bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome profiling reveals that foliar water uptake occurs with C3 and crassulacean acid metabolism facultative photosynthesis inTamarix ramosissimaunder extreme drought
Authors: Yan Xia , Chang Yan , Zhao Weijia , Qian Chaoju , Yin Xiaoyue , Fan Xingke , Zhu Xinyu , Zhao Xiangqiang , Ma Xiao-Fei
Published: January 2022

Tamarix ramosissima is a typical desert plant species that is widely distributed in the desert areas of Northwest China. It plays a significant role in sand fixation and soil water conservation. In particular, how it uses water to survive in the desert plays an important role in plant growth and ecosystem function. Previous studies have revealed that T. ramosissima can alleviate drought by absorbing water from its leaves under extreme drought conditions. To date, there is no clear molecular regulation mechanism to explain foliar water uptake (FWU). In the present study, we correlated diurnal meteorological data, sap flow and photosynthetic parameters to determine the physical and biological characteristics of FWU. Our results suggested that the lesser the groundwater, the easier it is for T. ramosissima to absorb water via the leaves. Gene ontology annotation and Kyoto Encyclopaedia of Genes and Genomes pathway analysis of the transcriptome profile of plants subjected to high humidity suggested that FWU was highly correlated to carbohydrate metabolism, energy transfer, pyruvate metabolism, hormone signal transduction and plant–pathogen interaction. Interestingly, as a C3 plant, genes such as PEPC, PPDK, MDH and RuBP, which are involved in crassulacean acid metabolism (CAM) photosynthesis, were highly upregulated and accompanied by FWU. Therefore, we proposed that in the case of sufficient water supply, C3 photosynthesis is used in T. ramosissima, whereas in cases of extreme drought, starch is degraded to provide CO2 for CAM photosynthesis to make full use of the water obtained via FWU and the water that was transported or stored to assimilating branches and stems. This study may provide not only an important theoretical foundation for FWU and conversion from C3 plants to CAM plants but also for engineering improved photosynthesis in high-yield drought-tolerant plants and mitigation of climate change-driven drought.
Nose Tip Elongation and Elevation: A Novel Filler Injection Technique
Authors: Yu Arthur Y
Published: January 2022

Background

Filler injection for nose tip improvement remains a difficult treatment due to efficacy and safety issues.

Objectives

The authors sought to better the techniques and safety for nose tip improvement with a filler.

Methods

Patients seeking nose tip improvement were recruited regardless of their pretreatment conditions. A hyaluronic acid filler was injected through the skin behind the nose tip into the potential septal space. To achieve tip elevation, the filler was retro-injected from the anterior nasal spine, stopping at the mid-level of medial crura. To elongate the nose, the filler was deposited just in front of the caudal septal cartilage. The tip extended in the sagittal plane, causing the nose tip to move either caudally (tip elongation) or anteriorly (tip elevation), or both, as directed by the surgeon.

Results

Depending on the patients, the nose could be elongated by 2 to 6 mm, and the tip could be elevated by 2 to 8 mm. Additionally, stronger columellar support, finer tip structures, and improved nasolabial angle were observed. Interestingly, the upper lip appeared shorter. The nostril shapes and the alar widths were also improved. A total of 1288 cases are reported. Only 2 patients expressed dissatisfaction.

Conclusions

This technique is easy and safe to perform, and the results are natural and comparable with those from rhinoplasty surgeries. Further, this report of filler nose lengthening may be the first large series in the world. Finally, this technique works well in all populations.

Level of Evidence: 4
50 Years of Luna legacy
Authors: Bell Samantha , Joy Katherine , Moore Keith
Published: January 2022

50 years since the USSR's Luna 16, 20 and 24 missions gifted the world an important set of Moon rock samples. Samantha Bell, Katherine Joy and Keith Moore discuss the efforts of UK researchers and how the sample are to be preserved.
Hyperexcitable superior colliculus and fatal brainstem spreading depolarization in a model of Sudden Unexpected Death in Epilepsy
Authors: Cain Stuart M. , Bernier Louis-Philippe , Zhang Yiming , Yung Andrew C. , Kass Jennifer , Bohnet Barry , Yang Yi , Gopaul Rayshad , Kozlowski Piotr , MacVicar Brian A. , Snutch Terrance P.
Published: January 2022

Cardiorespiratory arrest and death in mouse models of sudden unexpected death in epilepsy occur when spreading depolarization is triggered by cortical seizures and then propagates to the brainstem. However, the critical brain regions and the specific changes required to allow spreading depolarization to propagate to the brainstem under the relatively rare circumstances leading to a fatal seizure are unknown. We previously found that following cortical seizure-inducing electrical stimulation, spreading depolarization could occur in both the superior and inferior colliculi in Cacna1aS218L mice, but was never observed in wild-type animals or following non-seizure-inducing stimuli in Cacna1aS218L mice. Here, we show that optogenetic stimulation of the superior/inferior colliculi in Cacna1aS218L mice induces severe seizures, and resulting spreading depolarization in the superior/inferior colliculi that propagates to the brainstem and correlates with the respiratory arrest followed by cardiac arrest. Further, we show that neurons of the superior colliculus in Cacna1aS218L mice exhibit hyperexcitable properties that we propose underlie a distinct susceptibility to spreading depolarization. Our data suggest that the susceptibility of the superior colliculus to elicit fatal spreading depolarization is a result of either genetic or seizure-related alterations within the superior colliculus that may involve changes to structure, connectivity and/or excitability.
Replicable patterns of causal information flow between hippocampus and prefrontal cortex during spatial navigation and spatial–verbal memory formation
Authors: Das Anup , Menon Vinod
Published: January 2022

