bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Reprogramming of Apoptosis-Related Genes during Brain Development
Authors: Jiang Wei , Chen Liang , Zheng Sika
Published: October 2021

To enable long-term survival, mammalian adult neurons exhibit unique apoptosis competence. Questions remain as to whether and how neurons globally reprogram the expression of apoptotic genes during development. We systematically examined the in vivo expression of 1923 apoptosis-related genes and associated histone modifications at eight developmental ages of mouse brains. Most apoptotic genes displayed consistent temporal patterns across the forebrain, midbrain, and hindbrain, suggesting ubiquitous robust developmental reprogramming. Although both anti- and pro-apoptotic genes can be up- or downregulated, half the regulatory events in the classical apoptosis pathway are downregulation of pro-apoptotic genes. Reduced expression in initiator caspases, apoptosome, and pro-apoptotic Bcl-2 family members restrains effector caspase activation and attenuates neuronal apoptosis. The developmental downregulation of apoptotic genes is attributed to decreasing histone-3-lysine-4-trimethylation (H3K4me3) signals at promoters, where histone-3-lysine-27-trimethylation (H3K27me3) rarely changes. By contrast, repressive H3K27me3 marks are lost in the upregulated gene groups, for which developmental H3K4me3 changes are not predictive. Hence, developing brains remove epigenetic H3K4me3 and H3K27me3 marks on different apoptotic gene groups, contributing to their downregulation and upregulation, respectively. As such, neurons drastically alter global apoptotic gene expression during development to transform apoptosis controls. Research into neuronal cell death should consider maturation stages as a biological variable.
Therapeutic Potential of MRGPRX2 Inhibitors on Mast Cells
Authors: Ogasawara Hiroyuki , Noguchi Masato
Published: October 2021

Mast cells (MCs) act as primary effectors in inflammatory and allergic reactions by releasing intracellularly-stored inflammatory mediators in diseases. The two major pathways for MC activation are known to be immunoglobulin E (IgE)-dependent and -independent. Although IgE-dependent signaling is the main pathway to MC activation, IgE-independent pathways have also been found to serve pivotal roles in the pathophysiology of various inflammatory conditions. Recent studies have shown that human and mouse MCs express several regulatory receptors such as toll-like receptors (TLRs), CD48, C300a, and GPCRs, including mas-related GPCR-X2 (MRGPRX2). MRGPRX2 has been reported as a novel GPCR that is expressed in MCs activated by basic secretagogues, neurokinin peptides, host defense antimicrobial peptides, and small molecule compounds (e.g., neuromuscular blocking agents) and leads to MC degranulation and eicosanoids release under in vitro experimental condition. Functional analyses of MRGPRX2 and Mrgprb2 (mouse ortholog) indicate that MRGPRX2 is involved in MC hypersensitivity reactions causing neuroinflammation such as postoperative pain, type 2 inflammation, non-histaminergic itch, and drug-induced anaphylactic-like reactions. In this review, we discuss the roles in innate immunity through functional studies on MRGPRX2-mediated IgE-independent MC activation and also the therapeutic potential of MRGPRX2 inhibitors on allergic and inflammatory diseases.
Alzheimer’s Disease, Sleep Disordered Breathing, and Microglia: Puzzling out a Common Link
Authors: Ulland Tyler K. , Ewald Andrea C. , Knutson Andrew O. , Marino Kaitlyn M. , Smith Stephanie M. C. , Watters Jyoti J.
Published: October 2021

Sleep Disordered Breathing (SDB) and Alzheimer’s Disease (AD) are strongly associated clinically, but it is unknown if they are mechanistically associated. Here, we review data covering both the cellular and molecular responses in SDB and AD with an emphasis on the overlapping neuroimmune responses in both diseases. We extensively discuss the use of animal models of both diseases and their relative utilities in modeling human disease. Data presented here from mice exposed to intermittent hypoxia indicate that microglia become more activated following exposure to hypoxia. This also supports the idea that intermittent hypoxia can activate the neuroimmune system in a manner like that seen in AD. Finally, we highlight similarities in the cellular and neuroimmune responses between SDB and AD and propose that these similarities may lead to a pathological synergy between SDB and AD.
Novel Peptide Therapeutic Approaches for Cancer Treatment
Authors: Li Caroline M. , Haratipour Pouya , Lingeman Robert G. , Perry J. Jefferson P. , Gu Long , Hickey Robert J. , Malkas Linda H.
Published: October 2021

Peptides are increasingly being developed for use as therapeutics to treat many ailments, including cancer. Therapeutic peptides have the advantages of target specificity and low toxicity. The anticancer effects of a peptide can be the direct result of the peptide binding its intended target, or the peptide may be conjugated to a chemotherapy drug or radionuclide and used to target the agent to cancer cells. Peptides can be targeted to proteins on the cell surface, where the peptide–protein interaction can initiate internalization of the complex, or the peptide can be designed to directly cross the cell membrane. Peptides can induce cell death by numerous mechanisms including membrane disruption and subsequent necrosis, apoptosis, tumor angiogenesis inhibition, immune regulation, disruption of cell signaling pathways, cell cycle regulation, DNA repair pathways, or cell death pathways. Although using peptides as therapeutics has many advantages, peptides have the disadvantage of being easily degraded by proteases once administered and, depending on the mode of administration, often have difficulty being adsorbed into the blood stream. In this review, we discuss strategies recently developed to overcome these obstacles of peptide delivery and bioavailability. In addition, we present many examples of peptides developed to fight cancer.
Anti-Aggregative Effect of the Antioxidant DJ-1 on the TPPP/p25-Derived Pathological Associations of Alpha-Synuclein
Authors: Oláh Judit , Lehotzky Attila , Szénási Tibor , Ovádi Judit
Published: October 2021

DJ-1, a multi-functional protein with antioxidant properties, protects dopaminergic neurons against Parkinson’s disease (PD). The oligomerization/assembly of alpha-synuclein (SYN), promoted by Tubulin Polymerization Promoting Protein (TPPP/p25), is fatal in the early stage of PD. The pathological assembly of SYN with TPPP/p25 inhibits their proteolytic degradation. In this work, we identified DJ-1 as a new interactive partner of TPPP/p25, and revealed its influence on the association of TPPP/p25 with SYN. DJ-1 did not affect the TPPP/p25-derived tubulin polymerization; however, it did impede the toxic assembly of TPPP/p25 with SYN. The interaction of DJ-1 with TPPP/p25 was visualized in living human cells by fluorescence confocal microscopy coupled with Bifunctional Fluorescence Complementation (BiFC). While the transfected DJ-1 displayed homogeneous intracellular distribution, the TPPP/p25-DJ-1 complex was aligned along the microtubule network. The anti-aggregative effect of DJ-1 on the pathological TPPP/p25-SYN assemblies was established by the decrease in the intensity of their intracellular fluorescence (BiFC signal) and the increase in the proteolytic degradation of SYN complexed with TPPP/p25 due to the DJ-1-derived disassembly of SYN with TPPP/p25. These data obtained with HeLa and SH-SY5Y cells revealed the protective effect of DJ-1 against toxic SYN assemblies, which assigns a new function to the antioxidant sensor DJ-1.
Protein Binding to Cis-Motifs in mRNAs Coding Sequence Is Common and Regulates Transcript Stability and the Rate of Translation
Authors: Grzybowska Ewa A. , Wakula Maciej
Published: October 2021

Protein binding to the non-coding regions of mRNAs is relatively well characterized and its functionality has been described in many examples. New results obtained by high-throughput methods indicate that binding to the coding sequence (CDS) by RNA-binding proteins is also quite common, but the functions thereof are more obscure. As described in this review, CDS binding has a role in the regulation of mRNA stability, but it has also a more intriguing role in the regulation of translational efficiency. Global approaches, which suggest the significance of CDS binding along with specific examples of CDS-binding RBPs and their modes of action, are outlined here, pointing to the existence of a relatively less-known regulatory network controlling mRNA stability and translation on yet another level.
B Cell Response Induced by SARS-CoV-2 Infection Is Boosted by the BNT162b2 Vaccine in Primary Antibody Deficiencies
Authors: Pulvirenti Federica , Fernandez Salinas Ane , Milito Cinzia , Terreri Sara , Piano Mortari Eva , Quintarelli Concetta , Di Cecca Stefano , Lagnese Gianluca , Punziano Alessandra , Guercio Marika , Bonanni Livia , Auria Stefania , Villani Francesca , Albano Christian , Locatelli Franco , Spadaro Giuseppe , Carsetti Rita , Quinti Isabella
Published: October 2021

Background: Patients with primary antibody deficiencies are at risk in the current COVID-19 pandemic due to their impaired response to infection and vaccination. Specifically, patients with common variable immunodeficiency (CVID) generated poor spike-specific antibody and T cell responses after immunization. Methods: Thirty-four CVID convalescent patients after SARS-CoV-2 infection, 38 CVID patients immunized with two doses of the BNT162b2 vaccine, and 20 SARS-CoV-2 CVID convalescents later and immunized with BNT162b2 were analyzed for the anti-spike IgG production and the generation of spike-specific memory B cells and T cells. Results: Spike-specific IgG was induced more frequently after infection than after vaccination (82% vs. 34%). The antibody response was boosted in convalescents by vaccination. Although immunized patients generated atypical memory B cells possibly by extra-follicular or incomplete germinal center reactions, convalescents responded to infection by generating spike-specific memory B cells that were improved by the subsequent immunization. Poor spike-specific T cell responses were measured independently from the immunological challenge. Conclusions: SARS-CoV-2 infection primed a more efficient classical memory B cell response, whereas the BNT162b2 vaccine induced non-canonical B cell responses in CVID. Natural infection responses were boosted by subsequent immunization, suggesting the possibility to further stimulate the immune response by additional vaccine doses in CVID.
Plasmatic Magnesium Deficiency in 101 Outpatients Living with Type 2 Diabetes Mellitus
Authors: Zahra Hajer , Berriche Olfa , Mizouri Ramla , Boukhayatia Fatma , Khiari Marwa , Gamoudi Amel , Lahmar Ines , Ben Amor Nadia , Mahjoub Faten , Zayet Souheil , Jamoussi Henda
Published: October 2021

