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The large radius, and therefore low density, of the Martian core found in the InSight mission data analysis highlights the importance of considering other light elements besides sulfur (S), which has been considered as the main light element for Mars for decades. Hydrogen (H) is abundant in the solar system and becomes siderophile at high pressures. Although Fe‐S and Fe‐H systems have been studied individually, the Fe‐S‐H ternary system has only been investigated up to 16 GPa and 1723 K. We have investigated the Fe‐S‐H system at pressures and temperatures (P‐T) relevant to the cores of Mars‐sized planets (up to 45 GPa and well above the melting temperature of FeS) in the laser‐heated diamond anvil cell combined with in situ synchrotron X‐ray diffraction. We found that sufficient hydrogen leads to the disappearance of Fe3S at high P‐T. Instead, separate Fe‐H and Fe‐S phases appear at 23–35 GPa. At pressures above 35 GPa, we found a new phase appearing while Fe‐S phases disappear and Fe‐H phases remain. Our analysis indicates that the new phase likely contains both S and H in the crystal structure (tentatively FeSxHy where x ≈ 1 and y ≈ 1). The observed pressure‐dependent changes in the phase relation may be important for understanding the structure and dynamics of the Martian core and the cores of Mars‐sized exoplanets. Plain Language Summary: The metallic cores of planets and satellites are believed to contain significant amounts of light elements such as hydrogen and sulfur. To understand how a planetary core forms and evolves through time, it is important to know how iron alloys behave at the pressure‐temperature conditions of the cores. The iron‐hydrogen and the iron‐sulfur alloy systems are well‐known even at the Earth's core conditions. However, the iron alloy systems with both sulfur and hydrogen together have been studied only for depths of smaller bodies like Ganymede. Using new experimental techniques, we study the behavior of the iron‐hydrogen‐sulfur alloy system at higher pressures and temperatures. We found that at intermediate depths, sulfur and hydrogen form two separate iron alloys, while at greater depths, a new iron alloy with both sulfur and hydrogen may form in the cores of Mars‐sized planets. This change in mineralogy with depth, therefore, suggests that the structure and dynamics in the cores of Mars‐sized planets could be much more complex if hydrogen can be added to the region as a light element. Key Points: Fe3S is not present under sufficiently hydrogen‐rich conditions, being replaced by FeHx and FeS or FeSxHy and FeHxAt 23–35 GPa, separate FeS and FeHx phases exist stably, whereas above 35 GPa, a new Fe alloy phase appears, which may contain both S and HCrystallization from an Fe‐S‐H liquid would lead to a complex core structure [ABSTRACT FROM AUTHOR]

Carbapenem‐resistant Gram‐negative bacteria (GNB) are heading the list of pathogens for which antibiotics are the most critically needed. Many antibiotics are either unable to penetrate the outer‐membrane or are excluded by efflux mechanisms. Here, we report a cationic block β‐peptide (PAS8‐b‐PDM12) that reverses intrinsic antibiotic resistance in GNB by two distinct mechanisms of action. PAS8‐b‐PDM12 does not only compromise the integrity of the bacterial outer‐membrane, it also deactivates efflux pump systems by dissipating the transmembrane electrochemical potential. As a result, PAS8‐b‐PDM12 sensitizes carbapenem‐ and colistin‐resistant GNB to multiple antibiotics in vitro and in vivo. The β‐peptide allows the perfect alternation of cationic versus hydrophobic side chains, representing a significant improvement over previous antimicrobial α‐peptides sensitizing agents. Together, our results indicate that it is technically possible for a single adjuvant to reverse innate antibiotic resistance in all pathogenic GNB of the ESKAPE group, including those resistant to last resort antibiotics. [ABSTRACT FROM AUTHOR]

Abstract: Face centered cubic (fcc) FeHX was synthesized at pressures of 18–68 GPa and temperatures exceeding 1,500 K. Thermally quenched samples were evaluated using synchrotron X‐ray diffraction (XRD) and nuclear resonant inelastic X‐ray scattering (NRIXS) to determine sample composition and sound velocities to 82 GPa. To aid in the interpretation of nonideal (X ≠ 1) stoichiometries, two equations of state for fcc FeHX were developed, combining an empirical equation of state for iron with two distinct synthetic compression curves for interstitial hydrogen. Matching the density deficit of the Earth's core using these equations of state requires 0.8–1.1 wt % hydrogen at the core‐mantle boundary and 0.2–0.3 wt % hydrogen at the interface of the inner and outer cores. Furthermore, a comparison of Preliminary Reference Earth Model (PREM) to a Birch's law extrapolation of our experimental results suggests that an iron alloy containing ∼0.8–1.3 wt % hydrogen could reproduce both the density and compressional velocity (VP) of the Earth's outer core. [ABSTRACT FROM AUTHOR]

