Large Fragments Research Articles

Inactivation of Anisakis simplex Allergens in Fish Viscera by Acid Autolysis

The evisceration of infested species on board commercial fleets and the throwing of viscera into the sea, as is mostly the case for hake, is common practice for reducing the occurrence of Anisakis in fishery products. Moreover, the high levels of infestation and the lack of technically and economically feasible solutions hinder the possibility of recovering viscera with other fish processing byproducts as raw material for feed without the risk of transmission of allergens to humans, with the subsequent risk for public health. The aim of this work was to study the fate of Anisakis simplex allergens during 11 days of silage of infested hake (Merluccius merluccius) viscera, as a potential method for eliminating this risk. While the viscera were almost completely liquefied, an increase in the allergenicity of the soluble fraction was observed, which decreased only slightly after day 9. As we are aware of the resistance of parasite allergens to gastrointestinal enzymes, silage was also analyzed after 12 and 15 months. While the lower molecular weight fragments of Anisakis proteins are fully digested, some larger fragments with potential allergenicity resisted autolysis after long silage periods, but they were present in a very low concentration. The study concludes that there is the potential of silage as a method for recovering fish viscera infested with Anisakis.

Effect of particle materials on deposition behavior and microstructural features of films prepared via vacuum kinetic spraying

Vacuum kinetic spraying (VKS) is a particle deposition process by which various materials can be deposited as films, even at room temperature. In this study, Al2O3 (ceramic, completely brittle), Fe-based bulk metallic glass (BMG, brittle with some plastic deformability), and Ag (metal, completely ductile) were used as powder materials, and the effects of the particle materials on the deposition behavior and microstructural features of the film were investigated. Deposition tests were performed under identical experimental conditions, and the microstructural features were comprehensively analyzed. The deposition behavior and film microstructure of the three materials were completely different. The Al2O3 film formed at the lowest deposition rate was extremely dense and comprised nanocrystals with a relatively low surface roughness, indicating fragmentation-dominant deposition. The deposition rate of Ag was between those of the other two materials, and the film consisted of relatively dense large grains with nanopores and a smooth surface, resulting from plasticity-dominant deposition. The deposition rate of BMG was considerably high, and the resulting film consisted of a porous structure with relatively large fragments and an extremely rough film surface. These features of BMG were attributed to the insufficient fragmentation or plastic deformation of the particles. Consequently, even under identical deposition conditions, the deposition rate and behavior and the resulting film microstructure vary depending on the particle materials. Therefore, the microstructural features of the film must be examined before selecting powder materials and fabricating films through process optimization for each material.

Exploring the structural heterogeneity of IgG1s: A comprehensive analysis of glycosylated and deglycosylated forms using TIMS-TOF-MS technique

Denaturation of IgG is a complex and multistep process that involves various structural changes in the protein as it loses its native conformation. IgG denaturation is crucial in therapeutic antibody development, manufacturing, and storage. Glycosylated IgG is generally more resistant to denaturing conditions due to the stabilizing effect of its glycans. In contrast, deglycosylated IgG is more vulnerable to structural disruption. In this study, we examined the intact level and large fragments of IgG glycoforms. Our investigation focused on changes in structural heterogeneity through glycosylation under denaturing conditions. Collision cross-sections (CCS) of intact level and large fragments of IgG1 molecules have been determined using reversed phase-high performance liquid chromatography-electrospray ionization-trapped ion mobility-time-of-flight mass spectrometry (RP-HPLC-ESI-TIMS-TOF-MS) technique. At the intact level, deglycosylated bevacizumab (IgG1B) and trastuzumab (IgG1T) could be differentiated at specific charge states and CCS ranges. The deglycosylated IgG1B molecule showed a broader CCS range than the IgG1T molecule. This result demonstrated that the deglycosylated IgG1T was altered from deglycosylated IgG1B in the gas phase under denaturing conditions. The lowering in the collision cross-section distribution (CCSD) values indicates a decrease in the structural heterogeneity of the intact IgG after deglycosylation. The ion mobility-mass spectrometry (IM-MS) analyses performed in this study showed that the glycans on the Fc region of IgG1s can trigger structural changes in the molecule under denaturing conditions. Depending on whether they are glycosylated or deglycosylated, various conformations of IgG1 molecules could be distinguished in RP-HPLC-TIMS-TOF-MS analysis.

