bluuebunny/crossref_metadata_2025 huggingface dataset:
Caenorhabditis elegans
DSB-3 reveals conservation and divergence among protein complexes promoting meiotic double-strand breaks
Authors: Hinman Albert W. , Yeh Hsin-Yi , Roelens Baptiste , Yamaya Kei , Woglar Alexander , Bourbon Henri-Marc G. , Chi Peter , Villeneuve Anne M.
Published: August 2021

Significance

Faithful inheritance of chromosomes during meiosis depends on the formation and repair of double-strand DNA breaks (DSBs), which are generated through the activity of a topoisomerase-like protein known as Spo11. Spo11 exhibits strong conservation throughout eukaryotes, presumably reflecting constraints imposed by its biochemical activity, but auxiliary proteins that collaborate with Spo11 to promote and regulate DSB formation are less well conserved. Here we investigate a cohort of proteins comprising a complex required for meiotic DSB formation in
Caenorhabditis elegans
, providing evidence for both conservation with and divergence from homologous complexes in other organisms. This work highlights the evolutionary malleability of protein complexes that serve essential, yet auxiliary, roles in fundamental biological processes that are central to reproduction.
The epithelial potassium channel Kir7.1 is stimulated by progesterone
Authors: Björkgren Ida , Mendoza Sarah , Chung Dong Hwa , Haoui Monika , Petersen Natalie True , Lishko Polina V.
Published: August 2021

The choroid plexus (CP) epithelium secretes cerebrospinal fluid and plays an important role in healthy homeostasis of the brain. CP function can be influenced by sex steroid hormones; however, the precise molecular mechanism of such regulation is not well understood. Here, using whole-cell patch-clamp recordings from male and female murine CP cells, we show that application of progesterone resulted in specific and strong potentiation of the inwardly rectifying potassium channel Kir7.1, an essential protein that is expressed in CP and is required for survival. The potentiation was progesterone specific and independent of other known progesterone receptors expressed in CP. This effect was recapitulated with recombinant Kir7.1, as well as with endogenous Kir7.1 expressed in the retinal pigment epithelium. Current-clamp studies further showed a progesterone-induced hyperpolarization of CP cells. Our results provide evidence of a progesterone-driven control of tissues in which Kir7.1 is present.
Manifold alignment for heterogeneous single-cell multi-omics data integration using Pamona
Authors: Cao Kai , Hong Yiguang , Wan Lin
Published: August 2021

Motivation

Single-cell multi-omics sequencing data can provide a comprehensive molecular view of cells. However, effective approaches for the integrative analysis of such data are challenging. Existing manifold alignment methods demonstrated the state-of-the-art performance on single-cell multi-omics data integration, but they are often limited by requiring that single-cell datasets be derived from the same underlying cellular structure.

Results

In this study, we present Pamona, a partial Gromov-Wasserstein distance-based manifold alignment framework that integrates heterogeneous single-cell multi-omics datasets with the aim of delineating and representing the shared and dataset-specific cellular structures across modalities. We formulate this task as a partial manifold alignment problem and develop a partial Gromov-Wasserstein optimal transport framework to solve it. Pamona identifies both shared and dataset-specific cells based on the computed probabilistic couplings of cells across datasets, and it aligns cellular modalities in a common low-dimensional space, while simultaneously preserving both shared and dataset-specific structures. Our framework can easily incorporate prior information, such as cell type annotations or cell-cell correspondence, to further improve alignment quality. We evaluated Pamona on a comprehensive set of publicly available benchmark datasets. We demonstrated that Pamona can accurately identify shared and dataset-specific cells, as well as faithfully recover and align cellular structures of heterogeneous single-cell modalities in a common space, outperforming the comparable existing methods.

Availabilityand implementation

Pamona software is available at https://github.com/caokai1073/Pamona.

Supplementary information

Supplementary data are available at Bioinformatics online.
Criminal Careers and Early Death: Relationships In the Cambridge Study In Delinquent Development
Authors: Skinner Guy C M , Farrington David P , Jolliffe Darrick
Published: August 2021

Prior research shows that convicted and incarcerated persons tend to die early, but this research does not investigate the relationships between criminal career features and early death. The aim of this article is to utilize the Cambridge Study in Delinquent Development longitudinal sample of males to study this; 54 males who died early (up to age 65) are compared with 332 males who did not emigrate and did not die early. The results show that convicted offenders, early onset offenders, recidivists and chronic offenders tended to die early, but there were relatively weak relationships between early death and life-course-persistent offenders and career duration. It is concluded that much more research on the relationship between early death and criminal career features is needed, and further tests of criminological theories need to take account of the time at risk of offending.
Disrupted Timing of MET Signaling Derails the Developmental Maturation of Cortical Circuits and Leads to Altered Behavior in Mice
Authors: Ma Xiaokuang , Wei Jing , Cui Yuehua , Xia Baomei , Zhang Le , Nehme Antoine , Zuo Yi , Ferguson Deveroux , Levitt Pat , Qiu Shenfeng
Published: August 2021

