bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guanine Nucleotide‐Dependent Conformational Selection Regulates Distinct Alternate Ribosome Bound States of the Translation Factor BipA
Authors: Montovano Giancarlo , Buckley Theresa S. , Sharawy Mahmoud , May Eric R. , Anand Ganesh S. , Robinson Victoria L. 
Published: May 2022

BipA is a conserved translational GTPase necessary for securing bacterial survival and successful invasion of the host. Structural and biochemical studies indicate that GTP and ppGpp compete for binding to BipA to promote differential association of BipA to either the 70S or 30S ribosomal species. Exactly how guanine nucleotide binding to BipA prompts a change in the association of this protein with the ribosome is not understood. Crystallographic models show local structural rearrangements occur near the nucleotide‐binding pocket but unexpectedly the overall domain arrangement, and therefore intramolecular contacts are similar in the various guanine nucleotide bound states. One explanation is that the lattice contacts in the crystal restrict the conformational space available to the protein. Another is that the GTP‐ and ppGpp‐bound forms of BipA are dynamic meta‐stable or intermediate states poised to bind the ribosome. This model would account for a reverse flow of information evidenced by the increase in BipA’s rate of GTP hydrolysis upon ribosome binding.BipA’s hydrodynamic radius as measured by analytical ultracentrifugation and heat capacity changes assessed by isothermal titration calorimetry experimentally support our hypothesis that limited domain movements occur in solution upon guanine nucleotide binding. MD simulations utilizing the conformational end‐states provided by our GTP‐ and ppGpp‐bound crystal structures, coupled to a description of the solution dynamics of BipA using amide hydrogen/deuterium exchange mass spectrometry (HDX‐MS) indicate that this protein exists in an ensemble of states in solution as a metastable entity. The mutually exclusive binding of GTP or ppGpp produce unique allosteric relays within the protein directing the equilibria to alternate distinct conformations resulting in the formation of the two BipA:ribosome complexes. This intrinsic conformational fluidity is the origin of BipA’s ability to respond to ever changing environmental conditions synchronizing them with cellular physiology facilitating adaptation and long‐term survival of the bacteria.
Myoglobin knockout mice experience less damage and more immune infiltration in muscle pressure injury
Authors: Nasir Nurul Jannah M. , Heemskerk Johannes A. , So Peter T. , Tucker‐Kellogg Lisa 
Published: May 2022

IntroductionMuscle pressure ulcers are slow to heal and classified as “chronic” wounds, but the reasons for slow healing are not well understood. Elevated levels of extracellular hemoglobin have been implicated in the pathogenesis and impaired healing of sickle cell and vascular ulcers. We question whether extracellular release of myoglobin after muscle pressure injury might contribute to a hostile wound environment, analogous to hemoglobin. We hypothesise that knockout of myoglobin will decrease tissue damage and improve the microenvironment of muscle pressure ulcers.MethodsWe developed germline Myoglobin knockout (Mb–/–) mice via CRISPR deletion. Similar to previous studies, our adult Mb–/– mice show no phenotypic differences to Mb‐wildtype (Mb+/+) mice. Pressure injuries were created in mice by applying a pair of 12 mm magnets to the dorsal skinfold and panniculus carnosus muscle, in two intervals of 12 hours. We compared pressure ulcers in elderly 20‐month‐old mice carrying Mb–/– or Mb+/+. Ex vivo wound tissues were analysed at day 3 after injury.ResultsMb‐wildtype mice had high levels of ferric iron in the wound localized to the extracellular space and infiltrating cells (presumably macrophages). In knockout mice, iron was undetectable. The knockout mice had smaller pressure ulcers post‐injury and 50% less tissue damage at the wound centre (p < 0.01), compared to control Mb+/+ mice. In addition, the wounds of Mb–/– mice show a marked decrease in protein nitration (2.7‐fold decrease in nitrotyrosine levels; p < 0.0001) compared to Mb+/+ mice. Furthermore, Mb‐knockout wounds exhibited an almost 21‐fold decrease in DNA oxidation, measured by oxidised guanine (8‐oxoguanine; p < 0.0001) compared to Myoglobin+/+. We found 3.5‐fold greater infiltration of immune cells (p < 0.01) and higher CCL7 chemokine expression (p < 0.01) in Mb‐knockout tissues than Mb‐wildtype. Furthermore, Mb–/– wounds displayed a four‐fold decrease in citrullinated histone 3 (p < 0.0001), a marker of extracellular traps, compared to Mb+/+.ConclusionIn the absence of myoglobin, pressure‐injured tissues displayed less oxidative and nitrosative damage. Interestingly, they also showed higher immune infiltration and decreased extracellular traps, meaning that increased immune infiltration co‐occurred with decreased oxidative stress. We conclude that extracellular myoglobin contributes to oxidative stress and immune dysfunction in muscle pressure ulcers, and its removal causes less tissue death. This has important implications for the use of iron chelation therapy in the treatment of muscle pressure ulcers.
Effect of Alternative Therapeutic Exercise on the Older Adults – A Pilot Study
Authors: Sadacharan Chakravarthy M. 
Published: May 2022

