bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Possible Health Risks Potential of Electromagnetic Fields from High Voltage Power Transmission Lines in Akure, Nigeria
Authors: Popoola Jide Julius , Adu Michael Rotimi , Itodo Emmanuel Samson
Published: May 2021

The primary objective of this paper is to assess and predict the health risk potential of extremely low-frequency electromagnetic fields (ELF-EMFs) emitted from high voltage power transmission lines (HVPTLs) in Akure metropolis, Nigeria. The assessment was conducted using BENETECH GM3120 Electromagnetic Radiation Tester to measure both the electric field strength and magnetic flux density emitted from 33 kV, 132 kV, 132/330 kV and 330 kV power transmission lines within the metropolis. The data collected were analysed and compared with limiting tolerable values by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines for both occupational and the general public. The comparative result shows that the maximum measured electric field strength and magnetic flux density in this study are lower than 40% of the limiting tolerable values in ICNIRP guidelines. Thus, the result of this study has shown clearly that the emitted ELF-EMFs from HVPTLs is not strong enough to cause any adverse effect health on human. In addition, analysis of the measured data also shows that the emitted ELF-EMFs from the HVPTLs vanish completely at about 60 m radius from the transmission lines, which implies that 60 m radius from transmission lines is an ideal experimental shortest possible distance residential building and people should be from HVPTLs in order to reduce the exposure level of people to EMFs radiations from HVPTLs.
CFD Analysis of Phase Holdup Behaviour in a Gas-Liquid Bubble Column
Authors: Abd Halim Nur Khairunnisa , Siti Aslina Hussain
Published: May 2021

Experimental works on bubble column hydrodynamic are normally carried out on a laboratory scale less than 0.3 m with holes number less than 10. In this paper, we discuss several approaches to bubble column scale-up, relying on variables of parameters. Two spargers with different hole diameters (0.5 mm and 1.25 mm) and superficial gas velocities (0.0125 m/s and 0.0501 m/s) are used to determine the distribution of gas holdup and liquid flow pattern. An Insignificant level of bed heights is investigated for the efficiency of hydrodynamic performance. Computational Fluid Dynamic (CFD) is used as the realistic representation of the actual reactor. The flow of the gas-liquid interface is implemented using the VOF model using the finite volume method by tracking the volume fraction of each of the fluids throughout the domain. It is observed that the initial bed heights, superficial gas velocity, and hole diameter of the sparger influence the overall gas holdup. Although the difference in sparger hole diameter affects overall gas holdup, the results are weak relative to other operating conditions. The simulation work is then compared with experimental data to improve the accuracy in analyzing the hydrodynamics of multiphase system, as well as validated the multidimensional models.
Experimental and Modeling Analyses of Human Motion Across the Static Magnetic Field of an MRI Scanner
Authors: Gurrera Davide , Leardini Alberto , Ortolani Maurizio , Durante Stefano , Caputo Vittorio , Gallias Karmenos K. , Abbate Boris F. , Rinaldi Calogero , Iacoviello Giuseppina , Acri Giuseppe , Vermiglio Giuseppe , Marrale Maurizio
Published: May 2021

It is established that human movements in the vicinity of a permanent static magnetic field, such as those in magnetic resonance imaging (MRI) scanners induce electric fields in the human body; this raises potential severe risks of health to radiographers and cleaners exposed routinely to these fields in MRI rooms. The relevant directives and parameters, however, are based on theoretical models, and accurate studies on the simulation of the effects based on human movement data obtained in real conditions are still lacking. Two radiographers and one cleaner, familiar with MRI room activities and these directives, were gait analyzed during the execution of routine job motor tasks at different velocities. Full body motion was recorded in a gait laboratory arranged to reproduce the workspace of a room with an MRI full-body scanner. Body segments were tracked with clusters of at least three markers, from which position and velocity of the centroids were calculated. These were used as input in an established computer physical model able to map the stray field in an MRI room. The spatial peak values of the calculated electric field induced by motion of the head and of the entire body during these tasks, for both the health and sensory effects, were found smaller than the thresholds recommended by the European directives, for both 1.5 T and 3.0 T MRI. These tasks therefore seem to guarantee the safety of MRI room operators according to current professional good practice for exposure risks. Physical modeling and experimental measures of human motion can also support occupational medicine.
The Pharmacodynamics Study of Insect Defensin DLP4 Against Toxigenic Staphylococcus hyicus ACCC 61734 in Vitro and Vivo
Authors: Ma Xuanxuan , Yang Na , Mao Ruoyu , Hao Ya , Yan Xue , Teng Da , Wang Jianhua
Published: May 2021