(1) Background: Magnesium deficiency is usually associated with type 2 diabetes mellitus (T2DM). Individuals living with T2DM with hypomagnesemia show a more rapid disease progression and have an increased risk for diabetes complications. (2) Methods: This is a cross-sectional and descriptive study in the National Institute of Nutrition and Food Technology of Tunis in Tunisia, including all adult outpatients (≥18 years old) with a diagnosis of T2DM from 1 September 2018 to 31 August 2019. The aim of this study was to evaluate the prevalence of plasmatic magnesium deficiency in a Tunisian population of T2DM and to study the relationship between magnesium status and intake, glycemic control and long-term diabetes-related complications. (3) Results: Among the 101 T2DM outpatients, 13 (12.9%) presented with a plasmatic magnesium deficiency. The mean age was 56 ± 7.9 years with a female predominance (62%, n = 63). The mean of the plasmatic magnesium level was 0.79 ± 0.11 mmol/L (0.5–1.1), and the mean of 24 h urinary magnesium excretion was 87.8 ± 53.8 mg/24 h [4.8–486.2]. HbA1c was significantly higher in the plasmatic magnesium deficiency group than the normal magnesium status group (10% ± 1.3 vs. 8.3% ± 1.9; p = 0.04), with a significant difference in participants with a poor glycemic control (HbA1c > 7%) (100%, n = 13/13 vs. 53%, n = 47/88; p = 0.001). A weak negative relationship was also found between plasmatic magnesium and HbA1c (r = −0.2, p = 0.03). Peripheral artery disease was more commonly described in individuals with low plasmatic magnesium levels than in individuals with normal levels (39%, n = 5 vs. 0%, n = 0; p < 0.001). The mean plasmatic magnesium level in participants without diabetic nephropathy and also peripheral artery disease was significantly higher compared to individuals with each long-term diabetes-related complication (0.8 mmol/L ± 0.1 vs. 0.71 mmol/L ± 0.07; p = 0.006) and (0.8 mmol/L ± 0.1 vs. 0.6 mmol/L ± 0.08; p < 0.001), respectively. (4) Conclusions: Hypomagnesemia was identified in individuals with T2DM, causing poor glycemic control and contributing to the development and progression of diabetes-related microvascular and macrovascular complications.
Research on the Mechanism of Surfactant Warm Mix Asphalt Additive-Based on Molecular Dynamics Simulation
Authors: Zhao Pinhui , Dong Mingliang , Yang Yansheng , Shi Jingtao , Wang Junjie , Wu Wenxin , Zhao Xingchi , Zhou Xu , Wang Chenlong
Published: October 2021

Warm mix asphalt (WMA) technology can bring certain environmental and technical benefits through reducing the temperature of production, paving, and compaction of mixture asphalt. Recent studies have shown that some WMA additives are able to reduce the temperature by increasing the lubricating properties of asphalt binder-based on the tribological theory, this paper studied the mechanism of adsorbing and lubricating film of base asphalt and WMA on the surface of stone by molecular dynamics (MD) simulation method, and the effect of surfactant WMA additive on the lubrication performance of the shear friction system of “stone–asphalt–stone”. The model of base asphalt lubricating film, including saturates, aromatics, resin and asphaltene, as well as the model of warm mix asphalt lubricating film containing imidazoline-type surfactant WMA (IMDL WMA) additive molecule, were established. The shear friction system of “stone–asphalt–stone” of base asphalt and warm mix asphalt was built on the basis of an asphalt lubrication film model and representative calcite model. The results show that the addition of IMDL WMA additive can effectively improve the lubricity of asphalt, reduce the shear stress of asphalt lubricating film, and increase the stability of asphalt film. The temperature in the WMA lubricating film rises, while the adsorption energy on the stone surface decreases with the increase of shear rate, indicating that the higher the shear rate is, the more unfavorable it is for the WMA lubricating film to wrap on the stone surface. In addition, the shear stress of the WMA lubricating film decreased with increasing temperature, while the shear stress of the base asphalt lubricating film increased first and then decreased, demonstrating that the compactability of the asphalt mixture did not improve linearly with the increase of temperature.
Discovery of Disulfane (H2S2) in Fluid Inclusions in Rubies from Yuanjiang, China, and Its Implications
Authors: Huang Wenqing , Ni Pei , Zhou Jungui , Shui Ting , Ding Junying , Zhu Renzhi , Cai Yitao , Fan Mingsen
Published: October 2021

Raman spectra of fluid inclusions in gem rubies from Yuanjiang deposit (China) within the Ailao Shan-Red River (ASRR) metamorphic belt showed the presence of compounds such as CO2, COS, CH4, H2S, and elemental sulfur (S8), accompanied by two bands at approximately 2499 and 2570 cm−1. These two frequencies could be assigned to the vibrations of disulfane (H2S2). This is the second case of the sulfane-bearing fluid inclusions in geological samples reported, followed by the first in quartzite from Bastar Craton of India. The H2S2 was likely in situ enclosed by the host rubies rather than a reaction product that formed during the cooling of H2S and S8, suggesting sulfanes are stable at elevated temperatures (e.g., >600 °C). By comparing the lithologies and metamorphic conditions of these two sulfane-bearing cases (Bastar and Yuanjiang), it is suggested that amphibolite facies metamorphism of sedimentary sequence that deposited in a continental platform setting might favor the generation of sulfanes. Sulfanes may play an important role in the mobilization of Cr that is essential for ruby crystallization.
Detection of Mutual Exciting Structure in Stock Price Trend Dynamics
Authors: Li Shangzhe , Jiang Xin , Wu Junran , Tong Lin , Xu Ke
Published: October 2021

We investigated a comprehensive analysis of the mutual exciting mechanism for the dynamic of stock price trends. A multi-dimensional Hawkes-model-based approach was proposed to capture the mutual exciting activities, which take the form of point processes induced by dual moving average crossovers. We first performed statistical measurements for the crossover event sequence, introducing the distribution of the inter-event times of dual moving average crossovers and the correlations of local variation (LV), which is often used in spike train analysis. It was demonstrated that the crossover dynamics in most stock sectors are generally more regular than a standard Poisson process, and the correlation between variations is ubiquitous. In this sense, the proposed model allowed us to identify some asymmetric cross-excitations, and a mutually exciting structure of stock sectors could be characterized by mutual excitation correlations obtained from the kernel matrix of our model. Using simulations, we were able to substantiate that a burst of the dual moving average crossovers in one sector increases the intensity of burst both in the same sector (self-excitation) as well as in other sectors (cross-excitation), generating episodes of highly clustered burst across the market. Furthermore, based on our finding, an algorithmic pair trading strategy was developed and backtesting results on real market data showed that the mutual excitation mechanism might be profitable for stock trading.
Philosophy of Education in Times of Crises and Pandemics
Authors: Papastephanou Marianna
Published: October 2021

In much of the philosophy of education today, diagnoses of socio-political pathologies underpin visions of a more desirable, democratic future. However, the very philosophical act of making an educational vision responsive to (and dependent on) crises of the times is rarely, if ever, critiqued. On the contrary, a pattern of standardised research steps is being consolidated, one that reflects medicalised politics of identifying a critically “ill” present, offering “cures” that promise a better future. In this article, it is argued that this pattern has major epistemic and political risks. It may jeopardise the quality of educational–philosophical research, and it may make philosophy of education overlook new, undemocratic politics. This article briefly discusses the pattern, and then the risks of the medical metaphors on which the pattern relies. One such risk concerns what counts as politically “ill” in “pandemic times”, and new polarisations, such as “the vaccinated versus the unvaccinated”, may thus be introduced. Finally, the article suggests that philosophy of education should consider some de-medicalisation of the notion of pandemics.
A Novel MOS-Channel Diode Embedded in a SiC Superjunction MOSFET for Enhanced Switching Performance and Superior Short Circuit Ruggedness
Authors: Yoon Jongwoon , Kim Kwangsoo
Published: October 2021

In this study, a novel MOS-channel diode embedded in a SiC superjunction MOSFET (MCD SJ-MOSFET) is proposed and analyzed by means of numerical TCAD simulations. Owing to the electric field shielding effect of the P+ body and the P-pillar, the channel diode oxide thickness (tco) of MCD can be set to very thin while achieving a low maximum oxide electric field (EMOX) under 3 MV/cm. Therefore, the turn-on voltage (VF) of the proposed structure was 1.43 V, deactivating the parasitic PIN body diode. Compared with the SJ-MOSFET, the reverse recovery time (trr) and the reverse recovery charge (Qrr) were improved by 43% and 59%, respectively. Although there is a slight increase in specific on-resistance (RON), the MCD SJ-MOSFET shows very low input capacitance (CISS) and gate to drain capacitance (CGD) due to the reduced active gate. Therefore, significantly improved figures of merit RON × CGD by a factor of 4.3 are achieved compared to SJ-MOSFET. As a result, the proposed structure reduced the switching time as well as the switching energy loss (ESW). Moreover, electro-thermal simulation results show that the MCD SJ-MOSFET has a short circuit withstand time (tSC) more than twice that of the SJ-MOSFET at various DC bus voltages (400 and 600 V).
A Novel Approach for the Design of Fast-Settling Amplifiers for Biosignal Detection
Authors: Alonso Rivas Eduardo , Scandurra Graziella , Ciofi Carmine , Rodríguez-Morcillo García  Carlos , Giannetti Romano
Published: October 2021

The most common method used to pick up biomedical signals is through metallic electrodes coupled to the input of high-gain, low-noise amplifiers. Unfortunately, electrodes, amongst other effects, introduce an undesired contact resistance and a contact potential. The contact potential needs to be rejected since it would otherwise cause the saturation of the input stage of the amplifiers, and this is almost always obtained by inserting a simple RC high-pass filter in the input signal path. The contact resistance needs to be estimated to ensure that it does not impair correct measurements. Methods exist for estimating the contact resistance by dynamically modifying the input network configuration, but because of the presence of the input RC filter, long transients are induced any time a switch occurs between different input configurations, so that the measurement time may become unacceptably long. In this paper, we propose a new topology for a DC removal network at the input of the differential signal amplifier that results in an AC filter whose time constant can be continuously changed by means of a control voltage. As such, we can speed up the recovery from transients by setting very short time constants (during the input resistance estimation process) while maintaining the ability to obtain very low cut-in frequencies by setting a much larger time constant during actual measurements. A prototype of the system was built and tested in order to demonstrate the advantage of the approach we propose in terms of reduced measurement time.
Energy Efficiency in Cloud Computing: Exploring the Intellectual Structure of the Research Field and Its Research Fronts with Direct Citation Analysis
Authors: Kozakiewicz Adam , Lis Andrzej
Published: October 2021

