bluuebunny/crossref_metadata_2025 huggingface dataset:
The Transcriptomic and Phenotypic Response of the Melanized Yeast Exophiala dermatitidis to Ionizing Particle Exposure
Authors: Schultzhaus Zachary , Chen Amy , Shuryak Igor , Wang Zheng
Published: January 2021

Fungi can tolerate extremely high doses of ionizing radiation compared with most other eukaryotes, a phenomenon encompassing both the recovery from acute exposure and the growth of melanized fungi in chronically contaminated environments such as nuclear disaster sites. This observation has led to the use of fungi in radiobiology studies, with the goal of finding novel resistance mechanisms. However, it is still not entirely clear what underlies this phenomenon, as genetic studies have not pinpointed unique responses to ionizing radiation in the most resistant fungi. Additionally, little work has been done examining how fungi (other than budding yeast) respond to irradiation by ionizing particles (e.g., protons, α-particles), although particle irradiation may cause distinct cellular damage, and is more relevant for human risks. To address this paucity of data, in this study we have characterized the phenotypic and transcriptomic response of the highly radioresistant yeast Exophiala dermatitidis to irradiation by three separate ionizing radiation sources: protons, deuterons, and α-particles. The experiment was performed with both melanized and non-melanized strains of E. dermatitidis, to determine the effect of this pigment on the response. No significant difference in survival was observed between these strains under any condition, suggesting that melanin does not impart protection to acute irradiation to these particles. The transcriptomic response during recovery to particle exposure was similar to that observed after γ-irradiation, with DNA repair and replication genes upregulated, and genes involved in translation and ribosomal biogenesis being heavily repressed, indicating an attenuation of cell growth. However, a comparison of global gene expression showed clear clustering of particle and γ-radiation groups. The response elicited by particle irradiation was, in total, more complex. Compared to the γ-associated response, particle irradiation resulted in greater changes in gene expression, a more diverse set of differentially expressed genes, and a significant induction of gene categories such as autophagy and protein catabolism. Additionally, analysis of individual particle responses resulted in identification of the first unique expression signatures and individual genes for each particle type that could be used as radionuclide discrimination markers.
CopR, a Global Regulator of Transcription to Maintain Copper Homeostasis in Pyrococcus furiosus
Authors: Grünberger Felix , Reichelt Robert , Waege Ingrid , Ned Verena , Bronner Korbinian , Kaljanac Marcell , Weber Nina , El Ahmad Zubeir , Knauss Lena , Madej M. Gregor , Ziegler Christine , Grohmann Dina , Hausner Winfried
Published: January 2021

Although copper is in many cases an essential micronutrient for cellular life, higher concentrations are toxic. Therefore, all living cells have developed strategies to maintain copper homeostasis. In this manuscript, we have analyzed the transcriptome-wide response of Pyrococcus furiosus to increased copper concentrations and described the essential role of the putative copper-sensing metalloregulator CopR in the detoxification process. To this end, we employed biochemical and biophysical methods to characterize the role of CopR. Additionally, a copR knockout strain revealed an amplified sensitivity in comparison to the parental strain towards increased copper levels, which designates an essential role of CopR for copper homeostasis. To learn more about the CopR-regulated gene network, we performed differential gene expression and ChIP-seq analysis under normal and 20 μM copper-shock conditions. By integrating the transcriptome and genome-wide binding data, we found that CopR binds to the upstream regions of many copper-induced genes. Negative-stain transmission electron microscopy and 2D class averaging revealed an octameric assembly formed from a tetramer of dimers for CopR, similar to published crystal structures from the Lrp family. In conclusion, we propose a model for CopR-regulated transcription and highlight the regulatory network that enables Pyrococcus to respond to increased copper concentrations.
A Burkholderia thailandensis DedA Family Membrane Protein Is Required for Proton Motive Force Dependent Lipid A Modification
Authors: Panta Pradip R. , Doerrler William T.
Published: January 2021

The DedA family is a conserved membrane protein family found in most organisms. A Burkholderia thailandensis DedA family protein, named DbcA, is required for high-level colistin (polymyxin E) resistance, but the mechanism awaits elucidation. Modification of lipopolysaccharide lipid A with the cationic sugar aminoarabinose (Ara4N) is required for colistin resistance and is dependent upon protonmotive force (PMF) dependent transporters. B. thailandensis ΔdbcA lipid A contains only small amounts of Ara4N, likely leading to colistin sensitivity. Two B. thailandensis operons are required for lipid A modification with Ara4N, one needed for biosynthesis of undecaprenyl-P-Ara4N and one for transport of the lipid linked sugar and subsequent lipid A modification. Here, we directed overexpression of each arn operon by genomic insertion of inducible promoters. We found that overexpression of arn operons in ΔdbcA can partially, but not completely, restore Ara4N modification of lipid A and colistin resistance. Artificially increasing the PMF by lowering the pH of the growth media also increased membrane potential, amounts of Ara4N, and colistin resistance of ΔdbcA. In addition, the products of arn operons are essential for acid tolerance, suggesting a physiological function of Ara4N modification. Finally, we show that ΔdbcA is sensitive to bacitracin and expression of a B. thailandensis UppP/BacA homolog (BTH_I1512) can partially restore resistance to bacitracin. Expression of a different UppP/BacA homolog (BTH_I2750) can partially restore colistin resistance, without changing the lipid A profile. This work suggests that maintaining optimal membrane potential at slightly alkaline pH media by DbcA is responsible for proper modification of lipid A by Ara4N and provides evidence of lipid A modification-dependent and -independent mechanisms of colistin resistance in B. thailandensis.
Loss of Social/Non-social Context Discrimination by Movement Acceleration in the Valproate Model of Autism
Authors: Quezada Nelva T. , Salas-Ortíz Sebastiana F. , Peralta Francisco A. , Aguayo Felipe I. , Morgado-Gallardo Katherine P. , Mac-Rae Catherine A. , Fiedler Jenny L. , Aliaga Esteban E.
Published: January 2021

