bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the interaction between a SirR family transcriptional factor of Mycobacterium tuberculosis, encoded by Rv2788, and a pair of toxin–antitoxin proteins RelJ/K, encoded by Rv3357 and Rv3358
Authors: Yang Min , Gao Chun‐Hui , Hu Jialing , Dong Chao , He Zheng‐Guo 
Published: April 2014

Toxin–antitoxin (TA) systems play significant roles in the regulation of bacterial growth and persistence, and their functions usually depend on protein–protein interaction between their constituent TA proteins. However, the regulatory mechanisms of these systems, particularly their interaction with other cellular components, are still poorly understood. This study investigated cross‐talk between the TA module RelJ/K (Rv3357/Rv3358) and the transcriptional regulator staphylococcal iron regulator repressor (SirR, Rv2788) from Mycobacterium tuberculosis. We characterized the physical interaction of SirR with both RelJ and RelK using bacterial two‐hybrid, pull‐down and co‐immunoprecipitation assays. Similarly to RelK, SirR regulates the DNA‐binding activity of RelJ and alleviates its inhibitory effect on the activity of the Rv3357p promoter. Furthermore, SirR may replace RelJ to alleviate the inhibitory effect of the toxin RelK on bacterial growth. Conversely, both RelJ and RelK competitively inhibit the interaction between SirR and their respective promoters. Thus, our results show that SirR interacts with a pair of toxin and antitoxin proteins, and exhibits antitoxin‐like function to neutralize the toxin. These findings demonstrate a novel function of the SirR regulator of M. tuberculosis as well as a novel mechanism of regulation of TA systems.Structured digital abstract

SirR binds to RelJ by pull down (view interaction)

SirR binds to RelK by pull down (view interaction)

RelJ physically interacts with RelK by anti bait coimmunoprecipitation (1, 2)

SirR physically interacts with RelK by anti bait coimmunoprecipitation (view interaction)

SirR physically interacts with RelJ by anti bait coimmunoprecipitation (view interaction)

RelJ and SirR physically interact by two-hybrid (view interaction)

SirR and RelK physically interact by two-hybrid (view interaction)

RelK and RelJ physically interact by two-hybrid (view interaction)
Vigilin interacts with CCCTC‐binding factor (CTCF) and is involved in CTCF‐dependent regulation of the imprinted genes Igf2 and H19
Authors: Liu Qiuying , Yang Bo , Xie Xiaoyan , Wei Ling , Liu Wenquan , Yang Wenli , Ge Yajun , Zhu Qiang , Zhang Junzhe , Jiang Lei , Yu Xiaoqin , Shen Wenyan , Li Ran , Shi Xuejiao , Li Bo , Qin Yang 
Published: April 2014

CCCTC‐binding factor (CTCF), a highly conserved zinc finger protein, is a master organizer of genome spatial organization and has multiple functions in gene regulation. Mounting evidence indicates that CTCF regulates the imprinted genes Igf2 and H19 by organizing chromatin at the Igf2/H19 locus, although the mechanism by which CTCF carries out this function is not fully understood. By yeast two‐hybrid screening, we identified vigilin, a multi‐KH‐domain protein, as a new partner of CTCF. Subsequent coimmunoprecipitation and glutathione S‐transferase pulldown experiments confirmed that vigilin interacts with CTCF. Moreover, vigilin is present at several known CTCF target sites, such as the promoter regions of c‐myc and BRCA1, the locus control region of β‐globin, and several regions within the Igf2/H19 locus. In vivo depletion of vigilin did not affect CTCF binding; however, knockdown of CTCF reduced vigilin binding to the H19 imprinting control region. Furthermore, ectopic expression of vigilin significantly downregulated Igf2 and upregulated H19, whereas depletion of vigilin upregulated Igf2 and downregulated H19, in HepG2, CNE1 and HeLa cells. These results reveal the functional relevance of vigilin and CTCF, and show that the CTCF–vigilin complex contributes to regulation of Igf2/H19.Structured digital abstract

CTCF physically interacts with Vigilin by two hybrid (View interaction)

CTCF physically interacts with L31 by two hybrid (View interaction)

CTCF physically interacts with CHD1L by two hybrid (View interaction)

CTCF physically interacts with Ral A by two hybrid (View interaction)

CTCF physically interacts with DDX17 by two hybrid (View interaction)