The aim of the study is to explore the intellectual structure of the field and fronts in research on energy efficiency in the context of cloud computing and thus to contribute to science mapping of the research field. The research process was driven by the following study questions: (1) what are the most influential publications in the research field? and (2) what are the research fronts in the research field? The method of direct citation analysis was employed in the research process. Data for analysis were obtained from the Scopus database and analyzed with the use of VOSviewer science mapping software. In response to the first question, we identified the most influential publications in the research field and analyzed their types (i.e., whether they are original research papers or rather the “context” papers e.g., survey or review papers, framework papers, challenges papers, and study papers). Moreover, a comparison analysis between the types of papers among the most cited “classical” publications and “emerging stars” was conducted. In response to the second research question, we identified five research fronts concentrated around the issues of: virtual machine management (“VM”); task-focus, concerning data replication, task consolidation, and task scheduling (“task”); energy efficiency (“energy”); modelling and optimization (“model”); and energy efficiency in the networking context (“network”).
Investigation of the Mixing Height in the Planetary Boundary Layer by Using Sodar and Microwave Radiometer Data
Authors: Odintsov Sergey , Miller Eugene , Kamardin Andrey , Nevzorova Irina , Troitsky Arkady , Schröder Mathias
Published: October 2021

The height of the mixing layer is a significant parameter for describing the dynamics of the planetary boundary layer (PBL), especially for air quality control and for the parametrizations in numerical modeling. The problem is that the heights of the mixing layer cannot be measured directly. The values of this parameter are depending both on the applied algorithms for calculation and on the measuring instruments which have been used by the data source. To determine the height of a layer of intense turbulent heat exchange, data were used from acoustic meteorological locator (sodar) and from a passive single-channel scanning microwave radiometer MTP-5 (MWR) to measure the temperature profile in a layer of up to 1 km. Sodar can provide information on the structure of temperature turbulence in the PBL directly. These data have been compared with the mixing layer height calculated with the Parcel method by using the MTP-5 data. For the analysis, July and September 2020 were selected in the city of Tomsk in Siberia as characteristic periods of mid-summer and the transition period to autumn. The measurement results, calculations and inter-comparisons are shown and discussed in this work. During temperature inversions in the boundary layer, it was observed that turbulent heat transfer (increased dispersion of air temperature) is covering the inversion layers and the overlying ones. Moreover, this phenomenon is not only occurring during the morning destruction of inversions, but also in the process of their formation and development.
Overexpression of a Voltage-Dependent Anion-Selective Channel (VDAC) Protein-Encoding Gene, MsVDAC, from Medicago sativa Confers Cold and Drought Tolerance to Transgenic Tobacco
Authors: Yang Mei , Duan Xinhang , Wang Zhaoyu , Yin Hang , Zang Junrui , Zhu Kai , Wang Yumeng , Zhang Pan
Published: October 2021

Voltage-dependent anion channels (VDACs) are highly conserved proteins that are involved in the translocation of tRNA and play a key role in modulating plant senescence and multiple pathways. However, the functions of VDACs in plants are still poorly understood. Here, a novel VDAC gene was isolated and identified from alfalfa (Medicago sativa L.). MsVDAC localized to the mitochondria, and its expression was highest in alfalfa roots and was induced in response to cold, drought and salt treatment. Overexpression of MsVDAC in tobacco significantly increased MDA, GSH, soluble sugars, soluble protein and proline contents under cold and drought stress. However, the activities of SOD and POD decreased in transgenic tobacco under cold stress, while the O2- content increased. Stress-responsive genes including LTP1, ERD10B and Hxk3 were upregulated in the transgenic plants under cold and drought stress. However, GAPC, CBL1, BI-1, Cu/ZnSOD and MnSOD were upregulated only in the transgenic tobacco plants under cold stress, and GAPC, CBL1, and BI-1 were downregulated under drought stress. These results suggest that MsVDAC provides cold tolerance by regulating ROS scavenging, osmotic homeostasis and stress-responsive gene expression in plants, but the improved drought tolerance via MsVDAC may be mainly due to osmotic homeostasis and stress-responsive genes.
Genome Survey Sequencing of an Iconic ‘Trophy’ Sportfish, the Roosterfish Nematistius pectoralis: Genome Size, Repetitive Elements, Nuclear RNA Gene Operon, and Microsatellite Discovery
Authors: Baeza J. Antonio , Molina-Quirós José Luis , Hernández-Muñoz Sebastián
Published: October 2021

The ‘Pez Gallo’ or the Roosterfish, Nematistius pectoralis, is an ecologically relevant species in the shallow water soft-bottom environments and a target of a most lucrative recreational sport fishery in the Central Eastern Pacific Ocean. According to the International Union for Conservation of Nature, N. pectoralis is assessed globally as Data Deficient. Using low-coverage short Illumina 300 bp pair-end reads sequencing, this study reports, for the first time, the genome size, single/low-copy genome content, and nuclear repetitive elements, including the 45S rRNA DNA operon and microsatellites, in N. pectoralis. The haploid genome size estimated using a k-mer approach was 816.04 Mbp, which is within the range previously reported for other representatives of the Carangiformes order. Single/low-copy genome content (63%) was relatively high. A large portion of repetitive sequences could not be assigned to the known repeat element families. Considering only annotated repetitive elements, the most common were classified as Satellite DNA which were considerably more abundant than Class I-Long Interspersed Nuclear Elements and Class I-LTR Retroviral elements. The nuclear ribosomal operon in N. pectoralis consists of, in the following order: a 5′ ETS (length = 948 bp), ssrDNA (1835 bp), ITS1 (724 bp), a 5.8S rDNA (158 bp), ITS2 (508 bp), lsrDNA (3924 bp), and a 3′ ETS (32 bp). A total of 44 SSRs were identified. These newly developed genomic resources are most relevant for improving the understanding of biology, developing conservation plans, and managing the fishery of the iconic N. pectoralis.
Rat Infestation in Gauteng Province: Lived Experiences of Kathlehong Township Residents
Authors: Chelule Paul Kiprono , Mbentse Ayanda
Published: October 2021

