Follikulaarsest vedelikust pärinevate ekstratsellulaarsete vesiikulite iseloomustus ja nende panus perikonseptsiooni keskkonnas

Väitekirja elektrooniline versioon ei sisalda publikatsiooneViljatuse levimus on tänapäeval üheks suurimaks murekohaks. Maailma Terviseorganisatsiooni prognooside kohaselt on viljatus 21. sajandil suuruselt kolmas ülemaailmne terviseprobleem, mis jääb alla ainult vähi ja südame-veresoonkonna haigustele. Abistav reproduktiivtehnoloogia (Assisted Reproductive Technology - ART), sealhulgas in vitro viljastamine, on oluline terapeutiline meetod viljatuse ravis. ART edukuse määr ei ole aga endiselt piisavalt kõrgel tasemel ning on veel palju arenguruumi meetodi tõhusamaks muutmisel. Üks peamisi põhjuseid võib olla sugurakkude kvaliteedi tõstmise ebaõnnestumine ning ka ebasobiv implatatsioonieelne keskkond. Viimastel aastatel on EV-sid (membraaniga ümbritsetud nanosuuruses osakesed) üha enam tunnustatud kui alternatiivset rakkudevahelise suhtluse viisi. Mitmed uuringud on näidanud, et EV-sid on eraldatud peaaegu kõigist bioloogilistest vedelikest, sealhulgas follikulaarvedelikust (FF). FF-st pärinevad EV-d on olulised munarakkude küpsemiseks, viljastamiseks ja embrüo arenguks ning EVd on ka potentsiaalsed patofüsioloogiliste seisundite biomarkerid. Antud projektis uurisime FF EV-de rolli munajuha geeniekspressiooni reguleerimisel ning nende mõju spermatosoidide elutähtsatele funktsioonidele. Lisaks uurisime ka EV kaasas kantavate komponentide muutuseid polütsüstiliste munasarjade sündroomi (PCOS) patsientide FF EV-des võrreldes tervete inimestega. Meie esimene uuring näitas, et veiste FF ja FF EV-d muudavad veiste munajuhade epiteelirakkude geeniekspressiooni, mis võib kaasa aidata implantatsiooni eelse mikrokeskkonna, viljastamise ja embrüo varajase arengu ettevalmistamisele. Samamoodi näitas meie teine uuring, et veiste FF EV-d parendavad veiste spermatosoidide funktsionaalseid omadusi, eriti elujõulisust, kapatsitatsiooni ja akrosoomireaktsiooni. Lõpuks näitas meie kolmas uuring EV kaasas kantavate komponentide muutuseid erinevates patofüsioloogilistes seisundites (võrreldi PCOS patsiente ja viljakaid naisi) ja nende panust munasarjade signaali häiretesse. MiRNA-de analüüs näitas, et PCOS-i naistelt saadud FF EV-d kannavad tervete naistega võrreldes erinevaid miRNA-sid. Meie tulemused kinnitasid ka PCOS-i naiste puhul uudse FF EV-dest tuletatud miRNA, mida võiks kasutada PCOS-i diagnoosimise potentsiaalse biomarkerina. Kokkuvõtteks kinnitasid meie uuringute üldised leiud EV-de olemasolu FF-is ja nende mõju spermatosoididele ja munajuhade geeniekspressioonile ning erinevusi FF EV-de kaasas kantavates komponentides PCOS-i patsientide ja tervete naiste puhul.The prevalence of infertility is one of the most pressing issues in today’s society. Based on forecasts from the World Health Organization, infertility will rank third among the most serious global health problems in the twenty-first century, after cancer and cardiovascular disease. Assisted reproductive technology (ART), which includes in-vitro fertilization (IVF), is an essential therapeutic method for the treatment of infertility. However, the success rate of ART is still not up to the mark and there is abundant room for improvement in ART's. One of the main reasons hindering the success of ART’s could be the failure to enhance the quality of gametes, and undermining the factors present during preconception. Therefore, the current research identifies the bottleneck issues of infertility, methods for gametes improvement, and role of follicular fluid (FF) derived extracellular vesicles (EVs) in enhancing a suitable preconception environment that might be essential for fertilization and early embryo development. In recent years, EVs (membrane-bound nanosized particles) have become increasingly recognized as an alternative mode of intercellular communication. Many published studies have shown that EVs had been isolated from nearly every type of biological fluid, including FF. FF-derived EVs are essential for oocyte maturation, fertilization, embryo development and have potential to act as biomarkers. In this project, we investigated the role of FF EVs in regulating the gene expression of oviduct, its impact on vital functions of spermatozoa, and the cargo changes in FF derived EVs in Polycystic ovarian syndrome (PCOS) patients versus healthy people. Our first study showed that bovine FF and FF EVs alter the gene expression of bovine oviductal epithelial cells, which may contribute to the preparation of preconception microenvironment, fertilization and early embryo development. Similarly, our second study showed that bovine FF EVs enhances the functional properties of bovine spermatozoa, specifically viability, capacitation, and acrosome reaction. Finally, our third study showed EV cargo changes in different pathophysiological condition (PCOS and fertile women) and their contribution to ovarian signal disturbance. The miRNAs analysis revealed that FF EVs derived from PCOS women carry different miRNAs as compared to healthy women. Our results also confirmed novel miRNA derived from FF EVs in case of PCOS women, which could use as a potential biomarker for PCOS diagnosis. In conclusion, our studies overall findings confirmed the presence of EVs in FF and their effects on spermatozoa, and oviductal gene expression, and differences in cargo of FF EVs incase of PCOS patients versus healthy women.https://www.ester.ee/record=b551721

