bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Oncologic Outcomes After Laparoscopic and Robotic Tumor Enucleation for Renal Cell Carcinoma
Authors: Dong Wen , Chen Xiong , Huang Ming , Chen Xu , Gao Ming , Ou Dehua , Li Kaiwen , Wang Chenyang , Wu Shaoxu , Liu Hao , Xie Weibin , Xie Wenlian , Campbell Steven C. , Lin Tianxin , Huang Jian
Published: January 2021

Objectives

Tumor enucleation (TE) optimizes parenchymal preservation with promising short-term oncologic outcomes compared with standard partial nephrectomy (SPN). However, researches/literatures about long-term oncologic outcomes for TE after minimally invasive surgery are scarce. We aim to analyze long-term oncologic outcomes after laparoscopic and robotic tumor enucleation for renal cell carcinoma (RCC).

Patients and Methods

We retrospectively analyzed 146 patients who underwent TE with either laparoscopic or robotic approach for localized RCC in our center. Local recurrence, cancer specific survival (CSS), recurrence free survival (RFS), and overall survival (OS) were the main outcomes. Survival curves were generated using a Kaplan-Meier method. Perioperative outcomes and pathological outcomes were also analyzed.

Results

Overall, 98 male and 48 female patients were eligible for the study. The median tumor size was 3.4 cm with a median R.E.N.A.L. score of seven. Warm ischemia was used in 143 patients with a median ischemia time of 20 min and three patients had zero ischemia. Five patients (3.4%) had major complications (> Clavien IIIa) and only two were related to urinary system. The median global glomerular filtration rate (GFR) preserved after surgery was 93%. Pseudocapsule invasion was reported in 50 tumors (34%) and positive surgical margins were found in 3/146 (2.1%) tumors. At a median follow-up of 66 months, local recurrence happened in two patients (1.4%), and systemic recurrence happened in six patients (4.2%). The 5-year CSS, RFS, OS were 95.7, 89.6, and 91.9%, and the 10-year CSS, RFS, OS were 93.8, 89.6, and 90.0%, respectively.

Conclusion

This study indicates that tumor enucleation with laparoscopic or robotic approach in experienced hands for the treatment of RCC appears oncologically safe with a median follow-up of more than 5 years. Prospective studies with more patients and longer follow-up will be required to further evaluate oncologic safety after TE.
Machine Learning for Histologic Subtype Classification of Non-Small Cell Lung Cancer: A Retrospective Multicenter Radiomics Study
Authors: Yang Fengchang , Chen Wei , Wei Haifeng , Zhang Xianru , Yuan Shuanghu , Qiao Xu , Chen Yen-Wei
Published: January 2021

Background

Histologic phenotype identification of Non-Small Cell Lung Cancer (NSCLC) is essential for treatment planning and prognostic prediction. The prediction model based on radiomics analysis has the potential to quantify tumor phenotypic characteristics non-invasively. However, most existing studies focus on relatively small datasets, which limits the performance and potential clinical applicability of their constructed models.

Methods

To fully explore the impact of different datasets on radiomics studies related to the classification of histological subtypes of NSCLC, we retrospectively collected three datasets from multi-centers and then performed extensive analysis. Each of the three datasets was used as the training dataset separately to build a model and was validated on the remaining two datasets. A model was then developed by merging all the datasets into a large dataset, which was randomly split into a training dataset and a testing dataset. For each model, a total of 788 radiomic features were extracted from the segmented tumor volumes. Then three widely used features selection methods, including minimum Redundancy Maximum Relevance Feature Selection (mRMR), Sequential Forward Selection (SFS), and Least Absolute Shrinkage and Selection Operator (LASSO) were used to select the most important features. Finally, three classification methods, including Logistics Regression (LR), Support Vector Machines (SVM), and Random Forest (RF) were independently evaluated on the selected features to investigate the prediction ability of the radiomics models.

Results

When using a single dataset for modeling, the results on the testing set were poor, with AUC values ranging from 0.54 to 0.64. When the merged dataset was used for modeling, the average AUC value in the testing set was 0.78, showing relatively good predictive performance.

Conclusions

Models based on radiomics analysis have the potential to classify NSCLC subtypes, but their generalization capabilities should be carefully considered.
Integration Analysis of JAK2 or RUNX1 Mutation With Bone Marrow Blast Can Improve Risk Stratification in the Patients With Lower Risk Myelodysplastic Syndrome
Authors: Fang Ying , Guo Juan , Wu Dong , Wu Ling-Yun , Song Lu-Xi , Zhang Zheng , Zhao You-Shan , Chang Chun-Kang
Published: January 2021

Despite the improvements in prognostication of the revised International Prognostic Scoring System (IPSS-R) in myelodysplastic syndrome (MDS), there remain a portion of patients with lower risk (low/intermediate risk, LR) but poor prognostics. This study aimed to evaluate the relative contribution of mutational status when added to the IPSS-R, for estimating overall survival (OS) and progression-free survival (PFS) in patients with LR-MDS. We retrospectively analyzed clinical and laboratory variables of 328 patients diagnosed with MDS according to the FAB criteria. Twenty-nine-gene NGS assay was applied to bone marrow samples obtained at diagnosis. 233 (71.04%) patients were classified as LR-MDS. Univariate analysis showed association between inferior outcome (OS and PFS) and presence of JAK2 (p = 0.0177, p = 0.0002), RUNX1 (p = 0.0250, p = 0.0387), and U2AF1 (p = 0.0227, p = 0.7995) mutations. Multivariable survival analysis revealed JAK2 (p < 0.0001) and RUNX1 (p = 0.0215) mutations were independently prognostic for PFS in LR-MDS. Interestingly, bone marrow blast >1.5% could further predict disease progression of patients with LR-MDS (HR 8.06, 95%CI 2.95–22.04, p < 0.0001). Incorporation of JAK2, RUNX1 mutation and bone marrow blast in the IPSS-R can improve risk stratification in patients with LR-MDS. In summary, our result provided new risk factors for LR-MDS prognostics to identify candidates for early therapeutic intervention.
Exosomal Long Non-Coding RNA: Interaction Between Cancer Cells and Non-Cancer Cells
Authors: Han Shenqi , Qi Yongqiang , Luo Yiming , Chen Xiaoping , Liang Huifang
Published: January 2021

