bluuebunny/crossref_metadata_2025 huggingface dataset:
Methotrexate Management of Immune‐Mediated Cochleovestibular Disorders
Authors: Sismanis Aristides , Wise Christopher M. , Johnson Glenn D.
Published: September 2022

Immune‐mediated cochleovestibular disorders continue to present a management challenge to the otolaryngologist. The traditional treatment of these disorders, corticosteroids and/or cyclophosphamide (Cytoxan), has been associated with serious and occasionally life‐threatening complications. In this study we report our experience in treating 25 patients with immune‐mediated cochleovestibular disorders with methotrexate, a less toxic immunosuppressive agent that has been used extensively in patients with rheumatoid arthritis. Mean duration of treatment was 12.9 months, and adverse reactions were acceptable and reversible. Hearing improved in 69.6% of patients, and vestibular symptoms subsided or improved in 80% of patients. The results of this study suggest that methotrexate treatment is effective in a substantial number of patients with immune‐mediated cochleovestibular disorders and has acceptable adverse reactions. A prospective, randomized study is needed to compare the efficacy of methotrexate with that of other immunosuppressive agents.
Contribution of the Eighth Nerve and Cranial Nerve Nuclei to the Short‐Latency Vestibular Evoked Potentials in Cats
Authors: Li Gang , Elidan Josef , Meyler Yulia , Sohmer Haim
Published: September 2022

The object of this study was to assess the contributions of the vestibular nerve and various cranial nerve nuclei to the short‐latency vestibular evoked potentials in cat. The following nuclei were investigated: vestibular nuclei and the third, sixth, and tenth cranial nerve nuclei. In unilateral labyrinthectomized cats, we performed suboccipital craniectomy and partial cerebellectomy to place bipolar electrodes into the neural structures under investigation. The surface‐recorded vestibular evoked potentials (far field) were compared with the potentials recorded intracranially in response to the same acceleration impulses. The exact locations were later confirmed histologically. Reversible lesions also were induced by injection of lidocaine 2%. The results indicate that the first wave of the vestibular evoked potentials originates in the vestibular nerve, and the second wave is mainly generated in the superior and medial vestibular nuclei. The third, sixth, and tenth cranial nerve nuclei apparently contribute to the later waves of the vestibular evoked potentials, particularly waves 3 and 4.
Head and Neck Cancer Screening Among 4611 Tobacco Users Older than Forty Years
Authors: Prout Marianne N. , Sidari Joseph N. , Witzburg Robert A. , Grillone Gregory A. , Vaughan Charles W.
Published: September 2022

We implemented screening for squamous cell carcinomas of the oral cavity, pharynx, and larynx with symptom assessment and systematic inspection of the oral mucosa by primary care practitioners at health care sites serving inner‐city residents of Boston; 4611 tobacco users older than 40 years were screened, and 313 with specific criteria were referred to otolaryngology for diagnostic evaluations. In these screened patients, the prevalence of oral mucosal lesions was almost 13% and prevalence of persistent hoarseness was more than 11%. Although the identification of these cancers was rare (nearly 3%), abnormal findings were seen in more than 70% of referred patients. These clinical and histologic diagnoses are described. We have documented the range of pathologic conditions in high‐risk patients screened for upper aerodigestive tract malignancy.
Intraoperative Phototherapy: A Comparative Study of Intravenous and Topical Photofrin II and Aminolevulinic Acid
Authors: Davis R. Kim , Straight Richard , Sun Yongen
Published: September 2022

This study compares the systemic and topical application of photofrin II and aminolevulinic acid as an intraoperative adjuvant therapy in the C3H mouse radiation‐induced fibrosarcoma model. Dose‐development and time‐dependent studies were first conducted followed by intraoperative phototherapy studies with photofrin II and aminolevulinic acid. Study results clearly show that intraoperative phototherapy after aminolevulinic acid topical application is significantly more effective than treatment with photofrin II given intravenously or topically (p < 0.05) in this animal tumor model. The concept of topical application of photosensitizers and the rationale for intraoperative adjuvant phototherapy are discussed.
Immunotherapy in the Treatment of Allergic Fungal Sinusitis
Authors: Mabry Richard L. , Manning Scott C. , Mabry Cynthia S.
Published: September 2022

Recommendations to withhold immunotherapy with fungal antigens from patients with allergic fungal sinusitis (AFS) have been based primarily on retrospectively reviewed, anecdotal case reports and theoretical considerations. A study that was approved by the investigational review board of our institution is ongoing in our department to administer immunotherapy with relevant fungal antigens to patients with histologically proven AFS. After 1 year, no instances of worsening of symptoms as a result of this therapy have been observed. Objective measurement of improvement has been difficult, but our initial clinical impression is that this treatment regimen has resulted in significant reduction in the reaccumulation of crusts and allergic mucin within the sinuses, has led to a reduction in the use of topical nasal steroids, and has made systemic steroid therapy unnecessary, thereby improving the quality of life of the patient. A further study of immunotherapy for patients with AFS is recommended, and suggestions for modification of the current protocol are presented.
Synaptic Changes in Rat Maculae in Space and Medical Imaging: The Link
Authors: Ross Muriel D.
Published: September 2022