Interactions between the hippocampus and prefrontal cortex (PFC) play an essential role in both human spatial navigation and episodic memory, but the underlying causal flow of information between these regions across task domains is poorly understood. Here we use intracranial EEG recordings and spectrally resolved phase transfer entropy to investigate information flow during two different virtual spatial navigation and memory encoding/recall tasks and examine replicability of information flow patterns across spatial and verbal memory domains. Information theoretic analysis revealed a higher causal information flow from hippocampus to lateral PFC than in the reverse direction. Crucially, an asymmetric pattern of information flow was observed during memory encoding and recall periods of both spatial navigation tasks. Further analyses revealed frequency specificity of interactions characterized by greater bottom-up information flow from hippocampus to PFC in delta–theta band (0.5–8 Hz); in contrast, top-down information flow from PFC to hippocampus was stronger in beta band (12–30 Hz). Bayesian analysis revealed a high degree of replicability between the two spatial navigation tasks (Bayes factor > 5.46e+3) and across tasks spanning the spatial and verbal memory domains (Bayes factor > 7.32e+8). Our findings identify a domain-independent and replicable frequency-dependent feedback loop engaged during memory formation in the human brain.
Implementation and Short-term Adverse Events of Anti-SARS-CoV-2 Vaccines in Inflammatory Bowel Disease Patients: An International Web-based Survey
Authors: Ellul Pierre , Revés Joana , Abreu Bárbara , Chaparro María , Gisbert Javier P , Allocca Mariangela , Fiorino Gionata , Barberio Brigida , Zingone Fabiana , Pisani Anthea , Cassar David , Michalopoulos George , Mantzaris Gerassimos , Koutroubakis Ioannis , Karmiris Konstantinos , Katsanos Konstantinos , Ďuricova Dana , Burisch Johan , Madsen Gorm Roager , Maaser Christian , Naila Arebi , Orfanoudaki Eleni , Milivojevic Vladimir , Buisson Anthony , Avedano Luisa , Leone Salvo , Torres Joana
Published: January 2022

Introduction

Anti-SARS-CoV-2 vaccine clinical trials did not include patients with immune-mediated conditions such as inflammatory bowel disease [IBD]. We aimed to describe the implementation of anti-SARS-CoV-2 vaccination among IBD patients, patients’ concerns, and the side effect profile of the anti-SARS-CoV-2 vaccines, using real-world data.

Methods

An anonymous web-based self-completed survey was distributed in 36 European countries between June and July 2021. The results of the patient characteristics, concerns, vaccination status, and side effect profile were analysed.

Results

In all 3272 IBD patients completed the survey, 79.6% had received at least one dose of anti-SARS-CoV-2 vaccine, and 71.7% had completed the vaccination process. Patients over 60 years old had a significantly higher rate of vaccination [p < 0.001]. Patients’ main concerns before vaccination were the possibility of having worse vaccine-related adverse events due to their IBD [24.6%], an IBD flare after vaccination [21.1%], and reduced vaccine efficacy due to IBD or associated immunosuppression [17.6%]. After the first dose of the vaccine, 72.4% had local symptoms and 51.4% had systemic symptoms [five patients had non-specified thrombosis]. Adverse events were less frequent after the second dose of the vaccine and in older patients. Only a minority of the patients were hospitalised [0.3%], needed a consultation [3.6%], or had to change IBD therapy [13.4%] after anti-SARS-CoV-2 vaccination.

Conclusions

Although IBD patients raised concerns about the safety and efficacy of anti-SARS-CoV-2 vaccines, the implementation of vaccination in those responding to our survey was high and the adverse events were comparable to the general population, with minimal impact on their IBD.
Acute ischaemic stroke and its challenges for the intensivist
Authors: Robba Chiara , van Dijk Ewoud J , van der Jagt Mathieu
Published: January 2022

Acute ischaemic stroke (AIS) is responsible for almost 90% of all strokes and is one of the leading causes of death and disability. Acute ischaemic stroke is caused by a critical alteration in focal cerebral blood flow (ischaemia) from a variety of causes, resulting in infarction. The primary cerebral injury due to AIS occurs in the first hours, therefore early reperfusion importantly impacts on patient outcome (‘Time is brain’ concept). Secondary cerebral damage progressively evolves over the following hours and days due to cerebral oedema, haemorrhagic transformation, and cerebral inflammation. Systemic complications, such as pneumonia, sepsis, and deep venous thrombosis, could also affect outcome. The risk of a recurrent ischaemic stroke is in particular high in the first days, which necessitate particular attention. The role of intensive care unit physicians is therefore to avoid or reduce the risk of secondary damage, especially in the areas where the brain is functionally impaired and ‘at risk’ of further injury. Therapeutic strategies therefore consist of restoration of blood flow and a bundle of medical, endovascular, and surgical strategies, which—when applied in a timely and consistent manner—can prevent secondary deterioration due to cerebral and systemic complications and recurrent stroke and improve short- and long-term outcomes. A multidisciplinary collaboration between neurosurgeons, interventional radiologists, neurologists, and intensivists is necessary to elaborate the best strategy for the treatment of these patients.
Design of novel hybrid secondary metabolite targets to diguanylate cyclase ofAcinetobacter baumannii
Authors: Tiwari Monalisa , Joshi Richa , Tiwari Vishvanath
Published: January 2022

Biofilm formation in bacteria is a resistance determinant and is positively regulated by cyclic diguanylate signaling. This signaling is a near universal signaling, and c-di-GMP produced by diguanylate cyclase (DGC) in this signaling is involved in different bacterial behaviors. The present study aims to find a plant-based novel hybrid therapeutic agent that can target the DGC of Acinetobacter baumannii. In this study, we have tried to design a hybrid molecule from the anti-biofilm plant secondary metabolites and screened its binding with the DGC of A. baumannii. The modeled and validated DGC was used to identify the active site and docking grid. Designed hybrid compounds were analysed for their interaction with the active site residues of DGC of A. baumannii. Further, the binding free energies of the docked complexes obtained from the Generalized Born model and Solvent Accessibility (MMGBSA) were analysed. The results indicated that VR-QEg-180 has a predicted high binding affinity with enzyme DGC as compared to other hybrids, parent secondary metabolites and positive control. Molecular dynamics simulation (MDS) analysis confirmed the interaction of VR-QEg-180 with DGC of the A. baumannii. The designed lead has favorable ADMET properties, has no human off-targets and has no predicted cytotoxicity in cell lines. Therefore, the designed hybrid molecule (VR-QEg-180) targeting the DGC of A. baumannii may play a very significant role in controlling this pathogen.
Unraveling the potential of non-conventional yeasts in biotechnology
Authors: Geijer C , Ledesma-Amaro R , Tomás-Pejó E
Published: January 2022

Cost-effective microbial conversion processes of renewable feedstock into biofuels and biochemicals are of utmost importance for the establishment of a robust bioeconomy. Conventional baker's yeast Saccharomyces cerevisiae, widely employed in biotechnology for decades, lacks many of the desired traits for such bioprocesses like utilization of complex carbon sources or low tolerance towards challenging conditions. Many non-conventional yeasts (NCY) present these capabilities, and they are therefore forecasted to play key roles in future biotechnological production processes. For successful implementation of NCY in biotechnology, several challenges including generation of alternative carbon sources, development of tailored NCY and optimization of the fermentation conditions are crucial for maximizing bioproduct yields and titers. Addressing these challenges requires a multidisciplinary approach that is facilitated through the ‘YEAST4BIO’ COST action. YEAST4BIO fosters integrative investigations aimed at filling knowledge gaps and excelling research and innovation, which can improve biotechnological conversion processes from renewable resources to mitigate climate change and boost transition towards a circular bioeconomy. In this perspective, the main challenges and research efforts within YEAST4BIO are discussed, highlighting the importance of collaboration and knowledge exchange for progression in this research field.
Anatomy of the perirectal fascia at the level of rectosacral fascia revisited
Authors: Ghareeb Waleed M , Wang Xiaojie , Chi Pan , Zheng Zhifang , Zhao Xiaozhen
Published: January 2022

Background

The relative anatomical understanding of the perirectal fasciae is of paramount importance for the proper performance of total mesorectal excision (TME). This study was to demonstrate the planes of TME and validates the intraoperative findings using cadaveric observations.

Methods

In this combined retrospective and prospective study, bilateral attachment of the rectosacral fascia (RSF) was observed in 28 cadaveric specimens (male, n = 14; female, n = 14). From January 2018 to December 2019, surgical videos of 67 patients who underwent laparoscopic TME at the Affiliated Union Hospital of Fujian Medical University (Fuzhou, China) were reviewed and interpreted with the cadaveric findings.

Results

The RSF (synonym: Waldeyer's fascia) is the end of the pre-hypogastric fascia at the level of S4 and comprises two layers (upper and lower). These two layers provide double fascial protection for the venous sacral plexus. It inserts into the fascia propria of the rectum along a broad horizontal arc that merges anterolaterally in an oblique downward direction until it meets the posterolateral merge of Denonvilliers' fascia at the lateral rectal ligament (LRL). This ligament does not look like a true ligament but is more likely to be a fascial combination that cushions the rectal innervation and middle rectal vessels.

Conclusions

Understanding the lateral attachment of RSF and its contribution to LRL provides invaluable surgical guidance to dissect this critical area. Therefore, lateral dissection is proposed from the anterior to the posterior direction to find the correct plane that guarantees an intact mesorectal envelope to protect the important nearby nerve structures.
Fractional Leibniz Rules Associated to Bilinear Hermite Pseudo-Multipliers
Authors: Ly Fu Ken , Naibo Virginia
Published: January 2022

We obtain a fractional Leibniz rule associated to bilinear Hermite pseudo-multipliers in the context of Hermite Besov and Hermite Triebel–Lizorkin spaces. As a byproduct, we show that the classes of bounded functions in these spaces (which include Hermite Sobolev and Hermite Hardy–Sobolev spaces) are algebras under pointwise multiplication. To obtain these results we develop appropriate decompositions for bilinear pseudo-multipliers and molecular estimates for certain families of functions in the Hermite setting.
One Swab Fits All: Performance of a Rapid, Antigen-Based SARS-CoV-2 Test Using a Nasal Swab, Nasopharyngeal Swab for Nasal Collection, and RT–PCR Confirmation from Residual Extraction Buffer
Authors: Stokes William , Berenger Byron M , Scott Brittney , Szelewicki Jonas , Singh Takshveer , Portnoy Danielle , Turnbull LeeAnn , Pabbaraju Kanti , Shokoples Sandy , Wong Anita A , Gill Kara , Hu Jia , Tipples Graham
Published: January 2022

Background

Point-of-care SARS-CoV-2 antigen tests have great potential to help combat the COVID-19 pandemic. In the performance of a rapid, antigen-based SARS-CoV-2 test (RAT), our study had 3 main objectives: to determine the accuracy of nasal swabs, the accuracy of using nasopharyngeal swabs for nasal collection (nasalNP), and the effectiveness of using residual extraction buffer for real-time reverse-transcriptase PCR (RT–PCR) confirmation of positive RAT (rPan).

Methods

Symptomatic adults recently diagnosed with COVID-19 in the community were recruited into the study. Nasal samples were collected using either a nasalNP or nasal swab and tested immediately with the RAT in the individual’s home by a health care provider. 500 µL of universal transport media was added to the residual extraction buffer after testing and sent to the laboratory for SARS-CoV-2 testing using RT–PCR. Parallel throat swabs tested with RT–PCR were used as the reference comparators.

Results

One hundred and fifty-five individuals were included in the study (99 nasal swabs, 56 nasalNP). Sensitivities of nasal samples tested on the RAT using either nasal or nasalNP were 89.0% [95% confidence interval (CI) 80.7%–94.6%] and 90.2% (95% CI 78.6%–96.7%), respectively. rPan positivity agreement compared to throat RT–PCR was 96.2%.

Conclusions

RAT reliably detect SARS-CoV-2 from symptomatic adults in the community presenting within 7 days of symptom onset using nasal swabs or nasalNP. High agreement with rPan can avoid the need for collecting a second swab for RT–PCR confirmation or testing of variants of concern from positive RAT in this population.
Cherish JB, a unique journal that originated from Japan
Authors: Miyazono Kohei
Published: January 2022

I would like to congratulate the Journal of Biochemistry (JB) on its 100th anniversary. I served as the Editor-in-Chief for four years starting in 2010 and succeeded Dr Naoyuki Taniguchi.
Rodolphe (1845–1905) and Maurice Kann (1839–1906)
Authors: Prevost-Marcilhacy Pauline
Published: January 2022

This study of two important German–Jewish collectors who settled in Paris, after 1866, Maurice (1839–1906) and Rodolphe (1845–1905) Kann, examines their place in French society. Based on unpublished archives, in particular the discovery of their wills (Archives Nationales, Paris) and their correspondence with Wilhelm von Bode (Berlin), it helps us to understand the evolution of the brothers’ collections and their practice of donation. Paradoxically, these two collectors escape any classification. Are they collectors? Are they patrons? They appear on the fringes of the group of collector figures of the late 1800s, and their activities show that the frontier between personal pleasure and speculation is porous. The article also raises the question of the role of dealers in the construction of a business focused on collection at the fin-de-siècle.
Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab
Authors: Ueda Kosuke , Suekane Shigetaka , Kurose Hirofumi , Ito Naoki , Ogasawara Naoyuki , Hiroshige Tasuku , Chikui Katsuaki , Ejima Kazuhisa , Uemura Keiichiro , Nakiri Makoto , Nishihara Kiyoaki , Igawa Tsukasa
Published: January 2022

Background

Immune checkpoint inhibitors cause various immune-related adverse events. The present study examined the association between the incidence of immune-related adverse events and survival outcomes in patients treated with nivolumab plus ipilimumab for patients with advanced renal cell carcinoma. In addition, we compared the effect of adverse event profiles on survival for patients receiving nivolumab plus ipilimumab.

Methods

A total of 35 patients with advanced renal cell carcinoma who were treated with nivolumab plus ipilimumab from August 2018 to August 2021 were retrospectively reviewed and analyzed. Cox proportional hazards models were used for univariate and multivariate analyses, and hazard ratio and 95% confidence intervals were calculated.

Results

Of the 35 patients, 22 (62.9%) experienced immune-related adverse events. The median progression-free survival (P = 0.0012) and overall survival (P = 0.0147) were significantly longer in patients with immune-related adverse events than in those without immune-related adverse events. Multivariate analysis showed that the incidence of immune-related adverse events was an independent factor for progression-free survival (hazard ratio = 4.940, 95% confidence interval: 1.558–15.664, P = 0.0067). Skin reaction was a positive predictive immune-related adverse events for progression-free survival (hazard ratio = 9.322, 95% confidence interval: 1.954–44.475, P = 0.0051).

