicitation of contact hypersensitivity in which expression of IP-10 is primarily mediated by immune CD8+ T cells and inhibited by immune CD4+ T cells

Act1, a Negative Regulator in CD40- and BAFF-Mediated B Cell Survival

AbstractTNF receptor (TNFR) superfamily members, CD40, and BAFFR play critical roles in B cell survival and differentiation. Genetic deficiency in a novel adaptor molecule, Act1, for CD40 and BAFF results in a dramatic increase in peripheral B cells, which culminates in lymphadenopathy and splenomegaly, hypergammaglobulinemia, and autoantibodies. While the B cell-specific Act1 knockout mice displayed a similar phenotype with less severity, the pathology of the Act1-deficient mice was mostly blocked in CD40-Act1 and BAFF-Act1 double knockout mice. CD40- and BAFF-mediated survival is significantly increased in Act1-deficent B cells, with stronger IκB phosphorylation, processing of NF-κB2 (p100/p52), and activation of JNK, ERK, and p38 pathways, indicating that Act1 negatively regulates CD40- and BAFF-mediated signaling events. These findings demonstrate that Act1 plays an important role in the homeostasis of B cells by attenuating CD40 and BAFFR signaling

Acute Ozone-Induced Differential Gene Expression Profiles in Rat Lung

Ozone (O(3)) is an oxidant gas that can directly induce lung injury. Knowledge of the initial molecular events of the acute O(3) response would be useful in developing biomarkers of exposure or response. Toward this goal, we exposed rats to toxic concentrations of O(3) (2 and 5 ppm) for 2 hr and the molecular changes were assessed in lung tissue 2 hr postexposure using a rat cDNA expression array containing 588 characterized genes. Gene array analysis indicated differential expression in almost equal numbers of genes for the two exposure groups: 62 at 2 ppm and 57 at 5 ppm. Most of these genes were common to both exposure groups, suggesting common roles in the initial toxicity response. However, we also identified the induction of nine genes specific to 2-ppm (thyroid hormone-β receptor c-erb-A-β and glutathione reductase) or 5-ppm exposure groups (c-jun, induced nitric oxide synthase, macrophage inflammatory protein-2, and heat shock protein 27). Injury markers in bronchoalveolar lavage fluid (BALF) were used to assess immediate toxicity and inflammation in rats similarly exposed. At 2 ppm, injury was marked by significant increases in BALF total protein, N-acetylglucosaminidase, and lavageable ciliated cells. Because infiltration of neutrophils was observed only at the higher 5 ppm concentration, the distinctive genes suggested a potential amplification role for inflammation in the gene profile. Although the specific gene interactions remain unclear, this is the first report indicating a dose-dependent direct and immediate induction of gene expression that may be separate from those genes involved in inflammation after acute O(3) exposure

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Urinary-Cell mRNA Profile and Acute Cellular Rejection in Kidney Allografts

Background—The standard test for the diagnosis of acute rejection in kidney transplants is the renal biopsy. Noninvasive tests would be preferable. Methods—We prospectively collected 4300 urine specimens from 485 kidney-graft recipients from day 3 through month 12 after transplantation. Messenger RNA (mRNA) levels were measured in urinary cells and correlated with allograft-rejection status with the use of logistic regression. Results—A three-gene signature of 18S ribosomal (rRNA)–normalized measures of CD3ε mRNA and interferon-inducible protein 10 (IP-10) mRNA, and 18S rRNA discriminated between biopsy specimens showing acute cellular rejection and those not showing rejection (area under the curve [AUC], 0.85; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 by receiver-operatingcharacteristic curve analysis). The cross-validation estimate of the AUC was 0.83 by bootstrap resampling, and the Hosmer–Lemeshow test indicated good fit (P = 0.77). In an externalvalidation data set, the AUC was 0.74 (95% CI, 0.61 to 0.86; P<0.001) and did not differ significantly from the AUC in our primary data set (P = 0.13). The signature distinguished acute cellular rejection from acute antibody-mediated rejection and borderline rejection (AUC, 0.78; 95% CI, 0.68 to 0.89; P<0.001). It also distinguished patients who received anti–interleukin-2 receptor antibodies from those who received T-cell–depleting antibodies (P<0.001) and was diagnostic of acute cellular rejection in both groups. Urinary tract infection did not affect the signature (P = 0.69). The average trajectory of the signature in repeated urine samples remained below the diagnostic threshold for acute cellular rejection in the group of patients with no rejection, but in the group with rejection, there was a sharp rise during the weeks before the biopsy showing rejection (P<0.001). Conclusions—A molecular signature of CD3ε mRNA, IP-10 mRNA, and 18S rRNA levels in urinary cells appears to be diagnostic and prognostic of acute cellular rejection in kidney allografts

