bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Incubation Time on Ortho-Toluidine Blue Mediated Antimicrobial Photodynamic Therapy Directed against Selected Candida Strains—An In Vitro Study
Authors: Wiench Rafał , Nowicka Joanna , Pajączkowska Magdalena , Kuropka Piotr , Skaba Dariusz , Kruczek-Kazibudzka Anna , Kuśka-Kiełbratowska Anna , Grzech-Leśniak Kinga
Published: October 2021

(1) Background and the aim: The appropriate incubation time in the antimicrobial photodynamic therapy protocol seems to have a huge impact on the efficacy of this process. This is particularly important in relation to Candida strains, due to the size of these cells and the presence of the cell wall. The aims of this study were to determine the optimal incubation time needed for the absorption of toluidine blue by cells of C. albicans, C. glabrata, C. krusei and C. parapsilosis using direct observation by optical microscopy, and to evaluate the efficacy of TBO-mediated aPDT on planktonic cells of these strains. (2) Methods: The microscopic evaluation consisted of taking a series of images at a magnification of 600× and counting the % of stained cells. The in vitro effect of TBO-mediated aPDT combined with a diode laser (635 nm, 400mW, 12 J/cm2, CW) on the viability of yeast cells with different incubation times was evaluated. (3) Results: The presence of TBO within the cytoplasm was observed in all tested Candida strains and at all microscopic evaluation times. However, the highest percentages of cells were stained at 7 and 10 min. The highest % reduction of CFU/mL after TBO-mediated aPDT against Candida was obtained for the strain C. albicans ATCC 10,231 and it was 78.55%. (4) Conclusions: TBO-mediated aPDT against Candida was effective in reducing the number of CFU/mL at all assessed incubation times. However, the most efficient period for almost all strains was 7–10 min.
Palmitic Acid-Induced miR-429-3p Impairs Myoblast Differentiation by Downregulating CFL2
Authors: Nguyen Mai Thi , Min Kyung-Ho , Lee Wan
Published: October 2021

MicroRNAs are known to play a critical role in skeletal myogenesis and maintenance, and cofilin-2 (CFL2) is necessary for actin cytoskeleton dynamics and myogenic differentiation. Nonetheless, target molecules and the modes of action of miRNAs, especially those responsible for the inhibitory mechanism on the myogenesis by saturated fatty acids (SFA) or obesity, still remain unclear. Here, we reported the role played by miR-429-3p on CFL2 expression, actin filament dynamics, myoblast proliferation, and myogenic differentiation in C2C12 cells. Palmitic acid (PA), the most abundant SFA in diet, inhibited the myogenic differentiation of myoblasts, accompanied by CFL2 reduction and miR-429-3p induction. Interestingly, miR-429-3p suppressed the expression of CFL2 by targeting the 3′UTR of CFL2 mRNA directly. Transfection of miR-429-3p mimic in myoblasts increased F-actin formation and augmented nuclear YAP level, thereby promoting cell cycle progression and myoblast proliferation. Moreover, miR-429-3p mimic drastically suppressed the expressions of myogenic factors, such as MyoD, MyoG, and MyHC, and impaired myogenic differentiation of C2C12 cells. Therefore, this study unveiled the crucial role of miR-429-3p in myogenic differentiation through the suppression of CFL2 and provided implications of SFA-induced miRNA in the regulation of actin dynamics and skeletal myogenesis.
Organ Specificity and Heterogeneity of Cancer-Associated Fibroblasts in Colorectal Cancer
Authors: Miyashita Naoya , Saito Akira
Published: October 2021

Fibroblasts constitute a ubiquitous mesenchymal cell type and produce the extracellular matrix (ECM) of connective tissue, thereby providing the structural basis of various organs. Fibroblasts display differential transcriptional patterns unique to the organ of their origin and they can be activated by common stimuli such as transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF) signaling. Cancer-associated fibroblasts (CAFs) reside in the cancer tissue and contribute to cancer progression by influencing cancer cell growth, invasion, angiogenesis and tumor immunity. CAFs impact on the tumor microenvironment by remodeling the ECM and secreting soluble factors such as chemokines and growth factors. Differential expression patterns of molecular markers suggest heterogeneous features of CAFs in terms of their function, pathogenic role and cellular origin. Recent studies elucidated the bimodal action of CAFs on cancer progression and suggest a subgroup of CAFs with tumor-suppressive effects. This review attempts to describe cellular features of colorectal CAFs with an emphasis on their heterogeneity and functional diversity.
The Evolutionary History of the Chymase Locus -a Locus Encoding Several of the Major Hematopoietic Serine Proteases
Authors: Akula Srinivas , Fu Zhirong , Wernersson Sara , Hellman Lars
Published: October 2021

