bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Age and Temperamental Traits with Children’s Behaviour during Dental Treatment
Authors: Juárez-López Maria Lilia Adriana , Marin-Miranda Miriam , Lavalle-Carrasco Jesús , Pierdant Alberto , Sánchez-Pérez Leonor , Molina-Frechero Nelly
Published: January 2022

During paediatric dental treatment, cooperation by children is essential, and temperament can determine their behaviour style. This study aimed to associate temperamental traits and age with behaviour during paediatric dental treatment. This was an observational and cross-sectional study of patients aged 3–10 years. To determine the temperamental traits, an Emotionality Activity and Sociability Temperament Survey (EAS) was performed with the children’s parents. The type of behaviour was determined with Frankl’s criteria. The total scores for temperamental traits, means, and standard deviations were obtained. The chi-squared test, one-way ANOVA and Student’s t-test were applied. A total of 140 patients, who were 5 ± 2.1 years old, participated in the study. Age was determinant for negative behaviour, with a greater frequency in children ≤5 years old (p < 0.05), and a significant negative correlation between age and behaviour (rho = −0.245, p = 0.001). Patients with higher emotionality and activity presented negative and definitely negative behaviours more frequently (p < 0.01). The values for sociability and shyness were similar for positive or negative behaviours. In conclusion, the temperamental traits of emotionality and activity were more frequent in children with disruptive behaviours; therefore, conducting a survey on temperamental traits can be useful for planning behavioural approaches in paediatric dentistry.
Relationships between Volunteering, Neighbourhood Deprivation and Mental Wellbeing across Four British Birth Cohorts: Evidence from 10 Years of the UK Household Longitudinal Study
Authors: Mak Hei Wan , Coulter Rory , Fancourt Daisy
Published: January 2022

Volunteering is associated with greater mental, physical and social wellbeing. However, less is known about whether the health benefits of volunteering vary with two sets of factors known to shape population health and health-related behaviours: (1) age and birth cohort, and (2) place of residence. This study examined how these factors influence the relationship between volunteering and self-reported mental health using five waves of data from Understanding Society: The UK Household Longitudinal Study (UKHLS) enriched with information on neighbourhood deprivation (Index of Multiple Deprivation 2015). Two self-reported mental health and wellbeing outcomes were examined: mental distress (GHQ-12) and health-related quality of life (SF-12). The sample was stratified by cohort: pre-1945 (born before 1945), Baby Boomers (born 1945–1964), Gen X (born 1965–1979), and Millennials (born from 1980). Fixed-effects regressions revealed that volunteering was associated with reduced levels of mental distress and greater levels of health-related quality of life in older generations, but not amongst younger generations. No moderating effect of area deprivation was found. This study suggests that generational social attitudes and changes in how volunteering is portrayed and delivered could influence not only whether people volunteer, but also whether doing so bolsters health.
Acknowledgment to Reviewers of IJGI in 2021
Authors:   IJGI Editorial Office
Published: January 2022

Rigorous peer-reviews are the basis of high-quality academic publishing [...]
Repolarization of Unbalanced Macrophages: Unmet Medical Need in Chronic Inflammation and Cancer
Authors: Degboé Yannick , Poupot Rémy , Poupot Mary
Published: January 2022

Monocytes and their tissue counterpart macrophages (MP) constitute the front line of the immune system. Indeed, they are able to rapidly and efficiently detect both external and internal danger signals, thereby activating the immune system to eradicate the disturbing biological, chemical, or physical agents. They are also in charge of the control of the immune response and account for the repair of the damaged tissues, eventually restoring tissue homeostasis. The balance between these dual activities must be thoroughly controlled in space and time. Any sustained unbalanced response of MP leads to pathological disorders, such as chronic inflammation, or favors cancer development and progression. In this review, we take advantage of our expertise in chronic inflammation, especially in rheumatoid arthritis, and in cancer, to highlight the pivotal role of MP in the physiopathology of these disorders and to emphasize the repolarization of unbalanced MP as a promising therapeutic strategy to control these diseases.
The Potential Impact of Neuroimaging and Translational Research on the Clinical Management of Lacunar Stroke
Authors: Rudilosso Salvatore , Rodríguez-Vázquez Alejandro , Urra Xabier , Arboix Adrià
Published: January 2022

Lacunar infarcts represent one of the most frequent subtypes of ischemic strokes and may represent the first recognizable manifestation of a progressive disease of the small perforating arteries, capillaries, and venules of the brain, defined as cerebral small vessel disease. The pathophysiological mechanisms leading to a perforating artery occlusion are multiple and still not completely defined, due to spatial resolution issues in neuroimaging, sparsity of pathological studies, and lack of valid experimental models. Recent advances in the endovascular treatment of large vessel occlusion may have diverted attention from the management of patients with small vessel occlusions, often excluded from clinical trials of acute therapy and secondary prevention. However, patients with a lacunar stroke benefit from early diagnosis, reperfusion therapy, and secondary prevention measures. In addition, there are new developments in the knowledge of this entity that suggest potential benefits of thrombolysis in an extended time window in selected patients, as well as novel therapeutic approaches targeting different pathophysiological mechanisms involved in small vessel disease. This review offers a comprehensive update in lacunar stroke pathophysiology and clinical perspective for managing lacunar strokes, in light of the latest insights from imaging and translational studies.
Characterization of Five Meloidogyne incognita Effectors Associated with PsoRPM3
Authors: Pu Wenjiang , Xiao Kun , Luo Sifang , Zhu Haifeng , Yuan Zizhen , Gao Chaoyuan , Hu Jianfang
Published: January 2022