CTCF physically interacts with ND4 by two hybrid (View interaction)

CTCF physically interacts with Vigilin by pull down (View interaction)

CTCF physically interacts with Vigilin by anti bait coimmunoprecipitation (1, 2)
Cu(II) and dopamine bind to α‐synuclein and cause large conformational changes
Authors: Tavassoly Omid , Nokhrin Sergiy , Dmitriev Oleg Y. , Lee Jeremy S. 
Published: April 2014

α‐Synuclein (AS) is an intrinsically disordered protein that can misfold and aggregate to form Lewy bodies in dopaminergic neurons, a classic hallmark of Parkinson's disease. The binding of Cu(II) and dopamine to AS was evaluated by nanopore analysis with α‐hemolysin. In the absence of Cu(II), wild‐type AS (1 μm) readily translocated through the pore with a blockade current of − 85 pA, but mostly bumping events were observed in the presence of 25 μm Cu(II). A binding site in the N‐terminus was confirmed, because Cu(II) had no effect on the event profile of a peptide consisting of the C‐terminal 96–140 residues. In the presence of dopamine (25 μm), the translocation events at − 85 pA shifted to − 80 pA, which also represents translocation events, because the event time decreases with increasing voltage. Events at − 80 pA were also observed for the mutant A30P AS in the presence of dopamine. Event profiles for an N‐terminal 1–60‐residue peptide and a C‐terminal 96–140‐residue peptide were both altered in the presence of 25 μm dopamine. In contrast, dopamine had little effect on the CD spectrum of AS, and a single binding site with a Ka of 3.5 × 103 m−1 was estimated by isothermal titration calorimetry. Thus, dopamine can interact with both the N‐terminus and the C‐terminus. Two‐dimensional NMR spectroscopy of AS in the presence of dopamine showed that there were significant changes in the spectra in all regions of the protein. According to these findings, a model is presented in which dopamine induces folding between the N‐terminus and C‐terminus of AS. Partially folding conformations such as this may represent important intermediates in the misfolding of AS that leads to fibrillization.
Barite in hydrothermal environments as a recorder of subseafloor processes: a multiple‐isotope study from the Loki's Castle vent field
Authors: Eickmann B. , Thorseth I. H. , Peters M. , Strauss H. , Bröcker M. , Pedersen R. B. 
Published: April 2014

AbstractBarite chimneys are known to form in hydrothermal systems where barium‐enriched fluids generated by leaching of the oceanic basement are discharged and react with seawater sulfate. They also form at cold seeps along continental margins, where marine (or pelagic) barite in the sediments is remobilized because of subseafloor microbial sulfate reduction. We test the possibility of using multiple sulfur isotopes (δ34S, Δ33S, ∆36S) of barite to identify microbial sulfate reduction in a hydrothermal system. In addition to multiple sulfur isotopes, we present oxygen (δ18O) and strontium (87Sr/86Sr) isotopes for one of numerous barite chimneys in a low‐temperature (~20 °C) venting area of the Loki's Castle black smoker field at the ultraslow‐spreading Arctic Mid‐Ocean Ridge (AMOR). The chemistry of the venting fluids in the barite field identifies a contribution of at least 10% of high‐temperature black smoker fluid, which is corroborated by 87Sr/86Sr ratios in the barite chimney that are less radiogenic than in seawater. In contrast, oxygen and multiple sulfur isotopes indicate that the fluid from which the barite precipitated contained residual sulfate that was affected by microbial sulfate reduction. A sulfate reduction zone at this site is further supported by the multiple sulfur isotopic composition of framboidal pyrite in the flow channel of the barite chimney and in the hydrothermal sediments in the barite field, as well as by low SO4 and elevated H2S concentrations in the venting fluids compared with conservative mixing values. We suggest that the mixing of ascending H2‐ and CH4‐rich high‐temperature fluids with percolating seawater fuels microbial sulfate reduction, which is subsequently recorded by barite formed at the seafloor in areas where the flow rate is sufficient. Thus, low‐temperature precipitates in hydrothermal systems are promising sites to explore the interactions between the geosphere and biosphere in order to evaluate the microbial impact on these systems.
Modeling climate impact on an emerging disease, thePhytophthora alni‐induced alder decline
Authors: Aguayo Jaime , Elegbede Fabrice , Husson Claude , Saintonge François‐Xavier , Marçais Benoît 
Published: April 2014

