bluuebunny/crossref_metadata_2025 huggingface dataset:
Superstrate-based patch antenna array with reduced in-band radar cross section
Authors: Vyshnavi Das S. K. , Singh Avinash , Gurap Arti A. , Singh Hema
Published: June 2021

To design a low radar cross section (RCS) antenna, the major concern is not only to reduce scattering, but also to maintain its radiation parameters, viz. gain, voltage standing wave ratio (VSWR), etc. This paper presents a simple configuration of low RCS microstrip patch array with a periodic structure-based superstrate. The ground of the array is designed as reduced ground plane with high impedance surface elements, viz. rectangular patch and Jerusalem cross. The configuration of superstrate consists of multilayered, viz., two-layered and three-layered structures having partially absorbing and reflecting surfaces. In both the proposed configurations, the array gain of 12.5 dB is maintained with reduced structural RCS over the entire in-band frequency range. The reflection coefficient (~ −20 dB) and VSWR (~ 1.1) of the array are maintained. It is shown that the proposed superstrate-based patch array design has significantly reduced in-band RCS (−18 dBsm) at its resonant frequency.
Investigation of the cutting plane and tolerance analysis of cross-coupled W-band waveguide filters with multiple transmission zeros by source to load cross-coupling
Authors: Miek Daniel , Bartlett Chad , Kamrath Fynn , Boe Patrick , Höft Michael
Published: June 2021

In this paper, the influence of the cutting plane as well as the orientation of the cavities in cross-coupled W-band waveguide filters are investigated. When waveguide filters are manufactured with the commonly known CNC (computer numerical control) milling technique, at least one cutting plane is required. The position of this cutting plane has an impact on the composition of the cavities, the manufacturing accuracy, and on the maximal number of transmission zeros (TZs) introduced by a direct source to load (SL) cross-coupling. Similar filter set-ups therefore may show different performances depending on the position of this cutting plane. To examine all these effects, three similar fourth-order W-band filter set-ups are realized with distinct cutting planes and different oriented cavities. The filters are compared in terms of the sensitivity to manufacturing tolerances, the maximal number of TZs introduced by a direct SL cross-coupling as well as their spurious mode performance.
The Geography of Numerical Mixing in a Suite of Global Ocean Models
Authors: Holmes R. M. , Zika J. D. , Griffies S. M. , Hogg A. McC. , Kiss A. E. , England M. H.
Published: June 2021

Numerical mixing, defined here as the physically spurious tracer diffusion due to the numerical discretization of advection, is known to contribute to biases in ocean models. However, quantifying numerical mixing is nontrivial, with most studies utilizing targeted experiments in idealized settings. Here, we present a water mass transformation‐based method for quantifying numerical mixing that can be applied to any conserved variable in general circulation models. Furthermore, the method can be applied within individual fluid columns to provide spatial information. We apply the method to a suite of global ocean model simulations with differing grid spacings and subgrid‐scale parameterizations. In all configurations numerical mixing drives diathermal heat transport of comparable magnitude to that associated with explicit parameterizations. Numerical mixing is prominent in the tropical thermocline, where it is sensitive to the vertical diffusivity and resolution. At colder temperatures numerical mixing is sensitive to the presence of explicit neutral diffusion, suggesting that it may act as a proxy for neutral diffusion when it is explicitly absent. Comparison of otherwise equivalent 1/4° and 1/10° configurations with grid‐scale dependent horizontal viscosity shows only a modest enhancement in numerical mixing at 1/4°. However, if the lateral viscosity is maintained while resolution is increased then numerical mixing is reduced by almost 35%. This result suggests that the common practice of reducing viscosity in order to maximize permitted variability must be considered carefully. Our results provide a detailed view of numerical mixing in ocean models and pave the way for improvements in parameter choices and numerical methods.
Core binding factor acute myelogenous leukemia-2021 treatment algorithm
Authors: Borthakur Gautam , Kantarjian Hagop
Published: June 2021

Core binding factor acute myelogenous leukemia (CBF-AML), characterized by the presence of either t(8;21) (q22;q22) or inv(16) (p13q22)/t(16;16), is considered good-risk AML in the context of cytarabine based intensive chemotherapy. Still, outcome can be improved significantly through the effective implementation of available therapeutic measures and appropriate disease monitoring. The incorporation of gemtuzumab ozogamicin into frontline therapy should be standard. Cytarabine based induction/consolidation regimen may be combined with anthracycline (3 + 7 standard) or antimetabolite, fludarabine. Serial quantitative polymerase chain reaction (QPCR) monitoring of unique fusion transcripts allows monitoring for measurable residual disease clearance; this allows for better prognostication and well as treatment modifications.
Fusion gene map of acute leukemia revealed by transcriptome sequencing of a consecutive cohort of 1000 cases in a single center
Authors: Chen Xue , Wang Fang , Zhang Yang , Ma Xiaoli , Cao Panxiang , Yuan Lili , Wang Lan , Chen Jiaqi , Zhou Xiaosu , Wu Qisheng , Liu Ming , Jin David , Liu Hongxing
Published: June 2021

