bluuebunny/crossref_metadata_2025 huggingface dataset:
Ectopic expression of Triticum polonicum VRT-A2 underlies elongated glumes and grains in hexaploid wheat in a dosage-dependent manner
Authors: Adamski Nikolai M. , Simmonds James , Brinton Jemima F. , Backhaus Anna E. , Chen Yi , Smedley Mark , Hayta Sadiye , Florio Tobin , Crane Pamela , Scott Peter , Pieri Alice , Hall Olyvia , Barclay J. Elaine , Clayton Myles , Doonan John H. , Nibau Candida , Uauy Cristobal
Published: April 2021

Flower development is an important determinant of grain yield in crops. In wheat (Triticum spp.), natural variation for the size of spikelet and floral organs is particularly evident in Triticum turgidum ssp. polonicum (also termed Triticum polonicum), a tetraploid subspecies of wheat with long glumes, lemmas, and grains. Using map-based cloning, we identified VEGETATIVE TO REPRODUCTIVE TRANSITION 2 (VRT2), which encodes a MADS-box transcription factor belonging to the SHORT VEGETATIVE PHASE family, as the gene underlying the T. polonicum long-glume (P1) locus. The causal P1 mutation is a sequence rearrangement in intron-1 that results in ectopic expression of the T. polonicum VRT-A2 allele. Based on allelic variation studies, we propose that the intron-1 mutation in VRT-A2 is the unique T. polonicum subspecies-defining polymorphism, which was later introduced into hexaploid wheat via natural hybridizations. Near-isogenic lines differing for the P1 locus revealed a gradient effect of P1 across spikelets and within florets. Transgenic lines of hexaploid wheat carrying the T. polonicum VRT-A2 allele show that expression levels of VRT-A2 are highly correlated with spike, glume, grain, and floral organ length. These results highlight how changes in expression profiles, through variation in cis-regulation, can affect agronomic traits in a dosage-dependent manner in polyploid crops.
Synaptotagmins at the endoplasmic reticulum–plasma membrane contact sites maintain diacylglycerol homeostasis during abiotic stress
Authors: Ruiz-Lopez Noemi , Pérez-Sancho Jessica , del Valle Alicia Esteban , Haslam Richard P. , Vanneste Steffen , Catalá Rafael , Perea-Resa Carlos , Damme Daniël Van , García-Hernández Selene , Albert Armando , Vallarino José , Lin Jinxing , Friml Jiří , Macho Alberto P. , Salinas Julio , Rosado Abel , Napier Johnathan A. , Amorim-Silva Vitor , Botella Miguel A.
Published: April 2021

Endoplasmic reticulum–plasma membrane contact sites (ER–PM CS) play fundamental roles in all eukaryotic cells. Arabidopsis thaliana mutants lacking the ER–PM protein tether synaptotagmin1 (SYT1) exhibit decreased PM integrity under multiple abiotic stresses, such as freezing, high salt, osmotic stress, and mechanical damage. Here, we show that, together with SYT1, the stress-induced SYT3 is an ER–PM tether that also functions in maintaining PM integrity. The ER–PM CS localization of SYT1 and SYT3 is dependent on PM phosphatidylinositol-4-phosphate and is regulated by abiotic stress. Lipidomic analysis revealed that cold stress increased the accumulation of diacylglycerol at the PM in a syt1/3 double mutant relative to wild-type while the levels of most glycerolipid species remain unchanged. In addition, the SYT1-green fluorescent protein fusion preferentially binds diacylglycerol in vivo with little affinity for polar glycerolipids. Our work uncovers a SYT-dependent mechanism of stress adaptation counteracting the detrimental accumulation of diacylglycerol at the PM produced during episodes of abiotic stress.
The Meaning of Sedentary Behavior as Experienced by People in the Transition From Working Life to Retirement: An Empirical Phenomenological Study
Authors: Eklund Caroline , Elfström Magnus L , von Heideken Wågert Petra , Söderlund Anne , Gustavsson Catharina , Cederbom Sara , Thunborg Charlotta , Lööf Helena
Published: April 2021

Objective

Sedentary behavior (SB) is defined as a mean of >6 hours of daytime sitting or lying down. SB has been shown to increase with older age and is a risk factor for disease. During the transition from working life to retirement, changes in daily life activities occur, risking increased SB. The aim of the present study was to gain a deeper understanding of SB in relation to the transition from working life to retirement as experienced by persons in retirement.

Methods

The study was grounded in a phenomenological life-world perspective. Fourteen semi-structured interviews were conducted with participants aged 64–75. Data were analyzed using the empirical phenomenological psychological method.

Results

The participants described that voluntary sedentary time was positively related to general health and well-being, while involuntary sedentary time was negatively related to health. Increased sedentary time was described as natural when aging. Retirement was expressed as a time for rest after hard work and the ability to choose a slower pace in life. Internal and external demands and daily routines interrupted SB, whereas loneliness was perceived to increase SB. Participants strived to find a balance between physical activity and sedentary time. The variations in the participants’ descriptions formed three typologies: in light of meaningful sedentary behavior, in the shadow of involuntary sedentary behavior, and a dual process – postponing sedentary behavior with physical activity.

Conclusions

Increased SB was perceived as natural when aging, but something that may be postponed by conscious choices. SB was perceived as associated with health, rest and recovery but also with the risk of deteriorating health.