The molecular regulation of the temporal dynamics of circuit maturation is a key contributor to the emergence of normal structure–function relations. Developmental control of cortical MET receptor tyrosine kinase, expressed early postnatally in subpopulations of excitatory neurons, has a pronounced impact on the timing of glutamatergic synapse maturation and critical period plasticity. Here, we show that using a controllable overexpression (cto-Met) transgenic mouse, extending the duration of MET signaling after endogenous Met is switched off leads to altered molecular constitution of synaptic proteins, persistent activation of small GTPases Cdc42 and Rac1, and sustained inhibitory phosphorylation of cofilin. These molecular changes are accompanied by an increase in the density of immature dendritic spines, impaired cortical circuit maturation of prefrontal cortex layer 5 projection neurons, and altered laminar excitatory connectivity. Two photon in vivo imaging of dendritic spines reveals that cto-Met enhances de novo spine formation while inhibiting spine elimination. Extending MET signaling for two weeks in developing cortical circuits leads to pronounced repetitive activity and impaired social interactions in adult mice. Collectively, our data revealed that temporally controlled MET signaling as a critical mechanism for controlling cortical circuit development and emergence of normal behavior.
Twelve-Month Systemic Consequences of Coronavirus Disease 2019 (COVID-19) in Patients Discharged From Hospital: A Prospective Cohort Study in Wuhan, China
Authors: Liu Tingting , Wu Di , Yan Weiming , Wang Xiaojing , Zhang Xiaoyun , Ma Ke , Chen Huilong , Zeng Zhilin , Qin Yuanyuan , Wang Hongwu , Xing Mingyou , Xu Dong , Li Weina , Ni Ming , Zhu Lin , Chen Liang , Chen Guang , Qi Weipeng , Wu Ting , Yu Haijing , Huang Jiaquan , Han Meifang , Zhu Wenzhen , Guo Wei , Luo Xiaoping , Chen Tao , Ning Qin
Published: August 2021

Background

Follow-up study of coronavirus disease 2019 (COVID-19) survivors has rarely been reported. We aimed to investigate longitudinal changes in the characteristics of COVID-19 survivors after discharge.

Methods

A total of 594 COVID-19 survivors discharged from Tongji Hospital in Wuhan from February 10 to April 30, 2020 were included and followed up until May 17, 2021. Laboratory and radiological findings, pulmonary function tests, electrocardiogram, symptoms and signs were analyzed.

Results

257 (51.2%) patients had at least one symptom at 3 months post-discharge, which decreased to 169 (40.0%) and 138 (28.4%) at 6-month and 12-month visit respectively. During follow-up period, insomnia, chest tightness, and fatigue were the most prevalent symptoms. Most laboratory parameters returned to normal, whereas increased incidence of abnormal liver and renal function and cardiovascular injury was evidenced after discharge. Fibrous stripes (213; 42.4%), pleural thickening and adhesions (188; 37.5%) and enlarged lymph nodes (120; 23.9%) were the most common radiographical findings at 3 months post-discharge. The abnormalities of pulmonary function included obstructive, restrictive, and mixed, which were 5.5%, 4.0%, 0.9% at 6 months post, and 1.9%, 4.7%, 0.2% at 12 months. Electrocardiogram abnormalities occurred in 256 (51.0%) patients at 3 months post-discharge, including arrhythmia, ST-T change and conduction block, which increased to 258 (61.1%) cases at 6-month visit and were maintained at high frequency (242;49.8%) at 12-month visit.

Conclusions

Physiological, laboratory, radiological, or electrocardiogram abnormalities, particularly those related to renal, cardiovascular, and liver functions are common in patients who recovered from coronavirus disease 2019 (COVID-19) up to 12 months post-discharge.
Discrimination and ejection of eggs and nestlings by the fan-tailed gerygone from New Caledonia
Authors: Attisano Alfredo , Sato Nozomu J , Tanaka Keita D , Okahisa Yuji , Ueda Keisuke , Gula Roman , Theuerkauf Jörn
Published: August 2021

Nestling rejection is a rare type of host defense against brood parasitism compared with egg rejection. Theoretically, host defenses at both egg and nestling stages could be based on similar underlying discrimination mechanisms but, due to the rarity of nestling rejector hosts, few studies have actually tested this hypothesis. We investigated egg and nestling discrimination by the fan-tailed gerygone Gerygone flavolateralis, a host that seemingly accepts nonmimetic eggs of its parasite, the shining bronze-cuckoo Chalcites lucidus, but ejects mimetic parasite nestlings. We introduced artificial eggs or nestlings and foreign gerygone nestlings in gerygone nests and compared begging calls of parasite and host nestlings. We found that the gerygone ejected artificial eggs only if their size was smaller than the parasite or host eggs. Ejection of artificial nestlings did not depend on whether their color matched that of the brood. The frequency of ejection increased during the course of the breeding season mirroring the increase in ejection frequency of parasite nestlings by the host. Cross-fostered gerygone nestlings were frequently ejected when lacking natal down and when introduced in the nest before hatching of the foster brood, but only occasionally when they did not match the color of the foster brood. Begging calls differed significantly between parasite and host nestlings throughout the nestling period. Our results suggest that the fan-tailed gerygone accepts eggs within the size range of gerygone and cuckoo eggs and that nestling discrimination is based on auditory and visual cues other than skin color. This highlights the importance of using a combined approach to study discrimination mechanisms of hosts.
Dispersal patterns in Yunnan snub-nosed monkeys
Authors: Xia Wancai , Wang Fan , Wang Dali , Zeng Xiaoqin , Yang Chan , Krzton Ali , Ren Baoping , Li Dayong
Published: August 2021

