Hasil untuk "Biochemistry"

Chang-Xiao Shi, Shun-Ran Yang, Ying-Qi Li et al.

<i>Saccharomyces cerevisiae</i> (SC) can be incorporated into ruminant diets as a postbiotic product. This study aimed to explore the effects of supplementing different levels of SC in the diets of mid-fattening Angus steers under heat stress conditions. A total of twenty-seven steers were randomly allocated into 3 groups: control, 30 g SC addition and 60 g SC addition groups. After a 7-day adaptation period followed by a 120-day experimental period, including respiratory rate, rectal temperature, growth performance, apparent digestibility of nutrients, rumen fermentation parameters, urine metabolites, serum biochemistry and antioxidant were measured. The results showed that the rectal temperature and respiratory rate of cattle decreased upon the addition of SC during heat stress. Meanwhile, the growth performance of cattle was improved in the 30 g SC addition group. The serum energy metabolism related indexes, such as non-esterified fatty acids, glucose, and β-hydroxybutyric acid, were altered. Additionally, the activity of catalase was significantly enhanced with the addition of SC. Overall, the addition of SC to the diets of mid-fattening Angus steer did not negatively affect rumen fermentation and nutrient apparent digestibility. Instead, it was capable of improving physiological performance under heat stress by modifying the energy metabolism and augmenting antioxidant capacity, which ultimately led to an improvement in growth performance. In conclusion, the most suitable level of SC to be added to the diet of mid-fattening Angus steers is 30 g/steer/d.

Noah Peña, Yichen Hou, Christopher P. Watkins et al.

Abstract Transfer RNA (tRNA) is the most abundant cellular RNA family in terms of copy numbers. It not only folds into defined structures but also has complex cellular interaction networks involving aminoacyl-tRNA synthetases, translation factors, and ribosomes. The human tRNAome is comprised of chromosomal-encoded tRNAs with a large sequence diversity and mitochondrial-encoded tRNAs with A/U-rich sequences and noncanonical tertiary interactions. How tRNA folding and interactions in a eukaryotic cell respond to stress is poorly understood. Here, we develop DM-DMS-MaPseq, which utilizes in vivo dimethyl-sulfate (DMS) chemical probing and mutational profiling (MaP) coupled with demethylase (DM) treatment in transcriptome-wide tRNA sequencing to profile structures and the cellular interactions of human chromosomal and mitochondrial-encoded tRNAs. We found that tRNAs maintain stable structures in vivo, but the in vivo DMS profiles are vastly different from those in vitro, which can be explained by their interactions with cellular proteins and the ribosome. We also identify cytosolic and mitochondrial tRNA structure and interaction changes upon arsenite treatment, a type of oxidative stress that induces translational reprogramming, which is consistent with global translation repression in both compartments. Our results reveal variations of tRNA structurome and dynamic interactome that have functional consequences in translational regulation.

Paula Saffie-Awad, Spencer M. Grant, Mary B. Makarious et al.

Abstract Risk prediction models play a crucial role in advancing healthcare by enabling early detection and supporting personalized medicine. Nonetheless, polygenic risk scores (PRS) for Parkinson’s disease (PD) have not been extensively studied across diverse populations, contributing to health disparities. In this study, we constructed 105 PRS using individual-level data from seven ancestries and compared two different models. Model 1 was based on the cumulative effect of 90 known European PD risk variants, weighted by summary statistics from four independent ancestries (European, East Asian, Latino/Admixed American, and African/Admixed). Model 2 leveraged multi-ancestry summary statistics using a p-value thresholding approach to improve prediction across diverse populations. Our findings provide a comprehensive assessment of PRS performance across ancestries and highlight the limitations of a “one-size-fits-all” approach to genetic risk prediction. We observed variability in predictive performance between models, underscoring the need for larger sample sizes and ancestry-specific approaches to enhance accuracy. These results establish a foundation for future research aimed at improving generalizability in genetic risk prediction for PD.

Valery Gunas, Oleksandr Maievskyi, Nataliia Raksha et al.

