Comparative Functional Analysis Research Articles

Comparative Analysis of the Excitation Functions of 238U as Breeder Fuel Using OPTMAN Code.

Comparative Analysis of the Excitation Functions of 238U as Breeder Fuel Using OPTMAN Code.

Estimation of efficiency of the information exchange on digital networks of communication of terrestrial and air basing: algorithmic and the software

Article is devoted development algorithmic and the software for an estimation of information efficiency of digital networks of communication of a range meter and decimeter waves on existing means of relaying, and also digital networks of communication with usage of a network of retranslators for the unmanned aerial vehicles providing maintenance of demanded efficiency of an information exchange at changes of the input traffic and destabilizing actions. As a result of the led analysis the urgency of application of structurally steady network of relaying on the basis of unmanned aerial vehicles which provides formation of the spatially-distributed access point for terrestrial and air users, for the purpose of the decision of tasks of effective allocation of information highways and frictionless delivery of the information on considered digital networks of communication is formulated. Algorithms are developed for the proof of perspectivity of the given approach and models of estimation of efficiency of an information exchange on digital networks of communication on the basis of the generalized index, providing an adequate estimation in the conditions of change of the input traffic and influence of noises. The comparative analysis of functioning of considered digital networks of communication with usage of existing means of relaying and offered networks of retranslators on the basis of unmanned aerial vehicles is carried out. The main outputs by results of researches are formulated and practical recommendations for choice an optimal variant of creation of researched digital networks of communication are made. Perspectives of further usage of the received results are planned at the organization of complex multiple loop adaptation of digital networks of communication of high mobility with difficult and dynamic changing structures.

서킷 트레이닝을 통한 엘리트 수구 선수들의 신체 조성과 운동 체력, 심폐기능 및 혈중 젖산 농도 비교분석

서킷 트레이닝을 통한 엘리트 수구 선수들의 신체 조성과 운동 체력, 심폐기능 및 혈중 젖산 농도 비교분석

Comparative functional and structural analysis of Pseudomonas aeruginosa d-alanine-d-alanine ligase isoforms as prospective antibiotic targets.

Pseudomonas aeruginosa is a major human pathogen in the healthcare setting. The emergence of multi-drug-resistant and extensive drug-resistant P. aeruginosa is of great concern, and clearly indicates that new alternatives to current first-line antibiotics are required in the future. Inhibition of d-alanine-d-alanine production presents as a promising avenue as it is a key component in the essential process of cell wall biosynthesis. In P. aeruginosa, d-alanine-d-alanine production is facilitated by two isoforms, d-alanine-d-alanine ligase A (PaDdlA) and d-alanine-d-alanine ligase B (PaDdlA), but neither enzyme has been individually characterised to date. Here, we present the functional and structural characterisation of PaDdlA and PaDdlB, and assess their potential as antibiotic targets. This was achieved using a combination of in vitro enzyme-activity assays and X-ray crystallography. The former revealed that both isoforms effectively catalyse d-alanine-d-alanine production with near identical efficiency, and that this is effectively disrupted by the model d-alanine-d-alanine ligase inhibitor, d-cycloserine. Next, each isoform was co-crystallised with ATP and either d-alanine-d-alanine or d-cycloserine, allowing direct comparison of the key structural features. Both isoforms possess the same structural architecture and share a high level of conservation within the active site. Although residues forming the d-alanine pocket are completely conserved, the ATP-binding pocket possesses several amino acid substitutions resulting in a differing chemical environment around the ATP adenine base. Together, these findings support that the discovery of dual PaDdlA/PaDdlB competitive inhibitors is a viable approach for developing new antibiotics against P. aeruginosa.

Comparative Analysis of Functionality and Aspects for Hybrid Recommender Systems

Recommender systems are gradually becoming the backbone of profitable business which interact with users mainly on the web stack. These systems are privileged to have large amounts of user interaction data used to improve them. The systems utilize machine learning and data mining techniques to determine products and features to suggest different users correctly. This is an essential function since offering the right product at the right time might result in increased revenue. This paper gives focus on the importance of different kinds of hybrid recommenders. First, by explaining the various types of recommenders in use, then showing the need for hybrid systems and the multiple kinds before giving a comparative analysis of each of these. Keeping in mind that content-based, as well as collaborative filtering systems, are widely used, research is comparatively done with a keen interest on how this measures up to hybrid recommender systems.

