bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Effects of Sweet Potato (Ipomoea batatas) in Hyperglycemia and Dyslipidemia—A Systematic Review in Diabetic Retinopathy Context
Authors: Naomi Ruth , Bahari Hasnah , Yazid Muhammad Dain , Othman Fezah , Zakaria Zainul Amiruddin , Hussain Mohd Khairi
Published: October 2021

Hyperglycemia is a condition with high glucose levels that may result in dyslipidemia. In severe cases, this alteration may lead to diabetic retinopathy. Numerous drugs have been approved by officials to treat these conditions, but usage of any synthetic drugs in the long term will result in unavoidable side effects such as kidney failure. Therefore, more emphasis is being placed on natural ingredients due to their bioavailability and absence of side effects. In regards to this claim, promising results have been witnessed in the usage of Ipomoea batatas (I. batatas) in treating the hyperglycemic and dyslipidemic condition. Thus, the aim of this paper is to conduct an overview of the reported effects of I. batatas focusing on in vitro and in vivo trials in reducing high glucose levels and regulating the dyslipidemic condition. A comprehensive literature search was performed using Scopus, Web of Science, Springer Nature, and PubMed databases to identify the potential articles on particular topics. The search query was accomplished based on the Boolean operators involving keywords such as (1) Beneficial effect OR healing OR intervention AND (2) sweet potato OR Ipomoea batatas OR traditional herb AND (3) blood glucose OR LDL OR lipid OR cholesterol OR dyslipidemia. Only articles published from 2011 onwards were selected for further analysis. This review includes the (1) method of intervention and the outcome (2) signaling mechanism involved (3) underlying mechanism of action, and the possible side effects observed based on the phytoconstiuents isolated. The comprehensive literature search retrieved a total of 2491 articles using the appropriate keywords. However, on the basis of the inclusion and exclusion criteria, only 23 articles were chosen for further review. The results from these articles indicate that I. batatas has proven to be effective in treating the hyperglycemic condition and is able to regulate dyslipidemia. Therefore, this systematic review summarizes the signaling mechanism, mechanism of action, and phytoconstituents responsible for those activities of I. batatas in treating hyperglycemic based on the in vitro and in vivo study.
Vermiculite Filler Modified with Casein, Chitosan, and Potato Protein as a Flame Retardant for Polyurethane Foams
Authors: Miedzińska Karolina , Członka Sylwia , Strąkowska Anna , Strzelec Krzysztof
Published: October 2021

In this study, polyurethane (PU) composite foams were modified with 2 wt.% of vermiculite fillers, which were themselves modified with casein, chitosan, and potato protein. The impact of the fillers on selected properties of the obtained composites, including their rheological (foaming behavior, dynamic viscosity), thermal (temperature of thermal decomposition stages), flame-retardant (e.g., limiting oxygen index, ignition time, heat peak release), and mechanical properties (toughness, compressive strength (parallel and perpendicular), flexural strength) were investigated. Among all the modified polyurethane composites, the greatest improvement was noticed in the PU foams filled with vermiculite modified with casein and chitosan. For example, after the addition of modified vermiculite fillers, the foams’ compressive strength was enhanced by ~6–18%, their flexural strength by ~2–10%, and their toughness by ~1–5%. Most importantly, the polyurethane composites filled with vermiculite filler and modified vermiculite fillers exhibited improved flame resistance characteristics (the value of total smoke release was reduced by ~34%, the value of peak heat release was reduced by ~25%).
Tissue Sampling and Homogenization in the Sub-Microliter Scale with a Nanosecond Infrared Laser (NIRL) for Mass Spectrometric Proteomics
Authors: Hahn Jan , Moritz Manuela , Voß Hannah , Pelczar Penelope , Huber Samuel , Schlüter Hartmut
Published: October 2021

It was recently shown that ultrashort pulse infrared (IR) lasers, operating at the wavelength of the OH vibration stretching band of water, are highly efficient for sampling and homogenizing biological tissue. In this study we utilized a tunable nanosecond infrared laser (NIRL) for tissue sampling and homogenization with subsequent liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis for mass spectrometric proteomics. For the first time, laser sampling was performed with murine spleen and colon tissue. An ablation volume of 1.1 × 1.1 × 0.4 mm³ (approximately 0.5 µL) was determined with optical coherence tomography (OCT). The results of bottom-up proteomics revealed proteins with significant abundance differences for both tissue types, which are in accordance with the corresponding data of the Human Protein Atlas. The results demonstrate that tissue sampling and homogenization of small tissue volumes less than 1 µL for subsequent mass spectrometric proteomics is feasible with a NIRL.
SARS-CoV-2 Virus−Host Interaction: Currently Available Structures and Implications of Variant Emergence on Infectivity and Immune Response
Authors: Queirós-Reis Luís , Gomes da Silva Priscilla , Gonçalves José , Brancale Andrea , Bassetto Marcella , Mesquita João R.
Published: October 2021