Sex-biased dispersal is common in group-living animals. Due to differences in local demographic and environmental factors, sex-biased dispersal presents many irregular patterns. In this study, a habituated, individually identified Yunnan snub-nosed monkey Rhinopithecus bieti group was observed over 9 years; 192 dispersal events, including 97 male dispersal events (25 natal dispersal and 72 secondary dispersal) and 95 female dispersal events (34 natal dispersal and 61 secondary dispersal) were observed. Males and females showed different dispersal paths, dispersal ages, and dispersal patterns. Females had 2 dispersal paths, whereas males had 4 paths. In terms of age of dispersal, the male age of natal dispersal was younger than for females. Males prefer single dispersal, whereas females prefer parallel dispersal. Our study indicates that the dispersal pattern of R. bieti should be classified as a bisexual dispersal pattern. The differences in dispersal path, average age at dispersal, and dispersal path pattern indicate that Yunnan snub-nosed monkeys may still retain a loose matrilineal social system.
CeAid: a smartphone application for logging and plotting Caenorhabditis elegans assays
Authors: Sohrabi Salman , Moore Rebecca S , Murphy Coleen T
Published: August 2021

Caenorhabditis elegans is used as a model organism to study a wide range of topics in molecular and cellular biology. Conventional C. elegans assays often require a large sample size with frequent manipulations, rendering them labor-intensive. Automated high-throughput workflows may not be always the best solution to reduce benchwork labor, as they may introduce more complexity. Thus, most assays are carried out manually, where logging and digitizing experimental data can be as time-consuming as picking and scoring worms. Here we report the development of CeAid, C. elegans Application for inputting data, which significantly expedites the data entry process, utilizing swiping gestures and a voice recognition algorithm for logging data using a standard smartphone or Android device. This modular platform can also be adapted for a wide range of assays where recording data is laborious, even beyond worm research.
Subcellular patterns of SPE-6 localization reveal unexpected complexities inCaenorhabditis eleganssperm activation and sperm function
Authors: Peterson Jackson J , Tocheny Claire E , Prajapati Gaurav , LaMunyon Craig W , Shakes Diane C
Published: August 2021

To acquire and maintain directed cell motility, Caenorhabditis elegans sperm must undergo extensive, regulated cellular remodeling, in the absence of new transcription or translation. To regulate sperm function, nematode sperm employ large numbers of protein kinases and phosphatases, including SPE-6, a member of C. elegans’ highly expanded casein kinase 1 superfamily. SPE-6 functions during multiple steps of spermatogenesis, including functioning as a “brake” to prevent premature sperm activation in the absence of normal extracellular signals. Here, we describe the subcellular localization patterns of SPE-6 during wild-type C. elegans sperm development and in various sperm activation mutants. While other members of the sperm activation pathway associate with the plasma membrane or localize to the sperm’s membranous organelles, SPE-6 surrounds the chromatin mass of unactivated sperm. During sperm activation by either of two semiautonomous signaling pathways, SPE-6 redistributes to the front, central region of the sperm’s pseudopod. When disrupted by reduction-of-function alleles, SPE-6 protein is either diminished in a temperature-sensitive manner (hc187) or is mislocalized in a stage-specific manner (hc163). During the multistep process of sperm activation, SPE-6 is released from its perinuclear location after the spike stage in a process that does not require the fusion of membranous organelles with the plasma membrane. After activation, spermatozoa exhibit variable proportions of perinuclear and pseudopod-localized SPE-6, depending on their location within the female reproductive tract. These findings provide new insights regarding SPE-6’s role in sperm activation and suggest that extracellular signals during sperm migration may further modulate SPE-6 localization and function.
An Nphp1 knockout mouse model targeting exon 2–20 demonstrates characteristic phenotypes of human nephronophthisis
Authors: Li Dantong , Hu Miaoyue , Chen Huamu , Wu Xiaohong , Wei Xiaoya , Lin Hongrong , Gao Xuefei , Wang Haiyan , Li Min , Ong Albert C M , Yue Zhihui , Sun Liangzhong
Published: August 2021

Nephronophthisis (NPH) is the most prevalent monogenetic disorder leading to end-stage renal failure (ESRD) in childhood. Mutations in Nphp1, encoding a cilia-localized protein, account for the majority of NPH cases. Despite its identification many years ago, Nphp1 deletions targeting exon 4 or exon 20 have not reproduced the histological features of human NPH in murine models. In this study, we deleted exon 2–20 of Nphp1 by CRISPR/Cas9 gene editing to create a near-total knockout (KO) mouse model (Nphp1del2–20/del2–20). Nphp1del2–20/del2–20 mice faithfully reproduced the renal and extrarenal phenotypes associated with human NPH, including renal cyst development, tubular basement membrane thickening, retinal degeneration and abnormal spermatogenesis. Importantly, Nphp1 re-expression using an adenoviral-associated-virus-9 vector could partially rescue both renal and retinal phenotypes in Nphp1del2–20/del2–20 mice. Our results reported the first relevant Nphp1 mouse model with renal phenotypes for human disease. It will be a valuable model for future studies of Nphp1 function and to develop novel treatments for this common childhood disease.
Classification under uncertainty: data analysis for diagnostic antibody testing
Authors: Patrone Paul N , Kearsley Anthony J
Published: August 2021

