bluuebunny/crossref_metadata_2025 huggingface dataset:
The Gram-Negative Bacilli Isolated from Caves—Sphingomonas paucimobilis and Hafnia alvei and a Review of Their Involvement in Human Infections
Authors: Ionescu Mihaela Ileana , Neagoe Dan Ștefan , Crăciun Alexandra Marioara , Moldovan Oana Teodora
Published: February 2022

The opportunistic infections with Gram-negative bacilli are frequently reported. The clinical studies are focused on the course of human infectious and very often the source of infection remain unclear. We aim to see if the Gram-negative bacilli isolated from a non-contaminated environment—the caves—are reported in human infections. Eleven samples were collected from six Romanian caves. We used the standard procedure used in our clinical laboratory for bacterial identification and for antibiotic susceptibility testing of the cave isolates. Out of the 14 bacterial strains, three isolates are Gram-negative bacilli—one isolate belong to Hafnia alvei and two strains belong to Sphingomonas paucimobilis. We screened for the published studies—full-text original articles or review articles—that reported human infections with S. paucimobilis and H. alvei. Data sources—PubMed and Cochrane library. We retrieved 447 cases from 49 references—262 cases (58.61%) are S. paucimobilis infections and 185 cases (41.39%) are H. alvei infections. The types of infections are diverse but there are some infections more frequent; there are 116 cases (44.27%) and many infections of the bloodstream with S. paucimobilius (116 cases) and 121 cases (65.41%) are urinary tract infections with H. alvei. The acquired source of the bloodstream infections is reported for 93 of S. paucimobilis bloodstream infections—50 cases (43%) are hospital-acquired, and 40 cases (37%) are community-acquired. Most of the infections are reported in patients with different underlying conditions. There are 80 cases (17.9%) are reported of previously healthy persons. Out of the 72 cases of pediatric infections, 62 cases (86.11%) are caused by S. paucimobilis. There are ten death casualties—three are H. alvei infections, and seven are S. paucimobilis infections.
Associations between Metal Exposures and Cognitive Function in American Older Adults
Authors: Sasaki Nozomi , Carpenter David O.
Published: February 2022

Cognitive function frequently declines with older age, independently of the development of neurodegenerative diseases, and few interventions are known to counter this decline. Exposure to neurotoxic metals may contribute to this decline in cognitive function in older adults. Using the National Health and Nutrition Examination Survey (NHANES) data, the performance of 3042 adults aged 60 years and older on three cognitive tests for immediate, delayed, and working memory were examined in relation to blood concentrations of seven metals and metalloids and urinary concentrations of nineteen metals and metabolites. Using linear regression models, associations between cognitive tests and logarithms of metal exposures were adjusted for age, sex, ethnicity, education level, depression, diabetes, alcohol consumption, and cigarette use. Increased selenium was strongly associated with better performance on all three cognitive tests. Cadmium and lead were negatively associated with performance on all three cognitive tests. Some urinary metabolites of arsenic, urinary lead, cadmium, and tungsten were significantly associated with poor performance on some tests. In older adults, higher selenium levels were strongly associated with better cognitive performance.
Cost-Effectiveness of PET/CT Surveillance Schedules to Detect Distant Recurrence of Resected Stage III Melanoma
Authors: Dieng Mbathio , Turner Robin M. , Lord Sarah J. , Einstein Andrew J. , Menzies Alexander M. , Saw Robyn P. M. , Nieweg Omgo E. , Thompson John F. , Morton Rachael L.
Published: February 2022

Objective: To estimate the cost-effectiveness of three surveillance imaging strategies using whole-body positron emission tomography (PET) with computed tomography (CT) (PET/CT) in a follow-up program for adults with resected stage III melanoma. Methods: An analytic decision model was constructed to estimate the costs and benefits of PET/CT surveillance imaging performed 3-monthly, 6-monthly, or 12-monthly compared with no surveillance imaging. Results: At 5 years, 3-monthly PET/CT surveillance imaging incurred a total cost of AUD 88,387 per patient, versus AUD 77,998 for 6-monthly, AUD 52,560 for 12-monthly imaging, and AUD 51,149 for no surveillance imaging. When compared with no surveillance imaging, 12-monthly PET/CT imaging was associated with a 4% increase in correctly diagnosed and treated distant disease; a 0.5% increase with 6-monthly imaging and 1% increase with 3-monthly imaging. The incremental cost-effectiveness ratio (ICER) of 12-monthly PET/CT surveillance imaging was AUD 34,362 for each additional distant recurrence correctly diagnosed and treated, compared with no surveillance imaging. For the outcome of cost per diagnostic error avoided, the no surveillance imaging strategy was the least costly and most effective. Conclusion: With the ICER for this strategy less than AUD 50,000 per unit of health benefit, the 12-monthly surveillance imaging strategy is considered good value for money.
Adipokines as New Biomarkers of Immune Recovery: Apelin Receptor, RBP4 and ZAG Are Related to CD4+ T-Cell Reconstitution in PLHIV on Suppressive Antiretroviral Therapy
Authors: Yeregui Elena , Masip Jenifer , Viladés Consuelo , Domingo Pere , Pacheco Yolanda M. , Blanco Julià , Mallolas Josep , Alba Verónica , Vargas Montserrat , García-Pardo Graciano , Negredo Eugènia , Olona Montserrat , Vidal-González Judit , Peraire Maria , Martí Anna , Reverté Laia , Gómez-Bertomeu Fréderic , Leal Manuel , Vidal Francesc , Peraire Joaquim , Rull Anna
Published: February 2022

