bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic Epidemiology and Global Population Structure of Exfoliative Toxin A-Producing Staphylococcus aureus Strains Associated With Staphylococcal Scalded Skin Syndrome
Authors: Azarian Taj , Cella Eleonora , Baines Sarah L. , Shumaker Margot J. , Samel Carol , Jubair Mohammad , Pegues David A. , David Michael Z.
Published: August 2021

Staphylococci producing exfoliative toxins are the causative agents of staphylococcal scalded skin syndrome (SSSS). Exfoliative toxin A (ETA) is encoded by eta, which is harbored on a temperate bacteriophage ΦETA. A recent increase in the incidence of SSSS in North America has been observed; yet it is largely unknown whether this is the result of host range expansion of ΦETA or migration and emergence of established lineages. Here, we detail an outbreak investigation of SSSS in a neonatal intensive care unit, for which we applied whole-genome sequencing (WGS) and phylogenetic analysis of Staphylococcus aureus isolates collected from cases and screening of healthcare workers. We identified the causative strain as a methicillin-susceptible S. aureus (MSSA) sequence type 582 (ST582) possessing ΦETA. To then elucidate the global distribution of ΦETA among staphylococci, we used a recently developed tool to query extant bacterial WGS data for biosamples containing eta, which yielded 436 genomes collected between 1994 and 2019 from 32 countries. Applying population genomic analysis, we resolved the global distribution of S. aureus with lysogenized ΦETA and assessed antibiotic resistance determinants as well as the diversity of ΦETA. The population is highly structured with eight dominant sequence clusters (SCs) that generally aligned with S. aureus ST clonal complexes. The most prevalent STs included ST109 (24.3%), ST15 (13.1%), ST121 (10.1%), and ST582 (7.1%). Among strains with available data, there was an even distribution of isolates from carriage and disease. Only the SC containing ST121 had significantly more isolates collected from disease (69%, n = 46) than carriage (31%, n = 21). Further, we identified 10.6% (46/436) of strains as methicillin-resistant S. aureus (MRSA) based on the presence of mecA and the SCCmec element. Assessment of ΦETA diversity based on nucleotide identity revealed 27 phylogroups, and prophage gene content further resolved 62 clusters. ΦETA was relatively stable within lineages, yet prophage variation is geographically structured. This suggests that the reported increase in incidence is associated with migration and expansion of existing lineages, not the movement of ΦETA to new genomic backgrounds. This revised global view reveals that ΦETA is diverse and is widely distributed on multiple genomic backgrounds whose distribution varies geographically.
Grazing and Supplementation of Dietary Yeast Probiotics Shape the Gut Microbiota and Improve the Immunity of Black Fattening Goats (Capra hircus)
Authors: Emu Quzhe , Guan Hao , Zhu Jiangjiang , Zhang Lin , Fan Jinsheng , Ji Yang , Lin Yaqiu , Li Chunmei , Dan Xiaobo , Aguo Yueda , Wei Xiaolan , Zhang Min , Zhang Bin , Yang Chao , Li Bo , Xiong Chaorui
Published: August 2021

This study aimed to investigate the effects of different feeding modes on the growth performance, gut microbiota, and immunity of Black Fattening Goat (Capra hircus). A total of 30 goats were grouped in three groups by their feeding modes (pasture grazing group, PG; barn feeding group, BF; barn feeding + probiotics, BF + P; n = 10) and the study was performed for 114 days. After a 2-week adaptation period, the first growth performance test was conducted, and the blood and fecal samplings (day 0) were collected on January 17, 2020, while the second and third test and samplings were conducted on days 53 and 100 of feeding. The species-composition of fecal microbiota was analyzed by 16S ribosomal RNA gene-sequencing using PacBio single molecule real time (SMRT) sequencing technology. Both the BF and BF + P groups had the highest (P < 0.05) body’s weight and length, and chest circumference at days 53 and 100, especially at day 100, the body’s weight of both the BF groups were more than 18 kg. The levels of immunoglobulin A (IgA) and immunoglobulin G (IgG) were found to be significantly higher (P < 0.05) in the PG and BF + P groups at day 100. The PG group exhibited the highest number of operational taxonomic unit (OTUs) and alpha diversity. Firmicutes, Bacteroidetes, and Verrucomicrobia were the predominant phyla in all the fecal samples. The relative abundance of Akkermansia muciniphila and Ruminococcus flavefaciens were found to be significantly higher (P < 0.05) in PG group and BF + P group at day 100, respectively, which might partially explain the significantly higher (P < 0.05) levels of IgA and IgG in these two groups. These findings suggested that BF supplemented with 5 g probiotics (Saccharomyces cerevisiae and mannan oligosaccharides) per day has the potential to enhance the growth and immunity of Black Fattening Goats.
Bioleaching of E-Waste: Influence of Printed Circuit Boards on the Activity of Acidophilic Iron-Oxidizing Bacteria
Authors: Anaya-Garzon Juan , Hubau Agathe , Joulian Catherine , Guezennec Anne-Gwénaëlle
Published: August 2021

