Additional Candidate Research Articles

An optically dark merging system at z ∼ 6 detected by JWST

Context. Near- to mid-infrared observations (from Spitzer and JWST) have revealed a hidden population of galaxies at redshift z = 3 − 6 called optically dark objects, which are believed to be massive and dusty star-formers. They contribute substantially to the cosmic star-formation rate (SFR) density at z ∼ 4 − 5 (up to 30 − 40%). Aims. While optically dark sources are widely recognized as a significant component of the stellar mass function, the history of their stellar mass assembly (and the evolution of their interstellar medium) remains unexplored. However, they are thought to be the progenitors of the more massive early-type galaxies found in present-day groups and clusters. It is thus important to examine the possible connection between dark sources and merging events in order to understand the environment in which they live. Methods. Here, we report our search for close companions in a sample of 19 optically-dark objects identified in the SMACS0723 JWST deep field. They were selected in the NIRCam F444W band and undetected below 2 μm. We restricted our analysis to the reddest (i.e., F277W–F444W > 1.3) and brightest (F444W < 26 mag) objects. Results. We identified KLAMA, an optically dark source showing a very close companion (angular distance < 0.5″). The spatially resolved SED fitting procedure indicates that all components lying within 1.5″ of who is it the dark source are indeed at z ∼ 5.7. Tidal features (leading to a whale-shaped morphology) corroborate the hypothesis that KLAMA is the most massive (log(M⋆/M⊙) > 10.3) and dusty (AV ∼ 3 at the core) system of an ongoing merger with a mass ratio of ∼10. Thus, around ten similar merger events would be required to double the stellar mass of KLAMA. Merging systems with properties similar to KLAMA are identified in the SERRA simulations, allowing us to reconstruct their stellar-mass assembly history and predict their molecular gas properties (in particular, the [CII] emission for the simulated system). Conclusions. The discovery of mergers within dark galaxies at the end of the Epoch of Reionization highlights the importance of conducting a statistical search for additional candidates in deep NIRCam fields. Such research will aid in our understanding of the significance of merging processes during the obscured phase of stellar-mass accumulation.

The Type 1 Diabetes T Cell Receptor and B Cell Receptor Repository in the AIRR Data Commons: a practical guide for access, use and contributions through the Type 1 Diabetes AIRR Consortium.

Human molecular genetics has brought incredible insights into the variants that confer risk for the development of tissue-specific autoimmune diseases, including type 1 diabetes. The hallmark cell-mediated immune destruction that is characteristic of type 1 diabetes is closely linked with risk conferred by the HLA class II gene locus, in combination with a broad array of additional candidate genes influencing islet-resident beta cells within the pancreas, as well as function, phenotype and trafficking of immune cells to tissues. In addition to the well-studied germline SNP variants, there are critical contributions conferred by T cell receptor (TCR) and B cell receptor (BCR) genes that undergo somatic recombination to yield the Adaptive Immune Receptor Repertoire (AIRR) responsible for autoimmunity in type 1 diabetes. We therefore created the T1D TCR/BCR Repository (The Type 1 Diabetes T Cell Receptor and B Cell Receptor Repository) to study these highly variable and dynamic gene rearrangements. In addition to processed TCR and BCR sequences, the T1D TCR/BCR Repository includes detailed metadata (e.g. participant demographics, disease-associated parameters and tissue type). We introduce the Type 1 Diabetes AIRR Consortium goals and outline methods to use and deposit data to this comprehensive repository. Our ultimate goal is to facilitate research community access to rich, carefully annotated immune AIRR datasets to enable new scientific inquiry and insight into the natural history and pathogenesis of type 1 diabetes.

Synergistic Tribological Effects of Ti3C2Tx MXene and ZDDP under Simple Grafting Strategies for Efficient Lubrication.

