Assembly of the Auditory Circuitry by a Hox Genetic Network in the Mouse Brainstem

Rhombomeres (r) contribute to brainstem auditory nuclei during development. Hox genes are determinants of rhombomere-derived fate and neuronal connectivity. Little is known about the contribution of individual rhombomeres and their associated Hox codes to auditory sensorimotor circuitry. Here, we show that r4 contributes to functionally linked sensory and motor components, including the ventral nucleus of lateral lemniscus, posterior ventral cochlear nuclei (VCN), and motor olivocochlear neurons. Assembly of the r4-derived auditory components is involved in sound perception and depends on regulatory interactions between Hoxb1 and Hoxb2. Indeed, in Hoxb1 and Hoxb2 mutant mice the transmission of low-level auditory stimuli is lost, resulting in hearing impairments. On the other hand, Hoxa2 regulates the Rig1 axon guidance receptor and controls contralateral projections from the anterior VCN to the medial nucleus of the trapezoid body, a circuit involved in sound localization. Thus, individual rhombomeres and their associated Hox codes control the assembly of distinct functionally segregated sub-circuits in the developing auditory brainstem

Decomposition of carboxymethyl cellulose based on nano-knife principle

The traditional degradation of organic pollutants is based on the sacrifice of chemical or biological reagents. In this study, a purely physical technique was developed to break the chemical bonds and consequently decompose macromolecules in aqueous solution. Assisted with a high-speed mechanical blade, refined quartz sand grains with particularly sharp nano-scale edges can act as ‘nano-knives’, which are able to cut the long chain of carboxymethyl cellulose (CMC, as a model molecule). High performance size exclusion chromatography measurements evidenced that the original CMC molecules (41000 Da) were decomposed into a series of smaller molecules (460, 1000, 2200, 21,000, 27,000 and 31,000 Da). Consequently, the initial viscosity of the CMC solution (2 g/L) rapidly decreased by approximately 50% after 3 min treatment by the nano-knife materials along with the mechanical blade. Fourier transform infrared (FTIR) spectra indicated that the original functional groups were 1 still present and new functional groups were not produced after shearing. The intensity of the main functional group β-1-4-glycosidic bond (wavenumber 1062 cm-1) was observed to markedly decrease after shearing. These results indicated that the long-chain CMC was cleaved into short-chain CMC. A degradation mechanism was proposed whereby the cutting force generated by the rapid motion of the nano-knives may be responsible for the breakage of β-1-4-glycosidic bonds in the macromolecular cellulose backbone. These results provide support for a potentially more affordable and environment-friendly strategy for physical-based decomposition of recalcitrant organic pollutants from aqueous solution without the need of chemical or biological reagents

The importance of incorporating soil in the life cycle assessment procedure to improve the sustainability of agricultural management

The formidable ability of soil to store carbon has attracted an increasing number of studies, but few of them included soil organic carbon (SOC) sequestration as part of a carbon balance assessment in the agroecosystem. This raises some interesting questions: 1) how orchards conversion increase soil capacity to mitigate the green–house gases (GHG) emissions by storing C? 2) can it be considered in life cycle assessment (LCA)? 3) can SOC pools and soil biochemical properties determination improve LCA interpretation? To answer these questions, this study selected a ten– and fifteen–years–old peach orchards, a twenty–years–old pear orchard, a thirty–years–old kiwi orchard in south-east part of Emilia–Romagna Region (Italy), and a cereals’ field as reference. Soil samples were collected from 0 to 15 and 15–30 cm depths, and the SOC pool amounts (i.e., labile and recalcitrant) determined. LCA was used to estimate the GHG emissions (CO2eq) from the orchards. Results showed that the conversion from cereals to orchard production increased OC stock (+82 % on average) suggesting that orchards cultivation systems have the capacity to enrich soil organic matter. Fertilization had the greatest impact on CO2eq emission accounting for at least 40 % of total CO2eq emissions. Kiwi cultivation had the highest impact on GHG emissions mainly due to the high water and nutrient demand (0.045 and 0.149 kg CO2eq kg−1 fruit yr−1, respectively). When taking into account the C–CO2eq loss by fruit cultivation and C storage in soils, results would indicate that peach and pear orchard agroecosystems promote C sequestration. Conversely, kiwi cultivation showed large CO2eq emissions only partly counterbalanced by SOC sequestration. This study highlights the importance of including soils in LCA: if made mandatory this would allow a wider, yet more detailed, picture of the impact of agricultural practices on C budget. This simple step could help optimise resource management and at the same time improve agroecosystem sustainability

