bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors and Inequality of Underweight and Overweight among Women of Reproductive Age in Myanmar: Evidence from the Demographic Health Survey 2015–2016
Authors: Gupta Rajat Das , Haider Mohammad Rifat , Das Subhasish
Published: December 2020

(1) Background: This study aims to identify the factors of underweight and overweight/obesity among reproductive age (15–49 years) women in Myanmar, and assess the level of inequity in the double burden of malnutrition. (2) Methods: The study used Myanmar Demographic and Health Survey 2015–2016 data. Multinomial logistic regression models were fitted to identify the factors affecting underweight and overweight/obesity; and concentration indices (CI) were estimated to assess socioeconomic inequalities. (3) Results: A total of 12,643 reproductive age women were included in the analysis. Higher risk of underweight was found in women aged 20–29 years, aged 30–39 years, and 40–49 years compared to women aged 15–19 years; women who were unemployed or had manual occupation relative to those in non-manual employment. Women aged 40–49 years (compared to those who were 15–29 years); had primary education, and secondary education (compared to those who had no education); being married, and widowed/divorced/separated (compared to being never married); belonging to the poor quintile, middle quintile, richer, richest quintile (compared to the poorest quintile); having residence in urban areas (compared to rural areas) and in Kachin, Taninthayi, Yangon province (than those who lived in Naypytiaw province) had a higher risk of being overweight/obese. Socioeconomic inequalities were detected, with overweight/obesity strongly concentrated (CI: 0.19) amongst the higher quintiles and underweight concentrated (CI: −0.060) amongst the poorest. (4) Conclusions: Equity oriented nutrition interventions with a focus on improving the socioeconomic status of poor households may benefit undernourished women, while richer households should be focused to curb the overweight/obesity problem.
Functional Analysis of Aux/IAAs and SAURs on Shoot Growth of Lagerstroemia indica through Virus-Induced Gene Silencing (VIGS)
Authors: Feng Lu , Liang Xiaohan , Zhou Yang , Zhang Ye , Liu Jieru , Cai Ming , Wang Jia , Cheng Tangren , Zhang Qixiang , Pan Huitang
Published: December 2020

The plant hormone auxin plays an important role in cell division and the elongation of shoots to affect the plant architecture, which has a great impact on the plant yield, fruit quality and ornamental value; however, the regulatory mechanism of auxin controlling shoot growth is unclear in crape myrtle. In this study, two auxin/indole-3-acetic acid (Aux/IAA) genes and four small auxin upregulated RNA (SAUR) genes of auxin response gene families were isolated from dwarf and non-dwarf progenies of Lagerstroemia indica and then functionally characterized. Sequence alignment revealed that the six genes contain typical conserved domains. Different expression patterns of the six genes at three different tissue stages of two types of progenies showed that the regulation mechanism of these genes may be different. Functional verification of the six genes upon shoot growth of crape myrtle was performed via virus-induced gene silencing. When the LfiAUX22 gene was silenced, a short shoot phenotype was observed in non-dwarf progenies, accompanied by decreased auxin content. Therefore, we preliminarily speculated that LfiAUX22 plays an important role in the shoot growth of crape myrtle, which regulates the accumulation of indole-3-acetic acid (IAA) and the elongation of cells to eventually control shoot length.
Phytophthora Introductions in Restoration Areas: Responding to Protect California Native Flora from Human-Assisted Pathogen Spread
Authors: Frankel Susan J. , Conforti Christa , Hillman Janell , Ingolia Mia , Shor Alisa , Benner Diana , Alexander Janice M. , Bernhardt Elizabeth , Swiecki Tedmund J.
Published: December 2020

Over the past several years, plantings of California native plant nursery stock in restoration areas have become recognized as a pathway for invasive species introductions, in particular Phytophthora pathogens, including first in the U.S. detections (Phytophthora tentaculata, Phytophthora quercina), new taxa, new hybrid species, and dozens of other soilborne species. Restoration plantings may be conducted in high-value and limited habitats to sustain or re-establish rare plant populations. Once established, Phytophthora pathogens infest the site and are very difficult to eradicate or manage—they degrade the natural resources the plantings were intended to enhance. To respond to unintended Phytophthora introductions, vegetation ecologists took a variety of measures to prevent pathogen introduction and spread, including treating infested areas by solarization, suspending plantings, switching to direct seeding, applying stringent phytosanitation requirements on contracted nursery stock, and building their own nursery for clean plant production. These individual or collective actions, loosely coordinated by the Phytophthoras in Native Habitats Work Group ensued as demands intensified for protection from the inadvertent purchase of infected plants from commercial native plant nurseries. Regulation and management of the dozens of Phytophthora species and scores of plant hosts present a challenge to the state, county, and federal agriculture officials and to the ornamental and restoration nursery industries. To rebuild confidence in the health of restoration nursery stock and prevent further Phytophthora introductions, a voluntary, statewide accreditation pilot project is underway which, upon completion of validation, is planned for statewide implementation.
Identification and Characterization of the Basic Helix-Loop-Helix Transcription Factor Family in Pinus massoniana
Authors: Chen Yu , Zhu Peihuang , Wu Fan , Wang Xiaofeng , Zhang Jinfeng , Ji Kongshu
Published: December 2020

The basic helix-loop-helix (bHLH) protein transcription factor family is the most widely distributed transcription factor family in eukaryotes. Members of this family play important roles in secondary metabolic biosynthesis, signal transduction, and plant resistance. Research on the bHLH family in animals is more extensive than that in plants, and members of the family in plants are classified according to the classification criteria for those in animals. To date, no research on the bHLH gene family in Pinus massoniana (Masson pine) has been reported. In this study, we identified 88 bHLH genes from four transcriptomes of Masson pine and performed bioinformatics analysis. These genes were divided into 10 groups in total. RT-PCR analysis revealed that the expression levels of the six genes increased under abiotic stress and hormone treatments. These findings will facilitate further studies on the functions of bHLH transcription factors.
Effect of Glow-Discharge Plasma Treatment on Contact Angle and Micromorphology of Bamboo Green Surface
Authors: Wang Xuehua , Cheng Kenneth J.
Published: December 2020

The inner and outer surfaces of bamboo stems are usually removed prior to the manufacture of bamboo panels because the surfaces are hydrophobic and difficult to bond with glue. Hence, the recovery and utilization ratio of bamboo during processing is low. This study focused on using glow-discharge plasma to treat green bamboo surfaces to make them less hydrophobic. The effects of plasma treatment on green bamboo stems were examined using contact goniometry (wettability), non-contact confocal profilometry and scanning electron microscopy (SEM). Confocal profilometry and SEM revealed that the morphology of green bamboo surfaces varied between 3 different stems. Plasma was able to etch bamboo green surfaces, and make them rougher and more powdery. Plasma treatment was effective at converting green bamboo surfaces from hydrophobic (initial contact angle >110°) to hydrophilic (contact angle <20°). However, this effect was temporary and contact angle increased with time and recovered approximately 30% of its original value after 24 h. Based on our findings, we conclude that plasma treatment can alter parameters such as surface energy and roughness that could improve glue bonding of green bamboo, but delays between plasma treatment and further processing would need to be minimized.
Characterization of Phytochemicals in Berry Fruit Wines Analyzed by Liquid Chromatography Coupled to Photodiode-Array Detection and Electrospray Ionization/Ion Trap Mass Spectrometry (LC-DAD-ESI-MSn) and Their Antioxidant and Antimicrobial Activity
Authors: Czyżowska Agata , Wilkowska Agnieszka , Staszczak (Mianowska) Agnieszka , Nowak Agnieszka
Published: December 2020

Fruits are a valuable source of phytochemicals. However, there is little detailed information about the compounds contained in fruit wines. In this study, wines from six different berries were analyzed using HPLC-DAD-ESI-MSn. About 150 compounds were identified, including anthocyanins (34), hydroxycinnamic acids (12) and flavonols (36). Some of the compounds were identified for the first time in berry wines. The blackberry wines were found to contain the largest number of bioactive compounds (59). Elderberry wines where the richest source of polyphenols (over 1000 mg/L) and contained the largest amounts of all of the analyzed groups of compounds (hydroxycinnamic acids, anthocyanins and flavonols). The lowest concentration of polyphenols was observed in the wines made from cranberries and bilberries (less than 500 mg/L). The antioxidant activity was determined in relation to ABTS+, DPPH, and FRAP. The highest values were observed in the blackberry wines, and the lowest for the cranberry wines. The wines were analyzed to test their antimicrobial activity. Five of the six wines (with the exception of elderberry wine) inhibited Bacillus cereus growth and two (blackberry and cranberry wines) were active against Listeria monocytogenes.
In Vitro Evaluation of Facial Pressure and Air Leak with a Newly Designed Cushion for Non-Invasive Ventilation Masks
Authors: Lin Hui-Ling , Lee Yu-Chi , Wang Ssu-Hui , Chiang Li-Ying , Liu Jui-Fang
Published: December 2020

Background: The aim of this study was to evaluate the effect of a newly designed foam cushion on the air leakage and pressure when applied to the face. Methods: A teaching manikin connected to a bilevel positive airway pressure ventilator attached to four different brands of oronasal masks (Amara, Mirage, Forma, and Wizard) was used. The foam cushions of 5-mm and 10-mm-thickness were attached to the masks, and each mask was tested without a cushion. Six pressure sensors were placed on the manikin’s face, and data were recorded. Inspiratory volume and air leak flow from the ventilator were observed. Results: Air leakage was influenced by both the mask brand and the presence of a cushion. The presence of a cushion did not affect the Wizard mask in terms of leakage (p = 0.317) or inspiratory volume (p = 0.726). The Wizard and Amara masks generated the lowest contact pressure on the frontal forehead (p < 0.001) compared to the other five points. Conclusions: Utilisation of a cushion reduces air leakage and maintains greater inspiratory volume regardless of its thickness. The contact pressure varies depending on the brand of the mask, which would require a difference in the thickness of the cushion for pressure reduction.
The Relationship between Under-Nutrition and Hypertension among Ellisras Children and Adolescents Aged 9 to 17 Years
Authors: Mphahlele Tumisho Praise , Monyeki Kotsedi Daniel , Dibakwane Winnie Maletladi , Mokgoatšana Sekgothe
Published: December 2020

