Citation Statistics from 110 Years of Physical Review

Publicly available data reveal long-term systematic features about citation statistics and how papers are referenced. The data also tell fascinating citation histories of individual articles.Comment: This is esssentially identical to the article that appeared in the June 2005 issue of Physics Toda

Ensembles of Gustatory Cortical Neurons Anticipate and Discriminate Between Tastants in a Single Lick

The gustatory cortex (GC) processes chemosensory and somatosensory information and is involved in learning and anticipation. Previously we found that a subpopulation of GC neurons responded to tastants in a single lick (Stapleton et al., 2006). Here we extend this investigation to determine if small ensembles of GC neurons, obtained while rats received blocks of tastants on a fixed ratio schedule (FR5), can discriminate between tastants and their concentrations after a single 50 μL delivery. In the FR5 schedule subjects received tastants every fifth (reinforced) lick and the intervening licks were unreinforced. The ensemble firing patterns were analyzed with a Bayesian generalized linear model whose parameters included the firing rates and temporal patterns of the spike trains. We found that when both the temporal and rate parameters were included, 12 of 13 ensembles correctly identified single tastant deliveries. We also found that the activity during the unreinforced licks contained signals regarding the identity of the upcoming tastant, which suggests that GC neurons contain anticipatory information about the next tastant delivery. To support this finding we performed experiments in which tastant delivery was randomized within each block and found that the neural activity following the unreinforced licks did not predict the upcoming tastant. Collectively, these results suggest that after a single lick ensembles of GC neurons can discriminate between tastants, that they may utilize both temporal and rate information, and when the tastant delivery is repetitive ensembles contain information about the identity of the upcoming tastant delivery

From Gas Phase Observations to Solid State Reality: The Identification and Isolation of Trinuclear Salicylaldoximato Copper Complexes

Conditions have been identified in which phenolic aldoximes and ketoximes of the types used in commercial solvent extraction processes can be doubly deprotonated and generate polynuclear Cu complexes with lower extractant:Cu molar ratios than those found in commercial operations. Electrospray mass spectrometry has provided an insight into the solution speciation in extraction experiments and has identified conditions to allow isolation and characterization of polynuclear Cu-complexes. Elevation of pH is effective in enhancing the formation of trinuclear complexes containing planar {Cu3-μ3-O}4+ or {Cu3-μ3-OH}5+ units. DFT calculations suggest that such trinuclear complexes are more stable than other polynuclear species. Solid structures of complexes formed by a salicylaldoxime with a piperidino substituent ortho to the phenolic OH group (L9H2) contain two trinuclear units in a supramolecular assembly, {[Cu3OH(L9H)3(ClO4)](ClO4)} 2, formed by H-bonding between the central {Cu3-μ3-OH}5+ units and oxygen atoms in the ligands of an adjacent complex. Whilst the lower ligand:Cu molar ratios provide more efficient Cu-loading in solvent extraction processes, the requirement to raise the pH of the aqueous phase to achieve this will make it impractical in most commercial operations because extraction will be accompanied by the precipitation (as oxyhydroxides) of Fe(III) which is present in significant quantities in feed solutions generated by acid leaching of most Cu ores

Attenuation of myocardial reperfusion injury in pigs by Mirococept, a membrane-targeted complement inhibitor derived from human CR1

Objectives Membrane-targeted application of complement inhibitors may ameliorate ischemia/reperfusion (I/R) injury by directly targeting damaged cells. We investigated whether Mirococept, a membrane-targeted, myristoylated peptidyl construct derived from complement receptor 1 (CR1) could attenuate I/R injury following acute myocardial infarction in pigs. Methods In a closed-chest pig model of acute myocardial infarction, Mirococept, the non-tailed derivative APT154, or vehicle was administered intracoronarily into the area at risk 5 min pre-reperfusion. Infarct size, cardiac function and inflammatory status were evaluated. Results Mirococept targeted damaged vasculature and myocardium, significantly decreasing infarct size compared to vehicle, whereas APT154 had no effect. Cardioprotection correlated with reduced serum troponin I and was paralleled by attenuated local myocardial complement deposition and tissue factor expression. Myocardial apoptosis (TUNEL-positivity) was also reduced with the use of Mirococept. Local modulation of the pro-inflammatory and pro-coagulant phenotype translated to improved left ventricular end-diastolic pressure, ejection fraction and regional wall motion post-reperfusion. Conclusions Local modification of a pro-inflammatory and pro-coagulant environment after regional I/R injury by site-specific application of a membrane-targeted complement regulatory protein may offer novel possibilities and insights into potential treatment strategies of reperfusion-induced injur

