Exogenous Sources Research Articles

Abstract 4115027: Transcutaneous phototherapy improves left ventricular systolic function

Background: The emerging field of cardiac optogenetics uses pulses of light to stimulate optically-sensitive proteins in the heart, influencing cellular physiology with unprecedented spatiotemporal resolution. Potential benefits may include heart rhythm stabilization and relief from congestive heart failure (CHF). Transcutaneous phototherapy devices (LifeWave Inc, San Diego, USA) may provide similar benefit without the need for opsin expression in the heart or exogenous light sources. Objective: To investigate whether upregulation of carnosine activity using a wearable cutaneous phototherapy device may improve echocardiographic measures of left ventricular systolic function. Methods: The Carnosine ® adhesive skin patch (34 mm diameter) contain an organic crystalline material that reflects specific frequencies of infra-red light emitted through the skin, and known to activate carnosine dipeptides throughout the body. These function as a high-energy phosphate system known to enhance muscle function. Study participants (n=12 healthy volunteers, 40-66 years of age) underwent a focused baseline echocardiogram, which included atrial (A) and early (E) mitral valve inflow, peak tissue velocity (E’) at both the lateral and septal mitral annulus, and left ventricular ejection fraction (LVEF). 10-12 patches were then applied along the sternum and across the left thorax (3 rd -5 th interspace), incorporating the anterior axilla. The echocardiogram was repeated after 20-30 minutes. Results: LVEF was improved following application of the phototherapy device, increasing from 59.4±5.8% to 66.65±5.8% (Δ 6.3%, p<0.05), predicting an improvement in overall cardiac function. In those with normal diastolic function at baseline, septal E’ increased 7.3±0.57 cm/s to 8.2±0.58 cm/s (Δ 0.87 cm/s, p<0.05), indicating a direct effect on contractility. E and A wave velocities increased 2.46±0.14 cm/s and by 5.7±0.72 cm/s, indicating augmented hemodynamics trending towards significance. Conclusion: Cutaneous phototherapy devices may enhance left ventricular systolic function without the need for drug delivery, gene manipulation, or exogenous light sources.

TMET-17. LIPID METABOLIC HETEROGENEITY OF GLIOMA CELLULAR STATES REVEALS ENVIRONMENTAL DEPENDENCIES

Abstract Malignant growth and survival of cancer is supported through reprogrammed lipid metabolism. In gliomas, genetic alterations can drive lipid metabolic dysregulation revealing therapeutic opportunities to exploit lipid metabolic vulnerabilities within genetically defined subsets of glioma tumors. However, it remains unclear whether inter- and intra-tumoral transcriptomic heterogeneity in gliomas relates to distinct lipid programs and potential dependencies. Here we set out to characterize pan-glioma lipid metabolic heterogeneity through genomic, transcriptomic, and lipidomic profiling of a large and diverse cohort of patient tumor samples. We define key axes of lipid metabolic variability across gliomas and identify relationships between lipid metabolic gene expression programs and glioma lipidomic profiles. Intriguingly, intersection of lipid gene expression signatures with single cell RNA sequencing revealed patterns of lipid metabolic heterogeneity that distinguish neurodevelopmental cellular states of gliomas, mirroring patterns of lipid metabolic diversity across cell types within the normal brain. Consequently, tumors with opposing cellular state enrichment have distinct lipid metabolism and environmental dependencies. Tumors enriched for Radial Glia-like states have high capacity for de novo fatty acid synthesis while tumors enriched for oligodendrocyte progenitor-like states are dependent on exogenous sources of lipids for survival and growth. These findings connect inter- and intra-tumoral heterogeneity of cellular states to variability in lipid metabolic reprogramming to reveal future avenues for precision medicine.

Genomic insights into key mechanisms for carbon, nitrogen, and phosphate assimilation by the acidophilic, halotolerant genus Acidihalobacter members.