Autism spectrum disorder (ASD) is a neurodevelopmental alteration characterized by social/communicative deficits, repetitive/stereotyped movements, and restricted/obsessive interests. However, there is not much information about whether movement alterations in ASD comprise modifications at the basic kinematic level, such as trajectory and velocity, which may contribute to the higher level of processing that allows the perception and interpretation of actions performed by others, and hence, impact social interaction. In order to further explore possible motor alterations in ASD, we analyzed movement parameters in the Valproate (VPA) animal model of autism. We found that VPA-treated rats displayed greater movement acceleration, reduced distance between stops, spent more time in the corner of the open-field arena, and executed a number of particular behaviors; for example, supported rearing and circling, with no major changes in distance and velocity. However, in the social interaction test, we found other alterations in the movement parameters. In addition to increased acceleration, VPA-rats displayed reduced velocity, increased stops, reduced distance/stop and lost the social/non-social area discrimination that is characteristic of control rats in acceleration and stops variables. Hence, even if prenatal VPA-treatment could have a minor effect in motor variables in a non-social context, it has a crucial effect in the capacity of the animals to adjust their kinematic variables when social/non-social context alternation is required.
Less Is Better: Single-Digit Brain Functional Connections Predict T2DM and T2DM-Induced Cognitive Impairment
Authors: Qian Haotian , Qin Dongxue , Qi Shouliang , Teng Yueyang , Li Chen , Yao Yudong , Wu Jianlin
Published: January 2021

Type 2 diabetes mellitus (T2DM) leads to a higher risk of brain damage and adversely affects cognition. The underlying neural mechanism of T2DM-induced cognitive impairment (T2DM-CI) remains unclear. This study proposes to identify a small number of dysfunctional brain connections as imaging biomarkers, distinguishing between T2DM-CI, T2DM with normal cognition (T2DM-NC), and healthy controls (HC). We have recruited 22 T2DM-CI patients, 31 T2DM-NC patients, and 39 HCs. The structural Magnetic Resonance Imaging (MRI) and resting state fMRI images are acquired, and neuropsychological tests are carried out. Amplitude of low frequency fluctuations (ALFF) is analyzed to identify impaired brain regions implicated with T2DM and T2DM-CI. The functional network is built and all connections connected to impaired brain regions are selected. Subsequently, L1-norm regularized sparse canonical correlation analysis and sparse logistic regression are used to identify discriminative connections and Support Vector Machine is trained to realize three two-category classifications. It is found that single-digit dysfunctional connections predict T2DM and T2DM-CI. For T2DM-CI versus HC, T2DM-NC versus HC, and T2DM-CI versus T2DM-NC, the number of connections is 6, 7, and 5 and the area under curve (AUC) can reach 0.912, 0.901, and 0.861, respectively. The dysfunctional connection is mainly related to Default Model Network (DMN) and long-distance links. The strength of identified connections is significantly different among groups and correlated with cognitive assessment score (p< 0.05). Via ALFF analysis and further feature selection algorithms, a small number of dysfunctional brain connections can be identified to predict T2DM and T2DM-CI. These connections might be the imaging biomarkers of T2DM-CI and targets of intervention.
Electrophysiological Analysis of Brain Organoids: Current Approaches and Advancements
Authors: Passaro Austin P. , Stice Steven L.
Published: January 2021

Brain organoids, or cerebral organoids, have become widely used to study the human brain in vitro. As pluripotent stem cell-derived structures capable of self-organization and recapitulation of physiological cell types and architecture, brain organoids bridge the gap between relatively simple two-dimensional human cell cultures and non-human animal models. This allows for high complexity and physiological relevance in a controlled in vitro setting, opening the door for a variety of applications including development and disease modeling and high-throughput screening. While technologies such as single cell sequencing have led to significant advances in brain organoid characterization and understanding, improved functional analysis (especially electrophysiology) is needed to realize the full potential of brain organoids. In this review, we highlight key technologies for brain organoid development and characterization, then discuss current electrophysiological methods for brain organoid analysis. While electrophysiological approaches have improved rapidly for two-dimensional cultures, only in the past several years have advances been made to overcome limitations posed by the three-dimensionality of brain organoids. Here, we review major advances in electrophysiological technologies and analytical methods with a focus on advances with applicability for brain organoid analysis.
Quantification of Huntington’s Disease Related Markers in the R6/2 Mouse Model
Authors: Etxeberria-Rekalde Estibaliz , Alzola-Aldamizetxebarria Saioa , Flunkert Stefanie , Hable Isabella , Daurer Magdalena , Neddens Joerg , Hutter-Paier Birgit
Published: January 2021

Huntington’s disease (HD) is caused by an expansion of CAG triplets in the huntingtin gene, leading to severe neuropathological changes that result in a devasting and lethal phenotype. Neurodegeneration in HD begins in the striatum and spreads to other brain regions such as cortex and hippocampus, causing motor and cognitive dysfunctions. To understand the signaling pathways involved in HD, animal models that mimic the human pathology are used. The R6/2 mouse as model of HD was already shown to present major neuropathological changes in the caudate putamen and other brain regions, but recently established biomarkers in HD patients were yet not analyzed in these mice. We therefore performed an in-depth analysis of R6/2 mice to establish new and highly translational readouts focusing on Ctip2 as biological marker for motor system-related neurons and translocator protein (TSPO) as a promising readout for early neuroinflammation. Our results validate already shown pathologies like mutant huntingtin aggregates, ubiquitination, and brain atrophy, but also provide evidence for decreased tyrosine hydroxylase and Ctip2 levels as indicators of a disturbed motor system, while vesicular acetyl choline transporter levels as marker for the cholinergic system barely change. Additionally, increased astrocytosis and activated microglia were observed by GFAP, Iba1 and TSPO labeling, illustrating, that TSPO is a more sensitive marker for early neuroinflammation compared to GFAP and Iba1. Our results thus demonstrate a high sensitivity and translational value of Ctip2 and TSPO as new marker for the preclinical evaluation of new compounds in the R6/2 mouse model of HD.
E2F1 Induces KIF26A Transcription and Promotes Cell Cycle Progression via CDK–RB–E2Fs Feedback Loop in Breast Cancer
Authors: Xu Jing , Liu Lei , Ma Ranran , Wang Yawen , Chen Xu , Liu Haiting , Ji Youxin , Liu Tiantian , Gao Peng
Published: January 2021

Objective

The aim of this study was to investigate the role of KIF26A in breast cancer.

Method

qRT-PCR and immunohistochemistry were conducted to explore KIF26A expression and functional contribution to breast cancer development. MTS, EDU, colony formation assays, and flow cytometry analysis were conducted to assess cell proliferation characteristics and cell cycle progression. A series of 5′-flanking region deletion plasmids and mutating the binding site, with the luciferase reporter assay, were used to identify the core promotor region of KIF26A. The prediction by software and construction of the transcriptional factor plasmids were used to identify the transcriptional factor. Chromatin immunoprecipitation assay could demonstrate transcriptional factor directly binding to the KIF26A promoter. Human Genome Oligo Microarray Assay and gene ontology (GO) and pathway analyses were used to predict the downstream pathway.

Results

Our results showed that in breast cancer tissues, elevated KIF26A expression was significantly correlated with lymph node metastasis. KIF26A could promote proliferation and G0/G1 phase cell cycle progression in breast cancer cells. The core promoter region of the human KIF26A gene was located upstream of the transcription start site at position −395 to −385. The transcriptional factor E2F1 was shown to activate KIF26A expression. Furthermore, KIF26A was shown to inhibit the expression of p21, then activate CDK–RB–E2Fs pathway. The elevated E2F1 can activate the cell cycle progression and the KIF26A expression, forming feedback loop.

Conclusions

The present study demonstrated that KIF26A, directly upregulated by E2F1, promoted cell proliferation and cell cycle progression via CDK–RB–E2Fs feedback loop in breast cancer.
Development and Validation of a Nomogram for Predicting Survival in Gallbladder Cancer Patients With Recurrence After Surgery
Authors: Chen Mingyu , Li Shijie , Topatana Win , Lv Xiaozhong , Cao Jiasheng , Hu Jiahao , Lin Jian , Juengpanich Sarun , Shen Jiliang , Cai Xiujun
Published: January 2021

Background

The management of gallbladder cancer (GBC) patients with recurrence who need additional therapy or intensive follow-up remains controversial. Therefore, we aim to develop a nomogram to predict survival in GBC patients with recurrence after surgery.

Methods

A total of 313 GBC patients with recurrence from our center was identified as a primary cohort, which were randomly divided into a training cohort (N = 209) and an internal validation cohort (N = 104). In addition, 105 patients from other centers were selected as an external validation cohort. Independent prognostic factors, identified by univariate and multivariable analysis, were used to construct a nomogram. The performance of this nomogram was measured using Harrell’s concordance index (C-index) and calibration curves.

Results

Our nomogram was established by four factors, including time-to-recurrence, site of recurrence, CA19-9 at recurrence, and treatment of recurrence. The C-index of this nomogram in the training, internal and external validation cohort was 0.871, 0.812, and 0.754, respectively. The calibration curves showed an optimal agreement between nomogram prediction and actual observation. Notably, this nomogram could accurately stratify patients into different risk subgroups, which allowed more significant distinction of Kaplan-Meier curves than that of using T category. The 3-year post-recurrence survival (PRS) rates in the low-, medium-, and high-risk subgroups from the external validation cohort were 53.3, 26.2, and 4.1%, respectively.

Conclusion

This nomogram provides a tool to predict 1- and 3-year PRS rates in GBC patients with recurrence after surgery.
Insights Into the Impacts of BRCA Mutations on Clinicopathology and Management of Early-Onset Triple-Negative Breast Cancer
Authors: Ye Fugui , He Min , Huang Liang , Lang Guantian , Hu Xin , Shao Zhimin , Di Genhong , Cao Ayong
Published: January 2021

Background

Little is known regarding the clinicopathologic characteristics, oncologic outcomes, and treatment strategies that could be ascribed to BRCA mutation in early-onset triple-negative breast cancer (eTNBC).

