bluuebunny/crossref_metadata_2025 huggingface dataset:
Intramedullary Conus Medullaris Tuberculoma: A Case Report and Review of the Literature
Authors: Chotmongkol Verajit , Wanitpongpun Chinadol , Phuttharak Warinthorn , Khamsai Sittichai
Published: January 2021

Intramedullary tuberculoma (IMT) of the conus medullaris is extremely rare. We present a case of intramedullary conus medullaris tuberculoma in which the diagnosis was based on there being very high levels of adenosine deaminase (ADA) in the patient’s cerebrospinal fluid (CSF) and improvement with antituberculous therapy. A 78-year-old man presented after having had a dull ache in both thighs and progressive paraparesis. The patient’s medical history included diffuse large B-cell lymphoma, which had undergone remission due to chemotherapy two years earlier, and long-term, well-controlled diabetes. A chest X-ray showed no evidence of tuberculosis. The results of CSF analysis were compatible with Froin’s syndrome. An initial diagnosis was made of an intramedullary tumor of the conus medullaris, based on magnetic resonance imaging (MRI). A myelotomy and multiple punch out biopsy were performed, and histopathology of the tissues revealed mild reactive gliosis. Due to the patient having high levels of CSF-ADA, IMT of the conus medullaris was suspected. The patient was treated with an 18-month course of antituberculous therapy. The dull ache gradually disappeared, and motor power improved slightly. A follow-up MRI of the lumbosacral (LS) spine revealed that the lesion had completely disappeared. Intramedullary tuberculoma of the conus medullaris should be considered in patients with underlying malignancy and no symptoms of systemic tuberculosis. CSF adenosine deaminase levels can be helpful in determining the presence of central nervous system tuberculosis when other systemic signs of disease are lacking.
Ecotoxicological Studies on the Effect of Roundup® (Glyphosate Formulation) on Marine Benthic Microalgae
Authors: Sylwestrzak Zuzanna , Zgrundo Aleksandra , Pniewski Filip
Published: January 2021

Glyphosate is a very effective herbicide and the main active ingredient in Roundup®—the most extensively used herbicide in the world. Since glyphosate is highly water soluble it reaches water bodies easily in surface water runoff. This prompted us to undertake an experiment to evaluate the effects of glyphosate in Roundup® on natural communities of marine microphytobenthos. Microphytobenthos communities were obtained from the environment, and after transporting them to the laboratory and acclimatizing them, they were tested under controlled conditions. Changes in microphytobenthos composition and structure and the deteriorating condition of the cells of community-forming organisms (assessed by analyzing changes in chloroplast shape) were used to assess the impact of Roundup® on endpoints. The tests indicated that microphytobenthic communities were relatively resistant to herbicide. The species richness of the communities probably enabled them to rebuild effectively. Sensitive species were replaced by those more tolerant of glyphosate. Only at the highest glyphosate concentration (8.5 g·dm−3) tested was a strong negative effect noted that limited community abundance and eliminated some of the organisms. The dominant diatoms in the communities were replaced by intensively developing cyanobacteria, which ultimately comprised nearly 60% of all the cells observed in the communities.
Effect of Ambient Temperature on Daily Nebulized Asthma Hospital Visits in a Tropical City of Dhaka, Bangladesh
Authors: Kabir Ayesha Ferdosi , Ng Chris Fook Sheng , Yasumoto Shinya , Hayashi Taiichi , Watanabe Chiho
Published: January 2021

The acute effect of temperature on asthma morbidity in Bangladesh is not well understood. As climate varies extensively in different parts of the world, the relation between temperature and asthma might also differ. We investigated the association between temperature and asthma-related hospital visits in the tropical city of Dhaka. We analyzed information from a total of 5989 asthma patients who received ambulatory care in the form of nebulized medication at the National Asthma Center in Mohakhali, Dhaka from February to November 2013. A time-stratified case-crossover study was conducted to estimate the effect of daily temperature, with consideration of delayed effects and possible confounders such as relative humidity and political strikes. An inverse association was observed between temperature and the number of hospital visits. The effect was delayed for approximately a week. A degree centigrade decrease in mean temperature (averaged across lags 0-6) was associated with an increase of approximately 4.5% (95% CI 1.5, 7.5) in all asthma visits. The association was evident in adult males but marginal in elderly males. A positive association (lag 0) was observed among adult females, whereas no association was observed among children. Strikes significantly modified the effect among the elderly. Findings suggest temperature declines affect asthma outcomes in a warm climate, and this effect can be delayed and vary by sex and age group.
Age Differences in the Influence of Residential Environment and Behavior on the Life Quality of Older Adults: The Transfer from Physical-Environment to Social-Behavior
Authors: Zheng Zhenhua , Chen Hong , Gao Junling
Published: January 2021

With the development of the concept of “ageing-friendly communities”, increasing attention has been paid to the effect of residential environments on the life quality of older adults. However, the logical relationship between residential environment, individual behavior and life quality of older adults has not been clearly revealed. Based on data in Shanghai, China, this study explored the relationships between residential environments and the life quality of older adults in different age groups, and analyzed the mediating role of individual behaviors (neighborhood interaction and outdoor exercise). The findings confirmed that residential environment, neighborhood interactions and outdoor exercise have significant positive effects on the life quality of older adults. Meanwhile, the impact of residential environment on the life quality of older adults is exclusively realized through the mediating role of individual behavior. However, there were significant differences in the model paths among various age groups. With ageing, the positive effects of residential environment on the quality of life gradually weakened, while that of neighborhood interaction gradually improved. The findings prove that the influencing factors on the quality of life of older adults tend to shift from residential environment to neighborhood interaction as the age of residents advances. This knowledge is crucial with regard to the differentiated and accurate design of older communities.
The Relationships among Self-Worth Contingency on Others’ Approval, Appearance Comparisons on Facebook, and Adolescent Girls’ Body Esteem: A Cross-Cultural Study
Authors: Prieler Michael , Choi Jounghwa , Lee Hye Eun
Published: January 2021

The present study examined the relationship between appearance-related social comparison on social networking services (SNSs) and body esteem in a cross-cultural context (three European countries, i.e., Austria, Belgium, and Spain, versus one Asian country, i.e., South Korea). The role of self-worth contingency on others’ approval was considered to be a psychological and cultural factor. Utilizing a large-scale cross-national survey of early and middle adolescents in 2017, the responses of female adolescents (N = 981) were analyzed. The results generally support the findings from previous studies but also reveal cultural differences. Appearance comparison on Facebook negatively influenced girls’ body esteem in all European countries, but not in South Korea. Self-worth contingency on others’ approval negatively influenced girls’ body esteem across all four countries. Finally, a positive relationship between self-worth contingency on others’ approval and appearance comparison on Facebook was found in all European countries, but not among Korean girls. These findings suggest the importance of self-worth contingency on others’ approval and cultural contexts can be used to study the effects of body image-related SNS use.
Studyholism and Study Engagement: What about the Role of Perfectionism, Worry, Overstudy Climate, and Type of School in Adolescence?
Authors: Loscalzo Yura
Published: January 2021

This study aims to deepen the analysis of Studyholism (or obsession toward study) on a sample of 793 Italian adolescents (Mage = 16.30 ± 1.73; 53% boys). A path analysis model including potential antecedents (i.e., worry, study-related perfectionism, perfectionistic strivings and concerns, overstudy climate, type of school) and outcomes (e.g., grade point average, time spent studying, psychological well-being) of Studyholism was tested. In line with previous findings on college students, this study supported the conceptualization of problematic overstudying as an OCD-related disorder, since worry is the strongest predictor of Studyholism. Moreover, among the main findings, it confirmed that Studyholism is associated with negative academic outcomes, while Study Engagement predicts positive academic outcomes. Finally, it also confirmed that both Studyholism and Study Engagement predict social impairment. In conclusion, preventive interventions to favor students’ academic success and well-being should reduce perfectionistic concerns and study-related perfectionism and enhance time management skills (in Engaged students too). For reducing Studyholism, instead, the primary target should be trait worry. Finally, preventive interventions should be implemented across all the school types and possibly during childhood or pre-adolescence to avoid the increase in psychological and social impairment that has been found to be associated with Studyholism in youths. It is also essential to detect potential early risk indicators (especially among individual factors) of Studyholism in childhood.
Housing and Adult Health: Evidence from Chinese General Social Survey (CGSS)
Authors: Chen Nanqian , Shen Yanpei , Liang Hailun , Guo Rui
Published: January 2021

Housing is one of the social determinants of health and the most basic survival needs of human beings. Many studies have preliminarily confirmed that housing factors can influence residents’ health. The aims of this study were: to evaluate the housing factors associated with self-rated health and mental health among Chinese residents; to explore the regional heterogeneity of the impact of housing on health; and to assess the effects of housing on health among different age groups. Data was derived from the Chinese General Social Survey (CGSS). Housing factors were analyzed along six dimensions: housing property, living space, number of living people, number of houses, living region and housing price. Self-rated health and mental health were used to measure health outcomes. Multivariate ordered logistic regression was performed to assess the relationship between housing and health. The living space, living region and housing price was significantly associated with self-rated health. The number of living people living region and housing price were related to mental health. The influence of housing factors on health were more pronounced among residents living in eastern and central area and among the middle-aged group (41–65). Present findings support the notion that housing factors were related to health outcomes. Future studies may focus on the impact of interventions that target on these factors, and the impact of housing on health among special groups such as migrant population and low-and-middle income families.
Symptomatological Variants and Related Clinical Features in Adult Attention Deficit Hyperactive Disorder
Authors: Pallucchini Alessandro , Carli Marco , Scarselli Marco , Maremmani Icro , Perugi Giulio
Published: January 2021

