bluuebunny/crossref_metadata_2025 huggingface dataset:
Metric learning enables synthesis of heterogeneous single-cell modalities
Authors: Singh Rohit , Hie Brian , Narayan Ashwin , Berger Bonnie
Published: November 2019

A complete understanding of biological processes requires synthesizing information across heterogeneous modalities, such as age, disease status, or gene/protein expression. Until recently, single-cell profiling experiments could measure only a single modality, leading to analysis focused on integrating information across separate experiments. However, researchers can now measure multiple modalities simultaneously in a single experiment, providing a new data paradigm that enables biological discovery but also requires new conceptual and analytic models. We therefore present Schema, an algorithm that leverages a principled metric learning strategy to synthesize multimodal information from the same experiment. To demonstrate the flexibility and power of our approach, we use Schema to infer cell types by integrating gene expression and chromatin accessibility data, perform differential gene expression analysis while accounting for batch effects and developmental age, estimate evolutionary pressure on peptide sequences, and synthesize spliced and unspliced mRNA data to infer cell differentiation. Schema can synthesize arbitrarily many modalities and capture sophisticated relationships between them, is computationally efficient, and provides a valuable conceptual model for exploring and understanding complex biology.
Blinking Statistics and Molecular Counting in direct Stochastic Reconstruction Microscopy (dSTORM)
Authors: Patel Lekha , Williamson David , Owen Dylan M. , Cohen Edward A.K.
Published: November 2019

Motivation

Many recent advancements in single molecule localisation microscopy exploit the stochastic photo-switching of fluorophores to reveal complex cellular structures beyond the classical diffraction limit. However, this same stochasticity makes counting the number of molecules to high precision extremely challenging, preventing key insight into the cellular structures and processes under observation.

Results

Modelling the photo-switching behaviour of a fluorophore as an unobserved continuous time Markov process transitioning between a single fluorescent and multiple dark states, and fully mitigating for missed blinks and false positives, we present a method for computing the exact probability distribution for the number of observed localisations from a single photo-switching fluorophore. This is then extended to provide the probability distribution for the number of localisations in a dSTORM experiment involving an arbitrary number of molecules. We demonstrate that when training data is available to estimate photo-switching rates, the unknown number of molecules can be accurately recovered from the posterior mode of the number of molecules given the number of localisations. Finally, we demonstrate the method on experimental data by quantifying the number of adapter protein Linker for Activation of T cells (LAT) on the cell surface of the T cell immunological synapse.

Availability

Software available at https://github.com/lp1611/mol_count_dstorm.
Dynamic Bayesian networks for integrating multi-omics time-series microbiome data
Authors: Ruiz-Perez Daniel , Lugo-Martinez Jose , Bourguignon Natalia , Mathee Kalai , Lerner Betiana , Bar-Joseph Ziv , Narasimhan Giri
Published: November 2019

A key challenge in the analysis of longitudinal microbiome data is the inference of temporal interactions between microbial taxa, their genes, the metabolites they consume and produce, and host genes. To address these challenges we developed a computational pipeline, PALM, that first aligns multi-omics data and then uses dynamic Bayesian networks (DBNs) to reconstruct a unified model. Our approach overcomes differences in sampling and progression rates, utilizes a biologically-inspired multi-omic framework, reduces the large number of entities and parameters in the DBNs, and validates the learned network. Applying PALM to data collected from inflammatory bowel disease patients, we show that it accurately identifies known and novel interactions. Targeted experimental validations further support a number of the predicted novel metabolite-taxa interactions.

Source code and data will be freely available after publication under the MIT Open Source license agreement on our GitHub page.

IMPORTANCE

While a number of large consortia are collecting and profiling several different types of microbiome and genomic time series data, very few methods exist for joint modeling of multi-omics data sets. We developed a new computational pipeline, PALM, which uses Dynamic Bayesian Networks (DBNs) and is designed to integrate multi-omics data from longitudinal microbiome studies. When used to integrate sequence, expression, and metabolomics data from microbiome samples along with host expression data, the resulting models identify interactions between taxa, their genes and the metabolites they produce and consume, and their impact on host expression. We tested the models both by using them to predict future changes in microbiome levels, and by comparing the learned interactions to known interactions in the literature. Finally, we performed experimental validations for a few of the predicted interactions to demonstrate the ability of the method to identify novel relationships and their impact.
Lis1 regulates Phagocytosis by co-localising with actin in the Phagocytic cup
Authors: Chhatre Aditya , Sanghavi Paulomi , Mallik Roop
Published: November 2019

Phagocytosis, the ingestion of solid particles by cells, is essential for nutrient uptake, innate immune response, antigen presentation and organelle homeostasis. Here we show that Lissencephaly-1 (Lis1), a well-known regulator of the microtubule motor Dynein, also co-localises with actin at the phagocytic cup in the early stages of phagocytosis. Both knockdown and overexpression of Lis1 perturbs phagocytosis, suggesting that an optimum level of Lis1 is required to regulate actin dynamics within the phagocytic cup during particle engulfment. This requirement of Lis1 is replicated in mouse macrophage cells as well as in the amoebaDictyostelium, indicating an evolutionarily conserved role for Lis1 in phagocytosis. In support of these findings, a general role for Lis1 in regulating actin dynamics is suggested by observing defective migration of cells overexpressing Lis1. Taken together, Lis1 localises to the phagocytic cup and influences actin dynamics in a manner that is important for the uptake of solid particles in cells.
Biophysical models of cis-regulation as interpretable neural networks
Authors: Tareen Ammar , Kinney Justin B.
Published: November 2019

