Loop formulation of the supersymmetric nonlinear O(N) sigma model

We derive the fermion loop formulation for the supersymmetric nonlinear O(N) sigma model by performing a hopping expansion using Wilson fermions. In this formulation the fermionic contribution to the partition function becomes a sum over all possible closed non-oriented fermion loop configurations. The interaction between the bosonic and fermionic degrees of freedom is encoded in the constraints arising from the supersymmetry and induces flavour changing fermion loops. For N ≥ 3 this leads to fermion loops which are no longer self-avoiding and hence to a potential sign problem. Since we use Wilson fermions the bare mass needs to be tuned to the chiral point. For N = 2 we determine the critical point and present boson and fermion masses in the critical regime.

Trypanosoma brucei RRM1 is a nuclear RNA-binding protein and modulator of chromatin structure

TbRRM1 of Trypanosoma brucei is a nucleoprotein that was previously identified in a search for splicing factors in T. brucei. We show that TbRRM1 associates with mRNAs and with the auxiliary splicing factor polypyrimidine tract-binding protein 2, but not with components of the core spliceosome. TbRRM1 also interacts with several retrotransposon hot spot (RHS) proteins and histones. RNA immunoprecipitation of a tagged form of TbRRM1 from procyclic (insect) form trypanosomes identified ca. 1,500 transcripts that were enriched and 3,000 transcripts that were underrepresented compared to cellular mRNA. Enriched transcripts encoded RNA-binding proteins, including TbRRM1 itself, several RHS transcripts, mRNAs with long coding regions, and a high proportion of stage-regulated mRNAs that are more highly expressed in bloodstream forms. Transcripts encoding ribosomal proteins, other factors involved in translation, and procyclic-specific transcripts were underrepresented. Knockdown of TbRRM1 by RNA interference caused widespread changes in mRNA abundance, but these changes did not correlate with the binding of the protein to transcripts, and most splice sites were unchanged, negating a general role for TbRRM1 in splice site selection. When changes in mRNA abundance were mapped across the genome, regions with many downregulated mRNAs were identified. Two regions were analyzed by chromatin immunoprecipitation, both of which exhibited increases in nucleosome occupancy upon TbRRM1 depletion. In addition, subjecting cells to heat shock resulted in translocation of TbRRM1 to the cytoplasm and compaction of chromatin, consistent with a second role for TbRRM1 in modulating chromatin structure. IMPORTANCE: Trypanosoma brucei, the parasite that causes human sleeping sickness, is transmitted by tsetse flies. The parasite progresses through different life cycle stages in its two hosts, altering its pattern of gene expression in the process. In trypanosomes, protein-coding genes are organized as polycistronic units that are processed into monocistronic mRNAs. Since genes in the same unit can be regulated independently of each other, it is believed that gene regulation is essentially posttranscriptional. In this study, we investigated the role of a nuclear RNA-binding protein, TbRRM1, in the insect stage of the parasite. We found that TbRRM1 binds nuclear mRNAs and also affects chromatin status. Reduction of nuclear TbRRM1 by RNA interference or heat shock resulted in chromatin compaction. We propose that TbRRM1 regulates RNA polymerase II-driven gene expression both cotranscriptionally, by facilitating transcription and efficient splicing, and posttranscriptionally, via its interaction with nuclear mRNAs.

The Rice Transcription Factor WRKY53 Suppresses Herbivore-Induced Defenses by Acting as a Negative Feedback Modulator of Mitogen-Activated Protein Kinase Activity

The mechanisms by which herbivore-attacked plants activate their defenses are well studied. By contrast, little is known about the regulatory mechanisms that allow them to control their defensive investment and avoid a defensive overshoot. We characterized a rice (Oryza sativa) WRKY gene, OsWRKY53, whose expression is rapidly induced upon wounding and induced in a delayed fashion upon attack by the striped stem borer (SSB) Chilo suppressalis. The transcript levels of OsWRKY53 are independent of endogenous jasmonic acid but positively regulated by the mitogen-activated protein kinases OsMPK3/OsMPK6. OsWRKY53 physically interacts with OsMPK3/OsMPK6 and suppresses their activity in vitro. By consequence, it modulates the expression of defensive, MPK-regulated WRKYs and thereby reduces jasmonic acid, jasmonoyl-isoleucine, and ethylene induction. This phytohormonal reconfiguration is associated with a reduction in trypsin protease inhibitor activity and improved SSB performance. OsWRKY53 is also shown to be a negative regulator of plant growth. Taken together, these results show that OsWRKY53 functions as a negative feedback modulator of MPK3/MPK6 and thereby acts as an early suppressor of induced defenses. OsWRKY53 therefore enables rice plants to control the magnitude of their defensive investment during early signaling.

Intravenous Delta-9-Tetrahydrocannabinol to Prevent Postoperative Nausea and Vomiting: A Randomized Controlled Trial.