AbstractAlder decline caused byPhytophthora alniis one of the most important emerging diseases in natural ecosystems in Europe, where it has threatened riparian ecosystems for the past 20 years. Environmental factors, such as mean site temperature and soil characteristics, play an important role in the occurrence of the disease. The objective of the present work was to model and forecast the effect of environment on the severity of alderPhytophthoraoutbreaks, and to determine whether recent climate change might explain the disease emergence. Two alder sites networks inNEandSWFrance were surveyed to assess the crown health of trees; the oomycete soil inoculum was also monitored in theNEnetwork. The main factors explaining the temporal annual variation in alder crown decline or crown recovery were the mean previous winter and previous summer temperatures. Both low winter temperatures and high summer temperatures were unfavorable to the disease. Cold winters promoted tree recovery because of poor survival of the pathogen, while hot summer temperature limited the incidence of tree decline. AnSISmodel explaining the dynamics of theP. alni‐induced alder decline was developed using the data of theNEsite network and validated using theSWsite network. This model was then used to simulate the frequency of declining alder over time with historical climate data. The last 40 years' weather conditions have been generally favorable to the establishment of the disease, indicating that others factors may be implicated in its emergence. The model, however, showed that the climate ofSWFrance was much more favorable for the disease than that of the Northeast, because it seldom limited the overwintering of the pathogen. Depending on the European area, climate change could either enhance or decrease the severity of the alder decline.
Gold Standard Lessons for the Eurozone
Authors: Morys Matthias 
Published: April 2014

AbstractThis article explores some lessons of the gold standard for the eurozone crisis with specific focus on the interwar period. Resurrected in the 1920s, the interwar gold standard malfunctioned from the onset, contributing to theGreatDepression's quick propagation and severity, and its abandonment between 1929 and 1936 was a critical factor in ending theGreatDepression, with countries devaluing earlier and more sizeably recovering more quickly. The intricate combination of similarities and differences with the present situation makes one of two outcomes likely: either some countries will eventually leave the eurozone to boost their growth prospects; or, the eurozone will remain intact as a result of stronger political co‐operation today, but a poorly working internal adjustment mechanism could result in low growth rates for the foreseeable future, similar to the experience of the gold bloc countries in the 1930s.
Policy Options for the Euro: Heterodoxy Ahead
Authors: Urban Scott 
Published: April 2014

AbstractThis article compares the euro crisis to the Great Depression. The challenge in both is to depreciate the real exchange rate of crisis countries – regain ‘competitiveness’ – without depreciating the nominal exchange rate. The monetary arrangements in the Great Depression elicited zeal against nominal depreciation similar to that in the eurozone today. To anticipate the conclusion: recovery in the Great Depression depended upon nominal depreciation or imposition of currency controls. Similar heterodoxy is in store for the eurozone.
External Perceptions and EU Foreign Policy Effectiveness: The Case of Climate Change
Authors: Torney Diarmuid 
Published: April 2014

AbstractRecent research on external perceptions of the European Union (EU) has not explored sufficiently the implications of its findings for the effectiveness of EU external policies. To address this gap, this article explores the relationship between external perceptions and effectiveness by considering the case of climate change in which, despite broadly favourable external perceptions, EU external effectiveness has been somewhat limited. It uses the case of Chinese and Indian relations with the EU on climate change to illustrate that the findings of the external perceptions literature should be interpreted in the light of the dynamics of specific policy areas as well as broader changes in the context of world politics. The argument is illustrated using the example of negotiations on the continuation of the Kyoto Protocol beyond 2012, which shows how, under certain circumstances, positive external perceptions may in fact limit external effectiveness.
Evolution of phenotypic plasticity and environmental tolerance of a labile quantitative character in a fluctuating environment
Authors: Lande R. 
Published: April 2014

