Significant Similarity Research Articles

EMP3: A promising biomarker for tumor prognosis and targeted cancer therapy.

Epithelial membrane protein 3 (EMP3) belongs to the peripheral myelin protein 22 kDa (PMP22) gene family, characterized by four transmembrane domains and widespread expression across various human tissues and organs. Other members of the PMP22 family, including EMP1, EMP2, and PMP22, have been linked to various cancers, such as glioblastoma, laryngeal cancer, nasopharyngeal cancer, gastric cancer, breast cancer, and endometrial cancer. However, few studies report on the function and relevance of EMP3 in tumorigenicity. Given the significant structural similarities among members of the PMP22 family, there are likely potential functional similarities as well. Previous studies have established the regulatory role of EMP3 in immune cells like T cells and macrophages. Additionally, EMP3 is found to be involved in critical signaling pathways, including HER-2/PI3K/Akt, MAPK/ERK, and TGF-beta/Smad. Furthermore, EMP3 is associated with cell cycle regulation, cellular proliferation, and apoptosis. Hence, it is likely that EMP3 participates in cancer development through these aforementioned pathways and mechanisms. This review aims to systematically examine and summarize the structure and function of EMP3 and its association to various cancers. EMP3 is expected to emerge as a significant biological marker for tumor prognosis and a potential target in cancer therapeutics.

Molecular characterization of a novel gammapartitivirus infecting the fungus Nigrospora oryzae.

Here, we identified a new mycovirus infecting the phytopathogenic fungus Nigrospora oryzae, which we have designated "Nigrospora oryzae partitivirus 2" (NoPV2). The genome of NoPV2 consists of two dsRNA segments (dsRNA 1 and dsRNA 2), measuring 1771 and 1440 bp in length, respectively. dsRNA 1 and dsRNA 2 each contain a single open reading frame (ORF) that encodes the RNA-dependent RNA polymerase (RdRp) and capsid protein (CP), respectively. A BLASTp search showed that the RdRp of NoPV2 had significant sequence similarity to the RdRps of other partitiviruses, including Nigrospora sphaerica partitivirus 1 (75.61% identity) and Magnaporthe oryzae partitivirus 1 (67.53% identity). Phylogenetic analysis revealed that NoPV2 is a new member of the genus Gammapartitivirus in the family Partitiviridae. This study provides important information for understanding the diversity of mycoviruses in N. oryzae.

Genomic Exploration of a Chitinolytic Streptomyces albogriseolus PMB5 Strain from European mantis (Mantis religiosa).

The genus Streptomyces is renowned not only for its natural antibiotic production but also for its abundant chitinolytic enzymes, which break down stubborn chitin into chitooligosaccharides. Despite this, there have been limited studies utilizing whole-genome sequencing to explore the repertoire of chitin degradation and utilization genes in Streptomyces. A particularly compelling source of novel antimicrobials and enzymes lies in the microbiota of insects, where bacterial symbionts produce antimicrobials to protect against opportunistic pathogens and enzymes to adapt to the environment. In this study, we present the chitinolytic strain Streptomyces albogriseolus PMB5, isolated from the insectivorous Mantis religiosa (European mantis). Whole-genome sequencing revealed that PMB5 harbors a linear chromosome of 7,211,961 bp and a linear plasmid of 327,989 bp. The genome comprises 6683 genes, including 6592 protein-coding sequences and 91 RNA genes. Furthermore, genome analysis revealed 19 biosynthetic gene clusters covering polyketides, terpenes, and RiPPs, with 10 clusters showing significant gene similarity (>80%) to known clusters like antimycin, hopene, and geosmin. In the genome of S. albogriseolus PMB5, we were able to identify several antibiotic resistance genes; these included cml (resistance to phenicol), gimA (resistance to macrolides), parY (resistance to aminocoumarin), oleC/oleD (resistance to macrolides), novA (resistance to aminocoumarin) and bla/blc (resistance to beta-lactams). Additionally, three clusters displayed no similarity to known sequences, suggesting novel bioactive compound discovery potential. Remarkably, strain PMB5 is the first reported S. albogriseolus capable of thriving on a medium utilizing chitin as a carbon source, with over 50 chitin-utilizing genes identified, including five AA10 family LPMOs, five GH18 chitinases, and one GH19 chitinase. This study significantly enhances the genomic understanding of S. albogriseolus, a species previously underrepresented in research, paving the way to further exploration of the biotechnological potential of the species.

