Reduced splicing efficiency induced by synonymous substitutions may generate a substrate for natural selection of new splicing isoforms: the case of CFTR exon 12

Alternative splicing has been associated with increased evolutionary changes and with recent exon creation or loss. The addition of a new exon can be explained by its inclusion in only a fraction of the transcripts leaving the original form intact and giving to the new form the possibility to evolve independently but the exon loss phenomenon is less clear. To explore the mechanism that could be involved in CFTR exon 12 lower splicing efficiency in primates, we have analyzed the effect of multiple synonymous variations. Random patterns of synonymous variations were created in CFTR exon12 and the majority of them induced exon inclusion, suggesting a suboptimal splicing efficiency of the human gene. In addition, the effect of each single synonymous substitution on splicing is strongly dependent on the exonic context and does not correlate with available in silico exon splicing prediction programs. We propose that casual synonymous substitutions may lead to a reduced splicing efficiency that can result in a variable proportion of exon loss. If this phenomenon happens in in-frame exons and to an extent tolerated by the cells it can have an important evolutionary effect since it may generate a substrate for natural selection of new splicing isoforms

GSAreport: easy to use global sensitivity reporting

NWO19455Algorithms and the Foundations of Software technolog

Human NDE1 splicing and mammalian brain development.

Exploring genetic and molecular differences between humans and other close species may be the key to explain the uniqueness of our brain and the selective pressures under which it evolves. Recent discoveries unveiled the involvement of Nuclear distribution factor E-homolog 1 (NDE1) in human cerebral cortical neurogenesis and suggested a role in brain evolution; however the evolutionary changes involved have not been investigated. NDE1 has a different gene structure in human and mouse resulting in the production of diverse splicing isoforms. In particular, mouse uses the terminal exon 8 T, while Human uses terminal exon 9, which is absent in rodents. Through chimeric minigenes splicing assay we investigated the unique elements regulating NDE1 terminal exon choice. We found that selection of the terminal exon is regulated in a cell dependent manner and relies on gain/loss of splicing regulatory sequences across the exons. Our results show how evolutionary changes in cis as well as trans acting signals have played a fundamental role in determining NDE1 species specific splicing isoforms supporting the notion that alternative splicing plays a central role in human genome evolution, and possibly human cognitive predominance

Spectrophotometric properties of dwarf planet Ceres from the VIR spectrometer on board the Dawn mission

We study the spectrophotometric properties of dwarf planet Ceres in the VIS-IR spectral range by means of hyper-spectral images acquired by the VIR imaging spectrometer on board the NASA Dawn mission. Disk-resolved observations with a phase angle within the $7^{\circ}<\alpha<132^{\circ}$ interval were used to characterize Ceres' phase curve in the 0.465-4.05 $\mu$m spectral range. Hapke's model was applied to perform the photometric correction of the dataset, allowing us to produce albedo and color maps of the surface. The $V$-band magnitude phase function of Ceres was fitted with both the classical linear model and H-G formalism. The single-scattering albedo and the asymmetry parameter at 0.55$\mu$m are $w=0.14\pm0.02$ and $\xi=-0.11\pm0.08$, respectively (two-lobe Henyey-Greenstein phase function); the modeled geometric albedo is $0.094\pm0.007$; the roughness parameter is $\bar{\theta}=29^{\circ}\pm6^{\circ}$. Albedo maps indicate small variability on a global scale with an average reflectance of $0.034 \pm 0.003$. Isolated areas such as the Occator bright spots, Haulani, and Oxo show an albedo much higher than average. We measure a significant spectral phase reddening, and the average spectral slope of Ceres' surface after photometric correction is $1.1\%k\AA^{-1}$ and $0.85\%k\AA^{-1}$ at VIS and IR wavelengths, respectively. Broadband color indices are $V-R=0.38\pm0.01$ and $R-I=0.33\pm0.02$. H-G modeling of the $V$-band magnitude phase curve for $\alpha<30^{\circ}$ gives $H=3.14\pm0.04$ and $G=0.10\pm0.04$, while the classical linear model provides $V(1,1,0^{\circ})=3.48\pm0.03$ and $\beta=0.036\pm0.002$. The comparison with spectrophotometric properties of other minor bodies indicates that Ceres has a less back-scattering phase function and a slightly higher albedo than comets and C-type objects. However, the latter represents the closest match in the usual asteroid taxonomy.Comment: 14 pages, 20 figures, published online on Astronomy and Astrophysics on 13 February 2017. Revised to reflect minor changes in text and figures made in proofs, updated value of V-R and R-