Bioleaching is a promising strategy to recover valuable metals from spent printed circuit boards (PCBs). The performance of the process is catalyzed by microorganisms, which the toxic effect of PCBs can inhibit. This study aimed to investigate the capacity of an acidophilic iron-oxidizing culture, mainly composed of Leptospirillum ferriphilum, to oxidize iron in PCB-enriched environments. The culture pre-adapted to 1% (w/v) PCB content successfully thrived in leachates with the equivalent of 6% of PCBs, containing 8.5 g L–1 Cu, 8 g L–1 Fe, 1 g L–1 Zn, 92 mg L–1 Ni, 12.6 mg L–1 Pb, and 4.4 mg L–1 Co, among other metals. However, the inhibiting effect of PCBs limited the microbial activity by delaying the onset of the exponential iron oxidation. Successive subcultures boosted the activity of the culture by reducing this delay by up to 2.6 times under batch conditions. Subcultures also favored the rapid establishment of high microbial activity in continuous mode.
Can Top-Down Controls Expand the Ecological Niche of Marine N2 Fixers?
Authors: Landolfi Angela , Prowe A. E. Friederike , Pahlow Markus , Somes Christopher J. , Chien Chia-Te , Schartau Markus , Koeve Wolfgang , Oschlies Andreas
Published: August 2021

The ability of marine diazotrophs to fix dinitrogen gas (N2) is one of the most influential yet enigmatic processes in the ocean. With their activity diazotrophs support biological production by fixing about 100–200 Tg N/year and turning otherwise unavailable dinitrogen into bioavailable nitrogen (N), an essential limiting nutrient. Despite their important role, the factors that control the distribution of diazotrophs and their ability to fix N2 are not fully elucidated. We discuss insights that can be gained from the emerging picture of a wide geographical distribution of marine diazotrophs and provide a critical assessment of environmental (bottom-up) versus trophic (top-down) controls. We expand a simplified theoretical framework to understand how top-down control affects competition for resources that determine ecological niches. Selective mortality, mediated by grazing or viral-lysis, on non-fixing phytoplankton is identified as a critical process that can broaden the ability of diazotrophs to compete for resources in top-down controlled systems and explain an expanded ecological niche for diazotrophs. Our simplified analysis predicts a larger importance of top-down control on competition patterns as resource levels increase. As grazing controls the faster growing phytoplankton, coexistence of the slower growing diazotrophs can be established. However, these predictions require corroboration by experimental and field data, together with the identification of specific traits of organisms and associated trade-offs related to selective top-down control. Elucidation of these factors could greatly improve our predictive capability for patterns and rates of marine N2 fixation. The susceptibility of this key biogeochemical process to future changes may not only be determined by changes in environmental conditions but also via changes in the ecological interactions.
Genome-Based Characterization of Plant-Associated Rhodococcus qingshengii RL1 Reveals Stress Tolerance and Plant–Microbe Interaction Traits
Authors: Kuhl Theresa , Chowdhury Soumitra Paul , Uhl Jenny , Rothballer Michael
Published: August 2021

Stress tolerant, plant-associated bacteria can play an important role in maintaining a functional plant microbiome and protecting plants against various (a)biotic stresses. Members of the stress tolerant genus Rhodococcus are frequently found in the plant microbiome. Rhodococcus qingshengii RL1 was isolated from Eruca sativa and the complete genome was sequenced, annotated and analyzed using different bioinformatic tools. A special focus was laid on functional analyses of stress tolerance and interactions with plants. The genome annotation of RL1 indicated that it contains a repertoire of genes which could enable it to survive under different abiotic stress conditions for e.g., elevated mercury concentrations, to interact with plants via root colonization, to produce phytohormones and siderophores, to fix nitrogen and to interact with bacterial signaling via a LuxR-solo and quorum quenching. Based on the identified genes, functional analyses were performed in vitro with RL1 under different growth conditions. The R. qingshengii type strain djl6 and a closely related Rhodococcus erythropolis BG43 were included in the experiments to find common and distinct traits between the strains. Genome based phylogenetic analysis of 15 available and complete R. erythropolis and R. qingshengii genome sequences revealed a separation of the R. erythropolis clade in two subgroups. First one harbors only R. erythropolis strains including the R. erythropolis type strain. The second group consisted of the R. qingshengii type strain and a mix of R. qingshengii and R. erythropolis strains indicating that some strains of the second group should be considered for taxonomic re-assignment. However, BG43 was clearly identified as R. erythropolis and RL1 clearly as R. qingshengii and the strains had most tested traits in common, indicating a close functional overlap of traits between the two species.
Diversification of LytM Protein Functions in Polar Elongation and Cell Division of Agrobacterium tumefaciens
Authors: Figueroa-Cuilan Wanda M. , Randich Amelia M. , Dunn Caroline M. , Santiago-Collazo Gustavo , Yowell Andrew , Brown Pamela J. B.
Published: August 2021