Several hematopoietic cells of the immune system store large amounts of proteases in cytoplasmic granules. The absolute majority of these proteases belong to the large family of chymotrypsin-related serine proteases. The chymase locus is one of four loci encoding these granule-associated serine proteases in mammals. The chymase locus encodes only four genes in primates, (1) the gene for a mast-cell-specific chymotryptic enzyme, the chymase; (2) a T-cell-expressed asp-ase, granzyme B; (3) a neutrophil-expressed chymotryptic enzyme, cathepsin G; and (4) a T-cell-expressed chymotryptic enzyme named granzyme H. Interestingly, this locus has experienced a number of quite dramatic expansions during mammalian evolution. This is illustrated by the very large number of functional protease genes found in the chymase locus of mice (15 genes) and rats (18 genes). A separate expansion has also occurred in ruminants, where we find a new class of protease genes, the duodenases, which are expressed in the intestinal region. In contrast, the opossum has only two functional genes in this locus, the mast cell (MC) chymase and granzyme B. This low number of genes may be the result of an inversion, which may have hindered unequal crossing over, a mechanism which may have been a major factor in the expansion within the rodent lineage. The chymase locus can be traced back to early tetrapods as genes that cluster with the mammalian genes in phylogenetic trees can be found in frogs, alligators and turtles, but appear to have been lost in birds. We here present the collected data concerning the evolution of this rapidly evolving locus, and how these changes in gene numbers and specificities may have affected the immune functions in the various tetrapod species.
Short Daily Exposure to Environmental Enrichment, Fluoxetine, or Their Combination Reverses Deterioration of the Coat and Anhedonia Behaviors with Differential Effects on Hippocampal Neurogenesis in Chronically Stressed Mice
Authors: Ramírez-Rodríguez Gerardo Bernabé , Vega-Rivera Nelly Maritza , Meneses-San Juan David , Ortiz-López Leonardo , Estrada-Camarena Erika Montserrat , Flores-Ramos Mónica
Published: October 2021

Depression is a neuropsychiatric disorder with a high impact on the worldwide population. To overcome depression, antidepressant drugs are the first line of treatment. However, pre-clinical studies have pointed out that antidepressants are not entirely efficacious and that the quality of the living environment after stress cessation may play a relevant role in increasing their efficacy. As it is unknown whether a short daily exposure to environmental enrichment during chronic stress and antidepressant treatment will be more effective than just the pharmacological treatment, this study analyzed the effects of fluoxetine, environmental enrichment, and their combination on depressive-associated behavior. Additionally, we investigated hippocampal neurogenesis in mice exposed to chronic mild stress. Our results indicate that fluoxetine reversed anhedonia. Besides, fluoxetine reversed the decrement of some events of the hippocampal neurogenic process caused by chronic mild stress. Conversely, short daily exposure to environmental enrichment changed the deterioration of the coat and anhedonia. Although, this environmental intervention did not produce significant changes in the neurogenic process affected by chronic mild stress, fluoxetine plus environmental enrichment showed similar effects to those caused by environmental enrichment to reverse depressive-like behaviors. Like fluoxetine, the combination reversed the declining number of Ki67, doublecortin, calretinin cells and mature newborn neurons. Finally, this study suggests that short daily exposure to environmental enrichment improves the effects of fluoxetine to reverse the deterioration of the coat and anhedonia in chronically stressed mice. In addition, the combination of fluoxetine with environmental enrichment produces more significant effects than those caused by fluoxetine alone on some events of the neurogenic process. Thus, environmental enrichment improves the benefits of pharmacological treatment by mechanisms that need to be clarified.
The Role of MSCs and Cell Fusion in Tissue Regeneration
Authors: Dörnen Jessica , Dittmar Thomas
Published: October 2021

Regenerative medicine is concerned with the investigation of therapeutic agents that can be used to promote the process of regeneration after injury or in different diseases. Mesenchymal stem/stromal cells (MSCs) and their secretome—including extracellular vesicles (EVs) are of great interest, due to their role in tissue regeneration, immunomodulatory capacity and low immunogenicity. So far, clinical studies are not very conclusive as they show conflicting efficacies regarding the use of MSCs. An additional process possibly involved in regeneration might be cell fusion. This process occurs in both a physiological and a pathophysiological context and can be affected by immune response due to inflammation. In this review the role of MSCs and cell fusion in tissue regeneration is discussed.
ATP1A1 Mutant in Aldosterone-Producing Adenoma Leads to Cell Proliferation
Authors: Kobuke Kazuhiro , Oki Kenji , Gomez-Sanchez Celso E. , Gomez-Sanchez Elise P. , Itcho Kiyotaka , Ohno Haruya , Nagano Gaku , Yoshii Yoko , Baba Ryuta , Kodama Takaya , Arihiro Koji , Hattori Noboru , Yoneda Masayasu
Published: October 2021

The molecular mechanisms by which ATP1A1 mutation-mediated cell proliferation or tumorigenesis in aldosterone-producing adenomas (APAs) have not been elucidated. First, we investigated whether the APA-associated ATP1A1 L104R mutation stimulated cell proliferation. Second, we aimed to clarify the molecular mechanisms by which the ATP1A1 mutation-mediated cell proliferated. We performed transcriptome analysis in APAs with ATP1A1 mutation. ATP1A1 L104R mutation were modulated in human adrenocortical carcinoma (HAC15) cells (ATP1A1-mutant cells), and we evaluated cell proliferation and molecular signaling events. Transcriptome and immunohistochemical analysis showed that Na/K-ATPase (NKA) expressions in ATP1A1 mutated APA were more abundant than those in non-functioning adrenocortical adenoma or KCNJ5 mutated APAs. The significant increase of number of cells, amount of DNA and S-phase population were shown in ATP1A1-mutant cells. Fluo-4 in ATP1A1-mutant cells were significantly increased. Low concentration of ouabain stimulated cell proliferation in ATP1A1-mutant cells. ATP1A1-mutant cells induced Src phosphorylation, and low concentration of ouabain supplementation showed further Src phosphorylation. We demonstrated that NKAs were highly expressed in ATP1A1 mutant APA, and the mutant stimulated cell proliferation and Src phosphorylation in ATP1A1-mutant cells. NKA stimulations would be a risk factor for the progression and development to an ATP1A1 mutant APA.
Hijacking Sexual Immuno-Privilege in GBM—An Immuno-Evasion Strategy
Authors: Sharpe Martyn A. , Baskin David S. , Jenson Amanda V. , Baskin Alexandra M.
Published: October 2021

Regulatory T-cells (Tregs) are immunosuppressive T-cells, which arrest immune responses to ‘Self’ tissues. Some immunosuppressive Tregs that recognize seminal epitopes suppress immune responses to the proteins in semen, in both men and women. We postulated that GBMs express reproductive-associated proteins to manipulate reproductive Tregs and to gain immune privilege. We analyzed four GBM transcriptome databases representing ≈900 tumors for hypoxia-responsive Tregs, steroidogenic pathways, and sperm/testicular and placenta-specific genes, stratifying tumors by expression. In silico analysis suggested that the presence of reproductive-associated Tregs in GBM tumors was associated with worse patient outcomes. These tumors have an androgenic signature, express male-specific antigens, and attract reproductive-associated Related Orphan Receptor C (RORC)-Treg immunosuppressive cells. GBM patient sera were interrogated for the presence of anti-sperm/testicular antibodies, along with age-matched controls, utilizing monkey testicle sections. GBM patient serum contained anti-sperm/testicular antibodies at levels > six-fold that of controls. Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are associated with estrogenic tumors which appear to mimic placental tissue. We demonstrate that RORC-Tregs drive poor patient outcome, and Treg infiltration correlates strongly with androgen levels. Androgens support GBM expression of sperm/testicular proteins allowing Tregs from the patient’s reproductive system to infiltrate the tumor. In contrast, estrogen appears responsible for MDSC/TAM immunosuppression.
G-Quadruplex Targeting in the Fight against Viruses: An Update
Authors: Ruggiero Emanuela , Zanin Irene , Terreri Marianna , Richter Sara N.
Published: October 2021

G-quadruplexes (G4s) are noncanonical nucleic acid structures involved in the regulation of key cellular processes, such as transcription and replication. Since their discovery, G4s have been mainly investigated for their role in cancer and as targets in anticancer therapy. More recently, exploration of the presence and role of G4s in viral genomes has led to the discovery of G4-regulated key viral pathways. In this context, employment of selective G4 ligands has helped to understand the complexity of G4-mediated mechanisms in the viral life cycle, and highlighted the possibility to target viral G4s as an emerging antiviral approach. Research in this field is growing at a fast pace, providing increasing evidence of the antiviral activity of old and new G4 ligands. This review aims to provide a punctual update on the literature on G4 ligands exploited in virology. Different classes of G4 binders are described, with emphasis on possible antiviral applications in emerging diseases, such as the current COVID-19 pandemic. Strengths and weaknesses of G4 targeting in viruses are discussed.
Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion
Authors: Majali-Martinez Alejandro , Weiss-Fuchs Ursula , Miedl Heidi , Forstner Desiree , Bandres-Meriz Julia , Hoch Denise , Djelmis Josip , Ivanisevic Marina , Hiden Ursula , Gauster Martin , Desoye Gernot
Published: October 2021

Type 1 diabetes mellitus (T1DM) is associated with reduced fetal growth in early pregnancy, but a contributing role of the placenta has remained elusive. Thus, we investigated whether T1DM alters placental development in the first trimester. Using a protein array, the level of 60 cell-cycle-related proteins was determined in human first trimester placental tissue (gestational week 5–11) from control (n = 11) and T1DM pregnancies (n = 12). Primary trophoblasts (gestational week 7–12, n = 32) were incubated in the absence (control) or presence of hyperglycemia (25 mM D-glucose) and hyperosmolarity (5.5 mM D-glucose + 19.5 mM D-mannitol). We quantified the number of viable and dead trophoblasts (CASY Counter) and assessed cell cycle distribution (FACS) and trophoblast invasion using a transwell assay. T1DM was associated with a significant (p < 0.05) downregulation of Ki67 (−26%), chk1 (−25%), and p73 (−26%). The number of viable trophoblasts was reduced under hyperglycemia (−23%) and hyperosmolarity (−18%), whereas trophoblast invasion was increased only under hyperglycemia (+6%). Trophoblast cell death and cell cycle distribution remained unaffected. Collectively, our data demonstrate that hyperglycemia decreases trophoblast proliferation as a potential contributing factor to the reduced placental growth in T1DM in vivo.
5-Methoxyindole, a Chemical Homolog of Melatonin, Adversely Affects the Phytopathogenic Fungus Fusarium graminearum
Authors: Kong Mengmeng , Liang Jing , Ali Qurban , Wen Wen , Wu Huijun , Gao Xuewen , Gu Qin
Published: October 2021