Elevated blood pressure, cardiometabolic risk and target organ damage in youth with overweight and obesity

Background and aim: To compare cardiometabolic risk profile and preclinical signs of target organ damage in youth with normal and elevated blood pressure (BP), according to the American Academy of Pediatrics (AAP) guidelines. Methods and results: This cross-sectional multicenter study included 2739 youth (5-17 year-old; 170 normal-weight, 610 overweight and 1959 with obesity) defined non hypertensive by the AAP guidelines. Anthropometric, biochemical and liver ultrasound data were available in the whole population; carotid artery ultrasound and echocardiographic assessments were available respectively in 427 and 264 youth. Elevated BP was defined as BP 65 90th to <95th percentile for age, gender and height in children or BP 65 120/80 to <130/80 in adolescents. The overall prevalence of elevated BP was 18.3%, and significantly increased from normal-weight to obese youth. Young people with elevated BP showed higher levels of body mass index (BMI), insulin resistance and a higher prevalence of liver steatosis (45% vs 36%, p < 0.0001) than normotensive youth, whilst they did not differ for the other cardiometabolic risk factors, neither for carotid intima media thickness or left ventricular mass. Compared with normotensive youth, individuals with elevated BP had an odds ratio (95%Cl) of 3.60 (2.00\u20136.46) for overweight/obesity, 1.46 (1.19\u20131.78) for insulin-resistance and 1.45 (1.19\u20131.77) for liver steatosis, controlling for centers, age and prepubertal stage. The odds for insulin resistance and liver steatosis persisted elevated after correction for BMI-SDS. Conclusion: Compared to normotensive youth, elevated BP is associated with increased BMI, insulin resistance and liver steatosis, without significant target organ damage

LSST Survey Strategy in the Galactic Plane and Magellanic Clouds

Galactic science encompasses a wide range of subjects in the study of the Milky Way and Magellanic Clouds, from Young Stellar Objects to X-ray Binaries. Mapping these populations, and exploring transient phenomena within them, are among the primary science goals of the Vera C. Rubin Observatory's Legacy Survey of Space and Time (LSST). While early versions of the survey strategy dedicated relatively few visits to the Galactic Plane region, more recent strategies under consideration envision higher cadence within selected regions of high scientific interest. The range of galactic science presents a challenge in evaluating which strategies deliver the highest scientific returns. Here we present metrics designed to evaluate Rubin survey strategy simulations based on the cadence of observations they deliver within regions of interest to different topics in galactic science, using variability categories defined by timescale. We also compare the fractions of exposures obtained in each filter with those recommended for the different science goals. We find that the baseline_v2.x simulations deliver observations of the high-priority regions at sufficiently high cadence to reliably detect variability on timescales >10 d or more. Follow-up observations may be necessary to properly characterize variability, especially transients, on shorter timescales. Combining the regions of interest for all the science cases considered, we identify those areas of the Galactic Plane and Magellanic Clouds of highest priority. We recommend that these refined survey footprints be used in future simulations to explore rolling cadence scenarios, and to optimize the sequence of observations in different bandpasses.Comment: Accepted for publication in ApJS. 26 pages and 36 figure

Skeptical Look at the Clinical Implication of Metabolic Syndrome in Childhood Obesity

