bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of mouse Y chromosome geneZfy1andZfy2leads to spermatogenesis impairment, sperm defects, and infertility
Authors: Yamauchi Yasuhiro , Matsumura Takafumi , Bakse Jackson , Holmlund Hayden , Blanchet Genevieve , Carrot Emmaelle , Ikawa Masahito , Ward Monika A 
Published: March 2022

AbstractUsing mice with Y chromosome deficiencies and supplementing Zfy transgenes, we, and others, have previously shown that the loss of Y chromosome Zfy1 and Zfy2 genes is associated with infertility and spermiogenic defects and that the addition of Zfy transgenes rescues these defects. In these past studies, the absence of Zfy was linked to the loss of other Y chromosome genes, which might have contributed to spermiogenic phenotypes. Here, we used CRISPR/Cas9 to specifically remove open reading frame of Zfy1, Zfy2, or both Zfy1 and Zfy2, and generated Zfy knockout (KO) and double knockout (DKO) mice. Zfy1 KO and Zfy2 KO mice were both fertile, but the latter had decreased litters size and sperm number, and sperm headshape abnormalities. Zfy DKO males were infertile and displayed severe spermatogenesis defects. Postmeiotic arrest largely prevented production of sperm and the few sperm that were produced all displayed gross headshape abnormalities and structural defects within head and tail. Infertility of Zfy DKO mice could be overcome by injection of spermatids or sperm directly to oocytes, and the resulting male offspring had the same spermiogenic phenotype as their fathers. The study is the first describing detailed phenotypic characterization of mice with the complete Zfy gene loss. It provides evidence supporting that the presence of at least one Zfy homolog is essential for male fertility and development of normal sperm functional in unassisted fertilization. The data also show that while the loss of Zfy1 is benign, the loss of Zfy2 is mildly detrimental for spermatogenesis.
Protective antibody response to mRNA-1273 and BNT162b2 vaccines in patients on maintenance haemodialysis: a prospective cohort study
Authors: Dimitrov Yves , Krummel Thierry , Chantrel François , Faller Anne-Laure , Ott Julien , David Daniela , Bazin-Kara Dorothée , Hannedouche Thierry , Borni Claire 
Published: March 2022

ABSTRACT

Background
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is more frequent and severe in patients with chronic kidney disease (CKD) on maintenance haemodialysis (HD). Vaccines are now available, but the protective response rates and determinants of humoral response to the vaccine are poorly described.

Methods
This prospective observational study describes the response rates of detectable and protective antibody titres 1 month after each dose of an mRNA vaccine in a cohort of 851 patients on maintenance HD.

Findings
Among naïve SARS-CoV-2 patients, a vast majority produced detectable (95.2%) or protective levels of antibodies (69.6%) 1 month after the second vaccine dose. In addition, the response rate was significantly higher with the mRNA-1273 than with the BNT162b2 vaccine 1 month after the second dose (79.8 versus 59.1%, respectively; P &lt; 0.001). The main determinants for an inadequate humoral response were older age, treatment with immunosuppressants or oral anticoagulants and low serum albumin. All the patients who encountered coronavirus disease 2019 before vaccination also reached a highly protective humoral response.

Interpretation
We found an acceptable humoral response rate in patients on maintenance HD, much higher than in transplant recipients. Therefore the third dose of vaccine may be justified in those patients with an inadequate humoral response, particularly those with a history of organ transplantation or immunosuppressive treatment.
CWSOGG: Catching Web Shell Obfuscation Based on Genetic Algorithm and Generative Adversarial Network
Authors: Pang Bo , Liang Gang , Yang Jin , Chen Yijing , Wang Xinyi , He Wenbo 
Published: March 2022

