bluuebunny/crossref_metadata_2025 huggingface dataset:
A Hill Equation for Solid Specific Heat Capacity Calculation
Authors: Rowe Scott C. , Chubukov Boris A. , Telotte John C.
Published: July 2022

The Hill Equation and Hill Coefficient have been used extensively in biochemistry for the description of noncovalent binding. Previously, the Hill Coefficient was correlated with the Gibbs free energy, which suggests that the Hill Equation might be extensible to covalent binding phenomena. To evaluate this possibility, the Hill Equation was compared to the Debye Model and Einstein Solid in the calculation of heat capacity for 53 covalent solids, which included stainless steels and refractory ceramics. Hill Equation specific heat predictions showed a standard error of 0.37 J/(mole⋅Kelvin), whereas errors from the Debye Model and Einstein Solid were higher at 0.45 J/(mole⋅Kelvin) and 0.81 J/(mole⋅Kelvin), respectively. Furthermore, the Hill Equation is computationally efficient, a feature that can accelerate industrial chemical process simulation(s). Given its speed, simplicity, and accuracy, the Hill Equation likely offers an alternative means of specific heat calculation in chemical process models.
Preparation of Healable Shellac Microcapsules and Color-Changing Microcapsules and Their Effect on Properties of Surface Coatings on Hard Broad-Leaved Wood Substrates
Authors: Qin Yanzhao , Yan Xiaoxing
Published: July 2022

In order to protect the wood surface and improve the properties of coatings, microcapsules with healable and discoloration functions are produced, and their healable function is obtained using shellac, which can be cured at room temperature, as the repairing agent. In this paper, self-made shellac microcapsules and color-changing microcapsules were added to varnish in different proportions to form the composite coating on a wood board, and the color difference of the coating was measured at different temperatures to study the influence of microcapsules on the degree of surface color on the substrate. The effect of microcapsules on the healable performance of coatings on a wood board was studied by scratching the surface of the coating with a utility knife and observing the process of repair. The optimal sample was selected from the orthogonal experiment for the independent experiment. The surface roughness, hardness, infrared spectrum, and scanning electron microscopy of the optimal sample were tested, and the content in the optimal sample was further investigated. The results show that color-changing microcapsules have a color-changing effect on surface coatings based on wood boards, and shellac microcapsules inhibit the color-changing effect of color-changing microcapsules. Composite microcapsules can repair the cracks on the surface coatings of wood boards. In cases where shellac microcapsules can self-repair the coating, the color-changing effect is best when the content of color-changing powder is 15.0%.
Utilization of Steel Slag in Road Semi-Rigid Base: A Review
Authors: Li Haibin , Cui Canyang , Cai Jun , Zhang Mingming , Sheng Yanping
Published: July 2022

Steel slag (SS) is industrial waste, and there is a large amount of SS to be treated in China. Its disposal generates severe environmental pollution. One of the best ways to use SS is as a road base material. This paper reviews the possibility of using SS in semi-rigid base and evaluates the performance of SS base course. The interaction between three stabilizers (cement, lime–fly ash, and cement–fly ash) and SS is analyzed, and the influence of modifier content on the performance of base course is evaluated. The potential laws between SS, curing time, and unconfined compressive strength, as well as drying shrinkage and temperature shrinkage, are discussed and their effects on the performance of the base course are revealed. The finite element method, discrete element method, and molecular dynamics can be used to analyze the freeze-thaw, rutting resistance, and crack development of SS base. In addition, compared with traditional macadam base, the CO2 emissions for the use of SS base are slightly more, one of the disadvantages of its use in production, transportation, and compaction. However, considering the overall mechanical, economic, and environmental benefits, it is recommended to use SS in semi-rigid base course. The future research scope of SS as base material is suggested.
Improvement of Mechanical Properties and Microstructure of Cementitious Materials in a Hot-Dry Environment
Authors: Xu Zhanjun , Han Xiaokun , Feng Kaiwen , Zhang Weizhen , Ma Kunlin
Published: July 2022

The hot-dry environment in high geothermal tunnels negatively affects the development of properties of cementitious materials. In order to improve the mechanical properties of cementitious materials in such environments, a proper curing system was developed, the material compositions were taken into account, and the related mechanism was analyzed by microscopic tests. The results showed that the mechanical properties and microstructure of cementitious materials can be improved effectively by adopting film curing and an adequate dosage of fly ash in a hot-dry environment. Compared with standard curing, a hot-dry environment accelerates the evaporation of water in fresh cementitious materials and the early hydration rate of cementitious materials, resulting in lots of unhydrated cement particles and an uneven distribution of hydration products, seriously decreasing the properties of the cementitious materials. Film curing keeps the water from evaporating and ensures enough water is available for hydration at an early age. The addition of FA reduces the amount of cement clinker and decreases hydration reaction rate in high temperature environments at an early stage, avoiding the unevenness of hydration products. High temperatures stimulate the pozzolanic activity of fly ash and promote the degree of secondary hydration reaction, producing more hydration products, as well as contributing to the improvement of the mechanical properties and microstructure of cementitious materials. In this study, in a hot-dry environment, the mechanical properties of mortar with 25% fly ash and 2–3 d film curing are better than those of other experimental groups, including those of standard curing.
Land Snail Assemblages of Olive Orchards in Crete, Greece
Authors: Georgopoulou Elisavet , Gkisakis Vasileios D. , Kabourakis Emmanouil M.
Published: July 2022