Two different space life sciences missions (SLS‐1 and SLS‐2) have demonstrated that the synapses of the hair cells of rat vestibular maculae increase significantly in microgravity. The results also indicate that macular synapses are sensitive to stress. These findings argue that vestibular maculae exhibit neuroplasticity to macroenvironmental and microenvironmental changes. This capability should be clinically relevant to rehabilitative training and/or pharmacological treatments for vestibular disease. The results of this ultrastructural research also demonstrated that type I and type II hair cells are integrated into the same neuronal circuitry. The findings were the basis for development of three‐dimensional reconstruction software to learn details of macular wiring. This software, produced for scientific research, has now been adapted to reconstruct the face and skull directly from computerized tomography scans. In collaboration with craniofacial reconstructive surgeons at Stanford University Medical Center, an effort is under way to produce a virtual environment workbench for complex craniofacial surgery. When completed, the workbench will help surgeons train for and simulate surgery. The methods are patient specific. This research illustrates the value of basic research in leading to unanticipated medical applications. (Otolaryngol Head Neck Surg 1998;118:S25‐S28.)
Interaction of Methylprednisolone and Transient Asphyxia on the Inner Ear of the Adrenalectomized Rat
Authors: Gerhardt Kenneth J. , Ma Yi Long , Rybak Leonard P. , Rarey Kyle E.
Published: September 2022

Methylprednisolone has been shown clinically to have beneficial effects on certain types of hearing loss. In the current study, compound action potential (CAP) thresholds, endocochlear potentials (EPs), and potassium concentration (CK +) values in the endolymph were determined under conditions of transient asphyxia (45 seconds) and methylprednisolone treatment (24 hours) in bilateral adrenalectomized rats. Treatment with methylprednisolone significantly reduced the effect of transient asphyxia on CAP thresholds as compared with nontreated animals. Methylprednisolone did not alter the dramatic short‐term reduction in the EPs produced by anoxia. Potassium concentrations in treated adrenalectomized rats were significantly lower before transient asphyxia than in nontreated adrenalectomized rats. In the nontreated rats, transient asphyxia induced a reduction in CK + levels that was not seen in the methylprednisolone‐treated animals. The data support the clinical application of methylprednisolone for certain forms of hearing loss and for potassium imbalance in the endolymph.
Tracheostomy for Long‐Term Laryngeal Experimentation
Authors: Dahm J. David , Paniello Randal C.
Published: September 2022

To perform laryngeal research involving long‐term survival surgery, a permanent tracheostomy is often necessary. For experiments using a long‐term induced canine phonation model, we required a tracheostomy that was placed as low as possible, to maximize the subglottic space superior to the stoma. The ideal experimental tracheostomy would also be safe and easy to perform, require no tracheostomy tube, and be low maintenance, requiring minimal cleaning or suctioning. Tracheostomies were performed in 37 dogs based on previously published methods. If the stoma was placed below the twelfth tracheal ring, the perioperative mortality rate was 57% because of kinking of the trachea and subsequent airway obstruction. When the tracheostomy was performed above this level, the mortality rate was reduced to 3%. A number of significant modifications in technique were made to achieve this improvement and resulted in the last 12 dogs having no complications. Several of the tracheostomies were maintained for more than 18 months. The method derived meets the above criteria for the ideal experimental tracheostomy and also meets our needs for a long‐term induced phonation model.
No increased inbreeding avoidance during the ovulatory phase of the menstrual cycle
Authors: Holzleitner Iris J. , Driebe Julie C. , Arslan Ruben C. , Hahn Amanda C. , Lee Anthony J. , O'Shea Kieran J. , Gerlach Tanja M. , Penke Lars , Jones Benedict C. , DeBruine Lisa M.
Published: September 2022

Mate preferences and mating-related behaviors are hypothesized to change over the menstrual cycle to increase reproductive fitness. Recent large-scale studies suggest that previously reported hormone-linked behavioral changes are not robust. The proposal that women's preference for associating with male kin is down-regulated during the ovulatory (high-fertility) phase of the menstrual cycle to reduce inbreeding has not been tested in large samples. Consequently, we investigated the relationship between longitudinal changes in women's steroid hormone levels and their perceptions of faces experimentally manipulated to possess kinship cues (Study 1). Women viewed faces displaying kinship cues as more attractive and trustworthy, but this effect was not related to hormonal proxies of conception risk. Study 2 employed a daily diary approach and found no evidence that women spent less time with kin generally or with male kin specifically during the fertile phase of the menstrual cycle. Thus, neither study found evidence that inbreeding avoidance is up-regulated during the ovulatory phase of the menstrual cycle.
An assessment of hydrogen sulfide intrusion in the seagrass Halodule wrightii
Authors: Rubiano-Rincon Sebastian , Larkin Patrick D.
Published: September 2022

Hydrogen sulfide (H2S, “sulfide”) is a naturally occurring component of the marine sediment. Eutrophication of coastal waters, however, can lead to an excess of sulfide production that can prove toxic to seagrasses. We used stable sulfur isotope ratio (δ34S) measurements to assess sulfide intrusion in the seagrass Halodule wrightii, a semi-tropical species found throughout the Gulf of Mexico, Caribbean Sea, and both western and eastern Atlantic coasts. We found a gradient in δ34S values (−5.58 ± 0.54‰+13.58 ± 0.30‰) from roots to leaves, in accordance with prior observations and those from other species. The results may also represent the first values reported for H. wrightii rhizome tissue. The presence of sulfide-derived sulfur in varying proportions (15–55%) among leaf, rhizome, and root tissues suggests H. wrightii is able to assimilate sedimentary H2S into non-toxic forms that constitute a significant portion of the plant’s total sulfur content.
Superhydrophobic surface immobilisation by insoluble surfactant
Authors: Mayer Michael D. , Crowdy Darren G.
Published: September 2022

