Polycistronic microRNA (miRNA) clusters are a common feature of vertebrate genomes. The coordinated expression of miRNAs belonging to different seed families from a single transcriptional unit ...suggests functional cooperation, but this hypothesis has not been experimentally tested. Here we report the characterization of an allelic series of genetically engineered mice harboring selective targeted deletions of individual components of the miR-17 ∼ 92 cluster. Our results demonstrate the coexistence of functional cooperation and specialization among members of this cluster, identify a previously undescribed function for the miR-17 seed family in controlling axial patterning in vertebrates and show that loss of miR-19 selectively impairs Myc-driven tumorigenesis in two models of human cancer. By integrating phenotypic analysis and gene expression profiling, we provide a genome-wide view of how the components of a polycistronic miRNA cluster affect gene expression in vivo. The reagents and data sets reported here will accelerate exploration of the complex biological functions of this important miRNA cluster.
Coronavirus disease 2019 (COVID-19) pandemic is a global health emergency. The clinical course of COVID-19 in children is mild in most of the cases, but multisystem inflammatory syndrome in children ...(MIS-C) is recognized as a potential life-threatening complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Acute abdomen as a presentation of COVID-19 is rare, and its correlation to COVID-19 features and prognosis remains undetermined. Herein, we describe a case of appendicitis in a child with confirmed diagnosis of COVID-19 and subsequent SARS-CoV-2 identification in appendix tissue.
Searches for Supersymmetry Ventura, Andrea
International journal of modern physics. Conference series,
2018, Volume:
46
Journal Article
Peer reviewed
Open access
New and recent results on Supersymmetry searches are shown for the ATLAS and the CMS experiments. Analyses with about 36 fb
−
1
are considered for searches concerning light squarks and gluinos, ...direct pair production of 3
r
d
generation squarks, electroweak production of charginos, neutralinos, sleptons, R-parity violating scenarios and long-lived particles.
The miR-17∼92 cluster family is composed of three members encoding microRNAs that share seed sequences. To assess their role in cerebellar and medulloblastoma (MB) development, we deleted the ...miR-17∼92 cluster family in Nestin-positive neural progenitors and in mice heterozygous for the Sonic Hedgehog (SHH) receptor Patched 1 (Ptch1(+/-)). We show that mice in which we conditionally deleted the miR-17∼92 cluster (miR-17∼92(floxed/floxed); Nestin-Cre(+)) alone or together with the complete loss of the miR-106b∼25 cluster (miR-106b∼25(-/-)) were born alive but with small brains and reduced cerebellar foliation. Remarkably, deletion of the miR-17∼92 cluster abolished the development of SHH-MB in Ptch1(+/-) mice. Using an orthotopic transplant approach, we showed that granule neuron precursors (GNPs) purified from the cerebella of postnatal day 7 (P7) Ptch1(+/-); miR-106b∼25(-/-) mice and overexpressing Mycn induced MBs in the cortices of naïve recipient mice. In contrast, GNPs purified from the cerebella of P7 Ptch1(+/-); miR-17∼92(floxed/floxed); Nestin-Cre(+) animals and overexpressing Mycn failed to induce tumors in recipient animals. Taken together, our findings demonstrate that the miR-17∼92 cluster is dispensable for cerebellar development, but required for SHH-MB development.
Mid-infrared absorption spectroscopy for gas detection is reported in this study using a quantum cascade laser (QCL) coupled with a custom-made tellurite hollow-core antiresonant fiber (HC-ARF). The ...HC-ARF is fabricated from tellurite glass by extrusion and subsequent fiber drawing. The QCL emitting at 5.26 µm is coupled into the 21-cm long HC-ARF. As a proof-of-concept, this spectroscopic system is demonstrated for nitric oxide (NO) detection by exploiting its strong absorption line at 1900.08 cm -1 . By quickly filling gas mixtures into the HC-ARF, we first conduct direct absorption spectroscopy of NO and achieve a noise equivalent absorption (NEA) of 2.1 × 10 -5 cm -1 . Besides, we also conduct wavelength modulation spectroscopy to improve sensing performance. A minimum detection limit of 6 ppb NO is achieved at the integration time of 30 s, corresponding to 1.0 × 10 -7 cm -1 in NEA. The HC-ARF is tested to show a response time of only 0.3 s when applying a pressure difference of 11 kPa between the two fiber ends. Such a tellurite HC-ARF-coupled QCL spectroscopic system makes it attractive for developing optical gas sensors with compact size, fast response, and high sensitivity.