Background. The expansion of the territory of human habitation leads to inevitable interference in the natural range of distribution of one or another species of animals, some of which may be dangerous for human life. Scorpions—the Arachnida class and order Scorpiones—can be considered as such typical representatives. Scorpions of the Buthidae family pose a particular danger to humans. However, LD50 has not yet been defined for many species of this family, in particular, new representatives of the genus Leiurus. Leiurus macroctenus is a newly described species of scorpion distributed in Oman, and the toxicity of its venom is still unknown. Estimating the LD50 of the venom is the first and most important step in creating the antivenom and understanding the medical significance of the researched animal species. The purpose of this study was to determine the lethal dose (LD100), the maximum tolerated dose (LD0), and the average lethal dose (LD50) in rats when using Leiurus macroctenus scorpion venom. Methods and Results. 15 sexually mature scorpions were used in the study, which were kept in the same conditions and milked by a common method (electric milking). For the study, 60 male rats were used, which were injected intramuscularly with 0.5 ml of venom solution with a gradual increase in the dose (5 groups, 10 rats in each), and 10 rats were injected intramuscularly with physiological solution as control group. LD calculations were done using probit analysis method in the modification of the method by V.B. Prozorovsky. The LD0 of Leiurus macroctenus scorpion venom under the conditions of intramuscular injection was 0.02 mg/kg, LD100 was 0.13 mg/kg, and LD50 was 0.08 ± 0.01 mg/kg. Conclusions. The analysis of scientific publications and other sources of information gives reason to believe that Leiurus macroctenus has one of the highest values of LD50 not only among scorpions but also among all arthropods in the world. All these point to the significant clinical importance of this species of scorpion and require further research that will concern the toxic effect of its venom on various organ systems. Determining the LD50 of the venom for new scorpion species is crucial for creating effective antivenoms and understanding the medical implications of envenomation by this species.

Junyi Li, Ye Liu, Rui Zhang et al.

Abstract With the development of the economy and the increasing prevalence of skin problems, cutaneous medical aesthetics are gaining more and more attention. Skin disorders like poor wound healing, aging, and pigmentation have an impact not only on appearance but also on patients with physical and psychological issues, and even impose a significant financial burden on families and society. However, due to the complexities of its occurrence, present treatment options cannot produce optimal outcomes, indicating a dire need for new and effective treatments. Mesenchymal stem cells (MSCs) and their secretomics treatment is a new regenerative medicine therapy that promotes and regulates endogenous stem cell populations and/or replenishes cell pools to achieve tissue homeostasis and regeneration. It has demonstrated remarkable advantages in several skin-related in vivo and in vitro investigations, aiding in the improvement of skin conditions and the promotion of skin aesthetics. As a result, this review gives a complete description of recent scientific breakthroughs in MSCs for skin aesthetics and the limitations of their clinical applications, aiming to provide new ideas for future research and clinical transformation.

NAYAB RAZA, Mehreen Raza, ZARYAB RAZA et al.

United Nations Sustainable Goals. 06 emphasis on unbiased and even access of water and basic water sanitation and health sciences (WASH) facilities but, relentless reality is polar opposite where a stellar portion especially children are devoid of necessity facilities, especially in Pakistan. The most vulnerable group i-e children deprived of WASH facilities. The main objective of the study was, a WASH survey was conducted in two school settings i.e., Mehran and Sindh primary schools, using 100 forms comprising 21 Closed-ended questions directly linked with WASH facilities. The response was gathered from both boys and girls to maintain equity. Survey questionnaires are drafted as per international guild lines. The survey focused mainly on four dimensions: Handwashing, toilet, drinking water facilities, and Hygiene practice showing average (%) responses of boys to girls as 17.4:20.3, 29:14.6, 33.6:21, and 20.6:25.8, respectively showed the condition of mentioned dimensions improved in Mehran School rather than that of Sindh School. Bacteria were observed in water samples under a Fluorescence microscope that confirmed the presence of various bacteria species namely: Shigella, Escherichia coli, Vibrio, Salmonella, Cryptosporidium, Staphylococcus spp. Conclusively, there is a dire need to upgrade the WASH policy parallel to current scenario and need of society to lessen the severity of the problems, especially children facing in developing country like Pakistan.

José Escurra, Francisco P. Ferreira, Tomás R. López et al.

