Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biologically active compounds that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compound(s) produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liquid chromatography-high performance liquid chromatography (HILIC-HPLC) separation isolated TNF-inhibitory compounds, and HILIC-HPLC fraction composition was determined by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from L-histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA), histidine/histamine antiporter (hdcP), and hdcB in production of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2)-activated human monocytoid cells. Bacterial histamine suppressed TNF production via activation of the H2 receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA) and resulted in suppression of TNF production by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, L-histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF production. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases.

Despite considerable progress in the epidemiology of late life depressive disorders, the determinants and course of late life depressive symptoms remain unclear. The apparent reciprocal relationship between depression and disability, a consistent finding in cross-sectional studies further confounds efforts to estimate the importance of depressive symptoms in the elderly. In a longitudinal study of 1457 aged community residents who completed the Center for Epidemiologic Studies Depression scale at baseline and 24 months later, a significant level of depressive symptoms emerged in 163 respondents (11%), while 1080 (74%) remained symptom free. Unlike other studies, we found that the number of medical conditions, social support, life events, and demographic characteristics contributed little to distinguish those with emerging symptoms from those who remained symptom free. However, increasing disability and declining health preceded the emergence of depressive symptoms and accounted for seventy percent of the variance explained by discriminant analysis. These findings have etiologic implications for both the course and determinants of depression in late life.

The intestinal microbiota includes a diverse group of functional microorganisms, including candidate probiotics or viable microorganisms that benefit the host. Beneficial effects of probiotics include enhancing intestinal epithelial cell function, protecting against physiologic stress, modulating cytokine secretion profiles, influencing T lymphocyte populations, and enhancing antibody secretion. Probiotics have demonstrated significant potential as therapeutic options for a variety of diseases, but the mechanisms responsible for these effects remain to be fully elucidated. Accumulating evidence demonstrates that probiotics communicate with the host by modulating key signaling pathways, such as NFκB and MAPK, to either enhance or suppress activation and influence downstream pathways. Beneficial microbes can profoundly alter the physiology of the gastrointestinal tract, and understanding these mechanisms may result in new diagnostic and therapeutic strategies.

OBJECTIVE. Cognitive impairment among the elderly has been linked to mortality in studies of clinical populations. The purpose of this study was to examine the mortality risk associated with cognitive impairment among elderly populations in the community. METHODS. Cognitive impairment and other social and health factors were assessed in 1855 elderly community residents. This sample was reinterviewed periodically to assess changes in health and survival. RESULTS. At baseline 33% of the sample were mildly impaired and 8% were severely impaired. Across a 48-month observation period the survival probability was .85 for the cognitively unimpaired, .69 for the mildly impaired, and .51 for severely impaired respondents. When adjustments were made for the effects of other health and social covariates, severely impaired persons were twice as likely to die as unimpaired persons. Those who were mildly impaired were also at an increased risk. CONCLUSIONS. Other investigators have found that cognitive impairment is a significant predictor of dementia. We found that it is a significant predictor of mortality as well. Early detection of impaired cognition and attention to associated health problems could improve the quality of life of these older adults and perhaps extend their survival.

This paper deals with certain behavioral and ecological factors which may be relevant to the evolution and maintenance of social parasitism in ants. We will argue that some of the same factors which might predispose one species to evolve into a social parasite might make resistance to parasitism difficult for a closely related species.After their mating flight, the queens of most nonparasitic ant species found new colonies alone. A queen of such a species finds a suitable nesting place, excavates a small cavity, and seals herself inside. She then lays a clutch of eggs and feeds her first larvae a special "baby food" derived metabolically from the degeneration of her wing muscles and fat body. These larvae mature to become female workers which forage for food, enlarge the nest, feed the queen, and rear subsequent broods of workers and reproductives. Mature ant colonies usually occupy only one nest (monodomy). However, the number of queens in typical mature colonies varies.Colonies of some species never contain more than one functional queen (monogyny), while colonies of other species often have multiple queens (polygyny) (Buschinger 1974). However, the queens of all known obligatory slave-making, inquiline, and temporary-parasite species found colonies non-inde-1.