Quantifying Replication Slippage Error in Cryptosporidium Metabarcoding Studies.

Genetic variation in Cryptosporidium, a common protozoan gut parasite in humans, is often based on marker genes containing trinucleotide repeats, which differentiate subtypes and track outbreaks. However, repeat regions have high replication slippage rates, making it difficult to discern biological diversity from error. Here, we synthesized Cryptosporidium DNA in clonal plasmid vectors, amplified them in different mock community ratios, and sequenced them using next-generation sequencing to determine the rate of replication slippage with dada2. Our results indicate that slippage rates increase with the length of the repeat region and can contribute to error rates of up to 20%.

Species-specific variation in mitochondrial genome tandem repeat polymorphisms in hares (Lepus spp., Lagomorpha, Leporidae) provides insight into their evolution.

The non-coding regions of the mitochondrial DNAs (mtDNAs) of hares, rabbits, and pikas (Lagomorpha) contain short (∼20 bp) and long (130-160 bp) tandem repeats, absent in related mammalian orders. In the presented study, we provide in-depth analysis for mountain hare (Lepus timidus) and brown hare (L. europaeus) mtDNA non-coding regions, together with a species- and population-level analysis of tandem repeat variation. Mountain hare short tandem repeats (SRs) as well as other analyzed hare species consist of two conserved 10 bp motifs, with only brown hares exhibiting a single, more variable motif. Long tandem repeats (LRs) also differ in sequence and copy number between species. Mountain hares have four to seven LRs, median value five, while brown hares exhibit five to nine LRs, median value six. Interestingly, introgressed mountain hare mtDNA in brown hares obtained an intermediate LR length distribution, with median copy number being the same as with conspecific brown hare mtDNA. In contrast, transfer of brown hare mtDNA into cultured mtDNA-less mountain hare cells maintained the original LR number, whereas the reciprocal transfer caused copy number instability, suggesting that cellular environment rather than the nuclear genomic background plays a role in the LR maintenance. Due to their dynamic nature and separation from other known conserved sequence elements on the non-coding region of hare mitochondrial genomes, the tandem repeat elements likely to represent signatures of ancient genetic rearrangements. clarifying the nature and dynamics of these rearrangements may shed light on the possible role of NCR repeated elements in mitochondria and in species evolution.

Influence of slippage reduction and correction of lumbosacral kyphosis by single-level posterior lumbar interbody fusion on spinal alignment in patients with dysplastic spondylolisthesis.

PURPOSE: To investigate the influence of slippage reduction and correction of lumbosacral kyphosis by L5-S1 single-level posterior lumbar interbody fusion (PLIF) on spinal alignment and clinical outcomes including postoperative complications in patients with dysplastic spondylolisthesis (DS). METHODS: Twenty consecutive patients with symptomatic and severe DS who underwent L5-S1 single-level PLIF with a minimum of 2 years of follow-up after surgery were included. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) and visual analog scale (VAS) scores for low back and leg pain obtained on preoperative and postoperative examinations. Postoperative instrumentation failure and L5 radiculopathy were also evaluated. The preoperative and postoperative spinopelvic parameters were measured. RESULTS: The JOA score significantly improved from 21.5 ± 4.8 (preoperative) to 27.0 ± 2.5 (postoperative), with a mean recovery rate of 75.0% ± 30.4%. The VAS score for low back pain significantly improved from 44.5 ± 30.1 (preoperative) to 11.5 ± 15.9 (postoperative), and that for leg pain significantly improved from 31.0 ± 33.2 (preoperative) to 5.0 ± 10.2 (postoperative). The slip percentage (% slip) significantly improved from 59.6% ± 13.5% (preoperative) to 25.2% ± 15.0% (postoperative). The lumbosacral angle (LSA) significantly improved from 12.3° ± 9.5° (preoperative) to 1.0° ± 4.9° (postoperative). L5-S1 PLIF led to significant improvement of lumbar lordosis (from 52.0° ± 15.9° to 59.7° ± 8.0°) and pelvic incidence - lumbar lordosis mismatch (from 23.9° ± 20.6° to 13.3° ± 10.0°). Correction of lumbosacral kyphosis had a significant positive correlation with postoperative pelvic tilt (PT) (r = 0.50, P = 0.02), while postoperative % slip did not have a significant correlation with postoperative PT. CONCLUSIONS: L5-S1 PLIF for DS provided good clinical outcomes. Correction of lumbosacral kyphosis had a positive impact on regaining ideal spinopelvic balance and may be beneficial in the setting of treating DS.

