Are elevated plasma fibrinogen associated with lung function? An 8-year follow-up of the ELSA study

BACKGROUND: Fibrinogen is an important biomarker of inflammation, but findings from longitudinal studies that correlated fibrinogen with lung function in older adults are inconsistent. AIM: To investigate the relationship between fibrinogen plasma levels and lung function impairment later in life. METHODS: Longitudinal analysis of 2,150 participants of the English Longitudinal Study of Ageing (ELSA) aged 50 years and older. Associations between changes in plasma fibrinogen between waves 2 (2004-05) and 4 (2008-09) and lung function in wave 6 (2012-13) were performed using multiple linear regression adjusted by potential confounders. RESULTS: Regarding the fibrinogen profile, 18.5% of the participants presented higher levels in both waves. In the adjusted models, the maintenance of high fibrinogen levels was associated with a significant reduction of lung function only for men. FEV1 showed a reduction of 0.17L, FVC of 0.22L, and the percentages predicted were 5.16% for FEV1 and 6.21% for FVC compared to those that maintained normal levels of fibrinogen. DISCUSSION: To the best of our knowledge, this was the first study investigating the relationship between changes in fibrinogen levels over a long follow-up period and lung function in older adults without pre-existing chronic diseases. ELSA has information on critical demographic and clinical parameters, which allowed to adjust for potential confounding factors. CONCLUSION: It was found that the persistence of high levels of plasma fibrinogen in older English men, but not women, is associated with lung function decline. Therefore, plasma fibrinogen showed to be an important biomarker of pulmonary dysfunction in this population

Optimal interdependence between networks for the evolution of cooperation

Recent research has identified interactions between networks as crucial for the outcome of evolutionary games taking place on them. While the consensus is that interdependence does promote cooperation by means of organizational complexity and enhanced reciprocity that is out of reach on isolated networks, we here address the question just how much interdependence there should be. Intuitively, one might assume the more the better. However, we show that in fact only an intermediate density of sufficiently strong interactions between networks warrants an optimal resolution of social dilemmas. This is due to an intricate interplay between the heterogeneity that causes an asymmetric strategy flow because of the additional links between the networks, and the independent formation of cooperative patterns on each individual network. Presented results are robust to variations of the strategy updating rule, the topology of interdependent networks, and the governing social dilemma, thus suggesting a high degree of universality

Sister Mary Joseph's Nodule at a University Teaching Hospital in Northwestern Tanzania: A Retrospective Review of 34 cases.

Sister Mary Joseph's nodule is a metastatic tumor deposit in the umbilicus and often represents advanced intra-abdominal malignancy with dismal prognosis. There is a paucity of published data on this subject in our setting. This study was conducted to describe the clinicopathological presentation and treatment outcome of this condition in our environment and highlight challenges associated with the care of these patients, and to proffer solutions for improved outcome. This was a retrospective study of histologically confirmed cases of Sister Mary Joseph's nodule seen at Bugando Medical Centre between March 2003 and February 2013. Data collected were analyzed using descriptive statistics. A total of 34 patients were enrolled in the study. Males outnumbered females by a ratio of 1.4:1. The vast majority of patients (70.6%) presented with large umbilical nodule > 2 cm in size. The stomach (41.1%) was the most common location of the primary tumor. Adenocarcinoma (88.2%) was the most frequent histopathological type. Most of the primary tumors (52.9%) were poorly differentiated. As the disease was advanced and metastatic in all patients, only palliative therapy was offered. Out of 34 patients, 11 patients died in the hospital giving a mortality rate of 32.4%. Patients were followed up for 24 months. At the end of the follow-up period, 14(60.9%) patients were lost to follow-up and the remaining 9 (39.1%) patients died. Patients survived for a median period of 28 weeks (range, 2 to 64 weeks). The nodule recurred in 6 (26.1%) patients after complete excision. Sister Mary Joseph's nodule of the umbilicus is not rare in our environment and often represents manifestation of a variety of advanced intra-abdominal malignancies. The majority of the patients present at a late stage and many with distant metastases. The patient's survival is very short leading to a poor outcome. Early detection of primary cancer at an early stage may improve the prognosis

Temperature Covariance in Tree Ring Reconstructions and Model Simulations Over the Past Millennium

Spatial covariance in the simulated temperature evolution over the past millennium has been reported to exceed that of multiproxy-based reconstructions. Here we use tree ring-based temperature reconstructions and state-of-the-art climate model simulations to assess temporal changes in Northern Hemisphere intercontinental temperature covariance during the last 1000 years. Tree ring-only approaches reveal stronger agreement with model simulations compared to multiproxy networks. Although simulated temperatures exhibit a substantial spread among individual models, intercontinental temperature coherency is mainly driven by the cooling of large volcanic eruptions in 1257, 1452, 1600, and 1815 Common Era. The coherence of these synchronizing events appears to be elevated in several climate simulations relative to their own unforced covariance baselines and in comparison to the proxy reconstructions. This suggests that some models likely overestimate the amplitude of abrupt summer cooling in response to volcanic eruptions, particularly at larger spatial scales.Supported by the German Science Foundation, grant 161/9-1 and the U.S. National Science Foundation grant AGS-1602920. U. Büntgen received funding from the Ministry of Education, Youth and Sports of Czech Republic within the National Sustainability Program I (NPU I; GN LO1415)