Methods

eTNBC patients who underwent BRCA genetic testing were derived from our clinical database between 2012 and 2018. Differences in clinical features and pathologic characteristics were examined in groups divided by BRCA mutation status, and the contribution of germline mutations in conjunction with treatment modalities to survival outcomes was determined.

Results

Of the 355 qualifying eTNBC patients, 67 (18.87%) were BRCA mutated and 288 (81.13%) were BRCA wild. Overall, median age at diagnosis was 34 years (range, 24–40 years) in the BRCA mutated subgroup and 35 years (range, 21–40 years) in BRCA wild. The majority of clinicopathologic parameters were parallel; however, tumor size (P = 0.07) and nuclear grade (P =0.08) tend to be more aggressive in the BRCA mutated subgroup. Compared with BRCA wild patients, BRCA mutated patients had a higher likelihood of receiving anthracyclines and taxane-based combination chemotherapy (P = 0.04) and tend to be lower tumor burden (P =0.01). After approximately 5-year median follow-up, the overall survival (OS) (P = 0.021) and breast cancer-specific survival (BCSS) (P = 0.004) in BRCA mutated patients were superior to those in their BRCA wild counterparts. Intriguingly, the clinical outcomes were comparable in patients with breast conserving surgery (BCS) regardless of BRCA mutations and in patients with BRCA mutations in spite of surgical schedules.

Conclusions

These results suggest that eTNBC patients with BRCA mutations are prone to better OS and BCSS, which might be largely attributed to more benefit from anthracyclines and taxane-based chemotherapy. The BCS procedure could be a safe alternative surgical option for eTNBC patients with BRCA mutations. Future studies with substantial numbers of participants are urgently needed to validate whether BRCA mutation eTNBC patients are more sensitive to chemotherapy.
Tumor Profiling at the Service of Cancer Therapy
Authors: Fernandez-Rozadilla Ceres , Simões Ana Rita , Lleonart Matilde E. , Carnero Amancio , Carracedo Ángel
Published: January 2021

Cancer treatment options have evolved significantly in the past few years. From the initial surgical procedures, to the latest next-generation technologies, we are now in the position to analyze and understand tumors in a one-by-one basis and use that to our advantage to provide with individualized treatment options that may increase patient survival. In this review, we will focus on how tumor profiling has evolved over the past decades to deliver more efficient and personalized treatment options, and how novel technologies can help us envisage the future of precision oncology toward a better management and, ultimately, increased survival.
Vitamin C Administration by Intravenous Infusion Increases Tumor Ascorbate Content in Patients With Colon Cancer: A Clinical Intervention Study
Authors: Dachs Gabi U. , Gandhi Jamish , Wohlrab Christina , Carr Anitra C. , Morrin Helen R. , Pullar Juliet M. , Bayer Simone B. , Eglinton Tim W. , Robinson Bridget A. , Vissers Margreet C. M.
Published: January 2021

The use of high dose ascorbate infusions in cancer patients is widespread, but without evidence of efficacy. Several mechanisms whereby ascorbate could affect tumor progression have been proposed, including: (i) the localized generation of cytotoxic quantities of H2O2; (ii) ascorbate-dependent activation of the 2-oxoglutarate-dependent dioxygenases that control the hypoxia-inducible factors (HIFs) and that are responsible for the demethylation of DNA and histones; (iii) increased oxidative stress induced by dehydroascorbic acid. We hypothesize that the dysfunctional vasculature of solid tumors results in compromised delivery of ascorbate to poorly perfused regions of the tumor and that this ascorbate deficit acts as an additional driver of the hypoxic response via upregulation of HIFs. Using a randomized “therapeutic window of opportunity” clinical study design we aimed to determine whether ascorbate infusions affected tumor ascorbate content and tumor biology. Patients with colon cancer were randomized to receive infusions of up to 1 g/kg ascorbate for 4 days before surgical resection (n = 9) or to not receive infusions (n = 6). Ascorbate was measured in plasma, erythrocytes, tumor and histologically normal mucosa at diagnostic colonoscopy and at surgery. Protein markers of tumor hypoxia or DNA damage were monitored in resected tissue. Plasma ascorbate reached millimolar levels following infusion and returned to micromolar levels over 24 h. Pre-infusion plasma ascorbate increased from 38 ± 10 µM to 241 ± 33 µM (p < 0.0001) over 4 days and erythrocyte ascorbate from 18 ± 20 µM to 2509 ± 1016 µM (p < 0.005). Tumor ascorbate increased from 15 ± 6 to 28 ± 6 mg/100 g tissue (p < 0.0001) and normal tissue from 14 ± 6 to 21 ± 4 mg/100 g (p < 0.001). A gradient of lower ascorbate was evident towards the tumor centre in both control and infusion samples. Lower expression of hypoxia-associated proteins was seen in post-infusion tumors compared with controls. There were no significant adverse events and quality of life was unaffected by ascorbate infusion. This is the first clinical study to demonstrate that tumor ascorbate levels increase following infusion, even in regions of poor diffusion, and that this could modify tumor biology.