The human Src homology and collagen (Shc) gene encodes three protein isoforms of 46, 52, and 66 kDa that belong to a family of molecular adapters involved in several signal transduction pathways. ...Recently, the 66-kDa isoform has been shown to play a central role in controlling reactive oxygen species metabolism and life span in mammals. Despite the large amount of information available on the biology and biochemistry of Shc proteins, very little is known regarding the regulation of their subcellular localization. Here we demonstrate the specific and selective localization of p46Shc to the mitochondrial matrix. Through deletion mapping experiments, we show that targeting of p46Shc to mitochondria is mediated by its first 32 amino acids, which behave as a bona fide mitochondrial targeting sequence. We further demonstrate that the N-terminal location of the signal peptide is critical for its function. This accounts for the observation that p52Shc and p66Shc, containing the same sequence but more internally located, display a remarkably different subcellular localization. These findings indicate that p46Shc may exert a nonredundant biological function in signal transduction pathways involving mitochondria.
Laser dispersion spectroscopy provides an attractive way of gas sensing by measuring refractive index rather than absorption. The previous dispersion gas sensors were mostly developed with free-space ...optics. In this work, we demonstrated heterodyne phase-sensitive dispersion spectroscopy (HPSDS) for sensitive nitric oxide (NO) detection in a hollow-core fiber to take advantage of the enhanced light-gas interaction in a compact setup. A quantum cascade laser (QCL) at 5.26 µm was coupled into a 35 cm tellurite hollow-core antiresonant fiber to exploit the strong absorption line of NO. The injection current of the QCL was modulated at 1 GHz to generate the three-tone beam for dispersion measurements. We achieved a noise equivalent concentration (NEC) of 0.8 ppm at the measurement time of 80 s. A comparative study of HPSDS with wavelength modulation spectroscopy (WMS) was also conducted to evaluate these two methods in terms of sensitivity and dynamic range.
•Heterodyne phase-sensitive detection is demonstrated for dispersion gas sensing in a hollow-core fiber.•A tellurite hollow-core antiresonant fiber is used for mid-infrared dispersion spectroscopy at 5.2 µm.•A noise equivalent concentration of 0.8 ppm is achieved for the dispersion fiber sensor.
Photothermal spectroscopy provides an attractive way of sensitive gas detection with a large dynamic range. Previous photothermal gas sensors normally use an optical interferometer for measuring the ...slight phase change caused by gas absorption. However, an active opto-mechanical stabilization system is required in the photothermal interferometry, making the sensor complex, bulky and hard for field applications. Here, we report a new mid-infrared photothermal gas sensor based on core-cladding mode interference in a tellurite hollow-core antiresonant fiber (HC-ARF). This method relies on the co-propagation of the HE 11 mode of a mid-infrared pump laser and the core-cladding modes of a probe laser in the tellurite HC-ARF. As a proof-of-principle demonstration, we detect nitric oxide in the 35 cm long fiber by using a quantum cascade laser (5.2 μm, 21.7 mW) as the pump laser. We achieve a noise equivalent concentration of 50 ppbv, corresponding to a normalized noise equivalent absorption coefficient of 8.6 × 10 −9 cm −1 WHz −1/2 . Our technique has long-term stability without using any active stabilization devices and holds promise for fast, sensitive and background-free gas detection with a simplified configuration.
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