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In April 2023, Saudi Arabia and Iran announced the normalisation of diplomatic ties with China's mediation. Notably, Saudi Arabia sought China's mediation during Xi Jinping's visit in December 2022. Why did Saudi Arabia seek reconciliation while maintaining hostility with Iran? This study aims to uncover this puzzle using a case study approach. It examines the case through two mechanisms: reconciliation with one's enemy and reconciliation with a friend's enemy. According to the first approach, Saudi Arabia had to manage external threats to achieve the objectives of Vision 2030, an economic and social reform initiative implemented in response to political and economic shocks in the region. The second approach highlights Saudi Arabia's complex relationship with the United States. Through reconciliation, Saudi Arabia could attain considerable leverage in this relationship. Its approach to Iran serves as an effective example of foreign policy amid escalating tensions between the United States and China. [ABSTRACT FROM AUTHOR]

Purpose: Spinal fusion is the standard treatment for severe forms of adolescent idiopathic scoliosis (AIS). However, with the lowest instrumented vertebra that is usually located at L3 or L4, patients are prone to develop adjacent segment degeneration in the long term. Vertebral body tethering (VBT) as motion preserving technique has become an alternative for select patients with AIS. Several studies have presented the outcome after thoracic VBT but no study has analyzed the outcome after VBT for Lenke type 6 curves. Methods: This is a retrospective single center data analysis of patients who have had bilateral VBT for Lenke type 6 curves and a minimum follow up of 24 months. Radiographic analysis was performed on several time points. Suspected tether breakages were additionally analyzed with respect to location and time at occurrence. Results: 25 patients were included. Immediate thoracic curve correction was 55.4% and 71.7% for TL/L curves. Loss of correction was higher for TL/L curves and resulted in a correction rate of 48.3% for thoracic curves and 48.9% for TL/L curves at 24 months post-operatively. 22 patients were suspected to have at least one segment with a tether breakage. Three patients required a re-VBT but no patient received posterior spinal fusion. Conclusion: Bilateral VBT for Lenke type 6 curves is feasible and shows a significant curve correction for thoracic and TL/L curves at a minimum of 24 months post-operatively. Tether breakage rate and loss of correction remain an unfavorable observation that needs to be improved in the future. [ABSTRACT FROM AUTHOR]

Biological macromolecules, encompassing proteins, nucleic acids, lipids, and carbohydrates, have garnered increasing attention as tethering excipients within the realms of pharmaceuticals and biotechnology. This concise appraisal offers a comprehensive overview of their multifaceted role, highlighting the latest advancements in their applications. Biological macromolecules, long regarded as fundamental components of life, have transitioned into pivotal agents that contribute significantly to drug development, drug formulation stability and the optimization of pharmacokinetic profiles. This review delineates how these macromolecules serve as integral players in the enhancement of drug delivery systems, enabling controlled release, targeted delivery, and improved bioavailability. Furthermore, they play a critical role in the stabilization of sensitive compounds, preserving their efficacy and extending their shelf life. Additionally, the interactions between macromolecules and therapeutic agents are pivotal in mitigating issues of solubility and bioavailability, further propelling their utility as excipients. Despite these promising attributes, challenges such as immunogenicity, scalability, and regulatory compliance persist. Navigating these hurdles necessitates a concerted effort from researchers, engineers, and regulatory bodies alike. In conclusion, biological macromolecules stand as formidable contenders in the field of tethering excipients. Their versatile applications in drug delivery, formulation stability, and pharmacokinetic enhancement hold the promise of revolutionizing the pharmaceutical and biotechnological landscapes. To realize this potential fully, the scientific community must continue to probe their intricacies, address challenges proactively, and foster collaborative efforts to ensure their seamless integration into the future of healthcare and therapeutics. Ultimately, the enduring impact of biological macromolecules on patient care is poised to be transformative and far-reaching. [ABSTRACT FROM AUTHOR]

Introduction: Vertebral body tethering (VBT) has become an alternative option for select patients with idiopathic scoliosis. However, studies have shown a high number of tether breakages, specifically after thoracolumbar (TL) VBT, that can have a negative impact on the outcome, when the breakage occurs within the first year after surgery. In order to overcome this problem, we have started to apply an apical fusion (AF) in combination with TL VBT for select patients. This study aims to analyze the outcome after AF plus VBT. Methods: This is a retrospective single surgeon's data analysis. All patients were included who have had TL VBT after January 2022 and a follow-up of 12 months. Patients were grouped based on whether they only had VBT or VBT + AF. Results: Twenty-five patients were analyzed (15 VBT, 10 VBT + AF). Both groups showed a significant curve correction for thoracic and TL curves. Minor loss of correction was observed in both groups. A significant difference was seen regarding early tether breakages, which were found in 60% of VBT patients and 10% of VBT + AF patients. Conclusion: The preliminary data shows a significant reduction of early tether breakages when TL VBT is applied in combination with AF. [ABSTRACT FROM AUTHOR]

The emergence of antibiotic-resistant bacteria is a serious threat to public health. Antimicrobial peptides (AMP) are a powerful alternative to antibiotics due to their low propensity to induce bacterial resistance. However, cytotoxicity and short half-lives have limited their clinical translation. To overcome these problems, AMP conjugation has gained relevance in the biomaterials field. Nevertheless, few studies describe the influence of conjugation on enzymatic protection, mechanism of action and antimicrobial efficacy. This review addresses this gap by providing a detailed comparison between conjugated and soluble AMP. Additionally, commonly employed chemical reactions and factors to consider when promoting AMP conjugation are reviewed. The overall results suggested that AMP conjugated onto biomaterials are specifically protected from degradation by trypsin and/or pepsin. However, sometimes, their antimicrobial efficacy was reduced. Due to limited conformational freedom in conjugated AMP, compared to their soluble forms, they appear to act initially by creating small protuberances on bacterial membranes that may lead to the alteration of membrane potential and/or formation of holes, triggering cell death. Overall, AMP conjugation onto biomaterials is a promising strategy to fight infection, particularly associated to the use of medical devices. Nonetheless, some details need to be addressed before conjugated AMP reach clinical practice. Covalent conjugation of antimicrobial peptides (AMP) has been one of the most widely used strategies by bioengineers, in an attempt to not only protect AMP from proteolytic degradation, but also to prolong their residence time at the target tissue. However, an explanation for the mode of action of conjugated AMP is still lacking. This review extensively gathers works on AMP conjugation and puts forward a mechanism of action for AMP when conjugated onto biomaterials. The implications of AMP conjugation on antimicrobial activity, cytotoxicity and resistance to proteases are all discussed. A thorough review of commonly employed chemical reactions for this conjugation is also provided. Finally, details that need to be addressed for conjugated AMP to reach clinical practice are discussed. [Display omitted] [ABSTRACT FROM AUTHOR]

