bluuebunny/crossref_metadata_2025 huggingface dataset:
Size Selective Harvesting Does Not Result in Reproductive Isolation among Experimental Lines of Zebrafish, Danio rerio: Implications for Managing Harvest-Induced Evolution
Authors: Roy Tamal , Fromm Kim , Sbragaglia Valerio , Bierbach David , Arlinghaus Robert
Published: February 2021

Size-selective mortality is common in fish stocks. Positive size-selection happens in fisheries where larger size classes are preferentially targeted while gape-limited natural predation may cause negative size-selection for smaller size classes. As body size and correlated behavioural traits are sexually selected, harvest-induced trait changes may promote prezygotic reproductive barriers among selection lines experiencing differential size-selective mortality. To investigate this, we used three experimental lines of zebrafish (Danio rerio) exposed to positive (large-harvested), negative (small-harvested) and random (control line) size-selective mortality for five generations. We tested prezygotic preferences through choice tests and spawning trials. In the preference tests without controlling for body size, we found that females of all lines preferred males of the generally larger small-harvested line. When the body size of stimulus fish was statistically controlled, this preference disappeared and a weak evidence of line-assortative preference emerged, but only among large-harvested line fish. In subsequent spawning trials, we did not find evidence for line-assortative reproductive allocation in any of the lines. Our study suggests that size-selection due to fisheries or natural predation does not result in reproductive isolation. Gene flow between wild-populations and populations adapted to size-selected mortality may happen during secondary contact which can speed up trait recovery.
Bioecological and Behavioral Interaction between Pollinating Bees and the Pioneer Shrub Ludwigia nervosa in Degraded Area Suggests an Exotic Bee as Its Major Pollinator
Authors: Ferreira Eliana Aparecida , Boff Samuel , Verza Sandra S. , Mussury Rosilda Mara
Published: February 2021

The flowers of plants of the genus Ludwigia are an important source of food for several species of bees. In the current study, we conducted an experiment with the aim to describe the reproductive biology and phenology of L. nervosa; to identify the species of visiting bees; analyze the foraging behavior of bees; and to investigate whether the reproductive success of the species is related to the foraging activity of bees. We found that the flowers received visits from several native bee species (n = 7), in addition of the exotic honey bees which came to be the dominant species. During visits the majority of the bees foraged in both resources, pollen and nectar. The significantly higher production of fruits in open pollinated pollination experiment compared to artificial cross pollination, suggests honey bees as effective pollinator of this plant species in the study site. Pollen deposition occurs efficiently, given the absence of pollen limitation. Despite massive visitation of honey bees, Ludwigianervosa is attractive to native bees, and therefore it may help to sustain population of both native and exotic pollinators in fragmented humid areas.
In Silico Screening of Natural Products Isolated from Mexican Herbal Medicines against COVID-19
Authors: Rivero-Segura Nadia A. , Gomez-Verjan Juan C.
Published: February 2021

The COVID-19 pandemic has already taken the lives of more than 2 million people worldwide, causing several political and socio-economic disturbances in our daily life. At the time of publication, there are non-effective pharmacological treatments, and vaccine distribution represents an important challenge for all countries. In this sense, research for novel molecules becomes essential to develop treatments against the SARS-CoV-2 virus. In this context, Mexican natural products have proven to be quite useful for drug development; therefore, in the present study, we perform an in silico screening of 100 compounds isolated from the most commonly used Mexican plants, against the SARS-CoV-2 virus. As results, we identify ten compounds that meet leadlikeness criteria (emodin anthrone, kaempferol, quercetin, aesculin, cichoriin, luteolin, matricin, riolozatrione, monocaffeoyl tartaric acid, aucubin). According to the docking analysis, only three compounds target the key proteins of SARS-CoV-2 (quercetin, riolozatrione and cichoriin), but only one appears to be safe (cichoriin). ADME (absorption, distribution, metabolism and excretion) properties and the physiologically based pharmacokinetic (PBPK) model show that cichoriin reaches higher lung levels (100 mg/Kg, IV); therefore, it may be considered in developing therapeutic tools.
Receptor-Arrestin Interactions: The GPCR Perspective
Authors: Seyedabadi Mohammad , Gharghabi Mehdi , Gurevich Eugenia V. , Gurevich Vsevolod V.
Published: February 2021

Arrestins are a small family of four proteins in most vertebrates that bind hundreds of different G protein-coupled receptors (GPCRs). Arrestin binding to a GPCR has at least three functions: precluding further receptor coupling to G proteins, facilitating receptor internalization, and initiating distinct arrestin-mediated signaling. The molecular mechanism of arrestin–GPCR interactions has been extensively studied and discussed from the “arrestin perspective”, focusing on the roles of arrestin elements in receptor binding. Here, we discuss this phenomenon from the “receptor perspective”, focusing on the receptor elements involved in arrestin binding and emphasizing existing gaps in our knowledge that need to be filled. It is vitally important to understand the role of receptor elements in arrestin activation and how the interaction of each of these elements with arrestin contributes to the latter’s transition to the high-affinity binding state. A more precise knowledge of the molecular mechanisms of arrestin activation is needed to enable the construction of arrestin mutants with desired functional characteristics.
Deeper Insights on Alchornea cordifolia (Schumach. & Thonn.) Müll.Arg Extracts: Chemical Profiles, Biological Abilities, Network Analysis and Molecular Docking
Authors: Sinan Kouadio Ibrahime , Ak Gunes , Etienne Ouattara Katinan , Jekő József , Cziáky Zoltán , Gupcsó Katalin , João Rodrigues Maria , Custodio Luisa , Mahomoodally Mohamad Fawzi , Sharmeen Jugreet B. , Brunetti Luigi , Leone Sheila , Recinella Lucia , Chiavaroli Annalisa , Orlando Giustino , Menghini Luigi , Tacchini Massimo , Ferrante Claudio , Zengin Gokhan
Published: February 2021