Background: Globally, under-nutrition and hypertension in children has been associated with the risk of developing cardiovascular disease (CVD) in adulthood. The main objective of this study was to investigate the relationship between under-nutrition and hypertension, furthermore, to determine the risk of developing hypertension due to under-nutrition. Methods: The study comprised of 1701 participants (874 boys and 827 girls) between the ages of 9 and 17 years old. All anthropometric and blood pressure measurements were taken according to standard procedures. Mid-upper arm circumference (MUAC), body mass index (BMI), upper arm fat area (UFA), total upper arm area (TUAA) and upper arm muscle area (UMA) of Ellisras children were compared with the National Health and Nutrition Examination Survey III reference population. The linear regression models were used to determine the relationship between under-nutrition with hypertension for unadjusted and then adjusted for age and gender. The logistic regression model was used to determine the risk of under-nutrition on developing hypertension for unadjusted and adjusted for age and gender. Results: There was a positive significant (p < 0.0001) association between all under-nutrition variables (MUAC, BMI, UFA, TUAA and UMA) and systolic blood pressure (SBP; beta ranges between 0.84 and 2.78), and diastolic blood pressure (DBP; beta ranges between 0.3 and 1.08 before adjusting and after adjusting for age and gender (SBP, beta ranges between 0.59 and 2.00 and DBP (beta ranges between 0.24 and 0.80. Conclusion: The prevalence of under-nutrition was high while the prevalence of hypertension was low in this study. The mean under-nutrition variables (BMI, UFA, UMA and MUAC) of Ellisras children were far lower compared to the NHANES III reference population. Hypertension was significantly associated with under-nutrition in this study.
The Fractional Step Method versus the Radial Basis Functions for Option Pricing with Correlated Stochastic Processes
Authors: Kagraoka Yusho
Published: December 2020

In option pricing models with correlated stochastic processes, an option premium is commonly a solution to a partial differential equation (PDE) with mixed derivatives in more than two space dimensions. Alternating direction implicit (ADI) finite difference methods are popular for solving a PDE with more than two space dimensions; however, it is not straightforward to employ the ADI method for solving a PDE with mixed derivatives. The aim of this study is to find out which numerical method would be appropriate to solve PDEs with mixed derivatives based on the accuracy of the solutions and the computation time. This study applies the fractional step method and the radial basis functions to solve a PDE with a mixed derivative, and investigates the efficiency of these numerical methods. Numerical experiments are conducted by applying these methods to exchange option pricing; exchange options are selected because the exchange option premium has an analytical form. The numerical results show that the both methods calculate premiums with high accuracy in the presence of mixed derivatives. The fractional step method calculates the option premium more accurately and much faster than the radial basis functions. Therefore, from the numerical experiments, this study concludes that the fractional step method is more appropriate than the radial basis functions for solving a PDE with a mixed derivative.
Aerial Bombing Crater Identification: Exploitation of Precise Digital Terrain Models
Authors: Dolejš Martin , Pacina Jan , Veselý Martin , Brétt Dominik
Published: December 2020

Places of past conflicts and persistent objects that reflect such events often attract the attention of archaeological prospection which facilitates the construction of conflict narratives. Field prospection as a precise method for localization of aerial bombing craters (as an example of such persistent features) is a highly time- and resource-consuming task. Therefore, methods for automatic identification of such features are evolving. We present a comparison of three methods for possible automatic crater detection based on (a) extraterrestrial crater detection algorithms, (b) geomorphology-based edge extraction, and (c) image pattern recognition via a state-of-the-art convolutional neural network (CNN). All methods were preliminarily tested on a case study of eight Second World War (WWII) aerial bombing crater sites in NW Czechia via Airborne Laser Scanned LiDAR-derived digital terrain models with different spatial resolutions. We found that extraterrestrial crater detection algorithms and geomorphology-based edge extraction methods yield worse results given the standard indices of precision and recall. By comparison, the CNN method utilized for a particular task achieved satisfying results, predominantly with 0.5 m/px resolution (which is often available at the country level) of the input raster. Nevertheless, overall performance with this resolution varies significantly among the sites. Therefore, the quality and readability of the input data are crucial factors for the successful acquisition of precise ordinance location identification.
The Role of Extracellular Vesicles in Demyelination of the Central Nervous System
Authors: López-Guerrero José Antonio , Ripa Inés , Andreu Sabina , Bello-Morales Raquel
Published: December 2020

It is being increasingly demonstrated that extracellular vesicles (EVs) are deeply involved in the physiology of the central nervous system (CNS). Processes such as synaptic activity, neuron-glia communication, myelination and immune response are modulated by EVs. Likewise, these vesicles may participate in many pathological processes, both as triggers of disease or, on the contrary, as mechanisms of repair. EVs play relevant roles in neurodegenerative disorders such as Alzheimer’s or Parkinson’s diseases, in viral infections of the CNS and in demyelinating pathologies such as multiple sclerosis (MS). This review describes the involvement of these membrane vesicles in major demyelinating diseases, including MS, neuromyelitis optica, progressive multifocal leukoencephalopathy and demyelination associated to herpesviruses.
Molecular Determinants of West Nile Virus Virulence and Pathogenesis in Vertebrate and Invertebrate Hosts
Authors: Fiacre Lise , Pagès Nonito , Albina Emmanuel , Richardson Jennifer , Lecollinet Sylvie , Gonzalez Gaëlle
Published: December 2020