Background: Rat infestation is a major public health issue globally, and particularly in poor urban communities in South Africa. Rats pose significant threats to residents in the form of disease spread and sustained physical injuries. The dearth of knowledge about the experiences of affected residents may curtail the initiation of rat control programs. This study aimed to explore the lived experiences of rat infestation among residents of Katlehong Township in Gauteng Province. Methods: This was a qualitative research study where data were gathered from selected community participants from Katlehong Township in Gauteng Province. A semi-structured interview guide was used to collect data through in-depth interviews. The interviews were digitally recorded and transcribed verbatim, and thematic data analysis was conducted using NVivo12 data processing software. The data were presented in themes and quotations that reflect the views of the participants. Results: Exactly 20 community members aged between 18 and 56 years participated in the study, 80% being females. Over half of the participants were unemployed (60%), inclusive of students. Majority of the participants were either Zulu or Xhosa speakers. Several themes emerged from the data, which included the residents’ experiences of rat infestation, troublesome rats, dirty rats, reasons for rat infestation, and sustained physical injuries. Participants intimated that waste in the environment and overcrowding in homes contributed to rodent infestation. Conclusion: Rat infestation remains a problem that causes severe distress among the residents of Katlehong Township. The experiences reported varied from psychological trauma to bite injuries and destruction of household property. Effective rodent control strategies need to be put in place to manage both the physical and mental risks posed by rat infestation in socially underprivileged communities.
Immune Checkpoints Inhibitors and SRS/SBRT Synergy in Metastatic Non-Small-Cell Lung Cancer and Melanoma: A Systematic Review
Authors: Rodríguez Plá María , Dualde Beltrán Diego , Ferrer Albiach Eduardo
Published: October 2021

Background: Several immunotherapy (IT) agents are FDA approved for treatment of melanoma and non-small-cell lung cancer (NSCLC). The addition of stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT) to immunotherapy looks promising. A systematic review was conducted to evaluate the possible synergistic effects of immune checkpoints inhibitors (ICIs) and stereotactic radiation therapy in melanoma and NSCLC. Materials and methods: Pubmed databases from January 2010 to December 2020 were reviewed to identify English language studies reporting control of local and abscopal effect of the combination of ICI-SBRT/SRS in metastatic NSCLC and melanoma cancer. The inclusion criteria were followed according to PICO criteria. Results: Thirty-nine articles were included of the 2141 initial results. The reported rates for local control were 16.5–100% and 40–94% in brain and extracerebral metastases, respectively. Distant/abscopal response rates were 1–45% in extracerebral metastases. Abscopal effect could not be evaluated in brain metastases because it was not reported in studies. Treatments were well tolerated with few grade 4 toxicities and no grade 5. Conclusions: The combined treatment of ICI-SBRT/SRS achieves high local control and non-negligible abscopal response in patients with extracerebral metastases, with its benefit in cerebral metastases being more controversial. Clinical trials are needed to better characterize the potential synergism.
Tick Cell Culture Analysis of Growth Dynamics and Cellular Tropism of Rickettsia buchneri, an Endosymbiont of the Blacklegged Tick, Ixodes scapularis
Authors: Thorpe Cody J. , Wang Xin-Ru , Munderloh Ulrike G. , Kurtti Timothy J.
Published: October 2021

The blacklegged tick, Ixodes scapularis, a species of significant importance to human and animal health, harbors an endosymbiont Rickettsia buchneri sensu stricto. The symbiont is largely restricted to the ovaries, but all life stages can harbor various quantities or lack R. buchneri entirely. The endosymbiont is cultivable in cell lines isolated from embryos of Ixodes ticks. Rickettsia buchneri most readily grows and is maintained in the cell line IRE11 from the European tick, Ixodes ricinus. The line was characterized by light and electron microscopy and used to analyze the growth dynamics of wildtype and GFPuv-expressing R. buchneri. qPCR indicated that the genome copy doubling time in IRE11 was >7 days. Measurements of fluorescence using a plate reader indicated that the amount of green fluorescent protein doubled every 11 days. Two 23S rRNA probes were tested via RNA FISH on rickettsiae grown in vitro and adapted to evaluate the tissue tropism of R. buchneri in field-collected female I. scapularis. We observed strong positive signals of R. buchneri in the ovaries and surrounding the nucleus of the developing oocytes. Tissue tropism in I. scapularis and in vitro growth dynamics strengthen the contemporary understanding of R. buchneri as a transovarially transmitted, non-pathogenic endosymbiont.
Hemolymph Ecdysteroid Titer Affects Maternal mRNAs during Bombyx mori Oogenesis
Authors: Zhang Meirong , Xu Pingzhen , Chen Tao
Published: October 2021