AbstractQuantitative genetic models of evolution of phenotypic plasticity are used to derive environmental tolerance curves for a population in a changing environment, providing a theoretical foundation for integrating physiological and community ecology with evolutionary genetics of plasticity and norms of reaction. Plasticity is modelled for a labile quantitative character undergoing continuous reversible development and selection in a fluctuating environment. If there is no cost of plasticity, a labile character evolves expected plasticity equalling the slope of the optimal phenotype as a function of the environment. This contrasts with previous theory for plasticity influenced by the environment at a critical stage of early development determining a constant adult phenotype on which selection acts, for which the expected plasticity is reduced by the environmental predictability over the discrete time lag between development and selection. With a cost of plasticity in a labile character, the expected plasticity depends on the cost and on the environmental variance and predictability averaged over the continuous developmental time lag. Environmental tolerance curves derived from this model confirm traditional assumptions in physiological ecology and provide new insights. Tolerance curve width increases with larger environmental variance, but can only evolve within a limited range. The strength of the trade‐off between tolerance curve height and width depends on the cost of plasticity. Asymmetric tolerance curves caused by male sterility at high temperature are illustrated. A simple condition is given for a large transient increase in plasticity and tolerance curve width following a sudden change in average environment.
Selection from parasites favours immunogenetic diversity but not divergence among locally adapted host populations
Authors: Tobler M. , Plath M. , Riesch R. , Schlupp I. , Grasse A. , Munimanda G. K. , Setzer C. , Penn D. J. , Moodley Y. 
Published: April 2014

AbstractThe unprecedented polymorphism in the major histocompatibility complex (MHC) genes is thought to be maintained by balancing selection from parasites. However, do parasites also drive divergence at MHC loci between host populations, or do the effects of balancing selection maintain similarities among populations? We examined MHC variation in populations of the livebearing fish Poecilia mexicana and characterized their parasite communities. Poecilia mexicana populations in the Cueva del Azufre system are locally adapted to darkness and the presence of toxic hydrogen sulphide, representing highly divergent ecotypes or incipient species. Parasite communities differed significantly across populations, and populations with higher parasite loads had higher levels of diversity at class II MHC genes. However, despite different parasite communities, marked divergence in adaptive traits and in neutral genetic markers, we found MHC alleles to be remarkably similar among host populations. Our findings indicate that balancing selection from parasites maintains immunogenetic diversity of hosts, but this process does not promote MHC divergence in this system. On the contrary, we suggest that balancing selection on immunogenetic loci may outweigh divergent selection causing divergence, thereby hindering host divergence and speciation. Our findings support the hypothesis that balancing selection maintains MHC similarities among lineages during and after speciation (trans‐species evolution).
Murine solid tumours as a novel model to study bacterial biofilm formation in vivo
Authors: Pawar V. , Crull K. , Komor U. , Kasnitz N. , Frahm M. , Kocijancic D. , Westphal K. , Leschner S. , Wolf K. , Loessner H. , Rohde M. , Häussler S. , Weiss S. 
Published: April 2014

AbstractBacteria of many species are able to invade and colonize solid tumours in mice. We have focused on Salmonella enterica serovar Typhimurium. Detailed analysis revealed that such tumour‐invading Salmonella form biofilms, thus providing a versatile in vivo test system for studying bacterial phenotypes and host–pathogen interactions. It appears that biofilm formation by S. typhimurium is induced as a defence against the immune system of the host, and in particular against neutrophils. Further, we extended our work to the clinically more relevant biofilm infection by Pseudomonas aeruginosa. The induction of P. aeruginosa biofilms in neoplastic tissue appears to be elicited as a reaction against the immune system. Reconstitution experiments reveal that T cells are responsible for biofilm induction. Isogenic mutants that are no longer able to form biofilms can be used for comparison studies to determine antimicrobial resistance, especially therapeutic efficacy against P. aeruginosa located in biofilms.
In vitro antifungal effect and inhibitory activity on biofilm formation of seven commercial mouthwashes
Authors: Fu J , Wei P , Zhao C , He C , Yan Z , Hua H 
Published: April 2014