Coronavirus disease 19, or COVID-19, is an infection associated with an unprecedented worldwide pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has led to more than 215 million infected people and more than 4.5 million deaths worldwide. SARS-CoV-2 cell infection is initiated by a densely glycosylated spike (S) protein, a fusion protein, binding human angiotensin converting enzyme 2 (hACE2), that acts as the functional receptor through the receptor binding domain (RBD). In this article, the interaction of hACE2 with the RBD and how fusion is initiated after recognition are explored, as well as how mutations influence infectivity and immune response. Thus, we focused on all structures available in the Protein Data Bank for the interaction between SARS-CoV-2 S protein and hACE2. Specifically, the Delta variant carries particular mutations associated with increased viral fitness through decreased antibody binding, increased RBD affinity and altered protein dynamics. Combining both existing mutations and mutagenesis studies, new potential SARS-CoV-2 variants, harboring advantageous S protein mutations, may be predicted. These include mutations S13I and W152C, decreasing antibody binding, N460K, increasing RDB affinity, or Q498R, positively affecting both properties.
Processing and Bypass of a Site-Specific DNA Adduct of the Cytotoxic Platinum–Acridinylthiourea Conjugate by Polymerases Involved in DNA Repair: Biochemical and Thermodynamic Aspects
Authors: Hreusova Monika , Brabec Viktor , Novakova Olga
Published: October 2021

DNA-dependent DNA and RNA polymerases are important modulators of biological functions such as replication, transcription, recombination, or repair. In this work performed in cell-free media, we studied the ability of selected DNA polymerases to overcome a monofunctional adduct of the cytotoxic/antitumor platinum–acridinylthiourea conjugate [PtCl(en)(L)](NO3)2 (en = ethane-1,2-diamine, L = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) (ACR) in its favored 5′-CG sequence. We focused on how a single site-specific ACR adduct with intercalation potency affects the processivity and fidelity of DNA-dependent DNA polymerases involved in translesion synthesis (TLS) and repair. The ability of the G(N7) hybrid ACR adduct formed in the 5′-TCGT sequence of a 24-mer DNA template to inhibit the synthesis of a complementary DNA strand by the exonuclease-deficient Klenow fragment of DNA polymerase I (KFexo−) and human polymerases eta, kappa, and iota was supplemented by thermodynamic analysis of the polymerization process. Thermodynamic parameters of a simulated translesion synthesis across the ACR adduct were obtained by using microscale thermophoresis (MST). Our results show a strong inhibitory effect of an ACR adduct on enzymatic TLS: there was only small synthesis of a full-length product (less than 10%) except polymerase eta (~20%). Polymerase eta was able to most efficiently bypass the ACR hybrid adduct. Incorporation of a correct dCMP opposite the modified G residue is preferred by all the four polymerases tested. On the other hand, the frequency of misinsertions increased. The relative efficiency of misinsertions is higher than that of matched cytidine monophosphate but still lower than for the nonmodified control duplex. Thermodynamic inspection of the simulated TLS revealed a significant stabilization of successively extended primer/template duplexes containing an ACR adduct. Moreover, no significant decrease of dissociation enthalpy change behind the position of the modification can contribute to the enzymatic TLS observed with the DNA-dependent, repair-involved polymerases. This TLS could lead to a higher tolerance of cancer cells to the ACR conjugate compared to its enhanced analog, where thiourea is replaced by an amidine group: [PtCl(en)(L)](NO3)2 (complex AMD, en = ethane-1,2-diamine, L = N-[2-(acridin-9-ylamino)ethyl]-N-methylpropionamidine).
Novel DNA Aptameric Sensors to Detect the Toxic Insecticide Fenitrothion
Authors: Trinh Kien Hong , Kadam Ulhas Sopanrao , Song Jinnan , Cho Yuhan , Kang Chang Ho , Lee Kyun Oh , Lim Chae Oh , Chung Woo Sik , Hong Jong Chan
Published: October 2021

Fenitrothion is an insecticide belonging to the organophosphate family of pesticides that is widely used around the world in agriculture and living environments. Today, it is one of the most hazardous chemicals that causes severe environmental pollution. However, detection of fenitrothion residues in the environment is considered a significant challenge due to the small molecule nature of the insecticide and lack of molecular recognition elements that can detect it with high specificity. We performed in vitro selection experiments using the SELEX process to isolate the DNA aptamers that can bind to fenitrothion. We found that newly discovered DNA aptamers have a strong ability to distinguish fenitrothion from other organophosphate insecticides (non-specific targets). Furthermore, we identified a fenitrothion-specific aptamer; FenA2, that can interact with Thioflavin T (ThT) to produce a label-free detection mode with a Kd of 33.57 nM (9.30 ppb) and LOD of 14 nM (3.88 ppb). Additionally, the FenA2 aptamer exhibited very low cross-reactivity with non-specific targets. This is the first report showing an aptamer sensor with a G4-quadruplex-like structure to detect fenitrothion. Moreover, these aptamers have the potential to be further developed into analytical tools for real-time detection of fenitrothion from a wide range of samples.
Characterization of the Chimeric PriB-SSBc Protein
Authors: Lin En-Shyh , Huang Yen-Hua , Huang Cheng-Yang
Published: October 2021

PriB is a primosomal protein required for the replication fork restart in bacteria. Although PriB shares structural similarity with SSB, they bind ssDNA differently. SSB consists of an N-terminal ssDNA-binding/oligomerization domain (SSBn) and a flexible C-terminal protein–protein interaction domain (SSBc). Apparently, the largest difference in structure between PriB and SSB is the lack of SSBc in PriB. In this study, we produced the chimeric PriB-SSBc protein in which Klebsiella pneumoniae PriB (KpPriB) was fused with SSBc of K. pneumoniae SSB (KpSSB) to characterize the possible SSBc effects on PriB function. The crystal structure of KpSSB was solved at a resolution of 2.3 Å (PDB entry 7F2N) and revealed a novel 114-GGRQ-117 motif in SSBc that pre-occupies and interacts with the ssDNA-binding sites (Asn14, Lys74, and Gln77) in SSBn. As compared with the ssDNA-binding properties of KpPriB, KpSSB, and PriB-SSBc, we observed that SSBc could significantly enhance the ssDNA-binding affinity of PriB, change the binding behavior, and further stimulate the PriA activity (an initiator protein in the pre-primosomal step of DNA replication), but not the oligomerization state, of PriB. Based on these experimental results, we discuss reasons why the properties of PriB can be retrofitted when fusing with SSBc.
Systemic Administration of Recombinant Irisin Accelerates Fracture Healing in Mice
Authors: Colucci Silvia Concetta , Buccoliero Cinzia , Sanesi Lorenzo , Errede Mariella , Colaianni Graziana , Annese Tiziana , Khan Mohd Parvez , Zerlotin Roberta , Dicarlo Manuela , Schipani Ernestina , Kozloff Kenneth M. , Grano Maria
Published: October 2021

To date, pharmacological strategies designed to accelerate bone fracture healing are lacking. We subjected 8-week-old C57BL/6 male mice to closed, transverse, mid-diaphyseal tibial fractures and treated them with intraperitoneal injection of a vehicle or r-irisin (100 µg/kg/weekly) immediately following fracture for 10 days or 28 days. Histological analysis of the cartilaginous callus at 10 days showed a threefold increase in Collagen Type X (p = 0.0012) and a reduced content of proteoglycans (40%; p = 0.0018). Osteoclast count within the callus showed a 2.4-fold increase compared with untreated mice (p = 0.026), indicating a more advanced stage of endochondral ossification of the callus during the early stage of fracture repair. Further evidence that irisin induced the transition of cartilage callus into bony callus was provided by a twofold reduction in the expression of SOX9 (p = 0.0058) and a 2.2-fold increase in RUNX2 (p = 0.0137). Twenty-eight days post-fracture, microCT analyses showed that total callus volume and bone volume were increased by 68% (p = 0.0003) and 67% (p = 0.0093), respectively, and bone mineral content was 74% higher (p = 0.0012) in irisin-treated mice than in controls. Our findings suggest that irisin promotes bone formation in the bony callus and accelerates the fracture repair process, suggesting a possible use as a novel pharmacologic modulator of fracture healing.
Synthesis of Demissidine Analogues from Tigogenin via Imine Intermediates
Authors: Wojtkielewicz Agnieszka , Kiełczewska Urszula , Baj Aneta , Morzycki Jacek W.
Published: October 2021

A five-step transformation of a spiroketal side chain of tigogenin into an indolizidine system present in solanidane alkaloids such as demissidine and solanidine was elaborated. The key intermediate in the synthesis was spiroimine 3 readily obtained from tigogenin by its RuO4 oxidation to 5,6-dihydrokryptogenin followed by amination with aluminum amide generated in situ from DIBAlH and ammonium chloride. The mild reduction of spiroimine to a 26-hydroxy-dihydropyrrole derivative and subsequent mesylation resulted in the formation of 25-epidemissidinium salt or 23-sulfone depending on reaction conditions.
Characterizing Binding Interactions That Are Essential for Selective Transport through the Nuclear Pore Complex
Authors: Lennon Kathleen M. , Soheilypour Mohammad , Peyro Mohaddeseh , Wakefield Devin L. , Choo Grace E. , Mofrad Mohammad R. K. , Jovanovic-Talisman Tijana
Published: October 2021

Specific macromolecules are rapidly transported across the nuclear envelope via the nuclear pore complex (NPC). The selective transport process is facilitated when nuclear transport receptors (NTRs) weakly and transiently bind to intrinsically disordered constituents of the NPC, FG Nups. These two types of proteins help maintain the selective NPC barrier. To interrogate their binding interactions in vitro, we deployed an NPC barrier mimic. We created the stationary phase by covalently attaching fragments of a yeast FG Nup called Nsp1 to glass coverslips. We used a tunable mobile phase containing NTR, nuclear transport factor 2 (NTF2). In the stationary phase, three main factors affected binding: the number of FG repeats, the charge of fragments, and the fragment density. We also identified three main factors affecting binding in the mobile phase: the avidity of the NTF2 variant for Nsp1, the presence of nonspecific proteins, and the presence of additional NTRs. We used both experimentally determined binding parameters and molecular dynamics simulations of Nsp1FG fragments to create an agent-based model. The results suggest that NTF2 binding is negatively cooperative and dependent on the density of Nsp1FG molecules. Our results demonstrate the strengths of combining experimental and physical modeling approaches to study NPC-mediated transport.
Exosomes and Brain Metastases: A Review on Their Role and Potential Applications
Authors: Oliveira Filipa D. , Castanho Miguel A. R. B. , Neves Vera
Published: October 2021

Brain metastases (BM) are a frequent complication in patients with advanced stages of cancer, associated with impairment of the neurological function, quality of life, prognosis, and survival. BM treatment consists of a combination of the available cancer therapies, such as surgery, radiotherapy, chemotherapy, immunotherapy and targeted therapies. Even so, cancer patients with BM are still linked to poor prognosis, with overall survival being reported as 12 months or less. Intercellular communication has a pivotal role in the development of metastases, therefore, it has been extensively studied not only to better understand the metastization process, but also to further develop new therapeutic strategies. Exosomes have emerged as key players in intercellular communication being potential therapeutic targets, drug delivery systems (DDS) or biomarkers. In this Review, we focus on the role of these extracellular vesicles (EVs) in BM formation and their promising application in the development of new BM therapeutic strategies.
Exosome Degeneration in Mesenchymal Stem Cells Derived from Patients with Type 1 Diabetes Mellitus
Authors: Horiguchi Michiko , Okada Yuko , Turudome Yuya , Ushijima Kentaro
Published: October 2021