Conclusion

Patients with advanced renal cell carcinoma with immune-related adverse events had superior clinical outcomes of nivolumab plus ipilimumab treatment than those without immune-related adverse events. Skin immune-related adverse events may be effective biomarkers in patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab.
Development of tilt-scan system for differential phase contrast scanning transmission electron microscopy
Authors: Kohno Yuji , Nakamura Akiho , Morishita Shigeyuki , Shibata Naoya
Published: January 2022

Differential phase contrast (DPC) scanning transmission electron microscopy can directly visualize electromagnetic fields inside a specimen. However, their image contrast is not only sensitive to the electromagnetic fields in the sample, but also the changes in diffraction conditions such as sample bends or thickness changes. These additional contrasts are called diffraction contrasts, and sometimes make it difficult to extract pure electromagnetic field information from the experimental DPC images. In this study, we developed a beam scan system that can acquire many DPC images from the same sample region with arbitrarily varying incident beam tilt angles to the sample. Then, these images are precisely averaged to form tilt-scan averaged DPC images. It is shown that the diffraction contrast can be effectively reduced in the tilt-scan averaged DPC images.
Enhancing Conflict Resolution ‘ASEAN Way’: The Dispute Settlement System of the Regional Comprehensive Economic Partnership
Authors: Lando Massimo
Published: January 2022

This article examines the dispute settlement system of the Regional Comprehensive Economic Partnership (RCEP), adopted under the auspices of ASEAN on 15 November 2020. RCEP’s Chapter 19 on dispute settlement confirms and enhances the so-called ‘ASEAN way’, which promotes flexibility, consensus and the avoidance of direct confrontation in resolving inter-State controversies. This article discusses how RCEP enhances the ‘ASEAN way’ by reference to certain significant provisions of Chapter 19, also by comparison to the dispute settlement provisions of the WTO’s Dispute Settlement Understanding and other ASEAN+1 Free Trade Agreements.
Golgi anti-apoptotic proteins redundantly counteract cell death by inhibiting production of reactive oxygen species under endoplasmic reticulum stress
Authors: Tang Xiao-Han , Li Xin , Zhou Yan , He Yu-Ting , Wang Zhi-Ying , Yang Xue , Wang Wei , Guo Kun , Zhang Wei , Sun Yue , Li Hong-Qing , Li Xiao-Fang
Published: January 2022

Maintaining proteostasis in the endoplasmic reticulum (ER) is critical for cell viability and plant survival under adverse conditions. The unfolded protein response (UPR) pathways interact with reactive oxygen species (ROS) to precisely trigger adaptive outputs or cell death under ER stress with varying degrees. However, little information is known about the relationship between UPR signalling and ROS regulation. Here, Arabidopsis GOLGI ANTI-APOPTOTIC PROTEIN1 (GAAP1)-GAAP4 were found to play redundant positive roles under ER stress. Genetic analysis showed that GAAP4 played a role in INOSITOL-REQUIRING ENZYME (IRE1)-dependent and -independent pathways. In addition, GAAPs played negative roles to activate the adaptive UPR under conditions of stress. Quantitative biochemical analysis showed that mutations in GAAP genes decreased the oxidised glutathione content and altered the pattern of ROS and glutathione in early ER stress. When plants were challenged with unmitigated ER stress, mutations in GAAP advanced ROS accumulation, which was associated with a decline in adaptive UPR. These data indicated that GAAPs resist cell death by regulating glutathione content to inhibit ROS accumulation and maintain UPR during ER stress. They provide a basis for further analysis of the regulation of cell fate decision under ER stress.
Modelling annual scintillation arc variations in PSR J1643−1224 using the Large European Array for Pulsars
Authors: Mall G , Main R A , Antoniadis J , Bassa C G , Burgay M , Chen S , Cognard I , Concu R , Corongiu A , Gaikwad M , Hu H , Janssen G H , Karuppusamy R , Kramer M , Lee K J , Liu K , McKee J W , Melis A , Mickaliger M B , Perrodin D , Pilia M , Possenti A , Reardon D J , Sanidas S A , Sprenger T , Stappers B W , Wang L , Wucknitz O , Zhu W W
Published: January 2022

In this work, we study variations in the parabolic scintillation arcs of the binary millisecond pulsar PSR J1643−1224 over five years using the Large European Array for Pulsars (LEAP). The two-dimensional (2D) power spectrum of scintillation, called the secondary spectrum, often shows a parabolic distribution of power, where the arc curvature encodes the relative velocities and distances of the pulsar, ionized interstellar medium, and Earth. We observe a clear parabolic scintillation arc, which varies in curvature throughout the year. The distribution of power in the secondary spectra is inconsistent with a single scattering screen, which is fully 1D or entirely isotropic. We fit the observed arc curvature variations with two models: an isotropic scattering screen and a model with two independent 1D screens. We measure the distance to the scattering screen to be in the range 114–223 pc, depending on the model, consistent with the known distance of the foreground large-diameter H ii region Sh 2-27 (112 ± 17 pc), suggesting that it is the dominant source of scattering. We obtain only weak constraints on the pulsar’s orbital inclination and longitude of ascending node, since the scintillation pattern is not very sensitive to the pulsar’s motion and the screen is much closer to the Earth than the pulsar. More measurements of this kind – where scattering screens can be associated with foreground objects – will help to inform the origins and distribution of scattering screens within our galaxy.
On the origin of magnetic fields in stars – II. The effect of numerical resolution
Authors: Wurster James , Bate Matthew R , Price Daniel J , Bonnell Ian A
Published: January 2022