BACKGROUND Evidence suggests that cannabinoids can prevent chemotherapy-induced nausea and vomiting. The use of tetrahydrocannabinol (THC) has also been suggested for the prevention of postoperative nausea and vomiting (PONV), but evidence is very limited and inconclusive. To evaluate the effectiveness of IV THC in the prevention of PONV, we performed this double-blind, randomized, placebo-controlled trial with patient stratification according to the risk of PONV. Our hypothesis was that THC would reduce the relative risk of PONV by 25% compared with placebo. METHODS With IRB approval and written informed consent, 40 patients at high risk for PONV received either 0.125 mg/kg IV THC or placebo at the end of surgery before emergence from anesthesia. The primary outcome parameter was PONV during the first 24 hours after emergence. Secondary outcome parameters included early and late nausea, emetic episodes and PONV, and side effects such as sedation or psychotropic alterations. RESULTS The relative risk reduction of overall PONV in the THC group was 12% (95% confidence interval, -37% to 43%), potentially less than the clinically significant 25% relative risk reduction demonstrated by other drugs used for PONV prophylaxis. Calculation of the effect of treatment group on overall PONV by logistic regression adjusted for anesthesia time gave an odds ratio of 0.97 (95% confidence interval, 0.21 to 4.43, P = 0.97). Psychotropic THC side effects were clinically relevant and mainly consisted of sedation and confusion that were not tampered by the effects of anesthesia. The study was discontinued after 40 patients because of the inefficacy of THC against PONV and the finding of clinically unacceptable side effects that would impede the use of THC in the studied setting. CONCLUSIONS Because of an unacceptable side effect profile and uncertain antiemetic effects, IV THC administered at the end of surgery before emergence from anesthesia cannot be recommended for the prevention of PONV in high-risk patients.

T Cell Motility as Modulator of Interactions with Dendritic Cells

It is well established that the balance of costimulatory and inhibitory signals during interactions with dendritic cells (DCs) determines T cell transition from a naïve to an activated or tolerant/anergic status. Although many of these molecular interactions are well reproduced in reductionist in vitro assays, the highly dynamic motility of naïve T cells in lymphoid tissue acts as an additional lever to fine-tune their activation threshold. T cell detachment from DCs providing suboptimal stimulation allows them to search for DCs with higher levels of stimulatory signals, while storing a transient memory of short encounters. In turn, adhesion of weakly reactive T cells to DCs presenting peptides presented on major histocompatibility complex with low affinity is prevented by lipid mediators. Finally, controlled recruitment of CD8(+) T cells to cognate DC-CD4(+) T cell clusters shapes memory T cell formation and the quality of the immune response. Dynamic physiological lymphocyte motility therefore constitutes a mechanism to mitigate low avidity T cell activation and to improve the search for "optimal" DCs, while contributing to peripheral tolerance induction in the absence of inflammation.

Absence of Hepatitis Delta Infection in a Large Rural HIV Cohort in Tanzania

OBJECTIVES The epidemiological and clinical determinants of hepatitis delta virus (HDV) infection in sub-Saharan Africa are ill-defined. We determined the prevalence of HDV infection in HIV/hepatitis B virus (HBV)-co-infected individuals in rural Tanzania. DESIGN AND METHODS We screened all hepatitis B virus (HBV)-infected adults under active follow-up in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) for anti-HDV antibodies. In positive samples, we performed a second serological test and nucleic acid amplification. Demographic and clinical characteristics at initiation of antiretroviral therapy (ART) were compared between anti-HDV-negative and positive patients. RESULTS Among 222 HIV/HBV-coinfected patients on ART, 219 (98.6%) had a stored serum sample available and were included. Median age was 37 years, 55% were female, 46% had WHO stage III/IV HIV disease and median CD4 count was 179 cells/μL. The prevalence of anti-HDV positivity was 5.0% (95% confidence interval 2.8%-8.9%). There was no significant predictor of anti-HDV positivity. HDV could not be amplified in any of the anti-HDV-positive patients and the second serological test was negative in all of them. CONCLUSIONS We found no confirmed case of HDV infection among over 200 HIV/HBV-co-infected patients in Tanzania. As false-positive serology results are common, screening results should be confirmed with a second test.

Extracellular Iron is a Modulator of the Differentiation of Osteoclast Lineage Cells.

