Unknown Function Research Articles

Enhancing extracellular membrane vesicle productivity of Shewanella vesiculosa HM13, a prospective host for vesiculation-mediated protein secretion, by weakening outer membrane-peptidoglycan linkage

Shewanella vesiculosa HM13, a psychrotrophic gram-negative bacterium isolated from the intestinal contents of horse mackerel, produces abundant extracellular membrane vesicles (EMVs) by budding the outer membrane. The EMVs of this bacterium carry a single major cargo protein, P49, of unknown function, which may be useful as a carrier for the secretory production of heterologous proteins as cargoes of EMVs. In this study, to increase the utility of S.vesiculosa HM13 as a host for EMV-mediated protein production, we improved its EMV productivity by weakening the linkage between the outer membrane and underlying peptidoglycan layer. In gram-negative bacteria, the outer membrane is connected to peptidoglycans predominantly through Braun's lipoprotein (Lpp), and the formation of this linkage is catalyzed by an l,d-transpeptidase (Ldt). We constructed gene-disrupted mutants of Lpp and Ldt and assessed their EMV productivity. The EMVs of the lpp- and ldt-disrupted mutants grown at 18°C were evaluated using nanoparticle tracking analysis, and their morphologies were observed using transmission electron microscopy. As a result, an approximately 2.5-fold increase in EMV production was achieved, whereas the morphology of the EMVs of these mutants remained almost identical to that of the parent strain. In accordance with the increase in EMV production, the mutants secreted approximately 2-fold higher amounts of P49 than the parent strain into the culture broth as the EMV cargo. These findings will contribute to the development of an EMV-based secretory production system for heterologous proteins using S.vesiculosa HM13 as a host.

Transcriptome analysis of Phytophthora cactorum infecting strawberry identified RXLR effectors that induce cell death when transiently expressed in Nicotiana benthamiana

Phytophthora cactorum is a plant pathogenic oomycete that causes crown rot in strawberry leading to significant economic losses every year. To invade the host, P. cactorum secretes an arsenal of effectors that can manipulate host physiology and impair its defense system promoting infection. A transcriptome analysis was conducted on a susceptible wild strawberry genotype (Fragaria vesca) 48 hours post inoculation with P. cactorum to identify effectors expressed during the early infection stage. The analysis revealed 4,668 P. cactorum genes expressed during infection of F. vesca. A total of 539 secreted proteins encoded by transcripts were identified, including 120 carbohydrate-active enzymes, 40 RXLRs, 23 proteolytic enzymes, nine elicitins, seven cysteine rich proteins, seven necrosis inducing proteins and 216 hypothetical proteins with unknown function. Twenty of the 40 RXLR effector candidates were transiently expressed in Nicotiana benthamiana using agroinfiltration and five previously unreported RXLR effector genes (Pc741, Pc8318, Pc10890, Pc20813, and Pc22290) triggered cell death when transiently expressed. The identified cell death inducing RXLR effectors showed 31–66% identity to known RXLR effectors in different Phytophthora species having roles in pathogenicity including both activation and suppression of defense response in the host. Furthermore, homology analysis revealed that these cell death inducing RXLR effectors were highly conserved (82 - 100% identity) across 23 different strains of P. cactorum originating from apple or strawberry.

Cross-species transmission of a novel bisegmented orfanplasmovirus in the phytopathogenic fungus Exserohilum rostratum

Mycoviruses have been found in various fungal species across different taxonomic groups, while no viruses have been reported yet in the fungus Exserohilum rostratum. In this study, a novel orfanplasmovirus, namely Exserohilum rostratum orfanplasmovirus 1 (ErOrfV1), was identified in the Exserohilum rostratum strain JZ1 from maize leaf. The complete genome of ErOrfV1 consists of two positive single-stranded RNA segments, encoding an RNA-dependent RNA polymerase and a hypothetical protein with unknown function, respectively. Phylogenetic analysis revealed that ErOrfV1 clusters with other orfanplasmoviruses, forming a distinct phyletic clade. A new family, Orfanplasmoviridae, is proposed to encompass this newly discovered ErOrfV1 and its associated orfanplasmoviruses. ErOrfV1 exhibits effective vertical transmission through conidia, as evidenced by its 100% presence in over 200 single conidium isolates. Moreover, it can be horizontally transmitted to Exserohilum turcicum. Additionally, the infection of ErOrfV1 is cryptic in E. turcicum because there were no significant differences in mycelial growth rate and colony morphology between ErOrfV1-infected and ErOrfV1-free strains. This study represents the inaugural report of a mycovirus in E. rostratum, as well as the first documentation of the biological and transmission characteristics of orfanplasmovirus. These discoveries significantly contribute to our understanding of orfanplasmovirus.