The adoption of deep learning techniques in genomics has been hindered by the difficulty of mechanistically interpreting the models that these techniques produce. In recent years, a variety of post-hoc attribution methods have been proposed for addressing this neural network interpretability problem in the context of gene regulation. Here we describe a complementary way of approaching this problem. Our strategy is based on the observation that two large classes of biophysical models of cis-regulatory mechanisms can be expressed as deep neural networks in which nodes and weights have explicit physiochemical interpretations. We also demonstrate how such biophysical networks can be rapidly inferred, using modern deep learning frameworks, from the data produced by certain types of massively parallel reporter assays (MPRAs). These results suggest a scalable strategy for using MPRAs to systematically characterize the biophysical basis of gene regulation in a wide range of biological contexts. They also highlight gene regulation as a promising venue for the development of scientifically interpretable approaches to deep learning.
The pattern of interaction political actors on situations of tenurial conflict in watershed
Authors: Anwar Khairul
Published: November 2019

Purpose

This paper aims to find the pattern of interaction of political actors in situations of tenurial conflict in the watershed through a review of cases of social conflicts of plantation villages around Siak watershed 2009-2014.

Design/methodology/approach

In harmony with the Research Master Plan (RIP) of Riau University, the socio-political of Riau Malay society and the fundamental scientific pattern of Riau university, the development of the resources of area and waters and Malay culture, since 2001, the writer has conducted a study related to the issues of natural resources policy, especially oil palm in the era of regional autonomy and decentralization. This is in line with the umbrella of research developed by the University of Riau namely studying various aspects of natural resources (especially oil palm) and human resources of Watershed (DAS). The writer's review is; first, the dynamics of politics in relation to the issue of oil palm plantation policy in Riau. This study shows that there are many central policies when implemented at the local level including watersheds clashing with local interests such as forests and land ownership. Second, the writer has also reviewed the policy issues and problems of oil palm plantations in Riau watershed in 2000. This study shows there are many issues and problems formulated differently by different people.

Findings

Mapping and strategy are examined through the study of political strategies on oil palm plantations and use them to answer the following two questions: what kind of political model which can be used to manage the watershed conflict since regional autonomy is implemented. Economic factors are influential in mapping and management strategies for the emergence of tenurial conflicts in the Siak River Rivershed 2009-2014. The tenurial conflict management model of Siak rivershed, which is considered relevant, is a conflict-based model of cooperation with a partnership pattern between local government, watershed civil society and plantation business actors. The change of agrarian structure is directed to the effort to open the space for the accesibility of society in decision-making.

Originality/value

Some of these studies have not reached the tenurial conflicts in the watershed areas, especially Siak watershed. In fact, about 80 per cent of Riau province region consists of watershed. This becomes the originality and gap of this study with previous studies. This research was conducted further as an effort to synergize Riau's development policy with Riau University's research in harmony with RIP that was created and aimed to find the pattern of interaction of political actors in situations of tenurial conflict in Watershed through a review of cases of social conflicts of plantation around Siak watershed in 2009-2014.
Phylogenetic and structural diversity of aromatically dense pili from environmental metagenomes
Authors: Bray Marcus S. , Wu Jieying , Padilla Cory C. , Stewart Frank J. , Fowle David A. , Henny Cynthia , Simister Rachel L. , Thompson Katharine J. , Crowe Sean A. , Glass Jennifer B.
Published: November 2019

Electroactive type IV pili, or e‐pili, are used by some microbial species for extracellular electron transfer. Recent studies suggest that e‐pili may be more phylogenetically and structurally diverse than previously assumed. Here, we used updated aromatic density thresholds (≥9.8% aromatic amino acids, ≤22‐aa aromatic gaps and aromatic amino acids at residues 1, 24, 27, 50 and/or 51, and 32 and/or 57) to search for putative e‐pilin genes in metagenomes from diverse ecosystems with active microbial metal cycling. Environmental putative e‐pilins were diverse in length and phylogeny, and included truncated e‐pilins in Geobacter spp., as well as longer putative e‐pilins in Fe(II)‐oxidizing Betaproteobacteria and Zetaproteobacteria.
Development of a peri‐implantitis model in the rat
Authors: Sun Jingqing , Eberhard Joerg , Glage Silke , Held Nadine , Voigt Henning , Schwabe Kerstin , Winkel Andreas , Stiesch Meike
Published: November 2019

Objectives

The aim of the present study was to establish a rodent peri‐implantitis model induced by a mixed bacterial infection characterized by bone loss and semi‐quantitative graduation of peri‐implant inflammation in histological sections.

Materials and Methods

Two titanium implants were implanted in Sprague‐Dawley rats, bilaterally in each maxilla. After 3 weeks healing, the rats were randomized into three groups according to different treatments over the next 3 months: Antibiotic‐Group with oral lavage of antibiotics; Bacteria‐Group with oral lavage of Streptococcus oralis and Aggregatibacter actinomycetemcomitans; and Untreated Group with standard housing and no additional treatment. Maxillae were dissected to perform microscopic and histological analysis of bone height and peri‐implant tissues.

Results

The bone level, measured at one implant site per animal, in the Bacteria‐Group (2.60 ± 0.39 mm) was significantly reduced compared to the Antibiotic‐Group (2.29 ± 0.32 mm) after 3 months. The differences of bone height in the Bacteria‐Group and the Untreated Group (2.46 ± 0.27 mm) did not reach statistical significance. The inflammatory response with respect to the number of inflammatory cells and fibrous tissue compartments of the peri‐implant tissues in the Bacteria‐Group was significantly increased compared with the Antibiotic‐Group (p < .05). S. oralis and A. actinomycetemcomitans DNAs were detected in the Bacteria‐Group.

Conclusions

This rat model of peri‐implantitis used oral bacterial lavage for the induction of an inflammatory host response and bone loss. Additional bacterial treatment enhances the peri‐implant phenotype, so that significant differences to a reduced bacterial load similar to the human peri‐implantitis disease can be identified.
Daily activity performance in congenital and childhood forms of myotonic dystrophy type 1: a population‐based study
Authors: Eriksson Britt‐Marie , Ekström Anne‐Berit , Peny‐Dahlstrand Marie
Published: November 2019

Aims

To identify and describe the profile characterizing motor and process skills during daily activity performance in individuals with congenital and childhood forms of myotonic dystrophy type 1 (DM1) and to investigate differences in performance between subgroups.

Method

Sixty participants (34 males, 26 females, mean age=17y 8mo, SD=6y 0mo, range 5y 8mo–29y 0mo) were divided into severe congenital (n=9), mild congenital (n=20), and childhood (n=31) DM1 subgroups. Daily activity performance was evaluated using a standardized observational instrument: the Assessment of Motor and Process Skills.

Results

Deficits in performance were more pronounced in process than motor skills. Performance more than 2 SDs below age‐specific norms was seen in 65% of participants for process skills and 33% of participants for motor skills. The cut‐off scores indicated a potential need for assistance in daily activities for 79% of participants older than 18 years of age (n=28) due to deficient process skills.

Interpretation

Extensive deficits in daily activity performance were found in congenital and childhood forms of DM1, mainly owing to deficient process skills. Such skills impact on the ability to perform daily activities and could explain dependency in individuals with DM1. Process skills should be considered when evaluating daily activity performance.

What this paper adds

Young people with myotonic dystrophy type 1 show deficits in motor and process skills when performing daily activities, compared with normative data.

Deficits in process skills were more pronounced than deficits in motor skills.
Intramural jejunal leiomyoma as a cause of colic
Authors: Miles S. , Davis W. , Craft W. F.
Published: November 2019

A 15‐year‐old Thoroughbred gelding showjumper presented with colic after a history of chronic mild, intermittent colic. He was refractory to medical management. At surgery, he was found to have a 15‐cm intramural mass in the distal jejunum, approximately 3 m orad to the ileum. Histopathology post‐operatively revealed a leiomyoma. Leiomyomas in horses are rare. They have been reported most commonly in the reproductive tract, with other rare reports in the oesophagus and omentum. To the knowledge of the authors, there are no reports of identification and treatment of non‐strangulating obstruction of the jejunum caused by a leiomyoma. The horse recovered from his surgery and went on to compete at the same level of showjumping as previous to the surgery with no further episodes of colic. Based on this report, leiomyoma should be a differential for small intestinal obstruction in the future.
Animal transgenesis now and beyond in the era of genome editing: Snapshots from the 15th Transgenic Technology Meeting (TT2019) in Kobe, Japan
Authors: Kiyonari Hiroshi , Furuta Yasuhide
Published: November 2019

The 15th Transgenic Technology (TT) Meeting of the International Society for Transgenic Technologies (ISTT) was held for the first time in Japan in April of 2019 (TT2019). Delegates from around the world, including researchers, technicians and trainees, spent an exciting 4 days, engaging in scientific and technical discussions, information sharing and networking. In the era of genome editing, CRISPR technologies prevailed as popular subjects of discussion throughout the meeting on topics ranging from their applications in the mouse and growing number of other research and industrial animal species, technical challenges in the production of genome‐edited animals, to ethical considerations in biomedical research. In particular, impressive progress was reported on the use of CRISPR technologies in nonconventional animal models and large mammalian species in biomedical and industrial settings, indicating areas of expanding frontiers in animal transgenesis. Amid growing excitement with genome editing technologies, reports on conventional genetic engineering approaches and reproductive biology techniques demonstrated that these techniques remain essential to meet the demanding needs of generating complex genome modifications, complementing genome editing approaches. TT2019 was a great success, concluding with a widely shared appreciation of the current field and hints for future directions of animal transgenesis.
Missiological Framework in Africa
Authors: Isaak Paul John
Published: November 2019

This article has three parts. First, it deals with the understanding of mission in the context of Namibia. Second, it offers a profile of African spirituality and its politico‐socio‐economic implications, or with the missionary orthopraxis, in light of the African parable of the awakening giant. And third, it focuses on the African missional church and its missionary praxis. The paper argues that the triune God creates the church and sustains it through the gifts of word and sacrament by the power of the Spirit. Such a missional church understands its participation in God's mission (missio Dei) as contextual by addressing faithfully the challenges in a comprehensive and holistic way.
The Apostolic Faith Mission
Authors: Chikane Frank
Published: November 2019

The Apostolic Faith Mission (AFM) is a classical Pentecostal church born in May 1908, influenced by the April 1906 Azusa Street Revival in Los Angeles. It was also born two years before the Edinburgh World Missionary Conference. Between then and now, the AFM followed a lone mission and evangelism journey outside the World Missionary conferences and the conferences on World Mission and Evangelism. Although the AFM grew from South Africa to six continents, its growth was encumbered by racist and colonial perspectives of mission and evangelism. Its first wave of missions was led by Indigenous South Africans at the Revival in Doornfontein and those from the neighbouring countries who worked in mines in South Africa. The second wave included organized missions by white South Africans, who unfortunately had to pull back from Southern African countries because of intensified struggles for liberation. The third wave was by local congregations that formed hubs for missions to specific countries (India and Pakistan). The fourth wave was by Zimbabweans who left their country because of difficult economic conditions. The isolation of the black churches in South Africa based on the influence of apartheid policies allowed black members to develop their own local ecumenical perspectives, which enabled them to have a broader understanding of mission and evangelism. This helped the church to move into the ecumenical world following the unity of the church.
Local impedance guides catheter ablation in patients with ventricular tachycardia
Authors: Münkler Paula , Gunawardene Melanie A. , Jungen Christiane , Klatt Niklas , Schwarzl Jana M. , Akbulak Ruken Ö. , Dinshaw Leon , Hartmann Jens , Jularic Mario , Kahle Ann‐Kathrin , Riedel René , Merbold Lydia , Eickholt Christian , Willems Stephan , Meyer Christian
Published: November 2019

Aims

Catheter contact and local tissue characteristics are relevant information for successful radiofrequency current (RFC)‐ablation. Local impedance (LI) has been shown to reflect tissue characteristics and lesion formation during RFC‐ablation. Using a novel ablation catheter incorporating three mini‐electrodes, we investigated LI in relation to generator impedance (GI) in patients with ventricular tachycardia (VT) and its applicability as an indicator of effective RFC‐ablation.

Methods and Results

Baseline impedance, Δimpedance during ablation and drop rate (Δimpedance/time) were analyzed for 625 RFC‐applications in 28 patients with recurrent VT undergoing RFC‐ablation. LI was lower in scarred (87.0 Ω [79.0‐95.0]) compared to healthy myocardium (97.5 Ω ([82.75‐111.50]; P = .03) while GI did not differ between scarred and healthy myocardium. ΔLI was higher (18 Ω [9.4‐26.0]) for VT‐terminating as compared to non‐terminating RFC‐ablation (ΔLI 13 Ω [8.85‐18.0]; P = .03), but did not differ for ΔGI between terminating vs nonterminating RFC‐ablation. Correspondingly, LI drop rate was higher for RFC‐ablation terminating the VT compared with RFC‐ablation not terminating the VT (0.63 Ω/s [0.52‐0.76] vs 0.32 Ω [0.20‐0.58]; P = .008) while there was no difference for GI drop rate. ΔLI was higher in patients with nonischemic cardiomyopathy vs patients with ischemic cardiomyopathy (16 Ω [11.0‐20.0] vs 11.0 Ω [7.85‐17.00]; P = .003).

Conclusion

Our findings suggest that LI is a sensitive parameter to guide RFC‐ablation in patients with VT. LI indicates differences in tissue characteristics and generally is higher in patients with nonischemic cardiomyopathy. Hence, the etiology of the underlying cardiomyopathy needs to be considered when adopting LI for monitoring catheter ablation of VT.
The range of atlanto‐occipital joint motion in cetaceans reflects their feeding behavior
Authors: Okamura Taro , Fujiwara Shin‐ichi
Published: November 2019

The cetaceans display a wide variety of lifestyles, especially with regard to their feeding behavior. However, the evolutionary process of the feeding behavior in cetaceans is still poorly understood, in part because reconstructing the feeding behavior of extinct taxa remains difficult. In cetaceans, cranium mobility relative to the trunk largely depends on the range of motion permitted by the atlanto‐occipital joint, given the lack of flexibility of the cervical series. In this study, we examined 56 extant cetacean skeletal specimens from 30 species in 25 genera and nine families in order to investigate the relationships between anatomical traits and feeding behavior. Our results suggest that the range of dorso‐ventral motion allowed by the atlanto‐occipital joint (ROM) depends on prey habitat and the feeding technique of cetaceans. Cetaceans feeding on benthic/demersal prey had a relatively large ROM compared with those feeding on pelagic prey. In addition, ROM was largest in raptorial feeders, intermediate in suction feeders, and smallest in ram‐filter feeders. Among raptorial feeders, ROM tended to be larger in taxa that facultatively tear off the prey's flesh compared with taxa that swallow their prey whole. Therefore, we conclude that ROM is a powerful tool to reliably reconstruct the feeding behavior of extinct cetacean taxa.
Assessing the fate of recombinant plant DNA in rabbit’s tissues fed genetically modified cotton
Authors: Shahid Ahmad Ali , Salisu Ibrahim Bala , Yaqoob Amina , Rao Abdul Qayyum , Ullah Inayat , husnain Tayyab
Published: November 2019

Various feeding studies have been conducted with the different species of animals to evaluate the possible transfer of transgenic DNA (tDNA) from genetically modified (GM) feed into the animal tissues. However, the conclusions drawn from most of such studies are sometimes controversial. Thus, in the present study, an attempt has been made to evaluate the fate of tDNA in rabbits raised on GM cotton‐based diet through PCR analysis of the DNA extracted specifically from blood, liver, kidney, heart and intestine (jejunum). A total of 48 rabbits were fed a mixed diet consisting variable proportions of transgenic cottonseeds meal (i.e. 0% w/w, 20% w/w, 30% w/w and 40% w/w) for 180 days. The presence of transgenic DNA fragments (Cry1Ac, Cry2A and CP4 EPSPS) or plant endogenous gene (Sad1) was traced in those specific tissues and organs. The presence of β‐actin (ACTB) was also monitored as an internal control. Neither the transgenic fragments (459 bp of Cry1Ac gene, 167 bp of Cry2A gene and111 bp of CP4 EPSPS gene) nor cotton endogenous reference gene (155 bp of Sad1) could be detected in any of the DNA samples extracted from the rabbit's tissues in both control and transgenic groups. However, 155 bp fragment of the rabbit's reference gene (ACTB) was recovered in all the DNA samples extracted from rabbit tissues. The results obtained from this study revealed that both plant endogenous and transgenic DNA fragments have same fate in rabbit's tissues and were efficiently degraded in the gastrointestinal tract (GIT).
Characterization of weeds and rotational crops as alternative hosts of Spongospora subterranea, the causal agent of powdery scab in Israel
Authors: Tsror (Lahkim) L. , Shapira R. , Erlich O. , Hazanovsky M. , Lebiush S.
Published: November 2019

Alternative hosts of Spongospora subterranea may allow multiplication and survival of the pathogen over time; thus, host range is important from an epidemiological aspect. Weeds and rotational crops, such as wheat and barley, were sampled from potato fields with a history of powdery scab (PS) and examined for the presence of S. subterranea by root staining followed by microscopic observations and by qPCR analysis after DNA extraction. The pathogen was detected in plants of 16 weed species from eight families and in volunteer plants of potato and wheat. The ability of the pathogen to infect weeds and rotational crops was further examined by artificial inoculations with sporosori in pot experiments. Successful inoculations occurred with 13 weed species from eight families and with 12 rotational crops from five families. The findings of this study indicate a wide host range in Israel; the families Malvaceae and Zygophyllaceae and the following species are reported for the first time as S. subterranea hosts: Solanum elaeagnifolium, Triticum aestivum, Cynodon dactylon, Phalaris paradoxa, Phalaris minor, Setaria verticillata, Rostaria cristata, Sinapis nigra, Arachis hypogaea, Medicago sativa, Astragalus hauraensis, Amaranthus albus, Chenopodium murale, Chenopodium opulifolium, Salsola soda, Malva nicaeensis, Chrysanthemum segetum, Verbesina encelioides, Ammi majus and Tribulus terrestris. Controlling weeds and avoiding the relevant rotational crops observed to be S. subterranea‐positive and thus potential hosts, should be taken into consideration in the management of PS, to reduce pathogen inoculum build‐up.
Effects of L‐carnitine on the erythrocytes of stored human blood
Authors: Ravikumar Soumya , Prabhu Srinivasa , Vani Rajashekaraiah
Published: November 2019

Objectives

This study aimed to assess the effects of L‐carnitine on oxidative stress in human erythrocytes during storage.

Background

Using antioxidants as components of blood storage solutions may combat the effects of storage‐induced oxidative stress on erythrocytes.

Methods

Blood from male adults was stored at 4 °C for 55 days in citrate phosphate dextrose adenine solution, without L‐carnitine (Control) and with L‐carnitine as an additive (at concentrations of 10, 30 and 60 mM – Experiments). Every fifth day, erythrocyte markers (morphology, count, haemoglobin, haemolysis and osmotic fragility), antioxidant defences (antioxidant enzymes and total antioxidant capacity) and oxidative stress markers (superoxides, lipid peroxidation and protein oxidation products) were analysed.

Results

Oxidative damage was observed in controls (day 25 onwards) and in experiments (day 35 onwards). L‐carnitine (10 and 30 mM) protected erythrocytes from damage up to day 35 by maintaining haemoglobin and lipid peroxidation, assisting antioxidant enzymes and increasing antioxidant capacity by elevating sulfhydryls and ascorbic acid. L‐carnitine was beneficial in prolonging storage up to 55 days but could not prevent oxidative damage completely in terms of haemolysis and osmotic fragility.