Modeling of Transport in Anatomic Respiratory Airways: Applications in Targeted Drug Delivery and Airborne Pathogenic Transmissions

This thesis aims to explore the potential of improving the efficacy of drugs for treatment of viral infections by targeting the nasopharynx, which is commonly the first site of infection for many viral pathogens. Currently, intranasal sprays are used, but the standard protocol (“Current Use” or CU) results in suboptimal drug deposition at the nasopharynx. To address this issue, an “Improved Use” or, IU protocol has been proposed, which involves pointing the spray bottle at a shallower angle and aiming slightly towards the cheeks. The IU delivery is also robust to perturbations in spray direction, which highlights the practical utility of this new drug administration protocol. The results of the simulation are experimentally verified using a 3D-printed airway cavity of a different subject. Next with the smallpox virus as an example pathogen, a numerical modeling framework for airborne respiratory diseases has been made. This modeling framework shows that the regional deposition of virus-laden inhaled droplets at the initial infection site (for smallpox, this is the oropharynx and the lungs) peaks for the droplet size range (8–27 μm for oropharyngeal deposition, and ≤ 14 μm for lungs) and can be used to determine the number of virions required to launch the infection in a subject. Subsequently, to explore the mechanics of lower airway disease progression, we have considered SARS-CoV-2. We have investigated the spread of SARS-CoV-2 from the nasopharynx to the lower airway. Using computational models, the inhalation process has been tracked with quantification for the volume of nasopharyngeal liquid transmitted to the lower airspace during each aspiration. The results suggest that a significant amount of liquid may be aspirated each day, which could lead to an increased risk of aggressive and accelerated lung infections in individuals with conditions like dysphagia. Finally, in view of the high cost and time required for conducting numerous numerical simulations, we have checked Machine Learning platforms as an alternative method for predicting regional deposition at various anatomical regions based on the geometric features of the anatomic flow domains in respiratory physiology. As an ancillary topic, the thesis also explores the morphological characteristics of the nose and their influence on airflow patterns and heat transfer dynamics inside the nasal cavity of a pig’s nose. The findings indicate that tortuosity has a crucial role in particle capture efficiency, particularly in high-olfactory mammalian species such as pigs and opossums. Understanding the fluid-particle interactions in nasal cavities could lead to the development of nature-inspired designs for various engineering processes, such as the creation of novel filtration devices. Therefore, it is essential to continue investigating the significance of heat management and particle screening in nasal structures to reveal their mechanistic functions and translate this information into practical applications

Use of surfactants to remove chromium (VI), nickel (II) and zinc (II) from sandy soil

The present study focuses mainly on the efficiency of surfactants sodium dodecyl sulfate (SDS), sodium dioctyl sulfosuccinate (AOT) and Triton X-100 (Tx-100) for the extraction of heavy metals Cr (VI), Ni (II) and Zn (II) from an artificially contaminated sandy soil. In addition, it also discusses metal extraction by a complexing agent EDTA with or without the addition of surfactants. To investigate metal extraction efficiency, both batch and column studies were performed. In batch studies, all surfactants are found to be nearly 2 to 3 times more effective for Cr (VI) removal, 3.0 to 6.2 times more effective for Ni (II) removal and 1.75 to 2.88 times more effective for Zn (II) removal, compared to the metal extraction by distilled water alone. Compared to the metal extraction by distilled water alone, metal extraction by EDTA in combination with SDS was 11 times greater for Cr (VI) removal, 8.07 times greater for Ni (II) removal and 4.94 times greater for Zn (II) removal, Column studies showed that 50 pore volumes of water alone can remove about 18% of Cr (VI), 19% of Ni (II) and 20% of Zn (II). On the other hand, at 50 pore volumes, the amount of Cr (VI), Ni (II) and Zn (II) removal by SDS appears to be relatively high about 24%, 27% and 33% respectively. However, injections of 50 pore volumes of SDS with EDTA were able to elute about 57% of Cr (VI), 67% of Ni (II) and 71% of Zn (II). These results suggest that surfactants do improve the efficiency of soil washing by enhancing the extraction of heavy metals such as chromium, nickel and zin

