bluuebunny/crossref_metadata_2025 huggingface dataset:
Southern Ocean in-situ temperature trends over 25 years emerge from interannual variability
Authors: Auger Matthis , Morrow Rosemary , Kestenare Elodie , Sallée Jean-Baptiste , Cowley Rebecca
Published: January 2021

Despite playing a major role in global ocean heat storage, the Southern Ocean remains the most sparsely measured region of the global ocean. Here, a unique 25-year temperature time-series of the upper 800 m, repeated several times a year across the Southern Ocean, allows us to document the long-term change within water-masses and how it compares to the interannual variability. Three regions stand out as having strong trends that dominate over interannual variability: warming of the subantarctic waters (0.29 ± 0.09 °C per decade); cooling of the near-surface subpolar waters (−0.07 ± 0.04 °C per decade); and warming of the subsurface subpolar deep waters (0.04 ± 0.01 °C per decade). Although this subsurface warming of subpolar deep waters is small, it is the most robust long-term trend of our section, being in a region with weak interannual variability. This robust warming is associated with a large shoaling of the maximum temperature core in the subpolar deep water (39 ± 09 m per decade), which has been significantly underestimated by a factor of 3 to 10 in past studies. We find temperature changes of comparable magnitude to those reported in Amundsen–Bellingshausen Seas, which calls for a reconsideration of current ocean changes with important consequences for our understanding of future Antarctic ice-sheet mass loss.
SVIP is a molecular determinant of lysosomal dynamic stability, neurodegeneration and lifespan
Authors: Johnson Alyssa E. , Orr Brian O. , Fetter Richard D. , Moughamian Armen J. , Primeaux Logan A. , Geier Ethan G. , Yokoyama Jennifer S. , Miller Bruce L. , Davis Graeme W.
Published: January 2021

Missense mutations in Valosin-Containing Protein (VCP) are linked to diverse degenerative diseases including IBMPFD, amyotrophic lateral sclerosis (ALS), muscular dystrophy and Parkinson’s disease. Here, we characterize a VCP-binding co-factor (SVIP) that specifically recruits VCP to lysosomes. SVIP is essential for lysosomal dynamic stability and autophagosomal–lysosomal fusion. SVIP mutations cause muscle wasting and neuromuscular degeneration while muscle-specific SVIP over-expression increases lysosomal abundance and is sufficient to extend lifespan in a context, stress-dependent manner. We also establish multiple links between SVIP and VCP-dependent disease in our Drosophila model system. A biochemical screen identifies a disease-causing VCP mutation that prevents SVIP binding. Conversely, over-expression of an SVIP mutation that prevents VCP binding is deleterious. Finally, we identify a human SVIP mutation and confirm the pathogenicity of this mutation in our Drosophila model. We propose a model for VCP disease based on the differential, co-factor-dependent recruitment of VCP to intracellular organelles.
Myomerger promotes fusion pore by elastic coupling between proximal membrane leaflets and hemifusion diaphragm
Authors: Golani Gonen , Leikina Evgenia , Melikov Kamran , Whitlock Jarred M. , Gamage Dilani G. , Luoma-Overstreet Gracia , Millay Douglas P. , Kozlov Michael M. , Chernomordik Leonid V.
Published: January 2021

Myomerger is a muscle-specific membrane protein involved in formation of multinucleated muscle cells by mediating the transition from the early hemifusion stage to complete fusion. Here, we considered the physical mechanism of the Myomerger action based on the hypothesis that Myomerger shifts the spontaneous curvature of the outer membrane leaflets to more positive values. We predicted, theoretically, that Myomerger generates the outer leaflet elastic stresses, which propagate into the hemifusion diaphragm and accelerate the fusion pore formation. We showed that Myomerger ectodomain indeed generates positive spontaneous curvature of lipid monolayers. We substantiated the mechanism by experiments on myoblast fusion and influenza hemagglutinin-mediated cell fusion. In both processes, the effects of Myomerger ectodomain were strikingly similar to those of lysophosphatidylcholine known to generate a positive spontaneous curvature of lipid monolayers. The control of post-hemifusion stages by shifting the spontaneous curvature of proximal membrane monolayers may be utilized in diverse fusion processes.
Osteoclast fusion and bone loss are restricted by interferon inducible guanylate binding proteins
Authors: Place David E. , Malireddi R. K. Subbarao , Kim Jieun , Vogel Peter , Yamamoto Masahiro , Kanneganti Thirumala-Devi
Published: January 2021

Chronic inflammation during many diseases is associated with bone loss. While interferons (IFNs) are often inhibitory to osteoclast formation, the complex role that IFN and interferon-stimulated genes (ISGs) play in osteoimmunology during inflammatory diseases is still poorly understood. We show that mice deficient in IFN signaling components including IFN alpha and beta receptor 1 (IFNAR1), interferon regulatory factor 1 (IRF1), IRF9, and STAT1 each have reduced bone density and increased osteoclastogenesis compared to wild type mice. The IFN-inducible guanylate-binding proteins (GBPs) on mouse chromosome 3 (GBP1, GBP2, GBP3, GBP5, GBP7) are required to negatively regulate age-associated bone loss and osteoclastogenesis. Mechanistically, GBP2 and GBP5 both negatively regulate in vitro osteoclast differentiation, and loss of GBP5, but not GBP2, results in greater age-associated bone loss in mice. Moreover, mice deficient in GBP5 or chromosome 3 GBPs have greater LPS-mediated inflammatory bone loss compared to wild type mice. Overall, we find that GBP5 contributes to restricting age-associated and inflammation-induced bone loss by negatively regulating osteoclastogenesis.
Universal toxin-based selection for precise genome engineering in human cells
Authors: Li Songyuan , Akrap Nina , Cerboni Silvia , Porritt Michelle J. , Wimberger Sandra , Lundin Anders , Möller Carl , Firth Mike , Gordon Euan , Lazovic Bojana , Sieńska Aleksandra , Pane Luna Simona , Coelho Matthew A. , Ciotta Giovanni , Pellegrini Giovanni , Sini Marcella , Xu Xiufeng , Mitra Suman , Bohlooly-Y Mohammad , Taylor Benjamin J. M. , Sienski Grzegorz , Maresca Marcello
Published: January 2021

