bluuebunny/crossref_metadata_2025 huggingface dataset:
A DREaMR system to simplify combining mutations with rescue transgenes in Aedes aegypti
Authors: Chen Jieyan , Luo Junjie , Gurav Adishthi S , Chen Zijing , Wang Yijin , Montell Craig
Published: September 2021

In most experimental animals, it is challenging to combine mutations and rescue transgenes and to use bipartite systems to assess gene expression. To circumvent the difficulties in combining multiple genetic elements, we developed the DREaMR (Drug-on, REporter, Mutant, Rescue) system. Using Drosophila white as the initial model, we demonstrated that introduction of a single insertion by CRISPR/Cas9 created a null mutation, a tagged rescue construct, which could be induced with doxycycline, and which allowed assessment of protein expression. To create a DREaMR in an organism in which combining multiple genetic elements is more problematic than in Drosophila, we tested the mosquito, Aedes aegypti—the insect vector for dengue, yellow fever, Zika, and other viral diseases. We generated a DREaMR allele in the kh gene, which permitted us to induce expression of the rescue construct, and detect expression of Kh. Thus, this system avoids the need to perform genetic crosses to introduce an inducible rescue transgene in a mutant background, or to combine driver and reporter lines to examine expression of the targeted protein. We propose that DREaMR provides a system that can be applied to additional mosquito vectors as well as other organisms in which CRISPR/Cas9 is effective.
Deep structure of DNA for genomic analysis
Authors: Garzon Max , Mainali Sambriddhi
Published: September 2021

Recent advances in next-generation sequencing, deep networks and other bioinformatic tools have enabled us to mine huge amount of genomic information about living organisms in the post-microarray era. However, these tools do not explicitly factor in the role of the underlying DNA biochemistry (particularly, DNA hybridization) essential to life processes. Here, we focus more precisely on the role that DNA hybridization plays in determining properties of biological organisms at the macro-level. We illustrate its role with solutions to challenging problems in human disease. These solutions are made possible by novel structural properties of DNA hybridization landscapes revealed by a metric model of oligonucleotides of a common length that makes them reminiscent of some planets in our solar system, particularly Earth and Saturn. They allow a judicious selection of so-called noncrosshybridizing (nxh) bases that offer substantial reduction of DNA sequences of arbitrary length into a few informative features. The quality assessment of the information extracted by them is high because of their very low Shannon Entropy, i.e. they minimize the degree of uncertainty in hybridization that makes results on standard microarrays irreproducible. For example, SNP classification (pathogenic/non-pathogenic) and pathogen identification can be solved with high sensitivity (~77%/100%) and specificity (~92%/100%, respectively) for combined taxa on a sample of over 264 fully coding sequences in whole bacterial genomes and fungal mitochondrial genomes using machine learning (ML) models. These methods can be applied to several other interesting research questions that could be addressed with similar genomic analyses.
Pulmonary metastasectomy in bone and soft tissue sarcoma with metastasis to the lung
Authors: Gusho Charles A , Seder Christopher W , Lopez-Hisijos Nicolas , Blank Alan T , Batus Marta
Published: September 2021

OBJECTIVES

This study investigated the outcomes of sarcoma patients with lung metastases who underwent pulmonary metastasectomy (PM), compared to patients who underwent medical management alone. The secondary objective was to compare survival after PM between variables of interest.

METHODS

This was a retrospective review of 565 sarcoma patients with confirmed, isolated pulmonary metastasis identified from the Surveillance, Epidemiology and End Results database between 2010 and 2015. 1:4 propensity score matching was used to select PM and non-PM groups. The multivariable Cox proportional hazards model was used to analyse prognostic factors of disease-free survival (DFS).

RESULTS

Of the eligible 565 patients, 59 PM patients were matched to 202 non-PM patients in a final ratio of 3.4. After propensity matching, there were no significant differences in baseline characteristics between PM and non-PM patients. The median DFS after PM was 32 months (interquartile range 18–59), compared to 20 months (interquartile range 7–40) in patients without PM (P = 0.032). Using a multivariable Cox proportional hazards model, metastasectomy (hazard ratio 0.536, 95% confidence interval 0.33–0.85; P = 0.008) was associated with improved DFS. In a subset analysis of patients who underwent PM only, the median DFS was longer in males compared to females (P = 0.021), as well as in bone sarcoma compared to soft tissue sarcoma (P = 0.014).

CONCLUSIONS

For sarcoma patients with metastatic lung disease, PM appears to improve the prognosis compared to medical management. Furthermore, there may be a survival association with gender and tumour origin in patients who underwent PM. These data may be used to inform the surgical indications and eligibility criteria for metastasectomy in this setting.
Evidence for Human-to-Human Transmission of Hantavirus: A Systematic Review
Authors: Toledo Joao , Haby Michelle M , Reveiz Ludovic , Sosa Leon Leopoldo , Angerami Rodrigo , Aldighieri Sylvain
Published: September 2021

Background

Hantavirus is known to be transmitted from rodents to humans. However, some reports from Argentina and Chile have claimed that the hantavirus strain Andes virus (ANDV) can cause human-to-human transmission of the disease. The aim of this systematic review was to assess the evidence for human-to-human transmission of hantavirus.