Formulating accurate and robust classification strategies is a key challenge of developing diagnostic and antibody tests. Methods that do not explicitly account for disease prevalence and uncertainty therein can lead to significant classification errors. We present a novel method that leverages optimal decision theory to address this problem. As a preliminary step, we develop an analysis that uses an assumed prevalence and conditional probability models of diagnostic measurement outcomes to define optimal (in the sense of minimizing rates of false positives and false negatives) classification domains. Critically, we demonstrate how this strategy can be generalized to a setting in which the prevalence is unknown by either (i) defining a third class of hold-out samples that require further testing or (ii) using an adaptive algorithm to estimate prevalence prior to defining classification domains. We also provide examples for a recently published SARS-CoV-2 serology test and discuss how measurement uncertainty (e.g. associated with instrumentation) can be incorporated into the analysis. We find that our new strategy decreases classification error by up to a decade relative to more traditional methods based on confidence intervals. Moreover, it establishes a theoretical foundation for generalizing techniques such as receiver operating characteristics by connecting them to the broader field of optimization.
Melatonin alters bovine uterine artery hemodynamics, vaginal temperatures, and fetal morphometrics during late gestational nutrient restriction in a season-dependent manner
Authors: Contreras-Correa Zully E , Messman Riley D , Sidelinger Darcie R , Heath King E , Sánchez-Rodríguez Héctor L , Burnett Derris D , Lemley Caleb O
Published: August 2021

The objectives were to examine melatonin-mediated changes in temporal uterine blood flow (UBF), vaginal temperatures (VTs), and fetal morphometrics in 54 commercial Brangus heifers (Fall, n = 29; Summer, n = 25) during compromised pregnancy. At day 160 of gestation, heifers were assigned to one of the four treatments consisting of adequately fed (ADQ-CON; 100% National Research Council [NRC]; n = 13), global nutrient restricted (RES-CON; 60% NRC; n =13), and ADQ or RES supplemented with 20 mg/d of melatonin (ADQ-MEL, n = 13; RES-MEL, n = 15). In the morning (0500 hours; AM) and afternoon (1300 hours; PM) of day 220 of gestation, UBF was determined via Doppler ultrasonography, while temperature data loggers attached to progesterone-free controlled internal drug releases were used to record VTs. At day 240 of gestation, heifers underwent cesarean sections for fetal removal and morphometrics determination. The UBF and VT data were analyzed using repeated measures of analysis of variance (ANOVA), while the morphometrics was analyzed using the MIXED procedure of SAS. Seasons were analyzed separately. In Fall, a nutrition by treatment interaction was observed, where the RES-CON heifers exhibited reduced total UBF compared with ADQ-CON (5.67 ± 0.68 vs. 7.97 ± 0.54 L/min; P = 0.039). In Summer, MEL heifers exhibited increased total UBF compared with the CON counterparts (8.16 ± 0.73 vs. 6.00 ± 0.70 L/min; P = 0.048). Moreover, there was a nutrition by treatment by time interaction in VT for Fall and Summer heifers (P ≤ 0.005). In Fall, all groups had decreased VT in the morning compared with the afternoon (P < 0.05). Whereas, in Summer, VT increased for ADQ-CON and RES-CON (P < 0.0001) from morning to afternoon, the ADQ-MEL and RES-MEL remained constant throughout the day (P = 0.648). Furthermore, the RES-MEL-PM exhibited decreased VT compared with ADQ-CON-PM (38.91 ± 0.09 vs. 39.26 ± 0.09 °C; P = 0.018). Lastly, in Fall, a main effect of nutrition was observed on fetal weights, where the RES dams had fetuses with decreased body weight when compared with ADQ (24.08 ± 0.62 vs. 26.57 ± 0.64 kg; P = 0.0087). In Summer, a nutrition by treatment interaction was observed on fetal weights where the RES-CON dams had fetuses with reduced weight when compared with ADQ-CON and RES-MEL (P < 0.05). In summary, nutrient restriction decreased UBF and melatonin supplementation increased UBF depending on the season. Additionally, melatonin appeared to decrease VT and rescue fetal weights when supplemented in the Summer.
Trapezoid-grid finite difference frequency domain method for seismic wave simulation
Authors: Wu Bangyu , Tan Wenzhuo , Xu Wenhao
Published: August 2021

The large computational cost and memory requirement for the finite difference frequency domain (FDFD) method limit its applications in seismic wave simulation, especially for large models. For conventional FDFD methods, the discretisation based on minimum model velocity leads to oversampling in high-velocity regions. To reduce the oversampling of the conventional FDFD method, we propose a trapezoid-grid FDFD scheme to improve the efficiency of wave modeling. To alleviate the difficulty of processing irregular grids, we transform trapezoid grids in the Cartesian coordinate system to square grids in the trapezoid coordinate system. The regular grid sizes in the trapezoid coordinate system correspond to physical grid sizes increasing with depth, which is consistent with the increasing trend of seismic velocity. We derive the trapezoid coordinate system Helmholtz equation and the corresponding absorbing boundary condition, then get the FDFD stencil by combining the central difference method and the average-derivative method (ADM). Dispersion analysis indicates that our method can satisfy the requirement of maximum phase velocity error less than $1\%$ with appropriate parameters. Numerical tests on the Marmousi model show that, compared with the regular-grid ADM 9-point FDFD scheme, our method can achieve about $80\%$ computation efficiency improvement and $80\%$ memory reduction for comparable accuracy.
CAN E-PROCUREMENT REDUCE BID RIGGING IN PUBLIC AUCTIONS?
Authors: Ishii Rieko
Published: August 2021