Comparative Analysis of Structural Composition and Function of Intestinal Microbiota between Chinese Indigenous Laiwu Pigs and Commercial DLY Pigs.

Intestinal microbiota has an important impact on pig phenotypes. Previous studies mainly focused on the microbiota of feces and worldwide farmed commercial pigs, while research on the microbiota of various intestinal sections and indigenous pig breeds is very limited. This study aimed to characterize and compare the biogeography of intestinal microbiota in pigs of one Chinese indigenous breed and one commercial crossbred. In this study, we sequenced the microbiota of six intestinal segments in the grown-up pigs of a Chinese indigenous breed, Laiwu pigs, and the worldwide farmed crossbred Duroc × Landrace × Yorkshire (DLY) pigs by 16S rRNA sequencing, characterized the biogeography of intestinal microbiota, and compared the compositional and functional differences between the two breeds. The results showed that there were obvious differences in microbial structure and abundance between the small and large intestines. Laiwu pigs had higher large intestinal diversity than DLY pigs, while DLY pigs had higher small intestinal diversity than Laiwu pigs. Moreover, some specific bacterial taxa and Kyoto Encyclopedia of Genes and Genomes pathways were found to be related to the high fat deposition and good meat quality of Laiwu pigs and the high growth speed and lean meat rate of DLY pigs. This study provides an insight into the shifts in taxonomic composition, microbial diversity, and functional profile of intestinal microbiota in six intestinal segments of Laiwu and DLY pigs, which would be essential for exploring the potential influence of the host's genetic background on variation in microbiota composition and diversity.

A comparative analysis of form and function in Centrarchidae hearing ability: Does otolith variation affect auditory responsiveness?

There exists a wealth of knowledge on hearing ability in individual fish species, but the role of interspecific variation, and drivers behind it, remains understudied, making it difficult to understand evolutionary drivers. The current study quantified hearing thresholds for three species of sunfish in the family Centrarchidae [bluegill sunfish (Lepomis macrochirus), pumpkinseed sunfish (Lepomis gibbosus), and rock bass (Ambloplites rupestris)] using auditory evoked potentials and behavioral trials and saccular otolith size and hair cell density. In auditory physiological experiments, 10-ms tone bursts were played and responses monitored to measure hearing. In behavioral experiments, fish were exposed to the same tone bursts for 1 s, and changes in fish behaviors were monitored. Saccular otolith morphology and hair cell densities were also quantified. Physiological thresholds varied between species, but behavioral thresholds did not. Rock bass had larger S:O ratio (percentage of the saccular otolith surface occupied by the sulcus), but no differences in hair cell densities were found. Our study allows for a direct comparison between confamilial species, allowing a deeper understanding of sound detection abilities and possible mechanisms driving differential hearing. Using both approaches also allows future research into how these species may be impacted by increasing levels of anthropogenic noise.

Comparative Sequence and Functional Analysis of KCS6 and KCS5 from Arabidopsis thaliana and Brassica juncea Establishes Functional Equivalency and Role in Stress Management

Comparative Sequence and Functional Analysis of KCS6 and KCS5 from Arabidopsis thaliana and Brassica juncea Establishes Functional Equivalency and Role in Stress Management

Controlling the physical field using the shape function technique

Abstract A field is described as a region under the influence of some physical force, such as electricity, magnetism, or heat. It is a continuous distribution in the space of continuous quantities. The characteristics of the field are that the values vary continuously between neighboring points. However, because of the continuous nature of the field, it is possible to approximate a physical field of interpolation operations to reduce the cost of sampling and simplify the calculation. This article introduces the modeling of the parametric intensity of physical fields in a general form based on the interpolation shape function technique. Besides the node points with sample data, there are interpolation points, whose accuracy depends significantly on the type of interpolation function and the number of node points sampled. Therefore, a comparative analysis of theoretical shape functions (TSFs) and experimental shape functions (ESFs) is carried out to choose a more suitable type of shape function when interpolating. Specifically, the temperature field is the quantity selected to apply, analyze, and conduct experiments. Theoretical computations, experiments, and comparisons of results have been obtained for each type of shape function in the same physical model under the same experimental conditions. The results show that ESF has an accuracy (error of 0.66%) much better than TSF (error of 10.34%). Moreover, the field model surveyed by a generalized reduced gradient algorithm allows for identifying points with the required parameter values presented in detail. The illustrated calculations on temperature field control in the article show that the solution for both forward and reverse problems can be determined very quickly with high accuracy and stability. Therefore, this technique is expected to be entirely feasible when applied to thermal control processes such as drying in paint technology, kilns, and heat dissipation in practice.