Land snail biodiversity research in agroecosystems is limited, if non-existent. Here we investigate the land snail assemblages of olive orchards in Messara plain, Crete, Greece. Land snails were collected from 16 olive orchards. In addition, we performed a literature survey and recorded all species reported in the surrounding area. We found 18 species in the olive orchards among the 37 species found in the area and reported in the literature. Xerotricha conspurcata (Draparnaud, 1801) and Caracollina lenticula (Michaud, 1831) are reported for the first time in the study area. Their presence is probably a result of human-mediated dispersal. Olive orchards proved to be an important refuge for land snail diversity as they host 43% of the species found in the surrounding area. We highlight the importance of olive orchards as habitats with increased land snail richness. We suggest that land snails should be included in future biodiversity research in agricultural areas.
Information Bottleneck Signal Processing and Learning to Maximize Relevant Information for Communication Receivers
Authors: Lewandowsky Jan , Bauch Gerhard , Stark Maximilian
Published: July 2022

Digital communication receivers extract information about the transmitted data from the received signal in subsequent processing steps, such as synchronization, demodulation and channel decoding. Technically, the receiver-side signal processing for conducting these tasks is complex and hence causes bottleneck situations in terms of power, delay and chip area. Typically, many bits per sample are required to represent and process the received signal in the digital receiver hardware accurately. In addition, demanding arithmetical operations are required in the signal processing algorithms. A popular recent trend is designing entire receiver chains or some of their crucial building blocks from an information theoretical perspective. Signal processing blocks with very simple mathematical operations can be designed to directly maximize the relevant information that flows through them. At the same time, a strong quantization reduces the number of bits processed in the receiver to further lower the complexity. The described system design approach follows the principle of the information bottleneck method. Different authors proposed various ideas to design and implement mutual information-maximizing signal processing units. The first important aim of this article is to explain the fundamental similarities between the information bottleneck method and the functionalities of communication receivers. Based on that, we present and investigate new results on an entire receiver chain that is designed following the information bottleneck design principle. Afterwards, we give an overview of different techniques following the information bottleneck design paradigm from the literature, mainly dealing with channel decoding applications. We analyze the similarities of the different approaches for information bottleneck signal processing. This comparison leads to a general view on information bottleneck signal processing which goes back to the learning of parameters of trainable functions that maximize the relevant mutual information under compression.
Estimating the Individual Treatment Effect on Survival Time Based on Prior Knowledge and Counterfactual Prediction
Authors: Zhao Yijie , Zhou Hao , Gu Jin , Ye Hao
Published: July 2022

The estimation of the Individual Treatment Effect (ITE) on survival time is an important research topic in clinics-based causal inference. Various representation learning methods have been proposed to deal with its three key problems, i.e., reducing selection bias, handling censored survival data, and avoiding balancing non-confounders. However, none of them consider all three problems in a single method. In this study, by combining the Counterfactual Survival Analysis (CSA) model and Dragonnet from the literature, we first propose a CSA–Dragonnet to deal with the three problems simultaneously. Moreover, we found that conclusions from traditional Randomized Controlled Trials (RCTs) or Retrospective Cohort Studies (RCSs) can offer valuable bound information to the counterfactual learning of ITE, which has never been used by existing ITE estimation methods. Hence, we further propose a CSA–Dragonnet with Embedded Prior Knowledge (CDNEPK) by formulating a unified expression of the prior knowledge given by RCTs or RCSs, inserting counterfactual prediction nets into CSA–Dragonnet and defining loss items based on the bounds for the ITE extracted from prior knowledge. Semi-synthetic data experiments showed that CDNEPK has superior performance. Real-world experiments indicated that CDNEPK can offer meaningful treatment advice.
Teacher Uneasiness and Workplace Learning in Social Sciences: Towards a Critical Inquiry from Teachers’ Voices
Authors: Luna Diego , Pineda-Alfonso José Antonio , García-Pérez Francisco F. , Leal da Costa Conceição
Published: July 2022

The educational parameters of neoliberal schools have transformed traditional social expectations about teachers. As some authors have suggested, “teacher uneasiness” is an appropriate category of analysis to understand and interpret the effects that such expectations can have on teachers’ professional identity. In this research, autoethnography was specifically chosen as an investigative and, at the same time, formative modality, ideal for determining the way in which a Social Sciences teacher in Spanish secondary education experiences his own uneasiness. According to the information in the teacher/researcher’s diary, collected during fieldwork carried out over two years, and processed by content analysis, this phenomenon can be generated by causes that are still unnoticed in the existing literature. Specifically, we could identify up to four subcategories from the data itself: the weight of tradition; daily overexertion; no time; and resignation after wear and tear. We conclude with vindications both of the theoretical category used, and of the usefulness of autoethnography in this type of empirical project. In any case, we also recommend new research that allows us to compare and expand the results and conclusions obtained herein.
Economic Dispatch of Microgrid Based on Load Prediction of Back Propagation Neural Network–Local Mean Decomposition–Long Short-Term Memory
Authors: Xu Fengxia , Zhang Xinyu , Ma Xingming , Mao Xinyu , Lu Zhongda , Wang Lijing , Zhu Ling
Published: July 2022