Staphylococcus hyicus (S. hyicus), as the main pathogen of exudative epidermitis (EE) in piglet, can cause a wide variety of diseases, ranging from bovine mastitis, chicken arthritis and even human sepsis, which has brought serious threats to animals and human. The potential threat of S. hyicus infection to both public and animal health has aroused great concern. The aim of our study was to explore the efficacy of insect defensin DLP4 against S. hyicus ACCC 61734 in vitro and in vivo. The in vitro efficacies of DLP4 against S. hyicus ACCC 61734 showed high antibacterial activity (0.92 μM), a long postantibiotic effect (9.54 h), a synergistic effect with ceftriaxone, penicillin and amoxicillin, a stable bacteriostatic effect, and intracellular bacteriostatic activity against S. hyicus ACCC 61734 in HaCaT cells. Besides, the antibacterial mechanism of DLP4 against S. hyicus ACCC 61734 was explored for the first time, which indicated that the antibacterial effect of DLP4 was related to its ability to destroy cell wall and generate membrane vesicles. The in vivo therapeutic effect of DLP4 was evaluated through mouse abscess model, and the results showed that DLP4 could effectively alleviate the mouse skin abscess by inhibiting bacterial proliferation and regulating cytokines. This study first demonstrated that DLP4 may be a promising therapeutic agent against S. hyicus ACCC 61734 infection.
Misconceptions, Misinformation and Politics of COVID-19 on Social Media: A Multi-Level Analysis in Ghana
Authors: Tabong Philip Teg-Nefaah , Segtub Martin
Published: May 2021

Background: Ghana developed an Emergency Preparedness and Response Plan (EPRP) in response to the Severe Acute Respiratory Syndrome Coronavirus (SARS CoV-2) pandemic. A key strategy in the EPRP is to mobilize national resources and put in place strategies for improved risk and behavioral change communication. Nonetheless, concerns have been raised on social media about COVID-19 misinformation and misconceptions. This study used social media content to determine the types, forms and the effects of the myths, misconceptions and misinformation in Ghana's COVID-19 containment.

Method: The study was conducted in three phases involving the use of both primary and secondary data. Review of social media information on COVID-19 was done. This was complemented with document review and interviews with key stakeholders with expertise in the management of public health emergencies and mass communication experts (N = 18). All interviews were transcribed verbatim and analyzed using NVivo 12.

Results: The study showed a changing pattern in the misconceptions and misinformation about COVID-19. Initially myths were largely on causes and vulnerability. It was widely speculated that black people had some immunity against COVID-19. Also, the condition was perceived to cause severe disease among the elderly. These misconceptions served as risk attenuators among Ghanaians, especially the younger generation. As the infection evolved in the country, another misconception emerged that the hot climate in Africa inhibited viral replication and transmission only to be followed by speculations and conjectures that COVID-19 was being used as a biological weapon to target developed economics. For the management of COVID-19, the use of local remedies such as Neem tree (Azadirachta indica) and herbal preparation also emerged. Myths about the efficacy of locally manufactured gin (akpeteshie) and hydroxychloroquine as prophylaxis led to abuse of such substances. Interview segments revealed the use of myths to propagate political agenda in the country.

Conclusion: The study concludes that COVID-19 misconceptions and misinformation are widespread and cover the course of the condition. These myths necessitate culturally sensitive health communication strategies that take into account local perceptions of COVID-19 in order to tackle the circulation of misconceived messages about the pandemic in Ghana.
E-Commerce Design by Older Adults: The Selection and Placement of Web Objects on Shopping Sites
Authors: Osman Rozianawaty , Hwang Faustina
Published: May 2021

This study offers insights, gathered from co-design activities with older adults, on the design of e-commerce websites. Twenty older adults (aged 52–75 years) took part in a paper-based design activity in which they were presented with a web browser window, cutouts of a selection of web objects (e.g., product images and “add to cart” buttons) in a range of designs, and office stationery for making annotations and asked to select and place web objects onto the browser window to express their design ideas for two types of shopping experience: purchasing a grocery item that is inexpensive and typically purchased in multiples (carrots) and purchasing an assistive technology item which is considered expensive and normally purchased as a one-off (wheelchair). Objects selected frequently by the older adults for inclusion in both types of e-commerce websites included product images, price, and an “add to cart” button. Some objects were selected for inclusion depending on the type of website—quantity selection was selected for the cheap, multiple purchase item, whereas descriptions, reviews, and shipping/return information were deemed important only for the expensive, single-item purchase. Regarding the relative placement of the “add to cart” button, participants most often placed the button close to the quantity selection and/or the price. Furthermore, participants expressed that having these three elements presented within a visually distinctive “buy box” would be beneficial. This study offers insight into which website elements are deemed important by this older adult participant group for e-commerce websites and how the elements should be arranged, and the results also indicate that some design requirements may differ between different types of shopping experience. The findings can potentially benefit designers, developers, and industries to more fully grasp the potential of usable online shopping applications.
DRAGoM: Classification and Quantification of Noncoding RNA in Metagenomic Data
Authors: Liu Ben , Thippabhotla Sirisha , Zhang Jun , Zhong Cuncong
Published: May 2021

Noncoding RNAs (ncRNAs) play important regulatory and functional roles in microorganisms, such as regulation of gene expression, signaling, protein synthesis, and RNA processing. Hence, their classification and quantification are central tasks toward the understanding of the function of the microbial community. However, the majority of the current metagenomic sequencing technologies generate short reads, which may contain only a partial secondary structure that complicates ncRNA homology detection. Meanwhile, de novo assembly of the metagenomic sequencing data remains challenging for complex communities. To tackle these challenges, we developed a novel algorithm called DRAGoM (Detection of RNA using Assembly Graph from Metagenomic data). DRAGoM first constructs a hybrid graph by merging an assembly string graph and an assembly de Bruijn graph. Then, it classifies paths in the hybrid graph and their constituent readsinto differentncRNA families based on both sequence and structural homology. Our benchmark experiments show that DRAGoMcan improve the performance and robustness over traditional approaches on the classification and quantification of a wide class of ncRNA families.
Development and Validation of a Novel Prognostic Model for Acute Myeloid Leukemia Based on Immune-Related Genes
Authors: Li Ran , Ding Zuoyou , Jin Peng , Wu Shishuang , Jiang Ge , Xiang Rufang , Wang Wenfang , Jin Zhen , Li Xiaoyang , Xue Kai , Wu Xiaolu , Li Junmin
Published: May 2021