Distribution of methane in the upper water layer of the northern Black Sea: Seasonal and daily trends and seawater-air emissions

We report on methane (CH4) concentration measurements in the northern Black Sea area conducted during 6 cruises with R/V Professor Vodyanitsky from 2017 to 2019. Our work is a multi-season study at a uniform station grid covering an area of 88 × 103 km2 and including three latitudinal transects that comprises both surface and vertical profile water-column measurements. The main goal of the work was to assess the seasonal patterns of vertical CH4 structure in the aerobic water column (upper 100 m) and its emission to the atmosphere.In surface waters, the mean dissolved CH4 concentration ranged from 2.6 nmol L−1 detected in November 2018 to 11.5 nmol L−1 measured in June–July 2018, respectively. Calculated CH4 seawater-air fluxes and saturations were mostly positive (i.e. net flux to atmosphere), and winter fluxes (2.6 μmol m−2 d−1) were higher than summer fluxes (1.6 μmol m−2 d−1) due to the higher wind speed. The integral CH4 flux from the whole study area (88 × 103 km2) ranged from 84 to 235 kM day−1.It was shown that, on average, the methane concentration in the upper layer for deep-water stations where the seabed is located at depths >160 m (σt >16.2) was lower compared to stations at shallow water depths (28–140 m, σt <16.2). The most distinct difference was obtained for the summer season (June–July 2018) and a less significant difference – for spring (April–May 2019) and winter season (November–December 2018). During these seasons the water column was also considerably less saturated in CH4 compared to the entire monitoring period. We observed subsurface maxima, which were generally located at the base of the thermocline and exceeded 100 nmol L−1 at some stations. Exceptions were observed in October 2019 (cruise 110), when vertical CH4 distributions were characterized by two-peaks at ∼20 and ∼50 m depth. The strong influence of the thermohaline structure on the water column CH4 distribution has also been shown in studies of daily dynamics of CH4 vertical profiles in the shallow water region. Despite the high variability of CH4 concentrations, significant similarities in vertical distributions of CH4 and chlorophyll-a for which sub-surface maxima coincided at some stations, are shown. Extremely high concentrations of CH4 (up to 351 nmol L−1) in the near-bottom water layer were revealed during all seasons at the station near the Dnieper paleo-channel at the northwestern edge of the study area. This enrichment is assumed to be caused by methane emissions from gas seeps densely located in this region.

Insights from therapeutic strategies in superior canal dehiscence syndrome: is there anything beyond surgical treatment?

Superior semicircular canal dehiscence syndrome (SCDS) is a clinical syndrome that can cause instability, vertigo, fullness, tinnitus, autophony, hearing loss (HL), Tullio phenomenon, or Hennebert's sign. Historically, surgery has been the primary treatment reported in the literature, although some medical treatments may also be proposed. This study aims to comprehensively characterize SCDS in a large series of patients from clinical, auditory, and vestibular perspectives, and explore medical alternatives to conventional surgical treatments by comparing their results and evolution. A retrospective observational study was designed in a tertiary care center. Audiovestibular tests evaluated included pure-tone audiometry (PTA), VEMPs, video head impulse test (vHIT), and CT imaging. Improvement was assessed over a follow-up period of up to 6 months for seven cardinal symptoms to verify the efficacy of the proposed treatments. 71 subjects with SCDS and a mean age of 51.20 ± 12.22 years were included in the study. The most common symptom found in our sample was instability in 31 patients (43.66%), followed by aural fullness or tinnitus in 29 subjects (40.85%). 36 patients (43.66%) received medical treatment, with 28 of them (77.78%) showing symptom reduction. Surgical repair was indicated in five patients, with all showing symptom improvement. Statistically significant improvement (p < 0.05) was observed, particularly with surgical treatment and acetazolamide, in both symptoms and objective tests such as pure-tone audiometry and VEMPs. SCDS shows significant similarities with other otic capsule dehiscences. It is essential to perform VEMPs and CT scans to complete the diagnosis, which is usually accompanied by clearly recognizable clinical criteria. Surgery for SCDS is effective, safe, and without complications. However, in cases where symptoms are mild to moderate, addressing this condition with medical treatment using diuretics such as acetazolamide has shown promising results.

