Hasil untuk "Biochemistry"

F. Fleming, Lihua Yao, P. Ravikumar et al.

M. E. Wilkinson, C. Charenton, K. Nagai

The spliceosome removes introns from messenger RNA precursors (pre-mRNA). Decades of biochemistry and genetics combined with recent structural studies of the spliceosome have produced a detailed view of the mechanism of splicing. In this review, we aim to make this mechanism understandable and provide several videos of the spliceosome in action to illustrate the intricate choreography of splicing. The U1 and U2 small nuclear ribonucleoproteins (snRNPs) mark an intron and recruit the U4/U6.U5 tri-snRNP. Transfer of the 5' splice site (5'SS) from U1 to U6 snRNA triggers unwinding of U6 snRNA from U4 snRNA. U6 folds with U2 snRNA into an RNA-based active site that positions the 5'SS at two catalytic metal ions. The branch point (BP) adenosine attacks the 5'SS, producing a free 5' exon. Removal of the BP adenosine from the active site allows the 3'SS to bind, so that the 5' exon attacks the 3'SS to produce mature mRNA and an excised lariat intron. Expected final online publication date for the Annual Review of Biochemistry, Volume 89 is June 22, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Shraddha Surana, Ashwin Srinivasan, Michael Bain

Engineering information systems for scientific data analysis presents significant challenges: complex workflows requiring exploration of large solution spaces, close collaboration with domain specialists, and the need for maintainable, interpretable implementations. Traditional manual development is time-consuming, while "No Code" approaches using large language models (LLMs) often produce unreliable systems. We present iProg, a tool implementing Interactive Structured Inductive Programming. iProg employs a variant of a '2-way Intelligibility' communication protocol to constrain collaborative system construction by a human and an LLM. Specifically, given a natural-language description of the overall data analysis task, iProg uses an LLM to first identify an appropriate decomposition of the problem into a declarative representation, expressed as a Data Flow Diagram (DFD). In a second phase, iProg then uses an LLM to generate code for each DFD process. In both stages, human feedback, mediated through the constructs provided by the communication protocol, is used to verify LLMs' outputs. We evaluate iProg extensively on two published scientific collaborations (astrophysics and biochemistry), demonstrating that it is possible to identify appropriate system decompositions and construct end-to-end information systems with better performance, higher code quality, and order-of-magnitude faster development compared to Low Code/No Code alternatives. The tool is available at: https://shraddhasurana.github.io/dhaani/

Yunfei Li, Jun Wei, Shaohua Cheng et al.

Spectral detection technology offers non-destructive, in situ, and high-speed capabilities, making it widely applicable for detecting biological and chemical samples and quantifying their concentrations. Water resources, essential to life on Earth, are widely distributed across the planet. The application of spectral technology to underwater environments is useful for wide-area water resource monitoring. Although spectral detection technology is well-established, its underwater application presents challenges, including waterproof housing design, power supply, and data transmission, which limit widespread application of underwater spectral detection. Furthermore, underwater spectral detection necessitates the development of compatible computational methods for sample classification or regression analysis. Focusing on underwater spectral detection, this work involved the construction of a suitable hardware system. A compact spectrometer and LEDs (400 nm–800 nm) were employed as the detection and light source modules, respectively, resulting in a compact system architecture. Extensive tests confirmed that the miniaturized design-maintained system performance. Further, this study addressed the estimation of total phosphorus (TP) concentration in water using spectral data. Samples with varying TP concentrations were prepared and calibrated against standard detection instruments. Subsequently, classification algorithms applied to the acquired spectral data enabled the in situ underwater determination of TP concentration in these samples. This work demonstrates the feasibility of underwater spectral detection for future in situ, high-speed monitoring of aquatic biochemical indicators. In the future, after adding UV LED light source, more water quality parameter information can be obtained.

Gianluigi Giannelli, Elisa Fasani, Giovanni DalCorso

Nessreen S. Abdelhamid, Huda Salem AlSalem, Faisal K. Algethami et al.