The prognosis of acute myeloid leukemia (AML) is closely related to immune response changes. Further exploration of the pathobiology of AML focusing on immune-related genes would contribute to the development of more advanced evaluation and treatment strategies. In this study, we established a novel immune-17 signature based on transcriptome data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases. We found that immune biology processes and transcriptional dysregulations are critical factors in the development of AML through enrichment analyses. We also formulated a prognostic model to predict the overall survival of AML patients by using LASSO (Least Absolute Shrinkage and Selection Operator) regression analysis. Furthermore, we incorporated the immune-17 signature to improve the prognostic accuracy of the ELN2017 risk stratification system. We concluded that the immune-17 signature represents a novel useful model for evaluating AML survival outcomes and may be implemented to optimize treatment selection in the next future.
Sensing Acute Cellular Rejection in Liver Transplant Patients Using Liver-Derived Extracellular Particles: A Prospective, Observational Study
Authors: Kamali Kaan , Schmelzle Moritz , Kamali Can , Brunnbauer Philipp , Splith Katrin , Leder Annekatrin , Berndt Nadja , Hillebrandt Karl-Herbert , Raschzok Nathanael , Feldbrügge Linda , Felsenstein Matthäus , Gaßner Joseph , Ritschl Paul , Lurje Georg , Schöning Wenzel , Benzing Christian , Pratschke Johann , Krenzien Felix
Published: May 2021

Acute cellular rejection (ACR) after liver transplantation (LT) goes along with allograft dysfunction, which is diagnosed by liver biopsy and concomitant histological analysis, representing the gold standard in clinical practice. Yet, liver biopsies are invasive, costly, time-intensive and require expert knowledge. Herein we present substantial evidence that blood plasma residing peripheral liver-derived extracellular particles (EP) could be employed to diagnose ACR non-invasively. In vitro experiments showed organ-specific EP release from primary human hepatocytes under immunological stress. Secondly, analysis of consecutive LT patients (n=11) revealed significant heightened EP concentrations days before ACR. By conducting a diagnostic accuracy study (n = 69, DRKS00011631), we explored the viability of using EP as a liquid biopsy for diagnosing ACR following LT. Consequently, novel EP populations in samples were identified using visualization of t-distributed stochastic neighbor embedding (viSNE) and self-organizing maps (FlowSOM) algorithms. As a result, the ASGR1+CD130+Annexin V+ EP subpopulation exhibited the highest accuracy for predicting ACR (area under the curve: 0.80, 95% confidence interval [CI], 0.70–0.90), with diagnostic sensitivity and specificity of 100% (95% CI, 81.67–100.0%) and 68.5% (95% CI, 55.3–79.3%), respectively. In summary, this new EP subpopulation presented the highest diagnostic accuracy for detecting ACR in LT patients.
Evolving and Sustaining Ocean Best Practices to Enable Interoperability in the UN Decade of Ocean Science for Sustainable Development
Authors: Pearlman Jay , Buttigieg Pier Luigi , Bushnell Mark , Delgado Claudia , Hermes Juliet , Heslop Emma , Hörstmann Cora , Isensee Kirsten , Karstensen Johannes , Lambert Arno , Lara-Lopez Ana , Muller-Karger Frank , Munoz Mas Cristian , Pearlman Francoise , Pissierssens Peter , Przeslawski Rachel , Simpson Pauline , van Stavel Jordan , Venkatesan Ramasamy
Published: May 2021

The UN Decade of Ocean Science for Sustainable Development (Ocean Decade) challenges marine science to better inform and stimulate social and economic development while conserving marine ecosystems. To achieve these objectives, we must make our diverse methodologies more comparable and interoperable, expanding global participation and foster capacity development in ocean science through a new and coherent approach to best practice development. We present perspectives on this issue gleaned from the ongoing development of the UNESCO Intergovernmental Oceanographic Commission (IOC) Ocean Best Practices System (OBPS). The OBPS is collaborating with individuals and programs around the world to transform the way ocean methodologies are managed, in strong alignment with the outcomes envisioned for the Ocean Decade. However, significant challenges remain, including: (1) the haphazard management of methodologies across their lifecycle, (2) the ambiguous endorsement of what is “best” and when and where one method may be applicable vs. another, and (3) the inconsistent access to methodological knowledge across disciplines and cultures. To help address these challenges, we recommend that sponsors and leaders in ocean science and education promote consistent documentation and convergence of methodologies to: create and improve context-dependent best practices; incorporate contextualized best practices into Ocean Decade Actions; clarify who endorses which method and why; create a global network of complementary ocean practices systems; and ensure broader consistency and flexibility in international capacity development.
Reducing Data Deficiencies: Preliminary Elasmobranch Fisheries Surveys in India, Identify Range Extensions and Large Proportions of Female and Juvenile Landings
Authors: Johri Shaili , Livingston Isabella , Tiwari Anjani , Solanki Jitesh , Busch Anissa , Moreno Isabel , R. Fellows Sam , Doane Michael P. , Dinsdale Elizabeth A.
Published: May 2021

Chondrichthyes, an ancient and diverse class of vertebrates, are crucial to the health of marine ecosystems. Excessive demand for chondrichthyan products has increased fishing pressure, threatening ∼30% of species with extinction in recent decades. India is the second-largest shark landing nation globally and the province of Gujarat, is the largest contributor to its shark exports. Despite their significant contribution to global fish supplies, chondrichthyan fisheries in Gujarat remain understudied and many species, data deficient, posing challenges to the conservation of remaining populations in the region. Here, we report results from taxonomic assessment of elasmobranchs at four key landing sites in Gujarat. We identified thirty-one species of sharks and rays with a significant bias toward capture of females and juveniles by fisheries. Our data indicate the presence of nursery areas for species such as Sphyrna lewini and Rhynchobatus laevis in the neritic areas off Gujarat. Further, we discovered extensions of the current distribution range for three species -Torpedo sinuspersici, Carcharhinus sorrah, and Rhinobatos punctifer. Taxonomic identities for a subset of species were confirmed using genomic analyses conducted with portable DNA sequencing tools. We present assessments for six data deficient species in the region – Rhinobatos annandalei, Rhinoptera jayakari, Maculabatis bineeshi, Pateobatis bleekeri, T. sinuspersici, and Carcharhinus amboinensis. Our investigation underscores species with urgent conservation needs and reduces data deficiencies. These data will inform and pivot future scientific and conservation efforts to protect remaining populations of some of the most vulnerable Chondrichthyes in the Arabian Seas Region.
Liver Organoids: Recent Developments, Limitations and Potential
Authors: Harrison Sean Philip , Baumgarten Saphira Felicitas , Verma Rajneesh , Lunov Oleg , Dejneka Alexandr , Sullivan Gareth John
Published: May 2021

Liver cell types derived from induced pluripotent stem cells (iPSCs) share the potential to investigate development, toxicity, as well as genetic and infectious disease in ways currently limited by the availability of primary tissue. With the added advantage of patient specificity, which can play a role in all of these areas. Many iPSC differentiation protocols focus on 3 dimensional (3D) or organotypic differentiation, as these offer the advantage of more closely mimicking in vivo systems including; the formation of tissue like architecture and interactions/crosstalk between different cell types. Ultimately such models have the potential to be used clinically and either with or more aptly, in place of animal models. Along with the development of organotypic and micro-tissue models, there will be a need to co-develop imaging technologies to enable their visualization. A variety of liver models termed “organoids” have been reported in the literature ranging from simple spheres or cysts of a single cell type, usually hepatocytes, to those containing multiple cell types combined during the differentiation process such as hepatic stellate cells, endothelial cells, and mesenchymal cells, often leading to an improved hepatic phenotype. These allow specific functions or readouts to be examined such as drug metabolism, protein secretion or an improved phenotype, but because of their relative simplicity they lack the flexibility and general applicability of ex vivo tissue culture. In the liver field these are more often constructed rather than developed together organotypically as seen in other organoid models such as brain, kidney, lung and intestine. Having access to organotypic liver like surrogates containing multiple cell types with in vivo like interactions/architecture, would provide vastly improved models for disease, toxicity and drug development, combining disciplines such as microfluidic chip technology with organoids and ultimately paving the way to new therapies.
Organic Matter Type Defines the Composition of Active Microbial Communities Originating From Anoxic Baltic Sea Sediments
Authors: Suominen Saara , van Vliet Daan M. , Sánchez-Andrea Irene , van der Meer Marcel T. J. , Sinninghe Damsté Jaap S. , Villanueva Laura
Published: May 2021

Carbon cycling in anoxic marine sediments is dependent on uncultured microbial communities. Niches of heterotrophic microorganisms are defined by organic matter (OM) type and the different phases in OM degradation. We investigated how OM type defines microbial communities originating from organic-rich, anoxic sediments from the Baltic Sea. We compared changes in the sediment microbial community, after incubation with different stable isotope labeled OM types [i.e., particulate algal organic matter (PAOM), protein, and acetate], by using DNA stable isotope probing (DNA-SIP). Incorporation of 13C and/or 15N label was predominantly detected in members of the phyla Planctomycetes and Chloroflexi, which also formed the majority (>50%) of the original sediment community. While these phylum-level lineages incorporated label from all OM types, phylogenetic analyses revealed a niche separation at the order level. Members of the MSBL9 (Planctomycetes), the Anaerolineales (Chloroflexi), and the class Bathyarchaeota, were identified as initial degraders of carbohydrate-rich OM, while other uncultured orders, like the CCM11a and Phycisphaerales (Planctomycetes), Dehalococcoidia, and JG30-KF-CM66 (Chloroflexi), incorporated label also from protein and acetate. Our study highlights the importance of initial fermentation of complex carbon pools in shaping anoxic sediment microbial communities and reveals niche specialization at the order level for the most important initial degraders in anoxic sediments.
The Antifungal Activity of HMA, an Amiloride Analog and Inhibitor of Na+/H+ Exchangers
Authors: Vu Kiem , Blumwald Eduardo , Gelli Angie
Published: May 2021