#2240 The complex fluctuation of circulating T follicular cells in patients with lupus nephritis (LN)

Abstract Background and Aims Follicular T (TF) cells constitute a subgroup of cells recently discovered, located in the germinal center (GC) of lymphoid follicles, where they mediate B lymphocyte development, maturation, and antibody production. Meanwhile, T cells with similar markers have also been detected in the peripheral blood, considered as a circulating memory compartment with unknown origin or function. TF cells seem to be implicated in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN) by assisting the selection of high-affinity B cells in germinal centers; nonetheless, research about their circulating regimen is lacking. Herein, we describe the population of circulating TF cells in patients with LN and their association with disease hallmarks. Method Flow cytometry was performed to identify cTF (CD4+CD45RA-CXCR5+) cells and their subsets, defined as cTF1 (CD4+CD45RA-CXCR5+CXCR3+CCR6-), cTF2 (CD4+CD45RA-CXCR5+CXCR3-CCR6-), cTF17 (CD4+CD45RA-CXCR5+CXCR3-CCR6+), and activated-cTF, cTF-ICOS+ (CD4+CD45RA-CXCR5+ICOS+), as well as cTF-Regulatory (cTFR) (CD4+CD45RA-CXCR5+CD127-CD25+FOXP3+). Peripheral blood was collected from 25 LN patients (LN) and 25 healthy controls (HC) of similar age. Results Here are presented preliminary results analyzed in 15 LN patients (age = 38 ± 8yrs) and compared to 9 HC (age = 31.5 ± 7yrs). Although our findings were not significant in total and the percentage and total number of cTFH cells were similar between LN and HC [7.1 (0.6-22.4)% and 52.57 (3.38-412.7)cells/μL, vs. 6.6 (1.9-12.1)% and 45.65 (13.3-69.6)cells/μL, respectively], the fluctuation of the different subsets is interesting. cTF-ICOS+, cTF1, cTF2, and also surprisingly cTFR cells were upregulated in LN compared to HC [0.9 (0-5.2) vs 0.51 (0-1.45)cells/μL, 9.3 (0.2-31.6) vs. 3.02 (0.4-23.08)cells/μL, 10.89 (0-47.41) vs 3.37 (0.46-39.01)cells/μL, and 0.21 (0-12) vs 0.12 (0-1.53) cells/μL, respectively], while the cTF17 compartment was condensed [5.36 (0.79-213.8) vs 8.37 (0.22-29.2)cells/μL, respectively]. Clinical and laboratory markers of the disease were then assessed, resulting in a strong positive correlation of the SLEDAI score with the percentage of cTF2 and cTFR (r = 0.643 and 0.706, respectively) and of C3 levels with cTF percentage (r = 0.663) and cTF-ICOS (+) number (r = 0.719) while the correlation was negative between C4 levels with the percentage of cTF1 (r = −0.577) and cTF2 (r = −582) and between ANA antibody levels and cTF-ICOS (+) cells (r = −657). The analysis did not show any association between the anti-dsDNA antibody levels and the understudied subpopulations. Conclusion cTF cells tend towards 1 and 2 rather than the 17 phenotype in LN. From the various subsets, cTF2 appear to serve as a possible monitoring marker. Certainly, the complexity of the disease imposes further investigation.

Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates

SLC22A10 is an orphan transporter with unknown substrates and function. The goal of this study is to elucidate its substrate specificity and functional characteristics. In contrast to orthologs from great apes, human SLC22A10, tagged with green fluorescent protein, is not expressed on the plasma membrane. Cells expressing great ape SLC22A10 orthologs exhibit significant accumulation of estradiol-17β-glucuronide, unlike those expressing human SLC22A10. Sequence alignments reveal a proline at position 220 in humans, which is a leucine in great apes. Replacing proline with leucine in SLC22A10-P220L restores plasma membrane localization and uptake function. Neanderthal and Denisovan genomes show proline at position 220, akin to modern humans, indicating functional loss during hominin evolution. Human SLC22A10 is a unitary pseudogene due to a fixed missense mutation, P220, while in great apes, its orthologs transport sex steroid conjugates. Characterizing SLC22A10 across species sheds light on its biological role, influencing organism development and steroid homeostasis.

Splice variants of CK1α and CK1α-like: Comparative analysis of subcellular localization, kinase activity, and function in the Wnt signaling pathway

Members of the casein kinase 1 (CK1) family are important regulators of multiple signaling pathways. CK1α is a well-known negative regulator of the Wnt/β-catenin pathway, which promotes the degradation of β-catenin via its phosphorylation of Ser45. In contrast, the closest paralog of CK1α, CK1α-like, is a poorly characterized kinase of unknown function. In this study, we show that the deletion of CK1α, but not CK1α-like, resulted in a strong activation of the Wnt/β-catenin pathway. Wnt-3a treatment further enhanced the activation, which suggests there are at least two modes, a CK1α-dependent and Wnt-dependent, of β-catenin regulation. Rescue experiments showed that only two out of ten naturally occurring splice CK1α/α-like variants were able to rescue the augmented Wnt/β-catenin signaling caused by CK1α deficiency in cells. Importantly, the ability to phosphorylate β-catenin on Ser45 in the invitro kinase assay was required but not sufficient for such rescue. Our compound CK1α and GSK3α/β KO models suggest that the additional nonredundant function of CK1α in the Wnt pathway beyond Ser45-β-catenin phosphorylation includes Axin phosphorylation. Finally, we established NanoBRET assays for the three most common CK1α splice variants as well as CK1α-like. Target engagement data revealed comparable potency of known CK1α inhibitors for all CK1α variants but not for CK1α-like. In summary, our work brings important novel insights into the biology of CK1α, including evidence for the lack of redundancy with other CK1 kinases in the negative regulation of the Wnt/β-catenin pathway at the level of β-catenin and Axin.

Borrelia burgdorferi 0755, a Novel Cytotoxin with Unknown Function in Lyme Disease.

The pathophysiology of Lyme disease, especially in its persistent form, remains to be determined. As many of the neurologic symptoms are similar to those seen in other toxin-associated disorders, a hypothesis was generated that B. burgdorferi, the causative agent of Lyme disease, may produce a neurotoxin to account for some of the symptoms. Using primers against known conserved bacterial toxin groups, and PCR technology, a candidate neurotoxin was discovered. The purified protein was temporarily named BbTox, and was subsequently found to be identical to BB0755, a protein deduced from the genome sequence of B. burgdorferi that has been annotated as a Z ribonuclease. BbTox has cytotoxic activity against cells of neural origin in tissue culture. Its toxic activity appears to be directed against cytoskeletal elements, similar to that seen with toxins of Clostridioides difficile and Clostridioides botulinum, but differing from that of cholera and E. coli toxins, and other toxins. It remains to be determined whether BbTox has direct cytotoxic effects on neural or glial cells in vivo, or its activity is primarily that of a ribonuclease analogous to other bacterial ribonucleases that are involved in antibiotic tolerance remains to be determined.

