Hasil untuk "Biochemistry"

K. John-Alder

Objective To learn more about Biomedical Engineering and potentially obtain a lab position at the Tan Laboratory. I finished core classes for engineering and biology I took Engineering Calculus, General Chemistry and the Introductory Biology series. I learned a bit about synthetic and metabolic pathways in Bis2A. I also took Statistics and Upper-Division Economics. My professors were focused on using Excel to compute various statistics and spreadsheet calculations in Excel because that was what professionals were doing using the knowledge we learned in class. Thus, I am quite skilled in Excel. I continued on with classes, but my more relevant classes were organic chemistry, biochemistry, linear algebra, and econometrics. In organic chemistry, I learned about synthesis, NMR, IR, and I gained an understanding of how reaction mechanisms and protecting groups. In the last course of the series, the professor focused on bio-organic chemistry, which enabled me to better understand the reactions occurring in the human body. In biochemistry, I learned about the properties of the 20 amino acids, about protein purification, and about catalysts, enzymes, and how proteins function. In econometrics and linear algebra, I learned more about data analysis and how to compute regressions and other basic data analysis. My coursework was supplemented by learning a bit about Matlab and Stata. Over 300 hours of experience and community service from High School at UCI Med Center. I was a distinguished volunteer because I was the first volunteer to receive a thank you letter in all of the volunteer department's history. At UCD Med Center, I volunteered in the SICU. I am learning more about patient interactions, patient care, as well as secretarial work like answering phones and keeping track of multiple calls at once. With the College of Biology, I am currently enrolled in the Peer-Mentorship Program, where I offer advice to a freshman mentee to ease the transition from high school to college. I learned about what it takes to be a good role model and inspiration, and I intend to continue inspiring others in my life.\

H. K. Schachman

J. Harborne

Michael D. Miller, M. Krangel

G. Sembdner, B. Parthier

Khalishah Yusri, Sandra Jose, Karen S. Vermeulen et al.

Abstract Nicotinamide adenine dinucleotide (NAD+) is a coenzyme involved in a plethora of physiological reactions, with a key relevance in supporting mitochondrial function. Due to its critical role in these cellular processes, declining levels of NAD+ are associated with general aging and chronic disorders, including cognitive decline, sarcopenia, and metabolic diseases. These conditions are also typified by loss of mitochondrial health through dysfunction of homeostatic components such as mitophagy, unfolded protein response, and the antioxidant system. Therefore, raising cellular NAD+ through vitamin B3 family precursors or via drug-based interventions has become a broadly used strategy to restore mitochondrial and organismal homeostasis, with NAD+ precursors becoming a popular supplementation approach. As increasing components of the NAD+ biology are unraveled, this comprehensive review summarizes the advances in mechanisms of NAD+ metabolism and its modulation via compound-based strategies. Furthermore, it highlights the role of NAD+ in mitochondrial homeostasis in aging and disease conditions, the latest results of NAD+-boosting therapeutics in clinical trials, and areas of further translational development.

Carlos Antón-Plágaro, Kai-en Chen, Qian Guo et al.

Abstract Endosomal retrieval and recycling of integral cargo proteins is essential for cell and organism development and homeostasis and is orchestrated through a specialised endosomal nanodomain, the retrieval sub-domain. Sub-domain dysfunction is associated with human disease, but our mechanistic understanding of its function remains poorly described. Here, using proximity proteomics of retrieval sub-domain components Retromer and Retriever we identify mechanistic details of retrieval sub-domain composition and organization, including an unrecognised complexity in the interface with RAB GTPase switching. Combining X-ray crystallography and in silico predictions with biochemical and cellular analysis, we reveal that Retromer directly associates and recruits the RAB10 regulators DENND4A, DENND4C, TBC1D1, and TBC1D4, and the RAB35 regulator TBC1D13 to regulate retrieval sub-domain function. The retrieval sub-domain therefore constitutes a hub for integrating cargo recycling with the regulated switching of selected RAB GTPases. We propose this constitutes a major component of the neuroprotective role of the retrieval sub-domain.

