Anomalous relaxation kinetics and charge density wave correlations in underdoped BaPb1-xBixO3

Superconductivity often emerges in proximity of other symmetry-breaking ground states, such as antiferromagnetism or charge-density-wave (CDW) order. However, the subtle inter-relation of these phases remains poorly understood, and in some cases even the existence of short-range correlations for superconducting compositions is uncertain. In such circumstances, ultrafast experiments can provide new insights, by tracking the relaxation kinetics following excitation at frequencies related to the broken symmetry state. Here, we investigate the transient terahertz conductivity of BaPb1-xBixO3 - a material for which superconductivity is adjacent to a competing CDW phase - after optical excitation tuned to the CDW absorption band. In insulating BaBiO3 we observed an increase in conductivity and a subsequent relaxation, which are consistent with quasiparticles injection across a rigid semiconducting gap. In the doped compound BaPb0.72Bi0.28O3 (superconducting below Tc=7K), a similar response was also found immediately above Tc. This observation evidences the presence of a robust gap up to T=40 K, which is presumably associated with short-range CDW correlations. A qualitatively different behaviour was observed in the same material fo T>40 K. Here, the photo-conductivity was dominated by an enhancement in carrier mobility at constant density, suggestive of melting of the CDW correlations rather than excitation across an optical gap. The relaxation displayed a temperature dependent, Arrhenius-like kinetics, suggestive of the crossing of a free-energy barrier between two phases. These results support the existence of short-range CDW correlations above Tc in underdoped BaPb1-xBixO3, and provide new information on the dynamical interplay between superconductivity and charge order.Comment: 19 pages, 4 figure

Optical properties of V2O3 in its whole phase diagram

Vanadium sesquioxide V2O3 is considered a textbook example of Mott-Hubbard physics. In this paper we present an extended optical study of its whole temperature/doping phase diagram as obtained by doping the pure material with M=Cr or Ti atoms (V1-xMx)2O3. We reveal that its thermodynamically stable metallic and insulating phases, although macroscopically equivalent, show very different low-energy electrodynamics. The Cr and Ti doping drastically change both the antiferromagnetic gap and the paramagnetic metallic properties. A slight chromium content induces a mesoscopic electronic phase separation, while the pure compound is characterized by short-lived quasiparticles at high temperature. This study thus provides a new comprehensive scenario of the Mott-Hubbard physics in the prototype compound V2O3

Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung

Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (R(i)) from 19 to 7 h and improved organ dysfunction with enhanced alveolar–capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (R(i); 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation

Cell cycle progression or translation control is not essential for vesicular stomatitis virus oncolysis of hepatocellular carcinoma.

The intrinsic oncolytic specificity of vesicular stomatitis virus (VSV) is currently being exploited to develop alternative therapeutic strategies for hepatocellular carcinoma (HCC). Identifying key regulators in diverse transduction pathways that define VSV oncolysis in cancer cells represents a fundamental prerequisite to engineering more effective oncolytic viral vectors and adjusting combination therapies. After having identified defects in the signalling cascade of type I interferon induction, responsible for attenuated antiviral responses in human HCC cell lines, we have now investigated the role of cell proliferation and translation initiation. Cell cycle progression and translation initiation factors eIF4E and eIF2Bepsilon have been recently identified as key regulators of VSV permissiveness in T-lymphocytes and immortalized mouse embryonic fibroblasts, respectively. Here, we show that in HCC, decrease of cell proliferation by cell cycle inhibitors or siRNA-mediated reduction of G(1) cyclin-dependent kinase activities (CDK4) or cyclin D1 protein expression, do not significantly alter viral growth. Additionally, we demonstrate that translation initiation factors eIF4E and eIF2Bepsilon are negligible in sustaining VSV replication in HCC. Taken together, these results indicate that cellular proliferation and the initiation phase of cellular protein synthesis are not essential for successful VSV oncolysis of HCC. Moreover, our observations indicate the importance of cell-type specificity for VSV oncolysis, an important aspect to be considered in virotherapy applications in the future