Prokaryotic restriction enzymes, recombinases and Cas proteins are powerful DNA engineering and genome editing tools. However, in many primary cell types, the efficiency of genome editing remains low, impeding the development of gene- and cell-based therapeutic applications. A safe strategy for robust and efficient enrichment of precisely genetically engineered cells is urgently required. Here, we screen for mutations in the receptor for Diphtheria Toxin (DT) which protect human cells from DT. Selection for cells with an edited DT receptor variant enriches for simultaneously introduced, precisely targeted gene modifications at a second independent locus, such as nucleotide substitutions and DNA insertions. Our method enables the rapid generation of a homogenous cell population with bi-allelic integration of a DNA cassette at the selection locus, without clonal isolation. Toxin-based selection works in both cancer-transformed and non-transformed cells, including human induced pluripotent stem cells and human primary T-lymphocytes, as well as it is applicable also in vivo, in mice with humanized liver. This work represents a flexible, precise, and efficient selection strategy to engineer cells using CRISPR-Cas and base editing systems.
Oncogenic herpesvirus KSHV triggers hallmarks of alternative lengthening of telomeres
Authors: Lippert Timothy P. , Marzec Paulina , Idilli Aurora I. , Sarek Grzegorz , Vancevska Aleksandra , Bower Mark , Farrell Paul J. , Ojala Päivi M. , Feldhahn Niklas , Boulton Simon J.
Published: January 2021

To achieve replicative immortality, cancer cells must activate telomere maintenance mechanisms to prevent telomere shortening. ~85% of cancers circumvent telomeric attrition by re-expressing telomerase, while the remaining ~15% of cancers induce alternative lengthening of telomeres (ALT), which relies on break-induced replication (BIR) and telomere recombination. Although ALT tumours were first reported over 20 years ago, the mechanism of ALT induction remains unclear and no study to date has described a cell-based model that permits the induction of ALT. Here, we demonstrate that infection with Kaposi’s sarcoma herpesvirus (KSHV) induces sustained acquisition of ALT-like features in previously non-ALT cell lines. KSHV-infected cells acquire hallmarks of ALT activity that are also observed in KSHV-associated tumour biopsies. Down-regulating BIR impairs KSHV latency, suggesting that KSHV co-opts ALT for viral functionality. This study uncovers KSHV infection as a means to study telomere maintenance by ALT and reveals features of ALT in KSHV-associated tumours.
Large organized chromatin lysine domains help distinguish primitive from differentiated cell populations
Authors: Madani Tonekaboni Seyed Ali , Haibe-Kains Benjamin , Lupien Mathieu
Published: January 2021

The human genome is partitioned into a collection of genomic features, inclusive of genes, transposable elements, lamina interacting regions, early replicating control elements and cis-regulatory elements, such as promoters, enhancers, and anchors of chromatin interactions. Uneven distribution of these features within chromosomes gives rise to clusters, such as topologically associating domains (TADs), lamina-associated domains, clusters of cis-regulatory elements or large organized chromatin lysine (K) domains (LOCKs). Here we show that LOCKs from diverse histone modifications discriminate primitive from differentiated cell types. Active LOCKs (H3K4me1, H3K4me3 and H3K27ac) cover a higher fraction of the genome in primitive compared to differentiated cell types while repressive LOCKs (H3K9me3, H3K27me3 and H3K36me3) do not. Active LOCKs in differentiated cells lie proximal to highly expressed genes while active LOCKs in primitive cells tend to be bivalent. Genes proximal to bivalent LOCKs are minimally expressed in primitive cells. Furthermore, bivalent LOCKs populate TAD boundaries and are preferentially bound by regulators of chromatin interactions, including CTCF, RAD21 and ZNF143. Together, our results argue that LOCKs discriminate primitive from differentiated cell populations.
Controlling nanochannel orientation and dimensions in graphene-based nanofluidic membranes
Authors: Liu Muchun , Weston Paula J. , Hurt Robert H.
Published: January 2021

There is great interest in exploiting van der Waals gaps in layered materials as nanofluidic channels. Graphene oxide (GO) nanosheets are known to spontaneously assemble into stacked planar membranes with transport properties that are highly selective to molecular structure. Use of conventional GO membranes in liquid-phase applications is often limited by low flux values, due to intersheet nanochannel alignment perpendicular to the desired Z-directional transport, which leads to circuitous fluid pathways that are orders of magnitude longer than the membrane thickness. Here we demonstrate an approach that uses compressive instability in Zr-doped GO thin films to create wrinkle patterns that rotate nanosheets to high angles. Capturing this structure in polymer matrices and thin sectioning produce fully dense membranes with arrays of near-vertically aligned nanochannels. These robust nanofluidic devices offer pronounced reduction in fluid path-length, while retaining the high selectivity for water over non-polar molecules characteristic of GO interlayer nanochannels.
Alt-RPL36 downregulates the PI3K-AKT-mTOR signaling pathway by interacting with TMEM24
Authors: Cao Xiongwen , Khitun Alexandra , Luo Yang , Na Zhenkun , Phoodokmai Thitima , Sappakhaw Khomkrit , Olatunji Elizabeth , Uttamapinant Chayasith , Slavoff Sarah A.
Published: January 2021