To plan the work of power generation equipment, it is necessary to ensure that the power supply is sufficient and to achieve the minimum cost to ensure the safety and economy of the microgrid. Based on back propagation neural network–local mean decomposition–long short-term memory (BPNN–LMD–LSTM) load prediction, the design is based on a fixed-time consistency algorithm with random delay to predict the economic dispatch of microgrids. Firstly, the initial power load prediction sequence is obtained by continuous training of the back propagation neural network (BPNN); the residual sequence with other influencing factors is decomposed by local mean decomposition (LMD); and the long short-term memory neural network (LSTM) is used to predict the output prediction residual sequence, and the final short-term power load prediction is obtained. Based on predicting load, the fixed-time consistency algorithm with random delay is used to add supply and demand balance constraints to optimize the power distribution of the power generation units of the distributed microgrid and reduce the power generation cost of the microgrid. The results show that the prediction model has better prediction accuracy, and the scheduling algorithm based on the prediction model has a faster convergence rate to reach the lowest power generation cost.
Common-Mode Voltage Reduction and Neutral Point Voltage Balance Modulation Technology of Quasi-Z-Source T-Type Three-Level Inverter
Authors: Xie Lingling , Yao Junyi
Published: July 2022

The quasi-Z-source T-type inverter is a new type of three-level inverter. Compared with other three-level inverters, the quasi-z-source T-type inverter is characterized by its fault tolerance capability and boost capability. In the inverter, the modulation strategy greatly affects the performance. Aiming at the problems in three-level inverters such as excessive common-mode voltage and unbalanced neutral point potential, a space vector pulse width modulation (SVPWM) for a quasi-z-source T-type three-level inverter based via line voltage coordinate is proposed in this paper. The main research work and achievements of this paper include: (1) based on the existing research results, an SVPWM modulation strategy for the quasi-Z-source T-type inverter is proposed. The modulation method proposed by this paper can effectively reduce the common-mode voltage and balance the neutral point voltage. (2) This paper analyzes the principle of the line voltage coordinate system and makes some modifications to the line voltage coordinate system so that the proposed modulation scheme can be applied to the line voltage coordinate system. Compared with the traditional αβ coordinate system, the SVPWM algorithm in the line voltage coordinate system has the characteristic of simple calculation. The simulation and experiment results show that the control method has good performance under the conditions of dynamic response and imbalance.
The Achievements of Climate Change and Energy Policy in the European Union
Authors: Siksnelyte-Butkiene Indre , Karpavicius Tomas , Streimikiene Dalia , Balezentis Tomas
Published: July 2022

The European transition to green economy is based on long-term strategies. The Europe 2020 Strategy was launched in 2010 in order to promote smart, sustainable, and inclusive growth in the region. Later, the ambitions regarding this strategy were followed by the Green Deal and Sustainable Development Goals. Now, the effort of countries towards the green economy is even more relevant than ever because of the context of today’s global energy crisis and economic uncertainty due to many challenges such as the COVID-19 pandemic or Russia invasion of Ukraine. This paper seeks to assess the countries’ achievements in seeking climate change and energy targets of the Europe 2020 Strategy by applying the innovative multi-criteria decision-making (MCDM) technique. The kernel-based comprehensive assessment (KerCA) method was applied for the calculations of the progress achieved and countries’ rankings. It allows to evaluate countries’ achievements and compare them using the mathematical models. The analysis of the national target implementation in the countries allows to determine the compliance of countries with their commitments and liability towards other countries and the European Union (EU). An analysis of the implementation of the strategy can serve as a guide to further develop climate change and energy policy in the region. Furthermore, the added value of the article is systematic overview of scientific studies proposing different methodologies for the analysis of target implementation at the whole region level. The novelty of this paper also relies on the approach, which considers not only the level of achievement of the target, but also assesses the excess.
Carbon Emission Reduction by Bicycle-Sharing in China
Authors: Niu Ziheng , Chai Li
Published: July 2022

Bicycle-sharing plays an important role in solving the “last mile” problem of Chinese people and promoting the construction of an environment-friendly society. This study assesses the carbon emissions generated in the life cycle of bicycle-sharing, examines the substitution effect of bicycle-sharing, and quantifies the depletion rate of bicycle-sharing in combination with the current rate of electric vehicles in China. The depletion rate of shared bicycles in China is high, roughly 5–15% per year. In addition, we discuss scenarios where the annual growth rate of electric vehicles is 40%, 50%, and 60%. Results show that when electric vehicles’ depletion rate is 5% and the annual growth rate of electric vehicles is 40%, the largest net emission reduction in 2025 is 1.96 million tons. Additionally, when electric vehicles’ depletion rate is 5% and the annual growth rate of electric vehicles is 60%, the smallest net emission reduction totals 1.7 million tons.
Effects of Different Native Plants on Soil Remediation and Microbial Diversity in Jiulong Iron Tailings Area, Jiangxi
Authors: Wang Qian , Sun Qiwu , Wang Wenzheng , Liu Xiangrong , Song Liguo , Hou Lingyu
Published: July 2022