Osteoclasts originate from the hematopoietic stem cell and share a differentiation pathway with the cells of the monocyte/macrophage lineages. Development and activation of osteoclasts, and as a consequence regulation of bone resorption, depend on two growth factors: macrophage colony-stimulating factor and receptor activator of NF-κB ligand. Furthermore, cell development and activity are modulated by a microenvironment composed of cytokines and growth factors and of the extracellular matrix. Membrane transporters are a means for cells to interact with their environment. Within this study, the expression of proteins regulating cellular iron homeostasis in osteoclast-like cells grown from bone marrow-derived progenitors was compared to the expression of this set of proteins by monocyte/macrophage lineage cells. In differentiating osteoclasts, levels of transcripts encoding transferrin receptor 1 and divalent metal transporter 1 (Slc11A2) were increased, while levels of transcripts encoding ferroportin (Slc40A1) and natural resistance-associated macrophage protein 1 (Slc11A1) were decreased. Supplementation of the culture media with exogenous iron led to an increase in the proliferation of osteoclast progenitor cells and to the expression of a macrophage-like phenotype, while the development of osteoclasts was reduced. Upon transfer of mature OC onto a CaP substrate, iron depletion of the medium with the Fe(3+)-chelator Deferoxamine Mesylate decreased CaP dissolution by ~30 %, which could be restored by addition of exogenous iron. During the 24 h of the assay, no effects were observed on total TRAP activity. The data demonstrate transcriptional regulation of the components of cellular iron transporters during OC development and suggests that iron homeostasis may contribute to fine-tuning of the RANKL-induced OC development.

Characterization of fetal antigen 1/delta-like 1 homologue expressing cells in the rat nigrostriatal system: effects of a unilateral 6-hydroxydopamine lesion.

Fetal antigen 1/delta-like 1 homologue (FA1/dlk1) belongs to the epidermal growth factor superfamily and is considered to be a non-canonical ligand for the Notch receptor. Interactions between Notch and its ligands are crucial for the development of various tissues. Moreover, FA1/dlk1 has been suggested as a potential supplementary marker of dopaminergic neurons. The present study aimed at investigating the distribution of FA1/dlk1-immunoreactive (-ir) cells in the early postnatal and adult midbrain as well as in the nigrostriatal system of 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian adult rats. FA1/dlk1-ir cells were predominantly distributed in the substantia nigra (SN) pars compacta (SNc) and in the ventral tegmental area. Interestingly, the expression of FA1/dlk1 significantly increased in tyrosine hydroxylase (TH)-ir cells during early postnatal development. Co-localization and tracing studies demonstrated that FA1/dlk1-ir cells in the SNc were nigrostriatal dopaminergic neurons, and unilateral 6-OHDA lesions resulted in loss of both FA1/dlk1-ir and TH-ir cells in the SNc. Surprisingly, increased numbers of FA1/dlk1-ir cells (by 70%) were detected in dopamine-depleted striata as compared to unlesioned controls. The higher number of FA1/dlk1-ir cells was likely not due to neurogenesis as colocalization studies for proliferation markers were negative. This suggests that FA1/dlk1 was up-regulated in intrinsic cells in response to the 6-OHDA-mediated loss of FA1/dlk1-expressing SNc dopaminergic neurons and/or due to the stab wound. Our findings hint to a significant role of FA1/dlk1 in the SNc during early postnatal development. The differential expression of FA1/dlk1 in the SNc and the striatum of dopamine-depleted rats could indicate a potential involvement of FA1/dlk1 in the cellular response to the degenerative processes.

Twentieth Century Delta δC Variability in Surface Water Dissolved Inorganic Carbon Recorded by Coralline Algae in the Northern North Pacific Ocean and the Bering Sea

The oxygen isotopic composition and Mg/Ca ratios in the skeletons of long-lived coralline algae record ambient seawater temperature over time. Similarly, the carbon isotopic composition in the skeletons record delta(13)C values of ambient seawater dissolved inorganic carbon. Here, we measured delta(13)C in the coralline alga Clathromorphum nereostratum to test the feasibility of reconstructing the intrusion of anthropogenic CO(2) into the northern North Pacific Ocean and Bering Sea. The delta(13)C was measured in the high Mgcalcite skeleton of three C. nereostratum specimens from two islands 500 km apart in the Aleutian archipelago. In the records spanning 1887 to 2003, the average decadal rate of decline in delta(13)C values increased from 0.03% yr(-1) in the 1960s to 0.095% yr(-1) in the 1990s, which was higher than expected due to solely the delta(13)C-Suess effect. Deeper water in this region exhibits higher concentrations of CO(2) and low delta(13)C values. Transport of deeper water into surface water (i.e., upwelling) increases when the Aleutian Low is intensified. We hypothesized that the acceleration of the delta(13)C decline may result from increased upwelling from the 1960s to 1990s, which in turn was driven by increased intensity of the Aleutian Low. Detrended delta(13)C records also varied on 4-7 year and bidecadal timescales supporting an atmospheric teleconnection of tropical climate patterns to the northern North Pacific Ocean and Bering Sea manifested as changes in upwelling.

Understanding Molecular Orbitals; Sigma Orbitals

Various plots of sigma molecular orbitals in diatomic molecules are discussed.