A significant proportion of people living with HIV (PLHIV) who successfully achieve virological suppression fail to recover CD4+ T-cell counts. Since adipose tissue has been discovered as a key immune organ, this study aimed to assess the role of adipokines in the HIV immunodiscordant response. This is a multicenter prospective study including 221 PLHIV starting the first antiretroviral therapy (ART) and classified according to baseline CD4+ T-cell counts/µL (controls > 200 cells/µL and cases ≤ 200 cells/µL). Immune failure recovery was considered when cases did not reach more than 250 CD4+ T cells/µL at 144 weeks (immunological nonresponders, INR). Circulating adipokine concentrations were longitudinally measured using enzyme-linked immunosorbent assays. At baseline, apelin receptor (APLNR) and zinc-alpha-2-glycoprotein (ZAG) concentrations were significantly lower in INRs than in immunological responders (p = 0.043 and p = 0.034), and they remained lower during all ART follow-up visits (p = 0.044 and p = 0.028 for APLNR, p = 0.038 and p = 0.010 for ZAG, at 48 and 144 weeks, respectively). ZAG levels positively correlated with retinol-binding protein 4 (RBP4) levels (p < 0.01), and low circulating RBP4 concentrations were related to a low CD4+ T-cell gain (p = 0.018 and p = 0.039 at 48 and 144 weeks, respectively). Multiple regression adjusted for clinical variables and adipokine concentrations confirmed both low APLNR and RBP4 as independent predictors for CD4+ T cells at 144 weeks (p < 0.001). In conclusion, low APLNR and RBP4 concentrations were associated with poor immune recovery in treated PLHIV and could be considered predictive biomarkers of a discordant immunological response.
MicroRNA-199b Deregulation Shows Oncogenic Properties and Promising Clinical Value as Circulating Marker in Locally Advanced Rectal Cancer Patients
Authors: Santos Andrea , Cristóbal Ion , Rubio Jaime , Caramés Cristina , Luque Melani , Sanz-Alvarez Marta , Morales-Gallego Miriam , Madoz-Gúrpide Juan , Rojo Federico , García-Foncillas Jesús
Published: February 2022

The identification of robust prognostic markers still represents a need in locally advanced rectal cancer (LARC). MicroRNAs (miRs) have progressively emerged as promising circulating markers, overcoming some limitations that traditional biopsy comprises. Tissue miR-199b deregulation has been reported to predict outcome and response to neoadjuvant chemoradiotherapy (nCRT) in LARC, and was also found to be associated with disease progression in colorectal cancer. However, its biological and clinical relevance remains to be fully clarified. Thus, we observed here that miR-199b regulates cell migration, aggressiveness, and cell growth, and inhibits colonosphere formation and induces caspase-dependent apoptosis. Moreover, miR-199b expression was quantified by real-time PCR in plasma samples from LARC patients and its downregulation was observed in 22.7% of cases. This alteration was found to be associated with higher tumor size (p = 0.002) and pathological stage (p = 0.020) after nCRT. Notably, we observed substantially lower global miR-199b expression associated with patient downstaging (p = 0.009), as well as in non-responders compared to those cases who responded to nCRT in both pre- (p = 0.003) and post-treatment samples (p = 0.038). In concordance, we found that miR-199b served as a predictor marker of response to neoadjuvant therapy in our cohort (p = 0.011). Altogether, our findings here demonstrate the functional relevance of miR-199b in this disease and its potential value as a novel circulating marker in LARC.
Evaluation of Cell Migration and Cytokines Expression Changes under the Radiofrequency Electromagnetic Field on Wound Healing In Vitro Model
Authors: Costantini Erica , Aielli Lisa , Serra Federica , De Dominicis Lorenzo , Falasca Katia , Di Giovanni Pamela , Reale Marcella
Published: February 2022

Wound healing (WH) proceeds through four distinct phases: hemostasis, inflammation, proliferation, and remodeling. Impaired WH may be the consequence of the alteration of one of these phases and represents a significant health and economic burden to millions of individuals. Thus, new therapeutic strategies are the topics of intense research worldwide. Although radiofrequency electromagnetic field (RF-EMF) has many medical applications in rehabilitation, pain associated with musculoskeletal disorders, and degenerative joint disorders, its impact on WH is not fully understood. The process of WH begins just after injury and continues during the inflammatory and proliferative phases. A thorough understanding of the mechanisms by which RF-EMF can improve WH is required before it can be used as a non-invasive, inexpensive, and easily self-applicable therapeutic strategy. Thus, the aim of this study is to explore the therapeutic potential of different exposure setups of RF-EMF to drive faster healing, evaluating the keratinocytes migration, cytokines, and matrix metalloproteinases (MMPs) expression. The results showed that RF-EMF treatment promotes keratinocytes’ migration and regulates the expression of genes involved in healing, such as MMPs, tissue inhibitors of metalloproteinases, and pro/anti-inflammatory cytokines, to improve WH.
Improvement and Re-Evolution of Tetraploid Wheat for Global Environmental Challenge and Diversity Consumption Demand
Authors: Yang Fan , Zhang Jingjuan , Liu Qier , Liu Hang , Zhou Yonghong , Yang Wuyun , Ma Wujun
Published: February 2022