MXenes, a novel class of two-dimensional materials, possess exceptional physical and chemical properties, positioning them as promising candidates for lubricant additives. However, their potential is constrained by challenges in dispersion and stability, coupled with a paucity of research on interactions with additives in full-formula oils. In this study, hexadecylphosphonic acid (HDPA) is grafted onto Ti3C2Tx to formulate a polyalkylene glycol dispersion system. The findings reveal that the HDPA-modified Ti3C2Tx (HDPA-Ti3C2) is successfully synthesized, demonstrating superior dispersion stability and notable friction-reduction and antiwear properties. Notably, when combined with zinc dialkyl dithiophosphate (ZDDP), the HDPA-Ti3C2/ZDDP composite additive outperforms single additives in tribological performance, suggesting synergistic effects between them. This enhanced performance may be attributed to the formation of an amorphous polyphosphate tribofilm offering wear resistance, followed by the generation of a TiO2 tribofilm that further safeguards and repairs the worn surface, thereby enhancing the load-bearing capacity. Concurrently, the interlayer sliding mechanism of nanosheets, which substitutes the relative motion of the friction pair, reduces friction under boundary lubrication, ensuring prolonged effective lubrication. This work broadens the application prospects of Ti3C2Tx MXene for the design and development of commercial lubricating additives.

The ribosome profiling landscape of yeast reveals a high diversity in pervasive translation

BackgroundPervasive translation is a widespread phenomenon that plays a critical role in the emergence of novel microproteins, but the diversity of translation patterns contributing to their generation remains unclear. Based on 54 ribosome profiling (Ribo-Seq) datasets, we investigated the yeast Ribo-Seq landscape using a representation framework that allows the comprehensive inventory and classification of the entire diversity of Ribo-Seq signals, including non-canonical ones.ResultsWe show that if coding regions occupy specific areas of the Ribo-Seq landscape, noncoding regions encompass a wide diversity of Ribo-Seq signals and, conversely, populate the entire landscape. Our results show that pervasive translation can, nevertheless, be associated with high specificity, with 1055 noncoding ORFs exhibiting canonical Ribo-Seq signals. Using mass spectrometry under standard conditions or proteasome inhibition with an in-house analysis protocol, we report 239 microproteins originating from noncoding ORFs that display canonical but also non-canonical Ribo-Seq signals. Each condition yields dozens of additional microprotein candidates with comparable translation properties, suggesting a larger population of volatile microproteins that are challenging to detect. Our findings suggest that non-canonical translation signals may harbor valuable information and underscore the significance of considering them in proteogenomic studies. Finally, we show that the translation outcome of a noncoding ORF is primarily determined by the initiating codon and the codon distribution in its two alternative frames, rather than features indicative of functionality.ConclusionOur results enable us to propose a topology of a species’ Ribo-Seq landscape, opening the way to comparative analyses of this translation landscape under different conditions.

Integrative multi-omic analysis identifies genes associated with cuticular wax biogenesis in adult maize leaves.

Studying the genetic basis of leaf wax composition and its correlation with leaf cuticular conductance (gc) is crucial for improving crop productivity. The leaf cuticle, which comprises a cutin matrix and various waxes, functions as an extracellular hydrophobic layer, protecting against water loss upon stomatal closure. To address the limited understanding of genes associated with the natural variation of adult leaf cuticular waxes and their connection to gc, we conducted statistical genetic analyses using leaf transcriptomic, metabolomic, and physiological data sets collected from a maize (Zea mays L.) panel of ∼300 inbred lines. Through a random forest analysis with 60 cuticular wax traits, it was shown that high molecular weight wax esters play an important role in predicting gc. Integrating results from genome-wide and transcriptome-wide studies (GWAS and TWAS) via a Fisher's combined test revealed 231 candidate genes detected by all three association tests. Among these, 11 genes exhibit known or predicted roles in cuticle-related processes. Throughout the genome, multiple hotspots consisting of GWAS signals for several traits from one or more wax classes were discovered, identifying four additional plausible candidate genes and providing insights into the genetic basis of correlated wax traits. Establishing a partially shared genetic architecture, we identified 35 genes for both gc and at least one wax trait, with four considered plausible candidates. Our study enhances the understanding of how adult leaf cuticle wax composition relates to gc and implicates both known and novel candidate genes as potential targets for optimizing productivity in maize.