Combinations of β-lactam or aminoglycoside antibiotics with plectasin are synergistic against methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87-89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We demonstrated that plectasin strongly rejuvenates the therapeutic potencies of existing antibiotics in vitro and in vivo. This is a novel strategy that can have major clinical implications in our fight against bacterial infections

Catalytic Roles of Flexible Regions at the Active Site of Ribulose-Bisphosphate Carboxylase/Oxygenase (Rubisco)

Chemical and mutagenesis studies of Rubisco have identified Lys329 and Glu48 as active-site residues that are located in distinct, interacting domains from adjacent subunits. Crystallographic analyses have shown that Lys329 is the apical residue in a 12-residue flexible loop (loop 6) of the {Beta},{alpha}-barrel domain of the active site and that Glu48 resides at the end of helix B of the N-terminal domain of the active site. When phosphorylated ligands are bound by the enzyme, loop 6 adopts a closed conformation and, in concert with repositioning of helix B, thereby occludes the active site from the external environment. In this closed conformation, the {gamma}-carboxylate of Glu48 and the {epsilon}-amino group of Lys329 engage in intersubunit electrostatic interaction. By use of appropriate site-directed mutants of Rhodospirillum rubrum Rubisco, we are addressing several issues: the catalytic roles of Lys329 and Glu48, the functional significance of the intersubunit salt bridge comprised of these two residues, and the roles of loop 6 and helix B in stabilizing labile reaction intermediates. Characterization of novel products derived from misprocessing of D-ribulose-1,5-bisphosphate (RuBP) by the mutant proteins have illuminated the structure of the key intermediate in the normal oxygenase pathway

Plutonium in Soils from Northeast China and Its Potential Application for Evaluation of Soil Erosion

Surface and soil core samples from northeast China were analyzed for Pu isotopes. The measured Pu-240/Pu-239 atomic ratios and Pu239 + 240/Cs-137 activity ratios revealed that the global fallout is the dominant source of Pu and Cs-137 at these sites. Migration behavior of Pu varying with land type and human activities resulted in different distribution of Pu in surface soils. A sub-surface maximum followed by exponential decline of Pu239 + 240 concentrations was observed in an undisturbed soil core, with a total Pu239 + 240 inventory of 86.9 Bq/m(2) and more than 85% accumulated in 0 similar to 20 cm layers. While only half inventory of Pu was obtained in another soil core and no sub-surface maximum value occurred. Erosion of topsoil in the site should be the most possible reason for the significantly lower Pu inventory, which is also supported by the reported Cs-137 profiles. These results demonstrated that Pu could be applied as an ideal substitute of Cs-137 for soil erosion study in the future.</p

Rapid and efficient cancer cell killing mediated by high-affinity death receptor homotrimerizing TRAIL variants

The tumour necrosis factor family member TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in a variety of cancer cells through the activation of death receptors 4 (DR4) and 5 (DR5) and is considered a promising anticancer therapeutic agent. As apoptosis seems to occur primarily via only one of the two death receptors in many cancer cells, the introduction of DR selectivity is thought to create more potent TRAIL agonists with superior therapeutic properties. By use of a computer-aided structure-based design followed by rational combination of mutations, we obtained variants that signal exclusively via DR4. Besides an enhanced selectivity, these TRAIL-DR4 agonists show superior affinity to DR4, and a high apoptosis-inducing activity against several TRAIL-sensitive and -resistant cancer cell lines in vitro. Intriguingly, combined treatment of the DR4-selective variant and a DR5-selective TRAIL variant in cancer cell lines signalling by both death receptors leads to a significant increase in activity when compared with wild-type rhTRAIL or each single rhTRAIL variant. Our results suggest that TRAIL induced apoptosis via high-affinity and rapid-selective homotrimerization of each DR represent an important step towards an efficient cancer treatment

Formation of Supermassive Black Holes

Evidence shows that massive black holes reside in most local galaxies. Studies have also established a number of relations between the MBH mass and properties of the host galaxy such as bulge mass and velocity dispersion. These results suggest that central MBHs, while much less massive than the host (~ 0.1%), are linked to the evolution of galactic structure. In hierarchical cosmologies, a single big galaxy today can be traced back to the stage when it was split up in hundreds of smaller components. Did MBH seeds form with the same efficiency in small proto-galaxies, or did their formation had to await the buildup of substantial galaxies with deeper potential wells? I briefly review here some of the physical processes that are conducive to the evolution of the massive black hole population. I will discuss black hole formation processes for `seed' black holes that are likely to place at early cosmic epochs, and possible observational tests of these scenarios.Comment: To appear in The Astronomy and Astrophysics Review. The final publication is available at http://www.springerlink.co