Methods

We searched PubMed (inception to 28 February 2021), Cochrane Central, Embase, LILACS and SciELO (inception to 3 July 2020), and other sources. We included studies that assessed whether interpersonal contact with a person with laboratory-confirmed hantavirus infection led to human-to-human transmission. Two reviewers conducted screening, selection, data extraction, and risk of bias assessment.

Results

Twenty-two studies met the inclusion criteria. Meta-analysis was not possible due to heterogeneity. With the exception of 1 prospective cohort study of ANDV in Chile with serious risk of bias, evidence from comparative studies (strongest level of evidence available) does not support human-to-human transmission of hantavirus infection. Noncomparative studies with a critical risk of bias suggest that human-to-human transmission of ANDV may be possible.

Conclusions

The balance of the evidence does not support the claim of human-to-human transmission of ANDV. Well-designed cohort and case-control studies that control for co-exposure to rodents are needed to inform public health recommendations.
Incorporating qualitative research methods into the monitoring and evaluation of neglected tropical disease programmes: a scoping literature review
Authors: Baker Margaret C , Bardosh Kevin , Fitch Elizabeth , Mbabazi Pamela S , Mwingira Upendo , Direny Abdel , Dean Laura , Sutherland Elizabeth G , Krentel Alison
Published: September 2021

This publication addresses the limited use of qualitative methods in neglected tropical disease (NTD) programmes. It describes a scoping literature review conducted to inform the development of a guide to inform the use of rapid qualitative assessments to strengthen NTD mass drug administration (MDA) programmes. The review assessed how qualitative methods are currently used by NTD programmes and identified qualitative approaches from other health and development programmes with the potential to strengthen the design of MDA interventions. Systematic review articles were reviewed and searched using key terms conducted on Google Scholar and PubMed. Results show that methods used by NTD programmes rely heavily on focus group discussions and in-depth interviews, often with time-consuming analysis and limited information on how results are applied. Results from other fields offered insight into a wider range of methods, including participatory approaches, and on how to increase programmatic uptake of findings. Recommendations on how to apply these findings to NTD control are made. The topic of human resources for qualitative investigations is explored and a guide to improve MDAs using qualitative methods is introduced. This guide has direct applicability across the spectrum of NTDs as well as other public health programmes.
High prevalence of HIV-1 transmitted drug resistance and factors associated with time to virological failure and viral suppression in Taiwan
Authors: Huang Szu-Wei , Shen Mei-Chen , Wang Wen-Hung , Li Wei-You , Wang Jen-Hsien , Tseng Cheng-Yin , Liu Po-Yu , Wang Lih-Shinn , Lee Yu-Lin , Chen Yi-Ming Arthur , Lee Chun-Yuan , Lu Po-Liang , Wang Sheng-Fan
Published: September 2021

Background

Integrase strand transfer inhibitor (InSTI)-based regimens have become the major first-line treatment for HIV-1-infected patients in Taiwan. Transmitted drug resistance (TDR) and several clinical characteristics are associated with time to virological failure or viral suppression; however, these have not been investigated in Taiwan.

Objectives

To determine the impact of several factors on treatment outcomes in HIV-1-infected patients in Taiwan.

Methods

The cohort included 164 HIV-1 treatment-naive patients in Taiwan from 2018 to 2020. Blood specimens were collected to determine the genotypic drug resistance using the Stanford University HIV drug resistance database. Cox proportional hazards models were used to identify factors associated with time to virological failure or viral suppression.

Results

The prevalence of TDR in Taiwan was 27.4% and an increasing trend was seen from 2018 to 2020. TDR mutations related to NNRTIs were the most prevalent (21%) while TDR to InSTIs remained at a relatively low level (1.3%). A baseline HIV-1 viral load of ≥100 000 copies/mL was associated with a shorter time to virological failure [multivariate hazard ratio (mHR) 7.84; P = 0.018] and longer time to viral suppression (mHR 0.46; P < 0.001). Time to viral suppression was shorter in patients receiving InSTI-based regimens (mHR 2.18; P = 0.006). Different InSTI-based regimens as initial treatment did not affect the treatment outcomes.

Conclusions

This study found an increasing trend of HIV-1 TDR prevalence from 2018 to 2020 in Taiwan. Baseline HIV-1 viral load and receiving InSTI-based regimens are important factors associated with time to virological failure or viral suppression.
“Marshall Lecture 2020: The Measure of Monopsony”
Authors: Langella Monica , Manning Alan
Published: September 2021

There has been increasing interest in recent years in monopsony in the labour market. This paper discusses how we can measure monopsony power by combining insights from models based on both frictions and idiosyncrasies. It presents some evidence from the United Kingdom and the United States about how monopsony power varies across the wage distribution within markets, over the business cycle and over time.
Ancient Introgression Between Distantly Related White Oaks (Quercussect.Quercus) Shows Evidence of Climate-Associated Asymmetric Gene Exchange
Authors: O’Donnell Scott T , Fitz-Gibbon Sorel T , Sork Victoria L
Published: September 2021

