bluuebunny/crossref_metadata_2025 huggingface dataset:
The clinical phenotype of systemic sclerosis patients with anti-PM/Scl antibodies: results from the EUSTAR cohort
Authors: Lazzaroni Maria-Grazia , Marasco Emiliano , Campochiaro Corrado , DeVries-Bouwstra Jeska , Gonzalez-Perez Montserrat-Ixchel , Rojas-Serrano Jorge , Hachulla Eric , Zanatta Elisabetta , Barsotti Simone , Furini Federica , Triantafyllias Konstantinos , Abignano Giuseppina , Truchetet Marie-Elise , De Luca Giacomo , De Langhe Ellen , Hesselstrand Roger , Ingegnoli Francesca , Bertoldo Eugenia , Smith Vanessa , Bellando-Randone Silvia , Poormoghim Hadi , Colombo Enrico , Ceribelli Angela , Furloni Alessio , Zingarelli Stefania , Cavazzana Ilaria , Franceschini Franco , Del Galdo Francesco , Denton Christopher P , Cavagna Lorenzo , Distler Oliver , Allanore Yannick , Airò Paolo ,   for the EUSTAR co-authors
Published: February 2021

Objective

To evaluate clinical associations of anti-PM/Scl antibodies in patients with SSc in a multicentre international cohort, with particular focus on unresolved issues, including scleroderma renal crisis (RC), malignancies, and functional outcome of interstitial lung disease (ILD).

Methods

(1) Analysis of SSc patients from the EUSTAR database: 144 anti-PM/Scl+ without SSc-specific autoantibodies were compared with 7202 anti-PM/Scl−, and then to 155 anti-Pm/Scl+ with SSc-specific antibodies. (2) Case–control study: additional data were collected for 165 anti-PM/Scl+ SSc patients (85 from the EUSTAR registry) and compared with 257 anti-PM/Scl− SSc controls, matched for sex, cutaneous subset, disease duration and age at SSc onset.

Results

Patients with isolated anti-PM/Scl+, as compared with anti-Pm/Scl−, had higher frequency of muscle involvement, ILD, calcinosis and cutaneous signs of DM, but similar frequency of SRC and malignancies (either synchronous with SSc onset or not). The presence of muscle involvement was associated with a more severe disease phenotype. Although very frequent, ILD had a better functional outcome in cases than in controls. In patients with both anti-PM/Scl and SSc-specific antibodies, a higher frequency of typical SSc features than in those with isolated anti-PM/Scl was observed.

Conclusion

The analysis of the largest series of anti-PM/Scl+ SSc patients so far reported helps to delineate a specific clinical subset with muscle involvement, cutaneous DM, calcinosis and ILD characterized by a good functional outcome. SRC and malignancies do not seem to be part of this syndrome.
Learning from Feedback: Evidence from New Ventures*
Authors: Howell Sabrina T
Published: February 2021

This article studies how early-stage entrepreneurs respond to negative feedback about the quality of their ventures. We use data from new venture competitions, some of which privately inform founders of their relative rank. The empirical strategy compares lower and higher ranked losers across competitions in which they did and did not observe their standing. Receiving negative feedback increases average venture abandonment by 13%. Differences in responsiveness—for example, in venture risk, venture maturity, and signal precision—are consistent with particular theories about entrepreneurship, including the importance of experimentation.
Metabolic responses of date palm (Phoenix dactyliferaL.) leaves to drought differ in summer and winter climate
Authors: Du Baoguo , Kruse Joerg , Winkler Jana Barbro , Alfarraj Saleh , Albasher Gadah , Schnitzler Joerg-Peter , Ache Peter , Hedrich Rainer , Rennenberg Heinz
Published: February 2021

Drought negatively impacts growth and productivity of plants, particularly in arid and semi-arid regions. Although drought events can take place in summer and winter, differences in the impact of drought on physiological processes between seasons are largely unknown. The aim of this study was to elucidate metabolic strategies of date palms in response to drought in summer and winter season. To identify such differences, we exposed date palm seedlings to a drought-recovery regime, both in simulated summer and winter climate. Leaf hydration, carbon discrimination (${\Delta}$13C), and primary and secondary metabolite composition and contents were analyzed. Depending on season, drought differently affected physiological and biochemical traits of the leaves. In summer, drought induced significantly decreased leaf hydration, concentrations of ascorbate, most sugars, primary and secondary organic acids, as well as phenolic compounds, while thiol, amino acid, raffinose and individual fatty acid contents were increased compared with well-watered plants. In winter, drought had no effect on leaf hydration, ascorbate and fatty acids contents, but resulted in increased foliar thiol and amino acid levels as observed in summer. Compared with winter, foliar traits of plants exposed to drought in summer only partly recovered after re-watering. Memory effects on water relations, and primary and secondary metabolites seem to prepare foliar traits of date palms for repeated drought events in summer. Apparently, a well-orchestrated metabolic network, including the anti-oxidative system, compatible solutes accumulation and osmotic adjustment, and maintenance of cell-membrane stability strongly reduces the susceptibility of date palms to drought. These mechanisms of drought compensation may be more frequently required in summer.
iTRAQ-Based Quantitative Proteomics Reveals ChAcb1 as a Novel Virulence Factor in Colletotrichum higginsianum
Authors: Yan Yaqin , Tang Jintian , Yuan Qinfeng , Liu Liping , Liu Hao , Huang Junbin , Hsiang Tom , Zheng Lu
Published: February 2021

