The primary endpoint was time to major amputation or death at 1 year analysed by intention to treat with a log-rank test using a multivariate Cox proportional hazard model. This trial is registered with ClinicalTrials.gov, number NCT00566657.

Findings 259 patients were assigned to NV1FGF and 266 to placebo. All 525 patients were analysed. The mean age was 70 years (range 50-92), 365 (70%) were men, 280 (53%) had diabetes, and 248 (47%) had a history of coronary artery disease. The primary endpoint or components of

the primary did not differ between treatment groups, with major amputation or death in 86 patients (33%) in the placebo group, and 96 (36%) in the active group (hazard ratio 1.11, 95% CI 0.83-1.49; p=0.48). No significant safety issues were recorded.

Interpretation Proteases inhibitor TAMARIS provided no evidence that NV1FGF is Dibutyryl-cAMP cell line effective in reduction of amputation or death in patients with critical limb ischaemia. Thus, this group of patients remains a major therapeutic challenge for the clinician.”
“Surface display is a powerful technique that uses natural microbial functional components to express proteins or peptides on the cell exterior. Since the reporting of the first surface-display system in the mid-1980s, a variety of new systems have been reported

for yeast, Gram-positive and Gram-negative bacteria. Non-conventional display methods are emerging, eliminating the generation of genetically modified microorganisms. Cells with surface display are used as biocatalysts, biosorbents and biostimulants. Microbial cell-surface display has proven to be extremely important for numerous

applications, Bacterial neuraminidase ranging from combinatorial library screening and protein engineering to bioremediation and biofuels production.”
“Conspicuous deficits in face recognition characterize prosopagnosia. Information on whether agnosic deficits may extend to non-facial body parts is lacking. Here we report the neuropsychological description of FM, a patient affected by a complete deficit in face recognition in the presence of mild clinical signs of visual object agnosia. His deficit involves both overt and covert recognition of faces (i.e. recognition of familiar faces, but also categorization of faces for gender or age) as well as the visual mental imagery of faces. By means of a series of matching-to-sample tasks we investigated: (i) a possible association between prosopagnosia and disorders in visual body perception; (ii) the effect of the emotional content of stimuli on the visual discrimination of faces, bodies and objects; (iii) the existence of a dissociation between identity recognition and the emotional discrimination of faces and bodies. Our results document, for the first time, the co-occurrence of body agnosia, i.e. the visual inability to discriminate body forms and body actions, and prosopagnosia.

Site-specific conjugation of Df-Chx-Mal to thio-trastuzumab was complete within 1 h at pH 7.5, while Df-lac and Df-Bac respectively required 2 and 5 h at pH 9.

Each Df modified thio-trastuzumab was chelated with Zr-89 in yields exceeding 75%. Zr-89-Df-Ac-thio-trastuzumab and Zr-89-Df-Chx-Mal-thio-trastuzumab were stable in mouse serum and exhibited comparable PET imaging capabilities in a BT474M1 (HER2-positive) breast cancer learn more model reaching 20-25 %ID/g of tumor uptake and a tumor to blood ratio of 6.1-7.1.

Conclusions: The new reagents demonstrated good reactivity with engineered thiol groups of trastuzumab and very good chelation properties with 89Zr. The site-specifically Zr-89-labeled thio-antibodies were stable in serum and showed PET imaging properties comparable to lysine conjugates. (C) 2010 Elsevier Inc. All rights reserved.”
“The stability of 6 reference genes, 18S, beta-actin, RPS20, eEF1 alpha, G6PDH and selleck compound GAPDH, was examined in tissues from Atlantic salmon (Salmo salar) and Chinook salmon embryo cells (CHSE-214). The main objective of this study was to determine the most suitable reference genes for use for the normalisation of data in quantitative real-time RT-qPCR assays conducted on infected tissues. The tissue samples selected for analysis were taken from

head kidney and pylorus and collected at different time points during a challenge experiment with infectious pancreatic necrosis virus (IPNV). The stability of some of the reference genes was also studied in infected CHSE-214 cells. The ranking of the genes examined was carried out using the geNorm program. This program determines the most stable genes from a set of genes tested in a given cDNA sample. The stability of the reference genes varied in different tissues and in the cell line at different stages of infection with IPNV. This study demonstrated that Vildagliptin tissue-specific combinations of reference

genes must be used to normalise real time data for use for the quantitation of IPNV. (C) 2009 Elsevier B.V. All rights reserved.”
“Purpose: To evaluate the efficiency of baculovirus vectors in transducing FTC-133 cells and to examine the feasibility of using baculovirus vectors for the delivery of the sodium-iodide symporter (NIS) gene as a reporter through co-transduction to monitor the expression of the target gene.