Fusarium graminearum is a destructive fungal pathogen that threatens the production and quality of wheat, and controlling this pathogen is a significant challenge. As the cost-effective homolog of melatonin, 5-methoxyindole showed strong activity against F. graminearum. In the present study, our results showed the strong adverse activity of 5-methoxyindole against F. graminearum by inhibiting its growth, formation, and conidia germination. In addition, 5-methoxyindole could induce malformation, reactive oxygen species (ROS) accumulation, and cell death in F. graminearum hyphae and conidia. In response to 5-methoxyindole, F. graminearum genes involved in scavenging reactive oxygen species were significantly downregulated. Overall, these findings reveal the mechanism of antifungal action of melatonin-homolog 5-methoxyindole. To the best of our knowledge, this is the first report that a novel melatonin homolog confers strong antifungal activity against F. graminearum, and 5-methoxyindole is a potential compound for protecting wheat plants from F. graminearum infection.
Discovery of Lactoferrin as a Stimulant for hADSC-Derived EV Secretion and Proof of Enhancement of Resulting EVs through Skin Model
Authors: Kim Junho , You Ga Eun , Woo Minkyu , Chang Nicole Hyesoo , Lee Jungsun
Published: October 2021

Extracellular vesicles (EVs) are secreted from hADSCs in low concentrations, which makes it difficult to utilize them for the development of therapeutic products. To overcome the problem associated with low concentration, we proposed human lactoferrin (hLF) as a stimulant for the secretion of hADSC-derived EVs. hLF has been reported to upregulate intracellular Ca2+, which is known to be capable of increasing EV secretion. We cultured hADSCs in hLF-supplemented media and analyzed the changes in intracellular Ca2+ concentration. The characteristics of hADSC-derived EVs secreted by hLF stimulation were analyzed through their number, membrane protein markers, and the presence of hLFs to EVs. The function of hADSC-derived EVs was investigated through their effects on dermal fibroblasts. We found that hLF helped hADSCs effectively uptake Ca2+, resulting in an increase of EVs secretion by more than a factor of 4. The resulting EVs had enhanced proliferation and collagen synthesis effect on dermal fibroblasts when compared to the same number of hADSC-derived EVs secreted without hLF stimulation. The enhanced secretion of hADSC-derived EVs increased collagen synthesis through enhanced epidermal penetration, which resulted from increased EV numbers. In summary, we propose hLF to be a useful stimulant in increasing the secretion rate of hADSC-derived EVs.
Scalable Newborn Screening Solutions: Bioinformatics and Next-Generation Sequencing
Authors: Ruiz-Schultz Nicole , Asay Bryce , Rohrwasser Andreas
Published: October 2021

Expansion of the newborn disorder panel requires the incorporation of new testing modalities. This is especially true for disorders lacking robust biomarkers for detection in primary screening methods and for disorders requiring genotyping or sequencing as a second-tier and/or diagnostic test. In this commentary, we discuss how next-generation sequencing (NGS) methods can be used as a secondary testing method in NBS. Additionally, we elaborate on the importance of genomic variant repositories for the annotation and interpretation of variants. Barriers to the incorporation of NGS and bioinformatics within NBS are discussed, and ideas for a regional bioinformatics model and shared variant repository are presented as potential solutions.
Computational Prediction of New Series of Topological Ternary Compounds LaXS (X = Si, Ge, Sn) from First-Principles
Authors: Howard Jack , Steier Joshua , Haldolaarachchige Neel , Hettiarachchilage Kalani
Published: October 2021

Dirac materials and their advanced physical properties are one of the most active fields of topological matter. In this paper, we present an ab initio study of electronics properties of newly designed LaXS (X = Si, Ge, Sn) tetragonal structured ternaries, with the absence and presence of spin–orbit coupling. We design the LaXS tetragonal non-symophic p4/nmm space group (no. 129) structures and identify their optimization lattice parameters. The electronic band structures display several Dirac crossings with the coexistence of both type I and type II Dirac points identified by considering the effect of spin–orbit coupling toward the linear crossing. Additionally, we perform the formation energy calculation through the density functional theory (DFT) to predict the stability of the structures and the elastic constants calculations to verify the Born mechanical stability criteria of the compounds.
Coronary Artery Disease in Women: A Comprehensive Appraisal
Authors: Schamroth Pravda Nili , Karny-Rahkovich Orith , Shiyovich Arthur , Schamroth Pravda Miri , Rapeport Naomi , Vaknin-Assa Hana , Eisen Alon , Kornowski Ran , Porter Avital
Published: October 2021

Coronary artery disease (CAD) is a significant cause of illness and death amongst women. The pathophysiology, manifestations, and outcomes of CVD and CAD differ between sexes. These sex differences remain under-recognized. The aim of this review is to highlight and raise awareness of the burden and unique aspects of CAD in women. It details the unique pathophysiology of CAD in women, cardiovascular risk factors in women (both traditional and sex-specific), the clinical presentation of CAD in women, and the range of disease in obstructive and non-obstructive CAD in women.
Updates on the Current Treatments for Diabetic Retinopathy and Possibility of Future Oral Therapy
Authors: Tomita Yohei , Lee Deokho , Tsubota Kazuo , Negishi Kazuno , Kurihara Toshihide
Published: October 2021

