bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping and validation of the epistatic D and P genes controlling anthocyanin biosynthesis in the peel of eggplant (Solanum melongena L.) fruit
Authors: You Qian , Li Huimin , Wu Jun , Li Tao , Wang Yikui , Sun Guangwen , Li Zhiliang , Sun Baojuan
Published: December 2022

Fruit color is an important trait influencing the commercial value of eggplant fruits. Three dominant genes (D, P and Y) cooperatively control the anthocyanin coloration in eggplant fruits, but none has been mapped. In this study, two white-fruit accessions (19 141 and 19 147) and their F2 progeny, with 9:7 segregation ratio of anthocyanin pigmented versus non-pigmented fruits, were used for mapping the D and P genes. A high-density genetic map was constructed with 5270 SNPs spanning 1997.98 cM. Three QTLs were identified, including two genes on chromosome 8 and one on chromosome 10. Gene expression analyses suggested that the SmANS on chromosome 8 and SmMYB1 on chromosome 10 were the putative candidate genes for P and D, respectively. We further identified (1) a SNP leading to a premature stop codon within the conserved PLN03176 domain of SmANS in 19 141, (2) a G base InDel in the promoter region leading to an additional cis-regulatory element and (3) a 6-bp InDel within the R2-MYB DNA binding domain of SmMYB1, in 19 147. Subsequently, these three variations were validated by PARMS technology as related to phenotypes in the F2 population. Moreover, silencing of SmANS or SmMYB1 in the purple red fruits of F1 (E3316) led to inhibition of anthocyanin biosynthesis in the peels. Conversely, overexpression of SmANS or SmMYB1 restored anthocyanin biosynthesis in the calli of 19 141 and 19 147 respectively. Our findings demonstrated the epistatic interactions underlying the white color of eggplant fruits, which can be potentially applied to breeding of eggplant fruit peel color.
How design rules emerge and evolve: a coevolutionary architectural perspective on firm and industry organization
Authors: Sanchez Ron , Galvin Peter , Bach Norbert
Published: December 2022

This paper elaborates on how design rules emerge and evolve as firms’ micro-level choices of product and organization architectures coevolve with changes in product markets and an industry’s competitive and cooperative dynamics. We suggest that the design rules a firm adopts will vary according to firms’ strategic choices of product and organization architectures that they believe are or may become feasible in a given industry. Building on the mirroring hypothesis that product designs a firm adopts will influence the organization designs it uses, we develop a model that identifies key relationships that influence firms’ strategic choices of product and organization architectures and associated design rules. We then elaborate on key interactions between firm-level architectural choices and the architecture-enabled competitive and cooperative dynamics that obtain in an industry. Our model identifies strategically important aspects of open- and closed-system architectures and modular and nonmodular architectures that impact industry structures, interfirm interactions, and resulting industry dynamics. Drawing on these analyses, we suggest how firms’ strategic choices of architectures are influenced by their assessments of (i) the potential for capturing value through both gains from specialization and gains from trade that firms believe will be enabled by their architectural choices and (ii) both ex ante and ex post transaction costs implied by their architecture decisions. We conclude by suggesting how the perspective on firm’s strategic architectural decisions we develop here enables new approaches to understanding evolutions of both product markets and industry structures for serving product markets.
Management of Toxic Epidermal Necrolysis Using Early Combination Therapy of Intravenous Immunoglobulin and Amniotic Membrane Grafting: A Case Report
Authors: Bashiri Aliabadi Somaye , Haghani Dogahe Zahra , Feizkhah Alireza , Mobayen Mohammadreza , Mirbolouk Batoul
Published: December 2022

Toxic epidermal necrolysis (TEN) is a devastating challenge faced by wound care practitioners. However, surgical management with amniotic membrane graft (AMG) promises better results in scar healing, but there is a lack of additional intervention to reduce the high mortality rate in those patients who are admitted with poor prognosis clinical situation. There is supportive evidence that combination therapy with AMG and early high-dose intravenous immunoglobulin (IVIG) as early management in TEN could improve the prognosis. In this study, the authors present a 61-year-old female who presented with a widespread macular lesion on the trunk, upper extremities, and face. The patient was treated with early amniotic membrane grafting and high-dose IVIG and achieved satisfactory results. Complete wound healing was achieved in 21 days. There were no acute or chronic complications, consisting of infection of the skin areas, gastrointestinal bleeding, pleural effusion, and severe ocular mucous membrane damage.
Analysis of a large case series of fatal familial insomnia to determine tests with the highest diagnostic value
Authors: Kortazar-Zubizarreta Izaro , Eraña Hasier , Pereda Arrate , Charco Jorge M , Manero-Azua Africa , Ruiz-Onandi Rebeca , Aguirre Urko , Gonzalez-Chinchon Gonzalo ,   Basque Prionopathies Study Group, Prieto-Tedejo R , Somme J H , Perez Arantza Onaindia , Garcia-Moncó J C , Matute A , Uterga J M , Antigüedad A R , Losada J M , Velasco-Palacios L , Pinedo-Brochado A , Escalza I , González-Pinto T , López de Munain A , Moreno F , Zarranz Juan José , Pozo Nagore Siles , Jimenez Karol , Piñeiro Patricia , Perez de Nanclares Guiomar , Castilla Joaquín
Published: December 2022