Are the kG-strength magnetic fields observed in young stars a fossil field left over from their formation or are they generated by a dynamo? Our previous numerical study concluded that magnetic fields must originate by a dynamo process. Here, we continue that investigation by performing even higher numerical resolution calculations of the gravitational collapse of a 1 M⊙ rotating, magnetized molecular cloud core through the first and second collapse phases until stellar densities are reached. Each model includes Ohmic resistivity, ambipolar diffusion, and the Hall effect. We test six numerical resolutions, using between 105 and 3 × 107 particles to model the cloud. At all but the lowest resolutions, magnetic walls form in the outer parts of the first hydrostatic core, with the maximum magnetic field strength located within the wall rather than at the centre of the core. At high resolution, this magnetic wall is disrupted by the Hall effect, producing a magnetic field with a spiral-shaped distribution of intensity. As the second collapse occurs, this field is dragged inward and grows in strength, with the maximum field strength increasing with resolution. As the second core forms, the maximum field strength exceeds 1 kG in our highest resolution simulations, and the stellar core field strength exceeds this threshold at the highest resolution. Our resolution study suggests that kG-strength magnetic fields may be implanted in low-mass stars during their formation, and may persist over long time-scales given that the diffusion time-scale for the magnetic field exceeds the age of the Universe.
Cosmological forecasts on thermal axions, relic neutrinos and light elements
Authors: Giaré William , Renzi Fabrizio , Melchiorri Alessandro , Mena Olga , Valentino Eleonora Di
Published: January 2022

One of the targets of future Cosmic Microwave Background and Baryon Acoustic Oscillation measurements is to improve the current accuracy in the neutrino sector and reach a much better sensitivity on extra dark radiation in the Early Universe. In this paper we study how these improvements can be translated into constraining power for well motivated extensions of the Standard Model of elementary particles that involve axions thermalized before the QCD phase transition by scatterings with gluons. Assuming a fiducial ΛCDM cosmological model, we simulate future data for CMB-S4-like and DESI-like surveys and analyze a mixed scenario of axion and neutrino hot dark matter. We further account also for the effects of these QCD axions on the light element abundances predicted by Big Bang Nucleosynthesis. The most constraining forecasted limits on the hot relic masses are ma ≲ 0.92 eV and ∑mν ≲ 0.12 eV at 95%CL, showing that future cosmic observations can substantially improve the current bounds, supporting multi-messenger analyses of axion, neutrino and primordial light element properties.
Nuclear export restricts Gdown1 to a mitotic function
Authors: Ball Christopher B , Parida Mrutyunjaya , Santana Juan F , Spector Benjamin M , Suarez Gustavo A , Price David H
Published: January 2022

Approximately half of purified mammalian RNA polymerase II (Pol II) is associated with a tightly interacting sub-stoichiometric subunit, Gdown1. Previous studies have established that Gdown1 inhibits transcription initiation through competitive interactions with general transcription factors and blocks the Pol II termination activity of transcription termination factor 2 (TTF2). However, the biological functions of Gdown1 remain poorly understood. Here, we utilized genetic, microscopic, and multi-omics approaches to functionally characterize Gdown1 in three human cell lines. Acute depletion of Gdown1 caused minimal direct effects on transcription. We show that Gdown1 resides predominantly in the cytoplasm of interphase cells, shuttles between the cytoplasm and nucleus, and is regulated by nuclear export. Gdown1 enters the nucleus at the onset of mitosis. Consistently, genetic ablation of Gdown1 is associated with partial de-repression of mitotic transcription, and Gdown1 KO cells present with evidence of aberrant mitoses coupled to p53 pathway activation. Evidence is presented demonstrating that Gdown1 modulates the combined functions of purified productive elongation factors PAF1C, RTF1, SPT6, DSIF and P-TEFb in vitro. Collectively, our findings support a model wherein the Pol II-regulatory function of Gdown1 occurs during mitosis and is required for genome integrity.
Transcription factor Zfp276 drives oligodendroglial differentiation and myelination by switching off the progenitor cell program
Authors: Aberle Tim , Piefke Sandra , Hillgärtner Simone , Tamm Ernst R , Wegner Michael , Küspert Melanie
Published: January 2022

In oligodendrocytes of the vertebrate central nervous system a complex network of transcriptional regulators is required to ensure correct and timely myelination of neuronal axons. Here we identify Zfp276, the only mammalian ZAD-domain containing zinc finger protein, as a transcriptional regulator of oligodendrocyte differentiation and central myelination downstream of Sox10. In the central nervous system, Zfp276 is exclusively expressed in mature oligodendrocytes. Oligodendroglial deletion of Zfp276 led to strongly reduced expression of myelin genes in the early postnatal mouse spinal cord. Retroviral overexpression of Zfp276 in cultured oligodendrocyte precursor cells induced precocious expression of maturation markers and myelin genes, further supporting its role in oligodendroglial differentiation. On the molecular level, Zfp276 directly binds to and represses Sox10-dependent gene regulatory regions of immaturity factors and functionally interacts with the transcriptional repressor Zeb2 to enable fast transition of oligodendrocytes to the myelinating stage.
Low guanine content and biased nucleotide distribution in vertebrate mtDNA can cause overestimation of non-CpG methylation
Authors: Okada Takashi , Sun Xin , McIlfatrick Stephen , St. John Justin C
Published: January 2022