Conclusions

L‐carnitine ameliorated oxidative stress, but combinations with other antioxidants may provide comprehensive protection to erythrocytes during storage.
Molecular genetics to genomics – historical overview of the ABO research
Authors: Yamamoto Fumiichiro
Published: November 2019

Next‐generation sequencing (NGS) enables the sequencing of thousands of genes, the exomes and even entire genomes in single experiments for $2000 or less. Genome sequencing reveals not only the exome but also the regulatory elements of transcription/translation. RNA sequencing determines which genes and spliced transcripts are expressed. We have been studying the blood group ABO genes, A and B glycosyltransferases (AT/BT), and A/B oligosaccharide antigens since we cloned human AT cDNAs in 1990. We have applied diverse scientific disciplines including genetics, biochemistry, enzymology and glycobiology to those studies and demonstrated the central dogma of ABO: A/B alleles at the ABO genetic locus encode AT/BT, which synthesize A/B antigens, respectively. We identified 4 amino acid substitutions between AT and BT and inactivating mutations in O alleles, elucidating the allelic basis of ABO. We became the first who succeeded in genotyping the ABO locus, discriminating AA/AO genotypes, as well as BB/BO, which was impossible by the immunological approach. We have also demonstrated mutations in several subgroup alleles and cis‐AB and B(A) alleles. Taking advantage of big data recently generated on genome sequences and associated information deposited in public databases, we expanded our research from humans to other organisms, as well as from ATs/BTs and ABO genes to evolutionarily related α1,3‐Gal(NAc) transferases and their genes. Combining phylogenetic analyses with functional assays we developed, we have successfully scaled up our research to the genomic level, deciphering the molecular mechanisms responsible for important biological phenomena associated with ABO.
A Literature Review of Empirical Research on Trade of Cultural Goods
Authors: Wang Yanfen
Published: November 2019

UNESCO defines cultural goods as consumer products that spread ideas, symbols, and lifestyles. Cultural goods provide information and entertainment, which in turn form group identity and influence cultural behavior. The low energy dissipation, high added value and the property of value transmission of the cultural industry have made the cultural goods' status in the global trade higher annually. Meanwhile, the contribution made by cultural goods trade to the national economy has become increasingly prominent. This article provides accessible research directions and path for the follow-up study of Chinese cultural goods trade by reviewing the existing empirical research on the trade of cultural goods.
Lumbar Spine Response of Computational Finite Element Models in Multidirectional Spaceflight Landing Conditions
Authors: Ye Xin , Jones Derek A. , Gaewsky James P. , Koya Bharath , McNamara Kyle P. , Saffarzadeh Mona , Putnam Jacob B. , Somers Jeffrey T. , Gayzik F. Scott , Stitzel Joel D. , Weaver Ashley A.
Published: November 2019

The goals of this study are to compare the lumbar spine response variance between the hybrid III, test device for human occupant restraint (THOR), and global human body models consortium simplified 50th percentile (GHBMC M50-OS) finite element models and evaluate the sensitivity of lumbar spine injury metrics to multidirectional acceleration pulses for spaceflight landing conditions. The hybrid III, THOR, and GHBMC models were positioned in a baseline posture within a generic seat with side guards and a five-point restraint system. Thirteen boundary conditions, which were categorized as loading condition variables and environmental variables, were included in the parametric study using a Latin hypercube design of experiments. Each of the three models underwent 455 simulations for a total of 1365 simulations. The hybrid III and THOR models exhibited similar lumbar compression forces. The average lumbar compression force was 45% higher for hybrid III (2.2 ± 1.5 kN) and 51% higher for THOR (2.0 ± 1.6 kN) compared to GHBMC (1.3 ± 0.9 kN). Compared to hybrid III, THOR sustained an average 64% higher lumbar flexion moment and an average 436% higher lumbar extension moment. The GHBMC model sustained much lower bending moments compared to hybrid III and THOR. Regressions revealed that lumbar spine responses were more sensitive to loading condition variables than environmental variables across all models. This study quantified the intermodel lumbar spine response variations and sensitivity between hybrid III, THOR, and GHBMC. Results improve the understanding of lumbar spine response in spaceflight landings.
Top Israeli immunologist's views on vaccines trigger furor
Authors: Kupferschmidt Kai
Published: November 2019

Yehuda Shoenfeld has espoused ideas popular among vaccine skeptics and spoken at their meetings.
NIH administrator resigned after sexual misconduct probe
Authors: Wadman Meredith
Published: November 2019

National Institute on Drug Abuse silent on reasons for recent departure of scientific director Antonello Bonci.
The Church, intensive kinship, and global psychological variation
Authors: Schulz Jonathan F. , Bahrami-Rad Duman , Beauchamp Jonathan P. , Henrich Joseph
Published: November 2019

Cultural evolution

There is substantial variation in psychological attributes across cultures. Schulz
et al.
examined whether the spread of Catholicism in Europe generated much of this variation (see the Perspective by Gelfand). In particular, they focus on how the Church broke down extended kin-based institutions and encouraged a nuclear family structure. To do this, the authors developed measures of historical Church exposure and kin-based institutions across populations. These measures accounted for individual differences in 20 psychological outcomes collected in prior studies.

Science
, this issue p.
eaau5141
; see also p.
686
Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function
Authors: de Morree Antoine , Klein Julian D. D. , Gan Qiang , Farup Jean , Urtasun Andoni , Kanugovi Abhijnya , Bilen Biter , van Velthoven Cindy T. J. , Quarta Marco , Rando Thomas A.
Published: November 2019

Skeletal muscle during homeostasis

Muscle stem cells function in the regeneration of skeletal muscle after injury, but their role in homeostasis is unclear. De Morree
et al.
show that, in the absence of injury, stem cells in different muscles have different rates of spontaneous activation and fusion, which depend on the level of Pax3 protein (see the Perspective by Xi and Pyle). Regulation of Pax3 protein occurs posttranscriptionally through the small nucleolar RNA U1 and microRNA miR206. This work explains how muscle stem cells are maintained under normal conditions and shows that homeostatic muscle stem cell activation varies in different muscle groups.