Ancient introgression can be an important source of genetic variation that shapes the evolution and diversification of many taxa. Here, we estimate the timing, direction, and extent of gene flow between two distantly related oak species in the same section (Quercus sect. Quercus). We estimated these demographic events using genotyping by sequencing data, which generated 25 702 single nucleotide polymorphisms for 24 individuals of California scrub oak (Quercus berberidifolia) and 23 individuals of Engelmann oak (Quercus engelmannii). We tested several scenarios involving gene flow between these species using the diffusion approximation-based population genetic inference framework and model-testing approach of the Python package DaDi. We found that the most likely demographic scenario includes a bottleneck in Q. engelmannii that coincides with asymmetric gene flow from Q. berberidifolia into Q. engelmannii. Given that the timing of this gene flow coincides with the advent of a Mediterranean-type climate in the California Floristic Province, we propose that changing precipitation patterns and seasonality may have favored the introgression of climate-associated genes from the endemic into the non-endemic California oak.
Cancer Treatment: Preclinical & Clinical
Authors: Abrams Donald I , Velasco Guillermo , Twelves Chris , Ganju Ramesh K , Bar-Sela Gil
Published: September 2021

The first evidence that cannabinoids may have in vitro and in vivo antineoplastic activity against tumor cell lines and animal tumor models was published in the Journal of the National Cancer Institute nearly 50 years ago. Cannabinoids appear to induce apoptosis in rodent brain tumors by way of direct interaction with the cannabinoid receptor. They may inhibit angiogenesis and tumor cell invasiveness. Despite preclinical findings, attempts to translate the benefits from bench to bedside have been limited. This session provides a review of the basic science supporting the use of cannabinoids in gliomas, paired with the first randomized clinical trial of a cannabis-based therapy for glioblastoma multiforme. Another preclinical presentation reports the effects of cannabinoids on triple-negative breast cancer cell lines and how cannabidiol may affect tumors. The session’s second human trial raises concerns about the use of botanical cannabis in patients with advanced cancer receiving immunotherapy suggesting inferior outcomes.
Under Pressure: When Refugees Feel Pressured to Leave Their Host Countries
Authors: Braithwaite Alex , Ghosn Faten , Hameed Tuqa
Published: September 2021

A significant portion of the global population of 270 million migrants are refugees who were forcibly displaced from and are unable to return to their country of origin for reasons ranging from personal safety to economic instability. Almost 30 million refugees are protected by an international refugee regime, which obliges host states to provide safehaven and protections against forced expulsion. Nonetheless, refugee experiences in host countries are highly varied, including with respect to how welcome they feel in their host states. This matters because refugees that feel pressured to leave may be more likely to look to move on to a third country or return home involuntarily and before conditions are safe to do so. We argue that whether or not refugees feel pressured to leave host countries is affected by the varied nature of their quotidian interactions with authorities and regular citizens. To test the validity of this argument we draw upon approximately 1,700 responses to a survey administered among the Syrian refugee population throughout Lebanon in June and July 2018. Our statistical analyses demonstrate that individuals who are registered with the UN and the Lebanese government both feel more pressure to leave the country, as do individuals who are subject to ill treatment at the hands of Lebanese residents or authorities. We also find some tentative evidence that individuals who are not well socially connected within Lebanese society—those that live in predominantly Syrian neighbourhoods in Lebanon—also feel more pressure to leave the country.
Cross-validation of the high-capacity tensiometer and thermocouple psychrometer for continuous monitoring of xylem water potential in saplings
Authors: Dainese Roberta , de CFL Lopes Bruna , Tedeschi Giuseppe , Lamarque Laurent J , Delzon Sylvain , Fourcaud Thierry , Tarantino Alessandro
Published: September 2021

The pressure chamber, the most popular method used to measure xylem water potential, is a discontinuous and destructive technique and is therefore not suitable for automated monitoring. Continuous non-destructive monitoring could until very recently be achieved only by use of the thermocouple psychrometer (TP). Here we present the high-capacity tensiometer (HCT) as an alternative method for continuous non-destructive monitoring. This provided us with a unique chance to cross-validate the two instruments by installing them simultaneously on the same sapling stem. The HCT and the TP showed excellent agreement for xylem water potential less than –0.5 MPa. Response to day/night cycles and watering was remarkably in phase, indicating excellent response time of both instruments despite substantially different working principles. For xylem water potential greater than –0.5 MPa, the discrepancies sometimes observed between the HCT and TP were mainly attributed to the kaolin paste used to establish contact between the xylem and the HCT, which becomes hydraulically poorly conductive in this range of water potential once dried beyond its air-entry value and subsequently re-wetted. Notwithstanding this limitation, which can be overcome by selecting a clay paste with higher air-entry value, the HCT has been shown to represent a valid alternative to the TP.
Functional characterization of a cellulose synthase, CtCESA1, from the marine red alga Calliarthron tuberculosum (Corallinales)
Authors: Xue Jan , Purushotham Pallinti , Acheson Justin F , Ho Ruoya , Zimmer Jochen , McFarlane Ciaran , Van Petegem Filip , Martone Patrick T , Samuels A Lacey
Published: September 2021