The indication for surgery for tricuspid regurgitation (TR) has reached a major turning point. It has become clear that the presence of moderate or severe TR alone worsens the prognosis of life, and the previous guidelines of Japanese Circulation Society, in which the indication for surgery was recommended at the timing of "right heart failure difficult to treat medically," now recommends surgery with a trigger of "repeated right heart failure" in the 2020 edition. In addition, a new repair technique targeting at subvalvular structure has been developed for end-stage TR to overcome a high TR recurrence rate that is associated with severe right ventricular enlargement and leaflet tethering. This review focuses on the spiral suspension technique, in which the papillary muscles are spirally suspended towards the septal leaflet annulus to correct tethering and enhances the understanding of its application in the context of TR management. [ABSTRACT FROM AUTHOR]

Despite seawalls becoming ubiquitous coastal features, and having some physical similarities to natural rocky shores, it remains unclear how these urban habitats influence predator–prey interactions. Predators can affect intertidal mobile prey densities through two pathways: (1) successful predation directly influences prey mortality rates, and (2) direct and indirect effects of predation can scare and induce motile prey to seek safer areas. In this study, we investigated whether intertidal predators affect the density of the marine gastropod, Nerita undata, at four seawall sites in Singapore. Using a tethering method that we developed, we monitored the mortality and other evidence of predation (shell state) of tethered N. undata. Field experiments revealed high (22.5%–82.5%) predation potential of N. undata across the four sites, with significantly higher predation risk at lower shore heights and for snails with mixed shell coloration. Observations and analysis of the shell state after 3 days showed that predation on seawalls was primarily by crushing predators such as fish. Other predators of N. undata include predatory snails, with various feeding methods that left behind different predator signatures. Our results add substantially to the limited knowledge on predator–prey interactions on seawalls, particularly for Nerita undata, and suggest that seawall systems are more dynamic than previously thought. This further highlights the role of these artificial structures as important habitats and feeding grounds in urban coastal ecosystems. [ABSTRACT FROM AUTHOR]

The development of small-molecule inhibitors or stabilizers of selected protein-protein interactions (PPIs) of interest holds considerable promise for the development of research tools as well as candidate therapeutics. In this context, the covalent modification of selected residues within the target protein has emerged as a promising mechanism of action to obtain small-molecule modulators of PPIs with appropriate selectivity and duration of action. Different covalent labeling strategies are now available that can potentially allow for a rational, ground-up discovery and optimization of ligands as PPI inhibitors or stabilizers. This review article provides a synopsis of recent developments and applications of such tactics, with a particular focus on site-directed fragment tethering and proximity-enabled approaches.

Despite a slight decline in average consumption in recent years, milk remains a significant component of diets in Western countries, including Germany. Concurrently, there has been growing awareness of the impact of food choices on climate, environment, and animal welfare. This study examines how various attributes of milk—such as packaging, husbandry practices, feeding methods, price, and price transparency—affect consumer decisions, using fresh milk as a case study.We conducted a choice experiment with 250 participants, who selected from product alternatives varying in price, milk features, cow husbandry and feeding practices, packaging types, and labels. Contrary to previous studies, which identified price as a primary decision criterion, our findings indicate that price was secondary for most participants, except for a specific segment.Label influence was minimal, while packaging had a significant impact on consumer choices. Interestingly, most respondents preferred glass packaging, despite its potential environmental drawbacks, suggesting a need to explore whether this preference is based on misconceptions about its environmental benefits.The type of husbandry emerged as the most influential factor in consumer decisions. In terms of animal welfare, there was a strong preference for pasture milk, particularly for ''Year-round grazing with mother-bonded calf rearing.'' This preference not only explains the marketing trend towards pasture milk but also presents an opportunity for sustainable farms to differentiate themselves and attract customers amidst a decline in pasture-based milk production.

Study Design/setting. Retrospective Objective. Evaluate the surgical technique that has the greatest influence on the rate of junctional failure following ASD surgery. Summary of background data. Differing presentations of adult spinal deformity(ASD) may influence the extent of surgical intervention and the use of prophylaxis at the base or the summit of a fusion construct to influence junctional failure rates. Materials and Methods. ASD patients with two-year(2Y) data and at least 5-level fusion to the pelvis were included. Patients were divided based on UIV: [Longer Construct: T1-T4; Shorter Construct: T8-T12]. Parameters assessed included matching in ageadjusted PI-LL or PT, aligning in GAP-relative pelvic version or Lordosis Distribution Index. After assessing all lumbopelvic radiographic parameters, the combination of realigning the two parameters with the greatest minimizing effect of PJF constituted a good base. Good s was defined as having: (1) prophylaxis at UIV (tethers, hooks, cement), (2) no lordotic change(under-contouring) greater than 10° of the UIV, (3) preoperative UIV inclination angle<30°. Multivariable regression analysis assessed the effects of junction characteristics and radiographic correction individually and collectively on the development of PJK and PJF in differing construct lengths, adjusting for confounders. Results. In all, 261 patients were included. The cohort had lower odds of PJK(OR: 0.5,[0.2-0.9];P=0.044) and PJF was less likely (OR: 0.1,[0.0-0.7];P=0.014) in the presence of a good summit. Normalizing pelvic compensation had the greatest radiographic effect on preventing PJF overall (OR: 0.6,[0.3-1.0];P= 0.044). In shorter constructs, realignment had a greater effect on decreasing the odds of PJF(OR: 0.2,[0.02-0.9];P=0.036). With longer constructs, a good summit lowered the likelihood of PJK(OR: 0.3, [0.1-0.9];P=0.027). A good base led to zero occurrences of PJF. In patients with severe frailty/osteoporosis, a good summit lowered the incidence of PJK(OR: 0.4,[0.2-0.9]; P= 0.041) and PJF (OR: 0.1,[0.01-0.99];P=0.049). Conclusion. To mitigate junctional failure, our study demonstrated the utility of individualizing surgical approaches to emphasize an optimal basal construct. Achievement of tailored goals at the cranial end of the surgical construct may be equally important, especially for higher-risk patients with longer fusions. [ABSTRACT FROM AUTHOR]