West Nile virus (WNV), like the dengue virus (DENV) and yellow fever virus (YFV), are major arboviruses belonging to the Flavivirus genus. WNV is emerging or endemic in many countries around the world, affecting humans and other vertebrates. Since 1999, it has been considered to be a major public and veterinary health problem, causing diverse pathologies, ranging from a mild febrile state to severe neurological damage and death. WNV is transmitted in a bird–mosquito–bird cycle, and can occasionally infect humans and horses, both highly susceptible to the virus but considered dead-end hosts. Many studies have investigated the molecular determinants of WNV virulence, mainly with the ultimate objective of guiding vaccine development. Several vaccines are used in horses in different parts of the world, but there are no licensed WNV vaccines for humans, suggesting the need for greater understanding of the molecular determinants of virulence and antigenicity in different hosts. Owing to technical and economic considerations, WNV virulence factors have essentially been studied in rodent models, and the results cannot always be transported to mosquito vectors or to avian hosts. In this review, the known molecular determinants of WNV virulence, according to invertebrate (mosquitoes) or vertebrate hosts (mammalian and avian), are presented and discussed. This overview will highlight the differences and similarities found between WNV hosts and models, to provide a foundation for the prediction and anticipation of WNV re-emergence and its risk of global spread.
New 1,3,4-Oxadiazole Derivatives of Pyridothiazine-1,1-Dioxide with Anti-Inflammatory Activity
Authors: Glomb Teresa , Wiatrak Benita , Gębczak Katarzyna , Gębarowski Tomasz , Bodetko Dorota , Czyżnikowska Żaneta , Świątek Piotr
Published: December 2020

Numerous studies have confirmed the coexistence of oxidative stress and inflammatory processes. Long-term inflammation and oxidative stress may significantly affect the initiation of the neoplastic transformation process. Here, we describe the synthesis of a new series of Mannich base-type hybrid compounds containing an arylpiperazine residue, 1,3,4-oxadiazole ring, and pyridothiazine-1,1-dioxide core. The synthesis was carried out with the hope that the hybridization of different pharmacophoric molecules would result in a synergistic effect on their anti-inflammatory activity, especially the ability to inhibit cyclooxygenase. The obtained compounds were investigated in terms of their potencies to inhibit cyclooxygenase COX-1 and COX-2 enzymes with the use of the colorimetric inhibitor screening assay. Their antioxidant and cytotoxic effect on normal human dermal fibroblasts (NHDF) was also studied. Strong COX-2 inhibitory activity was observed after the use of TG6 and, especially, TG4. The TG11 compound, as well as reference meloxicam, turned out to be a preferential COX-2 inhibitor. TG12 was, in turn, a non-selective COX inhibitor. A molecular docking study was performed to understand the binding interaction of compounds at the active site of cyclooxygenases.
Cancer Stem Cell-Associated Pathways in the Metabolic Reprogramming of Breast Cancer
Authors: El-Sahli Sara , Wang Lisheng
Published: December 2020

Metabolic reprogramming of cancer is now considered a hallmark of many malignant tumors, including breast cancer, which remains the most commonly diagnosed cancer in women all over the world. One of the main challenges for the effective treatment of breast cancer emanates from the existence of a subpopulation of tumor-initiating cells, known as cancer stem cells (CSCs). Over the years, several pathways involved in the regulation of CSCs have been identified and characterized. Recent research has also shown that CSCs are capable of adopting a metabolic flexibility to survive under various stressors, contributing to chemo-resistance, metastasis, and disease relapse. This review summarizes the links between the metabolic adaptations of breast cancer cells and CSC-associated pathways. Identification of the drivers capable of the metabolic rewiring in breast cancer cells and CSCs and the signaling pathways contributing to metabolic flexibility may lead to the development of effective therapeutic strategies. This review also covers the role of these metabolic adaptation in conferring drug resistance and metastasis in breast CSCs.
Changes in the Physicochemical Properties of Blood and Skin Cell Membranes as a Result of Psoriasis Vulgaris and Psoriatic Arthritis Development
Authors: Dobrzyńska Izabela , Szachowicz-Petelska Barbara , Wroński Adam , Jarocka-Karpowicz Iwona , Skrzydlewska Elżbieta
Published: December 2020

Psoriasis is accompanied by disturbed redox homeostasis, with systemic and local oxidative stress promoting the modification of basic components of cellular membranes. Therefore, the aim of the study was to investigate the effect of development of psoriasis vulgaris and psoriatic arthritis on the composition and physicochemical properties of skin cell membranes (keratinocytes and fibroblasts) and blood cells (lymphocytes, granulocytes and erythrocytes). Both forms of psoriasis are characterized by decreased levels and changes in the localization of membrane phospholipids, and an increased level of sialic acid as well as the lipid peroxidation product (malondialdehyde), which resulted in an increase in the zeta potential of skin cells and blood cells, with granulocytes and lymphocytes affected more than erythrocytes. Using theoretical equations and the dependence of the cell membrane surface charge density as a function of pH, it was shown that patients with psoriatic arthritis have a greater increase in the concentration of negatively charged groups on the membrane surface and reduced the value of the association constant with H+ compared to patients with psoriasis vulgaris. Therefore, it can be suggested that the physicochemical parameters of membranes, skin and blood cells, especially lymphocytes, can be used to assess the severity of the disease.
Cross Talk at the Cytoskeleton–Plasma Membrane Interface: Impact on Neuronal Morphology and Functions
Authors: Di Giaimo Rossella , Penna Eduardo , Pizzella Amelia , Cirillo Raffaella , Perrone-Capano Carla , Crispino Marianna
Published: December 2020