Thousands of human small and alternative open reading frames (smORFs and alt-ORFs, respectively) have recently been annotated. Many alt-ORFs are co-encoded with canonical proteins in multicistronic configurations, but few of their functions are known. Here, we report the detection of alt-RPL36, a protein co-encoded with human RPL36. Alt-RPL36 partially localizes to the endoplasmic reticulum, where it interacts with TMEM24, which transports the phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) precursor phosphatidylinositol from the endoplasmic reticulum to the plasma membrane. Knock-out of alt-RPL36 increases plasma membrane PI(4,5)P2 levels, upregulates PI3K-AKT-mTOR signaling, and increases cell size. Alt-RPL36 contains four phosphoserine residues, point mutations of which abolish interaction with TMEM24 and, consequently, alt-RPL36 effects on PI3K signaling and cell size. These results implicate alt-RPL36 as an upstream regulator of PI3K-AKT-mTOR signaling. More broadly, the RPL36 transcript encodes two sequence-independent polypeptides that co-regulate translation via different molecular mechanisms, expanding our knowledge of multicistronic human gene functions.
MVP predicts the pathogenicity of missense variants by deep learning
Authors: Qi Hongjian , Zhang Haicang , Zhao Yige , Chen Chen , Long John J. , Chung Wendy K. , Guan Yongtao , Shen Yufeng
Published: January 2021

Accurate pathogenicity prediction of missense variants is critically important in genetic studies and clinical diagnosis. Previously published prediction methods have facilitated the interpretation of missense variants but have limited performance. Here, we describe MVP (Missense Variant Pathogenicity prediction), a new prediction method that uses deep residual network to leverage large training data sets and many correlated predictors. We train the model separately in genes that are intolerant of loss of function variants and the ones that are tolerant in order to take account of potentially different genetic effect size and mode of action. We compile cancer mutation hotspots and de novo variants from developmental disorders for benchmarking. Overall, MVP achieves better performance in prioritizing pathogenic missense variants than previous methods, especially in genes tolerant of loss of function variants. Finally, using MVP, we estimate that de novo coding variants contribute to 7.8% of isolated congenital heart disease, nearly doubling previous estimates.
A hybrid additive manufacturing platform to create bulk and surface composition gradients on scaffolds for tissue regeneration
Authors: Sinha Ravi , Cámara-Torres Maria , Scopece Paolo , Verga Falzacappa Emanuele , Patelli Alessandro , Moroni Lorenzo , Mota Carlos
Published: January 2021

Scaffolds with gradients of physico-chemical properties and controlled 3D architectures are crucial for engineering complex tissues. These can be produced using multi-material additive manufacturing (AM) techniques. However, they typically only achieve discrete gradients using separate printheads to vary compositions. Achieving continuous composition gradients, to better mimic tissues, requires material dosing and mixing controls. No such AM solution exists for most biomaterials. Existing AM techniques also cannot selectively modify scaffold surfaces to locally stimulate cell adhesion. A hybrid AM solution to cover these needs is reported here. A dosing- and mixing-enabled, dual-material printhead and an atmospheric pressure plasma jet to selectively activate/coat scaffold filaments during manufacturing were combined on one platform. Continuous composition gradients in both 2D hydrogels and 3D thermoplastic scaffolds were fabricated. An improvement in mechanical properties of continuous gradients compared to discrete gradients in the 3D scaffolds, and the ability to selectively enhance cell adhesion were demonstrated.
Author Correction: General destabilizing effects of eutrophication on grassland productivity at multiple spatial scales
Authors: Hautier Yann , Zhang Pengfei , Loreau Michel , Wilcox Kevin R. , Seabloom Eric W. , Borer Elizabeth T. , Byrnes Jarrett E. K. , Koerner Sally E. , Komatsu Kimberly J. , Lefcheck Jonathan S. , Hector Andy , Adler Peter B. , Alberti Juan , Arnillas Carlos A. , Bakker Jonathan D. , Brudvig Lars A. , Bugalho Miguel N. , Cadotte Marc , Caldeira Maria C. , Carroll Oliver , Crawley Mick , Collins Scott L. , Daleo Pedro , Dee Laura E. , Eisenhauer Nico , Eskelinen Anu , Fay Philip A. , Gilbert Benjamin , Hansar Amandine , Isbell Forest , Knops Johannes M. H. , MacDougall Andrew S. , McCulley Rebecca L. , Moore Joslin L. , Morgan John W. , Mori Akira S. , Peri Pablo L. , Pos Edwin T. , Power Sally A. , Price Jodi N. , Reich Peter B. , Risch Anita C. , Roscher Christiane , Sankaran Mahesh , Schütz Martin , Smith Melinda , Stevens Carly , Tognetti Pedro M. , Virtanen Risto , Wardle Glenda M. , Wilfahrt Peter A. , Wang Shaopeng
Published: January 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-20997-9.
Fibroblast growth factor receptor facilitates recurrence of minimal residual disease following trastuzumab emtansine therapy
Authors: Akhand Saeed S. , Chen Hao , Purdy Stephen Connor , Liu Zian , Anderson Joshua C. , Willey Christopher D. , Wendt Michael K.
Published: January 2021

Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate (ADC) that efficiently delivers a highly potent microtubule inhibitor to HER2 overexpressing cells. Herein, we utilize HER2 transformed human mammary epithelial cells (HME2) to demonstrate in vitro and in vivo response and recurrence upon T-DM1 treatment. Continuous in vitro dosing of HME2 cells with T-DM1 failed to produce a spontaneously resistant cell line. However, induction of epithelial–mesenchymal transition (EMT) via pretreatment with TGF-β1 was capable of promoting emergence of T-DM1-resistant (TDM1R) cells. Flow cytometric analyses indicated that induction of EMT decreased trastuzumab binding, prior to overt loss of HER2 expression in TDM1R cells. Kinome analyses of TDM1R cells indicated increased phosphorylation of ErbB1, ErbB4, and FGFR1. TDM1R cells failed to respond to the ErbB kinase inhibitors lapatinib and afatinib, but they acquired sensitivity to FIIN4, a covalent FGFR kinase inhibitor. In vivo, minimal residual disease (MRD) remained detectable via bioluminescent imaging following T-DM1-induced tumor regression. Upon cessation of the ADC, relapse occurred and secondary tumors were resistant to additional rounds of T-DM1. These recurrent tumors could be inhibited by FIIN4. Moreover, ectopic overexpression of FGFR1 was sufficient to enhance tumor growth, diminish trastuzumab binding, and promote recurrence following T-DM1-induced MRD. Finally, patient-derived xenografts from a HER2+ breast cancer patient who had progressed on trastuzumab failed to respond to T-DM1, but tumor growth was significantly inhibited by FIIN4. Overall, our studies strongly support therapeutic combination of TDM1 with FGFR-targeted agents in HER2+ breast cancer.
An asymmetric variation of hot and cold SST extremes in the China Seas during the recent warming hiatus period
Authors: Li Yan , Wang Qingyuan , Li Qingquan , Liu Yiwei , Wang Yan
Published: January 2021

Extreme sea surface temperatures (SSTs) attract much attention in recent years. However, the detailed spatial and temporal pattern of the extreme SSTs in China Seas has not been well understood. Using the daily SST data set of OISST v2 from January 1, 1982 to December 31, 2013, and based on four extreme SST indices, the frequency and intensity of SST extremes in the China Seas were examined. The analysis showed that the annual mean SST exhibited cooling trend, on pace with a trend of − 0.34 °C/decade during 1998–2013, confirming the previous studies that China Seas also experienced the recent global warming hiatus. But during this recent global warming hiatus, there was a notable asymmetric pattern of greater cooling trends in cold SSTs as compared to the hot SSTs in this region. During 1998–2013, the cold days (CDs) frequency increased significantly by 13 days per decade and cold SST extremes which were below the 10th percentile of each year (SST10p) notably decreased by 0.4 °C per decade. Hot days (HD) and hot SST extremes which were above the 90th percentile of each year (SST90p) slowed down, but without any distinct tendency. Meanwhile, the rates of SST10p and CDs were highly heterogeneous in space. Cold extremes in the near-shore areas are much more sensitive to the global warming hiatus than these in the eastern of the Kuroshio Current. Importantly, hot extremes do not reveal any distinct cooling tendency during 1998–2013, there were more frequent hot days and more intense hot SSTs in this region comparing with 1982–1997. These hot extremes could push some marine organisms, fisheries and ecosystems beyond the limits of their resilience, with cascading impacts on economies and societies.
Sea-level stands from the Western Mediterranean over the past 6.5 million years
Authors: Dumitru Oana A. , Austermann Jacqueline , Polyak Victor J. , Fornós Joan J. , Asmerom Yemane , Ginés Joaquín , Ginés Angel , Onac Bogdan P.
Published: January 2021

Sea-level reconstructions are important for understanding past ice sheet variability and its response to past and future warming. Here we present Neogene and Quaternary sea-level snapshots using phreatic overgrowths on speleothems (POS) from caves on Mallorca, Spain. POS are excellent sea level index points because of their clear relationship to sea level and precise U–Pb chronology. We find that local sea-level before and at the onset of the Messinian Salinity Crisis was at 33.3 ± 0.25 m (6.54 ± 0.37 Ma) and 31.8 ± 0.25 m (5.86 ± 0.60 Ma) above present levels, respectively. We further present global mean sea level (GMSL) estimates, i.e. local sea level corrected for glacial isostatic adjustment and long-term uplift, for three other POS. The results show that GMSL during the Pliocene–Pleistocene Transition was 6.4 m (− 2.0–8.8 m) at 2.63 ± 0.11 Ma and during the beginning and the end of the Mid-Pleistocene Transition was − 1.1 m (− 5.6–2.4 m) and 5 m (1.5–8.1 m), respectively. These estimates provide important constraints for the past evolution of sea level and show that local sea level prior to the MSC was similar to the highest stand during the Pliocene, with markedly lower position afterwards.
Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses
Authors: Gunawardana Hasitha , Romero Tahmineh , Yao Ning , Heidt Sebastiaan , Mulder Arend , Elashoff David A. , Valenzuela Nicole M.
Published: January 2021