Effects of impact and microphone positions on heavy-weight floor impact sound pressure levels in concrete buildings

This study aims to analyze the spatial distribution of heavy-weight impact sound transmitted to a receiving room in 59 households within a concrete residential building. The performance of buildings is generally regulated by single number quantities such as L′iA,Fmax. To enhance performance, it is important to understand the effect of the impact sound pressure level at designated impact positions and microphones. Therefore, this study proposes a method to quantify the impac sound pressure level for determining L′iA,Fmax according to the impact and microphone positions. Analysis of the data revealed that significant similarities in frequency spectra were observed when generating impacts at two positions near the window, in addition to two at the area near the corridor, both of which have similar boundary conditions. The central impact position exhibited the highest contribution at 24.6%, while other positions had contributions of 18.2–19.5%. For the microphone positions, those located at the corners on either side of the window showed contributions of 22.8–23.7%, whereas the remaining positions demonstrated lower contributions of 17.3–18.5%. These results can serve as basic data for developing construction methods to reduce floor impact sound.

Efficient separation of vanadium and chromium by the complexation with sulfate ions in solvent extraction using EHEHPA

The significant chemical similarity between vanadium and chromium complicates the process of efficient extracting V(Ⅳ) from the solution containing Cr(Ⅲ) to prepare high-purity vanadyl sulfate electrolyte. In this study, the separation of vanadium and chromium with 2-ethylhexyl phosphoric acid-2-ethylhexyl ester (EHEHPA) was enhanced by increasing the concentration of SO42−. Under the extraction equilibrium pH of 2.5, the extraction of Cr(III) was suppressed by increasing the concentration of SO42− anions, which hardly affected the extraction efficiency of V(IV), achieving a separation factor as high as 5780.6 at SO42− concentration of 1.75 mol·L−1. Furthermore, after pretreatment of the water-leaching solution of sodium-roasted vanadium slag, extraction was carried out under the conditions of equilibrium pH of 1.8 and SO42− concentration of about 2.00 mol·L−1, and after stripping, the vanadyl sulfate electrolyte containing 2.12 mol·L−1 of vanadium and only 0.11 mg·L−1 of chromium was obtained. It was proved that Cr(Ⅲ) mainly extracted in the form of CrSO4+ into organic phase by one EHEHPA dimer as [CrSO4(H2O)]+ under higher SO42− concentrations (e.g., ≥1.50 mol·L−1), while Cr(Ⅲ) was extracted by two EHEHPA dimers as Cr3+ without SO42− in the solution. Based on the density functional theory, the complex structures of Cr(III) were optimized and the energy changes of Cr(III) extraction reactions were calculated, indicating the complexation between SO42− and Cr(III) under higher SO42− concentrations resulting in the inhibition of Cr(III) extraction, and thus enhancing the separation of vanadium and chromium.

Association between liver fibrosis scores and short-term clinical outcomes in hospitalized chronic kidney disease patients: a prospective observational study.

In resource-constrained countries, inadequate access to healthcare and prognostic tools can be the Achilles' heel in effectively managing chronic kidney disease (CKD). There is a significant similarity in the pathogenesis of CKD and liver fibrosis. The role of liver fibrosis (LF) scores in predicting short-term clinical outcomes in hospitalized patients with CKD is unknown. Our study aimed at calculating LF scores and studying the association of liver fibrosis with short-term mortality and morbidity in CKD patients. Patients aged above 15 years diagnosed with CKD as per the KDIGO criteria were enrolled. LF scores, namely, NFS, GPRI, and FIB-4 scores were calculated. Patients were followed up for a period of 28 days for good and poor composite outcomes, namely, the requirement of hemodialysis, non-invasive ventilation, prolonged hospital stay, and neurological and cardiovascular outcomes including death. Among 163 patients, 70.5% were below 60 years of age, 82.2% were male and 35% were diabetic. At 28-day follow up, 52.1% had poor composite outcome. The AUROC for GPRI and FIB-4 in predicting poor outcomes was 0.783 (95% CI: 0.71-0.855) (p < 0.001) and 0.62 (95% CI: 0.534-0.706) (p = 0.008), respectively. The AUROC for GPRI and NFS in predicting all-cause mortality was 0.735 (95% CI: 0.627-0.843) (p = 0.001) and 0.876 (95% CI, 0.8-0.952) (p < 0.001), respectively. We found a positive association between LF scores and CKD outcomes in hospitalized patients. The LF scores significantly predicted poor outcomes in patients with CKD. Among the scores, GPRI was found to be a stronger predictor in predicting outcomes in both diabetic and non-diabetic patients with CKD. A high GPRI score was also associated with poor outcomes and increased mortality in both diabetics and non-diabetics.