Populations of the non-native Asian shore crab, Hemigrapsus sanguineus, now dominate the rocky intertidal of southern New England, USA. High abundances suggest the recent invader may have experienced enhanced success as a result of enemy release. While larvae and juveniles may serve as a food source for ecologically important species, little is known about predation of mature H. sanguineus or the influence of habitat on predation pressure. To assess natural predation rates of adult H. sanguineus, crabs were tethered in the intertidal at Clarks Cove in New Bedford, MA. Crabs were left in situ for half of a tidal cycle then observed for signs of predation. Results of separate high and low tide trials showed that adult crabs were preyed upon at both high and low tide, though at a significantly higher rate during high tide during both daytime and nighttime, suggesting predation by aquatic species is greater than that by terrestrial species. To investigate the role of habitat as refuge from predation, a laboratory experiment manipulated the complexity of habitat provided to crabs in the presence of a native fish predator. Results indicate better refuge is provided by more complex shelter. Together, findings suggest that fish, crabs, and/or diving birds are important predators for H. sanguineus in the invaded range and that habitat refuge acts to reduce predation pressure. [ABSTRACT FROM AUTHOR]

Abstract Despite seawalls becoming ubiquitous coastal features, and having some physical similarities to natural rocky shores, it remains unclear how these urban habitats influence predator–prey interactions. Predators can affect intertidal mobile prey densities through two pathways: (1) successful predation directly influences prey mortality rates, and (2) direct and indirect effects of predation can scare and induce motile prey to seek safer areas. In this study, we investigated whether intertidal predators affect the density of the marine gastropod, Nerita undata, at four seawall sites in Singapore. Using a tethering method that we developed, we monitored the mortality and other evidence of predation (shell state) of tethered N. undata. Field experiments revealed high (22.5%–82.5%) predation potential of N. undata across the four sites, with significantly higher predation risk at lower shore heights and for snails with mixed shell coloration. Observations and analysis of the shell state after 3 days showed that predation on seawalls was primarily by crushing predators such as fish. Other predators of N. undata include predatory snails, with various feeding methods that left behind different predator signatures. Our results add substantially to the limited knowledge on predator–prey interactions on seawalls, particularly for Nerita undata, and suggest that seawall systems are more dynamic than previously thought. This further highlights the role of these artificial structures as important habitats and feeding grounds in urban coastal ecosystems.

Populations of the non-native Asian shore crab, Hemigrapsus sanguineus, now dominate the rocky intertidal of southern New England, USA. High abundances suggest the recent invader may have experienced enhanced success as a result of enemy release. While larvae and juveniles may serve as a food source for ecologically important species, little is known about predation of mature H. sanguineus or the influence of habitat on predation pressure. To assess natural predation rates of adult H. sanguineus, crabs were tethered in the intertidal at Clarks Cove in New Bedford, MA. Crabs were left in situ for half of a tidal cycle then observed for signs of predation. Results of separate high and low tide trials showed that adult crabs were preyed upon at both high and low tide, though at a significantly higher rate during high tide during both daytime and nighttime, suggesting predation by aquatic species is greater than that by terrestrial species. To investigate the role of habitat as refuge from predation, a laboratory experiment manipulated the complexity of habitat provided to crabs in the presence of a native fish predator. Results indicate better refuge is provided by more complex shelter. Together, findings suggest that fish, crabs, and/or diving birds are important predators for H. sanguineus in the invaded range and that habitat refuge acts to reduce predation pressure.

How cells deal with DNA breaks during mitosis is not well understood. While canonical non-homologous end-joining predominates in interphase, it is inhibited in mitosis to avoid telomere fusions. DNA polymerase θ mediated end-joining appears to be repressed in interphase, but promotes break repair in mitosis. The nature and induction time of breaks might determine their fate during mitosis.

Objective We investigated the effects of outdoor access for 1 h per day on the animal welfare (AW) of tethered cows, in terms of lying and sleeping postures, and immune function. Methods A total of five dry cows were tethered all day indoors (tethering) for 30 days and then tethered indoors with 1 h daily outdoor access (ODA-1h) for 30 days. To analyze the effects of ODA-1h, we calculated the total duration and bout frequency per day, and bout duration of lying and sleeping postures during the last five days of each treatment period. We also analyzed the populations of T cells, B cells, and NK cells in peripheral blood mononuclear cells (PBMC) by fluorescence-activated cell sorting and determined the concanavalin A (Con A) -induced proliferation rate of T cells. Results The mean total time per day of lying during the ODA-1h treatment was significantly shorter than that during the tethering treatment (p

Study Design Retrospective cohort study. Purpose This study aimed to evaluate the clinical and radiological outcomes of nonfusion anterior scoliosis correction (NFASC) in patients with idiopathic scoliosis and comprehensively analyze its principles. Overview of Literature NFASC is a novel revolutionary motion-preserving surgery for idiopathic scoliosis. However, clinical data related to this procedure remain scarce, with no conclusive guidelines regarding case indications, proper technique, and possible complications. Methods This study included patients with adolescent idiopathic scoliosis (AIS) who were treated with NFASC for a structural major curve (Cobb angle, 40°–80°) with more than 50% flexibility on dynamic X-rays. The mean follow-up was 26±12.2 months (range, 12–60 months). Clinical and radiological data such as skeletal maturity, curve type, Cobb angle, surgery details, and Scoliosis Research Society-22 revised (SRS-22r) questionnaire were collected. Statistically significant trends were examined by post hoc analysis following repeated measures analysis of variance test. Results A total of 75 patients (70 females, five males) were included, with a mean age of 14.96±2.69 years. The mean Risser and Sanders scores were 4.22±0.7 and 7.15±0.74, respectively. The mean main thoracic Cobb angles at the first and second follow-up (17.2°±5.36° and 16.92°±5.06°, respectively) were significantly lower than the preoperative Cobb angles (52.11°±7.74°) (p