CRISPR-Cas9/Cas12a systems for efficient genome editing and large genomic fragment deletions in Aspergillus niger.

CRISPR technology has revolutionized fungal genetic engineering by accelerating the pace and expanding the feasible scope of experiments in this field. Among various CRISPR-Cas systems, Cas9 and Cas12a are widely used in genetic and metabolic engineering. In filamentous fungi, both Cas9 and Cas12a have been utilized as CRISPR nucleases. In this work we first compared efficacies and types of genetic edits for CRISPR-Cas9 and -Cas12a systems at the polyketide synthase (albA) gene locus in Aspergillus niger. By employing a tRNA-based gRNA polycistronic cassette, both Cas9 and Cas12a have demonstrated equally remarkable editing efficacy. Cas12a showed potential superiority over Cas9 protein when one gRNA was used for targeting, achieving an editing efficiency of 86.5% compared to 31.7% for Cas9. Moreover, when employing two gRNAs for targeting, both systems achieved up to 100% editing efficiency for single gene editing. In addition, the CRISPR-Cas9 system has been reported to induce large genomic deletions in various species. However, its use for engineering large chromosomal segments deletions in filamentous fungi still requires optimization. Here, we engineered Cas9 and -Cas12a-induced large genomic fragment deletions by targeting various genomic regions of A. niger ranging from 3.5kb to 40kb. Our findings demonstrate that targeted engineering of large chromosomal segments can be achieved, with deletions of up to 69.1% efficiency. Furthermore, by targeting a secondary metabolite gene cluster, we show that fragments over 100kb can be efficiently and specifically deleted using the CRISPR-Cas9 or -Cas12a system. Overall, in this paper, we present an efficient multi-gRNA genome editing system utilizing Cas9 or Cas12a that enables highly efficient targeted editing of genes and large chromosomal regions in A. niger.

Ecotoxicological risk assessment of active pharmaceutical ingredients (APIs) against different aquatic species leveraging intelligent consensus prediction and i-QSTTR modeling

The increasing presence of active pharmaceutical ingredients (APIs) in aquatic ecosystems, driven by widespread human use, poses significant risks, including acute and chronic toxicity to aquatic species. However, the scarcity of experimental toxicity data on APIs and related compounds due to the high costs, time requirements, and ethical concerns associated with animal testing hinders comprehensive risk assessment. In response, we developed quantitative structure-toxicity relationship (QSTR) and interspecies quantitative structure toxicity-toxicity relationship (i-QSTTR) models for three key aquatic species: zebrafish, water fleas, and green algae, using NOEC as an endpoint, following OECD guidelines. Algae, daphnia, and fish, recognized as standard organisms in toxicity testing, are crucial bio-indicators due to their size, transparency, adaptability, and regulatory acceptance. We used partial least squares (PLS) and multiple linear regression (MLR) methods for model development alongside machine learning techniques such as Random Forest (RF), Support Vector Machines (SVM), K-nearest Neighbor (kNN), and Neural Networks (NN) to enhance the predictivity. Lipophilicity, electronegativity, unsaturation, a molecular cyclized degree in molecular structure, large fragments, aliphatic secondary C(sp2), and R–CR–R groups were identified as critical biomarkers for API toxicity. Screening of the PPDB (pesticide properties databases) and DrugBank validated the practical application of these models, offering valuable tools for regulatory decisions, safer API design, and the preservation of aquatic biodiversity.

