bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigations Into Chemically Stabilized Four-Letter DNA for DNA-Encoded Chemistry
Authors: Potowski Marco , Kunig Verena B. K. , Eberlein Lukas , Škopić Mateja Klika , Vakalopoulos Alexandros , Kast Stefan M. , Brunschweiger Andreas
Published: June 2022

DNA-encoded libraries are a prime technology for target-based small molecule screening. Native DNA used as genetic compound barcode is chemically vulnerable under many reaction conditions. DNA barcodes that are composed of pyrimidine nucleobases, 7-deazaadenine, and 7-deaza-8-azaguanine have been investigated for their suitability for encoded chemistry both experimentally and computationally. These four-letter barcodes were readily ligated by T4 ligation, amplifiable by Taq polymerase, and the resultant amplicons were correctly sequenced. Chemical stability profiling showed a superior chemical stability compared to native DNA, though higher susceptibility to depurination than a three-letter code based on pyrimidine DNA and 7-deazaadenine.
Bioactive Bibenzyl Enantiomers From the Tubers of Bletilla striata
Authors: Zhou Mei , Jiang Sai , Chen Changfen , Li Jinyu , Lou Huayong , Wang Mengyun , Liu Gezhou , Liu Hanfei , Liu Ting , Pan Weidong
Published: June 2022

Six new bibenzyls (three pairs of enantiomers), bletstrins D–F (1–3), were isolated from the ethyl acetate-soluble (EtOAc) extract of tubers of Bletilla striata (Thunb.) Rchb f. Their structures, including absolute configurations, were determined by 1D/2D NMR spectroscopy, optical rotation value, and experimental electronic circular dichroism (ECD) data analyses, respectively. Compounds 1–3 possess a hydroxyl-substituted chiral center on the aliphatic bibenzyl bridge, which represented the first examples of natural bibenzyl enantiomers from the genus of Bletilla. The antibacterial, antitumor necrosis factor (anti-TNF-α), and neuroprotective effects of the isolates have been evaluated. Compounds 3a and 3b were effective against three Gram-positive bacteria with minimum inhibitory concentrations (MICs) of 52–105 μg/ml. Compounds 2a and 2b exhibited significant inhibitory effects on TNF-α-mediated cytotoxicity in L929 cells with IC50 values of 25.7 ± 2.3 μM and 21.7 ± 1.7 μM, respectively. Subsequently, the possible anti-TNF-α mechanism of 2 was investigated by molecular docking simulation. Furthermore, the neuroprotective activities were tested on the H2O2-induced PC12 cell injury model, and compounds 2b, 3a, and 3b (10 μM) could obviously protect the cells with the cell viabilities of 57.86 ± 2.08%, 64.82 ± 2.84%, and 64.11 ± 2.52%, respectively.
Efficacy and Safety of Granulocyte-Colony Stimulating Factor Therapy in Chagas Cardiomyopathy: A Phase II Double-Blind, Randomized, Placebo-Controlled Clinical Trial
Authors: Macedo Carolina T. , Larocca Ticiana F. , Noya-Rabelo Márcia , Aras Roque , Macedo Cristiano R. B. , Moreira Moisés I. , Caldas Alessandra C. , Torreão Jorge A. , Monsão Victor M. A. , Souza Clarissa L. M. , Vasconcelos Juliana F. , Bezerra Milena R. , Petri Daniela P. , Souza Bruno S. F. , Pacheco Antônio G. F. , Daher André , Ribeiro-dos-Santos Ricardo , Soares Milena B. P.
Published: June 2022

Aim

Previous studies showed that granulocyte-colony stimulating factor (G-CSF) improved heart function in a mice model of Chronic Chagas Cardiomyopathy (CCC). Herein, we report the interim results of the safety and efficacy of G-CSF therapy vs. placebo in adults with Chagas cardiomyopathy.

Methods

Patients with CCC, New York Heart Association (NYHA) functional class II to IV and left ventricular ejection fraction (LVEF) 50% or below were included. A randomization list using blocks of 2 and 4 and an allocation rate of 1:1 was generated by R software which was stratified by functional class. Double blinding was done to both arms and assessors were masked to allocations. All patients received standard heart failure treatment for 2 months before 1:1 randomization to either the G-CSF (10 mcg/kg/day subcutaneously) or placebo group (1 mL of 0.9% saline subcutaneously). The primary endpoint was either maintenance or improvement of NYHA class from baseline to 6–12 months after treatment, and intention-to-treat analysis was used.

Results

We screened 535 patients with CCC in Salvador, Brazil, of whom 37 were randomized. Overall, baseline characteristics were well-balanced between groups. Most patients had NYHA class II heart failure (86.4%); low mean LVEF was 32 ± 7% in the G-CSF group and 33 ± 10% in the placebo group. Frequency of primary endpoint was 78% (95% CI 0.60–0.97) vs. 66% (95% CI 0.40–0.86), p = 0.47, at 6 months and 68% (95% CI 0.43–0.87) vs. 72% (95% CI 0.46–0.90), p = 0.80, at 12 months in placebo and G-CSF groups, respectively. G-CSF treatment was safe, without any related serious adverse events. There was no difference in mortality between both arms, with five deaths (18.5%) in treatment vs. four (12.5%) in the placebo arm. Exploratory analysis demonstrated that the maximum rate of oxygen consumption during exercise (VO2 max) showed an improving trend in the G-CSF group.

