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Precession modes of rectangular nanodot arrays with diameters of 90 and 150 nm and varied dipolar interaction are systematically studied by vector network analyzer ferromagnetic resonance, and micromagnetic simulations. The large dots reveal two dominant modes: a low frequency edge mode and a high frequency center mode, while in the smaller dots only the edge mode is observed. With increasing dipolar interaction, the precession-mode frequencies increase. The interaction has a stronger influence on the edge mode than on the center mode, resulting in different precession behaviors in different ranges of magnetic fields: well-separated modes in high fields and a merging of edge and center modes at low fields. At low fields and for strong dipolar interaction, coherent precession of the whole dot array is observed. [ABSTRACT FROM AUTHOR]

We present the results of a Brillouin light scattering investigation of thermally excited spin wave eigenmodes in square arrays of either isolated rectangular dots of permalloy or twins of dipolarly coupled elements, placed side-by-side or head-to-tail. The nanodots, fabricated by e-beam lithography and lift-off, are 20nm thick and have the major size D in the range between 90nm and 150 nm. The experimental spectra show the presence of two main peaks, corresponding to modes localized either at the edges or in the center of the dots. Their frequency dependence on the dot size and on the interaction with adjacent elements has been measured and successfully interpreted on the basis of dynamical micromagnetic simulations. The latter enabled us also to describe the spatial profile of the eigenmodes, putting in evidence the effects induced by the dipolar interaction between coupled dots. In particular, in twinned dots the demagnetizing field is appreciably modified in proximity of the "internal edges" if compared to the "external" ones, leading to a splitting of the edge mode. These results can be relevant for the exploitation of sub-150 nm magnetic dots in new applications, such as magnonic metamaterials, bit-patterned storage media, and nano-magnetic logic devices. [ABSTRACT FROM AUTHOR]

Large White Yorkshire piglets belonging to three different litters aged 2 months (group A), 4 months (group B) and 6 months (group C) were considered for the study. The electrocardiogram was recorded in five male piglets selected from each litter. Highest P-wave amplitude was measured in group A and P-wave recorded positively in all age groups except in one case of group A where it recorded negatively. Highest duration of P-wave was obtained in piglets of group C. The amplitude of QRS complex of all the piglets in group A recorded negatively while in group B and C negative QRS complex featured in only one out of five cases. Incidence of negative amplitude of T wave was observed in one out of five cases in group A and two out of five cases in group B while the amplitude of T wave recorded positively in all the cases in group C. The Q-T interval was measured to be highest in group B. Group C recorded the highest heart rate. [ABSTRACT FROM AUTHOR]

To determine the presence of cardiac disease in hypertensive patients with disparities between physician and out-of-office blood pressures, we prospectively studied three groups of age-matched patients identified by both casual (office) and ambulatory blood pressures: (1) office blood pressure greater than 140/90 mm Hg and awake ambulatory blood pressure of 130/80 mm Hg or less ("office" hypertensives); (2) office blood pressure less than 135/85 mm Hg and awake ambulatory blood pressure of 130/80 mm Hg or less (normotensives); and (3) office blood pressure greater than 140/90 mm Hg and awake ambulatory blood pressure of 140/90 mm Hg or greater ("daytime" hypertensives). In the patients with office hypertension, both the left atrial index and left ventricular mass index were significantly less than in patients with daytime hypertension and not statistically different from those of the normotensive subjects. Left ventricular filling rate at rest and ejection fraction at peak exercise were significantly greater in the office hypertensive group than in the daytime hypertensive group but were no different from those of the normotensive subjects. These findings demonstrate that patients with blood pressure elevation only in the physician's office have cardiac size and function similar to those of normotensive individuals. Thus, the average daily blood pressure best predicts cardiac end-organ damage. [ABSTRACT FROM AUTHOR]

Abstract Background We previously demonstrated that p68 phosphorylation at threonine residues correlates with cancer cell apoptosis under the treatments of TNF-α and TRAIL (Yang, L. Mol Cancer Res Vol 3, pp 355–63 2005). Results In this report, we characterized the role of p68 phosphorylation in apoptosis induction under the treatment of oxaliplatin in the colon cancer cells. Our data suggest that oxaliplatin treatment activates p38 MAP kinase, which subsequently phosphorylates p68 at T564 and/or T446. The phosphorylation of p68, at least partially, mediates the effects of the drug on apoptosis induction, as mutations at these two sites greatly reduce the cancer cell death. Conclusion Our studies reveal an important molecular mechanism that mediates the effects of anti-cancer drug, providing a potential strategy for improving cancer treatment.