For the first time, two direct and eco-friendly chromatographic approaches were adapted for the simultaneous estimation of pheniramine maleate (PAM) and its major toxic impurity, 2-benzyl pyridine (BNZ). Method A used reversed-phase ultra-performance liquid chromatography; separation was achieved within 4 min using a C₁₈ column with a developing system of methanol/water (60:40 <i>v</i>/<i>v</i>) with a 0.1 mL/min flow rate. Photodiode array detection was adjusted at 215 nm. The method was linear in the ranges of 5.0–70.0 and 0.05–10.0 µg/mL for PAM and BNZ, correspondingly. Method B used thin-layer chromatography; separation was applied on silica gel TLC F₂₅₄ using ethanol/ethyl acetate/liquid ammonia (8:2:0.1, in volumes) at room temperature, at 265 nm. Linearity was assured at concentration ranges 0.5–8.0 and 0.1–3.0 µg/band for the two components, respectively. Generally, the new UPLC and TLC methods outperform the old ones in terms of quickness, greenness, and sensitivity. Concisely, the greenness features were partially achieved using the Green Analytical Procedure Index (GAPI) and the Analytical Greenness (AGREE) pictograms. In contrast, the usefulness of the novel approaches was assured via the Blue Applicability Grade Index (BAGI) tool.

Feyza Sarışık, Ayten Oğuz, Murat Şahin et al.

Objective: Betatrophin is a hepatokine that modulates hepatic glucose and lipid metabolism and contributes to non-alcoholic fatty liver disease (NAFLD) pathogenesis. Therefore, this study aimed to investigate the relationship between NAFLD and betatrophin levels in hypogonadal males. Methods: The study included 56 newly diagnosed hypogonadal males aged 18-60 and 60 eugonadal males of similar age and body mass index. All participants were assessed for anthropometric and metabolic parameters, liver function tests, and betatrophin levels. Transient elastography was used to evaluate liver steatosis [controlled attenuation parameter (CAP)] and fibrosis [liver stiffness measurement (LSM)]. Accordingly, hypogonadal and control groups were divided into NAFLD (n=64) and non-NAFLD (n=52). Results: Controlled attenuation parameter, LSM, waist circumference (WC), triglycerides (TG), IR index homeostasis model assessment (HOMA-IR), and betatrophin were significantly higher in the hypogonadal group than controls. Hepatic steatosis and fibrosis (67.9%-43.3%) were higher in hypogonadal males. Triglycerides, HOMA-IR, and betatrophin were higher, and total testosterone was significantly lower in the NAFLD group. Serum betatrophin was also significantly higher in patients with fibrosis than without. There was a significant positive correlation between WC, TG, HOMA-IR, betatrophin, and LSM and CAP. The predictive factors were TG (β=0.329, P < .001), betatrophin (β=0.221, P=.029), HOMA-IR (β=0.213, P=.019) for CAP, and betatrophin for LSM (β=0.466, P < .001). Conclusion: Non-alcoholic fatty liver disease is more common in hypogonadal males than in eugonadal males. Betatrophin is an independent risk factor for developing and progressing NAFLD. However, more research is needed to explain the causal relationship between betatrophin and NAFLD.

Ignacio E. Sánchez, Ezequiel A. Galpern, Diego U. Ferreiro

We propose that spontaneous folding and molecular evolution of biopolymers are two universal aspects that must concur for life to happen. These aspects are fundamentally related to the chemical composition of biopolymers and crucially depend on the solvent in which they are embedded. We show that molecular information theory and energy landscape theory allow us to explore the limits that solvents impose on biopolymer existence. We consider 54 solvents, including water, alcohols, hydrocarbons, halogenated solvents, aromatic solvents, and low molecular weight substances made up of elements abundant in the universe, which may potentially take part in alternative biochemistries. We find that along with water, there are many solvents for which the liquid regime is compatible with biopolymer folding and evolution. We present a ranking of the solvents in terms of biopolymer compatibility. Many of these solvents have been found in molecular clouds or may be expected to occur in extrasolar planets.

Audrey Short, Thomas P. Fay, Thien Crisanto et al.