Sensitization in Transplantation: Assessment of Risk (STAR) 2017 Working Group Meeting Report

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144684/1/ajt14752_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144684/2/ajt14752.pd

Recommendations for the Use of Serious Games in Neurodegenerative Disorders: 2016 Delphi Panel

The use of Serious Games (SG) in the health domain is expanding. In the field of neurodegenerative disorders (ND) such as Alzheimer’s disease, SG are currently employed both to support and improve the assessment of different functional and cognitive abilities, and to provide alternative solutions for patients’ treatment, stimulation, and rehabilitation. As the field is quite young, recommendations on the use of SG in people with ND are still rare. In 2014 we proposed some initial recommendations (Robert et al., 2014). The aim of the present work was to update them, thanks to opinions gathered by experts in the field during an expert Delphi panel. Results confirmed that SG are adapted to elderly people with mild cognitive impairment (MCI) and dementia, and can be employed for several purposes, including assessment, stimulation, and improving wellbeing, with some differences depending on the population (e.g., physical stimulation may be better suited for people with MCI). SG are more adapted for use with trained caregivers (both at home and in clinical settings), with a frequency ranging from 2 to 4 times a week. Importantly, the target of SG, their frequency of use and the context in which they are played depend on the SG typology (e.g., Exergame, cognitive game), and should be personalized with the help of a clinician

Fish assemblage stability over fifty years in the Lake Pontchartrain Estuary; comparisons among habitats using Canonical Correspondence Analysis