Fusion genes (FGs) are important genetic abnormalities in acute leukemias, but their variety and occurrence in acute leukemias remain to be systematically described. Whole transcriptome sequencing (WTS) provides a powerful tool for analyzing FGs. Here we report the FG map revealed by WTS in a consecutive cohort of 1000 acute leukemia cases in a single center, including 539 acute myeloid leukemia (AML), 437 acute lymphoblastic leukemia (ALL), and 24 mixed-phenotype acute leukemia (MPAL) patients. Bioinformatic analysis identified 792 high-confidence in-frame fusion events (296 distinct fusions) which were classified into four tiers. Tier A (pathogenic), B (likely pathogenic), and C (uncertain significance) FGs were identified in 61.8% cases of the total cohort (59.7% in AML, 64.5% in ALL, and 63.6% in MPAL). FGs involving protein kinase, transcription factor, and epigenetic genes were detected in 10.7%, 48.5%, and 15.1% cases, respectively. A considerable amount of novel FGs (82 in AML, 88 in B-ALL, 13 in T-ALL, and 9 in MPAL) was identified. This comprehensively described real map of FGs in acute leukemia revealed multiple FGs with clinical relevance that have not been previously recognized. WTS is a valuable tool and should be widely used in the routine diagnostic workup of acute leukemia.
OGA is associated with deglycosylation of NONO and the KU complex during DNA damage repair
Authors: Cui Yaqi , Xie Rong , Zhang Xuefang , Liu Yi , Hu Yixuan , Li Yuan , Liu Xiuhua , Yu Xiaochun , Wu Chen
Published: June 2021

Accumulated evidence shows that OGT-mediated O-GlcNAcylation plays an important role in response to DNA damage repair. However, it is unclear if the “eraser” O-GlcNAcase (OGA) participates in this cellular process. Here, we examined the molecular mechanisms and biological functions of OGA in DNA damage repair, and found that OGA was recruited to the sites of DNA damage and mediated deglycosylation following DNA damage. The recruitment of OGA to DNA lesions is mediated by O-GlcNAcylation events. Moreover, we have dissected OGA using deletion mutants and found that C-terminal truncated OGA including the pseudo HAT domain was required for the recruitment of OGA to DNA lesions. Using unbiased protein affinity purification, we found that the pseudo HAT domain was associated with DNA repair factors including NONO and the Ku70/80 complex. Following DNA damage, both NONO and the Ku70/80 complex were O-GlcNAcylated by OGT. The pseudo HAT domain was required to recognize NONO and the Ku70/80 complex for their deglycosylation. Suppression of the deglycosylation prolonged the retention of NONO at DNA lesions and delayed NONO degradation on the chromatin, which impaired non-homologus end joining (NHEJ). Collectively, our study reveals that OGA-mediated deglycosylation plays a key role in DNA damage repair.
A distinct growth physiology enhances bacterial growth under rapid nutrient fluctuations
Authors: Nguyen Jen , Fernandez Vicente , Pontrelli Sammy , Sauer Uwe , Ackermann Martin , Stocker Roman
Published: June 2021

It has long been known that bacteria coordinate their physiology with their nutrient environment, yet our current understanding offers little intuition for how bacteria respond to the second-to-minute scale fluctuations in nutrient concentration characteristic of many microbial habitats. To investigate the effects of rapid nutrient fluctuations on bacterial growth, we couple custom microfluidics with single-cell microscopy to quantify the growth rate of E. coli experiencing 30 s to 60 min nutrient fluctuations. Compared to steady environments of equal average concentration, fluctuating environments reduce growth rate by up to 50%. However, measured reductions in growth rate are only 38% of the growth loss predicted from single nutrient shifts. This enhancement derives from the distinct growth response of cells grown in environments that fluctuate rather than shift once. We report an unexpected physiology adapted for growth in nutrient fluctuations and implicate nutrient timescale as a critical environmental parameter beyond nutrient identity and concentration.
Identification of a dual orange/far-red and blue light photoreceptor from an oceanic green picoplankton
Authors: Makita Yuko , Suzuki Shigekatsu , Fushimi Keiji , Shimada Setsuko , Suehisa Aya , Hirata Manami , Kuriyama Tomoko , Kurihara Yukio , Hamasaki Hidefumi , Okubo-Kurihara Emiko , Yoshitake Kazutoshi , Watanabe Tsuyoshi , Sakuta Masaaki , Gojobori Takashi , Sakami Tomoko , Narikawa Rei , Yamaguchi Haruyo , Kawachi Masanobu , Matsui Minami
Published: June 2021

Photoreceptors are conserved in green algae to land plants and regulate various developmental stages. In the ocean, blue light penetrates deeper than red light, and blue-light sensing is key to adapting to marine environments. Here, a search for blue-light photoreceptors in the marine metagenome uncover a chimeric gene composed of a phytochrome and a cryptochrome (Dualchrome1, DUC1) in a prasinophyte, Pycnococcus provasolii. DUC1 detects light within the orange/far-red and blue spectra, and acts as a dual photoreceptor. Analyses of its genome reveal the possible mechanisms of light adaptation. Genes for the light-harvesting complex (LHC) are duplicated and transcriptionally regulated under monochromatic orange/blue light, suggesting P. provasolii has acquired environmental adaptability to a wide range of light spectra and intensities.
Stepwise maturation of the peptidyl transferase region of human mitoribosomes
Authors: Lenarčič Tea , Jaskolowski Mateusz , Leibundgut Marc , Scaiola Alain , Schönhut Tanja , Saurer Martin , Lee Richard G. , Rackham Oliver , Filipovska Aleksandra , Ban Nenad
Published: June 2021