Mycobacterial biotin synthases require an auxiliary protein to convert dethiobiotin into biotin

Lipid biosynthesis in the pathogen Mycobacterium tuberculosis depends on biotin for posttranslational modification of key enzymes. However, the mycobacterial biotin synthetic pathway is not fully understood. Here, we show that rv1590, a gene of previously unknown function, is required by M. tuberculosis to synthesize biotin. Chemical–generic interaction experiments mapped the function of rv1590 to the conversion of dethiobiotin to biotin, which is catalyzed by biotin synthases (BioB). Biochemical studies confirmed that in contrast to BioB of Escherichia coli, BioB of M. tuberculosis requires Rv1590 (which we named “biotin synthase auxiliary protein” or BsaP), for activity. We found homologs of bsaP associated with bioB in many actinobacterial genomes, and confirmed that BioB of Mycobacteriumsmegmatis also requires BsaP. Structural comparisons of BsaP-associated biotin synthases with BsaP-independent biotin synthases suggest that the need for BsaP is determined by the [2Fe–2S] cluster that inserts sulfur into dethiobiotin. Our findings open new opportunities to seek BioB inhibitors to treat infections with M. tuberculosis and other pathogens.

Analysis of a new negevirus-like sequence from Bemisia tabaci unveils a potential new taxon linking nelorpi- and centiviruses.

This study presents the complete genome sequence of a novel nege-like virus identified in whiteflies (Bemisia tabaci MEAM1), provisionally designated as whitefly negevirus 1 (WfNgV1). The virus possesses a single-stranded RNA genome comprising 11,848 nucleotides, organized into four open reading frames (ORFs). These ORFs encode the putative RNA-dependent-RNA-polymerase (RdRp, ORF 1), a glycoprotein (ORF 2), a structural protein with homology to those in the SP24 family, (ORF 3), and a protein of unknown function (ORF 4). Phylogenetic analysis focusing on RdRp and SP24 amino acid sequences revealed a close relationship between WfNgV1 and Bemisia tabaci negevirus 1, a negevirus sequence recently discovered in whiteflies from Israel. Both viruses form a clade sharing a most recent common ancestor with the proposed nelorpivirus and centivirus taxa. The putative glycoprotein from ORF 2 and SP24 (ORF 3) of WfNgV1 exhibit the characteristic topologies previously reported for negevirus counterparts. This marks the first reported negevirus-like sequence from whiteflies in the Americas.

Decentralized Output-Feedback Adaptive Event-Triggered Control for Interconnected Nonlinear Delay Systems with Actuator Failures

This paper investigates decentralized adaptive event-triggered fault-tolerant control for interconnected nonlinear delay systems with actuator failures. The actuator failures suffered include loss of effectiveness and bias faults. A control scheme based on the K-filter is proposed, which effectively compensates for the effects of unknown actuator failures. A hyperbolic tangent function and neural network are introduced to approximate the unknown interconnection function and nonlinear delay function. By introducing the dynamic surface control method, the “explosion of complexity” issue is addressed. Furthermore, our proposed controller can ensure that all states of the corresponding closed-loop system are semi-globally uniformly ultimately bounded and that the tracking error can converge to a small neighborhood of zero. Meanwhile, Zeno behavior can be effectively avoided. Finally, the validity of the proposed control scheme is verified using a simulation example.

New alternatives to the Lennard-Jones potential

We present a new method for approximating two-body interatomic potentials from existing ab initio data based on representing the unknown function as an analytic continued fraction. In this study, our method was first inspired by a representation of the unknown potential as a Dirichlet polynomial, i.e., the partial sum of some terms of a Dirichlet series. Our method allows for a close and computationally efficient approximation of the ab initio data for the noble gases Xenon (Xe), Krypton (Kr), Argon (Ar), and Neon (Ne), which are proportional to r-6\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$r^{-6}$$\\end{document} and to a very simple depth=1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$depth=1$$\\end{document} truncated continued fraction with integer coefficients and depending on n-r\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$n^{-r}$$\\end{document} only, where n is a natural number (with n=13\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$n=13$$\\end{document} for Xe, n=16\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$n=16$$\\end{document} for Kr, n=17\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$n=17$$\\end{document} for Ar, and n=27\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$n=27$$\\end{document} for Neon). For Helium (He), the data is well approximated with a function having only one variable n-r\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$n^{-r}$$\\end{document} with n=31\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$n=31$$\\end{document} and a truncated continued fraction with depth=2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$depth=2$$\\end{document} (i.e., the third convergent of the expansion). Also, for He, we have found an interesting depth=0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$depth=0$$\\end{document} result, a Dirichlet polynomial of the form k16-r+k248-r+k372-r\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$k_1 \\, 6^{-r} + k_2 \\, 48^{-r} + k_3 \\, 72^{-r}$$\\end{document} (with k1,k2,k3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$k_1, k_2, k_3$$\\end{document} all integers), which provides a surprisingly good fit, not only in the attractive but also in the repulsive region. We also discuss lessons learned while facing the surprisingly challenging non-linear optimisation tasks in fitting these approximations and opportunities for parallelisation.