Phytoremediation is an important solution to heavy metal pollution in soil. However, the impact of plants on microbial communities in contaminated soil also requires attention. Community-level physiological profiling (CLPP) based on the Biolog™ EcoPlate and high-throughput sequencing were used to study the soil microbial community in this article. The rhizosphere and bulk soil samples of six native species were collected from the iron mine tailings on Jiulong Mountain, Jiangxi Province. According to the average well color development (AWCD), all plants improved the activity and diversity of the contaminated soil microbial community to varying degrees. Cunninghamia lanceolate is considered to have good effects and led to the appearance of Cunninghamia lanceolata > Zelkova schneideriana > Toona ciliata > Alnus cremastogyne > Cyclobalanopsis myrsinifolia > Pinus elliottii. The Shannon–Wiener diversity index and principal component analysis (PCA) show that the evenness and dominance of soil microbial communities of several plants are structurally similar to those of uncontaminated soil (UNS). The results of high-throughput sequencing indicated that the bacterial community diversity of C. lanceolata, A. cremastogyne, and P. elliottii is similar to UNS, while fungal community diversity is different from UNS. C. lanceolata has a better effect on soil nutrients, C. myrsinifolia and P. elliottii may have a better effect on decreasing the Cu content. The objective of this study was to assess the influence of native plants on microbial communities in soils and the soil remediation capacity. Mortierellomycota was the key species for native plants to regulate Cu and microbial community functions. Native plants have decisive influence on microbial community diversity.
Current Outline of Exon Skipping Trials in Duchenne Muscular Dystrophy
Authors: Eser Gökçe , Topaloğlu Haluk
Published: July 2022

Molecular treatments for Duchenne muscular dystrophy (DMD) are already in clinical practice. One particular means is exon skipping, an approach which has more than 15 years of background. There are several promising clinical trials based on earlier works. The aim is to be able to initiate the production of enough dystrophin to change the rate of progression and create a clinical shift towards the better. Some of these molecules already have received at least conditional approval by health authorities; however, we still need new accumulating data.
The Effect of EGR1 on the Proliferation of Dermal Papilla Cells
Authors: Xu Yeling , Wang Shanhe , Cao Xiukai , Yuan Zehu , Getachew Tesfaye , Mwacharo Joram M. , Haile Aynalem , Lv Xiaoyang , Sun Wei
Published: July 2022

Early growth response factor 1 (EGR1) is a zinc-finger transcription factor that plays a vital role in the development of hair follicles. According to our previous studies, EGR1 is a transcriptional promoter of the bone morphogenetic protein 7 (BMP7), a candidate gene involved in the proliferation of dermal papilla cells. Since hair follicles are the basis of lambskin pattern formation and dermal papilla cells (DPCs) act on hair follicle growth, in order to elucidate the role of EGR1 and hair follicles, this study aimed to investigate the biological role of EGR1 in DPCs. In our study, the EGR1 coding sequence (CDS) region was firstly cloned by polymerase chain reaction, and bioinformatics analysis was performed. Then, the function of EGR1 was detected by 5-ethynyl-2’-deoxyuridine (EDU) and Cell Counting Kit-8 (CCK8), and Western blot (WB) was conducted to analyze the cellular effect of EGR1 on DPCs. The proliferative effect of EGR1 on DPCs was also further confirmed by detecting its expression by qPCR and WB on marker genes of proliferation, including PCNA and CDK2. The sequence of the EGR1 CDS region of a lamb was successfully cloned, and its nucleic acid sequence was analyzed and found to be highly homologous to Rattus norvegicus, Mus musculus, Bos taurus and Homo sapiens. Predictive analysis of the protein encoded by EGR1 revealed that it is an extra-membrane protein, and not a secretory protein, with subcellular localization in the nucleus and cytoplasm. The proliferative effect of DPCs was significantly stronger (p < 0.01) in EGR1 up-regulated DPCs compared to the controls, while the opposite result was observed in EGR1 down-regulated DPCs. Markers of proliferation including PCNA and CDK2 also appeared to be differentially upregulated in EGR1 gene overexpression compared to the controls, with the opposite result in EGR1 gene downregulation. In summary, our study revealed that EGR1 promotes the proliferation of DPCs, and we speculate that EGR1 may be closely associated with hair follicle growth and development.
In Silico Insights on the Pro-Inflammatory Potential of Polycyclic Aromatic Hydrocarbons and the Prospective Anti-Inflammatory Capacity of Andrographis paniculata Phytocompounds
Authors: Julaton Trixia , Taclendo Aibelou , Oyong Glenn , Rempillo Ofelia , Galvez Maria Cecilia , Vallar Edgar
Published: July 2022

