Judges as Bullies

It can’t be easy being a judge. The responsibility is enormous: to protect and maintain the rule of law; determine facts and law; resolve disputes large and small; and, in criminal matters, decide whether a fellow citizen remains free or not. In essence, we look to judges to articulate the meaning of “justice”—no doubt knowing all the while, as Clarence Darrow famously noted, “There is no such thing as justice, in or out of court.” I like and respect some judges, but not as many as I should. While some judges have the requisite ability and temperament for the bench—knowledge of the law, independence, fairness, patience, courage, compassion, and humility—too many do not. Too many are mean-spirited and arrogant, going out of their way to insult, ridicule, and demean those who come before them. In short, they are bullies. Bullies on the bench may be an inevitable result of our politicized process of judicial selection, especially on the state level, where most judges are elected. Politics doesn’t usually bring out the best judges or the best in judges. Becoming a bully may also be an occupational hazard. When your daily life consists of sitting in an elevated position in judicial robes, with people bowing and scraping before you, it likely goes to your head. As Steven Lubet says, judges are the “maximum boss” and “[e]veryone else is a supplicant.” This Essay is not about the judges I like and respect, but the ones who have become (or perhaps always were) bullies. Because I am a criminal defense lawyer who has practiced almost entirely in state criminal courts, my stories tend to come from those courts. It might also be that judges are at their worst when they preside over criminal matters

Putting the House in Order: Women’s Cooperative Extension Work in the Early Twentieth Century

Maine’s Cooperative Extension Service, in addition to its work with farm men, sent female agents into the countryside to teach women the principles of thrift, modernity, and efficiency in the home. How successful agents were at instilling modem principles is difficult to determine, but their experiences, recorded in Extension annual reports, reveal the tensions between women aspiring to professional standards and those whose work revolved around the home. In this article, Abbe L. Karmen explores the biases of the agents themselves and the force of traditional domestic patterns in rural Maine

Effect of β-glucan and black tea in a functional bread on short chain fatty acid production by the gut microbiota in a gut digestion/fermentation model

β-Glucan and black tea are fermented by the colonic microbiota producing short chain fatty acids (SCFA) and phenolic acids (PA). We hypothesized that the addition of β-glucan, a dietary fiber, and tea polyphenols to a food matrix like bread will also affect starch digestion in the upper gut and thus further influence colonic fermentation and SCFA production. This study investigated SCFA and PA production from locally developed breads: white bread (WB), black tea bread (BT), β-glucan bread (βG), β-glucan plus black tea bread (βGBT). Each bread was incubated in an in vitro system mimicking human digestion and colonic fermentation. Digestion with α-amylase significantly (p = 0.0001) increased total polyphenol and polyphenolic metabolites from BT bread compared with WB, βG, and βGBT. Total polyphenols in βGBT remained higher (p = 0.016; 1.3-fold) after digestion with pepsin and pancreatin compared with WB. Fermentations containing βG and βGBT produced similar propionate concentrations ranging from 17.5 to 18.6 mmol/L and total SCFA from 46.0 to 48.9 mmol/L compared with control WB (14.0 and 37.4 mmol/L, respectively). This study suggests that combination of black tea with β-glucan in this functional bread did not impact on SCFA production. A higher dose of black tea and β-glucan or in combination with other fibers may be needed to increase SCFA production

NK-Like T Cells and Plasma Cytokines, but Not Anti-Viral Serology, Define Immune Fingerprints of Resilience and Mild Disability in Exceptional Aging

Exceptional aging has been defined as maintenance of physical and cognitive function beyond the median lifespan despite a history of diseases and/or concurrent subclinical conditions. Since immunity is vital to individual fitness, we examined immunologic fingerprint(s) of highly functional elders. Therefore, survivors of the Cardiovascular Health Study in Pittsburgh, Pennsylvania, USA were recruited (n = 140; mean age = 86 years) and underwent performance testing. Blood samples were collected and examined blindly for humoral factors and T cell phenotypes. Based on results of physical and cognitive performance testing, elders were classified as “impaired” or “unimpaired”, accuracy of group assignment was verified by discriminant function analysis. The two groups showed distinct immune profiles as determined by factor analysis. The dominant immune signature of impaired elders consisted of interferon (IFN)-γ, interleukin (IL)-6, tumor necrosis factor-α, and T cells expressing inhibitory natural killer-related receptors (NKR) CD158a, CD158e, and NKG2A. In contrast, the dominant signature of unimpaired elders consisted of IL-5, IL-12p70, and IL-13 with co-expression of IFN-γ, IL-4, and IL-17, and T cells expressing stimulatory NKRs CD56, CD16, and NKG2D. In logistic regression models, unimpaired phenotype was predicted independently by IL-5 and by CD4+CD28nullCD56+CD57+ T cells. All elders had high antibody titers to common viruses including cytomegalovirus. In cellular bioassays, T cell receptor (TCR)-independent ligation of either CD56 or NKG2D elicited activation of T cells. Collectively, these data demonstrate the importance of immunological parameters in distinguishing between health phenotypes of older adults. NKR+ T cells and cytokine upregulation indicate a unique physiologic environment in old age. Correlation of particular NKR+ T cell subsets and IL-5 with unimpaired performance, and NKR-driven TCR-independent activation of T cells suggest novel immunopathway(s) that could be exploited to improve immunity in old age