Allotetraploid durum wheat is the second most widely cultivated wheat, following hexaploid bread wheat, and is one of the major protein and calorie sources of the human diet. However, durum wheat is encountered with a severe grain yield bottleneck due to the erosion of genetic diversity stemming from long-term domestication and especially modern breeding programs. The improvement of yield and grain quality of durum wheat is crucial when confronted with the increasing global population, changing climate environments, and the non-ignorable increasing incidence of wheat-related disorders. This review summarized the domestication and evolution process and discussed the durum wheat re-evolution attempts performed by global researchers using diploid einkorn, tetraploid emmer wheat, hexaploid wheat (particularly the D-subgenome), etc. In addition, the re-evolution of durum wheat would be promoted by the genetic enrichment process, which could diversify allelic combinations through enhancing chromosome recombination (pentaploid hybridization or pairing of homologous chromosomes gene Ph mutant line induced homoeologous recombination) and environmental adaptability via alien introgressive genes (wide cross or distant hybridization followed by embryo rescue), and modifying target genes or traits by molecular approaches, such as CRISPR/Cas9 or RNA interference (RNAi). A brief discussion of the future perspectives for exploring germplasm for the modern improvement and re-evolution of durum wheat is included.
Capsaicin and Zinc Promote Glucose Uptake in C2C12 Skeletal Muscle Cells through a Common Calcium Signalling Pathway
Authors: Ferdowsi Parisa Vahidi , Ahuja Kiran D. K. , Beckett Jeffrey M. , Myers Stephen
Published: February 2022

Capsaicin and zinc have recently been highlighted as potential treatments for glucose metabolism disorders; however, the effect of these two natural compounds on signalling pathways involved in glucose metabolism is still uncertain. In this study, we assessed the capsaicin- or zinc- induced activation of signalling molecules including calcium/calmodulin-dependent protein kinase 2 (CAMKK2), cAMP-response element-binding protein (CREB), and target of rapamycin kinase complex 1 (TORC1). Moreover, the expression status of genes associated with the control of glucose metabolism was measured in treated cells. The activation of cell signalling proteins was then evaluated in capsaicin- or zinc treated cells in the presence or absence of cell-permeant calcium chelator (BAPTA-AM) and the CAMKK inhibitor (STO-609). Finally, capsaicin- and zinc-induced glucose uptake was measured in the cells pre-treated with or without BAPTA-AM. Our results indicate that calcium flux induced by capsaicin or zinc led to activation of calcium signalling molecules and promoting glucose uptake in skeletal muscle cells. Pharmacological inhibition of CAMKK diminished activation of signalling molecules. Moreover, we observed an increase in intracellular cAMP levels in the cells after treatment with capsaicin and zinc. Our data show that capsaicin and zinc mediate glucose uptake in C2C12 skeletal muscle cells through the activation of calcium signalling.
BnERF114.A1, a Rapeseed Gene Encoding APETALA2/ETHYLENE RESPONSE FACTOR, Regulates Plant Architecture through Auxin Accumulation in the Apex in Arabidopsis
Authors: Lyu Jinyang , Guo Yuan , Du Chunlei , Yu Haibo , Guo Lijian , Liu Li , Zhao Huixian , Wang Xinfa , Hu Shengwu
Published: February 2022

Plant architecture is crucial for rapeseed breeding. Here, we demonstrate the involvement of BnERF114.A1, a transcription factor for ETHYLENE RESPONSE FACTOR (ERF), in the regulation of plant architecture in Brassica napus. BnERF114.A1 is a member of the ERF family group X-a, encoding a putative 252-amino acid (aa) protein, which harbours the AP2/ERF domain and the conserved CMX-1 motif. BnERF114.A1 is localised to the nucleus and presents transcriptional activity, with the functional region located at 142–252 aa of the C-terminus. GUS staining revealed high BnERF114.A1 expression in leaf primordia, shoot apical meristem, leaf marginal meristem, and reproductive organs. Ectopic BnERF114.A1 expression in Arabidopsis reduced plant height, increased branch and silique number per plant, and improved seed yield per plant. Furthermore, in Arabidopsis, BnERF114.A1 overexpression inhibited indole-3-acetic acid (IAA) efflux, thus promoting auxin accumulation in the apex and arresting apical dominance. Therefore, BnERF114.A1 probably plays an important role in auxin-dependent plant architecture regulation.
Multiomics Analysis of Endocytosis upon HBV Infection and Identification of SCAMP1 as a Novel Host Restriction Factor against HBV Replication
Authors: Yousaf Tanzeel , Sun Yuting , Naz Wajeeha , Liu Yang , Xu Jiaqi , Yuan Sen , Wu Kangwei , Wang Min , Wang Jun , Guo Mingxiong , Sun Guihong
Published: February 2022