Development of a protocol to obtain the composition of terrigenous detritus in marine sediments -a pilot study from International Ocean Discovery Program Expedition 361

The geochemical and isotopic composition of terrigenous clays from marine sediments can provide important information on the sources and pathways of sediments. International Ocean Discovery Program Expedition 361 drilled sites along the eastern margin of southern Africa that potentially provide archives of rainfall on the continent as well as dispersal in the Agulhas Current. We used standard methods to remove carbonate and ferromanganese oxides and Stokes settling to isolate the clay fractions. In comparison to most previous studies that aimed to extract the detrital signal from marine sediments, we additionally applied a cation exchange wash using CsCl as a final step in the sample preparation. The motivation behind the extra step, not frequently applied, is to remove ions that are gained on the clay surface due to adsorption of authigenic trace metals in the ocean or during the leaching procedure. Either would alter the composition of the detrital fraction if no cation exchange was applied. Moreover, using CsCl will provide an additional measure of the cation exchange capacity (CEC) of the samples. However, no study so far has evaluated the potential and the limitations of such a targeted protocol for marine sediments. Here, we explore the effects of removing and replacing adsorbed cations on the clay surfaces with Cs+, conducting measurements of the chemical compositions, and radiogenic isotopes on a set of eight clay sample pairs. Both sets of samples underwent the same full leaching procedure except that one batch was treated with a final CsCl wash step. In this study, organic matter was not leached because sediments at IODP Site U1478 have relatively low organic content. However, in general, we recommend including that step in the leaching procedure. As expected, significant portions of elements with high concentrations in seawater were replaced by Cs+ (2SD 2.8%.) from the wash, including 75% of the sodium and approximately 25% of the calcium, 10% of the magnesium, and 8% of the potassium. Trace metals such as Sr and Nd, whose isotopes are used for provenance studies, are also found to be in lower concentrations in the samples after the exchange wash. The exchange wash affected the radiogenic isotope compositions of the samples. Neodymium isotope ratios are slightly less radiogenic in all the washed samples. Strontium and Pb isotopes showed significant deviations to either more or less radiogenic values in different samples. The radiogenic isotopes from the CsCl-treated fractions gave more consistent correlations with each other, and we suggest this treatment offers a superior measure of provenance. Although we observed changes in the isotope ratios, the general trend in the data and hence the overall provenance interpretations remained the same. However, the chemical compositions are significantly different. We conclude that a leaching protocol including a cation exchange wash (e.g. CsCl) is useful for revealing the terrestrial fingerprint. CEC could, with further calibration efforts, be useful as a terrestrial chemical weathering proxy

TRPV4-Mediated Calcium Influx into Human Bronchial Epithelia upon Exposure to Diesel Exhaust Particles

BACKGROUND: Human respiratory epithelia function in airway mucociliary clearance and barrier function and have recently been implicated in sensory functions. OBJECTIVE: We investigated a link between chronic obstructive pulmonary disease (COPD) pathogenesis and molecular mechanisms underlying Ca2+ influx into human airway epithelia elicited by diesel exhaust particles (DEP). METHODS AND RESULTS: Using primary cultures of human respiratory epithelial (HRE) cells, we determined that these cells possess proteolytic signaling machinery, whereby proteinase-activated receptor-2 (PAR-2) activates Ca2+-permeable TRPV4, which leads to activation of human respiratory disease-enhancing matrix metalloproteinase-1 (MMP-1), a signaling cascade initiated by diesel exhaust particles (DEP), a globally relevant air pollutant. Moreover, we observed ciliary expression of PAR-2, TRPV4, and phospholipase-Cβ3 in human airway epithelia and their DEP-enhanced protein-protein complex formation. We also found that the chronic obstructive pulmonary disease (COPD)-predisposing TRPV4P19S variant enhances Ca2+ influx and MMP 1 activation, providing mechanistic linkage between man-made air pollution and human airway disease. CONCLUSION: DEP evoked protracted Ca2+ influx via TRPV4, enhanced by the COPD-predisposing human genetic polymorphism TRPV4P19S. This mechanism reprograms maladaptive inflammatory and extracellular-matrix-remodeling responses in human airways. The novel concept of air pollution-responsive ciliary signal transduction from PAR-2 to TRPV4 in human respiratory epithelia will accelerate rationally targeted therapies, possibly via the inhalatory route