Comparative transcriptome profiling and functional analysis in the blood of tiger puffer (Takifugu rubripes) in response to acute hypoxia

Dissolved oxygen (DO) is an essential ecological factor encountered by fish and other aquatic animals, and hypoxia can adversely affect the physiology, biochemistry and behavior of aquatic animals. Blood is an essential tissue for oxygen transportation and plays a key role in maintaining homeostasis and adapting the organism to hypoxia. However, studies focusing on the molecular regulatory mechanisms of blood under hypoxia are scant. Therefore, to explore the hypoxia adaptive mechanisms in the blood, we used RNA-Seq technology to investigate the transcriptome changes in the blood of Takifugu rubripes under acute hypoxia. In our study, 20 fish were selected and divided into four groups, including a control group (PPM5.4) and three experimental groups (PPM4, PPM2 and PPM0). In addition to GO and KEGG enrichment analysis, we further used GSEA enrichment analysis to screen the pathways mediated in T. rubripes under hypoxia. Results revealed that hypoxia had a greater effect on blood than other tissues, and T. rubripes could inhibit cell proliferation and down-regulated immune-related pathways (including IL-17 signaling pathway, C-type lectin receptor signaling pathway, B cell receptor signaling pathway and Toll-like receptor signaling pathway). However, the blood of T. rubripes could positively modulate the genes expression involved in energy regulation, angiogenesis and oxidative stress to resist hypoxic damage. Furthermore, T. rubripes could also up-regulate apoptosis and JAK−STAT signaling pathway to conduct self-protection in response to hypoxia. In conclusion, all these results indicated that immune processes, energy metabolism, angiogenesis and oxidative stress were significantly altered in the blood of acute hypoxic T. rubripes, which contributed to maintain cellular energy balance and oxygen supply during hypoxic conditions. The key regulatory genes and pathways identified in this study not only reveal the mechanism of hypoxia tolerance in T. rubripes, but also provide a theoretical basis for breeding hypoxia-tolerant T. rubripes and other fish.

A Comparative Analysis of Adjective Types and Functions in Print Media: The Star Newspaper and Reader’s Digest Magazine Headlines

Headlines play a crucial role in capturing reader attention in print media, often employing adjectives to create compelling content. Despite their importance, adjectives remain under-researched in comparison to other lexical categories, and their use in print media such as newspapers and magazines has received limited attention. This study aims to identify the types and functions of adjectives in The Star newspaper and Reader’s Digest magazine headlines, focusing on their semantic categories and syntactic functions based on the classification framework proposed by Biber, Conrad, and Leech. Data were collected through textual analysis of 20 print media samples, comprising The Star newspapers and Reader’s Digest magazines. Adjectives were sorted according to semantic categories and further classified based on their syntactic functions in headlines. A total of 651 adjectives were identified in 574 headlines from The Star newspapers, with 426 functioning as descriptors and the remaining 225 as classifiers. In 208 Reader's Digest magazine headlines, 228 adjectives were identified, of which 189 were descriptors and 39 classifiers. Most headlines in both print media predominantly featured emotive, miscellaneous, and size/quantity/extent descriptors. Regarding syntactic functions, 548 adjectives in The Star newspaper headlines functioned as attributive adjectives, followed by 76 as subject predicative, while in Reader’s Digest magazine headlines, 199 adjectives functioned as attributive adjectives and 17 as subject predicative. This research underscores the importance of print media-based analysis and provides valuable insights for future researchers interested in exploring the use of adjectives in print media.

Molecular Responses of Red Ripe Tomato Fruit to Copper Deficiency Stress.