The cytoskeleton and its associated proteins present at the plasma membrane not only determine the cell shape but also modulate important aspects of cell physiology such as intracellular transport including secretory and endocytic pathways. Continuous remodeling of the cell structure and intense communication with extracellular environment heavily depend on interactions between cytoskeletal elements and plasma membrane. This review focuses on the plasma membrane–cytoskeleton interface in neurons, with a special emphasis on the axon and nerve endings. We discuss the interaction between the cytoskeleton and membrane mainly in two emerging topics of neurobiology: (i) production and release of extracellular vesicles and (ii) local synthesis of new proteins at the synapses upon signaling cues. Both of these events contribute to synaptic plasticity. Our review provides new insights into the physiological and pathological significance of the cytoskeleton–membrane interface in the nervous system.
Dual Fluorescence Splicing Reporter Minigene Identifies an Antisense Oligonucleotide to Skip Exon v8 of the CD44 Gene
Authors: Fukushima Sachiyo , Farea Manal , Maeta Kazuhiro , Rani Abdul Qawee Mahyoob , Fujioka Kazumichi , Nishio Hisahide , Matsuo Masafumi
Published: December 2020

Splicing reporter minigenes are used in cell-based in vitro splicing studies. Exon skippable antisense oligonucleotide (ASO) has been identified using minigene splicing assays, but these assays include a time- and cost-consuming step of reverse transcription PCR amplification. To make in vitro splicing assay easier, a ready-made minigene (FMv2) amenable to quantitative splicing analysis by fluorescence microscopy was constructed. FMv2 was designed to encode two fluorescence proteins namely, mCherry, a transfection marker and split eGFP, a marker of splicing reaction. The split eGFP was intervened by an artificial intron containing a multicloning site sequence. Expectedly, FMv2 transfected HeLa cells produced not only red mCherry but also green eGFP signals. Transfection of FMv2CD44v8, a modified clone of FMv2 carrying an insertion of CD44 exon v8 in the multicloning site, that was applied to screen exon v8 skippable ASO, produced only red signals. Among seven different ASOs tested against exon v8, ASO#14 produced the highest index of green signal positive cells. Hence, ASO#14 was the most efficient exon v8 skippable ASO. Notably, the well containing ASO#14 was clearly identified among the 96 wells containing randomly added ASOs, enabling high throughput screening. A ready-made FMv2 is expected to contribute to identify exon skippable ASOs.
Procathepsin V Is Secreted in a TSH Regulated Manner from Human Thyroid Epithelial Cells and Is Accessible to an Activity-Based Probe
Authors: Al-Hashimi Alaa , Venugopalan Vaishnavi , Rehders Maren , Sereesongsaeng Naphannop , Hein Zeynep , Springer Sebastian , Weber Ekkehard , Führer Dagmar , Bogyo Matthew S. , Scott Christopher J. , Burden Roberta E. , Brix Klaudia
Published: December 2020

The significance of cysteine cathepsins for the liberation of thyroid hormones from the precursor thyroglobulin was previously shown by in vivo and in vitro studies. Cathepsin L is most important for thyroglobulin processing in mice. The present study aims at specifying the possible contribution of its closest relative, cysteine cathepsin L2/V, to thyroid function. Immunofluorescence analysis on normal human thyroid tissue revealed its predominant localization at the apical plasma membrane of thyrocytes and within the follicle lumen, indicating the secretion of cathepsin V and extracellular tasks rather than its acting within endo-lysosomes. To explore the trafficking pathways of cathepsin V in more detail, a chimeric protein consisting of human cathepsin V tagged with green fluorescent protein (GFP) was stably expressed in the Nthy-ori 3-1 thyroid epithelial cell line. Colocalization studies with compartment-specific markers and analyses of post-translational modifications revealed that the chimeric protein was sorted into the lumen of the endoplasmic reticulum and subsequently transported to the Golgi apparatus, while being N-glycosylated. Immunoblotting showed that the chimeric protein reached endo-lysosomes and it became secreted from the transduced cells. Astonishingly, thyroid stimulating hormone (TSH)-induced secretion of GFP-tagged cathepsin V occurred as the proform, suggesting that TSH upregulates its transport to the plasma membrane before it reaches endo-lysosomes for maturation. The proform of cathepsin V was found to be reactive with the activity-based probe DCG-04, suggesting that it possesses catalytic activity. We propose that TSH-stimulated secretion of procathepsin V is the default pathway in the thyroid to enable its contribution to thyroglobulin processing by extracellular means.
The Therapeutic Potential of Neuronal K-Cl Co-Transporter KCC2 in Huntington’s Disease and Its Comorbidities
Authors: Andrews Katie , Josiah Sunday Solomon , Zhang Jinwei
Published: December 2020

Intracellular chloride levels in the brain are regulated primarily through the opposing effects of two cation-chloride co-transporters (CCCs), namely K+-Cl− co-transporter-2 (KCC2) and Na+-K+-Cl− co-transporter-1 (NKCC1). These CCCs are differentially expressed throughout the course of development, thereby determining the excitatory-to-inhibitory γ-aminobutyric acid (GABA) switch. GABAergic excitation (depolarisation) is important in controlling the healthy development of the nervous system; as the brain matures, GABAergic inhibition (hyperpolarisation) prevails. This developmental switch in excitability is important, as uncontrolled regulation of neuronal excitability can have implications for health. Huntington’s disease (HD) is an example of a genetic disorder whereby the expression levels of KCC2 are abnormal due to mutant protein interactions. Although HD is primarily considered a motor disease, many other clinical manifestations exist; these often present in advance of any movement abnormalities. Cognitive change, in addition to sleep disorders, is prevalent in the HD population; the effect of uncontrolled KCC2 function on cognition and sleep has also been explored. Several mechanisms by which KCC2 expression is reduced have been proposed recently, thereby suggesting extensive investigation of KCC2 as a possible therapeutic target for the development of pharmacological compounds that can effectively treat HD co-morbidities. Hence, this review summarizes the role of KCC2 in the healthy and HD brain, and highlights recent advances that attest to KCC2 as a strong research and therapeutic target candidate.
Distinctive Features of Orbital Adipose Tissue (OAT) in Graves’ Orbitopathy
Authors: Zhang Lei , Evans Anna , von Ruhland Chris , Draman Mohd Shazli , Edkins Sarah , Vincent Amy E. , Berlinguer-Palmini Rolando , Rees D. Aled , Haridas Anjana S , Morris Dan , Tee Andrew R. , Ludgate Marian , Turnbull Doug M. , Karpe Fredrik , Dayan Colin M.
Published: December 2020