Hepatitis B virus (HBV) infection remains a major global health problem and the primary cause of cirrhosis and hepatocellular carcinoma (HCC). HBV intrusion into host cells is prompted by virus–receptor interactions in clathrin-mediated endocytosis. Here, we report a comprehensive view of the cellular endocytosis-associated transcriptome, proteome and ubiquitylome upon HBV infection. In this study, we quantified 273 genes in the transcriptome and 190 endocytosis-associated proteins in the proteome by performing multi-omics analysis. We further identified 221 Lys sites in 77 endocytosis-associated ubiquitinated proteins. A weak negative correlation was observed among endocytosis-associated transcriptome, proteome and ubiquitylome. We found 33 common differentially expressed genes (DEGs), differentially expressed proteins (DEPs), and Kub-sites. Notably, we reported the HBV-induced ubiquitination change of secretory carrier membrane protein (SCAMP1) for the first time, differentially expressed across all three omics data sets. Overexpression of SCAMP1 efficiently inhibited HBV RNAs/pgRNA and secreted viral proteins, whereas knockdown of SCAMP1 significantly increased viral production. Mechanistically, the EnhI/XP, SP1, and SP2 promoters were inhibited by SCAMP1, which accounts for HBV X and S mRNA inhibition. Overall, our study unveils the previously unknown role of SCAMP1 in viral replication and HBV pathogenesis and provides cumulative and novel information for a better understanding of endocytosis in response to HBV infection.
A Transcriptomic Approach to Elucidate the Mechanisms of Gefitinib-Induced Toxicity in Healthy Human Intestinal Organoids
Authors: Rodrigues Daniela , Herpers Bram , Ferreira Sofia , Jo Heeseung , Fisher Ciarán , Coyle Luke , Chung Seung-Wook , Kleinjans Jos C. S. , Jennen Danyel G. J. , de Kok Theo M.
Published: February 2022

Gefitinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits the epidermal growth factor receptor (EGFR), hampering cell growth and proliferation. Due to its action, gefitinib has been used in the treatment of cancers that present abnormally increased expression of EGFR. However, side effects from gefitinib therapy may occur, among which diarrhoea is most common, that can lead to interruption of the planned therapy in the more severe cases. The mechanisms underlying intestinal toxicity induced by gefitinib are not well understood. Therefore, this study aims at providing insight into these mechanisms based on transcriptomic responses induced in vitro. A 3D culture of healthy human colon and small intestine (SI) organoids was exposed to 0.1, 1, 10 and 30 µM of gefitinib, for a maximum of three days. These drug concentrations were selected using physiologically-based pharmacokinetic simulation considering patient dosing regimens. Samples were used for the analysis of viability and caspase 3/7 activation, image-based analysis of structural changes, as well as RNA isolation and sequencing via high-throughput techniques. Differential gene expression analysis showed that gefitinib perturbed signal transduction pathways, apoptosis, cell cycle, FOXO-mediated transcription, p53 signalling pathway, and metabolic pathways. Remarkably, opposite expression patterns of genes associated with metabolism of lipids and cholesterol biosynthesis were observed in colon versus SI organoids in response to gefitinib. These differences in the organoids’ responses could be linked to increased activated protein kinase (AMPK) activity in colon, which can influence the sensitivity of the colon to the drug. Therefore, this study sheds light on how gefitinib induces toxicity in intestinal organoids and provides an avenue towards the development of a potential tool for drug screening and development.
An Efficient Agrobacterium-Mediated Transformation Method for Hybrid Poplar 84K (Populus alba × P. glandulosa) Using Calli as Explants
Authors: Wen Shuang-Shuang , Ge Xiao-Lan , Wang Rui , Yang Hai-Feng , Bai Yu-E. , Guo Ying-Hua , Zhang Jin , Lu Meng-Zhu , Zhao Shu-Tang , Wang Liu-Qiang
Published: February 2022

A highly efficient Agrobacterium-mediated transformation method is needed for the molecular study of model tree species such as hybrid poplar 84K (Populus alba × P. glandulosa cv. ‘84K’). In this study, we report a callus-based transformation method that exhibits high efficiency and reproducibility. The optimized callus induction medium (CIM1) induced the development of calli from leaves with high efficiency, and multiple shoots were induced from calli growing on the optimized shoot induction medium (SIM1). Factors affecting the transformation frequency of calli were optimized as follows: Agrobacterium concentration sets at an OD600 of 0.6, Agrobacterium infective suspension with an acetosyringone (AS) concentration of 100 µM, infection time of 15 min, cocultivation duration of 2 days and precultivation duration of 6 days. Using this method, transgenic plants are obtained within approximately 2 months with a transformation frequency greater than 50%. Polymerase chain reaction (PCR), reverse transcription-PCR (RT-PCR) and β-galactosidase (GUS) histochemical staining analyses confirmed the successful generation of stable transformants. Additionally, the calli from leaves were subcultured and used to obtain new explants; the high transformation efficiency was still maintained in subcultured calli after 6 cycles. This method provides a reference for developing effective transformation protocols for other poplar species.
Adipsin Serum Concentrations and Adipose Tissue Expression in People with Obesity and Type 2 Diabetes
Authors: Milek Margarete , Moulla Yusef , Kern Matthias , Stroh Christine , Dietrich Arne , Schön Michael R , Gärtner Daniel , Lohmann Tobias , Dressler Miriam , Kovacs Peter , Stumvoll Michael , Blüher Matthias , Guiu-Jurado Esther
Published: February 2022

(1) Adipsin is an adipokine that may link increased fat mass and adipose tissue dysfunction to obesity-related cardiometabolic diseases. Here, we investigated whether adipsin serum concentrations and adipose tissue (AT) adipsin mRNA expression are related to parameters of AT function, obesity and type 2 diabetes (T2D). (2) Methods: A cohort of 637 individuals with a wide range of age and body weight (Age: 18–85 years; BMI: 19–70 kg/m2) with (n = 237) or without (n = 400) T2D was analyzed for serum adipsin concentrations by ELISA and visceral (VAT) and subcutaneous (SAT) adipsin mRNA expression by RT-PCR. (3) Results: Adipsin serum concentrations were significantly higher in patients with T2D compared to normoglycemic individuals. We found significant positive univariate relationships of adipsin serum concentrations with age (r = 0.282, p < 0.001), body weight (r = 0.264, p < 0.001), fasting plasma glucose (r = 0.136, p = 0.006) and leptin serum concentrations (r = 0.362, p < 0.001). Neither VAT nor SAT adipsin mRNA expression correlated with adipsin serum concentrations after adjusting for age, sex and BMI. Independent of T2D status, we found significantly higher adipsin expression in SAT compared to VAT (4) Conclusions: Our data suggest that adipsin serum concentrations are strongly related to obesity and age. However, neither circulating adipsin nor adipsin AT expression reflects parameters of impaired glucose or lipid metabolism in patients with obesity with or without T2D.
Cell Membrane-Cloaked Nanotherapeutics for Targeted Drug Delivery
Authors: Lee Na-Hyun , You Sumin , Taghizadeh Ali , Taghizadeh Mohsen , Kim Hye Sung
Published: February 2022