In-depth comparative genomic analysis was conducted to predict carbon, nitrogen, and phosphate assimilation pathways in the halotolerant, acidophilic genus Acidihalobacter. The study primarily aimed to understand how the metabolic capabilities of each species can determine their roles and effects on the microbial ecology of their unique saline and acidic environments, as well as in their potential application to saline water bioleaching systems. All four genomes encoded the genes for the complete tricarboxylic acid cycle, including 2-oxoglutarate dehydrogenase, a key enzyme absent in obligate chemolithotrophic acidophiles. Genes for a unique carboxysome shell protein, csoS1D, typically found in halotolerant bacteria but not in acidophiles, were identified. All genomes contained lactate and malate utilization genes, but only Ac. ferrooxydans DSM 14175T contained genes for the metabolism of propionate. Genes for phosphate assimilation were present, though organized differently across species. Only Ac. prosperus DSM 5130T and Ac. aeolianus DSM 14174T genomes contained nitrogen fixation genes, while Ac. ferrooxydans DSM 14175T and Ac. yilgarnensis DSM 105917T possessed genes for urease transporters and respiratory nitrate reductases, respectively. The findings suggest that all species can fix carbon dioxide but can also potentially utilize exogenous carbon sources and that the non-nitrogen-fixing species rely on alternative nitrogen assimilation mechanisms.

Enhanced bioremediation of bensulfuron-methyl contaminated soil by Hansschlegelia zhihuaiae S113: metabolic pathways and bacterial community structure

Bensulfuron-methyl (BSM), a widely used herbicide, can persist in soil and damag sensitive crops. Microbial degradation, supplemented with exogenous additives, provides an effective strategy to enhance BSM breakdown. Hansschlegelia zhihuaiae S113 has been shown to efficiently degrade this sulfonylurea herbicide. However, depending solely on a single strain for degradation proves inefficient and unlikely to achieve ideal remediation in practical applications. This study assessed the impact of various carbon sources on the degradation efficiency of S113 in BSM-polluted soil. Among these, glucose was the most effective, achieving a 98.7% degradation rate after 9 d of inoculation. In addition, seven intermediates were detected during BSM degradation in soil through the cleavage of the phenyl ring ester bond, the pyrimidine rings, and urea bridge peptide bond, among other pathways. 2-amino-4,6-dimethoxy pyrimidine (ADMP), and 2-(aminosulfonylmethyl)-methyl benzoate(MSMB) were the primary intermediates. These metabolites were less toxic to maize, sorghum, and bacteria than the BSM. Community structure analysis indicated that variations in exogenous carbon sources and environmental pollutants significantly improved the ecological functions of soil microbial communities, enhancing pollutant degradation. Addition of carbon sources notably affected soil microbial community structure, modifying metabolic activities and interaction patterns. Specifically, glucose substantially increased the richness and diversity of soil bacterial communities. These findings offer valuable insights for field remediation practices and contributed to the development of more robuste soil pollution management strategies.

Mannose-6-Phosphate Isomerase Functional Status Shapes a Rearrangement in the Proteome and Degradome of Mannose-Treated Melanoma Cells.

Metabolic reprogramming is a ubiquitous feature of transformed cells, comprising one of the hallmarks of cancer and enabling neoplastic cells to adapt to new environments. Accumulated evidence reports on the failure of some neoplastic cells to convert mannose-6-phosphate into fructose-6-phosphate, thereby impairing tumor growth in cells displaying low levels of mannose-6-phosphate isomerase (MPI). Thus, we performed functional analyses and profiled the proteome landscape and the repertoire of substrates of proteases (degradome) of melanoma cell lines with distinct mutational backgrounds submitted to treatment with mannose. Our results suggest a significant rearrangement in the proteome and degradome of melanoma cell lines upon mannose treatment including the activation of catabolic pathways (such as protein turnover) and differences in protein N-terminal acetylation. Even though MPI protein abundance and gene expression status are not prognostic markers, perturbation in the network caused by an exogenous monosaccharide source (i.e., mannose) significantly affected the downstream interconnected biological circuitry. Therefore, as reported in this study, the proteomic/degradomic mapping of mannose downstream effects due to the metabolic rewiring caused by the functional status of the MPI enzyme could lead to the identification of specific molecular players from affected signaling circuits in melanoma.