Impact

This knowledge of the experienced meaning of SB could guide the design of health promotion interventions and may be helpful in targeting those in need of support and individualizing interventions to decrease SB in retirement.

Lay Summary

This study reveals how persons in retirement describe sedentary behavior as something healthy but also as unhealthy and that sedentary behavior is natural in aging and can be postponed by physical activity.
KONINKLIJKE PHILIPS N.V. v ASUSTEK COMPUTER INCORPORATION
Authors:   Court of Appeal
Published: April 2021

H1 Patents – European patents – Standards essential patents – Technical trials – Obviousness – The skilled person – Common general knowledge – Mindset – “Lions in the path” – The relevance of commercial considerations – Hindsight – Secondary evidence – Essentiality – Construction – Appeal to Court of Appeal
Self-reported sleep relates to microstructural hippocampal decline in ß-amyloid positive Adults beyond genetic risk
Authors: Grydeland Håkon , Sederevičius Donatas , Wang Yunpeng , Bartrés-Faz David , Bertram Lars , Dobricic Valerija , Düzel Sandra , Ebmeier Klaus P , Lindenberger Ulman , Nyberg Lars , Pudas Sara , Sexton Claire E , Solé-Padullés Cristina , Sørensen Øystein , Walhovd Kristine B , Fjell Anders M
Published: April 2021

Study Objectives

A critical role linking sleep with memory decay and β-amyloid (Aβ) accumulation, two markers of Alzheimer’s disease (AD) pathology, may be played by hippocampal integrity. We tested the hypotheses that worse self-reported sleep relates to decline in memory and intra-hippocampal microstructure, including in the presence of Aβ.

Methods

Two-hundred and forty-three cognitively healthy participants, aged 19–81 years, completed the Pittsburgh Sleep Quality Index once, and two diffusion tensor imaging sessions, on average 3 years apart, allowing measures of decline in intra-hippocampal microstructure as indexed by increased mean diffusivity. We measured memory decay at each imaging session using verbal delayed recall. One session of positron emission tomography, in 108 participants above 44 years of age, yielded 23 Aβ positive. Genotyping enabled control for APOE ε4 status, and polygenic scores for sleep and AD, respectively.

Results

Worse global sleep quality and sleep efficiency related to more rapid reduction of hippocampal microstructure over time. Focusing on efficiency (the percentage of time in bed at night spent asleep), the relation was stronger in presence of Aβ accumulation, and hippocampal integrity decline mediated the relation with memory decay. The results were not explained by genetic risk for sleep efficiency or AD.

Conclusions

Worse sleep efficiency related to decline in hippocampal microstructure, especially in the presence of Aβ accumulation, and Aβ might link poor sleep and memory decay. As genetic risk did not account for the associations, poor sleep efficiency might constitute a risk marker for AD, although the driving causal mechanisms remain unknown.
Behavioral and Neural Signatures of Visual Imagery Vividness Extremes: Aphantasia versus Hyperphantasia
Authors: Milton Fraser , Fulford Jon , Dance Carla , Gaddum James , Heuerman-Williamson Brittany , Jones Kealan , Knight Kathryn F , MacKisack Matthew , Winlove Crawford , Zeman Adam
Published: April 2021

Although Galton recognized in the 1880s that some individuals lack visual imagery, this phenomenon was mostly neglected over the following century. We recently coined the terms “aphantasia” and “hyperphantasia” to describe visual imagery vividness extremes, unlocking a sustained surge of public interest. Aphantasia is associated with subjective impairment of face recognition and autobiographical memory. Here we report the first systematic, wide-ranging neuropsychological and brain imaging study of people with aphantasia (n = 24), hyperphantasia (n = 25), and midrange imagery vividness (n = 20). Despite equivalent performance on standard memory tests, marked group differences were measured in autobiographical memory and imagination, participants with hyperphantasia outperforming controls who outperformed participants with aphantasia. Face recognition difficulties and autistic spectrum traits were reported more commonly in aphantasia. The Revised NEO Personality Inventory highlighted reduced extraversion in the aphantasia group and increased openness in the hyperphantasia group. Resting state fMRI revealed stronger connectivity between prefrontal cortices and the visual network among hyperphantasic than aphantasic participants. In an active fMRI paradigm, there was greater anterior parietal activation among hyperphantasic and control than aphantasic participants when comparing visualization of famous faces and places with perception. These behavioral and neural signatures of visual imagery vividness extremes validate and illuminate this significant but neglected dimension of individual difference.
Sevoflurane Exerts Protective Effects in Murine Peritonitis-induced Sepsis via Hypoxia-inducible Factor 1α/Adenosine A2B Receptor Signaling
Authors: Ngamsri Kristian-Christos , Fabian Friederike , Fuhr Anika , Gamper-Tsigaras Jutta , Straub Andreas , Fecher David , Steinke Maria , Walles Heike , Reutershan Jörg , Konrad Franziska M.
Published: April 2021

Background

Sepsis is one of the leading causes of mortality in intensive care units, and sedation in the intensive care unit during sepsis is usually performed intravenously. The inhalative anesthetic sevoflurane has been shown to elicit protective effects in various inflammatory studies, but its role in peritonitis-induced sepsis remains elusive. The hypothesis was that sevoflurane controls the neutrophil infiltration by stabilization of hypoxia-inducible factor 1α and elevated adenosine A2B receptor expression.

Methods

In mouse models of zymosan- and fecal-induced peritonitis, male mice were anesthetized with sevoflurane (2 volume percent, 30 min) after the onset of inflammation. Control animals received the solvent saline. The neutrophil counts and adhesion molecules on neutrophils in the peritoneal lavage of wild-type, adenosine A2B receptor −/−, and chimeric animals were determined by flow cytometry 4 h after stimulation. Cytokines and protein release were determined in the lavage. Further, the adenosine A2B receptor and its transcription factor hypoxia-inducible factor 1α were evaluated by real-time polymerase chain reaction and Western blot analysis 4 h after stimulation.

Results

Sevoflurane reduced the neutrophil counts in the peritoneal lavage (mean ± SD, 25 ± 17 × 105
vs. 12 ± 7 × 105 neutrophils; P = 0.004; n = 19/17) by lower expression of various adhesion molecules on neutrophils of wild-type animals but not of adenosine A2B receptor −/− animals. The cytokines concentration (means ± SD, tumor necrosis factor α [pg/ml], 523 ± 227 vs. 281 ± 101; P = 0.002; n = 9/9) and protein extravasation (mean ± SD [mg/ml], 1.4 ± 0.3 vs. 0.8 ± 0.4; P = 0.002; n = 12/11) were also lower after sevoflurane only in the wild-type mice. Chimeric mice showed the required expression of the adenosine A2B receptor on the hematopoietic and nonhematopoietic compartments for the protective effects of the anesthetic. Sevoflurane induced the expression of hypoxia-inducible factor 1α and adenosine A2B receptor in the intestine, liver, and lung.

Conclusions

Sevoflurane exerts various protective effects in two murine peritonitis-induced sepsis models. These protective effects were linked with a functional adenosine A2B receptor.

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Applying a Nursing Perspective to Address the Challenges Experienced by Cisgender Women in the HIV Status Neutral Care Continuum: A Review of the Literature
Authors: Bond Keosha T. , Chandler Rasheeta , Chapman-Lambert Crystal , Jemmott Lorretta Sweet , Lanier Yzette , Cao Jiepin , Nikpour Jacqueline , Randolph Schenita D.
Published: April 2021

The field of HIV research has grown over the past 40 years, but there remains an urgent need to address challenges that cisgender women living in the United States experience in the HIV neutral status care continuum, particularly among women such as Black women, who continue to be disproportionately burdened by HIV due to multiple levels of systemic oppression. We used a social ecological framework to provide a detailed review of the risk factors that drive the women's HIV epidemic. By presenting examples of effective approaches, best clinical practices, and identifying existing research gaps in three major categories (behavioral, biomedical, and structural), we provide an overview of the current state of research on HIV prevention among women. To illustrate a nursing viewpoint and take into account the diverse life experiences of women, we provide guidance to strengthen current HIV prevention programs. Future research should examine combined approaches for HIV prevention, and policies should be tailored to ensure that women receive effective services that are evidence-based and which they perceive as important to their lives.
Large university with high COVID-19 incidence did not increase risk to non-student population
Authors: Bharti Nita , Lambert Brian , Exten Cara , Faust Christina , Ferrari Matt , Robinson Anthony
Published: April 2021

Large US colleges and universities that re-opened campuses in the fall of 2020 and the spring of 2021 experienced high per capita rates of COVID-19. Returns to campus were controversial because they posed a risk to the surrounding communities. A large university in Pennsylvania that returned to in-person instruction in the fall of 2020 and spring of 2021 reported high incidence of COVID-19 among students. However, the co-located non-student resident population in the county experienced fewer COVID-19 cases per capita than reported in neighboring counties. Activity patterns from mobile devices indicate that the non-student resident population near the university restricted their movements during the pandemic more than residents of neighboring counties. Preventing cases in student and non-student populations requires different, specifically targeted strategies.
An Artificial Intelligence-Assisted Diagnostic Platform for Rapid Near-Patient Hematology
Authors: Bachar Neta , Benbassat Dana , Brailovsky David , Eshel Yochay , Glück Dan , Levner Daniel , Levy Sarah , Pecker Sharon , Yurkovsky Evgeny , Zait Amir , Sever Cordelia , Kratz Alexander , Brugnara Carlo
Published: April 2021

Hematology analyzers capable of performing complete blood count (CBC) have lagged in their prevalence at the point-of-care. Sight OLO® (Sight Diagnostics, Israel) is a novel hematological platform which provides a 19 parameter, five-part differential CBC, and is designed to address the limitations in current point-of-care hematology analyzers using recent advances in artificial intelligence (AI) and computer vision. Accuracy, repeatability, and flagging capabilities of OLO were compared with the Sysmex XN-Series System (Sysmex, Japan). Matrix studies compared performance using venous, capillary and direct-from-finger-prick blood samples. Regression analysis shows strong concordance between OLO and the Sysmex XN, demonstrating that OLO performs with high accuracy for all CBC parameters. High repeatability and reproducibility were demonstrated for most of the testing parameters. The analytical performance of the OLO hematology analyzer was validated in a multicenter clinical laboratory setting, demonstrating its accuracy and comparability to clinical laboratory-based hematology analyzers. Furthermore, the study demonstrated the validity of CBC analysis of samples collected directly from fingerpricks.

One Sentence Summary

We present a novel diagnostic platform based on artificial intelligence-assisted image analysis that is capable of performing rapid complete blood count from venous, capillary, and finger-prick samples in near-patient settings.
Affordable and time-effective high throughput screening of SARS-CoV-2 variants using Denaturing High-Performance Liquid Chromatography analysis
Authors: Turba Maria Elena , Mion Domenico , Papadimitriou Stavros , Taddei Francesca , Dirani Giorgio , Sambri Vittorio , Gentilini Fabio
Published: April 2021

Introduction

Mutations in the receptor binding domain (RBD) region of SARS-CoV-2 have been shown to impact the infectivity, pathogenicity and transmissibility of new variants of concern (VOC). Even more worrisome, those mutations have the potential of causing immune escape, undermining the population immunity induced by ongoing mass vaccination programs.

Gap statement

The massive parallel sequencing techniques have taken a lead role in the detection strategies of the new variants. Nevertheless, they are still cumbersome and labour-demanding. There is an urgent need for novel strategies and techniques aimed at the surveillance of the active emergence and spread of the VOC.

Aim

The aim of this study was to provide a quick, cheap and straightforward Denaturing High-Performance Liquid Chromatography (DHPLC) method for the prompt identification of the SARS-CoV-2 VOC.

Methodology

Two PCRs were designed to target the RBD region, spanning residues N417 through N501 of the Spike protein. Furthermore, a DHPLC screening analysis was set up. The screening consisted of mixing the unknown sample with a standard sample of a known variant, denaturing at high temperature, renaturing at room temperature followed by a 2-minute run using the WAVE DHPLC system to detect the heteroduplexes which invariably originate whenever the unknown sample has a nucleotide difference with respect to the standard used.

Results

The workflow was able to readily detect new variants including the P.1, the B.1.585 and the B.1. 617.2 lineages at a very affordable cost. The DHPLC analysis was robust being able to identify variants even in case of samples with very unbalanced target concentration including those samples at the limit of detection.

Conclusions

This approach has the potential of greatly expediting surveillance of the SARS-CoV-2 variants.
Estimating local outbreak risks and the effects of non-pharmaceutical interventions in age-structured populations: SARS-CoV-2 as a case study
Authors: Lovell-Read Francesca A. , Shen Silvia , Thompson Robin N.
Published: April 2021

During the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) including school closures, workplace closures and social distancing policies have been employed worldwide to reduce transmission and prevent local outbreaks. However, transmission and the effectiveness of NPIs depend strongly on age-related factors including heterogeneities in contact patterns and pathophysiology. Here, using SARS-CoV-2 as a case study, we develop a branching process model for assessing the risk that an infectious case arriving in a new location will initiate a local outbreak, accounting for the age distribution of the host population. We show that the risk of a local outbreak depends on the age of the index case, and we explore the effects of NPIs targeting individuals of different ages. Social distancing policies that reduce contacts outside of schools and workplaces and target individuals of all ages are predicted to reduce local outbreak risks substantially, whereas school closures have a more limited impact. In the scenarios considered here, when different NPIs are used in combination the risk of local outbreaks can be eliminated. We also show that heightened surveillance of infectious individuals reduces the level of NPIs required to prevent local outbreaks, particularly if enhanced surveillance of symptomatic cases is combined with efforts to find and isolate nonsymptomatic infected individuals. Our results reflect real-world experience of the COVID-19 pandemic, during which combinations of intense NPIs have reduced transmission and the risk of local outbreaks. The general modelling framework that we present can be used to estimate local outbreak risks during future epidemics of a range of pathogens, accounting fully for age-related factors.
Massively Multiplexed Affinity Characterization of Therapeutic Antibodies Against SARS-CoV-2 Variants
Authors: Engelhart Emily , Lopez Randolph , Emerson Ryan , Lin Charles , Shikany Colleen , Guion Daniel , Kelley Mary , Younger David
Published: April 2021

Antibody therapies represent a valuable tool to reduce COVID-19 deaths and hospitalizations. Multiple antibody candidates have been granted emergency use authorization by the FDA and many more are in clinical trials. Most antibody therapies for COVID-19 are engineered to bind to the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein and disrupt its interaction with ACE2. Notably, several SARS-CoV-2 strains have accrued mutations throughout the RBD that improve ACE2 binding affinity, enhance viral transmission, and escape some existing antibody therapies. Here, we measure the binding affinity of 33 therapeutic antibodies against a large panel of SARS-CoV-2 variants and related strains of clinical significance to determine epitopic residues, determine which mutations result in loss of binding, and predict how future RBD variants may impact antibody efficacy.

One-Sentence Summary

By measuring protein binding in vitro, we identify which clinical antibodies retain binding to various mutant SARS-CoV-2 strains.
Regulation and impact of cardiac lymphangiogenesis in pressure-overload-induced heart failure
Authors: Heron C , Dumesnil A , Houssari M , Renet S , Lebon A , Godefroy D , Schapman D , Henri O , Riou G , Nicol L , Henry JP , Pieronne-Deperrois M , Ouvrard-Pascaud A , Hägerling R , Chiavelli H , Michel JB , Mulder P , Fraineau S , Richard V , Tardif V , Brakenhielm E
Published: April 2021

Rationale

Lymphatics are essential for cardiac health, and insufficient lymphatic expansion (lymphangiogenesis) contributes to development of heart failure (HF) after myocardial infarction. However, the regulation and impact of lymphatics in non-ischemic cardiomyopathy induced by pressure-overload remains to be determined.

Objective

Investigate cardiac lymphangiogenesis following transverse aortic constriction (TAC) in adult male or female C57Bl/6J or Balb/c mice, and in patients with end-stage HF.

Methods & Result

Cardiac function was evaluated by echocardiography, and cardiac hypertrophy, lymphatics, inflammation, edema, and fibrosis by immunohistochemistry, flow cytometry, microgravimetry, and gene expression analysis, respectively. Treatment with neutralizing anti-VEGFR3 antibodies was applied to inhibit cardiac lymphangiogenesis in mice.

The gender- and strain-dependent mouse cardiac hypertrophic response to TAC, especially increased ventricular wall stress, led to lymphatic expansion in the heart. Our experimental findings that ventricular dilation triggered cardiac lymphangiogenesis was mirrored by observations in clinical HF samples, with increased lymphatic density found in patients with dilated cardiomyopathy. Surprisingly, the striking lymphangiogenesis observed post-TAC in Balb/c mice, linked to increased cardiac Vegfc, did not suffice to resolve myocardial edema, and animals progressed to dilated cardiomyopathy and HF. Conversely, selective inhibition of the essentially Vegfd-driven capillary lymphangiogenesis observed post-TAC in male C57Bl/6J mice did not significantly aggravate cardiac edema. However, cardiac immune cell levels were increased, notably myeloid cells at 3 weeks and T lymphocytes at 8 weeks. Moreover, while the TAC-triggered development of interstitial cardiac fibrosis was unaffected by anti-VEGFR3, inhibition of lymphangiogenesis increased perivascular fibrosis and accelerated the development of left ventricular dilation and cardiac dysfunction.

Conclusions

We demonstrate for the first time that endogenous cardiac lymphangiogenesis limits pressure-overload-induced cardiac inflammation and perivascular fibrosis, thus delaying HF development. While these findings remain to be confirmed in a larger study of HF patients, we propose that under settings of pressure-overload poor cardiac lymphangiogenesis may accelerate HF development.
Microbiota links to neural dynamics supporting threat processing
Authors: Hall Caitlin V. , Harrison Ben J. , Iyer Kartik K. , Savage Hannah S. , Zakrzewski Martha , Simms Lisa A. , Radford-Smith Graham , Moran Rosalyn J. , Cocchi Luca
Published: April 2021

There is growing recognition that the composition of the gut microbiota influences behaviour, including responses to threat. The cognitive-interoceptive appraisal of threat-related stimuli relies on dynamic neural computations between the anterior insular (AIC) and the dorsal anterior cingulate (dACC) cortices. If, to what extent, and how microbial consortia influence the activity of this cortical threat processing circuitry is unclear. We addressed this question by combining a threat processing task, neuroimaging, 16S rRNA profiling, and computational modelling in healthy participants. Results showed interactions between high-level ecological indices with threat-related AIC-dACC neural dynamics. At finer taxonomic resolutions, the abundance ofRuminococcuswas differentially linked to connectivity between, and activity within the AIC and dACC during threat updating. Functional inference analysis provides a strong rationale to motivate future investigations of microbiota-derived metabolites in the observed relationship with threat-related brain processes.
Development of a transboundary model of livestock disease in Europe
Authors: Bradhurst Richard , Garner Graeme , Hóvári Márk , de la Puente Maria , Mintiens Koen , Yadav Shankar , Federici Tiziano , Kopacka Ian , Stockreiter Simon , Kuzmanova Ivanka , Paunov Samuil , Cacinovic Vladimir , Rubin Martina , Szilágyi Jusztina , Kókány Zsófia Szepesiné , Santi Annalisa , Sordilli Marco , Sighinas Laura , Spiridon Mihaela , Potocnik Marko , Sumption Keith
Published: April 2021

Epidemiological models of notifiable livestock disease are typically framed at a national level and targeted for specific diseases. There are inherent difficulties in extending models beyond national borders as details of the livestock population, production systems and marketing systems of neighbouring countries are not always readily available. It can also be a challenge to capture heterogeneities in production systems, control policies, and response resourcing across multiple countries, in a single transboundary model.

In this paper we describe EuFMDiS, a continental-scale modelling framework for transboundary animal disease, specifically designed to support emergency animal disease planning in Europe. EuFMDiS simulates the spread of livestock disease within and between countries and allows control policies to be enacted and resourced on per-country basis. It provides a sophisticated decision support tool that can be used to look at the risk of disease introduction, establishment and spread; control approaches in terms of effectiveness and costs; resource management; and post-outbreak management issues.
Antibody response to SARS-CoV-2 infection over six months among Nicaraguan outpatients
Authors: González Fredman , Zepeda Omar , Toval-Ruiz Christian , Matute Armando , Vanegas Hernan , Munguia Nancy , Centeno Edwing , Reyes Yaoska , Svensson Lennart , Nordgren Johan , de Silva Aravinda M. , Becker-Dreps Sylvia , Premkumar Lakshmanane , Bucardo Filemón
Published: April 2021