The adoption of e-procurement may reduce bid rigging in public auctions by limiting in-person meetings of bidders. Using the data from construction auctions tendered by a Japanese local government where paper-based manual procurement is replaced by e-procurement, we find that the adoption of e-procurement reduced bids in a section of the market where the bids were initially higher than the other section of the market. The degree of reduction was smaller in an auction when the bidders were likely to be in the same industrial community, suggesting that the effect of e-procurement by limiting in-person meetings is smaller when the bidders have chances to communicate through other than the procurement processes.
Patient-specific 3D-printed cutting guides for high oblique sagittal osteotomy—an innovative surgical technique for nerve preservation in orthognathic surgery
Authors: Kämmerer Peer W , Müller Daniel , Linz Friedemann , Peron Priscila Ferrari , Pabst Andreas
Published: August 2021

Bilateral sagittal split osteotomy (BSSO) of the mandible according to Obwegeser/Dal Pont is considered to be gold standard in orthognathic surgery. Frequently reported complications of BSSO are injuries of the mandibular nerve resulting in paresthesia/anesthesia as well as inadequate mandibular bone fracturing (‘bad split’). High oblique sagittal osteotomy (HOSO) was introduced to overcome these complications. We present an innovative HOSO modification using patient-specific 3D-printed cutting guides positioned on the outside of the ascending mandibular ramus and fixed in the incisura semilunaris, precisely marking the optimal height and angle of the osteotomy. Advantages are a decreased operation time due to the simplicity of this less invasive procedure, a potentially reduced frequency of mandibular nerve damage and bad splits as well as a lower bleeding risk.
Kiloparsec-scale AGN outflows and feedback in merger-free galaxies
Authors: Smethurst R J , Simmons B D , Coil A , Lintott C J , Keel W , Masters K L , Glikman E , Leung G C K , Shanahan J , Garland I L
Published: August 2021

Recent observations and simulations have challenged the long-held paradigm that mergers are the dominant mechanism driving the growth of both galaxies and supermassive black holes (SMBH), in favour of non-merger (secular) processes. In this pilot study of merger-free SMBH and galaxy growth, we use Keck Cosmic Web Imager spectral observations to examine four low-redshift (0.043 < z < 0.073) disc-dominated ‘bulgeless’ galaxies hosting luminous active galactic nucleus (AGN), assumed to be merger-free. We detect blueshifted broadened [O iii] emission from outflows in all four sources, which the $\mathrm{[O\, \small {III}]}$/$\rm {H}\beta$ ratios reveal are ionized by the AGN. We calculate outflow rates in the range $0.12{-}0.7~\rm {M}_{\odot }~\rm {yr}^{-1}$, with velocities of $675{-}1710~\rm {km}~\rm {s}^{-1}$, large radial extents of $0.6{-}2.4~\rm {kpc}$, and SMBH accretion rates of $0.02{-}0.07~\rm {M}_{\odot }~\rm {yr}^{-1}$. We find that the outflow rates, kinematics, and energy injection rates are typical of the wider population of low-redshift AGN, and have velocities exceeding the galaxy escape velocity by a factor of ∼30, suggesting that these outflows will have a substantial impact through AGN feedback. Therefore, if both merger-driven and non-merger-driven SMBH growth lead to co-evolution, this suggests that co-evolution is regulated by feedback in both scenarios. Simulations find that bars and spiral arms can drive inflows to galactic centers at rates an order of magnitude larger than the combined SMBH accretion and outflow rates of our four targets. This work therefore provides further evidence that non-merger processes are sufficient to fuel SMBH growth and AGN outflows in disc galaxies.
Structural basis for activation of Swi2/Snf2 ATPase RapA by RNA polymerase
Authors: Shi Wei , Zhou Wei , Chen Ming , Yang Yang , Hu Yangbo , Liu Bin
Published: August 2021

RapA is a bacterial RNA polymerase (RNAP)-associated Swi2/Snf2 ATPase that stimulates RNAP recycling. The ATPase activity of RapA is autoinhibited by its N-terminal domain (NTD) but activated with RNAP bound. Here, we report a 3.4-Å cryo-EM structure of Escherichia coli RapA–RNAP elongation complex, in which the ATPase active site of RapA is structurally remodeled. In this process, the NTD of RapA is wedged open by RNAP β' zinc-binding domain (ZBD). In addition, RNAP β flap tip helix (FTH) forms extensive hydrophobic interactions with RapA ATPase core domains. Functional assay demonstrates that removing the ZBD or FTH of RNAP significantly impairs its ability to activate the ATPase activity of RapA. Our results provide the structural basis of RapA ATPase activation by RNAP, through the active site remodeling driven by the ZBD-buttressed large-scale opening of NTD and the direct interactions between FTH and ATPase core domains.
Photonic orbital angular momentum with controllable orientation
Authors: Wan Chenhao , Chen Jian , Chong Andy , Zhan Qiwen
Published: August 2021

Vortices are whirling disturbances, commonly found in nature, ranging from tremendously small scales in Bose-Einstein condensations to cosmologically colossal scales in spiral galaxies. An optical vortex, generally associated with a spiral phase, can carry orbital angular momentum (OAM). The optical OAM can either be in the longitudinal direction if the spiral phase twists in the spatial domain or in the transverse direction if the phase rotates in the spatiotemporal domain. In this article, we demonstrate the intersection of spatiotemporal vortices and spatial vortices in a wave packet. As a result of this intersection, the wave packet hosts a tilted OAM that provides an additional degree of freedom to the applications that harness the OAM of photons.
Indonesia is already in a state of ‘Herd Stupidity’: is it a slump?
Authors: Situmorang Dominikus David Biondi
Published: August 2021