Clinical Trial Registration

ANZCTR Trial ID ACTRN12615001277538 (https://www.anzctr.org.au/).
Cancer Stemness: p53 at the Wheel
Authors: Ghatak Dishari , Das Ghosh Damayanti , Roychoudhury Susanta
Published: January 2021

The tumor suppressor p53 maintains an equilibrium between self-renewal and differentiation to sustain a limited repertoire of stem cells for proper development and maintenance of tissue homeostasis. Inactivation of p53 disrupts this balance and promotes pluripotency and somatic cell reprogramming. A few reports in recent years have indicated that prevalentTP53oncogenicgain-of-function(GOF) mutations further boosts the stemness properties of cancer cells. In this review, we discuss the role of wild type p53 in regulating pluripotency of normal stem cells and various mechanisms that control the balance between self-renewal and differentiation in embryonic and adult stem cells. We also highlight how inactivating and GOF mutations in p53 stimulate stemness in cancer cells. Further, we have explored the various mechanisms of mutant p53-driven cancer stemness, particularly emphasizing on the non-coding RNA mediated epigenetic regulation. We have also analyzed the association of cancer stemness with other crucialgain-of-functionproperties of mutant p53 such as epithelial to mesenchymal transition phenotypes and chemoresistance to understand how activation of one affects the other. Given the critical role of cancer stem-like cells in tumor maintenance, cancer progression, and therapy resistance of mutant p53 tumors, targeting them might improve therapeutic efficacy in human cancers withTP53mutations.
Hoxb3 Regulates Jag1 Expression in Pharyngeal Epithelium and Affects Interaction With Neural Crest Cells
Authors: Zhang Haoran , Xie Junjie , So Karl Kam Hei , Tong Ka Kui , Sae-Pang Jearn Jang , Wang Li , Tsang Sze Lan , Chan Wood Yee , Wong Elaine Yee Man , Sham Mai Har
Published: January 2021

Craniofacial morphogenesis depends on proper migration of neural crest cells and their interactions with placodes and other cell types.Hoxgenes provide positional information and are important in patterning the neural crest and pharyngeal arches (PAs) for coordinated formation of craniofacial structures.Hoxgenes are expressed in the surface ectoderm and epibranchial placodes, their roles in the pharyngeal epithelium and their downstream targets in regulating PA morphogenesis have not been established. We altered theHoxcode in the pharyngeal region of theHoxb3Tg/+mutant, in whichHoxb3is driven to ectopically expressed inHoxb2domain in the second pharyngeal arch (PA2). In the transgenic mutant, ectopicHoxb3expression was restricted to the surface ectoderm, including the proximal epibranchial placodal region and the distal pharyngeal epithelium. TheHoxb3Tg/+mutants displayed hypoplasia of PA2, multiple neural crest-derived facial skeletal and nerve defects. Interestingly, we found that in theHoxb3Tg/+mutant, expression of the Notch ligandJag1was specifically up-regulated in the ectodermal pharyngeal epithelial cells of PA2. By molecular experiments, we demonstrated that Hoxb3 could bind to an upstream genomic site S2 and directly regulateJag1expression. In theHoxb3Tg/+mutant, elevated expression ofJag1in the pharyngeal epithelium led to abnormal cellular interaction and deficiency of neural crest cells migrating into PA2. In summary, we showed thatHoxb3regulates Jag1 expression and proposed a model of pharyngeal epithelium and neural crest interaction during pharyngeal arch development.
Physical Activity Level Influences MTHFR Gene Methylation Profile in Diabetic Patients
Authors: Diniz Tainá Gomes , Silva Alexandre Sérgio , dos Santos Nunes Mayara Karla , Ribeiro Mateus Duarte , Filho João Modesto , do Nascimento Rayner Anderson Ferreira , Gomes Cecília Neta Alves Pegado , Evangelista Isabella Wanderley de Queiroga , de Oliveira Naila Francis Paulo , Persuhn Darlene Camati
Published: January 2021

Introduction

MTHFR methylation status is associated with microvascular complications in diabetes, but the factors influencing this profile remain unknown.

Objective

The aim of this study was to evaluate the influence of physical activity level and nutritional status on the methylation profile of the MTHFR gene in patients with type 2 diabetes mellitus (T2DM).

Methods

A total of 111 patients, 43 men and 68 women diagnosed with DM (7.0 ± 2.3 years), answered the International Physical Activity Questionnaire (IPAQ) and underwent blood collection for biochemical analysis, DNA extraction, and MTHFR gene methylation profile determination.

Result

The comparison of the methylation pattern showed that the partially methylated profile predominates in the insufficiently active group (85%), which does not occur in the sufficiently active group (54%) (p = 0.012). No differences were found in the nutritional status comparison. Logistic regression including overweight, waist circumference, gender, age, time of DM, hypertension, dyslipidemia, smoking, alcoholism, and family DM revealed that the association of the level of physical activity with methylation profile proved to be independent of these confounding variables. Considering the partially methylated profile as a result, being physically inactive favors the partially methylated MTHFR pattern in patients with DM.

