BLOSSOMSTTM HUB – AN ONLINE TOOL FOR DESIGNING STTM VECTORS AND VISUALIZING PHENOTYPIC CHANGES OF STTM TRANSGENIC LINES

Small RNAs including microRNAs (miRNAs) and short interfering RNAs (siRNAs) are widely present in plants. They are transcribed from non-coding small RNA genes and then play as regulators to modulate the levels of messenger RNAs (mRNAs) of protein-coding genes via sequence pairings. This is because a paired complementary double sequence helix structure can trigger mRNA degradation or interfere with mRNA translation. Short Tandem Target Mimic (STTM) is a recently developed technology that can be used to produce a complementary sequence to a miRNA and destroy it or reduce the expression level of this miRNA via the formation of paired double-strand structure. Research has shown success in plant species like Arabidopsis [1] and tomato [2]. The main motivation of this thesis report is to describe a web application named DesignSTTM portal, which has been developed to computerize and automate the design of a STTM sequence that enables one to target a given miRNA species for degradation via sequence complementarities mechanism. The DesignSTTM then inserts the designed STTM sequence immediately downstream of the Cauliflower mosaic virus promoter called 35S in a DNA plasmid vector that can carry 35S promoter + STTM expression cassette into nuclei, and then insert it into a genome, where 35S can drive a STTM sequence to express and produce complementary sequences to target miRNA for silencing. Before the DesignSTTM portal displays the designed plasmid vector carrying STTM sequence in the form of a circular map, it uses an algorithm called basic local alignment search tool (BLAST) to query a locally installed vector database and then annotate all the elements in the plasmid vector. The elements that will be identified and annotated include all the genes, restriction enzyme sites, promoters, and the location of the inserted STTM sequence, which will then be plotted as features of plasmid vector in a map. The portal also displays the plasmid DNA sequence resulting after the insertion of STTM sequence, with a highlight of the location of the STTM sequence. The DesignSTTM portal also has a function to design the primer sequences used to amplify the STTM sequence and majority of plasmid vector using Polymerase Chain Reaction (PCR) technology and transfer them to a binary vector. The DesignSTTM portal is also capable of producing a PDF document incorporating all the derived results, and sending the file as an attachment to users’ email. Blossom STTM Hub’s also maintains an account for each user to store all the obtained results. The other web portal that was implemented in this Blossom STTM Hub’s is called MaterialSTTM, which was designed to store and visualize both genotypic and phenotypic data collected from STTM transgenic lines generated through transformation of STTM plasmid vectors into different plant species. Users can purchase the transgenic seeds available on MaterialSTTM portal by placing an order through the e-commerce store set up through the MTU Touchnet service. This tool will be instrumental for numerous plant biologists who study the functions of miRNAs species through modulating their expression levels in plants

Heat integration and heat exchanger network design for oxyfuel cement plants

The cement sector needs to reduce its CO2 emissions. An oxyfuel CO2 capture technology allows to considerably reduce the emission. However, heat recovery and energy efficiency measures are essential to make the technology economically feasible. An approach to design heat exchanger networks applied to a 1st generation oxyfuel cement plant is described in this article. The approach consists of two steps: preliminary targeting and heat exchanger network design. For the studied cement plant, the steam Rankine cycle was identified to be superior to organic Rankine cycles. In the ideal case about 10.5 MW of power can be recovered. However, in a cost-efficient simple heat exchanger network recovery of only about 8.7 MW is economically reasonableHeat integration and heat exchanger network design for oxyfuel cement plantsacceptedVersio

Giving Contents From an Unlabelled Plastic Bottle Containing Toxic Substance: A Case Report

Accidental exposure to toxic chemicals is a major concern for all of us, particularly for our children. Many households in different parts of the globe store chemicals/drugs right from medicine, toiletries, corrosives, etc. in bottles of various sizes, shapes, and substances. Many a time such bottles are either newly purchased or are empty bottles of previously-stored liquids or other contents. Such used bottles or containers are frequently used for preserving corrosives or household cleaning substances in homes. Such unlabelled or used bottles can become culprits for causing accidental poisoning to anyone, especially children leading to grave harm to their health and safety. In the present case, a 3-month-old male infant was brought to our pediatric emergency unit with a history of difficulty of breathing, blackening of the tongue, with sudden onset of crying, and inconsolability after being given water from a plastic bottle by his aunt. After a detailed assessment, it was found that the infant has a blackish color corrosive injury in and around the mouth involving the anterior half of the tongue, and lips with evidence of trickling drop type corrosive injuries over the right side of the neck and right supraclavicular region.  Internally, except for epiglottic edema, no other significant findings were noted. On follow-up examination, the complication was noticed as the process of healing of the corrosive injury in and around the mouth as a fish mouth appearance. Upon investigation, it was found that the infant was sick with fever for which he was given contents from an unlabelled plastic bottle containing battery acid (sulfuric acid, H2SO4) thinking it was the water of Zam Zam. Dispensing contents from unlabelled containers can be a potential threat to the lives of children as well as adults

Risk of Recurrence of Resected Stage I Non-small Cell Lung Cancer in Elderly Patients as Compared with Younger Patients

Half of all patients with non-small cell lung cancer (NSCLC) are 70 years or older at the time of diagnosis. Surgery is an option for fit elderly patients with early stage disease, but rates of disease recurrence after surgical resection are not well described. We report the outcomes in elderly patients (70 years or older) with stage I NSCLC after surgical resection.We conducted a retrospective study of patients diagnosed with stage I NSCLC after surgical resection at Washington University School of Medicine-Alvin J. Siteman Cancer Center from 1990 to 2000. Demographic, pathologic, treatment, and follow-up data were collected. Recurrence rates and overall survival were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazards models were used to detect associations between potential prognostic factors and survival and recurrence.Of the 715 patients with stage I NSCLC, 286 were 70 years or older at diagnosis. In this elderly cohort, the median age was 74 years (range, 70–89 years) and 140 of them were women (49%). Lobectomy was performed in 237 patients (83%) whereas 43 patients (15%) had a wedge or segmental resection, and six patients (2%) underwent pneumonectomy. Clinical and pathologic characteristics were not statistically different between the elderly and younger cohorts, with the exception that older patients were more likely to be white (90% versus 80%, p = 0.0003) and less likely to be smokers (88% versus 95%, p = 0.019) compared with the younger cohort. With a median follow-up of 4.6 years, the overall 5-year survival rate was 52% with a 5-year recurrence rate of 24%. In comparison, the patients younger than 70 years had a 5-year survival rate of 67% (p < 0.001) and a 5-year recurrence rate of 24%.Although overall survival was worse in elderly patients, estimated disease recurrence rates after resection were identical

Direct Type I IFN but Not MDA5/TLR3 Activation of Dendritic Cells Is Required for Maturation and Metabolic Shift to Glycolysis after Poly IC Stimulation

We thank the Rockefeller University Center for Clinical and Translational Science (UL1 TR000043 NCATS, NIH) for technical support

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention

Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings

The cytoskeleton in cell-autonomous immunity: structural determinants of host defence

Host cells use antimicrobial proteins, pathogen-restrictive compartmentalization and cell death in their defence against intracellular pathogens. Recent work has revealed that four components of the cytoskeleton — actin, microtubules, intermediate filaments and septins, which are well known for their roles in cell division, shape and movement — have important functions in innate immunity and cellular self-defence. Investigations using cellular and animal models have shown that these cytoskeletal proteins are crucial for sensing bacteria and for mobilizing effector mechanisms to eliminate them. In this Review, we highlight the emerging roles of the cytoskeleton as a structural determinant of cell-autonomous host defence

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe