Fabrication and characterization of metallic nanowires

The shape of metallic constrictions of nanoscopic dimensions (necks) formed using a scanning tunneling microscope is shown to depend on the fabrication procedure. Submitting the neck to repeated plastic deformation cycles makes it possible to obtain long necks or nanowires. Point-contact spectroscopy results show that these long necks are quite crystalline, indicating that the repeated cycles of plastic deformation act as a “mechanical annealing” of the neck.This work was supported by the DGICYT under Contract Nos. MAT95-1542 and PB94-0382

One-carbon metabolism in children with marasmus and kwashiorkor

BACKGROUND: Kwashiorkor is a childhood syndrome of edematous malnutrition. Its precise nutritional precipitants remain uncertain despite nine decades of study. Remarkably, kwashiorkor\u27s disturbances resemble the effects of experimental diets that are deficient in one-carbon nutrients. This similarity suggests that kwashiorkor may represent a nutritionally mediated syndrome of acute one-carbon metabolism dysfunction. Here we report findings from a cross-sectional exploration of serum one-carbon metabolites in Malawian children. METHODS: Blood was collected from children aged 12-60 months before nutritional rehabilitation: kwashiorkor (N = 94), marasmic-kwashiorkor (N = 43) marasmus (N = 118), moderate acute malnutrition (N = 56) and controls (N = 46). Serum concentrations of 16 one-carbon metabolites were quantified using LC/MS techniques, and then compared across participant groups. FINDINGS: Twelve of 16 measured one-carbon metabolites differed significantly between participant groups. Measured outputs of one-carbon metabolism, asymmetric dimethylarginine (ADMA) and cysteine, were lower in marasmic-kwashiorkor (median µmol/L (± SD): 0·549 (± 0·217) P = 0·00045 & 90 (± 40) P \u3c 0·0001, respectively) and kwashiorkor (0·557 (± 0·195) P \u3c 0·0001 & 115 (± 50) P \u3c 0·0001), relative to marasmus (0·698 (± 0·212) & 153 (± 42)). ADMA and cysteine were well correlated with methionine in both kwashiorkor and marasmic-kwashiorkor. INTERPRETATION: Kwashiorkor and marasmic-kwashiorkor were distinguished by evidence of one-carbon metabolism dysfunction. Correlative observations suggest that methionine deficiency drives this dysfunction, which is implicated in the syndrome\u27s pathogenesis. The hypothesis that kwashiorkor can be prevented by fortifying low quality diets with methionine, along with nutrients that support efficient methionine use, such as choline, requires further investigation. FUNDING: The Hickey Family Foundation, the American College of Gastroenterology, the NICHD, and the USDA/ARS

Enhanced thermoelectricity in metal−[60]fullerene−graphene molecular junctions

The thermoelectric properties of molecular junctions consisting of a metal Pt electrode contacting [60]fullerene derivatives covalently bound to a graphene electrode have been studied by using a conducting-probe atomic force microscope (c-AFM). The [60]fullerene derivatives are covalently linked to the graphene via two meta-connected phenyl rings, two para-connected phenyl rings, or a single phenyl ring. We find that the magnitude of the Seebeck coefficient is up to nine times larger than that of Au-C60-Pt molecular junctions. Moreover, the sign of the thermopower can be either positive or negative depending on the details of the binding geometry and on the local value of the Fermi energy. Our results demonstrate the potential of using graphene electrodes for controlling and enhancing the thermoelectric properties of molecular junctions and confirm the outstanding performance of [60]fullerene derivativesThis work has been supported by the European Commission through FP7 ITN MOLESCO (Project Number 606728), the (MAD2D-CM)-UCM1-MRR project and through the EC H2020 FET Open Project Grant Agreement Number 767187 “QuIET”. The authors acknowledge support from the Spanish Ministry of Science and Innovation MCIN (Projects PID2020-114653RB-I00, PID2020-115120GB-I00, Centro de Excelencia Severo Ochoa SEV-2016-0686). L.R.-G. acknowledges support from Spanish MECD (Grant No. FPU14/03368) and, with N.A., funding from the Education and Research Council of the Comunidad de Madrid and the European Social Fund (ref. PEJD-2019-POST/IND-16353

