A comparative study on psychiatric disorders: Identification of shared pathways and common agents

Distinct but closely related diseases generally present shared symptoms, which address possible overlaps among their pathogenic mechanisms. Identification of significantly impacted shared pathways and other common agents are expected to elucidate etiology of these disorders and to help design better intervention strategies. In this research effort, we studied six psychiatric disorders including schizophrenia (SCZ), anorexia (AN), bipolar disorder (BD), depressive disorder (DD), autism (AU) and attention deficit hyperactivity disorder (ADHD). Our methodology can be classified into the following two parts: In Part I, common susceptibility genes; and in Part II, genome-wide association studies (GWAS) data were used to find enriched pathways of psychiatric disorders. 59 KEGG pathways were commonly identified in both parts. 31 of these pathways are disease pathways. Pathways related to cancer and infectious diseases were predominant compared to others. Most of the acquired pathways were in accordance with previous studies in literature. A combination of susceptibility genes and GWAS data is an effective approach to identify significantly impacted pathways in multifactorial diseases. In this respect, shared modules were determined after applying hierarchical clustering of the enriched pathways. These identified modules may tell us the association of psychiatric disorders with the enriched pathways. Taken all together, common pathways and shared modules are expected to highlight the causative factors and important mechanisms behind complex psychiatric diseases, leading to effective drug discovery. © 2022 IEEE

Development of loop-mediated isothermal amplification (LAMP) based biosendor set for detection of genetically modified organisms (GMO) and Escherichia coli (E. Coli)

The worldwide usage of products with genetically modified organisms (GMOs) is constrained by different legal frameworks. GMO's usage limits are determined by the related regulations in each countries. "Regulation on Genetically Modified Organisms and Products" named law – effective since 2010 – draws the aforementioned conditions in Turkey. As a consequence, a variety of products are monitored by undergoing a GMO detection and classification processes. Researchers have been proposing different works regarding the specifically important problem of GMO-based products’ detection. Various methods such as Polymerase Chain Reaction, Ligase Chain Reaction, Rotating Circle Amplification are commonly used for DNA amplification, a crucial preprocessing step of the detection process. In this work, the loop-based isothermal amplification (LAMP) method which provides fast results and requires fewer temperature cycles is used. For the LAMP method to be properly implemented, the sample should be kept at 60-65:C between 35-120 minutes. Conventional laboratory devices used for this purpose can be characterized - on average – to be heavy (1-12 kg), expensive (1300-15000 €), unmovable and only operable by trained experts. In this thesis, we present the design, implementation and performance analysis of two prototype GMO-based product and bacteria detection devices that are portable (108-240 g) , fast (<30-40 minutes), affordable (<25-30 €) and pocket-size (6x6x3-9.7x6.8x5 cm) provided with battery system that allows its functionality outside laboratory environment. The temperature level controller, heater design, feedback circuit and the exterior of the device are prepared via different mechanical and electronic design software. A Proportional control based feedback control scheme is used to adjust the temperature with a high accuracy of (± 0.2:C). In this work, we extended the devices uses to E.coli bacteria detection as well. The detection was done using the LAMP method and is presented as the second device with its customized design providing high output (105 microchannels). Roundup Ready Soybean (RRS), gts40-3-2) with 0%, 0.1%, 1% and 10% GMO content were used for GMO analysis part and E. Coli ATCC 10536 bacteria for bacterial analysis. Both GMO and Bacteria detection and analysis results were done by the proposed devices showed similar performance in terms of accuracy and sensitivity when compared to the laboratory or commercial correspondents in the market while successfully outperforming them in the other already mentioned aspect

Stochastic modulation evidences a transitory EGF-Ras-ERK MAPK activity induced by PRMT5

The extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway involves a three-step cascade of kinases that transduce signals and promote processes such as cell growth, development, and apoptosis. An aberrant response of this pathway is related to the proliferation of cell diseases and tumors. By using simulation modeling, we document that the protein arginine methyltransferase 5 (PRMT5) modulates the MAPK pathway and thus avoids an aberrant behavior. PRMT5 methylates the Raf kinase, reducing its catalytic activity and thereby, reducing the activation of ERK in time and amplitude. Two minimal computational models of the epidermal growth factor (EGF)-Ras-ERK MAPK pathway influenced by PRMT5 were proposed: a first model in which PRMT5 is activated by EGF and a second one in which PRMT5 is stimulated by the cascade response. The reported results show that PRMT5 reduces the time duration and the expression of the activated ERK in both cases, but only in the first model PRMT5 limits the EGF range that generates an ERK activation. Based on our data, we propose the protein PRMT5 as a regulatory factor to develop strategies to fight against an excessive activity of the MAPK pathway, which could be of use in chronic diseases and cancer

Denitrifioivien mikrobien talviaktiivisuus ja dityppioksidin tuotto Suomen subarktisissa tundramaissa