LytM-domain containing proteins are LAS peptidases (lysostaphin-type enzymes, D-Ala-D-Ala metallopeptidases, and sonic hedgehog) and are known to play diverse roles throughout the bacterial cell cycle through direct or indirect hydrolysis of the bacterial cell wall. A subset of the LytM factors are catalytically inactive but regulate the activity of other cell wall hydrolases and are classically described as cell separation factors NlpD and EnvC. Here, we explore the function of four LytM factors in the alphaproteobacterial plant pathogen Agrobacterium tumefaciens. An LmdC ortholog (Atu1832) and a MepM ortholog (Atu4178) are predicted to be catalytically active. While Atu1832 does not have an obvious function in cell growth or division, Atu4178 is essential for polar growth and likely functions as a space-making endopeptidase that cleaves amide bonds in the peptidoglycan cell wall during elongation. The remaining LytM factors are degenerate EnvC and NlpD orthologs. Absence of these proteins results in striking phenotypes indicative of misregulation of cell division and growth pole establishment. The deletion of an amidase, AmiC, closely phenocopies the deletion of envC suggesting that EnvC might regulate AmiC activity. The NlpD ortholog DipM is unprecedently essential for viability and depletion results in the misregulation of early stages of cell division, contrasting with the canonical view of DipM as a cell separation factor. Finally, we make the surprising observation that absence of AmiC relieves the toxicity induced by dipM overexpression. Together, these results suggest EnvC and DipM may function as regulatory hubs with multiple partners to promote proper cell division and establishment of polarity.
Inhibition of Thioredoxin Reductase by Santamarine Conferring Anticancer Effect in HeLa Cells
Authors: Zhang Junmin , Xu Qianhe , Yang Hong-Ying , Yang Minghao , Fang Jianguo , Gao Kun
Published: August 2021

Natural products frequently have unique physiological activities and new action mechanisms due to their structural diversity and novelty, and are an important source for innovative drugs and lead compounds. We present herein that natural product santamarine targeted thioredoxin reductase (TrxR) to weaken its antioxidative function in cells, accompanied by accumulation of high levels of reactive oxygen species (ROS), and finally induced a new mechanism of tumor cell oxidative stress-mediated apoptosis. TrxR knockdown or overexpression cell lines were employed to further evaluate the cytotoxicity of santamarine regulated by TrxR, demonstrated that TrxR played a key role in the physiological effect of santamarine on cells. Santamarine targeting TrxR reveals its previously unrecognized mechanism of antitumor and provides a basis for the further development of santamarine as a potential cancer therapeutic agent.
Fuzzle 2.0: Ligand Binding in Natural Protein Building Blocks
Authors: Ferruz Noelia , Michel Florian , Lobos Francisco , Schmidt Steffen , Höcker Birte
Published: August 2021

Modern proteins have been shown to share evolutionary relationships via subdomain-sized fragments. The assembly of such fragments through duplication and recombination events led to the complex structures and functions we observe today. We previously implemented a pipeline that identified more than 1,000 of these fragments that are shared by different protein folds and developed a web interface to analyze and search for them. This resource named Fuzzle helps structural and evolutionary biologists to identify and analyze conserved parts of a protein but it also provides protein engineers with building blocks for example to design proteins by fragment combination. Here, we describe a new version of this web resource that was extended to include ligand information. This addition is a significant asset to the database since now protein fragments that bind specific ligands can be identified and analyzed. Often the mode of ligand binding is conserved in proteins thereby supporting a common evolutionary origin. The same can now be explored for subdomain-sized fragments within this database. This ligand binding information can also be used in protein engineering to graft binding pockets into other protein scaffolds or to transfer functional sites via recombination of a specific fragment. Fuzzle 2.0 is freely available at https://fuzzle.uni-bayreuth.de/2.0.
Astrocytes in Down Syndrome Across the Lifespan
Authors: Ponroy Bally Blandine , Murai Keith K.
Published: August 2021

Down Syndrome (DS) is the most common genetic cause of intellectual disability in which delays and impairments in brain development and function lead to neurological and cognitive phenotypes. Traditionally, a neurocentric approach, focusing on neurons and their connectivity, has been applied to understanding the mechanisms involved in DS brain pathophysiology with an emphasis on how triplication of chromosome 21 leads to alterations in neuronal survival and homeostasis, synaptogenesis, brain circuit development, and neurodegeneration. However, recent studies have drawn attention to the role of non-neuronal cells, especially astrocytes, in DS. Astrocytes comprise a large proportion of cells in the central nervous system (CNS) and are critical for brain development, homeostasis, and function. As triplication of chromosome 21 occurs in all cells in DS (with the exception of mosaic DS), a deeper understanding of the impact of trisomy 21 on astrocytes in DS pathophysiology is warranted and will likely be necessary for determining how specific brain alterations and neurological phenotypes emerge and progress in DS. Here, we review the current understanding of the role of astrocytes in DS, and discuss how specific perturbations in this cell type can impact the brain across the lifespan from early brain development to adult stages. Finally, we highlight how targeting, modifying, and/or correcting specific molecular pathways and properties of astrocytes in DS may provide an effective therapeutic direction given the important role of astrocytes in regulating brain development and function.
Enroll-HD: An Integrated Clinical Research Platform and Worldwide Observational Study for Huntington's Disease
Authors: Sathe Swati , Ware Jen , Levey Jamie , Neacy Eileen , Blumenstein Robi , Noble Simon , Mühlbäck Alzbeta , Rosser Anne , Landwehrmeyer G. Bernhard , Sampaio Cristina
Published: August 2021