I hope this article can be an input for all of us, especially Indonesia, so that the phenomenon of ‘Herd Stupidity’ can end soon and the ‘positivity rate’ will decrease. If we all carry out disciplined behavior starting with ourselves, surely all of these things will be handled properly.
Consumption Imputation Errors in Administrative Data
Authors: Baker Scott R , Kueng Lorenz , Meyer Steffen , Pagel Michaela
Published: August 2021

Many research papers in household finance utilize annual snapshots of household wealth from administrative data, such as tax registries, to calculate “imputed consumption.” However, trading costs, unobserved intrayear trades, or unobserved security characteristics may cause measurement error. We document how such errors vary across groups of individuals by income, portfolio characteristics, and wealth and how they are correlated with individual income and balance sheets, asset prices, and the business cycle using transaction-level retail brokerage account data. We find that the economic significance of imputation error is small in many research settings, and we discuss robustness checks and econometric specifications to minimize the impact of imputation error in future research.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Addressing wicked problems. Collaboration, trust and the role of shared principles at the philanthropy and government interface
Authors: Strachwitz Rupert Graf , Alter Rolf , Unger Timo
Published: August 2021

Collaborative activities at the interface of philanthropy and government are increasingly assumed to be a desirable answer to complex—even wicked—public problems. Against this backdrop, this article discusses different types of collaborations, their accompanying levels of difficulty, and the roles that philanthropies might play in these efforts. Although this collaboration might hold promising potential, it will be argued that success will be very difficult to achieve. Consequently, indications are that philanthropies interested in increasing their collaborative activities at the interface of government might need to adjust their expectations and enhance their frustration tolerance. However, trust is seen as the central driver of collaborations across all sectors. By adopting a common approach to managing philanthropic practice, such as a joint performance management, that includes a broad understanding of performance beyond fixed indicators, it is argued that philanthropies are able to operationalize the resource trust. The Philanthropy. Insight Assessment Tool is proposed as a starting point for a joint conversation on the current and future philanthropic practice and its principles, including debates on the practical value of performance management systems.
Global spatiotemporal transmission patterns of human enterovirus 71 from 1963 to 2019
Authors: Xu Bing , Wang Jinfeng , Yan Bin , Xu Chengdong , Yin Qian , Yang Deyan
Published: August 2021

Enterovirus 71 (EV71) can cause large outbreaks of hand, foot, and mouth disease (HFMD) and severe neurological diseases, which is regarded as a major threat to public health, especially in Asia-Pacific regions. However, the global spatiotemporal spread of this virus has not been identified. In this study, we used large sequence datasets and a Bayesian phylogenetic approach to compare the molecular epidemiology and geographical spread patterns of different EV71 subgroups globally. The study found that subgroups of HFMD presented global spatiotemporal variation, subgroups B0, B1, and B2 have caused early infections in Europe and America, and then subgroups C1, C2, C3, and C4 replaced B0-B2 as the predominant genotypes, especially in Asia-Pacific countries. The dispersal patterns of genotype B and subgroup C4 showed the complicated routes in Asia and the source might in some Asian countries, while subgroups C1 and C2 displayed more strongly supported pathways globally, especially in Europe. This study found the predominant subgroup of EV71 and its global spatiotemporal transmission patterns, which may be beneficial to reveal the long-term global spatiotemporal transmission patterns of human EV71 and carry out the HFMD vaccine development.
Telomere to Telomere Genome Assembly of Fusarium musae F31, Causal Agent of Crown Rot Disease of Banana
Authors: Degradi Luca , Tava Valeria , Kunova Andrea , Cortesi Paolo , Saracchi Marco , Pasquali Matias
Published: August 2021

Fusarium musae causes crown rot of banana and it is also associated to clinical fusariosis. A chromosome-level genome assembly of F. musae F31 obtained combining Nanopore long reads and Illumina paired-end reads resulted in 12 chromosomes plus one contig with overall N50 of 4.36 Mb, and is presented together with its mitochondrial genome (58,072 bp). The F31 genome includes telomeric regions for 11 of the 12 chromosomes representing one of the most complete genomes available in the Fusarium fujikuroi species complex. The high-quality assembly of the F31 genome will be a valuable resource for studying the pathogenic interactions occurring between F. musae and banana. Moreover, it represents an important resource for understanding the genome evolution in the F. fujikuroi species complex.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Maize Seed Contamination and Seed Transmission of Maize Chlorotic Mottle Virus in Kenya
Authors: Kimani Esther N. , Kiarie Samuel M. , Micheni Cyrus , Muriki Laureen G. , Miano Douglas W. , Macharia Isaac , Munkvold Gary P. , Muiru William M. , Prasanna B. M. , Wangai Anne
Published: August 2021