The cytoskeleton is a fundamental component found in all eukaryotic organisms, serving as a critical factor in various essential cyto-biological mechanisms, particularly in the locomotion and morphological transformations of plant cells. The cytoskeleton is comprised of three main components: microtubules (MT), microfilaments (MF), and intermediate filaments (IF). The cytoskeleton plays a crucial role in the process of cell wall formation and remodeling throughout the growth and development of cells. It is a highly organized and regulated network composed of filamentous components. In the basic processes of intracellular transport, such as mitosis, cytokinesis, and cell polarity, the plant cytoskeleton plays a crucial role according to recent studies. The major flaws in the organization of the cytoskeletal framework are at the root of the aberrant organogenesis currently observed in plant mutants. The regulation of protein compartmentalization and abundance within cells is predominantly governed by the process of vesicle/membrane transport, which plays a crucial role in several signaling cascades.The regulation of membrane transport in eukaryotic cells is governed by a diverse array of proteins. Recent developments in genomics have provided new tools to study the evolutionary relationships between membrane proteins in different plant species. It is known that members of the GTPases, COP, SNAREs, Rabs, tethering factors, and PIN families play essential roles in vesicle transport between plant, animal, and microbial species. This Review presents the latest research on the plant cytoskeleton, focusing on recent developments related to the cytoskeleton and summarizing the role of various proteins in vesicle transport. In addition, the report predicts future research direction of plant cytoskeleton and vesicle trafficking, potential research priorities, and provides researchers with specific pointers to further investigate the significant link between cytoskeleton and vesicle trafficking.

The ras gene from rat brain (RAB) family of small GTPases is highly conserved among eukaryotes and regulates endomembrane trafficking pathways. RAB7, in particular, has been linked to various processes involved in regulating endocytic and autophagic pathways. Plants have several copies of RAB7 proteins that reflect the intricacy of their endomembrane transport systems. RAB7 activity regulates different pathways of endomembrane trafficking in plants: (1) endocytic traffic to the vacuole; (2) biosynthetic traffic to the vacuole; and (3) recycling from the late endosome to the secretory pathway. During certain developmental and stress related processes another pathway becomes activated (4) autophagic trafficking towards the vacuole that is also regulated by RAB7. RAB7s carry out these functions by interacting with various effector proteins. Current research reveals many unexplored RAB7 functions in connection with stress responses. Thus, this review describes a comprehensive summary of current knowledge of plant RAB7's functions, discusses unresolved challenges, and recommends prospective future research directions. [ABSTRACT FROM AUTHOR]

Bowel injury secondary to blunt trauma abdomen is a commonly encountered entity. However, small bowel obstruction secondary to traumatic incarceration of bowel loops between two translated vertebras in a case of road traffic accident is seldom reported. We report a case of small bowel obstruction in a patient who had suffered spondyloptosis at the L1–L2 level after a motor vehicle accident. We also discuss the diagnostic work up and interventions done to manage the patient. The report also reviews pertinent published literature on the incarceration of the bowel associated with vertebral fractures.

The ras gene from rat brain (RAB) family of small GTPases is highly conserved among eukaryotes and regulates endomembrane trafficking pathways. RAB7, in particular, has been linked to various processes involved in regulating endocytic and autophagic pathways. Plants have several copies of RAB7 proteins that reflect the intricacy of their endomembrane transport systems. RAB7 activity regulates different pathways of endomembrane trafficking in plants: (1) endocytic traffic to the vacuole; (2) biosynthetic traffic to the vacuole; and (3) recycling from the late endosome to the secretory pathway. During certain developmental and stress related processes another pathway becomes activated (4) autophagic trafficking towards the vacuole that is also regulated by RAB7. RAB7s carry out these functions by interacting with various effector proteins. Current research reveals many unexplored RAB7 functions in connection with stress responses. Thus, this review describes a comprehensive summary of current knowledge of plant RAB7’s functions, discusses unresolved challenges, and recommends prospective future research directions.

Macroautophagy is characterized by the de novo formation of double-membrane vesicles termed autophagosomes. The precursor structure of autophagosomes is a membrane cistern called phagophore, which elongates through a massive acquisition of lipids until closure. The phagophore establishes membrane-contact sites (MCSs) with the endoplasmic reticulum (ER), where conserved ATG proteins belonging to the ATG9 lipid scramblase, ATG2 lipid transfer and Atg18/WIPI4 β-propeller families concentrate. Several recent in vivo and in vitro studies have uncovered the relevance of these proteins and MCSs in the lipid supply required for autophagosome formation. Although important conceptual advances have been reached, the functional interrelationship between ATG9, ATG2 and Atg18/WIPI4 proteins at the phagophore-ER MCSs and their role in the phagophore expansion are not completely understood. In this review, we describe the current knowledge about the structure, interactions, localizations, and molecular functions of these proteins, with a particular emphasis on the yeast Saccharomyces cerevisiae and mammalian systems. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study. Purpose: This study aimed to evaluate the clinical and radiological outcomes of nonfusion anterior scoliosis correction (NFASC) in patients with idiopathic scoliosis and comprehensively analyze its principles. Overview of Literature: NFASC is a novel revolutionary motion-preserving surgery for idiopathic scoliosis. However, clinical data related to this procedure remain scarce, with no conclusive guidelines regarding case indications, proper technique, and possible complications. Methods: This study included patients with adolescent idiopathic scoliosis (AIS) who were treated with NFASC for a structural major curve (Cobb angle, 40°--80°) with more than 50% flexibility on dynamic X-rays. The mean follow-up was 26±12.2 months (range, 12-- 60 months). Clinical and radiological data such as skeletal maturity, curve type, Cobb angle, surgery details, and Scoliosis Research Society-22 revised (SRS-22r) questionnaire were collected. Statistically significant trends were examined by post hoc analysis following repeated measures analysis of variance test. Results: A total of 75 patients (70 females, five males) were included, with a mean age of 14.96±2.69 years. The mean Risser and Sanders scores were 4.22±0.7 and 7.15±0.74, respectively. The mean main thoracic Cobb angles at the first and second follow-up (17.2°±5.36° and 16.92°±5.06°, respectively) were significantly lower than the preoperative Cobb angles (52.11°±7.74°) ( p<0.05). Similarly, the mean thoracolumbar/lumbar Cobb angle significantly improved from the preoperative period (51.45°±11.26°) to the first follow-up (13.48°±5.11°) and last follow-up (14.24°±4.85°) ( p<0.05). The mean preoperative and postoperative SRS-22r scores were 78.0±3.2 and 92.5±3.1, respectively ( p<0.05). None of the patients had any complications until the most recent follow-up. Conclusions: NFASC offers promising curve correction and curve progression stabilization in patients with AIS, with a low risk for complications and preservation of spinal mobility and sagittal parameters. Thus, it proves to be a favorable alternative to fusion modality. [ABSTRACT FROM AUTHOR]