D. Voet, J. Voet, C. Pratt

Xue Yang, Zexuan Liu, Weiwei Tang et al.

Endometrial carcinoma (ECa) is the fourth most common cancer among women. The oncogene PELP1 is frequently overexpressed in a variety of cancers, including ECa. We recently generated SMIP34, a small‐molecule inhibitor of PELP1 that suppresses PELP1 oncogenic signaling. In this study, we assessed the effectiveness of SMIP34 in treating ECa. Treatment of established and primary patient‐derived ECa cells with SMIP34 resulted in a significant reduction of cell viability, colony formation ability, and induction of apoptosis. RNA‐seq analyses showed that SMIP34‐regulated genes were negatively correlated with ribosome biogenesis and eukaryotic translation pathways. Mechanistic studies showed that the Rix complex, which is essential for ribosomal biogenesis, is disrupted upon SMIP34 binding to PELP1. Biochemical assays confirmed that SMIP34 reduced ribosomal biogenesis and new protein synthesis. Further, SMIP34 enhanced the efficacy of mTOR inhibitors in reducing viability of ECa cells. SMIP34 is also effective in reducing cell viability in ECa organoids in vitro and explants ex vivo. Importantly, SMIP34 treatment resulted in a significant reduction of the growth of ECa xenografts. Collectively, these findings underscore the potential of SMIP34 in treating ECa.

Cecilia Benazzato, Fernando Lojudice, Felizia Pöehlchen et al.

Abstract Zika virus (ZIKV) infection was first reported in 2015 in Brazil as causing microcephaly and other developmental abnormalities in newborns, leading to the identification of Congenital Zika Syndrome (CZS). Viral infections have been considered an environmental risk factor for neurodevelopmental disorders outcome, such as Autism Spectrum Disorder (ASD). Moreover, not only the infection per se, but maternal immune system activation during pregnancy, has been linked to fetal neurodevelopmental disorders. To understand the impact of ZIKV vertical infection on brain development, we derived induced pluripotent stem cells (iPSC) from Brazilian children born with CZS, some of the patients also being diagnosed with ASD. Comparing iPSC-derived neurons from CZS with a control group, we found lower levels of pre- and postsynaptic proteins and reduced functional synapses by puncta co-localization. Furthermore, neurons and astrocytes derived from the CZS group showed decreased glutamate levels. Additionally, the CZS group exhibited elevated levels of cytokine production, one of which being IL-6, already associated with the ASD phenotype. These preliminary findings suggest that ZIKV vertical infection may cause long-lasting disruptions in brain development during fetal stages, even in the absence of the virus after birth. These disruptions could contribute to neurodevelopmental disorders manifestations such as ASD. Our study contributes with novel knowledge of the CZS outcomes and paves the way for clinical validation and the development of potential interventions to mitigate the impact of ZIKV vertical infection on neurodevelopment.

Ricardo D. Coletta, Ali-Farid Safi, Arnab Pal et al.

J. M.

C. Hall

G. Lambeau, M. Gelb

M. S. Clark, J. I. Hoffman, L. S. Peck et al.

Abstract Polar ecosystems are experiencing amongst the most rapid rates of regional warming on Earth. Here, we discuss ‘omics’ approaches to investigate polar biodiversity, including the current state of the art, future perspectives and recommendations. We propose a community road map to generate and more fully exploit multi-omics data from polar organisms. These data are needed for the comprehensive evaluation of polar biodiversity and to reveal how life evolved and adapted to permanently cold environments with extreme seasonality. We argue that concerted action is required to mitigate the impact of warming on polar ecosystems via conservation efforts, to sustainably manage these unique habitats and their ecosystem services, and for the sustainable bioprospecting of novel genes and compounds for societal gain.

Hayet Elkolli, Meriem Elkolli, Farid S. Ataya et al.