IntroductionRegular physical activity is essential for sedentary older adults (aged 65 years and above) who are at the risk for multiple comorbidities. By performing physical activity, older adults can maintain or improve their physical function and mobility that may help them to be independent for a long time and delay the occurrence of disability in the future.ObjectiveTo assess the effect of the eccentric exercises prior to tai chi and yoga performance in the activities of daily living (ADL), balance and gait, and muscle strength in older adults.MethodsNine sedentary independent older adults aged between 60 and 90 were recruited. The study included the medical pre‐protocol assessment, the eccentric (ECC) exercise protocol with and without tai chi and yoga, subjective (Health activities of daily living (ADL) difficulty scale), and objective (Tinetti balance and gait, muscle strength) assessments, and medical post‐protocol assessment.ResultsThe functional limitations, Tinetti balance and gait score, manual muscle strength testing, and active range of motion (AROM) were improved in the medical post‐protocol assessment. Muscle strength showed statistically significant differences on the shoulder abductors (P=0.035), the elbow extensors (P=0.046), the hip abductors (P=0.028) and the hip extensors (P=0.03).ConclusionsOur findings show low perceived exercises (ECC) prior to tai chi and yoga training are well suited to the sedentary independent older adults with chronic conditions.
Internal and External Iliac Arterial Variations in a Single Human Cadaver: A Case Study
Authors: Teran Chavez Morgan E. , Lesciotto Kate 
Published: May 2022

Introduction & ObjectiveThe common iliac arteries are the main source of blood supply to the pelvis, perineum, and gluteal region via the internal iliac arteries (IIAs) and lower limbs via the external iliac arteries (EIAs). While variation in the branching patterns of the IIA and EIA is common, previously documented studies only focus on one type of variation. The objective of this study was to document the combination of multiple IIA and EIA variations found in one human cadaver. During herniorrhaphies and other pelvic surgeries, surgeons must enter the retropubic space. This space often has significant variation in collateral circulation, making vasculature in the area susceptible to injury, especially those that cross or reside near the superior pubic ramus. Knowledge of variant IIA and EIA branching patterns will assist surgeons and interventional radiologists in modifying their approach to procedures involving the pelvic area and lower limb (e.g., hernia repairs, fixation of pelvic fractures, etc.), thereby improving patient morbidity and mortality.MethodsDetailed dissections of the IIA and EIA and their respective branches were performed in a single human cadaver following notation of bilaterally aberrant obturator arteries. All arterial variations were documented through notes, diagrams, and photography. An in‐depth literature review was performed to evaluate the significance and frequency of the observed variations.ResultsThe left lower extremity had the following variations: absence of an inferior gluteal artery, an aberrant path of the superior gluteal artery, the inferior epigastric artery sharing a common trunk with the obturator artery from the profunda femoris artery, and anomalous branching of the femoral artery consisting of three larger branches, one noted to be the medial circumflex artery and the other two noted to be unusually large muscular branches. The right lower extremity had a similar aberrant obturator artery, although the common trunk shared with the inferior epigastric artery arose from the EIA.Conclusion/SignificanceAdditional arterial variations of the EIAs and IIAs were found upon further dissection differing bilaterally. It is essential for these variations to be documented along with the many others discovered previously. Lack of knowledge about arterial variation can lead to complications, such as femoral head osteonecrosis or significant hemorrhage during herniorrhaphy, fixation of pelvic fractures, and other pelvic/lower limb procedures. Therefore, knowledge of possible arterial variations of the human body can improve patient morbidity and mortality during routine surgical procedures, emergent surgical procedures, and various injuries in patients with vascular anomalies such as those documented in this study.
Novel SARS‐CoV‐2 Inactivation Formulation Supports Extended COVID‐19 Testing/Surveillance
Authors: Yu Tian , Holt Stewart , Davis Ryan , Baker Tony 
Published: May 2022