In land plants and algae, cellulose is important for strengthening cell walls and preventing breakage due to physical forces. Though our understanding of cellulose production by cellulose synthases (CESAs) has seen significant advances for several land plant and bacterial species, functional characterization of this fundamental protein is absent in red algae. Here we identify CESA gene candidates in the calcifying red alga Calliarthron tuberculosum using sequence similarity-based approaches, and elucidate their phylogenetic relationship with other CESAs from diverse taxa. One gene candidate, CtCESA1, was closely related to other putative red algal CESA genes. To test if CtCESA1 encoded a true cellulose synthase, CtCESA1 protein was expressed and purified from insect and yeast expression systems. CtCESA1 showed glucan synthase activity in glucose tracer assays. CtCESA1 activity was relatively low when compared with plant and bacterial CESA activity. In an in vitro assay, a predicted N-terminal starch-binding domain from CtCESA1 bound red algal floridean starch extracts, representing a unique domain in red algal CESAs not present in CESAs from other lineages. When the CtCESA1 gene was introduced into Arabidopsis thaliana cesa mutants, the red algal CtCESA1 partially rescued the growth defects of the primary cell wall cesa6 mutant, but not cesa3 or secondary cell wall cesa7 mutants. A fluorescently tagged CtCESA1 localized to the plasma membrane in the Arabidopsis cesa6 mutant background. This study presents functional evidence validating the sequence annotation of red algal CESAs. The relatively low activity of CtCESA1, partial complementation in Arabidopsis, and presence of unique protein domains suggest that there are probably functional differences between the algal and land plant CESAs.
Of narrative time and space: geography meets history via linguistics
Authors: Franzosi Roberto
Published: September 2021

The article explores issues of narrative time and space. It embraces a conception of geography, of space, as place involving relations among people, with ‘their own stories to tell’. And as story, as narrative, geography can be captured by a ‘story grammar’: Who, What, When, Where, Why, and How (the 5 Ws + H). When and Where, time and space, are the fundamental axes of narrative, different cultures differently grounding narrative in time (the ‘once upon a time’ of Western culture) or in space (the Western Apaches of Arizona). The article explores the ways in which new computational tools allow us to understand and represent actors and their actions in the setting of time and space, ways for geography to meet history, via linguistics. The article illustrates the geographical and historical implications of the approach by focusing on lynching narratives from hundreds of newspaper articles (Georgia, 1875–1930).
On the origin of the Kreutz family of sungrazing comets
Authors: Fernández Julio A , Lemos Pablo , Gallardo Tabaré
Published: September 2021

We evaluate numerically three different models for the parent comet of the Kreutz family of sungrazers: (i) A Centaur on a highly inclined or retrograde orbit that diffuse to the inner planetary region where it became a sungrazer (Model 1). (ii) A parent comet injected from the Oort cloud straight into a near-parabolic, sungrazing orbit. Near perihelion the comet was disrupted by tidal forces from the Sun giving rise to a myriad of fragments that created the Kreutz family (Model 2). (iii) A two-step process by which an Oort cloud comet is first injected in a non-sungrazing, Earth-crossing orbit where its semimajor axis decreases from typical Oort cloud values (a ∼ 104 au) to around 102 au, and then it evolves to a sungrazing orbit by the Lidov–Kozai mechanism (Model 3). Model 1 fails to produce sungrazers of the Kreutz type. Model 2 produces some Kreutz sungrazers and has the appeal of being the most straightforward. Yet the impulses received by the fragments originated in the catastrophic disruption of the parent comet will tend to acquire a wide range of orbital energies or periods (from short-period to long-period orbits) that is in contradiction with the observations. Model 3 seems to be the most promising one since it leads to the generation of some sungrazers of the Kreutz type and, particularly, it reproduces the clustering of the argument of perihelion ω of the observed Kreutz family members around 60°–90°, as a natural consequence of the action of the Lidov–Kozai mechanism.
Properties of Thorne–Żytkow object explosions
Authors: Moriya Takashi J , Blinnikov Sergei I
Published: September 2021

Thorne–Żytkow objects are stars that have a neutron star core with an extended hydrogen-rich envelope. Massive Thorne–Żytkow objects are proposed to explode when the nuclear reactions sustaining their structure are terminated by the exhaustion of the seed elements. In this paper, we investigate the observational properties of the possible Thorne–Żytkow object explosions. We find that Thorne–Żytkow object explosions are observed as long-duration transients lasting for several years. If the accretion disc triggering the explosions does not last for a long time, Thorne–Żytkow object explosions have a luminosity plateau with about $10^{39}\, \mathrm{erg\, s^{-1}}$ lasting for a few years, and then they suddenly become faint. They would be observed as vanished stars after a bright phase lasting for a few years. If the accretion disc is sustained for long time, the Thorne–Żytkow object explosions become as bright as supernovae. They would be observed as supernovae with rise times of several hundred days. We found that their photospheric velocities are $2000\, \mathrm{km\, s^{-1}}$ at most, much smaller than those found in supernovae. Supernovae with extremely long rise times such as HSC16aayt and SN 2008iy may be related to the explosions of Thorne–Żytkow objects.
A method for finding anomalous astronomical light curves and their analogues
Authors: Martínez-Galarza J Rafael , Bianco Federica B , Crake Dennis , Tirumala Kushal , Mahabal Ashish A , Graham Matthew J , Giles Daniel
Published: September 2021