Endothelial cells (EC) coordinate vascular homeostasis and inflammation. In organ transplantation, EC are a direct alloimmune target. We posited that tissue specific heterogeneity of vascular EC may partly underlie the disparate organ-specific alloimmune risk. We examined the vascular endothelial response to inflammation across six primary endothelial beds from four major transplanted organs: the heart, lung, kidney and liver. First, we reanalyzed a public dataset of cardiac allograft rejection and found that endothelial inflammatory response genes were elevated in human cardiac allograft biopsies undergoing rejection compared with stable grafts. Next, the inducible inflammatory phenotypes of EC from heart, lung, kidney, and liver were characterized in vitro, focused on expression of adhesion molecules and chemokines, and recruitment of allogeneic peripheral blood mononuclear immune cells. Large vessel cardiac EC most highly upregulated VCAM-1, particularly compared with hepatic EC, supported greater leukocyte adhesion and had distinct chemokine profiles after stimulation with cytokines and complement. Differentially expressed gene candidates that are known regulators of cytokine signaling and inflammatory programming were verified in publicly available datasets of organ-specific endothelial transcriptomes. In summary, differential baseline expression of immune regulating genes may contribute to differential vascular inflammatory responses depending on organ.
Family graveyards form underappreciated local plant diversity hotspots in China's agricultural landscapes
Authors: Gong Cheng , Li Liangtao , Axmarcher Jan C. , Yu Zhenrong , Liu Yunhui
Published: January 2021

In the intensively farmed, homogenous agricultural landscape of the North China Plain, family graveyards form distinct cultural landscape features. In addition to their cultural value, these graveyards represent semi-natural habitat islands whose potential roles in biodiversity conservation and ecological functioning has remained poorly understood. In this study, we investigated plant species richness on 199 family graveyards of different ages and sizes. In accordance with biogeography theory, both overall and insect-pollinated plant species richness increased with area and age of graveyards. Even small graveyards show a strong potential for conserving local plant richness, and a mosaic of both large and small family graveyards could play an important role in the conservation of farmland biodiversity and related ecosystem functions. The launch of agri-environmental measures that conserve and create semi-natural habitats, in turn benefitting agricultural biodiversity and ecological functioning, has proven difficult in China due to the shortage of dispensable arable land. Given the great value of family graveyards as semi-natural habitats reflected in our study, we propose to focus preliminary efforts on conserving these landscape features as existing, widespread and culturally important semi-natural habitat islands. This would represent an effective, complementary policy to a subsequent re-establishment of other semi-natural habitats for the conservation of biodiversity and ecological functioning in agricultural landscapes.
Deficit saline water irrigation under reduced tillage and residue mulch improves soil health in sorghum-wheat cropping system in semi-arid region
Authors: Soni Pooja Gupta , Basak Nirmalendu , Rai Arvind Kumar , Sundha Parul , Narjary Bhaskar , Kumar Parveen , Yadav Gajender , Kumar Satyendra , Yadav Rajender Kumar
Published: January 2021

Judicious application of saline water except for critical growth stages, could be the only practical solution to meet the crop water demand in arid and semi-arid regions, due to limited access to freshwater, especially during dry winter months. A field experiment was conducted to study the effect of tillage [conventional (CT), reduced (RT), and zero (ZT)], rice straw mulch and deficit saline-water irrigation in wheat (100, 80 and 60% of wheat water requirement, CWR) followed by rainfed sorghum on soil properties and the yields of the cropping system. Yields of both the crops were comparable between RT and CT, but the wheat yield was reduced in ZT. The RT, mulching and deficit saline irrigation in wheat season (60% CWR) increased the sorghum fodder yield. Olsen’s P (8.7–20.6%) and NH4OAc-K (2.5–7.5%) increased in RT and ZT, respectively, over CT under both the crops. Deficit irrigation reduced soil salinity (ECe) by 0.73–1.19 dS m−1after each crop cycle, while soil microbial biomass C (MBC) and N (MBN), dehydrogenase, urease and alkaline phosphatase reduced with an increase in ECe. Theα-glucosidase, MBC, ECe, KMnO4oxidizable N, and urease were identified as major contributors in developing the soil health index. Deficit irrigation (60% CWR) and rice straw mulching under ZT and RT showed higher values of soil health index. Overall, deficit saline-water irrigation under reduced tillage and straw mulching had the greatest potential in maintaining soil health, saving fresh irrigation water without affecting the productivity of the sorghum-wheat system in the semi-arid regions of India. Results also demonstrated that salt affected areas of arid and semiarid countries can replicate the protocol for indexing and screening of soil health indicators to assess the sustainability of a cropping system. This integrated management based on the nature of the available resources also provided a practical approach to achieve the target of land degradation neutrality and land restoration.
Sudden sensorineural hearing loss in patients with vestibular schwannoma
Authors: Wasano Koichiro , Oishi Naoki , Noguchi Masaru , Hentona Ko , Shinden Seiichi , Kitama Tsubasa , Tsuzuki Nobuyoshi , Kawasaki Taiji , Hiraga Yoshihiko , Takei Yasuhiko , Ogawa Kaoru
Published: January 2021

Clinical features of sudden sensorineural hearing loss (SSNHL) associated with vestibular schwannoma (VS) are not fully understood. Determining a treatment plan and explaining it to patients requires clinicians to clearly understand the clinical features related to the tumor, including SSNHL. To identify the full range of clinical features of VS-associated SSNHL, especially recovery of hearing following multiple episodes of SSNHL and what factors predict recovery and recurrence. A multicenter retrospective chart review was conducted in seven tertiary care hospitals between April 1, 2011, and March 31, 2020. We collected and analyzed dose of administered steroid, pure-tone audiometry results, and brain MRIs of patients diagnosed with VS-associated SSNHL. Seventy-seven patients were included. They experienced 109 episodes of audiogram-confirmed SSNHL. The highest proportion of complete recoveries occurred in patients with U-shaped audiograms. The recovery rates for the first, second, and third and subsequent episodes of SSNHL were 53.5%, 28.0%, and 9.1%, respectively. Recovery rate decreased significantly with increasing number of SSNHL episodes (P =0 .0011; Cochran-Armitage test). After the first episode of SSNHL, the recurrence-free rate was 69.9% over 1 year and 57.7% over 2 years; the median recurrence time was 32 months. Logarithmic approximation revealed that there is a 25% probability that SSNHL would recur within a year. SSNHL in patients with VS is likely to recur within one year in 25% of cases. Also, recovery rate decreases as a patient experiences increasing episodes of SSNHL.
The number of osteoclasts in a biopsy specimen can predict the efficacy of neoadjuvant chemotherapy for primary osteosarcoma
Authors: Araki Yoshihiro , Yamamoto Norio , Hayashi Katsuhiro , Takeuchi Akihiko , Miwa Shinji , Igarashi Kentaro , Higuchi Takashi , Abe Kensaku , Taniguchi Yuta , Yonezawa Hirotaka , Morinaga Sei , Asano Yohei , Ikeda Hiroko , Nojima Takayuki , Tsuchiya Hiroyuki
Published: January 2021