Free radicals and oxidative stress: Mechanisms and therapeutic targets.

Free radicals are small extremely reactive species that have unpaired electrons. Free radicals include subgroups of reactive species, which are all a product of regular cellular metabolism. Oxidative stress happens when the free radicals production exceeds the capacity of the antioxidant system in the body's cells. The current review clarifies the prospective role of antioxidants in the inhibition and healing of diseases. Information on oxidative stress, free radicals, reactive oxidant species, and natural and synthetic antioxidants was obtained by searching electronic databases like PubMed, Web of Science, and Science Direct, with articles published between 1987 and 2023 being included in this review. Free radicals exhibit a dual role in living systems. They are toxic byproducts of aerobic metabolism that lead to oxidative injury and tissue disorders and act as signals to activate appropriate stress responses. Endogenous and exogenous sources of reactive oxygen species are discussed in this review. Oxidative stress is a component of numerous diseases, including diabetes mellitus, atherosclerosis, cardiovascular disease, Alzheimer's disease, Parkinson's disease, and cancer. Although various small molecules assessed as antioxidants have shown therapeutic prospects in preclinical studies, clinical trial outcomes have been inadequate. Understanding the mechanisms through which antioxidants act, where, and when they are active may reveal a rational approach that leads to more tremendous pharmacological success. This review studies the associations between oxidative stress, redox signaling, and disease, the mechanisms through which oxidative stress can donate to pathology, the antioxidant defenses, the limits of their effectiveness, and antioxidant defenses that can be increased through physiological signaling, dietary constituents, and probable pharmaceutical interference. Prospective clinical applications of enzyme mimics and current progress in metal- and non-metal-based materials with enzyme-like activities and protection against chronic diseases have been discussed. This review discussed oxidative stress as one of the main causes of illnesses, as well as antioxidant systems and their defense mechanisms that can be useful in inhibiting these diseases. Thus, the positive and deleterious effects of antioxidant molecules used to lessen oxidative stress in numerous human diseases are discussed. The optimal level of vitamins and minerals is the amount that achieves the best feed benefit, best growth rate, and health, including immune efficiency, and provides sufficient amounts to the body.

A conserved fungal morphogenetic kinase regulates pathogenic growth in response to carbon source diversity

Fungal pathogens must exhibit strong nutritional plasticity, effectively sensing and utilizing diverse nutrients to support virulence. How the signals generated by nutritional sensing are efficiently translated to the morphogenetic machinery for optimal growth and support of virulence remains incompletely understood. Here, we show that the conserved morphogenesis-related kinase, CotA, imparts isoform-specific control over Aspergillus fumigatus invasive growth in host-mimicking environments and during infection. CotA-mediated invasive growth is responsive to exogenous carbon source quality, with only preferred carbon sources supporting hyphal morphogenesis in a mutant lacking one of two identified protein isoforms. Strikingly, we find that the CotA protein does not regulate, nor is cotA gene expression regulated by, the carbon catabolite repression system. Instead, we show that CotA partially mediates invasive growth in specific carbon sources and virulence through the conserved downstream effector and translational repressor, SsdA. Therefore, A. fumigatus CotA accomplishes its conserved morphogenetic functions to drive pathogenic growth by translating host-relevant carbon source quality signals into morphogenetic outputs for efficient tissue invasive growth.