P3N-PIPO but not P3 is the avirulence determinant in melon carrying the Wmr resistance against watermelon mosaic virus, although they contain a common genetic determinant.

Viruses employ a series of diverse translational strategies to expand their coding capacity, which produces viral proteins with common domains and entangles virus-host interactions. P3N-PIPO, which is a transcriptional slippage product from the P3 cistron, is a potyviral protein dedicated to intercellular movement. Here, we show that P3N-PIPO from watermelon mosaic virus (WMV) triggers cell death when transiently expressed in Cucumis melo accession PI 414723 carrying the Wmr resistance gene. Surprisingly, expression of the P3N domain, shared by both P3N-PIPO and P3, can alone induce cell death, whereas expression of P3 fails to activate cell death in PI 414723. Confocal microscopy analysis revealed that P3N-PIPO targets plasmodesmata (PD) and P3N associates with PD, while P3 localizes in endoplasmic reticulum in melon cells. We also found that mutations in residues L35, L38, P41, and I43 of the P3N domain individually disrupt the cell death induced by P3N-PIPO, but do not affect the PD localization of P3N-PIPO. Furthermore, WMV mutants with L35A or I43A can systemically infect PI 414723 plants. These key residues guide us to discover some WMV isolates potentially breaking the Wmr resistance. Through searching the NCBI database, we discovered some WMV isolates with variations in these key sites, and one naturally occurring I43V variation enables WMV to systemically infect PI 414723 plants. Taken together, these results demonstrate that P3N-PIPO, but not P3, is the avirulence determinant recognized by Wmr, although the shared N terminal P3N domain can alone trigger cell death.IMPORTANCEThis work reveals a novel viral avirulence (Avr) gene recognized by a resistance (R) gene. This novel viral Avr gene is special because it is a transcriptional slippage product from another virus gene, which means that their encoding proteins share the common N-terminal domain but have distinct C-terminal domains. Amazingly, we found that it is the common N-terminal domain that determines the Avr-R recognition, but only one of the viral proteins can be recognized by the R protein to induce cell death. Next, we found that these two viral proteins target different subcellular compartments. In addition, we discovered some virus isolates with variations in the common N-terminal domain and one naturally occurring variation that enables the virus to overcome the resistance. These results show how viral proteins with common domains interact with a host resistance protein and provide new evidence for the arms race between plants and viruses.

The relationship between paraspinal muscle atrophy and degenerative lumbar spondylolisthesis at the L4/5 level.

