Neural stem cells (NSCs) are crucial for development, regeneration, and repair of the nervous system. Most NSCs in mammalian adult brains are quiescent, but in response to extrinsic stimuli, they can ...exit from quiescence and become reactivated to give rise to new neurons. The delicate balance between NSC quiescence and activation is important for adult neurogenesis and NSC maintenance. However, how NSCs transit between quiescence and activation remains largely elusive. Here, we discuss our current understanding of the molecular mechanisms underlying the reactivation of quiescent NSCs. We review recent advances on signaling pathways originated from the NSC niche and their crosstalk in regulating NSC reactivation. We also highlight new intrinsic paradigms that control NSC reactivation in Drosophila and mammalian systems. We also discuss emerging evidence on modeling human neurodevelopmental disorders using NSCs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Data mining with big data Wu, Xindong; Zhu, Xingquan; Wu, Gong-Qing ...
IEEE transactions on knowledge and data engineering,
2014-Jan., 2014-01-00, 20140101, Letnik:
26, Številka:
1
Journal Article
Recenzirano
Big Data concern large-volume, complex, growing data sets with multiple, autonomous sources. With the fast development of networking, data storage, and the data collection capacity, Big Data are now ...rapidly expanding in all science and engineering domains, including physical, biological and biomedical sciences. This paper presents a HACE theorem that characterizes the features of the Big Data revolution, and proposes a Big Data processing model, from the data mining perspective. This data-driven model involves demand-driven aggregation of information sources, mining and analysis, user interest modeling, and security and privacy considerations. We analyze the challenging issues in the data-driven model and also in the Big Data revolution.
Described herein is an imidazole ring formation strategy for the synthesis of axially chiral N‐arylbenzimidazoles by means of chiral phosphoric acid catalysis. Two sets of conditions were developed ...to transform two classes of 2‐naphthylamine derivatives into structurally diverse N‐arylbenzimidazole atropisomers with excellent chemo‐ and regioselectivity as well as high levels of enantiocontrol. It is worth reflecting on the unique roles played by the nitroso group in this domino reaction. It functions as a linchpin by first offering an electrophilic site (N) for the initial C−N bond formation while the resulting amine performs the nucleophilic addition to form the second C−N bond. Additionally, it could facilitate the final oxidative aromatization as an oxidant. The atropisomeric products could be conveniently elaborated to a series of axially chiral derivatives, enabling the exploitation of N‐arylbenzimidazoles for their potential utilities in asymmetric catalysis.
A benzimidazole ring formation strategy for the synthesis of axially chiral N‐arylbenzimidazoles by means of chiral phosphoric acid catalysis is presented. Two sets of conditions were developed to transform two classes of 2‐naphthylamine derivatives into structurally diverse N‐arylbenzimidazole atropisomers with excellent chemo‐ and regioselectivity as well as high levels of enantiocontrol.
Germline DNA damage repair (DDR) deficiency has been associated with increased cancer risk, poor prognosis and therapeutic opportunity for prostate cancer (PCa) patients. However, the landscape of ...germline mutations in PCa covering comprehensive DDR genes has not been reported. We performed whole‐exome sequencing in 246 patients who meet the National Cancer Center Network guidelines for genetic testing and analyzed variants in 276 DDR genes, which was from the Cancer Genome Atlas. A total of 79 deleterious germline alterations in 60 DDR genes were identified in 31% (76/246) patients. Mutations were found in nine DDR pathways, including 11.8% men in homologous recombination repair (HR) pathways, 2.4% men in mismatch repair (MMR) pathway and 16.7% (41/246) patients in non‐HR/MMR pathways. In HRR and MMR pathways, mutations were mostly identified in BRCA2 (5.3%), HFM1 (0.8%), ZSWIM7 (0.8%), MSH2 (0.8%) and MSH3 (0.8%). When compared with the cancer‐free cohort, POLN and POLG conferred high risk to PCa with odds ratio 6.9 and 20.5, respectively. We provided a comprehensive view of germline DDR gene mutations in PCa patients. We also identified two potential PCa predisposition genes: POLN and POLG, which have not been reported in the Western population, confirming the necessity of customizing a multigene panel for Chinese PCa patients.