BACKGROUND: Late age at first full-term birth and nulliparity are known to increase breast cancer risk. The frequency of these risk factors has increased in recent decades. METHODS: The purpose of this population-based case-control study was to examine associations between parity, age at first birth (AFB), and specific histological subtypes of breast cancer. Women with breast cancer were identified from cancer registries in Wisconsin, Massachusetts, and New Hampshire. Control subjects were randomly selected from population lists. Interviews collected information on reproductive histories and other risk factors. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of ductal, lobular, and mixed ductal-lobular breast cancer diagnosis in association with AFB and nulliparity. RESULTS: AFB ≥30 years was associated with a 2.4-fold increase in risk of lobular breast cancer compared with AFB <20 years (OR, 2.4; 95% CI, 1.9-2.9). The association was less pronounced for ductal breast cancer (OR, 1.3; 95% CI, 1.2-1.4). Nulliparity was associated with increased risk for all breast cancer subtypes, compared with women with AFB <20 years, but the association was stronger for lobular (OR, 1.7; 95% CI, 1.3-2.2) than for ductal (OR, 1.2; 95% CI, 1.1-1.3) subtypes (P = .004). The adverse effects of later AFB was stronger with obesity (P = .03) in lobular, but not ductal, breast cancer. CONCLUSIONS: Stronger associations observed for late AFB and nulliparity suggest that these factors preferentially stimulate growth of lobular breast carcinomas. Recent temporal changes in reproductive patterns and rates of obesity may impact the histological presentation of breast cancer. [ABSTRACT FROM AUTHOR]

The diamond anvil cell (DAC) technique coupled with laser heating has become the most successful method for studying materials in the multimegabar pressure range at high temperatures. However, so far all DAC laser-heating systems have been stationary: they are linked either to certain equipment or to a beamline. Here, a portable laser-heating system for DACs has been developed which can be moved between various analytical facilities, including transfer from in-house to a synchrotron or between synchrotron beamlines. Application of the system is demonstrated in an example of nuclear inelastic scattering measurements of ferropericlase (Mg0.88Fe0.12)O and h.c.p.-Fe0.9Ni0.1 alloy, and X-ray absorption near-edge spectroscopy of (Mg0.85Fe0.15)SiO3 majorite at high pressures and temperatures. Our results indicate that sound velocities of h.c.p.-Fe0.9Ni0.1 at pressures up to 50 GPa and high temperatures do not follow a linear relation with density. [ABSTRACT FROM AUTHOR]

In Pseudomonas aeruginosa quorum sensing (QS), the transcriptional regulator LasR controls the expression of more than 300 genes. Several of these genes are activated indirectly via a second, subordinate QS regulator, RhlR. Conserved sequence elements upstream of individual other genes have been shown to bind LasR in vitro. To comprehensively identify all regions that are bound by LasR in vivo, we employed chromatin immunoprecipitation in conjunction with microarray analysis. We identified 35 putative promoter regions that direct the expression of up to 74 genes. In vitro DNA binding studies allowed us to distinguish between cooperative and non-cooperative LasR binding sites, and allowed us to build consensus sequences according to the mode of binding. Five promoter regions were not previously recognized as QS-controlled. Two of the associated transcript units encode proteins involved in the cold-shock response and in Psl exopolysaccharide synthesis respectively. The LasR regulon includes seven genes encoding transcriptional regulators, while secreted factors and secretion machinery are the most over-represented functional categories overall. This supports the notion that the core function of LasR is to co-ordinate the production of extracellular factors, although many of its effects on global gene expression are likely mediated indirectly by regulatory genes under its control. [ABSTRACT FROM AUTHOR]

Tuberous Sclerosis Complex (TSC) is a multi-system disorder that is highly variable in its clinical presentation. Current molecular diagnostic methods permit identification of mutations in either TSC1 or TSC2 in 75–85% of TSC patients. Here we examine the clinical characteristics of those TSC patients who have no mutation identified (NMI). A retrospective review of our patient population that had comprehensive testing for mutations in TSC1/ TSC2 identified 23/157 (15%) that were NMI. NMI patients had a lower incidence of brain findings on imaging studies, neurological features, and renal findings than those with TSC2 mutations. In contrast, NMI patients had a lower incidence of seizures than TSC patients with TSC1 mutations, but had a higher incidence of both renal angiomyolipomas and pulmonary lymphangioleiomyomatosis. This distinct constellation of findings suggest that NMI patients may have a unique molecular pathogenesis, different from that seen in TSC patients with the usual mutations in TSC1 and TSC2. We suggest that the mechanisms of disease in these patients include both mosaicism for a TSC2 mutation, and unusual non-coding region mutations in TSC2. [ABSTRACT FROM AUTHOR]