Established in July 2012, Enroll-HD is both an integrated clinical research platform and a worldwide observational study designed to meet the clinical research requirements necessary to develop therapeutics for Huntington's disease (HD). The platform offers participants a low-burden entry into HD research, providing a large, well-characterized, research-engaged cohort with associated clinical data and biosamples that facilitates recruitment into interventional trials and other research studies. Additional studies that use Enroll-HD data and/or biosamples are built into the platform to further research on biomarkers and outcome measures. Enroll-HD is now operating worldwide in 21 countries at 159 clinical sites across four continents—Europe, North America, Latin America, and Australasia—and has recruited almost 25,000 participants, generating a large, rich clinical database with associated biosamples to expedite HD research; any researcher at a verifiable research organization can access the clinical datasets and biosamples from Enroll-HD and nested studies. Important operational features of Enroll-HD include a strong emphasis on standardization, data quality, and protecting participant identity, a single worldwide study protocol, a flexible EDC system capable of integrating multiple studies, a comprehensive monitoring infrastructure, an online portal to train and certify site personnel, and standardized study documents including informed consent forms and contractual agreements.
Predictors of Seizure Freedom in Patients Undergoing Surgery for Central Nervous System Infection-Related Epilepsy: A Systematic Review and Meta-Analysis
Authors: Hou Zhi , Duan Qing-Tian , Ke Yan-Yan , An Ning , Yang Hui , Liu Shi-Yong , Zhang Chun-Qing
Published: August 2021

Objective:Central nervous system infections (CNSIs), especially viral encephalitis and meningitis, are well-recognized causes of medically refractory epilepsy. Although surgery is an effective and durable intervention against these infections, the seizure control outcomes described in previous surgical series have been variable. Accordingly, it is not clear which variables are most valuable in predicting seizure control following surgery for CNSI. The aim of this meta-analysis was to identify the predictors of favorable surgical outcomes in CNSI-related epilepsy.

Methods:The PubMed, EMBASE, Cochrane Library, WANGFANG, VIP, CBM, and CNKI databases were searched for studies according to the inclusion criteria. Prognostic factors, surgical outcomes, and patient characteristics were extracted. Heterogeneity was detected by the I2and Q statistics.

Results:Seventeen studies were included in our meta-analysis. Eight predictors of favorable outcomes (Engel Class I/II) were determined, including abnormal MRI findings, meningitis, temporal location only, regional ictal pattern, unilateral ictal pattern, older age at epilepsy, longer silent period, and longer time from infection, as follows: OR = 3.34 (95% CI 1.44–7.74), OR = 0.31 (95% CI 0.13–0.70), OR = 0.34 (95% CI 0.16–0.74), OR = 5.65 (95% CI 1.75–18.30), and OR = 9.53 (95% CI 2.36–38.48), respectively, and MD = 2.15 (95% CI 0.20–4.11), MD = 2.40 (95% CI 0.09–4.70), and MD = 8.49 (95% CI 1.50–15.48), respectively. A subgroup analysis found the following associations: regional and unilateral ictal patterns in viral encephalitis, a younger age at infection in parasitic encephalopathy, an older age at surgery, a longer time from onset, and a longer time from infection in unexplained meningitis. A sensitivity analysis restricted to studies that included each variable yielded robust results. Little evidence of publication bias was observed.

Conclusions:This meta-analysis suggests that abnormal MRI findings, meningitis, temporal location only, regional and unilateral ictal patterns, older age at epilepsy, longer silent period, and longer time from infection are predictive factors in patients with favorable surgical outcomes in CNSI-related epilepsy. In addition, different infective agents influenced the results in regional and unilateral ictal patterns in ictal electroencephalography, as well as the relationship between age at infection and surgery and the time from epilepsy onset and infection.
Central Post-Stroke Pain: An Integrative Review of Somatotopic Damage, Clinical Symptoms, and Neurophysiological Measures
Authors: Betancur Daniel Fernando Arias , Tarragó Maria da Graça Lopes , Torres Iraci Lucena da Silva , Fregni Felipe , Caumo Wolnei
Published: August 2021

Introduction: The physiopathology of central post-stroke pain (CPSP) is poorly understood, which may contribute to the limitations of diagnostic and therapeutic advancements. Thus, the current systematic review was conducted to examine, from an integrated perspective, the cortical neurophysiological changes observed via transcranial magnetic stimulation (TMS), focusing on the structural damage, and clinical symptoms in patients with CPSP.

Methods: The literature review included the databases EMBASE, PubMed, and ScienceDirect using the following search terms by MeSH or Entree descriptors: [(“Cerebral Stroke”) AND (“Pain” OR “Transcranial Magnetic Stimulation”) AND (“Transcranial Magnetic Stimulation”)] (through September 29, 2020). A total of 297 articles related to CPSP were identified. Of these, only four quantitatively recorded cortical measurements.

Results: We found four studies with different methodologies and results of the TMS measures. According to the National Institutes of Health (NIH) guidelines, two studies had low methodological quality and the other two studies had satisfactory methodological quality. The four studies compared the motor threshold (MT) of the stroke-affected hemisphere with the unaffected hemisphere or with healthy controls. Two studies assessed other cortical excitability measures, such as cortical silent period (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). The main limitations in the interpretation of the results were the heterogeneity in parameter measurements, unknown cortical excitability measures as potential prognostic markers, the lack of a control group without pain, and the absence of consistent and validated diagnosis criteria.