Inflammation linked to various diseases is the biological response to certain stimuli. The pro-inflammatory potential of Polycyclic Aromatic Hydrocarbons (PAHs) as potential inducers of inflammation bound to the Toll-like Receptor 4 (TLR4) and the anti-inflammatory capacity of A. paniculata (AP) phytocompounds as prospective inhibitors of the Nuclear Factor Kappa B (NF-κB) p50 transcription factor are investigated via in silico techniques. The molecular docking of the PAHs and AP phytocompounds is performed in AutoDock Vina by calculating their binding energies. The molecular dynamics simulations (MDS) of the apo and ligand-bound complex of the top binding ligands were performed in CABS-flex. The agonists, which included the PAHs indeno(1,2,3-cd)pyrene (IP), and dibenz(a,h)anthracene (DahA), had the highest binding energies of −10 kcal/mol and −9.2 kcal/mol, respectively. The most stable antagonists in the binding site with binding energies to the NF-κB p50 were the AP phytocompounds with −5.6 kcal/mol for ergosterol peroxide and −5.3 kcal/mol for 14-deoxy-14,15-dehydroandrographolide. The MDS of the apo human TLR4 and PAH-bound TLR4, and the apo p50 and the AP phytocompound-bound NF-κB p50 showed minimal fluctuations. These results reveal that IP and DahA are significant inducers of inflammation, whereas ergosterol peroxide and 14-deoxy-14,15-dehydroandrographolide are inhibitors of the NF-κB pathway. Furthermore, the study theorizes that any inflammatory activity induced by PAH can be potentially inhibited by A. paniculata phytocompounds.
“It Depends on Where You Are and What Job You Do”: Differences in Tobacco Use across Career Fields in the United States Air Force
Authors: Horn Tori L. , Porter Kathleen J. , Pebley Kinsey N. , Krukowski Rebecca A. , Little Melissa A.
Published: July 2022

While tobacco use within the military is often discussed as being homogenously part of U.S. military culture, literature from civilian populations highlights that tobacco use varies by career field (e.g., “white collar” vs. “blue collar”). The objective of this qualitative study was to compare tobacco use by career fields in the U.S. Air Force. Airmen, Military Training Instructors, and Technical Training Instructors participated in 22 focus groups across five major Air Force Technical Training bases. Focus groups were conducted in-person using semi-structured interview guides and were audio-recorded. A conventional content-coding approach was used to code transcripts. Participants described substantial variation across the careers, which was attributed to social norms and the nature of jobs. Individuals in careers that spend most of their time outside were more likely to permit tobacco use. Conversely, tobacco use was seen as stigmatized in medical fields. Additionally, smokeless tobacco was identified as popular in certain careers because it could be used covertly on the job. Findings suggest that a one-size-fits-all approach to reducing tobacco use through policies and programs may not reflect the realities of military tobacco use. These findings may provide insights into other branches of the U.S. military with similar career fields.
Creation and Implementation of a New Sentinel Surveillance Model in Pharmacy Offices in Southern Europe
Authors: Jambrina Anna M. , Rams Neus , Rius Pilar , Perelló Maria , Gironès Montserrat , Pareja Clara , Pérez-Cano Francisco José , Franch Àngels , Rabanal Manel
Published: July 2022

Traditionally, health sentinel networks have focused on the reporting of data by primary care physicians and hospitals, ignoring the role of the community pharmacist as an expert in drugs. The objective of this study was to describe a method for creating a network of sentinel pharmacies in a region of Southern Europe in order to have a pharmaceutical surveillance system that is representative of the territory to be monitored and that can respond to any events or incidents that can be followed up by the community pharmacy. The creation process was carried out in three phases: a first phase of selection through a cluster and population analysis and a final adjustment, a second phase of voluntariness and random selection, and a third phase of training and implementation of the network. A sentinel network of 75 community pharmacies has been established in Catalonia. The network monitors 2.47% of the total population with a homogeneous proportion of urban (42), rural (30), and mountain-area (3) pharmacies based on the particular characteristics of the territory. This model allows increased surveillance in the territory, objectively and representatively detects problems arising from the use of medicines, and establishes improvement strategies of public health.
Methylation in the Promoter Region of the Dopamine Transporter DAT1 Gene in People Addicted to Nicotine
Authors: Chmielowiec Jolanta , Chmielowiec Krzysztof , Strońska-Pluta Aleksandra , Suchanecka Aleksandra , Humińska-Lisowska Kinga , Lachowicz Milena , Niewczas Marta , Białecka Monika , Śmiarowska Małgorzata , Grzywacz Anna
Published: July 2022

The dopaminergic system is a crucial element of the addiction processes. The dopamine transporter modulates the dynamics and levels of released dopamine in the synaptic cleft. Therefore, regulation of dopamine transporter (DAT1) gene expression is critical for maintaining homeostasis in the dopaminergic system. The aim of our study is evaluation of the methylation status of 33 CpG islands located in the DAT1 gene promoter region related to nicotine dependency. We investigated 142 nicotine-dependent subjects and 238 controls. Our results show that as many as 14 of the 33 CpG islands tested had statistically significantly higher methylation in the nicotine-dependent group compared to the control group. After applying Bonferroni correction, the total number of methylation sites was also significantly higher in the dependent subjects group. The analysis of the methylation status of particular CpG sites revealed a new direction of research regarding the biological aspects of nicotine addiction.
Complex Diagnostics of Non-Specific Intellectual Developmental Disorder
Authors: Levchenko Olga , Dadali Elena , Bessonova Ludmila , Demina Nina , Rudenskaya Galina , Matyushchenko Galina , Markova Tatiana , Anisimova Inga , Semenova Natalia , Shchagina Olga , Ryzhkova Oxana , Zinchenko Rena , Galkina Varvara , Voinova Victoria , Nagieva Sabina , Lavrov Alexander
Published: July 2022