BACKGROUND/CONTEXT: Degenerative lumbar spondylolisthesis (DLS) is a prevalent spinal condition that can result in significant disability. DLS is thought to result from a combination of disc and facet joint degeneration, as well as various biological, biomechanical, and behavioral factors. One hypothesis is the progressive degeneration of segmental stabilizers, notably the paraspinal muscles, contributes to a vicious cycle of increasing slippage. PURPOSE: To examine the correlation between paraspinal muscle status on MRI and severity of slippage in patients with symptomatic DLS. STUDY DESIGN/SETTING: Retrospective cross-sectional study at an academic tertiary care center. PATIENT SAMPLE: Patients who underwent surgery for DLS at the L4/5 level between 2016-2018 were included. Those with multilevel DLS or insufficient imaging were excluded. OUTCOME MEASURES: The percentage of relative slippage (RS) at the L4/5 level evaluated on standing lateral radiographs. Muscle morphology measurements including functional cross-sectional area (fCSA), body height normalized functional cross-sectional area (HI) of Psoas, erector spinae (ES) and multifidus muscle (MF) and fatty infiltration (FI) of ES and MF were measured on axial MR. Disc degeneration and facet joint arthritis were classified according to Pfirrmann and Weishaupt, respectively. METHODS: Descriptive and comparative statistics, univariable and multivariable linear regression models were utilized to examine the associations between RS and muscle parameters, adjusting for confounders sex, age, BMI, segmental degeneration, and back pain severity and symptom duration. RESULTS: The study analyzed 138 out of 183 patients screened for eligibility. The median age of all patients was 69.5 years (IQR 62 to 73), average BMI was 29.1 (SD±5.1) and average preoperative ODI was 46.4 (SD±16.3). Patients with Meyerding-Grade 2 (M2, N=25) exhibited higher Pfirrmann scores, lower MFfCSA and MFHI, and lower BMI, but significantly more fatty infiltration in the MF and ES muscles compared to those with Meyerding Grade 1 (M1). Univariable linear regression showed that each cm2 decrease in MFfCSA was associated with a 0.9%-point increase in RS (95% CI -1.4 to - 0.4, p<.001), and each cm2/m2 decrease in MFHI was associated with an increase in slippage by 2.2%-points (95% CI -3.7 to -0.7, p=.004). Each 1%-point rise in ESFI and MFFI corresponded to 0.17%- (95% CI 0.05-0.3, p=.01) and 0.20%-point (95% CI 0.1-0.3 p<.001) increases in relative slippage, respectively. Notably, after adjusting for confounders, each cm2 increase in PsoasfCSA and cm2/m2 in PsoasHI was associated with an increase in relative slippage by 0.3% (95% CI 0.1-0.6, p=.004) and 1.1%-points (95% CI 0.4-1.7, p=.001). While MFfCSA tended to be negatively associated with slippage, this did not reach statistical significance (p=.105). However, each 1%-point increase in MFFI and ESFI corresponded to increases of 0.15% points (95% CI 0.05-0.24, p=.002) and 0.14% points (95% CI 0.01-0.27, p=.03) in relative slippage, respectively. CONCLUSION: This study found a significant association between paraspinal muscle status and severity of slippage in DLS. Whereas higher degeneration of the ES and MF correlate with a higher degree of slippage, the opposite was found for the psoas. These findings suggest that progressive muscular imbalance between posterior and anterior paraspinal muscles could contribute to the progression of slippage in DLS.

Quantifying replication slippage error in Cryptosporidium metabarcoding studies.

Genetic variation in Cryptosporidium, a common protozoan gut parasite in humans, is often based on marker genes containing trinucleotide repeats, which differentiate subtypes and track outbreaks. However, repeat regions have high replication slippage rates, making it difficult to discern biological diversity from error. Here, we synthesised Cryptosporidium DNA in clonal plasmid vectors, amplified them in different mock community ratios and sequenced them using next generation sequencing to determine the rate of replication slippage with dada2. Our results indicate that slippage rates increase with the length of the repeat region and can contribute to error rates of up to 20%.

Noncanonical usage of stop codons in ciliates expands proteins with structurally flexible Q-rich motifs.

Serine(S)/threonine(T)-glutamine(Q) cluster domains (SCDs), polyglutamine (polyQ) tracts and polyglutamine/asparagine (polyQ/N) tracts are Q-rich motifs found in many proteins. SCDs often are intrinsically disordered regions that mediate protein phosphorylation and protein-protein interactions. PolyQ and polyQ/N tracts are structurally flexible sequences that trigger protein aggregation. We report that due to their high percentages of STQ or STQN amino acid content, four SCDs and three prion-causing Q/N-rich motifs of yeast proteins possess autonomous protein expression-enhancing activities. Since these Q-rich motifs can endow proteins with structural and functional plasticity, we suggest that they represent useful toolkits for evolutionary novelty. Comparative Gene Ontology (GO) analyses of the near-complete proteomes of 26 representative model eukaryotes reveal that Q-rich motifs prevail in proteins involved in specialized biological processes, including Saccharomyces cerevisiae RNA-mediated transposition and pseudohyphal growth, Candida albicans filamentous growth, ciliate peptidyl-glutamic acid modification and microtubule-based movement, Tetrahymena thermophila xylan catabolism and meiosis, Dictyostelium discoideum development and sexual cycles, Plasmodium falciparum infection, and the nervous systems of Drosophila melanogaster, Mus musculus and Homo sapiens. We also show that Q-rich-motif proteins are expanded massively in 10 ciliates with reassigned TAAQ and TAGQ codons. Notably, the usage frequency of CAGQ is much lower in ciliates with reassigned TAAQ and TAGQ codons than in organisms with expanded and unstable Q runs (e.g. D. melanogaster and H. sapiens), indicating that the use of noncanonical stop codons in ciliates may have coevolved with codon usage biases to avoid triplet repeat disorders mediated by CAG/GTC replication slippage.