Abstract
A web shell is a backdoor used by hackers to control Web servers and perform privilege escalation, and thus it is crucial to detect web shells effectively. However, the detection of obfuscated web shells has always been a challenge. Inspired by adversarial training methods in the field of computer vision, this paper proposes a generative adversarial network (GAN)-based web shell detection model training framework. Since there has been no method that can generate obfuscated web shells effectively, a generator based on the genetic algorithm, which combines and optimizes the pre-set obfuscation methods, is used to obtain new obfuscation combinations and generate obfuscated samples. The whole proposed framework is named the CWSOGG. When training the detection model, the generator generates web shells that can bypass the discriminator, and the discriminator catches the features of obfuscated samples. Through the adversarial training of the discriminator and generator, the detection model improves its ability to detect obfuscated web shells. To verify the proposed framework is flexible to different models, the discriminator based on four main neural networks has been implemented. Meanwhile, to build complete feature extraction models, both statistical and semantic features are extracted. Due to the lack of web shell data, a clean dataset containing 4,375 web shells is constructed and used to evaluate the CWSOGG. The results have shown that the detection accuracy of each model increases by 86.71% on the generated obfuscated web shells on average and by 7.50% on the simulated real-world obfuscated web shells on average.
After the Cambridge Controversies: Reflections Old and New
Authors: Gram Harvey 
Published: March 2022

Abstract
Perfect foresight is a consequence of applying the Pontryagin Maximum Principle to the analysis of an intertemporal general equilibrium. For this reason, the capital theory controversy ended in an intellectual impasse. The critique of mainstream theory largely ignored the perfect foresight entailments of intertemporal equilibrium analysis, while its defenders, with notable exceptions, too often failed to acknowledge this implication of the technique of dynamic programming. From this standpoint, the long debate over the existence or non-existence of an aggregate production function is secondary. This leaves open the theoretical question of how to proceed with an analysis of the actual dynamics of capitalist development. The critique of mainstream capital theory remains a ‘prelude’, caught up in an ever deeper analysis of the implications of alternative representations of the technique of production. The first part of this paper deals with the question of how perfect foresight came to infect mainstream theory; the second part turns to a consideration of a weakness in the dual representation of the technique of production in the simplest Sraffian framework. Neither part addresses the bigger questions of how to analyze the process of uneven development under the capitalist rules of the game.
Favourable Tolerability and Drug Survival of Tioguanine Versus Methotrexate After Failure of Conventional Thiopurines in Crohn’s Disease
Authors: Savelkoul E H J , Maas M H J , Bourgonje A R , Crouwel F , Biemans V B C , den Broeder N , Russel M G V M , Römkens T E H , de Boer N K , Dijkstra G , Hoentjen F 
Published: March 2022

AbstractBackground and AimsBoth methotrexate and tioguanine can be considered as treatment options in patients with Crohn’s disease after failure of conventional thiopurines. This study aimed to compare tolerability and drug survival of methotrexate and tioguanine therapy after failure of conventional thiopurines in patients with Crohn’s disease.MethodsWe conducted a retrospective, multicentre study, including patients with Crohn’s disease initiating monotherapy methotrexate or tioguanine after failure [all causes] of conventional thiopurines. Follow-up duration was 104 weeks or until treatment discontinuation. The primary outcome was cumulative therapy discontinuation incidence due to adverse events. Secondary outcomes included total number of [serious] adverse events, and ongoing monotherapy.ResultsIn total, 219 patients starting either methotrexate [n = 105] or tioguanine [n = 114] were included. In all 65 [29.7%] patients (methotrexate 43.8% [46/105 people], tioguanine 16.7% [19/114 people], p &lt;0.001) discontinued their treatment due to adverse events during follow-up. Median time until discontinuation due to adverse events was 16 weeks (interquartile range [IQR] 7-38, p = 0.812). Serious adverse events were not significantly different. Patients treated with methotrexate experienced adverse events more often [methotrexate 83%, tioguanine 46%, p &lt;0.001]. Total monotherapy drug survival after 104 weeks was 22% for methotrexate and 46% for tioguanine [p &lt;0.001].ConclusionsWe observed a higher cumulative discontinuation incidence due to adverse events for methotrexate [44%] compared with tioguanine [17%] in Crohn’s disease patients after failure of conventional thiopurines. The total adverse events incidence during methotrexate use was higher, whereas serious adverse events incidence was similar. These favourable results for tioguanine treatment may guide the selection of immunosuppressive therapy after failure of conventional thiopurines.
Bacterial extracellular polymeric substances as potential saliva substitute
Authors: Kardas Piotr , Astasov-Frauenhoffer Monika , Braissant Olivier , Bornstein Michael M , Waltimo Tuomas 
Published: March 2022