A large amount of the current literature has focused on the characteristic symptoms of attention deficit hyperactivity disorder (ADHD) in children and adolescents. In contrast, less attention has been devoted to ADHD clinical subtypes in adult patients. We evaluated 164 consecutive adult ADHD (A-ADHD) outpatients using DSM-5 criteria and many specific rating scales and questionnaires. A principal component factor analysis was performed on clinical and symptomatological variables to describe potential clinical variants. We sought to determine different A-ADHD variants focusing on demographic and clinical features. A four-factor solution was identified, and patients were clustered, according to their z-score, in 4 subgroups. The first was marked out by Emotional Dysregulation (ED), the second by Substance Use (SU), the third by Core-ADHD Symptoms (Co-ADHD) and the fourth by Positive Emotionality (PE). Predominantly ED patients showed worse overall function, early treatment with antidepressants and a greater presence of borderline personality disorder than predominantly Co-ADHD patients. Predominantly SU patients reported high rates of bipolar disorder and severe general psychopathology. The PE factor was related to hyperthymic temperament and hypomania and showed a higher level of functioning. Females with A-ADHD showed a lower risk of being included in SU, and A-ADHD patients with co-occurring delayed sleep phase had less risk of being included in the SU factor than the prevailing Co-ADHD group. Our empirically based description of four clinical A-ADHD variants shows several aspects beyond the definition given by the DSM-5 diagnostic criteria.
Relationships between Mindfulness, Purpose in Life, Happiness, Anxiety, and Depression: Testing a Mediation Model in a Sample of Women
Authors: Crego Antonio , Yela José Ramón , Gómez-Martínez María Ángeles , Riesco-Matías Pablo , Petisco-Rodríguez Cristina
Published: January 2021

Mindfulness is connected to positive outcomes related to mental health and well-being. However, the psychological mechanisms that account for these relationships are largely unknown. A multiple-step multiple mediator structural equation modeling (SEM) model was tested with mindfulness as the independent variable; purpose in life and behavioral activation as serial mediators; and happiness, anxiety, and depression as outcome measures. Data were obtained from 1267 women. Higher mindfulness was associated with higher levels of happiness and lower anxiety and depression symptoms. The association of mindfulness with the outcome variables could be partially accounted for by purpose in life and behavioral activation. The SEM model explained large proportions of variance in happiness (50%), anxiety (34%), and depression (44%) symptoms. Mindfulness is associated with both a sense of purpose in life and engagement in activities, which are also connected with positive outcomes. Moreover, having purposes in life is linked to higher levels of behavioral activation.
Bacterial Root Endophytes: Characterization of Their Competence and Plant Growth Promotion in Soybean (Glycine max (L.) Merr.) under Drought Stress
Authors: Dubey Anamika , Saiyam Diksha , Kumar Ashwani , Hashem Abeer , Abd_Allah Elsayed Fathi , Khan Mohammed Latif
Published: January 2021

Recently, the application of endophytes in the alleviation of different types of stresses has received considerable attention, but their role in drought stress alleviation and growth promotion in soybean is not well-stated. In this study, twenty bacterial endophytes were isolated from soybean root tissues and screened for plant growth-promoting (PGP) traits, biocontrol potential, and drought stress alleviation. Out of them, 80% showed PGP traits, and 20% showed antagonistic activity against Fusarium oxysporum (ITCC 2389), Macrophomina phaseolina (ITCC 1800), and Alternaria alternata (ITCC 3467), and only three of them showed drought tolerance up to 15% (−0.3 MPa). Results indicated that drought-tolerant PGP endophytic bacteria enhanced soybean seedling growth under drought stress conditions. Morphological, biochemical, and molecular characterization (16S rRNA) revealed that these three bacterial isolates, AKAD A1-1, AKAD A1-2, and AKAD A1-16, closely resemble Bacillus cereus (GenBank accession No. MN079048), Pseudomonas otitidis (MW301101), and Pseudomonas sp. (MN079074), respectively. We observed that the soybean seedlings were grown in well-watered and drought-stressed soil showed the adverse effect of drought stress on morphological (stem length, root length, plant fresh and dry weight) as well as on biochemical parameters (a decline of photosynthetic pigments, membrane damage, etc.). However, soybean seedlings inoculated with these endophytes have improved the biomass significantly (p ≤ 0.05) under normal as well as in drought stress conditions over control treatments by influencing several biochemical changes. Among these three endophytes, AKAD A1-16 performed better than AKAD A1-2 and AKAD A1-1, which was further validated by the ability to produce the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase in the following order: AKAD A1-16 > AKAD A1-2 > AKAD A1-1. Scanning electron microscopy images also showed a bacterial presence inside the roots of soybean seedlings. These findings supported the application of bacterial root endophytes as a potential tool to mitigate the effect of drought as well as of fungal diseases on the early seedling growth of soybean.
Comparison of Circulating Markers and Mucosal Immune Parameters from Skin and Distal Intestine of Atlantic Salmon in Two Models of Acute Stress
Authors: Djordjevic Brankica , Morales-Lange Byron , McLean Press Charles , Olson Jake , Lagos Leidy , Mercado Luis , Øverland Margareth
Published: January 2021

