Sumoylation Contributes to Timekeeping and Temperature Compensation of the Plant Circadian Clock

The transcriptional circadian clock network is tuned into a 24-h oscillator by numerous posttranslational modifications on the proteins encoded by clock genes, differentially influencing their subcellular localization or activity. Clock proteins in any circadian organism are subject to posttranslational regulation, and many of the key enzymes, notably kinases and phosphatases, are functionally conserved between the clocks of mammals, fungi, and plants. We now establish sumoylation, the posttranslational modification of target proteins by the covalent attachment of the small ubiquitin-like modifier protein SUMO, as a novel mechanism regulating key clock properties in the model plant Arabidopsis. Using 2 different approaches, we show that mutant plant lines with decreased or increased levels of global sumoylation exhibit shortened or lengthened circadian period, respectively. One known functional role of sumoylation is to protect the proteome from temperature stress. The circadian clock is characterized by temperature compensation, meaning that proper timekeeping is ensured over the full range of physiologically relevant temperatures. Interestingly, we observed that the period defects in sumoylation mutant plants are strongly differential across temperature. Increased global sumoylation leads to undercompensation of the clock against temperature and decreased sumoylation to overcompensation, implying that sumoylation buffers the plant clock system against differential ambient temperature

Cutaneous infection by Mycobacterium haemophilum and kansasii in an IgA-deficient man

<p>Abstract</p> <p>Background</p> <p>The prevalence of infections by nontuberculous mycobacteria (NTM) has steadily increased over the past decades, especially in immunocompromised patients.</p> <p>Case presentation</p> <p>We present a patient with IgA-deficiency and mixed cutaneous infection by two slowly growing mycobacteria, <it>Mycobacterium </it>(<it>M.</it>) <it>haemophilum </it>and <it>M. kansasii.</it></p> <p>Conclusions</p> <p>Cutaneous <it>M. haemophilum </it>infections most often result from HIV or transplantation-associated immunosuppression. Rarely, <it>M. haemophilum </it>may also infect healthy patients or iatrogenically immunosuppressed patients without transplantation. <it>M. kansasii </it>is one of the most frequent NTM and large awareness exists about its involvement in human diseases. Mycobacterial diagnosis of cutaneous infections should be considered in long-lasting skin lesions.</p

SDSS-IV MaNGA-resolved Star Formation and Molecular Gas Properties of Green Valley Galaxies: A First Look with ALMA and MaNGA

We study the role of cold gas in quenching star formation in the green valley by analyzing ALMA 12 CO (1-0) observations of three galaxies with resolved optical spectroscopy from the MaNGA survey. We present resolution-matched maps of the star formation rate and molecular gas mass. These data are used to calculate the star formation efficiency (SFE) and gas fraction (f gas ) for these galaxies separately in the central "bulge" regions and outer disks. We find that, for the two galaxies whose global specific star formation rate (sSFR) deviates most from the star formation main sequence, the gas fraction in the bulges is significantly lower than that in their disks, supporting an "inside-out" model of galaxy quenching. For the two galaxies where SFE can be reliably determined in the central regions, the bulges and disks share similar SFEs. This suggests that a decline in f gas is the main driver of lowered sSFR in bulges compared to disks in green valley galaxies. Within the disks, there exist common correlations between the sSFR and SFE and between sSFR and f gas on kiloparsec scales - the local SFE or f gas in the disks declines with local sSFR. Our results support a picture in which the sSFR in bulges is primarily controlled by f gas , whereas both SFE and f gas play a role in lowering the sSFR in disks. A larger sample is required to confirm if the trend established in this work is representative of the green valley as a whole.The work is supported by the Ministry of Science & Technology of Taiwan under the grant MOST 103-2112-M-001-031-MY3 and 106-2112-M-001-034. R.M. and F.B. acknowledge support by the UK Science and Technology Facilities Council (STFC). R.M. acknowledges ERC Advanced Grant 695671 "QUENCH.

Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes.

BackgroundGeneral translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood.ResultsHere, we show that these sequence features specify 42-81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25-60 nucleotide segments within mRNA 5' regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5' regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA.ConclusionsOur work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell

Biodegradable collagen matrix implant vs mitomycin-C as an adjuvant in trabeculectomy: a 24-month, randomized clinical trial

AIM: To verify the safety and efficacy of Ologen (OLO) implant as adjuvant compared with low-dosage mitomycin-C (MMC) in trabeculectomy. METHODS: This was a prospective randomized clinical trial with a 24-month follow-up. Forty glaucoma patients (40 eyes) were assigned to trabeculectomy with MMC or OLO. Primary outcome includes target IOP at ≤21, ≤17, and ≤15 mm Hg; complete (target IOP without medications), and qualified success (target IOP regardless of medications). Secondary outcomes include bleb evaluation, according to Moorfields Bleb Grading System (MBGS); spectral domain optical coherence tomography (SD-OCT) examination; number of glaucoma medications; and frequency of postoperative adjunctive procedures and complications. RESULTS: The mean preoperative IOP was 26.5 (±5.2) in MMC and 27.3 (±6.0) in OLO eyes, without statistical significance. One-day postoperatively, the IOP dropped to 5.2 (±3.5) and 9.2 (±5.5) mm Hg, respectively (P=0.009). The IOP reduction was significant at end point in all groups (P=0.01), with a mean IOP of 16.0 (±2.9) and 16.5 (±2.1) mm Hg in MMC and OLO, respectively. The rates and Kaplan-Meier curves did not differ for both complete and qualified success at any target IOP. The bleb height in OLO group was higher than MMC one (P<0.05). SD-OCT analysis of successful/unsuccessful bleb in patients with or without complete success at IOP ≤17  mm Hg indicated a sensitivity of 83% and 73% and a specificity of 75% and 67%, respectively, for MMC and OLO groups. No adverse reaction to OLO was noted. CONCLUSIONS: Our results suggest that OLO implant could be a new, safe, and effective alternative to MMC, with similar long-term success rate