We assessed fish assemblage stability over the last half century in Lake Pontchartrain, an environmentally degraded oligohaline estuary in southeastern Louisiana. Because assemblage instability over time has been consistently associated with severe habitat degradation, we attempted to determine whether fish assemblages in demersal, nearshore, and pelagic habitats exhibited change that was unrelated to natural fluctuations in environmental variables (e.g., assemblage changes between wet and dry periods). Collection data from three gear types (trawl, beach seine, and gill nets) and monthly environmental data (salinity, temperature, and Secchi depth) were compared for four collecting periods: 1954 (dry period), 1978 (wet period), 1996–1998 (wet period), and 1998–2000 (dry period). Canonical correspondence analysis (CCA) revealed that although the three environmental variables were significantly associated with the distribution and abundance patterns of fish assemblages in all habitats (with the exception of Secchi depth for pelagic samples), most fish assemblage change occurred among sampling periods (i.e., along a temporal gradient unrelated to changing environmental variables). Assemblage instability was the most pronounced for fishes collected by trawls from demersal habitats. A marked lack of cyclicity in the trawl data CCA diagram indicated a shift away from a baseline demersal assemblage of 50 yr ago. Centroid positions for the five most collected species indicated that three benthic fishes, Atlantic croaker (Micropogonias undulatus), spot (Leiostomus xanthurus), and hardhead catfish (Arius felis), were more dominant inWe assessed fish assemblage stability over the last half century in Lake Pontchartrain, an environmentally degraded oligohaline estuary in southeastern Louisiana. Because assemblage instability over time has been consistently associated with severe habitat degradation, we attempted to determine whether fish assemblages in demersal, nearshore, and pelagic habitats exhibited change that was unrelated to natural fluctuations in environmental variables (e.g., assemblage changes between wet and dry periods). Collection data from three gear types (trawl, beach seine, and gill nets) and monthly environmental data (salinity, temperature, and Secchi depth) were compared for four collecting periods: 1954 (dry period), 1978 (wet period), 1996–1998 (wet period), and 1998–2000 (dry period). Canonical correspondence analysis (CCA) revealed that although the three environmental variables were significantly associated with the distribution and abundance patterns of fish assemblages in all habitats (with the exception of Secchi depth for pelagic samples), most fish assemblage change occurred among sampling periods (i.e., along a temporal gradient unrelated to changing environmental variables). Assemblage instability was the most pronounced for fishes collected by trawls from demersal habitats. A marked lack of cyclicity in the trawl data CCA diagram indicated a shift away from a baseline demersal assemblage of 50 yr ago. Centroid positions for the five most collected species indicated that three benthic fishes, Atlantic croaker (Micropogonias undulatus), spot (Leiostomus xanthurus), and hardhead catfish (Arius felis), were more dominant in past demersal assemblages (1954 and 1978). A different situation was shown for planktivorous species collected by trawls with bay anchovy (Anchoa mitchilli) becoming more dominant in recent assemblages and Gulf enhaden (Brevoortia patronus) remaining equally represented in assemblages over time. Changes in fish assemblages from nearshore (beach seine) and pelagic (gill net) habitats were more closely related to environmental fluctuations, though the CCA for beach seine data also indicated a decrease in the dominance of M. undulatus and an increase in the proportion of A. mitchilli over time. The reduced assemblage role of benthic fishes and the marked assemblage change indicated by trawl data suggest that over the last half century demersal habitats in Lake Pontchartrain have been impacted more by multiple anthropogenic stressors than nearshore or pelagic habitats. past demersal assemblages (1954 and 1978). A different situation was shown for planktivorous species collected by trawls with bay anchovy (Anchoa mitchilli) becoming more dominant in recent assemblages and Gulf menhaden (Brevoortia patronus) remaining equally represented in assemblages over time. Changes in fish assemblages from nearshore (beach seine) and pelagic (gill net) habitats were more closely related to environmental fluctuations, though the CCA for beach seine data also indicated a decrease in the dominance of M. undulatus and an increase in the proportion of A. mitchilli over time. The reduced assemblage role of benthic fishes and the marked assemblage change indicated by trawl data suggest that over the last half century demersal habitats in Lake Pontchartrain have been impacted more by multiple anthropogenic stressors than nearshore or pelagic habitats

What is the potential of oligodendrocyte progenitor cells to successfully treat human spinal cord injury?

<p>Abstract</p> <p>Background</p> <p>Spinal cord injury is a serious and debilitating condition, affecting millions of people worldwide. Long seen as a permanent injury, recent advances in stem cell research have brought closer the possibility of repairing the spinal cord. One such approach involves injecting oligodendrocyte progenitor cells, derived from human embryonic stem cells, into the injured spinal cord in the hope that they will initiate repair. A phase I clinical trial of this therapy was started in mid 2010 and is currently underway.</p> <p>Discussion</p> <p>The theory underlying this approach is that these myelinating progenitors will phenotypically replace myelin lost during injury whilst helping to promote a repair environment in the lesion. However, the importance of demyelination in the pathogenesis of human spinal cord injury is a contentious issue and a body of literature suggests that it is only a minor factor in the overall injury process.</p> <p>Summary</p> <p>This review examines the validity of the theory underpinning the on-going clinical trial as well as analysing published data from animal models and finally discussing issues surrounding safety and purity in order to assess the potential of this approach to successfully treat acute human spinal cord injury.</p

Bostonia: The Boston University Alumni Magazine. Volume 6

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs