bluuebunny/crossref_metadata_2025 huggingface dataset:
Hindlimb Somatosensory Information Influences Trunk Sensory and Motor Cortices to Support Trunk Stabilization
Authors: Nandakumar Bharadwaj , Blumenthal Gary H , Pauzin Francois Philippe , Moxon Karen A
Published: June 2021

Sensorimotor integration in the trunk system is poorly understood despite its importance for functional recovery after neurological injury. To address this, a series of mapping studies were performed in the rat. First, the receptive fields (RFs) of cells recorded from thoracic dorsal root ganglia were identified. Second, the RFs of cells recorded from trunk primary sensory cortex (S1) were used to assess the extent and internal organization of trunk S1. Finally, the trunk motor cortex (M1) was mapped using intracortical microstimulation to assess coactivation of trunk muscles with hindlimb and forelimb muscles, and integration with S1. Projections from trunk S1 to trunk M1 were not anatomically organized, with relatively weak sensorimotor integration between trunk S1 and M1 compared to extensive integration between hindlimb S1/M1 and trunk M1. Assessment of response latency and anatomical tracing suggest that trunk M1 is abundantly guided by hindlimb somatosensory information that is derived primarily from the thalamus. Finally, neural recordings from awake animals during unexpected postural perturbations support sensorimotor integration between hindlimb S1 and trunk M1, providing insight into the role of the trunk system in postural control that is useful when studying recovery after injury.
Predisposing Variations in Fear-Related Brain Networks Prospectively Predict Fearful Feelings during the 2019 Coronavirus (COVID-19) Pandemic
Authors: Feng Pan , Chen Zhiyi , Becker Benjamin , Liu Xiqin , Zhou Feng , He Qinghua , Qiu Jiang , Lei Xu , Chen Hong , Feng Tingyong
Published: June 2021

The novel coronavirus (COVID-19) pandemic has led to a surge in mental distress and fear-related disorders, including posttraumatic stress disorder (PTSD). Fear-related disorders are characterized by dysregulations in fear and the associated neural pathways. In the present study, we examined whether individual variations in the fear neural connectome can predict fear-related symptoms during the COVID-19 pandemic. Using machine learning algorithms and back-propagation artificial neural network (BP-ANN) deep learning algorithms, we demonstrated that the intrinsic neural connectome before the COVID-19 pandemic could predict who would develop high fear-related symptoms at the peak of the COVID-19 pandemic in China (Accuracy rate = 75.00%, Sensitivity rate = 65.83%, Specificity rate = 84.17%). More importantly, prediction models could accurately predict the level of fear-related symptoms during the COVID-19 pandemic by using the prepandemic connectome state, in which the functional connectivity of lvmPFC (left ventromedial prefrontal cortex)—rdlPFC (right dorsolateral), rdACC (right dorsal anterior cingulate cortex)—left insula, lAMY (left amygdala)—lHip (left hippocampus) and lAMY—lsgACC (left subgenual cingulate cortex) was contributed to the robust prediction. The current study capitalized on prepandemic data of the neural connectome of fear to predict participants who would develop high fear-related symptoms in COVID-19 pandemic, suggesting that individual variations in the intrinsic organization of the fear circuits represent a neurofunctional marker that renders subjects vulnerable to experience high levels of fear during the COVID-19 pandemic.
Synapses from the Motor Cortex and a High-Order Thalamic Nucleus are Spatially Clustered in Proximity to Each Other in the Distal Tuft Dendrites of Mouse Somatosensory Cortex
Authors: Kim Nari , Bahn Sangkyu , Choi Joon Ho , Kim Jinseop S , Rah Jong-Cheol
Published: June 2021

The posterior medial nucleus of the thalamus (POm) and vibrissal primary motor cortex (vM1) convey essential information to the barrel cortex (S1BF) regarding whisker position and movement. Therefore, understanding the relative spatial relationship of these two inputs is a critical prerequisite for acquiring insights into how S1BF synthesizes information to interpret the location of an object. Using array tomography, we identified the locations of synapses from vM1 and POm on distal tuft dendrites of L5 pyramidal neurons where the two inputs are combined. Synapses from vM1 and POm did not show a significant branchlet preference and impinged on the same set of dendritic branchlets. Within dendritic branches, on the other hand, the two inputs formed robust spatial clusters of their own type. Furthermore, we also observed POm clusters in proximity to vM1 clusters. This work constitutes the first detailed description of the relative distribution of synapses from POm and vM1, which is crucial to elucidate the synaptic integration of whisker-based sensory information.
Factors Associated With Hearing Aid Use Among Medicare Beneficiaries
Authors: Assi Lama , Reed Nicholas S , Nieman Carrie L , Willink Amber
Published: June 2021

Background and Objectives

In the United States, up to two-thirds of older adults have hearing loss. Untreated hearing loss can have significant health outcomes, yet less than 20% of adults with hearing loss use hearing aids. In this study, we examined potential factors associated with hearing aid use, including detailed measures of health status, access to care, patient engagement, and technology use, in a nationally representative sample of Medicare beneficiaries.

Research Design and Methods

Cross-sectional study using the 2017 Medicare Current Beneficiary Survey. Participants with self-reported hearing loss were included. The primary outcome was hearing aid use. Factors potentially associated with hearing aid use included: sociodemographics, health determinants, access to care, patient activation, and technology access/use.

Results

Overall, 5,146 participants were included. Of them, 27% reported using hearing aids. In a multivariable logistic regression model, predisposing factors associated with greater odds of hearing aid use included older age, identifying as a man, identifying as White, having completed college, having 3 or more chronic conditions, having dementia, not having trouble seeing, not having limitations in activities of daily living, having moderate relative to low information-seeking scores, and having a personal computer at home (range of odds ratios [ORs]: 1.22–4.46). Enabling factors associated with greater odds of hearing aid use included higher income, living alone relative to living with family members other than a spouse, and having a usual source of care (range of ORs: 1.43–1.54).

Discussion and Implications

In addition to addressing previously identified factors associated with hearing aid use, improving access to health care, technology, and information about hearing aids may improve the uptake of hearing aids. These findings help further inform our understanding on how to address low treatment levels of hearing loss in the community by identifying new populations to target and potentially modifiable risk factors for hearing aid use.
Preparation and biological activities of anti-HER2 monoclonal antibodies with multibranched complex-typeN-glycans
Authors: Takashima Shou , Kurogochi Masaki , Tsukimura Wataru , Mori Masako , Osumi Kenji , Sugawara Shu-ichi , Amano Junko , Mizuno Mamoru , Takada Yoshio , Matsuda Akio
Published: June 2021

Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region. Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody’s effector functions, such as antibody-dependent cellular cytotoxicity. While the N-glycan structures attached to the IgG-Fc region are generally heterogenous, IgGs engineered to be homogenously glycosylated with functional N-glycans may improve the efficacy of antibodies. The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found. However, IgGs with tri-antennary complex-type N-glycans have been generated using the N-glycan remodeling technique, suggesting that more branched N-glycans might be artificially attached. At present, little is known about the properties of these IgGs. In this study, IgGs with multibranched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases. Among the IgGs produced by these methods, the largest N-glycan attached was a bisecting N-acetylglucosamine containing a sialylated penta-antennary structure. Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N-glycans.
Growth performance and gut health of Escherichia coli–challenged weaned pigs fed canola meal-containing diet
Authors: Hong Jinsu , Ariyibi Samuel , Antony Linto , Scaria Joy , Dilberger-Lawson Steven , Francis David , Woyengo Tofuko Awori
Published: June 2021

An experiment was conducted to evaluate the effects of including canola meal (CM) in diets for weaning pigs challenged with a F18 strain of Escherichia coli on growth performance and gut health. A total of 36 individually housed weaned pigs (initial body weight [BW] = 6.22 kg) were randomly allotted to one of the three diets (12 pigs/diet). The three diets were corn–soybean meal (SBM)-based basal diet (control diet) and the basal diet with 0.3% zinc oxide, 0.2% chlortetracycline, and 0.2% tiamulin (antibiotic diet) or with 20% CM diet. The diets were fed in two phases: Phase 1: days 0 to 7 and Phase 2: days 7 to 20. All pigs were given an oral dose of 2 × 109 CFU of F18 strain of E. coli on day 7. Fecal score was assessed daily throughout the trial. Dietary antibiotics increased (P < 0.05) overall average daily gain (ADG) and average daily feed intake (ADFI) compared by 48% and 47%, respectively. Dietary CM increased (P < 0.05) overall ADG and ADFI by 22% and 23%, respectively; but the ADG and ADFI values for CM-containing diet did not reach those for the antibiotics-containing diet. Dietary antibiotics reduced (P < 0.05) fecal score; however, dietary CM unaffected fecal score. Dietary antibiotics decreased (P < 0.05) liver weight per unit live BW by 16% at day 20, whereas dietary CM did not affect liver weight per unit live BW (29.2 vs. 28.6). Also, dietary antibiotics increased (P < 0.05) serum triiodothyronine and tetraiodothyronine levels for day 14, whereas dietary CM did not affect the serum level of these hormones. Dietary antibiotics reduced (P < 0.05) the number white blood cells and neutrophils by 38% and 43% at day 20, respectively, whereas dietary CM tended to reduce (P = 0.09) the number white blood cells by 19% at day 20. The number white blood cells for CM diet tended to be greater (P < 0.10) than that for antibiotics diet. The dietary antibiotics decreased (P < 0.05) the concentration of individual volatile fatty acids and hence of total volatile fatty acid in cecum by 61% at day 20, whereas dietary CM decreased (P < 0.05) cecal butyric acid concentration by 61% and tended to reduce (P < 0.10) total volatile fatty acid concentration by 30% at day 20. In conclusion, the dietary inclusion of 20% CM improved ADG and tended to reduce white blood cell counts. Thus, inclusion of CM in antibiotics-free corn-SBM-based diets for weaned pigs that are challenged with F18 strain of E. coli can result in their improved performance partly through a reduction of the inflammatory response.
Labral reconstruction with polyurethane implant
Authors: Tey-Pons Marc , Capurro Bruno , Torres-Eguia Raúl , Marqués-López Fernando , Leon-García Alfonso , Marín-Peña Oliver
Published: June 2021

Surgical treatment of labral injuries has shifted from debridement to preservation over the past decades. Primary repair and secondary augmentation or reconstruction techniques are aimed at restoring the labral seal and preserving or improving contact mechanics. Currently, the standard of care for non-repairable tears favours the use of auto- or allografts. As an alternative, we present our initial experience using a synthetic, off-the-shelf polyurethane scaffold for augmentation and reconstruction of segmental labral tissue loss or irreparable labral damage. Three patients aged 37–44 (two male, one female) with femoroacetabular impingement without associated dysplasia (Wiberg > 25°) or osteoarthritis (Tönnis <2) were included in this series. Labral reconstruction (one case) and augmentation (two cases) were performed using a synthetic polyurethane scaffold developed for meniscal substitution (Actifit®, Orteq Ltd, London, UK) and adapted to the hip. Clinical results were analysed with patient-reported outcomes (PROMs) using non-arthritic hip score (NAHS) and daily live activities hip outcome score (DLA HOS) and magnetic resonance images (MRI) at 2- and 4-year follow-up. Clinically improvement was seen in all PROMs at 4 years. The NAHS scores improved from 57.7 to 82.3 (50.9% improvement) and HOS from 59 to 79.3 (35.3% improvement). Last follow-up MRIs confirmed the presence of the scaffold; however, the scaffold signal was still hyperintense compared to native labrum. There was no shrinkage in any scaffold and no progression to hip osteoarthritis seen. Reconstruction or augmentation of segmental labral defects with a polyurethane scaffold may be an effective procedure. At 4 years after implantation, our small cases series resulted in improved hip joint function, reduced pain and scaffold preservation on follow-up imaging.
Sulfoquinovosyl diacylglycerol synthase 1 impairs glycolipid accumulation and photosynthesis in phosphate-deprived rice
Authors: Sun Yafei , Song Ke , Liu Lu , Sun Lijuan , Qin Qin , Jiang Tingting , Zhou Bin , Zhu Caihua , Xu Guohua , Sun Shubin , Xue Yong
Published: June 2021

Phosphate (Pi)-starved crops utilize phospholipids as a source for internal Pi supply by replacing non-phosphorus glycolipids. In rice, sulfoquinovosyl diacylglycerol synthase 1 (OsSQD1) functions as a key enzyme in the first step to catalyze sulfoquinovosyldiacylglycerol (SQDG) formation. Here we study differential expression of OsSQD1 in response to Pi, nitrogen, potassium, and iron-deficiencies in rice. Electrophoretic mobility shift assay suggested that OsSQD1 is regulated by OsPHR2 (Phosphate Starvation Response2), a MYB (v-myb avian myeloblastosis viral oncogene homolog) domain-containing transcription factor. The concentrations of different lipid species in ossqd1 knockout mutant demonstrated that OsSQD1 silencing increased the phospholipid content and altered fatty acid composition under Pi-deficiency. Moreover, OsSQD1 silencing reduces glycolipid accumulation under Pi-deficiency, and triggered the saturation of fatty acids in phospholipids and glycolipids treated with different Pi regimes. Relative amounts of transcripts related to phospholipid degradation and glycolipid synthesis were assessed to explore the mechanism by which OsSQD1 exerts an effect on lipid homeostasis under P-deficiency. Furthermore, OsSQD1 silencing inhibited photosynthesis, especially under Pi-deficient conditions, by down-regulating glycolipids in rice shoots. Taken together, our study reveals that OsSQD1 plays a key role in lipid homeostasis, especially glycolipid accumulation under Pi-deficiency, which results in the inhibition of photosynthesis.
Introduction
Authors: d'Aspremont Jean
Published: June 2021

This chapter depicts the discursive splendour of customary international law, which is portrayed as a splendid mechanism by virtue of the sophisticated discursive performances it enables and demands. It introduces the success and plausibility of any argument about customary international law in international legal thought and practice that commonly hinge on a myriad of discursive performances. It also sheds light on the discursive splendour of a legal doctrine that is too often perceived as miserably simple, plain, or malfunctioning doctrine. The chapter provides an overview of the discursive performances of customary international law, which are construed as responses to the formal requirement of ascertaining the constitutive elements of customary international law. It elaborates how the customary international law provides international law with a law-creative process that is not dependent of the adoption of a formal written instrument.
The Custom-making Moment
Authors: d'Aspremont Jean
Published: June 2021

This chapter zeroes in on the postulation of a moment in the past where the social reality actually engendered the norm as the discursive performance that is required for customary international law to be grounded in social reality. It discusses the grounding of customary international law in a social reality captured through practice and opinio juris that can only be upheld if there was a moment in the past where the practice and opinio juris of states have coalesced in a way that generates customary international law. It also argues that the actual moment where social reality has engendered a customary norm is never established or traced but is always presupposed. The chapter points out that the moment customary international law is made is located neither in time nor in space. It elaborates how customary international law is presupposed to have been made through actors' behaviours at some given point in the past and in a given place.
Self-confirmation
Authors: d'Aspremont Jean
Published: June 2021

This chapter talks about the move into self-confirmation as one of the most central discursive performances witnessed in arguments about customary international law. It explains that self-confirmation refers to the fact that testing the customary character of a rule entails an identity-check whereby the 'outside' world is interrogated according to a predetermined standard. It also mentions ascertaining practice and opinio juris amounts to a process of verifying a pre-existing representation of practice and opinio juris that is postulated by the rule whose customary status is being tested, demonstrated, or contested. The chapter considers self-confirmation as a common feature of modern thinking. It elaborates on the concrete implications of the self-confirmation at the heart of any argument about the customary status of international legal rules.
A Feminist Appraisal of International Refugee Law
Authors: Anderson Adrienne , Foster Michelle
Published: June 2021

This chapter appraises the gendering of refugee law, examining both feminist scholarship on cases involving persecution of people for their non-conformity to stereotypical gender roles and wider questions related to refugee experiences. While there is an evident link between gender and sexual orientation/gender identity, it primarily focuses on the experiences of women. Due in large part to feminist advocacy and scholarship, the Refugee Convention now reflects gender concerns. However, the precise meaning and content of gender is arguably less understood, and the full implications of a gendered approach have not been implemented. Tracking both normative movement and physical/geographical movement of refugees, the chapter evaluates scholarship, policy, and law to assess whether refugee law has continued to interrogate and update its understanding of ‘gender’.
Regional Refugee Regimes
Authors: Arakaki Osamu , Song Lili
Published: June 2021

The fives States and eight jurisdictions in East Asia are mostly densely populated and homogeneous, but are diverse in term of their political and legal systems, economic development and positions in relation to refugee movements. The region currently does not have its own regional arrangement relating to refugee protection or human rights. This chapter examines and compares aspects of the refugee protection system in East Asian States, focusing on China, Japan and South Korea, all of which are a party to the Refugee Convention and Protocol. It provides a brief history of refugee laws in these States, critically evaluates legal and policy measures they have taken to implement the Convention and Protocol and looks at the roles of the judiciary and civil society in refugee protection in these States. In conclusion, it outlines the areas of convergence and diversity of refugee protection system in these States as well as the implication of international refugee law in East Asia.
The Sharing of Responsibilities for the International Protection of Refugees
Authors: Garlick Madeline
Published: June 2021

This chapter examines the principle and practice of responsibility-sharing amongst States, defined broadly as efforts to achieve a more equitable distribution of responsibilities to provide refugees with protection and solutions and of associated costs and benefits. It analyses the legal and conceptual underpinnings of the concept, its treatment in scholarship, and its increasing prominence in international declarations and discussions amongst States. The chapter also considers several initiatives at the international level, which have aimed to give it practical effect in contemporary refugee situations, including in Africa and the Americas, based on the Global Compact on Refugees. It further considers how this may provide a firmer normative and institutional basis for responsibility-sharing in the future.

There is increasing recognition that responsibility-sharing, involving more predictable, substantial, and systematic support to States hosting large refugee populations, is a necessary precondition to the continued effective functioning of the international protection system. The chapter maintains that, in addition to strengthened action by States, recognition is required of the role of other actors, including civil society and private entities, faith-based and other actors, as well as refugees themselves, whose engagement has potential further to strengthen responses to the needs of refugees, notably in large and protracted situations.
Extraterritorial Migration Control and Deterrence
Authors: Gammeltoft-Hansen Thomas , Tan Nikolas Feith
Published: June 2021

Extraterritorial migration control represents a fundamental challenge to refugees’ ability to access asylum. The right to seek asylum, pivotal to the international protection of refugees, almost always requires that an asylum seeker reach a State’s territory to access protection. This chapter charts the emergence and evolution of different forms of extraterritorial migration control over the past three decades which render this access to protection increasingly dangerous and elusive. Equally, the chapter shows that international refugee law has not remained static in this period. From dynamic developments in the interpretation of key tenets of refugee law to the wider turn to international human rights law and litigation, refugee lawyers have consistently challenged restrictive developments in State practice. However, legal responses to extraterritorial migration control cannot stop here. This chapter sketches out a topographical approach to accountability, cutting across different legal regimes, different levels of national, transnational, regional, and international law, and different jurisdictions in both the Global North and the Global South, to confront the challenges thrown up by contemporary extraterritorial migration control and deterrence.
The Digital Transformation of Refugee Governance
Authors: Sandvik Kristin Bergtora
Published: June 2021

This chapter evaluates four selected issues arising from the digital transformation of refugee protection, in order to explore how this transformation shapes and challenges refugee law. It focuses on the following domains: UNHCR’s 2015 Data Protection Policy, a concept (legal identity), a platform (databases), and legal-bureaucratic processes (refugee status determination and resettlement procedures). Digital transformation generates new risks, in part because it is premised on a duty of refugee visibility. The chapter argues that international refugee law, conceptually and in practice, appears to be moving towards an idea of ‘algorithmic protection’. First, digitization and the integration of new technology create risks and harms that can compromise existing legal rights and procedural guarantees but also threaten the integrity of refugee protection in new ways. Secondly, algorithmic protection is a useful concept because the digital transformation of refugee protection means that the duty of visibility and acquiescence to become a data subject has become a requirement for being registered as a refugee, receiving aid (eg biometric banking), and having one’s claim for a durable solution processed.
Reimagining Voluntary Repatriation
Authors: Zieck Marjoleine
Published: June 2021

The Statute of UNHCR charges the High Commissioner for Refugees with the task of pursuing durable solutions to the problem of refugees: voluntary repatriation, local integration, and resettlement. Voluntary repatriation is generally considered to be the preferred one. UNHCR takes it, in accordance with this assignment, to mean the return of refugees rather than former refugees, that is, those who lost their refugee status because the circumstances in connection with which they had been recognized as refugees have ceased to exist. In short, UNHCR’s point of departure is promoting and encouraging the return of those who are by definition unrepatriable with the argument that this timing allows it to extend protection and assistance to the refugees before they formally cease to be refugees. In practice – both that of UNHCR and States – this point of departure appears prone to compromising the rights of refugees. It is therefore questioned by means of taking recourse to the repatriation practice of UNHCR’s immediate predecessors. On the basis of past practice, an alternative understanding of voluntary repatriation is offered that does not involve the return of those who are entitled to protection in exile, safeguards their rights, and is nonetheless in accordance with the Statute of UNHCR and the obligations of States under the relevant instruments.
The Accountability of International Organizations in Refugee and Migration Law
Authors: Klabbers Jan
Published: June 2021

This chapter highlights the accountability of international organizations in refugee and migration law. It sets out the general responsibility regime as it applies to international organizations with special reference to refugee protection. Several international organizations are pertinent: most prominently UNHCR and the International Organization for Migration (IOM), but also the EU through Frontex, its European Agency for the Management of Operational Cooperation at the External Borders, and the UN Office of the High Commissioner for Human Rights. Refugee protection also involves several different settings, from the running of refugee camps and the guarding of borders to the handling of individual asylum applications. In general, the chapter demonstrates that responsibility is highly elusive.
Prevalence and Risk Factors for Musculoskeletal Back Injury Among U.S. Army Personnel
Authors: Gun Baris K , Banaag Amanda , Khan Munziba , Koehlmoos Tracey Perez
Published: June 2021

Introduction

Physical and medical readiness have emerged as a top priority in the army over the last decade. With this emphasis on deployment readiness, it is important to understand key risk factors attributed to common medical problems that arise in our soldiers, including low back pain. The purpose of this study is to elucidate demographic and lifestyle risk factors which would result in seeking medical care for musculoskeletal low back pain among active duty army personnel.

Materials and Methods

A cross-sectional retrospective study investigating all active duty soldiers between October 1, 2016 and September 30, 2018 was performed using the existing Military Health System Data Repository to retrospectively review administrative claims data. Our study queried 39 unique International Classification of Disease codes, 10th Revision codes for low back pain to determine a positive case. We compared those with and without back pain across all variables using a chi-square analysis in SAS. Multivariate logistic analysis was performed to adjust for confounding within any single proposed risk factor and the six other proposed risk factors.

Results

Six hundred fifty seven thousand and six thirty soldiers met inclusion criteria; 228,184 of whom had a medical encounter for low back pain (34.7%). All of the proposed risk factors included statistically significant unadjusted and adjusted odds ratios (ORs) with age conferring the greatest risk in soldiers aged 50–59 with an OR of 2.89 (2.73–3.05) compared to those aged 20–29. Obesity-adjusted OR was 1.77 (1.74–1.80) compared to those who were normal weight. Senior Enlisted status–adjusted OR was 1.34 (1.32–1.36). Females were 66% more likely to have low back pain compared to males with an OR of 1.66 (1.63–1.68).

Conclusion

Disease burden for low back pain tends to be high in the U.S. Army with 34.7% of service members experiencing low back pain. Older age, obesity, and being an enlisted, female service member are risk factors for these musculoskeletal injuries, which is in agreement with previously reported literature on the topic. To mitigate the burden of low back pain, policies and incentives to encourage healthy body mass index and lifestyle are needed. The results of this work inform future studies aimed at further delineating the risk factors found in this study.
Raw bovine milk as a reservoir of yeast with virulence factors and decreased susceptibility to antifungal agents
Authors: Moravkova Monika , Huvarova Veronika , Vlkova Hana , Kostovova Iveta , Bacova Romana
Published: June 2021

In recent years, increased rates of yeast infections in humans and animals have been recognized worldwide. Since animals may represent a source of yeast infections for humans, knowing the antifungal susceptibility profile of yeast isolates from milk and evaluating their pathogenic potential would be of great medical importance. Therefore, the aim of this survey was to study yeast diversity in milk samples, analyze the hemolytic and phospholipase activities of isolates and determine minimal inhibition concentration (MIC) for fluconazole, voriconazole and flucytosine. Out of 66 yeast isolates obtained from 910 individual raw milk samples from subclinically infected cows, 26 different yeast species were determined based on sequencing of the D1/D2 and ITS regions. Among them, Pichia kudriavzevii (formerly known as Candida krusei), Kluyveromyces marxianus (formerly known as Candida kefyr) and Debaryomyces hansenii (formerly known as Candida famata) were the most commonly identified. Hemolysin and/or phospholipase activity was observed in 66.7% of isolates. The elevated MIC for fluconazole was determined in 16 isolates from 11 species. The findings of this study demonstrate that yeast isolates from raw milk have the potential to express virulence attributes such as hemolysin and phospholipase, and additionally, some of these strains showed elevated MIC to fluconazole or to flucytosine.

Lay summary

We identified 66 yeast isolates, including 26 different yeast species from 910 individual milk samples. Our results indicate that individual milk samples may serve as a source of yeasts with the potential to trigger infection and may have reduced sensitivity to tested antifungal agents.
New giant planet beyond the snow line for an extended MOA exoplanet microlens sample
Authors: Ranc Clément , Bennett David P , Barry Richard K , Koshimoto Naoki , Skowron Jan , Hirao Yuki , Bond Ian A , Sumi Takahiro , Bathe-Peters Lars , Abe Fumio , Bhattacharya Aparna , Donachie Martin , Fujii Hirosane , Fukui Akihiko , Ishitani Silva Stela , Itow Yoshitaka , Kirikawa Rintaro , Kondo Iona , Alex Li Man Cheung , Matsubara Yutaka , Muraki Yasushi , Miyazaki Shota , Olmschenk Greg , Rattenbury Nicholas J , Satoh Yuki , Shoji Hikaru , Suzuki Daisuke , Tanaka Yuzuru , Tristram Paul J , Yamawaki Tsubasa , Yonehara Atsunori
Published: June 2021

Characterizing a planet detected by microlensing is hard if the planetary signal is weak or the lens-source relative trajectory is far from caustics. However, statistical analyses of planet demography must include those planets to accurately determine occurrence rates. As part of a systematic modelling effort in the context of a >10-yr retrospective analysis of MOA’s survey observations to build an extended MOA statistical sample, we analyse the light curve of the planetary microlensing event MOA-2014-BLG-472. This event provides weak constraints on the physical parameters of the lens, as a result of a planetary anomaly occurring at low magnification in the light curve. We use a Bayesian analysis to estimate the properties of the planet, based on a refined Galactic model and the assumption that all Milky Way’s stars have an equal planet-hosting probability. We find that a lens consisting of a $1.9^{+2.2}_{-1.2}\, \mathrm{M}_\mathrm{J}$ giant planet orbiting a $0.31^{+0.36}_{-0.19}\, \mathrm{M}_\odot$ host at a projected separation of $0.75\pm 0.24\, \mathrm{au}$ is consistent with the observations and is most likely, based on the Galactic priors. The lens most probably lies in the Galactic bulge, at $7.2^{+0.6}_{-1.7}\,\mathrm{kpc}$ from Earth. The accurate measurement of the measured planet-to-host star mass ratio will be included in the next statistical analysis of cold planet demography detected by microlensing.
Exotic image formation in strong gravitational lensing by clusters of galaxies – II. Uncertainties
Authors: Meena Ashish Kumar , Ghosh Agniva , Bagla Jasjeet S , Williams Liliya L R
Published: June 2021

Due to the finite amount of observational data, the best-fitting parameters corresponding to the reconstructed cluster mass have uncertainties. In turn, these uncertainties affect the inferences made from these mass models. Following our earlier work, we have studied the effect of such uncertainties on the singularity maps in simulated and actual galaxy clusters. The mass models for both simulated and real clusters have been constructed using grale. The final best-fitting mass models created using grale give the simplest singularity maps and a lower limit on the number of point singularities that a lens has to offer. The simple nature of these singularity maps also puts a lower limit on the number of three image (tangential and radial) arcs that a cluster lens has. Hence, we estimate the number of galaxy sources giving rise to the three image arcs, which can be observed with the James Webb Space Telescope (JWST). We find that we expect to observe at least 20–30 tangential and 5–10 radial three-image arcs in the Hubble Frontier Fields cluster lenses with the JWST.
An Analysis of Methylome Evolution in Primates
Authors: Sahm Arne , Koch Philipp , Horvath Steve , Hoffmann Steve
Published: June 2021

Although the investigation of the epigenome becomes increasingly important, still little is known about the long-term evolution of epigenetic marks and systematic investigation strategies are still lacking. Here, we systematically demonstrate the transfer of classic phylogenetic methods such as maximum likelihood based on substitution models, parsimony, and distance-based to interval-scaled epigenetic data. Using a great apes blood data set, we demonstrate that DNA methylation is evolutionarily conserved at the level of individual CpGs in promotors, enhancers, and genic regions. Our analysis also reveals that this epigenomic conservation is significantly correlated with its transcription factor binding density. Binding sites for transcription factors involved in neuron differentiation and components of AP-1 evolve at a significantly higher rate at methylation than at the nucleotide level. Moreover, our models suggest an accelerated epigenomic evolution at binding sites of BRCA1, chromobox homolog protein 2, and factors of the polycomb repressor 2 complex in humans. For most genomic regions, the methylation-based reconstruction of phylogenetic trees is at par with sequence-based reconstruction. Most strikingly, phylogenetic reconstruction using methylation rates in enhancer regions was ineffective independently of the chosen model. We identify a set of phylogenetically uninformative CpG sites enriched in enhancers controlling immune-related genes.
Genome-wide CRISPR screens reveal cyclin C as synthetic survival target of BRCA2
Authors: Tang Mengfan , Pei Guangsheng , Su Dan , Wang Chao , Feng Xu , Srivastava Mrinal , Chen Zhen , Zhao Zhongming , Chen Junjie
Published: June 2021

Poly (ADP-ribose) polymerase inhibitor (PARPi)-based therapies initially reduce tumor burden but eventually lead to acquired resistance in cancer patients with BRCA1 or BRCA2 mutation. To understand the potential PARPi resistance mechanisms, we performed whole-genome CRISPR screens to discover genetic alterations that change the gene essentiality in cells with inducible depletion of BRCA2. We identified that several RNA Polymerase II transcription Mediator complex components, especially Cyclin C (CCNC) as synthetic survival targets upon BRCA2 loss. Total mRNA sequencing demonstrated that loss of CCNC could activate the transforming growth factor (TGF)-beta signaling pathway and extracellular matrix (ECM)-receptor interaction pathway, however the inhibition of these pathways could not reverse cell survival in BRCA2 depleted CCNC-knockout cells, indicating that the activation of these pathways is not required for the resistance. Moreover, we showed that the improved survival is not due to restoration of homologous recombination repair although decreased DNA damage signaling was observed. Interestingly, loss of CCNC could restore replication fork stability in BRCA2 deficient cells, which may contribute to PARPi resistance. Taken together, our data reveal CCNC as a critical genetic determinant upon BRCA2 loss of function, which may help the development of novel therapeutic strategies that overcome PARPi resistance.
Coupling of the engineered DNA “mutator” to a biosensor as a new paradigm for activation of silent biosynthetic gene clusters in Streptomyces
Authors: Sekurova Olga N , Sun Yi-Qian , Zehl Martin , Rückert Christian , Stich Anna , Busche Tobias , Kalinowski Jörn , Zotchev Sergey B
Published: June 2021

DNA replication fidelity in Streptomyces bacteria, prolific producers of many medically important secondary metabolites, is understudied, while in Escherichia coli it is controlled by DnaQ, the ϵ subunit of DNA polymerase III (DNA PolIII). Manipulation of dnaQ paralogues in Streptomyces lividans TK24, did not lead to increased spontaneous mutagenesis in this bacterium suggesting that S. lividans DNA PolIII uses an alternative exonuclease activity for proofreading. In Mycobacterium tuberculosis, such activity is attributed to the DnaE protein representing α subunit of DNA PolIII. Eight DnaE mutants designed based on the literature data were overexpressed in S. lividans, and recombinant strains overexpressing two of these mutants displayed markedly increased frequency of spontaneous mutagenesis (up to 1000-fold higher compared to the control). One of these ‘mutators’ was combined in S. lividans with a biosensor specific for antibiotic coelimycin, which biosynthetic gene cluster is present but not expressed in this strain. Colonies giving a positive biosensor signal appeared at a frequency of ca 10–5, and all of them were found to produce coelimycin congeners. This result confirmed that our approach can be applied for chemical- and radiation-free mutagenesis in Streptomyces leading to activation of orphan biosynthetic gene clusters and discovery of novel bioactive secondary metabolites.
Mobilizing or Chasing Voters on Facebook? Analysing Echo-Chamber Effects at the UK Parliamentary General Election 2019
Authors: Power Sam , Mason Ben
Published: June 2021