Colletotrichum higginsianum is an important hemibiotrophic fungal pathogen that causes anthracnose disease on various cruciferous plants. Discovery of new virulence factors could lead to strategies for effectively controlling anthracnose. Acyl-CoA binding proteins (ACBPs) are mainly involved in binding and trafficking acyl-CoA esters in eukaryotic cells. However, the functions of this important class of proteins in plant fungal pathogens remain unclear. In this study, we performed an isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomic analysis to identify differentially expressed proteins (DEPs) between a nonpathogenic mutant ΔCh-MEL1 and the wild type. Based on iTRAQ data, DEPs in the ΔCh-MEL1 mutant were mainly associated with melanin biosynthesis, carbohydrate and energy metabolism, lipid metabolism, redox processes, and amino acid metabolism. Proteomic analysis revealed that many DEPs might be involved in growth and pathogenesis of C. higginsianum. Among them, an acyl-CoA binding protein, ChAcb1, was selected for further functional studies. Deletion of ChAcb1 caused defects in vegetative growth and conidiation. ChAcb1 is also required for response to hyperosmotic and oxidative stresses, and maintenance of cell wall integrity. Importantly, the ΔChAcb1 mutant exhibited reduced virulence, and microscopic examination revealed that it was defective in appressorial penetration and infectious growth. Furthermore, the ΔChAcb1 mutant was impaired in fatty acid and lipid metabolism. Taken together, ChAcb1 was identified as a new virulence gene in this plant pathogenic fungus.
Comparison of qPCR and Metabarcoding Methods as Tools for the Detection of Airborne Inoculum of Forest Fungal Pathogens
Authors: Chandelier Anne , Hulin Julie , San Martin Gilles , Debode Frédéric , Massart Sébastien
Published: February 2021

Forest diseases caused by invasive fungal pathogens are becoming more common, sometimes with dramatic consequences to forest ecosystems. The development of early detection systems is necessary for efficient surveillance and to mitigate the impact of invasive pathogens. Windborne spores are an important pathway for introduction of fungal pathogens into new areas; the design of spore trapping devices adapted to forests, capable of collecting different types of spores, and aligned with development of efficient molecular methods for detection of the pathogen, should help forest managers anticipate new disease outbreaks. Two types of Rotorod samplers were evaluated for the collection of airborne inoculum of forest fungal pathogens with a range of spore sizes in five forest types. Detection was by specific quantitative PCR (qPCR) and by high-throughput sequencing (HTS) of amplified internal transcribed spacer sequences using a new bioinformatic pipeline, FungiSearch, developed for diagnostic purposes. Validation of the pipeline was conducted on mock communities of 10 fungal species belonging to different taxa. Although the sensitivity of the new HTS pipeline was lower than the specific qPCR, it was able to detect a wide variety of fungal pathogens. FungiSearch is easy to use, and the reference database is updatable, making the tool suitable for rapid identification of new pathogens. This new approach combining spore trapping and HTS detection is promising as a diagnostic tool for invasive fungal pathogens.
A Step Further—The Role of Trigeminocardiac Reflex in Therapeutic Implications: Hypothesis, Evidence, and Experimental Models
Authors: Chowdhury Tumul , Lemaître Frédéric , Golanov Eugene , Kuypers Kristel L.A.M. , Buchholz Bruno , Gelpi Ricardo J. , Schaller Bernhard
Published: February 2021

The trigeminocardiac reflex (TCR) is a well-recognized brainstem reflex that represents a unique interaction between the brain and the heart through the Vth and Xth cranial nerves and brainstem nuclei. The TCR has mainly been reported as an intraoperative phenomenon causing cardiovascular changes during skull-base surgeries. However, it is now appreciated that the TCR is implicated during non-neurosurgical procedures and in nonsurgical conditions, and its complex reflex pathways have been explored as potential therapeutic options in various neurological and cardiovascular diseases. This narrative review presents an in-depth overview of hypothetical and experimental models of the TCR phenomenon in relation to the Vth and Xth cranial nerves. In addition, primitive interactions between these 2 cranial nerves and their significance are highlighted. Finally, therapeutic models of the complex interactions of the TCR and areas for further research will be considered.
Implementing Evidence-Informed Discharge Preparedness Tools in the NICU
Authors: Mazur Kathleen M. , Desmadryl Megan , VanAntwerp Katherine , Ziegman Corrie , Nemshak Michelle , Shuman Clayton J.
Published: February 2021

Background:

Few studies address preparing parents of neonatal intensive care unit (NICU) infants for infant discharge. Inadequate or ineffective parental preparedness for discharge can result in preventable emergency department and primary care visits. Parents' perceptions are needed to inform development and implementation of effective educational tools to improve parent discharge preparedness in the NICU.

Purpose:

To describe the perceptions of parents of recently discharged NICU infants regarding discharge preparedness and implementation of the My Flight Plan for Home parent discharge preparedness tool.

Methods:

We used a qualitative descriptive design to collect individual interview data from 15 parents with infants discharged from a level 4 NICU in the Midwest. Individual interviews were conducted using a semistructured guide and were audio-recorded, transcribed verbatim, and thematically analyzed using the constant comparative method.

Results:

We identified 5 major themes: (1) family dynamics; (2) parenting in the NICU; (3) discharge preparedness; (4) engaging parents in infant care; and (5) implementation recommendations for the My Flight Plan for Home tool. Minor themes supported each of the major themes.

Implications for Practice:

To improve parents' confidence in caring for their infant after discharge, parents suggest nurses must engage parents in discharge education and infant care shortly following NICU admission and use parent-centered discharge preparedness tools.

Implications for Research:

Future studies are needed to develop and test parent-tailored strategies for implementing parent discharge preparedness tools in the NICU.
Chronic Infusion of Astaxanthin Into Hypothalamic Paraventricular Nucleus Modulates Cytokines and Attenuates the Renin–Angiotensin System in Spontaneously Hypertensive Rats
Authors: Gao Hong-Li , Yu Xiao-Jing , Liu Kai-Li , Zuo Yi-Yi , Fu Li-Yan , Chen Yan-Mei , Zhang Dong-Dong , Shi Xiao-Lian , Qi Jie , Li Ying , Yi Qiu-Yue , Tian Hua , Wang Xiao-Min , Yu Jia-Yue , Zhu Guo-Qing , Liu Jin-Jun , Kang Kai B. , Kang Yu-Ming
Published: February 2021

Oxidative stress, the renin–angiotensin system (RAS), and inflammation are some of the mechanisms involved in the pathogenesis of hypertension. The aim of this study is to examine the protective effect of the chronic administration of astaxanthin, which is extracted from the shell of crabs and shrimps, into hypothalamic paraventricular nucleus (PVN) in spontaneously hypertensive rats. Animals were randomly assigned to 2 groups and treated with bilateral PVN infusion of astaxanthin or vehicle (artificial cerebrospinal fluid) through osmotic minipumps (Alzet Osmotic Pumps, Model 2004, 0.25 μL/h) for 4 weeks. Spontaneously hypertensive rats had higher mean arterial pressure and plasma level of norepinephrine and proinflammatory cytokine; higher PVN levels of reactive oxygen species, NOX2, NOX4, IL-1β, IL-6, ACE, and AT1-R; and lower PVN levels of IL-10 and Cu/Zn SOD, Mn SOD, ACE2, and Mas receptors than Wistar–Kyoto rats. Our data showed that chronic administration of astaxanthin into PVN attenuated the overexpression of reactive oxygen species, NOX2, NOX4, inflammatory cytokines, and components of RAS within the PVN and suppressed hypertension. The present results revealed that astaxanthin played a role in the brain. Our findings demonstrated that astaxanthin had protective effect on hypertension by improving the balance between inflammatory cytokines and components of RAS.
Relationship Between Thiopurine S-Methyltransferase Genotype/Phenotype and 6-Thioguanine Nucleotide Levels in 316 Patients With Inflammatory Bowel Disease on 6-Thioguanine
Authors: Bayoumy Ahmed B. , Mulder Chris J. J. , Loganayagam Aathavan , Sanderson Jeremy D. , Anderson Simon , Boekema Paul J. , Derijks Luc J. J. , Ansari Azhar R.
Published: February 2021

Background:

In inflammatory bowel disease (IBD), conventional thiopurine users cease treatment in 60% of cases within 5 years, mostly because of adverse events or nonresponse. In this study, the authors aimed to investigate the role of 6-thioguanine nucleotide (TGN) measurements, geno/phenotyping of thiopurine S-methyltransferase (TPMT), and their mutual relationship with TG therapy in IBD.

Methods:

An international retrospective, multicenter cohort study was performed at 4 centers in the Netherlands (Máxima Medical Centre) and the United Kingdom (Guy's and St. Thomas' Hospital, Queen Elizabeth Hospital, and East Surrey Hospital).

Results:

Overall, 526 6-TGN measurements were performed in 316 patients with IBD. The median daily dosage of TG was 20 mg/d (range 10–40 mg/d), and the median duration of TG use was 21.1 months (SD, 28.0). In total, 129 patients (40.8%) had a known TPMT status. In the variant-type and wild-type TPMT genotype metabolism groups, median 6-TGN values were 1126 [interquartile range (IQR) 948–1562] and 467.5 pmol/8 × 10E8 red blood cells (RBCs) (IQR 334–593). A significant difference was observed between the 2 groups (P = 0.0001, t test). For TPMT phenotypes, in the slow, fast, and normal metabolism groups, the median 6-TGN values were 772.0 (IQR 459–1724), 296.0 (IQR 200–705), and 774.5 pmol/8 × 10E8 RBCs (IQR 500.5–981.5), with a significant difference observed between groups (P < 0.001, analysis of variance).

Conclusions:

Our findings indicated that TPMT measurements at TG initiation can be useful but are not necessary for daily practice. TPMT genotypes and phenotypes are both associated with significant differences in 6-TGN levels between metabolic groups. However, the advantage of TG remains that RBC 6-TGN measurements are not crucial to monitor treatments in patients with IBD because these measurements did not correlate with laboratory result abnormalities. This presents as a major advantage in countries where patients cannot access these diagnostic tests.
Initial Serum C-reactive Protein Level as a Predictor of Increasing Serum Vancomycin Concentration During Treatment
Authors: Isoda Kazuya , Nakade Junya , Suga Yukio , Fujita Arimi , Shimada Tsutomu , Sai Yoshimichi
Published: February 2021

Background:

Vancomycin has a narrow therapeutic window, and an increase in its serum concentration-to-dose ratio during treatment can cause renal toxicity. Therefore, this study was aimed at finding a marker to identify patients at risk of increasing serum vancomycin during treatment.

Methods:

This was a retrospective cohort study of patients treated with vancomycin at Kanazawa University Hospital, Japan, from April 2012 to May 2015. Spearman correlation coefficients were calculated to determine the correlations between changes in vancomycin concentration-to-dose ratio and initial values or changes in laboratory data and other parameters. In addition, a multiple regression analysis was conducted.