Syntaxin 3 is a member of a large protein family of syntaxin proteins that mediate fusion between vesicles and their target membranes. Mutations in the ubiquitously expressed syntaxin 3A splice form give rise to a serious gastrointestinal disorder in humans called microvillus inclusion disorder, while mutations that additionally involve syntaxin 3B, a splice form that is expressed primarily in retinal photoreceptors and bipolar cells, additionally give rise to an early onset severe retinal dystrophy. In this review, we discuss recent studies elucidating the roles of syntaxin 3B and the regulation of syntaxin 3B functionality in membrane fusion and neurotransmitter release in the vertebrate retina.

Complex microbiomes are part of the food we eat and influence our own microbiome, but their diversity remains largely unexplored. Here, we generated the open access curatedFoodMetagenomicData (cFMD) resource by integrating 1,950 newly sequenced and 583 public food metagenomes. We produced 10,899 metagenome-assembled genomes spanning 1,036 prokaryotic and 108 eukaryotic species-level genome bins (SGBs), including 320 previously undescribed taxa. Food SGBs displayed significant microbial diversity within and between food categories. Extension to >20,000 human metagenomes revealed that food SGBs accounted on average for 3% of the adult gut microbiome. Strain-level analysis highlighted potential instances of food-to-gut transmission and intestinal colonization (e.g., Lacticaseibacillus paracasei) as well as SGBs with divergent genomic structures in food and humans (e.g., Streptococcus gallolyticus and Limosilactobabillus mucosae). The cFMD expands our knowledge on food microbiomes, their role in shaping the human microbiome, and supports future uses of metagenomics for food quality, safety, and authentication., Competing Interests: Declaration of interests D.O. is an employee of QIAGEN GmbH. E.S.K. is an employee of BaseClear B.V., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Retinal neurons that form ribbon-style synapses operate over a wide dynamic range, continuously relaying visual information to their downstream targets. The remarkable signaling abilities of these neurons are supported by specialized presynaptic machinery, one component of which is syntaxin3B. Syntaxin3B is an essential t-SNARE protein of photoreceptors and bipolar cells that is required for neurotransmitter release. It has a light-regulated phosphorylation site in its N-terminal domain at T14 that has been proposed to modulate membrane fusion. However, a direct test of the latter has been lacking. Using a well-controlled in vitro fusion assay, we found that a phosphomimetic T14 syntaxin3B mutation leads to a small but significant enhancement of SNARE-mediated membrane fusion following the formation of the t-SNARE complex. While the addition of Munc18a had only a minimal effect on membrane fusion mediated by SNARE complexes containing wild-type syntaxin3B, a more significant enhancement was observed in the presence of Munc18a when the SNARE complexes contained a syntaxin3B T14 phosphomimetic mutant. Finally, we showed that the retinal-specific complexins (Cpx III and Cpx IV) inhibited membrane fusion mediated by syntaxin3B-containing SNARE complexes in a dose-dependent manner. Collectively, our results establish that membrane fusion mediated by syntaxin3B-containing SNARE complexes is regulated by the T14 residue of syntaxin3B, Munc18a, and Cpxs III and IV.

Introduction: Osteosarcoma is a rare disorder among cancer, but the most frequently occurring among sarcomas in children and adolescents. It has been reported to possess the relapsing capability as well as accompanying collateral adverse effects which hinder the development process of an effective treatment plan. Using networks of omics data to identify cancer biomarkers could revolutionize the field in understanding the cancer. Cancer biomarkers and the molecular mechanisms behind it can both be understood by studying the biological networks underpinning the etiology of the disease., Methods: In our study, we aimed to highlight the hub genes involved in gene-gene interaction network to understand their interaction and how they affect the various biological processes and signaling pathways involved in Osteosarcoma. Gene interaction network provides a comprehensive overview of functional gene analysis by providing insight into how genes cooperatively interact to elicit a response. Because gene interaction networks serve as a nexus to many biological problems, their employment of it to identify the hub genes that can serve as potential biomarkers remain widely unexplored. A dynamic framework provides a clear understanding of biological complexity and a pathway from the gene level to interaction networks., Results: Our study revealed various hub genes viz. TP53, CCND1, CDK4, STAT3, and VEGFA by analyzing various topological parameters of the network, such as highest number of interactions, average shortest path length, high cluster density, etc. Their involvement in key signaling pathways, such as the FOXM1 transcription factor network, FAK-mediated signaling events, and the ATM pathway, makes them significant candidates for studying the disease. The study also highlighted significant enrichment in GO terms (Biological Processes, Molecular Function, and Cellular Processes), such as cell cycle signal transduction, cell communication, kinase binding, transcription factor activity, nucleoplasm, PML body, nuclear body, etc., Conclusion: To develop better therapeutics, a specific approach toward the disease targeting the hub genes involved in various signaling pathways must have opted to unravel the complexity of the disease. Our study has highlighted the candidate hub genes viz. TP53, CCND1 CDK4, STAT3, VEGFA. Their involvement in the major signaling pathways of Osteosarcoma makes them potential candidates to be targeted for drug development. The highly enriched signaling pathways include FOXM1 transcription pathway, ATM signal-ling pathway, FAK mediated signaling events, Arf6 signaling events, mTOR signaling pathway, and Integrin family cell surface interactions. Targeting the hub genes and their associated functional partners which we have reported in our studies may be efficacious in developing novel therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dey, Vasudevan, Doss C., Kumar, El Allali, Alsamman and Zayed.)