Conclusion: Despite the limited number of studies that prevented us from conducting a meta-analysis, the dataset of this systematic review provides evidence to improve the understanding of CPSP physiopathology. Additionally, these studies support the construction of a framework for diagnosis and will help improve the methodological quality of future research in somatosensory sequelae following stroke. Furthermore, they offer a way to integrate dysfunctional neuroplasticity markers that are indirectly assessed by neurophysiological measures with their correlated clinical symptoms.
Monitoring the Neurotransmitter Response to Glycemic Changes Using an Advanced Magnetic Resonance Spectroscopy Protocol at 7T
Authors: Park Young Woo , Deelchand Dinesh K. , Joers James M. , Kumar Anjali , Alvear Alison Bunio , Moheet Amir , Seaquist Elizabeth R. , Öz Gülin
Published: August 2021

The primary excitatory and inhibitory neurotransmitters glutamate (Glu) and gamma-aminobutyric acid (GABA) are thought to be involved in the response of the brain to changes in glycemia. Therefore, their reliable measurement is critical for understanding the dynamics of these responses. The concentrations of Glu and GABA, as well as glucose (Glc) in brain tissue, can be measured in vivo using proton (1H) magnetic resonance spectroscopy (MRS). Advanced MRS methodology at ultrahigh field allows reliable monitoring of these metabolites under changing metabolic states. However, the long acquisition times needed for these experiments while maintaining blood Glc levels at predetermined targets present many challenges. We present an advanced MRS acquisition protocol that combines commercial 7T hardware (Siemens Scanner and Nova Medical head coil), BaTiO3 dielectric padding, optical motion tracking, and dynamic frequency and B0 shim updates to ensure the acquisition of reproducibly high-quality data. Data were acquired with a semi-LASER sequence [repetition time/echo time (TR/TE) = 5,000/26 ms] from volumes of interest (VOIs) in the prefrontal cortex (PFC) and hypothalamus (HTL). Five healthy volunteers were scanned to evaluate the effect of the BaTiO3 pads on B1+ distribution. Use of BaTiO3 padding resulted in a 60% gain in signal-to-noise ratio in the PFC VOI over the acquisition without the pad. The protocol was tested in six patients with type 1 diabetes during a clamp study where euglycemic (~100 mg/dL) and hypoglycemic (~50 mg/dL) blood Glc levels were maintained in the scanner. The new protocol allowed retention of all HTL data compared with our prior experience of having to exclude approximately half of the HTL data in similar clamp experiments in the 7T scanner due to subject motion. The advanced MRS protocol showed excellent data quality (reliable quantification of 11–12 metabolites) and stability (p > 0.05 for both signal-to-noise ratio and water linewidths) between euglycemia and hypoglycemia. Decreased brain Glc levels under hypoglycemia were reliably detected in both VOIs. In addition, mean Glu level trended lower at hypoglycemia than euglycemia for both VOIs, consistent with prior observations in the occipital cortex. This protocol will allow robust mechanistic investigations of the primary neurotransmitters, Glu and GABA, under changing glycemic conditions.
Reduced Cell Excitability of Cardiac Postganglionic Parasympathetic Neurons Correlates With Myocardial Infarction-Induced Fatal Ventricular Arrhythmias in Type 2 Diabetes Mellitus
Authors: Hu Wenfeng , Zhang Dongze , Tu Huiyin , Li Yu-Long
Published: August 2021

Objective

Withdrawal of cardiac vagal activity is considered as one of the important triggers for acute myocardial infarction (MI)-induced ventricular arrhythmias in type 2 diabetes mellitus (T2DM). Our previous study demonstrated that cell excitability of cardiac parasympathetic postganglionic (CPP) neurons was reduced in T2DM rats. This study investigated whether cell excitability of CPP neurons is associated with cardiac vagal activity and MI-induced ventricular arrhythmias in T2DM rats.

Methods

Rat T2DM was induced by a high-fat diet plus streptozotocin injection. MI-evoked ventricular arrhythmia was achieved by surgical ligation of the left anterior descending coronary artery. Twenty-four-hour, continuous ECG recording was used to quantify ventricular arrhythmic events and heart rate variability (HRV) in conscious rats. The power spectral analysis of HRV was used to evaluate autonomic function. Cell excitability of CPP neurons was measured by the whole-cell patch-clamp technique.

Results

Twenty-four-hour ECG data demonstrated that MI-evoked fatal ventricular arrhythmias are more severe in T2DM rats than that in sham rats. In addition, the Kaplan-Meier analysis demonstrated that the survival rate over 2 weeks after MI is significantly lower in T2DM rats (15% in T2DM+MI) compared to sham rats (75% in sham+MI). The susceptibility to ventricular tachyarrhythmia elicited by programmed electrical stimulation was higher in anesthetized T2DM+MI rats than that in rats with MI or T2DM alone (7.0 ± 0.58 in T2DM+MI group vs. 3.5 ± 0.76 in sham+MI). Moreover, as an index for vagal control of ventricular function, changes of left ventricular systolic pressure (LVSP) and the maximum rate of increase of left ventricular pressure (LV dP/dtmax) in response to vagal efferent nerve stimulation were blunted in T2DM rats. Furthermore, T2DM increased heterogeneity of ventricular electrical activities and reduced cardiac parasympathetic activity and cell excitability of CPP neurons (current threshold-inducing action potentials being 62 ± 3.3 pA in T2DM rats without MI vs. 27 ± 1.9 pA in sham rats without MI). However, MI did not alter vagal control of the ventricular function and CPP neuronal excitability, although it also induced cardiac autonomic dysfunction and enhanced heterogeneity of ventricular electrical activities.