Lifespan Extension by Retrotransposons under Conditions of Mild Stress Requires Genes Involved in tRNA Modifications and Nucleotide Metabolism

Retrotransposons are mobile DNA elements that are more active with increasing age and exacerbate aging phenotypes in multiple species. We previously reported an unexpected extension of chronological lifespan in the yeast, Saccharomyces paradoxus, due to the presence of Ty1 retrotransposons when cells were aged under conditions of mild stress. In this study, we tested a subset of genes identified by RNA-seq to be differentially expressed in S. paradoxus strains with a high-copy number of Ty1 retrotransposons compared with a strain with no retrotransposons and additional candidate genes for their contribution to lifespan extension when cells were exposed to a moderate dose of hydroxyurea (HU). Deletion of ADE8, NCS2, or TRM9 prevented lifespan extension, while deletion of CDD1, HAC1, or IRE1 partially prevented lifespan extension. Genes overexpressed in high-copy Ty1 strains did not typically have Ty1 insertions in their promoter regions. We found that silencing genomic copies of Ty1 prevented lifespan extension, while expression of Ty1 from a high-copy plasmid extended lifespan in medium with HU or synthetic medium. These results indicate that cells adapt to expression of retrotransposons by changing gene expression in a manner that can better prepare them to remain healthy under mild stress.

An "R-spondin code" for multimodal signaling ON-OFF states.

R-spondins (RSPOs) are a family of secreted proteins and stem cell growth factors that are potent co-activators of Wnt signaling. Recently, RSPO2 and RSPO3 were shown to be multifunctional, not only amplifying Wnt- but also binding BMP- and FGF receptors to downregulate signaling. The common mechanism underlying these diverse functions is that RSPO2 and RSPO3 act as "endocytosers" that link transmembrane proteins to ZNRF3/RNF43 E3 ligases and trigger target internalization. Thus, RSPOs are natural protein targeting chimeras for cell surface proteins. Conducting data mining and cell surface binding assays we report additional candidate RSPO targets, including SMO, PTC1,2, LGI1, ROBO4, and PTPR(F/S). We propose that there is an "R-spondin code" that imparts combinatorial signaling ON-OFF states of multiple growth factors. This code involves the modular RSPO domains, notably distinct motifs in the divergent RSPO-TSP1 domains to mediate target interaction and internalization. The RSPO code offers a novel framework for the understanding how diverse signaling pathways may be coordinately regulated in development and disease.

Analysis of Modular Hub Genes and Therapeutic Targets across Stages of Non-Small Cell Lung Cancer Transcriptome.

Non-small cell lung cancer (NSCLC), representing 85% of lung cancer cases, is characterized by its heterogeneity and progression through distinct stages. This study applied Weighted Gene Co-expression Network Analysis (WGCNA) to explore the molecular mechanisms of NSCLC and identify potential therapeutic targets. Gene expression data from the GEO database were analyzed across four NSCLC stages (NSCLC1, NSCLC2, NSCLC3, and NSCLC4), with the NSCLC2 dataset selected as the reference for module preservation analysis. WGCNA identified eight highly preserved modules-Cyan, Yellow, Red, Dark Turquoise, Turquoise, White, Purple, and Royal Blue-across datasets, which were enriched in key pathways such as "Cell cycle" and "Pathways in cancer", involving processes like cell division and inflammatory responses. Hub genes, including PLK1, CDK1, and EGFR, emerged as critical regulators of tumor proliferation and immune responses. Estrogen receptor ESR1 was also highlighted, correlating with improved survival outcomes, suggesting its potential as a prognostic marker. Signature-based drug repurposing analysis identified promising therapeutic candidates, including GW-5074, which inhibits RAF and disrupts the EGFR-RAS-RAF-MEK-ERK signaling cascade, and olomoucine, a CDK1 inhibitor. Additional candidates like pinocembrin, which reduces NSCLC cell invasion by modulating epithelial-mesenchymal transition, and citalopram, an SSRI with anti-carcinogenic properties, were also identified. These findings provide valuable insights into the molecular underpinnings of NSCLC and suggest new directions for therapeutic strategies through drug repurposing.

Genome-wide association study of hypersensitivity skin reactions induced by nonionic iodinated contrast media.