The upstream Variable Number Tandem Repeat polymorphism of the monoamine oxidase type A gene influences trigeminal pain-related evoked responses

Monoamines have an important role in neural plasticity, a key factor in cortical pain processing that promotes changes in neuronal network connectivity. Monoamine oxidase type A (MAOA) is an enzyme that, due to its modulating role in monoaminergic activity, could play a role in cortical pain processing. The X-linked MAOA gene is characterized by an allelic variant of length, the MAOA upstream Variable Number Tandem Repeat (MAOA-uVNTR) region polymorphism. Two allelic variants of this gene are known, the high-activity MAOA (HAM) and low-activity MAOA (LAM). We investigated the role of MAOA-uVNTR in cortical pain processing in a group of healthy individuals measured by the trigeminal electric pain-related evoked potential (tPREP) elicited by repeated painful stimulation. A group of healthy volunteers was genotyped to detect MAOA-uVNTR polymorphism. Electrical tPREPs were recorded by stimulating the right supraorbital nerve with a concentric electrode. The N2 and P2 component amplitude and latency as well as the N2-P2 inter-peak amplitude were measured. The recording was divided into three blocks, each containing 10 consecutive stimuli and the N2-P2 amplitude was compared between blocks. Of the 67 volunteers, 37 were HAM and 30 were LAM. HAM subjects differed from LAM subjects in terms of amplitude of the grand-averaged and first-block N2-P2 responses (HAM>LAM). The N2-P2 amplitude decreased between the first and third block in HAM subjects but not LAM subjects. The MAOA-uVNTR polymorphism seemed to influence the brain response in a repeated tPREP paradigm and suggested a role of the MAOA as a modulator of neural plasticity related to cortical pain processing

Delivery of sTRAIL variants by MSCs in combination with cytotoxic drug treatment leads to p53-independent enhanced antitumor effects

Mesenchymal stem cells (MSCs) are able to infiltrate tumor tissues and thereby effectively deliver gene therapeutic payloads. Here, we engineered murine MSCs (mMSCs) to express a secreted form of the TNF-related apoptosis-inducing ligand (TRAIL), which is a potent inducer of apoptosis in tumor cells, and tested these MSCs, termed MSC.sTRAIL, in combination with conventional chemotherapeutic drug treatment in colon cancer models. When we pretreated human colorectal cancer HCT116 cells with low doses of 5-fluorouracil (5-FU) and added MSC.sTRAIL, we found significantly increased apoptosis as compared with single-agent treatment. Moreover, HCT116 xenografts, which were cotreated with 5-FU and systemically delivered MSC.sTRAIL, went into remission. Noteworthy, this effect was protein 53 (p53) independent and was mediated by TRAIL-receptor 2 (TRAIL-R2) upregulation, demonstrating the applicability of this approach in p53-defective tumors. Consequently, when we generated MSCs that secreted TRAIL-R2-specific variants of soluble TRAIL (sTRAIL), we found that such engineered MSCs, labeled MSC.sTRAIL DR5, had enhanced antitumor activity in combination with 5-FU when compared with MSC.sTRAIL. In contrast, TRAIL-resistant pancreatic carcinoma PancTu1 cells responded better to MSC.sTRAIL DR4 when the antiapoptotic protein XIAP (X-linked inhibitor of apoptosis protein) was silenced concomitantly. Taken together, our results demonstrate that TRAIL-receptor selective variants can potentially enhance the therapeutic efficacy of MSC-delivered TRAIL as part of individualized and tumor-specific combination treatments. © 2013 Macmillan Publishers Limited All rights reserved

Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.

Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized. T-cell death in cultures of peripheral blood mononuclear cells (PBMC) showed 'classic' features of apoptosis following exposure to pneumococci. Conversely, purified CD3(+) T-cells cultured with pneumococci demonstrated necrosis with membrane permeabilization. The death of purified CD3(+) T-cells was not inhibited by necrostatin, but required the bacterial toxin pneumolysin. Apoptosis of CD3(+) T-cells in PBMC cultures required 'classical' CD14(+) monocytes, which enhanced T-cell activation. CD3(+) T-cell death was enhanced in HIV-seropositive individuals. Monocyte-mediated CD3(+) T-cell apoptotic death was Fas-dependent both in vitro and in vivo. In the early stages of the T-cell dependent host response to pneumococci reduced Fas ligand mediated T-cell apoptosis was associated with decreased bacterial clearance in the lung and increased bacteremia. In summary monocytes converted pathogen-associated necrosis into Fas-dependent apoptosis and regulated levels of activated T-cells at sites of acute bacterial infection. These changes were associated with enhanced bacterial clearance in the lung and reduced levels of invasive pneumococcal disease

Epidemiological situation of bovine brucellosis in the State of Bahia, Brazil

O trabalho consistiu em estratificar o Estado da Bahia em quatro regiões com características homogêneas (circuitos produtores) para que fossem amostradas aleatoriamente, em cada uma delas, 300 propriedades. Em cada propriedade foram escolhidas, de forma aleatória, 10 a 15 fêmeas bovinas adultas, das quais foi obtida uma amostra de sangue. No total, foram amostrados 10.816 animais, provenientes de 1.413 propriedades. O protocolo de testes utilizado foi o da triagem com o teste do antígeno acidificado tamponado (Rosa Bengala) e a confirmação dos positivos com o teste do 2-mercaptoetanol. O rebanho foi considerado positivo se pelo menos um animal reagiu às duas provas sorológicas. As prevalências de focos e a de fêmeas adultas soropositivas do Estado foram de 4,2% [3,1-5,3%] e 0,66% [0,41-0,93%], respectivamente. Para os circuitos produtores foram: circuito 1, 5,8% [3,6-8,7%] e 0,86% [0,41-1,3%]; circuito 2, 3,1% [1,5-5,6%] e 1,2% [0,25-2,1%]; circuito 3, 6,3% [4,0-9,3%] e 1,7% [0,66-2,7%]; e circuito 4, 0,60% [0,07-2,2%] e 0,07 [0,00-0,21%]. Para a análise de fatores de riscos associados à doença foi aplicado um questionário epidemiológico em cada propriedade visitada. Os fatores de risco (odds ratio, OR) associados à condição de foco foram: compra de reprodutores (OR= 2,27) e presença de áreas alagadiças (OR= 1,76). A vacinação de fêmeas de três até oito meses de idade foi um fator de proteção (OR= 0,53). ____________________________________________________________________________________________________________________ ABSTRACTA study to characterize the epidemiological situation of bovine brucellosis in the State of Bahia was carried out in 2004. The State was divided into four similar production regions, 300 herds were randomly sampled in each region, and 10 to 15 adult bovine females were sampled in each of these herds. A total of 10,816 serum samples from 1,413 herds were collected. The serum samples were screened for antibodies to Brucella spp. by the Rose-Bengal Test (RBT), and all RBT-positive sera were re-tested by the 2-mercaptoethanol test (2-ME) for confirmation. A herd was considered positive if at least one animal was positive on both RBT and 2-ME tests. The prevalence of infected herds and seropositive adult bovine females in Bahia State were: 4.2% [3.1-5.3%] and 0.66% [0.41-0.93%], respectively. In the production regions, prevalence of infected herds and animals were, respectively: region 1, 5.8% [3.6-8.7%] and 0.86% [0.41-1.3%]; region 2, 3.1% [1.5-5.6%] and 1.2% [0.25-2.1%]; region 3, 6.3% [4.0-9.3%] and 1.7% [0.66-2.7%]; and region 4, 0.60% [0.07-2.2%] and 0.07%[0.00-0.2%]. In each herd, an epidemiological questionnaire was applied. The risk factors (odds ratio, OR) associated with the presence of the infection were: purchase of breeding animals (OR = 2.27) and presence of flood areas (OR= 1.76). Vaccination of heifers from three to eight months of age was a protective factor (OR=0.53)