Pin penetration depths in the neurocranium using a three-pin head fixation device.

In estimated 10-15% of neurosurgical interventions employing a conventional three-pin head fixation device (HFD) the patient's head loses position due to slippage. At present no scientifically based stability criterion exists to potentially prevent the intraoperative loss of head position or skull fractures. Here, data on the skull penetration depth both on the single and two-pin side of a three-pin HFD are presented, providing scientific evidence for a stability criterion for the invasive three-pin head fixation. Eight fresh, chemically untreated human cadaveric heads were sequentially pinned 90 times in total in a noncommercially calibrated clamp screw applying a predefined force of 270 N (approximately 60 lbf) throughout. Three head positions were pinned each in standardized manner for the following approaches: prone, middle fossa, pterional. Titanium-aluminum alloy pins were used, varying the pin-cone angle on the single-pin side from 36° to 55° and on the two-pin side from 25° to 36°. The bone-penetration depths were directly measured by a dial gauge on neurocranium. The penetration depths on the single-pin side ranged from 0.00 mm (i.e., no penetration) to 6.17 mm. The penetration depths on the two-pin side ranged from 0.00 mm (no penetration) to 4.48 mm. We measured a significantly higher penetration depth for the anterior pin in comparison to the posterior pin on the two-pin side in prone position. One pin configuration (50°/25°) resulted in a quasi-homogenous pin depth distribution between the single- and the two-pin side. Emanating from the physical principle that pin depths behave proportionate to pin pressure distribution, a quasi-homogenous pin penetration depth may result in higher resilience against external shear forces or torque, thus reducing potential complications such as slippage and depressed skull fractures. The authors propose that the pin configuration of 50°/25° may be superior to the currently used uniform pin-cone angle distribution in common clinical practice (36°/36°). However, future research may identify additional influencing factors to improve head fixation stability.

Differential flatness-based adaptive robust tracking control for wheeled mobile robots with slippage disturbances.

Wheeled mobile robots (WMRs) have a wide range of applications in logistics transportation and industrial productions, among which the motion control has always been one of the hot spots in the current WMR researches. However, most of previous designed controllers assumed that the WMR motion had no slippage. Ignoring the slippage factors usually results in a decrease in control performance and even leads to unstable motion. To address such a challenge, a kinematic model with differential flatness is established through dynamic feedback-linearization, which comprehensively considers the multidirectional slippage of mobile robot, including longitudinal and steering slippage. Subsequently, benefited from the one-to-one mapping of states and inputs to flat outputs in differential flat system, an adaptive robust control (ARC) method is proposed to stabilize the system. Different from previous robust control studies, even if the knowledge of the upper bound of system uncertainties is unknown in advance, the proposed adaptive robust controller can still achieve satisfying performance by adaptive estimation of the upper bound of system uncertainties. The effectiveness and feasibility of the proposed method are confirmed by comparative experiments on WMR with slippage disturbance.

Knot holding capacity of two different high-strength sutures-a biomechanical analysis.