Fatal familial insomnia (FFI) is a rare prionopathy with unusually high incidence in the Basque Country. We report detailed data on clinical, diagnostic, histopathological, and biochemical characteristics of a recent FFI case series. The Basque Brain Bank database was screened for patients diagnosed from 2010 to 2021 with standard genetic and/or neuropathological criteria. This series includes 16 patients, 25% without family history, with 12 cases from 9 unrelated (but geographically-linked, Basque country) kindreds, onset ranging from 36 to 70 years, and disease course from 7 to 11.5 months. Insomnia was the initial symptom in most cases, with consistent polysomnography in 92% of the cases. In contrast, 14-3-3 and RT-QuIC from cerebrospinal fluid were negative. Most patients were homozygous for methionine. Gliosis and neuronal loss in basal ganglia and thalamus were the main histopathological findings; Western blotting identified preferentially the protease-resistant prion protein (PrPres) type 2, although detection of the scrapie isoform of the prion protein (PrPSc) identified using brain tissue RT-QuIC was more successful. This is one of the largest current studies on FFI patients performed to provide improvements in diagnostic reliability. Among the analyzed tests, polysomnography and the genetic study show the highest diagnostic value in FFI.
The Importance of Medical Laboratory Scientists and the Number of Doctoral Scientists that Began Their Career by Working on the Front Lines of Laboratory Medicine
Authors: Sautter Rl , Halstead Dc
Published: December 2022

Background

Due to dwindling numbers of medical laboratory scientists (MLS), we are faced with staffing issues due to lack of visibility, recognition, low wages, and perceived lack of opportunities for upward career mobility. A brief survey of doctoral-level clinical microbiologists showed a significant number were certified, worked “the bench,” and used this experience as a steppingstone to become a laboratory director or consultant.

Objectives

To help dispel the notion working as an MLS is a dead-end job, the authors developed an expanded national survey.

Methods

The survey was sent to 815 board-certified microbiologists and chemists to determine their career path. Results indicated that of 243 respondents, 41.3% were MLS certified, 47.1% had worked “the bench,” and 51.9% and 63.5% became laboratory or technical directors, respectively.

Conclusion

Survey results provide evidence to dispel the notion that MLS and bench working jobs lack upward career mobility and may inspire students for a career in laboratory medicine.
Surgical Training for a Disaster: Preparation of Surgical Trainees for Victims of Conflict
Authors: Franko Jace J P , Vu Michael M , Parsons Michael E , Sohn Vance Y , Bingham Jason R
Published: December 2022

Introduction

With increasing global unrest and military physician shortages potentially leading to a surgeon draft, we sought to evaluate the readiness of graduating general surgery residents to care for casualties of war.

Materials and Methods

We evaluated the National Data Reports of Surgery Case Logs for general surgery residents from 2009 to 2018 to quantify experience with key procedures that provide critical skills required for wartime surgery. Reported cases from the Accreditation Council for Graduate Medical Education for graduating residents from civilian and military residency programs were analyzed for 28 individual procedures determined to be critical for the care of combat casualties. These included central and peripheral vascular procedures, as well as neck, thoracic, abdominal, and peripheral interventions.

Results

From 2009 to 2018, there has been a significant decrease in wartime-relevant cases by graduating residents. Notably, these include aorto-iliac/femoral bypasses (50% reduction; 7.1%/year; P < .001), femoral-popliteal bypasses (60% reduction; 6.9%/year; P < .001), femoral-femoral bypasses (30% reduction; 2.6%/year; P < .001), upper extremity amputations (50% reduction; 6.4%/year; P = .016), fasciotomies for trauma (50% reduction; 4.5%/year; P = .013), open repair of ruptured infrarenal aorto-iliac aneurysms (70% reduction; 5.8%/year; P < .001), repair of traumatic aorta or vena cava injuries (70% reduction; 7%/year; P = .007), carotid endarterectomies (40% reduction; 4%/year; P < .001), lung resections (40% reduction; 3.7%/year; P = .001), trauma splenectomies/splenorrhaphy (30% reduction; 2.9%/year; P < .001), and repair of traumatic liver lacerations (30% reduction; 2.5%/year; P = .036).

Conclusions

Graduating general surgery residents has limited exposure to wartime critical skills due to a significant reduction in open vascular, head and neck, thoracic, and operative trauma cases. As the threat of global war persists and new graduates continue to deploy worldwide, residency training must be augmented to ensure adequate preparation in case a surgeon draft is required to fulfill demand for military surgeons.
Sporotrichosis in dogs: epidemiological and clinical-therapeutic profile and the emergence of itraconazole-resistant isolates
Authors: Baes Pereira Sergiane , dos Reis Gomes Angelita , Bressan Waller Stefanie , Batista Xavier Jose Raphael , Messias Rodrigues Anderson , Kutscher Ripoll Márcia , Ferreira Marcos Roberto Alves , Rochedo Conceição Fabricio , Osório de Faria Renata , Pascoti Bruhn Fabio Raphael
Published: December 2022