Walrycin B, as a novel separase inhibitor, exerts potent anticancer efficacy in a mouse xenograft model

Proper chromosome segregation during cell division relies on the timely dissolution of chromosome cohesion. Separase (EC3.4.22.49), a cysteine protease, plays a critical role in mitosis by cleaving the kleisin subunit of cohesin, thereby presenting a promising target for cancer therapy. However, challenges in isolating active human separase suitable for high-throughput screening have limited the identification of effective inhibitors. Here, we conducted a high-throughput screening of small-molecule inhibitors using the protease domain of Chaetomium thermophilum separase (ctSPD), which not only shares significant sequence similarity with human separase but is also readily available. After conducting a primary screening of a library containing 9,172 compounds and subsequent validation using human separase, we identified walrycin B and its analogs, toxoflavin, 3-methyltoxoflavin, and 3-phenyltoxoflavin, as potent inhibitors of human separase. Subsequent microscale thermophoresis assays and molecular dynamics simulations revealed that walrycin B binds to the active site of separase and competes with substrates for binding. Additionally, cell-based studies showed that walrycin B and its analogs effectively induce cell cycle arrest at the M phase, activate apoptosis, and ultimately lead to cell death in mitosis. Finally, in a mouse xenograft model, walrycin B exhibited significant antitumor efficacy with minimal side effects. Together, these findings highlight the therapeutic potential of walrycin B for cancer treatment and its utility as a chemical tool in future studies involving separase.

Hospital at home worldwide: Program and clinician characteristics from the World Hospital at Home Congress survey.

Hospital at home (HaH) delivers hospital-level care to acutely ill patients at home as a substitute for brick-and-mortar hospital care. The clinician and program characteristics of HaH programs worldwide are relatively unknown. We sought to describe the world's HaH clinicians and their programs' characteristics. We analyzed a survey administered to all attendees of the 2023 World Hospital at Home Congress. Clinician characteristics included age, years worked in HaH, profession, burnout, and experience. Program characteristics included location, daily census, types of care delivery, and clinical capabilities. Of 670 attendees, about 305 were clinicians and 129 responded (42% response rate for clinicians). The majority of clinicians were 30-49 years old (65.1%), new to the field (70.5% worked less than 10 years), and part-time (18% dedicated >74% effort to HaH). Clinicians reported overall satisfaction with their job and low burnout. About half of programs were in Europe (52.1%), newly operational (44.7% less than 5 years), mostly operated in urban environments (87.2%), and mostly had a daily census of less than 25 patients (62.8%). Most programs operated 7-days per week (88.3%), performed intermittent or continuous remote monitoring (81.4%), used video communication (63.8%), and had some advanced capabilities such as in-home imaging (47.9%) and advanced procedures (23.4%). Visit frequencies to the patient's home were variable: most programs had physicians visit the home, nearly all had nurses visit the home, and fewer performed virtual visits. HaH clinicians and programs have significant similarities but also a fair number of divergent practices, much like brick-and-mortar hospital care. Further standardization of the care model will help to unify the field across the globe.

Frequency synaptic behavior of ZnO/HfZrO memristor with pulsed stimuli

The synaptic response of ZnO/HfZrO memristor devices to electrical stimuli was studied. It was found that the frequency of the stimuli affects the rate of current increase, which can be explained by the cluster state of oxygen vacancies at the interface of ZnO/HfZrO. This variation in the synaptic response due to stimulus frequency was consistent with the dynamic adjustment of tolerance thresholds observed in the human brain's response to environmental stimuli. The rate of change in current, representing the sensitivity to stimuli, mirrors the biological nervous system's reaction to environmental changes, such as Ebbinghaus forgetting behavior. Additionally, frequent irregular changes in stimuli lead to a reduced lifespan of the devices, highly resembling the biological lifetime-injure on frequent environmental fluctuations. These findings highlight the memristors' significant similarity to biological nerves in response to stimuli, confirming their tremendous potential in bionic synaptic simulation applications.