Conclusion

We concluded that insufficient physical activity is associated with partially methylated pattern of MTHFR promoter.
Stimulating the Resolution of Inflammation Through Omega-3 Polyunsaturated Fatty Acids in COVID-19: Rationale for the COVID-Omega-F Trial
Authors: Arnardottir Hildur , Pawelzik Sven-Christian , Öhlund Wistbacka Ulf , Artiach Gonzalo , Hofmann Robin , Reinholdsson Ingalill , Braunschweig Frieder , Tornvall Per , Religa Dorota , Bäck Magnus
Published: January 2021

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 triggers an immune response with local inflammation in the lung, which may extend to a systemic hyperinflammatory reaction. Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications. In addition to the release of cytokines, referred to as cytokine release syndrome or “cytokine storm,” increased pro-inflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an “eicosanoid storm,” which contributes to the uncontrolled systemic inflammation. Specialized pro-resolving mediators, which are derived from omega-3 PUFA, limit inflammatory reactions by an active process called resolution of inflammation. Here, the rationale for omega-3 PUFA supplementation in COVID-19 patients is presented along with a brief overview of the study protocol for the trial “Resolving Inflammatory Storm in COVID-19 Patients by Omega-3 Polyunsaturated Fatty Acids - A single-blind, randomized, placebo-controlled feasibility study” (COVID-Omega-F). EudraCT: 2020-002293-28; clinicaltrials.gov: NCT04647604.
Relationship of the Pro12Ala Polymorphism on the PPARy2 Gene With the Body Composition of Practitioners of Cyclic Exercises
Authors: Silva Raquel Suelen Brito da , Persuhn Darlene Camati , Barbosa Francisca Karinny Lemos , Souza Marizângela Ferreira de , Sena Klécia de Farias , Costa Matheus da Silveira , Franca Gisele Augusta Maciel , de Assis Caroline Severo , Cardoso Glêbia Alexa , Silva Alexandre Sérgio
Published: January 2021

This study aimed to verify the association between the genotypic of the receptor gene activated by peroxisome proliferators gamma 2 (PPARy2) and the body composition and the specific indicators of adiposity in practitioners physical exercises, considering nutritional intake, age, and training load as influencing factors. It was conducted a cross-sectional study with 335 adults (47.9 ± 12.7 years, 138 men, body mass index/BMI = 27.0 ± 4.9 kg/m2), practitioners of aerobic exercises in cyclical modalities (running, walking and/or cycling, who spent 328.3 ± 193.6 kcal/day on physical training). The genotyping of the Pro12Ala polymorphism was performed using the PCR-RFLP technique and the body composition measured by bioimpedance (InBody 720). Energy expenditure was based on the compendium of physical activities and caloric intake was measured by 24 h recall questionnaire. The higher prevalence was for the Pro/Pro genotype (76.1% vs. 23.9% of Pro/Ala). Pro/Pro genotypic group showed significant higher mean values for body mass (BM) (p < 0.03 for men and p < 0.02 for women) and BMI (p < 0.00 for men and p < 0.02 for women) and %FAT (p < 0.00), waist-hip ratio (WHR) (p < 0.04), and visceral fat (VF) (p < 0.00) only in men compared to Pro/Ala. Higher frequency of Pro/Pro was observed in the category indicating BMI (p < 0.00 for men and p < 0.03 for women), WRH (p < 0.03 for men and p < 0.00 for women), and %FAT (p < 0.03) (in the latter case, only among men. It was also observed that the frequency of distribution of Pro/Ala in the eutrophic category of the BMI remained independent of all influencers, while WHR and %FAT were independent of the training load, but influenced by nutritional intake and age. In women, the frequency of Pro/Ala distribution at the lowest BMI and WHR values remained independent of all confounding variables. It is concluded that the Pro12Ala polymorphism in the PPARy2 gene consistently influences indicators of body composition and adiposity, regardless of the practitioners of physical training, but the relationship needs to be considered according to age and nutritional intake.
Effect of Photoperiod on Chinese Kale (Brassica alboglabra) Sprouts Under White or Combined Red and Blue Light
Authors: Chen Jiaxuan , Chen Zeyuan , Li Zunwen , Zhao Yijiao , Chen Xiaodong , Wang-Pruski Gefu , Guo Rongfang
Published: January 2021

To determine the response of Chinese kale (Brassica alboglabra) sprouts to photoperiods under different light sources, we used four photoperiods (0-h light/24-h dark, 8-h light/16-h dark, 12-h light/12-h dark, and 16-h light/8-h dark) to investigate their sprout growth and secondary metabolite glucosinolates (GSs) accumulation under white or combined red-and-blue (RB) light sources. We found that the 16-h light condition under RB light produced plants with the greatest dry matter. Sprouts grown under 16-h RB light condition achieved greater length than those under white light. To investigate the role of RB light in plant growth and GS accumulation, we applied RB light sources with different RB ratios (0:10, 2:8, 5:5, 8:2, and 10:0) to cultivate sprouts. The results showed that significant differential accumulation of GSs existed between sprouts grown under blue (RB, 0:10) and red (RB, 10:0) light; there was greater GS content under blue light. The underlying mechanism of differential GS content in sprouts under red or blue light condition was studied using RNA sequencing technique. Interestingly, abundant GS biosynthetic gene transcripts were observed in sprouts grown under red light compared with under blue light. The expression of β-glucosidase family homolog genes related to GS degradation differed under red and blue light conditions, among those TGG4 homolog was detected with higher expression under red light than with blue light. Taking into consideration, the lower GS accumulation in sprouts under red rather than blue light, we conclude that the degradation of GSs may play a key role in sprouts GS homeostasis.
Thinking Out of the Box: On the Ability of Zea mays L. to Biotrasform Aflatoxin B1 Into Its Modified Forms
Authors: Righetti Laura , Rolli Enrico , Dellafiora Luca , Galaverna Gianni , Suman Michele , Bruni Renato , Dall’Asta Chiara
Published: January 2021