Introduction: Multiple studies have analyzed the outcome after thoracic Vertebral Body Tethering (VBT). The results seem reproducible with most studies reporting coronal correction rates around 50% and a tether breakage rate near 20% at two years follow-up. There is a paucity of data on lumbar VBT, and no study has yet analyzed the radiographic outcome after lumbar VBT in a double tether technique at two years follow-up, which was the aim of this study. Methods: This is a retrospective, single surgeons' data analysis of all consecutive immature patients who have had VBT of the lumbar spine (to L3 or L4) between January 2019 and September 2020. Primary interest focused on coronal curve correction at two years post-operatively. Suspected tether breakages were analyzed separately and defined as an angular change of more than 5° between two adjacent screws. Results: Forty-one patients were eligible for this study and 35 (85%) had complete two-year follow-up data. Average age at surgery was 14.3 years. All patients had a Sanders stage of 7 or below. Average curve correction for thoracolumbar/lumbar curves at two years follow-up was 50%. 90% of patients had at least one level with a suspected tether breakage. No patient required a revision surgery within two years from surgery but two patients were surgically revised after two years. Conclusion: VBT in the lumbar spine resulted in 50% coronal curve correction two years post-operatively despite a tether breakage in 90% of patients. [ABSTRACT FROM AUTHOR]

The plant trans-Golgi Network/Early Endosome (TGN/EE), as an organizer of vesicle trafficking, fulfills a crucial role for plant development and adaptation. Because it coordinates the transport of cell material along different routes, it is expected that a number of TGN/EE associated factors function in the rapid organization of post-Golgi trafficking to ensure that proteins reach their destination. The roles of Transport Protein Particle (TRAPP) complexes in the regulation of plant post-Golgi trafficking start to emerge. We previously demonstrated that the plant TRAPPIII complex is involved in maintenance of TGN organization and function and has a role in endocytic trafficking mediated by the SYP61 TGN/EE compartment. Here we show that attrappc11 mutants display accumulation of the plasma membrane resident proteins CESA6, BRI1 and PIP1;4 in aberrant intracellular compartments. This adds further insights into the functions of TRAPPIII as a regulators of post-Golgi/endosomal traffic.

The endolysosomal system of eukaryotic cells has a key role in the homeostasis of the plasma membrane, in signaling and nutrient uptake, and is abused by viruses and pathogens for entry. Endocytosis of plasma membrane proteins results in vesicles, which fuse with the early endosome. If destined for lysosomal degradation, these proteins are packaged into intraluminal vesicles, converting an early endosome to a late endosome, which finally fuses with the lysosome. Each of these organelles has a unique membrane surface composition, which can form segmented membrane microcompartments by membrane contact sites or fission proteins. Furthermore, these organelles are in continuous exchange due to fission and fusion events. The underlying machinery, which maintains organelle identity along the pathway, is regulated by signaling processes. Here, we will focus on the Rab5 and Rab7 GTPases of early and late endosomes. As molecular switches, Rabs depend on activating guanine nucleotide exchange factors (GEFs). Over the last years, we characterized the Rab7 GEF, the Mon1-Ccz1 (MC1) complex, and key Rab7 effectors, the HOPS complex and retromer. Structural and functional analyses of these complexes lead to a molecular understanding of their function in the context of organelle biogenesis. [ABSTRACT FROM AUTHOR]

Bowel injury secondary to blunt trauma abdomen is a commonly encountered entity. However, small bowel obstruction secondary to traumatic incarceration of bowel loops between two translated vertebras in a case of road traffic accident is seldom reported. We report a case of small bowel obstruction in a patient who had suffered spondyloptosis at the L1–L2 level after a motor vehicle accident. We also discuss the diagnostic work up and interventions done to manage the patient. The report also reviews pertinent published literature on the incarceration of the bowel associated with vertebral fractures. [ABSTRACT FROM AUTHOR]

Uso1/p115 and RAB1 tether ER-derived vesicles to the Golgi. Uso1/p115 contains a globular-head-domain (GHD), a coiled-coil (CC) mediating dimerization/tethering, and a C-terminal region (CTR) interacting with golgins. Uso1/p115 is recruited to vesicles by RAB1. Genetic studies placed Uso1 paradoxically acting upstream of, or in conjunction with RAB1 (Sapperstein et al., 1996). We selected two missense mutations in uso1 resulting in E6K and G540S in the GHD that rescued lethality of rab1-deficient Aspergillus nidulans. The mutations are phenotypically additive, their combination suppressing the complete absence of RAB1, which emphasizes the key physiological role of the GHD. In living hyphae Uso1 recurs on puncta (60 s half-life) colocalizing partially with the Golgi markers RAB1, Sed5, and GeaA/Gea1/Gea2, and totally with the retrograde cargo receptor Rer1, consistent with Uso1 dwelling in a very early Golgi compartment from which ER residents reaching the Golgi recycle back to the ER. Localization of Uso1, but not of Uso1E6K/G540S, to puncta is abolished by compromising RAB1 function, indicating that E6K/G540S creates interactions bypassing RAB1. That Uso1 delocalization correlates with a decrease in the number of Gea1 cisternae supports that Uso1-and-Rer1-containing puncta are where the protein exerts its physiological role. In S-tag-coprecipitation experiments, Uso1 is an associate of the Sed5/Bos1/Bet1/Sec22 SNARE complex zippering vesicles with the Golgi, with Uso1E6K/G540S showing a stronger association. Using purified proteins, we show that Bos1 and Bet1 bind the Uso1 GHD directly. However, Bet1 is a strong E6K/G540S-independent binder, whereas Bos1 is weaker but becomes as strong as Bet1 when the GHD carries E6K/G540S. G540S alone markedly increases GHD binding to Bos1, whereas E6K causes a weaker effect, correlating with their phenotypic contributions. AlphaFold2 predicts that G540S increases the binding of the GHD to the Bos1 Habc domain. In contrast, E6K lies in an N-terminal, potentially alpha-helical, region that sensitive genetic tests indicate as required for full Uso1 function. Remarkably, this region is at the end of the GHD basket opposite to the end predicted to interact with Bos1. We show that, unlike dimeric full-length and CTR∆ Uso1 proteins, the GHD lacking the CC/CTR dimerization domain, whether originating from bacteria or Aspergillus extracts and irrespective of whether it carries or not E6K/G540S, would appear to be monomeric. With the finding that overexpression of E6K/G540S and wild-type GHD complement uso1∆, our data indicate that the GHD monomer is capable of providing, at least partially, the essential Uso1 functions, and that long-range tethering activity is dispensable. Rather, these findings strongly suggest that the essential role of Uso1 involves the regulation of SNAREs.