Effect of transcription factor MEOX on insulin gene expression in glucagon-like peptide 1-secreting cells.

Currently, the supply of beta cells for islet transplantation in the treatment of type 1 diabetes is limited. Enteroendocrine cells (EECs) are believed to have high potential as stem cells because they share significant developmental similarities with beta cells. In a previous study, we derived EEC cells that secrete individual gut hormones from STC-1 cells. This study aimed to examine intestinal hormone secretion and expression, investigate the expression of developmental-related transcription factors, and analyze the effect of MEOX on insulin gene expression in isolated EECs. The expression and secretion of enteroendocrine hormones were evaluated in L6 and K34 cells from STC-1 cells. Expression patterns of beta cell- and development-related genes in L6 and K34 cells were compared with beta cells. Comparisons of the MEOX-induced expression of Ins in beta cells and GLP-1-secreting cells were investigated. Both L6 and K34 cells predominantly expressed Glp1 and Gip, respectively. The secretion pattern of GLP-1 in L6 cells was similar to that of GLUTag cells. Previous microarray analysis confirmed MEOX as developmentally relevant transcription factors expressed in beta cells. Overexpression of MEOX showed a tendency to increase Ins expression in L6 and GLUTag cells, but not in MIN6 cells. However, when PDX1 and MEOX were co-expressed in GLUTag cells, insulin expression was suppressed, similar to that observed in MIN6 cells. These findings suggest a potential role for MEOX in regulating the expression of the Ins gene in both beta cells and GLP-1-secreting cells. Further studies are warranted to elucidate the underlying mechanism.

Unlocking Hidden Treasures: LC-MS/MS Molecular Networks for Exploring Novel Passiflora Species with Pharmaceutical Potential.

IIn this study, we report the metabolic profiling of several previously uncharacterized Passiflora species native to Brazil, employing molecular networks to delve deeper into chemical constituents. Using the GNPS platform, in silico tools, and substructure annotation techniques, we expanded the chemical annotations. Principal Coordinate Analysis (PCoA) revealed significant metabolic similarities between several species, including P. incarnata, suggesting shared pharmacological potential. Our identification of metabolic compounds facilitated comparisons between understudied species with medicinal properties. Notably, we documented 25 previously uncharacterized species, paving the way for the development of novel products aimed at improving human well-being. This research focused on several native Passiflora species from Brazil, highlighting their unexplored therapeutic potential.

Revisiting legume lectins: Structural organization and carbohydrate-binding properties

Legume lectins are a diverse family of carbohydrate-binding proteins that share significant similarities in their primary, secondary, and tertiary structures, yet exhibit remarkable variability in their quaternary structures and carbohydrate-binding specificities. The tertiary structure of legume lectins, characterized by a conserved β-sandwich fold, provides the scaffold for the formation of a carbohydrate-recognition domain (CRD) responsible for ligand binding. The structural basis for the binding is similar between members of the family, with key residues interacting with the sugar through hydrogen bonds, hydrophobic interactions, and van der Waals forces. Variability in substructures and residues within the CRD are responsible for the large array of specificities and enable legume lectins to recognize diverse sugar structures, while maintaining a consistent structural fold. Therefore, legume lectins can be classified into several specificity groups based on their preferred ligands, including mannose/glucose-specific, N-acetyl-d-galactosamine/galactose-specific, N-acetyl-d-glucosamine-specific, l-fucose-specific, and α-2,3 sialic acid-specific lectins. In this context, this review examined the structural aspects and carbohydrate-binding properties of representative legume lectins and their specific ligands in detail. Understanding the structure/binding relationships of lectins continues to provide valuable insights into their biological roles, while also assisting in the potential applications of these proteins in glycobiology, diagnostics, and therapeutics.

Extensive macular atrophy with pseudodrusen-like appearance: comprehensive review of the literature.