Alchornea cordifolia (Schumach. & Thonn.) Müll. Arg. is a well-known African medicinal plant traditionally used for various healing purposes. In the present study, methanolic, ethyl acetate and infusion extracts of A. cordifolia leaves were studied for their total phenolic and flavonoid contents and screened for their chemical composition. Moreover, the enzyme (acetyl- and butyryl-cholinesterases, α-amylase, α-glucosidase, and tyrosinase) inhibitory and cytotoxicity activities on HepG2: human hepatocellular carcinoma cells, B16 4A5: murine melanoma cells, and S17: murine bone marrow (normal) cells of extracts were evaluated. Finally, components-targets and docking analyzes were conducted with the aim to unravel the putative mechanisms underlying the observed bio-pharmacological effects. Interestingly, the infusion and methanolic extracts showed significantly higher total phenolic and flavonoid contents compared with the ethyl acetate extract (TPC: 120.38–213.12 mg GAE/g and TFC: 9.66–57.18 mg RE/g). Besides, the methanolic extracts followed by the infusion extracts were revealed to contain a higher number of compounds (84 and 74 compounds, respectively), while only 64 compounds were observed for the ethyl acetate extract. Gallic acid, ellagic acid, shikimic acid, rutin, quercetin, myricetin, vitexin, quercitrin, kaempferol, and naringenin were among the compounds that were commonly identified in all the studied extracts. Additionally, the methanolic and infusion extracts displayed higher antioxidant capacity than ethyl acetate extract in all assays performed. In ABTS and DPPH radical scavenging assays, the methanol extract (500.38 mg TE/g for DPPH and 900.64 mg TE/g for ABTS) exhibited the best ability, followed by the water and ethyl acetate extracts. Furthermore, the extracts exhibited differential enzyme inhibitory profiles. In particular, the methanolic and infusion extracts showed better cytotoxic selectivity activity against human hepatocellular carcinoma cells. Overall, this study demonstrated A cordifolia to be a species worthy of further investigations, given its richness in bioactive phytochemicals and wide potentialities for antioxidants and pharmacological agents.
Diethylstilbestrol Modifies the Structure of Model Membranes and Is Localized Close to the First Carbons of the Fatty Acyl Chains
Authors: Ausili Alessio , Rodríguez-González Inés , Torrecillas Alejandro , Teruel José A. , Gómez-Fernández Juan C.
Published: February 2021

The synthetic estrogen diethylstilbestrol (DES) is used to treat metastatic carcinomas and prostate cancer. We studied its interaction with membranes and its localization to understand its mechanism of action and side-effects. We used differential scanning calorimetry (DSC) showing that DES fluidized the membrane and has poor solubility in DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) in the fluid state. Using small-angle X-ray diffraction (SAXD), it was observed that DES increased the thickness of the water layer between phospholipid membranes, indicating effects on the membrane surface. DSC, X-ray diffraction, and 31P-NMR spectroscopy were used to study the effect of DES on the Lα-to-HII phase transition, and it was observed that negative curvature of the membrane is promoted by DES, and this effect may be significant to understand its action on membrane enzymes. Using the 1H-NOESY-NMR-MAS technique, cross-relaxation rates for different protons of DES with POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) protons were calculated, suggesting that the most likely location of DES in the membrane is with the main axis parallel to the surface and close to the first carbons of the fatty acyl chains of POPC. Molecular dynamics simulations were in close agreements with the experimental results regarding the location of DES in phospholipids bilayers.
Two Subpopulations of Human Monocytes That Differ by Mitochondrial Membrane Potential
Authors: Nikiforov Nikita G. , Ryabova Anastasia , Kubekina Marina V. , Romanishkin Igor D. , Trofimov Kirill A. , Chegodaev Yegor S. , Ivanova Ekaterina , Orekhov Alexander N.
Published: February 2021