Mitochondrial ribosomes are specialized for the synthesis of membrane proteins responsible for oxidative phosphorylation. Mammalian mitoribosomes have diverged considerably from the ancestral bacterial ribosomes and feature dramatically reduced ribosomal RNAs. The structural basis of the mammalian mitochondrial ribosome assembly is currently not well understood. Here we present eight distinct assembly intermediates of the human large mitoribosomal subunit involving seven assembly factors. We discover that the NSUN4-MTERF4 dimer plays a critical role in the process by stabilizing the 16S rRNA in a conformation that exposes the functionally important regions of rRNA for modification by the MRM2 methyltransferase and quality control interactions with the conserved mitochondrial GTPase MTG2 that contacts the sarcin-ricin loop and the immature active site. The successive action of these factors leads to the formation of the peptidyl transferase active site of the mitoribosome and the folding of the surrounding rRNA regions responsible for interactions with tRNAs and the small ribosomal subunit.
Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers
Authors: Rujas Edurne , Kucharska Iga , Tan Yong Zi , Benlekbir Samir , Cui Hong , Zhao Tiantian , Wasney Gregory A. , Budylowski Patrick , Guvenc Furkan , Newton Jocelyn C. , Sicard Taylor , Semesi Anthony , Muthuraman Krithika , Nouanesengsy Amy , Aschner Clare Burn , Prieto Katherine , Bueler Stephanie A. , Youssef Sawsan , Liao-Chan Sindy , Glanville Jacob , Christie-Holmes Natasha , Mubareka Samira , Gray-Owen Scott D. , Rubinstein John L. , Treanor Bebhinn , Julien Jean-Philippe
Published: June 2021

SARS-CoV-2, the virus responsible for COVID-19, has caused a global pandemic. Antibodies can be powerful biotherapeutics to fight viral infections. Here, we use the human apoferritin protomer as a modular subunit to drive oligomerization of antibody fragments and transform antibodies targeting SARS-CoV-2 into exceptionally potent neutralizers. Using this platform, half-maximal inhibitory concentration (IC50) values as low as 9 × 10−14 M are achieved as a result of up to 10,000-fold potency enhancements compared to corresponding IgGs. Combination of three different antibody specificities and the fragment crystallizable (Fc) domain on a single multivalent molecule conferred the ability to overcome viral sequence variability together with outstanding potency and IgG-like bioavailability. The MULTi-specific, multi-Affinity antiBODY (Multabody or MB) platform thus uniquely leverages binding avidity together with multi-specificity to deliver ultrapotent and broad neutralizers against SARS-CoV-2. The modularity of the platform also makes it relevant for rapid evaluation against other infectious diseases of global health importance. Neutralizing antibodies are a promising therapeutic for SARS-CoV-2.
Radioisotope constraints of Arctic deep water export to the North Atlantic
Authors: Kipp Lauren E. , McManus Jerry F. , Kienast Markus
Published: June 2021

The export of deep water from the Arctic to the Atlantic contributes to the formation of North Atlantic Deep Water, a crucial component of global ocean circulation. Records of protactinium-231 (231Pa) and thorium-230 (230Th) in Arctic sediments can provide a measure of this export, but well-constrained sedimentary budgets of these isotopes have been difficult to achieve in the Arctic Ocean. Previous studies revealed a deficit of 231Pa in central Arctic sediments, implying that some 231Pa is either transported to the margins, where it may be removed in areas of higher particle flux, or exported from the Arctic via deep water advection. Here we investigate this “missing sink” of Arctic 231Pa and find moderately increased 231Pa deposition along Arctic margins. Nonetheless, we determine that most 231Pa missing from the central basin must be lost via advection into the Nordic Seas, requiring deep water advection of 1.1 – 6.4 Sv through Fram Strait.
The long lives of primates and the ‘invariant rate of ageing’ hypothesis
Authors: Colchero Fernando , Aburto José Manuel , Archie Elizabeth A. , Boesch Christophe , Breuer Thomas , Campos Fernando A. , Collins Anthony , Conde Dalia A. , Cords Marina , Crockford Catherine , Thompson Melissa Emery , Fedigan Linda M. , Fichtel Claudia , Groenenberg Milou , Hobaiter Catherine , Kappeler Peter M. , Lawler Richard R. , Lewis Rebecca J. , Machanda Zarin P. , Manguette Marie L. , Muller Martin N. , Packer Craig , Parnell Richard J. , Perry Susan , Pusey Anne E. , Robbins Martha M. , Seyfarth Robert M. , Silk Joan B. , Staerk Johanna , Stoinski Tara S. , Stokes Emma J. , Strier Karen B. , Strum Shirley C. , Tung Jenny , Villavicencio Francisco , Wittig Roman M. , Wrangham Richard W. , Zuberbühler Klaus , Vaupel James W. , Alberts Susan C.
Published: June 2021

Is it possible to slow the rate of ageing, or do biological constraints limit its plasticity? We test the ‘invariant rate of ageing’ hypothesis, which posits that the rate of ageing is relatively fixed within species, with a collection of 39 human and nonhuman primate datasets across seven genera. We first recapitulate, in nonhuman primates, the highly regular relationship between life expectancy and lifespan equality seen in humans. We next demonstrate that variation in the rate of ageing within genera is orders of magnitude smaller than variation in pre-adult and age-independent mortality. Finally, we demonstrate that changes in the rate of ageing, but not other mortality parameters, produce striking, species-atypical changes in mortality patterns. Our results support the invariant rate of ageing hypothesis, implying biological constraints on how much the human rate of ageing can be slowed.
Supramolecular engineering of charge transfer in wide bandgap organic semiconductors with enhanced visible-to-NIR photoresponse
Authors: Yao Yifan , Ou Qi , Wang Kuidong , Peng Haijun , Fang Feier , Shi Yumeng , Wang Ye , Asperilla Daniel Iglesias , Shuai Zhigang , Samorì Paolo
Published: June 2021