Electric double-layer capacitance between an ionic liquid and few-layer graphene

Ionic-liquid gates have a high carrier density due to their atomically thin electric double layer (EDL) and extremely large geometrical capacitance C-g. However, a high carrier density in graphene has not been achieved even with ionic-liquid gates because the EDL capacitance C-EDL between the ionic liquid and graphene involves the series connection of C-g and the quantum capacitance C-q, which is proportional to the density of states. We investigated the variables that determine C-EDL at the molecular level by varying the number of graphene layers n and thereby optimising C-q. The C-EDL value is governed by C-q at n, 4, and by C-g at n > 4. This transition with n indicates a composite nature for C-EDL. Our finding clarifies a universal principle that determines capacitance on a microscopic scale, and provides nanotechnological perspectives on charge accumulation and energy storage using an ultimately thin capacitor

Development and Disease: How Susceptibility to an Emerging Pathogen Changes through Anuran Development

Ranaviruses have caused die-offs of amphibians across the globe. In North America, these pathogens cause more amphibian mortality events than any other pathogen. Field observations suggest that ranavirus epizootics in amphibian communities are common during metamorphosis, presumably due to changes in immune function. However, few controlled studies have compared the relative susceptibility of amphibians to ranaviruses across life stages. Our objectives were to measure differences in mortality and infection prevalence following exposure to ranavirus at four developmental stages and determine whether the differences were consistent among seven anuran species. Based on previous studies, we hypothesized that susceptibility to ranavirus would be greatest at metamorphosis. Our results did not support this hypothesis, as four of the species were most susceptible to ranavirus during the larval or hatchling stages. The embryo stage had the lowest susceptibility among species probably due to the protective membranous layers of the egg. Our results indicate that generalizations should be made cautiously about patterns of susceptibility to ranaviruses among amphibian developmental stages and species. Further, if early developmental stages of amphibians are susceptible to ranaviruses, the impact of ranavirus epizootic events may be greater than realized due to the greater difficulty of detecting morbid hatchlings and larvae compared to metamorphs

Assessment of pediatric asthma drug use in three European countries; a TEDDY study.

Asthma drugs are amongst the most frequently used drugs in childhood, but international comparisons on type and indication of use are lacking. The aim of this study was to describe asthma drug use in children with and without asthma in the Netherlands (NL), Italy (IT), and the United Kingdom (UK). We conducted a retrospective analysis of outpatient medical records of children 0-18 years from 1 January 2000 until 31 December 2005. For all children, prescription rates of asthma drugs were studied by country, age, asthma diagnosis, and off-label status. One-year prevalence rates were calculated per 100 children per patient-year (PY). The cohort consisted of 671,831 children of whom 49,442 had been diagnosed with asthma at any time during follow-up. ß2-mimetics and inhaled steroids were the most frequently prescribed asthma drug classes in NL (4.9 and 4.1/100 PY), the UK (8.7 and 5.3/100 PY) and IT (7.2 and 16.2/100 PY), respectively. Xanthines, anticholinergics, leukotriene receptor antagonists, and anti-allergics were prescribed in less than one child per 100 per year. In patients without asthma, ß2-mimetics were used most frequently. Country differences were highest for steroids, (Italy highest), and for ß2-mimetics (the UK highest). Off-label use was low, and most pronounced for ß2-mimetics in children <18 months (IT) and combined ß2-mimetics + anticholinergics in children <6 years (NL). CONCLUSION: This study shows that among all asthma drugs, ß2-mimetics and inhaled steroids are most often used, also in children without asthma, and with large variability between countries. Linking multi-country databases allows us to study country specific pediatric drug use in a systematic manner without being hampered by methodological differences. This study underlines the potency of healthcare databases in rapidly providing data on pediatric drug use and possibly safety

Pattern and levels of spending allocated to HIV prevention programs in low- and middle-income countries

