bluuebunny/crossref_metadata_2025 huggingface dataset:
LMP2 deficiency causes abnormal metabolism, oxidative stress, neuroinflammation, myelin loss and neurobehavioral dysfunctions
Authors: Chen Xingyong , Mao Yanguang , Guo Yueting , Xiao Dongyun , Lin Zejing , Huang Yiyi , Liu Ying Chun , Zhang Xu , Wang Yinzhou
Published: March 2023

Background

Substantial evidence suggests that immunoproteasome is implicated in the various neurological diseases such as stroke, multiple sclerosis and neurodegenerative diseases. However, whether the immunoproteasome itself deficiency causes brain disease is still unclear. Therefore, the aim of this study was to explore the contribution of the immunoproteasome subunit low molecular weight protein 2 (LMP2) in neurobehavioral functions.

Methods

Male LMP2 gene completed knockout (LMP2-KO) and littermate wild type (WT) Sprague–Dawley (SD) rats aged 12-month-old were used for neurobehavioral testing and detection of proteins expression by western blotting and immunofluorescence. A battery of neurobehavioral test tools including Morris water maze (MWM), open field maze, elevated plus maze were used to evaluate the neurobehavioral changes in rats. Evans blue (EB) assay, Luxol fast blue (LFB) and Dihydroethidium (DHE) staining were applied to explore the blood–brain barrier (BBB) integrity, brain myelin damage and brain intracellular reactive oxygen species (ROS) levels, respectively.

Results

We firstly found that LMP2 gene deletion did not cause significantly difference in rats’ daily feeding activity, growth and development as well as blood routine, but it led to metabolic abnormalities including higher levels of low-density lipoprotein cholesterol, uric acid and blood glucose in the LMP2-KO rats. Compared with the WT rats, LMP2-KO rats displayed obviously cognitive impairment and decreased exploratory activities, increased anxiety-like behavior and without strong effects on gross locomotor abilities. Furthermore, multiple myelin loss, increased BBB leakage, downregulation of tight junction proteins ZO-1, claudin-5 and occluding, and enhanced amyloid-β protein deposition were observed in brain regions of LMP2-KO rats. In addition, LMP2 deficiency significantly enhanced oxidative stress with elevated levels of ROS, caused the reactivation of astrocytes and microglials and markedly upregulated protein expression levels of interleukin (IL)-1 receptor-associated kinase 1 (IRAK1), IL-6 and tumor necrosis factor-α (TNF-α) compared to the WT rats, respectively.

Conclusion

These findings highlight LMP2 gene global deletion causes significant neurobehavioral dysfunctions. All these factors including metabolic abnormalities, multiple myelin loss, elevated levels of ROS, increased BBB leakage and enhanced amyloid-β protein deposition maybe work together and eventually led to chronic oxidative stress and neuroinflammation response in the brain regions of LMP2-KO rats, which contributed to the initial and progress of cognitive impairment.
Comparative study of acid- and alkali-catalyzed 1,4-butanediol pretreatment for co-production of fermentable sugars and value-added lignin compounds
Authors: Xie Xinyu , Chen Mingjun , Tong Wenyao , Song Kai , Wang Jing , Wu Shufang , Hu Jinguang , Jin Yongcan , Chu Qiulu
Published: March 2023

Background

Organosolv pretreatment is one of the most efficient methods for delignification and boosting biomass saccharification. As compared to typical ethanol organosolv pretreatments, 1,4-butanediol (BDO) organosolv pretreatment is a high-boiling-point solvent pretreatment, which can generate low pressure in the reactor during high temperature cooking that improves the operation safety. Although several studies showed that organosolv pretreatment can lead to effective delignification and enhancement in glucan hydrolysis, there has been no studies on acid- and alkali-catalyzed BDO pretreatment, as well as their comparison on promoting biomass saccharification and lignin utilization.

Results

It was shown that BDO organosolv pretreatment was more effective in removing lignin from poplar as compared with typical ethanol organosolv pretreatment under the same pretreatment conditions. HCl-BDO pretreatment with 40 mM acid loading led to 82.04% of original lignin removed from biomass, as compared to the lignin removal of 59.66% in HCl-Ethanol pretreatment. Besides, acid-catalyzed BDO pretreatment was more effective in improving the enzymatic digestibility of poplar than alkali-catalyzed BDO pretreatment. As a result, HCl-BDO with acid loading of 40 mM provided a good enzymatic digestibility of cellulose (91.16%) and the maximum sugar yield of 79.41% from original woody biomass. The linear correlations between physicochemical structure (e.g., fiber swelling, cellulose crystallinity, crystallite size, surface lignin coverage and cellulose accessibility) changes of BDO pretreated poplar and enzymatic hydrolysis were plotted to figure out the main factors that influenced biomass saccharification. Moreover, acid-catalyzed BDO pretreatment mainly brought about the phenolic hydroxyl (PhOH) groups formation in lignin structure, while alkali-catalyzed BDO pretreatment mostly led to the lower molecular weight of lignin.