While aflatoxin metabolism in animals has been clarified, very limited information is so far available on the possible biotransformation occurring in plants. Therefore, this work aimed at investigating whether AFB1 metabolites could occur in field-grown infected maize and the putative role of Zea mays L. metabolism in their production. For such scope, asymptomatic in vitro–grown plantlets and in silico evaluations of plant transforming enzymes were used to pinpoint how plants may handle these compounds. Our data demonstrated the role of maize plants in the production of Phase I hydroxylated aflatoxins, including, among others, AFM1, AFM2, and aflatoxicol, and suggest that plant cytochromes may be involved in this biotransformation of AFB1.
Arbuscular Mycorrhizal Fungi Regulate Polyamine Homeostasis in Roots of Trifoliate Orange for Improved Adaptation to Soil Moisture Deficit Stress
Authors: Zou Ying-Ning , Zhang Fei , Srivastava Anoop K. , Wu Qiang-Sheng , Kuča Kamil
Published: January 2021

Soil arbuscular mycorrhizal fungi (AMF) enhance the tolerance of plants against soil moisture deficit stress (SMDS), but the underlying mechanisms are still not fully understood. Polyamines (PAs) as low-molecular-weight, aliphatic polycations have strong roles in abiotic stress tolerance of plants. We aimed to investigate the effect of AMF (Funneliformis mosseae) inoculation on PAs, PA precursors, activities of PA synthases and degrading enzymes, and concentration of reactive oxygen species in the roots of trifoliate orange (Poncirus trifoliata) subjected to 15 days of SMDS. Leaf water potential and total chlorophyll levels were comparatively higher in AMF-inoculated than in non-AMF-treated plants exposed to SMDS. Mycorrhizal plants recorded a significantly higher concentration of precursors of PA synthesis such as L-ornithine, agmatine, and S-adenosyl methionine, besides higher putrescine and cadaverine and lower spermidine during the 15 days of SMDS. AMF colonization raised the PA synthase (arginine decarboxylase, ornithine decarboxylase, spermidine synthase, and spermine synthase) activities and PA-degrading enzymes (copper-containing diamine oxidase and FAD-containing polyamine oxidase) in response to SMDS. However, mycorrhizal plants showed a relatively lower degree of membrane lipid peroxidation, superoxide anion free radical, and hydrogen peroxide than non-mycorrhizal plants, whereas the difference between them increased linearly up to 15 days of SMDS. Our study concluded that AMF regulated PA homeostasis in roots of trifoliate orange to tolerate SMDS.
Potassium Alleviates Post-anthesis Photosynthetic Reductions in Winter Wheat Caused by Waterlogging at the Stem Elongation Stage
Authors: Gao Jingwen , Su Yao , Yu Man , Huang Yiqian , Wang Feng , Shen Alin
Published: January 2021

Waterlogging occurs frequently at the stem elongation stage of wheat in southern China, decreasing post-anthesis photosynthetic rates and constraining grain filling. This phenomenon, and the mitigating effect of nutrient application, should be investigated as it could lead to improved agronomic guidelines. We exposed pot-cultured wheat plants at the stem elongation stage to waterlogging treatment in combination with two rates of potassium (K) application. Waterlogging treatment resulted in grain yield losses, which we attributed to a reduction in the 1,000-grain weight caused by an early decline in the net photosynthetic rate (Pn) post-anthesis. These decreases were offset by increasing K application. Stomatal conductance (Gs) and the intercellular CO2 concentration (Ci) decreased in the period 7–21 days after anthesis (DAA), and these reductions were exacerbated by waterlogging. However, in the period 21–28 DAA, Gs and Ci increased, while Pn decreased continuously, suggesting that non-stomatal factors constrained photosynthesis. On DAA 21, Pn was reduced by waterlogging, but photochemical efficiency (ΦPSII) remained unchanged, indicating a reduction in the dissipation of energy captured by photosystem II (PSII) through the CO2 assimilation pathway. This reduction in energy dissipation increased the risk of photodamage, as shown by early reductions in ΦPSII in waterlogged plants on DAA 28. However, increased K application promoted root growth and nutrient status under waterlogging, thereby improving photosynthesis post-anthesis. In conclusion, the decrease in Pn caused by waterlogging was attributable to stomatal closure during early senescence; during later senescence, a reduction in CO2 assimilation accounted for the reduced Pn and elevated the risk of photodamage. However, K application mitigated waterlogging-accelerated photosynthetic reductions and reduced yield losses.
Future-Proofing Potato for Drought and Heat Tolerance by Overexpression of Hexokinase and SP6A
Authors: Lehretz Günter G. , Sonnewald Sophia , Lugassi Nitsan , Granot David , Sonnewald Uwe
Published: January 2021