Organic photodetectors displaying efficient photoelectric response in the near-infrared are typically based on narrow bandgap active materials. Unfortunately, the latter require complex molecular design to ensure sufficient light absorption in the near-infrared region. Here, we show a method combining an unconventional device architecture and ad-hoc supramolecular self-assembly to trigger the emergence of opto-electronic properties yielding to remarkably high near-infrared response using a wide bandgap material as active component. Our optimized vertical phototransistors comprising a network of supramolecular nanowires of N,N′-dioctyl-3,4,9,10-perylenedicarboximide sandwiched between a monolayer graphene bottom-contact and Au nanomesh scaffold top-electrode exhibit ultrasensitive light response to monochromatic light from visible to near-infrared range, with photoresponsivity of 2 × 105 A/W and 1 × 102 A/W, at 570 nm and 940 nm, respectively, hence outperforming devices based on narrow bandgap materials. Moreover, these devices also operate as highly sensitive photoplethysmography tool for health monitoring.
Controlling the pandemic during the SARS-CoV-2 vaccination rollout
Authors: Viana João , van Dorp Christiaan H. , Nunes Ana , Gomes Manuel C. , van Boven Michiel , Kretzschmar Mirjam E. , Veldhoen Marc , Rozhnova Ganna
Published: June 2021

There is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevalence data, hospital admissions, and projected vaccination coverage for Portugal. Our analyses suggest that the pressing need to restart socioeconomic activities could lead to new pandemic waves, and that substantial control efforts prove necessary throughout 2021. Using knowledge on control measures introduced in 2020, we anticipate that relaxing measures completely or to the extent as in autumn 2020 could launch a wave starting in April 2021. Additional waves could be prevented altogether if measures are relaxed as in summer 2020 or in a step-wise manner throughout 2021. We discuss at which point the control of COVID-19 would be achieved for each scenario.
Ultrafast coherent motion and helix rearrangement of homodimeric hemoglobin visualized with femtosecond X-ray solution scattering
Authors: Lee Yunbeom , Kim Jong Goo , Lee Sang Jin , Muniyappan Srinivasan , Kim Tae Wu , Ki Hosung , Kim Hanui , Jo Junbeom , Yun So Ri , Lee Hyosub , Lee Kyung Won , Kim Seong Ok , Cammarata Marco , Ihee Hyotcherl
Published: June 2021

Ultrafast motion of molecules, particularly the coherent motion, has been intensively investigated as a key factor guiding the reaction pathways. Recently, X-ray free-electron lasers (XFELs) have been utilized to elucidate the ultrafast motion of molecules. However, the studies on proteins using XFELs have been typically limited to the crystalline phase, and proteins in solution have rarely been investigated. Here we applied femtosecond time-resolved X-ray solution scattering (fs-TRXSS) and a structure refinement method to visualize the ultrafast motion of a protein. We succeeded in revealing detailed ultrafast structural changes of homodimeric hemoglobin involving the coherent motion. In addition to the motion of the protein itself, the time-dependent change of electron density of the hydration shell was tracked. Besides, the analysis on the fs-TRXSS data of myoglobin allows for observing the effect of the oligomeric state on the ultrafast coherent motion.
Evidence for the Fulde–Ferrell–Larkin–Ovchinnikov state in bulk NbS2
Authors: Cho Chang-woo , Lyu Jian , Ng Cheuk Yin , He James Jun , Lo Kwan To , Chareev Dmitriy , Abdel-Baset Tarob A. , Abdel-Hafiez Mahmoud , Lortz Rolf
Published: June 2021

We present measurements of the magnetic torque, specific heat and thermal expansion of the bulk transition metal dichalcogenide (TMD) superconductor NbS2 in high magnetic fields, with its layer structure aligned strictly parallel to the field using a piezo rotary positioner. The upper critical field of superconducting TMDs in the 2D form is known to be dramatically enhanced by a special form of Ising spin orbit coupling. This Ising superconductivity is very robust to the Pauli paramagnetic effect and can therefore exist beyond the Pauli limit for superconductivity. We find that superconductivity beyond the Pauli limit still exists in bulk single crystals of NbS2 for a precisely parallel field alignment. However, the comparison of our upper critical field transition line with numerical simulations rather points to the development of a Fulde-Ferrell-Larkin-Ovchinnikov state above the Pauli limit as a cause. This is also consistent with the observation of a magnetic field driven phase transition in the thermodynamic quantities within the superconducting state near the Pauli limit.
Remote whispering metamaterial for non-radiative transceiving of ultra-weak sound
Authors: Zhang Jin , Rui Wei , Ma Chengrong , Cheng Ying , Liu Xiaojun , Christensen Johan
Published: June 2021

Transceiving ultra-weak sound typically relies on signal pre-amplification at the transmitting end via active electro-acoustic devices, which inherently perturbs the environment in the form of noise that inevitably leads to information leakage. Here we demonstrate a passive remote-whispering metamaterial (RWM) enabling weak airborne sound at audible frequencies to reach unprecedented signal enhancement without altering the detected ambient soundscape, which is based on the extraordinary scattering properties of a metamaterial formed by a pair of self-resonating subwavelength Mie meta-cavities, constituting the acoustic analogy of Förster resonance energy transfer. We demonstrate efficient non-radiative sound transfer over distances hundreds times longer than the radius of the meta-cavities, which enables the RWM to recover weak sound signals completely overwhelmed by strong noise with enhanced signal-to-noise ratio from −3 dB below the detection limit of 0 dB in free space to 17.7 dB.
Proteomic analysis of chicken bone marrow-derived dendritic cells in response to an inactivated IBV + NDV poultry vaccine
Authors: van den Biggelaar Robin H. G. A. , van der Maas Larissa , Meiring Hugo D. , Pennings Jeroen L. A. , van Eden Willem , Rutten Victor P. M. G. , Jansen Christine A.
Published: June 2021