OsBBP1, a newly identified protein containing DUF630 and DUF632 domains confers drought tolerance in rice

Domain of unknown function (DUF) protein families, which are uncharacterized and numerous within the Pfam database. Recently, studies have demonstrated that DUFs played crucial roles in plant development, but whether, or how, they function in drought resistance remain unclear. In this study, we identified the Os03g0321500 gene, encoding OsbZIP72 binding protein 1 (OsBBP1), as a target of OsbZIP72 using chromatin immunoprecipitation sequencing in rice. OsBBP1 is a novel member of DUFs, which localize both in the nuclei and cytoplasm of rice protoplasts. Furthermore, yeast one-hybrid and electrophoretic mobility shift assays confirmed the specific binding between OsbZIP72 and OsBBP1. Additionally, a luciferase reporter analysis illustrated that OsbZIP72 activated the expression of OsBBP1. Drought tolerance experiments demonstrate that the OsBBP1 CRISPER-CAS9 transgenic mutants were sensitive to drought stress, but the transgenic OsBBP1 over-expressing rice plants showed enhanced drought resistance. Moreover, drought tolerance experiments in a paddy field suggested that OsBBP1 contributed to less yield or yield-related losses under drought conditions. Mechanistically, OsBBP1 might confer drought resistance by inducing more efficient reactive oxygen species (ROS) scavenging. Several ROS scavenging-related genes showed increased expression levels in OsBBP1 overexpression lines and decreased expression levels in OsBBP1 CRISPER-CAS9 mutants under drought conditions. Thus, OsBBP1, acting downstream of OsbZIP72, contributes to drought resistance and causes less yield or yield-related losses under drought conditions.

A circular single-stranded DNA mycovirus infects plants and confers broad-spectrum fungal resistance

Circular single-stranded DNA (ssDNA) viruses have been rarely found in fungi, and the evolutionary and ecological relationships among ssDNA viruses infecting fungi and other organisms remain unclear. In this study, a novel circular ssDNA virus, tentatively named Diaporthe sojae circular DNA virus 1 (DsCDV1), was identified in the phytopathogenic fungus Diaporthe sojae isolated from pear trees. DsCDV1 has a monopartite genome (3185 nt in size) encapsidated in isometric virions (21–26 nm in diameter). The genome comprises seven putative open reading frames encoding a discrete replicase (Rep) split by an intergenic region, a putative capsid protein (CP), several proteins of unknown function (P1–P4), and a long intergenic region. Notably, the two split parts of DsCDV1 Rep share high identities with the Reps of Geminiviridae and Genomoviridae, respectively, indicating an evolutionary linkage with both families. Phylogenetic analysis based on Rep or CP sequences placed DsCDV1 in a unique cluster, supporting the establishment of a new family, tentatively named Gegemycoviridae, intermediate to both families. DsCDV1 significantly attenuates fungal growth and nearly erases fungal virulence when transfected into the host fungus. Remarkably, DsCDV1 can systematically infect tobacco and pear seedlings, providing broad-spectrum resistance to fungal diseases. Subcellular localization analysis revealed that DsCDV1 P3 is systematically localized in the plasmodesmata, while its expression in trans-complementation experiments could restore systematic infection of a movement-deficient plant virus, suggesting that P3 is a movement protein. DsCDV1 exhibits unique molecular and biological traits not observed in other ssDNA viruses, serving as a link between fungal and plant ssDNA viruses and presenting an evolutionary connection between ssDNA viruses and fungi. These findings contribute to expanding our understanding of ssDNA virus diversity and evolution, offering potential biocontrol applications for managing crucial plant diseases.

Polysaccharide utilization loci encoded DUF1735 likely functions as membrane-bound spacer for carbohydrate active enzymes.