Diabetic retinopathy (DR) is a complication of diabetes and one of the leading causes of vision loss worldwide. Despite extensive efforts to reduce visual impairment, the prevalence of DR is still increasing. The initial pathophysiology of DR includes damage to vascular endothelial cells and loss of pericytes. Ensuing hypoxic responses trigger the expression of vascular endothelial growth factor (VEGF) and other pro-angiogenic factors. At present, the most effective treatment for DR and diabetic macular edema (DME) is the control of blood glucose levels. More advanced cases require laser, anti-VEGF therapy, steroid, and vitrectomy. Pan-retinal photocoagulation for non-proliferative diabetic retinopathy (NPDR) is well established and has demonstrated promising outcomes for preventing the progressive stage of DR. Furthermore, the efficacy of laser therapies such as grid and subthreshold diode laser micropulse photocoagulation (SDM) for DME has been reported. Vitrectomy has been performed for vitreous hemorrhage and tractional retinal detachment for patients with PDR. In addition, anti-VEGF treatment has been widely used for DME, and recently its potential to prevent the progression of PDR has been remarked. Even with these treatments, many patients with DR lose their vision and suffer from potential side effects. Thus, we need alternative treatments to address these limitations. In recent years, the relationship between DR, lipid metabolism, and inflammation has been featured. Research in diabetic animal models points to peroxisome proliferator-activated receptor alpha (PPARα) activation in cellular metabolism and inflammation by oral fenofibrate and/or pemafibrate as a promising target for DR. In this paper, we review the status of existing therapies, summarize PPARα activation therapies for DR, and discuss their potentials as promising DR treatments.
Efficacy of Repetitive Transcranial Magnetic Stimulation in Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Su Yu-Chi , Guo Yao-Hong , Hsieh Pei-Chun , Lin Yu-Ching
Published: October 2021

This article aimed to investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in fibromyalgia. The PubMed, Medline, Cochrane Library, and Web of Science databases were searched for articles published through 14 August 2021. We enrolled only randomized controlled trials. The Cochrane Collaboration risk of bias tool was used for quality assessment. Outcomes were analyzed as standardized mean differences (SMDs) with 95% CIs. The beta coefficient and p value were adopted for meta-regression. We included 18 studies comprising 643 participants. A significant reduction in disease influence, as measured by the Fibromyalgia Impact Questionnaire, was observed (SMD, −0.700, 95% CI, −1.173 to −0.228), and the reduction was larger in older patients (β = −0.1327, p = 0.008). The effect persisted at least two weeks after the final treatment session (SMD, −0.784, 95% CI, −1.136 to −0.432). Reductions in pain, depression, and anxiety were discovered, which persisted for at least two weeks after the last intervention. The effects on pain and depression remained significant up to one and a half months after the final session. No serious adverse events were reported by the included articles. In conclusion, our systematic review and meta-analysis revealed that rTMS is safe and effective for managing multiple domains of fibromyalgia-related symptoms and older patients may have a stronger treatment effect. Larger randomized controlled trials with sufficient male populations are warranted to confirm our findings, detect rare adverse events, and determine the optimal stimulation parameters.
Defining NASH from a Multi-Omics Systems Biology Perspective
Authors: Niu Lili , Sulek Karolina , Vasilopoulou Catherine G. , Santos Alberto , Wewer Albrechtsen Nicolai J. , Rasmussen Simon , Meier Florian , Mann Matthias
Published: October 2021

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease affecting up to 6.5% of the general population. There is no simple definition of NASH, and the molecular mechanism underlying disease pathogenesis remains elusive. Studies applying single omics technologies have enabled a better understanding of the molecular profiles associated with steatosis and hepatic inflammation—the commonly accepted histologic features for diagnosing NASH, as well as the discovery of novel candidate biomarkers. Multi-omics analysis holds great potential to uncover new insights into disease mechanism through integrating multiple layers of molecular information. Despite the technical and computational challenges associated with such efforts, a few pioneering studies have successfully applied multi-omics technologies to investigate NASH. Here, we review the most recent technological developments in mass spectrometry (MS)-based proteomics, metabolomics, and lipidomics. We summarize multi-omics studies and emerging omics biomarkers in NASH and highlight the biological insights gained through these integrated analyses.
Dynein Heavy Chain 64C Differentially Regulates Cell Survival and Proliferation of Wingless-Producing Cells in Drosophila melanogaster
Authors: Kim Ja-Young , Tsogtbaatar Orkhon , Cho Kyung-Ok
Published: October 2021

Dynein is a multi-subunit motor protein that moves toward the minus-end of microtubules, and plays important roles in fly development. We identified Dhc64Cm115, a new mutant allele of the fly Dynein heavy chain 64C (Dhc64C) gene whose heterozygotes survive against lethality induced by overexpression of Sol narae (Sona). Sona is a secreted metalloprotease that positively regulates Wingless (Wg) signaling, and promotes cell survival and proliferation. Knockdown of Dhc64C in fly wings induced extensive cell death accompanied by widespread and disorganized expression of Wg. The disrupted pattern of the Wg protein was due to cell death of the Wg-producing cells at the DV midline and overproliferation of the Wg-producing cells at the hinge in disorganized ways. Coexpression of Dhc64C RNAi and p35 resulted in no cell death and normal pattern of Wg, demonstrating that cell death is responsible for all phenotypes induced by Dhc64C RNAi expression. The effect of Dhc64C on Wg-producing cells was unique among components of Dynein and other microtubule motors. We propose that Dhc64C differentially regulates survival of Wg-producing cells, which is essential for maintaining normal expression pattern of Wg for wing development.
Trunk Angle Modulates Feedforward and Feedback Control during Single-Limb Squatting
Authors: Johnson Kristin , Nozu Shojiro , Shields Richard
Published: October 2021