Root-knot nematodes (RKNs) are devastating parasites that invade thousands of plants. In this study, five RKN effectors, which might interact with Prunussogdiana resistance protein PsoRPM3, were screened and identified. In situ hybridisation results showed that MiCal, MiGST_N_4, MiEFh and MiACPS are expressed in the subventral oesophageal glands (SvG), and MiTSPc hybridization signals are found in the dorsal esophageal gland (DG) of Meloidogyne incognita in the pre-J2. RT-qPCR data indicated that the expression of MiCal, MiGST_N_4, MiEFh, and MiACPS genes are highly expressed in M. incognita of pra-J2 and J3/J4 stages. The expression of MiTSPc increased significantly in the female stage of M. incognita. Moreover, all effectors found in this study localize in the cytoplasm and nucleus when transiently expressed in plant cells. In addition, MiGST_N_4, MiEFh, MiACPS and MiTSPc can elicit the ROS burst and strong hypersensitive response (HR), as well as significant ion leakage. Our data suggest that MiGST_N_4, MiEFh, MiACPS and MiTSPc effectors may be involved in triggering the immune response of the host plant.
Genes and Longevity of Lifespan
Authors: Bin-Jumah May Nasser , Nadeem Muhammad Shahid , Gilani Sadaf Jamal , Al-Abbasi Fahad A. , Ullah Inam , Alzarea Sami I. , Ghoneim Mohammed M. , Alshehri Sultan , Uddin Aziz , Murtaza Bibi Nazia , Kazmi Imran
Published: January 2022

Aging is a complex process indicated by low energy levels, declined physiological activity, stress induced loss of homeostasis leading to the risk of diseases and mortality. Recent developments in medical sciences and an increased availability of nutritional requirements has significantly increased the average human lifespan worldwide. Several environmental and physiological factors contribute to the aging process. However, about 40% human life expectancy is inherited among generations, many lifespan associated genes, genetic mechanisms and pathways have been demonstrated during last decades. In the present review, we have evaluated many human genes and their non-human orthologs established for their role in the regulation of lifespan. The study has included more than fifty genes reported in the literature for their contributions to the longevity of life. Intact genomic DNA is essential for the life activities at the level of cell, tissue, and organ. Nucleic acids are vulnerable to oxidative stress, chemotherapies, and exposure to radiations. Efficient DNA repair mechanisms are essential for the maintenance of genomic integrity, damaged DNA is not replicated and transferred to next generations rather the presence of deleterious DNA initiates signaling cascades leading to the cell cycle arrest or apoptosis. DNA modifications, DNA methylation, histone methylation, histone acetylation and DNA damage can eventually lead towards apoptosis. The importance of calorie restriction therapy in the extension of lifespan has also been discussed. The role of pathways involved in the regulation of lifespan such as DAF-16/FOXO (forkhead box protein O1), TOR and JNK pathways has also been particularized. The study provides an updated account of genetic factors associated with the extended lifespan and their interactive contributory role with cellular pathways.
Genome-Wide Identification and Functions against Tomato Spotted Wilt Tospovirus of PR-10 in Solanum lycopersicum
Authors: Islam Md. Monirul , Qi Shiming , Zhang Shijie , Amin Bakht , Yadav Vivek , El-Sappah Ahmed H. , Zhang Fei , Liang Yan
Published: January 2022

Tomato spotted wilt virus impacts negatively on a wide range of economically important plants, especially tomatoes. When plants facing any pathogen attack or infection, increase the transcription level of plant genes that are produced pathogenesis-related (PR) proteins. The aim of this study is a genome-wide identification of PR-10 superfamily and comparative analysis of PR-10 and Sw-5b gene functions against tomato responses to biotic stress (TSWV) to systemic resistance in tomato. Forty-five candidate genes were identified, with a length of 64–210 amino acid residues and a molecular weight of 7.6–24.4 kDa. The PR-10 gene was found on ten of the twelve chromosomes, and it was determined through a genetic ontology that they were involved in six biological processes and molecular activities, and nine cellular components. Analysis of the transcription level of PR-10 family members showed that the PR-10 gene (Solyc09g090980) has high expression levels in some parts of the tomato plant. PR-10 and Sw-5b gene transcription and activity in tomato leaves were strongly induced by TSWV infection, whereas H8 plants having the highest significantly upregulated expression of PR-10 and Sw-5b gene after the inoculation of TSWV, and TSWV inoculated in M82 plants showed significantly upregulated expression of PR-10 gene comparatively lower than H8 plants. There was no significant expression of Sw-5b gene of TSWV inoculated in M82 plants and then showed highly significant correlations between PR-10 and Sw-5b genes at different time points in H8 plants showed significant correlations compared to M82 plants after the inoculation of TSWV; a heat map showed that these two genes may also participate in regulating the defense response after the inoculation of TSWV in tomato.
circSLC41A1 Resists Porcine Granulosa Cell Apoptosis and Follicular Atresia by Promoting SRSF1 through miR-9820-5p Sponging
Authors: Wang Huiming , Zhang Yi , Zhang Jinbi , Du Xing , Li Qifa , Pan Zengxiang
Published: January 2022