Lactic acid is a compound used industrially due to its properties. There are two methods for its production: chemical synthesis and microbial fermentation. In microbial fermentation, food industry waste can be used as a substrate, providing a route towards achieving a circular economy. Thus, this study evaluated different substrates for <i>Lactobacillus plantarum</i> growth, a lactic acid producer, such as molasses, whey, glucose, and saccharose, either alone or supplemented with additional nutrients. Bacterial growth parameters were assessed using OD₆₂₀ measurement. It was shown that whey supplemented with yeast extract supported the best growth, allowing a μ_max = 0.63 h⁻¹.

Filip Vujovic, Neil Hunter, Ramin M. Farahani

Abstract Notch signalling pathway plays a key role in metazoan biology by contributing to resolution of binary decisions in the life cycle of cells during development. Outcomes such as proliferation/differentiation dichotomy are resolved by transcriptional remodelling that follows a switch from Notchon to Notchoff state, characterised by dissociation of Notch intracellular domain (NICD) from DNA-bound RBPJ. Here we provide evidence that transitioning to the Notchoff state is regulated by heat flux, a phenomenon that aligns resolution of fate dichotomies to mitochondrial activity. A combination of phylogenetic analysis and computational biochemistry was utilised to disclose structural adaptations of Notch1 ankyrin domain that enabled function as a sensor of heat flux. We then employed DNA-based micro-thermography to measure heat flux during brain development, followed by analysis in vitro of the temperature-dependent behaviour of Notch1 in mouse neural progenitor cells. The structural capacity of NICD to operate as a thermodynamic sensor in metazoans stems from characteristic enrichment of charged acidic amino acids in β-hairpins of the ankyrin domain that amplify destabilising inter-residue electrostatic interactions and render the domain thermolabile. The instability emerges upon mitochondrial activity which raises the perinuclear and nuclear temperatures to 50 °C and 39 °C, respectively, leading to destabilization of Notch1 transcriptional complex and transitioning to the Notchoff state. Notch1 functions a metazoan thermodynamic sensor that is switched on by intercellular contacts, inputs heat flux as a proxy for mitochondrial activity in the Notchon state via the ankyrin domain and is eventually switched off in a temperature-dependent manner. Video abstract

Robert P. J. Cormier, Camille M. Champigny, Chloé J. Simard et al.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Carrie V. Breton, Remy Landon, Linda G. Kahn et al.

Carrie Breton and colleagues review the literature supporting evidence for transgenerational health effects of environmental exposures by epigenetic mechanisms. This Review summarizes current knowledge based on animal and human cohort studies, and discusses the ethical, legal, and social implications of epigenetic research in humans

Sara Xapelli, Sara Xapelli, Maria J. Diógenes et al.

Ömercan Topaloğlu, Bahri Evren, İbrahim Şahin

Linagliptin is a member of “Dipeptidyl Peptidase-4” (DPP-4) inhibitors and may be preferred for certain advantages. We present a type 2 diabetes case with developed skin findings after initiation of linagliptin. A 66-year-old type 2 diabetic woman with coronary heart disease for 10 years was admitted to our clinic with dry mouth, polydipsia and polyuria. She was on metformin, acetylsalicylic acid and nitrate treatment. The physical examination was unremarkable. On admission, blood glucose was 319 mg/dL, urine ketone was negative, serum biochemistry and arterial blood gas results were within normal limits. Linagliptin was added to treatment after glycemic regulation was achieved with intensive insulin regimen. On the second day of linagliptin treatment, palpable purpuralike lesions were seen in the lower and upper extremities. Linagliptin was considered as an etiological factor. After discontinuation of linagliptin, the lesions gradually regressed. DPP-4 inhibitors may lead to some dermatological side effects due to inhibition of other DPP enzymes. To the best of our knowledge, our case is the first case in the literature to develop palpable purpura after linagliptin treatment.

Gamal Badr, Eman Abdo Sayed, Hanan Waly et al.

Wataru Nihei, Masakazu Nagafuku, Hirotaka Hayamizu et al.