Type 1 diabetes mellitus is characterized by the destruction of pancreatic β-cells and requires the regeneration of these destroyed pancreatic β-cells for radical treatment. The degeneration of organelles in stem cells compromises stem cell quality; however, organelles in the mesenchymal stem cells of patients with type 1 diabetes mellitus have not been characterized previously. In this study, we use transmission electron microscopy to evaluate the degeneration of organelles in adipose-derived stem cells of patients with type 1 diabetes mellitus (T1DM ADSCs). Compared to adipose-derived stem cells from healthy humans, T1DM ADSCs degenerate differently, characterized by prominent enlarged spherical vesicles. The exosomes of T1DM ADSCs are found to be enlarged, reduced in number, and increased in the percentage of those positive for tetraspanin CD9. The findings of this study provide insight into the characteristics of stem cells in patients with type 1 diabetes mellitus.
Optimizing Agrobacterium-Mediated Transformation and CRISPR-Cas9 Gene Editing in the tropical japonica Rice Variety Presidio
Authors: Molina-Risco Marco , Ibarra Oneida , Faion-Molina Mayra , Kim Backki , Septiningsih Endang M. , Thomson Michael J.
Published: October 2021

Bottlenecks in plant transformation and regeneration have slowed progress in applying CRISPR/Cas-based genome editing for crop improvement. Rice (Oryza sativa L.) has highly efficient temperate japonica transformation protocols, along with reasonably efficient indica protocols using immature embryos. However, rapid and efficient protocols are not available for transformation and regeneration in tropical japonica varieties, even though they represent the majority of rice production in the U.S. and South America. The current study has optimized a protocol using callus induction from mature seeds with both Agrobacterium-mediated and biolistic transformation of the high-yielding U.S. tropical japonica cultivar Presidio. Gene editing efficiency was tested by evaluating knockout mutations in the phytoene desaturase (PDS) and young seedling albino (YSA) genes, which provide a visible phenotype at the seedling stage for successful knockouts. Using the optimized protocol, transformation of 648 explants with particle bombardment and 532 explants with Agrobacterium led to a 33% regeneration efficiency. The YSA targets had ambiguous phenotypes, but 60% of regenerated plants for PDS showed an albino phenotype. Sanger sequencing of edited progeny showed a number of insertions, deletions, and substitutions at the gRNA target sites. These results pave the way for more efficient gene editing of tropical japonica rice varieties.
Biomarkers in AL Amyloidosis
Authors: Fotiou Despina , Theodorakakou Foteini , Kastritis Efstathios
Published: October 2021

Systemic AL amyloidosis is a rare complex hematological disorder caused by clonal plasma cells which produce amyloidogenic immunoglobulins. Outcome and prognosis is the combinatory result of the extent and pattern of organ involvement secondary to amyloid fibril deposition and the biology and burden of the underlying plasma cell clone. Prognosis, as assessed by overall survival, and early outcomes is determined by degree of cardiac dysfunction and current staging systems are based on biomarkers that reflect the degree of cardiac damage. The risk of progression to end-stage renal disease requiring dialysis is assessed by renal staging systems. Longer-term survival and response to treatment is affected by markers of the underlying plasma cell clone; the genetic background of the clonal disease as evaluated by interphase fluorescence in situ hybridization in particular has predictive value and may guide treatment selection. Free light chain assessment forms the basis of hematological response criteria and minimal residual disease as assessed by sensitive methods is gradually being incorporated into clinical practice. However, sensitive biomarkers that could aid in the early diagnosis and that could reflect all aspects of organ damage and disease biology are needed and efforts to identify them are continuous.
d-Amino Acids and pLG72 in Alzheimer’s Disease and Schizophrenia
Authors: Cheng Yu-Jung , Lin Chieh-Hsin , Lane Hsien-Yuan
Published: October 2021

Numerous studies over the last several years have shown that d-amino acids, especially d-serine, have been related to brain and neurological disorders. Acknowledged neurological functions of d-amino acids include neurotransmission and learning and memory functions through modulating N-methyl-d-aspartate type glutamate receptors (NMDARs). Aberrant d-amino acids level and polymorphisms of genes related to d-amino acids metabolism are associated with neurodegenerative brain conditions. This review summarizes the roles of d-amino acids and pLG72, also known as d-amino acid oxidase activator, on two neurodegenerative disorders, schizophrenia and Alzheimer’s disease (AD). The scope includes the changes in d-amino acids levels, gene polymorphisms of G72 genomics, and the role of pLG72 on NMDARs and mitochondria in schizophrenia and AD. The clinical diagnostic value of d-amino acids and pLG72 and the therapeutic importance are also reviewed.
Preclinical Study of Immunological Isoxazole Derivatives as a Potential Support for Melanoma Chemotherapy
Authors: Jęśkowiak Izabela , Wiatrak Benita , Szeląg Adam , Mączyński Marcin
Published: October 2021