PDGF-induced internalisation promotes proteolytic cleavage of PDGFRβ in mesenchymal cells

Platelet-derived growth factor (PDGF)-induced signalling via PDGF receptor β (PDGFRβ) leads to activation of downstream signalling pathways which regulate multiple cellular responses. It is unclear how PDGFRβ is degraded; both lysosomal and proteasomal degradation have been suggested. In this study, we have characterised the proteolytic cleavage of ligand-activated PDGFRβ, which results in two fragments: a larger fragment containing the extracellular domain, the transmembrane segment, and a part of the intracellular juxtamembrane region with a molecular mass of ∼130 kDa, and an intracellular ∼70 kDa fragment released into the cytoplasm. The proteolytic processing did not take place without internalisation of PDGFRβ. In addition, chelation of intracellular Ca2+ inhibited proteolytic processing. Inhibition of the proteasome affected signal transduction by increasing the phosphorylation of PDGFRβ, PLCγ, and STAT3 while reducing it on Erk1/2 and not affecting Akt. The proteolytic cleavage was observed in fibroblasts or cells that had undergone epithelial-mesenchymal transition.

Redescription of Rhabditis maupasi Seurat in Maupas, 1919 (Rhabditida: Rhabditidae) from northwest Iran

Summary Rhabditis maupasi is re-described and reviewed based on morphological, morphometric, and molecular (D2-D3 expansion segment of the rDNA 28S) analysis collected from northwest Iran. The species is characterised by having a 1.1-1.9 mm long body, lateral fields with three incisures, the lip region offset by a depression, 12-15 μm wide, with six globular lips, the stoma rhabditoid, 14-20 μm long, with distinct cheilo-, gymno- and stegostom; cheilostom slightly cuticularised, gymno-promesostegostom a short tube with well-cuticularised walls, metastegostom with glottoid apparatus bearing small teeth, stomatal or pharyngeal collar covering 40-60% of stoma; pharynx well developed, the pharyngeal corpus consisting of a more or less cylindrical procorpus and swollen metacorpus (median bulb), basal bulb ovoid to pyriform, with grinder and narrow haustrulum, excretory pore at basal bulb level; vulva a transverse slit with protruding lips, the female tail conical-elongated (65-75 μm, c = 16-26, c′ = 2.0-2.5), the male tail conoid, ventrally arcuate (29-34 μm, c = 22-41, c′ = 0.7-1.0); spicules free, with pointed end and dagger-shaped, 61-72 μm long, bursa pseudopeloderan, and with eight pairs of genital papillae plus the phasmid, and gubernaculum 34-36 μm long. Furthermore, its relationship with four closely related species of the genus is discussed. A molecular phylogenetic study using a partial sequence of large subunit ribosomal DNA fragments revealed that R. maupasi forms a clade with R. terricola, recorded previously from Iran.

Single-Particle Crushing Test of Coated Calcareous Sand Based on MICP

Calcareous sand is a crucial construction material for island and reef development and reinforcing it using Microbially Induced Calcite Precipitation (MICP) technology is a promising new method. This study employed 3D scanning technology to assess changes in the particle size and morphology of MICP-treated, coated calcareous sand particles. Single-particle crushing tests were conducted to analyze their crushing strength, crushing energy, crushing modes, and fragment fractal dimensions. The results indicated that MICP treatment significantly increased particle size, surface area, and volume, while reducing flatness. At a cementation solution concentration of 1 mol/L, both crushing strength and crushing energy were optimized. The coated particles exhibited three crushing modes: explosive crushing, mixed crushing, and splitting crushing. Thicker coatings led to a tendency for particles to break into larger fragments through the mixed and splitting crushing modes. Fractal analysis revealed that coating thickness directly affects the local crushing characteristics of the particles.