Our understanding of the Universe has profited from deliberate targeted studies of known phenomena, as well as from serendipitous unexpected discoveries, such as the discovery of a complex variability pattern in the direction of KIC 8462852 (Boyajian’s star). Upcoming surveys such as the Vera C. Rubin Observatory Legacy Survey of Space and Time will explore the parameter space of astrophysical transients at all time-scales, and offer the opportunity to discover even more extreme examples of unexpected phenomena. We investigate strategies to identify novel objects and to contextualize them within large time-series data sets in order to facilitate the discovery of new classes of objects as well as the physical interpretation of their anomalous nature. We develop a method that combines tree-based and manifold-learning algorithms for anomaly detection in order to perform two tasks: 1) identify and rank anomalous objects in a time-domain data set; and 2) group those anomalies according to their similarity in order to identify analogues. We achieve the latter by combining an anomaly score from a tree-based method with a dimensionality manifold-learning reduction strategy. Clustering in the reduced space allows for the successful identification of anomalies and analogues. We also assess the impact of pre-processing and feature engineering schemes and investigate the astrophysical nature of the objects that our models identify as anomalous by augmenting the Kepler data with Gaia colour and luminosity information. We find that multiple models, used in combination, are a promising strategy to identify novel light curves and light curve families.
Gaussian Process Regression for foreground removal in H i Intensity Mapping experiments
Authors: Soares Paula S , Watkinson Catherine A , Cunnington Steven , Pourtsidou Alkistis
Published: September 2021

We apply for the first time Gaussian Process Regression (GPR) as a foreground removal technique in the context of single-dish, low redshift H i intensity mapping, and present an open-source python toolkit for doing so. We use MeerKAT and SKA1-MID-like simulations of 21 cm foregrounds (including polarization leakage), H i cosmological signal, and instrumental noise. We find that it is possible to use GPR as a foreground removal technique in this context, and that it is better suited in some cases to recover the H i power spectrum than principal component analysis (PCA), especially on small scales. GPR is especially good at recovering the radial power spectrum, outperforming PCA when considering the full bandwidth of our data. Both methods are worse at recovering the transverse power spectrum, since they rely on frequency-only covariance information. When halving our data along frequency, we find that GPR performs better in the low-frequency range, where foregrounds are brighter. It performs worse than PCA when frequency channels are missing, to emulate RFI flagging. We conclude that GPR is an excellent foreground removal option for the case of single-dish, low-redshift H i intensity mapping in the absence of missing frequency channels. Our python toolkit gpr4im and the data used in this analysis are publicly available on GitHub.
Revisiting the evolution of non-radiative supernova remnants: a hydrodynamical-informed parametrization of the shock positions
Authors: Bandiera R , Bucciantini N , Martín J , Olmi B , Torres D F
Published: September 2021

Understanding the evolution of a supernova remnant shell in time is fundamental. Such understanding is critical to build reliable models of the dynamics of the supernova remnant shell interaction with any pulsar wind nebula it might contain. Here, we perform a large study of the parameter space for the 1D spherically symmetric evolution of a supernova remnant, accompanying it by analytical analysis. Assuming, as is usual, an ejecta density profile with a power-law core and an envelope, and a uniform ambient medium, we provide a set of highly accurate approximations for the evolution of the main structural features of supernova remnants, such as the reverse and forward shocks and the contact discontinuity. We compare our results with previously adopted approximations, showing that existing simplified prescriptions can easily lead to large errors. In particular, in the context of pulsar wind nebulae modelling, an accurate description for the supernova remnant reverse shock is required. We also study in depth the self-similar solutions for the initial phase of evolution, when the reverse shock propagates through the envelope of the ejecta. Since these self-similar solutions are exact, but not fully analytical, we here provide highly accurate approximations as well.
Measuring the baryonic Tully–Fisher relation below the detection threshold
Authors: Pan Hengxing , Jarvis Matt J , Ponomareva Anastasia A , Santos Mario G , Allison James R , Maddox Natasha , Frank Bradley S
Published: September 2021

We present a novel 2D flux density model for observed H i emission lines combined with a Bayesian stacking technique to measure the baryonic Tully–Fisher relation below the nominal detection threshold. We simulate a galaxy catalogue, which includes H i lines described with either Gaussian or busy function profiles, and H i data cubes with a range of noise and survey areas similar to the MeerKAT International Giga-Hertz Tiered Extragalactic Exploration (MIGHTEE) survey. With prior knowledge of redshifts, stellar masses, and inclinations of spiral galaxies, we find that our model can reconstruct the input baryonic Tully–Fisher parameters (slope and zero-point) most accurately in a relatively broad redshift range from the local Universe to z = 0.3 for all the considered levels of noise and survey areas and up to z = 0.55 for a nominal noise of 90 $\mu$Jy/channel over 5 deg2. Our model can also determine the $M_{\rm H\, \small {I}} - M_{\star }$ relation for spiral galaxies beyond the local Universe and account for the detailed shape of the H i emission line, which is crucial for understanding the dynamics of spiral galaxies. Thus, we have developed a Bayesian stacking technique for measuring the baryonic Tully–Fisher relation for galaxies at low stellar and/or H i masses and/or those at high redshift, where the direct detection of H i requires prohibitive exposure times.
Animal-eRNAdb: a comprehensive animal enhancer RNA database
Authors: Jin Weiwei , Jiang Guanghui , Yang Yanbo , Yang Jianye , Yang Wenqian , Wang Dongyang , Niu Xiaohui , Zhong Rong , Zhang Zhao , Gong Jing
Published: September 2021