New information is emerging about SARS-CoV-2 epidemiology and immunity, but little of this information comes from low- and middle-income countries or from patients receiving care in the outpatient setting. The current study investigated the SARS-CoV-2 infection status and antibody responses in 157 patients seeking care for a respiratory disease suggestive of COVID-19 in private healthcare clinics during the first wave (June–October 2020) of infections in Nicaragua. We examined nasal swabs for the presence of viral RNA via RT-PCR and longitudinally collected sera for the changes in SARS-CoV-2 Spike antibody levels over six months. Among patients with confirmed SARS-CoV-2 infections, we evaluated if clinical symptoms were associated with age, hematological parameters and co-morbidities. The combination of PCR and paired serology identified 60 (38%) of the 157 outpatients as acute COVID-19. While both PCR and serology identified the majority (n = 38, 64%) of the acute infections, a notable number of outpatients were identified by RT-qPCR (n = 13, 22%) or by serology (n = 9, 14%) only. During the longitudinal study, we identified 6 new infections by serology among the 97 non-COVID-19 subjects. In conclusion, this study report that more than one third of the outpatients seeking care for acute respiratory disease during the first epidemic wave of SARS-CoV-2 in Nicaragua had an acute mild COVID-19 infection that correlate with prolonged humoral response. This immune response to the RBD antigen, more likely IgG dependent, significantly increased between the acute to convalescent and decay in the late convalescent but still remained seropositive.
Human interictal epileptiform discharges are bidirectional traveling waves echoing ictal discharges
Authors: Smith Elliot H , Liou Jyun-You , Merricks Edward M , Davis Tyler S , Thomson Kyle , Greger Bradley , House Paul A , Emerson Ronald G , Goodman Robert R , McKhann Guy M , Sheth Sameer A , Schevon Catherine A , Rolston John D
Published: April 2021

Interictal epileptiform discharges (IEDs), also known as interictal spikes, are large intermittent electrophysiological events observed between seizures in patients with epilepsy. Though they occur far more often than seizures, IEDs are less studied, and their relationship to seizures remains unclear. To better understand this relationship, we examined multi-day recordings of microelectrode arrays implanted in human epilepsy patients, allowing us to precisely observe the spatiotemporal propagation of IEDs, spontaneous seizures, and how they relate. These recordings showed that the majority of IEDs are traveling waves, traversing the same path as ictal discharges during seizures, and with a fixed direction relative to seizure propagation. Moreover, the majority of IEDs, like ictal discharges, were bidirectional, with one predominant and a second, less frequent antipodal direction. These results reveal a fundamental spatiotemporal similarity between IEDs and ictal discharges. These results also imply that most IEDs arise in brain tissue outside the site of seizure onset and propagate toward it, indicating that the propagation of IEDs provides useful information for localizing the seizure focus.
A re-analysis of the data in Sharkey et al.’s (2021) minimalist revision reveals that BINs do not deserve names, but BOLD Systems needs a stronger commitment to open science
Authors: Meier Rudolf , Blaimer Bonnie B. , Buenaventura Eliana , Hartop Emily , von Rintelen Thomas , Srivathsan Amrita , Yeo Darren
Published: April 2021

Halting biodiversity decline is one of the most critical challenges for humanity, but monitoring biodiversity is hampered by taxonomic impediments. One impediment is the large number of undescribed species (here called “dark taxon impediment”) while another is caused by the large number of superficial species descriptions which can only be resolved by consulting type specimens (“superficial description impediment”). Recently, Sharkey et al. (2021) proposed to address the dark taxon impediment for Costa Rican braconid wasps by describing 403 species based on barcode clusters (“BINs”) computed by BOLD Systems. More than 99% of the BINs (387 of 390) are converted into species by assigning binominal names (e.g., BIN “BOLD:ACM9419” becomesBracon federicomatarritai) and adding a minimal diagnosis (usually consisting only of a consensus barcode). We here show that many of Sharkey et al.’s species are unstable when the underlying data are analyzed using different species delimitation algorithms. Add the insufficiently informative diagnoses, and many of these species will become the next “superficial description impediment” for braconid taxonomy because they will have to be tested and redescribed after obtaining sufficient evidence for confidently delimiting species. We furthermore show that Sharkey et al.’s approach of using consensus barcodes as diagnoses is not functional because it cannot be consistently applied. Lastly, we reiterate that COI alone is not suitable for delimiting and describing species and voice concerns over Sharkey et al.’s uncritical use of BINs because they are calculated by a proprietary algorithm (RESL) that uses a mixture of public and private data. We urge authors, reviewers, and editors to maintain high standards in taxonomy by only publishing new species that are rigorously delimited with open-access tools and supported by publicly available evidence.
Using 3D geometric morphometrics to aid taxonomic and ecological understanding of a recent speciation event within a small Australian marsupial (genusAntechinus)
Authors: Viacava Pietro , Baker Andrew M. , Blomberg Simone P. , Phillips Matthew J. , Weisbecker Vera
Published: April 2021

Taxonomic distinction of species forms the foundation of biodiversity assessments and conservation priorities. However, traditional morphological and/or genetics-based taxonomic assessments frequently miss the opportunity of elaborating on the ecological and functional context of species diversification. Here, we used 3D geometric morphometrics of the cranium to improve taxonomic differentiation and add eco-morphological characterisation of a young cryptic divergence within the marsupial carnivorous genusAntechinus. Specifically, we used 168 museum specimens to characterise the recently proposed cladesA. stuartii“south”,A. stuartii“north” andA. subtropicus. Beyond slight differences attributable to overall size (and therefore not necessarily diagnostic), we also found clear allometry-independent shape variation. This allowed us to define new, easily measured diagnostic traits in the palate, which differentiate the three clades. Contrary to previous suggestions, we found no support for a latitudinal gradient as causing the differentiation between the clades. However, skull shape co-varied with temperature and precipitation seasonality, suggesting that the clades may be adapted to environmental variables that are likely to be impacted by climate change. Our study demonstrates the use of 3D geometric morphometrics to improve taxonomic diagnosis of cryptic mammalian species, while providing perspectives on the adaptive origins and potential future threats of mammalian diversity.
Generation of specialized blood vessels through transdifferentiation of lymphatic endothelial cells
Authors: Das Rudra N. , Bassi Ivan , Han Yanchao , Lambiase Giuseppina , Tevet Yaara , Moshe Noga , Safriel Stav , Nicenboim Julian , Brückner Matthias , Hirsch Dana , Eilam-Altstadter Raya , Herzog Wiebke , Poss Kenneth D. , Yaniv Karina
Published: April 2021