Atherosclerosis is associated with a chronic local inflammatory process in the arterial wall. Our previous studies have demonstrated the altered proinflammatory activity of circulating monocytes in patients with atherosclerosis. Moreover, atherosclerosis progression and monocyte proinflammatory activity were associated with mitochondrial DNA (mtDNA) mutations in circulating monocytes. The role of mitochondria in the immune system cells is currently well recognized. They can act as immunomodulators by releasing molecules associated with bacterial infection. We hypothesized that atherosclerosis can be associated with changes in the mitochondrial function of circulating monocytes. To test this hypothesis, we performed live staining of the mitochondria of CD14+ monocytes from healthy donors and atherosclerosis patients with MitoTracker Orange CMTMRos dye, which is sensitive to mitochondrial membrane potential. The intensity of such staining reflects mitochondrial functional activity. We found that parts of monocytes in the primary culture were characterized by low MitoTracker staining (MitoTracker-low monocytes). Such cells were morphologically similar to cells with normal staining and able to metabolize 5-aminolevulinic acid and accumulate the heme precursor protoporphyrin IX (PplX), indicative of partially preserved mitochondrial function. We assessed the proportion of MitoTracker-low monocytes in the primary culture for each study subject and compared the results with other parameters, such as monocyte ability to lipopolysaccharide (LPS)-induced proinflammatory activation and the intima-media thickness of carotid arteries. We found that the proportion of MitoTracker-low monocytes was associated with the presence of atherosclerotic plaques. An increased number of such monocytes in the primary culture was associated with a reduced proinflammatory activation ability of cells. The obtained results indicate the presence of circulating monocytes with mitochondrial dysfunction and the association of such cells with chronic inflammation and atherosclerosis development.
2D Nanomaterial, Ti3C2 MXene-Based Sensor to Guide Lung Cancer Therapy and Management
Authors: Sadiq Mahek , Pang Lizhi , Johnson Michael , Sathish Venkatachalem , Zhang Qifeng , Wang Danling
Published: February 2021

Major advances in cancer control can be greatly aided by early diagnosis and effective treatment in its pre-invasive state. Lung cancer (small cell and non-small cell) is a leading cause of cancer-related deaths among both men and women around the world. A lot of research attention has been directed toward diagnosing and treating lung cancer. A common method of lung cancer treatment is based on COX-2 (cyclooxygenase-2) inhibitors. This is because COX-2 is commonly overexpressed in lung cancer and also the abundance of its enzymatic product prostaglandin E2 (PGE2). Instead of using traditional COX-2 inhibitors to treat lung cancer, here, we introduce a new anti-cancer strategy recently developed for lung cancer treatment. It adopts more abundant omega-6 (ω-6) fatty acids such as dihomo-γ-linolenic acid (DGLA) in the daily diet and the commonly high levels of COX-2 expressed in lung cancer to promote the formation of 8-hydroxyoctanoic acid (8-HOA) through a new delta-5-desaturase (D5Di) inhibitor. The D5Di does not only limit the metabolic product, PGE2, but also promote the COX-2 catalyzed DGLA peroxidation to form 8-HOA, a novel anti-cancer free radical byproduct. Therefore, the measurement of the PGE2 and 8-HOA levels in cancer cells can be an effective method to treat lung cancer by providing in-time guidance. In this paper, we mainly report on a novel sensor, which is based on a newly developed functionalized nanomaterial, 2-dimensional nanosheets, or Ti3C2 MXene. The preliminary results have proven to sensitively, selectively, precisely, and effectively detect PGE2 and 8-HOA in A549 lung cancer cells. The capability of the sensor to detect trace level 8-HOA in A549 has been verified in comparison with the traditional gas chromatography–mass spectrometry (GC–MS) method. The sensing principle could be due to the unique structure and material property of Ti3C2 MXene: a multilayered structure and extremely large surface area, metallic conductivity, and ease and versatility in surface modification. All these make the Ti3C2 MXene-based sensor selectively adsorb 8-HOA molecules through effective charge transfer and lead to a measurable change in the conductivity of the material with a high signal-to-noise ratio and excellent sensitivity.
Inflammatory Brain Lesions as Omen of Primary Central Nervous System Lymphoma: A Case Report and Literature Review
Authors: Kim Yeong , Kim Seul , Jung Tae-Young , Kim In-Young , Lee Kyung-Hwa , Moon Kyung-Sub
Published: February 2021

We report a rare case that was initially diagnosed as an inflammatory lesion and ultimately confirmed as primary central nervous system lymphoma (PCNSL) in an immunocompetent patient who was not treated with corticosteroid prior to the initial biopsy. A 70-year-old female patient presented with numbness in the left side of face, arm, and leg. Brain magnetic resonance imaging (MRI) revealed a lesion with intense gadolinium (Gd)-enhancement in the ventral portion of the midbrain. A stereotactic biopsy demonstrated mixed T-cell and B-cell infiltrating inflammatory lesions without demyelination. Three months after postoperative treatment with steroid, the lesion markedly decreased on follow-up MRI. Twenty-six months after the initial attack, she complained of dysarthria and urinary incontinence. Repetitive MRI showed a lesion with homogeneous enhancement, extensively involving the bilateral cerebral hemisphere, corpus callosum, and the right middle cerebellar peduncle. The confirmed diagnosis was diffuse large B-cell lymphoma on the second biopsy. Despite our best efforts, she died 38 months after disease onset. Based on review of the literature and our case, preceding inflammatory lesions are not always demyelinating and T-cell dominant inflammatory lesions. When the initial biopsy reveals an inflammatory lesion in an old-aged patient, the clinician should keep in mind the development of PCNSL and perform close clinical and radiological observations for a timely diagnosis.
Brain Structural Covariance Networks in Behavioral Variant of Frontotemporal Dementia
Authors: Nigro Salvatore , Tafuri Benedetta , Urso Daniele , De Blasi Roberto , Frisullo Maria Elisa , Barulli Maria Rosaria , Capozzo Rosa , Cedola Alessia , Gigli Giuseppe , Logroscino Giancarlo
Published: February 2021