BackgroundWith the spread of highly infectious strains such as the Delta variant of SARS‐CoV‐2, rapid antigen testing and variant tracking are gaining more attention from infectious disease specialists and the general public as essentials for disease control and prevention amidst the COVID‐19 pandemic. The lateral flow based antigen tests provide fast turnaround of results within minutes, but it’s open ‐faced assay format means that the test operators are more prone to accidental exposure to pathogen‐containing samples. The viral inactivation transport media (ITMs) provide much needed protection against exposure to highly transmissive live viruses during sample collection, transport, and storage. However, the current ITMs were designed for PCR tests and share a harsh chemical formulation that denatures protein analytes, making them incompatible with antigen tests.We developed an innovative viral transport media that is designed for a variety of tests, such as antigen testing and PCR. The new formulation can be used to safely inactivate SARS‐CoV‐2 virus while maintaining compatibility with many different formats beyond rt‐PCR.DesignTo evaluate the viral inactivation performance of the novel inactivation transport media formulation, a cytopathic effect assay was conducted using VERO E6 cells in presence of SARS‐CoV‐2 samples incubated in our novel formulation and log reduction were reported.To assess its compatibility with different SARS‐CoV‐2 related assays, the novel formulation was used as inactivation transport media in antigen, PCR, and NGS based Swab‐Seq tests with known controls.ResultsThe results for the inactivation study confirmed > 3.0 log reduction in viral titer after 30 min exposure in novel transport media formulation and demonstrated 99.5% effectiveness in SARS‐CoV‐2 inactivation. The results for the PCR and antigen test compatibility studies showed comparable and/or superior performance in detection limits for the novel formulation when compared to other sample media. The Swab‐Seq result offers preliminary support on the novel formulation’s compatibility with NGS based assays.ConclusionUsing a novel viral transport medium, we were able to completely inactivate the SARS‐CoV‐2 virus. The new formulation was compatible with both nucleic acid and protein assays while protecting cells from infection. This viral transport media could allow more test types to be done from a single specimen, resulting in safer and reliable outcomes. Additionally, it would reduce the need for multiple samples collected from patients while supporting SARS‐CoV‐2 variant tracking via NGS.
Gene expression correlation analysis of livers undergoing normothermic machine perfusion identifies interactions between donor demographics and liver function
Authors: Santiago John C. , Raigani Siavash , Ohman Anders , Uygun Korkut , Yeh Heidi , Sanders Jennifer 
Published: May 2022