Conclusion

The reduction of CPP neuron excitability is involved in decreased cardiac vagal function, including cardiac parasympathetic activity and vagal control of ventricular function, which is associated with MI-induced high mortality and malignant ventricular arrhythmias in T2DM.
RETRACTED: The Role of LINC00284 in the Development of Thyroid Cancer via Its Regulation of the MicroRNA-30d-5p-Mediated ADAM12/Notch Axis
Authors: Hu Chunmei , Kang Zhichen , Guo Lixin , Qu Fuling , Qu Rongfeng
Published: August 2021

Thyroid cancer is a commonly diagnosed endocrine malignancy with increasing incidence worldwide. Long noncoding RNAs (lncRNAs) are known to function in the invasion and metastasis of thyroid cancer. According to the GSE66783 microarray dataset, long intergenic nonprotein coding RNA 284 (LINC00284) is aberrantly upregulated in thyroid cancer tissues. However, information regarding the specific role of LINC00284 in thyroid cancer remains elusive. Therefore, the current study set out to determine the role of LINC00284 in the development of thyroid cancer, along with an investigation of the underlying molecular mechanism. In parallel with the microarray data from GSE66783, LINC00284 was observed to be expressed at high levels in thyroid cancer cell lines. Moreover, loss-of-function experiments revealed that the downregulation of LINC00284 reduced aldehyde dehydrogenase (ALDH) activity and thyroid cancer cell proliferation, colony formation, and invasiveness, which promoted cell apoptosis. Mechanistically, using dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays, LINC00284 was identified to competitively bind to microRNA-30d-5p (miR-30d-5p), which was observed to be expressed at low levels in thyroid cancer tissues and cells and directly targets the oncogene a disintegrin and metalloproteinase 12 (ADAM12). Overexpression of miR-30d-5p exerted tumor-suppressive effects on the malignant activity of thyroid cancer cells, changes that were reversed by LINC00284 overexpression or ADAM12 overexpression. Furthermore, LINC00284 activated the Notch signaling pathway by competitively binding to miR-30d-5p and increasing the expression of ADAM12. Finally, by performing in vivo experiments, we found that LINC00284 silencing or miR-30d-5p overexpression suppressed the tumorigenic ability of thyroid cancer cells and that overexpression of miR-30d-5p inhibited the LINC00284-induced tumorigenesis of thyroid cancer cells. Collectively, our findings indicate that LINC00284 competitively binds to miR-30d-5p and activates the ADAM12-dependent Notch signaling pathway, thereby promoting the development of thyroid cancer.
Prognostic Function of Programmed Cell Death-Ligand 1 in Esophageal Squamous Cell Carcinoma Patients Without Preoperative Therapy: A Systematic Review and Meta-Analysis
Authors: Cui Hongxia , Li Yarong , Li Su , Liu Guangxuan
Published: August 2021

Background

Studies investigating the correlation between the expression of programmed cell death-ligand 1 (PD-L1) and prognosis in patients with esophageal squamous cell carcinoma (ESCC) not receiving preoperative therapy have increased significantly, but conclusions remain inconclusive. Therefore, this study aimed to determine the association between clinical outcomes and expression of PD-L1 in ESCC patients without preoperative therapy.

Methods

We conducted a comprehensive literature search using four databases up to May 2020. Quality assessment was carried out according to the Newcastle–Ottawa Quality Assessment Scale (NOS). Hazard ratios (HRs) were used to analyze the association between PD-L1 expression with prognosis. Furthermore, we evaluated the correlation between PD-L1 and clinicopathological characteristics using odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Twenty studies (19 publications) comprising 3,677 patients were included in this meta-analysis. We found that the expression of PD-L1 was not related to overall survival (OS, HR: 1.16, 95% CI: 0.94–1.42, p = 0.16) or disease-free survival (DFS, HR: 0.85, 95% CI: 0.66–1.10, p = 0.21) in ESCC. Furthermore, although PD-L1 expression was not significantly associated with sex, degree of differentiation, TNM stage, T stage, lymph node status, smoking, or alcohol use, the merged OR demonstrated that the expression of PD-L1 was higher in older patients compared to younger patients (OR: 1.40, 95% CI: 1.07–1.83, p = 0.01). No obvious publication bias was observed.

Conclusions

Our present study illustrated that PD-L1 expression was not related to poor prognosis of ESCC patients not receiving preoperative therapy, albeit the association only showed a tendency for statistical significance. Notably, PD−L1 expression showed a significant association with age. This meta-analysis had several limitations; therefore, our results need to be verified through further large-scale and prospective studies.
Improvement in Health-Related Quality of Life After Community Acquired Pediatric Septic Shock
Authors: Pinto Neethi P. , Berg Robert A. , Zuppa Athena F. , Newth Christopher J. , Pollack Murray M. , Meert Kathleen L. , Hall Mark W. , Quasney Michael , Sapru Anil , Carcillo Joseph A. , McQuillen Patrick S. , Mourani Peter M. , Chima Ranjit S. , Holubkov Richard , Nadkarni Vinay M. , Reeder Ron W. , Zimmerman Jerry J. ,   the Life After Pediatric Sepsis Evaluation (LAPSE) Investigators
Published: August 2021

Background: Although some pediatric sepsis survivors experience worsening health-related quality of life (HRQL), many return to their pre-illness HRQL. Whether children can improve beyond baseline is not known. We examined a cohort of pediatric sepsis survivors to determine if those with baseline HRQL scores below the population mean could exhibit ≥10% improvement and evaluated factors associated with improvement.

