Once more on the Witten index of 3d supersymmetric YM-CS theory

The problem of counting the vacuum states in the supersymmetric 3d Yang-Mills-Chern-Simons theory is reconsidered. We resolve the controversy between its original calculation by Witten at large volumes and the calculation based on the evaluation of the effective Lagrangian in the small volume limit. We show that the latter calculation suffers from uncertainties associated with the singularities in the moduli space of classical vacua where the Born-Oppenheimer approximation breaks down. We also show that these singularities can be accurately treated in the Hamiltonian Born-Oppenheimer method, where one has to match carefully the effective wave functions on the Abelian valley and the wave functions of reduced non-Abelian QM theory near the singularities. This gives the same result as original Witten's calculation.Comment: 27 page

Caspase-2 is upregulated after sciatic nerve transection and its inhibition protects dorsal root ganglion neurons from Apoptosis after serum withdrawal

Sciatic nerve (SN) transection-induced apoptosis of dorsal root ganglion neurons (DRGN) is one factor determining the efficacy of peripheral axonal regeneration and the return of sensation. Here, we tested the hypothesis that caspase-2(CASP2) orchestrates apoptosis of axotomised DRGN both in vivo and in vitro by disrupting the local neurotrophic supply to DRGN. We observed significantly elevated levels of cleaved CASP2 (C-CASP2), compared to cleaved caspase-3 (C-CASP3), within TUNEL+DRGN and DRG glia (satellite and Schwann cells) after SN transection. A serum withdrawal cell culture model, which induced 40% apoptotic death in DRGN and 60% in glia, was used to model DRGN loss after neurotrophic factor withdrawal. Elevated C-CASP2 and TUNEL were observed in both DRGN and DRG glia, with C-CASP2 localisation shifting from the cytosol to the nucleus, a required step for induction of direct CASP2-mediated apoptosis. Furthermore, siRNAmediated downregulation of CASP2 protected 50% of DRGN from apoptosis after serum withdrawal, while downregulation of CASP3 had no effect on DRGN or DRG glia survival. We conclude that CASP2 orchestrates the death of SN-axotomised DRGN directly and also indirectly through loss of DRG glia and their local neurotrophic factor support. Accordingly, inhibiting CASP2 expression is a potential therapy for improving both the SN regeneration response and peripheral sensory recovery

Analytic Continuation of Liouville Theory

Correlation functions in Liouville theory are meromorphic functions of the Liouville momenta, as is shown explicitly by the DOZZ formula for the three-point function on the sphere. In a certain physical region, where a real classical solution exists, the semiclassical limit of the DOZZ formula is known to agree with what one would expect from the action of the classical solution. In this paper, we ask what happens outside of this physical region. Perhaps surprisingly we find that, while in some range of the Liouville momenta the semiclassical limit is associated to complex saddle points, in general Liouville's equations do not have enough complex-valued solutions to account for the semiclassical behavior. For a full picture, we either must include "solutions" of Liouville's equations in which the Liouville field is multivalued (as well as being complex-valued), or else we can reformulate Liouville theory as a Chern-Simons theory in three dimensions, in which the requisite solutions exist in a more conventional sense. We also study the case of "timelike" Liouville theory, where we show that a proposal of Al. B. Zamolodchikov for the exact three-point function on the sphere can be computed by the original Liouville path integral evaluated on a new integration cycle.Comment: 86 pages plus appendices, 9 figures, minor typos fixed, references added, more discussion of the literature adde

Hypoxia increases neutrophil-driven matrix destruction after exposure to Mycobacterium tuberculosis.

The importance of neutrophils in the pathology of tuberculosis (TB) has been recently established. We demonstrated that TB lesions in man are hypoxic, but how neutrophils in hypoxia influence lung tissue damage is unknown. We investigated the effect of hypoxia on neutrophil-derived enzymes and tissue destruction in TB. Human neutrophils were stimulated with M. tuberculosis (M.tb) or conditioned media from M.tb-infected monocytes (CoMTB). Neutrophil matrix metalloproteinase-8/-9 and elastase secretion were analysed by luminex array and gelatin zymography, gene expression by qPCR and cell viability by flow cytometry. Matrix destruction was investigated by confocal microscopy and functional assays and neutrophil extracellular traps (NETs) by fluorescence assay. In hypoxia, neutrophil MMP-8 secretion and gene expression were up-regulated by CoMTB. MMP-9 activity and neutrophil elastase (NE) secretion were also increased in hypoxia. Hypoxia inhibited NET formation and both neutrophil apoptosis and necrosis after direct stimulation by M.tb. Hypoxia increased TB-dependent neutrophil-mediated matrix destruction of Type I collagen, gelatin and elastin, the main structural proteins of the human lung. Dimethyloxalylglycin (DMOG), which stabilizes hypoxia-inducible factor-1α, increased neutrophil MMP-8 and -9 secretion. Hypoxia in our cellular model of TB up-regulated pathways that increase neutrophil secretion of MMPs that are implicated in matrix destruction

Dietary soy and meat proteins induce distinct physiological and gene expression changes in rats

This study reports on a comprehensive comparison of the effects of soy and meat proteins given at the recommended level on physiological markers of metabolic syndrome and the hepatic transcriptome. Male rats were fed semi-synthetic diets for 1 wk that differed only regarding protein source, with casein serving as reference. Body weight gain and adipose tissue mass were significantly reduced by soy but not meat proteins. The insulin resistance index was improved by soy, and to a lesser extent by meat proteins. Liver triacylglycerol contents were reduced by both protein sources, which coincided with increased plasma triacylglycerol concentrations. Both soy and meat proteins changed plasma amino acid patterns. The expression of 1571 and 1369 genes were altered by soy and meat proteins respectively. Functional classification revealed that lipid, energy and amino acid metabolic pathways, as well as insulin signaling pathways were regulated differently by soy and meat proteins. Several transcriptional regulators, including NFE2L2, ATF4, Srebf1 and Rictor were identified as potential key upstream regulators. These results suggest that soy and meat proteins induce distinct physiological and gene expression responses in rats and provide novel evidence and suggestions for the health effects of different protein sources in human diets