Epidemiologic situation of bovine brucellosis in the State of Mato Grosso, Brazil

Caracterizou-se a brucelose bovina em Mato Grosso por meio de um estudo transversal realizado em 2003 para auxiliar na implementação do Programa Nacional de Controle e Erradicação da Brucelose e Tuberculose. No Estado, estratificado em quatro circuitos pecuários, foram amostrados 13.684 animais, provenientes de 1.152 rebanhos. O protocolo de testes utilizado foi o da triagem com o teste do antígeno acidificado tamponado e os soros reagentes foram testados pelo 2-mercaptoetanol (ME) e concomitantemente retestados pelo teste de Rosa Bengala para resultado conclusivo. As prevalências de focos e de animais infectados foram: 41,2% [38,0-44,4%] e 10,2% [7,4-13,1%], respectivamente. Nos circuitos produtivos, as prevalências de focos foram 36,9% [29,2-45,2%], 27,2% [22,8-32,1%], 40,4% [38,8-46,2%] e 50,3% [44,5-56,1%]; e as prevalências de animais 7,9% [3,0-12,9%], 4,1% [2,8-5,4%], 8,1% [5,2-11,1%] e 15,3% [9,2-21,3%], respectivamente, para os circuitos 1, 2, 3 e 4. Os fatores de risco (odds ratio, OR) associados à condição de foco no Estado foram: exploração de gado de corte (OR= 1,8 [1,2-2,5]), exploração mista (OR=1,8 [1,2-2,7]), número de fêmeas no rebanho de 11 a 50 (OR=4,8 [1,1-20,8]), número de fêmeas no rebanho acima de 51 (OR=6,8 [1,6-29,0]), ocorrência de aborto (OR=1,7 [1,3-2,2]). A brucelose está homogeneamente distribuída no Estado, o que permite uniformidade de medidas sanitárias. Adicionalmente, sugere-se a intensificação da vacinação de fêmeas para todo o Estado. _______________________________________________________________________________________________________ ABSTRACTA study to characterize bovine brucellosis in the State of Mato Grosso was carried out in 2003 in order to support the implementation of the National Program for the Control and Eradication of Bovine Brucellosis. The State was divided into four productive regions, and 13,684 bovines from 1,152 herds were sampled. The serum samples were screened for antibodies to Brucella spp. by the Rose-Bengal test (RBT) and all RBT-positive sera were re-tested by the 2-mercaptoethanol test (2-ME), and again by RBT for confirmation. The prevalence of infected herds and animals in the State of Mato Grosso were 41.2% [38.0-44.4%] and 10.2% [7.4-13.1%], respectively. In the productive regions, the prevalence of infected herds were 36.9% [29.2-45.2%], 27.2% [22.8-32.1%], 40.4% [38.8-46.2%], and 50.3% [44.5-56.1%], respectively; and the prevalence of infected animals were 7.9% [3.0-12.9%], 4.1% [2.8-5.4%], 8.1% [5.2-11.1%], and 15.3% [9.2-21.3%], respectively, for regions 1, 2, 3, and 4. The risk factors (odds ratio, OR) associated with the presence of the infection in the State were: beef cattle farming (OR=1.8 [1.2-2.5]), mixed (beef and dairy) cattle farming (OR=1.8 [1.2-2.7]), farms with 11 to 50 females (OR=4.8 [1.1-20.8]), farms with more than 51 females (OR=6.8 [1.6-29.0]), and occurrence of abortion (OR=1.7 [1.3-2.2]). Given that brucellosis is homogeneously distributed in the State, uniform sanitary measures might be adopted. As a homogeneous additional measure for the State, the intensification of female vaccination is suggested

Asymmetric triplex metallohelices with high and selective activity against cancer cells

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and ​p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 ​p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli. At a glanc