Trunk positioning and unexpected perturbations are high-risk conditions at the time of anterior cruciate ligament injury. The influence of trunk positioning on motor control responses to perturbation during dynamic performance is not known. We tested the influence of trunk position on feedforward and feedback control during unexpected perturbations while performing a novel single-limb squatting task. We also assessed the degree that feedforward control was predictive of feedback responses. In the flexed trunk condition, there were increased quadriceps (p < 0.026) and gluteus medius long-latency reflexes (p < 0.001) and greater quadriceps-to-hamstrings co-contraction during feedforward (p = 0.017) and feedback (p = 0.007) time bins. Soleus long-latency reflexes increased more than 100% from feedforward muscle activity regardless of trunk condition. Feedforward muscle activity differentially predicted long-latency reflex responses depending on the muscle (R2: 0.47–0.97). These findings support the concept that trunk positioning influences motor control responses to perturbation and that feedback responses may be invariant to the feedforward control strategy.
Are People-Centered Intelligences Psychometrically Distinct from Thing-Centered Intelligences? A Meta-Analysis
Authors: Bryan Victoria M. , Mayer John D.
Published: October 2021

The Cattell–Horn–Carroll (CHC) or three-stratum model of intelligence envisions human intelligence as a hierarchy. General intelligence (g) is situated at the top, under which are a group of broad intelligences such as verbal, visuospatial processing, and quantitative knowledge that pertain to more specific areas of reasoning. Some broad intelligences are people-centered, including personal, emotional, and social intelligences; others concern reasoning about things more generally, such as visuospatial and quantitative knowledge. In the present research, we conducted a meta-analysis of 87 studies, including 2322 effect sizes, to examine the average correlation between people-to-people intelligences relative to the average correlation between people-to-thing-centered intelligences (and similar comparisons). Results clearly support the psychometric distinction between people-centered and thing-centered mental abilities. Coupled with evidence for incremental predictions from people-centered intelligences, our findings provide a secure foundation for continued research focused on people-centered mental abilities.
Low-Power FPGA Architecture Based Monitoring Applications in Precision Agriculture
Authors: Saddik Amine , Latif Rachid , El Ouardi Abdelhafid
Published: October 2021

Today’s on-chip systems technology has grounded impressive advances in computing power and energy consumption. The choice of the right architecture depends on the application. In our case, we were studying vegetation monitoring algorithms in precision agriculture. This study presents a system based on a monitoring algorithm for agricultural fields, an electronic architecture based on a CPU-FPGA SoC system and the OpenCL parallel programming paradigm. We focused our study on our own dataset of agricultural fields to validate the results. The fields studied in our case are in the Guelmin-Oued noun region in the south of Morocco. These fields are divided into two areas, with a total surface of 3.44 Ha2 for the first field and 3.73 Ha2 for the second. The images were collected using a DJI-type unmanned aerial vehicle and an RGB camera. Performance evaluation showed that the system could process up to 86 fps versus 12 fps or 20 fps in C/C++ and OpenMP implementations, respectively. Software optimizations have increased the performance to 107 fps, which meets real-time constraints.
An Effective Mesh Deformation Approach for Hull Shape Design by Optimization
Authors: Villa Diego , Furcas Francesco , Pralits Jan Oscar , Vernengo Giuliano , Gaggero Stefano
Published: October 2021

A method for the morphing of surface/volume meshes suitable to be used in hydrodynamic shape optimization is proposed. Built in the OpenFOAM environment, it relies on a Laplace equation that propagates the modifications of the surface boundaries, realized by applying a free-form deformation to a subdivision surface description of the geometry, into the computational volume mesh initially built through a combination of BlockMesh with cfMesh. The feasibility and robustness of this mesh morphing technique, used as a computationally efficient pre-processing tool, is demonstrated in the case of the resistance minimization of the DTC hull. All the hull variations generated within a relatively large design space are efficiently and successfully realized, i.e., without mesh inconsistencies and quality issues, only by deforming the initial mesh of the reference geometry. Coupled with a surrogate model approach, a significant reduction in the calm water resistance, in the extent of 10%, has been achieved in a reasonable computational time.
Simultaneous Biological Pretreatment and Saccharification of Rice Straw by Ligninolytic Enzymes from Panus neostrigosus I9 and Commercial Cellulase
Authors: Terasawat Ariyah , Phoolphundh Sivawan
Published: October 2021