Ensuring salmon health and welfare is crucial to maximize production in recirculation aquaculture systems. Healthy and robust mucosal surfaces of the skin and intestine are essential to achieve this goal because they are the first immunological defenses and are constantly exposed to multistressor conditions, such as infectious diseases, suboptimal nutrition, and environmental and handling stress. In this work, Atlantic salmon, split from a single cohort, were subjected to acute hypoxia stress or 15-min crowding stress and observed over a 24-h recovery period. Samples were collected from fish at 0, 1, 3, 6, 12 and 24 h post-stress to analyze plasma-circulating markers of endocrine function (cortisol), oxidative stress (glutathione peroxidase) and immune function (interleukin 10 (IL-10), annexin A1). In addition, mucosal barrier function parameters were measured in the skin mucus (Muc-like protein and lysozyme) and distal intestine (simple folds, goblet cell size and goblet cell area). The results showed that both acute stress models induced increases of circulating cortisol in plasma (1 h post-stress), which then returned to baseline values (initial control) at 24 h post-stress. Moreover, the hypoxia stress was mostly related to increased oxidative stress and IL-10 production, whereas the crowding stress was associated with a higher production of Muc-like protein and lysozyme in the skin mucus. Interestingly, in the distal intestine, smaller goblet cells were detected immediately and one hour after post-hypoxia stress, which could be related to rapid release of the cellular content to protect this organ. Finally, the correlation of different markers in the hypoxic stress model showed that the circulating levels of cortisol and IL-10 were directly proportional, while the availability of Muc-like proteins was inversely proportional to the size of the goblet cells. On the other hand, in the crowding stress model, a proportional relationship was established between plasma cortisol levels and skin mucus lysozyme. Our results suggest key differences in energy partitioning between the two acute stress models and support the need for further investigation into the interplay of multistressor conditions and strategies to modulate immunological aspects of mucosal surfaces.
Rheum rhaponticum Root Extract Improves Vasomotor Menopausal Symptoms and Estrogen-Regulated Targets in Ovariectomized Rat Model
Authors: Wilson Mickey , Konda Veera , Heidt Kathryn , Rathinasabapathy Thirumurugan , Desai Anuradha , Komarnytsky Slavko
Published: January 2021

Ovarian insufficiency and ovariectomy are characterized by deregulated heat loss mechanisms. Unlike hormone therapy, ERr 731 (a standardized botanical extract of Siberian rhubarb Rheum rhaponticum L. high in rhaponticin) acts like a selective estrogen receptor modulator for ERβ receptors and may offer a higher degree of safety while maintaining the desired efficacy profile. In this study, we examined the relationship between oral administration of ERr 731 and the underlying components of skin vasomotion responses in an ovariectomized (OVX) rat model. ERr 731 dose-dependently reduced tail skin temperature (Tskin) values by an average of 1 °C. The rapid onset of this effect was observed in 1 and 3 mg/kg/day ERr 731 groups as early as day 2 of administration, and remained in place for the duration of the treatment (2 weeks). Substituting ERr 731 after E2 withdrawal helped maintain body temperature similarly to E2 alone, suggesting the usefulness of ERr 731 for replacing existing hormonal therapy in humans. ERr 731 also acted as a highly selective agonist for ERβ in the hypothalamus of OVX rats, as well as in ERα/β cell-based reporter assays. These data validate the OVX/Tskin rat model as a suitable screening platform to evaluate botanical and pharmaceutical treatments of menopause, while providing further evidence for the efficacy of ERr 731 towards alleviating vasomotor menopausal symptoms and improving wellbeing during the menopausal transition.
GPR119 and GPR55 as Receptors for Fatty Acid Ethanolamides, Oleoylethanolamide and Palmitoylethanolamide
Authors: Im Dong-Soon
Published: January 2021

Oleoylethanolamide and palmitoylethanolamide are members of the fatty acid ethanolamide family, also known as acylethanolamides. Their physiological effects, including glucose homeostasis, anti-inflammation, anti-anaphylactic, analgesia, and hypophagia, have been reported. They have affinity for different receptor proteins, including nuclear receptors such as PPARα, channels such as TRPV1, and membrane receptors such as GPR119 and GPR55. In the present review, the pathophysiological functions of fatty acid ethanolamides have been discussed from the perspective of receptor pharmacology and drug discovery.
Low Basicity as a Characteristic for Atypical Ligands of Serotonin Receptor 5-HT2
Authors: Podlewska Sabina , Bugno Ryszard , Lacivita Enza , Leopoldo Marcello , Bojarski Andrzej J. , Handzlik Jadwiga
Published: January 2021

Serotonin receptors are extensively examined by academic and industrial researchers, due to their vital roles, which they play in the organism and constituting therefore important drug targets. Up to very recently, it was assumed that the basic nitrogen in compound structure is a necessary component to make it active within this receptor system. Such nitrogen interacts in its protonated form with the aspartic acid from the third transmembrane helix (D3x32) forming a hydrogen bond tightly fitting the ligand in the protein binding site. However, there are several recent studies that report strong serotonin receptor affinity also for compounds without a basic moiety in their structures. In the study, we carried out a comprehensive in silico analysis of the low-basicity phenomenon of the selected serotonin receptor ligands. We focused on the crystallized representatives of the proteins of 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT2C receptors, and examined the problem both from the ligand- and structure-based perspectives. The study was performed for the native proteins, and for D3x32A mutants. The investigation resulted in the determination of nonstandard structural requirements for activity towards serotonin receptors, which can be used in the design of new nonbasic ligands.
Altering the Sex Pheromone Cyclo(l-Pro-l-Pro) of the Diatom Seminavis robusta towards a Chemical Probe
Authors: Bonneure Eli , De Baets Amber , De Decker Sam , Van den Berge Koen , Clement Lieven , Vyverman Wim , Mangelinckx Sven
Published: January 2021