What's new?
Germline DNA damage repair (DDR) deficiency is associated with increased cancer risk and poor prognosis inprostate cancer. However, a comprehensive view of DNA DDR germline gene mutations has not been reported. Through sequencing germline DNA from 246 Chinese prostate cancer patients, here the authors identified 79 pathogenic variants in 60 genes involved in nine DNA repair pathways. Almost a third of patients carried germline pathogenic DDR gene mutations—40% of them in homologous recombination or mismatch repair genes and 60%in other DNA repair pathways. The findings indicate the potential benefit of developing new drugs targeting other DDR pathways.
Pnictogen-bonding catalysis based on σ-hole interactions has recently attracted the attention of synthetic chemists. As a proof-of-concept for asymmetric pnictogen-bonding catalysis, we report herein ...an enantioselective transfer hydrogenation of benzoxazines catalyzed by a novel chiral antimony cation/anion pair. The chiral pnictogen catalyst library could be rapidly accessed from triarylstibine with readily available mandelic acid analogues, and the catalyst displays remarkable efficiency and enantiocontrol potency even at 0.05 mol % loading. Moreover, the properties of the catalyst and the mechanistic insights have been investigated by nonlinear effect studies, 1H NMR, LC-MS, and control experiments.
To improve the seismic performance of steel frame buildings in rural areas, an energy-dissipating composite wall (EDCW) assembled from concrete-filled steel tubular columns and concrete sheet walls ...was designed. Cyclic loading tests were simulated using the finite element method (FEM) to analyse the seismic performance of the EDCW. The reliability of numerical modelling and analysis was verified by comparing the hysteretic curves obtained by the finite element model with those obtained by previous experiments. The EDCW was designed for installation in a two-storey steel frame, and the FEM was used to determine the seismic performance of the steel frame, including the deformation and failure characteristics, hysteresis curves, and skeleton curves. The numerical simulation results showed that the EDCW dissipated most of the seismic energy and thus substantially improved the seismic performance of the frame. The seismic performances of 16 frames were compared to investigate the effects of the span ratio of the steel frame to the EDCW, the installation location of the EDCW, and the stiffness of the steel frame on the seismic performance of the frame.
The use of edible insects has a long history in China, where they have been consumed for more than 2000 years. In general, the level of acceptance is high for the consumption of insects in China. ...Many studies on edible insects have been conducted in the last 20 years, and the scope of the research includes the culture of entomophagy and the identification, nutritional value, farming and breeding of edible insects, in addition to food production and safety. Currently, 324 species of insects from 11 orders are documented that are either edible or associated with entomophagy in China, which include the common edible species, some less commonly consumed species and some medicinal insects. However, only approximately 10 to 20 types of insects are regularly consumed. The nutritional values for 174 species are available in China, including edible, feed and medicinal species. Although the nutritional values vary among species, all the insects examined contain protein, fat, vitamins and minerals at levels that meet human nutritional requirements. Edible insects were, and continue to be, consumed by different ethnic groups in many parts of China. People directly consume insects or food products made from insects. The processing of products from insect protein powder, oil and chitin, and the development of healthcare foods has been studied in China. People also consume insects indirectly by eating livestock that were fed insects, which may be a more acceptable pathway to use insects in human diets. Although limited, the data on the food safety of insects indicate that insects are safe for food or feed. Incidences of allergic reactions after consuming silkworm pupae, cicadas and crickets have been reported in China. Insect farming is a unique breeding industry in rural China and is a source of income for local people. Insects are reared and bred for human food, medicine and animal feed using two approaches in China: the insects are either fully domesticated and reared completely in captivity or are partially raised in captivity, and the insect habitat is manipulated to increase production. Depending on the type of relationship the insect has with humans, plants and the environment, different farming strategies are used. The social and scientific communities must work together to promote the use of insects as food and feed.