The effects of insoluble surfactants, satisfying a Langmuir equation of state, on transverse Stokes flow over a superhydrophobic surface of unidirectional grooves with flat menisci are examined. The phenomenon of surface immobilisation, whereby surfactants cause part or all of the Cassie-state menisci to become effectively no-slip zones thereby degrading the slip properties of the surface, is of primary interest. The study employs a combined analytical and numerical approach allowing an exploration of surfactant effects over the full range of surface Péclet numbers, Marangoni numbers and surfactant loads. For small surface Péclet and Marangoni numbers, perturbation theory is used to gain basic insights into the physical mechanisms at work. That analysis also provides checks on a robust numerical scheme, built around a complex variable formulation of the problem, used to compute solutions across a wide range of non-dimensional parameter values. Two distinct mechanisms are found to be responsible for surface immobilisation. In the first, most commonly seen at higher surface Péclet numbers, a stagnant cap forms because swept surfactant immobilises a section of the meniscus before any portion of the meniscus reaches maximum packing. Such a cap exists even for a linear equation of state and grows in length with increasing Marangoni number. A second immobilisation mechanism is associated with the nonlinear equation of state: an immobilised region forms because the surfactant concentration reaches its maximum value near the downstream edge of the meniscus. Immobilisation of the latter form can occur at much lower surface Péclet numbers, even if the Marangoni number is small, as long as there is sufficient surfactant in the system. The study enhances understanding of how insoluble surfactants can degrade slip over superhydrophobic surfaces.
Electro-vortex flows in a cylindrical cell under axial magnetic field
Authors: Frick Peter , Mandrykin Sergei , Eltishchev Vladislav , Kolesnichenko Ilya
Published: September 2022

Liquid metal flows, generated in a cylindrical cell by a strong electric current flowing from the central bottom electrode to the sidewall, are studied experimentally and numerically. In the absence of an external magnetic field, the flow is caused by the interaction of the electric current with its own magnetic field and is known as electro-vortex flows (EVF), which has a pure poloidal configuration. It is also well known that even a relatively weak azimuthal force (which immediately arises if a vertical external magnetic field is applied) induces a swirl that completely changes the structure of the flow, suppressing the poloidal motion (Davidson et al., Eur. J. Mech. B Fluids, vol. 18, 1999, pp. 693–711). We study the steady-state modes and analyse the dynamics of transient modes, following the evolution of the flow structure at different ratios of azimuthal and poloidal Lorentz forces, governed by the applied current and vertical magnetic field. In the considered problem, the peculiarities of transient modes, leading to the suppression of the poloidal flow, are associated with the fact that the domain of acting forces is localized in the vicinity of the bottom electrode. The scenario of flow evolution strongly depends on the ratio of electro-vortex and rotational forces (whether the EVF has time to form before a noticeable swirl of the metal, or the swirl dominates from the beginning of flow evolution).
A multi-purposed unsupervised framework for comparing embeddings of undirected and directed graphs
Authors: Kamiński Bogumił , Kraiński Łukasz , Prałat Paweł , Théberge François
Published: September 2022

Graph embedding is a transformation of nodes of a network into a set of vectors. A good embedding should capture the underlying graph topology and structure, node-to-node relationship, and other relevant information about the graph, its subgraphs, and nodes themselves. If these objectives are achieved, an embedding is a meaningful, understandable, and often compressed representation of a network. Unfortunately, selecting the best embedding is a challenging task and very often requires domain experts. In this paper, we extend the framework for evaluating graph embeddings that was recently introduced in [15]. Now, the framework assigns two scores, local and global, to each embedding that measure the quality of an evaluated embedding for tasks that require good representation of local and, respectively, global properties of the network. The best embedding, if needed, can be selected in an unsupervised way, or the framework can identify a few embeddings that are worth further investigation. The framework is flexible and scalable and can deal with undirected/directed and weighted/unweighted graphs.
Left atrial thrombosis with invasive pulmonary aspergillosis in children with immunodeficiency
Authors: Yun Kyoung Sung , Kwon Hye Won , Kwak Jae Gun , Park June Dong , Koh Jaemoon
Published: September 2022

Invasive aspergillosis is a major cause of infectious disease in immunocompromised patients; however, cardiac involvement in pulmonary aspergillosis is not well-known. Two paediatric patients undergoing chemotherapy were diagnosed with cardiac aspergilloma, accompanied by pulmonary aspergillosis. In both patients, antibiotic and antifungal treatments were initiated immediately after the pneumonia was diagnosed; however, both died of multiple cerebral thromboembolisms.
The MITRIS RESILIA mitral valve is a safe and effective option for mitral valve replacement in young patients requiring mitral valve replacement
Authors: Heye Thomas , Reemtsen Brian , Greiten Lawrence
Published: September 2022

We report the first successful implantation in the United States of a novel mitral valve (MITRIS RESILIA by Edwards Lifesciences) in a patient with history of mitral valve replacement at a young age. This new bioprosthetic valve offers a unique profile and innovative option for mitral valve replacement in patients who are at risk of left ventricular outflow tract obstruction.
Predictors of increased postoperative length of stay after complete atrioventricular canal repair
Authors: Habermann Alyssa C. , Meza James M. , Dischinger Ashley N. , Kang Lillian , Prabhu Neel K. , Benkert Abigail R. , Turek Joseph W. , Andersen Nicholas D.
Published: September 2022

Background:

The optimal timing of surgical repair for infants with complete atrioventricular canal defect remains controversial, as there are risks to both early and late repair. We address this debate by investigating the association of various risk factors, including age and weight at surgery, markers of failure to thrive, and pulmonary vascular disease, with postoperative length of stay following complete atrioventricular canal repair.