Silkworm larval–pupal metamorphosis and the first half of pupal–adult development occur during oogenesis from previtellogenesis to vitellogenesis and include two peaks of the hemolymph ecdysteroid titer. Moreover, a rise in 20-hydroxyecdysone titer in early pupae can trigger the first major transition from previtellogenesis to vitellogenesis in silkworm oogenesis. In this study, we first investigated the expression patterns of 66 maternal genes in the ovary at the wandering stage. We then examined the developmental expression profiles in six time-series samples of ovaries or ovarioles by reverse transcription–quantitative PCR. We found that the transcripts of 22 maternal genes were regulated by 20-hydroxyecdysone in the isolated abdomens of the pupae following a single injection of 20-hydroxyecdysone. This study is the first to determine the relationship between 20-hydroxyecdysone and maternal genes during silkworm oogenesis. These findings provide a basis for further research into the embryonic development of Bombyx mori.
The Effect of Ultrasonic Agitation on the Porosity Distribution in Apically Perforated Root Canals Filled with Different Bioceramic Materials and Techniques: A Micro-CT Assessment
Authors: Drukteinis Saulius , Bilvinaite Goda , Shemesh Hagay , Tusas Paulius , Peciuliene Vytaute
Published: October 2021

The present study evaluated the effect of ultrasonic agitation on the porosity distribution of BioRoot RCS/single gutta-percha cone (BR/SC) and MTA Flow (MF) root canals fillings used as apical plugs in moderately curved and apically perforated roots. Eighty mesial root canals of mandibular first molars were enlarged up to ProTaper NEXT X5 rotary instrument 2 mm beyond the apical foramen, simulating apical perforations. Specimens were randomly divided into four experimental groups (20 canals per group) according to the material and technique used for root canal obturation: BR/SC, BR/SC with ultrasonic agitation (BR/SC-UA), MF and MF with ultrasonic agitation (MF-UA). The ultrasonic tip was passively inserted into the root canal after the injection of flowable cement and activated for 10 s. The specimens were scanned before and after obturation with a high-resolution micro-computed tomography scanner, and the porosity of the apical plugs was assessed. The differences between groups were analyzed using the Kruskal-Wallis and Mann-Whitney tests, with the significance level set at 5%. None of the obturation materials and techniques used in this study was able to provide a pore-free root canal filling in the apical 5 mm. Considerably higher percentages of open and closed pores were observed in the MF and MF-UA groups, with the highest porosity being in the MF-UA group (p < 0.05). No significant differences were observed between the BR/SC and BR/SC-UA groups, where the quantity of open and closed pores remained similar (p > 0.05).
A Practical Guide to Therapeutic Drug Monitoring of Biologic Medications for Inflammatory Bowel Disease
Authors: Vaughn Byron P.
Published: October 2021

Therapeutic drug monitoring (TDM) is a useful strategy to optimize biologic medications for inflammatory bowel disease not responsive to standard dosing regimens. TDM is cost effective for anti-tumor necrosis factor agents in the setting of loss of response (reactive TDM). Optimizing drug dosing when patients are in remission (proactive TDM) may be beneficial in certain circumstances. However, frequently the serum drug concentration in isolation becomes the focus TDM. Additionally, the lines of reactive and proactive TDM can quickly blur in many common clinical settings. Physicians employing a TDM based strategy need to place the drug concentration in context with the inflammatory status of the patient, the underlying pharmacokinetics and pharmacodynamics of the drug, the risk of immunogenicity, and the therapeutic goals for the patient. Physicians should understand the limits of TDM and feel comfortable making therapeutic decisions with imperfect information. The goal of this narrative review is to provide a framework of questions that physicians can use to employ TDM effectively in practice.
A Prospective, Single Arm, Multi-Center Study Evaluating the Clinical Outcomes of Ventral Hernias Treated with OviTex® 1S Permanent Reinforced Tissue Matrix: The BRAVO Study 12-Month Analysis
Authors: DeNoto George , Ceppa Eugene P. , Pacella Salvatore J. , Sawyer Michael , Slayden Geoffrey , Takata Mark , Tuma Gary , Yunis Jonathan
Published: October 2021

Background: Conflicting results from previous studies have led to dissent over whether surgical mesh is safe and effective in ventral hernia repair. A newer class of mesh known as a reinforced tissue matrix, combining a biologic scaffold and minimal polymer reinforcement, offers promise in reducing inflammatory response and increasing abdominal wall support. This study sought to assess the clinical utility of a reinforced tissue matrix (OviTex) in ventral hernia repair 12 months after implantation. Methods: This is a prospective, single-arm, multi-center study to evaluate the clinical performance of OviTex® 1S Permanent (OviTex) in the repair of primary or recurrent ventral hernias (VH) in consecutive patients (ClinicalTrials.gov/NCT03074474). The rate of surgical site occurrences (SSOs) was evaluated 90 days post-surgery as the primary endpoint. Hernia recurrence and the incidence of postoperative events were evaluated between three and 12 months as secondary endpoints. The incidence of other complications and patient-reported outcomes were also recorded. Results: Ninety-two (92) patients were enrolled in the study, of whom seventy-six (76) reached the 12-month follow-up. All patients were at least 18 years of age with a BMI of <40 kg/m2. Hernia defects were <20 × 20 cm, classified as class I–III according to the CDC wound classification system. Of the 76 patients who reached 12-month follow-up, twenty-six (34%) had previous VH repairs and thirteen (17%) had previous surgical infection. Sixty (79%) had factors known to increase the risk of recurrence. Twenty patients (26%) experienced SSOs, with ten (13%) requiring procedural intervention. Two of the 75 patients (2.7%) experienced a recurrence. Conclusions: The low rate of hernia recurrence and SSOs requiring intervention illustrates the potential that reinforced tissue matrices, and OviTex 1S, in particular, have to improve outcomes in VH repairs. Follow-up to 24 months is ongoing.
Differential Expression of the Sphingolipid Pathway Is Associated with Sensitivity to the PP2A Activator FTY720 in Colorectal Cancer Cell Lines
Authors: Sciberras Peter , Grech Laura , Grech Godfrey
Published: October 2021

