Using Shifts in Amino Acid Frequency and Substitution Rate to Identify Latent Structural Characters in Base-Excision Repair Enzymes

Protein evolution includes the birth and death of structural motifs. For example, a zinc finger or a salt bridge may be present in some, but not all, members of a protein family. We propose that such transitions are manifest in sequence phylogenies as concerted shifts in substitution rates of amino acids that are neighbors in a representative structure. First, we identified rate shifts in a quartet from the Fpg/Nei family of base excision repair enzymes using a method developed by Xun Gu and coworkers. We found the shifts to be spatially correlated, more precisely, associated with a flexible loop involved in bacterial Fpg substrate specificity. Consistent with our result, sequences and structures provide convincing evidence that this loop plays a very different role in other family members. Second, then, we developed a method for identifying latent protein structural characters (LSC) given a set of homologous sequences based on Gu's method and proximity in a high-resolution structure. Third, we identified LSC and assigned states of LSC to clades within the Fpg/Nei family of base excision repair enzymes. We describe seven LSC; an accompanying Proteopedia page (http://proteopedia.org/wiki/index.php/Fpg_Nei_Protein_Family) describes these in greater detail and facilitates 3D viewing. The LSC we found provided a surprisingly complete picture of the interaction of the protein with the DNA capturing familiar examples, such as a Zn finger, as well as more subtle interactions. Their preponderance is consistent with an important role as phylogenetic characters. Phylogenetic inference based on LSC provided convincing evidence of independent losses of Zn fingers. Structural motifs may serve as important phylogenetic characters and modeling transitions involving structural motifs may provide a much deeper understanding of protein evolution

Nanostring-based multigene assay to predict recurrence for gastric cancer patients after surgery

10.1371/journal.pone.0090133PLoS ONE93-POLN

An Earth-mass planet in a time of COVID-19: KMT-2020-BLG-0414Lb

We report the discovery of KMT-2020-BLG-0414Lb, with a planet-to-host mass ratio q2 = 0:9- 1:2 × 10-5 = 3-4 q⊕ at 1σ, which is the lowest mass-ratio microlensing planet to date. Together with two other recent discoveries (4. q=q⊕. 6), it fills out the previous empty sector at the bottom of the triangular (log s; log q) diagram, where s is the planet-host separation in units of the angular Einstein radius θE. Hence, these discoveries call into question the existence, or at least the strength, of the break in the mass-ratio function that was previously suggested to account for the paucity of very low-q planets. Due to the extreme magnification of the event, Amax ∼ 1450 for the underlying single-lens event, its light curve revealed a second companion with q3 ∼ 0:05 and j log s3j ∼ 1, i.e., a factor ∼ 10 closer to or farther from the host in projection. The measurements of the microlens parallax ∼E and the angular Einstein radius ∼E allow estimates of the host, planet and second companion masses, (M1;M2;M3) ∼ (0:3M⊙; 1:0M⊙; 17MJ ), the planet and second companion projected separations, (a⊥;2; a⊥;3) ∼ (1:5; 0:15 or 15) au, and system distance DL ∼ 1 kpc. The lens could account for most or all of the blended light (I ∼ 19:3) and so can be studied immediately with high-resolution photometric and spectroscopic observations that can further clarify the nature of the system. The planet was found as part of a new program of high-cadence follow-up observations of high-magnification events. The detection of this planet, despite the considerable difficulties imposed by COVID-19 (two KMT sites and OGLE were shut down), illustrates the potential utility of this program

Third national surveillance of risk factors of non-communicable diseases (SuRFNCD-2007) in Iran: methods and results on prevalence of diabetes, hypertension, obesity, central obesity, and dyslipidemia

<p>Abstract</p> <p>Background</p> <p>The burden of non-communicable diseases is rising globally. This trend seems to be faster in developing countries of the Middle East. In this study, we presented the latest prevalence rates of a number of important non-communicable diseases and their risk factors in the Iranian population.</p> <p>Methods</p> <p>The results of this study are extracted from the third national Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD-2007), conducted in 2007. A total of 5,287 Iranian citizens, aged 15–64 years, were included in this survey. Interviewer-administered questionnaires were applied to collect the data of participants including the demographics, diet, physical activity, smoking, history of hypertension, and history of diabetes. Anthropometric characteristics were measured and serum biochemistry profiles were determined on venous blood samples. Diabetes (fasting plasma glucose ≥ 126 mg/dl), hypertension (systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or use of anti-hypertensive drugs), dyslipidemia (hypertriglyceridemia: triglycerides ≥ 150 mg/dl, hypercholesterolemia: total cholesterol ≥ 200 mg/dl), obesity (body mass index ≥ 30 kg/m²), and central obesity (waist circumference ≥ 80 cm in females and ≥ 94 cm in males) were identified and the national prevalence rates were estimated.</p> <p>Results</p> <p>The prevalence of diabetes, hypertension, obesity, and central obesity was 8.7% (95%CI = 7.4–10.2%), 26.6% (95%CI = 24.4–28.9%), 22.3% (95%CI = 20.2–24.5%), and 53.6% (95%CI = 50.4–56.8%), respectively. The prevalence of hypertriglyceridemia and hypercholesterolemia was 36.4% (95%CI = 34.1–38.9%) and 42.9% (95%CI = 40.4–45.4%), respectively. All of the mentioned prevalence rates were higher among females (except hypertriglyceridemia) and urban residents.</p> <p>Conclusion</p> <p>We documented a strikingly high prevalence of a number of chronic non-communicable diseases and their risk factors among Iranian adults. Urgent preventive interventions should be implemented to combat the growing public health problems in Iran.</p