Sporotrichosis is a neglected and emerging mycosis caused by the traumatic implantation of Sporothrix propagules into the (sub)cutaneous tissues of humans and animals. We evaluated canine sporotrichosis's clinical-therapeutic, epidemiological profile, and in vitro susceptibility of isolates to itraconazole. The variables were evaluated by a chi-square test. A total of 69 dogs were infected with Sporothrix spp., and the molecular identification revealed an overwhelming occurrence of S. brasiliensis as the etiological agent. The epidemiological profile was male (56.5%), adults (4.9 ± 1.92 years old; 69.6%), and mongrels (53.6%). The clinical signs were 76.8%, ulcers, draining tracts, and nodules were predominant, mainly in the nasal region (82.2%). Dogs were diagnosed late with an evolution time of up to 3 months (34.8%). According to the prior therapeutic information, 52.2% received empirical therapy, 79.2% antibiotics, and had a 0.29 significantly greater chance of presenting lesion evolution time ˃ 3 months (P < .05; Odds Ratio [OR] 1/0.29). Additionally, 25 S. brasiliensis isolates recovered between 2006–2012 (n = 15; Minimal inhibitory concentration (MIC): 0.06–2 μg/ml) and 2013–2018 (n = 10; MIC: 2→16 μg/ml) were tested against itraconazole (ITZ). These findings highlighted the resistance to ITZ in clinical cases due to S. brasiliensis occurring after 2013, showing the temporal evolution of ITZ-resistance. We warn of the importance of accurate and early diagnosis in Sporothrix-affected areas, and we report the emergence of ITZ-resistant isolates in Southern Brazil.
On the peculiar rotational evolution of PSR B0950+08
Authors: Gügercinoğlu Erbil , Köksal Elif , Güver Tolga
Published: December 2022

The long-term rotational evolution of the old, isolated pulsar, PSR B0950+08, is intriguing in that its spin-down rate displays sinusoidal-like oscillations due to alternating variations, both in magnitude and sign, of the second time derivative of the pulse frequency. We show that the large internal temperature to pinning energy ratio towards the base of the crust implied by the recent high surface temperature measurement of PSR B0950+08 leads to linear creep interaction between vortex lines and pinning sites to operate in this pulsar. Vortex lines assume a parabolic shape due to pinning to nuclear clusters and finite tension of vortices acts as a restoring force that tends to bring a vortex back to its straight shape. The resulting low-frequency oscillations of vortex lines combined with the time variable coupling between the internal superfluid components and the external pulsar braking torque give rise to an oscillatory spin-down rate. We apply this model to PSR B0950+08 observations for several external torque models. Our model has potential to constrain the radial extension of the closed magnetic field region in the outer core of neutron stars from the oscillation period of the spin-down rate.
A galactic breeze origin for the Fermi bubbles emission
Authors: Tourmente Olivier , Rodgers-Lee D , Taylor Andrew M
Published: December 2022

The origin of the Fermi bubbles, which constitute two gamma-ray emitting lobes above and below the Galactic plane, remains unclear. The possibility that this Fermi bubbles gamma-ray emission originates from hadronic cosmic rays advected by a subsonic Galactic outflow, or breeze, is here explored. The simulation of a breeze solution and subsequent cosmic ray transport is carried out using the hydrodynamical code, PLUTO, in combination with a cosmic ray transport code. The Galactic outflow model obtained is found to be compatible with both inferences of the decelerating outflow velocity profile of the gas in the Fermi bubbles region, and evidence for the presence of a large amount of hot ionized gas out in the Galactic halo region. Although simple, this model is found to be able to reproduce the observed Fermi-LAT energy flux at high Galactic latitudes. Following these results a prediction concerning the gamma-ray emission for 1–3 TeV photons is made for future comparison with CTA/SWGO measurements.
A Fisher matrix for gravitational-wave population inference
Authors: Gair Jonathan R , Antonelli Andrea , Barbieri Riccardo
Published: December 2022

We derive a Fisher matrix for the parameters characterizing a population of gravitational-wave events. This provides a guide to the precision with which population parameters can be estimated with multiple observations, which becomes increasingly accurate as the number of events and the signal-to-noise ratio of the sampled events increase. The formalism takes into account individual event measurement uncertainties and selection effects, and can be applied to arbitrary population models. We illustrate the framework with two examples: an analytical calculation of the Fisher matrix for the mean and variance of a Gaussian model describing a population affected by selection effects, and an estimation of the precision with which the slope of a power-law distribution of supermassive black hole masses can be measured using extreme-mass-ratio inspiral observations. We compare the Fisher predictions to results from Monte Carlo analyses, finding very good agreement.
Teens Less Susceptible to Vaping When Restricted to Tobacco-Flavored E-cigarettes: Implications for Flavored Tobacco Policies
Authors: Helgertz Sharrilyn , Kingsbury John
Published: December 2022

Introduction

Flavors added to tobacco products increase their appeal to youth and contribute to the youth vaping epidemic. To address this problem, over 340 localities have implemented various policies to restrict access to flavored tobacco products. Few studies have examined the extent to which restricting available e-cigarette flavors might affect e-cigarette initiation or cessation among youth.

Aims and Methods

A representative sample of Minnesota teens were asked about their use of e-cigarettes, symptoms of e-cigarette dependence and their willingness to use an e-cigarette under four flavor conditions: unspecified (any flavor); menthol, tobacco, or unflavored. Respondents with data on all four flavor conditions were included in the analysis (N = 2151).

Results

Cochran’s Q, McNemar, and exact binomial tests revealed that susceptibility to e-cigarette use was highest when the flavor was unspecified (38.2%), lower for unflavored (29.7%) and menthol-flavored e-cigarettes (26.7%), and lowest when the flavor was tobacco (21.0%). Among the subsets of students who had never tried e-cigarettes and students who reported signs of e-cigarette dependence, the largest decrease in susceptibility from unspecified flavor e-cigarettes was observed for tobacco-flavor, a decrease of 12.7 and 19.6 percentage points, respectively.