Osteosarcoma is the most common primary malignant bone tumor, and its standard treatment is a combination of surgery and chemotherapy. A poor response to chemotherapy causes unfavorable oncological outcomes. We investigated the correlation between osteoclast differentiation in biopsy specimens and the efficacy of neoadjuvant chemotherapy in resected specimens. Forty-nine patients who underwent neoadjuvant chemotherapy and subsequent surgical treatment at our institution between 1999 and 2018 were enrolled. Using medical records, we investigated the age, sex, tumor size, location, subtype, staging, chemotherapy agents (doxorubicin, cisplatin, ifosfamide, and methotrexate), number of neoadjuvant chemotherapy courses, number of osteoclasts in biopsy specimens, and efficacy of neoadjuvant chemotherapy according to the Rosen and Huvos classification (Grade I-IV) in resected specimens. Univariate and multivariate analyses were performed to identify factors predictive of a good response in resected specimens after neoadjuvant chemotherapy. A good response (Grade III/IV) was detected in 25, while a poor response (Grade I/II) was detected in 24. According to the multivariate analysis, ≥ 46 years old (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.01–0.45; p < 0.01) and ≥ 5 mature osteoclasts in a biopsy specimen (OR, 36.9; 95% CI, 6.03–225; p < 0.01) were significantly associated with the neoadjuvant chemotherapy efficacy. The accuracy for predicting a good response to chemotherapy based on ≥ 5 osteoclasts in a biopsy specimen in patients < 46 years old was 85%. The number of mature osteoclasts in biopsy specimens is a simple factor for predicting the efficacy of chemotherapy before treatment, although further studies will be required to determine the underlying mechanism.
Reduced sampling rate Kalman filters for carrier phase and frequency offset tracking in 200 Gbps 16 QAM coherent communication system
Authors: Sharma Srishti , Krishnamurthy Pradeep Kumar
Published: January 2021

We propose 1 state and 2 state multi-step Kalman filters (MKFs) to estimate and compensate CFO, LPN and NLPN in long-haul coherent fiber-optic communication systems. The proposed filters generate state estimates once everymsymbols and therefore operate at a reduced sampling rate compared to conventional KFs that perform symbol by symbol processing. No computations are performed to obtain phase estimates of the intermediate$$m-1$$m-1samples; instead, the present and previous estimates are averaged and used to derotate the intermediate$$m-1$$m-1samples which are then demodulated to recover the transmitted symbols. This reduces the computational load on the receiver DSP. Further, in order to improve estimation accuracy, we adaptively vary the process noise covarianceQ. Simulation results of 200 Gbps PDM 16 QAM system over 12 spans shows that the proposed 1 state MKF can reduce the sampling rate requirement by a factor of$$m = 20$$m=20with Q-factor degradation of 1.32 dB compared to single-step KF at linewidth of 100 kHz. The 2 state MKF tracks PN and CFO with a maximum step size of$$m=10$$m=10for a CFO of 100 MHz at linewidth of 100 kHz. We also study the dynamic performance of the proposed algorithms by applying step change to CFO. The 2 state MKF with adaptiveQis able to track a step change of 400 MHz of CFO with$$m = 1$$m=1and 3 with high estimation accuracy but slower convergence time compared to the non-adaptive 2 state MKF. Finally, we study the computational requirements of the proposed MKFs and show that they offer significant reduction in computations compared to single-step KF thus making the proposed filters suitable for hardware implementation.
Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants
Authors: Russell Jordan T. , Lauren Ruoss J. , de la Cruz Diomel , Li Nan , Bazacliu Catalina , Patton Laura , McKinley Kelley Lobean , Garrett Timothy J. , Polin Richard A. , Triplett Eric W. , Neu Josef
Published: January 2021

Antibiotic use in neonates can have detrimental effects on the developing gut microbiome, increasing the risk of morbidity. A majority of preterm neonates receive antibiotics after birth without clear evidence to guide this practice. Here microbiome, metabolomic, and immune marker results from the routine early antibiotic use in symptomatic preterm Neonates (REASON) study are presented. The REASON study is the first trial to randomize symptomatic preterm neonates to receive or not receive antibiotics in the first 48 h after birth. Using 16S rRNA sequencing of stool samples collected longitudinally for 91 neonates, the effect of such antibiotic use on microbiome diversity is assessed. The results illustrate that type of nutrition shapes the early infant gut microbiome. By integrating data for the gut microbiome, stool metabolites, stool immune markers, and inferred metabolic pathways, an association was discovered betweenVeillonellaand the neurotransmitter gamma-aminobutyric acid (GABA). These results suggest early antibiotic use may impact the gut-brain axis with the potential for consequences in early life development, a finding that needs to be validated in a larger cohort.