The utilization of rice straw for biofuel production is limited by its composition. The pretreatment process is required to improve the enzymatic accessibility of polysaccharides in the biomass prior to enzymatic saccharification. In this study, simultaneous biological pretreatment and saccharification (SPS) of rice straw starting from laccase production by Panus neostrigosus I9 was operated in a 2-L fermenter. It was found that fungal physiology was strongly influenced by the agitation, and that the highest laccase production was obtained at an agitation speed of 750 rpm (209.96 ± 0.34 U/L). The dilution rate of 0.05 h−1 was set in continuous fermentation which resulted in laccase activity of 678.49 ± 20.39 U/L, approximately three times higher than that in batch culture. Response surface methodology (RSM) was applied to achieve the condition for maximum percentage of delignification. The maximum percentage of delignification of 45.55% was accomplished after pretreatment of rice straw with laccase enzyme 39.40 U/g rice straw at 43.70 °C for 11.19 h. Reducing sugar of 3.85 ± 0.15 g/L was obtained from the digested rice straw in a SPS reactor, while non-pretreated rice straw gave only 1.13 ± 0.10 g/L within 12 h of incubation. The results indicated that simultaneous biological pretreatment and saccharification (SPS) of rice straw by laccase helped to improve the accessibility of cellulose by cellulolytic enzymes.
Role of microRNAs in Disorders of Gut–Brain Interactions: Clinical Insights and Therapeutic Alternatives
Authors: Singh Rajan , Zogg Hannah , Ro Seungil
Published: October 2021

Disorders of gut–brain interactions (DGBIs) are heterogeneous in nature and intertwine with diverse pathophysiological mechanisms. Regular functioning of the gut requires complex coordinated interplay between a variety of gastrointestinal (GI) cell types and their functions are regulated by multiple mechanisms at the transcriptional, post-transcriptional, translational, and post-translational levels. MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally regulate gene expression by binding to specific mRNA targets to repress their translation and/or promote the target mRNA degradation. Dysregulation of miRNAs might impair gut physiological functions leading to DGBIs and gut motility disorders. Studies have shown miRNAs regulate gut functions such as visceral sensation, gut immune response, GI barrier function, enteric neuronal development, and GI motility. These biological processes are highly relevant to the gut where neuroimmune interactions are key contributors in controlling gut homeostasis and functional defects lead to DGBIs. Although extensive research has explored the pathophysiology of DGBIs, further research is warranted to bolster the molecular mechanisms behind these disorders. The therapeutic targeting of miRNAs represents an attractive approach for the treatment of DGBIs because they offer new insights into disease mechanisms and have great potential to be used in the clinic as diagnostic markers and therapeutic targets. Here, we review recent advances regarding the regulation of miRNAs in GI pacemaking cells, immune cells, and enteric neurons modulating pathophysiological mechanisms of DGBIs. This review aims to assess the impacts of miRNAs on the pathophysiological mechanisms of DGBIs, including GI dysmotility, impaired intestinal barrier function, gut immune dysfunction, and visceral hypersensitivity. We also summarize the therapeutic alternatives for gut microbial dysbiosis in DGBIs, highlighting the clinical insights and areas for further exploration. We further discuss the challenges in miRNA therapeutics and promising emerging approaches.
Movement Verbs as Discourse Markers in Spanish: The Case of Vamos in the City of Granada, Spain
Authors: Ruiz-González Natalia
Published: October 2021

The discourse marker vamos is the first-person present indicative plural of the verb ir (“to go”) and acts as a guide throughout the discourse. We studied its use in the PRESEEA corpus of Granada, analyzing 54 interviews and rescuing 270 occurrences of vamos. Mainly, we detected that its use was higher in the speech of people with only a primary education, while its use among the university educated represented 27% of cases. It was also used more frequently by young people, particularly females, although only age was found to be influential because of the intrinsic and original value of the first-person plural form, by which speakers are integrated and form part of a group. Among the pragmatic values of the marker is its use as a reformulator in more than 60% of cases; 22% as a structurer that helps to continue and conclude the discourse; and approximately 13% when used as a modalizer to convey the speaker’s attitude. Its main linguistic characteristic is its appearance preceded by conjunctions such as pero and y, and its main position is initial, as it accounts for 90% of occurrences.
The Use of the Future Subjunctive in Colonial Spanish Texts: Evidence of Vitality or Demise?
Authors: Kania Sonia
Published: October 2021

This article examines the use of the future subjunctive in two corpora of colonial Mexican texts. The first corpus consists of 255 documents dated 1561–1646 pertaining primarily to the historical area of New Galicia and dealing with matters of the Real Audiencia of Guadalajara. The second consists of 191 documents dated 1681–1816 written in the altiplano central of Mexico, which covers a large geographical area from Mexico City to Zacatecas. After describing the syntactic distribution of the future subjunctive in Medieval Spanish, we examine the evidence of its patterns of usage in Peninsular Spanish in the sixteenth and seventeenth centuries. From there, we analyze the quantitative and qualitative data related to the 428 tokens of -re forms found in our corpora and the syntactic structures in which they appear. The data support findings that the future subjunctive first fell out of use in temporal adverbial clauses, while exhibiting the most apparent productivity in relative clauses. However, the corpora examined provide no evidence that the paradigm survived longer in Latin American Spanish than in Peninsular Spanish, as has been argued. Rather, this study suggests that by the eighteenth century, the future subjunctive was a highly stylized marker of formality or politeness in written Spanish.
Lexical Category-Governed Neutralization to Coronal and Non-Coronal Place of Articulation in Latent Consonants: The Case of Shipibo-Konibo and Capanahua (Pano)
Authors: Elias-Ulloa Jose
Published: October 2021