Endemic and threatened birds as surrogates for identifying conservation priority areas and ecological corridors in the America’s most endangered habitat

Investigating multi-taxa macroecological patterns can provide critical insights for spatial conservation planning and landscape management across biodiversity hotspots. The Pernambuco Endemism Center (PEC) is a biogeographic region of the Brazilian Atlantic Forest known to harbor the most threatened habitats in the Americas and a considerable number of recent bird extinctions. Here, we modeled the distribution of 30 threatened forest-dependent birds, 29 of which endemic to the PEC, to reveal key habitats/resources for their survival, identify conservation priority areas, and design ecological corridors. We found variations in the responses of the taxa to landscape characteristics when we addressed these organisms separately and when we grouped them by conservation status. Overall, the environmental variables related to forest quality (e.g., distance to large fragments, distance to the forest edge, percentage of tree cover, percentage of older forests) were important predictors of habitat suitability for the regional threatened avifauna. Additionally, we revealed forest fragments of high ecological importance for the PEC’s threatened birds, and we propose the creation of the Pernambuco Endemism Center Restoration Arc (PEC-ARC) that may maximize the investments in conservation and guarantee the connectivity of crucial areas for long-term species survival.

Succinate Dehydrogenase-Deficient Renal Cell Carcinoma: Clinicopathological Analysis of 11 Cases

To investigate the clinicopathological features, immunophenotypes, molecular genetic alterations, and prognosis of succinate dehydrogenase-deficient renal cell carcinoma (SDH-RCC). A total of 11 cases of SDH-RCC diagnosed at West China Hospital, Sichuan University between 2016 and 2023 were selected for clinicopathological, immunohistochemical, and DNA sequencing analyses. Among the 11 cases of SDH-RCC, there were 5 male patients and 6 female patients. The patients' ages ranged from 12 to 71 years, with an average age of 39.7 years. Among them, 5 patients had tumors located in the right kidney, 5 had tumors located in the left kidney, and 1 patient had bilateral tumors. Microscopic observation showed that the tumor cells of the SDH-RCC patients displayed a wide spectrum of structures, forming sheet-like, nested, and glandular structures. In addition, tumor cells in papillary structures were observed in some cases. The tumor cells had abundant cytoplasm, was eosinophilic, and contained flocculent materials. Intracytoplasmic vacuolations were observed in some of the cells. Among all the patients, 7 (7/11, 63.6%) showed typical low-grade features (grade 1-2 according to the International Society of Urological Pathology [ISUP]/WHO 2016 classification), and 4 (4/11, 36.4%) showed high-grade features (grade 3 according to the ISUP/WHO 2016 classification). The average ages of patients with low-grade and high-grade features were 32.1 years and 58.0 years, respectively. Immunohistochemical staining of all 11 cases demonstrated negative results for SDHB and cytokeratin 7 (CK7), and positive staining results for paired box 8 (PAX-8), fumarate hydratase (FH), and epithelial membrane antigen (EMA). Their Ki-67 index was 1%-30%. In one case, the loss of SDHB expression was also accompanied by a loss of SDHA expression. Sanger sequencing was performed to examine all the exons of SDHB in 7 cases. One case showed a frameshift mutation, c.236Tdel (p.K80Rfs*), and another case harbored a missense mutation, c.725G>A (p.Arg242His). In another case, next generation sequencing revealed that large fragments of SDHB (Exon 4-8 del) were missing. Follow-up data were available for 10 patients. The follow-up time ranged from 4 to 138 months, with the average being 32.8 months, and all patients survived. Metastasis and recurrence were reported in 5 cases, with 3 of them showing high-grade features and 2 showing low-grade features. SDH-RCC is rare and the patients demonstrate a relatively young age of onsets. Patients may present with bilateral tumors. Tumors with low-grade features usually occur in young patients, with their Ki-67 index usually being lower than 5%. Individual cases may experience tumor recurrence and metastasis over a long period of follow-up. Tumors with high-grade features tend to occur in older patients who have a higher Ki-67 index, and who are prone to recurrence and metastasis. Negative immunohistochemical staining results for SDHB can assist in tumor diagnosis, but the loss of SDHB protein expression does not necessarily lead to the detection of SDHB gene mutation.