Purpose Controversy exists regarding the role preoperative urodynamic study for asymptomatic closed spinal dysraphism as it has failed to reveal the benefit in surgical decision and expectation of urological outcomes. We explore the relationship between preoperative videourodynamic study and postoperative urological outcomes after toilet training completed, focusing on their capability of spontaneous voiding. Methods We retrospectively reviewed the data of 181 patients who underwent preventive spinal cord untethering and followed at least till the completion of toilet training. Before untethering, patients underwent preoperative videourodynamic study. Postoperative voiding function was evaluated in 3 phases: (1) till postoperative 6 months, (2) till the completion of toilet training, and (3) 2 years after toilet training. Changing distribution of emptying pattern at each period was described. Also, relevance to preoperative urodynamic parameters on spontaneous voiding and urinary continence after toilet training was assessed. Results Spinal lipoma and low lying conus were found in 145 (80%) and 128 patients (70.7%), respectively. Spontaneous voiding was found in 125 (69.1%), 164 (90.6%), and 162 patients (89.5%) at postoperative 6 months, till the toilet training, and 2 years after toilet training, respectively. Videourodynamics helped to clarify the presence of vesicourethral synergy. This was correlated with spontaneous voiding at postoperative 6 months and better urinary continence after 2 years of toilet training. Conclusions Eventual spontaneous voiding was achieved till toilet training in 90% patients following preventive untethering. Those showing preoperative vesicourethral synergy was associated with faster achievement of spontaneous voiding and better urinary continence when they enter elementary school.

We report the refinement of a high-throughput, liquid chromatography/mass spectrometry (LC/MS)-based screening method for the identification of covalent small-molecule binders to proteins. Using a custom library of 1600 disulfide-capped fragments targeting surface cysteine residues, we optimize sample preparation, chromatography, and ionization conditions to maximize the reliability and flexibility of the approach. Data collection at a rate of 84 s per sample balances speed with reliability for sustained screening over multiple, diverse projects run over a 24-month period. The method is applicable to protein targets of various classes and a range of molecular masses. Data are processed in a custom pipeline that calculates a percent bound value for each compound and identifies false positives by calculating significance of detected masses (signal significance). An example pipeline is available through Biovia's ScienceCloud Protocol Exchange. Data collection and analysis methods for the screening of covalent adducts of intact proteins are now fast enough to screen the largest covalent compound libraries in 1 to 2 days.

The treatment of scoliosis has been explored and debated in medicine since the first recorded texts. Scoliosis treatment has shifted over time from external modalities, such as traction and bracing, to internal stabilization techniques that leverage surgical advances. Surgical fixation constructs can generally be separated into two different modalities: dynamic vs. static constructs. For skeletally immature individuals with progressive deformities, surgical options range from traditional or magnetically controlled growing rods to vertebral body staples or tethering. For individuals who have reached skeletal maturity, many devices have been developed that provide static length constructs. Understanding the surgical options available is critical for the appropriate management of this varied patient population. With this article, we sought to provide a summary of past and present techniques and devices used in the treatment of scoliosis. [ABSTRACT FROM AUTHOR]

Study Design: Observational cohort study.Objective: To test the hypothesis that anterior vertebral body growth modulation (AVBGM) achieves 3D deformity correction after 2-year follow-up while brace treatment limits curve progression for moderate idiopathic scoliosis (30-50°).Summary Of Background Data: For idiopathic scoliosis, bracing and AVBGM have overlapping indications in skeletally immature patients with moderate scoliosis curve angles, creating a grey zone in clinical practice between them. The relative 3D deformity control performance over a 2-year period between these fusionless treatments is still uncertain.Methods: A retrospective review of a prospective idiopathic scoliosis patients database, recruited between 2013 and 2018 was performed. Inclusion criteria were skeletally immature patients (Risser 0-2), with Cobb angles between 30° and 50° and a 2-year follow-up after bracing or AVBGM. 3D radiological parameters and health related quality of life (HRQoL) scores were evaluated. Unpaired t test was used.Results: Thirty nine patients (12.7 ± 1.3 y.o.) with Cobb angles more than or equal to 30° treated with brace and 41 patients (11.8 ± 1.2 y.o.) with presenting Cobb angles less than or equal to 50° who received AVBGM were reviewed. The statistical analysis of 3D deformity measurements showed that at 2-year follow-up, only the 3D spine length and both sides apical vertebral heights changed significantly with brace treatment. While AVBGM treatment achieved statistically significant correction differences in thoracic and lumbar Cobb angles, TrueKyphosis, 3D spine length, and selective left apical vertebral height ( P < 0.05). 35% of brace patients had a curve progression of more than 5° at final follow-up while it was 0% for AVBGM. HRQoL assessment showed no statistically significant differences between pre and post SRS-22 total scores for each group ( P > 0.05).Conclusion: Even though these two cohorts are not fully comparable, bracing seems to control progression for a significant portion of patients with moderate scoliosis curves, while AVBGM significantly corrected and maintained 3D deformity parameters at 2-year follow-up. [ABSTRACT FROM AUTHOR]