Conclusion

G-CSF therapy was safe and well-tolerated in 12 months of follow-up. Although prevention of symptom progression could not be demonstrated in the present study, our results support further investigation of G-CSF therapy in Chagas cardiomyopathy patients.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [NCT02154269].
Indications, Complications, and Outcomes of Cardiac Surgery After Heart Transplantation: Results From the Cash Study
Authors: Gökler Johannes , Aliabadi-Zuckermann Arezu Z. , Kaider Alexandra , Ambardekar Amrut V. , Antretter Herwig , Artemiou Panagiotis , Bertolotti Alejandro M. , Boeken Udo , Brossa Vicens , Copeland Hannah , Generosa Crespo-Leiro Maria , Eixerés-Esteve Andrea , Epailly Eric , Farag Mina , Hulman Michal , Khush Kiran K. , Masetti Marco , Patel Jignesh , Ross Heather J. , Rudež Igor , Silvestry Scott , Suarez Sofia Martin , Vest Amanda , Zuckermann Andreas O.
Published: June 2022

Background

Allograft pathologies, such as valvular, coronary artery, or aortic disease, may occur early and late after cardiac transplantation. Cardiac surgery after heart transplantation (CASH) may be an option to improve quality of life and allograft function and prolong survival. Experience with CASH, however, has been limited to single-center reports.

Methods

We performed a retrospective, multicenter study of heart transplant recipients with CASH between January 1984 and December 2020. In this study, 60 high-volume cardiac transplant centers were invited to participate.

Results

Data were available from 19 centers in North America (n = 7), South America (n = 1), and Europe (n = 11), with a total of 110 patients. A median of 3 (IQR 2–8.5) operations was reported by each center; five centers included ≥ 10 patients. Indications for CASH were valvular disease (n = 62), coronary artery disease (CAD) (n = 16), constrictive pericarditis (n = 17), aortic pathology (n = 13), and myxoma (n = 2). The median age at CASH was 57.7 (47.8–63.1) years, with a median time from transplant to CASH of 4.4 (1–9.6) years. Reoperation within the first year after transplantation was performed in 24.5%. In-hospital mortality was 9.1% (n = 10). 1-year survival was 86.2% and median follow-up was 8.2 (3.8–14.6) years. The most frequent perioperative complications were acute kidney injury and bleeding revision in 18 and 9.1%, respectively.

Conclusion

Cardiac surgery after heart transplantation has low in-hospital mortality and postoperative complications in carefully selected patients. The incidence and type of CASH vary between international centers. Risk factors for the worse outcome are higher European System for Cardiac Operative Risk Evaluation (EuroSCORE II) and postoperative renal failure.
Pre-transplant Type 2 Diabetes Mellitus Is Associated With Higher Graft Failure and Increased 5-Year Mortality After Heart Transplantation
Authors: Rivinius Rasmus , Gralla Carolin , Helmschrott Matthias , Darche Fabrice F. , Ehlermann Philipp , Bruckner Tom , Sommer Wiebke , Warnecke Gregor , Kopf Stefan , Szendroedi Julia , Frey Norbert , Kihm Lars P.
Published: June 2022

Aims

Cardiac transplant recipients often suffer from type 2 diabetes mellitus (T2DM) but its influence on graft failure and post-transplant mortality remains unknown. The aim of this study was to investigate the long-term effects of pre-transplant T2DM in patients after heart transplantation (HTX).

Methods

This study included a total of 376 adult patients who received HTX at Heidelberg Heart Center between 01/01/2000 and 01/10/2016. HTX recipients were stratified by diagnosis of T2DM at the time of HTX. Patients with T2DM were further subdivided by hemoglobin A1c (HbA1c ≥ 7.0%). Analysis included donor and recipient data, immunosuppressive drugs, concomitant medications, post-transplant mortality, and causes of death. Five-year post-transplant mortality was further assessed by multivariate analysis (Cox regression) and Kaplan–Meier estimator.

Results

About one-third of all HTX recipients had T2DM (121 of 376 [32.2%]). Patients with T2DM showed an increased 5-year post-transplant mortality (41.3% versus 29.8%; P = 0.027) and had a higher percentage of death due to graft failure (14.9% versus 7.8%; P = 0.035). Multivariate analysis showed T2DM (HR: 1.563; 95% CI: 1.053–2.319; P = 0.027) as an independent risk factor for 5-year mortality after HTX. Kaplan–Meier analysis showed a significantly better 5-year post-transplant survival of patients with T2DM and a HbA1c < 7.0% than patients with T2DM and a HbA1c ≥ 7.0% (68.7% versus 46.3%; P = 0.008) emphasizing the clinical relevance of a well-controlled T2DM in HTX recipients.

Conclusion

Pre-transplant T2DM is associated with higher graft failure and increased 5-year mortality after HTX.
Arterial Stiffness, Biomarkers of Liver Fat, and the Development of Metabolic Dysfunction in Metabolically Healthy Population: A Prospective Study
Authors: Lin Lin , Wang Long , Du Rui , Hu Chunyan , Lu Jieli , Wang Tiange , Li Mian , Zhao Zhiyun , Xu Yu , Xu Min , Bi Yufang , Wang Weiqing , Ning Guang , Chen Yuhong
Published: June 2022

Background

Metabolic dysfunction is known to be associated with arterial stiffness. However, the risks of metabolic syndrome and diabetes due to arterial stiffness and the potential mechanism remain unclear. We aimed to investigate the association of arterial stiffness with the risk of metabolic syndrome and diabetes, and determine whether this association is mediated by liver fat.

Methods

A prospective study was conducted with 4,139 Chinese adults who were metabolically healthy at baseline. Arterial stiffness was measured by brachial–ankle pulse wave velocity (baPWV). Obesity was defined as body mass index ≥25 kg/m2. The primary outcomes were incident metabolic syndrome and diabetes.

Results

During a median follow-up of 4.4 years, 1,022 (24.7%) and 354 (9.5%) participants developed metabolic syndrome and diabetes, respectively. Compared with those in the lowest quartile of baPWV, participants in the highest quartile had 85 and 91% higher risks of metabolic syndrome and diabetes [risk ratio (RR) 1.85, 95% confidence interval (CI) 1.41, 2.42 for metabolic syndrome; RR 1.91, 95% CI 1.16, 3.15 for diabetes]. Mediation analyses indicated that fatty liver significantly mediated the association of arterial stiffness with metabolic syndrome and diabetes risk. Specifically, 18.4% of metabolic syndrome and 12.6% of diabetes risk due to arterial stiffness were mediated through fatty liver.

Conclusions

Arterial stiffness was associated with higher risks of metabolic syndrome and diabetes in individuals with obesity. This association may be partially mediated by fatty liver.
Development and Maintenance Mechanisms of a Long-Lived Mesoscale Vortex Which Governed the Earlier Stage of the “21.7” Henan Torrential Rainfall Event
Authors: Li Wanli , Ma Hui , Fu Rui , Han Hong , Wang Xiuming
Published: June 2022

From 17 to 22 July 2021, a series of disastrous rainstorms appeared within Henan Province and its surroundings, which rendered 398 dead/missing and a direct economic loss of up to ∼114 billion Yuan. This event was named as the “21.7” Henan torrential rainfall event (TRE), and it could be divided roughly into three stages according to the precipitation features and dominant weather systems. This study mainly focused on the development and maintenance mechanisms of a long-lived (72 h) quasi-stationary mesoscale vortex that governed the earlier stage of the “21.7” TRE. Main results are as follows: 1) the mesoscale vortex formed/maintained in a favorable environment which was characterized by the South-Asia-high associated divergence in the upper troposphere, and the relay transport of relatively cold air by the trough and high-pressure system in the middle troposphere. 2) the vertical stretching due to lower-level convergence and the upward transport of cyclonic vorticity by ascending motions served as the first and second dominant factors for the mesoscale vortex’s rapid development and long-time maintenance, whereas, the import/export transport of anticyclonic/cyclonic vorticity into/from the vortex’s central region and the tilting effects were mainly detrimental for the vortex’s development/maintenance. 3) the air particles that formed the mesoscale vortex mainly came from the levels below 1,500 m, within the regions in lower latitudes. The air particles experienced notable precipitation before the formation of the mesoscale vortex, which contributed to the vortex’s formation through latent heat release.
T-MOOC for Initial Teacher Training in Digital Competences: Technology and Educational Innovation
Authors: Martínez-Pérez Sandra , Cabero-Almenara Julio , Barroso-Osuna Julio , Palacios-Rodríguez Antonio
Published: June 2022

Massive open online courses (MOOCs) are perceived as emerging technologies for training and innovation in the educational context. They have become approaches for distance education in the face of the new challenges, changes, and crises experienced by the COVID-19 pandemic. They represent, in turn, new emerging opportunities as a response to the United Nations recommendations for open education and the development of sustainable goals. The presence of technologies in the development of educational tasks means that the acquisition of Digital Competences (DC) by teachers and students in training goes beyond the mere mastery of content and teaching methodologies. The research presented aims to analyze the educational possibilities of T-MOOCs for the development of DC in teachers, and as resources that favor autonomous and collaborative learning in innovative scenarios. The study sample is made up of 313 students of the Primary Education Degree at the University of Seville (Spain). For this purpose, two online questionnaires (Google Forms) were applied at the beginning of the course: the Digital Teaching Competence Questionnaire (DigCompEdu), and the Content Questionnaire: Digital Resources and Digital Pedagogy. The results obtained show that the students’ level of both digital competences and subject content is low to medium, so that training in educational technology is required for the acquisition of key digital competences. Based on the data obtained, the following actions are proposed: (a) The concretion of the contents structured by means of a learning guide and e-activities to be developed by the student body, taking into account the United Nations guidelines with regard to the Development of Sustainable Objectives; (b) The creation of a training and innovative environment under the T-MOOC architecture, based on open and distance learning due to the current health situation of COVID-19, which, on the one hand, empowers students to use digital tools, and on the other hand, facilitates the acquisition of the SDGs; and (c) The evaluation of the T-MOOC designed as a resource for autonomous, collaborative, guided learning in emerging contexts in which technologies and educational innovation play an important role for sustainable development.
Principles of Endocrine Regulation: Reconciling Tensions Between Robustness in Performance and Adaptation to Change
Authors: Hoermann Rudolf , Pekker Mark J. , Midgley John E. M. , Larisch Rolf , Dietrich Johannes W.
Published: June 2022