The lineage and developmental trajectory of a cell are key determinants of cellular identity. Yet, the functional relevance of deriving a specific cell type from ontologically distinct progenitors, remains an open question. In the case of the vascular system, blood and lymphatic vessels are composed of endothelial cells (ECs) that differentiate and diversify to cater the different physiological demands of each organ. While lymphatic vessels have been shown to originate from multiple cell sources, lymphatic ECs (LECs) themselves seem to have a unipotent cell fate. In this work we uncover a novel mechanism of blood vessel formation through transdifferentiation of LECs. Using advanced long-term reiterative imaging and lineage-tracing of ECs in zebrafish, from embryonic development through adulthood, we reveal a hitherto unknown process of LEC-to-BEC transdifferentiation, underlying vascularization of the anal fin (AF). Moreover, we demonstrate distinct functional implications for deriving AF vessels from either LECs or BECs, uncovering for the first time a clear link between cell ontogeny and functionality. Molecularly, we identify Sox17 as a negative regulator of lymphatic fate specification, whose specific expression in AF LECs suppresses its lymphatic cell fate. Finally, we show that akin to the developmental process, during adult AF regeneration the vasculature is re-derived from lymphatics, demonstrating that LECs in the mature fish retain both potency and plasticity for generating specialized blood vessels. Overall, our work highlights a novel mechanism of blood vessel formation through LEC trans-differentiation, and provides the firstin vivoevidence for a link between cell ontogeny and functionality in ECs.
Distinct functions of cardiac β-adrenergic receptors in the T-tubulevs.outer surface membrane
Authors: Barthé Marion , Lefebvre Flora , Langlois Emilie , Lefebvre Florence , Lechêne Patrick , Iturrioz Xavier , Llorens-Cortes Catherine , Ha-Duong Tâp , Moine Laurence , Tsapis Nicolas , Fischmeister Rodolphe
Published: April 2021

β-adrenoceptors (β-ARs) regulate cardiac function during sympathetic nerve stimulation. β-ARs are present in both cardiac T-tubule (TTM) and outer surface membrane (OSM), but how their location impacts on their function is unknown. Here, we developed a technology based on size exclusion to explore the function of β-ARs located in the OSM. We synthetized a PEG-Iso molecule by covalent linking isoprenaline (Iso) to a 5000 Da PolyEthylene-Glycol (PEG) chain to increase the size of the β-AR agonist and prevent it from accessing the TT network. The affinity of PEG-Iso and Iso on β1- and β2-ARs was measured using radioligand binding. Molecular dynamics simulation was used to assess PEG-Iso conformation and visualise the accessibility of the Iso moiety to water. Using confocal microscopy, we show that PEGylation constrains molecules outside the T-tubule network due to the presence of the extracellular matrix. β-AR activation in OSM with PEG-Iso produced a lower stimulation of [cAMP]ithan Iso but a larger stimulation of cytosolic PKA at equivalent levels of [cAMP]Iand similar effects on excitation-contraction coupling parameters. However, PEG-Iso produced a much lower stimulation of nuclear PKA than Iso. Thus, OSM β-ARs control mainly cytosolic cAMP/PKA pathway and contractility, while TTM β-ARs control mainly nuclear PKA and nuclear protein phosphorylation. Size exclusion strategy using ligand PEGylation provides a unique approach to evaluate the respective contribution of T-tubulevs.outer surface membrane proteins in cardiac cells.

Significance Statement

β-adrenoceptors (β-ARs) regulate cardiac function during sympathetic nerve stimulation. They are present in both cardiac T-tubule and outer surface membranes, but how their location impacts on their function is unknown. By linking the β-AR agonist isoprenaline (Iso) to a PolyEthylene-Glycol (PEG) chain, we increased the size of the agonist to prevent it from entering the T-tubules. Thus, PEG-Iso is only able to activate β-ARs in the outer surface membrane. With this size exclusion strategy, we show that β-ARs located in the outer surface membrane control mainly cytosolic cAMP/PKA pathway and contractility, while those located in the T-tubule membrane control mainly nuclear PKA and nuclear protein phosphorylation.
Nanoscale ligand density modulates gap junction intercellular communication of cell condensates during chondrogenesis
Authors: Casanellas Ignasi , Lagunas Anna , Vida Yolanda , Pérez-Inestrosa Ezequiel , Rodríguez-Pereira Cristina , Magalhaes Joana , Andrades José A. , Becerra José , Samitier Josep
Published: April 2021

To unveil the influence of cell-matrix adhesions in the establishment of gap junction intercellular communication (GJIC) during cell condensation in chondrogenesis.

Materials & Methods

Previously developed nanopatterns of the cell adhesive ligand arginine-glycine-aspartic acid (RGD) were used as cell culture substrates to control cell adhesion at the nanoscale. We conductedin vitrochondrogenesis of mesenchymal stem cells on the nanopatterns. We evaluated cohesion and GJIC in cell condensates.