Intellectual development disorder (IDD) is characterized by a general deficit in intellectual and adaptive functioning. In recent years, there has been a growing interest in studying the genetic structure of IDD. Of particular difficulty are patients with non-specific IDD, for whom it is impossible to establish a clinical diagnosis without complex genetic diagnostics. We examined 198 patients with non-specific IDD from 171 families using whole-exome sequencing and chromosome microarray analysis. Hereditary forms of IDD account for at least 35.7% of non-specific IDD, of which 26.9% are monogenic forms. Variants in the genes associated with the BAF (SWI/SNF) complex were the most frequently identified. We were unable to identify phenotypic features that would allow differential diagnosis of monogenic and microstructural chromosomal rearrangements in non-specific IDD at the stage of clinical examination, but due to its higher efficiency, exome sequencing should be the diagnostic method of the highest priority study after the standard examination of patients with NIDD in Russia.
Moderate Soil Drying-Induced Alternative Splicing Provides a Potential Novel Approach for the Regulation of Grain Filling in Rice Inferior Spikelets
Authors: Teng Zhenning , Zheng Qin , Liu Bohan , Meng Shuan , Zhang Jianhua , Ye Nenghui
Published: July 2022

Poor grain filling of inferior spikelets, especially in some large-panicle rice varieties, is becoming a major limitation in breaking the ceiling of rice production. In our previous studies, we proved that post-anthesis moderate soil drying (MD) was an effective way to promote starch synthesis and inferior grain filling. As one of the most important regulatory processes in response to environmental cues and at different developmental stages, the function of alternative splicing (AS) has not yet been revealed in regulating grain filling under MD conditions. In this study, AS events at the most active grain-filling stage were identified in inferior spikelets under well-watered control (CK) and MD treatments. Of 16,089 AS events, 1840 AS events involving 1392 genes occurred differentially between the CK and MD treatments, many of which function on spliceosome, ncRNA metabolic process, starch, and sucrose metabolism, and other functions. Some of the splicing factors and starch synthesis-related genes, such as SR protein, hnRNP protein, OsAGPL2, OsAPS2, OsSSIVa, OsSSIVb, OsGBSSII, and OsISA1 showed differential AS changes under MD treatment. The expression of miR439f and miR444b was reduced due to an AS event which occurred in the intron where miRNAs were located in the MD-treated inferior spikelets. On the contrary, OsAGPL2, an AGPase encoding gene, was alternatively spliced, resulting in different transcripts with or without the miR393b binding site, suggesting a potential mechanism for miRNA-mediated gene regulation on grain filling of inferior spikelets in response to MD treatment. This study provides some new insights into the function of AS on the MD-promoted grain filling of inferior spikelets, and potential application in agriculture to increase rice yields by genetic approaches.
Investigation of Biomarkers Associated with Low Platelet Counts in Normal Karyotype Acute Myeloid Leukemia
Authors: Park Chang-Hun , Yun Jae Won
Published: July 2022

Acute myeloid leukemia (AML) patients are at risk of bleeding due to disease-related lack of platelets and systemic coagulopathy. Platelets play a role in hemostasis. Leukemic blasts have been shown to alter platelet activation in vitro. Here we investigated biomarkers associated with thrombocytopenia in normal karyotype AML (NK-AML). From The Cancer Genome Atlas database, case-control study was performed between normal karyotype (NK) platelet-decreased AML (PD-AML, platelet count < 100 × 109/L, n = 24) and NK platelet-not-decreased AML (PND-AML, with platelet count ≥ 100 × 109/L, n = 13). Differentially expressed gene analysis, pathway analysis and modelling for predicting platelet decrease in AML were performed. DEG analysis and pathway analysis revealed 157 genes and eight pathways specific for PD-AML, respectively. Most of the eight pathways were significantly involved in G-protein-coupled receptor-related pathway, cytokine-related pathway, and bone remodeling pathway. Among the key genes involved in at least one pathway, three genes including CSF1R, TNFSF15 and CLEC10A were selected as promising biomarkers for predicting PD-AML (0.847 of AUC in support vector machine model). This is the first study that identified biomarkers using RNA expression data analysis and could help understand the pathophysiology in AML with low platelet count.
α/β-Hydrolase D16B Truncation Results in Premature Sperm Capacitation in Cattle
Authors: Shan Shuwen , Xu Fangzheng , Hirschfeld Marc , Herrmann Claudia , Schulze Martin , Sharifi Ahmad Reza , Hoelker Michael , Brenig Bertram
Published: July 2022