Ovarian granulosa cell (GC) apoptosis is the major cause of follicular atresia. Regulation of non-coding RNAs (ncRNAs) was proved to be involved in regulatory mechanisms of GC apoptosis. circRNAs have been recognized to play important roles in cellular activity. However, the regulatory network of circRNAs in follicular atresia has not been fully validated. In this study, we report a new circRNA, circSLC41A1, which has higher expression in healthy follicles compared to atretic follicles, and confirm its circular structure using RNase R treatment. The resistant function of circSLC41A1 during GC apoptosis was detected by si-RNA transfection and the competitive binding of miR-9820-5p by circSLC41A1 and SRSF1 was detected with a dual-luciferase reporter assay and co-transfection of their inhibitors or siRNA. Additionally, we predicted the protein-coding potential of circSLC41A1 and analyzed the structure of circSLC41A1-134aa. Our study revealed that circSLC41A1 enhanced SRSF1 expression through competitive binding of miR-9820-5p and demonstrated a circSLC41A1–miR-9820-5p–SRSF1 regulatory axis in follicular GC apoptosis. The study adds to knowledge of the post-transcriptional regulation of follicular atresia and provides insight into the protein-coding function of circRNA.
Slipknot or Crystallographic Error: A Computational Analysis of the Plasmodium falciparum DHFR Structural Folds
Authors: Tata Rolland B. , Alsulami Ali F. , Sheik Amamuddy Olivier , Blundell Tom L. , Tastan Bishop Özlem
Published: January 2022

The presence of protein structures with atypical folds in the Protein Data Bank (PDB) is rare and may result from naturally occurring knots or crystallographic errors. Proper characterisation of such folds is imperative to understanding the basis of naturally existing knots and correcting crystallographic errors. If left uncorrected, such errors can frustrate downstream experiments that depend on the structures containing them. An atypical fold has been identified in P. falciparum dihydrofolate reductase (PfDHFR) between residues 20–51 (loop 1) and residues 191–205 (loop 2). This enzyme is key to drug discovery efforts in the parasite, necessitating a thorough characterisation of these folds. Using multiple sequence alignments (MSA), a unique insert was identified in loop 1 that exacerbates the appearance of the atypical fold-giving it a slipknot-like topology. However, PfDHFR has not been deposited in the knotted proteins database, and processing its structure failed to identify any knots within its folds. The application of protein homology modelling and molecular dynamics simulations on the DHFR domain of P. falciparum and those of two other organisms (E. coli and M. tuberculosis) that were used as molecular replacement templates in solving the PfDHFR structure revealed plausible unentangled or open conformations of these loops. These results will serve as guides for crystallographic experiments to provide further insights into the atypical folds identified.
Roles of α-Synuclein and Disease-Associated Factors in Drosophila Models of Parkinson’s Disease
Authors: Suzuki Mari , Sango Kazunori , Nagai Yoshitaka
Published: January 2022

α-Synuclein (αSyn) plays a major role in the pathogenesis of Parkinson’s disease (PD), which is the second most common neurodegenerative disease after Alzheimer’s disease. The accumulation of αSyn is a pathological hallmark of PD, and mutations in the SNCA gene encoding αSyn cause familial forms of PD. Moreover, the ectopic expression of αSyn has been demonstrated to mimic several key aspects of PD in experimental model systems. Among the various model systems, Drosophila melanogaster has several advantages for modeling human neurodegenerative diseases. Drosophila has a well-defined nervous system, and numerous tools have been established for its genetic analyses. The rapid generation cycle and short lifespan of Drosophila renders them suitable for high-throughput analyses. PD model flies expressing αSyn have contributed to our understanding of the roles of various disease-associated factors, including genetic and nongenetic factors, in the pathogenesis of PD. In this review, we summarize the molecular pathomechanisms revealed to date using αSyn-expressing Drosophila models of PD, and discuss the possibilities of using these models to demonstrate the biological significance of disease-associated factors.
Multidimensional Phylogenetic Metrics Identify Class I Aminoacyl-tRNA Synthetase Evolutionary Mosaicity and Inter-Modular Coupling
Authors: Carter Charles W. , Popinga Alex , Bouckaert Remco , Wills Peter R.
Published: January 2022

The role of aminoacyl-tRNA synthetases (aaRS) in the emergence and evolution of genetic coding poses challenging questions concerning their provenance. We seek evidence about their ancestry from curated structure-based multiple sequence alignments of a structurally invariant “scaffold” shared by all 10 canonical Class I aaRS. Three uncorrelated phylogenetic metrics—mutation frequency, its uniformity, and row-by-row cladistic congruence—imply that the Class I scaffold is a mosaic assembled from successive genetic sources. Metrics for different modules vary in accordance with their presumed functionality. Sequences derived from the ATP– and amino acid– binding sites exhibit specific two-way coupling to those derived from Connecting Peptide 1, a third module whose metrics suggest later acquisition. The data help validate: (i) experimental fragmentations of the canonical Class I structure into three partitions that retain catalytic activities in proportion to their length; and (ii) evidence that the ancestral Class I aaRS gene also encoded a Class II ancestor in frame on the opposite strand. A 46-residue Class I “protozyme” roots the Class I tree prior to the adaptive radiation of the Rossmann dinucleotide binding fold that refined substrate discrimination. Such rooting implies near simultaneous emergence of genetic coding and the origin of the proteome, resolving a conundrum posed by previous inferences that Class I aaRS evolved after the genetic code had been implemented in an RNA world. Further, pinpointing discontinuous enhancements of aaRS fidelity establishes a timeline for the growth of coding from a binary amino acid alphabet.
Induction of PLXNA4 Gene during Neural Differentiation in Human Umbilical-Cord-Derived Mesenchymal Stem Cells by Low-Intensity Sub-Sonic Vibration
Authors: Cho Hyunjin , Park Hee-Jung , Seo Young-Kwon
Published: January 2022