Conclusions

Whether teens had no experience using e-cigarettes or showed signs of dependence, the percentage of teens who were susceptible to using e-cigarettes was significantly lower when the flavor available was restricted. Susceptibility was lower for tobacco- and menthol-flavored than unflavored e-cigarettes, suggesting that teens consider these flavors aversive.

Implications

These results suggest that policies that eliminate all e-cigarette flavors except tobacco may be a powerful tool for advancing youth e-cigarette prevention and cessation goals by reducing the appeal of e-cigarettes to teens with different levels of experience with them, including teens who have never tried e-cigarettes and those who may find it difficult to quit using them.
Comments on the exact solutions of Mathieu’s equation by D. J. Daniel (2020)
Authors: Shin Ho-Chul
Published: December 2022

So-called exact solutions of Mathieu’s equation proposed by D. J. Daniel [Prog. Theor. Exp. Phys. 2020, 043A01 (2020)] are flawed and not computable.
Differentiation of central disorders of hypersomnolence with manual and artificial-intelligence-derived polysomnographic measures
Authors: Cesari Matteo , Egger Kristin , Stefani Ambra , Bergmann Melanie , Ibrahim Abubaker , Brandauer Elisabeth , Högl Birgit , Heidbreder Anna
Published: December 2022

Differentiation of central disorders of hypersomnolence (DOH) is challenging but important for patient care. This study aimed to investigate whether biomarkers derived from sleep structure evaluated both by manual scoring as well as with artificial intelligence (AI) algorithms allow distinction of patients with different DOH. We included video-polysomnography data of 40 narcolepsy type 1 (NT1), 26 narcolepsy type 2 (NT2), 23 patients with idiopathic hypersomnia (IH) and 54 participants with subjective excessive daytime sleepiness (sEDS). Sleep experts manually scored sleep stages. A previously validated AI algorithm was employed to obtain automatic hypnograms and hypnodensity graphs (where each epoch is represented as a mixture of sleep stage probabilities). One-thousand-three features describing sleep architecture and instability were extracted from manual/automatic hypnogram and hypnodensity graphs. After feature selection, random forest classifiers were trained and tested in a 5-fold-cross-validation scheme to distinguish groups pairwise (NT1-vs-NT2, NT1-vs-IH, …) and single groups from the pooled remaining ones (NT1-vs-rest, NT2-vs-rest,…). The accuracy/F1-score values obtained in the test sets were: 0.74 ± 0.04/0.79 ± 0.05 (NT1-vs-NT2), 0.89 ± 0.09/0.91 ± 0.08 (NT1-vs-IH), 0.93 ± 0.06/0.91 ± 0.07 (NT1-vs-sEDS), 0.88 ± 0.04/0.80 ± 0.07 (NT1-vs-rest), 0.65 ± 0.10/0.70 ± 0.09 (NT2-vs-IH), 0.72 ± 0.12/0.60 ± 0.10 (NT2-vs-sEDS), 0.54 ± 0.19/0.38 ± 0.13 (NT2-vs-rest), 0.57 ± 0.11/0.35 ± 0.18 (IH-vs-sEDS), 0.71 ± 0.08/0.35 ± 0.10 (IH-vs-rest) and 0.76 ± 0.08/0.71 ± 0.13 (sEDS-vs-rest). The results confirm previous findings on sleep instability in patients with NT1 and show that combining manual and automatic AI-based sleep analysis could be useful for better distinction of NT2 from IH, but no precise sleep biomarker of NT2 or IH could be identified. Validation in a larger and multi-centric cohort is needed to confirm these findings.
Tare Soil Alters the Composition of the Developing Potato Rhizosphere Microbiome
Authors: Delventhal Kayla , Busby Posy E. , Frost Kenneth
Published: December 2022

Understanding the factors influencing microbial community composition in the rhizosphere is an important step toward managing the microbiomes of globally important crops such as potato ( Solanum tuberosum). Potato is vegetatively propagated and seed tubers are planted with tare soil, or soil adhering to the tuber surface, from their field of origin. Bulk soil is known to influence rhizosphere microbiome composition but whether tare soil additionally contributes to compositional variation is not known. We tested this hypothesis in a greenhouse experiment where tare soil was removed (or remained intact for controls) prior to planting in either soil from a potato field or soil from a previously uncultivated area next the potato field. We used internal transcribed spacer and 16S metabarcoding to characterize the fungal and bacterial rhizosphere communities of plants grown from the experimental seed tubers. We found that tare soil influenced rhizosphere microbial composition, more strongly for fungi than bacteria. As expected, bulk soil origin explained the greatest amount of variation in the rhizosphere microbiome overall but we found no evidence that the impact of tare soil on microbial community composition differed between bulk soil origins. However, the magnitude of the tare soil effect did depend, in part, on seed tuber origin. Our findings reveal that tare soil explains a significant, though modest, amount of variation in rhizosphere composition, and sets the stage for future work addressing functional consequences for plant health and productivity.
Diabetes self-management education for adults with type 2 diabetes via telehealth in conjunction with remote patient monitoring: a best practice implementation project
Authors: Longwitz Ashley , Palokas Michelle
Published: December 2022

Objectives:

The purpose of this evidence implementation project was to promote evidence-based practices regarding the delivery of diabetes self-management education via telehealth in conjunction with remote patient monitoring within the University of Mississippi Medical Center, Center for Telehealth.