Expression of nicotinamide N-methyltransferase in hepatocellular carcinoma is associated with poor prognosis

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is the most common tumor in the adult liver, with high relapse and mortality rates despite diverse treatment modalities. In this study, nicotinamide N-methyltransferase (NNMT), a key enzyme in drug metabolism, was investigated as a potential prognostic factor.</p> <p>Methods</p> <p>Frozen tumors and non-cancerous surrounding tissues from 120 patients with primary HCC were studied. Expressions of NNMT and internal control genes were measured by real-time reverse-transcription PCR (RT-PCR). The relationship of NNMT mRNA level with clinicopathologic parameters and clinical outcome was evaluated.</p> <p>Results</p> <p>NNMT mRNA level is markedly reduced in HCCs compared to non-cancerous surrounding tissues (P < 0.0001), and NNMT expression in tumors was significantly correlated with tumor stage (P = 0.010). Moreover, stratification of patients based on tumor NNMT mRNA levels revealed that the patients who expressed higher NNMT mRNA levels tended to have a shorter overall survival (OS) time (P = 0.053) and a significantly shorter disease-free survival (DFS) time (P = 0.016). Both NNMT expression (P = 0.0096) and tumor stage (P = 0.0017) were found to be significant prognostic factors for DFS in a multivariate analysis.</p> <p>Conclusion</p> <p>The results of this study indicated that NNMT gene expression is associated with tumor stage and DFS time in HCC cases. Because of the broad substrate specificity of NNMT, which could alter the efficacy and adverse effects of chemotherapy, NNMT merits further investigation regarding its role as a prognostic factor with a larger cohort of HCC patients.</p

A standardized pathology report for gastric cancer: 2nd edition

The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies

The JCMT BISTRO Survey: Studying the Complex Magnetic Field of L43

We present observations of polarized dust emission at 850 μm from the L43 molecular cloud, which sits in the Ophiuchus cloud complex. The data were taken using SCUBA-2/POL-2 on the James Clerk Maxwell Telescope as a part of the BISTRO large program. L43 is a dense (NH 10 22 2 ~ –1023 cm−2) complex molecular cloud with a submillimeter-bright starless core and two protostellar sources. There appears to be an evolutionary gradient along the isolated filament that L43 is embedded within, with the most evolved source closest to the Sco OB2 association. One of the protostars drives a CO outflow that has created a cavity to the southeast. We see a magnetic field that appears to be aligned with the cavity walls of the outflow, suggesting interaction with the outflow. We also find a magnetic field strength of up to ∼160 ± 30 μG in the main starless core and up to ∼90 ± 40 μG in the more diffuse, extended region. These field strengths give magnetically super- and subcritical values, respectively, and both are found to be roughly trans-Alfvénic. We also present a new method of data reduction for these denser but fainter objects like starless cores

Wetlands for wastewater treatment and subsequent recycling of treated effluent : a review

Due to water scarcity challenges around the world, it is essential to think about non-conventional water resources to address the increased demand in clean freshwater. Environmental and public health problems may result from insufficient provision of sanitation and wastewater disposal facilities. Because of this, wastewater treatment and recycling methods will be vital to provide sufficient freshwater in the coming decades, since water resources are limited and more than 70% of water are consumed for irrigation purposes. Therefore, the application of treated wastewater for agricultural irrigation has much potential, especially when incorporating the reuse of nutrients like nitrogen and phosphorous, which are essential for plant production. Among the current treatment technologies applied in urban wastewater reuse for irrigation, wetlands were concluded to be the one of the most suitable ones in terms of pollutant removal and have advantages due to both low maintenance costs and required energy. Wetland behavior and efficiency concerning wastewater treatment is mainly linked to macrophyte composition, substrate, hydrology, surface loading rate, influent feeding mode, microorganism availability, and temperature. Constructed wetlands are very effective in removing organics and suspended solids, whereas the removal of nitrogen is relatively low, but could be improved by using a combination of various types of constructed wetlands meeting the irrigation reuse standards. The removal of phosphorus is usually low, unless special media with high sorption capacity are used. Pathogen removal from wetland effluent to meet irrigation reuse standards is a challenge unless supplementary lagoons or hybrid wetland systems are used