Unravelling the threat of contamination in elite sports: Exploring diverse sources impacting adverse analytical findings and the risk of inadvertent exposure to prohibited substances

In recent years, increasing concerns have emerged regarding athletes being exposed to various sources of contamination that could result in an adverse analytical finding (AAF), which is considered a positive doping test and may lead to the athlete's sanction. This review aims to examine the potential sources of contamination. Firstly, exogenous sources such as food, water, supplements, and medications will be described, along with endogenous sources, primarily arising from the athlete’s physiological condition via the biotransformation of Medications. Finally, other hypothetical contaminations arising from sample collection procedures, poor transport or storage, and laboratory conditions will be discussed. Despite some legislative efforts to regulate the production of food and supplements, contamination remains a significant concern in the context of anti-doping, necessitating athletes to stay vigilant against the risks of inadvertent uptake of illicit products. Increased knowledge of the potential sources of contamination is essential for all parties involved in the fight against doping, including athletes, support personnel, legitimate supplement product manufacturers, and the anti-doping and scientific community. Such insights can contribute to developing the most effective strategy for preventing contamination and, most importantly, reducing the risk of inadvertent AAFs.

The methionine cycle and its cancer implications.

The essential amino acid methionine is a crucial regulator of sulfur metabolism in a variety of interconnected biochemical pathways. The methionine cycle is intricately linked to the folate cycle, forming the one-carbon metabolism, a crucial regulator of S-adenosylmethionine, SAM. Recent work highlights methionine's critical role in tumor growth and progression, maintaining polyamine synthesis, and playing a crucial role in the regulation of SAM both in altered chromatin states, depending on p53 status, as well as facilitating m6A methylation of NR4A2 mRNA, hence regulating proliferation in esophageal carcinoma. Accordingly, Celecoxib, a specific NR4A2 inhibitor, is a potentially powerful inhibitor of tumor growth at least in this specific model. Additionally, formaldehyde, from endogenous or exogenous sources, can directly regulate both SAM steady-state-levels and the one-carbon metabolism, with relevant implication in cancer progression. These recent scientific advancements have provided a deeper understanding of the molecular mechanisms involved in cancer development, and its potential therapeutic regulation.

Computational exploration of acefylline derivatives as MAO-B inhibitors for Parkinson's disease: insights from molecular docking, DFT, ADMET, and molecular dynamics approaches.

Monoamine oxidase B (MAO-B) plays a pivotal role in the deamination process of monoamines, encompassing crucial neurotransmitters like dopamine and norepinephrine. The heightened interest in MAO-B inhibitors emerged after the revelation that this enzyme could potentially catalyze the formation of neurotoxic compounds from endogenous and exogenous sources. Computational screening methodologies serve as valuable tools in the quest for novel inhibitors, enhancing the efficiency of this pursuit. In this study, 43 acefylline derivatives were docked against the MAO-B enzyme for their chemotherapeutic potential and binding affinities that yielded GOLD fitness scores ranging from 33.21 to 75.22. Among them, five acefylline derivatives, namely, MAO-B14, MAO-B15, MAO-B16, MAO-B20, and MAO-B21, displayed binding affinities comparable to the both standards istradefylline and safinamide. These derivatives exhibited hydrogen-bonding interactions with key amino acids Phe167 and Ile197/198, suggesting their strong potential as MAO-B inhibitors. Finally, molecular dynamics (MD) simulations were conducted to evaluate the stability of the examined acefylline derivatives over time. The simulations demonstrated that among the examined acefylline derivatives and standards, MAO-B21 stands out as the most stable candidate. Density functional theory (DFT) studies were also performed to optimize the geometries of the ligands, and molecular docking was conducted to predict the orientations of the ligands within the binding cavity of the protein and evaluate their molecular interactions. These results were also validated by simulation-based binding free energies via the molecular mechanics energies combined with generalized Born and surface area solvation (MM-GBSA) method. However, it is necessary to conduct in vitro and in vivo experiments to confirm and validate these findings in future studies.

Oxidative stress: fundamentals and advances in quantification techniques.