Methods:

Infants who underwent repair of complete atrioventricular canal were identified from our institutional Society of Thoracic Surgeons Congenital Heart Surgery Database. Additional clinical data were collected from the electronic medical record. Descriptive statistics were computed. Associations between postoperative length of stay and covariates of interest were evaluated using linear regression with bootstrap aggregation.

Results:

From 2001 to 2020, 150 infants underwent isolated complete atrioventricular canal repair at our institution. Pre-operative failure to thrive and evidence of pulmonary disease were common. Surgical mortality was 2%. In univariable analysis, neither weight nor age at surgery were associated with mortality, postoperative length of stay, duration of mechanical ventilation, or post-operative severe valvular regurgitation. In multivariable analysis of demographic and preoperative clinical factors using bootstrap aggregation, increased postoperative length of stay was only significantly associated with previous pulmonary artery banding (33.9 day increase, p = 0.03) and preoperative use of supplemental oxygen (19.9 day increase, p = 0.03).

Conclusions:

Our analysis shows that previous pulmonary artery banding and preoperative use of supplemental oxygen were associated with increased postoperative length of stay after complete atrioventricular canal repair, whereas age and weight were not. These findings suggest operation prior to the onset of pulmonary involvement may be more important than reaching age or weight thresholds.
PONTRYAGIN DUALITY FOR VARIETIES OVER p-ADIC FIELDS
Authors: Geisser Thomas H. , Morin Baptiste
Published: September 2022

We define cohomological complexes of locally compact abelian groups associated with varieties over p-adic fields and prove a duality theorem under some assumption. Our duality takes the form of Pontryagin duality between locally compact motivic cohomology groups.
Species Traits and Geomorphic Setting as Drivers of Global Soil Carbon Stocks in Seagrass Meadows
Authors: Kennedy H. , Pagès J. F. , Lagomasino D. , Arias‐Ortiz A. , Colarusso P. , Fourqurean J. W. , Githaiga M. N. , Howard J. L. , Krause‐Jensen D. , Kuwae T. , Lavery P. S. , Macreadie P. I. , Marbà N. , Masqué P. , Mazarrasa I. , Miyajima T. , Serrano O. , Duarte C. M.
Published: September 2022

Our knowledge of the factors that can influence the stock of organic carbon (OC) that is stored in the soil of seagrass meadows is evolving, and several causal effects have been used to explain the variation of stocks observed at local to national scales. To gain a global‐scale appreciation of the drivers that cause variation in soil OC stocks, we compiled data on published species‐specific traits and OC stocks from monospecific and mixed meadows at multiple geomorphological settings. Species identity was recognized as an influential driver of soil OC stocks, despite their large intraspecific variation. The most important seagrass species traits associated with OC stocks were the number of leaves per seagrass shoot, belowground biomass, leaf lifespan, aboveground biomass, leaf lignin, leaf breaking force and leaf OC plus the coastal geomorphology of the area, particularly for lagoon environments. A revised estimate of the global average soil OC stock to 20 cm depth of 15.4 Mg C ha−1 is lower than previously reported. The largest stocks were still recorded in Mediterranean seagrass meadows. Our results specifically identify Posidonia oceanica from the Mediterranean and, more generally, large and persistent species as key in providing climate regulation services, and as priority species for conservation for this specific ecosystem service.
Impact of Resolution on the Representation of the Mean and Extreme Winds Along Nares Strait
Authors: Moore G. W. K. , Imrit A. A.
Published: September 2022

Nares Strait is the long and narrow strait bounded by steep topography that connects the Arctic Ocean's Lincoln Sea to the North Atlantic's Baffin Bay. The winds that blow along the strait play an important role in modulating ice and water exports from the Arctic Ocean as well as in helping to establish the Arctic's largest and most productive polynya that forms at its southern terminus. However, its remote location has limited our knowledge of the winds along the strait. Here we use weather station data from the region as well as two reanalyses and an operational analysis with nominal horizontal resolutions that vary from ∼30 to ∼2.5 km to characterize the wind field in the vicinity of the strait. The strait has a width that varies from ∼40 to ∼100 km and as such the wind field is typically ageostrophic and controlled by the pressure gradient in the along‐strait direction. We show that model resolution plays a role in the representation of both the mean and extreme winds along the strait through the ability to represent this ageostrophic flow. Higher windspeeds occur in the vicinity of Smith Sound and are associated with a left‐hand corner jet. Kane Basin, the widest section of the strait, is characterized by a gradient in windspeed with higher speeds in the center of the basin and lower winds in the eastern basin that is the result of sheltering by the steep topography of the upstream Washington Land peninsula.
On the Resolution of Triangular Meshes
Authors: Danilov S.
Published: September 2022