Mimics of antimicrobial peptides (AMPs) have been proposed as a promising class of antimicrobial agents. We report the analysis of five tetrasubstituted, cationic, amphipathic heterocycles as potential AMP mimics. The analysis showed that the heterocyclic scaffold had a strong influence on the haemolytic activity of the compounds, and the hydantoin scaffold was identified as a promising template for drug lead development. Subsequently, a total of 20 hydantoin derivatives were studied for their antimicrobial potency and haemolytic activity. We found 19 of these derivatives to have very low haemolytic toxicity and identified three lead structures, 2dA, 6cG, and 6dG with very promising broad-spectrum antimicrobial activity. Lead structure 6dG displayed minimum inhibitory concentration (MIC) values as low as 1 μg/mL against Gram-positive bacteria and 4-16 μg/mL against Gram-negative bacteria. Initial mode of action (MoA) studies performed on the amine derivative 6cG, utilizing a luciferase-based biosensor assay, suggested a strong membrane disrupting effect on the outer and inner membrane of Escherichia coli. Our findings show that the physical properties and structural arrangement induced by the heterocyclic scaffolds are important factors in the design of AMP mimics., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Morten B Strøm and Annette Bayer have patent #Barbituric acid derivatives comprising cationic and lipophilic groups. WO2018178198A1. Issued to UiT., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Reporter genes are important tools in many biological disciplines. The discovery of novel reporter genes is relatively rare. However, known reporter genes are constantly applied to novel applications. This study reports the performance of the bilirubin-dependent fluorescent protein UnaG from the Japanese eel Anguilla japonicas in live Escherichia coli cells in response to the disruption of outer membrane (OM) integrity at low bilirubin (BR) concentrations. Using the E. coli wild-type strain MC4100, its isogenic OM-deficient mutant strain NR698, and different OM-active compounds, we show that BR uptake and UnaG fluorescence depend on a leaky OM at concentrations of 10 µM BR and below, while fluorescence is mostly OM integrity-independent at concentrations above 50 µM BR. We suggest that these properties of the UnaG-BR couple might be applied as a biosensor as an alternative to the OM integrity assays currently in use.

Antimicrobial resistance (AMR) in microorganisms is an urgent global health threat. AMR of Mycobacterium tuberculosis is associated with significant morbidity and mortality. It is of great importance to underpin the resistance pathways involved in the mechanisms of AMR and identify the genes that are directly involved in AMR. The focus of the current study was the bacteria M. tuberculosis, which carries AMR genes that give resistance that lead to multidrug resistance. We, therefore, built a network of 43 genes and examined for potential gene-gene interactions. Then we performed a clustering analysis and identified three closely related clusters that could be involved in multidrug resistance mechanisms. Through the bioinformatics pipeline, we consistently identified six-hub genes (dnaN, polA, ftsZ, alr, ftsQ, and murC) that demonstrated the highest number of interactions within the clustering analysis. This study sheds light on the multidrug resistance of MTB and provides a protocol for discovering genes that might be involved in multidrug resistance, which will improve the treatment of resistant strains of TB., (Copyright © 2022. Published by Elsevier Inc.)