(1) Background: Melanoma is an aggressive neoplasm derived from melanocyte precursors with a high metastatic potential. Responses to chemotherapy and immunotherapy for melanoma remain weak, underlining the urgent need to develop new therapeutic strategies for the treatment of melanoma. (2) Methods: The viability of NHDF and A375 cell cultures after the administration of the tested isoxazole derivatives was assessed after 24-h and 48-h incubation periods with the test compounds in the MTT test. ROS and NO scavenging analyses, a glycoprotein-P activity analysis, a migration assay, a test of apoptosis, and a multiple-criteria decision analysis were also performed. (3) Results: All compounds that were tested resulted in a slower migration of melanoma neoplastic cells. The mechanism of the antitumor activity of the tested compounds was confirmed—i.e., the pro-apoptotic activity of the compounds in A375 cell cultures. Compound O7K qualified for further research. (4) Conclusions: All the tested compounds inhibited the formation of melanoma metastases and demonstrated the ability to reduce the risk of developing drug resistance in the tumor. The MCDA results showed that O7K showed the strongest antitumor activity.
AMPK Localization: A Key to Differential Energy Regulation
Authors: Afinanisa Qonita , Cho Min Kyung , Seong Hyun-A
Published: October 2021

As the central node between nutrition signaling input and the metabolic pathway, AMP-activated protein kinase (AMPK) is tightly regulated to maintain energy homeostasis. Subcellular compartmentalization of AMPK is one of the critical regulations that enables AMPK to access proper targets and generate appropriate responses to specific perturbations and different levels of stress. One of the characterized localization mechanisms is RanGTPase-driven CRM1 that recognizes the nuclear export sequence (NES) on the α subunit to translocate AMPK into the cytoplasm. Nuclear localization putatively employs RanGTPase-driven importin that might recognize the nuclear localization signal (NLS) present on the AMPKα2 kinase domain. Nucleo-cytoplasmic shuttling of AMPK is influenced by multiple factors, such as starvation, exercise, heat shock, oxidant, cell density, and circadian rhythm. Tissue-specific localization, which distributes AMPK trimers with different combinations, has also been shown to be vital in maintaining tissue-specific metabolism. Tissue-specific and subcellular distribution of AMPK might be attributed to differences in the expression of the subunit, the stabilization by protein regulators, tissue activity, and the localization of AMPK activators. Considering the importance of AMPK localization in coordinating signaling and metabolism, further research is due to fully elucidate the largely unknown complex mechanism underlying this regulation.
Cytokine Networks in the Pathogenesis of Rheumatoid Arthritis
Authors: Kondo Naoki , Kuroda Takeshi , Kobayashi Daisuke
Published: October 2021

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic systemic inflammation causing progressive joint damage that can lead to lifelong disability. The pathogenesis of RA involves a complex network of various cytokines and cells that trigger synovial cell proliferation and cause damage to both cartilage and bone. Involvement of the cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 is central to the pathogenesis of RA, but recent research has revealed that other cytokines such as IL-7, IL-17, IL-21, IL-23, granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1β, IL-18, IL-33, and IL-2 also play a role. Clarification of RA pathology has led to the development of therapeutic agents such as biological disease-modifying anti-rheumatic drugs (DMARDs) and Janus kinase (JAK) inhibitors, and further details of the immunological background to RA are emerging. This review covers existing knowledge regarding the roles of cytokines, related immune cells and the immune system in RA, manipulation of which may offer the potential for even safer and more effective treatments in the future.
Successful Treatment of Persistent SARS-CoV-2 Infection in a B-Cell Depleted Patient with Activated Cytotoxic T and NK Cells: A Case Report
Authors: Jassem Jacek , Marek-Trzonkowska Natalia Maria , Smiatacz Tomasz , Arcimowicz Łukasz , Papak Ines , Jassem Ewa , Zaucha Jan Maciej
Published: October 2021

We report a lymphoma patient with profound B-cell deficiency after chemotherapy combined with anti-CD20 antibody successfully treated with remdesivir and convalescent plasma for prolonged SARS-CoV-2 infection. Viral clearance was likely attributed to the robust expansion and activation of TCR Vβ2 CD8+ cytotoxic T cells and CD16 + CD56- NK cells. This is the first presentation of TCR-specific T cell oligoclonal response in COVID-19. Our study suggests that B-cell depleted patients may effectively respond to anti-SARS-CoV-2 treatment when NK and antigen-specific Tc cell response is induced.
Butyrate Alters Pyruvate Flux and Induces Lipid Accumulation in Cultured Colonocytes
Authors: Bekebrede Anna F. , Deuren Thirza van , Gerrits Walter J. J. , Keijer Jaap , Boer Vincent C. J. de
Published: October 2021