Introduction:

Diabetes self-management education plays a critical role in supporting self-care behaviors that can improve glycemic control, but certain patient populations have poor access to this service. Telehealth offers an innovative approach to addressing geographical and socioeconomic barriers to diabetes self-management education.

Methods:

This evidence implementation project used the JBI Practical Application of Clinical Evidence System (JBI PACES) and Getting Research into Practice (GRiP) framework for promoting evidence-based healthcare.

Application:

A baseline audit was conducted to identify areas of strengths where best practices were already being implemented and areas of opportunity for improvement. The project team aligned on practical and sustainable interventions for delivering optimal diabetes self-management education via telehealth. Postimplementation audits were conducted to determine success of the interventions.

Results:

Baseline audits revealed an average compliance of 47.7% with five best practices for diabetes self-management education for adults with type 2 diabetes via telehealth. After strategies to improve compliance were implemented, compliance improved to 80%.

Conclusions:

The objectives of this project were realized. The team was able to promote evidence-based practices regarding the delivery of education via telehealth in conjunction with remote patient monitoring, as evidenced by a measurable improvement in adherence to best practices. The primary intervention focused on individualization of education based on patient-specific needs.
Ecological and genetic trade-offs driveArabidopsis thalianarange expansion in Europe
Authors: Bastias Cristina C. , Estarague Aurélien , Vile Denis , Lee Cheng-Ruei , Exposito-Alonso Moises , Violle Cyrille , Vasseur François
Published: December 2022

How trade-offs between traits constrain adaptation to contrasted environments is critical to understand the distribution range of a given species. InArabidopsis thaliana, genetic analyses recently revealed that a group of genotypes successfully recolonized Europe from its center after the last glaciation, outcompeting older lineages and leaving them only at the distribution margins, where environmental conditions are more stressing. However, whether trade-offs between traits related to dispersal, competition, and stress tolerance explain the success and persistence of different lineages across the species geographic range remains an open question. Here, we compared the genetic and phenotypic differentiation between 72 ecotypes originating from three geographical groups in Europe (North, South and Center). We measured key traits related to fecundity, dispersal ability, competition tolerance, and stress tolerance, and used genomic data to infer the effect of selection on these traits. We showed that a trade-off between plant fecundity and seed mass constrains the diversification ofA. thalianain Europe. In particular, the success of the cosmopolitan genotypes that recolonized Europe can be explained by their higher dispersal ability at the expense of their competitive ability and stress tolerance. Inversely, peripheral ecotypes exhibited the opposite trait syndrome: high competition and stress tolerance but low dispersal ability. Moreover, peripheral genotypes tend to differentiate from central ones at genes involved in dispersal and competitive traits such as seed mass. Combining ecological and genomic approaches, our study demonstrated the role of key ecological trade-offs as evolutionary drivers of the distribution of plant populations along a geographic gradient.

Significance

Across geographic gradients, differential adaptive phenotypes among populations can reduce the risk of local extinctions and favor niche dynamics. However, a phenotypic advantage often comes at a cost. For instance, the competition-colonization trade-off is proposed as an important driver of plant interspecific diversity, but its role for local adaptation at the intraspecific level is still unclear. Using the broadly-distributed speciesArabidopsis thaliana, we evaluate how ecological trade-offs have shaped the demography and evolution of central and peripheral populations in its native geographic gradient. Our study demonstrates that the competition-colonization trade-off is responsible of the spatially-structured phenotypic variation ofA. thalianaacross its geographical range. Our study highlights seed mass as a key trait for plant adaptation across environmental conditions.
DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood
Authors: Issarapu Prachand , Arumalla Manisha , Elliott Hannah R. , Nongmaithem Suraj S. , Sankareswaran Alagu , Betts Modupeh , Sajjadi Sara , Kessler Noah J. , Bayyana Swati , Mansuri Sohail R. , Derakhshan Maria , Krishnaveni G. V. , Shrestha Smeeta , Kumaran Kalyanaraman , Gravio Chiara Di , Sahariah Sirazul A. , Sanderson Eleanor , Relton Caroline L. , Ward Kate A. , Moore Sophie E. , Prentice Andrew M , Lillycrop Karen A. , Fall Caroline H. D. , Silver Matt J. , Chandak Giriraj R. ,   EMPHASIS study group
Published: December 2022

Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigated links between blood DNA methylation and child height in four LMIC cohorts (n=1927) and identified a robust association at three CpGs in the suppressor of cytokine signalling 3 (SOCS3) gene which replicated in a high-income country cohort (n=879).SOCS3methylation (SOCS3m) – height associations were independent of genetic effects. Mendelian randomization analysis confirmed a causal effect ofSOCS3mon height. In longitudinal analysis in a LMIC cohort,SOCS3mexplained a maximum 9.5% of height variance in mid-childhood while the variance explained by height polygenic risk score increased from birth to 21 years (2% to 18%). Children’sSOCS3mwas associated with prenatal maternal folate and socio-economic status.In-vitrocharacterization confirmed a regulatory effect ofSOCS3mon gene expression. Our findings suggest that epigenetic modifications may play an important role in driving child height in LMIC.
Universal closed-tube barcoding for monitoring the shark and ray trade in megadiverse conservation hotspots
Authors: Prasetyo Andhika P. , Cusa Marine , Murray Joanna M. , Agung Firdaus , Muttaqin Efin , Mariani Stefano , McDevitt Allan D.
Published: December 2022