Background and Objective: The relationship between diabetes and periodontal diseases is well established. Our aim in this study was to explore the diabetes-related parameters that are associated with accelerated periodontal destruction in diabetic youth. Material and Methods: Three-hundred and fifty 6–18-year-old children with diabetes received a periodontal examination. Data on important diabetes-related variables were collected. Analyses were performed using logistic regression, with gingival/periodontal disease as the dependent variable, for the whole cohort and separately for two subgroups (6–11 and 12–18 years of age). Results: Regression analyses, adjusting for age, gender, ethnicity, frequency of prior dental visits, dental plaque, and dental examiner, revealed a strong positive association between mean hemoglobin A1c over the 2 years prior to inclusion in the study and periodontitis (odds ratio = 1.31, p = 0.030). This association approached significance in the younger subgroup (odds ratio = 1.56, p = 0.052, n = 183). There was no significant relationship between diabetes duration or body mass index-for-age and measures of gingival/periodontal disease in this cohort. Conclusion: These findings suggest that accelerated periodontal destruction in young people with diabetes is related to the level of metabolic control. Good metabolic control may be important in addressing periodontal complications in young patients with diabetes, similarly to what is well established for other systemic complications of this disease. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the levels of subgingival plaque bacteria and serum IgG responses in patients with type 1 diabetes and non-diabetic controls of comparable periodontal status. Material and Methods: Fifty type 1 diabetes patients (mean duration 20.3 years, range 6-41) were age-and gender-matched with 50 non-diabetic individuals with similar levels of periodontal disease. Full-mouth clinical periodontal status was recorded, and eight plaque samples/person were collected and analysed by checkerboard hybridization with respect to 12 species. Homologous serum IgG titres were assessed by checkerboard immunoblotting. In a sub-sample of pairs, serum cytokines and selected markers of cardiovascular risk were assessed using multiplex technology. Results: Among the investigated species, only levels of Eubacterium nodatum were found to be higher in diabetic patients, while none of the IgG titres differed between the groups, both before and after adjustments for microbial load. Patients with diabetes had significantly higher serum levels of soluble E-selectin ( p=0.04), vascular cell adhesion molecule-1 (VCAM-1; p=0.0008), adiponectin ( p=0.01) and lower levels of plasminogen activator inhibitor-1 (PAI-1; p=0.02). Conclusions: After controlling for the severity of periodontal disease, patients with type 1 diabetes and non-diabetic controls showed comparable subgingival infection patterns and serum antibody responses. [ABSTRACT FROM AUTHOR]

The opportunistic pathogen Pseudomonas aeruginosa has two acyl-homoserine lactone (acyl-HSL) signalling systems, LasR-I and RhlR-I. LasI catalyses the synthesis of N-3-oxododecanoyl homoserine lactone (3OC12) and LasR is a transcription factor that requires 3OC12 as a ligand. RhlI catalyses the synthesis of N-butanoyl homoserine lactone (C4) and RhlR is a transcription factor that responds to C4. LasR and RhlR control the transcription of hundreds of P. aeruginosa genes. There is a third P. aeruginosa LasR-RhlR homologue encoded by qscR for which there is no cognate acyl-HSL synthase gene. To test the hypothesis that QscR functions by direct control of specific promoters in an acyl-HSL-dependent manner we purified QscR and characterized QscR activity in vitro. We also studied QscR activity in recombinant Escherichia coli. QscR binds to promoters that have elements similar in sequence to those found in LasR- or RhlR-dependent promoters but QscR does not bind to the LasR- or RhlR-specific promoters we examined. QscR binding to DNA requires 3OC12, but QscR exhibits a relaxed acyl-HSL specificity compared with the 3OC12-cognate signal receptor LasR. Our results support the hypothesis that there is a specific QscR-dependent regulon. We show that QscR controls genes in this regulon directly and that regulation is dependent on an acyl-HSL produced by LasI. Because of its relaxed signal specificity QscR may also respond to acyl-HSLs made by other bacteria in mixed bacterial communities. [ABSTRACT FROM AUTHOR]