Purpose: Pubic symphysis disruption is common in pelvic trauma. Open reduction and internal fixation with a plate is the gold standard technique. Despite increasing interest in an endoscopic approach, the challenges of specific endoscopic instrumentation, reduction and fixation remains. In this feasibility cadaveric study, we aimed to describe a novel endoscopic technique of fixation of pubic symphysis disruption with a spinal vertebral tethering system., Methods: Endoscopic pubic symphysis fixation with the tethering method was performed on a female cadaver specimen as well as an artificial pelvic model., Results: We describe a step-by-step technique where three abdominal portals were utilized in order to insert screws in the pubic body and superior pubic ramus under endoscopic visualization. The synthetic tether ligament was introduced through a lateral portal and fixed and tensioned to reduce and compress the pubic symphysis., Conclusions: While open plate fixation is the current gold standard of pubic symphysis disruption there is increasing interest in the minimally invasive endoscopic approach. In this feasibility cadaveric study, we present a new minimally invasive endoscopic fixation method to treat pubic symphysis disruption with a synthetic ligament., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Lysosomes are essential for cellular recycling, nutrient signaling, autophagy, and pathogenic bacteria and viruses invasion. Lysosomal fusion is fundamental to cell survival and requires HOPS, a conserved heterohexameric tethering complex. On the membranes to be fused, HOPS binds small membrane-associated GTPases and assembles SNAREs for fusion, but how the complex fulfills its function remained speculative. Here, we used cryo-electron microscopy to reveal the structure of HOPS. Unlike previously reported, significant flexibility of HOPS is confined to its extremities, where GTPase binding occurs. The SNARE-binding module is firmly attached to the core, therefore, ideally positioned between the membranes to catalyze fusion. Our data suggest a model for how HOPS fulfills its dual functionality of tethering and fusion and indicate why it is an essential part of the membrane fusion machinery.

Effective marine protected areas (MPAs) increase top predator density. Accordingly, a large abundance of predatory fish potentially increases predation risk for sea urchins inside an MPA.Intensity of predation was investigated for the sea urchin Paracentrotus lividus at a Mediterranean MPA. Predation rates were estimated for three levels of protection (full, partial, and absent) and two habitats (rocky reefs and Posidonia oceanica meadows). The natural density of sea urchins was correlated with predator biomass (fish sparids Diplodus spp. and Sparus aurata and the gastropod Hexaplex trunculus), and predation risk was evaluated through a tethering experiment.Significantly higher fish predation was found on the rocky reefs of the fully and non‐protected areas than in the partially protected area. These findings are consistent with the sparid biomass estimated in the fully and partially protected areas. However, a discrepancy between high predation risk and low sparid biomass was detected outside of the MPA's northern boundary, where marine farms (fish and mussels) are present. Benthic predator biomass also increased significantly across the northern boundary, but its predation activity was negligible.The low predatory fish biomass and low sea urchin density suggest a top‐down control by roving predatory fish on the rocky reefs of the non‐protected area, in proximity to the fish farms. Similarly, a significant gradient of benthic predator biomass and low sea urchin density suggest potential predation interactions inside the P. oceanica meadows across the northern MPA boundary near the mussel farms.This study highlights deviations from the expected trophic interactions outside the MPA that could be caused by aquaculture activities. Our understanding of the potential synergies between the MPAs and the nearby human activities needs to be broadened to improve the effectiveness of both ecosystem conservation and resource management. [ABSTRACT FROM AUTHOR]

Ventricular twisting, essential for cardiac function, is attributed to the contraction of myocardial helical fibers. The exact relationship between ventricular anatomy and function remains to be determined, but one commonly used explanatory model is the helical ventricular myocardial band (HVMB) model of Torrent-Guasp. This model has been successful in explaining many aspects of ventricular function, (Torrent-Guasp et al. Eur. J. Cardiothorac. Surg., 25, 376, 2004; Buckberg et al. Eur. J. Cardiothorac. Surg., 47, 587, 2015; Buckberg et al. Eur. J. Cardiothorac. Surg. 47, 778, 2015) but the model ignores important aspects of ventricular anatomy and should probably be replaced. The purpose of this review is to compare the HVMB model with a different model (nested layers). A complication when interpreting experimental observations that relate anatomy to function is that, in the myocardium, shortening does not always imply activation and lengthening does not always imply inactivation.

Red king crab, Paralithodes camtschaticus , was commercially important around Kodiak, Alaska, USA, in the 1960s and 1970s; however, the stock crashed in the late 1970 s and has remained closed since 1983. The lack of recovery inspired consideration of stock enhancement through the release of hatchery-reared juveniles as a means to bolster the wild population. We examined the effects of release timing on in situ survival of hatchery-reared red king crab by releasing juveniles in June, August, and September 2015 in Trident Basin, Kodiak. We monitored densities inside and outside of release plots for six months using quadrat counts to determine loss and emigration rates. Relative predation risk was determined using tethering experiments performed after each release, and predator densities were quantified using quadrat counts and predator transect counts. Initial mortality over the first 24 h was approximately 53%, and subsequent mortality rates decreased with month-of-release, likely due to a combination of larger size-at-release and seasonal changes in predation. Although predator density was consistent over time, relative predation risk of tethered crabs decreased with season, suggesting later releases may be beneficial. However, the extended hatchery rearing period needed for later releases presents other challenges, including cannibalism, and the potential for developing maladaptive traits. Stock enhancement programs must balance these trade-offs to maximize overall success. Early releases of small juveniles immediately after settlement may be optimal if large-scale hatchery communal rearing results in significant juvenile production loss and/or hatchery conditioning is impractical. • We performed a field experiment examining stock enhancement in red king crab. • Crab were released at three different times/sizes and tracked post release. • Crab survived best when released later and at a larger size. • However, account for holding mortality, earlier release times are more effective. [ABSTRACT FROM AUTHOR]

Proximal junctional kyphosis (PJK) is a common and devastating complication after spinal deformity surgery with a high need for revision surgery. PJK often leads to poor patient outcomes and large societal costs, which has led to the development of multiple prophylactic methods which have yet to eliminate PJK. A novel method for PJK prevention includes placing suture anchors, rather than pedicle screws, above the spinal construct to function as a tether. This biomechanical investigation examined the insertional torque and pullout strength of pedicle screws compared to suture anchors on 6 cadaveric vertebrae (12 pedicles). The mean insertional torque was 0.802 ± 0.477 N*m for pedicle screws and 0.368 ± 0.310 N*m for suture anchors (p = 0.047). The mean pullout strength was 973.16 ± 202.03 N for pedicle screws and 206.94 ± 181.78 N for suture anchors (p