Science
, this issue p.
734
; see also p.
684
Direct observation of changing NO

x

lifetime in North American cities
Authors: Laughner Joshua L. , Cohen Ronald C.
Published: November 2019

A shifting lifetime for NO

x

Nitrogen oxides (NO

x

) have a central role in controlling air quality, so designing effective strategies to combat air pollution, especially by ozone and particulate matter, depends on knowing their atmospheric abundances. Those abundances depend not only on NO

x

production rates but also on their lifetimes. Laughner and Cohen report that NO

x

lifetimes can be measured directly from satellite observations of nitrogen dioxide. They used data on 49 North American cities to show how NO

x

lifetimes there changed between 2005 and 2014. Accounting for this change in lifetime should help to reconcile conflicting trends between bottom-up and top-down emissions estimates.

Science
, this issue p.
723
Stereosequenced crystalline polyhydroxyalkanoates from diastereomeric monomer mixtures
Authors: Tang Xiaoyan , Westlie Andrea H. , Watson Eli M. , Chen Eugene Y.-X.
Published: November 2019

Toward less brittle degradable plastic

Bacteria produce a class of polyesters, termed polyhydroxyalkanoates, that are particularly appealing on account of how easily they undergo biodegradation. Unfortunately, these polymers also tend to be overly brittle for many applications. Tang
et al.
report that a molecular lanthanide catalyst can sequentially polymerize chiral and then achiral diastereomers to form polyhydroxyalkanoate varieties that are substantially more ductile. The catalyst selectively produces these copolymers directly from diastereomeric mixtures of monomers, obviating the need for a wasteful separation process ahead of time.

Science
, this issue p.
754
Explaining the puzzle of human diversity
Authors: Gelfand Michele J.
Published: November 2019

Centuries of Church exposure promote more individualistic and less conforming psychology
Formation of Escherichia coli O157:H7 Persister Cells in the Lettuce Phyllosphere and Application of Differential Equation Models To Predict Their Prevalence on Lettuce Plants in the Field
Authors: Munther Daniel S. , Carter Michelle Q. , Aldric Claude V. , Ivanek Renata , Brandl Maria T.
Published: November 2019

Despite causing outbreaks of foodborne illness linked to lettuce consumption,
E. coli
O157:H7 (EcO157) declines rapidly when applied onto plants in the field, and few cells survive over prolonged periods of time. We hypothesized that these cells are persisters, which are in a dormant state and which arise naturally in bacterial populations. When lettuce plants were inoculated with EcO157 in the laboratory, the greatest persister fraction in the population was observed during population decline on dry leaf surfaces. Using mathematical modeling, we calculated the switch rate from an EcO157 normal to persister cell on dry lettuce plants based on our laboratory data. The model was applied to published studies in which lettuce was inoculated with EcO157 in the field, and switch rates similar to those obtained in our study were obtained. Our results contribute important new knowledge about the physiology of this virulent pathogen on plants to be considered to enhance produce safety.
Early transient intraocular pressure spike after cataract surgery in highly myopic cataract eyes and associated risk factors
Authors: Zhu Xiangjia , Qi Jiao , He Wenwen , Zhang Shaohua , Zhang Keke , Lu Qiang , Lu Yi
Published: November 2019

Purpose

To investigate the incidence of the early transient intraocular pressure (IOP) spike after cataract surgery in eyes with highly myopic cataract (HMC) and associated risk factors.

Methods

Consecutive patients treated with phacoemulsification were recruited. IOP was measured before and 1 day, 3 days, 1 week and 3 months after surgery. Axial length (AL) and anterior chamber depth (ACD) were recorded, and optic disc tilt, rotation and beta-zone peripapillary atrophy (β-PPA) were measured from fundus photographs taken 1 week after surgery. Backward stepwise multiple linear regression was used to investigate the risk factors for early transient IOP spike in the HMC group.

Results

Finally, 94 eyes of 94 HMC patients and 67 eyes of 67 age-related cataract (ARC) controls were included in analysis. The incidence of early IOP spike was 10% in the ARC group and 28% in the HMC group (OR=3.277, p<0.05) at 1 day after surgery. In the HMC group with IOP spikes, more males were seen and affected eyes showed longer AL, shallower ACD, greater optic disc tilt, and larger β-PPA than those without (all p<0.05). Multivariate analysis showed that sex, AL, ACD, and area of β-PPA were significantly associated with an early transient IOP spike in HMC eyes (all p<0.05).

Conclusions

Highly myopic eyes are more susceptible to early transient IOP spike after cataract surgery, and male sex, longer AL, shallower ACD, and greater β-PPA are associated risk factors.