Endocrine regulation in the hypothalamic-pituitary-thyroid (HPT) axis is orchestrated by physiological circuits which integrate multiple internal and external influences. Essentially, it provides either of the two responses to overt biological challenges: to defend the homeostatic range of a target hormone or adapt it to changing environmental conditions. Under certain conditions, such flexibility may exceed the capability of a simple feedback control loop, rather requiring more intricate networks of communication between the system’s components. A new minimal mathematical model, in the form of a parametrized nonlinear dynamical system, is here formulated as a proof-of-concept to elucidate the principles of the HPT axis regulation. In particular, it allows uncovering mechanisms for the homeostasis of the key biologically active hormone free triiodothyronine (FT3). One mechanism supports the preservation of FT3 homeostasis, whilst the other is responsible for the adaptation of the homeostatic state to a new level. Together these allow optimum resilience in stressful situations. Preservation of FT3 homeostasis, despite changes in FT4 and TSH levels, is found to be an achievable system goal by joining elements of top-down and bottom-up regulation in a cascade of targeted feedforward and feedback loops. Simultaneously, the model accounts for the combination of properties regarded as essential to endocrine regulation, namely sensitivity, the anticipation of an adverse event, robustness, and adaptation. The model therefore offers fundamental theoretical insights into the effective system control of the HPT axis.
Acromegaly Caused by Ectopic Growth Hormone Releasing Hormone Secretion: A Review
Authors: Zendran Iga , Gut Gabriela , Kałużny Marcin , Zawadzka Katarzyna , Bolanowski Marek
Published: June 2022

Introduction

Ectopic acromegaly is a rare condition caused most frequently by growth hormone releasing hormone (GHRH) secretion from neuroendocrine tumors. The diagnosis is often difficult to establish as its main symptoms do not differ from those of acromegaly of pituitary origin.

Objectives

To determine most common clinical features and diagnostic challenges in ectopic acromegaly.

Patients and Methods

A search for ectopic acromegaly cases available in literature was performed using PubMed, Cochrane, and MEDline database. In this article, 127 cases of ectopic acromegaly described after GHRH isolation in 1982 are comprehensively reviewed, along with a summary of current state of knowledge on its clinical features, diagnostic methods, and treatment modalities. The most important data were compiled and compared in the tables.

Results

Neuroendocrine tumors were confirmed in 119 out of 121 patients with histopathological evaluation, mostly of lung and pancreatic origin. Clinical manifestation comprise symptoms associated with pituitary hyperplasia, such as headache or visual field disturbances, as well as typical signs of acromegaly. Other endocrinopathies may also be present depending on the tumor type. Definitive diagnosis of ectopic acromegaly requires confirmation of GHRH secretion from a tumor using either histopathological methods or GHRH plasma concentration assessment. Hormonal evaluation was available for 84 patients (66%) and histopathological confirmation for 99 cases (78%). Complete tumor resection was the main treatment method for most patients as it is a treatment of choice due to its highest effectiveness. When not feasible, somatostatin receptor ligands (SRL) therapy is the preferred treatment option. Prognosis is relatively favorable for neuroendocrine GHRH-secreting tumors with high survival rate.

Conclusion

Although ectopic acromegaly remains a rare disease, one should be aware of it as a possible differential diagnosis in patients presenting with additional symptoms or those not responding to classic treatment of acromegaly.
The Impact of Energy Innovations and Environmental Performance on the Sustainable Development of the EU Countries in a Globalized Digital Economy
Authors: Noja Gratiela Georgiana , Cristea Mirela , Panait Mirela , Trif Simona Mihaela , Ponea Constantin Ștefan
Published: June 2022

The research conducted in this paper aims to examine the role of energy innovations, digital technological transformation, and environmental performance in enhancing the sustainable economic development of the European Union (EU) countries, widely shaped by the globalization process. An advanced empirical analysis is configured on a cross-sectional dataset of EU-27 Member States compiled at the level of 2018 based on several modern econometric procedures, namely robust regression, structural equation modelling (SEM) and network analysis through Gaussian graphical models (GGM). We apply the econometric procedures to firstly identify and assess the direct, indirect, and total interlinkages between all considered variables, as well as their further cumulated spillover impact on sustainable economic development. EU countries are afterward clustered according to the Ward method inset on hierarchical clustering for an in-depth assessment and tailored policy design by accounting for the level of financial and trade globalization (captured through the KOF Index of Globalization), environmental performance and sustainability (captured through the Environmental Performance Index—EPI), and the degree of integration of digital technologies (proxied through the Digital Economy and Society Index—DESI). Main results highlight that there are significant beneficial effects induced by energy innovations, increased environmental performance and digital transformation on the sustainable development of EU countries, with notable differentiation among them. Policy guidelines and strategic directions are also enhanced and largely presented within the paper.
Odor-Pollution From Fungicides Disrupts Learning and Recognition of a Common Floral Scent in Bumblebees (Bombus impatiens)
Authors: David Natalie F. , Henry Timothy J. , Sprayberry Jordanna D. H.
Published: June 2022

Background and Aims

Bumblebees provide vital pollination services to both natural and agricultural ecosystems. Consequently their declines in species-diversity and population size over the last five decades is alarming. Direct contributors to these declines include pesticides, habitat loss, and disease. However, given that colony fitness is linked to foraging success, successful conservation requires mitigation of any anthropogenic practices that negatively impact foraging. Previous work has shown that agrochemical odor-pollution, including that of fungicides, can modulate bumblebee foraging behavior. This study investigates how odor pollution from three common fungicides (Safer® Brand Garden Fungicide II, Scotts® Lawn Fungus Control, and Reliant® Systemic Fungicide) affects Bombus impatiens’ floral-odor learning and recognition using an associative learning paradigm.

Methods

The effects of fungicide-odor pollution were tested in three ways: (1) background pollution during floral-odor learning; (2) background pollution during floral-odor recognition; and (3) point (localized) pollution during floral-odor recognition. Electroantennogram (EAG) recordings from B. impatiens confirmed the salience of all odor-stimuli and examined impacts of background fungicide-odor on antennal responses to floral-odor. To better understand how fungicide-odor structure related to behavioral data, scents were sampled (Solid Phase Microextraction) and analyzed using gas chromatography–mass spectrometry. Odors were then characterized using the Compounds Without Borders (CWB) vectorization method.