One path toward identifying effective and easily accessible antifungals is to repurpose commonly used drugs. Amiloride, a widely used diuretic, inhibits different isoforms of Na+/H+ exchangers, Na+ channels, and Na+/Ca2+ exchangers. Here, we found that amiloride had poor antifungal activity against isolates of Cryptococcus prompting the examination of the amiloride analog, HMA [5-(N,N-hexamethylene)amiloride]. HMA possesses strong activity against Na+/H+ exchangers (NHEs) and little K+-associated toxicity since HMA has only minimal inhibitory effects toward epithelial sodium channels (ENaC), the diuretic and antikaliuretic target of amiloride. Although HMA produced a robust dose-dependent growth inhibition of several fungal isolates, susceptibility assays revealed modest MICs against isolates of Cryptococcus. A checkerboard dilution strategy resulted in fractional inhibitory concentrations (FIC) < 0.5, suggesting that HMA displays synergy with several antifungal azole drugs including posaconazole, voriconazole, and ketoconazole. Itraconazole and ravuconazole showed moderate synergy with HMA across all tested fungal isolates. In combination with HMA, ravuconazole had MICs of 0.004–0.008 μg/ml, a ∼16-fold reduction compared to MICs of ravuconazole when used alone and significantly more effective than the overall MIC90 (0.25 μg/ml) reported for ravuconazole against 541 clinical isolates of Cryptococcus neoformans. In combination with azole drugs, MICs of HMA ranged from 3.2 μM (1 μg/ml) to 26 μM (16 μg/ml), HMA was not cytotoxic at concentrations ≤ 8 μg/ml, but MICs were above the reported HMA Ki of 0.013–2.4 μM for various Na+/H+ exchangers. Our results suggest that HMA has limited potential as a monotherapy and may have additional targets in fungal/yeast cells since strains lacking NHEs remained sensitive to HMA. We determined that the hydrophobic substituent at the 5-amino group of HMA is likely responsible for the observed antifungal activity and synergy with several azoles since derivatives with bulky polar substitutions showed no activity against Cryptococcus, indicating that other 5-substituted HMA derivatives could possess stronger antifungal activity. Moreover, substitution of other positions around the pyrazine core of HMA has not been investigated but could reveal new leads for antifungal drug development.
Artificial Intelligence in Epigenetic Studies: Shedding Light on Rare Diseases
Authors: Brasil Sandra , Neves Cátia José , Rijoff Tatiana , Falcão Marta , Valadão Gonçalo , Videira Paula A. , dos Reis Ferreira Vanessa
Published: May 2021

More than 7,000 rare diseases (RDs) exist worldwide, affecting approximately 350 million people, out of which only 5% have treatment. The development of novel genome sequencing techniques has accelerated the discovery and diagnosis in RDs. However, most patients remain undiagnosed. Epigenetics has emerged as a promise for diagnosis and therapies in common disorders (e.g., cancer) with several epimarkers and epidrugs already approved and used in clinical practice. Hence, it may also become an opportunity to uncover new disease mechanisms and therapeutic targets in RDs. In this “big data” age, the amount of information generated, collected, and managed in (bio)medicine is increasing, leading to the need for its rapid and efficient collection, analysis, and characterization. Artificial intelligence (AI), particularly deep learning, is already being successfully applied to analyze genomic information in basic research, diagnosis, and drug discovery and is gaining momentum in the epigenetic field. The application of deep learning to epigenomic studies in RDs could significantly boost discovery and therapy development. This review aims to collect and summarize the application of AI tools in the epigenomic field of RDs. The lower number of studies found, specific for RDs, indicate that this is a field open to expansion, following the results obtained for other more common disorders.
Early Evolution of Transcription Systems and Divergence of Archaea and Bacteria
Authors: Lei Lei , Burton Zachary F.
Published: May 2021

DNA template-dependent multi-subunit RNA polymerases (RNAPs) found in all three domains of life and some viruses are of the two-double-Ψ-β-barrel (DPBB) type. The 2-DPBB protein format is also found in some RNA template-dependent RNAPs and a major replicative DNA template-dependent DNA polymerase (DNAP) from Archaea (PolD). The 2−DPBB family of RNAPs and DNAPs probably evolved prior to the last universal common cellular ancestor (LUCA). Archaeal Transcription Factor B (TFB) and bacterial σ factors include homologous strings of helix-turn-helix units. The consequences of TFB-σ homology are discussed in terms of the evolution of archaeal and bacterial core promoters. Domain-specific DPBB loop inserts functionally connect general transcription factors to the RNAP active site. Archaea appear to be more similar to LUCA than Bacteria. Evolution of bacterial σ factors from TFB appears to have driven divergence of Bacteria from Archaea, splitting the prokaryotic domains.
m6A-Related lncRNAs Are Potential Biomarkers for the Prognosis of Metastatic Skin Cutaneous Melanoma
Authors: Huang Suyang , Lyu Shanshan , Gao Zhe , Zha Weifeng , Wang Ping , Shan Yunyun , He Jianzhong , Li Yang
Published: May 2021

Background: The incidence of skin cutaneous melanoma (SKCM) has risen more rapidly than any other solid tumor in the past few decades. The median survival for metastatic melanoma is only six to nine months and the 5°years survival rate of patients with conventional therapy is less than 5%. Our aim was to reveal the potential molecular mechanism in m6A modification of lncRNA and provide candidate prognostic biomarkers for metastatic SKCM.