Butyrate is considered the primary energy source of colonocytes and has received wide attention due to its unique health benefits. Insight into the mechanistic effects of butyrate on cellular and metabolic function relies mainly on research in in-vitro-cultured cells. However, cells in culture differ from those in vivo in terms of metabolic phenotype and nutrient availability. For translation, it is therefore important to understand the impact of different nutrients on the effects of butyrate. We investigated the metabolic consequences of butyrate exposure under various culturing conditions, with a focus on the interaction between butyrate and glucose. To investigate whether the effects of butyrate were different between cells with high and low mitochondrial capacity, we cultured HT29 cells under either low- (0.5 mM) or high- (25 mM) glucose conditions. Low-glucose culturing increased the mitochondrial capacity of HT29 cells compared to high-glucose (25 mM) cultured HT29 cells. Long-term exposure to butyrate did not alter mitochondrial bioenergetics, but it decreased glycolytic function, regardless of glucose availability. In addition, both high- and low-glucose-grown HT29 cells showed increased lipid droplet accumulation following long-term butyrate exposure. Acute exposure of cultured cells (HT29 and Caco-2) to butyrate increased their oxygen consumption rate (OCR). A simultaneous decrease in extracellular acidification rate (ECAR) was observed. Furthermore, in the absence of glucose, OCR did not increase in response to butyrate. These results lead us to believe that butyrate itself was not responsible for the observed increase in OCR, but, instead, butyrate stimulated pyruvate flux into mitochondria. Indeed, blocking of the mitochondrial pyruvate carrier prevented a butyrate-induced increase in oxygen consumption. Taken together, our results indicate that butyrate itself is not oxidized in cultured cells but instead alters pyruvate flux and induces lipid accumulation.
A Systematic Approach: Molecular Dynamics Study and Parametrisation of Gemini Type Cationic Surfactants
Authors: Rzycki Mateusz , Kaczorowska Aleksandra , Kraszewski Sebastian , Drabik Dominik
Published: October 2021

The spreading of antibiotic-resistant bacteria strains is one of the most serious problem in medicine to struggle nowadays. This triggered the development of alternative antimicrobial agents in recent years. One of such group is Gemini surfactants which are massively synthesised in various structural configurations to obtain the most effective antibacterial properties. Unfortunately, the comparison of antimicrobial effectiveness among different types of Gemini agents is unfeasible since various protocols for the determination of Minimum Inhibitory Concentration are used. In this work, we proposed alternative, computational, approach for such comparison. We designed a comprehensive database of 250 Gemini surfactants. Description of structure parameters, for instance spacer type and length, are included in the database. We parametrised modelled molecules to obtain force fields for the entire Gemini database. This was used to conduct in silico studies using the molecular dynamics to investigate the incorporation of these agents into model E. coli inner membrane system. We evaluated the effect of Gemini surfactants on structural, stress and mechanical parameters of the membrane after the agent incorporation. This enabled us to select four most likely membrane properties that could correspond to Gemini’s antimicrobial effect. Based on our results we selected several types of Gemini spacers which could demonstrate a particularly strong effect on the bacterial membranes.
EGFR-Targeted Pentacyclic Triterpene Analogues for Glioma Therapy
Authors: Ciftci Halil I. , Radwan Mohamed O. , Sever Belgin , Hamdy Ahmed K. , Emirdağ Safiye , Ulusoy N. Gokce , Sozer Ece , Can Mustafa , Yayli Nurettin , Araki Norie , Tateishi Hiroshi , Otsuka Masami , Fujita Mikako , Altintop Mehlika Dilek
Published: October 2021

Glioma, particularly its most malignant form, glioblastoma multiforme (GBM), is the most common and aggressive malignant central nervous system tumor. The drawbacks of the current chemotherapy for GBM have aroused curiosity in the search for targeted therapies. Aberrantly overexpressed epidermal growth factor receptor (EGFR) in GBM results in poor prognosis, low survival rates, poor responses to therapy and recurrence, and therefore EGFR-targeted therapy stands out as a promising approach for the treatment of gliomas. In this context, a series of pentacyclic triterpene analogues were subjected to in vitro and in silico assays, which were conducted to assess their potency as EGFR-targeted anti-glioma agents. In particular, compound 10 was the most potent anti-glioma agent with an IC50 value of 5.82 µM towards U251 human glioblastoma cells. Taking into account its low cytotoxicity to peripheral blood mononuclear cells (PBMCs), compound 10 exerts selective antitumor action towards Jurkat human leukemic T-cells. This compound also induced apoptosis and inhibited EGFR with an IC50 value of 9.43 µM compared to erlotinib (IC50 = 0.06 µM). Based on in vitro and in silico data, compound 10 stands out as a potential orally bioavailable EGFR-targeted anti-glioma agent endowed with the ability to cross the blood–brain barrier (BBB).
Text Mining and Sentiment Analysis of Newspaper Headlines
Authors: Hossain Arafat , Karimuzzaman Md. , Hossain Md. Moyazzem , Rahman Azizur
Published: October 2021

Text analytics are well-known in the modern era for extracting information and patterns from text. However, no study has attempted to illustrate the pattern and priorities of newspaper headlines in Bangladesh using a combination of text analytics techniques. The purpose of this paper is to examine the pattern of words that appeared on the front page of a well-known daily English newspaper in Bangladesh, The Daily Star, in 2018 and 2019. The elucidation of that era’s possible social and political context was also attempted using word patterns. The study employs three widely used and contemporary text mining techniques: word clouds, sentiment analysis, and cluster analysis. The word cloud reveals that election, kill, cricket, and Rohingya-related terms appeared more than 60 times in 2018, whereas BNP, poll, kill, AL, and Khaleda appeared more than 80 times in 2019. These indicated the country’s passion for cricket, political turmoil, and Rohingya-related issues. Furthermore, sentiment analysis reveals that words of fear and negative emotions appeared more than 600 times, whereas anger, anticipation, sadness, trust, and positive-type emotions came up more than 400 times in both years. Finally, the clustering method demonstrates that election, politics, deaths, digital security act, Rohingya, and cricket-related words exhibit similarity and belong to a similar group in 2019, whereas rape, deaths, road, and fire-related words clustered in 2018 alongside a similar-appearing group. In general, this analysis demonstrates how vividly the text mining approach depicts Bangladesh’s social, political, and law-and-order situation, particularly during election season and the country’s cricket craze, and also validates the significance of the text mining approach to understanding the overall view of a country during a particular time in an efficient manner.
Short Word-Length Entering Compressive Sensing Domain: Improved Energy Efficiency in Wireless Sensor Networks
Authors: Alwan Nuha A. S. , Hussain Zahir M.
Published: October 2021

