4,231 research outputs found
The genetic basis of energy conservation in the sulfate-reducing bacterium Desulfovibrio alaskensis G20.
Sulfate-reducing bacteria play major roles in the global carbon and sulfur cycles, but it remains unclear how reducing sulfate yields energy. To determine the genetic basis of energy conservation, we measured the fitness of thousands of pooled mutants of Desulfovibrio alaskensis G20 during growth in 12 different combinations of electron donors and acceptors. We show that ion pumping by the ferredoxin:NADH oxidoreductase Rnf is required whenever substrate-level phosphorylation is not possible. The uncharacterized complex Hdr/flox-1 (Dde_1207:13) is sometimes important alongside Rnf and may perform an electron bifurcation to generate more reduced ferredoxin from NADH to allow further ion pumping. Similarly, during the oxidation of malate or fumarate, the electron-bifurcating transhydrogenase NfnAB-2 (Dde_1250:1) is important and may generate reduced ferredoxin to allow additional ion pumping by Rnf. During formate oxidation, the periplasmic [NiFeSe] hydrogenase HysAB is required, which suggests that hydrogen forms in the periplasm, diffuses to the cytoplasm, and is used to reduce ferredoxin, thus providing a substrate for Rnf. During hydrogen utilization, the transmembrane electron transport complex Tmc is important and may move electrons from the periplasm into the cytoplasmic sulfite reduction pathway. Finally, mutants of many other putative electron carriers have no clear phenotype, which suggests that they are not important under our growth conditions, although we cannot rule out genetic redundancy
The human fear-circuitry and fear-induced fainting in healthy individuals The paleolithic-threat hypothesis
The Paleolithic-Threat
hypothesis reviewed here posits
that habitual efferent fainting can
be traced back to fear-induced
allelic polymorphisms that were
selected into some genomes of
anatomically, mitochondrially, and
neurally modern humans (Homo
sapiens sapiens) in the Mid-Paleolithic because of the survival
advantage they conferred during
periods of inescapable threat. We
posit that during Mid-Paleolithic
warfare an encounter with “a
stranger holding a sharp object”
was consistently associated with
threat to life. A heritable hard-
wired or firm-wired (prepotentiated) predisposition to abruptly
increase vagal tone and collapse
flaccidly rather than freeze or
attempt to flee or fight in response
to an approaching sharp object, a
minor injury, or the sight of blood,
polymorphism for the hemodynamically “paradoxical” flaccid-
immobility in response to these
stimuli may have increased some
non-combatants’ chances of survival. This is consistent with the
unusual age and sex pattern of
fear-induced fainting. The Paleolithic-Threat hypothesis also predicts a link to various hypo-androgenic states (e.g. low dehydroxyepiandrosterone-sulfate. We offer
five predictions testable via epidemiological, clinical, and ethological/primatological methods. The
Paleolithic-Threat hypothesis has
implications for research in the
aftermath of man-made disasters,
such as terrorism against civilians,
a traumatic event in which this
hypothesis predicts epidemics of
fear-induced faintin
Accelerated Calvarial Healing in Mice Lacking Toll-Like Receptor 4
The bone and immune systems are closely interconnected. The immediate inflammatory response after fracture is known to trigger a healing cascade which plays an important role in bone repair. Toll-like receptor 4 (TLR4) is a member of a highly conserved receptor family and is a critical activator of the innate immune response after tissue injury. TLR4 signaling has been shown to regulate the systemic inflammatory response induced by exposed bone components during long-bone fracture. Here we tested the hypothesis that TLR4 activation affects the healing of calvarial defects. A 1.8 mm diameter calvarial defect was created in wild-type (WT) and TLR4 knockout (TLR4-/-) mice. Bone healing was tested using radiographic, histologic and gene expression analyses. Radiographic and histomorphometric analyses revealed that calvarial healing was accelerated in TLR4-/- mice. More bone was observed in TLR4-/- mice compared to WT mice at postoperative days 7 and 14, although comparable healing was achieved in both groups by day 21. Bone remodeling was detected in both groups on postoperative day 28. In TLR4-/- mice compared to WT mice, gene expression analysis revealed that higher expression levels of IL-1β, IL-6, TNF-α,TGF-β1, TGF-β3, PDGF and RANKL and lower expression level of RANK were detected at earlier time points (≤ postoperative 4 days); while higher expression levels of IL-1β and lower expression levels of VEGF, RANK, RANKL and OPG were detected at late time points (> postoperative 4 days). This study provides evidence of accelerated bone healing in TLR4-/- mice with earlier and higher expression of inflammatory cytokines and with increased osteoclastic activity. Further work is required to determine if this is due to inflammation driven by TLR4 activation. © 2012 Wang et al