Inactivated poultry vaccines are subject to routine potency testing for batch release, requiring large numbers of animals. The replacement of in vivo tests for cell-based alternatives can be facilitated by the identification of biomarkers for vaccine-induced immune responses. In this study, chicken bone marrow-derived dendritic cells were stimulated with an inactivated vaccine for infectious bronchitis virus and Newcastle disease virus, as well as inactivated infectious bronchitis virus only, and lipopolysaccharides as positive control, or left unstimulated for comparison with the stimulated samples. Next, the cells were lysed and subjected to proteomic analysis. Stimulation with the vaccine resulted in 66 differentially expressed proteins associated with mRNA translation, immune responses, lipid metabolism and the proteasome. For the eight most significantly upregulated proteins, mRNA expression levels were assessed. Markers that showed increased expression at both mRNA and protein levels included PLIN2 and PSMB1. Stimulation with infectious bronchitis virus only resulted in 25 differentially expressed proteins, which were mostly proteins containing Src homology 2 domains. Stimulation with lipopolysaccharides resulted in 118 differentially expressed proteins associated with dendritic cell maturation and antimicrobial activity. This study provides leads to a better understanding of the activation of dendritic cells by an inactivated poultry vaccine, and identified PLIN2 and PSMB1 as potential biomarkers for cell-based potency testing.
A distributed saccade-associated network encodes high velocity conjugate and monocular eye movements in the zebrafish hindbrain
Authors: Leyden Claire , Brysch Christian , Arrenberg Aristides B.
Published: June 2021

Saccades are rapid eye movements that redirect gaze. Their magnitudes and directions are tightly controlled by the oculomotor system, which is capable of generating conjugate, monocular, convergent and divergent saccades. Recent studies suggest a mainly monocular control of saccades in mammals, although the development of binocular control and the interaction of different functional populations is less well understood. For zebrafish, a well-established model in sensorimotor research, the nature of binocular control in this key oculomotor behavior is unknown. Here, we use the optokinetic response and calcium imaging to characterize how the developing zebrafish oculomotor system encodes the diverse repertoire of saccades. We find that neurons with phasic saccade-associated activity (putative burst neurons) are most frequent in dorsal regions of the hindbrain and show elements of both monocular and binocular encoding, revealing a mix of the response types originally hypothesized by Helmholtz and Hering. Additionally, we observed a certain degree of behavior-specific recruitment in individual neurons. Surprisingly, calcium activity is only weakly tuned to saccade size. Instead, saccade size is apparently controlled by a push–pull mechanism of opposing burst neuron populations. Our study reveals the basic layout of a developing vertebrate saccade system and provides a perspective into the evolution of the oculomotor system.
Surface mass balance analysis at Naradu Glacier, Western Himalaya, India
Authors: Kumar Rajesh , Singh Shruti , Singh Atar , Kumar Ramesh , Singh Shaktiman , Randhawa Surjeet Singh
Published: June 2021

In the present study, we analyze a field-based seven-year data series of surface mass-balance measurements collected during 2011/12 to 2017/18 on Naradu Glacier, western Himalaya, India. The average annual specific mass balance for the said period is  − 0.85 m w.e. with the maximum ablation of  − 1.15 m w.e. The analysis shows that the topographic features, south and southeast aspects and slopes between 7 to 24 degrees are the reasons behind the maximum ablation from a particular zone. The causes of surface mass balance variability have been analyzed through multiple linear regression analyses (MLRA) by taking temperature and precipitation as predictors. The MLRA demonstrates that 71% of the observed surface mass balance variance can be explained by temperature and precipitation. It clearly illustrates the importance of summer temperature, which alone explains 64% variance of surface mass balance. The seasonal analysis shows that most of the surface mass balance variability is described by summer temperature and winter precipitation as two predictor variables. Among monthly combinations, surface mass balance variance is best characterized by June temperature and September precipitation.
A reporter system for enriching CRISPR/Cas9 knockout cells in technically challenging settings like patient models
Authors: Liu Wen-Hsin , Völse Kerstin , Senft Daniela , Jeremias Irmela
Published: June 2021

CRISPR/Cas9 represents a valuable tool to determine protein function, but technical hurdles limit its use in challenging settings such as cells unable to grow in vitro like primary leukemia cells and xenografts derived thereof (PDX). To enrich CRISPR/Cas9-edited cells, we improved a dual-reporter system and cloned the genomic target sequences of the gene of interest (GOI) upstream of an out-of-frame fluorochrome which was expressed only upon successful gene editing. To reduce rounds of in vivo passaging required for PDX leukemia growth, targets of 17 GOI were cloned in a row, flanked by an improved linker, and PDX cells were lentivirally transduced for stable expression. The reporter enriched scarce, successfully gene-edited PDX cells as high as 80%. Using the reporter, we show that KO of the SRC-family kinase LYN increased the response of PDX cells of B precursor cell ALL towards Vincristine, even upon heterozygous KO, indicating haploinsufficiency. In summary, our reporter system enables enriching KO cells in technically challenging settings and extends the use of gene editing to highly patient-related model systems.
Recovery and analysis of ancient beetle DNA from subfossil packrat middens using high-throughput sequencing
Authors: Smith Aaron D. , Kamiński Marcin J. , Kanda Kojun , Sweet Andrew D. , Betancourt Julio L. , Holmgren Camille A. , Hempel Elisabeth , Alberti Federica , Hofreiter Michael
Published: June 2021