Exosomes are small membranous vesicles released by many kinds of cells, and are indispensable in cell-to-cell communication by delivering functional biological components both locally and systemically. Long non-coding RNAs (lncRNAs) are long transcripts over 200 nucleotides that exhibit no or limited protein-coding potentials. LncRNAs are dramatic gene expression regulators, and can be selectively sorted into exosomes. Exosomal lncRNAs derived from cancer cells and stromal cells can mediate the generation of pre-metastatic niches (PMNs) and thus promote the progression of cancer. In this review, we summarized the fundamental biology and characteristics of exosomal lncRNAs. Besides, we provided an overview of current research on functions of exosomal lncRNAs between cancer cells and non-cancer cells. A deep understanding of exosomal lncRNAs’ role in cancer will be facilitated to find important implications for cancer development and treatment.
The Role of Stellate Cells in Pancreatic Ductal Adenocarcinoma: Targeting Perspectives
Authors: Wu Yang , Zhang Chun , Jiang Kuirong , Werner Jens , Bazhin Alexandr V. , D’Haese Jan G.
Published: January 2021

Pancreatic ductal adenocarcinoma (PDAC) is a gastrointestinal malignancy with a dismal clinical outcome. Accumulating evidence suggests that activated pancreatic stellate cells (PSCs), the major producers of extracellular matrix (ECM), drive the severe stromal/desmoplastic reaction in PDAC. Furthermore, the crosstalk among PSCs, pancreatic cancer cells (PCCs) as well as other stroma cells can establish a growth-supportive tumor microenvironment (TME) of PDAC, thereby enhancing tumor growth, metastasis, and chemoresistance via various pathways. Recently, targeting stroma has emerged as a promising strategy for PDAC therapy, and several novel strategies have been proposed. The aim of our study is to give a profound review of the role of PSCs in PDAC progression and recent advances in stroma-targeting strategies.
The Understanding of Peak Oxygen Uptake in Children Aged 8–16
Authors: Wong Simpson W. L. , Yu Clare C. W. , Li Albert M.
Published: January 2021

Objective: To examine the understanding of the concept peak oxygen uptake (peak VO2) among children and adolescents at different ages from a developmental perspective.

Methods: A total of 549 children and adolescents aged 8 to 16 were recruited and instructed to fill in a 20-item Peak VO2Understanding Inventory developed with reference to the research literature on peak VO2. We presented the participants with twenty scenarios and asked them to indicate whether peak VO2 would “remain unchanged,” “increase,” or “decrease,” or that there was “insufficient information for a definite answer.” The cross-sectional data was analyzed by employing a series of ANOVA analyses and chi-square association tests. Additional statistical analyses were performed to examine the error patterns and if there were gender differences.

Results: Except for the 8-year-old group, the overall accuracy rate did not improve with age. Age-related differences in the choice of answers (“increase,” “decrease,” “unchanged,” and “uncertain”) for determining the resulting peak VO2 after a change of antecedent were observed. Error analysis by item showed that prefactual thinking that is important to understand the concept was emerging rather than fully developed in our child and adolescent samples.

Conclusion: The mastery of peak VO2 is not subject to age-related maturation but might demand the acquisition of specific logical reasoning skill such as perfactual thinking. Early introduction of peak VO2 and related concepts is advocated and should be emphasized on the reasoning rather than providing model answers in physical literacy education.
Home Albumin Infusion Therapy, Another Alternative Treatment in Patients With Congenital Nephrotic Syndrome of the Finnish Type
Authors: Serramontmany Eugènia , Muñoz Marina , Fernández-Polo Aurora , Morillo María , Gómez-Ganda Laura , Cañete-Ramírez Carme , Ariceta Gema
Published: January 2021

Background:Congenital nephrotic syndrome of the Finnish type (CNF) is a rare, severe glomerular disease caused by mutations in the NPHS1 gene, which codes for nephrin. It is characterised by massive proteinuria and severe edoema. Progression to end-stage kidney failure occurs during early childhood and the only curative treatment is kidney transplantation. Nowadays, patients need aggressive medical treatment, which includes daily albumin infusions (for months) until they get clinical stability to receive transplant.

Objective:In our paediatric hospital, we implemented a multidisciplinary program for the home infusion of albumin with outpatient follow-up. The aim of the study was to assess the safety and efficacy of this program for the first four years of its implementation.

Material and Methods:Retrospective observational study of CNF paediatric patients treated with home albumin infusion therapy from March 2014 to July 2018 at a tertiary care paediatric hospital. Information on albumin administration was obtained from the electronic prescription assistance program and details on clinical and care-related variables from the hospital's electronic information systems.

Results:Four patients with CNF received albumin infusions for 18, 21, 22 months, and 3 years. The treatment was safe, and the complication rates were to be expected considering the severity of disease. Patients required a median of two hospital admissions a year (19 in total); 47% due to catheter-related complications, but there were just three catheter infections.