Macrophage transactivation for chemokine production identified as a negative regulator of granulomatous inflammation using agent-based modeling
Cellular activation in trans by interferons, cytokines and chemokines is a commonly recognized mechanism to amplify immune effector function and limit pathogen spread. However, an optimal host response also requires that collateral damage associated with inflammation is limited. This may be particularly so in the case of granulomatous inflammation, where an excessive number and / or excessively florid granulomas can have significant pathological consequences. Here, we have combined transcriptomics, agent-based modeling and in vivo experimental approaches to study constraints on hepatic granuloma formation in a murine model of experimental leishmaniasis. We demonstrate that chemokine production by non-infected Kupffer cells in the Leishmania donovani-infected liver promotes competition with infected KCs for available iNKT cells, ultimately inhibiting the extent of granulomatous inflammation. We propose trans-activation for chemokine production as a novel broadly applicable mechanism that may operate early in infection to limit excessive focal inflammation
Dissecting a complex chemical stress: chemogenomic profiling of plant hydrolysates.
The efficient production of biofuels from cellulosic feedstocks will require the efficient fermentation of the sugars in hydrolyzed plant material. Unfortunately, plant hydrolysates also contain many compounds that inhibit microbial growth and fermentation. We used DNA-barcoded mutant libraries to identify genes that are important for hydrolysate tolerance in both Zymomonas mobilis (44 genes) and Saccharomyces cerevisiae (99 genes). Overexpression of a Z. mobilis tolerance gene of unknown function (ZMO1875) improved its specific ethanol productivity 2.4-fold in the presence of miscanthus hydrolysate. However, a mixture of 37 hydrolysate-derived inhibitors was not sufficient to explain the fitness profile of plant hydrolysate. To deconstruct the fitness profile of hydrolysate, we profiled the 37 inhibitors against a library of Z. mobilis mutants and we modeled fitness in hydrolysate as a mixture of fitness in its components. By examining outliers in this model, we identified methylglyoxal as a previously unknown component of hydrolysate. Our work provides a general strategy to dissect how microbes respond to a complex chemical stress and should enable further engineering of hydrolysate tolerance
A Non-Relativistic Weyl Anomaly
We examine the Weyl anomaly for a four-dimensional z=3 Lifshitz scalar
coupled to Horava's theory of anisotropic gravity. We find a one-loop
break-down of scale-invariance at second order in the gravitational background.Comment: LaTeX, 23 pages, no figures, JHEP style; v2: typos fixed to match the
published versio
Saturation of front propagation in a reaction-diffusion process describing plasma damage in porous low-k materials
We propose a three-component reaction-diffusion system yielding an asymptotic
logarithmic time-dependence for a moving interface. This is naturally related
to a Stefan-problem for which both one-sided Dirichlet-type and von
Neumann-type boundary conditions are considered. We integrate the dependence of
the interface motion on diffusion and reaction parameters and we observe a
change from transport behavior and interface motion \sim t^1/2 to logarithmic
behavior \sim ln t as a function of time. We apply our theoretical findings to
the propagation of carbon depletion in porous dielectrics exposed to a low
temperature plasma. This diffusion saturation is reached after about 1 minute
in typical experimental situations of plasma damage in microelectronic
fabrication. We predict the general dependencies on porosity and reaction
rates.Comment: Accepted for publication in Phys. Rev.
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