In Taiwan, nonionic iodinated contrast media (ICMs) are commonly used but can occasionally cause severe side effects. The infrequency of these adverse events, coupled with the complexities in establishing direct causality, poses significant challenges for genetic research. : To investigate the genetic factors associated with skin reactions mediated by nonionic ICMs on a genome-wide scale. A hospital-based cohort from the China Medical University Hospital biobank was utilized to conduct a comprehensive genome-wide association study (GWAS) using PLINK v1.9. The study incorporated two distinct cohorts: one based on adverse drug reaction (ADR) reports, capturing immediate reactions, and the other based on self-reports, which primarily reflected delayed reactions. Known loci were determined by the GWAS catalog. Fine mapping was conducted by FINEMAP to predict causal variants. Pathway enrichment analysis was performed by clusterProfiler to reveal the biological function of the identified genetic signatures. The ADR-based cohort included 120 cases and 3640 controls. GWAS identified 6 candidate risk loci, namely rs150515068, rs6847491, rs192044153, rs191908641, rs376660317, and rs368821335. The self-report-based cohort, consisting of 275 cases and 8338 controls, revealed 36 additional candidate risk loci. Fine mapping further identified 4 causal variants within each cohort. Pathway analysis showed that immediate HSR-related genes are linked to growth hormone response and signaling, while non-immediate HSR genes are involved in neurotransmission. This study offers new perspectives on the genetic foundation of nonionic ICM-induced skin reactions within the Taiwanese population, suggesting that the genes contributing to immediate and non-immediate HSRs might have different functional roles.

Real-time measurement of electron temperature using a coupled centre-tapped emissive probe and a Langmuir probe (CCTELP)

Abstract Conventional electrostatic probes are commonly used for measuring the plasma parameters like plasma density, electron temperature, plasma potential and floating potential respectively in a laboratory plasma to unveil physical processes of relevance to magnetosphere and fusion plasmas. With such probes, real-time measurement of electron temperature and its fluctuating AC component becomes very difficult. These measurements are significant as they directly give the measure of energy flux and hence can be utilized in estimating the turbulence-induced energy loss in any plasma system, especially useful for electron temperature gradient plasmas. Although Triple Langmuir Probe (TLP) diagnostics provide information on real-time measurement of electron temperature, this involves many complications. These complications of TLP are suitably overcome by the proposed diagnostic, which makes use of a combination of a closely separated centre tap emissive probe (CTEP) and Langmuir probe (LP) installed on a single probe head. The coupled centre-tapped emissive and Langmuir probe (CCTELP) provides direct measurement of electron temperature (T_e) and its fluctuations (T ̃_e). The design of the proposed diagnostic is very simple and it is almost free of rigorous control electronics and post-data analysis otherwise needed to estimate the electron temperature. These features make this diagnostic an additional and simple candidate for real-time measurement of electron temperature and its fluctuation. The paper will highlight details on this novel diagnostics, called CCTELP for the measurement in Maxwellian plasmas.

Modulatory effects of Enteromorpha prolifera powder and its enzymatic hydrolysate on growth performance, antioxidant capacity, and non-specific immunity of Trachinotus ovatus

The excessive proliferation of the genus Enteromorpha serves as the primary catalyst for the occurrence of red tides. Nonetheless, this genus is abundant in sulfated polysaccharides, phenolic compounds, peptides, and alkaloids, which exhibit remarkable efficacy in antioxidation, anti-inflammation, and immune response modulation. Consequently, Enteromorpha-derived products hold promising application prospects as aquatic feed additives. The primary objective of this study was to evaluate the impact of E. prolifera powder (EPM) and its enzymatic hydrolysate (EPH) on the growth, antioxidant capacity, intestinal morphology, and immunity of juvenile Trachinotus ovatus. Four isonitrogenous and isolipidic diets were formulated with varying levels of Enteromorpha products: 0 % (Control), 0.1 % EPH (EPH0.1), 0.3 % EPH (EPH0.3), and 3 % EPM, and were administered to juvenile T. ovatus for eight weeks. The findings revealed that growth performance in the EPH0.3 and EPM groups surpassed that of the control group, concomitant with increased feed intake and elongated intestinal villi. Notably, Enteromorpha-derived products supplementation significantly bolstered the antioxidant capacity of T. ovatus through activation of the Nrf2-Keap1 signaling pathway, leading to elevations in antioxidant enzymes such as SOD and CAT, as well as T-AOC. Conversely, MDA levels were conspicuously reduced in the Enteromorpha-treated groups. Moreover, Enteromorpha-derived products supplementation exhibited pronounced anti-inflammatory effects, marked by the downregulation of proinflammatory cytokine expression and upregulation of anti-inflammatory cytokines, along with decreased apoptotic gene expression. These observations highlight the potential anti-inflammatory properties of EPM and EPH, which may contribute to the preservation of hepatic tissue health and homeostasis. In summary, the optimal growth performance and antioxidant capacity were achieved with 0.3 % EPH supplementation, indicating the efficacy of this concentration in promoting the overall wellbeing of T. ovatus. Remarkably, the employment of processing methodologies, notably enzymatic hydrolysis, has not only facilitated the manifestation but also potentially augmented the inherent beneficial attributes traditionally ascribed to EPM. Furthermore, this refinement process has enabled a reduction in the inclusion rate of EPM within feed formulations, thereby enhancing cost-effectiveness. Consequently, Enteromorpha-derived products emerge as highly promising candidates for aquatic feed additives, with the potential to mitigate the economic burdens imposed by red tide management strategies. Their utilization represents a strategic approach towards sustainable aquaculture practices.