Prior studies suggest that histamines may modulate the development of colorectal neoplasia. To assess whether histamine receptor antagonist use was associated with adenoma formation. Patients ( n = 2366) were drawn from three adenoma chemoprevention trials. All underwent baseline colonoscopy with removal of adenoma(s) and were deemed free of remaining lesions; they were followed with surveillance colonoscopy. Medication use was assessed by questionnaire. Adjusted risk ratios for adenoma formation related to histamine receptor antagonist use (histamine H1 and H2 receptor, H1RA and H2RA) were determined using log linear models. In pooled analyses, H1RA exposure was not associated with subsequent adenoma risk (RR = 1.10; 95% CI 0.97–1.25) or multiple adenoma formation (RR = 0.85; 95% CI 0.67–1.07). H2RA use also was not associated with adenoma (RR = 0.90; 95% CI 0.77–1.06), or multiple adenoma (RR = 0.77; 95% CI 0.57–1.04) in the pooled analyses, but H2RA users in the first trial had a decreased risk of adenoma (RR = 0.70; 95% CI 0.48–1.03) and multiple adenoma (RR = 0.31; 95% CI 0.12–0.79). H2RA use was associated with reduced risk for adenoma in one trial, but not in the pooled analyses. Further study would be warranted before undertaking randomized trials of H2RAs for adenoma chemoprevention. [ABSTRACT FROM AUTHOR]

In Escherichia coli and some other γ-Proteobacteria, the alternative σ factor RpoS functions as a regulator of the general stress response. The role of RpoS in Pseudomonas aeruginosa is not clear. Although P. aeruginosa RpoS contributes to the resistance to several environmental stresses, its role appears to be less pivotal than in E. coli . In P. aeruginosa , RpoS also regulates the production of several virulence factors and influences the expression of individual genes that are controlled by quorum sensing. Some quorum-controlled genes are induced by RpoS, whereas others are repressed. To gain insights about RpoS function in P. aeruginosa and to understand better the regulation of quorum-controlled genes, we used transcript profiling to define an RpoS regulon. We identified 772 genes regulated by RpoS in stationary but not in logarithmic growth phase (504 were induced and 268 were repressed), and we identified putative RpoS promoter sequence elements with similarity to the E. coli RpoS consensus in several of these genes. Many genes in the regulon, for example a set of chemotaxis genes, have assigned functions that are distinct from those in E. coli and are not obviously related to a stress response. Furthermore, RpoS affects the expression of more than 40% of all quorum-controlled genes identified in our previous transcriptome analysis. This highlights the significance of RpoS as a global factor that controls quorum-sensing gene expression at the onset of stationary phase. The transcription profiling results have allowed us to build a model that accommodates previous seemingly conflicting reports. [ABSTRACT FROM AUTHOR]

Summary Bacterial quorum sensing using acyl-homoserine lactones (acyl-HSLs) as cell-density dependent signalling molecules is important for the transcriptional regulation of many genes essential in the establishment and the maintenance of bacteria–host associations. Vibrio fischeri , the symbiotic partner of the Hawaiian bobtail squid Euprymna scolopes , possesses two distinct acyl-HSL synthase proteins, LuxI and AinS. Whereas the cell density-dependent regulation of luminescence by the LuxI-produced signal is a well-described phenomenon, and its role in light organ symbiosis has been defined, little is known about the ain system. We have investigated the impact of the V. fischeri acyl-HSL synthase AinS on both luminescence and symbiotic colonization. Through phenotypic studies of V. fischeri mutants we have found that the AinS-signal is the predominant inducer of luminescence expression in culture, whereas the impact of the LuxI-signal is apparent only at the high cell densities occurring in symbiosis. Furthermore, our studies revealed that ainS regulates activities essential for successful colonization of E. scolopes , i.e. the V. fischeri ainS mutant failed to persist in the squid light organ. Mutational inactivation of the transcriptional regulator protein LuxO in the ainS mutant partially or completely reversed all the observed phenotypes, demonstrating that the AinS-signal regulates expression of downstream genes through the inactivation of LuxO. Taken together, our results suggest that the two quorum-sensing systems in V. fischeri, ain and lux , sequentially induce the expression of luminescence genes and possibly other colonization factors. [ABSTRACT FROM AUTHOR]

Background: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a vexing problem that continues to pose a diagnostic and therapeutic enigma for the otologist. The aim of the study, adopting the viral theory, was to discover whether patients with ISSNHL would benefit from early treatment with acyclovir and hydrocortisone compared with patients treated by hydrocortisone alone.Methods: Sixty patients with ISSNHL were treated in a prospective controlled randomized manner. Patients were seen within 7 days of onset and were divided randomly into 2 groups. The study group patients were treated with acyclovir and hydrocortisone, whereas those in the control group were treated with hydrocortisone alone.Results: We compared the 2 groups before and after treatment regarding SRT, mean hearing level at each frequency, speech reception threshold improvement, gender, age, tinnitus, and balance complaints. The overall improvement was 78%.Conclusion: We conclude that there probably is no benefit from the addition of acyclovir in the treatment of ISSNHL. [ABSTRACT FROM AUTHOR]

Examines the properties of an estimation procedure used in observations on variables with high level of aggregation. Stretching of data by repeating of observations on variables; Presence of smaller covariance matrix in estimation based on stretched data; Significance of unknown coefficients in comparing mean squared errors.

