Living standards in Black and White: Evidence from the heights of Ohio Prison inmates, 1829–1913

The use of height data to measure living standards is now a well-established method in the economic history literature. Moreover, a number of core findings are widely agreed upon. There are still some populations, places, and times, however, for which anthropometric evidence remains limited. One such example is 19th century African-Americans in the Northern US. Here, we use new data from the Ohio state prison to track heights of Black and White men incarcerated between 1829 and 1913. We corroborate the well-known mid-century height decline among White men. We find that Black men were shorter than White men, throughout the century controlling for a number of characteristics. We also find a pattern of height decline among Black men in mid-century similar to that found for White men.     

The MUC1 HMFG1 glycoform is a precursor to the 214D4 glycoform in the human uterine epithelial cell line, HES

MUC1, a type I transmembrane glycoprotein expressed on most epithelia and many cancer cells, is involved in embryo implantation and tumor progression. A series of antibodies directed against the MUC1 ectodomain have been used to study MUC1 expression in the female reproductive tract, sometimes with apparently contradictory results. In the current study, we used two monoclonal MUC1 antibodies, 214D4 and HMFG1, to study the relationship between these MUC1 glycoforms in the human uterine epithelial cell line, HES, and human endometrial extracts. In response to tumor necrosis factor stimulation, accumulation of the HMFG1-reactive forms preceded that of the 214D4-reactive forms. Following inhibition of protein synthesis by cycloheximide, HMFG1-reactive species were lost rapidly (metabolic half-life [T(1/2)] = 20 min), while there was no change in the level of the 214D4-reactive forms even after 80 min. HMFG1-reactive forms had smaller oligosaccharide chains than the 214D4-reactive forms, and could not be detected on the cell surface of intact cells or in the shed (media) fraction, although they were readily detected in permeabilized cells. Both 214D4- and HMFG1-reactive species were detected in human endometrial extracts throughout the cycle; however, consistent with the HES cell studies, the HMFG1-reactive species were both smaller and less abundant than the 214D4-reactive species. Consistent with this observation, we found that HMFG1-reactive species were difficult to detect in tissue sections unless predigested with neuraminidase, indicating that these structures are rapidly sialylated during synthesis. In contrast, 214D4-reactive species were robustly detected in both proliferative and secretory stages. Collectively, these studies indicate that the HMFG1-reactive glycoform is a precursor of the 214D4-reactive glycoform in HES cells and normal uterine epithelia. Therefore, discrepancies in patterns of MUC1 expression in other studies may be due to failure to account for these glycoform relationships.     

Benefits of oat beta-glucan on respiratory infection following exercise stress: role of lung macrophages

Exercise stress is associated with an increased risk for upper respiratory tract infection (URTI). We have shown that consumption of the soluble oat fiber beta-glucan (ObetaG) can offset the increased risk for infection and decreased macrophage antiviral resistance following stressful exercise; however, the direct role of macrophages is unknown. This study examined the effect of macrophage depletion on the benefits of orally administered ObetaG on susceptibility to infection (morbidity, symptom severity, and mortality) following exercise stress. CL(2)MDP (Ex- H(2)O-CL(2)MDP, Ex-ObetaG-CL(2)MDP, Con-H(2)O-CL(2)MDP, Con-ObetaG-CL(2)MDP)-encapsulated liposomes were administered intranasally to deplete macrophages, and PBS (Ex-H(2)O-PBS, Ex-ObetaG-PBS, Con-H(2)O-PBS, Con-ObetaG-PBS)-encapsulated liposomes were given to macrophage-intact groups. Ex mice ran to volitional fatigue on a treadmill for 3 consecutive days, and ObetaG mice were fed a solution of 50% ObetaG in their drinking water for 10 consecutive days before infection. Fifteen minutes following the final bout of Ex or rest, mice were intranasally inoculated with 50 microl of a standardized dose of herpes simplex virus-1. Ex increased morbidity (P < 0.001) and symptom severity (P < 0.05) but not mortality (P = 0.09). The increase in morbidity and symptom severity was blocked by ObetaG consumption for 10 consecutive days before exercise and infection [morbidity (P < 0.001) and symptom severity (P < 0.05)]. Depletion of macrophages negated the beneficial effects of ObetaG on reducing susceptibility to infection following exercise stress, as evidenced by an increase in morbidity (P < 0.01) and symptom severity (P < 0.05). Results indicate that lung macrophages are at least partially responsible for mediating the beneficial effects of ObetaG on susceptibility to respiratory infection following exercise stress.     

Mast cell-dependent anorexia and hypothermia induced by mucosal activation of Toll-like receptor 7

Systemic viral infections produce a highly regulated set of responses in sickness behavior, such as fever, anorexia, and adipsia. Toll-like receptor (TLR)7, activated by viral RNA during infection, potently stimulates the innate and adaptive immune responses that aid in viral clearance. However, the physiological consequences of TLR7 activation have not been thoroughly studied. In these experiments, we used a potent synthetic TLR7 ligand, 9-benzyl-8-hydroxy-2-(2-methoxyethoxy)adenine (SM360320; 1V136), to investigate the consequences of TLR7 activation in genetically defined strains of mice. Administration of the drug by the nasal, intragastric, or intraperitoneal routes caused transient hypophagia, hypodypsia, and hypothermia. Analyses of mutant mouse strains indicated that these effects were dependent on the expression of TLR7, its adaptor protein MyD88, and TNF-alpha, and independent of IL-1beta, IL-6 and cyclo-oxygenase-1 (COX1). Partial roles were also implied for mast cells and COX2. Although plasma TNF-alpha levels were significantly higher after systemic drug delivery, the behavioral effects were maximal when the agent was administered to the mucosa. Tissue and mucosal mast cells are known to express high levels of TLR7 and to rapidly release TNF-alpha upon TLR7 ligation. Mice deficient in tissue mast cells, W/W(v), had significantly less anorexia after TLR7 activation, and this response was restored with mast cell reconstitution. Our results thus suggest that tissue mast cells may play a role in the anorexia induced by mucosal activation of TLR7.     