Method: Two recombinant baculoviruses were constructed to express NIS and green fluorescent protein (GFP) respectively. FTC-133, 8050C, SW1116. A549 cells, were infected with Bac-GFP. The infection efficiency of Bac-GFP and the intensity of fluorescence, in either the presence or absence of sodium butyrate, were monitored by flow cytometry. The iodine uptake by FTC-133 cells infected with Bac-NIS was measured using a gamma counter. FTC-133 cells were infected with a mixture of equal amounts of Bac-NIS and Bac-GFP at different setting of multiplicity of infection (MOI).

Although most aged mice failed to develop clinical disease during

their life spans, many OSI-906 cost showed histopathological signs of TSE disease in their brains. Thus, the effects of age on intravenous TSE pathogenesis may lead to significant levels of subclinical disease in the population. After peripheral exposure, many TSE agents accumulate upon follicular dendritic cells (FDCs) in lymphoid tissues before they infect the brain. In aged spleens, PrPC expression and TSE agent accumulation upon FDCs were reduced. Furthermore, the splenic marginal zone microarchitecture was substantially disturbed, adversely affecting the delivery of immune complexes to FDCs. This study is the first to suggest that the effects of aging on the microarchitecture and the function of the splenic marginal zone significantly influence the pathogenesis of an important pathogen.”
“The underrepresentation of women at the top of math-intensive fields is controversial, with competing claims of biological and sociocultural causation. The authors develop a framework to delineate possible causal pathways and evaluate evidence

for each. Biological evidence is contradictory and inconclusive. Although cross-cultural and cross-cohort differences suggest a powerful effect of sociocultural selleck kinase inhibitor context, evidence for specific factors is inconsistent and contradictory. Factors unique to underrepresentation in math-intensive fields include the following: (a) Math-proficient women disproportionately prefer careers in non-math-intensive fields and are more likely to leave math-intensive careers as they advance; (b) more men than women score in the extreme math-proficient range on gatekeeper tests, such as the SAT Mathematics and the Graduate Record Examinations Quantitative Reasoning sections; (c) women with high math competence are disproportionately more likely to have high verbal competence, allowing greater choice of professions; and (d) in some math-intensive

fields, women with Decitabine solubility dmso children are penalized in promotion rates. The evidence indicates that women’s preferences, potentially representing both free and constrained choices, constitute the most powerful explanatory factor; a secondary factor is performance on gatekeeper tests, most likely resulting from sociocultural rather than biological causes.”
“Recent advances in understanding the etiology of obesity, metabolic syndrome, and type 2 diabetes (T2D) have established involvement of the immune system. These developments highlight the potential of immunomodulatory therapies for treatment of these conditions. Here, we discuss current and new immunotherapeutic strategies for the treatment of T2D, the need for stratification of patients based on immune and autoimmune status, and biomarkers for evaluating treatment efficiency.

Owing to the poorer metabolizability than oseltamivir, large contribution of the benzene core template and fine synergistic effects of the functional groups, the 4-(N-acetylamino)-5-guanidino-3-(3-pentyloxy)benzoic acid should be an ideal lead compound for optimizing NA drugs. (C) 2010 Elsevier Ltd. All rights reserved.”
“Resilience is often associated with extreme trauma or overcoming extraordinary odds. This way of thinking about resilience leaves most of the ontogenetic picture

a mystery. In the following review we put forth the Everyday Stress Resilience Hypothesis where resilience is analyzed from a systems perspective and seen as a process of regulating everyday life stressors. Successful regulation accumulates into regulatory resilience which emerges during early development from successful coping with the inherent stress in typical interactions. https://www.selleckchem.com/products/Vorinostat-saha.html These quotidian stressful events lead to activation of behavioral www.selleckchem.com/products/ink128.html and physiologic