Conclusion

All fungicides tested disrupted floral-odor learning and recognition for at least one concentration tested, and Scotts® was universally disruptive at all tested concentrations. All fungicides induced EAG responses, indicating they provide perceivable odor stimuli. Interestingly, two of three tested fungicides (Scotts® and Reliant®) inhibit antennal responses to Monarda fistulosa odor. Odor characterization supports previous findings that sulfurous scents could be disruptive to odor-driven foraging behaviors. Inability for foraging bumblebees to associate to rewarding floral odors in the presence of fungicidal odor pollution could have negative large-scale implications for colony health and reproductive fitness.
Genomic Insights Into the Unique Demographic History and Genetic Structure of Five Hmong-Mien-Speaking Miao and Yao Populations in Southwest China
Authors: Yang Meiqing , He Guanglin , Ren Zheng , Wang Qiyan , Liu Yubo , Zhang Hongling , Zhang Han , Chen Jing , Ji Jingyan , Zhao Jing , Guo Jianxin , Zhu Kongyang , Yang Xiaomin , Wang Rui , Ma Hao , Wang Chuan-Chao , Huang Jiang
Published: June 2022

Southern China was the original center of multiple ancestral populations related to modern Hmong-Mien, Tai-Kadai, Austroasiatic, and Austronesian people. More recent genetic surveys have focused on the fine-scale genetic structure and admixture history of southern Chinese populations, but the genetic formation and diversification of Hmong-Mien speakers are far from clear due to the sparse genetic sampling. Here, we reported nearly 700,000 single-nucleotide polymorphisms (SNPs) data from 130 Guizhou Miao and Yao individuals. We used principal component analysis, ADMIXTURE, f-statistics, qpAdm, phylogenetic tree, fineSTRUCTURE, and ALDER to explore the fine-scale population genetic structure and admixture pattern of Hmong-Mien people. The sharing allele patterns showed that our studied populations had a strong genetic affinity with ancient and modern groups from southern and southeastern East Asia. We identified one unique ancestry component maximized in Yao people, which widely existed in other Hmong-Mien-speaking populations in southern China and Southeast Asia and ancient samples of Guangxi. Guizhou Hmong-Mien speakers harbored the dominant proportions of ancestry related to southern indigenous East Asians and minor proportions of northern ancestry related to Yellow River farmers, suggesting the possibility of genetic admixture between Hmong-Mien people and recent southward Sino-Tibetan-related populations. Furthermore, we found a genetic substructure among geographically different Miao and Yao people in Leishan and Songtao. The Yao and Miao people in Leishan harbored more southern East Asian ancestry, but Miao in Songtao received more northern East Asian genetic influence. We observed high mtDNA but low Y-chromosome diversity in studied Hmong-Mien groups, supporting the role of sex-specific residence in influencing human genetic variation. Our data provide valuable clues for further exploring population dynamics in southern China.
Partitioning of Space Among Trees in an Old-Growth Spruce Forest in Subarctic Fennoscandia
Authors: Pouta Pasi , Kulha Niko , Kuuluvainen Timo , Aakala Tuomas
Published: June 2022

The distribution of space among forest trees is linked to the availability of resources, among-tree competition, and hence forest dynamics. We studied partitioning of horizontal space among trees and related spatial structures in an old-growth Picea abies (L.) Karst -dominated forest in northeastern subarctic Fennoscandia, where Betula pubescens (Ehrh.) is an important co-dominant. Specifically, we asked (1) how does growing space occupied by trees vary by tree species and size in an old-growth forest with open canopy structure, and (2) at what scales does the variation in tree growing space occur? We mapped an 8.8 ha forest plot with 4,884 live trees. We used Voronoi polygons to quantify the horizontal space potentially available to each tree. We modeled the Voronoi polygon area as a function of tree size and species by using generalized additive models (GAM). We used i-to-any L-functions to study the scale-dependence of tree densities around focal trees, and mark correlation functions to study the relative sizes of trees close to each other. The GAM models showed that tree growing space increased non-linearly with tree size before saturating, and that overall growing space was larger for B. pubescens than for P. abies. Mean space occupied by trees roughly doubled from the smallest diameter class (0–5 cm) to the largest (>25 cm), from 13.7 to 26.7 m2. Depending on diameter class, shade-intolerant B. pubescens occupied on average 5–10 m2 more space than shade-tolerant P. abies. Trees close to each other were smaller than average. Size- and species-dependent differences in local tree densities accumulated mostly at the scale of a few meters but showed also broader-scale variation possibly related to edaphic variation within the study plot. The tree species- and size-related variation in the trees’ growing space suggests that among-tree competition, together with clustering of trees, shape the spatial assembly of the forest.
Cambioxylophagous Pests of Scots Pine: Ecological Physiology of European Populations—A Review
Authors: Hlávková Daniela , Doležal Petr
Published: June 2022