This study documents and accounts for the behavior of the place of articulation of latent segments in the Panoan languages Shipibo-Konibo and Capanahua. In these languages, the lexical category of the word governs the place of articulation (PoA) of latent consonants. Latent segments only surface when they are syllabified as syllable onsets. They surface as coronal consonants when they are part of verbs; but they occur as non-coronal consonants when they belong to nouns or adjectives. In non-verb forms, by default, they are neutralized to dorsal in Shipibo-Konibo, and to labial in Capanahua. The analysis proposed consists in using the well-known markedness hierarchy on PoA, |Labial, Dorsal > Coronal > Pharyngeal|, and harmonically aligning it with a morphological markedness hierarchy in which non-verb forms are more marked than verb forms: |NonVerb > Verb|. This creates two fixed rankings of markedness constraints: one on verb forms in which, as expected, coronal/laryngeal is deemed the least marked PoA, and another one on non-verb forms in which the familiar markedness on PoA is reversed so that labial and dorsal become the least marked places of articulation. The study shows that although both Panoan languages follow the general cross-linguistic tendency to have coronal as a default PoA, this default can be overridden by morphology.
The Effects of Digitally Mediated Multimodal Indirect Feedback on Narrations in L2 Spanish Writing: Eye Tracking as a Measure of Noticing
Authors: Valentin-Rivera Laura E. , Yang Li
Published: October 2021

Written corrective feedback (CF) could pave the way for L2 development, especially when embedded in multimodality. Building on prior research, this descriptive study drew a relationship between specific types of errors that were most successfully revised and noticing measured by eye-tracking techniques. Additionally, this study furthers our understanding of the impact of indirect CF (i.e., codes accompanied by metalinguistic hints) delivered by two multimodal components: (a) a video tutorial on how to approach teachers’ comments and (b) a soundless video displaying individualized teacher feedback. To this end, three L2 learners of Spanish completed a narration in the target language, watched a tutorial on attending to CF, received indirect feedback via the personalized soundless video (i.e., option “b” above), and corrected their errors. An eye tracker recorded all ocular activity while the participants watched both recordings. The results suggested that receiving training on approaching teachers’ comments may enhance the overall success rate of revisions, especially in verb and vocabulary-related errors. Last, a detailed unfolding of the revision process unveiled by eye-tracking data accounted for (1) an explanation of why two specific types of errors were more successfully revised and (2) some pedagogical recommendations.
The Old and the New: Considerations in Arabic Historical Dialectology
Authors: Magidow Alexander
Published: October 2021

Arabic historical dialectology has long been based on a historical methodology, one which seeks to link historical population movements with modern linguistic behavior. This article argues that a nexus of interrelated issues, centered around a general theme of “oldness,” has impaired this work, and proposes basic principles to avoid the misinterpretation of linguistic data. This article argues that there is a strong tendency to essentialize the idea of linguistic conservatism and attribute it to the groups that have archaic features. Against this view, it proposes that linguistic conservatism should be seen as a failure to participate in otherwise widespread innovations. It critiques the assumption that the modern dialect distribution is directly derived from the earliest settlements established during the Islamic conquests in the seventh century, arguing instead that long-term linguistic durability is unlikely. The article further challenges the assumption that highly conservative dialects such as those of Yemen are ancestral to modern dialects in a meaningful way, arguing instead that either more proximate ancestors or wave-like diffusion had a greater impact on the development of modern dialects. Finally, the paper suggests that a heuristic approach based on typical processes of language diffusion and human migration offers a more productive approach to understanding the history of Arabic dialects than a model based on historical events; many of the existing linguistic classifications may be directly derived from this heuristic.
Identifying Salient Aktionsart Properties in Anindilyakwa
Authors: Bednall James
Published: October 2021

This article considers the identification and classification of salient Aktionsart properties in Anindilyakwa (Gunwinyguan, Australia). Through examining the grammatically permissible (and impermissible) distribution and co-occurrence of various temporal adverbials and morpho-syntactic structures, I identify key Aktionsart properties exhibited in Anindilyakwa. I demonstrate that the properties of dynamism and atomicity are particularly important to consider in this language, while telicity is less prominent. The detailed description and analysis of Aktionsart properties in this article contributes towards a more nuanced understanding of the aspectuo-temporal system of Anindilyakwa. In addition, it provides novel perspectives with which to consider cross-linguistic aspectuo-temporal research, particularly with a focus on smaller-scale, under-described languages.
The L2 Acquisition of French Interrogatives: Pragmatic Inferences in Clefted wh-Questions
Authors: Destruel Emilie , Donaldson Bryan
Published: October 2021

The present study aims to elaborate on the understanding of the second language (L2) acquisition of French interrogatives by focusing on clefted (subject) wh-questions, structures that are largely absent in prior L2 literature. Our research question addresses how L2 learners of French understand two specific properties associated with these interrogatives: existence and exhaustivity. Using two rating tasks, we examined whether a total of 48 L2 learners converge towards the native norm for these properties, which occur at the syntax-discourse interface and may therefore be vulnerable to incomplete acquisition, following the Interface Hypothesis. Our findings suggest that L2 learners at the intermediate level acquire an understanding of the existential inference before an understanding of exhaustivity.