Clinical trial registration number

NCT02182921.
Quadriceps tendon grafts does not cause patients to have inferior subjective outcome after anterior cruciate ligament (ACL) reconstruction than do hamstring grafts: a 2-year prospective randomised controlled trial
Authors: Lind Martin , Nielsen Torsten Grønbech , Soerensen Ole Gade , Mygind-Klavsen Bjarne , Faunø Peter
Published: November 2019

Objective

We performed a randomised controlled trial (RCT) in patients undergoing ACL reconstruction (ACLR) using either quadriceps tendon graft (QT) or semitendinosus/gracilis hamstring (STG) graft. We compared subjective outcome (primary outcome) and knee stability, donor site morbidity and function (secondary outcomes).

Methods

From 2013 to 2015, we included 99 adults with isolated ACL injuries in the RCT. Fifty patients were randomised to QT grafts and 49 to STG grafts and followed for 2 years. Patient evaluated outcomes were performed by subjective International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, Kujala and Tegner activity scores. Knee laxity was measured with a KT-1000 arthrometer. Donor site morbidity was evaluated by the ‘donor site-related functional problems following ACLR score’. One-leg hop test tested limp strength symmetry.

Results

At 2-year follow-up, there was no difference between the two graft groups regarding subjective patient outcome, knee stability and reoperations. Also, at 2 years, donor site symptoms were present in 27% of patients in the QT group and 50% of patients in the STG group. The donor site morbidity score was 14 and 22 for the QT and STG, respectively. Hop test demonstrated lower limp symmetry for QT graft than STG graft of 91% and 97% respectively.

Conclusion

QT graft for ACLR did not result in inferior subjective outcome compared with STG graft. However, QT graft was associated with lower donor site morbidity than STG grafts but resulted in more quadriceps muscle strength deficiency than hamstring grafts. Both graft types had similar knee stability outcome.

Trial registration number

NCT02173483.
Routine use of progesterone does not prevent miscarriage
Authors: Cook Rob , Thomas Vaughan , Taft Rachel
Published: November 2019

The study

Coomarasamy A, Devall AJ, Cheed V, et al. A randomised trial of progesterone in women with bleeding in early pregnancy N Engl J Med 2019;380:1815-24.

This project was funded by the NIHR Health Technology Assessment Programme (project number 12/167/26).

To read the full NIHR Signal, go to https://discover.dc.nihr.ac.uk/content/signal-000792/miscarriage-not-prevented-by-routine-use-of-progesterone
Homozygous mutations in REC114 cause female infertility characterised by multiple pronuclei formation and early embryonic arrest
Authors: Wang Wenjing , Dong Jie , Chen Biaobang , Du Jing , Kuang Yanping , Sun Xiaoxi , Fu Jing , Li Bin , Mu Jian , Zhang Zhihua , Zhou Zhou , Lin Zhao , Wu Ling , Yan Zheng , Mao Xiaoyan , Li Qiaoli , He Lin , Wang Lei , Sang Qing
Published: November 2019

Background

Abnormal pronuclear formation during fertilisation and subsequent early embryonic arrest results in female infertility. In recent years, with the prevalence of assisted reproductive technology, a few genes have been identified that are involved in female infertility caused by abnormalities in oocyte development, fertilisation and embryonic development. However, the genetic factors responsible for multiple pronuclei formation during fertilisation and early embryonic arrest remain largely unknown.

Objective

We aim to identify genetic factors responsible for multiple pronuclei formation during fertilisation or early embryonic arrest.

Methods

Whole-exome sequencing was performed in a cohort of 580 patients with abnormal fertilisation and early embryonic arrest. Effects of mutations were investigated in HEK293T cells by western blotting and immunoprecipitation, as well as minigene assay.

Results

We identified a novel homozygous missense mutation (c.397T>G, p.C133G) and a novel homozygous donor splice-site mutation (c.546+5G>A) in the meiotic gene REC114. REC114 is involved in the formation of double strand breaks (DSBs), which initiate homologous chromosome recombination. We demonstrated that the splice-site mutation affected the normal alternative splicing of REC114, while the missense mutation reduced the protein level of REC114 in vitro and resulted in the loss of its function to protect its partner protein MEI4 from degradation.

Conclusions

Our study has identified mutations in REC114 responsible for human multiple pronuclei formation and early embryonic arrest, and these findings expand our knowledge of genetic factors that are responsible for normal human female meiosis and fertility.
Gestation, equality and freedom: ectogenesis as a political perspective
Authors: Cavaliere Giulia
Published: November 2019

The benefits of full ectogenesis, that is, the gestation of human fetuses outside the maternal womb, for women ground many contemporary authors’ arguments on the ethical desirability of this practice. In this paper, I present and assess two sets of arguments advanced in favour of ectogenesis: arguments stressing ectogenesis’ equality-promoting potential and arguments stressing its freedom-promoting potential. I argue that although successfully grounding a positive case for ectogenesis, these arguments have limitations in terms of their reach and scope. Concerning their limited reach, I contend that ectogenesis will likely benefit a small subset of women and, arguably, not the group who most need to achieve equality and freedom. Concerning their limited scope, I contend that these defences do not pay sufficient attention to the context in which ectogenesis would be developed and that, as a result, they risk leaving the status quo unchanged. After providing examples of these limitations, I move to my proposal concerning the role of ectogenesis in promoting women’s equality and freedom. This proposal builds on Silvia Federici’s, Mariarosa Dalla Costa’s and Selma James’ readings of the international feminist campaign ‘Wages for Housework’. It maintains that the political perspective and provocation that ectogenesis can advance should be considered and defended.