Fruit nutritional value, plant growth, and yield can be compromised by deficient copper (Cu) bioavailability, which often appears in arable lands. This condition causes low Cu content and modifications in the ripening-associated processes in tomato fruit. This research studies the transcriptomic changes that occur in red ripe tomato fruit grown under suboptimal Cu conditions to shed light on the molecular mechanisms underlying this stress. Comparative RNA-sequencing and functional analyses revealed that Cu deficiency during cultivation activates signals for metal ion transport, cellular redox homeostasis, pyridoxal phosphate binding, and amino acid metabolism while repressing the response to phosphate starvation in harvested fruit. Transcriptomic analyses highlighted a number of novel Cu stress-responsive genes of unknown function and indicated that Cu homeostasis regulation in tomato fruit may involve additional components than those described in model plants. It also studied the regulation of high-affinity Cu transporters and a number of well-known Cu stress-responsive genes during tomato fruit ripening depending on Cu availability, which allowed potential candidates to be targeted for biotechnological improvements in reproductive tissues. We provide the first study characterizing the molecular responses of fruit to Cu deficiency stress for any fruit crop.

In silico comparative structural and functional analysis of arsenite methyltransferase from bacteria, fungi, fishes, birds, and mammals

BackgroundArsenic, a ubiquitous toxic metalloid, is a threat to the survival of all living organisms. Bioaccumulation of arsenic interferes with the normal physiological pathway. To overcome arsenic toxicity, organisms have developed arsenite methyltransferase enzyme, which methylates inorganic arsenite to organic arsenic MMA (III) in the presence of S-adenosylmethionine (SAM). Bacteria-derived arsM might be horizontally transported to different domains of life as arsM or as3mt (animal ortholog). A systematic study on the functional diversity of arsenite methyltransferase from various sources will be used in arsenic bioremediation. ResultsSeveral arsenite methyltransferase protein sequences of bacteria, fungi, fishes, birds, and mammals were retrieved from the UniProt database. In silico physicochemical studies confirmed the acidic, hydrophilic, and thermostable nature of these enzymes. Interkingdom relationships were revealed by performing phylogenetic analysis. Homology modeling was performed by SWISS-MODEL, and that was validated through SAVES-v.6.0. QMEAN values ranged from − 0.93 to − 1.30, ERRAT score (83–96), PROCHECK (88–92%), and other parameters suggested models are statistically significant. MOTIF and PrankWeb discovered several functional motifs and active pockets within the proteins respectively. The STRING database showed protein–protein interaction networks. ConclusionAll of our in silico studies confirmed the fact that arsenite methyltransferase is a cytosolic stable enzyme with conserved sequences over a wide range of organisms. Thus, because of its stable and ubiquitous nature, arsenite methyltransferase could be employed in arsenic bioremediation.

A relict subterranean spider (Araneae: Linyphiidae: Troglohyphantes) reveals a unique component of the biogeography of Corsica

Abstract Spiders of the genus Troglohyphantes (Araneae: Linyphiidae) exemplify one of the largest subterranean adaptive radiation across European mountain ranges, counting over 130 species and representing about one fifth of total species richness of cave spiders in Europe. Despite the emerging potential of Troglohyphantes as a biogeographical model, no attempt has been made to reconstruct the geological events underlying the current distribution patterns of the genus. By coupling traditional taxonomy with target gene sequence data and comparative functional trait analyses, we describe a new species of Troglohyphantes, the first reported from the island of Corsica (France). The species is characterized by a high level of subterranean adaptation and distinct morphological affinities with geographically distant congenerics. By means of time-stamped phylogenies, we tested contrasting hypotheses about the origin of the new species. The most parsimonious explanation suggests that the species diverged from an ancestral group of species originating in the Adriatic plate in the lower Miocene (~19 Ma), colonizing Corsica from the east. In the absence of relevant fossil records, the well-known geochronology of Corsica and the Western Mediterranean basin can be used in future studies to reconstruct the biogeography of the whole genus and for inferring the timeline of its diversification.

Comparative Functional Genome Analysis Reveals the Habitat Adaptation and Biocontrol Characteristics of Plant Growth-Promoting Bacteria in NCBI Databases.