Impact of neutrophil‐activating protein conservation on diagnostic tests and vaccine design

AbstractBACKGROUNDThe neutrophil activating protein (NAP) is a highly immunogenic and virulence factor of Helicobacter pylori, presenting inflammatory and immunomodulatory activity. Consequently, NAP has been explored as a diagnostic and therapeutic target. However, when evaluating a target protein to design diagnostic methods or vaccines, it is critical to determine the protein conservation among the bacterial population, as well the impact of alterations of amino acid residues on the protein antigenic profile.RESULTSIn the present work, NAP conservation and theoretical antigenicity were determined among 51 sequences from H. pylori isolated from patients worldwide. A high NAP conservation (83%) was observed, where 17 amino acid residues, among the 144 residues of the protein, were polymorphic. Alterations at these polymorphic sites had a theoretically low impact on predicted antigenicity, where only 5 NAPs out of 51 NAPs presented a slightly different antigenic profile in relation to the consensus sequence. According to that, it was possible to recognize in western blotting 93% of NAP from different bacteria (n = 15) using polyclonal antibodies developed against a specific NAP.CONCLUSIONSIt was predicted that when working with polyclonal antibodies or large NAP fragments for diagnostic and vaccine design, slight variation in protein sequence will have a minimal impact on NAP recognition. However, if a NAP monoclonal antibody or small NAP epitopes are considered, it is critical to select the most conserved and antigenic NAP regions, to maximize the coverage of NAP variants. © 2024 Society of Chemical Industry (SCI).

MEHunter: Transformer-based mobile element variant detection from long reads.

Mobile genetic elements (MEs) are heritable mutagens that significantly contribute to genetic diseases. The advent of long-read sequencing technologies, capable of resolving large DNA fragments, offers promising prospects for the comprehensive detection of ME variants (MEVs). However, achieving high precision while maintaining recall performance remains challenging mainly brought by the variable length and similar content of MEV signatures, which are often obscured by the noise in long reads. Here, we propose MEHunter, a high-performance MEV detection approach utilizing a fine-tuned transformer model adept at identifying potential MEVs with fragmented features. Benchmark experiments on both simulated and real datasets demonstrate that MEHunter consistently achieves higher accuracy and sensitivity than the state-of-the-art tools. Furthermore, it is capable of detecting novel potentially individual-specific MEVs that have been overlooked in published population projects. MEHunter is available from https://github.com/120L021101/MEHunter. Supplementary data are available at Bioinformatics online.

Identification of John and Matthew in Some Nubian Paintings of Twelve Apostles

This paper aims to show how, in certain Nubian paintings depicting apostolic colleges, the evangelists John and Matthew can be identified by the attributes they hold, namely books. Theoretically, a book is an attribute that can define many figures involved in writing or preaching, such as saints (especially bishops in Nubian paintings), apostles, evangelists and Christ. However, in these particular paintings I am describing, only two of the apostles are holding books and these are the evangelists John and Matthew. The other apostles hold rotuli, while Peter is singled out through the key. My argument is based not only on the attributes, but also on an analysis of other elements such as the position of the apostles in the whole college, their physiognomic types, and finally the surviving inscriptions. However, we should remember that not all Nubian paintings are preserved intact. In many cases, large fragments of figures, including their faces, are missing.Therefore, several elements must be taken into consideration during the interpretationof the content of the paintings. The research I have carried out can be helpful inidentifying the individual figures that make up the apostolic college. It also shows howNubian iconographers consciously used the language of symbols by differentiatingbetween the earthly and heavenly hierarchies.

Evidence suggesting that earth had a ring in the Ordovician

All large planets in our Solar System have rings, and it has been suggested that Mars may have had a ring in the past. This raises the question of whether Earth also had a ring in the past. Here, we examine the paleolatitudes of 21 asteroid impact craters from an anomalous ∼40 m.y. period of enhanced meteor impact cratering known as the Ordovician impact spike, and find that all craters fall in an equatorial band at ≤30°, despite ∼70 % of exposed, potentially crater-preserving crust lying outside this band. The beginning of this period is marked by a large increase in L chondrite material accumulated in sedimentary rocks at 465.76 ± 0.30 Ma, which, together with the impact spike, has long been suggested to result from break-up of the L chondrite parent body in the asteroid belt. Our binomial probability calculation indicates that it is highly unlikely that the observed crater distribution was produced by bolides on orbits directly from the asteroid belt (P = 4 × 10–8). We therefore propose that instead, a large fragment of the L chondrite parent body broke up due to tidal forces during a near-miss encounter with the Earth at ∼466 Ma. Given the longevity of the impact spike and sediment-hosted L chondrite debris accumulation, we suggest that a debris ring formed after this break up event, from which material deorbited to produce the observed crater distribution. We further speculate that shading of Earth by this ring may have triggered cooling into the Hirnantian global icehouse period.