Recent research on behavioral variant frontotemporal dementia (bvFTD) has shown that personality changes and executive dysfunctions are accompanied by a disease-specific anatomical pattern of cortical and subcortical atrophy. We investigated the structural topological network changes in patients with bvFTD in comparison to healthy controls. In particular, 25 bvFTD patients and 20 healthy controls underwent structural 3T MRI. Next, bilaterally averaged values of 34 cortical surface areas, 34 cortical thickness values, and six subcortical volumes were used to capture single-subject anatomical connectivity and investigate network organization using a graph theory approach. Relative to controls, bvFTD patients showed altered small-world properties and decreased global efficiency, suggesting a reduced ability to combine specialized information from distributed brain regions. At a local level, patients with bvFTD displayed lower values of local efficiency in the cortical thickness of the caudal and rostral middle frontal gyrus, rostral anterior cingulate, and precuneus, cuneus, and transverse temporal gyrus. A significant correlation was also found between the efficiency of caudal anterior cingulate thickness and Mini-Mental State Examination (MMSE) scores in bvFTD patients. Taken together, these findings confirm the selective disruption in structural brain networks of bvFTD patients, providing new insights on the association between cognitive decline and graph properties.
Gender Affirmative Action and Management: A Systematic Literature Review on How Diversity and Inclusion Management Affect Gender Equity in Organizations
Authors: Furtado Julia V. , Moreira António C. , Mota Jorge
Published: February 2021

Gender affirmative action (AA) in management remains a controversial topic among scholars, practitioners, and employees. While some individuals may support the use of AA policies as a means of increasing representation of women, others are not supportive at all, further understanding gender AA as an unacceptable violation of merit—even when targeted by it. With the aim of analyzing how scholars have approached the subject, we systematically reviewed 76 published articles (SCOPUS database), covering the extant literature on gender AA and management. Findings indicate a consensus regarding the common antecedents of attitudes towards gender AA with prior experiences with AA and diversity management (DM) (as well as general perceptions of AA). Performance and satisfaction appear as the predominant outcomes. In addition, while investigating the differences among AA, equal employment opportunity (EEO) and diversity management (DM), scholars are mainly focused on the effectiveness of AA as a means of increasing the inclusion of minorities in general. We conclude that despite marginal studies on employees’ attitudes toward gender AA, there is a gap in the literature, particularly an absence of research on the bivalent position of meritocracy (or merit violation) as both an antecedent and outcome of attitudes towards AA, which deserves further scrutiny.
Evaluation of the Legal Framework for Building Fire Safety Regulations in Spain
Authors: Osácar Amaya , Echeverria Trueba Juan Bautista , Meacham Brian
Published: February 2021

There is a trend in Europe towards increasing the quality and performance of regulations. At the same time, regulatory failure has been observed in the area of building fire safety regulation in England and elsewhere. As a result, an analysis of the appropriateness of fire safety regulations in Spain is warranted, with the objective being to assess whether a suitable level of fire safety is currently being delivered. Three basic elements must be considered in such analysis: the legal and regulatory framework, the level of fire risk/safety of buildings that is expected and the level which actually results, and a suitable method of analysis. The focus of this paper is creating a legal and regulatory framework, in particular with respect to fire safety in buildings. Components of an ”ideal” building regulatory framework to adequately control fire risk are presented, the existing building regulatory framework is summarized, and an analysis of the gaps between the ideal and the existing systems is presented. It is concluded that the gaps between the ideal and the existing framework are significant, and that the current fire safety regulations are not appropriate for assuring delivery of the intended level of fire risk mitigation.
Mechanical Behavior and Frost-Resistance of Alkali-Activated Cement Concrete with Blended Binder at Ambient Curing Condition
Authors: Tekle Biruk Hailu , Holschemacher Klaus , Löber Philipp , Heiden Björn
Published: February 2021

Concrete is the most commonly used construction material because of its various advantages, such as versatility, familiarity, strength, and durability, and it will continue to be in demand far into the future. However, with today’s sensitivity to environmental protection, this material faces unprecedented challenges because of its high greenhouse gas emissions, mainly during cement production. This paper investigates one of the promising cement replacement materials, alkali-activated cement (AAC) concrete. Being produced mainly from byproduct materials and having a comparable structural performance to conventional concrete, AAC concrete can transform the construction industry. Mechanical properties such as compressive and flexural strength and the relationship between them are studied. Different source materials such as fly ash (FA), ground granulated blast furnace slag (GGBS), silica fume (SF), and Metakaolin (MK) are used. The effect of the source materials and the activator solutions on the concrete performance is studied. Furthermore, the freeze-thaw resistance of the concrete is studied. The study results showed that the behavior of AAC depends highly on the source material combinations and type used. The effect of the alkaline solution is also dependent on the source material used. Mixes with higher GGBS content showed the highest strength, while mixes with MK showed the highest flexural strength. The freeze-thaw test results showed that proper design of AAC concrete with lower water content is critical to achieving a good resistance.
Microbe–Mucus Interface in the Pathogenesis of Colorectal Cancer
Authors: Coleman Olivia I. , Haller Dirk
Published: February 2021