Alongside the growth of online campaigning has been an increased anxiety around its effects on democratic institutions and processes. Many have suggested that in a (new) media environment that privileges choice, citizens will increasingly segment themselves into echo chambers, tuning out dissenting voices. But the debate on the existence of echo chambers is mixed, and the extent to which political parties campaign to easily persuadable (and pre-disposed) electorates is unclear. In this article, we present a case study of the Facebook campaign activity of the Conservatives, Labour and the Liberal Democrats at the UK’s parliamentary general election in 2019. Utilising an analysis of the Facebook Ad Archive’s Graph Application Programming Interface (API), we find that political parties do not consistently campaign to their easily persuadable electorates—often chasing votes as much as they mobilise supporters. The evidence that parties campaign to specific echo chambers online is therefore, at best, mixed.
Use of Virtual Reality Distraction to Reduce Child Pain and Fear during Painful Medical Procedures in Children with Physical Disabilities in Uganda: A Feasibility Study
Authors: Bannink Mbazzi Femke , Nimusiima Claire , Akellot Daniella , Kawesa Elizabeth , Abaasa Andrew , Hodges Sarah , Seeley Janet , Vervoort Tine
Published: June 2021

Objective

This study explored the acceptability and feasibility of the use of low-cost virtual reality (VR) glasses, and the Wong-Baker Faces Pain Scale and Children’s Fear Scale scales, for pain and fear reduction in children admitted at the septic ward of CoRSU Rehabilitation Hospital in Uganda.

Methods

In total, 79 children aged 4–17 years of age were offered to watch cartoons using VR glasses while undergoing painful dressing procedures. Before and after the procedure, children were asked to index current pain; children and their caregivers were asked to rate anticipated fear. Focus group discussions with 13 children, 10 caregivers and 9 nurses explored acceptability and feasibility. Quantitative data were analyzed using STATA15, NVIVO12 was used for qualitative data analysis.

Results

The VR glasses were accepted by 76 (96%) of the children. Children, caregivers, and nurses mentioned the glasses were helpful in distracting children from the medical procedure and felt the use of the glasses helped reduce child fear and pain. Nurses felt it made their work easier. The Wong-Baker Faces Pain Scale was an acceptable and feasible method to measure pain, while the Children’s Fear Scale was more difficult to interpret for our study population as they felt the faces on the scale were hard to read and identify with.

Conclusions

The use of VR glasses may offer an acceptable and effective pain and fear reduction method in resource-constrained settings and should be further explored in a randomized controlled trial.
Optimization of multi-site nicking mutagenesis for generation of large, user-defined combinatorial libraries
Authors: Kirby Monica B , Medina-Cucurella Angélica V , Baumer Zachary T , Whitehead Timothy A
Published: June 2021

Generating combinatorial libraries of specific sets of mutations are essential for addressing protein engineering questions involving contingency in molecular evolution, epistatic relationships between mutations, as well as functional antibody and enzyme engineering. Here we present optimization of a combinatorial mutagenesis method involving template-based nicking mutagenesis, which allows for the generation of libraries with >99% coverage for tens of thousands of user-defined variants. The non-optimized method resulted in low library coverage, which could be rationalized by a model of oligonucleotide annealing bias resulting from the nucleotide mismatch free-energy difference between mutagenic oligo and template. The optimized method mitigated this thermodynamic bias using longer primer sets and faster annealing conditions. Our updated method, applied to two antibody fragments, delivered between 99.0% (32451/32768 library members) to >99.9% coverage (32757/32768) for our desired libraries in 2 days and at an approximate 140-fold sequencing depth of coverage.
The role of the UA(1) breaking term in dynamical chiral symmetry breaking of chiral effective theories
Authors: Kono Shinnosuke , Jido Daisuke , Kuroda Yoshiki , Harada Masayasu
Published: June 2021

The spontaneous breaking of chiral symmetry is examined by chiral effective theories, such as the linear $\sigma$ model and the Nambu–Jona-Lasinio (NJL) model. We discuss the properties of the sigma meson regarded as the quantum fluctuation of the chiral condensate when the chiral symmetry is spontaneously broken, mainly by the U$_{A}$(1) anomaly. We derive a mass relation among the SU(3) flavor singlet mesons, $\eta_{0}$ and $\sigma_{0}$, in the linear $\sigma$ model to be satisfied for the anomaly-driven symmetry breaking in the chiral limit, and find that it is also supported in the NJL model. With the explicit breaking of chiral symmetry, we show that both of the chiral effective models reproducing the observed physical quantities suggest that the $\sigma_{0}$ meson should have a mass smaller than $\sim$800 MeV when anomaly-driven symmetry breaking takes place.
Varieties of capitalism and growth regimes: the role of income distribution
Authors: Behringer Jan , van Treeck Till
Published: June 2021

This article proposes a comparative political economy framework for analyzing the links between varieties of capitalism (VoC) and growth models, with a focus on the role of income distribution in the international trade imbalances leading up to the global financial crisis of 2008. For a panel of 18 countries over the period 1981–2007, we find that strongly rising top income shares contributed to debt-led growth and current account deficits in major liberal market economies (LMEs), whereas pronounced falls in the wage share contributed to export-led growth and current account surpluses in coordinated market economies (CMEs). We discuss how, against a global trend of liberalization and de-unionization, the institutional features originally thought to establish prosperous (and stable) VoC were linked to the emergence of distinct but similarly inequitable (and unstable) growth models in LMEs and CMEs.