As a major group of algae, diatoms are responsible for a substantial part of the primary production on the planet. Pennate diatoms have a predominantly benthic lifestyle and are the most species-rich diatom group, with members of the raphid clades being motile and generally having heterothallic sexual reproduction. It was recently shown that the model species Seminavis robusta uses multiple sexual cues during mating, including cyclo(l-Pro-l-Pro) as an attraction pheromone. Elaboration of the pheromone-detection system is a key aspect in elucidating pennate diatom life-cycle regulation that could yield novel fundamental insights into diatom speciation. This study reports the synthesis and bio-evaluation of seven novel pheromone analogs containing small structural alterations to the cyclo(l-Pro-l-Pro) pheromone. Toxicity, attraction, and interference assays were applied to assess their potential activity as a pheromone. Most of our analogs show a moderate-to-good bioactivity and low-to-no phytotoxicity. The pheromone activity of azide- and diazirine-containing analogs was unaffected and induced a similar mating behavior as the natural pheromone. These results demonstrate that the introduction of confined structural modifications can be used to develop a chemical probe based on the diazirine- and/or azide-containing analogs to study the pheromone-detection system of S. robusta.
Racial Disparity in Drug Disposition in the Digestive Tract
Authors: Gao Song , Bell Edward C. , Zhang Yun , Liang Dong
Published: January 2021

The major determinants of drug or, al bioavailability are absorption and metabolism in the digestive tract. Genetic variations can cause significant differences in transporter and enzyme protein expression and function. The racial distribution of selected efflux transporter (i.e., Pgp, BCRP, MRP2) and metabolism enzyme (i.e., UGT1A1, UGT1A8) single nucleotide polymorphisms (SNPs) that are highly expressed in the digestive tract are reviewed in this paper with emphasis on the allele frequency and the impact on drug absorption, metabolism, and in vivo drug exposure. Additionally, preclinical and clinical models used to study the impact of transporter/enzyme SNPs on protein expression and function are also reviewed. The results showed that allele frequency of the major drug efflux transporters and the major intestinal metabolic enzymes are highly different in different races, leading to different drug disposition and exposure. The conclusion is that genetic polymorphism is frequently observed in different races and the related protein expression and drug absorption/metabolism function and drug in vivo exposure can be significantly affected, resulting in variations in drug response. Basic research on race-dependent drug absorption/metabolism is expected, and FDA regulations of drug dosing adjustment based on racial disparity are suggested.
Amiodarone Enhances Anticonvulsive Effect of Oxcarbazepine and Pregabalin in the Mouse Maximal Electroshock Model
Authors: Banach Monika , Rudkowska Monika , Sumara Agata , Borowicz-Reutt Kinga
Published: January 2021

Accumulating experimental studies show that antiarrhythmic and antiepileptic drugs share some molecular mechanisms of action and can interact with each other. In this study, the influence of amiodarone (a class III antiarrhythmic drug) on the antiseizure action of four second-generation antiepileptic drugs was evaluated in the maximal electroshock model in mice. Amiodarone, although ineffective in the electroconvulsive threshold test, significantly potentiated the antielectroshock activity of oxcarbazepine and pregabalin. Amiodarone, given alone or in combination with oxcarbazepine, lamotrigine, or topiramate, significantly disturbed long-term memory in the passive-avoidance task in mice. Brain concentrations of antiepileptic drugs were not affected by amiodarone. However, the brain concentration of amiodarone was significantly elevated by oxcarbazepine, topiramate, and pregabalin. Additionally, oxcarbazepine and pregabalin elevated the brain concentration of desethylamiodarone, the main metabolite of amiodarone. In conclusion, potentially beneficial action of amiodarone in epilepsy patients seems to be limited by neurotoxic effects of amiodarone. Although results of this study should still be confirmed in chronic protocols of treatment, special precautions are recommended in clinical conditions. Coadministration of amiodarone, even at low therapeutic doses, with antiepileptic drugs should be carefully monitored to exclude undesired effects related to accumulation of the antiarrhythmic drug and its main metabolite, desethylamiodarone.
Corticotropin-Releasing Hormone Receptor Alters the Tumor Development and Growth in Apcmin/+ Mice and in a Chemically-Induced Model of Colon Cancer
Authors: Lee Yunna , Ma Elise L. , Patel Marisa , Kim Gayoung , Howe Cody , Pothoulakis Charalabos , Kim Yong Sung , Im Eunok , Rhee Sang Hoon
Published: January 2021

The neuroendocrine circuit of the corticotropin-releasing hormone (CRH) family peptides, via their cognate receptors CRHR1 and CRHR2, copes with psychological stress. However, peripheral effects of the CRH system in colon cancer remains elusive. Thus, we investigate the role of CRHR1 and CRHR2 in colon cancer. Human colon cancer biopsies were used to measure the mRNA levels of the CRH family by quantitative real-time PCR. Two animal models of colon cancer were used: Apcmin/+ mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. The mRNA levels of CRHR2 and UCN III are reduced in human colon cancer tissues compared to those of normal tissues. Crhr1 deletion suppresses the tumor development and growth in Apcmin/+ mice, while Crhr2 deficiency exacerbates the tumorigenicity. Crhr1 deficiency not only inhibits the expression of tumor-promoting cyclooxygenase 2, but also upregulates tumor-suppressing phospholipase A2 in Apcmin/+ mice; however, Crhr2 deficiency does not change these expressions. In the AOM/DSS model, Crhr2 deficiency worsens the tumorigenesis. In conclusion, Crhr1 deficiency confers tumor-suppressing effects in Apcmin/+ mice, but Crhr2 deficiency worsens the tumorigenicity in both Apcmin/+ and AOM/DSS-treated mice. Therefore, pharmacological inhibitors of CRHR1 or activators of CRHR2 could be of significance as anti-colon cancer drugs.
Genome-Wide Identification and Characterization of Calcium-Dependent Protein Kinase (CDPK) and CDPK-Related Kinase (CRK) Gene Families in Medicago truncatula
Authors: Zhao Pengcheng , Liu Yajie , Kong Weiyi , Ji Jiayi , Cai Tianyu , Guo Zhenfei
Published: January 2021