This work combines compressive sensing and short word-length techniques to achieve localization and target tracking in wireless sensor networks with energy-efficient communication between the network anchors and the fusion center. Gradient descent localization is performed using time-of-arrival (TOA) data which are indicative of the distance between anchors and the target thereby achieving range-based localization. The short word-length techniques considered are delta modulation and sigma-delta modulation. The energy efficiency is due to the reduction of the data volume transmitted from anchors to the fusion center by employing any of the two delta modulation variants with compressive sensing techniques. Delta modulation allows the transmission of one bit per TOA sample. The communication energy efficiency is increased by RⱮ, R ≥ 1, where R is the sample reduction ratio of compressive sensing, and Ɱ is the number of bits originally present in a TOA-sample word. It is found that the localization system involving sigma-delta modulation has a superior performance to that using delta-modulation or pure compressive sampling alone, in terms of both energy efficiency and localization error in the presence of TOA measurement noise and transmission noise, owing to the noise shaping property of sigma-delta modulation.
An Approach to Ranking the Sources of Information Dissemination in Social Networks
Authors: Vitkova Lidia , Kotenko Igor , Chechulin Andrey
Published: October 2021

The problem of countering the spread of destructive content in social networks is currently relevant for most countries of the world. Basically, automatic monitoring systems are used to detect the sources of the spread of malicious information, and automated systems, operators, and counteraction scenarios are used to counteract it. The paper suggests an approach to ranking the sources of the distribution of messages with destructive content. In the process of ranking objects by priority, the number of messages created by the source and the integral indicator of the involvement of its audience are considered. The approach realizes the identification of the most popular and active sources of dissemination of destructive content. The approach does not require the analysis of graphs of relationships and provides an increase in the efficiency of the operator. The proposed solution is applicable both to brand reputation monitoring systems and for countering cyberbullying and the dissemination of destructive information in social networks.
Phylogenetic Position of the Genus Alulacris (Orthoptera: Acrididae: Melanoplinae: Podismini) Revealed by Complete Mitogenome Evidence
Authors: Xu Haiyang , Mao Benyong , Storozhenko Sergey Yu. , Huang Yuan , Chen Zhilin , Huang Jianhua
Published: October 2021

Whole mitogenomes are a useful data source for a wide variety of research goals due to the vastly cheaper sequencing cost and the far less demanding high-quality templates. The mitogenome has demonstrated great potential in resolving phylogenetic questions in Orthoptera at different taxonomic scales as well as exploring patterns of molecular and morphological character evolutions. In this study, the complete mitogenome of Alulacrisshilinensis (Zheng, 1977) was sequenced using next-generation sequencing, the characteristics of the mitogenome are presented briefly, and the phylogeny of the Melanoplinae and Catantopinae was reconstructed using a selected dataset of mitogenome sequences under maximum likelihood and Bayesian inference frameworks. The results show that the genus was consistently assigned to the subfamily Melanoplinae rather than Catantopinae in all phylogenetic trees deduced from different datasets under different frameworks, and this finding is entirely consistent with its morphological characters. Therefore, it is more appropriate to place the genus Alulacris in Melanoplinae rather than in Catantopinae.
Spatial Distribution of Aedes aegypti Oviposition Temporal Patterns and Their Relationship with Environment and Dengue Incidence
Authors: Andreo Verónica , Porcasi Ximena , Guzman Claudio , Lopez Laura , Scavuzzo Carlos M.
Published: October 2021

Aedes aegypti, the mosquito species transmitting dengue, zika, chikungunya and yellow fever viruses, is fully adapted to thrive in urban areas. The temporal activity of this mosquito, however, varies within urban areas which might imply different transmission risk. In this work, we hypothesize that temporal differences in mosquito activity patterns are determined by local environmental conditions. Hence, we explore the existence of groups of temporal patterns in weekly time series of Ae. aegypti ovitraps records (2017–2019) by means of time series clustering. Next, with the aim of predicting risk in places with no mosquito field data, we use machine learning classification tools to assess the association of temporal patterns with environmental variables derived from satellite imagery and predict temporal patterns over the city area to finally test the relationship with dengue incidence. We found three groups of temporal patterns that showed association with land cover diversity, variability in vegetation and humidity and, heterogeneity measured by texture indices estimated over buffer areas surrounding ovitraps. Dengue incidence on a neighborhood basis showed a weak but positive association with the percentage of pixels belonging to only one of the temporal patterns detected. The understanding of the spatial distribution of temporal patterns and their environmental determinants might then become highly relevant to guide the allocation of prevention and potential interventions. Further investigation is still needed though to incorporate other determinants not considered here.
Enterobacter sp. AA26 as a Protein Source in the Larval Diet of Drosophila suzukii
Authors: Nikolouli Katerina , Sassù Fabiana , Ntougias Spyridon , Stauffer Christian , Cáceres Carlos , Bourtzis Kostas
Published: October 2021