Overlying gastrointestinal epithelial cells is the transparent mucus layer that separates the lumen from the host. The dynamic mucus layer serves to lubricate the mucosal surface, to protect underlying epithelial cells, and as a transport medium between luminal contents and epithelial cells. Furthermore, it provides a habitat for commensal bacteria and signals to the underlying immune system. Mucins are highly glycosylated proteins, and their glycocode is tissue-specific and closely linked to the resident microbiota. Aberrant mucin expression and glycosylation are linked to chronic inflammation and gastrointestinal cancers, including colorectal cancer (CRC). Aberrant mucus production compromises the mucus layer and allows bacteria to come into close contact with the intestinal epithelium, potentially triggering unfavorable host responses and the subsequent development of tumors. Here, we review our current understanding of the interaction between the intestinal microbiota and mucus in healthy and CRC subjects. Deep knowledge of the intricate mechanisms of microbe–mucus interactions may contribute to the development of novel treatment strategies for CRC, in which a dysfunctional mucus layer is observed.
Activation of the S100A7/RAGE Pathway by IGF-1 Contributes to Angiogenesis in Breast Cancer
Authors: Muoio Maria Grazia , Talia Marianna , Lappano Rosamaria , Sims Andrew H. , Vella Veronica , Cirillo Francesca , Manzella Livia , Giuliano Marika , Maggiolini Marcello , Belfiore Antonino , De Francesco Ernestina Marianna
Published: February 2021

Background: Breast cancer (BC) mortality is increased among obese and diabetic patients. Both obesity and diabetes are associated with dysregulation of both the IGF-1R and the RAGE (Receptor for Advanced Glycation End Products) pathways, which contribute to complications of these disorders. The alarmin S100A7, signaling through the receptor RAGE, prompts angiogenesis, inflammation, and BC progression. Methods: We performed bioinformatic analysis of BC gene expression datasets from published studies. We then used Estrogen Receptor (ER)-positive BC cells, CRISPR-mediated IGF-1R KO BC cells, and isogenic S100A7-transduced BC cells to investigate the role of IGF-1/IGF-1R in the regulation of S100A7 expression and tumor angiogenesis. To this aim, we also used gene silencing and pharmacological inhibitors, and we performed gene expression and promoter studies, western blotting analysis, ChIP and ELISA assays, endothelial cell proliferation and tube formation assay. Results: S100A7 expression correlates with worse prognostic outcomes in human BCs. In BC cells, the IGF-1/IGF-1R signaling engages STAT3 activation and its recruitment to the S100A7 promoter toward S100A7 increase. In human vascular endothelial cells, S100A7 activates RAGE signaling and prompts angiogenic effects. Conclusions: In ER-positive BCs the IGF-1 dependent activation of the S100A7/RAGE signaling in adjacent endothelial cells may serve as a previously unidentified angiocrine effector. Targeting S100A7 may pave the way for a better control of BC, particularly in conditions of unopposed activation of the IGF-1/IGF-1R axis.
Correction: Hu, W., et al. Targeting Dopamine Receptor D2 by Imipridone Suppresses Uterine Serous Cancer Malignant Phenotype. Cancers 2020, 12, 2436
Authors: Hu Wen , Zhang Li , Ferri-Borgogno Sammy , Kwan Suet-Ying , Lewis Kelsey E. , Cun Han T. , Yeung Tsz-Lun , Soliman Pamela T. , Tarapore Rohinton S. , Allen Joshua E. , Guan Xinyuan , Lu Karen H. , Mok Samuel C. , Au-Yeung Chi-Lam
Published: February 2021

In the original article, there was a mistake in Figure 2B as published [...]
Tumor Suppressor Protein p53 and Inhibitor of Apoptosis Proteins in Colorectal Cancer—A Promising Signaling Network for Therapeutic Interventions
Authors: Güllülü Ömer , Hehlgans Stephanie , Rödel Claus , Fokas Emmanouil , Rödel Franz
Published: February 2021

Despite recent advances in the treatment of colorectal cancer (CRC), patient’s individual response and clinical follow-up vary considerably with tumor intrinsic factors to contribute to an enhanced malignancy and therapy resistance. Among these markers, upregulation of members of the inhibitor of apoptosis protein (IAP) family effects on tumorigenesis and radiation- and chemo-resistance by multiple pathways, covering a hampered induction of apoptosis/autophagy, regulation of cell cycle progression and DNA damage response. These mechanisms are tightly controlled by the tumor suppressor p53 and thus transcriptional and post-translational regulation of IAPs by p53 is expected to occur in malignant cells. By this, cellular IAP1/2, X-linked IAP, Survivin, BRUCE and LIVIN expression/activity, as well as their intracellular localization is controlled by p53 in a direct or indirect manner via modulating a multitude of mechanisms. These cover, among others, transcriptional repression and the signal transducer and activator of transcription (STAT)3 pathway. In addition, p53 mutations contribute to deregulated IAP expression and resistance to therapy. This review aims at highlighting the mechanistic and clinical importance of IAP regulation by p53 in CRC and describing potential therapeutic strategies based on this interrelationship.
Arabidopsis Mitochondrial Transcription Termination Factor mTERF2 Promotes Splicing of Group IIB Introns
Authors: Lee Kwanuk , Leister Dario , Kleine Tatjana
Published: February 2021