Human umbilical-cord-derived mesenchymal stem cells (hUC-MSC) are a type of mesenchymal stem cells and are more primitive than other MSCs. In this study, we identify novel genes and signal-activating proteins involved in the neural differentiation of hUC-MSCs induced by Low-Intensity Sub-Sonic Vibration (LISSV). RNA sequencing was used to find genes involved in the differentiation process by LISSV. The changes in hUC-MSCs caused by LISSV were confirmed by PLXNA4 overexpression and gene knockdown through small interfering RNA experiments. The six genes were increased among genes related to neurons and the nervous system. One of them, the PLXNA4 gene, is known to play a role as a guide for axons in the development of the nervous system. When the PLXNA4 recombinant protein was added, neuron-related genes were increased. In the PLXNA4 gene knockdown experiment, the expression of neuron-related genes was not changed by LISSV exposure. The PLXNA4 gene is activated by sema family ligands. The expression of SEMA3A was increased by LISSV, and its downstream signaling molecule, FYN, was also activated. We suggest that the PLXNA4 gene plays an important role in hUC-MSC neuronal differentiation through exposure to LISSV. The differentiation process depends on SEMA3A-PLXNA4-dependent FYN activation in hUC-MSCs.
Plant Executor Genes
Authors: Ji Zhiyuan , Guo Wei , Chen Xifeng , Wang Chunlian , Zhao Kaijun
Published: January 2022

Executor (E) genes comprise a new type of plant resistance (R) genes, identified from host–Xanthomonas interactions. The Xanthomonas-secreted transcription activation-like effectors (TALEs) usually function as major virulence factors, which activate the expression of the so-called “susceptibility” (S) genes for disease development. This activation is achieved via the binding of the TALEs to the effector-binding element (EBE) in the S gene promoter. However, host plants have evolved EBEs in the promoters of some otherwise silent R genes, whose expression directly causes a host cell death that is characterized by a hypersensitive response (HR). Such R genes are called E genes because they trap the pathogen TALEs in order to activate expression, and the resulting HR prevents pathogen growth and disease development. Currently, deploying E gene resistance is becoming a major component in disease resistance breeding, especially for rice bacterial blight resistance. Currently, the biochemical mechanisms, or the working pathways of the E proteins, are still fuzzy. There is no significant nucleotide sequence homology among E genes, although E proteins share some structural motifs that are probably associated with the signal transduction in the effector-triggered immunity. Here, we summarize the current knowledge regarding TALE-type avirulence proteins, E gene activation, the E protein structural traits, and the classification of E genes, in order to sharpen our understanding of the plant E genes.
Anti-Inflammatory Effect of an O-2-Substituted (1-3)-β-D-Glucan Produced by Pediococcus parvulus 2.6 in a Caco-2 PMA-THP-1 Co-Culture Model
Authors: Notararigo Sara , Varela Encarnación , Otal Anna , Antolín María , Guarner Francisco , López Paloma
Published: January 2022

Bacterial β-glucans are exopolysaccharides (EPSs), which can protect bacteria or cooperate in biofilm formation or in bacterial cell adhesion. Pediococcus parvulus 2.6 is a lactic acid bacterium that produces an O-2-substituted (1-3)-β-D-glucan. The structural similarity of this EPS to active compounds such as laminarin, together with its ability to modulate the immune system and to adhere in vitro to human enterocytes, led us to investigate, in comparison with laminarin, its potential as an immunomodulator of in vitro co-cultured Caco-2 and PMA-THP-1 cells. O-2-substituted (1-3)-β-D-glucan synthesized by the GTF glycosyl transferase of Pediococcus parvulus 2.6 or that by Lactococcus lactis NZ9000[pGTF] were purified and used in this study. The XTT tests revealed that all β-glucans were non-toxic for both cell lines and activated PMA-THP-1 cells’ metabolisms. The O-2-substituted (1-3)-β-D-glucan modulated production and expression of IL-8 and the IL-10 in Caco-2 and PMA-THP-1 cells. Laminarin also modulated cytokine production by diminishing TNF-α in Caco-2 cells and IL-8 in PMA-THP-1. All these features could be considered with the aim to produce function foods, supplemented with laminarin or with another novel β-glucan-producing strain, in order to ameliorate an individual’s immune system response toward pathogens or to control mild side effects in remission patients affected by inflammatory bowel diseases.
Pharmacological Effects of Cisplatin Combination with Natural Products in Cancer Chemotherapy
Authors: Dasari Shaloam , Njiki Sylvianne , Mbemi Ariane , Yedjou Clement G. , Tchounwou Paul B.
Published: January 2022