PURPOSE: The number of seven required throws per knot was previously reported as providing sufficient security against slippage. A novel high-strength suture featuring dynamic tightening may allow for throw number reduction without compromising stability. The aims of this study were to (1) investigate the influence of the throw number and the effect of different ambient conditions on the knot security of two different high-strength sutures, and (2) compare their biomechanical competence. METHODS: Two sutures (FiberWire (FW) and DynaCord (DC)) were considered for preparing alternating surgical knots. The specimens were stratified for exposure to different media during biomechanical testing-namely air (dry), saline solution (wet), and fat (fatty-wet). A monotonic tensile ramp loading to failure was applied in each test run. For each suture and ambient condition, seven specimens with three to seven throws each were tested (n = 7), evaluating their slippage and ultimate force to failure. The minimum number of throws preventing suture unraveling was determined for each suture type and condition. RESULTS: For each suture type and condition, failure occurred via rupture in all specimens for the following minimum number of throws: FW-dry-7, wet-7, fatty-wet-7; DC-dry-6, wet-4, fatty-wet-5. When applying seven throws, FW demonstrated significantly larger slippage (6.5 ± 2.2 mm) versus DC (3.5 ± 0.4 mm) in wet (p = 0.004) but not in dry and fatty-wet conditions (p ≥ 0.313). CONCLUSIONS: The lower number of throws providing knot security of DC versus FW in the more realistic wet and fatty-wet conditions indicates that the novel DC suture may allow to decrease the foreign body volume and save surgical time without compromising the biomechanical competence.

Uncovering the Genetic and Molecular Features of Huntington's Disease in Northern Colombia.

Huntington's disease (HD) is a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene. Juan de Acosta, Atlántico, a city located on the Caribbean coast of Colombia, is home to the world's second-largest HD pedigree. Here, we include 291 descendants of this pedigree with at least one family member with HD. Blood samples were collected, and genomic DNA was extracted. We quantified the HTT CAG expansion using an amplicon sequencing protocol. The genetic heterogeneity was measured as the ratio of the mosaicism allele's read peak and the slippage ratio of the allele's read peak from our sequence data. The statistical and bioinformatic analyses were performed with a significance threshold of p < 0.05. We found that the average HTT CAG repeat length in all participants was 21.91 (SD = 8.92). Of the 291 participants, 33 (11.3%, 18 females) had a positive molecular diagnosis for HD. Most affected individuals were adults, and the most common primary and secondary alleles were 17/7 (CAG/CCG) and 17/10 (CAG/CCG), respectively. The mosaicism increased with age in the participants with HD, while the slippage analyses revealed differences by the HD allele type only for the secondary allele. The slippage tended to increase with the HTT CAG repeat length in the participants with HD, but the increase was not statistically significant. This study analyzed the genetic and molecular features of 291 participants, including 33 with HD. We found that the mosaicism increased with age in the participants with HD, particularly for the secondary allele. The most common haplotype was 17/7_17/10. The slippage for the secondary allele varied by the HD allele type, but there was no significant difference in the slippage by sex. Our findings offer valuable insights into HD and could have implications for future research and clinical management.

An alternative method of Bakri balloon placement for postpartum hemorrhage after vaginal delivery.

OBJECTIVES: We developed a new Bakri balloon tamponade (BBT) placement technique after vaginal delivery, which aimed to be faster without balloon slippage. This study compared the new method with standard placement of BBT in women with postpartum hemorrhage (PPH) after vaginal delivery. MATERIAL AND METHODS: This study was undertaken of women who underwent vaginal delivery at the obstetrics and gynecology departments of the Hospital of Chengdu University of Traditional Chinese Medicine, Sichuan Provincial Hospital for Women and Children, and Si Chuan JINXIN Women and Children Hospital between January 2014 and December 2020. Women who underwent BBT for PPH were grouped according to placement method into the old-BBT group and the new-BBT group. RESULTS: Of 20487 childbirths by vaginal delivery, 512 (2.50%) had PPH, 77 women underwent BBT (old-BBT n = 28, new-BBT n = 49). Background characteristics were similar except prothrombin time (PT, p < 0.01) and activated partial thromboplastin time (APTT, p < 0.004) were lower in the new-BBT group than the old-BBT group. The operation time was shorter in the new-BBT group (p < 0.001) with less bleeding (p < 0.003) and saline injection (p < 0.001). A balloon slippage was less likely (p < 0.008) and postoperative bleeding (p < 0.01), transfusion rate (p < 0.03), transfusion volume (p < 0.002), and hospital stay was lower in the new-BBT group (p < 0.015). Multivariate analysis suggested PT (OR = 0.039, 95% CI: 0.002-0.730, p < 0.030), international normalized ratio (OR = 8.244, 95% CI: 3.807-17.850, p < 0.009), and BBT method (OR = 5.200, 95% CI: 1.745-15.493, p < 0.003), were associated with requiring a blood transfusion. CONCLUSIONS: This method of BBT placement reduced operation time, balloon slippage, bleeding, and hospital stay in women with PPH after vaginal delivery.