A GaN blue laser diode (BLD)-based visible-light communication link is demonstrated in a seawater environment to provide 16-quadrature amplitude modulation orthogonal frequency-division multiplexing ...(QAM OFDM) data transmission at 14.8 Gbps over 1.7 m. Lengthening the seawater distance to 10.2 m only decreases the transmission data rate by 4 Gbps, as caused by the frquency response limitation of the used avalanche photodiode. To optimize the QAM-OFDM transmission, the sampling rate of the encoded data is compromised to avoid the aliasing and oversampling effects during the waveform extraction procedure. The sampling rate is optimized to 3-5 times of the encoded data bandwidth for suppressing peak-to-average power ratio. Oversampling not only filters out background noise but also attenuates data amplitude to degrade transmission performance. Without using the multicarrier spectrally filtered OFDM, the 16-QAM OFDM data format only promotes the transmission capacity of BLD up to 7.6 Gbps in seawater. With spectrally filtering out the sidelobes of each OFDM subcarrier, the allowable modulation bandwidth is greatly improved from 1.9 to 2.7 GHz, as the intercarrier interference induced crosstalk between subbands is relieved to improve the SNR of the carried data with a raw data rate of up to 10.8 Gbps.
FOXO3a is a member of the FOXO subfamily of forkhead transcription factors that mediate a variety of cellular processes including apoptosis, proliferation, cell cycle progression, DNA damage and ...tumorigenesis. It also responds to several cellular stresses such as UV irradiation and oxidative stress. The function of FOXO3a is regulated by a complex network of processes, including post-transcriptional suppression by microRNAs (miRNAs), post-translational modifications (PTMs) and protein-protein interactions. FOXO3a is widely implicated in a variety of diseases, particularly in malignancy of breast, liver, colon, prostate, bladder, and nasopharyngeal cancers. Emerging evidences indicate that FOXO3a acts as a tumor suppressor in cancer. FOXO3a is frequently inactivated in cancer cell lines by mutation of the FOXO3a gene or cytoplasmic sequestration of FOXO3a protein. And its inactivation is associated with the initiation and progression of cancer. In experimental studies, overexpression of FOXO3a inhibits the proliferation, tumorigenic potential, and invasiveness of cancer cells, while silencing of FOXO3a results in marked attenuation in protection against tumorigenesis. The role of FOXO3a in both normal physiology as well as in cancer development have presented a great challenge to formulating an effective therapeutic strategy for cancer. In this review, we summarize the recent findings and overview of the current understanding of the influence of FOXO3a in cancer development and progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Suppression of viral infection by RNA in a nucleotide sequence homology-dependent manner was first reported in plants in early 1990s. Studies in the past 15 years have established a completely new ...RNA-based immune system against viruses that is mechanistically related to RNA silencing or RNA interference (RNAi). This viral immunity begins with recognition of viral double-stranded or structured RNA by the Dicer nuclease family of host immune receptors. In fungi, plants and invertebrates, the viral RNA trigger is processed into small interfering RNAs (siRNAs) to direct specific silencing of the homologous viral genomic and/or messenger RNAs by an RNaseH-like Argonaute protein. Deep sequencing of virus-derived siRNAs indicates that the immunity against viruses with a positive-strand RNA genome is induced by Dicer recognition of dsRNA formed during the initiation of viral progeny (+)RNA synthesis. The RNA-based immune pathway in these organisms overlaps the canonical dsRNA-siRNA pathway of RNAi and may require amplification of viral siRNAs by host RNA-dependent RNA polymerase in plants and nematodes. Production of virus-derived small RNAs is undetectable in mammalian cells infected with RNA viruses. However, infection of mammals with several nucleus-replicating DNA viruses induces production of virus-derived microRNAs capable of silencing host and viral mRNAs as found for viral siRNAs. Remarkably, recent studies indicate that prokaryotes also produce virus-derived small RNAs known as CRISPR RNAs to guide antiviral defense in a manner that has yet to be defined. In this article, we review the recent progress on the identification and mechanism of the key components including viral sensors, viral triggers, effectors, and amplifiers, of the small RNA-directed viral immunity. We also highlight some of the many unresolved questions.
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