Plastid gene expression (PGE) is essential for chloroplast biogenesis and function and, hence, for plant development. However, many aspects of PGE remain obscure due to the complexity of the process. A hallmark of nuclear-organellar coordination of gene expression is the emergence of nucleus-encoded protein families, including nucleic-acid binding proteins, during the evolution of the green plant lineage. One of these is the mitochondrial transcription termination factor (mTERF) family, the members of which regulate various steps in gene expression in chloroplasts and/or mitochondria. Here, we describe the molecular function of the chloroplast-localized mTERF2 in Arabidopsis thaliana. The complete loss of mTERF2 function results in embryo lethality, whereas directed, microRNA (amiR)-mediated knockdown of MTERF2 is associated with perturbed plant development and reduced chlorophyll content. Moreover, photosynthesis is impaired in amiR-mterf2 plants, as indicated by reduced levels of photosystem subunits, although the levels of the corresponding messenger RNAs are not affected. RNA immunoprecipitation followed by RNA sequencing (RIP-Seq) experiments, combined with whole-genome RNA-Seq, RNA gel-blot, and quantitative RT-PCR analyses, revealed that mTERF2 is required for the splicing of the group IIB introns of ycf3 (intron 1) and rps12.
Prolactin Rescues Immature B Cells from Apoptosis-Induced BCR-Aggregation through STAT3, Bcl2a1a, Bcl2l2, and Birc5 in Lupus-Prone MRL/lpr Mice
Authors: Flores-Fernández Rocio , Aponte-López Angélica , Suárez-Arriaga Mayra C. , Gorocica-Rosete Patricia , Pizaña-Venegas Alberto , Chávez-Sanchéz Luis , Blanco-Favela Francico , Fuentes-Pananá Ezequiel M. , Chávez-Rueda Adriana K.
Published: February 2021

Self-reactive immature B cells are eliminated through apoptosis by tolerance mechanisms, failing to eliminate these cells results in autoimmune diseases. Prolactin is known to rescue immature B cells from B cell receptor engagement-induced apoptosis in lupus-prone mice. The objective of this study was to characterize in vitro prolactin signaling in immature B cells, using sorting, PCR array, RT-PCR, flow cytometry, and chromatin immunoprecipitation. We found that all B cell maturation stages in bone marrow express the prolactin receptor long isoform, in both wild-type and MRL/lpr mice, but its expression increased only in the immature B cells of the latter, particularly at the onset of lupus. In these cells, activation of the prolactin receptor promoted STAT3 phosphorylation and upregulation of the antiapoptotic Bcl2a1a, Bcl2l2, and Birc5 genes. STAT3 binding to the promoter region of these genes was confirmed through chromatin immunoprecipitation. Furthermore, inhibitors of prolactin signaling and STAT3 activation abolished the prolactin rescue of self-engaged MRL/lpr immature B cells. These results support a mechanism in which prolactin participates in the emergence of lupus through the rescue of self-reactive immature B cell clones from central tolerance clonal deletion through the activation of STAT3 and transcriptional regulation of a complex network of genes related to apoptosis resistance.
Characterization of Early-Onset Finger Osteoarthritis-Like Condition Using Patient-Derived Induced Pluripotent Stem Cells
Authors: Rim Yeri Alice , Nam Yoojun , Park Narae , Lee Kijun , Jung Hyerin , Jung Seung Min , Lee Jennifer , Ju Ji Hyeon
Published: February 2021

Early osteoarthritis (OA)-like symptoms are difficult to study owing to the lack of disease samples and animal models. In this study, we generated induced pluripotent stem cell (iPSC) lines from a patient with a radiographic early-onset finger osteoarthritis (efOA)-like condition in the distal interphalangeal joint and her healthy sibling. We differentiated those cells with similar genetic backgrounds into chondrogenic pellets (CPs) to confirm efOA. CPs generated from efOA-hiPSCs (efOA-CPs) showed lower levels of COL2A1, which is a key marker of hyaline cartilage after complete differentiation, for 21 days. Increase in pellet size and vacuole-like morphologies within the pellets were observed in the efOA-CPs. To analyze the changes occurred during the development of vacuole-like morphology and the increase in pellet size in efOA-CPs, we analyzed the expression of OA-related markers on day 7 of differentiation and showed an increase in the levels of COL1A1, RUNX2, VEGFA, and AQP1 in efOA-CPs. IL-6, MMP1, and MMP10 levels were also increased in the efOA-CPs. Taken together, we present proof-of-concept regarding disease modeling of a unique patient who showed OA-like symptoms.
A Transcription Regulatory Sequence in the 5′ Untranslated Region of SARS-CoV-2 Is Vital for Virus Replication with an Altered Evolutionary Pattern against Human Inhibitory MicroRNAs
Authors: Mohammadi-Dehcheshmeh Manijeh , Moghbeli Sadrollah Molaei , Rahimirad Samira , Alanazi Ibrahim O. , Shehri Zafer Saad Al , Ebrahimie Esmaeil
Published: February 2021