Conclusions:In our experience, home albumin infusion therapy is safe and effective and helps to improve children health and quality of life.
SARS-CoV-2 Infections in Italian Schools: Preliminary Findings After 1 Month of School Opening During the Second Wave of the Pandemic
Authors: Buonsenso Danilo , De Rose Cristina , Moroni Rossana , Valentini Piero
Published: January 2021

Introduction: The impact of school opening on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is still unknown. This study aims to provide preliminary information about the number of SARS-CoV-2 cases among students attending Italian schools.

Methods: Data are extracted and analyzed from an open-access, online dataset that monitor, on a daily basis, media news about SARS-CoV-2 infections of students attending Italian schools.

Results: As of October 5, 2020, a total of 1,350 cases of SARS-CoV-2 infections have been registered in the Italian territory schools (involving 1,059 students, 145 teachers, and 146 other school members), for a total of 1,212 out of 65,104 (1.8%) Italian schools involved. National schools reported only one case of SARS-CoV-2 infection in more than 90% of cases, and only in one high school a cluster of more than 10 cases has been described (P = 0.015). The detection of one or more SARS-CoV-2 infections led to the closure of 192 (15.8%) entire schools, more frequently nursery/kindergartens (P < 0.0005).

Discussion: Our preliminary data support low transmission of SARS-CoV-2 within schools, at least among younger students. However, entire schools are frequently closed in the fear of larger outbreaks. Continuous monitoring of school settings, hopefully through daily updated open-access datasets, is needed to better understand the impact of schools on the pandemic and provide guidelines that better consider different risks within different age groups.
Transcatheter Closure of Patent Ductus Arteriosus in Premature Infants With Very Low Birth Weight
Authors: Wang Jieh-Neng , Lin Yung-Chieh , Hsieh Min-Ling , Wei Yu-Jen , Ju Ying-Tzu , Wu Jing-Ming
Published: January 2021

Background: The aim of this study was to describe our experience with transcatheter device closure of patent ductus arteriosus (PDA) in symptomatic low-birth-weight premature infants.

Methods: We performed a retrospective study of infants born with a birth body weight of < 2,000 g and admitted to National Cheng Kung University Hospital from September 2014 to December 2019. Basic demographic and clinical information as well as echocardiographic and angiographic data were recorded.

Results: Twenty-five premature infants (11 boys and 14 girls) born at gestational ages ranging between 22 and 35 weeks (mean, 25 weeks) were identified. The mean age at procedure was 34.5 ± 5.5 days, and the mean weight was 1,209 ± 94 g (range, 478–1,980 g). The mean diameter of the PDA was 3.4 ± 0.2 mm (range, 2.0–5.4 mm). The following devices were used in this study: Amplatzer Ductal Occluder II additional size (n = 20), Amplatzer Vascular Plug I (n = 1), and Amplatzer Vascular Plug II (n = 4). Complete closure was achieved in all patients. The mean follow-up period was 30.1 ± 17.3 months (range, 6–68 months). In total, 3 patients had left pulmonary artery (LPA) stenosis and 1 patient had coarctation of the aorta during the follow-up period. Younger procedure age and smaller procedure body weight were significantly associated with these obstructions.

Conclusions: Performing transcatheter PDA closure in symptomatic premature infants weighing more than 478 g is feasible using currently available devices; moreover, the procedure serves as an alternative to surgery.
Saponins in Chinese Herbal Medicine Exerts Protection in Myocardial Ischemia–Reperfusion Injury: Possible Mechanism and Target Analysis
Authors: Wang Ruiying , Wang Min , Zhou Jiahui , Wu Daoshun , Ye Jingxue , Sun Guibo , Sun Xiaobo
Published: January 2021

Myocardial ischemia is a high-risk disease among middle-aged and senior individuals. After thrombolytic therapy, heart tissue can potentially suffer further damage, which is called myocardial ischemia-reperfusion injury (MIRI). At present, the treatment methods and drugs for MIRI are scarce and cannot meet the current clinical needs. The mechanism of MIRI involves the interaction of multiple factors, and the current research hotspots mainly include oxidative stress, inflammation, calcium overload, energy metabolism disorders, pyroptosis, and ferroptosis. Traditional Chinese medicine (TCM) has multiple targets and few toxic side effects; clinical preparations containing Panax ginseng C. A. Mey., Panax notoginseng (Burk.) F. H. Chen, Aralia chinensis L., cardioprotection, and other Chinese herbal medicines have been used to treat patients with coronary heart disease, angina pectoris, and other cardiovascular diseases. Studies have shown that saponins are the main active substances in TCMs containing Panax ginseng C. A. Mey., Panax notoginseng (Burk.) F. H. Chen, Aralia chinensis L., and Radix astragali. In the present review, we sorted the saponin components with anti-MIRI effects and their regulatory mechanisms. Each saponin can play a cardioprotective role via multiple mechanisms, and the signaling pathways involved in different saponins are not the same. We found that more active saponins in Panax ginseng C. A. Mey. are mainly dammar-type structures and have a strong regulatory effect on energy metabolism. The highly active saponin components of Aralia chinensis L. are oleanolic acid structures, which have significant regulatory effects on calcium homeostasis. Therefore, saponins in Chinese herbal medicine provide a broad application prospect for the development of highly effective and low-toxicity anti-MIRI drugs.
Drug Repositioning for the Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy: A Mechanism- and Screening-Based Strategy
Authors: Yamamoto Shota , Egashira Nobuaki
Published: January 2021