Maize chlorotic mottle virus (MCMV) causes maize lethal necrosis disease in combination with a cereal-infecting potyvirus, leading to high yield losses. There is limited information on seed infection or contamination rate by MCMV and its comparison with transmission rate to maize seedlings. This study was conducted to determine the extent of seed contamination in seed lots from MCMV-infected maize fields in Kenya and the transmission of MCMV from seeds to seedlings. To determine the contamination levels, whole seeds were ground and the extract tested for the presence of MCMV using double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA). Seedling grow-outs were tested for seed transmission of MCMV using DAS-ELISA and real-time reverse transcription polymerase chain reaction (real-time RT-PCR) methods. The seed contamination rates of the four seed lots tested ranged from 4.9 to 15.9%. MCMV transmission frequency for 37,617 seedlings, tested in 820 pools of varying seed amounts by DAS-ELISA, was 0.17%, whereas a transmission frequency of 0.025% was obtained from 8,322 seedlings tested in 242 pools by real-time RT-PCR. Seeds from plants mechanically inoculated with MCMV had an overall seed transmission rate of 0.04% in 7,846 seedlings tested in 197 pools. The study showed that even with substantial contamination of maize seed with MCMV, the transmission of the virus from the seed to seedlings was low. Nevertheless, even low rates of transmission can be significant under field conditions where insect vectors can further spread the disease from infected seedlings, unless diseased plants are detected in time and properly managed.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Towards Improved Detection and Identification of Rust Fungal Pathogens in Environmental Samples Using a Metabarcoding Approach
Authors: Chen Wen , Radford Devon , Hambleton Sarah
Published: August 2021

The dispersion of fungal inocula such as the airborne spores of rust fungi (Pucciniales) can be monitored through metabarcoding of the internal transcribed spacer 2 (ITS2) of the rRNA gene in environmental DNAs. This method is largely dependent on a high-quality reference database (refDB) and primers with proper taxonomic coverage and specificity. For this study, a curated ITS2 reference database (named CR-ITS2-refDB) comprising representatives of the major cereal rust fungi and phylogenetically related species was compiled. Interspecific and intraspecific variation analyses suggested that the ITS2 region had reasonable discriminating power for the majority of the Puccinia species or species complexes in the database. In silico evaluation of nine forward and seven reverse ITS2 primers, including three newly designed, revealed marked variation in DNA amplification efficiency for the rusts. We validated the theoretical assessment of rust-enhanced (Rust2inv/ITS4var_H) and universal fungal (ITS9F/ITS4) ITS2 primer pairs by profiling the airborne rust fungal communities from environmental samples via a metabarcoding approach. Species- or subspecies-level identification of the rusts was improved by use of CR-ITS2-refDB and the Automated Oligonucleotide Design Pipeline (AODP), which identified all mutations distinguishing highly conserved DNA markers between close relatives. A generic bioinformatics pipeline was developed, including all steps used in this study from in silico evaluation of primers to accurate identification of short metabarcodes at the level of interest for defining phytopathogens. The results highlight the importance of primer selection, refDBs that are resolved to reflect phylogenetic relationships, and the use of AODP for improving the reliability of metabarcoding in phytopathogen biosurveillance.
Where to Invest Project Efforts for Greater Benefit: A Framework for Management Performance Mapping with Examples for Potato Seed Health
Authors: Buddenhagen C. E. , Xing Y. , Andrade-Piedra J. L. , Forbes G. A. , Kromann P. , Navarrete I. , Thomas-Sharma S. , Choudhury R. A. , Andersen Onofre K. F. , Schulte-Geldermann E. , Etherton B. A. , Plex Sulá A. I. , Garrett K. A.
Published: August 2021

Policymakers and donors often need to identify the locations where technologies are most likely to have important effects, to increase the benefits from agricultural development or extension efforts. Higher-quality information may help to target the high-benefit locations, but often actions are needed with limited information. The value of information (VOI) in this context is formalized by evaluating the results of decision making guided by a set of specific information compared with the results of acting without considering that information. We present a framework for management performance mapping that includes evaluating the VOI for decision making about geographic priorities in regional intervention strategies, in case studies of Andean and Kenyan potato seed systems. We illustrate the use of recursive partitioning, XGBoost, and Bayesian network models to characterize the relationships among seed health and yield responses and environmental and management predictors used in studies of seed degeneration. These analyses address the expected performance of an intervention based on geographic predictor variables. In the Andean example, positive selection of seed from asymptomatic plants was more effective at high altitudes in Ecuador. In the Kenyan example, there was the potential to target locations with higher technology adoption rates and with higher potato cropland connectivity, i.e., a likely more important role in regional epidemics. Targeting training to high management performance areas would often provide more benefits than would random selection of target areas. We illustrate how assessing the VOI can contribute to targeted development programs and support a culture of continuous improvement for interventions.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Generation of Mild Recombinants of Papaya Ringspot Virus to Minimize the Problem of Strain-Specific Cross-Protection
Authors: Tran Thi-Thu-Yen , Lin Tzu-Tung , Chang Chung-Ping , Chen Chun-Hung , Nguyen Van-Hoa , Yeh Shyi-Dong
Published: August 2021

Papaya ringspot virus (PRSV) causes severe damage to papaya (Carica papaya L.) and is the primary limiting factor for papaya production worldwide. A nitrous acid-induced mild strain, PRSV HA 5-1, derived from Hawaii strain HA, has been applied to control PRSV by cross-protection for decades. However, the problem of strain-specific protection hampers its application in Taiwan and other geographic regions outside Hawaii. Here, sequence comparison of the genomic sequence of HA 5-1 with that of HA revealed 69 nucleotide changes, resulting in 31 aa changes, of which 16 aa are structurally different. The multiple mutations of HA 5-1 are considered to result from nitrous acid induction because 86% of nucleotide changes are transition mutations. The stable HA 5-1 was used as a backbone to generate recombinants carrying individual 3′ fragments of Vietnam severe strain TG5, including NIa, NIb, and CP3′ regions, individually or in combination. Our results indicated that the best heterologous fragment for the recombinant is the region of CP3′, with which symptom attenuation of the recombinant is like that of HA 5-1. This mild recombinant HA51/TG5-CP3′ retained high levels of protection against the homologous HA in papaya plants and significantly increased the protection against the heterologous TG-5. Similarly, HA 5-1 recombinants carrying individual CP3′ fragments from Thailand SMK, Taiwan YK, and Vietnam ST2 severe strains also significantly increase protection against the corresponding heterologous strains in papaya plants. Thus, our recombinant approach for mild strain generation is a fast and effective way to minimize the problem of strain-specific protection.
CircFOXM1 silencing represses cell proliferation, migration and invasion by regulating miR-515-5p/ADAM10 axis in prostate cancer
Authors: Liu Gong-xue , Zheng Tao , Zhang Yong , Hao Peng
Published: August 2021