Plant growth-promoting bacteria (PGPB) are a group of beneficial microorganisms that include 60 bacterial genera, such as Bacillus, Pseudomonas, and Burkholderia, which widely colonize plant leaves and soil, promote plant growth, and/or inhibit pathogen infection. However, the genetic factors underpinning adaptation of PGPB to plant leaves and soil remain poorly understood. In this study, we performed a comparative functional genome analysis approach to investigate the functional genes of 195 leaf-associated (LA) and 283 soil-associated (SA) PGPB strains and their roles in adapting to their environment, using 95 strains from other-associated (OA) environmental habitats with growth-promoting or antimicrobial functions as negative controls. Comparison analysis of the enrichment of nonredundant (NR) protein sequence databases showed that cytochrome P450, DNA repair, and motor chemotaxis genes were significantly enriched in LA PGPB strains related to environmental adaptation, while cell wall-degrading enzymes, TetR transcriptional regulatory factors, and sporulation-related genes were highly enriched in SA PGPB strains. Additionally, analysis of carbohydrate-active enzymes demonstrated that glycosyltransferases (GTs) and glycoside hydrolases (GHs) were abundant families in all PGPB strains, which is in favor of plant growth, and enriched in SA PGPB strains. Except for most Bacillus strains, SA PGPB genomes contained significantly more secondary metabolism clusters than LA PGPB. Most LA PGPB contained hormone biosynthesis genes, which may contribute to plant growth promotion, while SA PGPB harbored numerous carbohydrate and antibiotic metabolism genes. In summary, this study further deepens our understanding of the habitat adaptation and biocontrol characteristics of LA and SA PGPB strains. IMPORTANCE Plant growth-promoting bacteria (PGPB) are essential for the effectiveness of biocontrol agents in plant phyllosphere and rhizosphere. However, little is known about the ecological adaptation of PGPB to different habitats. In this study, comparative functional genome analysis of leaf-associated (LA), soil-associated (SA), and other-associated (OA) PGPB strains was performed. We found that genes related to the metabolism of hormones were enriched in LA PGPB. Carbohydrate and antibiotic metabolism genes were enriched in SA PGPB, which likely facilitated their adaptation to the plant growth environment. Our findings provide genetic insights on LA and SA PGPB strains' ecological adaptation and biocontrol characteristics.

Comparative Analysis of Molecular Functions and Biological Role of Proteins from Cell-Free DNA-Protein Complexes Circulating in Plasma of Healthy Females and Breast Cancer Patients.

Cell-free DNA (cfDNA) circulates in the bloodstream packed in membrane-coated structures (such as apoptotic bodies) or bound to proteins. To identify proteins involved in the formation of deoxyribonucleoprotein complexes circulating in the blood, native complexes were isolated using affinity chromatography with immobilized polyclonal anti-histone antibodies from plasma of healthy females (HFs) and breast cancer patients (BCPs). It was found that the nucleoprotein complexes (NPCs) from HF plasma samples contained shorter DNA fragments (~180 bp) than BCP NPCs. However, the share of DNA in the NPCs from cfDNA in blood plasma in HFs and BCPs did not differ significantly, as well as the share of NPC protein from blood plasma total protein. Proteins were separated by SDS-PAGE and identified by MALDI-TOF mass spectrometry. Bioinformatic analysis showed that in the presence of a malignant tumor, the proportion of proteins involved in ion channels, protein binding, transport, and signal transduction increased in the composition of blood-circulating NPCs. Moreover, 58 (35%) proteins are differentially expressed in a number of malignant neoplasms in the NPCs of BCPs. Identified NPC proteins from BCP blood can be recommended for further testing as breast cancer diagnostic/prognostic biomarkers or as being useful in developing gene-targeted therapy approaches.

Comparative functional analysis of PdeNAC2 and AtVND6 in the tracheary element formation.

