Mai1 Protein Acts Between Host Recognition of Pathogen Effectors and Mitogen-Activated Protein Kinase Signaling.

The molecular mechanisms acting between host recognition of pathogen effectors by nucleotide-binding leucine-rich repeat receptor (NLR) proteins and mitogen-activated protein kinase (MAPK) signaling cascades are unknown. MAPKKKα (M3Kα) activates MAPK signaling leading to programmed cell death (PCD) associated with NLR-triggered immunity. We identified a tomato M3Kα-interacting protein, SlMai1, that has 80% amino acid identity with brassinosteroid kinase 1 (AtBsk1).

Synthesis of Heterologous Mevalonic Acid Pathway Enzymes in Clostridium ljungdahlii for the Conversion of Fructose and of Syngas to Mevalonate and Isoprene.

There is a growing interest in the use of microbial fermentation for the generation of high-demand, high-purity chemicals using cheap feedstocks in an environmentally friendly manner. One example explored here is the production of isoprene (CH), a hemiterpene, which is primarily polymerized to polyisoprene in synthetic rubber in tires but which can also be converted to C and C biofuels. The strictly anaerobic, acetogenic bacterium , used in all of the work described here, is capable of glycolysis using the Embden-Meyerhof-Parnas pathway and of carbon fixation using the Wood-Ljungdahl pathway.

Viral DNA Sensors IFI16 and Cyclic GMP-AMP Synthase Possess Distinct Functions in Regulating Viral Gene Expression, Immune Defenses, and Apoptotic Responses during Herpesvirus Infection.

Unlabelled: The human interferon-inducible protein IFI16 is an important antiviral factor that binds nuclear viral DNA and promotes antiviral responses. Here, we define IFI16 dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS). Live-cell imaging reveals a multiphasic IFI16 redistribution, first to viral entry sites at the nuclear periphery and then to nucleoplasmic puncta upon herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) infections.

Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion.

Unlabelled: Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at epithelial surfaces and continues into the peripheral nervous system (PNS). Inflammatory responses are induced at the infected peripheral site prior to invasion of the PNS. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which includes the interferons (IFNs).

Gaseous ammonia pretreatment lowers the required energy input for fine milling-enhanced enzymatic saccharification of switchgrass.

Background: Fine milling of dry lignocellulosic biomass, without prior chemical pretreatment, can produce a high percent theoretical yield of sugars during subsequent enzymatic saccharification. However, the high sugar yields, necessary for a commercial biofuels process, are costly, with the milling energy input, necessary to achieve such yields even exceeding the energy content of the biomass. In this study, we show that low moisture gaseous ammonia pretreatment of switchgrass, in advance of the milling step, significantly reduces the milling energy required to give high sugar titers.

Blowing Off Steam: Virus Inhibition of cGAS DNA Sensing.

Detection of viral DNA is essential for eliciting mammalian innate immunity. However, viruses have acquired effective mechanisms for blocking host defense. Indeed, in this issue of Cell Host & Microbe, Wu et al.

The emerging role of nuclear viral DNA sensors.

Detecting pathogenic DNA by intracellular receptors termed "sensors" is critical toward galvanizing host immune responses and eliminating microbial infections. Emerging evidence has challenged the dogma that sensing of viral DNA occurs exclusively in sub-cellular compartments normally devoid of cellular DNA. The interferon-inducible protein IFI16 was shown to bind nuclear viral DNA and initiate immune signaling, culminating in antiviral cytokine secretion.

cGAS-mediated stabilization of IFI16 promotes innate signaling during herpes simplex virus infection.

Interferon γ-inducible protein 16 (IFI16) and cGMP-AMP synthase (cGAS) have both been proposed to detect herpesviral DNA directly in herpes simplex virus (HSV)-infected cells and initiate interferon regulatory factor-3 signaling, but it has been unclear how two DNA sensors could both be required for this response. We therefore investigated their relative roles in human foreskin fibroblasts (HFFs) infected with HSV or transfected with plasmid DNA. siRNA depletion studies showed that both are required for the production of IFN in infected HFFs.

Interactions of the Antiviral Factor Interferon Gamma-Inducible Protein 16 (IFI16) Mediate Immune Signaling and Herpes Simplex Virus-1 Immunosuppression.

The interferon-inducible protein IFI16 has emerged as a critical antiviral factor and sensor of viral DNA. IFI16 binds nuclear viral DNA, triggering expression of antiviral cytokines during infection with herpesviruses. The knowledge of the mechanisms and protein interactions through which IFI16 exerts its antiviral functions remains limited.

The functional interactome of PYHIN immune regulators reveals IFIX is a sensor of viral DNA.

The human PYHIN proteins, AIM2, IFI16, IFIX, and MNDA, are critical regulators of immune response, transcription, apoptosis, and cell cycle. However, their protein interactions and underlying mechanisms remain largely uncharacterized. Here, we provide the interaction network for all PYHIN proteins and define a function in sensing of viral DNA for the previously uncharacterized IFIX protein.

The Impact of Mass Spectrometry-Based Proteomics on Fundamental Discoveries in Virology.

In recent years, mass spectrometry has emerged as a core component of fundamental discoveries in virology. As a consequence of their coevolution, viruses and host cells have established complex, dynamic interactions that function either in promoting virus replication and dissemination or in host defense against invading pathogens. Thus, viral infection triggers an impressive range of proteome changes.

Histone deacetylases in herpesvirus replication and virus-stimulated host defense.

Emerging evidence highlights a critical role for protein acetylation during herpesvirus infection. As prominent modulators of protein acetylation, histone deacetylases (HDACs) are essential transcriptional and epigenetic regulators. Not surprisingly, viruses have evolved a wide array of mechanisms to subvert HDAC functions.