systems. Stress that is effectively resolved in the short run and with reiteration over the long-term increases children’s as well as adults’ capacity to cope with more intense stressors. Infants, however, lack the regulatory capacities to take on this task by themselves. Therefore, through communicative and regulatory processes during infant-adult interactions, we demonstrate that the roots of regulatory resilience originate in infants’ relationship with their caregiver and that maternal Protirelin sensitivity can help or hinder the growth of resilience. (C) 2011 Elsevier Ltd. All rights reserved.”
“The influence of diversity on ecosystem functioning and ecosystem services is now well established. Yet predictive mechanistic models that link species traits and community-level processes remain scarce, particularly for multitrophic systems. Here we revisit MacArthur’s classical consumer resource model and

develop a trait-based approach to predict the effects of consumer diversity on cascading extinctions and aggregated ecosystem processes in a two-trophic-level system. We show that functionally redundant efficient consumers generate top-down cascading extinctions. This counterintuitive result reveals the limits of the functional redundancy concept to predict the consequences of species deletion. Our model also predicts that the biodiversity-ecosystem functioning relationship is different for different ecosystem processes and depends on the range of variation of consumer traits in the regional species pool, which determines the sign of selection effects. Lastly, competition among resources and consumer generalism both weaken complementarity effects, which suggests that selection effects may prevail at higher trophic levels. Our work emphasizes the potential of trait-based approaches for transforming biodiversity and ecosystem functioning research into a more predictive science. (C) 2010 Elsevier Ltd. All rights reserved.

“
“One main complication of a flow-diverting device (FD) in treating intracranial aneurysm is stenosis of parent artery (PA) or occlusion of side branches. The use of a biodegradable device may satisfy the need for aneurysm occlusion and eliminate potential complications.

Twenty elastase-induced aneurysm rabbit models were divided into three groups: in group 1 (n = 7), polyglycolic acid FDs (PGA-FDs) were implanted across the necks of aneurysms and the abdominal aortas (AA), covering the ostium of a lumbar artery; in group 2 (n = 7), the PGA-FDs were

replaced by metal FDs; and in group 3 (n = 6), the PGA-FDs were only implanted across the necks of aneurysms. Animals in group 3 underwent angiography at 6 weeks; those in find more groups 1 and 2 underwent angiography at 3 months. The status of aneurysm embolization and patency of side branches were assessed.

Complete aneurysm occlusion rates in groups 1 and 3 were 83.3 and 66.7 %, respectively, compared with 0 % in group 2. No side branch occlusions were noted. PA neointimal Enzalutamide in vitro hyperplasia was minimal, and there were no significant differences between groups

1 and 2 (P = 0.233). The neointimal coverage ratio of the branch ostium in AA in group 1 was not significantly different from that in group 2 (P = 0.605). The neointima comprised predominantly smooth muscle cells and collagen fibers.

The PGA-FD was an effective device for the treatment of aneurysms and was safe for side branches at the 3-month follow-up.”
“Brain imaging techniques Progesterone allow the in vivo evaluation of the human brain, leading to a better understanding of its anatomical, functional and metabolic substrate. The aim of this current report is to present a systematic and critical review of neuroimaging findings in Social Anxiety Disorder (SAD). A literature review was performed in the PubMed Medline, Scielo and Web of Science databases using the following keywords: ‘MRI’, ‘functional’, ‘tomography’, ‘PET’, ‘SPECT’, ‘spectroscopy’, ‘relaxometry’, ‘tractography’ and ‘voxel’ crossed one by one with the terms ‘social anxiety’ and ‘social phobic’, with no limit of time. We selected 196 articles

and 48 of them were included in our review. Most of the included studies have explored the neural response to facial expressions of emotion, symptoms provocation paradigms, and disorder-related abnormalities in dopamine or serotonin neurotransmission. The most coherent finding among the brain imaging techniques reflects increased activity in limbic and paralimbic regions in SAD. The predominance of evidence implicating the amygdala strengthens the notion that it plays a crucial role in the pathophysiology of SAD. The observation of alterations in pre-frontal regions and the reduced activity observed in striatal and parietal areas show that much remains to be investigated within the complexity of SAD. Interesting, follow-up designed studies observed a decrease in perfusion in these same areas after either by pharmacological or psychological treatment.