Tracheary elements (i.e. vessel elements and tracheids) are highly specialized, non-living cells present in the water-conducting xylem tissue. In angiosperms, proteins in the VASCULAR-RELATED NAC-DOMAIN (VND) subgroup of the NAC (NAM, ATAF1,2, and CUC2) transcription factor family (e.g. AtVND6) are required for the differentiation of vessel elements through transcriptional regulation of genes responsible for secondary cell wall formation and programmed cell death. Gymnosperms, however, produce only tracheids, the mechanism of which remains elusive. Here, we report functional characteristics of PdeNAC2, a VND homolog in Pinus densiflora, as a key regulator of tracheid formation. Interestingly, our molecular genetic analyses show that PdeNAC2 can induce the formation of vessel element-like cells in angiosperm plants, demonstrated by transgenic overexpression of either native or NAC domain-swapped synthetic genes of PdeNAC2 and AtVND6 in both Arabidopsis and hybrid poplar. Subsequently, genome-wide identification of direct target (DT) genes of PdeNAC2 and AtVND6 revealed 138 and 174 genes as putative DTs, respectively, but only 17 genes were identified as common DTs. Further analyses have found that PdeNAC2 does not control some AtVND6-dependent vessel differentiation genes in angiosperm plants, such as AtVRLK1, LBD15/30 and pit-forming Rho-like GTPases from plant (ROP) signaling genes. Collectively, our results suggest that different target gene repertoires of PdeNAC2 and AtVND6 may contribute to the evolution of tracheary elements.

Deciphering the complete human-monkeypox virus interactome: Identifying immune responses and potential drug targets.

Monkeypox virus (MPXV) is a dsDNA virus, belonging to Poxviridae family. The outbreak of monkeypox disease in humans is critical in European and Western countries, owing to its origin in African regions. The highest number of cases of the disease were found in the United States, followed by Spain and Brazil. Understanding the complete infection mechanism of diverse MPXV strains and their interaction with humans is important for therapeutic drug development, and to avoid any future epidemics. Using computational systems biology, we deciphered the genome-wide protein-protein interactions (PPIs) between 22 MPXV strains and human proteome. Based on phylogenomics and disease severity, 3 different strains of MPXV: Zaire-96-I-16, MPXV-UK_P2, and MPXV_USA_2022_MA001 were selected for comparative functional analysis of the proteins involved in the interactions. On an average, we predicted around 92,880 non-redundant PPIs between human and MPXV proteomes, involving 8014 host and 116 pathogen proteins from the 3 strains. The gene ontology (GO) enrichment analysis revealed 10,624 common GO terms in which the host proteins of 3 strains were highly enriched. These include significant GO terms such as platelet activation (GO:0030168), GABA-A receptor complex (GO:1902711), and metalloendopeptidase activity (GO:0004222). The host proteins were also significantly enriched in calcium signaling pathway (hsa04020), MAPK signaling pathway (hsa04010), and inflammatory mediator regulation of TRP channels (hsa04750). These significantly enriched GO terms and KEGG pathways are known to be implicated in immunomodulatory and therapeutic role in humans during viral infection. The protein hubs analysis revealed that most of the MPXV proteins form hubs with the protein kinases and AGC kinase C-terminal domains. Furthermore, subcellular localization revealed that most of the human proteins were localized in cytoplasm (29.22%) and nucleus (26.79%). A few drugs including Fostamatinib, Tamoxifen and others were identified as potential drug candidates against the monkeypox virus disease. This study reports the genome-scale PPIs elucidation in human-monkeypox virus pathosystem, thus facilitating the research community with functional insights into the monkeypox disease infection mechanism and augment the drug development.

Demonstrating new-onset or worsened sudomotor function post-COVID-19 on comparative analysis of autonomic function pre-and post-SARS-CoV-2 infection.