Oxidative species, generated endogenously via metabolism or from exogenous sources, play crucial roles in the body. At low levels, these species support immune functions by participating in phagocytosis. They also aid in cellular signaling and contribute to vasomodulation. However, when the levels of oxidative species exceed the body's antioxidant capacity to neutralize them, oxidative stress occurs. This stress can damage cellular macromolecules such as lipids, DNA, RNA, and proteins, driving the pathogenesis of diseases and aging through the progressive deterioration of physiological functions and cellular structures. Therefore, the body's ability to manage oxidative stress and maintain it at optimal levels is essential for overall health. Understanding the fundamentals of oxidative stress, along with its reliable quantification, can enable consistency and comparability in clinical practice across various diseases. While direct quantification of oxidant species in the body would be ideal for assessing oxidative stress, it is not feasible due to their high reactivity, short half-life, and the challenges of quantification using conventional techniques. Alternatively, quantifying lipid peroxidation, damage products of nucleic acids and proteins, as well as endogenous and exogenous antioxidants, serves as appropriate markers for indicating the degree of oxidative stress in the body. Along with the conventional oxidative stress markers, this review also discusses the role of novel markers, focusing on their biological samples and detection techniques. Effective quantification of oxidative stress may enhance the understanding of this phenomenon, aiding in the maintenance of cellular integrity, prevention of age-associated diseases, and promotion of longevity.

Spontaneous movement synchrony as an exogenous source for interbrain synchronization in cooperative learning.

Learning through cooperation with conspecifics-'cooperative learning'-is critical to cultural evolution and survival. Recent progress has established that interbrain synchronization (IBS) between individuals predicts success in cooperative learning. However, the likely sources of IBS during learning interactions remain poorly understood. To address this dearth of knowledge, we tested whether movement synchrony serves as an exogenous factor that drives IBS, taking an embodiment perspective. We formed dyads of individuals with varying levels of prior knowledge (high-high (HH), high-low (HL), low-low (LL) dyads) and instructed them to collaboratively analyse an ancient Chinese poem. During the task, we simultaneously recorded their brain activity using functional near-infrared spectroscopy and filmed the entire experiment to parse interpersonal movement synchrony using the computer-vision motion energy analysis. Interestingly, the homogeneous groups (HH and/or LL) exhibited stronger movement synchrony and IBS compared with the heterogeneous group. Importantly, mediation analysis revealed that spontaneous and synchronized body movements between individuals contribute to IBS, hence facilitating learning. This study therefore fills a critical gap in our understanding of how interpersonal transmission of information between individual brains, associated with behavioural entrainment, shapes social learning. This article is part of the theme issue 'Minds in movement: embodied cognition in the age of artificial intelligence'.

Comparison between endogenous and exogenous nitrogen of nitrogen-doped carbon catalyst in the process of activating PMS

BackgroundAdvanced oxidation processes (AOPs) based on sulfate radicals (SO4•–) have proven to be highly effective in degrading organics in wastewater. Carbon-based materials have emerged as promising catalysts for activating persulfate, which generates environmentally friendly sulfate radicals (SO4•–), for remediation purposes. The nitrogen doping technique is an effective method for site-specific regulation and can significantly enhance the performance of carbon-based catalysts, which could promote the application of carbon-based catalysts in the future. Endogenous and exogenous nitrogen sources can provide nitrogen sources for N doping. However, there are few reports on the comparison of the structure and catalytic mechanism of these two types of N-doped biochar. It is also of great significance to reveal the mechanisms of constructing catalytic sites using endogenous and exogenous nitrogen. MethodsHerein, the preparation of endogenous nitrogen-doped biochar (BC) was achieved by using soybean as the precursor material, which is rich in natural nitrogen-containing components of proteins. Subsequently, the BC was doped by mixing it with urea and pyrolysis, resulting in the preparation of exogenous nitrogen-doped biochar (NBC). Significant findingsThe characterization of XRD and HRTEM showed that g-C3N4 formed in NBC. The results of catalytic degradation and quenching experiments demonstrate that the exogenous nitrogen-doped catalysts have a better performance than endogenous nitrogen-doped catalysts. The OFL removal rate in BC/PMS was higher than that in the BC/PMS system (71.68% vs. 61.83 %). The kobs in NBC/PMS are also higher than that in BC/PMS (0.00943 min−1vs. 0.01369 min−1). The NBC could be a promising catalyst for PMS activation in practical application. DFT results showed that the g-C3N4 generated from exogenous nitrogen can improve PMS activation performance in the g-C3N4/graphene bilayer structure. The influence on the charge distribution of surrounding carbon materials makes endogenous nitrogen doping a good choice for optimizing the local performance of the material in the absence of natural nitrogen components.