Conclusions

Results indicated that the acid-catalyzed BDO organosolv pretreatment could significantly improve enzymatic digestibility of the highly recalcitrant woody biomass. The great enzymatic hydrolysis of glucan resulted from increased cellulose accessibility, which mostly associated with the higher degree of delignification and hemicellulose solubilization, as well as the more increase in fiber swelling. Besides, lignin was recovered from the organic solvent, which could be used as natural antioxidants. The formation of phenolic hydroxyl groups in lignin structure and the lower molecular weight of lignin contributed to its greater radical scavenging capacity.
Deep generative model for drug design from protein target sequence
Authors: Chen Yangyang , Wang Zixu , Wang Lei , Wang Jianmin , Li Pengyong , Cao Dongsheng , Zeng Xiangxiang , Ye Xiucai , Sakurai Tetsuya
Published: March 2023

Drug discovery for a protein target is a laborious and costly process. Deep learning (DL) methods have been applied to drug discovery and successfully generated novel molecular structures, and they can substantially reduce development time and costs. However, most of them rely on prior knowledge, either by drawing on the structure and properties of known molecules to generate similar candidate molecules or extracting information on the binding sites of protein pockets to obtain molecules that can bind to them. In this paper, DeepTarget, an end-to-end DL model, was proposed to generate novel molecules solely relying on the amino acid sequence of the target protein to reduce the heavy reliance on prior knowledge. DeepTarget includes three modules: Amino Acid Sequence Embedding (AASE), Structural Feature Inference (SFI), and Molecule Generation (MG). AASE generates embeddings from the amino acid sequence of the target protein. SFI inferences the potential structural features of the synthesized molecule, and MG seeks to construct the eventual molecule. The validity of the generated molecules was demonstrated by a benchmark platform of molecular generation models. The interaction between the generated molecules and the target proteins was also verified on the basis of two metrics, drug–target affinity and molecular docking. The results of the experiments indicated the efficacy of the model for direct molecule generation solely conditioned on amino acid sequence.
Xenarthrans of the collection of Santiago Roth from the Pampean Region of Argentina (Pleistocene), in Zurich, Switzerland
Authors: Le Verger Kévin
Published: March 2023

The present work concerns xenarthrans from the collection of Santiago (Kaspar Jakob) Roth (1850–1924) housed at the Palaeontological Institute and Museum of the University of Zurich, one of the most important collections of Pleistocene mammals from Argentina in Europe. Roth was a paleontologist originally from Switzerland who prospected and collected a large amount of Pleistocene megafauna of the Pampean Region of Argentina. The xenarthrans are the main representatives of this collection in Zurich, with 150 specimens. Since 1920, this material has not been revised and is under studied. The present investigation corresponds to a taxonomic revision resulting in 114 reassignments, leading to document xenarthran diversity and discuss their paleoecologies. The high diversity reflects the paleoecology of the Pampean Region during the Pleistocene, with the various abiotic events that impacted the paleoenvironment of this region. Within the Cingulata, the Pampean Region fauna was probably dominated by glyptodonts with a high representation of Glyptodontinae and Neosclerocalyptinae while within the sloths the highest diversity and abundance is found in the Mylodontinae and Scelidotheriinae. These four clades represent both species with high ecological tolerance (e.g.,Glyptodon munizi;Catonyx tarijensis) and ecologically highly specialized species (e.g.,Neosclerocalyptus paskoensis;Scelidotherium leptocephalum). The presence of such ecological diversity underlines the status of the Pampean Region as a major interest for paleoecological and paleoenvironmental reconstruction.
Stepanov-like doubly weighted pseudo almost automorphic mild solutions for fractional stochastic neutral functional differential equations
Authors: Zhu Ping
Published: March 2023