Cell membrane cloaking technique is bioinspired nanotechnology that takes advantage of naturally derived design cues for surface modification of nanoparticles. Unlike modification with synthetic materials, cell membranes can replicate complex physicochemical properties and biomimetic functions of the parent cell source. This technique indeed has the potential to greatly augment existing nanotherapeutic platforms. Here, we provide a comprehensive overview of engineered cell membrane-based nanotherapeutics for targeted drug delivery and biomedical applications and discuss the challenges and opportunities of cell membrane cloaking techniques for clinical translation.
Nucleotide Excision Repair Pathway Activity Is Inhibited by Airborne Particulate Matter (PM10) through XPA Deregulation in Lung Epithelial Cells
Authors: Quezada-Maldonado Ericka Marel , Chirino Yolanda I. , Gonsebatt María Eugenia , Morales-Bárcenas Rocío , Sánchez-Pérez Yesennia , García-Cuellar Claudia M.
Published: February 2022

Airborne particulate matter with a diameter size of ≤10 µm (PM10) is a carcinogen that contains polycyclic aromatic hydrocarbons (PAH), which form PAH–DNA adducts. However, the way in which these adducts are managed by DNA repair pathways in cells exposed to PM10 has been partially described. We evaluated the effect of PM10 on nucleotide excision repair (NER) activity and on the levels of different proteins of this pathway that eliminate bulky DNA adducts. Our results showed that human lung epithelial cells (A549) exposed to 10 µg/cm2 of PM10 exhibited PAH–DNA adducts as well as an increase in RAD23 and XPD protein levels (first responders in NER). In addition, PM10 increased the levels of H4K20me2, a recruitment signal for XPA. However, we observed a decrease in total and phosphorylated XPA (Ser196) and an increase in phosphatase WIP1, aside from the absence of XPA–RPA complex, which participates in DNA-damage removal. Additionally, an NER activity assay demonstrated inhibition of the NER functionality in cells exposed to PM10, indicating that XPA alterations led to deficiencies in DNA repair. These results demonstrate that PM10 exposure induces an accumulation of DNA damage that is associated with NER inhibition, highlighting the role of PM10 as an important contributor to lung cancer.
Transcriptional Alterations in X-Linked Dystonia–Parkinsonism Caused by the SVA Retrotransposon
Authors: Pozojevic Jelena , Algodon Shela Marie , Cruz Joseph Neos , Trinh Joanne , Brüggemann Norbert , Laß Joshua , Grütz Karen , Schaake Susen , Tse Ronnie , Yumiceba Veronica , Kruse Nathalie , Schulz Kristin , Sreenivasan Varun K. A. , Rosales Raymond L. , Jamora Roland Dominic G. , Diesta Cid Czarina E. , Matschke Jakob , Glatzel Markus , Seibler Philip , Händler Kristian , Rakovic Aleksandar , Kirchner Henriette , Spielmann Malte , Kaiser Frank J. , Klein Christine , Westenberger Ana
Published: February 2022

X-linked dystonia–parkinsonism (XDP) is a severe neurodegenerative disorder that manifests as adult-onset dystonia combined with parkinsonism. A SINE-VNTR-Alu (SVA) retrotransposon inserted in an intron of the TAF1 gene reduces its expression and alters splicing in XDP patient-derived cells. As a consequence, increased levels of the TAF1 intron retention transcript TAF1-32i can be found in XDP cells as compared to healthy controls. Here, we investigate the sequence of the deep intronic region included in this transcript and show that it is also present in cells from healthy individuals, albeit in lower amounts than in XDP cells, and that it undergoes degradation by nonsense-mediated mRNA decay. Furthermore, we investigate epigenetic marks (e.g., DNA methylation and histone modifications) present in this intronic region and the spanning sequence. Finally, we show that the SVA evinces regulatory potential, as demonstrated by its ability to repress the TAF1 promoter in vitro. Our results enable a better understanding of the disease mechanisms underlying XDP and transcriptional alterations caused by SVA retrotransposons.
Cannabidiol Downregulates Myocardial de Novo Ceramide Synthesis Pathway in a Rat Model of High-Fat Diet-Induced Obesity
Authors: Charytoniuk Tomasz , Sztolsztener Klaudia , Bielawiec Patrycja , Chabowski Adrian , Konstantynowicz-Nowicka Karolina , Harasim-Symbor Ewa
Published: February 2022