Fingerprint-based Wi-Fi indoor localization using map and inertial sensors

It is a common understanding that the localization accuracy can be improved by indoor maps and inertial sensors. However, there is a lack of concrete and generic solutions that combine these two features together and practically demonstrate its validity. This article aims to provide such a solution based on the mainstream fingerprint-based indoor localization approach. First, we introduce the theorem called reference points placement, which gives a theoretical guide to place reference points. Second, we design a Wi-Fi signal propagation-based cluster algorithm to reduce the amount of computation. The paper gives a parameter called reliability to overcome the skewing of inertial sensors. Then we also present Kalman filter and Markov chain to predict the system status. The system is able to provide high-accuracy real-time tracking by integrating indoor map and inertial sensors with Wi-Fi signal strength. Finally, the proposed work is evaluated and compared with the previous Wi-Fi indoor localization systems. In addition, the effect of inertial sensors’ reliability is also discussed. Results are drawn from a campus office building which is about 80 m×140 m with 57 access points

Caregiver awareness of reproductive health issues for women with intellectual disabilities

<p>Abstract</p> <p>Background</p> <p>Limited attention has been paid to the issue of reproductive health as it affects women with intellectual disabilities, despite reproductive health being a vital issue in public health policy for women in the general population. This paper describes caregiver awareness of reproductive health issues relative to women with intellectual disabilities who are being cared for in welfare institutions in Taiwan.</p> <p>Methods</p> <p>The study employed a cross-sectional, questionnaire-based study which recruited 1,152 caregivers (response rate = 71.87%) from 32 registered disability welfare institutions in Taiwan. We classified their understanding/awareness of reproductive health issues into four domains: menstrual (1) and menopause (2) issues, sex education (3), and reproductive health services (4). Each domain had five associated yes/no questions and the total score for the four domains was out of a maximum of 20. Data were analyzed using SPSS 15.0 software.</p> <p>Results</p> <p>We found that most of the caregivers were familiar with matters concerning sex education, menopause, and reproductive health services, but they lacked adequate understanding of issues associated with menstruation in women with ID. Many aspects of reproductive health such as "menstrual pain", "age at menarche", "masturbation", "diet during perimenopause", and "publicly available reproductive health services" were issues in which caregivers lacked adequate knowledge and required further instruction. Logistic regression analysis revealed that female caregivers with a university degree, and those who had experience assisting with reproductive health care were more inclined to have higher reproductive health awareness scores than their counterparts.</p> <p>Conclusions</p> <p>This study highlights that service providers should offer appropriate reproductive health education to institutional caregivers, and that more attention be focused on the personal experiences and concerns of intellectually disabled women in future research.</p

Overexpression of the Lung Cancer-Prognostic miR-146b MicroRNAs Has a Minimal and Negative Effect on the Malignant Phenotype of A549 Lung Cancer Cells

INTRODUCTION:Expression levels of miR-146b-5p and -3p microRNAs in human non-small cell lung cancer (NSCLC) are associated with recurrence of the disease after surgery. To understand this, the effect of miR-146b overexpression was studied in A549 human lung cancer cells. METHODS:A549 cells, engineered with lentiviruses to overexpress the human pre-miR-146b precursor microRNA, were examined for proliferation, colony formation on plastic surface and in soft agar, migration and invasiveness in cell culture and in vivo in mice, chemosensitivity to cisplatin and doxorubicin, and global gene expression. miR-146b expressions were assessed in microdissected stroma and epithelia of human NSCLC tumors. Association of miR-146b-5p and -3p expression in early stage NSCLC with recurrence was analyzed. PRINCIPAL FINDINGS:A549 pre-miR-146b-overexpressors had 3-8-fold higher levels of both miR-146b microRNAs than control cells. Overexpression did not alter cellular proliferation, chemosensitivity, migration, or invasiveness; affected only 0.3% of the mRNA transcriptome; and, reduced the ability to form colonies in vitro by 25%. In human NSCLC tumors, expression of both miR-146b microRNAs was 7-10-fold higher in stroma than in cancerous epithelia, and higher miR-146b-5p but lower -3p levels were predictive of recurrence. CONCLUSIONS:Only a minimal effect of pre-miR-146b overexpression on the malignant phenotype was seen in A549 cells. This could be because of opposing effects of miR-146b-5p and -3p overexpression as suggested by the conflicting recurrence-predictive values of the two microRNAs, or because miR-146b expression changes in non-cancerous stroma and not cancerous epithelia of tumors are responsible for the prognostic value of miR-146b