8132 Prolonged Refractory Hypoglycemia For Seven Days After Discontinuation Of Neutral Protamine Hagedorn (NPH) Insulin And Injectable Semaglutide

Abstract Disclosure: A. Musleh: None. M.T. Rauf: None. E. Afroze: None. S. Al-Bacha: None. A 75-year-old male with Type 2 Diabetes was brought to the emergency department (ED) by emergency medical services (EMS) due to altered mentation. The patient’s wife found him unresponsive with seizure-like activity. EMS was called to the scene and obtained a capillary blood glucose reading of 31 mg/dL. Despite initial treatment with 50% dextrose the patient’s capillary blood glucose came down to 21 mg/dL in the ED and was confirmed by venous glucose. Workup including Computed Tomography (CT) imaging was inconsistent with a cerebrovascular accident. Given refractory hypoglycemia and delirium, the patient was started on a dextrose 10% infusion at 150 milliliters per hour. He was admitted to the intensive care unit for closer monitoring. His wife states that the patient had a few episodes of mild hypoglycemia overnight for the past several weeks, which improved after eating. His home medications included NPH insulin 46 units twice daily, empagliflozin 25 mg once daily, and injectable semaglutide 2 mg once weekly. The last dose of NPH insulin was the night before the presentation and the last dose of semaglutide was 5 days prior to admission. Serum creatinine levels were stable at 1.3-1.5 mg/dL throughout the hospitalization, which was below his baseline creatinine of 1.7 mg/dL. Laboratory results were as follows: hemoglobin A1c 5.9%, c-peptide level was 0.3 ng/mL (normal range 0.8-3.9 ng/mL) with a glucose of 68 mg/dL (normal range 70-100 mg/dL), insulin 203.8 mcIU/mL (normal range less than 24 mcIU/mL), proinsulin 3.2 pmol/L (normal range less than or equal to 8 pmol/L), beta-hydroxybutyrate 0.06 mmol/L (normal range 0.02-0.27), cortisol 66.6 mcg/dL (normal range 6.7-22.6 mcg/dL), insulin-like growth factor 1 123 ng/mL (normal range 53-222), and hypoglycemic agent panel was negative. On ICU Day 2, his mentation improved, he was allowed to eat but continued to require dextrose infusion to prevent hypoglycemia. Repeat fasting insulin levels even four days from prior showed an incremental decrease to 59.4 mcIU/mL with a glucose of 77 mg/dL. It took 7 days before the patient was able to maintain glucose above 70 mg/dL off of dextrose infusion. After which he had hyperglycemia requiring gradual reintroduction of his diabetes medicines other than insulin. It is rare to see such prolonged refractory hypoglycemia from an exogenous source of insulin as exhibited in this case. Notably, the patient was on semaglutide and had stable chronic kidney disease without acute kidney injury. Although multiple mechanisms explain the prolonged insulin duration of action in kidney disease, the effects of semaglutide on insulin action are unknown. Presentation: 6/3/2024

Tracing potentially toxic elements in button mushroom cultivation and environmental implications: Insights via stable lead (Pb) isotope analysis