Recently it was shown that a specific form of male infertility in Holstein cattle was caused by a nonsense variant in the α/β-hydrolase domain-containing 16B (ABHD16B) gene resulting in a protein truncation at amino acid position 218 (p.218Q*) and loss of function. Lipidomics showed that the absence of ABHD16B influenced the content of phosphatidylcholine (PC), ceramide (Cer), diacylglycerol (DAG), and sphingomyelin (SM) in variant carrier sperm membranes. However, the exact cause of infertility in affected sires has remained unclear until now. To elucidate the cause of infertility, we analyzed (i) standard sperm parameters (i.e., total sperm number, morphological intact sperm, total sperm motility), (ii) in vitro fertilizability and effects on early embryonic development, and (iii) sperm survival rates (i.e., capacitation time). The affected spermatozoa showed no changes in the usual sperm parameters and were also capable of fertilization in vitro. Furthermore, the absence of ABHD16B did not affect early embryonic development. Based on these results, it was concluded that the affected spermatozoa appeared to be fertilizable per se. Consequently, the actual cause of the inability to fertilize could only be due to a time- and/or place-dependent process after artificial insemination and before fertilization. A process fundamental to the ability to fertilize after insemination is capacitation. Capacitation is a biochemical maturation process that spermatozoa undergo in the female genital tract and is inevitable for the successful fertilization of the oocyte. It is known that the presence and concentration of certain sperm membrane lipids are essential for the correct course of capacitation. However, precisely these lipids are absent in the membrane of spermatozoa affected by the ABHD16B truncation. Since all other causes of fertilization inability were excluded in the previous experiments, consequently, the only remaining hypothesis was that the loss of function of ABHD16B leads to a capacitation disruption. We were able to show that heterozygous and homozygous affected spermatozoa exhibit premature capacitation and therefore decay before fertilization. This effect of the loss of function of ABHD16B has not been described before and our studies now revealed why sires harboring the variant in the ABHD16B gene are infertile.
Potent CCR3 Receptor Antagonist, SB328437, Suppresses Colonic Eosinophil Chemotaxis and Inflammation in the Winnie Murine Model of Spontaneous Chronic Colitis
Authors: Filippone Rhiannon T. , Dargahi Narges , Eri Rajaraman , Uranga Jose A. , Bornstein Joel C. , Apostolopoulos Vasso , Nurgali Kulmira
Published: July 2022

Eosinophils and their regulatory molecules have been associated with chronic intestinal inflammation and gastrointestinal dysfunctions; eosinophil accumulation in the gut is prominent in inflammatory bowel disease (IBD). The chemokine receptor CCR3 plays a pivotal role in local and systemic recruitment and activation of eosinophils. In this study, we targeted CCR3-ligand interactions with a potent CCR3 receptor antagonist, SB328437, to alleviate eosinophil-associated immunological responses in the Winnie model of spontaneous chronic colitis. Winnie and C57BL/6 mice were treated with SB328437 or vehicle. Clinical and histopathological parameters of chronic colitis were assessed. Flow cytometry was performed to discern changes in colonic, splenic, circulatory, and bone marrow-derived leukocytes. Changes to the serum levels of eosinophil-associated chemokines and cytokines were measured using BioPlex. Inhibition of CCR3 receptors with SB328437 attenuated disease activity and gross morphological damage to the inflamed intestines and reduced eosinophils and their regulatory molecules in the inflamed colon and circulation. SB328437 had no effect on eosinophils and their progenitor cells in the spleen and bone marrow. This study demonstrates that targeting eosinophils via the CCR3 axis has anti-inflammatory effects in the inflamed intestine, and also contributes to understanding the role of eosinophils as potential end-point targets for IBD treatment.
Comparative Analysis of the pIgR Gene from the Antarctic Teleost Trematomus bernacchii Reveals Distinctive Features of Cold-Adapted Notothenioidei
Authors: Ametrano Alessia , Picchietti Simona , Guerra Laura , Giacomelli Stefano , Oreste Umberto , Coscia Maria Rosaria
Published: July 2022

The IgM and IgT classes were previously identified and characterized in the Antarctic teleost Trematomus bernacchii, a species belonging to the Perciform suborder Notothenoidei. Herein, we characterized the gene encoding the polymeric immunoglobulin receptor (pIgR) in the same species and compared it to the pIgR of multiple teleost species belonging to five perciform suborders, including 11 Antarctic and 1 non-Antarctic (Cottoperca gobio) notothenioid species, the latter living in the less-cold peri-Antarctic sea. Antarctic pIgR genes displayed particularly long introns marked by sites of transposable elements and transcription factors. Furthermore, analysis of T. bernacchii pIgR cDNA unveiled multiple amino acid substitutions unique to the Antarctic species, all introducing adaptive features, including N-glycosylation sequons. Interestingly, C. gobio shared most features with the other perciforms rather than with the cold-adapted relatives. T. bernacchii pIgR transcripts were predominantly expressed in mucosal tissues, as indicated by q-PCR and in situ hybridization analysis. These results suggest that in cold-adapted species, pIgR preserved its fundamental role in mucosal immune defense, although remarkable gene structure modifications occurred.
Nitrobenzoate-Derived Compound X8 Impairs Vascular Development in Zebrafish
Authors: Chiu Chien-Chih , Chin Hsieng-Kuo , Chung Sen-Yuan , Hsieh Kuan-Hsuan , Huang Yi-Shan , Huang Mei-Feng , Lo Yi-Hao , Wen Zhi-Hong , Wu Chang-Yi
Published: July 2022