Trial RegistrationThis project is registered at clinicaltrials.gov under the name “Antibiotic ‘Dysbiosis’ in Preterm Infants” with trial number NCT02784821.
Muscle metabolic remodelling patterns in Duchenne muscular dystrophy revealed by ultra-high-resolution mass spectrometry imaging
Authors: Dabaj Ivana , Ferey Justine , Marguet Florent , Gilard Vianney , Basset Carole , Bahri Youssef , Brehin Anne-Claire , Vanhulle Catherine , Leturcq France , Marret Stéphane , Laquerrière Annie , Schmitz-Afonso Isabelle , Afonso Carlos , Bekri Soumeya , Tebani Abdellah
Published: January 2021

Duchenne muscular dystrophy (DMD) is a common and severe X-linked myopathy, characterized by muscle degeneration due to altered or absent dystrophin. DMD has no effective cure, and the underlying molecular mechanisms remain incompletely understood. The aim of this study is to investigate the metabolic changes in DMD using mass spectrometry-based imaging. Nine human muscle biopsies from DMD patients and nine muscle biopsies from control individuals were subjected to untargeted MSI using matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry. Both univariate and pattern recognition techniques have been used for data analysis. This study revealed significant changes in 34 keys metabolites. Seven metabolites were decreased in the Duchenne biopsies compared to control biopsies including adenosine triphosphate, and glycerophosphocholine. The other 27 metabolites were increased in the Duchenne biopsies, including sphingomyelin, phosphatidylcholines, phosphatidic acids and phosphatidylserines. Most of these dysregulated metabolites are tightly related to energy and phospholipid metabolism. This study revealed a deep metabolic remodelling in phospholipids and energy metabolism in DMD. This systems-based approach enabled exploring the metabolism in DMD in an unprecedented holistic and unbiased manner with hypothesis-free strategies.
Bayesian inference of the viscoelastic properties of a Jeffrey’s fluid using optical tweezers
Authors: Paul Shuvojit , Narinder N , Banerjee Ayan , Nayak K Rajesh , Steindl Jakob , Bechinger Clemens
Published: January 2021

Bayesian inference is a conscientious statistical method which is successfully used in many branches of physics and engineering. Compared to conventional approaches, it makes highly efficient use of information hidden in a measured quantity by predicting the distribution of future data points based on posterior information. Here we apply this method to determine the stress-relaxation time and the solvent and polymer contributions to the frequency dependent viscosity of a viscoelastic Jeffrey’s fluid by the analysis of the measured trajectory of an optically trapped Brownian particle. When comparing the results to those obtained from the auto-correlation function, mean-squared displacement or the power spectrum, we find Bayesian inference to be much more accurate and less affected by systematic errors.
Recording site placement on planar silicon-based probes affects signal quality in acute neuronal recordings
Authors: Fiáth Richárd , Meszéna Domokos , Somogyvári Zoltán , Boda Mihály , Barthó Péter , Ruther Patrick , Ulbert István
Published: January 2021

Multisite, silicon-based probes are widely used tools to record the electrical activity of neuronal populations. Several physical features of these devices are designed to improve their recording performance. Here, our goal was to investigate whether the position of recording sites on the silicon shank might affect the quality of the recorded neural signal in acute experiments. Neural recordings obtained with five different types of high-density, single-shank, planar silicon probes from anesthetized rats were analyzed. Wideband data were filtered to extract spiking activity, then the amplitude distribution of samples and quantitative properties of the recorded brain activity (single unit yield, spike amplitude and isolation distance) were compared between sites located at different positions of the silicon shank, focusing particularly on edge and center sites. Edge sites outperformed center sites: for all five probe types there was a significant difference in the signal power computed from the amplitude distributions, and edge sites recorded significantly more large amplitude samples both in the positive and negative range. Although the single unit yield was similar between site positions, the difference in spike amplitudes was noticeable in the range corresponding to high-amplitude spikes. Furthermore, the advantage of edge sites slightly decreased with decreasing shank width. Our results might aid the design of novel neural implants in enhancing their recording performance by identifying more efficient recording site placements.
Cellular automaton decoders for topological quantum codes with noisy measurements and beyond
Authors: Vasmer Michael , Browne Dan E. , Kubica Aleksander
Published: January 2021

We propose an error correction procedure based on a cellular automaton, the sweep rule, which is applicable to a broad range of codes beyond topological quantum codes. For simplicity, however, we focus on the three-dimensional toric code on the rhombic dodecahedral lattice with boundaries and prove that the resulting local decoder has a non-zero error threshold. We also numerically benchmark the performance of the decoder in the setting with measurement errors using various noise models. We find that this error correction procedure is remarkably robust against measurement errors and is also essentially insensitive to the details of the lattice and noise model. Our work constitutes a step towards finding simple and high-performance decoding strategies for a wide range of quantum low-density parity-check codes.
Evaluation of smartphone interactions on drivers’ brain function and vehicle control in an immersive simulated environment
Authors: Baker Joseph M. , Bruno Jennifer L. , Piccirilli Aaron , Gundran Andrew , Harbott Lene K. , Sirkin David. M. , Marzelli Matthew , Hosseini S. M. Hadi , Reiss Allan L.
Published: January 2021