Circular FOXM1 (circFOXM1) has been demonstrated to participate in the initiation and development of cancers, including prostate cancer (PCa). However, there is no relevant information on the regulation of PCa by circFOXM1. The RNA level of circFOXM1 was detected by qRT-PCR in PCa tissues and cells. The protein expression was performed by western blot and immunohistochemistry assay. Cell proliferation was examined by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide, colony formation and flow cytometry assays. The abilities of cell migration and invasion were determined by transwell assay. The relationship between circFOXM1 and miR-515-5p or ADAM10 was predicted by starBaseV2.0 online database, and identified by dual-luciferase reporter assay or RNA pull-down assay. The effects of circFOXM1 silencing and ADAM10 knockdown on PCa growth in vivo were evaluated by in-vivo tumor formation assay. As a result, we found that circFOXM1 and ADAM10 expression were upregulated in PCa tissues and cells. Functional analysis showed that circFOXM1 silencing repressed proliferation, migration and invasion, and induced cell cycle arrest, whereas these effects were partly reversed by miR-515-5p inhibitor. Additionally, circFOXM1 directly sponged miR-515-5p, and miR-515-5p bound to ADAM10. ADAM10 absence also repressed PCa process. Furthermore, in-vivo tumor formation assay revealed that both circFOXM1 silencing and ADAM10 knockdown repressed tumor growth in vivo. Thus, we came a conclusion that circFOXM1 contributed to PCa progression via regulating miR-515-5p/ADAM10 axis. These results may provide a theoretical basis for further studying the progression of PCa.
Circular RNA circ_0008450 regulates the proliferation, migration, invasion, apoptosis and chemosensitivity of CDDP-resistant nasopharyngeal carcinoma cells by the miR-338-3p/SMAD5 axis
Authors: Liu Lin , Lu Bin , Li Yan
Published: August 2021

Circular RNAs have recently been implicated in the tumorigenesis and chemoresistance of nasopharyngeal carcinoma (NPC). In this report, we identified the precise action of circ_0008450 in NPC progression and cisplatin (CDDP) resistance. The levels of circ_0008450, microRNA (miR)-338-3p and SMAD family member 5 (SMAD5) were gauged by quantitative real-time PCR or western blot. Cell proliferation and IC50 value for CDDP were detected by the Cell Counting Kit-8 assay. Cell colony formation, cell cycle progression, apoptosis, migration and invasion were assessed by colony formation, flow cytometry and transwell assays, respectively. Targeted relationships among circ_0008450, miR-338-3p and SMAD5 were determined by dual-luciferase reporter and RNA immunoprecipitation assays. Tumor models were assayed to evaluate the role of circ_0008450 in tumor growth. Our data indicated that up-regulated circ_0008450 was correlated with NPC CDDP resistance. Moreover, the knockdown of circ_0008450 suppressed cell proliferation, migration, invasion, and promoted apoptosis and CDDP sensitivity in vitro, as well as weakened tumor growth in vivo. Mechanistically, circ_0008450 directly bound to miR-338-3p, and the regulatory effects of circ_0008450 on cell malignant behaviors and CDDP sensitivity were mediated by miR-338-3p in vitro. SMAD5 was a direct target of miR-338-3p and circ_0008450 mediated SMAD5 expression through miR-338-3p. Furthermore, the enforced level of miR-338-3p regulated cell malignant behaviors and CDDP sensitivity in vitro via down-regulating SMAD5. Additionally, the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway was modulated by the circ_0008450/miR-338-3p axis in the two CDDP-resistant NPC cell lines. Our current study suggested that circ_0008450 modulated the malignant behaviors and drug sensitivity of CDDP-resistant NPC cells at least in part by targeting the miR-338-3p/SMAD5 axis, providing potential targets for improving the treatment of chemoresistant NPC.
Platinum-based adjuvant chemotherapy for upper tract urothelial carcinoma: a change of paradigm? A meta-analysis of aggregate data
Authors: Ricci Angela Dalia , Rizzo Alessandro , Mollica Veronica , Schiavina Riccardo , Fiorentino Michelangelo , Brunocilla Eugenio , Ardizzoni Andrea , Massari Francesco
Published: August 2021

We performed a systematic review and meta-analysis to evaluate the role of platinum-based adjuvant chemotherapy (AC) in upper tract urothelial carcinoma. Eligible studies were identified using Pubmed/Medline, Cochrane library, Embase and meeting abstracts. Outcomes of interest included: overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). Platinum-based AC was associated with improved DFS, while the benefit in OS and CSS was not statistically significant compared to observation. Conversely, platinum-based AC showed a modest OS benefit in an analysis combing multivariable HRs with estimated HRs from Kaplan–Meier curves. Our results suggest that platinum-based AC is associated with improved DFS and a modest OS benefit in patients with locally advanced urothelial carcinomas.