Proper growth and patterning of blood vessels are critical for embryogenesis. Chemicals or environmental hormones may interfere with vascular growth and cause developmental defects. Nitrobenzoate-based compounds have been demonstrated to have a wide range of biological and pharmacological functions, leading to the development of numerous 4-nitrobenzoate derivatives for clinical application. In this study, we tested a novel nitrobenzoate-derived compound, X8, and investigated its effects on vascular development using zebrafish as a model organism. We first determined the survival rate of embryos after the addition of exogenous X8 (0.5, 1, 3, 5, and 10 μM) to the fish medium and determined a sublethal dose of 3 μM for use in further assays. We used transgenic fish to examine the effects of X8 treatment on vascular development. At 25–32 h postfertilization (hpf), X8 treatment impaired the growth of intersegmental vessels (ISVs) and caudal vein plexuses (CVPs). Moreover, X8-treated embryos exhibited pericardial edema and circulatory defects at 60–72 hpf, suggesting the effects of X8 in vasculature. Apoptosis tests showed that the vascular defects were likely caused by the inhibition of proliferation and migration. To investigate the molecular impacts underlying the defects in the vasculature of X8-treated fish, the expression levels of vascular markers, including ephrinb2, mrc1, and stabilin, were assessed, and the decreased expression of those genes was detected, indicating that X8 inhibited the expression of vascular genes. Finally, we showed that X8 treatment disrupted exogenous GS4012-induced angiogenesis in Tg(flk:egfp) zebrafish embryos. In addition, vascular defects were enhanced during cotreatment with X8 and the VEGFR2 inhibitor SU5416, suggesting that X8 treatment causes vascular defects mediated by disruption of VEGF/VEGFR2 signaling. Collectively, our findings indicate that X8 could be developed as a novel antiangiogenic agent.
The Chaperone System in Breast Cancer: Roles and Therapeutic Prospects of the Molecular Chaperones Hsp27, Hsp60, Hsp70, and Hsp90
Authors: Alberti Giusi , Vergilio Giuseppe , Paladino Letizia , Barone Rosario , Cappello Francesco , Conway de Macario Everly , Macario Alberto J. L. , Bucchieri Fabio , Rappa Francesca
Published: July 2022

Breast cancer (BC) is a major public health problem, with key pieces of information needed for developing preventive and curative measures still missing. For example, the participation of the chaperone system (CS) in carcinogenesis and anti-cancer responses is poorly understood, although it can be predicted to be a crucial factor in these mechanisms. The chief components of the CS are the molecular chaperones, and here we discuss four of them, Hsp27, Hsp60, Hsp70, and Hsp90, focusing on their pro-carcinogenic roles in BC and potential for developing anti-BC therapies. These chaperones can be targets of negative chaperonotherapy, namely the elimination/blocking/inhibition of the chaperone(s) functioning in favor of BC, using, for instance, Hsp inhibitors. The chaperones can also be employed in immunotherapy against BC as adjuvants, together with BC antigens. Extracellular vesicles (EVs) in BC diagnosis and management are also briefly discussed, considering their potential as easily accessible carriers of biomarkers and as shippers of anti-cancer agents amenable to manipulation and controlled delivery. The data surveyed from many laboratories reveal that, to enhance the understanding of the role of the CS in BS pathogenesis, one must consider the CS as a physiological system, encompassing diverse members throughout the body and interacting with the ubiquitin–proteasome system, the chaperone-mediated autophagy machinery, and the immune system (IS). An integrated view of the CS, including its functional partners and considering its highly dynamic nature with EVs transporting CS components to reach all the cell compartments in which they are needed, opens as yet unexplored pathways leading to carcinogenesis that are amenable to interference by anti-cancer treatments centered on CS components, such as the molecular chaperones.
Uptake of Phosphate, Calcium, and Vitamin D by the Pregnant Uterus of Sheep in Late Gestation: Regulation by Chorionic Somatomammotropin Hormone
Authors: Stenhouse Claire , Halloran Katherine M. , Tanner Amelia R. , Suva Larry J. , Rozance Paul J. , Anthony Russell V. , Bazer Fuller W.
Published: July 2022

Minerals are required for the establishment and maintenance of pregnancy and regulation of fetal growth in mammals. Lentiviral-mediated RNA interference (RNAi) of chorionic somatomammotropin hormone (CSH) results in both an intrauterine growth restriction (IUGR) and a non-IUGR phenotype in sheep. This study determined the effects of CSH RNAi on the concentration and uptake of calcium, phosphate, and vitamin D, and the expression of candidate mRNAs known to mediate mineral signaling in caruncles (maternal component of placentome) and cotyledons (fetal component of placentome) on gestational day 132. CSH RNAi Non-IUGR pregnancies had a lower umbilical vein–umbilical artery calcium gradient (p < 0.05) and less cotyledonary calcium (p < 0.05) and phosphate (p < 0.05) compared to Control RNAi pregnancies. CSH RNAi IUGR pregnancies had less umbilical calcium uptake (p < 0.05), lower uterine arterial and venous concentrations of 25(OH)D (p < 0.05), and trends for lower umbilical 25(OH)D uptake (p = 0.059) compared to Control RNAi pregnancies. Furthermore, CSH RNAi IUGR pregnancies had decreased umbilical uptake of calcium (p < 0.05), less uterine venous 25(OH)D (vitamin D metabolite; p = 0.055), lower caruncular expression of SLC20A2 (sodium-dependent phosphate transporter; p < 0.05) mRNA, and lower cotyledonary expression of KL (klotho; p < 0.01), FGFR1 (fibroblast growth factor receptor 1; p < 0.05), FGFR2 (p < 0.05), and TRPV6 (transient receptor potential vanilloid member 6; p < 0.05) mRNAs compared to CSH RNAi Non-IUGR pregnancies. This study has provided novel insights into the regulatory role of CSH for calcium, phosphate, and vitamin D utilization in late gestation.