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe adverse effect observed in most patients treated with neurotoxic anti-cancer drugs. Currently, there are no therapeutic options available for the prevention of CIPN. Furthermore, few drugs are recommended for the treatment of existing neuropathies because the mechanisms of CIPN remain unclear. Each chemotherapeutic drug induces neuropathy by distinct mechanisms, and thus we need to understand the characteristics of CIPN specific to individual drugs. Here, we review the known pathogenic mechanisms of oxaliplatin- and paclitaxel-induced CIPN, highlighting recent findings. Cancer chemotherapy is performed in a planned manner; therefore, preventive strategies can be planned for CIPN. Drug repositioning studies, which identify the unexpected actions of already approved drugs, have increased in recent years. We have also focused on drug repositioning studies, especially for prevention, because they should be rapidly translated to patients suffering from CIPN.
Activation of Tripartite Motif Containing 63 Expression by Transcription Factor EB and Transcription Factor Binding to Immunoglobulin Heavy Chain Enhancer 3 Is Regulated by Protein Kinase D and Class IIa Histone Deacetylases
Authors: Pablo Tortola Cristina , Fielitz Britta , Li Yi , Rüdebusch Julia , Luft Friedrich C. , Fielitz Jens
Published: January 2021

Rationale

The ubiquitin–proteasome system (UPS) is responsible for skeletal muscle atrophy. We showed earlier that the transcription factor EB (TFEB) plays a role by increasing E3 ubiquitin ligase muscle really interesting new gene-finger 1(MuRF1)/tripartite motif-containing 63 (TRIM63) expression. MuRF 1 ubiquitinates structural proteins and mediates their UPS-dependent degradation. We now investigated how TFEB-mediated TRIM63 expression is regulated.

Objective

Because protein kinase D1 (PKD1), histone deacetylase 5 (HDAC5), and TFEB belong to respective families with close structural, regulatory, and functional properties, we hypothesized that these families comprise a network regulating TRIM63 expression.

Methods and Results

We found that TFEB and transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3) activate TRIM63 expression. The class IIa HDACs HDAC4, HDAC5, and HDAC7 inhibited this activity. Furthermore, we could map the HDAC5 and TFE3 physical interaction. PKD1, PKD2, and PKD3 reversed the inhibitory effect of all tested class IIa HDACs toward TFEB and TFE3. PKD1 mediated nuclear export of all HDACs and lifted TFEB and TFE3 repression. We also mapped the PKD2 and HDAC5 interaction. We found that the inhibitory effect of PKD1 and PKD2 toward HDAC4, HDAC5, and HDAC7 was mediated by their phosphorylation and 14-3-3 mediated nuclear export.

Conclusion

TFEB and TFE3 activate TRIM63 expression. Both transcription factors are controlled by HDAC4, HDAC5, HDAC7, and all PKD-family members. We propose that the multilevel PKD/HDAC/TFEB/TFE3 network tightly controls TRIM63 expression.
Physiological Tradeoffs of Immune Response Differs by Infection Type in Pieris napi
Authors: Keehnen Naomi L. P. , Kučerová Lucie , Nylin Sören , Theopold Ulrich , Wheat Christopher W.
Published: January 2021

Understanding the tradeoffs that result from successful infection responses is central to understanding how life histories evolve. Gaining such insights, however, can be challenging, as they may be pathogen specific and confounded with experimental design. Here, we investigated whether infection from gram positive or negative bacteria results in different physiological tradeoffs, and whether these infections impact life history later in life (post-diapause development), in the butterfly Pieris napi. During the first 24 h after infection (3, 6, 12, and 24 h), after removing effects due to injection, larvae infected with Micrococcus luteus showed a strong suppression of all non-immunity related processes while several types of immune responses were upregulated. In contrast, this tradeoff between homeostasis and immune response was much less pronounced in Escherichia coli infections. These differences were also visible long after infection, via weight loss and slower development, as well as an increased mortality at higher infection levels during later stages of development. Individuals infected with M. luteus, compared to E. coli, had a higher mortality rate, and a lower pupal weight, developmental rate and adult weight. Further, males exhibited a more negative impact of infection than females. Thus, immune responses come at a cost even when the initial infection has been overcome, and these costs are likely to affect later life history parameters with fitness consequences.
Rapid Gardos Hereditary Xerocytosis Diagnosis in 8 Families Using Reticulocyte Indices
Authors: Picard Véronique , Guitton Corinne , Mansour-Hendili Lamisse , Jondeau Bernard , Bendélac Laurence , Denguir Maha , Demagny Julien , Proulle Valérie , Galactéros Frédéric , Garçon Loic
Published: January 2021