Calcium-dependent protein kinase (CDPK or CPK) and CDPK-related kinase (CRK) play an important role in plant growth, development, and adaptation to environmental stresses. However, their gene families had been yet inadequately investigated in Medicago truncatula. In this study, six MtCRK genes were computationally identified, they were classified into five groups with MtCDPKs based on phylogenetic relationships. Six pairs of segmental duplications were observed in MtCDPK and MtCRK genes and the Ka/Ks ratio, an indicator of selection pressure, was below 0.310, indicating that these gene pairs underwent strong purifying selection. Cis-acting elements of morphogenesis, multiple hormone responses, and abiotic stresses were predicted in the promoter region. The spatial expression of MtCDPKs and MtCRKs displays diversity. The expression of MtCDPKs and MtCRKs could be regulated by various stresses. MtCDPK4, 14, 16, 22, and MtCRK6 harbor both N-myristoylation site and palmitoylation site and were anchored on plasma membrane, while MtCDPK7, 9, and 15 contain no or only one N-acylation site and were distributed in cytosol and nucleus, suggesting that the N-terminal acylation sites play a key role in subcellular localization of MtCDPKs and MtCRKs. In summary, comprehensive characterization of MtCDPKs and MtCRKs provide a subset of candidate genes for further functional analysis and genetic improvement against drought, cold, salt and biotic stress.
Magnesium Deficiency Induces Lipid Accumulation in Vascular Endothelial Cells via Oxidative Stress—The Potential Contribution of EDF-1 and PPARγ
Authors: Locatelli Laura , Fedele Giorgia , Castiglioni Sara , Maier Jeanette A.
Published: January 2021

Background: Magnesium deficiency contributes to atherogenesis partly by promoting the dysfunction of endothelial cells, which are critical in vascular homeostasis and diseases. Since EDF-1 and PPARγ regulate crucial endothelial activities, we investigated the modulation of these proteins involved in lipogenesis as well the deposition of lipids in human endothelial cells cultured in different concentrations of magnesium. Methods: Human endothelial cells from the umbilical vein were cultured in medium containing from 0.1 to 5 mM magnesium for 24 h. The levels of EDF-1 and PPARγ were visualized by Western blot. Reactive oxygen species (ROS) were measured by DCFDA. Lipids were detected after O Red Oil staining. Results: Magnesium deficiency leads to the accumulation of ROS which upregulate EDF-1. Further, PPARγ is increased after culture in low magnesium, but independently from ROS. Moreover, lipids accumulate in magnesium-deficient cells. Conclusions: Our results suggest that magnesium deficiency leads to the deposition of lipids by inducing EDF-1 and PPARγ. The increase in intracellular lipids might be interpreted as an adaptive response of endothelial cells to magnesium deficiency.
Natural and Synthetic Lactones Possessing Antitumor Activities
Authors: Kim Younghoon , Sengupta Sandip , Sim Taebo
Published: January 2021

Cancer is one of the leading causes of death globally, accounting for an estimated 8 million deaths each year. As a result, there have been urgent unmet medical needs to discover novel oncology drugs. Natural and synthetic lactones have a broad spectrum of biological uses including anti-tumor, anti-helminthic, anti-microbial, and anti-inflammatory activities. Particularly, several natural and synthetic lactones have emerged as anti-cancer agents over the past decades. In this review, we address natural and synthetic lactones focusing on their anti-tumor activities and synthetic routes. Moreover, we aim to highlight our journey towards chemical modification and biological evaluation of a resorcylic acid lactone, L-783277 (4). We anticipate that utilization of the natural and synthetic lactones as novel scaffolds would benefit the process of oncology drug discovery campaigns based on natural products.
Epstein–Barr Virus-Positive Mucocutaneous Ulcer: A Unique and Curious Disease Entity
Authors: Ikeda Tomoka , Gion Yuka , Nishimura Yoshito , Nishimura Midori Filiz , Yoshino Tadashi , Sato Yasuharu
Published: January 2021

Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) was first described as a lymphoproliferative disorder in 2010. EBVMCU is a unifocal mucosal or cutaneous ulcer that often occurs after local trauma in patients with immunosuppression; the patients generally have a good prognosis. It is histologically characterized by proliferating EBV-positive atypical B cells accompanied by ulcers. On the basis of conventional pathologic criteria, EBVMCU may be misdiagnosed as EBV-positive diffuse large B-cell lymphoma or other lymphomas. However, its prognosis differs from that of EBV-associated lymphomas, in that patients with EBVMCU frequently show spontaneous regression or complete remission without chemotherapy. Therefore, EBVMCU is now recognized as a low-grade malignancy or a pseudo-malignant lesion. Avoiding unnecessary chemotherapy by distinguishing EBVMCU from other EBV-associated lymphomas will reduce the burden and unnecessary harm on patients. On the basis of these facts, EBVMCU was first described as a new clinicopathological entity by the World Health Organization in 2017. In this review, we discuss the clinicopathological characteristics of previously reported EBVMCU cases, while focusing on up-to-date clinical, pathological, and genetic aspects.
Physiological and Proteomic Analyses of Two Acanthus Species to Tidal Flooding Stress
Authors: Liu Yi-ling , Zheng Hai-lei
Published: January 2021