It is known that metabolic disturbances, including obesity, predispose to an increased incidence of cardiovascular diseases. Elevated consumption of dietary fat results in intramyocardial accumulation of lipids and their biologically active derivatives, which can disrupt the contractile function of the heart, its metabolism, and intracellular signaling pathways. Therefore, alternative methods, such as phytocannabinoids, are being sought for the treatment of obesity-related effects. In a model of rodent obesity (seven weeks of high-fat-diet (HFD) regime), we used cannabidiol—CBD therapy (intraperitoneal injections for 14 days; 10 mg/kg). High-performance and gas-liquid chromatographies were applied in order to determine sphingolipids in the heart and plasma as well as Western blotting for protein expression. Two-week CBD administration significantly inhibited the de novo ceramide synthesis pathway in the heart of HFD fed rats by lowering sphinganine and sphinganine-1-phosphate contents. The above reductions were accompanied by markedly diminished expressions of myocardial serine palmitoyltransferase 1 and 2 as well as ceramide synthase 5 and 6 in the HFD group with 2-week CBD treatment. To our knowledge, this research is the first that reveals unknown effects of CBD treatment on the heart, i.e., amelioration of de novo ceramide synthesis pathway in obese rats.
Hematopoietic Progenitors and the Bone Marrow Niche Shape the Inflammatory Response and Contribute to Chronic Disease
Authors: Xu Yangsong , Murphy Andrew J. , Fleetwood Andrew J.
Published: February 2022

It is now well understood that the bone marrow (BM) compartment can sense systemic inflammatory signals and adapt through increased proliferation and lineage skewing. These coordinated and dynamic alterations in responding hematopoietic stem and progenitor cells (HSPCs), as well as in cells of the bone marrow niche, are increasingly viewed as key contributors to the inflammatory response. Growth factors, cytokines, metabolites, microbial products, and other signals can cause dysregulation across the entire hematopoietic hierarchy, leading to lineage-skewing and even long-term functional adaptations in bone marrow progenitor cells. These alterations may play a central role in the chronicity of disease as well as the links between many common chronic disorders. The possible existence of a form of “memory” in bone marrow progenitor cells is thought to contribute to innate immune responses via the generation of trained immunity (also called innate immune memory). These findings highlight how hematopoietic progenitors dynamically adapt to meet the demand for innate immune cells and how this adaptive response may be beneficial or detrimental depending on the context. In this review, we will discuss the role of bone marrow progenitor cells and their microenvironment in shaping the scope and scale of the immune response in health and disease.
Tunneling Nanotubes: A New Target for Nanomedicine?
Authors: Ottonelli Ilaria , Caraffi Riccardo , Tosi Giovanni , Vandelli Maria Angela , Duskey Jason Thomas , Ruozi Barbara
Published: February 2022

Tunneling nanotubes (TNTs), discovered in 2004, are thin, long protrusions between cells utilized for intercellular transfer and communication. These newly discovered structures have been demonstrated to play a crucial role in homeostasis, but also in the spreading of diseases, infections, and metastases. Gaining much interest in the medical research field, TNTs have been shown to transport nanomedicines (NMeds) between cells. NMeds have been studied thanks to their advantageous features in terms of reduced toxicity of drugs, enhanced solubility, protection of the payload, prolonged release, and more interestingly, cell-targeted delivery. Nevertheless, their transfer between cells via TNTs makes their true fate unknown. If better understood, TNTs could help control NMed delivery. In fact, TNTs can represent the possibility both to improve the biodistribution of NMeds throughout a diseased tissue by increasing their formation, or to minimize their formation to block the transfer of dangerous material. To date, few studies have investigated the interaction between NMeds and TNTs. In this work, we will explain what TNTs are and how they form and then review what has been published regarding their potential use in nanomedicine research. We will highlight possible future approaches to better exploit TNT intercellular communication in the field of nanomedicine.
Enzymatic Synthesis and Molecular Modelling Studies of Rhamnose Esters Using Lipase from Pseudomonas stutzeri
Authors: García-Oliva Cecilia , Perona Almudena , Rumbero Ángel , Hoyos Pilar , Hernáiz María J.
Published: February 2022

Rhamnolipids are becoming an important class of glycolipid biosurfactants. Herein, we describe for the first time the enzymatic synthesis of rhamnose fatty acid esters by the transesterification of rhamnose with fatty acid vinyl esters, using lipase from Pseudomonas stutzeri as a biocatalyst. The use of this lipase allows excellent catalytic activity in the synthesis of 4-O-acylrhamnose (99% conversion and full regioselectivity) after 3 h of reaction using tetrahydrofuran (THF) as the reaction media and an excess of vinyl laurate as the acyl donor. The role of reaction conditions, such as temperature, the substrates molar ratio, organic reaction medium and acyl donor chain-length, was studied. Optimum conditions were found using 35 °C, a molar ratio of 1:3 (rhamnose:acyldonor), solvents with a low logP value, and fatty acids with chain lengths from C4 to C18 as acyl donors. In hydrophilic solvents such as THF and acetone, conversions of up to 99–92% were achieved after 3 h of reaction. In a more sustainable solvent such as 2-methyl-THF (2-MeTHF), high conversions were also obtained (86%). Short and medium chain acyl donors (C4–C10) allowed maximum conversions after 3 h, and long chain acyl donors (C12–C18) required longer reactions (5 h) to get 99% conversions. Furthermore, scaled up reactions are feasible without losing catalytic action and regioselectivity. In order to explain enzyme regioselectivity and its ability to accommodate ester chains of different lengths, homology modelling, docking studies and molecular dynamic simulations were performed to explain the behaviour observed.
Kidney Injury in COVID-19: Epidemiology, Molecular Mechanisms and Potential Therapeutic Targets
Authors: Teixeira J. Pedro , Barone Sharon , Zahedi Kamyar , Soleimani Manoocher
Published: February 2022