Quantitative Analysis of RNA Polymerase Slippages for Production of P3N-PIPO Trans-frame Fusion Proteins in Potyvirids.

Potyvirids, members of the family Potyviridae, produce the P3N-PIPO protein, which is crucial for the cell-to-cell transport of viral genomic RNAs. The production of P3N-PIPO requires an adenine (A) insertion caused by RNA polymerase slippage at a conserved GAAAAAA (GA6) sequence preceding the PIPO open reading frame. Presently, the slippage rate of RNA polymerase has been estimated in only a few potyvirids, ranging from 0.8 to 2.1%. In this study, we analyzed publicly available plant RNA-seq data and identified 19 genome contigs from 13 distinct potyvirids. We further investigated the RNA polymerase slippage rates at the GA6 motif. Our analysis revealed that the frequency of the A insertion variant ranges from 0.53 to 4.07% in 11 potyviruses (genus Potyvirus). For the two macluraviruses (genus Macluravirus), the frequency of the A insertion variant was found to be 0.72% and 10.96% respectively. Notably, the estimated RNA polymerase slippage rates for 12 out of the 13 investigated potyvirids were reported for the first time in this study. Our findings underscore the value of plant RNA-seq data for quantitative analysis of potyvirid genome variants, specifically at the GA6 slippage site, and contribute to a more comprehensive understanding of the RNA polymerase slippage phenomenon in potyvirids.

Comparison between a dedicated stent positioning system and conventional stenting of aorto-ostial lesions: a prospective, multi-center, randomized controlled study.

Background: The accurate placement of stents for treatment of coronary aorto-ostial lesions (AOLs) is technically challenging. The purpose of this study was to evaluate the efficacy and safety of a stent positioning system with a dedicated nitinol device and compare them with those of the conventional approach for stenting of coronary AOLs. Methods: In this prospective, multi-center, open-label, randomized study, conducted from November 2015 to April 2019, patients with coronary AOLs that underwent percutaneous coronary intervention (PCI) were randomly allocated (allocation ratio 1:1) using block randomization method to either a stent positioning system group or a conventional technique group. The primary endpoint was the range of stent slippage when positioning. The following secondary endpoints were applied: (I) the extent of swing of the guiding catheters during stent positioning; (II) the rate of accurate stent placement; (III) the procedure time; and (IV) the incidence of major adverse cardiovascular events (MACEs) including cardiac death, myocardial infarction, target lesion revascularization, and stent thrombosis. Results: During the study period, 139 patients with aorto-ostial coronary artery stenosis were included at 5 centers. A total of 69 patients were allocated to the stent positioning system group and 70 patients to the conventional technique group. Angiographic and clinical success were achieved in 100% of the patients included in both groups. The range of stent slippage was significantly shorter in the stent positioning system group than it was in the conventional technique group [0.64 (0.22; 1.35) vs. 1.11 (0.48; 1.72) mm, P=0.01]. The rate of accurate placement of stents was higher in the stent positioning system group than it was in the conventional technique group (74.6% vs. 57.1%, P=0.03). The extent of guiding catheter swing during the stent positioning [0.24 (0.19; 0.53) vs. 0.23 (0.19; 0.53) mm; P=0.95] and the MACEs rates (1.4% vs. 2.9%, P>0.99) were similar between the 2 groups. The procedural time of the stent positioning system was longer than that of the conventional approach [1.00 (0.50; 1.50) vs. 0.80 (0.50; 1.50) min, P=0.09]. Conclusions: The dedicated stent positioning system was is safer and provides more accurate placement of stents for coronary AOLs than the conventional approach, and the associated prolongation of procedure time is insignificant. Trial Registration: Chinese Clinical Trial Registry (ChiCTR), Unique identifier: ChiCTR2100053869. URL: https://www.chictr.org.cn/showproj.html?proj=133280.