Methods: In this secondary analysis of the Life After Pediatric Sepsis Evaluation prospective study, children aged 1 month to 18 years admitted to 12 academic PICUs in the United States with community-acquired septic shock who survived to 3 months and had baseline HRQL scores ≤ 80 (i.e., excluding those with good baseline HRQL to allow for potential improvement) were included. HRQL was measured using the Pediatric Quality of Life Inventory or Stein-Jessop Functional Status Scale.

Findings: One hundred and seventeen children were eligible. Sixty-one (52%) had ≥ 10% improvement in HRQL by 3 months. Lower pre-sepsis HRQL was associated with increased odds of improvement at 3 months [aOR = 1.08, 95% CI (1.04–1.11), p < 0.001] and 12 months [OR = 1.05, 95% CI (1.02–1.11), p = 0.005]. Improvement in HRQL was most prevalent at 3 month follow-up; at 12 month follow-up, improvement was more sustained among children without severe developmental delay compared to children with severe developmental delay.

Interpretation: More than half of these children with community acquired septic shock experienced at least a 10% improvement in HRQL from baseline to 3 months. Children with severe developmental delay did not sustain this improvement at 12 month follow-up.
Reduced Effect of Anticonvulsants on AMPA Receptor Palmitoylation-Deficient Mice
Authors: Iizumi Madoka , Oota-Ishigaki Akiko , Yamashita Mariko , Hayashi Takashi
Published: August 2021

AMPA receptors are responsible for fast excitatory synaptic transmission in the mammalian brain. Post-translational protein S-palmitoylation of AMPA receptor subunits GluA1-4 reversibly regulates synaptic AMPA receptor expression, resulting in long-lasting changes in excitatory synaptic strengths. Our previous studies have shown that GluA1 C-terminal palmitoylation-deficient (GluA1C811S) mice exhibited hyperexcitability in the cerebrum and elevated seizure susceptibility without affecting brain structure or basal synaptic transmission. Moreover, some inhibitory GABAergic synapses-targeting anticonvulsants, such as valproic acid, phenobarbital, and diazepam, had less effect on these AMPA receptor palmitoylation-deficient mutant mice. This work explores pharmacological effect of voltage-gated ion channel-targeted anticonvulsants, phenytoin and trimethadione, on GluA1C811S mice. Similar to GABAergic synapses-targeting anticonvulsants, anticonvulsive effects were also reduced for both sodium channel- and calcium channel-blocking anticonvulsants, which suppress excess excitation. These data strongly suggest that the GluA1C811S mice generally underlie the excessive excitability in response to seizure-inducing stimulation. AMPA receptor palmitoylation site could be a novel target to develop unprecedented type of anticonvulsants and GluA1C811S mice are suitable as a model animal for broadly evaluating pharmacological effectiveness of antiepileptic drugs.
How Perturbated Metabolites in Diabetes Mellitus Affect the Pathogenesis of Hypertension?
Authors: Ning Zhangchi , Song Zhiqian , Wang Chun , Peng Shitao , Wan Xiaoying , Liu Zhenli , Lu Aiping
Published: August 2021

The presence of hypertension (HTN) in type 2 diabetes mellitus (DM) is a common phenomenon in more than half of the diabetic patients. Since HTN constitutes a predictor of vascular complications and cardiovascular disease in type 2 DM patients, it is of significance to understand the molecular and cellular mechanisms of type 2 DM binding to HTN. This review attempts to understand the mechanism via the perspective of the metabolites. It reviewed the metabolic perturbations, the biological function of perturbated metabolites in two diseases, and the mechanism underlying metabolic perturbation that contributed to the connection of type 2 DM and HTN. DM-associated metabolic perturbations may be involved in the pathogenesis of HTN potentially in insulin, angiotensin II, sympathetic nervous system, and the energy reprogramming to address how perturbated metabolites in type 2 DM affect the pathogenesis of HTN. The recent integration of the metabolism field with microbiology and immunology may provide a wider perspective. Metabolism affects immune function and supports immune cell differentiation by the switch of energy. The diverse metabolites produced by bacteria modified the biological process in the inflammatory response of chronic metabolic diseases either. The rapidly evolving metabolomics has enabled to have a better understanding of the process of diseases, which is an important tool for providing some insight into the investigation of diseases mechanism. Metabolites served as direct modulators of biological processes were believed to assess the pathological mechanisms involved in diseases.
RETRACTED: High Glucose Activated Cardiac Fibroblasts by a Disruption of Mitochondria-Associated Membranes
Authors: Zhang Ling-Yu , Lin Rui-Ting , Chen Hao-Ran , Yang Yong-Cong , Lin Meng-Fei , Tian Lei-Gang , Pan Zhi-Qiong , Lin Lin , Zhu Liang-Liang , Gu Zhen-Jie , Chen Xue-Wen , Li Yu-Jing , Chen Shuai , Cai Shi-Yun
Published: August 2021