Gardos channelopathy (Gardos-HX) or type 2 stomatocytosis/xerocytosis is a hereditary hemolytic anemia due to mutations in the KCNN4 gene. It is rarer than inherited type 1 xerocytosis due to PIEZO1 mutations (Piezo1-HX) and its diagnosis is difficult given the absence of a specific clinical or biological phenotype. We report here that this diagnosis can be sped up using red blood cell (RBC) indices performed on an ADVIA 2120 (Siemens®) analyzer, which measures reticulocyte mean corpuscular volume (rMCV) and mean corpuscular hemoglobin concentration (rMCHC). We studied reticulocyte indices in 3 new and 12 described patients (8 families) with Gardos-HX, 11 subjects presented the recurrent p.Arg352His mutation, 4 cases (two families) carried a private KCNN4 mutation. They were compared to 79 described patients (49 families) with Piezo1-HX. Surprisingly, in Gardos-HX cases, rMCV revealed to be smaller than MCV and rMCHC higher than MCHC, in contrast with normal or Piezo1-HX RBC. Consequently, ΔMCV (rMCV-MCV) was −0.9 ± 5 fL vs. 19.8 ± 3 fL (p < 0.001) in Gardos compared with Piezo1-HX and ΔMCHC (rMCHC-MCHC) was 18.7 ± 13 vs. −50 ± 8.7 g/L (p < 0.001). A threshold of 8.6 fL for ΔMCV and −5.5 g/L for ΔMCHC could discriminate between Gardos and Piezo1-HX with 100% sensitivity and specificity, regardless of age, mutation or splenectomy status. Consequently, we showed that reticulocytes indices are useful to suggest Gardos-HX on blood count results, allowing to rapidly target these patients for gene analysis. In addition, these parameters may prove useful as a ‘functional tool’ in interpreting new KCNN4 variants.
Evaluation of Cardiac Circadian Rhythm Deconditioning Induced by 5-to-60 Days of Head-Down Bed Rest
Authors: Solbiati Sarah , Martin-Yebra Alba , Vaïda Pierre , Caiani Enrico G.
Published: January 2021

Head-down tilt (HDT) bed rest elicits changes in cardiac circadian rhythms, generating possible adverse health outcomes such as increased arrhythmic risk. Our aim was to study the impact of HDT duration on the circadian rhythms of heart beat (RR) and ventricular repolarization (QTend) duration intervals from 24-h Holter ECG recordings acquired in 63 subjects during six different HDT bed rest campaigns of different duration (two 5-day, two 21-day, and two 60-day). Circadian rhythms of RR and QTend intervals series were evaluated by Cosinor analysis, resulting in a value of midline (MESOR), oscillation amplitude (OA) and acrophase (φ). In addition, the QTc (with Bazett correction) was computed, and day-time, night-time, maximum and minimum RR, QTend and QTc intervals were calculated. Statistical analysis was conducted, comparing: (1) the effects at 5 (HDT5), 21 (HDT21) and 58 (HDT58) days of HDT with baseline (PRE); (2) trends in recovery period at post-HDT epochs (R) in 5-day, 21-day, and 60-day HDT separately vs. PRE; (3) differences at R + 0 due to bed rest duration; (4) changes between the last HDT acquisition and the respective R + 0 in 5-day, 21-day, and 60-day HDT. During HDT, major changes were observed at HDT5, with increased RR and QTend intervals’ MESOR, mostly related to day-time lengthening and increased minima, while the QTc shortened. Afterward, a progressive trend toward baseline values was observed with HDT progression. Additionally, the φ anticipated, and the OA was reduced during HDT, decreasing system’s ability to react to incoming stimuli. Consequently, the restoration of the orthostatic position elicited the shortening of RR and QTend intervals together with QTc prolongation, notwithstanding the period spent in HDT. However, the magnitude of post-HDT changes, as well as the difference between the last HDT day and R + 0, showed a trend to increase with increasing HDT duration, and 5/7 days were not sufficient for recovering after 60-day HDT. Additionally, the φ postponed and the OA significantly increased at R + 0 compared to PRE after 5-day and 60-day HDT, possibly increasing the arrhythmic risk. These results provide evidence that continuous monitoring of astronauts’ circadian rhythms, and further investigations on possible measures for counteracting the observed modifications, will be key for future missions including long periods of weightlessness and gravity transitions, for preserving astronauts’ health and mission success.
Molecular Basis for the Therapeutic Effects of Exercise on Mitochondrial Defects
Authors: Memme Jonathan M. , Hood David A.
Published: January 2021

Mitochondrial dysfunction is common to many organ system disorders, including skeletal muscle. Aging muscle and diseases of muscle are often accompanied by defective mitochondrial ATP production. This manuscript will focus on the pre-clinical evidence supporting the use of regular exercise to improve defective mitochondrial metabolism and function in skeletal muscle, through the stimulation of mitochondrial turnover. Examples from aging muscle, muscle-specific mutations and cancer cachexia will be discussed. We will also examine the effects of exercise on the important mitochondrial regulators PGC-1α, and Parkin, and summarize the effects of exercise to reverse mitochondrial dysfunction (e.g., ROS production, apoptotic susceptibility, cardiolipin synthesis) in muscle pathology. This paper will illustrate the breadth and benefits of exercise to serve as “mitochondrial medicine” with age and disease.
M/M/Infinity Birth-Death Processes – A Quantitative Representational Framework to Summarize and Explain Phase Singularity and Wavelet Dynamics in Atrial Fibrillation
Authors: Dharmaprani Dhani , Jenkins Evan , Aguilar Martin , Quah Jing X. , Lahiri Anandaroop , Tiver Kathryn , Mitchell Lewis , Kuklik Pawel , Meyer Christian , Willems Stephan , Clayton Richard , Nash Martyn , Nattel Stanley , McGavigan Andrew D. , Ganesan Anand N.
Published: January 2021

Rationale

A quantitative framework to summarize and explain the quasi-stationary population dynamics of unstable phase singularities (PS) and wavelets in human atrial fibrillation (AF) is at present lacking. Building on recent evidence showing that the formation and destruction of PS and wavelets in AF can be represented as renewal processes, we sought to establish such a quantitative framework, which could also potentially provide insight into the mechanisms of spontaneous AF termination.