Elevated levels of potentially toxic elements (PTEs) have been frequently detected in substrates used for cultivating edible mushrooms. However, the distribution and accumulation pathways of PTEs within mushrooms and their cultivation substrates remain inadequately understood. This study specifically aims to clarify these aspects of button mushrooms (Agaricus bisporus). A systematic analysis was conducted on the distribution of PTEs (As, Cd, Cr, Cu, Ni, Pb, and Zn) and stable Pb isotope fingerprints across various components of the button mushroom cultivation systems, including the cultivation substrates (a mixture of wheat straw, chicken manure, soil, and additives), fruiting bodies (MR), and spent mushroom substrate (SMS). The methodology involved inductively coupled plasma mass‒spectrometry for PTE quantification and Pb isotope ratio analysis for source identification. The results demonstrated that wheat straw and additives were the main contributors to the endogenous accumulation of PTEs in MR, accounting for 35.0% and 33.2% of Pb accumulation, respectively. Furthermore, MR, wheat straw, and soil together contributed to more than 67% of the Pb loads in SMS. The study also revealed that the occurrence of PTEs in these substrates is predominantly driven by exogenous sources, particularly the significant contribution from anthropogenic activities. Overall, these findings provide valuable biogeochemical insights into the accumulation pathways and patterns of PTEs in button mushroom cultivation systems, with potential applications for cleaner food management and environmentally sustainable practices.

Production and utilization of pseudocobalamin in marine Synechococcus cultures and communities.

Cobalamin influences marine microbial communities because an exogenous source is required by most eukaryotic phytoplankton, and demand can exceed supply. Pseudocobalamin is a cobalamin analogue produced and used by most cyanobacteria but is not directly available to eukaryotic phytoplankton. Some microbes can remodel pseudocobalamin into cobalamin, but a scarcity of pseudocobalamin measurements impedes our ability to evaluate its importance for marine cobalamin production. Here, we perform simultaneous measurements of pseudocobalamin and methionine synthase (MetH), the key protein that uses it as a co-factor, in Synechococcus cultures and communities. In Synechococcus sp. WH8102, pseudocobalamin quota decreases in low temperature (17°C) and low nitrogen to phosphorus ratio, while MetH did not. Pseudocobalamin and MetH quotas were influenced by culture methods and growth phase. Despite the variability present in cultures, we found a comparably consistent quota of 300 ± 100 pseudocobalamin molecules per cyanobacterial cell in the Northwest Atlantic Ocean, suggesting that cyanobacterial cell counts may be sufficient to estimate pseudocobalamin inventories in this region. This work offers insights into cellular pseudocobalamin metabolism, environmental and physiological conditions that may influence it, and provides environmental measurements to further our understanding of when and how pseudocobalamin can influence marine microbial communities.

Genomic characterization and proteomic analysis of Bacillus amyloliquefaciens in response to lignin

This study examined the lignin degradation characteristics of Bacillus amyloliquefaciens MN-13. Specifically, whole-genome sequencing and comparative proteomic analysis were performed to investigate the responses of the MN-13 strain to lignin. A maximum lignin removal of 38.0 % was achieved after 36 h of inoculation in mineral salt medium with 0.2 g/L alkaline lignin, under the following conditions: the carbon to nitrogen ratio C/N = 1/1; inoculum size 6 %; addition of glucose as an exogenous carbon source. When the MN-13 strain was inoculated into mineral salt medium with and without lignin, respectively, 831 differentially expressed proteins were identified, 404 of which were up-regulated and 427 were down-regulated. Enrichment analysis revealed that up-regulated proteins were associated with microbial metabolism in diverse environment, biosynthesis of amino acids, and pathways related to energy production, including carbon metabolism, pyruvate metabolism, the TCA cycle etc. Genomic analysis revealed that the MN-13 strain possesses many ligninolytic enzymes and aromatics degradation pathway, including benzoate degradation and aminobenzoate degradation etc. Taken together, the proteomic and genomic analyses indicated that the meta-cleavage pathway of catechol, including benzoate degradation, etc., is the main lignin degradation pathway. These findings provide new insight into lignin degradation mediated by B. amyloliquefaciens.