Cisplatin and other platinum-based drugs, such as carboplatin, ormaplatin, and oxaliplatin, have been widely used to treat a multitude of human cancers. However, a considerable proportion of patients often relapse due to drug resistance and/or toxicity to multiple organs including the liver, kidneys, gastrointestinal tract, and the cardiovascular, hematologic, and nervous systems. In this study, we sought to provide a comprehensive review of the current state of the science highlighting the use of cisplatin in cancer therapy, with a special emphasis on its molecular mechanisms of action, and treatment modalities including the combination therapy with natural products. Hence, we searched the literature using various scientific databases., such as MEDLINE, PubMed, Google Scholar, and relevant sources, to collect and review relevant publications on cisplatin, natural products, combination therapy, uses in cancer treatment, modes of action, and therapeutic strategies. Our search results revealed that new strategic approaches for cancer treatment, including the combination therapy of cisplatin and natural products, have been evaluated with some degree of success. Scientific evidence from both in vitro and in vivo studies demonstrates that many medicinal plants contain bioactive compounds that are promising candidates for the treatment of human diseases, and therefore represent an excellent source for drug discovery. In preclinical studies, it has been demonstrated that natural products not only enhance the therapeutic activity of cisplatin but also attenuate its chemotherapy-induced toxicity. Many experimental studies have also reported that natural products exert their therapeutic action by triggering apoptosis through modulation of mitogen-activated protein kinase (MAPK) and p53 signal transduction pathways and enhancement of cisplatin chemosensitivity. Furthermore, natural products protect against cisplatin-induced organ toxicity by modulating several gene transcription factors and inducing cell death through apoptosis and/or necrosis. In addition, formulations of cisplatin with polymeric, lipid, inorganic, and carbon-based nano-drug delivery systems have been found to delay drug release, prolong half-life, and reduce systemic toxicity while other formulations, such as nanocapsules, nanogels, and hydrogels, have been reported to enhance cell penetration, target cancer cells, and inhibit tumor progression.
Teriflunomide Preserves Neuronal Activity and Protects Mitochondria in Brain Slices Exposed to Oxidative Stress
Authors: Malla Bimala , Liotta Agustin , Bros Helena , Ulshöfer Rebecca , Paul Friedemann , Hauser Anja E. , Niesner Raluca , Infante-Duarte Carmen
Published: January 2022

Teriflunomide (TFN) limits relapses in relapsing–remitting multiple sclerosis (RRMS) by reducing lymphocytic proliferation through the inhibition of the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) and the subsequent modulation of de novo pyrimidine synthesis. Alterations of mitochondrial function as a consequence of oxidative stress have been reported during neuroinflammation. Previously, we showed that TFN prevents alterations of mitochondrial motility caused by oxidative stress in peripheral axons. Here, we aimed to validate TFN effects on mitochondria and neuronal activity in hippocampal brain slices, in which cellular distribution and synaptic circuits are largely preserved. TFN effects on metabolism and neuronal activity were investigated by assessing oxygen partial pressure and local field potential in acute slices. Additionally, we imaged mitochondria in brain slices from the transgenic Thy1-CFP/COX8A)S2Lich/J (mitoCFP) mice using two-photon microscopy. Although TFN could not prevent oxidative stress-related depletion of ATP, it preserved oxygen consumption and neuronal activity in CNS tissue during oxidative stress. Furthermore, TFN prevented mitochondrial shortening and fragmentation of puncta-shaped and network mitochondria during oxidative stress. Regarding motility, TFN accentuated the decrease in mitochondrial displacement and increase in speed observed during oxidative stress. Importantly, these effects were not associated with neuronal viability and did not lead to axonal damage. In conclusion, during conditions of oxidative stress, TFN preserves the functionality of neurons and prevents morphological and motility alterations of mitochondria.
R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1
Authors: Marabitti Veronica , Valenzisi Pasquale , Lillo Giorgia , Malacaria Eva , Palermo Valentina , Pichierri Pietro , Franchitto Annapaola
Published: January 2022

Maintenance of genome stability is crucial for cell survival and relies on accurate DNA replication. However, replication fork progression is under constant attack from different exogenous and endogenous factors that can give rise to replication stress, a source of genomic instability and a notable hallmark of pre-cancerous and cancerous cells. Notably, one of the major natural threats for DNA replication is transcription. Encounters or conflicts between replication and transcription are unavoidable, as they compete for the same DNA template, so that collisions occur quite frequently. The main harmful transcription-associated structures are R-loops. These are DNA structures consisting of a DNA–RNA hybrid and a displaced single-stranded DNA, which play important physiological roles. However, if their homeostasis is altered, they become a potent source of replication stress and genome instability giving rise to several human diseases, including cancer. To combat the deleterious consequences of pathological R-loop persistence, cells have evolved multiple mechanisms, and an ever growing number of replication fork protection factors have been implicated in preventing/removing these harmful structures; however, many others are perhaps still unknown. In this review, we report the current knowledge on how aberrant R-loops affect genome integrity and how they are handled, and we discuss our recent findings on the role played by two fork protection factors, the Werner syndrome protein (WRN) and the Werner helicase-interacting protein 1 (WRNIP1) in response to R-loop-induced genome instability.
Challenges in Discovering Drugs That Target the Protein–Protein Interactions of Disordered Proteins
Authors: Oláh Judit , Szénási Tibor , Lehotzky Attila , Norris Victor , Ovádi Judit
Published: January 2022