Objectives

Here, we hypothesized that the observed number of PS or wavelets in AF could be governed by a common set of renewal rate constants λf (for PS or wavelet formation) and λd (PS or wavelet destruction), with steady-state population dynamics modeled as an M/M/∞ birth–death process. We further hypothesized that changes to the M/M/∞ birth–death matrix would explain spontaneous AF termination.

Methods and Results

AF was studied in in a multimodality, multispecies study in humans, animal experimental models (rats and sheep) and Ramirez-Nattel-Courtemanche model computer simulations. We demonstrated: (i) that λf and λd can be combined in a Markov M/M/∞ process to accurately model the observed average number and population distribution of PS and wavelets in all systems at different scales of mapping; and (ii) that slowing of the rate constants λf and λd is associated with slower mixing rates of the M/M/∞ birth–death matrix, providing an explanation for spontaneous AF termination.

Conclusion

M/M/∞ birth–death processes provide an accurate quantitative representational architecture to characterize PS and wavelet population dynamics in AF, by providing governing equations to understand the regeneration of PS and wavelets during sustained AF, as well as providing insight into the mechanism of spontaneous AF termination.
The Role of Glycocalyx and Caveolae in Vascular Homeostasis and Diseases
Authors: Potje Simone Regina , Paula Tiago Dal-Cin , Paulo Michele , Bendhack Lusiane Maria
Published: January 2021

This review highlights recent findings about the role that endothelial glycocalyx and caveolae play in vascular homeostasis. We describe the structure, synthesis, and function of glycocalyx and caveolae in vascular cells under physiological and pathophysiological conditions. Special focus will be given in glycocalyx and caveolae that are associated with impaired production of nitric oxide (NO) and generation of reactive oxygen species (ROS). Such alterations could contribute to the development of cardiovascular diseases, such as atherosclerosis, and hypertension.
Mercury-Tolerant Ensifer medicae Strains Display High Mercuric Reductase Activity and a Protective Effect on Nitrogen Fixation in Medicago truncatula Nodules Under Mercury Stress
Authors: Arregui Gabriela , Hipólito Pablo , Pallol Beatriz , Lara-Dampier Victoria , García-Rodríguez Diego , Varela Higinio P. , Tavakoli Zaniani Parinaz , Balomenos Dimitrios , Paape Timothy , Coba de la Peña Teodoro , Lucas M. Mercedes , Pueyo José J.
Published: January 2021

Mercury (Hg) is extremely toxic for all living organisms. Hg-tolerant symbiotic rhizobia have the potential to increase legume tolerance, and to our knowledge, the mechanisms underlying Hg tolerance in rhizobia have not been investigated to date. Rhizobial strains of Ensifer medicae, Rhizobium leguminosarum bv. trifolii and Bradyrhizobium canariense previously isolated from severely Hg-contaminated soils showed different levels of Hg tolerance. The ability of the strains to reduce mercury Hg2+ to Hg0, a volatile and less toxic form of mercury, was assessed using a Hg volatilization assay. In general, tolerant strains displayed high mercuric reductase activity, which appeared to be inducible in some strains when grown at a sub-lethal HgCl2 concentration. A strong correlation between Hg tolerance and mercuric reductase activity was observed for E. medicae strains, whereas this was not the case for the B. canariense strains, suggesting that additional Hg tolerance mechanisms could be playing a role in B. canariense. Transcript abundance from merA, the gene that encodes mercuric reductase, was quantified in tolerant and sensitive E. medicae and R. leguminosarum strains. Tolerant strains presented higher merA expression than sensitive ones, and an increase in transcript abundance was observed for some strains when bacteria were grown in the presence of a sub-lethal HgCl2 concentration. These results suggest a regulation of mercuric reductase in rhizobia. Expression of merA genes and mercuric reductase activity were confirmed in Medicago truncatula nodules formed by a sensitive or a tolerant E. medicae strain. Transcript accumulation in nodules formed by the tolerant strain increased when Hg stress was applied, while a significant decrease in expression occurred upon stress application in nodules formed by the Hg-sensitive strain. The effect of Hg stress on nitrogen fixation was evaluated, and in our experimental conditions, nitrogenase activity was not affected in nodules formed by the tolerant strain, while a significant decrease in activity was observed in nodules elicited by the Hg-sensitive bacteria. Our results suggest that the combination of tolerant legumes with tolerant rhizobia constitutes a potentially powerful tool in the bioremediation of Hg-contaminated soils.
Metabolic Modeling of the C3-CAM Continuum Revealed the Establishment of a Starch/Sugar-Malate Cycle in CAM Evolution
Authors: Tay Ignacius Y. Y. , Odang Kristoforus Bryant , Cheung C. Y. Maurice
Published: January 2021

The evolution of Crassulacean acid metabolism (CAM) is thought to be along a C3-CAM continuum including multiple variations of CAM such as CAM cycling and CAM idling. Here, we applied large-scale constraint-based modeling to investigate the metabolism and energetics of plants operating in C3, CAM, CAM cycling, and CAM idling. Our modeling results suggested that CAM cycling and CAM idling could be potential evolutionary intermediates in CAM evolution by establishing a starch/sugar-malate cycle. Our model analysis showed that by varying CO2 exchange during the light period, as a proxy of stomatal conductance, there exists a C3-CAM continuum with gradual metabolic changes, supporting the notion that evolution of CAM from C3 could occur solely through incremental changes in metabolic fluxes. Along the C3-CAM continuum, our model predicted changes in metabolic fluxes not only through the starch/sugar-malate cycle that is involved in CAM photosynthetic CO2 fixation but also other metabolic processes including the mitochondrial electron transport chain and the tricarboxylate acid cycle at night. These predictions could guide engineering efforts in introducing CAM into C3 crops for improved water use efficiency.
Importin-β From the Recretohalophyte Limonium bicolor Enhances Salt Tolerance in Arabidopsis thaliana by Reducing Root Hair Development and Abscisic Acid Sensitivity
Authors: Xu Yanyu , Jiao Xiangmei , Wang Xi , Zhang Haonan , Wang Baoshan , Yuan Fang
Published: January 2021