Assessment of the antibacterial and antioxidant activities of seaweed-derived extracts

In swine farming, animals develop diseases that require the use of antibiotics. In-feed antibiotics as growth promoters have been banned due to the increasing concern of antimicrobial resistance. Seaweeds offer bioactive molecules with antibacterial and antioxidant properties. The aim was to estimate the in vitro properties of seaweed extracts: Ascophyllum nodosum (AN), Palmaria palmata (PP), Ulva lactuca (UL), and 1:1 mixes (ANPP, ANUL, PPUL). Escherichia coli strains were used to test for growth inhibitory activity, and chemical-based assays were performed for antioxidant properties. The treatments were 2 (with/without Escherichia coli) × 2 (F4 + and F18 +) × 5 doses (0, 1.44, 2.87, 5.75, 11.50, and 23.0 mg/mL). Bacteria were supplemented with seaweed extracts, and growth was monitored. The antioxidant activity was assessed with 6 doses (0, 1, 50, 100, 200, 500, and 600 mg/mL) × 6 compounds using two chemical assays. Data were evaluated through SAS. The results showed that AN and UL significantly inhibited (p < 0.05) the growth of F4 + and F18 +. PP and mixes did not display an inhibition of the bacteria growth. AN, PP, UL extracts, and mixes exhibited antioxidant activities, with AN showing the strongest dose–response. Thus, AN and UL seaweed extracts reveal promising antibacterial and antioxidant effects and may be candidates for in-feed additives.

The Valuable Long-period Cluster Cepheid KQ Scorpii and other Calibration Candidates

The classical Cepheid KQ Sco is a valuable anchor for the distance scale because of its long pulsation period (28.ͩ7) and evidence implying membership in the open cluster UBC 1558. Analyses tied to Gaia DR3 astrometry, photometry, spectroscopy, radial velocities, and 2MASS-VVV photometry indicate a common distance of 2.15 ± 0.15 kpc (L21 DR3 corrections applied). Additional cluster Cepheid candidates requiring follow-up are identified, and it is suggested that a team of international researchers could maintain a cluster Cepheid database to guide the broader community to cases where consensus exists.

Analysis and profiling of the purple acid phosphatase gene family in wheat (Triticum aestivum L.).

Purple acid phosphatases (PAPs) play a vital role in plant phosphorus nutrition, serving as a crucial family of metallo-phosphoesterase enzymes. This research aimed to identify the PAP genes from the A/B/D genomes of Triticum aestivum to elucidate evolutionary mechanisms of the gene family in plants and provide genomic information for subsequent research on phosphorous-use efficiency in wheat crops. In total, 105 PAP genes (TaPAPs) were identified from the A/B/D genomes by using the Arabidopsis thaliana and Oryza sativa PAP protein sequences as queries for BLASTP against the wheat protein database. The TaPAPs were grouped into six subfamilies, Ia (17), Ib (26), IIa (11), IIb (30), IIIa (12), and IIIb (9), based on their similarities in the structure of genes and the presence of conserved protein motifs. A majority of TaPAPs were derived from tandemly (20) or segmentally (87) duplicated, with the homoeologous chromosomes 5A/B/D harboring the most duplicated PAP genes. Further analysis indicated that TaPAPs were responsible for the modulation of seed, root, and leaf development and hormone synthesis and signaling, as well as plant responses to abiotic stresses, including low temperatures, drought, and anaerobic conditions. Nine TaPAPs (TaPAP9-4A/4B/4D, TaPAP24-6A/6B/6D, and TaPAP28-7A/7B/7D) were constitutively expressed in diverse tissues such as root, shoot, leaf, spike, and seed, while the remaining genes exhibited tissue-specific expression patterns. Concerning the response to phosphate (Pi) deprivation, 57 TaPAPs were highly expressed in roots under Pi stress, including TaPAP31-4A, 4B, and 4D homeologs from the subfamily IIIb. A TaPAP31-4A transgene in A. thaliana promoted plant growth and development while increasing plant resistance to Pi-deficiency stress by enhancing the secretion of phosphatase. These discoveries provide a scientific foundation for comprehending the role of TaPAPs, offering valuable insights for identifying additional candidate genes and fostering the development of new wheat varieties with enhanced tolerance to low phosphorus conditions.