Protein–protein interactions (PPIs) outnumber proteins and are crucial to many fundamental processes; in consequence, PPIs are associated with several pathological conditions including neurodegeneration and modulating them by drugs constitutes a potentially major class of therapy. Classically, however, the discovery of small molecules for use as drugs entails targeting individual proteins rather than targeting PPIs. This is largely because discovering small molecules to modulate PPIs has been seen as extremely challenging. Here, we review the difficulties and limitations of strategies to discover drugs that target PPIs directly or indirectly, taking as examples the disordered proteins involved in neurodegenerative diseases.
Autophagy in Virus Infection: A Race between Host Immune Response and Viral Antagonism
Authors: Chawla Karan , Subramanian Gayatri , Rahman Tia , Fan Shumin , Chakravarty Sukanya , Gujja Shreyas , Demchak Hayley , Chakravarti Ritu , Chattopadhyay Saurabh
Published: January 2022

Virus-infected cells trigger a robust innate immune response and facilitate virus replication. Here, we review the role of autophagy in virus infection, focusing on both pro-viral and anti-viral host responses using a select group of viruses. Autophagy is a cellular degradation pathway operated at the basal level to maintain homeostasis and is induced by external stimuli for specific functions. The degradative function of autophagy is considered a cellular anti-viral immune response. However, autophagy is a double-edged sword in viral infection; viruses often benefit from it, and the infected cells can also use it to inhibit viral replication. In addition to viral regulation, autophagy pathway proteins also function in autophagy-independent manners to regulate immune responses. Since viruses have co-evolved with hosts, they have developed ways to evade the anti-viral autophagic responses of the cells. Some of these mechanisms are also covered in our review. Lastly, we conclude with the thought that autophagy can be targeted for therapeutic interventions against viral diseases.
Post-Editese in Literary Translations
Authors: Castilho Sheila , Resende Natália
Published: January 2022

In the present study, we investigated the post-editese phenomenon, i.e., the unique features that set machine translated post-edited texts apart from human-translated texts. We used two literary texts, namely, the English children’s novel by Lewis Carroll Alice’s Adventures in Wonderland (AW) and Paula Hawkins’ popular book The Girl on the Train (TGOTT). Both literary texts were Google translated from English into Brazilian Portuguese to investigate whether the post-editese features can be found on the surface of the post-edited (PE) texts. In addition, we examined how the features found in the PE texts differ from the features encountered in the human-translated (HT) and machine translation (MT) versions of the same source text. Results revealed evidence for post-editese for TGOTT only with PE versions being more similar to the MT output than to the HT texts.
Reference Genes for Expression Analyses by qRT-PCR in Phthorimaea operculella (Lepidoptera: Gelechiidae)
Authors: Shen Chen-Hui , Peng Li-Juan , Zhang Yu-Xing , Zeng Hua-Rui , Yu Hong-Fei , Jin Lin , Li Guo-Qing
Published: January 2022

Due to a lack of effective internal references, studies on functional genes in Phthorimaea operculella, a serious Lepidopteran pest attacking potatoes worldwide, have been greatly limited. To select suitable endogenous controls, ten housekeeping genes of actin (ACT), α-tubulin (α-TUB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), elongation factor 1α (EF1α), 18S and 28S ribosomal RNA (18S, 28S), ribosomal protein genes RPL4, RPL13 and RPL27 and superoxide dismutase (SOD) were tested. Their expression levels were determined under three different experimental conditions (developmental stages, tissues/organs and temperatures) using qRT-PCR technology. The stability was evaluated with five methods (Ct value, geNorm, NormFinder, BestKeeper and RefFinder). The results clarified that RPL13, EF1α and RPL27 are ranked as the best reference gene combination for measuring gene expression levels among different developing stages and under various temperatures; EF1α and RPL13 are recommended to normalize the gene expression levels among diverse tissues. EF1α and RPL13 are the best reference genes in all the experimental conditions. To validate the utility of the selected reference pair, EF1α and RPL13, we estimated the tissue-biased expression level of chitin synthase A gene (PoChSA). As expected, PoChSA was abundantly expressed in ectodermally derived epidermal cells, and lowly transcribed in the midgut. These findings will lay the foundation for future research on the molecular physiology and biochemistry of P. operculella.
Drosophila melanogaster Chemosensory Pathways as Potential Targets to Curb the Insect Menace
Authors: Ali Md Zeeshan , Anushree  , Bilgrami Anwar L. , Ahsan Jawaid
Published: January 2022

From a unicellular bacterium to a more complex human, smell and taste form an integral part of the basic sensory system. In fruit flies Drosophila melanogaster, the behavioral responses to odorants and tastants are simple, though quite sensitive, and robust. They explain the organization and elementary functioning of the chemosensory system. Molecular and functional analyses of the receptors and other critical molecules involved in olfaction and gustation are not yet completely understood. Hence, a better understanding of chemosensory cue-dependent fruit flies, playing a major role in deciphering the host-seeking behavior of pathogen transmitting insect vectors (mosquitoes, sandflies, ticks) and crop pests (Drosophila suzukii, Queensland fruit fly), is needed. Using D. melanogaster as a model organism, the knowledge gained may be implemented to design new means of controlling insects as well as in analyzing current batches of insect and pest repellents. In this review, the complete mechanisms of olfactory and gustatory perception, along with their implementation in controlling the global threat of disease-transmitting insect vectors and crop-damaging pests, are explained in fruit flies.
Evaluation of Hyperspectral Imaging for Follow-Up Assessment after Revascularization in Peripheral Artery Disease
Authors: Grambow Eberhard , Sandkühler Niels Arne , Groß Justus , Thiem Daniel G. E. , Dau Michael , Leuchter Matthias , Weinrich Malte
Published: January 2022