Abstract
This proof-of-principle study aims to find commensal oral bacteria that can produce extracellular polymeric substances (EPS), which have similar lubrication properties to saliva and could serve as saliva substitutes. Saliva and plaque samples were collected from 21 generally healthy individuals. Primary screening was done by conventional culturing and Gram-staining; all species selected for further analysis were identified by MALDI-TOF and deposited in DSMZ. Lactobacillus gasseri (DSM32453 and DSM32455), Lactobacillus rhamnosus (DSM32452), Lactobacillus paracasei (DSM32454), and Streptococcus sanguinis (DSM32456) produced 413.6, 415.7, 431.1, 426.8, and 877.6 µg/ml of EPS, respectively. At the same time calcium dissolution could not be detected for both L. gasseri strains, minimal dissolution for the other three: S. sanguinis 0.3 mm, and 3.7 mm for L. rhamnosus and L. paracasei. There were no differences found between the EPS samples and the saliva for the effect of shear rate on the viscosity and for the effect of sliding speed on lubrication properties. In conclusion, five commensal bacterial strains have been isolated, all able to produce EPS and lead to no or to low calcium dissolution. EPS produced exhibits rheological and tribological properties comparable to human saliva. A total of four out of five selected strains are probiotic and, therefore, may exhibit additional beneficial influence within the oral cavity.
Gene Body Methylation in Plants: Mechanisms, Functions, and Important Implications for Understanding Evolutionary Processes
Authors: Muyle Aline M , Seymour Danelle K , Lv Yuanda , Huettel Bruno , Gaut Brandon S 
Published: March 2022

Abstract
Gene body methylation (gbM) is an epigenetic mark where gene exons are methylated in the CG context only, as opposed to CHG and CHH contexts (where H stands for A, C, or T). CG methylation is transmitted transgenerationally in plants, opening the possibility that gbM may be shaped by adaptation. This presupposes, however, that gbM has a function that affects phenotype, which has been a topic of debate in the literature. Here, we review our current knowledge of gbM in plants. We start by presenting the well-elucidated mechanisms of plant gbM establishment and maintenance. We then review more controversial topics: the evolution of gbM and the potential selective pressures that act on it. Finally, we discuss the potential functions of gbM that may affect organismal phenotypes: gene expression stabilization and upregulation, inhibition of aberrant transcription (reverse and internal), prevention of aberrant intron retention, and protection against TE insertions. To bolster the review of these topics, we include novel analyses to assess the effect of gbM on transcripts. Overall, a growing body of literature finds that gbM correlates with levels and patterns of gene expression. It is not clear, however, if this is a causal relationship. Altogether, functional work suggests that the effects of gbM, if any, must be relatively small, but there is nonetheless evidence that it is shaped by natural selection. We conclude by discussing the potential adaptive character of gbM and its implications for an updated view of the mechanisms of adaptation in plants.
Properties of 2-locus genealogies and linkage disequilibrium in temporally structured samples
Authors: Biddanda Arjun , Steinrücken Matthias , Novembre John 
Published: March 2022

Abstract
Archeogenetics has been revolutionary, revealing insights into demographic history and recent positive selection. However, most studies to date have ignored the nonrandom association of genetic variants at different loci (i.e. linkage disequilibrium). This may be in part because basic properties of linkage disequilibrium in samples from different times are still not well understood. Here, we derive several results for summary statistics of haplotypic variation under a model with time-stratified sampling: (1) The correlation between the number of pairwise differences observed between time-staggered samples (πΔt) in models with and without strict population continuity; (2) The product of the linkage disequilibrium coefficient, D, between ancient and modern samples, which is a measure of haplotypic similarity between modern and ancient samples; and (3) The expected switch rate in the Li and Stephens haplotype copying model. The latter has implications for genotype imputation and phasing in ancient samples with modern reference panels. Overall, these results provide a characterization of how haplotype patterns are affected by sample age, recombination rates, and population sizes. We expect these results will help guide the interpretation and analysis of haplotype data from ancient and modern samples.
Laterally constrained surface wave inversion
Authors: Cruz-Hernández Favio , Gallardo Luis A , Calò Marco , Castro Raúl R , Romo-Jones José M 
Published: March 2022