At 3 months, all the patients were clinically followed up and 14 underwent repeat MRI. 10 patients improved, 1 remained stable and 5 deteriorated. There was worsening with respect to tuberculoma Selleck PXD101 in 3, infarction in

2 and exudate in 1 patient. TNF-alpha was expressed in 32% patients, IL-6, IL-10, IL-1 beta and IL-8 were significantly expressed in patients and declined after 3 months following treatment. The cytokine levels did not correlate with stage of meningitis, outcome and radiological deterioration or improvement. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“The pandemic H1N1 virus of 2009 (2009 H1N1) continues to cause illness worldwide, primarily in younger age groups. To better understand the pathogenesis of these viruses in mammals, we used a mouse model to evaluate the relative virulence Sotrastaurin clinical trial of selected 2009 H1N1 viruses and compared them to a representative human triple-reassortant

swine influenza virus that has circulated in pigs in the United States for over a decade preceding the current pandemic. Additional comparisons were made with the reconstructed 1918 virus, a 1976 H1N1 swine influenza virus, and a highly pathogenic H5N1 virus. Mice were inoculated intranasally with each virus and monitored for morbidity, mortality, viral replication, hemostatic parameters, cytokine production, and lung histology. All 2009 H1N1 viruses replicated efficiently in the lungs of mice and possessed a high degree of infectivity but did not cause lethal disease or exhibit extrapulmonary virus spread. Transient weight loss, lymphopenia, and proinflammatory cytokine and chemokine production were present following 2009 H1N1 virus infection, but these levels were generally muted compared with a triple-reassortant swine virus and the 1918 virus. 2009 H1N1 viruses isolated from fatal cases did not demonstrate enhanced virulence in this model compared with isolates from mild human cases.

Histologically, infection with the 2009 viruses resulted in lesions in the lung varying from mild to selleck inhibitor moderate bronchiolitis with occasional necrosis of bronchiolar epithelium and mild to moderate peribronchiolar alveolitis. Taken together, these studies demonstrate that the 2009 H1N1 viruses exhibited mild to moderate virulence in mice compared with highly pathogenic viruses.”
“Multichannel EEG recordings from 18 healthy subjects were used to investigate brain activity in four delta subbands during two mental arithmetic tasks (number comparison and two-digit multiplication) and a control condition. The spatial redistribution of signal-power (SP) was explored based on four consecutives subbands of the delta rhythm. Additionally, network analysis was performed, independently for each subband, and the related graphs reflecting functional connectivity were characterized in terms of local structure (i.e. the clustering coefficient), overall integration (i.e. the path length) and the optimality of network organization (i.e.

This study investigated the effects of curcumin on restraint stress-induced spatial learning and memory dysfunction in a water maze task and on measures related neuroendocrine and plasticity changes. The results showed that memory deficits were reversed with

curcumin in a dose dependent manner, as were stress-induced increases in serum corticosterone levels. These effects were similar to positive antidepressant imipramine. Additionally, curcumin prevented adverse changes in the dendritic morphology of CA3 pyramidal neurons in the hippocampus, as assessed by the changes in branch points and dendritic length. In primary hippocampal neurons it was shown that curcumin or imipramine protected hippocampal neurons against corticosterone-induced toxicity. Furthermore, the portion of calcium/calmodulin kinase II (CaMKII) that is activated (phosphorylated JPH203 price CaMKII, pCaMKII), and the glutamate receptor sub-type (NMDA(2B)) expressions were increased in the presence of corticosterone. These effects were also blocked by curcumin or imipramine treatment. Thus, curcumin may be an effective therapeutic for learning and memory disturbances as was seen within these stress models, and its neuroprotective effect was mediated in part by MK5108 normalizing the corticosterone response, resulting in down-regulating of the pCaMKII and

glutamate receptor levels. (C) 2009 Elsevier Ltd. All rights reserved.”
“The mechanism by which herpesviruses