The study of ancient DNA is revolutionizing our understanding of paleo-ecology and the evolutionary history of species. Insects are essential components in many ecosystems and constitute the most diverse group of animals. Yet they are largely neglected in ancient DNA studies. We report the results of the first targeted investigation of insect ancient DNA to positively identify subfossil insects to species, which includes the recovery of endogenous content from samples as old as ~ 34,355 ybp. Potential inhibitors currently limiting widespread research on insect ancient DNA are discussed, including the lack of closely related genomic reference sequences (decreased mapping efficiency) and the need for more extensive collaborations with insect taxonomists. The advantages of insect-based studies are also highlighted, especially in the context of understanding past climate change. In this regard, insect remains from ancient packrat middens are a rich and largely uninvestigated resource for exploring paleo-ecology and species dynamics over time.
A systematic review and meta-analysis of surgical morbidity of primary versus patch repaired congenital diaphragmatic hernia patients
Authors: Heiwegen Kim , de Blaauw Ivo , Botden Sanne M. B. I.
Published: June 2021

Large studies comparing the surgical outcome of primary versus patch repair in congenital diaphragmatic hernia (CDH) patients are rare. This study aims to evaluate the incidence of surgical complications in both types of CDH repair. PubMed, EMBASE, Cochrane and Web of Science were searched for peer-reviewed articles. Studies on CDH between 1991 and August 2020 were systematically screened and meta-analyses were performed. Primary outcomes of this review were: haemorrhage, chylothorax, recurrences and small bowel obstruction (SBO). A total of 6436 abstracts were screened, after which 25 publications were included (2910 patients). Patch repaired patients have a 2.8 times higher risk on developing a recurrence (20 studies) and a 2.5 times higher risk on developing a chylothorax (five studies). Moreover, they have a two times higher risk on developing a SBO. No studies could be included that evaluated the incidence of surgical haemorrhage between these patients. Although the quality of the studies was relatively low, patch repaired patients have a higher risk on developing a recurrence, chylothorax and small bowel obstruction. Large prospective studies are required to adjust for severity of disease, to reveal the true causative factors in order to minimize the risk on these surgical complications in both types of patients.
Mutant p53s and chromosome 19 microRNA cluster overexpression regulate cancer testis antigen expression and cellular transformation in hepatocellular carcinoma
Authors: Jinesh Goodwin G. , Napoli Marco , Smallin Marian T. , Davis Andrew , Ackerman Hayley D. , Raulji Payal , Montey Nicole , Flores Elsa R. , Brohl Andrew S.
Published: June 2021

A subset of hepatocellular carcinoma (HCC) overexpresses the chromosome 19 miRNA cluster (C19MC) and is associated with an undifferentiated phenotype marked by overexpression of cancer testis antigens (CTAs) including anti-apoptotic melanoma-A antigens (MAGEAs). However, the regulation of C19MC miRNA and MAGEA expression in HCCs are not understood. Here we show that, C19MC overexpression is tightly linked to a sub-set of HCCs with transcription-incompetent p53. Using next-generation and Sanger sequencing we found that, p53 in Hep3B cells is impaired by TP53-FXR2 fusion, and that overexpression of the C19MC miRNA-520G in Hep3B cells promotes the expression of MAGEA-3, 6 and 12 mRNAs. Furthermore, overexpression of p53-R175H and p53-R273H mutants promote miR-520G and MAGEA RNA expression and cellular transformation. Moreover, IFN-γ co-operates with miR-520G to promote MAGEA expression. On the other hand, metals such as nickel and zinc promote miR-526B but not miR-520G, to result in the suppression of MAGEA mRNA expression, and evoke cell death through mitochondrial membrane depolarization. Therefore our study demonstrates that a MAGEA-promoting network involving miR-520G, p53-defects and IFN-γ that govern cellular transformation and cell survival pathways, but MAGEA expression and survival are counteracted by nickel and zinc combination.
2D weak anti-localization in thin films of the topological semimetal Pd$$_{3}$$Bi$$_{2}$$S$$_{2}$$
Authors: Shama  , Gopal R. K. , Sheet Goutam , Singh Yogesh
Published: June 2021

Pd$$_{3}$$

3

Bi$$_{2}$$

2

S$$_{2}$$

2

(PBS) is a recently proposed topological semimetal candidate. However, evidence for topological surface states have not yet been revealed in transport measurements due to the large mobility of bulk carriers. We report the growth and magneto-transport studies of PBS thin films where the mobility of the bulk carriers is reduced by two orders of magnitude, revealing for the first time, contributions from the 2-dimensional (2D) topological surface states in the observation of the 2D weak anti-localization (WAL) effect in magnetic field and angle dependent conductivity measurements. The magnetotransport data is analysed within the 2D Hikami-Larkin-Nagaoka (HLN) theory. The analysis suggests that multiple conduction channels contribute to the transport. It is also found that the temperature dependence of the dephasing length can’t be explained only by electron-electron scattering and that electron-phonon scattering also contributes to the phase relaxation mechanism in PBS films.
Investigating the impact of long term exposure to chemical agents on the chromosomal radiosensitivity using human lymphoblastoid GM1899A cells
Authors: Nuta Otilia , Bouffler Simon , Lloyd David , Ainsbury Elizabeth , Sepai Ovnair , Rothkamm Kai
Published: June 2021