Proteins featuring the Domain of Unknown Function 1735 are frequently found in Polysaccharide Utilization Loci, yet their role remains unknown. The domain and vicinity analyzer programs we developed mine the Kyoto Encyclopedia of Genes and Genomes and UniProt to enhance the functional prediction of DUF1735. Our datasets confirmed the exclusive presence of DUF1735 in Bacteroidota genomes, with Bacteroidetes thetaiotaomicron harboring 46 copies. Notably, 97.8% of DUF1735 are encoded in PULs, and 89% are N-termini of multimodular proteins featuring C-termini like Laminin_G_3, F5/8-typeC, and GH18 domains. Predominantly possessing a predicted lipoprotein signal peptide and sharing an immunoglobulin-like β-sandwich fold with the BACON domain and the N-termini of SusE/F, DUF1735 likely functions as N-terminal, membrane-bound spacer for diverse C-termini involved in PUL-mediated carbohydrate utilization.

Contrastive learning based open-set recognition with unknown score

Open-set recognition (OSR) is designed to classify the seen classes and identify the unseen classes as unknown. However, existing open-set classifiers rely on deep networks trained using supervised learning techniques for known classes present in the training samples. This factor tends to specialize the learned features of the model toward known classes, making it challenging to differentiate between unknown classes. In this study, we propose a novel open-set recognition framework based on contrastive learning with an unknown score. First, we propose a novel training framework based on contrastive learning to learn more informative features and preserve beneficial information to separate unknown from known. Second, we propose an unknown score function based on multi-layer features to detect unknown samples by considering the difference between the known and unknown classes of intermediate-layer features. Based on extensive experiments conducted on multiple benchmark datasets, the proposed method has been demonstrated to outperform existing methods and achieve state-of-the-art results.

Impact of warranty and green level of the product with nonlinear demand via optimal control theory and Artificial Hummingbird Algorithm

Due to the current environmental situation and human health, a green manufacturing system is very essential in the manufacturing world. Several researchers have developed various types of green manufacturing models by considering green products, green investments, carbon emission taxes, etc. Motivated by this topic, a green production model is formulated by considering selling price, time, warranty period and green level dependent demand with a carbon emission tax policy. Also, the production rate of the system is an unknown function of time. Per unit production cost of the products is taken as increasing function of production rate and green level of the products. In our proposed model, carbon emission rate is taken as linear function of time. Then, an optimization problem of the production model is constructed. To validate of our proposed model, a numerical example is considered and solved it by AHA. Further, other five metaheuristics algorithms (AEFA, FA, GWOA, WOA and EOA) are taken to compare the results obtained from AHA. Also, concavity of the average profit function and convergence graph of different metaheuristics algorithms are presented. Finally, a sensitivity analysis is carried out to investigate the impact of different system parameters on our optimal policy and reach a fruitful conclusion from this study.

Molecular characterization and distribution of motilin and motilin receptor in the Japanese medaka Oryzias latipes.

Motilin (MLN) is a peptide hormone originally isolated from the mucosa of the porcine intestine. Its orthologs have been identified in various vertebrates. Although MLN regulates gastrointestinal motility in tetrapods from amphibians to mammals, recent studies indicate that MLN is not involved in the regulation of isolated intestinal motility in zebrafish, at least in vitro. To determine the unknown function of MLN in teleosts, we examined the expression of MLN and the MLN receptor (MLNR) at the cellular level in Japanese medaka (Oryzias latipes). Quantitative PCR revealed that mln mRNA was limitedly expressed in the gut, whereas mlnr mRNA was not detected in the gut but was expressed in the brain and kidney. By in situ hybridization and immunohistochemistry, mlnr mRNA was detected in the dopaminergic neurons of the area postrema in the brain and the noradrenaline-producing cells in the interrenal gland of the kidney. Furthermore, we observed efferent projections of mlnr-expressing dopaminergic neurons in the lobus vagi (XL) and nucleus motorius nervi vagi (NXm) of the medulla oblongata by establishing a transgenic medaka expressing the enhanced green fluorescence protein driven by the mlnr promoter. The expression of dopamine receptor mRNAs in the XL and cholinergic neurons in NXm was confirmed by in situ hybridization. These results indicate novel sites of MLN activity other than the gastrointestinal tract. MLN may exert central and peripheral actions through the regulation of catecholamine release in medaka.