As of December 2021, SARS-CoV-2 had caused over 250 million infections and 5 million deaths worldwide. Furthermore, despite the development of highly effective vaccines, novel variants of SARS-CoV-2 continue to sustain the pandemic, and the search for effective therapies for COVID-19 remains as urgent as ever. Though the primary manifestation of COVID-19 is pneumonia, the disease can affect multiple organs, including the kidneys, with acute kidney injury (AKI) being among the most common extrapulmonary manifestations of severe COVID-19. In this article, we start by reflecting on the epidemiology of kidney disease in COVID-19, which overwhelmingly demonstrates that AKI is common in COVID-19 and is strongly associated with poor outcomes. We also present emerging data showing that COVID-19 may result in long-term renal impairment and delve into the ongoing debate about whether AKI in COVID-19 is mediated by direct viral injury. Next, we focus on the molecular pathogenesis of SARS-CoV-2 infection by both reviewing previously published data and presenting some novel data on the mechanisms of cellular viral entry. Finally, we relate these molecular mechanisms to a series of therapies currently under investigation and propose additional novel therapeutic targets for COVID-19.
Transcription Profiles Reveal Age-Dependent Variations of Photosynthetic Properties and Sugar Metabolism in Grape Leaves (Vitis vinifera L.)
Authors: Li You-Mei , You Jia-Ling , Nie Wen-Feng , Sun Meng-Hao , Xie Zhao-Sen
Published: February 2022

Leaves, considered as the ‘source’ organs, depend on the development stages because of the age-dependent photosynthesis and assimilation of leaves. However, the molecular mechanisms of age-dependent limitations on the function of leaves are seldom reported. In the present study, the photosynthesis-related characteristics and photoassimilates were investigated in grape leaves at six different age groups (Ll to L6) at micro-morphological, biochemical, and molecular levels. These results showed lower expression levels of genes associated with stomatal development, and chl biosynthesis resulted in fewer stomata and lowered chlorophyll a/b contents in L1 when compared to L3 and L5. The DEGs between L5 and L3/L1 were largely distributed at stomatal movement, carbon fixation, and sucrose and starch metabolism pathways, such as STOMATAL ANION CHANNEL PROTEIN 1 (SLAC1), FRUCTOSE-1,6-BISPHOSPHATE ALDOLASE (FBA1), SUCROSE-PHOSPHATE SYNTHASE (SPP1), and SUCROSE-PHOSPHATE PHOSPHATASE (SPS2, 4). These genes could be major candidate genes leading to increased photosynthesis capacity and sugar content in L5. The accumulation of starch grains in the chloroplast and palisade tissue of L5 and higher transcription levels of genes related to starch biosynthesis in L5 further supported the high ability of L5 to produce photoassimilates. Hence, our results provide insights for understanding different photosynthetic functions in age-dependent leaves in grape plants at the molecular level.
Promising Treatment for Multiple Sclerosis: Mitochondrial Transplantation
Authors: Picone Pasquale , Nuzzo Domenico
Published: February 2022

In recent years, several studies have examined the multifaceted role of mitochondria in Multiple Sclerosis (MS), suggesting that, besides inflammation and demyelination, mitochondrial aberration is a crucial factor in mediating axonal degeneration, the latter being responsible for persistent disabilities in MS patients. Therefore, mitochondria have been recognized as a possible multiple sclerosis therapeutic target. Recently, mitochondrial transplantation has become a new term for the transfer of live mitochondria into damaged cells for the treatment of various diseases, including neurodegenerative diseases. In this hypothesis, we propose mitochondrial transplantation as a new, potentially applicable approach to counteract axonal degeneration in multiple sclerosis.
Overcoming Radiation Resistance in Gliomas by Targeting Metabolism and DNA Repair Pathways
Authors: Meng Wei , Palmer Joshua D. , Siedow Michael , Haque Saikh Jaharul , Chakravarti Arnab
Published: February 2022

Gliomas represent a wide spectrum of brain tumors characterized by their high invasiveness, resistance to chemoradiotherapy, and both intratumoral and intertumoral heterogeneity. Recent advances in transomics studies revealed that enormous abnormalities exist in different biological layers of glioma cells, which include genetic/epigenetic alterations, RNA expressions, protein expression/modifications, and metabolic pathways, which provide opportunities for development of novel targeted therapeutic agents for gliomas. Metabolic reprogramming is one of the hallmarks of cancer cells, as well as one of the oldest fields in cancer biology research. Altered cancer cell metabolism not only provides energy and metabolites to support tumor growth, but also mediates the resistance of tumor cells to antitumor therapies. The interactions between cancer metabolism and DNA repair pathways, and the enhancement of radiotherapy sensitivity and assessment of radiation response by modulation of glioma metabolism are discussed herein.
Brixia Score in Outcomes of Alpha versus Delta Variant of Infection in Pregnant Critical COVID-19 Patients
Authors: Covali Roxana , Socolov Demetra , Pavaleanu Ioana , Akad Mona , Boiculese Lucian Vasile , Socolov Razvan
Published: February 2022