<i>Eucalyptus</i>, a therapeutic plant mentioned in the ancient Algerian pharmacopeia, specifically two species belonging to the <i>Myrtaceae</i> family, <i>E</i>. <i>radiata</i> and <i>E</i>. <i>cinerea</i>, were investigated in this study for their antibacterial, antioxidant, and anti-inflammatory properties. The study used aqueous extracts (AE) obtained from these plants, and the extraction yields were found to be different. The in vitro antibacterial activity was evaluated using a disc diffusion assay against three typical bacterial strains. The results showed that the two extracts were effective against all three strains. Both extracts displayed significant antioxidant activity compared to BHT. The anti-inflammatory impact was evaluated using a protein (BSA) inhibition denaturation test. The <i>E</i>. <i>radiata</i> extract was found to inhibit inflammation by 85% at a concentration of 250 µg/mL, significantly higher than the Aspirin. All phytoconstituents present good pharmacokinetic characteristics without toxicity except very slight toxicity of terpineol and cineol and a maximum binding energy of −7.53 kcal/mol for its anti-TyrRS activity in silico. The study suggests that the extracts and their primary phytochemicals could enhance the efficacy of antibiotics, antioxidants, and non-steroidal anti-inflammatory drugs (NSAIDs). As pharmaceutical engineering experts, we believe this research contributes to developing natural-based drugs with potential therapeutic benefits.

Zvereva Elvira, Makarova Anastasiya, Ilyin Nikolay et al.

The possibility of reuse of heavy residues (oily sludge) of low-sulfur, highly paraffinic Mangyshlak oils as a basis for fuel with improved environmental characteristics for engines to marine, river and railway transport, gas turbine and boiler plants, steam boilers and industrial furnaces was shown. A variant of the joint application of the methods of nuclear magnetic resonance, laser confocal microscopy and rheology for study of micro- and mesoscopic structure and some physicochemical properties of crude oil products has been developed. It has been shown that preliminary heating to 90 ° C leads to disruption of the structure and hydrogen bonds between oil associates and complexes, increasing sample homogeneity due to precipitation of solid impurities, partial removal of water content, air bubbles and dissolved gases. The addition of medium distillate diesel fractions to preliminary heated oil residues will make it possible to obtain a higher quality version of the fuel with a reduced resinous and asphaltene substances, lower pour point, good energy content and low sulfur content. Thus, valuable energy-containing raw materials can be reused. It should also be noted that the reuse of accumulated oil waste will reduce the harmful effects of landfills, will preserve the natural landscape, and will cut the cost of extracting natural resources.

Naibin Zhang BS, Qiang Bian BS, Yankun Gao BS et al.

Human cancer statistics show that an increased incidence of urologic cancers such as bladder cancer, prostate cancer, and renal cell carcinoma. Due to the lack of early markers and effective therapeutic targets, their prognosis is poor. Fascin-1 is an actin-binding protein, which functions in the formation of cell protrusions by cross-linking with actin filaments. Studies have found that fascin-1 expression is elevated in most human cancers and is related to outcomes such as neoplasm metastasis, reduced survival, and increased aggressiveness. Fascin-1 has been considered as a potential therapeutic target for urologic cancers, but there is no comprehensive review to evaluate these studies. This review aimed to provide an enhanced literature review, outline, and summarize the mechanism of fascin-1 in urologic cancers and discuss the therapeutic potential of fascin-1 and the possibility of its use as a potential marker. We also focused on the correlation between the overexpression of fascin-1 and clinicopathological parameters. Mechanistically, fascin-1 is regulated by several regulators and signaling pathways (such as long noncoding RNA, microRNA, c-Jun N-terminal kinase, and extracellular regulated protein kinases). The overexpression of fascin-1 is related to clinicopathologic parameters such as pathological stage, bone or lymph node metastasis, and reduced disease-free survival. Several fascin-1 inhibitors (G2, NP-G2-044) have been evaluated in vitro and in preclinical models. The study proved the promising potential of fascin-1 as a newly developing biomarker and a potential therapeutic target that needs further investigation. The data also highlight the inadequacy of fascin-1 to serve as a novel biomarker for prostate cancer.

Andrea Hermann, H. Gowher, Albert Jeltsch et al.

J. Peled, Fei Li Kuang, M. Iglesias-Ussel et al.