Membranous Dysmenorrhea: An Underdiagnosed Condition

Dysmenorrhea is the most prevalent gynecological symptom in menopausal women. Currently defined as menstrual cramps, it is on the list of the main complaints in gynecological consultations. A sub-classification forgotten in medical dictionaries is membranous dysmenorrhea (MD), which corresponds to the elimination of membranes through the vaginal canal. The definitive diagnosis requires anatomopathological study, and abortion is the main differential diagnosis. As there are few cases in the literature, this study aims to present a series of eight cases, highlighting the pathophysiology and comparing the data with other studies to encourage discussion on the subject. This is an observational, longitudinal, retrospective study including women with clinical membranous dysmenorrhea (spontaneous elimination of fibroelastic material via the vagina). The results show that of the eight patients, seven had used or were using exogenous female hormones; 62.5% of the total had MD in the 2nd - 3rd decade of life, two had had previous abortions, and one was nulliparous. All these facts have been associated in the literature as etiological or contributing factors to MD. However, while diverging from the literature, our article showed that the infection factor is not mandatory for the occurrence of MD. In conclusion, proposing a single pathophysiological and etiological mechanism based on a series of cases and in comparison with other data in the literature is a challenge. However, consistently with what has been published, most of the cases presented were the result of an increased vascular response of the endometrium when exposed to an exogenous source of estrogen and progesterone, and this could be a hypothesis which, of course, requires further studies to establish the exact casuistry, but which contributes greatly as a source of data for future research.

Protection of the genome and the central exome by peripheral non-coding DNA against DNA damage in health, ageing and age-related diseases.

DNA in eukaryotic genomes is under constant assault from both exogenous and endogenous sources, leading to DNA damage, which is considered a major molecular driver of ageing. Fortunately, the genome and the central exome are safeguarded against these attacks by abundant peripheral non-coding DNA. Non-coding DNA codes for small non-coding RNAs that inactivate foreign nucleic acids in the cytoplasm and physically blocks these attacks in the nucleus. Damage to non-coding DNA produced during such blockage is removed in the form of extrachromosomal circular DNA (eccDNA) through nucleic pore complexes. Consequently, non-coding DNA serves as a line of defence for the exome against DNA damage. The total amount of non-coding DNA/heterochromatin declines with age, resulting in a decrease in both physical blockage and eccDNA exclusion, and thus an increase in the accumulation of DNA damage in the nucleus during ageing and in age-related diseases. Here, we summarize recent evidence supporting a protective role of non-coding DNA in healthy and pathological states and argue that DNA damage is the proximate cause of ageing and age-related genetic diseases. Strategies aimed at strengthening the protective role of non-coding DNA/heterochromatin could potentially offer better systematic protection for the dynamic genome and the exome against diverse assaults, reduce the burden of DNA damage to the exome, and thus slow ageing, counteract age-related genetic diseases and promote a healthier life for individuals.

Cold atmospheric plasma activated media selectively affects human head and neck cancer cell lines.

Cold atmospheric plasma (CAP) is a novel approach for cancer treatment. It can be used to treat liquids-plasma-activated media (PAM)-which are then transferred to the target as an exogenous source of reactive oxygen and nitrogen species (RONS). The present study aimed at chemically characterizing different PAM and assessing their invitro selectivity against head and neck cancer cells (HNC). PAM were obtained by exposing 2 and 5 mL of cell culture medium to CAP for 5, 10 and 20 min at a 6 mm working distance. Anions kinetics was evaluated by ion chromatography. Cell proliferation inhibition, apoptosis occurrence, and cell cycle modifications were assessed by MTS and flow cytometry, on human epidermal keratinocyte (HaCaT) and HNC cell lines HSC3, HSC4 and A253. The 2 mL conditions showed a significant reduction in cell proliferation whereas for the 5 mL the effect was milder, but the time-dependence was more evident. HaCaT were unaffected by the 5 mL PAM, indicating a selectivity for cancer cells. The media chemical composition modified by CAP exposure influenced cell proliferation by modulating cell cycle and inducing apoptosis in cancer cells, without affecting normal cells.