Enhancer RNAs (eRNAs) are a class of non-coding RNAs transcribed from enhancers. As the markers of active enhancers, eRNAs play important roles in gene regulation and are associated with various complex traits and characteristics. With increasing attention to eRNAs, numerous eRNAs have been identified in different human tissues. However, the expression landscape, regulatory network and potential functions of eRNAs in animals have not been fully elucidated. Here, we systematically characterized 185 177 eRNAs from 5085 samples across 10 species by mapping the RNA sequencing data to the regions of known enhancers. To explore their potential functions based on evolutionary conservation, we investigated the sequence similarity of eRNAs among multiple species. In addition, we identified the possible associations between eRNAs and transcription factors (TFs) or nearby genes to decipher their possible regulators and target genes, as well as characterized trait-related eRNAs to explore their potential functions in biological processes. Based on these findings, we further developed Animal-eRNAdb (http://gong_lab.hzau.edu.cn/Animal-eRNAdb/), a user-friendly database for data searching, browsing and downloading. With the comprehensive characterization of eRNAs in various tissues of different species, Animal-eRNAdb may greatly facilitate the exploration of functions and mechanisms of eRNAs.
A simple and rapid method for enzymatic synthesis of CRISPR-Cas9 sgRNA libraries
Authors: Yates Joshua D , Russell Robert C , Barton Nathaniel J , Yost H Joseph , Hill Jonathon T
Published: September 2021

CRISPR-Cas9 sgRNA libraries have transformed functional genetic screening and have enabled several innovative methods that rely on simultaneously targeting numerous genetic loci. Such libraries could be used in a vast number of biological systems and in the development of new technologies, but library generation is hindered by the cost, time, and sequence data required for sgRNA library synthesis. Here, we describe a rapid enzymatic method for generating robust, variant-matched libraries from any source of cDNA in under 3 h. This method, which we have named SLALOM, utilizes a custom sgRNA scaffold sequence and a novel method for detaching oligonucleotides from solid supports by a strand displacing polymerase. With this method, we constructed libraries targeting the E. coli genome and the transcriptome of developing zebrafish hearts, demonstrating its ability to expand the reach of CRISPR technology and facilitate methods requiring custom libraries.
USP37 regulates DNA damage response through stabilizing and deubiquitinating BLM
Authors: Wu Chenming , Chang Yiming , Chen Junliang , Su Yang , Li Lei , Chen Yuping , Li Yunhui , Wu Jinhuan , Huang Jinzhou , Zhao Fei , Wang Wenrui , Yin Hui , Wang Shunli , Jin Mingpeng , Lou Zhenkun , Zhu Wei-Guo , Luo Kuntian , Zhang Jie , Yuan Jian
Published: September 2021

The human RecQ helicase BLM is involved in the DNA damage response, DNA metabolism, and genetic stability. Loss of function mutations in BLM cause the genetic instability/cancer predisposition syndrome Bloom syndrome. However, the molecular mechanism underlying the regulation of BLM in cancers remains largely elusive. Here, we demonstrate that the deubiquitinating enzyme USP37 interacts with BLM and that USP37 deubiquitinates and stabilizes BLM, thereby sustaining the DNA damage response (DDR). Mechanistically, DNA double-strand breaks (DSB) promotes ATM phosphorylation of USP37 and enhances the binding between USP37 and BLM. Moreover, knockdown of USP37 increases BLM polyubiquitination, accelerates its proteolysis, and impairs its function in DNA damage response. This leads to enhanced DNA damage and sensitizes breast cancer cells to DNA-damaging agents in both cell culture and in vivo mouse models. Collectively, our results establish a novel molecular mechanism for the USP37–BLM axis in regulating DSB repair with an important role in chemotherapy and radiotherapy response in human cancers.
Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease
Authors: Mabillard Holly , Sayer John A , Olinger Eric
Published: September 2021

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a clinical entity defined by interstitial fibrosis with tubular damage, bland urinalysis and progressive kidney disease. Mutations in UMOD and MUC1 are the most common causes of ADTKD but other rarer (REN, SEC61A1), atypical (DNAJB11) or heterogeneous (HNF1B) subtypes have been described. Raised awareness, as well as the implementation of next-generation sequencing approaches, have led to a sharp increase in reported cases. ADTKD is now believed to be one of the most common monogenic forms of kidney disease and overall it probably accounts for ∼5% of all monogenic causes of chronic kidney disease. Through international efforts and systematic analyses of patient cohorts, critical insights into clinical and genetic spectra of ADTKD, genotype–phenotype correlations as well as innovative diagnostic approaches have been amassed during recent years. In addition, intense research efforts are addressed towards deciphering and rescuing the cellular pathways activated in ADTKD. A better understanding of these diseases and of possible commonalities with more common causes of kidney disease may be relevant to understand and target mechanisms leading to fibrotic kidney disease in general. Here we highlight recent advances in our understanding of the different subtypes of ADTKD with an emphasis on the molecular underpinnings and its clinical presentations.
Constitutional Transformation and Gender Equality: The Case of the Post-Arab Uprisings North African Constitutions
Authors: Porras-Gómez Antonio-Martín
Published: September 2021