Trade restrictions for many endangered elasmobranch species exist to disincentivise their exploitation and curb their declines. However, the variety of products and the complexity of import/export routes make trade monitoring challenging. We investigate the use of a portable, universal, DNA-based tool which would greatly facilitatein-situmonitoring. We collected shark and ray samples across the Island of Java, Indonesia, and selected 28 species (including 22 CITES-listed species) commonly encountered in landing sites and export hubs to test a recently developed real-time PCR single-assay originally developed for screening bony fish. We employed a deep learning algorithm to recognize species based on DNA melt-curve signatures. By combining visual and machine learning assignment methods, we distinguished 25 out of 28 species, 20 of which were CITES-listed. With further refinement, this method can provide a practical tool for monitoring elasmobranch trade worldwide, without the need for a lab or the bespoke design of species-specific assays.

Highlights

We applied a portable, universal, closed-tube DNA barcoding approach originally developed for bony fishes to distinguish between shark and ray species traded in Indonesia.

We built a deep machine learning model to automatically assign species from the qPCR fluorescence spectra produced by two barcodes

The model achieved 79.41% accuracy for classifying 28 elasmobranch species, despite the barcode regions being designed for teleost species

This tool can serve as a potent single-assayin-situdiagnostic tool to regulate trade operations and it will be significantly enhanced by further optimisation of the barcode regions to fit elasmobranch DNA sequence variation
A chromatic feature detector in the retina signals visual context changes
Authors: Hoefling Larissa , Szatko Klaudia P , Behrens Christian , Qiu Yongrong , Klindt David Alexander , Jessen Zachary , Schwartz Gregory S , Bethge Matthias , Berens Philipp , Franke Katrin , Ecker Alexander S , Euler Thomas
Published: December 2022

The retina transforms patterns of light into visual feature representations supporting behaviour. These representations are distributed across various types of retinal ganglion cells (RGCs), whose spatial and temporal tuning properties have been extensively studied in many model organisms, including the mouse. However, it has been difficult to link the potentially nonlinear retinal transformations of natural visual inputs to specific ethological purposes. Here, we discover a novel selectivity to chromatic contrast in an RGC type that allows the detection of transitions of the horizon across a retinal region. We trained a convolutional neural network (CNN) model on large-scale functional recordings of RGC responses to natural mouse movies, and then used this model to search in silico for stimuli that maximally excite distinct types of RGCs. This procedure predicted centre colour-opponency in transient Suppressed-by-Contrast RGCs (tSbC), a cell type whose function is being debated. We confirmed experimentally that these cells indeed responded very selectively to Green-OFF, UV-ON contrasts, which we found to be characteristic of transitions from ground to sky in the visual scene, as might be elicited by head- or eye-movements across the horizon. Because tSbCs reliably detected these transitions, we suggest a role for this RGC type in providing contextual information (i.e. sky or ground) necessary for the selection of appropriate behavioural responses to other stimuli, such as looming objects. Our work showcases how a combination of experiments with natural stimuli and computational modelling allows discovering novel types of stimulus selectivity and identifying their potential ethological relevance.
The Class VIII myosin ATM1 is required for root apical meristem function
Authors: Olatunji Damilola , Clark Natalie M. , Kelley Dior R.
Published: December 2022

Myosins are evolutionarily conserved motor proteins that interact with actin filaments to regulate organelle transport, cytoplasmic streaming and cell growth. Plant-specific Class XI myosin proteins direct cell division and root organogenesis. However, the roles of plantspecific Class VIII myosin proteins in plant growth and development are less understood. Here, we investigated the function of an auxin-regulated Class VIII myosin, Arabidopsis thaliana Myosin 1 (ATM1), using genetics, transcriptomics, and live cell microscopy.ATM1is expressed in the primary root, adventitious roots and throughout lateral root development. ATM1 is a plasma membrane localized protein that is enriched in actively dividing cells in the root apical meristem (RAM). Loss ofATM1function results in impaired primary root growth due to decreased RAM size and reduced cell proliferation in a sugar-dependent manner. InATM1loss-of-function roots, columella reporter gene expression is diminished, and fewer columella stem cell divisions occur. In addition,atm1-1roots displayed reduced auxin responses and auxin marker gene expression. Complementation ofatm1-1with a tagged ATM1 driven under the nativeATM1promoter restored root growth and cell cycle progression in the root meristem. Collectively, these results provide novel evidence that ATM1 functions to influence cell proliferation and columella differentiation in primary roots in response to auxin and sugar cues.
Time of day analysis over a field grown developmental time course in rice
Authors: Michael Todd P.
Published: December 2022

Plants integrate time of day (TOD) information over an entire season to ensure optimal growth, flowering time, and grain fill. However, most TOD expression studies have focused on a limited number of combinations of daylength and temperature under laboratory conditions. Here we re-analyze anOryza sativa(rice) expression study that followed TOD expression in the field over an entire growing season. We find that likeArabidopsis thaliana, almost all rice genes have a TOD specific expression over the developmental time course. As has been suggested in other grasses, thermocycles were a stronger cue for TOD expression than the photocycles over the growing season. All the core circadian clock genes display consistent TOD expression over the season with the interesting exception that the two grass paralogs ofEARLY FLOWERING 3(ELF3) display a distinct phasing based on the interaction between thermo- and photo-cycles. The dataset also revealed how specific pathways are modulated to distinct TOD over the season consistent with the changing biology. The data presented here provides a resource for researchers to study how TOD expression changes under natural conditions over a developmental time course, which will guide approaches to engineer more resilient and prolific crops.
Two common issues in synchronized multimodal recordings with EEG: Jitter and Latency
Authors: Iwama Seitaro , Takemi Mitsuaki , Eguchi Ryo , Hirose Ryotaro , Morishige Masumi , Ushiba Junichi
Published: December 2022