In agriculture, various chemicals are used to control the weeds. Out of which, glyphosate is an important herbicide invariably used in the cultivation of glyphosate-resistant crops to control weeds. Overuse of glyphosate results in the evolution of glyphosate-resistant weeds. Evolution of glyphosate resistance (GR) in Amaranthus palmeri (AP) is a serious concern in the USA. Investigation of the mechanism of GR in AP identified different resistance mechanisms of which 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene amplification is predominant. Molecular analysis of GR AP identified the presence of a 5- to >160-fold increase in copies of the EPSPS gene than in a glyphosate-susceptible (GS) population. This increased copy number of the EPSPS gene increased the genome size ranging from 3.5 to 11.8%, depending on the copy number compared to the genome size of GS AP. FISH analysis using a 399-kb EPSPS cassette derived from bacterial artificial chromosomes (BACs) as probes identified that amplified EPSPS copies in GR AP exist in extrachromosomal circular DNA (eccDNA) in addition to the native copy in the chromosome. The EPSPS gene-containing eccDNA having a size of ∼400 kb is termed EPSPS-eccDNA and showed somatic mosacism in size and copy number. EPSPS-eccDNA has a genetic mechanism to tether randomly to mitotic or meiotic chromosomes during cell division or gamete formation and is inherited to daughter cells or progeny generating copy number variation. These eccDNAs are stable genetic elements that can replicate and exist independently. The genomic characterization of the EPSPS locus, along with the flanking regions, identified the presence of a complex array of repeats and mobile genetic elements. The cytogenomics approach in understanding the biology of EPSPS-eccDNA sheds light on various characteristics of EPSPS-eccDNA that favor GR in AP. [ABSTRACT FROM AUTHOR]

Insuficiența mitrală deseori este percepută ca o patologie organică cauzată de afectarea primară a foițelor mitrale şi aparatului subvalvular, fiind ignorate cauzele de regurgitare funcțională cum ar fi tethering-ul. Infarctul miocardic acut şi ischemia cronică stau la baza dezvoltării remodelării cardiace cu implicarea schimbărilor structurale şi funcţionale ale complexului mitral. Regurgitarea funcţională mitrală este a doua după boala degenerativă cea mai frecventă cauza de dezvoltare a insuficienței mitrale. În ultimii ani se atestă o creștere progresivă a prevalenței insuficienței mitrale ischemice. Această afecțiune are un impact major asupra supravieţuirii şi dezvoltării insuficienței cardiace post-infarct. Prezenţa acesteia este asociată cu o mortalitate mai înaltă comparativ cu pacienţii care nu au dezvoltat această complicaţie al infarctului miocardic. Diagnosticarea precoce a regurgitării mitrale funcționale poate fi o adevărată provocare pentru specialist. Rezolvarea chirurgicală la timp este asociată cu o rată de supravieţuire mai mare.

Abstract Background Caffeic acid is industrially recognized for its antioxidant activity and therefore its potential to be used as an anti-inflammatory, anticancer, antiviral, antidiabetic and antidepressive agent. It is traditionally isolated from lignified plant material under energy-intensive and harsh chemical extraction conditions. However, over the last decade bottom-up biosynthesis approaches in microbial cell factories have been established, that have the potential to allow for a more tailored and sustainable production. One of these approaches has been implemented in Escherichia coli and only requires a two-step conversion of supplemented l-tyrosine by the actions of a tyrosine ammonia lyase and a bacterial Cytochrome P450 monooxygenase. Although the feeding of intermediates demonstrated the great potential of this combination of heterologous enzymes compared to others, no de novo synthesis of caffeic acid from glucose has been achieved utilizing the bacterial Cytochrome P450 thus far. Results The herein described work aimed at improving the efficiency of this two-step conversion in order to establish de novo caffeic acid formation from glucose. We implemented alternative tyrosine ammonia lyases that were reported to display superior substrate binding affinity and selectivity, and increased the efficiency of the Cytochrome P450 by altering the electron-donating redox system. With this strategy we were able to achieve final titers of more than 300 µM or 47 mg/L caffeic acid over 96 h in an otherwise wild type E. coli MG1655(DE3) strain with glucose as the only carbon source. We observed that the choice and gene dose of the redox system strongly influenced the Cytochrome P450 catalysis. In addition, we were successful in applying a tethering strategy that rendered even a virtually unproductive Cytochrome P450/redox system combination productive. Conclusions The caffeic acid titer achieved in this study is about 10% higher than titers reported for other heterologous caffeic acid pathways in wildtype E. coli without l-tyrosine supplementation. The tethering strategy applied to the Cytochrome P450 appears to be particularly useful for non-natural Cytochrome P450/redox partner combinations and could be useful for other recombinant pathways utilizing bacterial Cytochromes P450.

How cells deal with DNA breaks during mitosis is not well understood. While canonical non-homologous end-joining predominates in interphase, it is inhibited in mitosis to avoid telomere fusions. DNA polymerase θ mediated end-joining appears to be repressed in interphase, but promotes break repair in mitosis. The nature and induction time of breaks might determine their fate during mitosis.

Background: Although the optimal timing of prophylactic untethering surgery for limited dorsal myeloschisis (LDM) with intact or subtle neurological findings diagnosed at birth remains undetermined, intentional delayed surgery is commonly used for flat and tail-like LDM. Conversely, for saccular LDM, early surgery is indicated during the postnatal period because it prevents rupture of the sac. We treated a saccular LDM patient, in whom intentional delayed surgery was selected because the sac was thickly covered with normal skin. We describe the clinical course of the case and discuss the optimal timing of the surgery. Case Description: The patient had a dorsal midline sac in the upper lumbar region. Initial magnetic resonance imaging (MRI) after birth revealed a tethering tract that began at the dome of the sac and joined the lumbar cord. Dorsal bending of the cord at the stalk-cord union and invagination of the cord into the sac were noted. At 2 months, he was neurologically normal; however, the second MRI examination revealed that the cord tethering was aggravated. The cord was markedly displaced dorsally and to the left, with deviation of the cord to the sac out of the spinal canal. Following untethering surgery, the spinal cord deformity markedly improved. Conclusion: Early surgery may be recommended for saccular LDM when tethering is present, including dorsal bending of the cord at the stalk-cord union and invagination of the cord into the sac observed on detailed MRI examination, even if the sac has no risk of rupture. [ABSTRACT FROM AUTHOR]