acquire their tegument is not yet clear. One model is that outer tegument proteins are recruited by the cytoplasmic tails of viral glycoproteins. In the case of herpes simplex virus tegument protein VP22, interactions with the glycoproteins gE and gD have been shown. We have previously shown that the C-terminal half of VP22 contains the necessary signal for assembly into the virus. Here, we show that during infection VP22 interacts with gE and gM, as well as its tegument partner VP16. However, by using a range of techniques we were unable to demonstrate VP22 binding to gD. By using pulldown assays, we show that while the cytoplasmic tails of both gE and gM interact with VP22, only gE interacts efficiently with the 4��8C C-terminal packaging domain of VP22. Furthermore, gE but not gM can recruit VP22 to the Golgi/trans-Golgi network region of the cell in the absence of other virus proteins. To examine the role of the gE-VP22 interaction in infection, we constructed a recombinant virus expressing a mutant VP22 protein with a 14-residue deletion that is unable to bind gE (Delta gEbind). Coimmunoprecipitation assays confirmed that this variant of VP22 was unable to complex with gE. Moreover, VP22 was no longer recruited to its characteristic cytoplasmic trafficking complexes but exhibited a diffuse localization.

04) and an increase in P300 latency (p < p38 MAPK inhibitor 0.03). Furthermore, resting EEG activity in the beta band (13-30 Hz) was reduced ( p < 0.04). The change between 1st and 2nd investigation was significantly different in the

three groups of patients/subjects (p < 0.03). Patients receiving intensified treatment for glycemic control had an improvement of cognitive ability in visuospatial ability (p < 0.02) and semantic memory performance (p < 0.04) together with increased resting EEG activity in the alpha band (8-13 Hz, p < 0.02) and connectivity in the theta (4-8 Hz, p < 0.03) and alpha bands (p < 0.03) over central and lateral regions. Furthermore, there was an increase in the connectivity in the beta band (p < 0.04) over the central regions of the scalp.

In conclusion, subjects this website with T2DM had a similar type of cognitive function impairment and EEG/ERP abnormality as previously demonstrated for subjects with type 1

diabetes (T1DM). Intensified therapy showed cognitive improvement not shown for regular treatment, suggesting that the negative effect of T2DM on cognition is reversible by means of improved glycemic control. Furthermore, there was an improvement in electro-physiological measures, suggesting increased availability of compensatory mechanisms in subjects with intensified treatment. (C) 2010 Elsevier Ltd. All rights reserved.”
“We recently reported a newly developed enzyme-linked immunosorbent assay (ELISA) for high molecular weight amyloid-beta (A beta) oligomers in which the same A beta monoclonal antibody, BAN50, was used for both capture and detection in a single antibody sandwich enzyme linked immunosorbent assay (ELISA) system. Although our previous data have suggested that this assay will be useful for the early diagnosis Exoribonuclease of Alzheimer disease (AD) in cerebrospinal fluid (CSF) samples,

the invasive CSF sampling procedure, with associated potential complications, limits use of these samples in routine clinical practice. In this study, we have demonstrated that our ELISA can detect signals in 60% of serum samples and in 80% of CSF samples obtained from non-demented subjects. Heterophilic antibodies that are reported to be a primary confounding factor in this type of ELISA system did not affect the signals obtained. Although the levels of serum A beta oligomers were unexpectedly high, suggesting the possible detection of non-pathological A beta complexes associated with serum carrier proteins, they did show a significant positive correlation with the levels obtained from matched CSF samples. This correlation between CSF and serum A beta oligomer levels implies that the levels of serum A beta oligomers measured with our ELISA might be useful as a marker for AD that reflects an intact system of A beta transport across the blood brain barrier. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Population-based studies of cortisol and psychological health over long periods are rare.

Markers of renal dysfunction (plasma [creatinine] and [urea]), damage (tubular histology)and inflammation (cell recruitment) were elevated following IRI in WT mice; effects significantly reduced following nitrite treatment. Chemiluminescence analysis of cortical and medullary sections of the kidney demonstrated rapid (within I min) distribution of nitrite following application. Whilst IRI caused a significant (albeit substantially reduced compared to WT mice) elevation of markets

of renal dysfunction and damage in eNOS KO mice, the beneficial effects of nitrite were absent or reduced, respectively. Moreover, nitrite treatment enhanced renal dysfunction in the form of increased plasma [creatinine] in eNOS KO mice. Confirmation of nitrite reductase activity of eNOS was provided by demonstration of nitrite (100 mu M)-derived NO production by kidney homogenates learn more of WT mice, that was significantly reduced by L-NMMA. L-NMMA was without effect using kidney homogenates of eNOS KO mice. These results support a role for eNOS in the pathways activated

during renal IRI and also identify eNOS as a nitrite reductase in ischernic conditions activity which in part underlies the protective effects of nitrite. (C) 2009 Elsevier Inc. All rights reserved.”
“Aims:

In this study we demonstrate the interference of yeast extract in enumeration of Saccharomyces cerevisiae using real-time PCR and develop a method for its removal from the media filipin using ethidium monoazide (EMA).