<p>Abstract</p> <p>Background</p> <p>AIDS continues to spread at an estimated 2.6 new million infections per year, making the prevention of HIV transmission a critical public health issue. The dramatic growth in global resources for AIDS has produced a steady scale-up in treatment and care that has not been equally matched by preventive services. This paper is a detailed analysis of how countries are choosing to spend these more limited prevention funds.</p> <p>Methods</p> <p>We analyzed prevention spending in 69 low- and middle-income countries with a variety of epidemic types, using data from national domestic spending reports. Spending information was from public and international sources and was analyzed based on the National AIDS Spending Assessment (NASA) methods and classifications.</p> <p>Results</p> <p>Overall, prevention received 21% of HIV resources compared to 53% of funding allocated to treatment and care. Prevention relies primarily on international donors, who accounted for 65% of all prevention resources and 93% of funding in low-income countries. For the subset of 53 countries that provided detailed spending information, we found that 60% of prevention resources were spent in five areas: communication for social and behavioral change (16%), voluntary counselling and testing (14%), prevention of mother-to-child transmission (13%), blood safety (10%) and condom programs (7%). Only 7% of funding was spent on most-at-risk populations and less than 1% on male circumcision. Spending patterns did not consistently reflect current evidence and the HIV specific transmission context of each country.</p> <p>Conclusions</p> <p>Despite recognition of its importance, countries are not allocating resources in ways that are likely to achieve the greatest impact on prevention across all epidemic types. Within prevention spending itself, a greater share of resources need to be matched with interventions that approximate the specific needs and drivers of each country's epidemic.</p

Sleep and immune function

Sleep and the circadian system exert a strong regulatory influence on immune functions. Investigations of the normal sleep–wake cycle showed that immune parameters like numbers of undifferentiated naïve T cells and the production of pro-inflammatory cytokines exhibit peaks during early nocturnal sleep whereas circulating numbers of immune cells with immediate effector functions, like cytotoxic natural killer cells, as well as anti-inflammatory cytokine activity peak during daytime wakefulness. Although it is difficult to entirely dissect the influence of sleep from that of the circadian rhythm, comparisons of the effects of nocturnal sleep with those of 24-h periods of wakefulness suggest that sleep facilitates the extravasation of T cells and their possible redistribution to lymph nodes. Moreover, such studies revealed a selectively enhancing influence of sleep on cytokines promoting the interaction between antigen presenting cells and T helper cells, like interleukin-12. Sleep on the night after experimental vaccinations against hepatitis A produced a strong and persistent increase in the number of antigen-specific Th cells and antibody titres. Together these findings indicate a specific role of sleep in the formation of immunological memory. This role appears to be associated in particular with the stage of slow wave sleep and the accompanying pro-inflammatory endocrine milieu that is hallmarked by high growth hormone and prolactin levels and low cortisol and catecholamine concentrations

Role of Sphingomyelin Synthase in Controlling the Antimicrobial Activity of Neutrophils against Cryptococcus neoformans

The key host cellular pathway(s) necessary to control the infection caused by inhalation of the environmental fungal pathogen Cryptococcus neoformans are still largely unknown. Here we have identified that the sphingolipid pathway in neutrophils is required for them to exert their killing activity on the fungus. In particular, using both pharmacological and genetic approaches, we show that inhibition of sphingomyelin synthase (SMS) activity profoundly impairs the killing ability of neutrophils by preventing the extracellular release of an antifungal factor(s). We next found that inhibition of protein kinase D (PKD), which controls vesicular sorting and secretion and is regulated by diacylglycerol (DAG) produced by SMS, totally blocks the extracellular killing activity of neutrophils against C. neoformans. The expression of SMS genes, SMS activity and the levels of the lipids regulated by SMS (namely sphingomyelin (SM) and DAG) are up-regulated during neutrophil differentiation. Finally, tissue imaging of lungs infected with C. neoformans using matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS), revealed that specific SM species are associated with neutrophil infiltration at the site of the infection. This study establishes a key role for SMS in the regulation of the killing activity of neutrophils against C. neoformans through a DAG-PKD dependent mechanism, and provides, for the first time, new insights into the protective role of host sphingolipids against a fungal infection