Effect of variety and nutrient sources on growth and yield of broccoli in southern belt of Bangladesh

Ongoing use of synthetic fertilizers affects soil structure. Organic manures can serve as an alternative to synthetic fertilizers. The study evaluated performance of five different types of nutrient sources (T0 =control, T1 = Urea @ 250 kg/ha, TSP @ 150 kg/ha, MoP @ 200 kg/ha, T2 = Cowdung @ 25 t/ha, T3 = Vermi compost @ 5 t/ha, T4 = fermented plant juice @ 500 ml/ha and T5 =Liquid fertilizer (Flora: consists of 20% nitrobenzene) @ 200 ml/ha) on growth and yield of broccoli, cvs. “V1=Known You” and “V2=Early Green”. Yield and yield contributing parameters such as plant height, number of leaves per plant, leaves fresh weight, length of stem, stem diameter, stem fresh weight, days taken for primary curd initiation, curd diameter, fresh weight of primary curd, no. of secondary curd per plant, fresh weight of secondary curd and yield per plot as well as hectare were measured in this experiment. In case of variety, the highest yield/plot 5.83kg and yield/ha 20.23 tons were recorded from “Early green”. Considering the nutrient factor, the highest curd weight (290.4g) per plant and yield/plot (5.01kg) were found in fermented plant juice nutrient sources. The highest benefit cost ratio BCR (3.21:1) was found in V2T4, among all other treatment combinations in respect of net return (Tk. 228934.97/ha) through the use of  fermented plant juice. Therefore, it can be concluded that fermented plant juice @ 500 ml/hacan be used to improve vegetative growth, and yield quality and quantity, and the broccoli cv. “Early Green” appears to be the best of the cultivars tested

ANTI-DEPRESSANTS AND COVID-19: A NEW RAY OF HOPE

The coronavirus disease pandemic has grown worldwide. As we understand the exact pathophysiology of the disease and how it affects the systems in the human body, we are in the process of discovering and repositioning drugs potentially effective in these regards. A few targets of these drugs are excessive inflammation following SARS-CoV-2 infection and sigma-1 receptor ER chaperone protein, which plays a role in replication. The recent discovery of antidepressants like fluvoxamine and clomipramine acting through these targets may provide a new ray of hope to decrease mortality and morbidity in severe COVID patients

Session 11: \u3cem\u3eCan machine learning predict particle deposition at specific intranasal regions based on computational fluid dynamics inputs/outputs and nasal geometry measurements?\u3c/em\u3e

Along with machine learning modeling, numerical simulations of respiratory airflow and particle transport can be used to improve targeted deposition at the upper respiratory infection site of numerous airborne diseases. Given the need for more patient data from varied demographics, we propose a machine learning-enabled protocol for determining optimal formulation design parameters that may match nasal spray device settings for successful drug delivery. We measured 11 anatomical parameters (including nasopharyngeal volume, nostril heights, and mid-nasal cavity volume) for 10 CT-based nasal geometries representative of the population for this aim. We also ran 160 computational fluid dynamics simulations of drug delivery on the same geometries for various breathing situations, using varied pressure gradients to drive inhaled air transport to evaluate drug deposition at the various upper airway areas for nasal inhalers. Using this test data, we constructed 18 machine-learning models to estimate the targeted deposition at the different regions of the upper airway. This study contributes to developing a customized, efficient intranasal delivery system for prophylactics, treatments, and immunizations; the findings will apply to a broad spectrum of respiratory disorders

iBitter-Fuse: A Novel Sequence-Based Bitter Peptide Predictor by Fusing Multi-View Features.

Accurate identification of bitter peptides is of great importance for better understanding their biochemical and biophysical properties. To date, machine learning-based methods have become effective approaches for providing a good avenue for identifying potential bitter peptides from large-scale protein datasets. Although few machine learning-based predictors have been developed for identifying the bitterness of peptides, their prediction performances could be improved. In this study, we developed a new predictor (named iBitter-Fuse) for achieving more accurate identification of bitter peptides. In the proposed iBitter-Fuse, we have integrated a variety of feature encoding schemes for providing sufficient information from different aspects, namely consisting of compositional information and physicochemical properties. To enhance the predictive performance, the customized genetic algorithm utilizing self-assessment-report (GA-SAR) was employed for identifying informative features followed by inputting optimal ones into a support vector machine (SVM)-based classifier for developing the final model (iBitter-Fuse). Benchmarking experiments based on both 10-fold cross-validation and independent tests indicated that the iBitter-Fuse was able to achieve more accurate performance as compared to state-of-the-art methods. To facilitate the high-throughput identification of bitter peptides, the iBitter-Fuse web server was established and made freely available online. It is anticipated that the iBitter-Fuse will be a useful tool for aiding the discovery and de novo design of bitter peptides