Climatic extremes have been gathering momentum since the 1880s and are believed to be a long-term factor increasing the mortality of Scots pine trees, Pinus sylvestris (L.) in Europe. Weather monitoring over the past 120 years shows that, in Central Europe, surface air temperatures grow at a rate of 0.18°C per decade. Many changes due to these abiotic stressors are already visible in the forests’ canopy and biodiversity. But the influence of the rise in temperature and in precipitation deficiency brings one more player into this die-back scheme. Bark beetles, and their increasing outbreaks, are further agents acting to accelerate and expand the impacts of weather on trees. While P. sylvestris react to abiotic stressors by decreasing functions of the hydraulic system, mainly the defense system, for bark beetles, warming is a profitable condition. Various bionomy processes are modified: vegetation seasons prolong, larval growth and development rates accelerate, reproductive potential rises, and overwintering success increases. Thus, the insect populations grow, and the infestation pressure on weakened hosts intensifies. Finally, even species of small ecologic importance can cause extensive losses of forest cover. Furthermore, international trade and intercontinental transportation support the potential threat of spreading forest pests far away from their original geographic range. Together with climatic amelioration, pests may adapt to new conditions, establish new prosperous populations, disperse rapidly, and cause prodigious losses. However, detailed information about cambioxylophagous pests on P. sylvestris in Central Europe is still missing. The purpose of our review is to map the bionomy and behavior of six bark beetle species—in particular, the sharp-dentated bark beetle, Ips acuminatus (Gyllenhal, 1827), the six-toothed bark beetle, Ips sexdentatus (Börner, 1767), the common pine shoot beetle, Tomicus piniperda (Linnaeus, 1758), the lesser pine shoot beetle, Tomicus minor (Hartig, 1834), the pine shoot beetle, Tomicus destruens (Wollaston, 1865), the Mediterranean pine engraver, Orthotomicus erosus (Wollaston, 1857) (Coleoptera: Curculionidae: Scolytinae), and the steel-blue jewel beetle, Phaenops cyanea (Fabricius, 1775) (Coleoptera: Buprestidae)—on P. sylvestris in Central Europe, to compare and summarize the available data on European populations, and to try to propose ideas and directions for future research.
Direct and Indirect Effects of Long-Term Field Warming Methods on the Physical Environment and Biological Responses in a Subtropical Forest
Authors: Wu Ting , Tissue David Thomas , Zhou Guoyi , Yan Junhua , Zheng Mianhai , Li Xu , Song Yuting , Li Yuelin , Tang Xuli , Liu Shizhong , Chu Guowei , Meng Ze , Ye Qing , Liu Juxiu
Published: June 2022

Tree growth may be affected by rising temperature. We conducted two long-term, independent warming experiments in a subtropical forest; one experiment used translocation warming and one experiment used infra-red (IR) warming. Both warming techniques are designed to increase air and soil temperatures (Tair and Tsoil), but may also differentially affect other environmental variables, including soil volumetric water content (SVWC), air relative humidity (RH) and vapor pressure deficit (VPD). Hence, tree response ascribed to Tair and Tsoil may be dependent on the indirect effects of the warming techniques. We experimentally tested these ideas on three native tree species (Machilus breviflora, Syzygium rehderianum, and Schima superba), which occurred at all experimental sites, in subtropical China. We translocated trees from higher elevation sites to lower elevation sites in the coniferous and broadleaf mixed forest (Tair was 0.68 ± 0.05°C higher; 8 years) and mountain evergreen broadleaf forest (Tair was 0.95 ± 0.06°C and 1.63 ± 0.08°C higher; 8 years). IR warming was imposed at an experimental site in a monsoon evergreen broadleaf forest (Tair was 1.82 ± 0.03°C higher; 5 years). We found that both methods directly increased Tair and Tsoil (although to varying degrees), while translocation warming indirectly dried the soil (lower SVWC) and IR warming indirectly dried the air (lower RH and higher VPD). Machilus breviflora exposed to translocation warming exhibited lower photosynthesis due to higher Tsoil and lower SVWC, leading to declining growth. Higher Tair and Tsoil due to translocation warming increased photosynthesis and growth for S. superba. Trees exposed to IR warming exhibited reduced photosynthesis due to lower RH (M. breviflora) and to lower stomatal conductance (gs) as a function of higher Tair (S. rehderianum and S. superba). This study highlights the potential direct and indirect effects of different warming techniques on the physical environment of forest ecosystems, and subsequently their impacts on biological traits of trees. Hence, different warming techniques may provide different outcomes when assessing the impact of warming on trees in future climates.
Genomic Prediction Using LD-Based Haplotypes in Combined Pig Populations
Authors: Ye Haoqiang , Zhang Zipeng , Ren Duanyang , Cai Xiaodian , Zhu Qianghui , Ding Xiangdong , Zhang Hao , Zhang Zhe , Li Jiaqi
Published: June 2022

The size of reference population is an important factor affecting genomic prediction. Thus, combining different populations in genomic prediction is an attractive way to improve prediction ability. However, combining multireference population roughly cannot increase the prediction accuracy as well as expected in pig. This may be due to different linkage disequilibrium (LD) pattern differences between population. In this study, we used the imputed whole-genome sequencing (WGS) data to construct LD-based haplotypes for genomic prediction in combined population to explore the impact of different single-nucleotide polymorphism (SNP) densities, variant representation (SNPs or haplotype alleles), and reference population size on the prediction accuracy for reproduction traits. Our results showed that genomic best linear unbiased prediction (GBLUP) using the WGS data can improve prediction accuracy in multi-population but not within-population. Not only the genomic prediction accuracy of the haplotype method using 80 K chip data in multi-population but also GBLUP for the multi-population (3.4–5.9%) was higher than that within-population (1.2–4.3%). More importantly, we have found that using the haplotype method based on the WGS data in multi-population has better genomic prediction performance, and our results showed that building haploblock in this scenario based on low LD threshold (r2 = 0.2–0.3) produced an optimal set of variables for reproduction traits in Yorkshire pig population. Our results suggested that whether the use of the haplotype method based on the chip data or GBLUP (individual SNP method) based on the WGS data were beneficial for genomic prediction in multi-population, while simultaneously combining the haplotype method and WGS data was a better strategy for multi-population genomic evaluation.
FOXO1 and FOXO3 Cooperatively Regulate Innate Lymphoid Cell Development
Authors: Luu Thuy T. , Søndergaard Jonas Nørskov , Peña-Pérez Lucía , Kharazi Shabnam , Krstic Aleksandra , Meinke Stephan , Schmied Laurent , Frengen Nicolai , Heshmati Yaser , Kierczak Marcin , Bouderlique Thibault , Wagner Arnika Kathleen , Gustafsson Charlotte , Chambers Benedict J. , Achour Adnane , Kutter Claudia , Höglund Petter , Månsson Robert , Kadri Nadir
Published: June 2022