Results

Mechanical stability and GJIC are enhanced by a nanopattern configuration in which 90% of the surface area presents adhesion sites separated less than 70 nm, thus providing an onset for cell signaling.

Conclusion

Cell-matrix adhesions regulate GJIC of mesenchymal cell condensates duringin vitrochondrogenesis from a threshold configuration at the nanoscale.
Recovery from form-deprivation myopia in chicks is dependent upon the fullness and correlated colour temperature of the light spectrum
Authors: Muralidharan Arumugam R. , Yu Shermaine Low Wan , Chong Lee Yong , Barathi Veluchamy A. , Saw Seang-Mei , Milea Dan , Najjar Raymond P.
Published: April 2021

Background

To evaluate the impact of full-spectrum light-emitting diodes (LEDs) mimicking sunlight on ocular axial elongation and refractive error development in a chicken model of myopia.

Methods

A total of 39 chicks (Lohmann brown), 1 day-old, were randomly distributed into 3 groups. Animals were housed for 28 days in a temperature-controlled enclosure, under a 12/12h light/dark cycle of isoluminant (∼285 Lux) fluorescent [n = 18, (4000K, FL-4000)] or Sunlike-LED [n=12, (4000K, SL-4000); n = 9, (6500K, SL-6500)] white lights. Myopia was induced monocularly in all chicks by random occlusion of one eye with a frosted diffuser, from day 1 post-hatching (D1) until D14. On D14, diffusers were removed, and recovery from myopia was monitored under the same experimental light condition. Axial length (AL), refractive status, choroidal thickness and anterior chamber depth were recorded on days 1, 7, 14, 22 and 28.Ex vivoscleral collagen fibre thicknesses were measured from scanning electron microscopy images. Differences in outcome measures between eyes and groups were compared using 2-way repeated-measures ANOVA.

Results

There was no significant difference between groups in the AL and refraction of form-deprived (FD) eyes during form-deprivation (D1 to D14). FD eyes of animals raised under SL-4000 and SL-6500 recovered more rapidly from excessive axial elongation than those of animals raised under FL-4000, by D22 and D28. Correspondingly, the refractive status of FD eyes exposed to SL-4000 and SL-6500 was close to that of control eyes by D28. The choroid became thicker during recovery in FD eyes compared to control eyes, in all groups. Choroidal thickness was significantly greater in FD eyes of chickens raised under SL-6500 than in animals raised under FL-4000 (P< 0.01). The diameter of scleral collagen fibrils was significantly greater in recovering FD eyes of chickens raised under SL-6500, than in those raised under FL-4000 (P= 0.04) and SL-4000 (P= 0.002).

Conclusions

Compared to fluorescent light, moderate intensities of full-spectrum Sunlike-LEDs can accelerate recovery from form-deprivation myopia in chickens, potentially through choroid-mediated pathways increasing the diameter of scleral collagen fibrils. This study highlights an important implication of the spectral content of white light on ocular growth and emmetropization.
Experience-dependent plasticity modulates ongoing activity in the antennal lobe and enhances odor representations
Authors: Franco Luis M. , Yaksi Emre
Published: April 2021

Ongoing neural activity has been observed across several brain regions and thought to reflect the internal state of the brain. Yet, it is not fully understood how ongoing brain activity interacts with sensory experience and shape sensory representations. Here, we show that projection neurons of the fruit fly antennal lobe exhibit spatiotemporally organized ongoing activity in the absence of odor stimulation. Upon repeated exposure to odors, we observe a gradual and long-lasting decrease in the amplitude and frequency of spontaneous calcium events, as well as a reorganization of correlations between olfactory glomeruli during ongoing activity. Accompanying these plastic changes, we find that repeated odor experience reduces trial-to-trial variability and enhances the specificity of odor representations. Our results reveal a previously undescribed experience-dependent plasticity of ongoing and sensory driven activity at peripheral levels of the fruit fly olfactory system.
Effect of anthropogenic vibratory noise on plant development and herbivory
Authors: Velilla Estefania , Bellato Laura , Collinson Eleanor , Halfwerk Wouter
Published: April 2021

A growth in anthropogenic activities and infrastructure has led to increasing subterranean vibratory noise levels. Inland wind energy turbines, which are mostly located in agricultural fields, are a fast growing source of vibrational noise. Plants, which are rooted in the soil are constantly exposed to windmill-induced vibrations propagating through the ground. We have little understanding on how anthropogenic seismic vibrations affect plant development and how that in turn can affect plant-insect interactions. In this study we investigated the effect of windmill-like underground vibrational noise on plant development and on a plant-herbivore interaction. We experimentally exposedPisum sativumplants from seed stage to seed production stage to high and low vibrational noise levels and monitored them daily. We recorded germination, flowering and fruiting time, as well as daily shoot-length growth. Moreover, we tested the direct and indirect effects of vibrational noise on herbivory intensity by the generalist caterpillarSpodoptera exigua. We found that plants exposed to high vibrational noise grew significantly faster and taller than plants exposed to low vibrational noise. Additionally, plants treated with high noise germinated, flowered and produced fruits quicker than those treated with low noise. However, the differences in germination time, flowering time and fruiting time between the treatments were not statistically significant. Furthermore, we did not find an effect of vibrational noise on herbivory intensity. Vibrational noise could have consequences for both natural plant communities and agricultural crops by altering interspecific competition and by shifting growth-defence activation trade-offs.