Characterization and Modeling of Ply/Tool and Ply/Ply Slippage Phenomena of Unidirectional Polycarbonate CF Tapes.

Thermoplastic tapes are commonly processed by the rapid and efficient stamp forming process. During this forming process, the individual unidirectional tapes of the composite stack move relative to each other and relative to the surface of the tool while being in contact with the corresponding counterpart. As a result, the material exhibits a certain resistance against this movement, which is generally dependent on velocity, normal pressure, and temperature. Therefore, this work investigates the ply/tool and ply/ply slippage of unidirectional, carbon fiber reinforced polycarbonate tapes and provides an alternative implementation of the experimentally observed slippage using cohesive zone modeling. The backbone of the modeling approach is an experimental data set obtained from pull-through experiments. In comparison to common slippage or friction theories, the force plateau of thermoplastic UD tapes at elevated temperatures is observed after an initial force peak has been overcome. For both configurations, ply/tool and ply/ply, a reduction of the initial force peak was observed for increasing temperature. Furthermore, the resulting plateau force value is at least 36% higher in the ply/ply configuration compared to the ply/tool configuration at 200 °C. The derived cohesive zone model allows for accurate modeling of the initial force peak and the plateau.

Genomic Instability of G-Quadruplex Sequences in Escherichia coli: Roles of DinG, RecG, and RecQ Helicases.

Guanine-rich DNA can fold into highly stable four-stranded DNA structures called G-quadruplexes (G4). Originally identified in sequences from telomeres and oncogene promoters, they can alter DNA metabolism. Indeed, G4-forming sequences represent obstacles for the DNA polymerase, with important consequences for cell life as they may lead to genomic instability. To understand their role in bacterial genomic instability, different G-quadruplex-forming repeats were cloned into an Escherichia coli genetic system that reports frameshifts and complete or partial deletions of the repeat when the G-tract comprises either the leading or lagging template strand during replication. These repeats formed stable G-quadruplexes in single-stranded DNA but not naturally supercoiled double-stranded DNA. Nevertheless, transcription promoted G-quadruplex formation in the resulting R-loop for (G3T)4 and (G3T)8 repeats. Depending on genetic background and sequence propensity for structure formation, mutation rates varied by five orders of magnitude. Furthermore, while in vitro approaches have shown that bacterial helicases can resolve G4, it is still unclear whether G4 unwinding is important in vivo. Here, we show that a mutation in recG decreased mutation rates, while deficiencies in the structure-specific helicases DinG and RecQ increased mutation rates. These results suggest that G-quadruplex formation promotes genetic instability in bacteria and that helicases play an important role in controlling this process in vivo.

Irreducible L5/S1 Spondyloptosis in Over 20 Years After Neglected Trauma Treated with Modified Grob's Technique - Case Report.

Introduction: Spondyloptosis, characterized by complete slippage of the upper vertebral body relative to the lower vertebral body, is an exceedingly rare condition. Typically, it occurs as a result of a high-energy injury and is promptly managed. It is uncommon for a patient to present to a spinal surgery unit several decades after the initial incident. Case Report: In this case report, we describe the case of a 62-year-old man who experienced a lumbosacral injury from a fall twenty years prior to seeking treatment. The patient had multiple comorbidities, including obesity and internal medicine conditions. He presented with severe back pain radiating to the lower extremities, accompanied by significant neurogenic chroma and lower extremity weakness. Imaging studies revealed spondyloptosis at the L5/S1 level, along with bony fusion and spinal canal stenosis at the L3/L4 level. Conclusion: The patient underwent surgical intervention using Grob's direct pediculo-body fixation technique. The postoperative period was uneventful, and over the course of one year of follow-up, the patient experienced a resolution of symptoms and significant improvement in functional capacity.