Mitochondrial DNA (mtDNA) methylation in vertebrates has been hotly debated for over 40 years. Most contrasting results have been reported following bisulfite sequencing (BS-seq) analyses. We addressed whether BS-seq experimental and analysis conditions influenced the estimation of the levels of methylation in specific mtDNA sequences. We found false positive non-CpG methylation in the CHH context (fpCHH) using unmethylated Sus scrofa mtDNA BS-seq data. fpCHH methylation was detected on the top/plus strand of mtDNA within low guanine content regions. These top/plus strand sequences of fpCHH regions would become extremely AT-rich sequences after BS-conversion, whilst bottom/minus strand sequences remained almost unchanged. These unique sequences caused BS-seq aligners to falsely assign the origin of each strand in fpCHH regions, resulting in false methylation calls. fpCHH methylation detection was enhanced by short sequence reads, short library inserts, skewed top/bottom read ratios and non-directional read mapping modes. We confirmed no detectable CHH methylation in fpCHH regions by BS-amplicon sequencing. The fpCHH peaks were located in the D-loop, ATP6, ND2, ND4L, ND5 and ND6 regions and identified in our S. scrofa ovary and oocyte data and human BS-seq data sets. We conclude that non-CpG methylation could potentially be overestimated in specific sequence regions by BS-seq analysis.
Short-term outcomes associated with temozolomide or PCV chemotherapy for 1p/19q-codeleted WHO grade 3 oligodendrogliomas: A national evaluation
Authors: Lamba Nayan , McAvoy Malia , Kavouridis Vasileios K , Smith Timothy R , Touat Mehdi , Reardon David A , Iorgulescu J Bryan
Published: January 2022

Background

The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for WHO grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data.

Methods

Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010 and 2018 were identified from the National Cancer Database. The overall survival (OS) associated with first-line single-agent temozolomide vs multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression.

Results

One thousand five hundred ninety-six radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n = 1414) treated with temozolomide and 11.4% (n = 182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at the time of analysis. There was a significant difference in unadjusted OS between temozolomide (5-year OS 58.9%, 95%CI: 55.6-62.0) and PCV (5-year OS 65.1%, 95%CI: 54.8-73.5; P = .04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs temozolomide HR 0.81, 95%CI: 0.59-1.11, P = .18). PCV was more frequently used for younger Olig3s but otherwise was not associated with patient’s insurance status or care setting.

Conclusions

In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial.
Crucial control measures to contain China's first Delta variant outbreak
Authors: Luo Lei , Yang Zifeng , Liang Jingyi , Ma Yu , Wang Hui , Hon Chitin , Jiang Mei , Lin Zhengshi , Guan Wenda , Mai Zhitong , Li Yongming , Mai Kailin , Zeng Zhiqi , Tu Chuanmeizi , Song Jian , Liu Bin , Liu Yong , He Jianfeng , Li Huiyuan , Li Bosheng , Dong Hang , Miao Yutian , Fan Shujun , Fan Lirui , Liang Xingyi , Li Ke , Chen Chun , Deng Huihong , Yang Zhicong , Zhong Nanshan
Published: January 2022

The SARS-CoV-2 B.1.617.2 (Delta) variant flared up in late May in Guangzhou, China. Transmission characteristics of Delta variant were analysed for 153 confirmed cases and two complete transmission chains with seven generations were fully presented. A rapid transmission occurred in five generations within 10 days. The basic reproduction number (R0) was 3.60 (95% confidence interval: 2.50–5.30). After redefining the concept of close contact, the proportion of confirmed cases discovered from close contacts increased from 43% to 100%. With the usage of a yellow health code, the potential exposed individuals were self-motivated to take a nucleic acid test and regained public access with a negative testing result. Facing the massive requirement of screening, novel facilities like makeshift inflatable laboratories were promptly set up as a vital supplement and 17 cases were found, with 1 pre-symptomatic. The dynamic adjustment of these three interventions resulted in the decline of Rt from 5.00 to 1.00 within 9 days. By breaking the transmission chain and eliminating the transmission source through extending the scope of the close-contact tracing, health-code usage and mass testing, the Guangzhou Delta epidemic was effectively contained.
Advanced HIV Infection in Treatment-Naïve Individuals: Effectiveness and Persistence of Recommended 3-Drug Regimens
Authors: Mounzer Karam , Brunet Laurence , Fusco Jennifer S , Mcnicholl Ian R , Diaz Cuervo Helena , Sension Michael , Mccurdy Lewis , Fusco Gregory P
Published: January 2022

Background

Approximately 20% of newly diagnosed people with HIV (PWH) in the United States have advanced HIV infection, yet the literature on current antiretroviral therapy (ART) options is limited. The discontinuation/modification and effectiveness of common regimens were compared among ART-naïve people with advanced HIV infection (CD4 cell count <200 cells/μL).