It is generally agreed that the resolution of a regular quadrilateral mesh is the side length of quadrilateral cells. There is less agreement on the resolution of triangular meshes, exacerbated by the fact that the numbers of edges or cells on triangular meshes are approximately three or two times larger than that of vertices. However, the geometrical resolution of triangular meshes, that is, maximum wavenumbers or smallest wavelengths that can be represented on such meshes, is a well defined quantity, known from solid state physics. These wavenumbers are related to a smallest common mesh cell (primitive unit cell), and the set of mesh translations that map it into itself. They do not depend on whether discrete degrees of freedom are placed on vertices, cells or edges. For equilateral triangles the smallest wavelength equals twice the triangle height. Resolutions of quadrilateral and triangular meshes approximately agree if they have the same numbers of vertices.
Backed‐Up, Saturated, and Stagnant: Effect of Milldams on Upstream Riparian Groundwater Hydrologic and Mixing Regimes
Authors: Sherman Melissa , Hripto Johanna , Peck Erin K. , Gold Arthur J. , Peipoch Marc , Imhoff Paul , Inamdar Shreeram
Published: September 2022

How milldams alter riparian hydrologic and groundwater mixing regimes is not well understood. Understanding the effects of milldams and their legacies on riparian hydrology is key to assessing riparian pollution buffering potential and for making appropriate watershed management decisions. We examined the spatiotemporal effects of milldams on groundwater gradients, flow directions, and mixing regime for two dammed sites on Chiques Creek, Pennsylvania (2.4 m tall milldam), and Christina River, Delaware (4 m tall dam), USA. Riparian groundwater levels were recorded every 30 min for multiple wells and transects. Groundwater mixing regime was characterized using 30‐min specific conductance data and selected chemical tracers measured monthly for about 2 years. Three distinct regimes were identified for riparian groundwaters—wet, dry, and storm. Riparian groundwater gradients above the dam were low but were typically from the riparian zone to the stream. These flow directions were reversed (stream to riparian) during dry periods due to riparian evapotranspiration losses and during peak stream flows. Longitudinal (parallel to the stream) riparian flow gradients and directions also varied across the hydrologic regimes. Groundwater mixing varied spatially and temporally between storms and seasons. Near‐stream groundwater was poorly flushed or mixed during storms whereas that in the adjacent swales revealed greater mixing. This differential groundwater behavior was attributed to milldam legacies that include: berm and swale topography that influenced the routing of surface waters, varying riparian legacy sediment depths and hydraulic conductivities, evapotranspiration losses from riparian vegetation, and runoff input from adjoining roads.
The resurrection of RIP kinase 1 as an early cell death checkpoint regulator—a potential target for therapy in the necroptosis era
Authors: Ju Eunjin , Park Kyeong Ah , Shen Han-Ming , Hur Gang Min
Published: September 2022

Receptor-interacting serine threonine protein kinase 1 (RIPK1) has emerged as a central molecular switch in controlling the balance between cell survival and cell death. The pro-survival role of RIPK1 in maintaining cell survival is achieved via its ability to induce NF-κB-dependent expression of anti-apoptotic genes. However, recent advances have identified the pro-death function of RIPK1: posttranslational modifications of RIPK1 in the tumor necrosis factor receptor 1 (TNFR1)-associated complex-I, in the cytosolic complex-IIb or in necrosomes regulate the cytotoxic potential of RIPK1, forming an early cell death checkpoint. Since the kinase activity of RIPK1 is indispensable in RIPK3- and MLKL-mediated necroptosis induction, while it is dispensable in apoptosis, a better understanding of this early cell death checkpoint via RIPK1 might lead to new insights into the molecular mechanisms controlling both apoptotic and necroptotic modes of cell death and help develop novel therapeutic approaches for cancer. Here, we present an emerging view of the regulatory mechanisms for RIPK1 activity, especially with respect to the early cell death checkpoint. We also discuss the impact of dysregulated RIPK1 activity in pathophysiological settings and highlight its therapeutic potential in treating human diseases.
HMG20B stabilizes association of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block
Authors: Maiques-Diaz Alba , Nicosia Luciano , Basma Naseer J. , Romero-Camarero Isabel , Camera Francesco , Spencer Gary J. , Amaral Fabio M. R. , Simeoni Fabrizio , Wingelhofer Bettina , Williamson Andrew J. K. , Pierce Andrew , Whetton Anthony D. , Somervaille Tim C. P.
Published: September 2022

Pharmacologic inhibition of LSD1 induces molecular and morphologic differentiation of blast cells in acute myeloid leukemia (AML) patients harboring MLL gene translocations. In addition to its demethylase activity, LSD1 has a critical scaffolding function at genomic sites occupied by the SNAG domain transcription repressor GFI1. Importantly, inhibitors block both enzymatic and scaffolding activities, in the latter case by disrupting the protein:protein interaction of GFI1 with LSD1. To explore the wider consequences of LSD1 inhibition on the LSD1 protein complex we applied mass spectrometry technologies. We discovered that the interaction of the HMG-box protein HMG20B with LSD1 was also disrupted by LSD1 inhibition. Downstream investigations revealed that HMG20B is co-located on chromatin with GFI1 and LSD1 genome-wide; the strongest HMG20B binding co-locates with the strongest GFI1 and LSD1 binding. Functional assays demonstrated that HMG20B depletion induces leukemia cell differentiation and further revealed that HMG20B is required for the transcription repressor activity of GFI1 through stabilizing LSD1 on chromatin at GFI1 binding sites. Interaction of HMG20B with LSD1 is through its coiled-coil domain. Thus, HMG20B is a critical component of the GFI1:LSD1 transcription repressor complex which contributes to leukemia cell differentiation block.
Unveiling caspase-2 regulation by non-coding RNAs
Authors: Zhao Yun , Dhani Shanel , Zhivotovsky Boris
Published: September 2022