Background: Assessment of tissue oxygenation is an important aspect of detection and monitoring of patients with peripheral artery disease (PAD). Hyperspectral imaging (HSI) is a non-contact technology for assessing microcirculatory function by quantifying tissue oxygen saturation (StO2). This study investigated whether HSI can be used to monitor skin oxygenation in patients with PAD after appropriate treatment of the lower extremities. Methods: For this purpose, 37 patients with PAD were studied by means of ankle–brachial index (ABI) and HSI before and after surgical or endovascular therapy. Thereby, the oxygenation parameter StO2 and near infrared (NIR) perfusion index were quantified in seven angiosomes on the diseased lower leg and foot. In addition, the effects of skin temperature and physical activity on StO2 and the NIR perfusion index and the respective inter-operator variability of these parameters were investigated in 25 healthy volunteers. Results: In all patients, the ABI significantly increased after surgical and endovascular therapy. In parallel, HSI revealed significant changes in both StO2 and NIR perfusion index in almost all studied angiosomes depending on the performed treatment. The increase in tissue oxygenation saturation was especially pronounced after surgical treatment. Neither heat nor cold, nor physical activity, nor repeated assessments of HSI parameters by independent investigators significantly affected the results on StO2 and the NIR perfusion index. Conclusions: Tissue oxygen saturation data obtained with HSI are robust to external confounders, such as temperature and physical activity, and do not show inter-operator variability; therefore, can be used as an additional technique to established methods, such as the ABI, to monitor peripheral perfusion in patients with PAD.
The Effect of Fibrates on Kidney Function and Chronic Kidney Disease Progression: A Systematic Review and Meta-Analysis of Randomised Studies
Authors: Hadjivasilis Alexandros , Kouis Panayiotis , Kousios Andreas , Panayiotou Andrie
Published: January 2022

Aim: Fibrates have proven efficacy in cardiovascular risk reduction and are commonly used, in addition to statins, to control hypertriglyceridaemia. Their use is often limited due to reduction in glomerular filtration rate at treatment initiation. However, recent studies suggest benign changes in kidney function and improvement of proteinuria, an established early marker of microvascular disease and kidney disease progression. We summarize the evidence from existing trials and provide a summary of effects of fibrates, alone or in combination, on kidney disease progression and proteinuria. Methods and Results: Systematic review and meta-analysis of randomized, controlled trials (PROSPERO CRD42020187764). Out of 12,243 potentially eligible studies, 29 were included in qualitative and quantitative analysis, with a total of 20,176 patients. Mean creatinine increased by 1.05 (95% CI (0.63 to 1.46)) units in patients receiving fibrates vs. comparator, and this was similar in all other subgroups. eGFR showed a bigger decrease in the fibrates arm (SMD −1.99; 95% CI (−3.49 to −0.48)) when all studies were pooled together. Notably, short-term serum creatinine and eGFR changes remained constant in the long-term. Pooled estimates show that fibrates improve albuminuria progression, RR 0.86; 95% CI (0.76 to 0.98); albuminuria regression, RR 1.19; 95% CI (1.08 to 1.310). Conclusions: Fibrates improve albuminuria in patients with and without diabetes when used to treat hyperlipidaemia. The modest creatinine increase should not be a limiting factor for fibrate initiation in people with preserved renal function or mild CKD. The long-term effects on kidney disease progression warrant further study.
Long-Term Follow-Up of Fractional CO2 Laser Therapy for Genitourinary Syndrome of Menopause in Breast Cancer Survivors
Authors: Quick Allison M. , Hundley Andrew , Evans Cynthia , Stephens Julie A. , Ramaswamy Bhuvaneswari , Reinbolt Raquel E. , Noonan Anne M. , Van Deusen Jeffrey Bryan , Wesolowski Robert , Stover Daniel G. , Williams Nicole Olivia , Sardesai Sagar D. , Faubion Stephanie S. , Loprinzi Charles L. , Lustberg Maryam B.
Published: January 2022