Efficiently balancing photochemistry and photoprotection is crucial for survival and productivity of photosynthetic organisms in the rapidly fluctuating light levels found in natural environments. The ability to respond quickly to sudden changes in light level is clearly advantageous. In the alga Nannochloropsis oceanica we observed an ability to respond rapidly to sudden increases in light level which occur soon after a previous high-light exposure. This ability implies a kind of memory. In this work, we explore the xanthophyll cycle in N. oceanica as a short-term photoprotective memory system. By combining snapshot fluorescence lifetime measurements with a biochemistry-based quantitative model, we show that short-term "memory" arises from the xanthophyll cycle. In addition, the model enables us to characterize the relative quenching abilities of the three xanthophyll cycle components. Given the ubiquity of the xanthophyll cycle in photosynthetic organisms the model described here will be of utility in improving our understanding of vascular plant and algal photoprotection with important implications for crop productivity.

Yoav Ravid, Samo Penič, Yuko Mimori-Kiyosue et al.

Eukaryotic cells intrinsically change their shape, by changing the composition of their membrane and by restructuring their underlying cytoskeleton. We present here further studies and extensions of a minimal physical model, describing a closed vesicle with mobile curved membrane protein complexes. The cytoskeletal forces describe the protrusive force due to actin polymerization which is recruited to the membrane by the curved protein complexes. We characterize the phase diagrams of this model, as function of the magnitude of the active forces, nearest-neighbor protein interactions and the proteins' spontaneous curvature. It was previously shown that this model can explain the formation of lamellipodia-like flat protrusions, and here we explore the regimes where the model can also give rise to filopodia-like tubular protrusions. We extend the simulation with curved components of both convex and concave species, where we find the formation of complex ruffled clusters, as well as internalized invaginations that resemble the process of endocytosis and macropinocytosis. We alter the force model representing the cytoskeleton to simulate the effects of bundled instead of branched structure, resulting in shapes which resemble filopodia.

Margareta Wagner, Bernd Meyer, Martin Setvin et al.

The state of protonation/deprotonation of surfaces has far-ranging implications in all areas of chemistry: from acid-base catalysis$^1$ and the electro- and photocatalytic splitting of water$^2$, to the behavior of minerals$^3$ and biochemistry$^4$. The acidity of a molecule or a surface site is described by its proton affinity (PA) and pK$_\mathrm{a}$ value (the negative logarithm of the equilibrium constant of the proton transfer reaction in solution). For solids, in contrast to molecules, the acidity of individual sites is difficult to assess. For mineral surfaces such as oxides they are estimated by semi-empirical concepts such as bond-order valence sums$^5$, and also increasingly modeled with first-principles molecular dynamics simulations$^{6,7}$. Currently such predictions cannot be tested - the experimental measures used for comparison are typically average quantities integrated over the whole surface or, in some cases, individual crystal facets$^8$, such as the point of zero charge (pzc)$^9$. Here we assess individual hydroxyls on In$_2$O$_3$(111), a model oxide with four different types of surface oxygen atoms, and probe the strength of their hydrogen bond with the tip of a non-contact atomic force microscope (AFM). The force curves are in quantitative agreement with density-functional theory (DFT) calculations. By relating the results to known proton affinities and pK$_\mathrm{a}$ values of gas-phase molecules, we provide a direct measure of proton affinity distributions at the atomic scale.

Chao Li, Christoph Kaspar, Ping Zhou et al.

Abstract Electron-vibration coupling is of critical importance for the development of molecular electronics, spintronics, and quantum technologies, as it affects transport properties and spin dynamics. The control over charge-state transitions and subsequent molecular vibrations using scanning tunneling microscopy typically requires the use of a decoupling layer. Here we show the vibronic excitations of tetrabromotetraazapyrene (TBTAP) molecules directly adsorbed on Ag(111) into an orientational glassy phase. The electron-deficient TBTAP is singly-occupied by an electron donated from the substrate, resulting in a spin 1/2 state, which is confirmed by a Kondo resonance. The TBTAP•− discharge is controlled by tip-gating and leads to a series of peaks in scanning tunneling spectroscopy. These occurrences are explained by combining a double-barrier tunneling junction with a Franck-Condon model including molecular vibrational modes. This work demonstrates that suitable precursor design enables gate-dependent vibrational excitations of molecules on a metal, thereby providing a method to investigate electron-vibration coupling in molecular assemblies without a decoupling layer.