Non-coding RNAs (ncRNAs) are a group of RNA molecules, such as small nucleolar RNAs, circular RNAs (circRNAs), microRNAs (miRNAs) and long-noncoding RNAs (ncRNAs), that do not encode proteins. Although their biofunctions are not well-understood, many regulatory ncRNAs appear to be highly involved in regulating the transcription and translation of several genes that have essential biological roles including cell differentiation, cell death, metabolism, tumorigenesis and so on. A growing number of studies have revealed the associations between dysregulated ncRNAs and caspases involved in cell death in numerous human diseases. As one of the initiator and executor caspases, caspase-2 is the most evolutionally conserved caspase in mammals, exerting both apoptotic and non-apoptotic functions. A great deal of studies has shown the involvement of caspase-2 as a tumor suppressor in multiple oncogene-driven cancers, and yet a comprehensive understanding of its biological roles remains largely unknown. In this review, we highlight a compilation of studies focused on the interaction between caspase-2 and miRNAs/lncRNAs in the context of different diseases in order to deepen our knowledge on the regulatory biofunctions of caspase-2 and, furthermore, provide more insight into understanding the role that ncRNAs/caspase-2 axis plays in the development of human diseases.
TrkC, a novel prognostic marker, induces and maintains cell survival and metastatic dissemination of Ewing sarcoma by inhibiting EWSR1-FLI1 degradation
Authors: Kim Min Soo , Lee Won Sung , Lee Hanki , Jin Wook
Published: September 2022

Upregulation of EWSR1-FLI1 expression has been associated with invasiveness, induced cell survival, metastatic dissemination, and acquisition of self-renewal traits in Ewing sarcoma (ES). Although existing evidence implies that TrkC expression is linked to the pathogenesis of other cancer types, its role and the mechanism behind its correlation with EWSR1-FLI1 in the pathogenesis of ES remain unclear. In this study, we uncovered a novel physiological role of TrkC as a key regulator of EWSR1-FLI1 involved in the survival and metastatic dissemination of ES. TrkC was observed to be frequently overexpressed in human metastatic ES cells in vitro and in vivo, facilitating enhanced survival, tumorigenicity, and metastasis of ES cells. TrkC-mediated metastasis of ES cells was induced by the inhibition of the proteasomal degradation of EWSR1-FLI1 via the TrkC/EWSR1-FLI1 complex, which subsequently enabled the induction of the target proteins, EGR2 and NKX2.2. Moreover, TrkC significantly inhibited tumor suppressor activity of TGF-β through reduction of the mRNA expression of one of its receptors, TGFBR2 via TrkC-induced stabilization of EWSR1-FLI1. Furthermore, loss of TrkC expression inhibited tumor growth and metastasis in experimental mouse models. This study is the first to report the involvement and functional role of TrkC in the pathogenesis of ES, suggesting important implications for understanding the alterations of TrkC in Ewing tumors.
Loss of SNAI1 induces cellular plasticity in invasive triple-negative breast cancer cells
Authors: Tsirigoti Chrysoula , Ali Mohamad Moustafa , Maturi Varun , Heldin Carl-Henrik , Moustakas Aristidis
Published: September 2022

The transcription factor SNAI1 mediates epithelial-mesenchymal transition, fibroblast activation and controls inter-tissue migration. High SNAI1 expression characterizes metastatic triple-negative breast carcinomas, and its knockout by CRISPR/Cas9 uncovered an epithelio-mesenchymal phenotype accompanied by reduced signaling by the cytokine TGFβ. The SNAI1 knockout cells exhibited plasticity in differentiation, drifting towards the luminal phenotype, gained stemness potential and could differentiate into acinar mammospheres in 3D culture. Loss of SNAI1 de-repressed the transcription factor FOXA1, a pioneering factor of mammary luminal progenitors. FOXA1 induced a specific gene program, including the androgen receptor (AR). Inhibiting AR via a specific antagonist regenerated the basal phenotype and blocked acinar differentiation. Thus, loss of SNAI1 in the context of triple-negative breast carcinoma cells promotes an intermediary luminal progenitor phenotype that gains differentiation plasticity based on the dual transcriptional action of FOXA1 and AR. This function of SNAI1 provides means to separate cell invasiveness from progenitor cell de-differentiation as independent cellular programs.
Observations of a Magellanic Corona
Authors: Krishnarao Dhanesh , Fox Andrew J. , D’Onghia Elena , Wakker Bart P. , Cashman Frances H. , Howk J. Christopher , Lucchini Scott , French David M. , Lehner Nicolas
Published: September 2022