Aims

To elucidate the genetics underlying salt tolerance in recretohalophytes and assess its relevance to non-halophytes, we cloned the Limonium bicolor homolog of Arabidopsis thaliana (Arabidopsis) SUPER SENSITIVE TO ABA AND DROUGHT2 (AtSAD2) and named it LbSAD2, an importin-β gene associated with trichome initiation and reduced abscisic acid (ABA) sensitivity, and then we assessed the heterologously expressed LbSAD2 in Arabidopsis.

Methods

We examined LbSAD2 expression and assessed the effect of heterologous LbSAD2 expression in Arabidopsis on root hair/trichome induction; the expression levels of possible related genes in trichome/root hair development; some physiological parameters involved in salt tolerance including germination rate, root length, and contents of Na+, proline, and malondialdehyde; and the response of ABA at the germination stage.

Results

The LbSAD2 gene is highly expressed in the salt gland development stage and salt treatment, especially located in the salt gland by in situ hybridization, and the LbSAD2 protein contains some special domains compared with AtSAD2, which may suggest the involvement of LbSAD2 in salt tolerance. Compared with the SAD2/GL1 mutant CS65878, which lacks trichomes, CS65878-35S:LbSAD2 had higher trichome abundance but lower root hair abundance. Under 100 mM NaCl treatment, CS65878-35S:LbSAD2 showed enhanced germination and root lengths; improved physiological parameters, including high proline and low contents of Na+ and malondialdehyde; higher expression of the salt-tolerance genes Δ1-PYRROLINE-5-CARBOXYLATE SYNTHETASE 1 (P5CS1) and GST CLASS TAU 5 (GSTU5); reduced ABA sensitivity; and increased expression of the ABA signaling genes RESPONSIVE TO ABA 18 (RAB18) and SNF1-RELATED PROTEIN KINASE 2 (SRK2E), but not of the ABA biosynthesis gene 9-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (NCED3).

Conclusion

LbSAD2 enhances salt tolerance in Arabidopsis by specifically reducing root hair development, Na+ accumulation, and ABA sensitivity.
Phenotypic Selection on Flower Color and Floral Display Size by Three Bee Species
Authors: Brunet Johanne , Flick Andrew J. , Bauer Austin A.
Published: January 2021

Plants exhibit a wide array of floral forms and pollinators can act as agent of selection on floral traits. Two trends have emerged from recent reviews of pollinator-mediated selection in plants. First, pollinator-mediated selection on plant-level attractants such as floral display size is stronger than on flower-level attractant such as flower color. Second, when comparing plant species, distinct pollinators can exert different selection patterns on floral traits. In addition, many plant species are visited by a diverse array of pollinators but very few studies have examined selection by distinct pollinators. In the current study, we examined phenotypic selection on flower color and floral display size by three distinct bee species, the European honey bee,Apis mellifera, the common eastern bumble bee,Bombus impatiens, and the alfalfa leafcutting bee,Megachile rotundata, foraging onMedicago sativa.To estimate phenotypic selection by each bee species and for all bees combined simultaneously and on the same group of plants, we introduce a new method that combines pollinator visitation data to seed set and floral trait measurements data typical of phenotypic selection study. When comparing floral traits, all bee species selected on the number of racemes per stem and the number of stems per plant, two components of floral display size. However, only leafcutting bees selected on hue or flower color and only bumble bees selected on chroma or darkness of flowers. Selection on chroma occurred via correlational selection between chroma and number of open flowers per raceme and we examine how correlational selection may facilitate the evolution of flower color in plant populations. When comparing bee species, the three bee species exerted similar selection pattern on some floral traits but different patterns on other floral traits and differences in selection patterns were observed between flower-level and plant-level attractants. The trends detected were consistent with previous studies and we advocate the approach introduced here for future studies examining the impact of distinct pollinators on floral trait evolution.
Endoplasmic Reticulum-Mediated Protein Quality Control and Endoplasmic Reticulum-Associated Degradation Pathway Explain the Reduction of N-glycoprotein Level Under the Lead Stress
Authors: Du Hong , Zheng Canqi , Aslam Muhmmad , Xie Xihui , Wang Wanna , Yang Yingquan , Liu Xiaojuan
Published: January 2021