Mixed exciton-charge-transfer states in photosystem II: Stark spectroscopy on site-directed mutants.

We investigated the electronic structure of the photosystem II reaction center (PSII RC) in relation to the light-induced charge separation process using Stark spectroscopy on a series of site-directed PSII RC mutants from the cyanobacterium Synechocystis sp. PCC 6803. The site-directed mutations modify the protein environment of the cofactors involved in charge separation (P(D1), P(D2), Chl(D1), and Phe(D1)).

Acetylation modulates cellular distribution and DNA sensing ability of interferon-inducible protein IFI16.

Detection of pathogenic nucleic acids is essential for mammalian innate immunity. IFN-inducible protein IFI16 has emerged as a critical sensor for detecting pathogenic DNA, stimulating both type I IFN and proinflammatory responses. Despite being predominantly nuclear, IFI16 can unexpectedly sense pathogenic DNA in both the cytoplasm and the nucleus.

Behavioral archives link the chemistry and clonal structure of trembling aspen to the food choice of North American porcupine.

Understanding the links among plant genotype, plant chemistry, and food selection by vertebrate herbivores is critical to assess the role of herbivores in the evolution of plant secondary chemistry. Some specialized vertebrate herbivores have been shown to select plants differentially according to plant genotype, but examples from generalists, which constitute the vast majority of vertebrate herbivores, are few, especially in natural conditions. We examined the relationship between the North American porcupine (Erethizon dorsatum), a generalist mammalian herbivore, and clonal trembling aspen (Populus tremuloides), a preferred food source of porcupines.

Probing the coupling between proton and electron transfer in photosystem II core complexes containing a 3-fluorotyrosine.

The catalytic cycle of numerous enzymes involves the coupling between proton transfer and electron transfer. Yet, the understanding of this coordinated transfer in biological systems remains limited, likely because its characterization relies on the controlled but experimentally challenging modifications of the free energy changes associated with either the electron or proton transfer. We have performed such a study here in Photosystem II.

Molecular origin of the pH dependence of tyrosine D oxidation kinetics and radical stability in photosystem II.

A role for redox-active tyrosines has been demonstrated in many important biological processes, including water oxidation carried out by photosystem II (PSII) of oxygenic photosynthesis. The rates of tyrosine oxidation and reduction and the Tyr/Tyr reduction potential are undoubtedly controlled by the immediate environment of the tyrosine, with the coupling of electron and proton transfer, a critical component of the kinetic and redox behavior. It has been demonstrated by Faller et al.

Spectroscopic properties of reaction center pigments in photosystem II core complexes: revision of the multimer model.

Absorbance difference spectra associated with the light-induced formation of functional states in photosystem II core complexes from Thermosynechococcus elongatus and Synechocystis sp. PCC 6803 (e.g.

Primary charge separation in the photosystem II core from Synechocystis: a comparison of femtosecond visible/midinfrared pump-probe spectra of wild-type and two P680 mutants.

It is now quite well accepted that charge separation in PS2 reaction centers starts predominantly from the accessory chlorophyll B(A) and not from the special pair P(680). To identify spectral signatures of B(A,) and to further clarify the process of primary charge separation, we compared the femtosecond-infrared pump-probe spectra of the wild-type (WT) PS2 core complex from the cyanobacterium Synechocystis sp. PCC 6803 with those of two mutants in which the histidine residue axially coordinated to P(B) (D2-His(197)) has been changed to Ala or Gln.

Influence of redox molecules on the electronic conductance of single-walled carbon nanotube field-effect transistors: application to chemical and biological sensing.

In an effort to develop sensitive nanoscale devices for chemical and biological sensing, we have examined, using liquid gating, the conductance of semiconducting single-walled carbon nanotube-based field-effect transistors (SWCNT-FETs) in the presence of redox mediators. As examples, redox couples K3Fe(CN)6/K4Fe(CN)6 and K2IrCl6/K3IrCl6 are shown to modulate the SWCNT-FET conductance in part through their influence via the electrolyte gate on the electrostatic potential of the solution, as described by Larrimore et al. (Nano Lett.

Site-directed mutations at D1-Thr179 of photosystem II in Synechocystis sp. PCC 6803 modify the spectroscopic properties of the accessory chlorophyll in the D1-branch of the reaction center.

D1-Thr179, which overlies the reaction center chlorophyll Chl D1 of Photosystem II was replaced with His and Glu through site-directed mutation in Synechocystis sp. PCC 6803. Spectroscopic characterization of the mutants indicates that, compared to wild type, the main bleaching in the triplet-minus-singlet absorbance difference spectrum and the electrochromic band shift in the (P680 (+)Q A (-)-P680Q A) absorbance difference spectrum are displaced to the red by approximately 2 nm in the D1-Thr179His mutant and to the blue by approximately 1 nm in the D1-Thr179Glu mutant.

Effective synthesized/preappraised evidence formats in emergency medicine and the use of supplemental knowledge translation techniques.

Most clinicians, and especially emergency physicians, are increasingly faced with the need for valid and reliable evidence upon which to base practice decisions in a timely fashion. Despite the accumulation of synthesized evidence in emergency medicine over the past decade, knowledge gaps still exist between what is known and what is practiced. In many cases, this failure in knowledge uptake relates to barriers in uptake as well as the difficulty of translating evidence from research to the bedside.

Graduate medical education and knowledge translation: role models, information pipelines, and practice change thresholds.

This article reflects the proceedings of a workshop session, Postgraduate Education and Knowledge Translation, at the 2007 Academic Emergency Medicine Consensus Conference on knowledge translation (KT) in emergency medicine (EM). The objective was to develop a research strategy that incorporates KT into EM graduate medical education (GME). To bridge the gap between the best evidence and optimal patient care, Pathman et al.