Depot specific expansion of orbital-adipose-tissue (OAT) in Graves’ Orbitopathy (GO) is associated with lipid metabolism signaling defects. We hypothesize that the unique adipocyte biology of OAT facilitates its expansion in GO. A comprehensive comparison of OAT and white-adipose-tissue (WAT) was performed by light/electron-microscopy, lipidomic and transcriptional analysis using ex vivo WAT, healthy OAT (OAT-H) and OAT from GO (OAT-GO). OAT-H/OAT-GO have a single lipid-vacuole and low mitochondrial number. Lower lipolytic activity and smaller adipocytes of OAT-H/OAT-GO, accompanied by similar essential linoleic fatty acid (FA) and (low) FA synthesis to WAT, revealed a hyperplastic OAT expansion through external FA-uptake via abundant SLC27A6 (FA-transporter) expression. Mitochondrial dysfunction of OAT in GO was apparent, as evidenced by the increased mRNA expression of uncoupling protein 1 (UCP1) and mitofusin-2 (MFN2) in OAT-GO compared to OAT-H. Transcriptional profiles of OAT-H revealed high expression of Iroquois homeobox-family (IRX-3&5), and low expression in HOX-family/TBX5 (essential for WAT/BAT (brown-adipose-tissue)/BRITE (BRown-in-whITE) development). We demonstrated unique features of OAT not presented in either WAT or BAT/BRITE. This study reveals that the pathologically enhanced FA-uptake driven hyperplastic expansion of OAT in GO is associated with a depot specific mechanism (the SLC27A6 FA-transporter) and mitochondrial dysfunction. We uncovered that OAT functions as a distinctive fat depot, providing novel insights into adipocyte biology and the pathological development of OAT expansion in GO.
Neuroinflammation and Precision Medicine in Pediatric Neurocritical Care: Multi-Modal Monitoring of Immunometabolic Dysfunction
Authors: Woodward Kristine E. , de Jesus Pauline , Esser Michael J.
Published: December 2020

The understanding of molecular biology in neurocritical care (NCC) is expanding rapidly and recognizing the important contribution of neuroinflammation, specifically changes in immunometabolism, towards pathological disease processes encountered across all illnesses in the NCC. Additionally, the importance of individualized inflammatory responses has been emphasized, acknowledging that not all individuals have the same mechanisms contributing towards their presentation. By understanding cellular processes that drive disease, we can make better personalized therapy decisions to improve patient outcomes. While the understanding of these cellular processes is evolving, the ability to measure such cellular responses at bedside to make acute care decisions is lacking. In this overview, we review cellular mechanisms involved in pathological neuroinflammation with a focus on immunometabolic dysfunction and review non-invasive bedside tools that have the potential to measure indirect and direct markers of shifts in cellular metabolism related to neuroinflammation. These tools include near-infrared spectroscopy, transcranial doppler, elastography, electroencephalography, magnetic resonance imaging and spectroscopy, and cytokine analysis. Additionally, we review the importance of genetic testing in providing information about unique metabolic profiles to guide individualized interpretation of bedside data. Together in tandem, these modalities have the potential to provide real time information and guide more informed treatment decisions.
NF-Y Overexpression in Liver Hepatocellular Carcinoma (HCC)
Authors: Bezzecchi Eugenia , Ronzio Mirko , Mantovani Roberto , Dolfini Diletta
Published: December 2020

NF-Y is a pioneer trimeric transcription factor formed by the Histone Fold Domain (HFD) NF-YB/NF-YC subunits and NF-YA. Three subunits are required for DNA binding. CCAAT-specificity resides in NF-YA and transactivation resides in Q-rich domains of NF-YA and NF-YC. They are involved in alternative splicing (AS). We recently showed that NF-YA is overexpressed in breast and lung carcinomas. We report here on the overexpression of all subunits in the liver hepatocellular carcinoma (HCC) TCGA database, specifically the short NF-YAs and NF-YC2 (37 kDa) isoforms. This is observed at all tumor stages, in viral-infected samples and independently from the inflammatory status. Up-regulation of NF-YAs and NF-YC, but not NF-YB, is associated to tumors with mutant p53. We used a deep-learning-based method (DeepCC) to extend the partitioning of the three molecular clusters to all HCC TCGA tumors. In iCluster3, CCAAT is a primary matrix found in promoters of up-regulated genes, and cell-cycle pathways are enriched. Finally, clinical data indicate that, globally, only NF-YAs, but not HFD subunits, correlate with the worst prognosis; in iCluster1 patients, however, all subunits correlate. The data show a difference with other epithelial cancers, in that global overexpression of the three subunits is reported and clinically relevant in a subset of patients; yet, they further reinstate the regulatory role of the sequence-specific subunit.
Investigation Strategy for Structural Assessment of Historic Towers
Authors: Saisi Antonella , Gentile Carmelo
Published: December 2020