Instantaneous visual genotyping and facile site-specific transgenesis via CRISPR-Cas9 and phiC31 integrase.

Here, we introduce 'TICIT', targeted integration by CRISPR-Cas9 and integrase technologies, which utilizes the site-specific DNA recombinase - phiC31 integrase - to insert large DNA fragments into CRISPR-Cas9 target loci. This technique, which relies on first knocking in a 39-basepair phiC31 landing site via CRISPR-Cas9, enables researchers to repeatedly perform site-specific transgenesis at the exact genomic location with high precision and efficiency. We applied this approach to devise a method for the instantaneous determination of a zebrafish's genotype simply by examining its color. When a zebrafish mutant line must be propagated as heterozygotes due to homozygous lethality, employing this method allows facile identification of a population of homozygous mutant embryos even before the mutant phenotypes manifest. Thus, it should facilitate various downstream applications, such as large-scale chemical screens. We demonstrated that TICIT could also create reporter fish driven by an endogenous promoter. Further, we identified a landing site in the tyrosinase gene that could support transgene expression in a broad spectrum of tissue and cell types. In sum, TICIT enables site-specific DNA integration without requiring complex donor DNA construction. It can yield consistent transgene expression, facilitate diverse applications in zebrafish, and may be applicable to cells in culture and other model organisms.

Mitogenomics of a declining species, the Rio Grande silvery minnow (Hybognathus amarus), with boom–bust population dynamics

Abstract Large mitochondrial DNA fragments and nearly complete mitogenomes were obtained from nextera-tagmented reductively amplified DNA (nextRAD) data from the Rio Grande silvery minnow (Hybognathus amarus). We used these data to characterize variation across the mitogenome and to evaluate changes in mitochondrial diversity across a 20 year time series punctuated by marked species decline. We observed different evolutionary rates among protein-coding genes and inflated values of the ratio of non-synonymous change to non-synonymous sites to synonymous changes per synonymous site for several protein-coding genes, violating assumptions of selective neutrality. Analyses suggested that non-synonymous substitutions are effectively neutral, and our results were not consistent with genetic draft. Mitogenomes revealed large long-term effective population size for Rio Grande silvery minnow, and time-series data indicated recent reductions in mitochondrial diversity via genetic drift associated with population bottlenecks. The results presented in this study show that in some cases, nextRAD sequences contain informative mitochondrial DNA data.

Adequacy Assessment in Lymph Node Aspirates: An Exploratory Cytomorphologic Analysis of Negative Cervical Node Aspirates of Head and Neck Carcinomas

Introduction: Fine-needle aspiration cytology (FNAC) of lymph node is sensitive for detection of metastatic carcinoma but not without a significant false-negative rate. This study reviews clinicocytological features of negative node aspirates to identify predictive factors for establishing adequacy criteria. Methods: Negative FNAC specimens matched with neck dissection from a primary diagnosis of head and neck squamous cell, or undifferentiated (nasopharyngeal) carcinoma were reviewed for clinical and cytological parameters including lymphoid, inflammatory, and background components. Results: Slides from 86 lymph node aspirates including 50 positive for metastasis on follow-up were retrieved. Higher total lymphocyte count, lymphoid fragment count, germinal center fragment count, undifferentiated histology, presence of histiocytes and absence of blood were associated with a true negative cytologic diagnosis (p < 0.05), but not node size or location (p > 0.05). Undifferentiated histology, small lymphoid and germinal center fragments were independent factors indicative of a true negative diagnosis (p < 0.05). Large lymphoid fragments (p = 0.052) demonstrated a trend. Assessment of lymphoid components over five hotspots high-power fields (HPFs) was more robust in predictive value than only one hotspot. Receiver operating characteristic curve identified >10 small lymphoid, >20 large lymphoid and >2 germinal center fragment per five HPFs as optimal adequacy thresholds. Stricter total lymphocyte count cutoff accompanies increase of diagnostic accuracy, up to 0.67 for ≥5 HPFs with >500 lymphocytes. Conclusion: Total counts of lymphoid and germinal center fragments from multiple HPFs are useful in adequacy assessment of lymph node aspirates and improve diagnostic performance of FNAC in exclusion of metastatic carcinoma.