The mangrove plant Acanthus ilicifolius and its relative, Acanthus mollis, have been previously proved to possess diverse pharmacological effects. Therefore, evaluating the differentially expressed proteins of these species under tidal flooding stress is essential to fully exploit and benefit from their medicinal values. The roots of A. ilicifolius and A. mollis were exposed to 6 h of flooding stress per day for 10 days. The dry weight, hydrogen peroxide (H2O2) content, anatomical characteristics, carbon and energy levels, and two-dimensional electrophoresis coupled with MALDI-TOF/TOF MS technology were used to reveal the divergent flooding resistant strategies. A. ilicifolius performed better under tidal flooding stress, which was reflected in the integrity of the morphological structure, more efficient use of carbon and energy, and a higher percentage of up-regulated proteins associated with carbon and energy metabolism. A. mollis could not survive in flooding conditions for a long time, as revealed by disrupting cell structures of the roots, less efficient use of carbon and energy, and a higher percentage of down-regulated proteins associated with carbon and energy metabolism. Energy provision and flux balance played a role in the flooding tolerance of A. ilicifolius and A. mollis.
Characterization and Expression Analysis of Insulin Growth Factor Binding Proteins (IGFBPs) in Pacific White Shrimp Litopenaeus vannamei
Authors: Pang Ying , Zhang Xiaojun , Yuan Jianbo , Zhang Xiaoxi , Xiang Jianhai , Li Fuhua
Published: January 2021

The insulin signaling (IIS) pathway plays an important role in the metabolism, growth, development, reproduction, and longevity of an organism. As a key member of the IIS pathway, insulin-like growth factor binding proteins (IGFBPs) are widely distributed a family in invertebrates and vertebrates that are critical in various aspects of physiology. As an important mariculture species, the growth of Pacific white shrimp, Litopenaeus vannamei, is one of the most concerning characteristics in this area of study. In this study, we identified three IGFBP genes in the genome of L. vannamei and analyzed their gene structures, phylogenetics, and expression profiles. LvIGFBP1 was found to contain three domains (the insulin growth factor binding (IB) domain, the Kazal-type serine proteinase inhibitor (Kazal) domain, and the immunoglobulin C-2 (IGc2) domain), while LvIGFBP2 and LvIGFBP3 only contained a single IB domain. LvIGFBP1 exhibited high expression in most tissues and different developmental stages, while LvIGFBP2 and LvIGFBP3 were only slightly expressed in hemocytes. The RNA interference of LvIGFBP1 resulted in a significantly smaller increment of body weight than that of control groups. These results will improve our understanding of the conservative structure and function of IGFBPs and show potential applications for the growth of shrimp.
Identification of the Genetic Basis of Response to de-Acclimation in Winter Barley
Authors: Wójcik-Jagła Magdalena , Daszkowska-Golec Agata , Fiust Anna , Kopeć Przemysław , Rapacz Marcin
Published: January 2021

Mechanisms involved in the de-acclimation of herbaceous plants caused by warm periods during winter are poorly understood. This study identifies the genes associated with this mechanism in winter barley. Seedlings of eight accessions (four tolerant and four susceptible to de-acclimation cultivars and advanced breeding lines) were cold acclimated for three weeks and de-acclimated at 12 °C/5 °C (day/night) for one week. We performed differential expression analysis using RNA sequencing. In addition, reverse-transcription quantitative real-time PCR and enzyme activity analyses were used to investigate changes in the expression of selected genes. The number of transcripts with accumulation level changed in opposite directions during acclimation and de-acclimation was much lower than the number of transcripts with level changed exclusively during one of these processes. The de-acclimation-susceptible accessions showed changes in the expression of a higher number of functionally diverse genes during de-acclimation. Transcripts associated with stress response, especially oxidoreductases, were the most abundant in this group. The results provide novel evidence for the distinct molecular regulation of cold acclimation and de-acclimation. Upregulation of genes controlling developmental changes, typical for spring de-acclimation, was not observed during mid-winter de-acclimation. Mid-winter de-acclimation seems to be perceived as an opportunity to regenerate after stress. Unfortunately, it is competitive to remain in the cold-acclimated state. This study shows that the response to mid-winter de-acclimation is far more expansive in de-acclimation-susceptible cultivars, suggesting that a reduced response to the rising temperature is crucial for de-acclimation tolerance.
Potential Physiological Relevance of ERAD to the Biosynthesis of GPI-Anchored Proteins in Yeast
Authors: Nakatsukasa Kunio
Published: January 2021