This review focuses on extensive macular atrophy with pseudodrusen-like appearance (EMAP), a recently described maculopathy presenting with pseudodrusen-like lesions and chorioretinal atrophy more pronounced in the vertical axis. Narrative review of the literature published until May 2024. The early onset age of EMAP (50-55 years) and its distinctive natural history, which includes night blindness followed by severe vision loss, differentiate it from atrophic age-related macular degeneration (AMD). A clear pathogenesis has not been determined, but risk factors include female gender and complement system abnormalities (altered levels of C3 and CH50). Moreover, lifelong exposure to pesticides has been suggested as risk factor for direct neuronal degeneration involving rods and cones. In the early phase of the disease, reticular pseudodrusen-like lesions appear in the superior perifovea and tend to coalescence horizontally into a flat, continuous, reflective material localized between the retinal pigmented epithelium and Bruch's membrane. Over time, EMAP causes profound RPE and outer retinal atrophy in the macular area, with a recent classification reporting a 3-stages evolution pattern. Blue autofluorescence showed rapidly evolving atrophy with either hyperautofluorescent or isoautofluorescent borders. Significant similarities between the diffuse-trickling phenotype of geographic atrophy and EMAP have been reported. Macular neovascularization is a possible complication. EMAP is specific form of early-onset atrophic macular degeneration with rapid evolution and no treatment. Further studies are needed to assess the best management.

FAST (fast analytical simulator of tracer)-PET: an accurate and efficient PET analytical simulation tool

Objective. Simulation of positron emission tomography (PET) images is an essential tool in the development and validation of quantitative imaging workflows and advanced image processing pipelines. Existing Monte Carlo or analytical PET simulators often compromise on either efficiency or accuracy. We aim to develop and validate fast analytical simulator of tracer (FAST)-PET, a novel analytical framework, to simulate PET images accurately and efficiently. Approach. FAST-PET simulates PET images by performing precise forward projection, scatter, and random estimation that match the scanner geometry and statistics. Although the same process should be applicable to other scanner models, we focus on the Siemens Biograph Vision-600 in this work. Calibration and validation of FAST-PET were performed through comparison with an experimental scan of a National Electrical Manufacturers Association (NEMA) Image Quality (IQ) phantom. Further validation was conducted between FAST-PET and Geant4 Application for Tomographic Emission (GATE) quantitatively in clinical image simulations in terms of intensity-based and texture-based features and task-based tumor segmentation. Main results. According to the NEMA IQ phantom simulation, FAST-PET’s simulated images exhibited partial volume effects and noise levels comparable to experimental images, with a relative bias of the recovery coefficient RC within 10% for all spheres and a coefficient of variation for the background region within 6% across various acquisition times. FAST-PET generated clinical PET images exhibit high quantitative accuracy and texture comparable to GATE (correlation coefficients of all features over 0.95) but with ∼100-fold lower computation time. The tumor segmentation masks comparison between both methods exhibited significant overlap and shape similarity with high concordance CCC > 0.97 across measures. Significance. FAST-PET generated PET images with high quantitative accuracy comparable to GATE, making it ideal for applications requiring extensive PET image simulations such as virtual imaging trials, and the development and validation of image processing pipelines.

The TOM complex from an evolutionary perspective and the functions of TOMM70.

In humans, up to 1,500 mitochondrial precursor proteins are synthesized at cytosolic ribosomes and must beimported into the organelle. This is not only essential formitochondrial but also for many cytosolic functions. The majority of mitochondrial precursor proteins are imported over the translocase of the outer membrane (TOM). In recent years, high-resolution structure analyses from different organisms shed light on the composition and arrangement ofthe TOM complex. Although significant similarities have been found, differences were also observed, which have been favored during evolution and could reflect the manifold functions of TOM with cellular signaling and its response to altered metabolic situations. A key component within these regulatory mechanisms is TOMM70, which is involved in protein import, forms contacts to the ER and the nucleus, but is also involved in cellular defense mechanisms during infections.

Comparative study of electrogas and shielded metal arc welding processes on steel A537 welded joints

In this research, the electro-gas welding process was compared with a shielded metal arc welding process for welding steel A573 from a mechanical properties point of view. Visual and radiographic inspections confirmed the soundness of weldments produced by electro-gas welding and shielded metal arc welding techniques. Various assessments were performed, including hardness, tensile strength, V-notch impact toughness, macrostructure, microstructure, and electrochemical tests. The mechanical properties of the two welding processes were closely matched, with an average tensile strength of 590 MPa for electro-gas welding and 585 MPa for shielded metal arc welding. Furthermore, the influence of welding variables, such as groove design and heat input, on the welded joints’ quality, mechanical properties, and electrochemical behavior was thoroughly examined. Dilution estimates, particularly for the electro-gas welding process, were around 35%, and a significant similarity was observed between the chemical composition determined through dilution calculations and that obtained from chemical analysis using an arc spark emission spectrometer. Notably, the electro-gas welding process demonstrated exceptional productivity, surpassing the shielded metal arc welding process by more than elevenfold. The optimum welding parameters for the electro-gas welding process were identified to achieve superior mechanical properties, low corrosion rates, and reduced consumption of the welding electrodes. This included adopting a single V type and groove angle of 30° instead of 60°, resulting in a 23% reduction in economic costs. Selecting an appropriate heat input within the range of 12 to 14 kJ/mm further contributed to enhancing overall welding efficiency.