The recognition of gender equality has become one of the most important trends in contemporary constitutional law. Nonetheless, a crucial question lingers: is it leading to material constitutional transformation? In order to better understand it, this article presents a case study on the constitutional reconfigurations undergone in Morocco, Tunisia and Egypt after the Arab uprisings. The main vectors of constitutional change are identified from a descriptive-analytical perspective. Even if they kept idiosyncratic elements of persistent discrimination, the new charters were inserted in the globalised trends of constitutional design, bringing about a strong formal expansion of gender equality rights. On the whole, however, little material progress has been made. This suboptimal material transformation is explained by means of research arguments framed in legal evolutionist theories. Finally, the article elucidates why the greater constitutional verbosity in the recognition of gender equality did not translate into greater parity.
‘A General Insurrection in the Countries with Slaves’: The US Civil War and the Origins of an Atlantic Revolution, 1861–1866
Authors: Payne Samantha
Published: September 2021

This article reveals how the beginning of US Reconstruction precipitated a revolutionary crisis in Cuba and Brazil, the last two slave societies in the Atlantic World. Throughout the US Civil War, slave-owners in Cuba and Brazil faced the immense challenge of containing black revolutionary currents across the Atlantic. Despite their intensive policing of black transnational networks, many slaves in Cuba and Brazil learned of the Civil War and became convinced that it heralded their emancipation. In response, they walked off plantations, fled to maroon communities, and organized and launched revolts. Although the scale of this insurrectionary violence never reached the same heights as in the Confederacy, the beginning of Reconstruction transformed the political implications of slave rebellion across the hemisphere. The fall of the Confederacy forced slave-owners in Cuba and Brazil to confront the possibility of their violent destruction at the same moment that the apparent radicalization of Republican politics stirred fears of US support for an international slave insurrection. It was in this context that many white elites in both nations became convinced of the necessity for a gradual abolition measure, which they hoped would ensure subaltern loyalty at a moment when revolutionary violence threatened the future of slavery.
Super-resolution imaging illuminates new dynamic behaviors of cellulose synthase
Authors: Duncombe Sydney G , Chethan Samir G , Anderson Charles T
Published: September 2021

Confocal imaging has shown that CELLULOSE SYNTHASE (CESA) particles move through the plasma membrane as they synthesize cellulose. However, the resolution limit of confocal microscopy circumscribes what can be discovered about these tiny biosynthetic machines. Here, we applied Structured Illumination Microscopy (SIM), which improves resolution two-fold over confocal or widefield imaging, to explore the dynamic behaviors of CESA particles in living plant cells. SIM imaging reveals that Arabidopsis thaliana CESA particles are more than twice as dense in the plasma membrane as previously estimated, helping explain the dense arrangement of cellulose observed in new wall layers. CESA particles tracked by SIM display minimal variation in velocity, suggesting coordinated control of CESA catalytic activity within single complexes and that CESA complexes might move steadily in tandem to generate larger cellulose fibrils or bundles. SIM data also reveal that CESA particles vary in their overlaps with microtubule tracks and can complete U-turns without changing speed. CESA track patterns can vary widely between neighboring cells of similar shape, implying that cellulose patterning is not the sole determinant of cellular growth anisotropy. Together, these findings highlight SIM as a powerful tool to advance CESA imaging beyond the resolution limit of conventional light microscopy.
Plant cell mechanobiology: Greater than the sum of its parts
Authors: Codjoe Jennette M , Miller Kari , Haswell Elizabeth S
Published: September 2021

The ability to sense and respond to physical forces is critical for the proper function of cells, tissues, and organisms across the evolutionary tree. Plants sense gravity, osmotic conditions, pathogen invasion, wind, and the presence of barriers in the soil, and dynamically integrate internal and external stimuli during every stage of growth and development. While the field of plant mechanobiology is growing, much is still poorly understood—including the interplay between mechanical and biochemical information at the single-cell level. In this review, we provide an overview of the mechanical properties of three main components of the plant cell and the mechanoperceptive pathways that link them, with an emphasis on areas of complexity and interaction. We discuss the concept of mechanical homeostasis, or “mechanostasis,” and examine the ways in which cellular structures and pathways serve to maintain it. We argue that viewing mechanics and mechanotransduction as emergent properties of the plant cell can be a useful conceptual framework for synthesizing current knowledge and driving future research.
A Poem by Sir Julius Caesar, Judge of the Admiralty, 1589
Authors: Bajetta Carlo M
Published: September 2021

A courtier of Elizabeth I and later James I, Sir Julius Caesar (Giulio Cesare Adelmare, 1558–1636) is remembered today chiefly for his place in the history of the English legal system. His role as a lover and writer of poetry, however, has been almost entirely ignored by historians and literary scholars alike, even though a poem of his was found and published as early as the nineteenth century. A manuscript collection containing many of Caesar’s business and family papers confirms his authorship of these verses and provides a date, a new context, and a far superior (and longer) text. Surrounded by documents relating to the literary exchanges of the Adelmare family, original letters by members of the Elizabethan élite, and presenting some disquieting references to treason, this apparently naive composition proves to be deeply connected with both Caesar’s life and the politics of his time.
Composing Well-being: Mental Health and the Mass Observation Project in Twentieth-Century Britain
Authors: Burchell Andrew , Thomson Mathew
Published: September 2021