This study aimed to investigate the impact of chronic low-level exposure to chemical carcinogens with different modes of action on the cellular response to ionising radiation. Human lymphoblastoid GM1899A cells were cultured in the presence of 4-nitroquinoline N-oxide (4NQO), N-nitroso-N-methylurea (MNU) and hydrogen peroxide (H2O2) for up to 6 months at the highest non-(geno)toxic concentration identified in pilot experiments. Acute challenge doses of 1 Gy X-rays were given and chromosome damage (dicentrics, acentric fragments, micronuclei, chromatid gaps/breaks) was scored. Chronic exposure to 20 ng/ml 4NQO, 0.25 μg/ml MNU or 10 μM H2O2 hardly induced dicentrics and did not significantly alter the yield of X-ray-induced dicentrics. Significant levels of acentric fragments were induced by all chemicals, which did not change during long-term exposure. Fragment data in combined treatment samples compared to single treatments were consistent with an additive effect of chemical and radiation exposure. Low level exposure to 4NQO induced micronuclei, the yields of which did not change throughout the 6 month exposure period. As for fragments, micronuclei yields for combined treatments were consistent with an additive effect of chemical and radiation. These results suggest that cellular radiation responses are not affected by long-term low-level chemical exposure.
A structural deep network embedding model for predicting associations between miRNA and disease based on molecular association network
Authors: Li Hao-Yuan , Chen Hai-Yan , Wang Lei , Song Shen-Jian , You Zhu-Hong , Yan Xin , Yu Jin-Qian
Published: June 2021

Previous studies indicated that miRNA plays an important role in human biological processes especially in the field of diseases. However, constrained by biotechnology, only a small part of the miRNA-disease associations has been verified by biological experiment. This impel that more and more researchers pay attention to develop efficient and high-precision computational methods for predicting the potential miRNA-disease associations. Based on the assumption that molecules are related to each other in human physiological processes, we developed a novel structural deep network embedding model (SDNE-MDA) for predicting miRNA-disease association using molecular associations network. Specifically, the SDNE-MDA model first integrating miRNA attribute information by Chao Game Representation (CGR) algorithm and disease attribute information by disease semantic similarity. Secondly, we extract feature by structural deep network embedding from the heterogeneous molecular associations network. Then, a comprehensive feature descriptor is constructed by combining attribute information and behavior information. Finally, Convolutional Neural Network (CNN) is adopted to train and classify these feature descriptors. In the five-fold cross validation experiment, SDNE-MDA achieved AUC of 0.9447 with the prediction accuracy of 87.38% on the HMDD v3.0 dataset. To further verify the performance of SDNE-MDA, we contrasted it with different feature extraction models and classifier models. Moreover, the case studies with three important human diseases, including Breast Neoplasms, Kidney Neoplasms, Lymphoma were implemented by the proposed model. As a result, 47, 46 and 46 out of top-50 predicted disease-related miRNAs have been confirmed by independent databases. These results anticipate that SDNE-MDA would be a reliable computational tool for predicting potential miRNA-disease associations.
Helminth derived factors inhibit neutrophil extracellular trap formation and inflammation in bacterial peritonitis
Authors: Chauhan Arun , Sharma Atul , Tripathi Jitendra K. , Sun Yuyang , Sukumran Pramod , Singh Brij B. , Mishra Bibhuti B. , Sharma Jyotika
Published: June 2021

Despite their protective antimicrobial function, neutrophil extracellular traps (NETs) have been implicated in propagation of inflammatory responses in several disease conditions including sepsis. Highly diffusible exogenous ROS produced under such inflammatory conditions, can induce exuberant NETs, thus making inhibition of NETs desirable in inflammatory diseases. Here we report that helminth parasite excretory/secretory factors termed as parasitic ligands (PL) inhibit ROS-induced NETs by blocking the activation of nonselective calcium permeable channel Transient Receptor Potential Melastatin 2 (TRPM2). Therapeutic implication of PL mediated blockage of NET formation was tested in preclinical model of septic peritonitis, where PL treatment regulated neutrophil cell death modalities including NET formation and mitigated neutrophil mediated inflammatory response. This translated into improved survival and reduced systemic and local bacterial load in infected mice. Overall, our results posit PL as an important biological regulator of neutrophil functions with implications to a variety of inflammatory diseases including peritonitis.
Marker-assisted pyramiding of lycopene-ε-cyclase, β-carotene hydroxylase1 and opaque2 genes for development of biofortified maize hybrids
Authors: Singh Jagveer , Sharma Shikha , Kaur Amandeep , Vikal Yogesh , Cheema Amandeep Kaur , Bains Balraj Kaur , Kaur Noorpreet , Gill Gurjit Kaur , Malhotra Pawan Kumar , Kumar Ashok , Sharma Priti , Muthusamy Vignesh , Kaur Amarjeet , Chawla Jasbir Singh , Hossain Firoz
Published: June 2021