Evaluation of quantitative models of the effect of insulin on lipolysis and glucose disposal

The effects of insulin on the suppression of lipolysis are neither fully understood nor quantified. We examined a variety of mathematical models analogous to the minimal model of glucose disposal (MMG) to quantify the combined influence of insulin on lipolysis and glucose disposal during an insulin-modified frequently sampled intravenous glucose tolerance test. The tested models, which include two previously published ones, consisted of separate compartments for plasma free fatty acids (FFA), glucose, and insulin. They differed in the number of compartments and in the action of insulin to suppress lipolysis that decreased the plasma FFA level. In one category of models, a single insulin compartment acted on both glucose and FFA simultaneously. In a second category, there were two insulin compartments, each acting on FFA and glucose independently. For each of these two categories, we tested 11 variations of how insulin suppressed lipolysis. We also tested a model with an additional glucose compartment that acted on FFA. These 23 models were fit to the plasma FFA and glucose concentrations of 102 subjects individually. Using Bayesian model comparison methods, we selected the model that best balanced fit and minimized model complexity. In the best model, insulin suppressed lipolysis via a Hill function through a remote compartment that acted on both glucose and FFA simultaneously, and glucose dynamics obeyed the classic MMG.     

RhoA expression during recovery from skeletal muscle disuse.

Functional overload and anabolic steroid administration induce signaling pathways that regulate skeletal muscle RhoA expression. The purpose of this study was to determine RhoA and associated protein expression at the onset of disuse and after a brief period of reloading. Male Sprague-Dawley rats were randomly assigned to cage control (Con), 3 days of hindlimb suspension (Sus), or 3 days of hindlimb suspension with 12 h of reloading (12-h Reload). The reloading stimuli consisted of 12 h of resumed normal locomotion after 3 days of hindlimb suspension. Plantaris muscle-to-body weight (mg/g) ratio decreased 17% from Con with Sus but returned to Con with 12-h Reload, increasing 13% from Sus. Sus decreased RhoA protein concentration 46%, whereas 12-h Reload induced a 24% increase compared with Sus. The ratio of cytosolic- to membrane-associated RhoA protein was not changed with either Sus or 12-h Reload. RhoA mRNA concentration was decreased 48% by Sus, and 12-h Reload induced a 170% increase from Sus. beta(1)-Integrin protein, a transmembrane protein associated with RhoA activation, was not altered by Sus but increased 155% with 12-h Reload. Although beta(1)-integrin mRNA was not altered by Sus, it increased 70% from Con with 12-h Reload. Rho family member Cdc42 protein associated with the muscle membrane was decreased 60% with Sus, and 12-h Reload induced a 172% increase compared with Sus. In conclusion, decreased RhoA protein expression and mRNA abundance are early adaptations to disuse but recover rapidly after normal locomotion is resumed.     

Mechanism of inhibition of human KSP by ispinesib

KSP, also known as HsEg5, is a kinesin that plays an essential role in the formation of a bipolar mitotic spindle and is required for cell cycle progression through mitosis. Ispinesib is the first potent, highly specific small-molecule inhibitor of KSP tested for the treatment of human disease. This novel anticancer agent causes mitotic arrest and growth inhibition in several human tumor cell lines and is currently being tested in multiple phase II clinical trials. In this study we have used steady-state and pre-steady-state kinetic assays to define the mechanism of KSP inhibition by ispinesib. Our data show that ispinesib alters the ability of KSP to bind to microtubules and inhibits its movement by preventing the release of ADP without preventing the release of the KSP-ADP complex from the microtubule. This type of inhibition is consistent with the physiological effect of ispinesib on cells, which is to prevent KSP-driven mitotic spindle pole separation. A comparison of ispinesib to monastrol, another small-molecule inhibitor of KSP, reveals that both inhibitors share a common mode of inhibition.     

A ligand for the chemokine receptor CCR7 can influence the homeostatic proliferation of CD4 T cells and progression of autoimmunity.

Homeostasis of T cell numbers in the periphery implies an ability of lymphocytes to sense cell numbers. Although the mechanisms are unknown, we find that the chemokine CCL21 (also known as TCA4, SLC, 6Ckine), a ligand for the chemokine receptor CCR7, can regulate homeostasis of CD4 (but not CD8) T cells. In the absence of CCR7 ligands, transferred CD4 T cells failed to expand in lymphopenic hosts, whereas in the presence of CCL21 overexpression, homeostatic CD4 T cell proliferation occurred even in nonlymphopenic recipients. Ag-specific CD4 T cells transferred into Ag-expressing mice proliferated and induced autoimmunity only in lymphopenic recipients. Pancreatic expression of CCL21 was sufficient to replace the requirement for lymphopenia in the progression of autoimmune disease. These results suggest that CD4 T cells use local concentrations of CCR7 ligands as an index of T cell steady state numbers and that homeostatic expansion of the T cell population may be a contributing factor in the development of autoimmune disease.