Historical masonry towers are relevant architectural heritage often in a strategic position within city centres. Their height and position require specific controls in order to define the state of preservation. The paper describes the investigation procedures developed by the authors in selected case studies. According to the timing and to the complexity of the structure, the approach requires preliminary visual inspections, geometric, crack pattern survey supplemented by historical research and stratigraphic survey. Operational modal testing evaluates the overall structural behaviour, indicating eventual local (or global) problems to study in depth by monitoring or further local tests. Emergency operations, such as controls after earthquakes, could require prompt procedures. In this case, the combination of visual inspection, geometric and damage survey with dynamic testing is a reliable procedure for structural assessment. Additional investigation increases the knowledge of local problems or gives information for further activity such as structural modelling. For instance, relevant data are the evaluation of the masonry quality or the control of the local state of stress to estimate through non-destructive or minor destructive testing in selected positions. Nevertheless, such activities require accurate projects of the investigation too, planning and localising several tests in order to solve the problems detected in the preliminary steps of the diagnosis process.
CuII Complexes and Coordination Polymers with Pyridine or Pyrazine Amides and Amino Benzamides—Structures and EPR Patterns
Authors: Wackerbarth Ines , Widhyadnyani Ni Nyoman Agnes Tri , Schmitz Simon , Stirnat Kathrin , Butsch Katharina , Pantenburg Ingo , Meyer Gerd , Klein Axel
Published: December 2020

Isonicotine amide, picoline amide, pyrazine 2-amide, 2- and 4-amino benzamides and various CuII salts were used to target CuII complexes of these ligands alongside with 1D and 2D coordination polymers. Under the criterion of obtaining crystalline and single phased materials a number of new compounds were reliably reproduced. Remarkably, for some of these compounds the ideal Cu:ligand ratio of the starting materials turned out to be very different from Cu:ligand ratio in the products. Crystal and molecular structures from single-crystal XRD were obtained for all new compounds; phase purity was checked using powder XRD. We observed exclusively the Oamide and not the NH2amide function binding to CuII. In most of the cases; this occurred in chelates with the second pyridine, pyrazine or aminophenyl N function. µ-O,N ditopic bridging was frequently observed for the N = pyridine, pyrazine or aminophenyl functions, but not exclusively. The geometry around CuII in these compounds was very often axially elongated octahedral or square pyramidal. X-band EPR spectra of powder samples revealed various spectral symmetry patterns ranging from axial over rhombic to inverse axial. Although the EPR spectra cannot be unequivocally correlated to the observed geometry of CuII in the solid state structures, the EPR patterns can help to support assumed structures as shown for the compound [Cu(Ina)2Br2] (Ina = isonicotine amide). As UV-vis absorption spectroscopy and magnetic measurement in the solid can also be roughly correlated to the surrounding of CuII, we suggest the combination of EPR, UV-vis spectroscopy and magnetic measurements to elucidate possible structures of CuII compounds with such ligands.
Metastatic Colorectal Cancer. First Line Therapy for Unresectable Disease
Authors: Aparicio Jorge , Esposito Francis , Serrano Sara , Falco Esther , Escudero Pilar , Ruiz-Casado Ana , Manzano Hermini , Fernandez-Montes Ana
Published: December 2020

Colorectal cancer (CRC) is a commonly diagnosed malignancy. The prognosis of patients with unresectable, metastatic colorectal cancer (mCRC) is dismal and medical treatment is mainly palliative in nature. Although chemotherapy remains the backbone of treatment, the landscape is changing with the understanding of its heterogeneity and molecular biology. First-line therapy relies on a combination of chemotherapy and targeted therapies, according to clinical patient characteristics and tumor molecular profile. Here we review current evidence from randomized clinical trials for using chemotherapy doublets or triplets, and for the addition of bevacizumab or anti-epidermal growth factor receptor (EGFR) agents. Novel therapies developed for small, selected populations are also discussed.
Nailfold Videocapillaroscopy in Patients with Central Serous Chorioretinopathy and Its Relationship to Morphological and Functional Findings
Authors: Latalska Małgorzata , Bartosińska Joanna , Kosior-Jarecka Ewa , Krasowska Dorota , Mackiewicz Jerzy
Published: December 2020

The aim of the study was to evaluate the results of nailfold videocapillaroscopy (NVC) in patients with central serous chorioretinopathy (CSC) and their correlation with different functional, morphological features and general risk factors. Material and methods: The examined group included 59 CSC patients (14 F, 45 M, mean age 47.2 ± 9.4) and 53 healthy controls (13 F, 40 M, mean age 46 ± 11.5). The NVC was qualified as a normal or abnormal pattern. In the CSC group, the ophthalmoscopy, angio-Optical Coherence Tomography (OCT-A), OCT and microperimetry were performed. The medical history regarding CSC, chronic general disorders and known risk factors was recorded. Results: In the CSC group an abnormal NVC pattern was more common (33.88% CSC vs. 7.54%, p < 0.001). Dilated apical part of capillaries, microaneurysmal dilatation, megacapillaries, fresh microhaemorrhages, bizarre and broken capillaries were observed only in CSC patients. Dilation of capillaries (47.56% vs. 13.21%, p = 0.004), ramified capillaries and neoangiogenesis (38.98% vs. 5.66%, p < 0.001), glomerular loops (32.20% vs. 1.88% p < 0.001) were more frequent in the CSC group. Conclusions: The presence of various NVC abnormalities confirms microvascular involvement in CSC pathogenesis. The results correlate with visual acuity, microperimetry, OCT data and stress. The NVC technique may play a useful diagnostic and prognostic role in CSC.
Considerations for Cannabis Use to Treat Pain in Sickle Cell Disease
Authors: Argueta Donovan A. , Aich Anupam , Muqolli Fjolla , Cherukury Hemanth , Sagi Varun , DiPatrizio Nicholas V. , Gupta Kalpna
Published: December 2020