Sex-specific associations between circadian-related genes and depression in UK Biobank participants highlight links to glucose metabolism, inflammation and neuroplasticity pathways

Depressive disorders have increased in global prevalence, making improved management of these disorders a public health priority. Prior research has linked circadian clock genes to depression, either through direct interactions with mood-related pathways in the brain or by modulating the phase of circadian rhythms. Using machine learning and statistical techniques, we explored associations between 157,347 SNP variants from 51 circadian-related genes and depression scores from the patient health questionnaire 9 (PHQ-9) in 99,939 UK Biobank participants. Our results highlight multiple pathways linking the circadian system to mood, including metabolic, monoamine, immune, and stress-related pathways. Notably, genes regulating glucose metabolism and inflammation (GSK3B, LEP, RORA, and NOCT) were prominent factors in females, in addition to DELEC1 and USP46, two genes of unknown function. In contrast, FBXL3 and DRD4 emerged as significant risk factors for male depression. We also found epistatic interactions involving RORA, NFIL3, and ZBTB20 as either risk or protective factors for depression, underscoring the importance of transcription factors (ZBTB20, NFIL3) and hormone receptors (RORA) in depression etiology. Understanding the complex, sex-specific links between circadian genes and mood disorders will facilitate the development of therapeutic interventions and enhance the efficacy of multi-target treatments for depression.

SVEN_5003 is a Major Developmental Regulator in Streptomyces venezuelae.

Many regulatory genes that affect cellular development in Streptomyces, such as the canonical bld genes, have already been identified. However, in this study, we identified sven_5003 in Streptomyces venezuelae as a major new developmental regulatory gene, the deletion of which leads to a bald phenotype, typical of bld mutants, under multiple growth conditions. Our data indicated that disruption of sven_5003 also has a differential impact on the production of the two antibiotics jadomycin and chloramphenicol. Enhanced production of jadomycin but reduced production of chloramphenicol were detected in our sven_5003 mutant strain (S. venezuelae D5003). RNA-Seq analysis indicated that SVEN_5003 impacts expression of hundreds of genes, including genes involved in development, primary and secondary metabolism, and genes of unknown function, a finding confirmed by real-time PCR analysis. Transcriptional analysis indicated that sven_5003 is an auto-regulatory gene, repressing its own expression. Despite the evidence indicating that SVEN_5003 is a regulatory factor, a putative DNA-binding domain was not predicted from its primary amino acid sequence, implying an unknown regulatory mechanism by SVEN_5003. Our findings revealed that SVEN_5003 is a pleiotropic regulator with a critical role in morphological development in S. venezuelae.

Glucose-induced RYBP suppresses tumor cell aerobic glycolysis and migration

RYBP (Ring 1 and YY1 binding protein) has been frequently reported to play an important role during body development, stem cell differentiation, apoptosis and tumorigenesis, but whether RYBP carries out additional functions remains mysterious. Here, we demonstrated that RYBP protein levels elevate with increasing glucose concentration in cell culture medium in human tumorigenic cell lines, but an opposite trend was observed in non-tumorigenic cells. Mechanistic exploration disclosed that glucose inhibits polyubiquitination and proteasomal degradation, leading to RYBP stabilization in tumor cells. Further study showed that RYBP inhibits the glycolysis of tumor cells, as both extracellular acidification rate (ECAR) and lactate production increase when RYBP is knocked down, and decrease when RYBP is over-expressed, and this effect is unrelated to the glucose uptake ability of tumor cells. The functional study showed that RYBP is involved in the regulation of glucose on tumor cell migration. Compared to low glucose culture and their wildtypes, high glucose significantly enhanced tumor cell migration in RYBP knockdown or knockout tumor cells. Taken together, our current study uncovered a previously unknown function of RYBP in tumor metabolism, and this finding will enhance the exploration of the interplay between RYBP and nutrients during tumor cell metabolic reprogramming.