The Large Magellanic Cloud (LMC) and the Small Magellanic Cloud (SMC) are the closest massive satellite galaxies of the Milky Way. They are probably on their first passage on an infalling orbit towards our Galaxy1 and trace the continuing dynamics of the Local Group2. Recent measurements of a high mass for the LMC (Mhalo ≈ 1011.1–11.4 M⊙)3–6 imply that the LMC should host a Magellanic Corona: a collisionally ionized, warm-hot gaseous halo at the virial temperature (105.3–5.5 K) initially extending out to the virial radius (100–130 kiloparsecs (kpc)). Such a corona would have shaped the formation of the Magellanic Stream7, a tidal gas structure extending over 200° across the sky2,8,9 that is bringing in metal-poor gas to the Milky Way10. Here we show evidence for this Magellanic Corona with a potential direct detection in highly ionized oxygen (O+5) and indirectly by means of triply ionized carbon and silicon, seen in ultraviolet (UV) absorption towards background quasars. We find that the Magellanic Corona is part of a pervasive multiphase Magellanic circumgalactic medium (CGM) seen in many ionization states with a declining projected radial profile out to at least 35 kpc from the LMC and a total ionized CGM mass of log10(MH II,CGM/M⊙) ≈ 9.1 ± 0.2. The evidence for the Magellanic Corona is a crucial step forward in characterizing the Magellanic group and its nested evolution with the Local Group.
Universal control of a six-qubit quantum processor in silicon
Authors: Philips Stephan G. J. , Mądzik Mateusz T. , Amitonov Sergey V. , de Snoo Sander L. , Russ Maximilian , Kalhor Nima , Volk Christian , Lawrie William I. L. , Brousse Delphine , Tryputen Larysa , Wuetz Brian Paquelet , Sammak Amir , Veldhorst Menno , Scappucci Giordano , Vandersypen Lieven M. K.
Published: September 2022

Future quantum computers capable of solving relevant problems will require a large number of qubits that can be operated reliably1. However, the requirements of having a large qubit count and operating with high fidelity are typically conflicting. Spins in semiconductor quantum dots show long-term promise2,3but demonstrations so far use between one and four qubits and typically optimize the fidelity of either single- or two-qubit operations, or initialization and readout4–11. Here, we increase the number of qubits and simultaneously achieve respectable fidelities for universal operation, state preparation and measurement. We design, fabricate and operate a six-qubit processor with a focus on careful Hamiltonian engineering, on a high level of abstraction to program the quantum circuits, and on efficient background calibration, all of which are essential to achieve high fidelities on this extended system. State preparation combines initialization by measurement and real-time feedback with quantum-non-demolition measurements. These advances will enable testing of increasingly meaningful quantum protocols and constitute a major stepping stone towards large-scale quantum computers.
Galaxy clusters enveloped by vast volumes of relativistic electrons
Authors: Cuciti V. , de Gasperin F. , Brüggen M. , Vazza F. , Brunetti G. , Shimwell T. W. , Edler H. W. , van Weeren R. J. , Botteon A. , Cassano R. , Di Gennaro G. , Gastaldello F. , Drabent A. , Röttgering H. J. A. , Tasse C.
Published: September 2022

The central regions of galaxy clusters are permeated by magnetic fields and filled with relativistic electrons1. When clusters merge, the magnetic fields are amplified and relativistic electrons are re-accelerated by turbulence in the intracluster medium2,3. These electrons reach energies of 1–10 GeV and, in the presence of magnetic fields, produce diffuse radio halos4 that typically cover an area of  around 1 Mpc2. Here we report observations of four clusters whose radio halos are embedded in much more extended, diffuse radio emission, filling a volume 30 times larger than that of radio halos. The emissivity in these larger features is about 20 times lower than the emissivity in radio halos. We conclude that relativistic electrons and magnetic fields extend far beyond radio halos, and that the physical conditions in the outer regions of the clusters are quite different from those in the radio halos.
Thalamus-driven functional populations in frontal cortex support decision-making
Authors: Yang Weiguo , Tipparaju Sri Laasya , Chen Guang , Li Nuo
Published: September 2022

Neurons in frontal cortex exhibit diverse selectivity representing sensory, motor and cognitive variables during decision-making. The neural circuit basis for this complex selectivity remains unclear. We examined activity mediating a tactile decision in mouse anterior lateral motor cortex in relation to the underlying circuits. Contrary to the notion of randomly mixed selectivity, an analysis of 20,000 neurons revealed organized activity coding behavior. Individual neurons exhibited prototypical response profiles that were repeatable across mice. Stimulus, choice and action were coded nonrandomly by distinct neuronal populations that could be delineated by their response profiles. We related distinct selectivity to long-range inputs from somatosensory cortex, contralateral anterior lateral motor cortex and thalamus. Each input connects to all functional populations but with differing strength. Task selectivity was more strongly dependent on thalamic inputs than cortico-cortical inputs. Our results suggest that the thalamus drives subnetworks within frontal cortex coding distinct features of decision-making.
Time-dependent exchange creates the time-frustrated state of matter
Authors: Valiulin V. E. , Chtchelkatchev N. M. , Mikheyenkov A. V. , Vinokur V. M.
Published: September 2022

Magnetic systems governed by exchange interactions between magnetic moments harbor frustration that leads to ground state degeneracy and results in the new topological state often referred to as a frustrated state of matter (FSM). The frustration in the commonly discussed magnetic systems has a spatial origin. Here we demonstrate that an array of nanomagnets coupled by the real retarded exchange interactions develops a new state of matter, time frustrated matter (TFM). In a spin system with the time-dependent retarded exchange interaction, a single spin-flip influences other spins not instantly but after some delay. This implies that the sign of the exchange interaction changes, leading to either ferro- or antiferromagnetic interaction, depends on time. As a result, the system’s temporal evolution is essentially non-Markovian. The emerging competition between different magnetic orders leads to a new kind of time-core frustration. To establish this paradigmatic shift, we focus on the exemplary system, a granular multiferroic, where the exchange transferring medium has a pronounced frequency dispersion and hence develops the TFM.
Comprehensive transcriptome analysis of sika deer antler using PacBio and Illumina sequencing
Authors: Zhang Ranran , Dong Yimeng , Xing Xiumei
Published: September 2022