Metabolic syndrome (MetS) is defined by a cluster of several cardio-metabolic risk factors, specifically visceral obesity, hypertension, dyslipidemia, and impaired glucose metabolism, which together increase risks of developing future cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D). This article is a narrative review of the literature and a summary of the main observations, conclusions, and perspectives raised in the literature and the study projects of the Working Group of Childhood Obesity (WGChO) of the Italian Society of Paediatric Endocrinology and Diabetology (ISPED) on MetS in childhood obesity. Although there is an agreement on the distinctive features of MetS, no international diagnostic criteria in a pediatric population exist. Moreover, to date, the prevalence of MetS in childhood is not certain and thus the true value of diagnosis of MetS in youth as well as its clinical implications, is unclear. The aim of this narrative review is to summarize the pathogenesis and current role of MetS in children and adolescents with particular reference to applicability in clinical practice in childhood obesity

A posteriori error estimates for the virtual element method

An a posteriori error analysis for the virtual element method (VEM) applied to general elliptic problems is presented. The resulting error estimator is of residual-type and applies on very general polygonal/polyhedral meshes. The estimator is fully computable as it relies only on quantities available from the VEM solution, namely its degrees of freedom and element-wise polynomial projection. Upper and lower bounds of the error estimator with respect to the VEM approximation error are proven. The error estimator is used to drive adaptive mesh refinement in a number of test problems. Mesh adaptation is particularly simple to implement since elements with consecutive co-planar edges/faces are allowed and, therefore, locally adapted meshes do not require any local mesh post-processing

Clinical and epidemiological correlates of antibody response to human papillomaviruses (HPVs) as measured by a novel ELISA based on denatured recombinant HPV16 late (L) and early (E) antigens

<p>Abstract</p> <p>Background</p> <p>At present, seroreactivity is not a valuable parameter for diagnosis of Human Papillomavirus (HPV) infection but, it is potentially valuable as marker of viral exposure in elucidating the natural history of this infection. More data are needed to asses the clinical relevance of serological response to HPV.</p> <p>Objectives</p> <p>The objective was to assess the clinical and epidemiological correlates of HPV-seroreactivity in a cohort of HIV-negative and HIV-positive women.</p> <p>Methods</p> <p>Seroreactivity of 96 women, evaluated in an ELISA test based on denatured HPV16 late (L) and early (E) antigens, was correlated with their clinical and epidemiological data previously collected for a multi-centre Italian study, HPV-PathogenISS study.</p> <p>Results</p> <p>No significant correlation was found between HPV DNA detection and seroreactivity. Women, current smokers showed significantly less seroreactivity to L antigens as compared with the non-smokers. HIV-positive women showed significantly less (66.7%) antibody response as compared with HIV-negative women (89.3%), with particularly impaired response to L antigens. Women, HIV-positive and current smokers, showed by far the lowest seroprevalence (33.3%) as compared to 75.9% among all other women (OR = 0.158; 95%CI 0.036–0.695, p = 0.014; Fisher's exact test). Importantly, this association did not loose its significance when controlled for confounding from age (continuous variable) in multivariate analysis or using Mantel-Haenszel test for age-groups.</p> <p>Conclusion</p> <p>It is tempting to speculate that HIV-positive current smokers comprise a special high-risk group, with highly impaired immunological response that could prevent eradication of persistent HPV infections and thus contribute to development of CIN3/CC.</p

Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial

<p>Abstract</p> <p>Background</p> <p>To evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer.</p> <p>Methods</p> <p>Patients with locally advanced or metastatic breast cancer, aged ≤ 70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed.</p> <p>Results</p> <p>From February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03); patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p < 0.001). Neutropenia and stomatitis were worse in the 3-weekly arm, where two toxic deaths were observed. Overall response rate was 39.1% and 33.3% in 3-weekly and weekly arms; hazard ratio of progression was 1.29 (95% CI: 0.84-1.97) and hazard ratio of death was 1.38 (95% CI: 0.82-2.30) in the weekly arm.</p> <p>Conclusions</p> <p>In this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer.</p> <p>Trial registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00540800">NCT00540800</a>.</p