Bilateral asymmetric traumatic hip dislocation associated with epiphysiolysis of the femoral head in an adolescent patient.

Background: Bilateral asymmetric hip dislocation is uncommon in childhood, even more when associated with epiphyseal slippage, leading to catastrophic complications of the affected joints, requiring additional surgical interventions, and increasing patient morbidity. In this article, we present the case of a 15 years-old patient with a post-traumatic bilateral hip dislocation with epiphyseal slippage, initially managed with open reduction and fixation, with subsequent need of total hip arthroplasty. Afterward, the patient presented satisfactory outcomes. Conclusion: Hip dislocation associated with transphyseal fracture is an injury that leads to joint destruction, and despite timely management, the prognosis is poor; however, efforts should be made to provide opportune care to obtain the best outcome.

Inhibition of non-homologous end joining mitigates paclitaxel resistance resulting from mitotic slippage in non-small cell lung cancer.

Mitotic slippage, which enables cancer cells to bypass cell death by transitioning from mitosis to the G1 phase without undergoing normal cytokinesis, is one likely mechanism of paclitaxel (PTX) resistance. DNA double-strand breaks (DSBs) in the G1 phase are mainly repaired through non-homologous end joining (NHEJ). Therefore, inhibiting NHEJ could augment the PTX-induced cytotoxicity by impeding the repair of PTX-induced DSBs during the G1 phase following mitotic slippage. We aimed to evaluate the effects of NHEJ inhibition on mitotic slippage after PTX treatment in non-small cell lung cancer (NSCLC). H1299, A549, H1975, and H520 NSCLC cell lines were employed. In addition, A-196 and JQ1 were used as NHEJ inhibitors. H1299 cells were PTX-resistant and exhibited an increased frequency of mitotic slippage upon PTX treatment. NHEJ inhibitors significantly augmented the PTX-induced cytotoxicity, DSBs, and apoptosis in H1299 cells. The newly generated PTX-resistant cells were even more prone to mitotic slippage following PTX treatment and susceptible to the combined therapy. Docetaxel further demonstrated synergistic effects with the NHEJ inhibitor in PTX-resistant cells. NHEJ inhibition may overcome intrinsic or acquired PTX resistance resulting from mitotic slippage by synergistically increasing the cytotoxic effects of antimitotic drugs in NSCLC.

Classification of Slippage Following Laparoscopic BariClip Gastroplasty.

INTRODUCTION: Laparoscopic BariClip gastroplasty (LBCG) is a new reversible gastric sleeve-like procedure without gastrectomy proposed to minimize the risk of severe complications. Still one of the possible complications described with LBCG is slippage. The purpose of the current manuscript is to analyze different cases of slippage and propose a classification of this complication. METHODS: A number of 381 patients who underwent LBCG in 8 different centers were analyzed concerning the risk of slippage. All cases with documented slippage were carefully reviewed in terms of patients' symptomatology (presence of satiety, vomiting), history of weight loss, radiological data, and management of their slippage. A new classification was proposed depending on the anatomy, the symptomatology, and the time of occurrence. RESULTS: We have identified a total of 17 cases (4.46%) of slippage following LBCG. In 11 patients, the slippage was symptomatic with repetitive vomiting and nausea, and in the remaining 6 patients, the slippage was identified by radiological studies for insufficient weight loss, weight regain, or routine radiological follow-up. Depending on the interval time, the slippage was classified as either immediate (in first 7 days) in 6 cases, early (in less than 90 days) in 4 cases, and late (after 3 months) in 7 cases. Evaluation of the radiological studies in these cases identified the following: anterosuperior displacement (type A) in 9 cases, posteroinferior displacement (type B) in 6 cases (one case after 3 months), and lateral displacement (type C) in the remaining 2 cases. The management of the slippage consisted of BariClip removal in 7 cases, repositioning in 5 cases, and conservative treatment in the remaining 5 cases. All patients with conservative treatment were recorded at the beginning of the experience. CONCLUSIONS: Slippage is a possible complication after LBCG. This classification of the different types of slippage can benefit the surgeon in the management and treatment of this complication of LBCG.