Our knowledge of the evolution and the role of untranslated region (UTR) in SARS-CoV-2 pathogenicity is very limited. Leader sequence, originated from UTR, is found at the 5′ ends of all encoded SARS-CoV-2 transcripts, highlighting its importance. Here, evolution of leader sequence was compared between human pathogenic and non-pathogenic coronaviruses. Then, profiling of microRNAs that can inactivate the key UTR regions of coronaviruses was carried out. A distinguished pattern of evolution in leader sequence of SARS-CoV-2 was found. Mining all available microRNA families against leader sequences of coronaviruses resulted in discovery of 39 microRNAs with a stable thermodynamic binding energy. Notably, SARS-CoV-2 had a lower binding stability against microRNAs. hsa-MIR-5004-3p was the only human microRNA able to target the leader sequence of SARS and to a lesser extent, also SARS-CoV-2. However, its binding stability decreased remarkably in SARS-COV-2. We found some plant microRNAs with low and stable binding energy against SARS-COV-2. Meta-analysis documented a significant (p < 0.01) decline in the expression of MIR-5004-3p after SARS-COV-2 infection in trachea, lung biopsy, and bronchial organoids as well as lung-derived Calu-3 and A549 cells. The paucity of the innate human inhibitory microRNAs to bind to leader sequence of SARS-CoV-2 can contribute to its high replication in infected human cells.
TREM2 Mediates Microglial Anti-Inflammatory Activations in Alzheimer’s Disease: Lessons Learned from Transcriptomics
Authors: Xue Feng , Du Heng
Published: February 2021

Alzheimer’s disease (AD) is a lethal neurodegenerative disorder primarily affecting the aged population. The etiopathogenesis of AD, especially that of the sporadic type, remains elusive. The triggering receptor expressed on myeloid cells 2 (TREM2), a member of TREM immunoglobulin superfamily, plays a critical role in microglial physiology. Missense mutations in human TREM2 are determined as genetic risk factors associated with the development of sporadic AD. However, the roles of TREM2 in the pathogenesis of AD are still to be established. In this review, we outlined the influence of Trem2 on balance of pro- and anti-inflammatory microglial activations from a perspective of AD mouse model transcriptomics. On this basis, we further speculated the roles of TREM2 in different stages of AD, which may shed light to the development of TREM2-targeted strategy for the prevention and treatment of this neurodegenerative disorder.
Light-Dependent Translation Change of Arabidopsis psbA Correlates with RNA Structure Alterations at the Translation Initiation Region
Authors: Gawroński Piotr , Enroth Christel , Kindgren Peter , Marquardt Sebastian , Karpiński Stanisław , Leister Dario , Jensen Poul , Vinther Jeppe , Scharff Lars
Published: February 2021

mRNA secondary structure influences translation. Proteins that modulate the mRNA secondary structure around the translation initiation region may regulate translation in plastids. To test this hypothesis, we exposed Arabidopsis thaliana to high light, which induces translation of psbA mRNA encoding the D1 subunit of photosystem II. We assayed translation by ribosome profiling and applied two complementary methods to analyze in vivo RNA secondary structure: DMS-MaPseq and SHAPE-seq. We detected increased accessibility of the translation initiation region of psbA after high light treatment, likely contributing to the observed increase in translation by facilitating translation initiation. Furthermore, we identified the footprint of a putative regulatory protein in the 5′ UTR of psbA at a position where occlusion of the nucleotide sequence would cause the structure of the translation initiation region to open up, thereby facilitating ribosome access. Moreover, we show that other plastid genes with weak Shine-Dalgarno sequences (SD) are likely to exhibit psbA-like regulation, while those with strong SDs do not. This supports the idea that changes in mRNA secondary structure might represent a general mechanism for translational regulation of psbA and other plastid genes.
AAV-Mediated CRISPRi and RNAi Based Gene Silencing in Mouse Hippocampal Neurons
Authors: Deutsch Matthias , Günther Anne , Lerchundi Rodrigo , Rose Christine R. , Balfanz Sabine , Baumann Arnd
Published: February 2021

Uncovering the physiological role of individual proteins that are part of the intricate process of cellular signaling is often a complex and challenging task. A straightforward strategy of studying a protein’s function is by manipulating the expression rate of its gene. In recent years, the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9-based technology was established as a powerful gene-editing tool for generating sequence specific changes in proliferating cells. However, obtaining homogeneous populations of transgenic post-mitotic neurons by CRISPR/Cas9 turned out to be challenging. These constraints can be partially overcome by CRISPR interference (CRISPRi), which mediates the inhibition of gene expression by competing with the transcription machinery for promoter binding and, thus, transcription initiation. Notably, CRISPR/Cas is only one of several described approaches for the manipulation of gene expression. Here, we targeted neurons with recombinant Adeno-associated viruses to induce either CRISPRi or RNA interference (RNAi), a well-established method for impairing de novo protein biosynthesis by using cellular regulatory mechanisms that induce the degradation of pre-existing mRNA. We specifically targeted hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels, which are widely expressed in neuronal tissues and play essential physiological roles in maintaining biophysical characteristics in neurons. Both of the strategies reduced the expression levels of three HCN isoforms (HCN1, 2, and 4) with high specificity. Furthermore, detailed analysis revealed that the knock-down of just a single HCN isoform (HCN4) in hippocampal neurons did not affect basic electrical parameters of transduced neurons, whereas substantial changes emerged in HCN-current specific properties.
Identification of Mint Scents Using a QCM Based E-Nose
Authors: Okur Salih , Sarheed Mohammed , Huber Robert , Zhang Zejun , Heinke Lars , Kanbar Adnan , Wöll Christof , Nick Peter , Lemmer Uli
Published: February 2021