Methods: lncRNAs expression level was obtained by re-annotation in TCGA and CCLE datasets. m6A-related lncRNAs were selected though correlation analysis. Univariate cox regression analysis was used to screen out independent prognostic factors. LASSO Cox regression was performed to construct an m6A-related lncRNA model (m6A-LncM). Univariate survival analysis and ROC curve were used to assess the prognostic efficacy of this model and candidate lncRNAs. Enrichment analysis was used to explore the candidate genes’ functions.

Results: We obtained 1,086 common m6A-related lncRNAs after Pearson correlation analysis in both two datasets. 130 out of the 1,086 lncRNAs are independent prognostic factors. 24 crucial lncRNAs were filtered after LASSO Cox regression analysis. All the m6A-LncM and the 24 lncRNAs were related to overall survival. Stratified survival analysis of m6A-LncM showed that the model retains its prognostic efficacy in recurrence, radiation therapy and other subgroups. Enrichment analysis also found that these lncRNAs were immune associated.

Conclusion: Here, we obtained 24 crucial lncRNAs that may be potential biomarkers to predict survival of metastatic SKCM and may provide a new insight to improve the prognosis of it.
A Painful Beginning: Early Life Surgery Produces Long-Term Behavioral Disruption in the Rat
Authors: Ririe Douglas G. , Eisenach James C. , Martin Thomas J.
Published: May 2021

Early life surgery produces peripheral nociceptive activation, inflammation, and stress. Early life nociceptive input and inflammation have been shown to produce long-term processing changes that are not restricted to the dermatome of injury. Additionally stress has shown long-term effects on anxiety, depression, learning, and maladaptive behaviors including substance abuse disorder and we hypothesized that early life surgery would have long-term effects on theses complex behaviors in later life. In this study surgery in the rat hindpaw was performed to determine if there are long-term effects on anxiety, depression, audiovisual attention, and opioid reward behaviors. Male animals received paw incision surgery and anesthesia or anesthesia alone (sham) at postnatal day 6. At 10 weeks after surgery, open field center zone entries were decreased, a measure of anxiety (n = 20) (P = 0.03) (effect size, Cohen’s d = 0.80). No difference was found in the tail suspension test as a measure of depression. At 16–20 weeks, attentional performance in an operant task was similar between groups at baseline and decreased with audiovisual distraction in both groups (P < 0.001) (effect size, η2 = 0.25), but distraction revealed a persistent impairment in performance in the surgery group (n = 8) (P = 0.04) (effect size, η2 = 0.13). Opioid reward was measured using heroin self-administration at 16–24 weeks. Heroin intake increased over time in both groups during 24-h free access (P < 0.001), but was greater in the surgery group (P = 0.045), with a significant interaction between time and treatment (P < 0.001) (effect size, Cohen f2 = 0.36). These results demonstrate long-term disruptions in complex behaviors from surgical incision under anesthesia. Future studies to explore sex differences in early life surgery and the attendant peripheral neuronal input, stress, and inflammation will be valuable to understand emerging learning deficits, anxiety, attentional dysfunction, and opioid reward and their mechanisms. This will be valuable to develop optimal approaches to mitigate the long-term effects of surgery in early life.
Neural Design Principles for Subjective Experience: Implications for Insects
Authors: Key Brian , Zalucki Oressia , Brown Deborah J.
Published: May 2021

How subjective experience is realized in nervous systems remains one of the great challenges in the natural sciences. An answer to this question should resolve debate about which animals are capable of subjective experience. We contend that subjective experience of sensory stimuli is dependent on the brain’s awareness of its internal neural processing of these stimuli. This premise is supported by empirical evidence demonstrating that disruption to either processing streams or awareness states perturb subjective experience. Given that the brain must predict the nature of sensory stimuli, we reason that conscious awareness is itself dependent on predictions generated by hierarchically organized forward models of the organism’s internal sensory processing. The operation of these forward models requires a specialized neural architecture and hence any nervous system lacking this architecture is unable to subjectively experience sensory stimuli. This approach removes difficulties associated with extrapolations from behavioral and brain homologies typically employed in addressing whether an animal can feel. Using nociception as a model sensation, we show here that theDrosophilabrain lacks the required internal neural connectivity to implement the computations required of hierarchical forward models. Consequently, we conclude thatDrosophila, and those insects with similar neuroanatomy, do not subjectively experience noxious stimuli and therefore cannot feel pain.
Organoids for the Study of Retinal Development and Developmental Abnormalities
Authors: Vielle Anne , Park Yuna K. , Secora Conner , Vergara M. Natalia
Published: May 2021

The cumulative knowledge of retina development has been instrumental in the generation of retinal organoid systems from pluripotent stem cells; and these three-dimensional organoid models, in turn, have provided unprecedented opportunities for retinal research and translational applications, including the ability to model disease in a human setting and to apply these models to the development and validation of therapeutic drugs. In this review article, we examine how retinal organoids can also contribute to our understanding of retinal developmental mechanisms, how this knowledge can be applied to modeling developmental abnormalities, and highlight some of the avenues that remain to be explored.
Effectiveness of Virtual Reality in the Rehabilitation of Motor Function of Patients With Subacute Stroke: A Meta-Analysis
Authors: Peng Quan-cheng , Yin Ling , Cao Yi
Published: May 2021