Misfolded and/or unassembled secretory and membrane proteins in the endoplasmic reticulum (ER) may be retro-translocated into the cytoplasm, where they undergo ER-associated degradation, or ERAD. The mechanisms by which misfolded proteins are recognized and degraded through this pathway have been studied extensively; however, our understanding of the physiological role of ERAD remains limited. This review describes the biosynthesis and quality control of glycosylphosphatidylinositol (GPI)-anchored proteins and briefly summarizes the relevance of ERAD to these processes. While recent studies suggest that ERAD functions as a fail-safe mechanism for the degradation of misfolded GPI-anchored proteins, several pieces of evidence suggest an intimate interaction between ERAD and the biosynthesis of GPI-anchored proteins.
Decreased Levels of Thioredoxin o1 Influences Stomatal Development and Aperture but Not Photosynthesis under Non-Stress and Saline Conditions
Authors: Sánchez-Guerrero Antonio , Nadal Miquel , Florez-Sarasa Igor , Ribas-Carbó Miquel , Vallarino José G. , Brasi-Velasco Sabrina De , Fernie Alisdair R. , Flexas Jaume , Jiménez Ana , Sevilla Francisca
Published: January 2021

Salinity has a negative impact on plant growth, with photosynthesis being downregulated partially due to osmotic effect and enhanced cellular oxidation. Redox signaling contributes to the plant response playing thioredoxins (TRXs) a central role. In this work we explore the potential contribution of Arabidopsis TRXo1 to the photosynthetic response under salinity analyzing Arabidopsis wild-type (WT) and two Attrxo1 mutant lines in their growth under short photoperiod and higher light intensity than previous reported works. Stomatal development and apertures and the antioxidant, hormonal and metabolic acclimation are also analyzed. In control conditions mutant plants displayed less and larger developed stomata and higher pore size which could underlie their higher stomatal conductance, without being affected in other photosynthetic parameters. Under salinity, all genotypes displayed a general decrease in photosynthesis and the oxidative status in the Attrxo1 mutant lines was altered, with higher levels of H2O2 and NO but also higher ascorbate/glutathione (ASC/GSH) redox states than WT plants. Finally, sugar changes and increases in abscisic acid (ABA) and NO may be involved in the observed higher stomatal response of the TRXo1-altered plants. Therefore, the lack of AtTRXo1 affected stomata development and opening and the mutants modulate their antioxidant, metabolic and hormonal responses to optimize their adaptation to salinity.
Acknowledgment to Reviewers of International Journal of Neonatal Screening in 2020
Authors:   International Journal of Neonatal Screening Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that International Journal of Neonatal Screening maintains its standards for the high quality of its published papers [...]
Expanded Newborn Screening and Genomic Sequencing in Latin America and the Resulting Social Justice and Ethical Considerations
Authors: Cabello Juan , Novoa Fernando , Huff Hanalise , Colombo Marta
Published: January 2021

Newborn screening (NBS) has widely been utilized in developed countries as a cost-effective public health strategy that reduces morbidity and mortality. Developing countries, however, are new to the NBS scene and have their own unique challenges, both in instituting the program as well as effectively acting on the results. NBS offers numerous ethical issues on a global scale, however, here we argue that there are unique ethical issues surrounding the development and expansion of newborn screening in Latin America given its highly heterogenous population. Once a NBS program is effectively instated, ethical considerations continue when pursuing expansion of screening to include further conditions. While Latin America grapples with the ethics of expanded newborn screening (ENBS), some developed countries discuss utility of genomic sequencing technologies in the newborn population. When the ability to detect further pathology is expanded, one must know what to do with this information. As rare diseases are identified either on ENBS or via genome sequencing, access to treatments for these rare diseases can be a real challenge. If we consider newborn screening as a global initiative, then we need more than a deontology approach to analyze these challenges; we need an approach that considers the unique characteristics of each territory and tremendous heterogeneity that exists prior to the implementation of these programs. As genomic technology advances further in the developed world, while some developing countries still lack even basic newborn screening, there is a further widening of the gap in global health disparities. The question is posed as to who has responsibility for these newborns’ lives on an international level. Without an approach towards newborn screening that accounts for the diverse global population, we believe optimal outcomes for newborns and families across the world will not be achieved.
A Secure and Computable Blockchain-Based Data Sharing Scheme in IoT System
Authors: Sun Shuang , Du Rong , Chen Shudong
Published: January 2021

The internet of things (IoT) devices are expected to collect vast amounts of data that support different kinds of applications such as health monitor, smart home, and traffic management. However, its characteristics such as resource-constrained nature, dynamicity, and large-scale growth bring challenges to secure IoT data sharing. Nowadays, blockchain-based ciphertext-policy attribute-based encryption (CP-ABE) was proposed to realize secure IoT data sharing. In blockchain-based CP-ABE data sharing schemes, the data are encrypted and stored in the cloud. Once users want to process the data, they should download and then decrypt the ciphertext in the client-end, and after processing the data, users encrypt and upload the ciphertext onto the cloud. This outweighs the advantage of using cloud computing resources. Fully homomorphic encryption (FHE) and homomorphic signature technology may be adopted to realize ciphertext computation and for correctness checking of ciphertext computation results. In this paper, we propose a secure and computable IoT data sharing system to ensure users enjoying the computation convenience of the cloud-end. Specifically, the proposed system integrates CP-ABE and FHE to realize secure IoT data sharing and ciphertext computation. In addition, we generated homomorphic signatures of ciphertexts to enable users to check the correctness of the ciphertext computation results. Moreover, to supervise the cloud, providing the honest IoT data access control, storage, and computing services for users, we recorded the access policy of the data, the hash of the data, the signature of the ciphertext, and the homomorphic signature of the ciphertext on the blockchain. The performance evaluation and security analysis show the proposed scheme is practical and secure.