Multimodal recording using electroencephalogram (EEG) and other biological signals (e.g., electromyograms, eye movement, pupil information, or limb kinematics) is ubiquitous in human neuroscience research. However, the precise time alignment of data from heterogeneous sources is limited due to variable recording parameters of commercially available research devices and experimental setups. Here, we introduced the versatility of a Lab Streaming Layer (LSL)-based application for multimodal recordings of high-density EEG and other devices such as eye trackers or hand kinematics. To introduce the benefit of recording multiple devices in a time-synchronized manner, we discuss two common issues in measuring multimodal data: jitter and latency. The LSL-based system can be used for research on precise time-alignment of datasets, such as detecting stimulus-induced transient neural responses and testing hypotheses well-formulated in time by leveraging the millisecond time resolution of the system.
Mechanism of receptor assembly via the pleiotropic adipokine Leptin
Authors: Tsirigotaki Alexandra , Dansercoer Ann , Verschueren Koen H.G. , Marković Iva , Pollmann Christoph , Hafer Maximillian , Felix Jan , Birck Catherine , Van Putte Wouter , Catteeuw Dominiek , Tavernier Jan , Bazan J. Fernando , Piehler Jacob , Savvides Savvas N. , Verstraete Kenneth
Published: December 2022

The adipokine Leptin activates its type I cytokine receptor (LEP-R) in the hypothalamus to regulate body weight and exerts additional pleiotropic functions in immunity, fertility, and cancer. However, the structure and mechanism of Leptin-mediated LEP-R assemblies has remained unclear. Here, we show that Leptin:LEP-R assemblies adopt an unprecedented structure within the type I cytokine receptor family featuring 3:3 stoichiometry. We validate Leptin-induced trimerization of LEP-R in the plasma membrane of living cells via multicolor single molecule microscopy. In mediating such assemblies Leptin undergoes drastic restructuring that activates its site III for binding to the Ig-domain of an adjacent LEP-R molecule in the complex. These interactions are abolished by pathological mutations linked to obesity. Collectively, our study uncovers an evolutionarily conserved Leptin:LEP-R assembly as a new mechanistic blueprint for Leptin-mediated signaling in physiology and disease, including insights into how the lowly abundant signaling-competent isoforms of LEP-R can productively participate in signaling.
The potential role of human immune cells in the systemic dissemination of enterovirus-D68
Authors: Laksono Brigitta M. , Na Ayudhya Syriam Sooksawasdi , Aguilar-Bretones Muriel , Embregts Carmen W. E. , van Nierop Gijsbert P , van Riel Debby
Published: December 2022

Enterovirus-D68 (EV-D68) often causes mild respiratory infections, but can also cause severe respiratory infections and extra-respiratory complications, including acute flaccid myelitis (AFM). Systemic dissemination of EV-D68 is crucial for the development of extra-respiratory diseases, but it is currently unclear how EV-D68 viremia occurs. We hypothesize that immune cells contribute to the systemic dissemination of EV-D68, as this is a mechanism commonly used by other enteroviruses. Therefore, we investigated the susceptibility and permissiveness of human primary immune cells for different EV-D68 isolates. In human peripheral blood mononuclear cells (PBMC) inoculated with EV-D68, only B cells were susceptible but virus replication was limited. However, B cell-rich cultures, such as Epstein-Barr virus-transformed B-lymphoblastoid cell line (BLCL) and primary lentivirus-transduced B cells, were productively infected. In BLCL, neuraminidase treatment to remove α2,6- and α2,3-linked sialic acids resulted in a significant decrease of EV-D68 infected cells, suggesting that sialic acids are the functional receptor on B cells. Subsequently, we showed that dendritic cells (DCs), particularly immature DCs, are susceptible and permissive for EV-D68 infection and that they can spread EV-D68 to autologous BLCL. Altogether, our findings suggest that immune cells, especially B cells and DCs, play an important role in the development the systemic dissemination of EV-D68 during an infection, which is an essential step towards the development of extra-respiratory complications.

Author summary

Enterovirus D68 (EV-D68) is an emerging respiratory virus that has caused outbreaks worldwide since 2014. EV-D68 infects primarily respiratory epithelial cells and the infection commonly results in mild respiratory diseases. However, EV-D68 infection is also associated with complications outside the respiratory tract, including a polio-like paralysis. Despite the severity of these extra-respiratory complications, it is unclear how EV-D68 is able to spread outside the respiratory tract and infect other organs, like the central nervous system (CNS). To understand this, we investigated if immune cells play a role in the extra-respiratory spread of EV-D68. We showed that EV-D68 can infect and replicate in specific immune cells,i.e. B cells and dendritic cells (DCs), and that the virus can be transferred from DCs to B cells. Our findings suggest that lymphoid tissues, which harbor many immune cells, can be a secondary replication site for EV-D68, from where virus is released in the circulation. Our data reveal the importance of immune cells in the systemic spread of EV-D68, which is essential for infection of extra-respiratory tissues. Intervention strategies that prevent EV-D68 infection of immune cells will therefore potentially prevent virus spread from the respiratory tract to other organs.
Prior Knowledge Biases the Perception of Body Postures
Authors: Han Qiu , Gandolfo Marco , Peelen Marius V.
Published: December 2022