Crop yield is largely affected by global climate change. Especially periods of heat and drought limit crop productivity worldwide. According to current models of future climate scenarios, heatwaves and periods of drought are likely to increase. Potato, as an important food crop of temperate latitudes, is very sensitive to heat and drought which impact tuber yield and quality. To improve abiotic stress resilience of potato plants, we aimed at co-expressing hexokinase 1 from Arabidopsis thaliana (AtHXK1) in guard cells and SELF-PRUNING 6A (SP6A) using the leaf/stem-specific StLS1 promoter in order to increase water use efficiency as well as tuberization under drought and heat stress. Guard cell-specific expression of AtHXK1 decreased stomatal conductance and improved water use efficiency of transgenic potato plants as has been shown for other crop plants. Additionally, co-expression with the FT-homolog SP6A stimulated tuberization and improved assimilate allocation to developing tubers under control as well as under single and combined drought and heat stress conditions. Thus, co-expression of both proteins provides a novel strategy to improve abiotic stress tolerance of potato plants.
Using Gene Expression to Study Specialized Metabolism—A Practical Guide
Authors: Delli-Ponti Riccardo , Shivhare Devendra , Mutwil Marek
Published: January 2021

Plants produce a vast array of chemical compounds that we use as medicines and flavors, but these compounds’ biosynthetic pathways are still poorly understood. This paucity precludes us from modifying, improving, and mass-producing these specialized metabolites in suitable bioreactors. Many of the specialized metabolites are expressed in a narrow range of organs, tissues, and cell types, suggesting a tight regulation of the responsible biosynthetic pathways. Fortunately, with unprecedented ease of generating gene expression data and with >200,000 publicly available RNA sequencing samples, we are now able to study the expression of genes from hundreds of plant species. This review demonstrates how gene expression can elucidate the biosynthetic pathways by mining organ-specific genes, gene expression clusters, and applying various types of co-expression analyses. To empower biologists to perform these analyses, we showcase these analyses using recently published, user-friendly tools. Finally, we analyze the performance of co-expression networks and show that they are a valuable addition to elucidating multiple the biosynthetic pathways of specialized metabolism.
Saying “I Don’t Know”: A Video-Based Study on Physicians’ Claims of No-Knowledge in Assisted Reproductive Technology Consultations
Authors: Menichetti Julia , Gerwing Jennifer , Borghi Lidia , Gulbrandsen Pål , Vegni Elena
Published: January 2021

Introduction

The assisted reproductive technology (ART) field deals with consistent and predictable gaps in knowledge. Expressing lack of knowledge with a sentence like “I don’t know” can be challenging for doctors. This study examined physicians’ negative epistemic disclaimer “non lo so” in Italian ART doctor-couple interactions. In particular, it aimed to reveal specific features of “non lo so”: function, topic, temporality, responsibility, and interactional aspects.

Methods

This was a video-based observational study. We used microanalysis of face-to-face dialogue to analyze 20 purposively selected triadic consultations from a corpus of 85. This inductive analysis focused on the function, the content (topic and temporality) and some selected interactional aspects of the “non lo so”, quantifying and capturing the interaction between these qualitative features.

Results

We found 82 doctors’ “non lo so” in the corpus (mean = 4.4; range = 0–15). We discovered three main functions of this expression: propositional (n = 73/82), relational (n = 6/82), discursive (n = 3/82). The most frequent topics raising doctors’ “non lo so” were costs (n = 11/82), treatment-related aspects (n = 10/82), and timing issues (n = 9/82). In more than half of the cases (n = 44/82), present issues emerged. The majority (n = 70/82) of “non lo so” was framed using the “I,” with doctors’ taking personal responsibility. Patients played a role in these expressions from doctors: Patients initiated more than one third of them, and in one fourth of the cases, patients followed up immediately.

Conclusion

Our findings may be related to characteristics of the specific field of ART. Doctors in this setting must frequently express a direct lack of knowledge to their patients, and when they do, they mean it literally. Patients contribute to such disclosures, and their responses suggest that they find them acceptable, showing that they may expect limitations in their potential to conceive.
Playing Ludomotor Activities in Lleida During the Spanish Civil War: An Ethnomotor Approach
Authors: Ormo-Ribes Enric , Lavega-Burgués Pere , Rodríguez-Arregi Rosa , Luchoro-Parrilla Rafael , Rillo-Albert Aaron , Pic Miguel
Published: January 2021

The traditional ludomotor activities (LA) are recognized by UNESCO as an intangible piece of cultural heritage. The ethnomotricity analyzes LA in its sociocultural context, taking into account the proprieties of rules or motor conditions (internal logic) and the link with local culture (external logic). The aim of this research was to identify and reveal the distinctive ethnomotor features of LA in order to understand the adaptations that occurred in the social scenario of the Spanish Civil War (1936–1939) in Lleida. The corpus of the research was constituted by 101 LA which were collected from the analysis of 20 semi-structured interviews. An “ad hoc” tool was designed and agreed upon by expert observers. It was comprised of a total of 27 ethnomotor variables related to LA. The experts achieved high reliability [Cohen’s kappa coefficient (κ) and Spearman’s correlation coefficient = 1] when the classification of LA was carried out on two different occasions. Descriptive statistics, cross-tabulations (Pearson’s chi-squared) effect sizes, and two-step clusters were performed by external and internal logic variables. The presence or absence of motor interaction (X2= 9.029;df= 1;p< 0.003;ES= 0.298) was enlightening when comparing LA with and without a war connotation. On the other hand, the hierarchy of variables rested primarily on IL-Domain (Psycho-Coop-Oppo-Coop/Oppo) (PI = 1). Among other singularities, while two-step cluster analysis revealed a corresponding ethnomotor silhouette with cluster 1, with the warlike connotation (n= 48; 96.0%), its homologous structure was expressed (Cluster 2) in the absence of the warlike character (n= 26; 50%).