Intestinal cholesterol absorption is a key regulator of systemic cholesterol homeostasis. Excessive dietary cholesterol and its intestinal uptake lead to hypercholesterolemia, a major risk factor for cardiovascular disease. Intestinal cholesterol uptake is mediated by Niemann-Pick C1-like 1 (NPC1L1), a transmembrane protein localized in membrane microdomains (lipid rafts) enriched in gangliosides and cholesterol. The roles of gangliosides, such as monosialodihexosylganglioside (GM3) and its synthesizing enzyme GM3 synthase (GM3S), in NPC1L1-dependent cholesterol uptake have not been examined previously. Here, we examined NPC1L1-dependent cholesterol uptake in a cell model as well as in wild-type and apoE-deficient mice fed normal or high-cholesterol diets. We showed that NPC1L1-dependent cholesterol uptake was impaired in GM3S-deficient cells and that GM3S deficiency promoted resistance to hypercholesterolemia in both wild-type and apoE-deficient mice fed the high-cholesterol but not the normal diet. Our findings suggest that GM3 and related gangliosides are essential for NPC1L1-mediated intestinal cholesterol absorption and are potential targets for hypercholesterolemia therapy.

Ping Chai, Mykola Abramchuk, Michael Shatruk

Ternary intermetallics R117Co52+δSn112+γ (R = Y, La, Pr, Nd, and Ho) have been prepared by arc-melting followed by annealing at 800 °C. All the compounds belong to the Tb117Fe52Ge112 structure type (space group Fm 3 ¯ m) characterized by a complex giant cubic unit cell with a ~ 30 Å. The single-crystal structure determination of Y- and La-containing compounds reveals a significant structural disorder. A comparison of these and earlier reported crystal structures of R117Co52+δSn112+γ suggests that more extensive disorder occurs for structures that contain larger lanthanide atoms. This observation can be explained by the need to maintain optimal bonding interactions as the size of the unit cell increases. Y117Co56Sn115 exhibits weak paramagnetism due to the Co sublattice and does not show magnetic ordering in the 1.8–300 K range. Ho117Co55Sn108 shows ferromagnetic ordering at 10.6 K. Both Pr117Co54Sn112 and Nd117Co54Sn111 exhibit antiferromagnetic ordering at 17 K and 24.7 K, respectively, followed by a spin reorientation transition at lower temperature.

Lars-Anders Carlson, Yun Bai, Sarah C Keane et al.

HIV-1 Gag selects and packages a dimeric, unspliced viral RNA in the context of a large excess of cytosolic human RNAs. As Gag assembles on the plasma membrane, the HIV-1 genome is enriched relative to cellular RNAs by an unknown mechanism. We used a minimal system consisting of purified RNAs, recombinant HIV-1 Gag and giant unilamellar vesicles to recapitulate the selective packaging of the 5’ untranslated region of the HIV-1 genome in the presence of excess competitor RNA. Mutations in the CA-CTD domain of Gag which subtly affect the self-assembly of Gag abrogated RNA selectivity. We further found that tRNA suppresses Gag membrane binding less when Gag has bound viral RNA. The ability of HIV-1 Gag to selectively package its RNA genome and its self-assembly on membranes are thus interdependent on one another.

Sven Kruspe, Cindy Meyer, Ulrich Hahn

Photodynamic therapy (PDT) uses the therapeutic properties of light in combination with certain chemicals, called photosensitizers, to successfully treat brain, breast, prostate, and skin cancers. To improve PDT, current research focuses on the development of photosensitizers to specifically target cancer cells. In the past few years, aptamers have been developed to directly deliver cargo molecules into target cells. We conjugated the photosensitizer chlorin e6 (ce6) with a human interleukin-6 receptor (IL-6R) binding RNA aptamer, AIR-3A yielding AIR-3A-ce6 for application in high efficient PDT. AIR-3A-ce6 was rapidly and specifically internalized by IL-6R presenting (IL-6R+) cells. Upon light irradiation, targeted cells were selectively killed, while free ce6 did not show any toxic effect. Cells lacking the IL-6R were also not affected by AIR-3A-ce6. With this approach, we improved the target specificity of ce6-mediated PDT. In the future, other tumor-specific aptamers might be used to selectively localize photosensitizers into cells of interest and improve the efficacy and specificity of PDT in cancer and other diseases.