Antler is the fastest growing and ossifying tissue in animals and it is a valuable model for cartilage/bone development. To understand the molecular mechanisms of chondrogenesis and osteogenesis of antlers, the PacBio Sequel II and Illumina sequencing technology were combined and used to investigate the mRNA expression profiles in antler tip, middle, and base at six different developmental stages, i.e., at 15th, 25th, 45th, 65th, 100th and 130th growth days. Consequently, we identified 24,856 genes (FPKM > 0.1), including 8778 novel genes. Besides, principal component analysis (PCA) revealed a significant separation between the growth stage (25th, 45th and 65th days) and ossification stage (100th and 130th days). COL2A1 gene was significantly abundant in the growth stage, whereas S100A7, S100A12, S100A8, and WFDC18 genes were abundant at the ossification stage. Subsequently screened to 14,765 significantly differentially expressed genes (DEGs), WGCNA and GO functional enrichment analyses revealed that genes related to cell division and chondrocyte differentiation were up-regulated, whereas those with steroid hormone-mediated signaling pathways were down-regulated at ossification stages. Additionally, 25 tumor suppressor genes and 11 oncogenes were identified and were predicted to interact with p53. Co-regulation of tumor suppressor genes and oncogenes is responsible for the special growth pattern of antlers. Together, we constructed the most complete sika deer antler transcriptome database so far. The database provides data support for subsequent studies on the molecular mechanism of sika deer antler chondrogenesis and osteogenesis.
tDCS modulates speech perception and production in second language learners
Authors: Borodkin Katy , Gassner Tamar , Ershaid Hadeel , Amir Noam
Published: September 2022

Accurate identification and pronunciation of nonnative speech sounds can be particularly challenging for adult language learners. The current study tested the effects of a brief musical training combined with transcranial direct current stimulation (tDCS) on speech perception and production in a second language (L2). The sample comprised 36 native Hebrew speakers, aged 18–38, who studied English as L2 in a formal setting and had little musical training. Training encompassed musical perception tasks with feedback (i.e., timbre, duration, and tonal memory) and concurrent tDCS applied over the left posterior auditory-related cortex (including posterior superior temporal gyrus and planum temporale). Participants were randomly assigned to anodal or sham stimulation. Musical perception, L2 speech perception (measured by a categorical AXB discrimination task) and speech production (measured by a speech imitation task) were tested before and after training. There were no tDCS-dependent effects on musical perception post-training. However, only participants who received active stimulation showed increased accuracy of L2 phoneme discrimination and greater change in the acoustic properties of L2 speech sound production (i.e., second formant frequency in vowels and center of gravity in consonants). The results of this study suggest neuromodulation can facilitate the processing of nonnative speech sounds in adult learners.
Functional connectivity of brain networks with three monochromatic wavelengths: a pilot study using resting-state functional magnetic resonance imaging
Authors: Argilés Marc , Sunyer-Grau Bernat , Arteche-Fernandez Sílvia , Peña-Gómez Cleofé
Published: September 2022

Exposure to certain monochromatic wavelengths can affect non-visual brain regions. Growing research indicates that exposure to light can have a positive impact on health-related problems such as spring asthenia, circadian rhythm disruption, and even bipolar disorders and Alzheimer’s. However, the extent and location of changes in brain areas caused by exposure to monochromatic light remain largely unknown. This pilot study (N = 7) using resting-state functional magnetic resonance shows light-dependent functional connectivity patterns on brain networks. We demonstrated that 1 min of blue, green, or red light exposure modifies the functional connectivity (FC) of a broad range of visual and non-visual brain regions. Largely, we observed: (i) a global decrease in FC in all the networks but the salience network after blue light exposure, (ii) a global increase in FC after green light exposure, particularly noticeable in the left hemisphere, and (iii) a decrease in FC on attentional networks coupled with a FC increase in the default mode network after red light exposure. Each one of the FC patterns appears to be best arranged to perform better on tasks associated with specific cognitive domains. Results can be relevant for future research on the impact of light stimulation on brain function and in a variety of health disciplines.
Smart joints: auto-cleaning mechanism in the legs of beetles
Authors: Nadein Konstantin , Gorb Stanislav
Published: September 2022

The auto-cleaning system in digging forelegs of the Congo rose chaferPachnoda marginatafemoro-tibial joint is described. The cleaning system consists of four subsystems: three external ones represented by microsetal pad, hairy brush and scraper and one internal one. They work proactively not only removing contaminants, but also preventing them from entering the joint. The principle of functioning of the cleaning system is based on the sliding of the contacting surfaces of the joint, equipped with hairs, bristles and scrapers. The mutual movement of such surfaces leads to the shift of contaminating particles and, ultimately, to their removal from surfaces of the joint. The key feature of the joint cleaning system is its complete autonomy, in which cleaning is performed constantly with each movement of the femoro-tibial joint without special actions required from the insect. The difference between the auto-cleaning system and self-cleaning and active grooming is also discussed.