Effects of Intracoronary Alteplase on Microvascular Function in Acute Myocardial Infarction

Background—Impaired microcirculatory reperfusion worsens prognosis following acute ST‐segment–elevation myocardial infarction. In the T‐TIME (A Trial of Low‐Dose Adjunctive Alteplase During Primary PCI) trial, microvascular obstruction on cardiovascular magnetic resonance imaging did not differ with adjunctive, low‐dose, intracoronary alteplase (10 or 20 mg) versus placebo during primary percutaneous coronary intervention. We evaluated the effects of intracoronary alteplase, during primary percutaneous coronary intervention, on the index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio. Methods and Results—A prespecified physiology substudy of the T‐TIME trial. From 2016 to 2017, patients with ST‐segment–elevation myocardial infarction ≤6 hours from symptom onset were randomized in a double‐blind study to receive alteplase 20 mg, alteplase 10 mg, or placebo infused into the culprit artery postreperfusion, but prestenting. Index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio were measured after percutaneous coronary intervention. Cardiovascular magnetic resonance was performed at 2 to 7 days and 3 months. Analyses in relation to ischemic time (<2, 2–4, and ≥4 hours) were prespecified. One hundred forty‐four patients (mean age, 59±11 years; 80% male) were prospectively enrolled, representing 33% of the overall population (n=440). Overall, index of microcirculatory resistance (median, 29.5; interquartile range, 17.0–55.0), coronary flow reserve(1.4 [1.1–2.0]), and resistive reserve ratio (1.7 [1.3–2.3]) at the end of percutaneous coronary intervention did not differ between treatment groups. Interactions were observed between ischemic time and alteplase for coronary flow reserve (P=0.013), resistive reserve ratio (P=0.026), and microvascular obstruction (P=0.022), but not index of microcirculatory resistance. Conclusions—In ST‐segment–elevation myocardial infarction with ischemic time ≤6 hours, there was overall no difference in microvascular function with alteplase versus placebo

Apoptosis-Like Death in Bacteria Induced by HAMLET, a Human Milk Lipid-Protein Complex

Background: Apoptosis is the primary means for eliminating unwanted cells in multicellular organisms in order to preserve tissue homeostasis and function. It is characterized by distinct changes in the morphology of the dying cell that are orchestrated by a series of discrete biochemical events. Although there is evidence of primitive forms of programmed cell death also in prokaryotes, no information is available to suggest that prokaryotic death displays mechanistic similarities to the highly regulated programmed death of eukaryotic cells. In this study we compared the characteristics of tumor and bacterial cell death induced by HAMLET, a human milk complex of alpha-lactalbumin and oleic acid. Methodology/Principal Findings: We show that HAMLET-treated bacteria undergo cell death with mechanistic and morphologic similarities to apoptotic death of tumor cells. In Jurkat cells and Streptococcus pneumoniae death was accompanied by apoptosis-like morphology such as cell shrinkage, DNA condensation, and DNA degradation into high molecular weight fragments of similar sizes, detected by field inverse gel electrophoresis. HAMLET was internalized into tumor cells and associated with mitochondria, causing a rapid depolarization of the mitochondrial membrane and bound to and induced depolarization of the pneumococcal membrane with similar kinetic and magnitude as in mitochondria. Membrane depolarization in both systems required calcium transport, and both tumor cells and bacteria were found to require serine protease activity (but not caspase activity) to execute cell death. Conclusions/Significance: Our results suggest that many of the morphological changes and biochemical responses associated with apoptosis are present in prokaryotes. Identifying the mechanisms of bacterial cell death has the potential to reveal novel targets for future antimicrobial therapy and to further our understanding of core activation mechanisms of cell death in eukaryote cells

Health service use in indigenous Sami and non-indigenous youth in North Norway: A population based survey

<p>Abstract</p> <p>Background</p> <p>This is the first population based study exploring health service use and ethno-cultural factors in indigenous Sami and non-Sami youth in North Norway. The first aim of the present study was to compare the frequency of health service use between Sami adolescents and their non-indigenous peers. The second aim was to explore the relationships between health service use and ethno-cultural factors, such as ethnic context, Sami self-identification, perceived discrimination and Sami language competence. Finally, we wanted to explore the relationship between use of health services and emotional and behavioural problems.</p> <p>Method</p> <p>The Norwegian Arctic Adolescent Health Study was conducted among 10th graders (15-16 years old) in junior high schools in North Norway. The sample consisted of 4,449 adolescents, of whom 450 (10.1%) were indigenous Sami and 3,999 (89.9%) were non-Sami.</p> <p>Results</p> <p>Sami and non-Sami youth used all health services with equal frequency. However, several ethno-cultural factors were found to influence health service use. Sami youth in more assimilated ethnic contexts used general practitioners more than non-Sami youth. Youth with Sami self-identification had a higher probability of using the school health service compared with other youth. Ethnic barriers to health service use were also identified. Sami speaking youth with a high degree of perceived discrimination had lower probability of using school health services than non-Sami speaking youth. Sami youth with conduct problems were less likely than non-Sami to use psychologist/psychiatrist. The present study demonstrated a relationship between health need and actual health service use.</p> <p>Conclusion</p> <p>Culture-specific factors influenced the help-seeking process in indigenous youth; some factors acted as barriers against health service use and other factors increased the probability of health service use.</p