The Spotted-Wing Drosophila fly, Drosophila suzukii, is an invasive pest species infesting major agricultural soft fruits. Drosophila suzukii management is currently based on insecticide applications that bear major concerns regarding their efficiency, safety and environmental sustainability. The sterile insect technique (SIT) is an efficient and friendly to the environment pest control method that has been suggested for the D. suzukii population control. Successful SIT applications require mass-rearing of the strain to produce competitive and of high biological quality males that will be sterilized and consequently released in the wild. Recent studies have suggested that insect gut symbionts can be used as a protein source for Ceratitis capitata larval diet and replace the expensive brewer’s yeast. In this study, we exploited Enterobacter sp. AA26 as partial and full replacement of inactive brewer’s yeast in the D. suzukii larval diet and assessed several fitness parameters. Enterobacter sp. AA26 dry biomass proved to be an inadequate nutritional source in the absence of brewer’s yeast and resulted in significant decrease in pupal weight, survival under food and water starvation, fecundity, and adult recovery.
Responses to Developmental Temperature Fluctuation in Life History Traits of Five Drosophila Species (Diptera: Drosophilidae) from Different Thermal Niches
Authors: Manenti Tommaso , Kjærsgaard Anders , Schou Toke Munk , Pertoldi Cino , Moghadam Neda N. , Loeschcke Volker
Published: October 2021

Temperature has profound effects on biochemical processes as suggested by the extensive variation in performance of organisms across temperatures. Nonetheless, the use of fluctuating temperature (FT) regimes in laboratory experiments compared to constant temperature (CT) regimes is still mainly applied in studies of model organisms. We investigated how two amplitudes of developmental temperature fluctuation (22.5/27.5 °C and 20/30 °C, 12/12 h) affected several fitness-related traits in five Drosophila species with markedly different thermal resistance. Egg-to-adult viability did not change much with temperature except in the cold-adapted D. immigrans. Developmental time increased with FT among all species compared to the same mean CT. The impact of FT on wing size was quite diverse among species. Whereas wing size decreased quasi-linearly with CT in all species, there were large qualitative differences with FT. Changes in wing aspect ratio due to FT were large compared to the other traits and presumably a consequence of thermal stress. These results demonstrate that species of the same genus but with different thermal resistance can show substantial differences in responses to fluctuating developmental temperatures not predictable by constant developmental temperatures. Testing multiple traits facilitated the interpretation of responses to FT in a broader context.
Expression Levels of Detoxification Enzyme Genes from Dendroctonus armandi (Coleoptera: Curculionidae) Fed on a Solid Diet Containing Pine Phloem and Terpenoids
Authors: Dai Lulu , Gao Haiming , Chen Hui
Published: October 2021

Bark beetles overcome the toxic terpenoids produced by pine trees by both detoxifying and converting them into a pheromone system. Detoxification enzymes such as cytochrome P450s, glutathione S-transferases, and carboxylesterases are involved in the ability of Dendroctonus armandi to adapt to its chemical environment. Ten genes from these three major classes of detoxification enzymes were selected to study how these enzymes help D. armandi to respond to the host defenses. The expression profile of these detoxification enzyme genes was observed in adult beetles after feeding on different types of diet. Significant differences were observed between two types of seminatural diet containing the phloem of pines, and a purely artificial diet containing five monoterpenes ((−)-α-pinene, (−)-β-pinene, (+)-3-carene, (±)-limonene, and turpentine oil) also caused differential transcript levels in the detoxification enzyme genes. The results suggest that monoterpenes enter the beetles through different routes (i.e., respiratory and digestive systems) and cause the expression of different genes in response, which might be involved in pheromone metabolism. In addition, the xenobiotic metabolism in bark beetles should be considered as a system comprising multiple detoxifying enzymes.
Sleep Quality and Eating Disorder-Related Psychopathologies in Patients with Night Eating Syndrome and Binge Eating Disorders
Authors: Tzischinsky Orna , Tokatly Latzer Itay , Alon Sigal , Latzer Yael
Published: October 2021

Night eating syndrome (NES) is an eating disorder (ED) characterized by nocturnal ingestion (NI), evening hyperphagia, morning anorexia, as well as mood and sleep disturbances. This study compared subjective and objective sleep quality and ED-related psychopathologies in patients seeking treatment for ED. Method: The sample was composed of 170 women, aged 18–68, who were referred for an ED assessment from 2011 to 2020. The participants were divided into three subgroups: NES-NI only (n = 30), NES+ binge eating (BE) (including binge eating disorders or bulimia nervosa (n = 52), and BE-only (n = 88). The measures consisted of a psychiatric evaluation, objective sleep monitoring measured by an actigraph for 1 week, a subjective sleep self-report, and ED-related psychopathology questionnaires. Results: Objective sleep monitoring revealed significant group differences, with higher sleep efficiency in participants with BE-only and longer sleep durations for the NES-NI only group. Subjectively, the BE-only group described a significantly lower sleep quality than either the NES-NI only or the NES+BE groups. ED-related psychopathology was lower in the NES-NI-only group. A stepwise linear regression revealed that general psychopathology (the brief symptom inventory total score) was a significant predictor of subjective sleep quality. Conclusion: NES-NI-only was correlated with less psychopathology, but with more subjective and objective sleep disturbances. These results lend weight to the supposition that NES lies on a continuum of ED psychopathologies, and that NES-NI-only appears to be a separate entity from NES+BE and BE-only in terms of its psychopathology.