Methods

ART-naïve adults with advanced HIV infection initiating bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or a boosted darunavir (bDRV)-, dolutegravir (DTG)-, or elvitegravir/cobicistat (EVG/c)-based 3-drug regimen between January 1, 2018, and July 31, 2019, in the OPERA cohort were included. The association between regimen and discontinuation or viral suppression (<50 or <200 copies/mL) was assessed using Cox proportional hazards models with inverse probability of treatment weights.

Results

Overall, 961 PWH were included (416 B/F/TAF, 106 bDRV, 271 DTG, 168 EVG/c); 70% achieved a CD4 cell count ≥200 cells/μL over a 16-month median follow-up. All regimens were associated with a statistically higher likelihood of discontinuation than B/F/TAF (bDRV: adjusted hazard ratio [aHR], 2.65; 95% CI, 1.75–4.02; DTG: aHR, 2.42; 95% CI, 1.75–3.35; EVG/c: aHR, 3.52; 95% CI, 2.44–5.07). Compared with B/F/TAF, bDRV initiators were statistically less likely to suppress to <50 copies/mL (aHR, 0.72; 95% CI, 0.52–0.99) and <200 copies/mL (aHR, 0.55; 95% CI, 0.43–0.70); no statistically significant difference was detected with DTG or EVG/c.

Conclusions

Among people with advanced HIV infection, those initiating B/F/TAF were less likely to discontinue/modify their regimen than those on any other regimen, and more likely to achieve viral suppression compared with those on bDRV but not compared with those on other integrase inhibitors.
Cardiotoxicity from Capecitabine Chemotherapy: Prospective Study of Incidence at Rest and During Physical Exercise
Authors: Lestuzzi Chiara , Stolfo Davide , De Paoli Antonino , Banzato Alberto , Buonadonna Angela , Bidoli Ettore , Tartuferi Lucia , Viel Elda , De Angelis Giulia , Lonardi Sara , Innocente Roberto , Berretta Massimiliano , Bergamo Francesca , Guglielmi Alessandra , Sinagra Gianfranco , Herrmann Joerg
Published: January 2022

Background

Physical activity may increase the risk of cardiotoxicity (myocardial ischemia, major arrhythmias) of 5-Fluorouracil, but this risk has never been investigated for its prodrug capecitabine.

Patients and Methods

One hundred and ninety-two consecutive patients undergoing capecitabine chemotherapy from December 1, 2010 through July 31, 2016 were prospectively evaluated. The baseline evaluation included electrocardiography (ECG) and echocardiography (2DE); a follow-up evaluation, including ECG and exercise stress testing (2DE in case of ECG abnormalities), was done after ≥10 days of treatment. Cardiotoxicity was suspected from ischemic ECG changes, new kinetic abnormalities at 2DE, Lown classification ≥2 ventricular arrhythmia, symptomatic arrhythmias, or positive stress test, and confirmed by a negative stress test after capecitabine washout.

Results

Cardiotoxicity was diagnosed in 32 patients (16.7%): six at rest and 26 during exercise. All 32 patients had ECG abnormalities: ST-segment changes (24 patients), negative T-waves (2) and/or arrhythmias: ventricular arrhythmias (14 cases), supraventricular tachycardia (2), complete heart block (1). Eight patients had typical symptoms, 6 had atypical symptoms, 1 had syncope, 17 (53%) were asymptomatic. Cardiotoxicity was more common in patients with atypical symptoms during daily life (OR = 15.7) and in those on a therapeutic schedule of 5 days/week (OR = 9.44).

Conclusion

Capecitabine cardiotoxicity is frequent, and often elicited by physical effort. Oncologists, cardiologists, and general practitioners should be aware of this risk. Active cardiotoxicity surveillance with ECG (and echocardiogram and/or stress testing in suspected cases) during therapy is recommended.

Clinical Trials registration number

CRO-2010-17.
The Gender Gap in Self-Promotion
Authors: Exley Christine L , Kessler Judd B
Published: January 2022

We run a series of experiments involving over 4,000 online participants and over 10,000 school-aged youth. When individuals are asked to subjectively describe their performance on a male-typed task relating to math and science, we find a large gender gap in self-evaluations. This gap arises when self-evaluations are provided to potential employers, and thus measure self-promotion, and when self-evaluations are not driven by incentives to promote. The gender gap in self-evaluations proves to be persistent and arises as early as the sixth grade. No gender gap arises if individuals are asked about their performance on a more female-typed task.
CHARACTERISATION OF RADIOACTIVE CAESIUM IN SEDIMENTS AT THE NOGAWA RIVER, JAPAN
Authors: Inose Satoshi , Nanri Yusuke , Saito Rintaro , Matsuda Wataru , Honda Takayuki , Koike Yuya
Published: January 2022

The TEPCO Fukushima Daiichi Nuclear Power Plant accident that occurred in March 2011 resulted in the release of radioactive caesium into the environment. The radioactive caesium has been detected in the Tama River watershed. Previous investigations have shown that the concentration of radioactive caesium in sediment was relatively high in the Nogawa River. In this study, the relationship between the concentration of radioactive caesium in the sediment and the sediment characteristics was investigated. We found that 137Cs concentration in the tributary sediment has difficulty migrating downstream, while exhibiting a strong correlation with the amount of organic matter and a correlation with the clay, silt layer. Based on the results, we inferred that 137Cs is deposited together with the organic matter and clay, silt layer in the sediment and migrates at a slower pace than that in the mainstem.