SUMMARYIn the last 15 yr, the use of surface waves retrieved from the cross-correlation of ambient seismic noise has significantly increased its applications to determine or monitor changes in the elastic properties of the Earth's interior. We designed a methodology for laterally constrained surface wave inversion based on a two-stage technique to estimate the 3-D distribution of the S-wave velocity (Vs). The first stage inverts traveltimes to estimate group or phase velocity dispersion maps and their inverse covariance matrix for different periods. The inverse covariance matrix is constructed explicitly using the ray tracing information. The inverse covariance matrix adds the lateral sensitivity of the maps to the structure, whereas the period-dependency provides sensitivity to the structure at depth. The second stage applies a nonlinear conjugate gradient scheme to estimate the 3-D distribution of S-wave velocity using the ensemble of velocity dispersion maps and their estimated inverse covariance matrix. We validate the methodology using a synthetic model. The results show an improved estimation of subsurface S-wave velocity structures compared to conventional point-wise inversion.
Membrane glycome is impacted by the cell culturing mode of neuroblastoma cells with differing migration and invasion potential
Authors: Sumer-Bayraktar Zeynep , Fife Christopher M , Byrne Frances L , Kavallaris Maria , Packer Nicolle H 
Published: March 2022

Abstract
Neuroblastoma is a highly metastatic childhood cancer for which studies indicate an association between protein glycosylation and tumor behavior. However, there is a lack of detailed glycome analysis on neuroblastoma cells that have varying metastatic potential. Furthermore, the impact of the cell culturing mode, i.e. 2-dimensional (2D) versus 3-dimensional (3D) spheroids, on the membrane protein glycome is unknown. To address these gaps in knowledge, we mapped membrane protein N- and O-glycosylation of neuroblastoma cells that have lower invasive and metastatic potential (Stathmin shRNA-expressing cells, StmnSeq2SH, and StmnSeq3SH) compared with control cells (control shRNA-expressing cells, CtrlSH). We showed that the neuroblastoma cells with different migratory and invasive potential underwent drastic changes in their membrane protein N-glycosylation exclusively when cultured in 3D spheroids. We also investigated the impact of 2D and 3D cell culture methods on cellular glycosylation using the neuroblastoma cells and found the cell N-glycome was markedly impacted by the culture method, with the 2D grown cells showing an abundance of oligomannosidic glycans, whereas 3D spheroids expressed more complex type glycans on their membrane proteins. In summary, this study provides the first comprehensive protein glycome profiling of neuroblastoma cells that have varying invasiveness and migratory potential and unravels the distinct membrane glycan features of cells that are grown under 2D versus 3D culture conditions.
Grafting with rootstocks promotes phenolic compound accumulation in grape berry skin during development based on integrative multi-omics analysis
Authors: Zhang Fuchun , Zhong Haixia , Zhou Xiaoming , Pan Mingqi , Xu Juan , Liu Mingbo , Wang Min , Liu Guotian , Xu Tengfei , Wang Yuejin , Wu Xinyu , Xu Yan 
Published: March 2022