Results:

One hundred ninety-nine patients for whom 2 or more points of data on therapeutic drug monitoring (TDM) of intravenous vancomycin treatment were available and did not undergo dialysis were included in the study. Changes in vancomycin concentration-to-dose ratio were associated with C-reactive protein (CRP) and sodium (Na) levels on the initial day of TDM and with changes in white blood cell count, Na, and estimated glomerular filtration rates (eGFRs). Multiple regression analysis helped identify CRP and Na levels on the initial day of TDM and change in eGFR as independent influencing variables.

Conclusions:

A high serum CRP level on the initial day of TDM is an independent predictor of increasing vancomycin concentration-to-dose ratio in patients receiving intravenous vancomycin treatment, even if eGFR remains unchanged.
Epidemiology of Achilles Tendon Rupture in Italian First Division Football (Soccer) Players and Their Performance After Return to Play
Authors: Grassi Alberto , Caravelli Silvio , Fuiano Mario , D'Hooghe Pieter , Filippini Matteo , Della Villa Francesco , Mosca Massimiliano , Zaffagnini Stefano
Published: February 2021

Objective:

To evaluate the epidemiology, incidence rate, incidence proportion, and prevalence of Achilles tendon ruptures (ATRs) in professional footballers and their performance after the injury.

Data Sources:

Professional male footballers participating in Serie A in 11 consecutive seasons (2008/2009-2018/2019) were screened to identify ATRs through the online football archive transfermarkt.com. Exposure in matches and training was calculated. The number of matches played in the 5 seasons before and after ATRs was obtained, when possible, together with transfers to a different team or participation in lower Divisions.

Main Results:

Eleven ATRs were found in 11 footballers with a mean age of 29.8 ± 4.4 years; 72% of ATR involved the nondominant leg; 58% occurred during matches and 42% during training, with no peculiar distribution along the playing season. The overall incidence proportion was 0.17% (0.11% during matches and 0.06% during training). The overall incidence rate was 0.007 injuries per 1000 hours of play (0.051 during matches and 0.003during training; P < 0.0001). All players returned to play soccer after a mean of 170 ± 35 days after ATRs and participated in an official match after a mean of 274 ± 98 days. However, 2 seasons after ATRs, 3 footballers were playing in a lower Division; 1 played less than 10 matches (compared with >25 matches in the 5 seasons before an ATR) and 1 had retired.

Conclusions:

An overall ATR rate of 0.007 per 1000 hours of soccer play and an incidence proportion of 0.17% were reported. All footballers return to play; however, up to 40% players decreased the level of play by reducing the number of games or participating in a lower Division 2 seasons after an ATR.
Pleural Drainage Strategy After IPC Placement
Authors: Gilbert Christopher R. , Miller Russell J.
Published: February 2021

The first indwelling pleural catheter (IPC) received Federal Drug Administration approval in 1997, nearly 40 years after John Chambers first described instillation of talc into the pleural space for palliation of malignant pleural effusions. Since then IPCs have revolutionized the management of malignant pleural effusions, providing an effective means of controlling dyspnea in the end stages of life without the pain and prolonged hospital stays long associated with chemical sclerosing agents. While palliation of symptoms is the primary purpose of IPCs, development of pleurodesis in the outpatient setting is often an important secondary goal. Historically, decisions regarding IPC drainage frequency have been largely arbitrary and only recently has the evidence started to emerge regarding the effects of specific drainage strategies on both symptom control and pleurodesis development. This focused clinical review explores the current literature regarding IPC drainage strategies as well as novel methods designed to improve the efficacy of IPCs in a thorough and systematic manner. In addition, this review provides an in-depth analysis and synthesis of the data focusing on key considerations needed to develop patient-centered and cost-effective strategies for the use of IPCs in malignancy.
Effects of Laser Therapy on Rheumatoid Arthritis
Authors: Chia Wen-Chun , Chang Ching-Hsiang , Hou Wen-Hsuan
Published: February 2021

Objective

The aim of the study was to examine the effects of laser therapy on rheumatoid arthritis.

Design

A search of controlled trials was conducted in different medical electronic databases. The primary outcome was immediate pain relief after treatment. Secondary outcomes were level of functional disability, morning stiffness duration, and 3-mo follow-up for pain.

Results

Ten trials met the inclusion criteria. Rheumatoid arthritis treatment with laser therapy significantly improved immediate pain relief (standardized mean difference = −0.839, 95% confidence interval = −1.336 to −0.343) and overall functional score (standardized mean difference = −0.309, 95% confidence interval = −0.587 to −0.031). There was no significant improvement in morning stiffness duration (standardized mean difference = −0.519, 95% confidence interval = −1.176 to 0.138), and 3-mo follow-up for pain (standardized mean difference = −1.125, 95% confidence interval = −2.311 to 0.061). There was no publication bias (Egger regression, P = 0.277). However, heterogeneity was noted despite the removal of an outlier (Q = 18.646, I
2 = 57.096). Results of subgroup analyses suggested that high-intensity laser therapy and nerve irradiation are better suited for immediate pain relief. Meta-regression analyses showed no significant linear relationship between the treatment effect with laser wavelength or number of treatment sessions.

Conclusions

Laser therapies provide significant immediate pain relief and improve function for rheumatoid arthritis patients, but without significant improvement in morning stiffness duration and 3-mo follow-up for pain.

Systematic review registration number: CRD42020192906.
How FAIR are plant sciences in the twenty-first century? The pressing need for reproducibility in plant ecology and evolution
Authors: Manzano Saúl , Julier Adele C. M.
Published: February 2021

The need for open, reproducible science is of growing concern in the twenty-first century, with multiple initiatives like the widely supported FAIR principles advocating for data to be Findable, Accessible, Interoperable and Reusable. Plant ecological and evolutionary studies are not exempt from the need to ensure that the data upon which their findings are based are accessible and allow for replication in accordance with the FAIR principles. However, it is common that the collection and curation of herbarium specimens, a foundational aspect of studies involving plants, is neglected by authors. Without publicly available specimens, huge numbers of studies that rely on the field identification of plants are fundamentally not reproducible. We argue that the collection and public availability of herbarium specimens is not only good botanical practice but is also fundamental in ensuring that plant ecological and evolutionary studies are replicable, and thus scientifically sound. Data repositories that adhere to the FAIR principles must make sure that the original data are traceable to and re-examinable at their empirical source. In order to secure replicability, and adherence to the FAIR principles, substantial changes need to be brought about to restore the practice of collecting and curating specimens, to educate students of their importance, and to properly fund the herbaria which house them.
No severe genetic bottleneck in a rapidly range-expanding bumblebee pollinator
Authors: Brock Ryan E. , Crowther Liam P. , Wright David J. , Richardson David S. , Carvell Claire , Taylor Martin I. , Bourke Andrew F. G.
Published: February 2021

Genetic bottlenecks can limit the success of populations colonizing new ranges. However, successful colonizations can occur despite bottlenecks, a phenomenon known as the genetic paradox of invasion. Eusocial Hymenoptera such as bumblebees (Bombusspp.) should be particularly vulnerable to genetic bottlenecks, since homozygosity at the sex-determining locus leads to costly diploid male production (DMP). The Tree Bumblebee (Bombus hypnorum) has rapidly colonized the UK since 2001 and has been highlighted as exemplifying the genetic paradox of invasion. Using microsatellite genotyping, combined with the first genetic estimates of DMP in UKB. hypnorum, we tested two alternative genetic hypotheses (‘bottleneck’ and ‘gene flow’ hypotheses) forB. hypnorum's colonization of the UK. We found that the UK population has not undergone a recent severe genetic bottleneck and exhibits levels of genetic diversity falling between those of widespread and range-restrictedBombusspecies. Diploid males occurred in 15.4% of reared colonies, leading to an estimate of 21.5 alleles at the sex-determining locus. Overall, the findings show that this population is not bottlenecked, instead suggesting that it is experiencing continued gene flow from the continental European source population with only moderate loss of genetic diversity, and does not exemplify the genetic paradox of invasion.
Schoolchildren cooperate more successfully with non-kin than with siblings
Authors: Barragan-Jason Gladys , Cauchoix Maxime , Regnier Anne , Bourjade Marie , Hopfensitz Astrid , Chaine Alexis S.
Published: February 2021

Cooperation plays a key role in the development of advanced societies and can be stabilized through shared genes (kinship) or reciprocation. In humans, cooperation among kin occurs more readily than cooperation among non-kin. In many organisms, cooperation can shift with age (e.g. helpers at the nest); however, little is known about developmental shifts between kin and non-kin cooperation in humans. Using a cooperative game, we show that 3- to 10-year-old French schoolchildren cooperated less successfully with siblings than with non-kin children, whether or not non-kin partners were friends. Furthermore, children with larger social networks cooperated better and the perception of friendship among non-friends improved after cooperating. These results contrast with the well-established preference for kin cooperation among adults and indicate that non-kin cooperation in humans might serve to forge and extend non-kin social relationships during middle childhood and create opportunities for future collaboration beyond kin. Our results suggest that the current view of cooperation in humans may only apply to adults and that future studies should focus on how and why cooperation with different classes of partners might change during development in humans across cultures as well as other long-lived organisms.
Solimonas marina sp. nov., isolated from deep seawater of the Pacific Ocean
Authors: Liu Xiupian , Lai Qiliang , Sun Fengqin , Du Yaping , Gai Yingbao , Li Guangyu , Shao Zongze
Published: February 2021

A taxonomic study was carried out on strain C16B3T, which was isolated from deep seawater of the Pacific Ocean. The bacterium was Gram-stain-negative, oxidase- and catalase- positive and rod-shaped. Growth was observed at salinities of 0–8.0 % and at temperatures of 10–45 °C. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain C16B3T belonged to the genus

Solimonas

, with the highest sequence similarity to

Solimonas terrae

KIS83-12T (97.2 %), followed by

Solimonas variicoloris

MN28T (97.0 %) and the other four species of the genus

Solimonas

(94.5 –96.8 %). The average nucleotide identity and estimated DNA–DNA hybridization values between strain C16B3T and the type strains of the genus

Solimonas

were 74.05−79.48 % and 19.5–22.5 %, respectively. The principal fatty acids (>5 %) were summed feature 8 (C18 : 1
 ω7c/C18 : 1
 ω6c; 20.9 %), iso-C16 : 0 (14.6 %), C16 : 1
 ω5c (9.4 %), iso-C12 : 0 (8.4 %), summed feature 2 (C14 : 0 3-OH/iso I-C16 : 1 and C12 : 0 aldehyde; 6.8 %) and C16 : 0 (5.5 %). The G+C content of the chromosomal DNA was 65.37 mol%. The respiratory quinone was determined to be Q-8 (100 %). The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, four unidentified aminolipids, six unidentified phospholipids and one unidentified polar lipid. The combined genotypic and phenotypic data show that strain C16B3T represents a novel species within the genus

Solimonas

, for which the name Solimonas marina sp. nov. is proposed, with the type strain C16B3T (=MCCC 1A04678T=KCTC 52314T).
In vitroevaluation of grapevine endophytes, epiphytes and sap micro-organisms for potential use to control grapevine trunk disease pathogens
Authors: Blundell Robert , Arreguin Molly , Eskalen Akif
Published: February 2021

Grapevine trunk diseases (GTDs) threaten the economic sustainability of viticulture worldwide causing a significant reduction of both yields and quality of grapes. Biological control presents a promising sustainable alternative to cultural and chemical methods to mitigate the effects of pathogens causing GTDs, including Botryosphaeria dieback, Eutypa dieback and Esca. This study aimed to identify naturally occurring potential biological control agents from a variety of grapevine tissues, including sap, cane and pith and evaluate their antagonistic activity against selected fungal pathogens responsible for GTDsin vitro. Bacterial and fungal isolates were preliminary screenedin vitroto determine their antifungal activity via a dual culture assay againstNeofusicoccum parvumandEutypa lata. Among the fungal isolates,Trichodermaspp. inhibitedE. latamycelial growth up to 64% andN. parvummycelial growth up to 73% with overgrowth and stopped growth being the likely antagonistic mechanisms. Among the bacterial isolates,Bacillusspp. inhibitedE. latamycelial growth up to 20% andN. parvummycelial growth up to 40%. Select antagonistic isolates ofTrichoderma, Bacillus and Aureobasidiumspp. were subject to further dual culture antifungal analysis againstDiplodia seriataandDiaporthe ampelina, withTrichodermaisolates consistently causing the greatest inhibition. Volatile organic compound antifungal analysis revealed that theseTrichodermaisolates resulted significantly inhibited mycelial growthof N. parvum, E. lata andD. ampelinacausing up to 20.11%, 60.55% and 70.9% inhibition respectively (P≤0.05). Multilocus sequence analysis revealed that theTrichodermaisolates are most closely related toTrichoderma asperellumandTrichoderma hamatum. This study identifies grapevine sap as a novel source of potential biological control agents for control of GTDs to support existing efforts to control GTDs. Further testing will be necessary to fully characterize these microbes mode of antagonism and assess their efficacy for pruning wound protectionin planta.
Catestatin regulates the colonic mucus layer in inflammatory bowel disease
Authors: Muntjewerff Elke M. , Lutter Lisanne , Tang Kechun , Lindert Mariska Kea-te , Fransen Jack , Oldenburg Bas , Mahata Sushil K. , van den Bogaart Geert
Published: February 2021

Background

The pro-hormone chromogranin A (CgA) and its bioactive cleavage product catestatin (CST) are both associated with inflammatory bowel disease (IBD) and dysregulated barrier functions, but their exact role has remained elusive. Here, we demonstrate that CST regulates the colonic mucus layer.

Methods

CST levels were measured in feces of IBD patients. The mucus layer, goblet cells, and immune cell infiltration were analyzed by histology and electron microscopy in colon tissue from IBD patients and mice with selective deletion of the CST-coding region of the CgA gene.

Results

CST levels were elevated in feces of IBD patients compared to healthy controls. The thickness of the mucus layer was increased in non-affected, but not in inflamed, regions of the colon in IBD patients. The thickness of the mucus layer and concomitant mucus production were also increased in the CST-KO mouse. This mucus phenotype in CST-KO mice could be reversed by bone marrow transplantation from wildtype mice.

Conclusions

CST produced by bone-marrow derived immune cells reduces production of the mucus layer in the intestine. This might contribute to the reduced mucus layer in inflamed colon regions of IBD patients. Additionally, CST feces levels might be a biomarker for IBD.
In-silicoStructural and Molecular Docking-Based Drug Discovery Against Viral Protein (VP35) of Marburg Virus: A potent Agent of MAVD
Authors: Quazi Sameer , Malik Javed , Capuzzo Arnaud Martino , Suman Kamal Singh , Haider Zeshan
Published: February 2021

The Marburg virus (MARV) is a highly etiological agent of hemorrhagic fever in humans. MARV has spread across the world, including America, Australia, Europe, and different Asia countries. However, there is no approved vaccine to combat MARV, combined with a high mortality rate, which makes antiviral drugs against MARV urgent. The viral protein (VP35) is a core protein of MARV that involves multiple functions of the infection cycle. This research used anin-silicodrug design technique to discover the new drug-like small molecules that inhibit VP35 replication. First, several combinations of ∼ 4260 showed that structure-based similarity above 90% was retrieved from an online “PubChem” database. Molecular docking was performed using AutoDock 4.2, and ligands were selected based on docking / S score lower than reference CID_5477931 and RMSD value between 1-2. Finally, about 50 compounds showed greater bonding producing hydrogen, Van der Waals, and polar interactions with VP35. After evaluating their binding energy strength and ADMET analysis, only CID_ 3007938 and CID_11427396 were finalized, which showed the most vital binding energy and a strong inhibitory effect with MARV’s VP35. The higher binding energy, suitable ADMET, and drug similarity parameters suggest that these “CID_ 3007938 and CID_11427396” candidates have incredible latency to inhibit MARV replication; hence, these strengths led to the treatment of MAVD.
DNA repair enzyme NEIL3 enables a stable neural representation of space by shaping transcription in hippocampal neurons
Authors: Kunath Nicolas , Bugaj Anna Maria , Bigonah Pegah , Fernandez-Berrocal Marion Silvana , Bjørås Magnar , Ye Jing
Published: February 2021

DNA repair enzymes are essential for the maintenance of neuronal genome and thereby proper brain functions. NEIL3 is a member of the NEIL family DNA glycosylases initiating oxidative DNA base excision repair. Recent studies show that NEIL3-deficiency leads to impaired spatial performance in mice, decreased adult neurogenesis and altered synaptic composition in the hippocampus. However, it remains elusive how NEIL3 contributes to spatial information coding in hippocampal neurons. Here, we revealed impaired spatial stability inNeil3−/−CA1 place cells, demonstrating a functional interference of NEIL3 with spatial representations. We identified NEIL3-dependent transcriptional changes in response to spatial exploration and defined its regulatory role specifically for NMDA receptor subunits and immediate early genes. Our work demonstrates a non-canonical role of NEIL3 in modulating the functional plasticity of place cells by shaping the neuronal transcriptome, thus sheds light on the molecular determinants enabling a stable neural representation of space.
Differential gene regulation in DAPT-treated Hydra reveals molecular pathways dependent on Notch signalling during interstitial cell differentiation and formation of the oral-aboral axis inHydra
Authors: Moneer Jasmin , Siebert Stefan , Krebs Stefan , Cazet Jack , Prexl Andrea , Pan Qin , Juliano Celina , Böttger Angelika
Published: February 2021

The Notch pathway is highly conserved and essential for animal development. We investigated the function of Notch-signalling inHydraby using the presenilin inhibitor DAPT, which efficiently blocks propagation of Notch-signals. InHydra, DAPT treatment prevents differentiation of proliferating nematocyte progenitor cells into mature nematocytes. Moreover, it causes defects in theHydrahead by compromising the head organizer. In order to understand the molecular mechanisms by which the Notch pathway regulates these processes we performed RNAseq to identify genes that are differentially regulated in response to 48 hours of DAPT-exposure. This revealed downregulation of 624 genes and upregulation of 207 genes. To identify candidate direct regulators of Notch-signalling, we also profiled gene expression changes that occur during restoration of Notch-activity 3 and 6 hours after DAPT-removal. We then analysed gene expression patterns of these Notch-responsive genes in untreated animals by interrogating the available single cell sequencing data set for untreated animals and found that almost half of the Notch responsive genes were specifically expressed in nematocytes and nematocyte progenitors. This confirms the critical role for Notch-signalling in nematocyte development. Promoter analyses and gene expression profiling after DAPT-removal suggested an indirect role for Notch in regulating aPOU-transcription factor, which is critical for nematogenesis. In support of a role for Notch-signalling in head organizer formation, we identified several head organizer genes in the Notch regulated gene data set, includingCngsc, a homologue ofgoosecoid,a gene associated with the Spemann organizer, and the Wnt pathway genesSp5, TcfandWnt-7.Finally, the expression levels of the tentacle patterning genesHyAlxandSp5rapidly recovered after DAPT removal. Given that these genes possess Notch-responsive RBPJ transcription factor binding sites in their regulatory regions, these genes are likely directly targeted by Notch signalling. In summary, our data provide a comprehensive picture of the molecular pathways regulated by Notch signalling in interstitial cell differentiation and formation of the oral-aboral axis inHydra.
The Asian gypsy moth (Lymantria disparL.) populations: resistance of eggs to extreme winter temperatures
Authors: Ananko G.G. , Kolosov A.V.
Published: February 2021

Gypsy mothLymantria dispar(GM) is a polyphagous insect and one of the most significant pests in the forests of Eurasia and North America. Accurate information on GM cold hardiness is needed to improve methods for the prediction of population outbreaks, as well as for forecasting possible GM range displacements due to climate change.

As a result of laboratory and field studies, we found that the lower lethal temperature (at which allL. dispar asiaticaeggs die) range from –29.0 °C to –29.9 °C for three studied populations, and no egg survived cooling to –29.9 °C. These limits agree to within one degree with the previously established cold hardiness limits of the European subspeciesL. dispar dispar, which is also found in North America. This coincidence indicates that the lower lethal temperature ofL. disparis conservative.

Thus, we found that the Siberian populations of GM inhabit an area where winter temperatures go beyond the limits of egg physiological tolerance, because temperature often fall below –30 °C. Apparently, it is due to the flexibility of ovipositional behavior thatL. dispar asiaticasurvives in Siberia: the lack of physiological tolerance of eggs is compensated by choosing warm biotopes for oviposition. One of the most important factors contributing to the survival of GM eggs in Siberia is the stability of snow cover.

Within the geographical range of Siberian gypsy moth populations, extreme temperatures go beyond the limits of the physiological tolerance of wintering eggs (–29.9 °C), and their survival depends on the choice of warm biotopes for oviposition.
An endogenous basis for synchronization manners of the circadian rhythm in proliferatingLemna minorplants
Authors: Ueno Kenya , Ito Shogo , Oyama Tokitaka
Published: February 2021