Methods and Results:

Using real-time Volasertib order PCR and primers to S. cerevisiae we demonstrate the presence of yeast DNA in various media as well as the media impact on S. cerevisiae real-time PCR standard curves. By pretreatment with EMA, we were able to remove this interference.

Conclusions:

Saccharomyces

cerevisiae DNA can be found in a number of common laboratory media and may impact the enumeration of this yeast by real-time PCR. However, pretreatment with EMA eliminates this concern.

Significance and Impact of the Study:

We have developed a method for removal of contaminating DNA in yeast growth media.”
“Recent data Suggests that reactions of nitrite with ferric hemoglobin are potentially important in hemeprotein dependent NO signaling. Our group and others are evaluating the role of reductive nitrosylation reactions in the generation of N(2)O(3) as a signaling molecule. The latter reaction is hypothesized to involve reactions on NO, nitrite and methemoglobin to form N(2)O(3) in an anhydrase reaction. Of potential importance to these reactions is the affinity of methemoglobin for nitrite and the reactivity of nitrite-bound methemoglobin with nitric oxide. In this paper, we review work related to the electronic structure of nitrite-bound methemoglobin and its dissociation constant.

The levels of these factors regulate multiple events of the MBT, including the slowing of the cell cycle, the onset of zygotic transcription, and the developmental activation of the kinase Chk1. This work provides a mechanism for how the N/C ratio controls the MBT and shows that the

regulation of replication initiation is fundamental for normal embryogenesis.”
“Phosphorylated MAPK inhibitor O-mannosyl trisaccharide [N-acetylgalactosamine-beta 3-N-acetylglucosamine-beta 4-(phosphate-6-)mannose] is required for dystroglycan to bind laminin-G domain-containing extracellular proteins with high affinity in muscle and brain. However, the enzymes that produce this structure have not been fully elucidated. We found that glycosyltransferase-like domain-containing 2 (GTDC2) is a protein O-linked mannose beta 1,4-N-acetylglucosaminyltransferase

whose product could be extended by beta 1,3-N-acetylgalactosaminyltransferase2 (B3GALNT2) to form the O-mannosyl trisaccharide. Furthermore, we identified SGK196 as an atypical kinase that phosphorylated the 6-position selleck inhibitor of O-mannose, specifically after the mannose had been modified by both GTDC2 and B3GALNT2. These findings suggest how mutations in GTDC2, B3GALNT2, and SGK196 disrupt dystroglycan receptor function and lead to congenital muscular dystrophy.”
“Many studies have implicated a role for conformational motions during the catalytic cycle, acting to optimize the binding pocket or facilitate product release, but a more intimate role in the chemical reaction has not been described. We address this by monitoring active-site loop motion in two protein tyrosine phosphatases (PTPs) using nuclear magnetic resonance spectroscopy. The PTPs, YopH and PTP1B, have very different catalytic rates; however, we find in both that the active-site loop closes to its catalytically competent position at rates that mirror the phosphotyrosine cleavage kinetics. This loop contains the catalytic acid, suggesting that loop closure occurs concomitantly

through with the protonation of the leaving group tyrosine and explains the different kinetics of two otherwise chemically and mechanistically indistinguishable enzymes.”
“Retroviruses, including HIV, can activate innate immune responses, but the host sensors for retroviruses are largely unknown. Here we show that HIV infection activates cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein STING to induce type I interferons and other cytokines. Inhibitors of HIV reverse transcriptase, but not integrase, abrogated interferon-beta induction by the virus, suggesting that the reverse-transcribed HIV DNA triggers the innate immune response. Knockout or knockdown of cGAS in mouse or human cell lines blocked cytokine induction by HIV, murine leukemia virus, and simian immunodeficiency virus. These results indicate that cGAS is an innate immune sensor of HIV and other retroviruses.