There is increasing evidence for an association between the alteration of cytokine concentrations in blood and the pathophysiology of depressive disorders. Studies in humans have not investigated CSF cytokine concentrations and their relationship to depressive disorders. This study reports on the association of the CSF concentration of proinflammatory cytokines, IL-1β, IL-6 and TNFα, and major depressive disorders. CSF samples were obtained from 13 hospitalized patients with acute unmedicated severe depression and were compared with 10 control subjects. Compared to the control group, the depressed patient group had higher CSF concentrations of IL-1β, lower IL-6 and no change in TNFα. A positive correlation was found between serum IL-1β and the severity of depression. These results indicate a unique profile for CSF proinflammatory cytokines in acute depression. These findings merit further investigation and if replicated may possibly offer immunological treatment options for depression.

The nature of the stress experienced by Escherichia coli K-12 exposed to chromate, and mechanisms that may enable cells to withstand this stress, were examined. Cells that had been preadapted by overnight growth in the presence of chromate were less stressed than nonadapted controls. Within 3 h of chromate exposure, the latter ceased growth and exhibited extreme filamentous morphology; by 5 h there was partial recovery with restoration of relatively normal cell morphology. In contrast, preadapted cells were less drastically affected in their morphology and growth. Cellular oxidative stress, as monitored by use of an H 2 O 2 -responsive fluorescent dye, was most severe in the nonadapted cells at 3 h postinoculation, lower in the partially recovered cells at 5 h postinoculation, and lower still in the preadapted cells. Chromate exposure depleted cellular levels of reduced glutathione and other free thiols to a greater extent in nonadapted than preadapted cells. In both cell types, the SOS response was activated, and levels of proteins such as SodB and CysK, which can counter oxidative stress, were increased. Some mutants missing antioxidant proteins (SodB, CysK, YieF, or KatE) were more sensitive to chromate. Thus, oxidative stress plays a major role in chromate toxicity in vivo, and cellular defense against this toxicity involves activation of antioxidant mechanisms. As bacterial chromate bioremediation is limited by the toxicity of chromate, minimizing oxidative stress during bacterial chromate reduction and bolstering the capacity of these organisms to deal with this stress will improve their effectiveness in chromate bioremediation.Chromate [Cr(VI)] is a widespread environmental pollutant, as it is a by-product of numerous industrial processes and nuclear weapons production (5). Because chromate is soluble, environmental contamination is difficult to contain. This solubility also promotes the active transport of chromate across biological membranes (7), and once internalized by cells, Cr(VI) exhibits a variety of toxic, mutagenic, and carcinogenic effects (34, 44). In contrast, most cells are impermeable to Cr(III), which is insoluble under typical environmental conditions (30); as measured by the Ames test, it is therefore some 1,000-fold less mutagenic than Cr(VI) (19). Thus, strategies for decontamination of environmental chromate focus on reducing it to Cr(III). Chemical methods for this are prohibitively expensive for large-scale environmental application and frequently have damaging consequences of their own (7), and so bacterial bioremediation is of considerable interest as an environmentally friendly and affordable solution to chromate pollution.Several bacteria, including Escherichia coli, Shewanella oneidensis, and numerous species of Pseudomonas and Bacillus, can reduce Cr(VI) to Cr(III) (17, 39); nonetheless, an effective bacterial system for in situ reduction has not yet been developed. One reason is that chromate is also toxic to the remediating bacteria (17). Our in vitro studies have strongly i...

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Dementia is a major contributor to dependence and disability in older people, with aging societies characterized by growing numbers of people living with the condition. Dementia rates are highest in those with low education early in life, midlife hypertension, midlife hearing loss, depression, obesity, loneliness, a sedentary lifestyle, or sustained exposure to smoking or diabetes. Tooth loss is a putative risk factor for dementia which has received increasing research attention, but systematic review findings are mixed. Three main mechanisms have been proposed, involving 1) tooth loss leading to compromised nutrition and then leading to poorer central nervous system (CNS) function; 2) tooth loss resulting in fewer interocclusal contacts and so less somatosensory feedback to the CNS, leading to impaired cognition; and (3) chronic periodontitis resulting in tooth loss, but not before the inflammation has affected the CNS, impairing cognition. None of these is supported by compelling empirical evidence. Here, we use the life course approach to propose a plausible, empirically supported explanation for the associations between missing teeth and poorer cognitive function in older people. Evidence from longstanding cohort studies demonstrates that the putative association arises from cognitive function much earlier in life, in childhood. People with better childhood cognitive function have better oral health and access to routine dental care as they go through life, losing fewer teeth along the life course. They are also much more likely to have better cognitive function in old age. Their less cognitively able childhood counterparts will experience higher disease rates and poorer access to care, resulting in greater incremental tooth loss. Comparison of the 2 groups at any age from the mid-20s on will show greater numbers of missing teeth in the group who were less cognitively able in childhood. Those differences will be most pronounced in old age.