Preliminary Biomarkers for Identification of Human Ascending Thoracic Aortic Aneurysm

Background: Human ascending thoracic aortic aneurysms (ATAAs) are life threatening and constitute a leading cause of mortality in the United States. Previously, we demonstrated that collagens α2(V) and α1(XI) mRNA and protein expression levels are significantly increased in ATAAs. Methods and Results: In this report, the authors extended these preliminary studies using high‐throughput proteomic analysis to identify additional biomarkers for use in whole blood real‐time RT‐PCR analysis to allow for the identification of ATAAs before dissection or rupture. Human ATAA samples were obtained from male and female patients aged 65±14 years. Both bicuspid and tricuspid aortic valve patients were included and compared with nonaneurysmal aortas (mean diameter 2.3 cm). Five biomarkers were identified as being suitable for detection and identification of ATAAs using qRT‐PCR analysis of whole blood. Analysis of 41 samples (19 small, 13 medium‐sized, and 9 large ATAAs) demonstrated the overexpression of 3 of these transcript biomarkers correctly identified 79.4% of patients with ATAA of ≥4.0 cm (P<0.001, sensitivity 0.79, CI=0.62 to 0.91; specificity 1.00, 95% CI=0.42 to 1.00). Conclusion: A preliminary transcript biomarker panel for the identification of ATAAs using whole blood qRT‐PCR analysis in men and women is presented

Diesel Exhaust Particles Activate the Matrix-Metalloproteinase-1 Gene in Human Bronchial Epithelia in a β-Arrestin–Dependent Manner via Activation of RAS

BACKGROUND: Diesel exhaust particles (DEPs) are globally relevant air pollutants that exert a detrimental human health impact. However, mechanisms of damage by DEP exposure to human respiratory health and human susceptibility factors are only partially known. Matrix metalloproteinase-1 (MMP-1) has been implied as an (etio)pathogenic factor in human lung and airway diseases such as emphysema, chronic obstructive pulmonary disease, chronic asthma, tuberculosis, and bronchial carcinoma and has been reported to be regulated by DEPs. OBJECTIVE: We elucidated the molecular mechanisms of DEPs' up-regulation of MMP-1. METHODS/RESULTS: Using permanent and primary human bronchial epithelial (HBE) cells at air-liquid interface, we show that DEPs activate the human MMP-1 gene via RAS and subsequent activation of RAF-MEK-ERK1/2 mitogen-activated protein kinase signaling, which can be scaffolded by beta-arrestins. Short interfering RNA mediated beta-arrestin1/2 knockout eliminated formation, subsequent nuclear trafficking of phosphorylated ERK1/2, and resulting MMP-1 transcriptional activation. Transcriptional regulation of the human MMP-1 promoter was strongly influenced by the presence of the -1607GG polymorphism, present in 60-80% of humans, which led to striking up-regulation of MMP-1 transcriptional activation. CONCLUSION: Our results confirm up-regulation of MMP-1 in response to DEPs in HBE and provide new mechanistic insight into how these epithelia, the first line of protection against environmental insults, up-regulate MMP-1 in response to DEP inhalation. These mechanisms include a role for the human -1607GG polymorphism as a susceptibility factor for an accentuated response, which critically depends on the ability of beta-arrestin1/2 to generate scaffolding and nuclear trafficking of phosphorylated ERK1/2