Optimized search for a binary black hole merger population in LIGO-Virgo O3 data

Maximizing the number of detections in matched filter searches for compact binary coalescence (CBC) gravitational wave signals requires a model of the source population distribution. In previous searches using the framework, sensitivity to the population of binary black hole (BBH) mergers was improved by restricting the range of filter template mass ratios and use of a simple one-dimensional population model. However, this approach does not make use of our full knowledge of the population and cannot be extended to a full parameter space search. Here, we introduce a new ranking method, based on kernel density estimation with adaptive bandwidth, to accurately model the probability distributions of binary source parameters over a template bank, both for signals and for noise events. We demonstrate this ranking method by conducting a search over LIGO-Virgo O3 data for BBHs with unrestricted mass ratio, using a signal model derived from previous significant detected events. We achieve over 10% increase in sensitive volume for a simple power-law simulated signal population, compared to the previous BBH search. Correspondingly, with the new ranking, eight additional candidate events above an inverse false alarm rate threshold 0.5 yr are identified. Published by the American Physical Society 2024

Term Candidate Generation to Enrich Clinical Terminologies with Large Language Models.

Annotated language resources derived from clinical routine documentation form an intriguing asset for secondary use case scenarios. In this investigation, we report on how such a resource can be leveraged to identify additional term candidates for a chosen set of ICD-10 codes. We conducted a log-likelihood analysis, considering the co-occurrence of approximately 1.9 million de-identified ICD-10 codes alongside corresponding brief textual entries from problem lists in German. This analysis aimed to identify potential candidates with statistical significance set at p < 0.01, which were used as seed terms to harvest additional candidates by interfacing to a large language model in a second step. The proposed approach can identify additional term candidates at suitable performance values: hypernyms MAP@5=0.801, synonyms MAP@5 = 0.723 and hyponyms MAP@5 = 0.507. The re-use of existing annotated clinical datasets, in combination with large language models, presents an interesting strategy to bridge the lexical gap in standardized clinical terminologies and real-world jargon.

The growth-promoting effect of water extract of Chuanminshen violaceum stem and leaf on broilers

Currently, developing non-antibiotic growth promoters is a broad consensus in broiler industry, which is one of the effective ways to reduce drug-resistant strains. Chuanminshen violaceum is a traditional Chinese medicinal herb that is commonly used for its roots, while the stems and leaves are often discarded, resulting in a huge amount of waste. This study optimized the preparation process of water extract of Chuanminshen violaceum stems and leaves (CVSLE) by response surface analysis based on the yields of polysaccharide and protein. The CVSLE and herbal powder (CVSL) were then processed into granules before being used as feed additives. The Macleaya cordata powder was used as positive control. The results showed that the addition of CVSLE (0.5% of the feed) showed the highest growth-promoting activity than other CVSLE groups (0.2% and 1%), 1% CVSL group and positive control (0.05%). CVSLE at the dosage of 0.5% could significantly increase the ADG and reduce the FCR from d 21 to 42, d 0 to 42. The HI antibody titers against Newcastle disease virus and avian influenza virus were significantly enhanced at 21, 28 and 42d. CVSLE did not affect the slaughtering performances, but could significantly elevate the spleen, thymus and bursa of Fabricius indices and the transcriptional levels of IL-2, IL-4, IL-10 and IFN-γ in spleen. The intestinal barrier function of broilers was significantly enhanced by increased levels of immune barrier (sIgA), physical barrier (ZO-1, OCL and Muc-2) and flora barrier (Lactobacillus and Bifidobacterium). These results suggest that CVSLE was a promising herbal additive candidate for broilers.

Chemical optimization and derivatization of micrococcin p2 to target multiple bacterial infections: new antibiotics from thiopeptides.