Protein phosphatase 2A (PP2A) is a ubiquitously expressed intracellular serine/threonine phosphatase. Deregulation of PP2A is a common event associated with adenocarcinomas of the colon and rectum. We have previously shown that breast cancer cell lines are sensitive to the PP2A activator FTY720, and that sensitivity is predicted by high Aurora kinase A (AURKA) mRNA expression. In this study, we hypothesized that high relative AURKA expression could predict sensitivity to FTY720-induced apoptosis in colorectal cancer (CRC). The CRC cell lines NCI H716, COLO320DM, DLD-1, SW480, and HT-29 show a high relative AURKA expression as compared to LS411N, T84, HCT116, SW48, and LOVO. Following viability assays, LS411N, T84, HCT116, and SW480 were shown to be sensitive to FTY720, whereas DLD-1 and HT-29 were non-sensitive. Hence, AURKA mRNA expression does not predict sensitivity to FTY720 in CRC cell lines. Differentially expressed genes (DEGs) were obtained by comparing the sensitive CRC cell lines (LS411N and HCT116) against the non-sensitive (HT-29 and DLD-1). We found that 253 genes were significantly altered in expression, and upregulation of CERS4, PPP2R2C, GNAZ, PRKCG, BCL2, MAPK12, and MAPK11 suggests the involvement of the sphingolipid signaling pathway, known to be activated by phosphorylated-FTY720. In conclusion, although AURKA expression did not predict sensitivity to FTY720, it is evident that specific CRC cell lines are sensitive to 5 µM FTY720, potentially because of the differential expression of genes involved in the sphingolipid pathway.
Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance
Authors: Zhong Shangwei , Huang Changhao , Chen Zhikang , Chen Zihua , Luo Jun-Li
Published: October 2021

Although castration-resistant prostate cancer (CRPC) as a whole, by its name, refers to the tumors that relapse and/or regrow independently of androgen after androgen deprivation therapy (ADT), untreated tumor, even in early-stage primary prostate cancer (PCa), contains androgen-independent (AI) PCa cells. The transformation of androgen-dependent (AD) PCa to AI PCa under ADT is a forced evolutionary process, in which the small group of AI PCa cells that exist in primary tumors has the unique opportunity to proliferate and expand selectively and dominantly, while some AD PCa cells that have escaped from ADT-induced death acquire the capability to survive in an androgen-depleted environment. The adaptation and reprogramming of both PCa cells and the tumor microenvironment (TME) under ADT make PCa much stronger than primary tumors so that, currently, there are no effective therapeutic methods available for the treatment of CRPC. Many mechanisms have been found to be related to the emergence and maintenance of PCa castration resistance; in this review, we focus on the role of inflammatory signaling in both PCa cells and the TME for the emergence and maintenance of CRPC and summarize the recent advances of therapeutic strategies that target inflammatory signaling for the treatment of CRPC.
Distortion Product Otoacoustic Emissions and Their Suppression as Predictors of Peripheral Auditory Damage in Migraine: A Case-Control Study
Authors: Albanese Maria , Di Girolamo Stefano , Silvani Lorenzo , Ciaschi Eleonora , Chiaramonte Barbara , Conti Matteo , Passali Francesco Maria , Di Gioia Battista , Mercuri Nicola Biagio , Di Stadio Arianna
Published: October 2021

Although several cochleo-vestibular symptoms are commonly associated with migraine, only a limited number of studies have been done in this regard. Some reported abnormalities in audiometry, auditory brainstem response and vestibular tests, considering these manifestations mainly related to central etiology. However, increasing evidence also suggests a peripheral involvement of the inner ear in migraine. The aim of this study was to investigate the peripheral auditory pathway in migraineurs using otoacoustic emissions (OAEs), to detect alteration of cochlear functioning and possible relationship with disease severity. Sixty-two migraineurs and sixty matched controls were enrolled in the study and underwent a routine neuro-otolaryngology examination; self-administered questionnaires were used to evaluate subjective perception of hearing disability. DPOAE and their suppression were lower in migraineurs compared to controls and significantly related to the disease duration. Altered DPOAE exposed migraineurs to the risk of affecting by migraine without aura, of presenting with ocular and/or auditory symptoms during attack and of using more painkillers. Concomitant dopaminergic symptoms and/or allodynia such as the acute non-consumption of triptans were significant determinants of decreased contralateral suppression of DPOAE among migraineurs. This potential subclinical cochlear impairment in migraine detected by OAEs may represent the earliest sign of sensorineural damage in these patients, providing a promising tool for the initial diagnosis and an opportunity to monitor disease course and treatment response over time.