Biochemical characterization of ClpB and DnaK from Anaplasma phagocytophilum.

Anaplasma phagocytophilum is an intracellular tick-transmitted bacterial pathogen that infects neutrophils in mammals and causes granulocytic anaplasmosis. In this study, we investigated the molecular chaperones ClpB and DnaK from A. phagocytophilum. In Escherichia coli, ClpB cooperates with DnaK and its co-chaperones DnaJ and GrpE in ATP-dependent reactivation of aggregated proteins. Since ClpB is not produced in metazoans, it is a promising target for developing antimicrobial therapies, which generates interest in studies on that chaperone's role in pathogenic bacteria. We found that ClpB and DnaK are transcriptionally upregulated in A. phagocytophilum 3-5 days after infection of human HL-60 and tick ISE6 cells, which suggests an essential role of the chaperones in supporting the pathogen's intracellular life cycle. Multiple sequence alignments show that A. phagocytophilum ClpB and DnaK contain all structural domains that were identified in their previously studied orthologs from other bacteria. Both A. phagocytophilum ClpB and DnaK display ATPase activity, which is consistent with their participation in the ATP-dependent protein disaggregation system. However, despite a significant sequence similarity between the chaperones from A. phagocytophilum and those from E. coli, the former were not as effective as their E. coli orthologs during reactivation of aggregated proteins in vitro and in supporting the survival of E. coli cells under heat stress. We conclude that the A. phagocytophilum chaperones might have evolved with distinct biochemical properties to maintain the integrity of pathogenic proteins under unique stress conditions of an intracellular environment of host cells.

Chromosome-contiguous genome for the Haecon-5 strain of Haemonchus contortus reveals marked genetic variability and enables the discovery of essential gene candidates

Millions of livestock animals worldwide are infected with the haematophagous barber’s pole worm, Haemonchus contortus, the aetiological agent of haemonchosis. Despite the major significance of this parasite worldwide and its widespread resistance to current treatments, the lack of a high-quality genome for the well-defined strain of this parasite from Australia, called Haecon-5, has constrained research in a number of areas including host-parasite interactions, drug discovery and population genetics. To enable research in these areas, we report here a chromosome-contiguous genome (∼280 Mb) for Haecon-5 with high-quality models for 19,234 protein-coding genes. Comparative genomic analyses show significant genomic similarity (synteny) with a UK strain of H. contortus, called MHco3(ISE).N1 (abbreviated as “ISE”), but we also discover marked differences in genomic structure/gene arrangements, distribution of nucleotide variability (single nucleotide polymorphisms (SNPs) and indels) and orthology between Haecon-5 and ISE. We used the genome and extensive transcriptomic resources for Haecon-5 to predict a subset of essential single-copy genes employing a “cross-species” machine learning (ML) approach using a range of features from nucleotide/protein sequences, protein orthology, subcellular localisation, single-cell RNA-seq and/or histone methylation data available for the model organisms Caenorhabditis elegans and Drosophila melanogaster. From a set of 1,464 conserved single copy genes, transcribed in key life-cycle stages of H. contortus, we identified 232 genes whose homologs have critical functions in C. elegans and/or D. melanogaster, and prioritised 10 of them for further characterisation; nine of the 10 genes likely play roles in neurophysiological processes, germline, hypodermis and/or respiration, and one is an unknown (orphan) gene for which no detailed functional information exists. Future studies of these genes/gene products are warranted to elucidate their roles in parasite biology, host-parasite interplay and/or disease. Clearly, the present Haecon-5 reference genome and associated resources now underpin a broad range of fundamental investigations of H. contortus and could assist in accelerating the discovery of novel intervention targets and drug candidates to combat haemonchosis.