Four-port bimanual phaco-chop fragmentation for dropped nucleus using standard phaco chopper and assistant handheld 23G endoilluminator

Abstract: PURPOSE: To describe a bimanual method for management of posteriorly dislocated large nucleus fragment using standard chopper. METHODS: A 23G assistant handheld endoilluminator was used as light source through inferonasal self-sealing port, while the large nuclear fragment was broken into smaller fragments using phacofragmatome and standard phaco chopper. RESULTS: A case of posteriorly dislocated large nuclear fragment was operated using this technique. The time taken for phacofragmentation was significantly reduced, as well as the ultrasound energy required for the same. There was no port site complication. CONCLUSION: This technique allows greater maneuverability and reduces amount of ultrasound energy used by dividing nucleus into small fragments in vitreous cavity.

N-Terminal Fragments of TDP-43-In Vitro Analysis and Implication in the Pathophysiology of Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration.

Abnormal cytoplasmic aggregates containing the TDP-43 protein and its fragments are present in the central nervous system of the majority of patients with amyotrophic lateral sclerosis (ALS) and in patients with frontotemporal lobar degeneration (FTLD). Many studies have focused on the C-terminal cleavage products of TDP-43 (CTFs), but few have focused on the N-terminal products (NTFs), yet several works and their protein domain composition support the involvement of NTFs in pathophysiology. In the present study, we expressed six NTFs of TDP-43, normally generated in vivo by proteases or following the presence of pathogenic genetic truncating variants, in HEK-293T cells. The N-terminal domain (NTD) alone was not sufficient to produce aggregates. Fragments containing the NTD and all or part of the RRM1 domain produced nuclear aggregates without affecting cell viability. Only large fragments also containing the RRM2 domain, with or without the glycine-rich domain, produced cytoplasmic aggregates. Of these, only NTFs containing even a very short portion of the glycine-rich domain caused a reduction in cell viability. Our results provide insights into the involvement of different TDP-43 domains in the formation of nuclear or cytoplasmic aggregates and support the idea that work on the development of therapeutic molecules targeting TDP-43 must also take into account NTFs and, in particular, those containing even a small part of the glycine-rich domain.

Management of Intraoperative Acetabular Fractures in Total Hip Arthroplasty: A Current Concept Review.

Intraoperative acetabular fractures (IAFs), a complication seldomly encountered in total hip arthroplasty, are typically a result of the impact of insertion of a cementless press-fit cup. Factors that contribute to the risk of these types of fractures include poor bone quality, highly sclerotic bone, and the use of a press-fit cup that is excessively large. The approach to management of these fractures is dependent on when they are identified. Immediate stabilization measures should be implemented for management of fractures detected during surgery. When fractures are detected postoperatively, the decision regarding conservative treatment is dependent on the stability of the implant and the specific fracture pattern. In the majority of cases, effective treatment of an acetabular fracture detected intraoperatively can be administered using a multi-hole revision cup along with anchoring screws in the various regions of the acetabulum. Selection of plate osteosynthesis of the posterior column is recommended when there is a large posterior wall fragment or pelvic discontinuity. In cases where anatomical dimensions allow, cup-cage reconstruction may offer a promising alternative to a combined hip procedure. The number of reports addressing the management of IAFs is limited. This review focuses on outlining the strategies that are currently available for management of this seldomly encountered complication.