Smartphones and other modern technologies have introduced multiple new forms of distraction that color the modern driving experience. While many smartphone functions aim to improve driving by providing the driver with real-time navigation and traffic updates, others, such as texting, are not compatible with driving and are often the cause of accidents. Because both functions elicit driver attention, an outstanding question is the degree to which drivers’ naturalistic interactions with navigation and texting applications differ in regard to brain and behavioral indices of distracted driving. Here, we employed functional near-infrared spectroscopy to examine the cortical activity that occurs under parametrically increasing levels of smartphone distraction during naturalistic driving. Our results highlight a significant increase in bilateral prefrontal and parietal cortical activity that occurs in response to increasingly greater levels of smartphone distraction that, in turn, predicts changes in common indices of vehicle control.
Comparative analysis on the anti-inflammatory/immune effect of mesenchymal stem cell therapy for the treatment of pulmonary arterial hypertension
Authors: Oh Seyeon , Jang Albert Y. , Chae Sehyun , Choi Seungbum , Moon Jeongsik , Kim Minsu , Spiekerkoetter Edda , Zamanian Roham T. , Yang Phillip C. , Hwang Daehee , Byun Kyunghee , Chung Wook-Jin
Published: January 2021

Despite the advancement of targeted therapy for pulmonary arterial hypertension (PAH), poor prognosis remains a reality. Mesenchymal stem cells (MSCs) are one of the most clinically feasible alternative treatment options. We compared the treatment effects of adipose tissue (AD)-, bone marrow (BD)-, and umbilical cord blood (UCB)-derived MSCs in the rat monocrotaline-induced pulmonary hypertension (PH) model. The greatest improvement in the right ventricular function was observed in the UCB-MSCs treated group. The UCB-MSCs treated group also exhibited the greatest improvement in terms of the largest decrease in the medial wall thickness, perivascular fibrosis, and vascular cell proliferation, as well as the lowest levels of recruitment of innate and adaptive immune cells and associated inflammatory cytokines. Gene expression profiling of lung tissue confirmed that the UCB-MSCs treated group had the most notably attenuated immune and inflammatory profiles. Network analysis further revealed that the UCB-MSCs group had the greatest therapeutic effect in terms of the normalization of all three classical PAH pathways. The intravenous injection of the UCB-MSCs, compared with those of other MSCs, showed superior therapeutic effects in the PH model for the (1) right ventricular function, (2) vascular remodeling, (3) immune/inflammatory profiles, and (4) classical PAH pathways.
Population difference gratings created on vibrational transitions by nonoverlapping subcycle THz pulses
Authors: Arkhipov Rostislav , Pakhomov Anton , Arkhipov Mikhail , Babushkin Ihar , Demircan Ayhan , Morgner Uwe , Rosanov Nikolay
Published: January 2021

We study theoretically a possibility of creation and ultrafast control (erasing, spatial frequency multiplication) of population density gratings in a multi-level resonant medium having a resonance transition frequency in the THz range. These gratings are produced by subcycle THz pulses coherently interacting with a nonlinear medium, without any need for pulses to overlap, thereby utilizing an indirect pulse interaction via an induced coherent polarization grating. High values of dipole moments of the transitions in the THz range facilitate low field strength of the needed THz excitation. Our results clearly show this possibility in multi-level resonant media. Our theoretical approach is based on an approximate analytical solution of time-dependent Schrödinger equation (TDSE) using perturbation theory. Remarkably, as we show here, quasi-unipolar subcycle pulses allow more efficient excitation of higher quantum levels, leading to gratings with a stronger modulation depth. Numerical simulations, performed for THz resonances of the$$H_20$$H20molecule using Bloch equations for density matrix elements, are in agreement with analytical results in the perturbative regime. In the strong-field non-perturbative regime, the spatial shape of the gratings becomes non-harmonic. A possibility of THz radiation control using such gratings is discussed. The predicted phenomena open novel avenues in THz spectroscopy of molecules with unipolar and quasi-unipolar THz light bursts and allow for better control of ultra-short THz pulses.
Biosynthesis and characterization of gold nanoparticles using Brazilian red propolis and evaluation of its antimicrobial and anticancer activities
Authors: Botteon C. E. A. , Silva L. B. , Ccana-Ccapatinta G. V. , Silva T. S. , Ambrosio S. R. , Veneziani R. C. S. , Bastos J. K. , Marcato P. D.
Published: January 2021

Gold nanoparticles (AuNPs) are highlighted due to their low toxicity, compatibility with the human body, high surface area to volume ratio, and surfaces that can be easily modified with ligands. Biosynthesis of AuNPs using plant extract is considered a simple, low-cost, and eco-friendly approach. Brazilian Red Propolis (BRP), a product of bees, exhibits anti-inflammatory, anti-tumor, antioxidant, and antimicrobial activities. Here, we described the biosynthesis of AuNPs using BRP extract (AuNPextract) and its fractions (AuNPhexane, AuNPdichloromethane, AuNPethyl acetate) and evaluated their structural properties and their potential against microorganisms and cancer cells. AuNPs showed a surface plasmon resonance (SPR) band at 535 nm. The sizes and morphologies were influenced by the BRP sample used in the reaction. FTIR and TGA revealed the involvement of bioactive compounds from BRP extract or its fractions in the synthesis and stabilization of AuNPs. AuNPdichloromethaneand AuNPhexaneexhibited antimicrobial activities against all strains tested, showing their efficacy as antimicrobial agents to treat infectious diseases. AuNPs showed dose-dependent cytotoxic activity both in T24 and PC-3 cells. AuNPdichloromethaneand AuNPextractexhibited the highest in vitro cytotoxic effect. Also, the cytotoxicity of biogenic nanoparticles was induced by mechanisms associated with apoptosis. The results highlight a potential low-cost green method using Brazilian red propolis to synthesize AuNPs, which demonstrated significant biological properties.