Cardiac fibrosis is evident even in the situation without a significant cardiomyocyte loss in diabetic cardiomyopathy and a high glucose (HG) level independently activates the cardiac fibroblasts (CFs) and promotes cell proliferation. Mitochondrial respiration and glycolysis, which are key for cell proliferation and the mitochondria-associated membranes (MAMs), are critically involved in this process. However, the roles and the underlying mechanism of MAMs in the proliferation of HG-induced CFs are largely unknown. The proliferation and apoptosis of CFs responding to HG treatment were evaluated. The MAMs were quantified, and the mitochondrial respiration and cellular glycolytic levels were determined using the Seahorse XF analyzer. The changes of signal transducer and activator of transcription 3 (STAT3) and mitofusin-2 (MFN2) in responding to HG were also determined, the effects of which on cell proliferation, MAMs, and mitochondrial respiration were assessed. The effects of STAT3 on MFN2 transcription was determined by the dual-luciferase reporter assay (DLRA) and chromatin immunoprecipitation (CHIP). HG-induced CFs proliferation increased the glycolytic levels and adenosine triphosphate (ATP) production, while mitochondrial respiration was inhibited. The MAMs and MFN2 expressions were significantly reduced on the HG treatment, and the restoration of MFN2 expression counteracted the effects of HG on cell proliferation, mitochondrial respiration of the MAMs, glycolytic levels, and ATP production. The mitochondrial STAT3 contents were not changed by HG, but the levels of phosphorylated STAT3 and nuclear STAT3 were increased. The inhibition of STAT3 reversed the reduction of MFN2 levels induced by HG. The DLRA and CHIP directly demonstrated the negative regulation of MFN2 by STAT3 at the transcription levels via interacting with the sequences in the MFN2 promoter region locating at about −400 bp counting from the start site of transcription. The present study demonstrated that the HG independently induced CFs proliferation via promoting STAT3 translocation to the nucleus, which switched the mitochondrial respiration to glycolysis to produce ATP by inhibiting MAMs in an MFN2-depression manner.
Young Climate Protesters’ Mobilization Availability: Climate Marches and School Strikes Compared
Authors: Rainsford Emily , Saunders Clare
Published: August 2021

Although there is a developing strand of literature on young people’s participation in environmental activism, there have been few systematic comparisons of their participation in different forms of environmental activism. This article compares the participation of young people and their older counterparts in climate change marches and Global Climate Strikes (GCSs). The agential and structural factors that draw people into protest participation are, in general terms, well recognized. However, it is also recognized that the factors that lead to particular types of protest on certain issues might not be the same as those that lead to different types of protest on different issues. In this article, we keep the protest issue constant (climate change), and make comparisons across different forms of climate protest (marches and school strikes). We coin the term “mobilization availability”, which is a useful way to understand why young people are differentially mobilized into different types of climate change protest. Our notion of mobilization availability invites scholars to consider the importance of the interplay of the supply and demand for protest in understanding who protests and why. We analyse data collected using standardized protest survey methodology (n = 643). In order to account for response rate bias, which is an acute problem when studying young people’s protest survey responses, we weighted the data using propensity score adjustments. We find that the youth-oriented supply of protest evoked by GCS mobilized higher numbers of young people into climate protest than did the more adult-dominated climate marches. GCS did this by providing accessible forms of protest, which reduced the degree of structural availability required to encourage young people to protest on the streets, and by emotionally engaging them. Indeed, the young people we surveyed at the GCSs were considerably more angry than their adult counterparts, and also angrier than young people on other climate protests. Our conceptual and empirical innovations make this paper an important contribution to the literature on young people’s political participation.
Challenges and Opportunities for Academic Parents During COVID-19
Authors: Lantsoght Eva O. L. , Tse Crepaldi Yvonne , Tavares Silvia G. , Leemans Kathleen , Paig-Tran E. W. Misty
Published: August 2021

Parents in academic careers face notable challenges that may go unrecognized by university management and/or policy makers. The COVID-19 pandemic has shed light on some of these challenges, as academic parents shifted to working from home while simultaneously caring for children. On the other hand, many parents found that the shift to working from home offered new opportunities such as working more flexible hours, development of digital skillsets, and increased involvement in the education of their children. In this article we explore the work-related challenges and opportunities experienced by academic parents as a result of the COVID-19 pandemic and offer potential long-term solutions for academic parents and their universities. We use the following methods: (1) a literature review focused on identifying the work-related challenges academic parents faced prior to the pandemic, as well as the impact of the pandemic on scientists and working parents and (2) administer a world-wide survey with the goal of identifying the challenges and opportunities associated with parenting and academic work through the COVID-19 lockdown (304 total responses; 113 complete). Moving forward these findings have enabled conclusions to be drawn in order to shape a new normal. Our aim is to offer university administrators, policy makers, and community service providers with ways to provide additional support for academic parents as well as provide tools for academic parents to learn successful strategies directly from their peers.
Decision Maker Profiling Using Their Mental Behavior Pattern
Authors: Mello Flávio Luis de , Souza Sebastião Alves de
Published: August 2021

This study describes a method to assist the task of predicting the result of the decision-making process of an individual based on psychological and emotional aspects and using artificial intelligence (AI) techniques. This study presents indicators created for profile identification, which are organized in primary and circumstantial categories. These indicators are merged according to the ultimate purpose of profile identification, including the expected behavioral pattern for a person who performs a decision-making process. The person behavior hypothesis was successfully tested and can be approximated by an indicator such as mental functioning pattern, and the mental functioning pattern hypothesis can signal the most likely decisions of an individual. Four debtor decision variables were assessed in a debt negotiation process, in order to validate the method, which is applicable to other decision-making domains. The best signaling of the most likely decision of the debtor was seven times greater than that of a random prediction, while the gain of the worst decision signaling variable was 20%.