(1) Background: The objective of this study was to determine the long-term efficacy of fractional CO2 laser therapy in breast cancer survivors. (2) Methods: This was a single-arm study of breast cancer survivors. Participants received three treatments of fractional CO2 laser therapy and returned for a 4 week follow-up. Participants were contacted for follow-up at annual intervals. The Vaginal Assessment Scale (VAS), the Female Sexual Function Index (FSFI), the Female Sexual Distress Scare Revised (FSDS-R), the Urinary Distress Inventory (UDI), and adverse events were collected and reported for the two-year follow-up. The changes in scores were compared between the four-week and two-year and the one-year and two-year follow-ups using paired t-tests. (3) Results: In total, 67 BC survivors were enrolled, 59 completed treatments and the four week follow-up, 39 participated in the one-year follow-up, and 33 participated in the two-year follow-up. After initial improvement in the VAS from baseline to the four week follow-up, there was no statistically significant difference in the VAS score (mean Δ 0.23; 95% CI [−0.05, 0.51], p = 0.150) between the four week follow-up and the two-year follow-up. At the two-year follow-up, the FSFI and FSDS-R scores remained improved from baseline and there was no statistically significant change in the FSFI score (mean Δ −0.83; 95% CI [−3.07, 2.38] p = 0.794) or the FSDS-R score (mean Δ −2.85; 95% CI [−1.88, 7.59] p = 0.227) from the one to two-year follow-up. The UDI scores approached baseline at the two-year follow-up; however, the change between the one- and two-year follow-ups was not statistically significant (mean Δ 4.76; 95% CI [−1.89, 11.41], p = 0.15). (4) Conclusions: Breast cancer survivors treated with fractional CO2 laser therapy have sustained improvement in sexual function two years after treatment completion, suggesting potential long-term benefit.
Angiotensin-Converting Enzyme 2 (ACE2), Transmembrane Peptidase Serine 2 (TMPRSS2), and Furin Expression Increases in the Lungs of Patients with Idiopathic Pulmonary Fibrosis (IPF) and Lymphangioleiomyomatosis (LAM): Implications for SARS-CoV-2 (COVID-19) Infections
Authors: Lu Wenying , Eapen Mathew Suji , Singhera Gurpreet Kaur , Markos James , Haug Greg , Chia Collin , Larby Josie , Brake Samuel James , Westall Glen P. , Jaffar Jade , Kalidhindi Rama Satyanarayana Raju , Fonseka Nimesha De , Sathish Venkatachalem , Hackett Tillie L. , Sohal Sukhwinder Singh
Published: January 2022

We previously reported higher ACE2 levels in smokers and patients with COPD. The current study investigates if patients with interstitial lung diseases (ILDs) such as IPF and LAM have elevated ACE2, TMPRSS2, and Furin levels, increasing their risk for SARS-CoV-2 infection and development of COVID-19. Surgically resected lung tissue from IPF, LAM patients, and healthy controls (HC) was immunostained for ACE2, TMPRSS2, and Furin. Percentage ACE2, TMPRSS2, and Furin expression was measured in small airway epithelium (SAE) and alveolar areas using computer-assisted Image-Pro Plus 7.0 software. IPF and LAM tissue was also immunostained for myofibroblast marker α-smooth muscle actin (α-SMA) and growth factor transforming growth factor beta1 (TGF-β1). Compared to HC, ACE2, TMPRSS2 and Furin expression were significantly upregulated in the SAE of IPF (p < 0.01) and LAM (p < 0.001) patients, and in the alveolar areas of IPF (p < 0.001) and LAM (p < 0.01). There was a significant positive correlation between smoking history and ACE2 expression in the IPF cohort for SAE (r = 0.812, p < 0.05) and alveolar areas (r = 0.941, p < 0.01). This, to our knowledge, is the first study to compare ACE2, TMPRSS2, and Furin expression in patients with IPF and LAM compared to HC. Descriptive images show that α-SMA and TGF-β1 increase in the IPF and LAM tissue. Our data suggests that patients with ILDs are at a higher risk of developing severe COVID-19 infection and post-COVID-19 interstitial pulmonary fibrosis. Growth factors secreted by the myofibroblasts, and surrounding tissue could further affect COVID-19 adhesion proteins/cofactors and post-COVID-19 interstitial pulmonary fibrosis. Smoking seems to be the major driving factor in patients with IPF.
The Evolution of Molecular Recognition: From Antibodies to Molecularly Imprinted Polymers (MIPs) as Artificial Counterpart
Authors: Parisi Ortensia Ilaria , Francomano Fabrizio , Dattilo Marco , Patitucci Francesco , Prete Sabrina , Amone Fabio , Puoci Francesco
Published: January 2022

Molecular recognition is a useful property shared by various molecules, such as antibodies, aptamers and molecularly imprinted polymers (MIPs). It allows these molecules to be potentially involved in many applications including biological and pharmaceutical research, diagnostics, theranostics, therapy and drug delivery. Antibodies, naturally produced by plasma cells, have been exploited for this purpose, but they present noticeable drawbacks, above all production cost and time. Therefore, several research studies for similar applications have been carried out about MIPs and the main studies are reported in this review. MIPs, indeed, are more versatile and cost-effective than conventional antibodies, but the lack of toxicity studies and their scarce use for practical applications, make it that further investigations on this kind of molecules need to be conducted.
An Extension of Reversible Image Enhancement Processing for Saturation and Brightness Contrast
Authors: Sugimoto Yuki , Imaizumi Shoko
Published: January 2022

This paper proposes a reversible image processing method for color images that can independently improve saturation and enhance brightness contrast. Image processing techniques have been popularly used to obtain desired images. The existing techniques generally do not consider reversibility. Recently, many reversible image processing methods have been widely researched. Most of the previous studies have investigated reversible contrast enhancement for grayscale images based on data hiding techniques. When these techniques are simply applied to color images, hue distortion occurs. Several efficient methods have been studied for color images, but they could not guarantee complete reversibility. We previously proposed a new method that reversibly controls not only the brightness contrast, but also saturation. However, this method cannot fully control them independently. To tackle this issue, we extend our previous work without losing its advantages. The proposed method uses the HSV cone model, while our previous method uses the HSV cylinder model. The experimental results demonstrate that our method flexibly controls saturation and brightness contrast reversibly and independently.
Acknowledgment to Reviewers of Journal of Molecular Pathology in 2021
Authors:   Journal of Molecular Pathology Editorial Office
Published: January 2022

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