Malnutrition affects growth and development in humans and causes socio-economic losses. Normal maize is deficient in essential amino acids, lysine and tryptophan; and vitamin-A. Crop biofortification is a sustainable and economical approach to alleviate micronutrient malnutrition. We combined favorable alleles of crtRB1 and lcyE genes into opaque2 (o2)-based four inbreds viz. QLM11, QLM12, QLM13, and QLM14 using marker-assisted backcross breeding. These are parents of quality protein maize versions of two elite hybrids viz. Buland and PMH1, grown in India. Gene-based SSRs for o2 and InDel markers for crtRB1 and lcyE were successfully employed for foreground selection in BC1F1, BC2F1, and BC2F2 generations. The recurrent parent genome recovery ranged from 88.9 to 96.0% among introgressed progenies. Kernels of pyramided lines possessed a high concentration of proA (7.14–9.63 ppm), compared to 1.05 to 1.41 ppm in the recurrent parents, while lysine and tryptophan ranged from 0.28–0.44% and 0.07–0.09%, respectively. The reconstituted hybrids (RBuland and RPMH1) showed significant enhancement of endosperm proA (6.97–9.82 ppm), tryptophan (0.07–0.09%), and lysine (0.29–0.43%), while grain yield was at par with their original versions. The dissemination of reconstituted hybrids holds significant promise to alleviate vitamin-A deficiency and protein-energy malnutrition in developing countries.
Improvement in aqueous solubility of achiral symmetric cyclofenil by modification to a chiral asymmetric analog
Authors: Morimoto Junki , Miyamoto Kazunori , Ichikawa Yuki , Uchiyama Masanobu , Makishima Makoto , Hashimoto Yuichi , Ishikawa Minoru
Published: June 2021

Decreasing the partition coefficient (LogP) by the introduction of a hydrophilic group is the conventional approach for improving the aqueous solubility of drug candidates, but is not always effective. Since melting point is related to aqueous solubility, we and other groups have developed alternative strategies to improve solubility by means of chemical modification to weaken intermolecular interaction in the solid state, thereby lowering the melting point and increasing the solubility. Here, we show that converting the symmetrical molecular structure of the clinically used estrogen receptor (ER) antagonist cyclofenil (1) into asymmetrical form by introducing an alkyl group enhances the aqueous solubility. Among the synthesized analogs, the chiral methylated analog (R)-4c shows the highest solubility, being 3.6-fold more soluble than 1 even though its hydrophobicity is increased by the methylation. Furthermore, (R)-4c also showed higher membrane permeability than 1, while retaining a comparable metabolic rate, and equivalent biological activity of the active forms (R)-13a to 2. Further validation of this strategy using lead compounds having symmetric structures is expected.
Optomechanical switching of adsorption configurations of polar organic molecules by UV radiation pressure
Authors: Arumugam Kowsalya , Goyal Abhishake , Chen Hong-Ming , Dai Jing-Huan , Gao Mau-Fu , Nakayama Yasuo , Pi Tun-Wen , Papadopoulos Theodoros A. , Jeng Horng-Tay , Tang Shu-Jung
Published: June 2021

Using photoemission spectroscopy (PES), we have systematically investigated the behavior of polar organic molecule, chloroaluminum phthalocyanine (ClAlPc), adsorbed in the Cl-down configuration on the Ag(111) substrate at low temperature − 195 °C under UV irradiation with a range of different photon fluxes. Judging from the evolution of photoemission spectral line shapes of molecular energy states, we discovered that the Cl atoms are so robustly anchored at Ag(111) that the impinging photons cannot flip the ClAlPc molecules, but instead they crouch them down due to radiation pressure; we observe that the phthalocyanine (Pc) lobes bend down to interact with Ag atoms on the substrate and induce charge transfer from them. As photon flux is increased, radiation pressure on the Pc plane initiates tunneling of the Cl atom through the molecular plane to turn the adsorption configuration of ClAlPc from Cl-down to an upheld Cl-up configuration, elucidating an optomechanical way of manipulating the dipole direction of polar molecules. Finally, work function measurements provide a distinct signature of the resulting upheld Cl-up configuration as it leads to a large increase in vacuum level (VL), ~ 0.4 eV higher than that of a typical flat-on Cl-up configuration driven by thermal annealing.
The impact of socioeconomic and phenotypic traits on self-perception of ethnicity in Latin America
Authors: Paschetta Carolina , de Azevedo Soledad , Ramallo Virginia , Cintas Celia , Pérez Orlando , Navarro Pablo , Bandieri Lucas , Sánchez Mirsha Quinto , Adhikari Kaustubh , Bortolini M. Catira , Ferrara Giovanni Poletti , Gallo Carla , Bedoya Gabriel , Rothhammer Francisco , Alonzo Victor Acuña , Ruiz-Linares Andrés , González-José Rolando
Published: June 2021

Self-perception of ethnicity is a complex social trait shaped by both, biological and non-biological factors. We developed a comprehensive analysis of ethnic self-perception (ESP) on a large sample of Latin American mestizos from five countries, differing in age, socio-economic and education context, external phenotypic attributes and genetic background. We measured the correlation of ESP against genomic ancestry, and the influence of physical appearance, socio-economic context, and education on the distortion observed between both. Here we show that genomic ancestry is correlated to aspects of physical appearance, which in turn affect the individual ethnic self-perceived ancestry. Also, we observe that, besides the significant correlation among genomic ancestry and ESP, specific physical or socio-economic attributes have a strong impact on self-perception. In addition, the distortion among ESP and genomic ancestry differs across age ranks/countries, probably suggesting the underlying effect of past public policies regarding identity. Our results indicate that individuals’ own ideas about its origins should be taken with caution, especially in aspects of modern life, including access to work, social policies, and public health key decisions such as drug administration, therapy design, and clinical trials, among others.