Different anthropogenic activities result in the continuous increase of metal lead (Pb) in the environment and adversely affect living organisms. Therefore, it is important to investigate the tolerance mechanism in a model organism. Chlamydomonas reinhardtii is an important green eukaryotic model microalga for studying different kinds of biological questions. In this study, the responses of C. reinhardtii were revealed via a comprehensive approach, including physiological, genomic, transcriptomic, glycomic, and bioinformatic techniques. Physiological results showed that the growth rate and soluble protein content were significantly reduced under the high lead stress. Also, the results obtained from the genomic and transcriptomic analyses presented that the endoplasmic reticulum-mediated protein quality control (ERQC) system and endoplasmic reticulum-associated degradation (ERAD) pathway were activated under the third day of high lead stress. The unique upregulated protein disulfide isomerase genes on the ERQC system were proposed to be important for the protein level and protein quality control. The accumulation of specific N-glycans indicated that specific N-glycosylation of proteins might alter the biological functions of proteins to alleviate the Pb stress in alga and/or lead to the degradation of incomplete/misfolded proteins. At the same time, it was observed that genes involved in each process of ERAD were upregulated, suggesting that the ERAD pathway was activated to assist the degradation of incomplete/misfolded proteins. Therefore, it is reasonable to speculate that the reduction of protein level under the high lead stress was related to the activated ERQC system and QRAD pathway. Our findings will provide a solid and reliable foundation and a proposed ERAD working model for further in-depth study of the ERQC system and ERAD pathway under the Pb stress and even other biotic and abiotic stresses.
Comparative Analyses of Chloroplast Genomes From 14 Zanthoxylum Species: Identification of Variable DNA Markers and Phylogenetic Relationships Within the Genus
Authors: Zhao Kaihui , Li Lianqiang , Quan Hong , Yang Junbo , Zhang Zhirong , Liao Zhihua , Lan Xiaozhong
Published: January 2021

Zanthoxylum L. is an economic crop with a long history of cultivation and domestication and has important economic, ecological, and medicinal value. To solve the classification problems caused by the similar morphological characteristics of Zanthoxylum and establish a credible phylogenetic relationship, we sequenced and annotated six Zanthoxylum chloroplast (cp) genomes (Z. piasezkii, Z. armatum, Z. motuoense, Z. oxyphyllum, Z. multijugum, and Z. calcicola) and combined them with previously published genomes for the Zanthoxylum species. We used bioinformatics methods to analyze the genomic characteristics, contraction, and expansion of inverted repeat (IR) regions; differences in simple sequence repeats (SSRs) and long repeat sequences; species pairwise Ka/Ks ratios; divergence hotspots; and phylogenetic relationships of the 14 Zanthoxylum species. The results revealed that cp genomes of Zanthoxylum range in size from 158,071 to 158,963 bp and contain 87 protein-coding, 37 tRNA, and 8 rRNA genes. Seven mutational hotspots were identified as candidate DNA barcode sequences to distinguish Zanthoxylum species. The phylogenetic analysis strongly supported the genus Fagara as a subgenus of Zanthoxylum and proposed the possibility of a new subgenus in Zanthoxylum. The availability of these genomes will provide valuable information for identifying species, molecular breeding, and evolutionary analysis of Zanthoxylum.
Unraveling Reticulate Evolution in Opuntia (Cactaceae) From Southern Mexico
Authors: Granados-Aguilar Xochitl , Granados Mendoza Carolina , Cervantes Cristian Rafael , Montes José Rubén , Arias Salvador
Published: January 2021

The process of hybridization occurs in approximately 40% of vascular plants, and this exchange of genetic material between non-conspecific individuals occurs unequally among plant lineages, being more frequent in certain groups such asOpuntia(Cactaceae). This genus is known for multiple taxonomic controversies due to widespread polyploidy and probable hybrid origin of several of its species. Southern Mexico species of this genus have been poorly studied despite their great diversity in regions such as the Tehuacán-Cuicatlán Valley which contains around 12% of recognized Mexico’s nativeOpuntiaspecies. In this work, we focus on testing the hybrid status of two putative hybrids from this region,Opuntia tehuacanaandOpuntia pilifera, and estimate if hybridization occurs among sampled southern opuntias using two newly identified nuclear intron markers to construct phylogenetic networks with HyDe and Dsuite and perform invariant analysis under the coalescent model with HyDe and Dsuite. For the test of hybrid origin inO. tehuacana, our results could not recover hybridization as proposed in the literature, but we found introgression intoO. tehuacanaindividuals involvingO. decumbensandO. huajuapensis. RegardingO. pilifera, we identifiedO. decumbensas probable parental species, supported by our analysis, which sustains the previous hybridization hypothesis betweenNopaleaandBasilaresclades. Finally, we suggest new hybridization and introgression cases among southern Mexican species involvingO. tehuantepecanaandO. depressaas parental species ofO. velutinaandO. decumbens.
Regulation of Exocyst Function in Pollen Tube Growth by Phosphorylation of Exocyst Subunit EXO70C2
Authors: Saccomanno Antonietta , Potocký Martin , Pejchar Přemysl , Hála Michal , Shikata Hiromasa , Schwechheimer Claus , Žárský Viktor
Published: January 2021

Exocyst is a heterooctameric protein complex crucial for the tethering of secretory vesicles to the plasma membrane during exocytosis. Compared to other eukaryotes, exocyst subunit EXO70 is represented by many isoforms in land plants whose cell biological and biological roles, as well as modes of regulation remain largely unknown. Here, we present data on the phospho-regulation of exocyst isoform EXO70C2, which we previously identified as a putative negative regulator of exocyst function in pollen tube growth. A comprehensive phosphoproteomic analysis revealed phosphorylation of EXO70C2 at multiple sites. We have now performed localization and functional studies of phospho-dead and phospho-mimetic variants of Arabidopsis EXO70C2 in transiently transformed tobacco pollen tubes and stably transformed Arabidopsis wild type and exo70C2 mutant plants. Our data reveal a dose-dependent effect of AtEXO70C2 overexpression on pollen tube growth rate and cellular architecture. We show that changes of the AtEXO70C2 phosphorylation status lead to distinct outcomes in wild type and exo70c2 mutant cells, suggesting a complex regulatory pattern. On the other side, phosphorylation does not affect the cytoplasmic localization of AtEXO70C2 or its interaction with putative secretion inhibitor ROH1 in the yeast two-hybrid system.