Colorectal cancer (CRC) is third cancer causing death in the world. CRC is associated with disrupting the circadian rhythm (CR), closely associating the CRC progression and the dysregulation of genes involved in the biological clock. In this study, we aimed to understand the circadian rhythm changes in patients diagnosed with CRC. We used the GEO database with the ID GSE46549 for our analysis, which consists of 32 patients with CRC and one as normal control. Our study has identified five essential genes involved in CRC, HAPLN1, CDH12, IGFBP5, DCHS2, and DOK5, and had different enriched pathways, such as the Wnt-signaling pathway, at different time points of study. As a part of our study, we also identified various related circadian genes, such as CXCL12, C1QTNF2, MRC2, and GLUL, from the Circadian Gene Expression database, that played a role in circadian rhythm and CRC development. As circadian timing can influence the host tissue's ability to tolerate anticancer medications, the genes reported can serve as a potential drug target for treating CRC and become beneficial to translational settings., Competing Interests: Conflict of Interest The authors declare that the study has no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Antimicrobial resistance (AMR) among microorganisms has become one of the worldwide concerns of this century and continues to challenge us. To properly understand this problem, it is essential to know the genes that cause AMR and their resistance mechanisms. Our present study focused on Klebsiella pneumoniae, which possesses AMR genes conferring resistance against multiple antibiotics. A gene interaction network of 42 functional partners was constructed and analyzed to broaden our understanding. Three closely related clusters (C1-C3) having an association with multi-drug resistance mechanisms were identified by clustering analysis. The enrichment analysis illustrated 30 genes in biological processes, 24 genes in molecular function, and 25 genes in cellular components having a significant role. The analysis of the gene interaction network revealed genes birA2, folP, pabC, folA, gyrB, glmM, gyrA, thyA_2 had maximum no. of interactions with their functional partners viz. 26, 25, 25, 24, 23, 23, 23, 23 respectively and can be considered as hub genes. Analyzing the enriched pathways and Gene Ontologies provides insight into AMR's molecular basis. In addition, the proposed study could aid the researchers in developing new treatment options to combat multi-drug resistant K. pneumoniae., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We have synthesised short analogues of the marine antimicrobial peptide Turgencin A from the colonial Arctic ascidian Synoicum turgens. In this study, we focused on a central, cationic 12-residue Cys-Cys loop region within the sequence. Modified (tryptophan- and arginine-enriched) linear peptides were compared with Cys-Cys cyclic derivatives, and both linear and Cys-cyclic peptides were N-terminally acylated with octanoic acid (C 8 ), decanoic acid (C 10 ) or dodecanoic acid (C 12 ). The highest antimicrobial potency was achieved by introducing dodecanoic acid to a cyclic Turgencin A analogue with low intrinsic hydrophobicity, and by introducing octanoic acid to a cyclic analogue displaying a higher intrinsic hydrophobicity. Among all tested synthetic Turgencin A lipopeptide analogues, the most promising candidates regarding both antimicrobial and haemolytic activity were C 12 -cTurg-1 and C 8 -cTurg-2 . These optimized cyclic lipopeptides displayed minimum inhibitory concentrations of 4 µg/mL against Staphylococcus aureus , Escherichia coli and the fungus Rhodothorula sp. Mode of action studies on bacteria showed a rapid membrane disruption and bactericidal effect of the cyclic lipopeptides. Haemolytic activity against human erythrocytes was low, indicating favorable selective targeting of bacterial cells.

An amphipathic barbiturate mimic of the marine eusynstyelamides is reported as a promising class of antimicrobial agents. We hereby report a detailed analysis of the structure-activity relationship for cationic amphipathic N,N'-dialkylated-5,5-disubstituted barbiturates. The influence of various cationic groups, hydrocarbon linkers and lipophilic side chains on the compounds' antimicrobial potency and haemolytic activity was studied. A comprehensive library of 58 compounds was prepared using a concise synthetic strategy. We found cationic amine and guanidyl groups to yield the highest broad-spectrum activity and cationic trimethylated quaternary amine groups to exert narrow-spectrum activity against Gram-positive bacteria. n-Propyl hydrocarbon linkers proved to be the best compromise between potency and haemolytic activity. The combination of two different lipophilic side chains allowed for further fine-tuning of the biological properties. Using these insights, we were able to prepare both, the potent narrow-spectrum barbiturate 8a and the broad-spectrum barbiturates 11lG, 13jA and 13jG, all having low or no haemolytic activity. The guanidine derivative 11lG demonstrated a strong membrane disrupting effect in luciferase-based assays. We believe that these results may be valuable in further development of antimicrobial lead structures., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)