Point prevalence study of antibiotic use in a paediatric hospital in Italy

n/

Alert sign and symptoms for the early diagnosis of pulmonary tuberculosis: analysis of patients followed by a tertiary pediatric hospital

Background Intercepting earlier suspected TB (Tuberculosis) cases clinically is necessary to reduce TB incidence, so we described signs and symptoms of retrospective cases of pulmonary TB and tried to evaluate which could be early warning signs. Methods We conducted a retrospective descriptive study of pulmonary TB cases in children in years 2005-2017; in years 2018-2020 we conducted a cohort prospective study enrolling patients &lt; 18 years accessed to Emergency Department (ED) with signs/symptoms suggestive of pulmonary TB. Results In the retrospective analysis, 226 patients with pulmonary TB were studied. The most frequently described items were contact history (53.5%) and having parents from countries at risk (60.2%). Cough was referred in 49.5% of patients at onset, fever in 46%; these symptoms were persistent (lasting &gt;= 10 days) in about 20%. Lymphadenopathy is described in 15.9%. The prospective study enrolled 85 patients of whom 14 (16.5%) were confirmed to be TB patients and 71 (83.5%) were non-TB cases. Lymphadenopathy and contact history were the most correlated variables. Fever and cough lasting &gt;= 10 days were less frequently described in TB cases compared to non-TB patients (p &lt; 0.05). Conclusions In low TB endemic countries, pulmonary TB at onset is characterized by different symptoms, i.e. persistent fever and cough are less described, while more relevant are contact history and lymphadenopathy. It was not possible to create a score because signs/symptoms usually suggestive of pulmonary TB (considered in the questionnaire) were not significant risk factors in our reality, a low TB country

The Spectral Properties of Pitted Impact Deposits on Vesta as Seen by the Dawn VIR Instrument

Pitted impact deposits (PIDs) on Vesta have been shown to exhibit distinct spectral characteristics with respect to their surrounding host deposits and other typical Vestan areas regarding the first major pyroxene absorption near 0.9 μm. The PIDs, especially those in the ejecta blanket of the large crater Marcia, show higher reflectance and pyroxene band strength with respect to their impact deposit surroundings. This study complements the spectral characterization of the PIDs on Vesta with Visible and Infrared Spectrometer observations obtained by NASA’s Dawn mission. In particular, we focus on the second major pyroxene absorption near 1.9 μm. We analyze nine PIDs in the ejecta blanket of the crater Marcia, as well as PIDs within the crater-fill deposits of the craters Marcia, Cornelia, and Licinia. We find that the second pyroxene absorption behaves in similar ways as the first major pyroxene absorption. The PIDs in Marcia’s ejecta blanket show higher reflectance and pyroxene band strength with respect to their immediate impact deposit surroundings. The PIDs present in the crater-fill deposits of Marcia, Cornelia, and Licinia, however, do not show such spectral characteristics. This is also consistent with previous observations of the first pyroxene absorption band. Based on the experimental results of other studies, we speculate that the observed spectral distinctness arises from an oxidation process in the interior of impact deposits, where Fe cations migrate within their host pyroxene grains. Thus, the surfaces of (melt-bearing) impact deposits might be different from their interiors, apart from space-weathering effects

A case of persistent bacteraemia by Ralstonia mannitolilytica and Ralstonia pickettii in an intensive care unit

The Ralstonia spp. genus is a group of non-fermentative, Gram-negative bacteria often resistant to many antibiotics, which are emerging as opportunistic pathogens frequently associated with infections in hospital settings. We present herein a case of combined R. pickettii and R. mannitolilytica persisting and relapsing bacteraemia, possibly caused by a septic arterial thrombosis secondary to the rupture of an internal carotid artery aneurysm. Microbiology studies showed that both Ralstonia isolates produced biofilm and carried class D oxacillinase genes. When confronted with infections caused by members of the Ralstonia genus, identification to the species level is crucial for correct clinical management, as the two species show different antibiotic susceptibility patterns