AbstractIn viticulture, grafting has been practiced widely and influences grape development as well as berry and wine quality. However, there is limited understanding of the effects of rootstocks on grape phenolic compounds, which are located primarily in the berry skin and contribute to certain sensory attributes of wine. In this study, scion–rootstock interactions were investigated at the green-berry stage and the veraison stage when grapevines were hetero-grafted with three commonly used rootstock genotypes (5BB, 101-14MG, and SO4). Physiological investigations showed that hetero-grafts, especially CS/5BB, contained higher concentrations of total proanthocyanidins (PAs) and various PA components in berry skins compared with the auto-grafted grapevines. Further metabolomics analysis identified 105 differentially accumulated flavonoid compounds, the majority of which, including anthocyanins, PAs, and flavonols, were significantly increased in the berry skins of hetero-grafted grapevines compared with auto-grafted controls. In addition, transcriptomic analysis of the same samples identified several thousand differentially expressed genes between hetero-grafted and auto-grafted vines. The three rootstocks not only increased the transcript levels of stilbene, anthocyanin, PA, and flavonol synthesis genes but also affected the expression of numerous transcription factor genes. Taken together, our results suggest that hetero-grafting can promote phenolic compound accumulation in grape berry skin during development. These findings provide new insights for improving the application value of grafting by enhancing the accumulation of nutritious phenolic components in grape.
Leveraging a graft collection to develop metabolome-based trait prediction for the selection of tomato rootstocks with enhanced salt tolerance
Authors: Song Chao , Acuña Tania , Adler-Agmon Michal , Rachmilevitch Shimon , Barak Simon , Fait Aaron 
Published: March 2022

AbstractGrafting has been demonstrated to significantly enhance the salt tolerance of crops. However, breeding efforts to develop enhanced graft combinations are hindered by knowledge-gaps as to how rootstocks mediate scion-response to salt stress. We grafted the scion of cultivated M82 onto rootstocks of 254 tomato accessions and explored the morphological and metabolic responses of grafts under saline conditions (EC = 20 dS m−1) as compared to self-grafted M82 (SG-M82). Correlation analysis and Least Absolute Shrinkage and Selection Operator were performed to address the association between morphological diversification and metabolic perturbation. We demonstrate that grafting the same variety onto different rootstocks resulted in scion phenotypic heterogeneity and emphasized the productivity efficiency of M82 irrespective of the rootstock. Spectrophotometric analysis to test lipid oxidation showed largest variability of malondialdehyde (MDA) equivalents across the population, while the least responsive trait was the ratio of fruit fresh weight to total fresh weight (FFW/TFW). Generally, grafts showed greater values for the traits measured than SG-M82, except for branch number and wild race-originated rootstocks; the latter were associated with smaller scion growth parameters. Highly responsive and correlated metabolites were identified across the graft collection including malate, citrate, and aspartate, and their variance was partly related to rootstock origin. A group of six metabolites that consistently characterized exceptional graft response was observed, consisting of sorbose, galactose, sucrose, fructose, myo-inositol, and proline. The correlation analysis and predictive modelling, integrating phenotype- and leaf metabolite data, suggest a potential predictive relation between a set of leaf metabolites and yield-related traits.
Characterization and functional validation of β-carotene hydroxylase AcBCH genes in Actinidia chinensis
Authors: Xia Hui , Zhou Yuanjie , Lin Zhiyi , Guo Yuqi , Liu Xinling , Wang Tong , Wang Jin , Deng Honghong , Lin Lijin , Deng Qunxian , Lv Xiulan , Xu Kunfu , Liang Dong 
Published: March 2022

Abstract
Carotenoids are the pigment substances of yellow-fleshed kiwifruit, and among them β-cryptoxanthin has only been detected in the brighter yellow-fleshed variety ‘Jinshi 1’. β-Carotene hydroxylase (BCH) catalyzes the formation of β-cryptoxanthin and zeaxanthin, but its molecular characteristics and functions have not been fully explained. Here we isolated two β-carotene hydroxylase genes, AcBCH1 and AcBCH2 from kiwifruit (Actinidia chinensis), and their relative expression levels exhibited a close correlation with the content of β-cryptoxanthin. AcBCH1 catalyzed the formation of β-cryptoxanthin when transformed into β-carotene-accumulating yeast cells. Moreover, silenced expression of AcBCH1 in kiwifruit caused decreases in the contents of zeaxanthin, lutein, and β-cryptoxanthin, and an increase in β-carotene content. The content of β-carotene decreased significantly after the AcBCH1/2 genes were overexpressed in tomato. The content of zeaxanthin increased and β-carotene decreased in transgenic kiwifruit seedlings. The results will enrich our knowledge of the molecular mechanisms of carotenoid biosynthesis in kiwifruit.