The opportunistic human pathogen Pseudomonas aeruginosa possesses two cell density-dependent genetic regulatory systems that control expression of a number of secreted virulence factors. These two systems, the lasl-lasR and rhil-rhlR gene pairs, are members of the luxl-tuxR family of quorum-sensing signal generators and signal receptors. The rhll gene in P. aeruginosa encodes a 201-amino-acid protein that catalyses the synthesis of an autoinducer, butyrylhomoserine lactone. Through a programme of random and site-specific mutagenesis of rhll we have gained a better understanding of how its protein product functions. Eight residues critical to butyrylhomoserine lactone synthesis by Rhll were identified by random mutagenesis, and all mapped to a conserved region that spans residues 24-104. Seven of the eight residues were charged amino acids and the other was a glycine. By using site-specific mutagenesis we showed that an active-site cysteine or serine was not required for butyrylhomoserine lactone synthesis, and that two conserved aromatic amino acids in the postulated active site region could be altered without complete loss of Rhll activity. Furthermore, two residues towards the C-terminus that align with critical residues in Luxl can be altered in Rhll without loss of activity. These studies suggest that as opposed to the current models for acyl substrate binding to quorum-sensing signal generators, charged amino acid residues participate directly in the catalysis of butyrylhomoserine lactone synthesis rather than cysteines, serines or hydrophobic amino acids. [ABSTRACT FROM AUTHOR]

Kinetic studies of immune tolerance induction to HSA in sublethally X-rayed rabbits revealed that tolerance can be induced in this system with small amounts of antigen which in non-irradiated animals would constitute small immunizing doses. This, however, depends on a proper schedule of antigen administration which has to be spread over the 8 weeks of post-radiation recovery, although tolerance can be induced by this method even when this antigen treatment is postponed as long as 4 weeks after X-irradiation. Since the lymphoid system recovers rapidly from sublethal radiation injury, and since it was found that by the end of 4 weeks the lymphoid organs demonstrate good cellular repopulation, the conclusion was arrived at that the two processes, namely that of lymphoid recuperation and that of transition from susceptibility to tolerance into the state of immunocompetence, progress independently. These observations raise some questions relevant to theories of the cellular basis of immune tolerance. [ABSTRACT FROM AUTHOR]

Ramsay Hunt syndrome is an herpetic disease with ominous prognosis regarding the facial nerve. Treatment with acyclovir, a well-known virostatic agent, has been given in a small number of patients in recent years with excellent results. We report on the administration of acyclovir intravenously for 7 days in 31 patients with Ramsay Hunt syndrome, with overall recovery rate of 82.6%. There were no side effects regarding this treatment. [ABSTRACT FROM AUTHOR]

The article states that "The Two-Component Response Regulator PprB Modulates Quorum-Sensing Signal Production and Global Gene Expression in Pseudomonas aeruginosa" which was first published online on March 30, 2005 has been retracted by agreement between the authors, the Journal Editor-in-Chief, Anthony Pugsley and Blackwell Publishing Ltd. They discovered that there is an additional spontaneous point mutation that causes an amino acid substitution (Pro74Ser) in the QA regulator LasR of the mutant (M97) in which the pprB gene was disrupted by transposon.

Diving-related inner ear barotrauma (IEB) and inner ear decompression sickness (IEDS) most often result in permanent severe cochleovestibular deficits, unless immediate diagnosis is reached and the correct treatment is commenced early. Nine cases of sport-diving-induced inner ear injuries that were referred to the Israeli Naval Hyperbaric Institute between October 1987 and September 1989 are presented with regard to evaluation, treatment, and follow-up. The diagnosis was IEB in five divers and IEDS in four. Explorative tympanotomy was carried out with remarkable results in two patients with IEB, while the remaining three were relieved by bed rest alone. Three of the four IEDS patients were recompressed according to the extended US Navy Table 6 with good short-term results. The role of complete otoneurological evaluation in the decision-making process leading to the correct diagnosis and treatment is emphasized.