BackgroundLiver transplantation is currently the only cure for end‐stage liver disease, but the shortage of donor livers severely limits the effectiveness of transplantation. This shortage is made worse by challenges in preserving and assessing livers pre‐transplant that can result in discarding of functional livers. Normothermic machine perfusion (NMP) is a method of liver preservation that aims to provide physiological conditions while allowing real‐time assessment of transplant viability criteria. The aim of this study was to understand the effect of machine perfusion on the transcriptome and to correlate changes in gene expression with functional liver metrics.MethodsTen discarded livers (5 steatotic, 5 non‐steatotic), rejected by local transplant centers, were obtained from donation after circulatory death (DCD). The livers underwent 12 hours of NMP with oxygenated red blood cells. Serial tissue and plasma samples were collected at various times during perfusion. Plasma lactate samples were used to categorize liver as meeting viability criteria (viable) or not (nonviable) following NMP. Transcriptome sequencing was performed on serial biopsies taken at 0, 3, and 6hr during perfusion. Weighted gene co‐expression network analysis (WGCNA) was performed to correlate each module with demographics and functional metrics. Pathway and transcription factor analysis were performed on significant modules of interest.ResultsExpression data at 0, 3 and 6 hr of perfusion was used to construct the weighted co‐expression network. Gene co‐expression modules were then correlated with various clinical demographics and functional data collected during NMP. To evaluate the functional association of genes in the modules that significantly correlated with arterial lactate levels, we performed Gene Ontology enrichment analysis. By using lactate clearance as an indicator of transplant viability we were able to identify co‐expression gene sets enriched for biological processes including drug metabolism, immune response, autophagy, vascular development, nutrient metabolism, and gene expression.ConclusionsCurrent donor liver assessment models are limited by traditionally accessible parameters and can often lead to discarding potentially viable organs. NMP provides a novel data collection platform that could be used to improve traditional assessment models. By performing WGCNA, we were able to capitalize on an extensive set of metrics to identify interactions between the diverse donor demographics, the functional data collected during NMP and changes in gene expression. This may ultimately allow us to identify novel biomarkers to improve our current methods of donor liver assessment and assist the development of targeted therapeutics for more successful preservation and utilization of diverse donor livers.
Morphological Characteristics of Tubular Polymeric Scaffold to Improve Peripheral Nerve Regeneration
Authors: Dias Fernando J. , Alarcón Apablaza Josefa B. , Lezcano Maria F. , Lopez Alex , Godoy Karina , Oporto Gonzalo H. , Fazan Valéria P. S. 
Published: May 2022

IntroductionPeripheral nerve damage causes loss of quality of life due to loss of function. An innovative and promising solution has been the “nerve guide conduits” (NGC) that morphologically must mimic the characteristics of the extracellular matrix to enhance nerve regeneration.ObjectiveTo gather and describe the main features that should be considered when preparing polymeric NGC to improve peripheral nerve regeneration.MethodsFor this purpose, a Scoping Review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA‐ScR) using the following databases: PubMed, Web of Science, Science Direct, and Scientific Electronic Library Online. Only primary studies that analyzed the morphological characteristics of polymeric NGC associated with peripheral nerve regeneration were included.Results704 studies were found in the different databases, and only 52 were selected following the inclusion/exclusion criteria. The review of selected studies showed that the polymeric NGC morphological characteristics found were: 1. NGC diameter affects the mechanical properties of the scaffold. 2. Wall thickness of NGC determines the exchange of nutrients, molecules, and neurotrophins between the internal and external environment; and influences the mechanical properties and biodegradation. NGC 3. porosity, 4. pore size, and 5. pore distribution also affects exchanges of substances, their mechanical properties, and biodegradation. The 6. alignment of the NGC fibers influences the phenotype of cells involved in nerve regeneration. And finally, the 7. thickness of the polymeric fiber influences neurite extension and orientation.ConclusionConsidering the revised literature, a polymeric NGC should consider its diameter adjusted to the nerve with wall thickness, porosity, pore size, and distribution of pores, to favor vascularization, permeability, and exchange of nutrients, and retention of neurotrophic factors, also favoring its mechanical properties and biodegradability.
Rare Forearm Muscle Variations Seen in Two Cadaveric Dissections
Authors: Sanderson Drew B. , Nation Haley , Rahimi Omid B. , Occhialini Annette 
Published: May 2022