Autonomic dysfunction including sudomotor abnormalities have been reported in association with SARS-CoV-2 infection. There are no previous studies that have compared autonomic function objectively in patients pre- and post- SARS-CoV-2 infection.We aimed to identify if SARS-CoV-2 virus is triggering and/or worsening dysautonomia by comparing autonomic function tests in a group of patients pre-and post-SARS-CoV-2 infection. Six participants were enrolled and divided into two groups. The first group of 4 participants reported worsened autonomic symptoms post-SARS-CoV-2 infection. These individuals had their first autonomic test prior to COVID-19 pandemic outbreak (July 2019-December 2019). Autonomic function testing was repeated in these participants, 6months to 1-year post-SARS-CoV-2 infection (June 2021).The second group of 2 participants reported new-onset autonomic symptoms post-COVID-19 infection and were also tested within 6months post-SARS-CoV-2 infection.All participants had mild COVID-19 infection per WHO criteria. They had no evidence of large fiber neuropathy as demonstrated by normal neurophysiological studies (EMG/NCS). They were all screened for known causes of autonomic dysfunction and without risk factors of hypertension/hyperlipidemia, thyroid dysfunction, diabetes/prediabetes, vitamin deficiencies, history of HIV, hepatitis, or syphilis, prior radiation or chemical exposure or evidence of monoclonal gammopathy, or autoimmune condition. Participants were female (age: 21-37y) and all endorsed orthostatic intolerance (6/6). Gastrointestinal symptoms (⅚), new-onset paresthesias, (3/6), and sexual dysfunction (2/6) were reported. Parasympathetic autonomic function remained stable 6-months to 1-year post-COVID-19 infection and no parasympathetic dysfunction was demonstrated in participants with new-onset dysautonomia symptoms. Postural orthostatic tachycardia was noted in half of the patients, being observed in one patient pre- SARS-CoV-2 infection and persisting post-SARS-CoV-2 infection; while new-onset postural tachycardia was observed in 1/3rd of patients. Sympathetic cholinergic (sudomotor) dysfunction was demonstrated in ALL participants. Worsened, or new-onset, sudomotor dysfunction was demonstrated in those with mild or normal sudomotor function on pre-COVID-19 autonomic testing. Sympathetic adrenergic and cholinergic dysautonomia probably account for some of the symptoms of Long COVID-19. Sudomotor dysfunction was demonstrated as consistently worsened or new-sequelae to COVID-19 infection. COVID-19 may be responsible for triggering new-onset or worsened small-fiber neuropathy in this sample, supporting previously reported studies with similar findings. However, the findings in our study are preliminary, and studies with larger sample size are needed to confirm these observations.

Comparative and Functional Analyses Reveal Conserved and Variable Regulatory Systems That Control Lasalocid Biosynthesis in Different Streptomyces Species.

Lasalocid, a representative polyether ionophore, has been successfully applied in veterinary medicine and animal husbandry and also displays promising potential for cancer therapy. Nevertheless, the regulatory system governing lasalocid biosynthesis remains obscure. Here, we identified two conserved (lodR2 and lodR3) and one variable (lodR1, found only in Streptomyces sp. strain FXJ1.172) putative regulatory genes through a comparison of the lasalocid biosynthetic gene cluster (lod) from Streptomyces sp. FXJ1.172 with those (las and lsd) from Streptomyces lasalocidi. Gene disruption experiments demonstrated that both lodR1 and lodR3 positively regulate lasalocid biosynthesis in Streptomyces sp. FXJ1.172, while lodR2 plays a negative regulatory role. To unravel the regulatory mechanism, transcriptional analysis and electrophoretic mobility shift assays (EMSAs) along with footprinting experiments were performed. The results revealed that LodR1 and LodR2 could bind to the intergenic regions of lodR1-lodAB and lodR2-lodED, respectively, thereby repressing the transcription of the lodAB and lodED operons, respectively. The repression of lodAB-lodC by LodR1 likely boosts lasalocid biosynthesis. Furthermore, LodR2 and LodE constitute a repressor-activator system that senses changes in intracellular lasalocid concentrations and coordinates its biosynthesis. LodR3 could directly activate the transcription of key structural genes. Comparative and parallel functional analyses of the homologous genes in S. lasalocidi ATCC 31180T confirmed the conserved roles of lodR2, lodE, and lodR3 in controlling lasalocid biosynthesis. Intriguingly, the variable gene locus lodR1-lodC from Streptomyces sp. FXJ1.172 seems functionally conserved when introduced into S. lasalocidi ATCC 31180T. Overall, our findings demonstrate that lasalocid biosynthesis is tightly controlled by both conserved and variable regulators, providing valuable guidance for further improving lasalocid production. IMPORTANCE Compared to its elaborated biosynthetic pathway, the regulation of lasalocid biosynthesis remains obscure. Here, we characterize the roles of regulatory genes in lasalocid biosynthetic gene clusters of two distinct Streptomyces species and identify a conserved repressor-activator system, LodR2-LodE, which could sense changes in the concentration of lasalocid and coordinate its biosynthesis with self-resistance. Furthermore, in parallel, we verify that the regulatory system identified in a new Streptomyces isolate is valid in the industrial lasalocid producer and thus applicable for the construction of high-yield strains. These findings deepen our understanding of regulatory mechanisms involved in the production of polyether ionophores and provide novel clues for the rational design of industrial strains for scaled-up production.