Serum protein profile in systemic-onset juvenile idiopathic arthritis differentiates response versus nonresponse to therapy

Systemic-onset juvenile idiopathic arthritis (SJIA) is a disease of unknown etiology with an unpredictable response to treatment. We examined two groups of patients to determine whether there are serum protein profiles reflective of active disease and predictive of response to therapy. The first group (n = 8) responded to conventional therapy. The second group (n = 15) responded to an experimental antibody to the IL-6 receptor (MRA). Paired sera from each patient were analyzed before and after treatment, using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Despite the small number of patients, highly significant and consistent differences were observed before and after response to therapy in all patients. Of 282 spectral peaks identified, 23 had mean signal intensities significantly different (P < 0.001) before treatment and after response to treatment. The majority of these differences were observed regardless of whether patients responded to conventional therapy or to MRA. These peaks represent potential biomarkers of active disease. One such peak was identified as serum amyloid A, a known acute-phase reactant in SJIA, validating the SELDI-TOF MS platform as a useful technology in this context. Finally, profiles from serum samples obtained at the time of active disease were compared between the two patient groups. Nine peaks had mean signal intensities significantly different (P < 0.001) between active disease in patients who responded to conventional therapy and in patients who failed to respond, suggesting a possible profile predictive of response. Collectively, these data demonstrate the presence of serum proteomic profiles in SJIA that are reflective of active disease and suggest the feasibility of using the SELDI-TOF MS platform used as a tool for proteomic profiling and discovery of novel biomarkers in autoimmune diseases

Identification of and Molecular Basis for SIRT6 Loss-of-Function Point Mutations in Cancer

SummaryChromatin factors have emerged as the most frequently dysregulated family of proteins in cancer. We have previously identified the histone deacetylase SIRT6 as a key tumor suppressor, yet whether point mutations are selected for in cancer remains unclear. In this manuscript, we characterized naturally occurring patient-derived SIRT6 mutations. Strikingly, all the mutations significantly affected either stability or catalytic activity of SIRT6, indicating that these mutations were selected for in these tumors. Further, the mutant proteins failed to rescue sirt6 knockout (SIRT6 KO) cells, as measured by the levels of histone acetylation at glycolytic genes and their inability to rescue the tumorigenic potential of these cells. Notably, the main activity affected in the mutants was histone deacetylation rather than demyristoylation, pointing to the former as the main tumor-suppressive function for SIRT6. Our results identified cancer-associated point mutations in SIRT6, cementing its function as a tumor suppressor in human cancer

T Cell Receptor-Independent, CD31/IL-17A-Driven Inflammatory Axis Shapes Synovitis in Juvenile Idiopathic Arthritis

T cells are considered autoimmune effectors in juvenile idiopathic arthritis (JIA), but the antigenic cause of arthritis remains elusive. Since T cells comprise a significant proportion of joint-infiltrating cells, we examined whether the environment in the joint could be shaped through the inflammatory activation by T cells that is independent of conventional TCR signaling. We focused on the analysis of synovial fluid (SF) collected from children with oligoarticular and rheumatoid factor-negative polyarticular JIA. Cytokine profiling of SF showed dominance of five molecules including IL-17A. Cytometric analysis of the same SF samples showed enrichment of αβT cells that lacked both CD4 and CD8 co-receptors [herein called double negative (DN) T cells] and also lacked the CD28 costimulatory receptor. However, these synovial αβT cells expressed high levels of CD31, an adhesion molecule that is normally employed by granulocytes when they transit to sites of injury. In receptor crosslinking assays, ligation of CD31 alone on synovial CD28nullCD31+ DN αβT cells effectively and sufficiently induced phosphorylation of signaling substrates and increased intracytoplasmic stores of cytokines including IL-17A. CD31 ligation was also sufficient to induce RORγT expression and trans-activation of the IL-17A promoter. In addition to T cells, SF contained fibrocyte-like cells (FLC) expressing IL-17 receptor A (IL-17RA) and CD38, a known ligand for CD31. Stimulation of FLC with IL-17A led to CD38 upregulation, and to production of cytokines and tissue-destructive molecules. Addition of an oxidoreductase analog to the bioassays suppressed the CD31-driven IL-17A production by T cells. It also suppressed the downstream IL-17A-mediated production of effectors by FLC. The levels of suppression of FLC effector activities by the oxidoreductase analog were comparable to those seen with corticosteroid and/or biologic inhibitors to IL-6 and TNFα. Collectively, our data suggest that activation of a CD31-driven, αβTCR-independent, IL-17A-mediated T cell-FLC inflammatory circuit drives and/or perpetuates synovitis. With the notable finding that the oxidoreductase mimic suppresses the effector activities of synovial CD31+CD28null αβT cells and IL-17RA+CD38+ FLC, this small molecule could be used to probe further the intricacies of this inflammatory circuit. Such bioactivities of this small molecule also provide rationale for new translational avenue(s) to potentially modulate JIA synovitis