Body postures provide information about others’ actions, intentions, and emotional states. However, little is known about how postures are represented in the brain’s visual system. Considering our extensive visual and motor experience with body postures, we hypothesized that priors derived from this experience may systematically bias visual body posture representations. We examined two priors: gravity and biomechanical constraints. Gravity pushes lifted body parts downwards, while biomechanical constraints limit the range of possible postures (e.g., an arm raised far behind the head cannot go down further). Across three experiments (N = 246) we probed participants’ memory of briefly presented postures using change discrimination and adjustment tasks. Results showed that lifted arms were misremembered as lower and as more similar to biomechanically plausible postures. Inverting the body stimuli eliminated both biases, implicating holistic body processing. Together, these findings show that knowledge shapes body posture representations, reflecting modulation from a combination of category-general and category-specific priors.
Reduced GS domain serine/threonine requirements of Fibrodysplasia Ossificans Progressiva mutant type I BMP receptor ACVR1 in the zebrafish
Authors: Allen Robyn S. , Jones William D. , Hale Maya , Warder Bailey N. , Shore Eileen M. , Mullins Mary C.
Published: December 2022

Fibrodysplasia ossificans progressiva (FOP) is a rare human genetic condition characterized by altered skeletal development and extra-skeletal bone formation. All cases of FOP are caused by mutations in the type I BMP receptor geneACVR1that result in over-activation of the BMP signaling pathway. Activation of the wild-type ACVR1 kinase requires assembly of a tetrameric type I and II BMP receptor complex followed by phosphorylation of the ACVR1 GS domain by type II BMP receptors. Previous studies showed that the FOP mutant ACVR1-R206H requires type II BMP receptors and presumptive GS domain phosphorylation for over-active signaling. Structural modeling of the FOP-ACVR1 mutant kinase domain supports that FOP mutations alter the conformation of the GS domain, but it is unclear how this leads to overactive signaling. Here we show using a developing zebrafish embryo BMP signaling assay that the FOP mutant receptors ACVR1-R206H and -G328R have reduced requirements for GS domain phosphorylation sites to signal compared to wild-type ACVR1. Further, ligandindependent and ligand-dependent signaling through the FOP ACVR1 receptors have distinct GS domain phosphorylation site requirements. Moreover, ACVR1-G328 showed increased GS domain serine/threonine requirements for ligand-independent signaling compared to ACVR1-R206H, whereas it exhibited reduced serine/threonine requirements for ligand-dependent signaling. Remarkably, while ACVR1-R206H does not require the type I BMP receptor partner, Bmpr1, to signal, a ligand-dependent GS domain mutant of ACVR1-R206H could signal independently of Bmpr1 only when Bmp7 ligand was overexpressed. Of note, unlike human ACVR1-R206H, the zebrafish paralog Acvr1l-R203H does not show increased signaling activity. However, in domain-swapping studies the human kinase domain, but not the human GS domain, was sufficient to confer overactive signaling to the Acvr1l-R203H receptor. Together these results reflect the importance of GS domain activation and kinase domain functions in regulating ACVR1 signaling and identify mechanisms of reduced regulatory constraints conferred by FOP mutations.
Specialized metabolic convergence in the gut microbiomes of cycad-feeding insects tolerant to β-methylamino-L-alanine (BMAA)
Authors: Gutiérrez-García Karina , Whitaker Melissa R.L. , Bustos-Díaz Edder D. , Salzman Shayla , Ramos-Aboites Hilda E. , Reitz Zachary L. , Pierce Naomi E. , Cibrián-Jaramillo Angélica , Barona-Gómez Francisco
Published: December 2022

Ingestion of the cycad toxins β-methylamino-L-alanine (BMAA) and azoxyglycosides is harmful to diverse organisms. However, some insects are specialized to feed on toxin-rich cycads with apparent immunity. Some cycad-feeding insects possess a common set of gut bacteria, which might play a role in detoxifying cycad toxins. Here, we investigated the composition of gut microbiota from a worldwide sample of cycadivorous insects and characterized the biosynthetic potential of bacteria isolated as putative keystone taxa. Cycadivorous insects shared a core gut microbiome consisting of six bacterial taxa, mainly belonging to the Proteobacteria, which we were able to isolate. To further investigate these potential keystone taxa from diverging lineages, we performed shotgun metagenomic sequencing of co-cultured bacterial sub-communities. We postulate and characterize four putative keystone bacteria fromSerratia, Pantoea, and two differentStenotrophomonaslineages. The biosynthetic potential of these microorganisms includes a suite of biosynthetic gene clusters notably rich in siderophores and carotenoid-like aryl polyene pathways. Siderophore semi-untargeted metabolomics revealed a broad range of chemically related yet diverse iron-chelating metabolites, indicating a complex evolutionary landscape in which siderophores may have converged within the guts of cycadivorous insects. Among these, we provide evidence of the occurrence of an unprecedent desferrioxamine-like biosynthetic pathway that remains to be identified. These results provide a foundation for future investigations into how cycadivorous insects tolerate diets rich in azoxyglycosides, BMAA, and other cycad toxins, and highlight convergent evolution underlying chemical diversity.