Endogenous circadian rhythms in plants play a role in adaptation to day-night cycles. The circadian clock is a cell-autonomous system that functions through the coordination of time information in the plant body. Synchronization of cellular clocks is based on coordination mechanisms; the synchronization manners in proliferating plants remain unclear. We performed spatiotemporal analysis of the circadian rhythm of fronds (leaf-like plant units) of proliferatingLemna minorplants carrying a circadian bioluminescence reporter,AtCCA1:LUC. Noninvasive observations of the bioluminescence of fast-growing two-dimensional plants allowed us to analyze the circadian rhythms at a cell-level resolution and obtain information regarding frond lineage. We focused on spontaneous circadian organization under constant light conditions for plants with light/dark treatment (LD-grown) or without it (LL-grown). Even fronds developing from an LL-grown parental frond showed coherent circadian rhythms among them. This allowed the maintenance of circadian rhythmicity in proliferating plants. Inside a frond, a centrifugal phase/period pattern was observed in LD-grown plants, whereas various phase patterns with traveling waves were formed in LL-grown plants. These patterns were model-simulated by local coupling of cellular circadian oscillators with different initial synchronous states in fronds. Taken together with similar patterning previously reported for detached leaves ofArabidopsis, it is strongly suggested that local coupling is the primary force for the development of these phase patterns in plants lacking long-distance communication. We propose a basic framework of spontaneous phase patterning with three stages of circadian organization: initial phasing, evolution of patterning, and desynchronization/randomizing of phase, in association with altering cell-cell coupling.
A Unit Pipe Pneumatic model to simulate gas kinetics during measurements of embolism in excised angiosperm xylem
Authors: Yang Dongmei , Pereira Luciano , Peng Guoquan , Ribeiro Rafael V. , Kaack Lucian , Jansen Steven , Tyree Melvin T.
Published: February 2021

The Pneumatic method has been introduced to quantify embolism resistance in plant xylem of various organs. Despite striking similarity in vulnerability curves between the Pneumatic and hydraulic methods, a modeling approach is highly needed to demonstrate that xylem embolism resistance can be accurately quantified based on gas diffusion kinetics.

A Unit Pipe Pneumatic (UPPn) model was developed to estimate gas diffusion from intact conduits, which were axially interconnected by interconduit pit membranes. The physical laws used included Fick’s law for diffusion, Henry’s law for gas concentration partitioning between liquid and gas phases at equilibrium, and the ideal gas law.

The UPPn model showed that 91% of the extracted gas came from the first two series of embolized, intact conduits, and only 9% from the aqueous phase after 15 s of simulation. Embolism resistance measured with a Pneumatic apparatus was systematically overestimated by 2 to 17%, corresponding to a typical measuring error of 0.11 MPa forP50(the water potential equivalent to 50% of the maximum amount of gas extracted).

Because results from the UPPn model are supported by experimental evidence, there is a good theoretical and experimental basis for applying the pneumatic method to research on embolism resistance of angiosperms.
Multiplatform Computational Analysis of Mast Cells in Adrenocortical Carcinoma Tumor Microenvironment
Authors: Baechle Jordan J. , Hanna David N. , Sekhar Konjeti R. , Rathmell Jeffrey C. , Rathmell W. Kimryn , Baregamian Naira
Published: February 2021

Introduction

Immunotherapeutic response failure of adrenocortical carcinomas (ACC) highlights a need for novel strategies targeting immune cell populations in the tumor microenvironment (TME) to overcome tumor resistance and enhance therapeutic response. A recent study explored a new link between tumor mast cell (MC) infiltration and improved outcomes in patients with ACC. We further dissect the role of MC in TME of ACC by examining the tumor MC expression signatures and MC activity within TME to provide additional insight into potential novel immunotherapeutic targets.

Methods

UsingCIBERSORTxcomputational immunogenomic deconvolution algorithm to analyze ACC tumor gene mRNA expression data (TCGA, N=79), we estimated the abundance of tumor immune infiltrating MC, and assessed prognostic potential of MC signaling genes as pro- or anti- tumor signatures, as well as the impact on overall (OS) and disease-free (DFS) survival.

Results

We stratified MC signaling genes with survival prognostic values (OS, DFS, p<0.05) into anti-tumor (ALOX5, CCL2, CCL5, CXCL10, HDC, IL16, TNF, TPSAB1, VEGFD) and pro-tumor (CXCL1, CXCL3, CXCL8, IL4, IL13, PTGS3, TNSF4, VEGFD) groups. Anti-tumor MC signature, as the predominant phenotype, was associated with improved OS and DFS.

Conclusion

The deconvolution analysis of TCGA data identified MC infiltration in ACC microenvironment as predominantly associated with anti-tumor activity. Future studies stemming from our findings may help define the role of MC in TME and the impact on patient survival in patients with ACC. Modulation of tumor MC infiltration may serve as a potential target for novel synergistic immunotherapies for the treatment and improved survival of patients with ACC.
Identification and Evaluation of a Panel of Strong Constitutive Promoters inListeria monocytogenesfor Improving the Expression of Foreign Antigens
Authors: Ma Junfei , Ji Qianyu , Wang Shuying , Qiu Jingxuan , Liu Qing
Published: February 2021

AttenuatedListeria monocytogenes(L. monocytogenes) could be used as a vaccine vector for immunotherapy of tumors or pathogens. However, the lack of reliable promoters limits its ability to express foreign antigens. In this work, 21 promoters fromL. monocytogeneswere identified by RNA-seq analysis under two conditions of pH 7.4 and pH 5.5. Based on the constructed fluorescence report system, 7 constitutive promoters showed higher strength than that of Phelp, a previously reported strong promoter. Further, the selected 5 constitutive promoters also showed high activity in the production of UreB, a widely used antigen againstHelicobacter pylori(H. pylori). In particular, a well-characterized constitutive promoter P18, which performed best in both fluorescence intensity and UreB production, was proved to be highly active in vitro and in vivo. In summary, we provide a useful promoter library forListeriaspecies and offer a reference for constitutive promoter mining in other organisms.

Key points

21 promoters fromL. monocytogeneswere identified by RNA-seq.

Fluorescent tracer ofL. monocytogenes(P18) was performed in vitro and in vivo.

A well-characterized constitutive promoter P18could improve the expression level of a foreign antigen UreB inL. monocytogenes