Natural killer (NK) cells play roles in viral clearance and early surveillance against malignant transformation, yet our knowledge of the underlying mechanisms controlling their development and functions remain incomplete. To reveal cell fate-determining pathways in NK cell progenitors (NKP), we utilized an unbiased approach and generated comprehensive gene expression profiles of NK cell progenitors. We found that the NK cell program was gradually established in the CLP to preNKP and preNKP to rNKP transitions. In line with FOXO1 and FOXO3 being co-expressed through the NK developmental trajectory, the loss of both perturbed the establishment of the NK cell program and caused stalling in both NK cell development and maturation. In addition, we found that the combined loss of FOXO1 and FOXO3 caused specific changes to the composition of the non-cytotoxic innate lymphoid cell (ILC) subsets in bone marrow, spleen, and thymus. By combining transcriptome and chromatin profiling, we revealed that FOXO TFs ensure proper NK cell development at various lineage-commitment stages through orchestrating distinct molecular mechanisms. Combined FOXO1 and FOXO3 deficiency in common and innate lymphoid cell progenitors resulted in reduced expression of genes associated with NK cell development including ETS-1 and their downstream target genes. Lastly, we found that FOXO1 and FOXO3 controlled the survival of committed NK cells via gene regulation of IL-15Rβ (CD122) on rNKPs and bone marrow NK cells. Overall, we revealed that FOXO1 and FOXO3 function in a coordinated manner to regulate essential developmental genes at multiple stages during murine NK cell and ILC lineage commitment.
Clinical Presentation and Outcomes of Acute Disseminated Encephalomyelitis in Adults Worldwide: Systematic Review and Meta-Analysis
Authors: Li Kunyi , Li Maolin , Wen Lan , Wang Qiancheng , Ding Xin , Wang Jian
Published: June 2022

Background

Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disorder that is often misdiagnosed. To improve early diagnosis, we performed a systematic review and meta-analysis of clinical features, outcomes for ADEM in adults.

Methods

The PubMed, Embase, Web of Science and Cochrane Library databases were searched for studies reporting the clinical features of adults with ADEM between January 1990 and May 2021. A random-effects meta-analysis model was used to pool data on clinical features and functional outcomes.

Results

Twelve studies examining 437 adults with ADEM met the inclusion criteria. Overall, the clinical features and diagnostic findings observed in more than two-thirds of the patients were white matter lesions [87.1%, 95% confidence interval (CI)=75-95.6], polyfocal onset (80.5%, 95% CI=50.5-98.9) and pyramidal signs (68.7%, 95% CI =40.0-91.9). The mortality rate was 7.8% (95% CI = 3.3–13.5), and the risk of residual deficits was 47.5% (95% CI = 31.8–63.4).

Conclusions

Adults with ADEM had worse outcomes than children. Clinicians should maintain high clinical suspicion for patients presenting with certain clinical features and diagnostic findings.
Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome
Authors: Fernández-Santos Maria Eugenia , Garcia-Arranz Mariano , Andreu Enrique J. , García-Hernández Ana Maria , López-Parra Miriam , Villarón Eva , Sepúlveda Pilar , Fernández-Avilés Francisco , García-Olmo Damian , Prosper Felipe , Sánchez-Guijo Fermin , Moraleda Jose M. , Zapata Agustin G.
Published: June 2022

MSCs products as well as their derived extracellular vesicles, are currently being explored as advanced biologics in cell-based therapies with high expectations for their clinical use in the next few years. In recent years, various strategies designed for improving the therapeutic potential of mesenchymal stromal cells (MSCs), including pre-conditioning for enhanced cytokine production, improved cell homing and strengthening of immunomodulatory properties, have been developed but the manufacture and handling of these cells for their use as advanced therapy medicinal products (ATMPs) remains insufficiently studied, and available data are mainly related to non-industrial processes. In the present article, we will review this topic, analyzing current information on the specific regulations, the selection of living donors as well as MSCs from different sources (bone marrow, adipose tissue, umbilical cord, etc.), in-process quality controls for ensuring cell efficiency and safety during all stages of the manual and automatic (bioreactors) manufacturing process, including cryopreservation, the use of cell banks, handling medicines, transport systems of ATMPs, among other related aspects, according to European and US legislation. Our aim is to provide a guide for a better, homogeneous manufacturing of therapeutic cellular products with special reference to MSCs.
Silencing of Mitochondrial Trifunctional Protein A Subunit (HADHA) Increases Lipid Stores, and Reduces Oviposition and Flight Capacity in the Vector Insect Rhodnius prolixus
Authors: Arêdes Daniela S. , De Paula Iron F. , Santos-Araujo Samara , Gondim Katia C.
Published: June 2022