Stroke is a major cause of death and disability in adults. Conventional therapy (CT) has limited effectiveness, and therefore, various virtual reality (VR) rehabilitation programs have been designed. However, their efficacy in regaining motor function in patients with subacute stroke is questionable. Therefore, we conducted this meta-analysis to determine the efficacy of VR, compared to CT, in restoring motor function in this patient population. Up to October 10, 2020, nine electronic databases were searched for relevant articles reporting the effectiveness of VR in regaining motor function in patients with subacute stroke. This search was updated on March 7, 2021, with no additional added articles. The control group included CT, physical therapy, occupational therapy, or a combination of them. Effectiveness is defined as the positive change from baseline values to the last follow-up point. The Cochrane's revised risk-of-bias tool was used to determine the quality of included trials. A metaregression analysis was conducted to determine the effect of “time since last stroke” on reported outcomes. Publication bias and sensitivity analyses were also carried out. A total of 19 studies (17 randomized controlled trials, 1 cohort study, and 1 crossover trial) were included in the qualitative analysis, whereas 16 trials were meta-analyzed. A great improvement in motor function was noted in the VR group, when compared to preintervention values [standardized mean difference (SMD) = 1.14; 95% confidence interval (CI) = 0.77–1.52; I2 = 82%; P < 0.001]. When compared to CT, VR resulted in mild improvement in motor function (SMD = 0.47; 95% CI = 0.22–0.72; I2 = 75%; P < 0.001). However, upon trim-and-fill adjustment, this finding was deemed insignificant (SMD = 0.08; 95% CI = −0.16 to 0.33; I2 = 82.6%; P < 0.001). Ten studies had low risk, five had some concerns, three had high risk, and one had a moderate risk of bias. VR programs can be used jointly with CT for the rehabilitation of the motor function of patients with subacute stroke. However, more studies are still warranted to determine the effectiveness of these interventions in retaining the cognitive function and physical performance of such patients.
New Prediction Models of Functional Outcome in Acute Intracerebral Hemorrhage: The dICH Score and uICH Score
Authors: Yang Wen-Song , Shen Yi-Qing , Wei Xiao , Zhao Li-Bo , Liu Qing-Jun , Xie Xiong-Fei , Zhang Zhi-Wei , Deng Lan , Lv Xin-Ni , Zhang Shu-Qiang , Li Xin-Hui , Li Qi , Xie Peng
Published: May 2021

Objectives: The original intracerebral hemorrhage (oICH) score is the severity score most commonly used in clinical intracerebral hemorrhage (ICH) research but may be influenced by hematoma expansion or intraventricular hemorrhage (IVH) growth in acute ICH. Here, we aimed to develop new clinical scores to improve the prediction of functional outcomes in patients with ICH.

Methods: Patients admitted to the First Affiliated Hospital of Chongqing Medical University with primary ICH were prospectively enrolled in this study. Hematoma volume was measured using a semiautomated, computer-assisted technique. The dynamic ICH (dICH) score was developed by incorporating hematoma expansion and IVH growth into the oICH score. The ultra-early ICH (uICH) score was developed by adding the independent non-contrast CT markers to the oICH score. Receiver operating characteristic curve analysis was used to compare performance among the oICH score, dICH score, and uICH score.

Results: There were 310 patients in this study which included 72 patients (23.2%) with hematoma expansion and 58 patients (18.7%) with IVH growth. Of 31 patients with two or more non-contrast computed tomography markers, 61.3% died, and 96.8% had poor outcomes at 90 days. After adjustment for potential confounding variables, we found that age, baseline Glasgow Coma Scale score, presence of IVH on initial CT, baseline ICH volume, infratentorial hemorrhage, hematoma expansion, IVH growth, blend sign, black hole sign, and island sign could independently predict poor outcomes in multivariate analysis. In comparison with the oICH score, the dICH score and uICH score exhibited better performance in the prediction of poor functional outcomes.

Conclusions: The dICH score and uICH score were useful clinical assessment tools that could be used for risk stratification concerning functional outcomes and provide guidance in clinical decision-making in acute ICH.
Participation of Acoustic and Electric Hearing in Perceiving Musical Sounds
Authors: Duret Sonia , Bigand Emmanuel , Guigou Caroline , Marty Nicolas , Lalitte Philippe , Bozorg Grayeli Alexis
Published: May 2021

Introduction: The objective of our study was to evaluate musical perception and its relation to the quality of life in patients with bimodal binaural auditory stimulation.

Materials and Methods: Nineteen adult patients with a cochlear implant (CI) for minimum 6 months, and moderate to severe contralateral hearing loss with a hearing aid (HA), and 21 normal hearing adults were included in this prospective, cross-sectional study. Pure-tone and speech audiometry, musical test evaluating sound perception characteristics and musical listening abilities, Munich questionnaire for musical habits, and the APHAB questionnaire were recoded. Performance in musical perception test with HA, CI, and HA + CI, and potential correlations between music test, audiometry and questionnaires were investigated.