Gomaa Mostafa-Hedeab, Amany Behairy, Yasmina M. Abd-Elhakim et al.

This study assessed the possible protective role of green synthesized zinc oxide nanoparticles using <i>Moringa olifera</i> leaf extract (MO-ZNPs) in acrylamide (ACR)-induced reproductive dysfunctions in male rats. ACR (20 mg/kg b.wt/day) and/or MO-ZNPs (10 mg/kg b.wt/day) were given orally by gastric gavage for 60 days. Then, sperm parameters; testicular enzymes; oxidative stress markers; reproductive hormones including testosterone, luteinizing hormone (LH)-estradiol, and follicle-stimulating hormone (FSH) concentration; testis histology; steroidogenesis-related gene expression; and apoptotic markers were examined. The findings revealed that MO-ZNPs significantly ameliorated the ACR-induced decline in the gonadosomatic index and altered the pituitary–gonadal axis, reflected by decreased serum testosterone and FSH with increased estradiol and LH, and sperm analysis disruption. Furthermore, a notable restoration of the tissue content of antioxidants (catalase and reduced glutathione) but depletion of malondialdehyde was evident in MO-ZNPs+ACR-treated rats compared to ACR-exposed ones. In addition, MO-ZNPs oral dosing markedly rescued the histopathological changes and apoptotic caspase-3 reactions in the testis resulting from ACR exposure. Furthermore, in MO-ZNPs+ACR-treated rats, ACR-induced downregulation of testicular steroidogenesis genes and proliferating cell nuclear antigen (PCNA) immune-expression were reversed. Conclusively, MO-ZNPs protected male rats from ACR-induced reproductive toxicity by suppressing oxidative injury and apoptosis while boosting steroidogenesis and sex hormones.

Martin Hessling, Ben Sicks, Anna-Maria Gierke et al.

(1) Background: Hand hygiene with chemical disinfectants is an important measure to reduce the spread of infections, but frequent use can cause skin irritation. In recent years, it has become widely accepted that visible light can also have an antimicrobial effect, and visible light has even been applied to the disinfection of wounds. The present study aims to evaluate whether hand disinfection with visible light is a realistic alternative to chemical disinfectants. (2) Methods: Human hands were irradiated with a dose of 10 or 33 J/cm² of visible violet light (405 nm) for 3 or 10 min, respectively. The reducing effect of the visible violet light was determined by comparing the contact agar plate results of irradiated and non-irradiated hands. Comparative experiments with a conventional hand disinfecting gel were also performed. Applicable standards were consulted to evaluate skin exposure to the irradiation. (3) Results: Irradiation of the hands with 10 and 33 J/cm² resulted in an average reduction of microorganisms on the skin of 0.43 and 0.76 log-levels, respectively. These disinfection results with visible violet light are far behind those of the disinfectant gel, which achieved a reduction of 2.17 log-levels. Additionally, due to legal limits, a 3-min irradiation can only be performed five times per day and a 10-min procedure only once. (4) Conclusion: Since the irradiation doses applied up to now have not provided a substantial antimicrobial effect, and since an increase in the dose in a short time period is not arbitrarily possible without heating the hand unpleasantly, visible light of 405 nm seems rather unsuitable for repeated hand disinfection.

Hakan Çelebi, Tolga Bahadır, İsmail Şimşek et al.