Pain in Sickle Cell Disease (SCD) is a major comorbidity and unique with acute pain due to recurrent and episodic vaso-occlusive crises as well as chronic pain, which can span an individual’s entire life. Opioids are the mainstay treatment for pain in SCD. Due to recent health crises raised by adverse effects including deaths from opioid use, pain management in SCD is adversely affected. Cannabis and its products are most widely used for pain in multiple conditions and also by patients with SCD on their own. With the availability of “Medical Cannabis” and approval to use cannabis as medicine across majority of States in the United States as well as over-the-counter preparations, cannabis products are being used increasingly for SCD. The reliability of many of these products remains questionable, which poses a major health risk to the vulnerable individuals seeking pain relief. Therefore, this review provides up to date insights into available categories of cannabis-based treatment strategies, their mechanism of action and pre-clinical and clinical outcomes in SCD. It provides evidence for the benefits and risks of cannabis use in SCD and cautions about the unreliable and unvalidated products that may be adulterated with life-threatening non-cannabis compounds.
CLSTM: Deep Feature-Based Speech Emotion Recognition Using the Hierarchical ConvLSTM Network
Authors: Mustaqeem  , Kwon Soonil
Published: December 2020

Artificial intelligence, deep learning, and machine learning are dominant sources to use in order to make a system smarter. Nowadays, the smart speech emotion recognition (SER) system is a basic necessity and an emerging research area of digital audio signal processing. However, SER plays an important role with many applications that are related to human–computer interactions (HCI). The existing state-of-the-art SER system has a quite low prediction performance, which needs improvement in order to make it feasible for the real-time commercial applications. The key reason for the low accuracy and the poor prediction rate is the scarceness of the data and a model configuration, which is the most challenging task to build a robust machine learning technique. In this paper, we addressed the limitations of the existing SER systems and proposed a unique artificial intelligence (AI) based system structure for the SER that utilizes the hierarchical blocks of the convolutional long short-term memory (ConvLSTM) with sequence learning. We designed four blocks of ConvLSTM, which is called the local features learning block (LFLB), in order to extract the local emotional features in a hierarchical correlation. The ConvLSTM layers are adopted for input-to-state and state-to-state transition in order to extract the spatial cues by utilizing the convolution operations. We placed four LFLBs in order to extract the spatiotemporal cues in the hierarchical correlational form speech signals using the residual learning strategy. Furthermore, we utilized a novel sequence learning strategy in order to extract the global information and adaptively adjust the relevant global feature weights according to the correlation of the input features. Finally, we used the center loss function with the softmax loss in order to produce the probability of the classes. The center loss increases the final classification results and ensures an accurate prediction as well as shows a conspicuous role in the whole proposed SER scheme. We tested the proposed system over two standard, interactive emotional dyadic motion capture (IEMOCAP) and ryerson audio visual database of emotional speech and song (RAVDESS) speech corpora, and obtained a 75% and an 80% recognition rate, respectively.
Efficacy and Mechanism of Action of Marine Alkaloid 3,10-Dibromofascaplysin in Drug-Resistant Prostate Cancer Cells
Authors: Dyshlovoy Sergey A. , Kaune Moritz , Hauschild Jessica , Kriegs Malte , Hoffer Konstantin , Busenbender Tobias , Smirnova Polina A. , Zhidkov Maxim E. , Poverennaya Ekaterina V. , Oh-Hohenhorst Su Jung , Spirin Pavel V. , Prassolov Vladimir S. , Tilki Derya , Bokemeyer Carsten , Graefen Markus , von Amsberg Gunhild
Published: December 2020

Efficacy and mechanism of action of marine alkaloid 3,10-dibromofascaplysin (DBF) were investigated in human prostate cancer (PCa) cells harboring different levels of drug resistance. Anticancer activity was observed across all cell lines examined without signs of cross-resistance to androgen receptor targeting agents (ARTA) or taxane based chemotherapy. Kinome analysis followed by functional investigation identified JNK1/2 to be one of the molecular targets of DBF in 22Rv1 cells. In contrast, no activation of p38 and ERK1/2 MAPKs was observed. Inhibition of the drug-induced JNK1/2 activation or of the basal p38 activity resulted in increased cytotoxicity of DBF, whereas an active ERK1/2 was identified to be important for anticancer activity of the alkaloid. Synergistic effects of DBF were observed in combination with PARP-inhibitor olaparib most likely due to the induction of ROS production by the marine alkaloid. In addition, DBF intensified effects of platinum-based drugs cisplatin and carboplatin, and taxane derivatives docetaxel and cabazitaxel. Finally, DBF inhibited AR-signaling and resensitized AR-V7-positive 22Rv1 prostate cancer cells to enzalutamide, presumably due to AR-V7 down-regulation. These findings propose DBF to be a promising novel drug candidate for the treatment of human PCa regardless of resistance to standard therapy.