Results: Bimodal stimulation improved musical perception in several features (sound brightness, roughness, and clarity) in comparison to unimodal hearing, but CI did not add to HA performances in texture, polyphony or musical emotion and even appeared to interfere negatively in pitch perception with HA. Musical perception performances (sound clarity, instrument recognition) appeared to be correlated to hearing-related quality of life (APHAB RV and EC subdomains) but not with speech performances suggesting that the exploration of musical perception complements speech understanding evaluation to better describe every-day life hearing handicap.

Conclusion: Testing musical sound perception provides important information on hearing performances as a complement to speech audiometry and appears to be related to hearing-related quality of life.
Environmental Enrichment Induces Epigenomic and Genome Organization Changes Relevant for Cognition
Authors: Espeso-Gil Sergio , Holik Aliaksei Z. , Bonnin Sarah , Jhanwar Shalu , Chandrasekaran Sandhya , Pique-Regi Roger , Albaigès-Ràfols Júlia , Maher Michael , Permanyer Jon , Irimia Manuel , Friedländer Marc R. , Pons-Espinal Meritxell , Akbarian Schahram , Dierssen Mara , Maass Philipp G. , Hor Charlotte N. , Ossowski Stephan
Published: May 2021

In early development, the environment triggers mnemonic epigenomic programs resulting in memory and learning experiences to confer cognitive phenotypes into adulthood. To uncover how environmental stimulation impacts the epigenome and genome organization, we used the paradigm of environmental enrichment (EE) in young mice constantly receiving novel stimulation. We profiled epigenome and chromatin architecture in whole cortex and sorted neurons by deep-sequencing techniques. Specifically, we studied chromatin accessibility, gene and protein regulation, and 3D genome conformation, combined with predicted enhancer and chromatin interactions. We identified increased chromatin accessibility, transcription factor binding including CTCF-mediated insulation, differential occupancy of H3K36me3 and H3K79me2, and changes in transcriptional programs required for neuronal development. EE stimuli led to local genome re-organization by inducing increased contacts between chromosomes 7 and 17 (inter-chromosomal). Our findings support the notion that EE-induced learning and memory processes are directly associated with the epigenome and genome organization.
Beyond Neuronal Microtubule Stabilization: MAP6 and CRMPS, Two Converging Stories
Authors: Cuveillier Camille , Boulan Benoit , Ravanello Charlotte , Denarier Eric , Deloulme Jean-Christophe , Gory-Fauré Sylvie , Delphin Christian , Bosc Christophe , Arnal Isabelle , Andrieux Annie
Published: May 2021

The development and function of the central nervous system rely on the microtubule (MT) and actin cytoskeletons and their respective effectors. Although the structural role of the cytoskeleton has long been acknowledged in neuronal morphology and activity, it was recently recognized to play the role of a signaling platform. Following this recognition, research into Microtubule Associated Proteins (MAPs) diversified. Indeed, historically, structural MAPs—including MAP1B, MAP2, Tau, and MAP6 (also known as STOP);—were identified and described as MT-binding and -stabilizing proteins. Extensive data obtained over the last 20 years indicated that these structural MAPs could also contribute to a variety of other molecular roles. Among multi-role MAPs, MAP6 provides a striking example illustrating the diverse molecular and cellular properties of MAPs and showing how their functional versatility contributes to the central nervous system. In this review, in addition to MAP6’s effect on microtubules, we describe its impact on the actin cytoskeleton, on neuroreceptor homeostasis, and its involvement in signaling pathways governing neuron development and maturation. We also discuss its roles in synaptic plasticity, brain connectivity, and cognitive abilities, as well as the potential relationships between the integrated brain functions of MAP6 and its molecular activities. In parallel, the Collapsin Response Mediator Proteins (CRMPs) are presented as examples of how other proteins, not initially identified as MAPs, fall into the broader MAP family. These proteins bind MTs as well as exhibiting molecular and cellular properties very similar to MAP6. Finally, we briefly summarize the multiple similarities between other classical structural MAPs and MAP6 or CRMPs.In summary, this review revisits the molecular properties and the cellular and neuronal roles of the classical MAPs, broadening our definition of what constitutes a MAP.
Anabolic Resistance of Muscle Protein Turnover Comes in Various Shapes and Sizes
Authors: Paulussen Kevin J. M. , McKenna Colleen F. , Beals Joseph W. , Wilund Kenneth R. , Salvador Amadeo F. , Burd Nicholas A.
Published: May 2021

Anabolic resistance is defined by a blunted stimulation of muscle protein synthesis rates (MPS) to common anabolic stimuli in skeletal muscle tissue such as dietary protein and exercise. Generally, MPS is the target of most exercise and feeding interventions as muscle protein breakdown rates seem to be less responsive to these stimuli. Ultimately, the blunted responsiveness of MPS to dietary protein and exercise underpins the loss of the amount and quality of skeletal muscle mass leading to decrements in physical performance in these populations. The increase of both habitual physical activity (including structured exercise that targets general fitness characteristics) and protein dense food ingestion are frontline strategies utilized to support muscle mass, performance, and health. In this paper, we discuss anabolic resistance as a common denominator underpinning muscle mass loss with aging, obesity, and other disease states. Namely, we discuss the fact that anabolic resistance exists as a dimmer switch, capable of varying from higher to lower levels of resistance, to the main anabolic stimuli of feeding and exercise depending on the population. Moreover, we review the evidence on whether increased physical activity and targeted exercise can be leveraged to restore the sensitivity of skeletal muscle tissue to dietary amino acids regardless of the population.