Background: Critical COVID-19 patients account for 1.7 to 13% of all pregnant COVID-19 patients. Methods: Patients admitted to the COVID-19 intensive care unit of Elena Doamna Obstetrics and Gynecology University Hospital in Iasi between 1 January and 1 December 2021, with critical forms of the disease, were included and retrospectively studied. The patients’ age range was 25–44 years in the Alpha group (n = 12) and 27–52 years in the Delta group (n = 9). Results: Most critically ill pregnant COVID-19 patients in the Alpha group delivered when admitted to the intensive care unit, while less than half of those in the Delta group delivered when admitted; the rest were released home and continued their pregnancy normally. There was a significant difference regarding the number of patients released to home care and the number of days after admission when delivery occurred (p = 0.02 and 0.022, respectively). Conclusions: There was no significant difference in maternal and fetal outcomes between the two groups, except for the number of patients released to home care and the number of days after admission when delivery occurred. There was no correlation between any Brixia scores (H, L, A, E) and any maternal or fetal outcomes in both groups.
Detecting Learning Patterns in Tertiary Education Using K-Means Clustering
Authors: Tuyishimire Emmanuel , Mabuto Wadzanai , Gatabazi Paul , Bayisingize Sylvie
Published: February 2022

We are in the era where various processes need to be online. However, data from digital learning platforms are still underutilised in higher education, yet, they contain student learning patterns, whose awareness would contribute to educational development. Furthermore, the knowledge of student progress would inform educators whether they would mitigate teaching conditions for critically performing students. Less knowledge of performance patterns limits the development of adaptive teaching and learning mechanisms. In this paper, a model for data exploitation to dynamically study students progress is proposed. Variables to determine current students progress are defined and are used to group students into different clusters. A model for dynamic clustering is proposed and related cluster migration is analysed to isolate poorer or higher performing students. K-means clustering is performed on real data consisting of students from a South African tertiary institution. The proposed model for cluster migration analysis is applied and the corresponding learning patterns are revealed.
Material Properties and Morphology of Prestomal Teeth in Relation to the Feeding Habits of Diptera (Brachycera)
Authors: Lehnert Matthew S. , Tarver Lauren A. , Feng Jiansheng
Published: February 2022

Prestomal teeth are cuticular projections on the mouthparts of some fly species that rasp surfaces when feeding. Although prestomal teeth morphology has been reported for several fly species, their material properties have not been investigated. Here we report the morphology, elemental composition, extent of sclerotization, hardness, and elastic modulus of prestomal teeth and relate these findings to feeding habits. Scanning electron microscopy revealed that species categorized as flower visitors have a large labellum with numerous pseudotracheae and lack prestomal teeth, generalist species have these same features but with prestomal teeth, and specialist species that feed on blood or other insects have a smaller labellum with few or no pseudotracheae and relatively large prestomal teeth. Confocal microscopy revealed that prestomal teeth are heavily sclerotized and the labellum contains resilin, an elastomeric protein. Hardness and elastic modulus were explored with nanoindentation and showed that the insectivorous Scathophaga stercoraria had the hardest prestomal teeth and the highest modulus. Energy dispersive x-ray spectroscopy revealed that prestomal teeth had low concentrations of inorganic elements, suggesting that hardness might be partially supplemented by inorganic elements. Our findings indicate that prestomal teeth morphology and material properties relate more to feeding habits than to phylogeny.
Manufacturing of a Granular Fertilizer Based on Organic Slurry and Hardening Agent
Authors: Moure Abelenda Alejandro , Amaechi Chiemela Victor
Published: February 2022

The manufacturing of a granular fertilizer based on organic slurry (OS) and sorptive materials aims to enhance the circular economy. This article describes a technology that was conceived after appraising the chemistry of the anaerobic digestate and wood ash and the synergies of combining both materials. The information available in the literature about similar materials such as cattle slurry and lime was also considered to build a better understanding of the underlying science. The processes and machinery designed were optimized from the points of view of energy and material consumption, cost of storage, transportation and land application. The system was sized to process 1 tonne of OS (97% moisture) in a 10 h batch-shift, consuming 140 kg of wood pellets and 0.55 kW of electricity for the fan blowing preheated air. The results of the market research allowed us to reach the most economically viable routes for the commercialization of granular fertilizers. Based on the financial study, an initial investment of GBP 20,000 is needed to successfully implement the value proposition and business plan. The wide adoption of the composite fertilizer improves the management of the OS and reduces the contamination of air, soil, and water derived from intensive agricultural practices.
Characterization of Recycled/Virgin Polyethylene Terephthalate Composite Reinforced with Glass Fiber for Automotive Applications
Authors: Volpe Valentina , Lanzillo Maria Sofia , Molaro Alfonso , Affinita Giovanni , Pantani Roberto
Published: February 2022

The use of recycled polyethylene terephthalate (PET) as a matrix for composite materials based on glass fiber reinforced virgin PET could be a cost-effective and environmentally friendly way to upgrade the bottle-grade recycled PET into engineering-grade PET for injection molding. In this work, a commercial virgin PET reinforced with 50%wt of glass fibers was compounded by mechanical mixing with a recycled PET, in order to minimize breakage of the glass fibers. The obtained compound, composed by 60%wt of recycled pet and 40%wt glass fiber reinforced virgin PET, was injection molded at three different mold temperatures (4, 40 and 80 °C) to analyze the effect of crystallization of the material during the production process. The results in terms of thermal and mechanical properties were compared with those obtained from recycled PET molded in the same conditions. The flexural tests and the analysis of thermal resistance showed that by adding 40%wt of glass fiber reinforced virgin PET to the recycled PET causes a noticeable improvement of crystallization kinetics and of mechanical properties with respect to that of the pure recycled PET, making it suitable for technical applications.