Rhodnius prolixus is an obligatory hematophagous insect, vector of Chagas disease. After blood meal, lipids are absorbed, metabolized, synthesized, and accumulated in the fat body. When necessary, stored lipids are mobilized, transported to other organs, or are oxidized to provide energy. Mitochondrial β-oxidation is a cyclic conserved pathway, where degradation of long-chain fatty acids occurs to contribute to cellular energetic demands. Three of its reactions are catalyzed by the mitochondrial trifunctional protein (MTP), which is composed by hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunits alpha and beta (HADHA and HADHB, respectively). Here, we investigated the role of HADHA in lipid metabolism and reproduction of Rhodnius prolixus females. The expression of HADHA gene (RhoprHadha) was determined in the organs of starving adult insects. The flight muscle and ovary had higher expression levels when compared to the anterior and posterior midguts or the fat body. RhoprHadha gene expression was upregulated by blood meal in the flight muscle and fat body. We generated insects with RNAi-mediated knockdown of RhoprHadha to address the physiological role of this gene. RhoprHadha deficiency resulted in higher triacylglycerol content and larger lipid droplets in the fat body during starvation. After feeding, lifespan of the knockdown females was not affected, but they exhibited a decrease in oviposition, although hatching was the same in both groups. Silenced females showed lower forced flight capacity than the control ones, and their fat bodies had lower gene expression levels of Brummer lipase (RhoprBmm) and long-chain acyl-CoA synthetase 2 (RhoprAcsl2). Taken together, these findings indicate that HADHA is important to guarantee successful reproduction and efficient mobilization of lipid stores during starvation and flight.
Behaviour Impact Analysis of Tuna Purse Seiners in the Western and Central Pacific Based on the BRT and GAM Models
Authors: Yang Shenglong , Zhang Han , Fan Wei , Shi Huimin , Fei Yingjie , Yuan Sanling
Published: June 2022

Understanding the spatial pattern of human fishing activity is very important for fisheries resource monitoring and spatial management. To understand the spatial distribution of tuna purse seiner operations in the western and central Pacific Ocean and its relationship with the marine environment, this paper uses the AIS data of the western and central Pacific Tuna purse seiners from 2015 to 2020 to excavate spatial fishing effort information, which is combined with 24 marine environmental factors in the same period, including sea surface and subsurface levels using the boosted regression trees (BRT) model and general additive model (GAM) to construct the nonlinear relationship between the spatial distribution of fishing effort and marine ecological environmental factors and to discuss and analyse the niche of tuna purse seiners in the high seas. The results show that the average score of cv-AUC (cross-validated area under the curve) obtained by the BRT model training reaches 0.93, the average accuracy rate is 0.84, and the explained deviance is 43%; the average score of AUC (area under the curve) obtained by the GAM model training reaches 0.81, the average accuracy rate is 0.77, and the explained deviance is 34%. The results of BRT prior to GAM model. Using the BRT model for prediction, the results show that the average cv-AUC score for forecasting fishing effort in 2020 reaches 0.83, and the average accuracy rate of overall classification reaches 0.77. The results of factor analysis show that the water temperature at 100 m depth and longitude are the most important factors affecting the fishing effort of tuna purse seiners, and their contribution rates to the fishing effort of vessels are 12.38% and 9.76%, respectively, followed by sea surface temperature, latitude and DSH. The contribution to the fishing effort of tuna purse seiners was also large, accounting for 9.57%, 8.75%, and 7.11%, respectively; the 100-meter-deep chlorophyll and temperature gradient value contributed the least, 1.44% and 1.16%, respectively; tuna purse seiners are more likely to operate in the 100-metre water temperature of 25-29°C and sea surface temperature of 29-31°C. In terms of space, tuna purse seiners are more likely to operate in the 5°S-5°N latitudinal region and near the western sea area of 180°E. It is predicted that the modelled fishing effort of fishing vessels in 2020 and the actual fishing effort of fishing vessels have a relatively good spatial distribution. Research helps to understand the environmental impact of changes in the spatial distribution of tuna purse seiners and provides support for the management of tuna purse seine vessels in the western and central Pacific.
Impact of Environmental Regulation on Coastal Marine Pollution—A Case of Coastal Prefecture-Level Cities in China
Authors: Ma Jintao , Hu Qiuguang , Wei Xinyi
Published: June 2022

Based on the data on the level of environmental regulation and the degree of coastal marine pollution in 46 coastal prefecture-level cities in China from 2004 to 2016, this study uses the mediation effect model and the spatial Durbin model to analyze the impact and role of environmental regulation on offshore pollution from multiple dimensions and mechanisms. The findings are as follows: (1) Environmental regulation has an inverted “U”-shaped nonlinear effect on coastal marine pollution, which first intensifies and then inhibits. (2) Promoting green technology innovation is an important mechanism for environmental regulation to improve the quality of the marine environment, and the impact of environmental regulation on green technology innovation is characterized by a “U” shape. (3) Environmental regulation of coastal cities can affect coastal marine pollution in adjacent areas through spatial spillover effects, and the impact trajectory also shows an inverted “U”-shaped curve. This study proposes that in the process of marine environ-mental governance, first, a scientific and strict environmental regulation system should be constructed, and differentiated environmental regulation policies should be implemented. Second, giving full play to the conduction effect of green technology innovation and promoting the research and development, diffusion, and application of green technology are necessary. Third, we must attach importance to the cross-regional transfer and control of offshore pollution and promote regional joint prevention and control work.