58 research outputs found
Otitis Media in Sperm-Associated Antigen 6 (Spag6)-Deficient Mice
Mammalian SPAG6 protein is localized to the axoneme central apparatus, and it is required for normal flagella and cilia motility. Recent studies demonstrated that the protein also regulates ciliogenesis and cilia polarity in the epithelial cells of brain ventricles and trachea. Motile cilia are also present in the epithelial cells of the middle ear and Eustachian tubes, where the ciliary system participates in the movement of serous fluid and mucus in the middle ear. Cilia defects are associated with otitis media (OM), presumably due to an inability to efficiently transport fluid, mucus and particles including microorganisms. We investigated the potential role of SPAG6 in the middle ear and Eustachian tubes by studying mice with a targeted mutation in theSpag6 gene. SPAG6 is expressed in the ciliated cells of middle ear epithelial cells. The orientation of the ciliary basal feet was random in the middle ear epithelial cells of Spag6-deficient mice, and there was an associated disrupted localization of the planar cell polarity (PCP) protein, FZD6. These features are associated with disordered cilia orientation, confirmed by scanning electron microscopy, which leads to uncoordinated cilia beating. The Spag6 mutant mice were also prone to develop OM. However, there were no significant differences in bacterial populations, epithelial goblet cell density, mucin expression and Eustachian tube angle between the mutant and wild-type mice, suggesting that OM was due to accumulation of fluid and mucus secondary to the ciliary dysfunction. Our studies demonstrate a role for Spag6 in the pathogenesis of OM in mice, possibly through its role in the regulation of cilia/basal body polarity through the PCP-dependent mechanisms in the middle ear and Eustachian tubes
S-nitrosylation may inhibit the activity of COP1 in plant photomorphogenesis
Protein S-nitrosylation, which is defined by the covalent attachment of nitric oxide (NO) to the thiol group of cysteine residues, is known to play critical roles in plant development and stress responses. NO promotes seedling photomorphogenesis and NO emission is enhanced by light. However, the function of protein S-nitrosylation in plant photomorphogenesis is largely unknown. E3 ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) and transcription factor ELONGATED HYPOCOTYL 5 (HY5) antagonistically regulate seedling photomorphogenesis. COP1 inhibits plant photomorphogenesis by targeting photomorphogenic promoters like HY5 for 26S proteasome degradation. Here, we report that COP1 is S-nitrosylated in vitro. Mass spectrometry analyses revealed that two evolutionarily well conserved residues, cysteine 425 and cysteine 607, in the WD40 domain of COP1 are S-nitrosylated. S-nitrosylated glutathione (GSNO) is an important physiological NO donor for protein S-nitrosylation. The Arabidopsis (Arabidopsis thaliana) gsnor1-3 mutant, which accumulates higher level of GSNO, accumulated higher HY5 levels than wildtype (WT), indicating that COP1 activity is inhibited. Protein S-nitrosylation can be reversed by Thioredoxin-h5 (TRXh5) in plants. Indeed, COP1 interacts directly with TRXh5 and its close homolog TRXh3. Moreover, catalase 3 (CAT3) acts as a transnitrosylase that transfers NO to its target proteins like GSNO reductase (GSNOR). We found that CAT3 interacts with COP1 in plants. Taken together, our data indicate that the activity of COP1 is likely inhibited by NO via S-nitrosylation to promote the accumulation of HY5 and photomorphogenesis
PSR J1926-0652: A Pulsar with Interesting Emission Properties Discovered at FAST
We describe PSR J1926-0652, a pulsar recently discovered with the
Five-hundred-meter Aperture Spherical radio Telescope (FAST). Using sensitive
single-pulse detections from FAST and long-term timing observations from the
Parkes 64-m radio telescope, we probed phenomena on both long and short time
scales. The FAST observations covered a wide frequency range from 270 to 800
MHz, enabling individual pulses to be studied in detail. The pulsar exhibits at
least four profile components, short-term nulling lasting from 4 to 450 pulses,
complex subpulse drifting behaviours and intermittency on scales of tens of
minutes. While the average band spacing P3 is relatively constant across
different bursts and components, significant variations in the separation of
adjacent bands are seen, especially near the beginning and end of a burst. Band
shapes and slopes are quite variable, especially for the trailing components
and for the shorter bursts. We show that for each burst the last detectable
pulse prior to emission ceasing has different properties compared to other
pulses. These complexities pose challenges for the classic carousel-type
models.Comment: 13pages with 12 figure
Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery
The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300∼700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features
The Tianlai Cylinder Pathfinder array: System functions and basic performance analysis
The Tianlai Cylinder Pathfinder is a radio interferometer array designed to test techniques for 21 cm intensity mapping in the
post-reionization Universe, with the ultimate aim of mapping the large scale structure and measuring cosmological parameters
such as the dark energy equation of state. Each of its three parallel cylinder reflectors is oriented in the north-south direction, and
the array has a large field of view. As the Earth rotates, the northern sky is observed by drift scanning. The array is located in
Hongliuxia, a radio-quiet site in Xinjiang, and saw its first light in September 2016. In this first data analysis paper for the Tianlai
cylinder array, we discuss the sub-system qualification tests, and present basic system performance obtained from preliminary
analysis of the commissioning observations during 2016-2018. We show typical interferometric visibility data, from which we
derive the actual beam profile in the east-west direction and the frequency band-pass response. We describe also the calibration
process to determine the complex gains for the array elements, either using bright astronomical point sources, or an artificial on
site calibrator source, and discuss the instrument response stability, crucial for transit interferometry. Based on this analysis, we
find a system temperature of about 90 K, and we also estimate the sensitivity of the array
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Association between glycolysis markers and prognosis of liver cancer: a systematic review and meta-analysis
Abstract Background In recent years, the capacity of tumor cells to maintain high levels of glycolysis, even in the presence of oxygen, has emerged as one of the main metabolic traits and garnered considerable attention. The purpose of this meta-analysis is to investigate the prognostic value of glycolysis markers in liver cancer. Methods PubMed, Embase, and Cochrane Library databases were searched for articles on glycolytic marker expression levels associated with the prognosis of liver cancer until April 2023. Stata SE14.0 was used to calculate the aggregate hazard ratios and 95% confidence intervals. Results Thirty-five studies were included. The worse overall survival (OS) (P < 0.001), disease-free survival (DFS) (P = 0.001), recurrence-free survival (RFS) (P = 0.004), and time to recurrence (TTR) (P < 0.001) were significantly associated with elevated expression of glycolysis markers. Higher expression of PKM2 (P < 0.001), STMN1 (P = 0.002), MCT4 (P < 0.001), GLUT1 (P = 0.025), HK-2 (P < 0.001), and CA9 (P < 0.001) were significantly related to shorter OS. Increased levels of PKM2 (P < 0.001), CA9 (P = 0.005), and MCT4 (P < 0.001) were associated with worse DFS. Elevated PKM2 expression (P = 0.002) was also associated with poorer RFS in hepatocellular carcinoma patients. GLUT2 expression was not correlated with the prognosis of liver cancer (P = 0.134). Conclusions Elevated expression of glycolysis markers was associated with worse OS, DFS, RFS, and TTR in patients with liver cancer. Therefore, these glycolysis markers could serve as potential prognostic markers and therapeutic targets in liver cancer. Trial registration PROSPERO registration: CRD42023469645
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