Mints emit diverse scents that exert specific biological functions and are relevance for applications. The current work strives to develop electronic noses that can electronically discriminate the scents emitted by different species of Mint as alternative to conventional profiling by gas chromatography. Here, 12 different sensing materials including 4 different metal oxide nanoparticle dispersions (AZO, ZnO, SnO2, ITO), one Metal Organic Frame as Cu(BPDC), and 7 different polymer films, including PVA, PEDOT:PSS, PFO, SB, SW, SG, and PB were used for functionalizing of Quartz Crystal Microbalance (QCM) sensors. The purpose was to discriminate six economically relevant Mint species (Mentha x piperita, Mentha spicata, Mentha spicata ssp. crispa, Mentha longifolia, Agastache rugosa, and Nepeta cataria). The adsorption and desorption datasets obtained from each modified QCM sensor were processed by three different classification models, including Principal Component Analysis (PCA), Linear Discriminant Analysis (LDA), and k-Nearest Neighbor Analysis (k-NN). This allowed discriminating the different Mints with classification accuracies of 97.2% (PCA), 100% (LDA), and 99.9% (k-NN), respectively. Prediction accuracies with a repeating test measurement reached up to 90.6% for LDA, and 85.6% for k-NN. These data demonstrate that this electronic nose can discriminate different Mint scents in a reliable and efficient manner.
Psychopathological Risk Factors Associated with Body Image, Body Dissatisfaction and Weight-Loss Dieting in School-Age Adolescents
Authors: Cabaco Antonio S. , Urchaga José D. , Guevara Raquel M. , Moral-García José E.
Published: February 2021

Determining the comorbidity patterns leading to suffering behavioural eating disorders (BED) that are identifiable in the early stages of life, can help prevent their becoming chronic, as well as preventing the consequences deriving from the cost and effectiveness of intervention programs. The paper focuses mainly on analysing the association between behavioural/emotional risk factors and body image, body satisfaction and diet in school children, as well as confirming whether there are differences based on sex. Several questionnaires (Strengths and Difficulties Questionnaire and several items of Health Behaviour in School-age Children) including these variables were distributed and completed by the 647 adolescents (16 year olds on average) who took part in the research project. The findings confirmed a differentiated risk profile in adolescent girls in that they had greater prevalence of emotional symptoms as a general psychopathological trait, although this was offset with their prosocial behaviour. Additionally, the findings also allowed us to conclude that the factors that predict vulnerability to BEDs are sex, the presence of emotional symptoms and social and behavioural issues. At the end of this paper, we discuss some implications and consequences that should be taken into account for future work.
Prenatal Opioid Exposure and ADHD Childhood Symptoms: A Meta-Analysis
Authors: Schwartz Ashlyn N. , Reyes Lucia M. , Meschke Laurie L. , Kintziger Kristina W.
Published: February 2021

To systematically investigate the association between prenatal opioid exposure (POE) and attention-deficit hyperactivity disorder (ADHD) symptoms in children 2–18 years old, studies were searched using PubMed, CINAHL, PsycINFO, and Web of Science from January of 1950 to October of 2019. Inclusion criteria were observational studies reporting ADHD symptoms of children with POE compared with non-exposed children or normative data. The study protocol was registered with PROSPERO: CRD42018115967. Two independent reviewers extracted data on hyperactivity/impulsivity, inattention symptoms, ADHD combined subscale symptoms, and sample characteristics. Of 223 articles screened, seven met the inclusion criteria. Data represent 319 children with POE and 1308 non-exposed children from 4.3 to 11.2 mean years from five countries. POE was positively associated with childhood hyperactivity/impulsivity (d = 1.40; 95% CI, 0.49–2.31; p = 0.003), inattention (d = 1.35; 95% CI, 0.69–2.01; p < 0.0001), and combined ADHD symptoms scores (d = 1.27; 95% CI = 0.79–1.75; p < 0.0001). POE was positively associated with ADHD combined symptom scores at preschool (d = 0.83, 95% CI, 0.57, 1.09; p < 0.0001) and school age (d = 1.45, 95% CI, 0.85 to 2.04; p < 0.0001). Results suggest increased risk of ADHD symptoms during school age. Future research is needed to clarify the relationship between biological, social, and environmental risk and ADHD symptoms for children who experienced POE.
Comparison and Selection of Data Processing Methods for the Application of Cr3+ Photoluminescence Piezospectroscopy to Thermal Barrier Coatings
Authors: Lu Ning , Zhang Yanheng , Qiu Wei
Published: February 2021

Thermal barrier coatings (TBCs) are an indispensable part of the blades used in aeroengines. Under a high-temperature service environment, the thermal oxidation stress at the interface is the main cause of thermal barrier failure. Cr3+ photoluminescence piezospectroscopy has been successfully used to analyze the thermal oxidation stress of TBCs, but systematic and quantitative analysis results for use in data processing are still lacking, especially with respect to the identification of peak positions. The processing methods used to fit spectral data were studied in this work to accurately characterize TBC thermal oxidation stress using Cr3+ photoluminescence spectroscopy. Both physical and numerical experiments were carried out, where Cr3+ photoluminescence spectra were detected from alumina ceramic samples under step-by-step uniaxial loading, and the simulated spectra were numerically deduced from the measured spectral data. Then, the peak shifts were obtained by fitting all spectral data by using Lorentzian, Gaussian and Psd-Voigt functions. By comparing the fitting results and then discussing the generation mechanism, the Lorentzian function—not the Psd-Voigt function that is most widely utilized—was regarded as the most applicable method for the application of Cr3+ photoluminescence piezospectroscopy to TBCs because of its sufficient sensitivity, stability and confidence for quantitative stress analysis.