IntroductionAnatomical variations of the forearm muscles have been widely reported within the scientific literature, including variations or absence of the extensor pollicis brevis (EPB) and extensor pollicis longus (EPL) muscles. Rare instances have been found of an additional extensor forearm muscle, the extensor carpi radialis accessorius (ECRA). The authors describe a unique extra muscle originating from the muscle belly of the extensor carpi radialis longus (ECRL) and the distal humerus in two cadavers. One of these cadavers also had a complete absence of the EPB and an EPL with two sites of insertion.Case PresentationsDuring a cadaveric dissection course, two cadavers were found to have an extra extensor muscle of the left forearm. In both cases this muscle originated from the lateral surface of the ECRL muscle belly and the distal humerus; both muscles had a single tendon that traveled through the first extensor tunnel with the tendons of the abductor pollicis longus (APL) to insert onto the base of the first metacarpal. In addition, in one cadaver the EPB muscle was absent and the tendon of the EPL divided distally to insert into both the proximal and distal phalanx of the thumb.DiscussionThe ECRA is a rare additional extensor forearm muscle described to originate from the humerus below the ECRL and inserts into the first metacarpal bone of the thumb. The ECRA found in each of our two cadavers had an unusual origin from the muscle belly of the ECRL and from the distal humerus superior to the ECRL. This finding adds to the handful of known variations in the ECRA. The EPL and EPB are deep posterior forearm muscles. The EPL usually originates from the middle third of the ulna and inserts onto the base of the distal phalanx of the thumb. The EPB usually originates from the dorsal surface of the interosseous membrane and inserts onto the proximal phalanx of the thumb. In addition to the ECRA found in the left forearm, one of the cadavers also had anatomical variations in the extensor pollicis muscles on the same side. The EPB was absent and the EPL tendon divided distally to insert into the proximal and distal phalanx of the thumb. Variations in the EPB are common, and instances of an absent EPB have been cited in the literature. The EPL variation is most consistent with Turker Classification 1g. It’s possible this represents an anatomical adaptation to compensate for the absent EPB.ConclusionWhile an ECRA muscle is already rare, even more unusual is an ECRA originating from the ECRL and from the distal humerus superior to the ECRL and has not been reported. In addition, the concurrent existence of the three anatomic abnormalities within the same forearm has not been described previously. Knowledge of possible variants in forearm anatomy is crucial for surgeons to have a full understanding of possible causes of pathology. Alternatively, lack of awareness may cause diagnostic confusion or treatment failures.
The primary astrocytic mitochondrial transplantation ameliorates ischemic stroke
Authors: Lee Eun‐Hye , Kim Minkyung , Ko Seung Hwan , Lee Minhyung , Park Chang‐Hwan 
Published: May 2022

Mitochondria are important organelle which regulate adenosine triphosphate (ATP) production, intracellular calcium buffering, cell survival and apoptosis. They are known to deliver the potential therapeutic role in injured cells through transcellular transfer via extracellular vesicles (EVs), gap junctions, and tunneling nanotubes (TNTs).Astrocytes secrete numerous factors that promote neuron survival, synapse formation, and plasticity. Recent studies have demonstrated that astrocytes transfer mitochondria into damaged neurons to enhance cell viability and recovery. In this study, we observed that treatment of isolated mitochondria from rat primary astrocytes enhance cell viability and ameliorate H2O2‐damaged neurons. Interestingly, the isolated astrocytic mitochondria increased cell number in damaged neurons but not normal neurons, even though the mitochondrial transfer efficiency was no difference between them. Furthermore, this effect showed in astrocytic mitochondrial transplantation to rat middle cerebral artery occlusion (MCAO) models. These findings suggest that mitochondrial transfer therapy can be used to acute ischemic stroke and other diseases treatment.