All over the world, environmental engineers, environmental biologists, biochemists, and other scientists are concerned about environmental pollution. In particular, different treatment technologies and applications in terms of water and soil health have been investigated for years. Studies show that the bioprocess (biosorption, bioremediation, bioaccumulation, etc.) approach is more advantageous (economical, easy design, and environmentally friendly, etc.) than many treatment methods. Thanks to these advantages, bioprocesses have been preferred for the removal of different pollutants in the receiving environment. Effective microorganisms (EMOs) are defined as mixed cultures of advantageous and naturally occurring microorganisms that can be used as vaccine material. An EMO is a natural fermentation product that is not chemically or genetically modified in the form of a concentrated solution. An EMO consists of 10 species, including photosynthetic (<i>Rhodopseudomonas palustrus</i> and <i>Rhodobacter spaeroides</i>, etc.) and lactic acid (<i>Lactobacillus plantarum</i>, <i>Lactobacillus casei</i> and <i>Streptoccus lactis</i>, etc.) bacterial groups, yeasts (<i>Saccharomyces cerevisiae</i> and <i>Candida utilis</i>, etc.), actinomycetes, and fermenting fungi The main components of an EMO are lactic acid bacteria, yeasts, and photosynthetic bacteria. In a liquid solution, they are in harmony. This article aims to review the literature on “Effective Microorganisms (EMOs)” from different scientific databases and discuss the effectiveness of using EMOs for bioprocess.

Hania Benmebarek, Karima Kharroub

Halophiles are microorganisms that inhabit saline and hypersaline environments, requiring salinity to survive in such extreme conditions. These microorganisms are mainly researched for their biotechnological potential. This study aims to investigate the phenology of the studied strain, <i>Idiomarina loihiensis</i>, and to demonstrate its extracellular proteolytic activity, as well as the production of a protease via batch fermentation in halophilic microorganisms. Macroscopic studies revealed small colonies (≤5 mm) with a convex spherical structure, regular outline, smooth surface, and color ranging from beige to opaque cream. Protease production was investigated in high-salinity conditions with a moderately halophilic bacterium using basal media with varying nitrogen sources. This study found that the highest proteolytic activity occurred in media with tryptone and casein peptone as nitrogen sources, at pH 10, a temperature of 70 °C, and 22.5% salt concentration. The results also demonstrated that the studied protease was a thermostable enzyme.

G. Fasman

Yves-Henri Sanejouand

Xenon can produce general anesthesia. Its main protein target is the N-methyl-D-aspartate receptor, a ionotropic channel playing a pivotal role in the function of the central nervous system. The molecular mechanisms allowing this noble gas to have such a specific effect remain obscure, probably as a consequence of the lack of structural data at the atomic level of detail. Herein, as a result of five independent molecular dynamics simulations, three different binding sites were found for xenon in the glycine binding domain of the N-methyl-D-aspartate receptor. The absolute binding free energy of xenon in these sites ranges between -8 and -14 kJ/mole. However, it depends significantly upon the protein conformer chosen for performing the calculation, suggesting that larger values could probably be obtained, if other conformers were considered. These three sites are next to each other, one of them being next to the glycine site. This could explain why the F758W and F758Y mutations can prevent competitive inhibition by xenon without affecting glycine binding.

Alan J. Weaver, Timothy R. Borgogna, Galen O’Shea-Stone et al.

The rise in bacterial resistance to common antibiotics has raised an increased need for alternative treatment strategies. The natural antibacterial product, 18β-glycyrrhetinic acid (GRA) has shown efficacy against community-associated methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), although its interactions against planktonic and biofilm modes of growth remain poorly understood. This investigation utilized biochemical and metabolic approaches to further elucidate the effects of GRA on MRSA. Prolonged exposure of planktonic MRSA cell cultures to GRA resulted in increased production of staphyloxanthin, a pigment known to exhibit antioxidant and membrane-stabilizing functions. Then, 1D ¹H NMR analyses of intracellular metabolite extracts from MRSA treated with GRA revealed significant changes in intracellular polar metabolite profiles, including increased levels of succinate and citrate, and significant reductions in several amino acids, including branch chain amino acids. These changes reflect the MRSA response to GRA exposure, including potentially altering its membrane composition, which consumes branched chain amino acids and leads to significant energy expenditure. Although GRA itself had no significant effect of biofilm viability, it seems to be an effective biofilm disruptor. This may be related to interference with cell–cell aggregation, as treatment of planktonic MRSA cultures with GRA leads to a significant reduction in micro-aggregation. The dispersive nature of GRA on MRSA biofilms may prove valuable for treatment of such infections and could be used to increase susceptibility to complementary antibiotic therapeutics.