ObjectiveTo investigate the antifungal ability of seven over‐the‐counter mouthwashes against planktonic and sessile Candida albicans and Candida krusei.Materials and MethodsThe seven mouthwashes studied were Listerine®, compound chlorhexidine solution, povidone iodine solution (PV‐I), cetylpyridinium chloride solution, Colgate® Plax, Crest® Prohealth Mouthwash, and NaHCO3. The antifungal ability of each mouthwash against ATCC90028, ATCC6258, and 10 clinical C. albicans isolates was tested using disk diffusion tests, the broth microdilution method, and biofilm testing with two different XTT‐reduction assays. Fluconazole was used as a positive control, and the experiments were performed in triplicate.ResultsChlorhexidine and cetylpyridinium chloride had the largest inhibition zones for ATCC90028 and ATCC6258 (18.6 ± 3.5 and 19 ± 1.6 mm, respectively). Cetylpyridinium chloride was the most effective at inhibiting all of the planktonic C. albicans strains and ATCC6258 with the minimum inhibitory concentration (MIC). As the maturity of the biofilms increased, the change in sessile cell MIC of the mouthwashes was much smaller than that of fluconazole. For the mature biofilms, chlorhexidine, PV‐I, and cetylpyridinium chloride produced the greatest reductions in metabolism (60–80%).ConclusionMost of these seven mouthwashes had significant antifungal activity for both planktonic and sessile Candida species.
The secret of the care of the patient is in knowing and applying the evidence about effective clinical communication
Authors: Frankel RM , Sherman HB 
Published: April 2014

American physicians and dentists conduct approximately 140 000–160 000 patient interviews in a practice lifetime, making the interview the most frequently performed medical procedure. Over the past 75 years, a steadily growing stream of scientific research has confirmed the fact that patient–clinician communication affects the course, direction, and both biomedical and functional outcomes of care. The field of clinical communication research has matured from anecdotes and aphorisms about ‘bedside manner’ to sophisticated randomized control trials and evidence‐based outcomes that have been translated into reliable practice guidelines. Several key skills or habits of practice have been identified and studied in terms of their efficacy and effectiveness. These include the importance of agenda‐setting, eliciting patients' perspectives about the nature of their ailments, communicating caring and concern, and testing for patient comprehension and agreement with proposed treatments. In addition to being effective, interpersonal communication can be deeply satisfying as well as offering a lower probability of law suits in the event of an adverse outcome.
Protective immunity and use of bortezomib for antibody‐mediated rejection in a pediatric kidney transplant recipient
Authors: Claes Donna J. , Yin Hong , Goebel Jens 
Published: April 2014

AbstractStandard treatments for AMR—rituximab, intravenous immunoglobulin, and/or plasmapheresis—aim to suppress the production and modulate the effect of donor‐specific antibodies and remove them, respectively. Proteasome inhibitors such as bortezomib are potent therapeutic agents that target plasma cells more effectively than rituximab to reduce measurable donor‐specific antibody production. Little is known in adults, and no data exist in children about effects of proteasome inhibition to treat AMR on protective antibody titers. We present a pediatric renal transplant recipient who received bortezomib for relatively early AMR and whose antibody titers to measles and tetanus were tracked. The AMR was treated successfully, and we noted no clinical decrease in the overall level of protective immunity from pretransplant baseline levels at almost one yr after AMR treatment cessation. Larger studies will elucidate more clearly how proteasome inhibition to treat AMR affects protective immunity in pediatric transplant recipients.
Reduced NK Cell Percentage at Birth is Associated with Late Onset Infection in Very Preterm Neonates
Authors: Ma L. , Chen R. , Liu F. , Li Y. , Wu Z. , Zhong W. , Lu G. , Wang B. 
Published: April 2014

AbstractImmune status in the early life of preterm infants and its association with late onset infection has not been fully described. To investigate immune status of lymphocyte subsets in the first week in preterm neonates and its association with late onset infection, 143 preterm neonates (84 neonates ≤32 weeks, 59 neonates of 33–36 weeks) and 49 term neonates were recruited. Absolute counts and percentages of lymphocyte subsets were measured by flow cytometry in umbilical cord or venous blood at birth (in all neonates), on day 3 and 7 (in preterm neonates). The presence of late onset infection was recorded in very preterm neonates ≤32 weeks. At birth, absolute counts of most lymphocyte subsets in all preterm neonates and percentages of B cell and NK cell in those ≤32 weeks were reduced compared with term neonates. Absolute counts of all the subsets in preterm neonates showed decline after birth then beginning to rise after day 3. Late onset infections were documented in 33 of 84 very preterm infants ≤32 weeks and 27 of 45 very preterm infants ≤30 weeks. Percentages of NK cell at birth in very preterm neonates ≤30 weeks with late onset infection were significantly reduced compared with those without infection (P < 0.01). In conclusion, immune status of lymphocyte subsets in preterm neonates at birth is less developmental than in term neonates, in spite of the ability of getting improvement in the first week. Reduced NK cell percentage at birth would increase the risk of subsequent infection in very preterm infants.