Dityppioksidi (N₂O) on voimakas kasvihuonekaasu, jonka lämmityspotentiaali on lähes 300 kertaa suurempi verrattuna hiilidioksidiin. Maaperässä N₂O:ta vapautuu ilmakehään pääasiassa mikrobiologisessa prosessissa, denitrifikaatiossa. Arktiset ja subarktiset maaperät ovat tärkeitä N₂O:n lähteitä ja ilmaston lämpenemisen vuoksi niistä voi vapautua N₂O:ta tulevaisuudessa yhä enemmän. Lumipeite ja jääkerrokset vaikuttavat kasvihuonekaasujen tuotantoon talvella. Tässä pro gradu - työssä tutkittiin aktiivisia mikrobiyhteisöjä ja niiden toiminnallisia geenejä viidessä eri kasvillisuustyypissä subarktisilta tundramailta Pohjois-Suomessa huhtikuun alussa. Lisäksi erilaisia ympäristötekijöitä (pH, lämpötila, maaperän orgaaninen aines, maaperän vesipitoisuus ja lumen syvyys), sekä dityppioksidi- , metaani- ja hiilidioksidikaasuja tarkasteltiin yhdessä metatranskriptomidatan kanssa. Tutkimus keskittyi geeneihin jotka osallistuvat denitrifikaatioon, sillä se on pääasiallinen N₂O:n vapautumisprosessi. Tutkielman tulokset osoittivat, että mikrobiaktiivisuus oli huomattavaa jo huhtikuun alussa näissä tundramaissa. Mikro-organismit olivat aktiivisia talvella ja voivat tuottaa kasvihuonekaasuja läpi vuoden. Kilpisjärven tundramaat ovat monimutkaisia ekosysteemejä, ja erilaiset ympäristötekijät vaikuttivat aktiivisten denitrifioivien mikrobien runsauteen ja monimuotoisuuteen, sekä niiden toiminnallisiin geeneihin ja typpioksidin tuotantoon. Denitrifikaatioon osallistuvia entsyymejä koodaavat geenit olivat aktiiviisia ja N₂O kaasut vaihtelivat välillä - 4 - 21 μg m-2 d -1 . N₂O:n kokonaistuotanto näissä tundramaissa oli alhainen, mutta ilmeinen, ja nämä maaperät voivat olla merkittäviä N₂O-lähteitä talvisin.Nitrous oxide (N₂O) is a powerful greenhouse gas, and its global warming potential is almost 300 times more compared to carbon dioxide. In the soil ecosystem, N₂O is mainly released into the atmosphere in the microbiological process, denitrification. Subarctic tundra soils are important sources of N₂O and due to global warming, N₂O can be released an increasing amount from these soils in the future. Snow cover and ice layers influence to production of greenhouse gases during winter. In this master’s thesis, active microbial communities and their functional genes were studied from subarctic tundra soils across the five different vegetation types in northern Finland in early April. Additionally, various environmental factors (pH, soil temperature, soil organic matter, soil water content, and snow depth) and gas fluxes of nitrous oxide, methane, and carbon dioxide were studied together with metatranscriptomic data. The study focuses on the genes involved in denitrification, as it is the main process of releasing N₂O. This study showed that microbial activity was notable already in early April and indicated that microorganisms stayed active in these subarctic soils in winter and can continue producing greenhouse gases throughout the year. Kilpisjärvi tundra soils are complex systems, and various environmental factors shaped the abundance and diversity of active denitrifiers, their functional genes, and the production of N₂O. Transcripts of genes involved in denitrification were active and N₂O fluxes ranged from -4 to 21 μg m-2 d-1. Overall production of N₂O from these tundra soils was small, yet evident, and the soils can be notable sources of N₂O in winter

Proposta de ligante para o receptor de Neuropilina-1, alvo molecular do SARS-CoV-2 / Proposed ligand for the Neuropilin-1 receptor, molecular target of SARS-CoV-2

A COVID-19 é uma doença causada pelo vírus SARS-CoV-2, que veio a se tornar o maior problema de saúde pública da atualidade. No final de 2019 a doença se propagou por diversos países rapidamente, sendo decretado como pandemia poucos meses após o seu surgimento. Um dos mecanismos de entrada do vírus no sistema respiratório humano ocorre pela interação com a enzima conversora de angiotensina 2 (ECA2), presente na superfície das células do hospedeiro. Posteriormente, foi identificada uma via de entrada alternativa para o vírus, sendo o alvo específico a neuropilina-1 (NRP-1), um receptor ao qual se atribuem diversas atividades fisiológicas. Neste trabalho foi investigada a capacidade de derivados de kaempferol, um flavonoide ricamente encontrado na espécie arbustiva Baccharis dracunculifolia, de se ligar a essa proteína por meio de ancoragem molecular. As modificações na molécula de kaempferol foram realizadas com base na estrutura do ligante, sendo a primeira a ocorrência da formação de grupamento éter pela síntese de Williamson, a segunda por meio de uma halogenação no anel B do kaempferol, e a última, com a adição de fenol em relação ao anel B do kaempferol. Desta forma, obteve-se um derivado do subgrupo flavonol, com energia de ligação igual a –7,1 Kcal/mol, caracterizado pelos anéis aromáticos A e B, além do anel C, possuindo estes, ligações com hidroxilas e grupamento éteres que caracterizam suas atividades antioxidantes e antivirais, portanto, acredita-se que esta é um bom ligante para NRP-1, tendo potencial para inibir a replicação do vírus SARS-CoV-2

AI Enabled Drug Design and Side Effect Prediction Powered by Multi-Objective Evolutionary Algorithms & Transformer Models

Due to the large search space and conflicting objectives, drug design and discovery is a difficult problem for which new machine learning (ML) approaches are required. Here, the problem is to invent a method by which new, therapeutically useful, compounds can be discovered; and to simultaneously avoid compounds which will fail clinical trials or pass unwanted effects onto the end patient. By extending current technologies as well as adding new ones, more design criteria can be included, and more promising novel drugs can be discovered. This work advances the field of computational drug design by (1) developing MOEA-DT, a non-deep learning application for multi-objective molecular optimization, which generates new molecules with high performance in a variety of design criteria; and (2) developing SEMTL-BERT, a side effect prediction algorithm which leverages the latest ML techniques and datasets to accomplish its task. Experiments performed show that MOEA-DT either matches or outperforms other similar methods, and that SEMTL-BERT can enhance predictive ability