Purpose To determine if magnetotactic bacteria can target tumors in mice and provide positive contrast for visualization using magnetic resonance imaging. Experimental Design The ability of the magnetotactic bacterium, Magnetospirillum magneticum AMB-1 (referred to from here as AMB-1), to confer positive magnetic resonance imaging contrast was determined in vitro and in vivo. For the latter studies, AMB-1 were injected either i.t. or i.v. Bacterial growth conditions were manipulated to produce small (~25-nm diameter) magnetite particles, which were observed using transmission electron microscopy. Tumor targeting was confirmed using 64Cu-labeled bacteria and positron emission tomography and by determination of viable cell counts recovered from different organs and the tumor. Results We show that AMB-1 bacteria with small magnetite particles generate T1-weighted positive contrast, enhancing in vivo visualization by magnetic resonance imaging. Following i.v. injection of 64Cu-labeled AMB-1, positron emission tomography imaging revealed increasing colonization of tumors and decreasing infection of organs after 4 hours. Viable cell counts showed that, by day 6, the bacteria had colonized tumors but were cleared completely from other organs. Magnetic resonance imaging showed a 1.22-fold (P = 0.003) increased positive contrast in tumors on day 2 and a 1.39-fold increase (P = 0.0007) on day 6. Conclusion Magnetotactic bacteria can produce positive magnetic resonance imaging contrast and colonize mouse tumor xenografts, providing a potential tool for improved magnetic resonance imaging visualization in preclinical and translational studies to track cancer.

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Most polluted sites contain mixed waste. This is especially true of the U.S. Department of Energy (DOE) waste sites which hold a complex mixture of heavy metals, radionuclides, and organic solvents. In such environments enzymes that can remediate multiple pollutants are advantageous. We report here evolution of an enzyme, ChrR6 (formerly referred to as Y6), which shows a markedly enhanced capacity for remediating two of the most serious and prevalent DOE contaminants, chromate and uranyl. ChrR6 is a soluble enzyme and reduces chromate and uranyl intracellularly. Thus, the reduced product is at least partially sequestered and nucleated, minimizing the chances of reoxidation. Only one amino acid change, Tyr 128 Asn , was responsible for the observed improvement. We show here that ChrR6 makes Pseudomonas putida and Escherichia coli more efficient agents for bioremediation if the cellular permeability barrier to the metals is decreased.Environmental pollution with toxic agents is a widespread and serious problem that defies simple solutions. The ability of bacteria to mineralize many of these contaminants or to transform them into a valence state that is insoluble and can therefore be localized offers a promising solution. As pointed out elsewhere (2,3,8,11,17,27), several measures can increase bacterial effectiveness for bioremediation. These measures include decreasing the toxicity of the pollutants to the remediating bacteria; improving the kinetics of the enzymes of the bacteria for the desired reactions; and, since most polluted environments contain mixed waste, generating individual bacterial enzymes with enhanced capacities for remediating multiple pollutants.Our work has focused on improving the bacterial capacity for chromate [Cr(VI)] remediation. A by-product of numerous industrial and military projects, such as the manufacture of nuclear weapons, chromate is a ubiquitous environmental pollutant (11, 13). It is soluble and bioavailable and upon cellular uptake leads to toxic effects that include mutagenesis and carcinogenesis (23,26,40). Bacteria can reduce chromate to the Cr(III) valence state, which is often less soluble and can be confined to initial contamination sites. Cr(III) is also much less toxic.The membrane-bound electron transport chain of certain bacteria can reduce Cr(VI) and may enable some of these bacteria to use it as a terminal electron acceptor for energy generation (9). In addition, many soluble enzymes in nearly all bacteria can vicariously reduce Cr(VI). Some examples are lipoyl dehydrogenase and cytochrome c and glutathione reductases, whose physiological roles are to catalyze energetic or biosynthetic reactions. These enzymes reduce chromate by one-electron transfer, generating Cr(V) (18, 33). Cr(V) is a highly reactive radical that redox cycles in the presence of appropriate electron acceptors, such as molecular oxygen. In this process, Cr(V) transfers its electron to dioxygen, regenerating Cr(VI) and producing reactive oxygen species (ROS). With the continued activity of the one-...

Intermediate nitrite accumulation during denitrification by Pseudomonas stutzeri isolated from a denitrifying fluidized bed reactor was examined in the presence of different volatile fatty acids. Nitrite accumulated when acetate or propionate served as the carbon and electron source but did not accumulate in the presence of butyrate, valerate, or caproate. Nitrite accumulation in the presence of acetate was caused by differences in the rates of nitrate and nitrite reduction and, in addition, by competition between nitrate and nitrite reduction pathways for electrons. Incubation of the cells with butyrate resulted in a slower nitrate reduction rate and a faster nitrite reduction rate than incubation with acetate. Whereas nitrate inhibited the nitrite reduction rate in the presence of acetate, no such inhibition was found in butyrate-supplemented cells. Cytochromes b and c were found to mediate electron transport during nitrate reduction by the cells. Cytochrome c was reduced via a different pathway when nitrite-reducing cells were incubated with acetate than when they were incubated with butyrate. Furthermore, addition of antimycin A to nitrite-reducing cells resulted in partial inhibition of electron transport to cytochrome c in acetate-supplemented cells but not in butyrate-supplemented cells. On the basis of these findings, we propose that differences in intermediate nitrite accumulation are caused by differences in electron flow to nitrate and nitrite reductases during oxidation of either acetate or butyrate.