Antimicrobial resistance poses a significant threat to humanity, and the development of new antibiotics is urgently needed. Our research has focused on thiopeptide antibiotics such as micrococcin P2 (MP2) and derivatives thereof as new anti-infective agents. Thiopeptides are sulfur-rich, structurally complex substances that exhibit potent activity against Gram-positive pathogens and Mycobacteria species, including clinically resistant strains. The clinical development of thiopeptides has been hampered by the lack of efficient synthetic platforms to conduct detailed structure-activity relationship studies of these natural products. The present contribution touches upon efficient synthetic routes to MP2 that laid the groundwork for clinical translation. The medicinal chemistry campaign on MP2 has been guided by computational molecular dynamic simulations and parallel investigations to improve drug-like properties, such as enhancing the aqueous solubility and optimizing antibacterial activity. Such endeavors have enabled identification of promising lead compounds, AJ-037 and AJ-206, against Mycobacterium avium complex (MAC). Extensive in vitro studies revealed that these compounds exert potent activity against MAC species, a subspecies of non-tuberculous mycobacteria (NTM) that proliferate inside macrophages. Two additional pre-clinical candidates have been identified: AJ-024, for the treatment of Clostridioides difficile infections, and AJ-147, for methicillin-resistant Staphylococcus aureus impetigo. Both compounds compare quite favorably with current first-line treatments. In particular, the ability of AJ-147 to downregulate pro-inflammatory cytokines adds a valuable dimension to its clinical use. In light of above, these new thiopeptide derivatives are well-poised for further clinical development.

Positive and unlabelled machine learning reveals new fast radio burst repeater candidates

ABSTRACT Fast radio bursts (FRBs) are astronomical radio transients of unknown origin. A minority of FRBs have been observed to originate from repeating sources, and it is unknown which apparent one-off bursts are hidden repeaters. Recent studies increasingly suggest that there are intrinsic physical differences between repeating and non-repeating FRBs. Previous research has used machine learning classification techniques to identify apparent non-repeaters with repeater characteristics, whose sky positions would be ideal targets for future observation campaigns. However, these methods have not sufficiently accounted for the positive and unlabelled (PU) nature of the data, wherein true labels are only available for repeaters. Modified techniques that do not inadvertently learn properties of hidden repeaters as characteristic of non-repeaters are likely to identify additional repeater candidates with greater accuracy. We present in this paper the first known attempt at applying PU-specific machine learning techniques to study FRBs. We train an ensemble of five PU-specific classifiers on the available data and use them to identify 66 repeater candidates in burst data from the CHIME/FRB collaboration, 18 of which were not identified with the use of machine learning classifiers in past research. Our results additionally support repeaters and non-repeaters having intrinsically different physical properties, particularly spectral index, frequency width, and burst width. This work additionally opens new possibilities to study repeating and non-repeating FRBs using the framework of PU learning.

Diketopyrrolopyrroles As Performance Enhancing Additives for Lithium-Sulfur Batteries

Although the lithium-ion battery (LIB) has been instrumental in global electrification, more premium applications (such as electrification of aircraft) require capacities and performance beyond the capabilities of traditional LIB chemistries[1]. Lithium-sulfur (Li-S) batteries are a front runner among next generation battery technologies thanks to their very high theoretical capacities (1675 mAh g-1) and impressive gravimetric energy densities (2,700 Wh kg-1) [2,3]. Despite their potential, there are numerous chemical challenges (polysulfide shuttle, dendrite formation etc.) that must be overcome before widespread adoption of the technology [4]. Electrolyte additives have been explored as a means to facilitate the electron transfer reactions that occur within the cell and improve cell capacity and cyclability [5].Diketopyrrolopyrroles (DPPs) are a class of organic π-conjugated compounds that have garnered significant interest in a variety of electrical applications, including solar cells and sensors [6]. The high electrochemical tunability, made possible through the editable organic structure, makes them suitable candidates for redox active electrolyte additives. Here, we explore DPP derivatives as a novel class of electrolyte additive for improving the cell cycling performance of Li-S batteries. A variety of electrochemical and analytical techniques have been utilised to assess the suitability of DPPs as redox active additives, building an understanding of their interactions with active materials in a Li-S cell. Galvanostatic cycling allows us to connect these electrochemical findings to cell cycling performance, where we observe a large enhancement in capacity. We also present an alternative statistical approach to cell data analysis, providing a more concrete method to assessing cycling enhancement than that shown throughout literature. Figure 1. A box plot displaying the discharge capacities at specific cycle numbers for standard (light grey) and DPP (dark grey) cells to provide a statistical comparison.