This article argues that the Mass Observation Project (MOP) at the University of Sussex offers a unique window onto the history of mental health and the voices of those who have lived with mental health conditions during the late-twentieth century. This article analyses how a sample of MOP participants use their writing to reflect on their experiences, and compose narratives about, mental illness over time. More specifically, we suggest that MOP’s capacity for the longitudinal study of individual respondents (underutilised by historians of mental health) offers exciting historiographical and methodological possibilities, not just in the history of mental health but for historians of medicine more generally. We conclude by considering how, for a handful of the participants in the project, mental health is entwined with MOP, as project participants deploy the archive to write about their experiences and even find something akin to therapy in the narrative act.
XVI American Literature: The Twentieth Century
Authors: Gifford James , Clawson James M , Foltz Mary , Kidder Orion Ussner , Peppard Anna , Parker Lindsay
Published: September 2021

This chapter has eight sections: 1. Poetry; 2. Fiction 1900–1945; 3. Fiction since 1945; 4. Drama; 5. Comics; 6. African American Writing; 7. Native Writing; 8. Latino/a, Asian American, and General Ethnic Writing. Section 1 is by James Gifford; section 2 is by James M. Clawson; section 3 is by Mary Foltz; section 4 will resume next year; section 5(a) is by Anna Peppard; section 5(b) is by Orion Ussner Kidder; section 6 is by Adam Rudder; section 7 is by James Gifford and Lindsay Parker; section 8 will resume next year.
Evaluation of a Risk-Stratified, Heparin-Based, Obstetric Thromboprophylaxis Protocol
Authors: Lu Michelle Y. , Blanchard Christina T. , Ausbeck Elizabeth B. , Oglesby Kacie R. , Page Margaret R. , Lazenby Allison J. , Cozzi Gabriella D. , Muñoz Rogers Rodrigo D. , Bushman Elisa T. , Kaplan Elle R. , Ruzic Martha F. , Mahalingam Mythreyi , Dunk Sarah , Champion Macie , Casey Brian M. , Tita Alan T. , Kim Dhong-Jin , Szychowski Jeff M. , Subramaniam Akila
Published: September 2021

OBJECTIVE:

To evaluate outcomes before and after implementation of a risk-stratified heparin-based obstetric thromboprophylaxis protocol.

METHODS:

We performed a retrospective cohort study of all patients who delivered at our tertiary care center from 2013 to 2018. Deliveries were categorized as preprotocol (2013–2015; no standardized heparin-based thromboprophylaxis) and postprotocol (2016–2018). Patients receiving outpatient anticoagulation for active venous thromboembolism (VTE) or high VTE risk were excluded. Coprimary effectiveness and safety outcomes were postpartum VTEs and wound hematomas, respectively, newly diagnosed after delivery and up to 6 weeks postpartum. Secondary outcomes were other wound or bleeding complications, including unplanned surgical procedures (eg, hysterectomies, wound explorations) and blood transfusions. Outcomes were compared between groups, and adjusted odds ratios (aORs) and 95% CIs were calculated using the preprotocol group as reference.

RESULTS:

Of 24,229 deliveries, 11,799 (49%) occurred preprotocol. Although patients were more likely to receive heparin-based prophylaxis postprotocol (15.6% vs 1.2%, P<.001), there was no difference in VTE frequency between groups (0.1% vs 0.1%, odds ratio 1.0, 95% CI 0.5–2.1). However, patients postprotocol experienced significantly more wound hematomas (0.7% vs 0.4%, aOR 2.34, 95% CI 1.54–3.57), unplanned surgical procedures (aOR 1.29, 95% CI 1.06–1.57), and blood transfusions (aOR 1.34, 95% CI 1.16–1.55).

CONCLUSION:

Risk-stratified heparin-based thromboprophylaxis in a general obstetric population was associated with increased wound and bleeding complications without a complementary decrease in postpartum VTE. Guidelines recommending this strategy should be reconsidered.
Evaluation of Respiratory Emissions During Labor and Delivery
Authors: Mok Thalia , Harris Elijah , Vargas Andres , Afshar Yalda , Han Christina S. , Karagozian Ann , Rao Rashmi
Published: September 2021

OBJECTIVE:

To characterize respiratory emissions produced during labor and vaginal delivery vis-à-vis the potential for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

METHODS:

Observational study of three women who tested negative for SARS-CoV-2 and had uncomplicated vaginal deliveries. Using background-oriented schlieren imaging, we evaluated the propagation of respiratory emissions produced during the labor course and delivery. The primary outcome was the speed and propagation of breath over time, calculated through processed images collected throughout labor and delivery.

RESULTS:

In early labor with regular breathing, the speed of the breath was 1.37 meters/s (range 1.20–1.55 meters/s). The breath appeared to propagate faster with a cough during early labor at a speed of 1.69 meters/s (range 1.22–2.27 meters/s). During the second stage of labor with Valsalva and forced expiration, the propagation speed was 1.79 meters/s (range 1.71–1.86 meters/s).

CONCLUSION:

Labor and vaginal delivery increase the propagation of respiratory emissions that may increase risk of respiratory transmission of SARS-CoV-2.