This paper first investigates the equivalence of the space and translation invariance of Stepanov-like doubly weighted pseudo almost automorphic stochastic processes for nonequivalent weight functions; secondly, based on semigroup theory, fractional calculations, and the Krasnoselskii fixed-point theorem, we obtain the existence and uniqueness of Stepanov-like doubly weighted pseudo almost automorphic mild solutions for a class of nonlinear fractional stochastic neutral functional differential equations under non-Lipschitz conditions. These results enrich the complex dynamics of Stepanov-like doubly weighted pseudo almost automorphic stochastic processes.
Variations of the surface characteristics of Ryugu returned samples
Authors: Nakato Aiko , Yada Toru , Nishimura Masahiro , Yogata Kasumi , Miyazaki Akiko , Nagashima Kana , Hatakeda Kentaro , Kumagai Kazuya , Hitomi Yuya , Soejima Hiromichi , Bibring Jean-Pierre , Pilorget Cedric , Hamm Vincent , Brunetto Rosario , Riu Lucie , Lourit Lionel , Loizeau Damien , Le Pivert-Jolivet Tania , Lequertier Guillaume , Moussi-Soffys Aurelie , Abe Masanao , Okada Tatsuaki , Usui Tomohiro , Nakazawa Satoru , Saiki Takanao , Tanaka Satoshi , Terui Fuyuto , Yoshikawa Makoto , Watanabe Sei-ichiro , Tsuda Yuichi
Published: March 2023

Hayabusa2 spacecraft successfully collected rock samples from the surface of C-type near-Earth asteroid 162173 Ryugu through two touchdowns and brought them back to Earth in 2020. At the Extraterrestrial Sample Curation Center in JAXA, we performed initial description of all samples to obtain fundamental information and prepare the database for sample allocation. We propose morphological classifications for the returned samples based on the initial description of 205 grains described in the first 6 months. The returned samples can be distinguished by four morphological characteristics: dark, glossy, bright, and white. According to coordinated study to provide an initial description and detailed investigation by scanning electron microscopy and X-ray diffraction analysis in this study, these features reflect the differences in the degree of space weathering and mineral assemblages. The degree of space weathering of the four studied grain types is heterogeneous: weak for A0042 (dark group) and C0041 (white group); moderate for C0094 (glossy); and severe for A0017 (bright). The white phase, which is the mineral characteristic of the white group grains, is identified as large carbonate minerals. This is the first effort to classify Ryugu returned samples into distinct categories. Based on these results, researchers can estimate sample characteristics only from the information on the JAXA curation public database. It will be an important reference for sample selection for further investigation.

Graphical Abstract
Prevalence of under-nutrition and its associated factors among 6–23 months old children of employed and unemployed mothers in town kebeles of Dera district, northwest Ethiopia: a comparative cross-sectional study
Authors: Zelalem Habtamu , Demilew Yeshalem Mulugeta , Dagne Samuel , Dessie Anteneh Mengist
Published: March 2023

Background

Child under-nutrition remains a widespread problem around the globe. Improving child nutrition and empowering women are two important and closely connected development goals. These two interconnected goals will affect one another through different mechanisms, and the net effect may not necessarily be positive. Yet, the impact of maternal employment, one method of empowering mothers, on children’s nutritional is not well studied in Ethiopia. Hence, this study is to compare the prevalence of under-nutrition and its associated factors among 6–23 months old children of employed and unemployed mothers in town kebeles of Dera district, Northwest Ethiopia, 2022.

Methods

A community-based comparative cross-sectional study design was conducted among 356 employed and 356 unemployed mothers having 6–23 months old children. A systematic random sampling technique was used to select study participants. Epi-data version 3.1 and SPSS version 25.0 statistical software were used for data entry and analysis, respectively. Both bi-variable and multivariable binary logistic regression was done to assess the association between independent and dependent variables. A p-value of less than 0.05 in a multivariable binary logistic regression was declared as the level of statistical significance.

Result

The prevalence of under-nutrition was 69.8% (95% CI: 65.0, 74.7) among children of unemployed mothers, compared to 27.4% (95% CI: 22.7, 32.2) among children of employed mothers. Under-nutrition among children of unemployed mothers was significantly associated with being a male child, age increase by one month, household food insecurity, lack of ANC follow-up, and not exclusively breastfed. Whereas, among children of employed mothers, being a male child, age increase by one month, being sick during the last two weeks prior to data collection, not immunized to their age, and low meal frequency were significantly associated with their under-nutrition.

Conclusion

The prevalence of under-nutrition among children of unemployed women is significantly higher than those children of employed women which consolidate the evidence that women’s employment status have a positive association with child nutrition. Different factors were also identified as significant predictors of child under-nutrition among these two groups (employed and unemployed women). Thus, multi-sectoral intervention approach together with agriculture and education offices should be strengthened.
Nutritional status and its determinants among adolescents with HIV on anti-retroviral treatment in low- and middle-income countries: a systematic review and meta-analysis
Authors: Gebrie Meless , Perry Lin , Xu Xiaoyue , Kassa Andargachew , Cruickshank Marilyn
Published: March 2023

Purpose

This review aimed to determine what methods are used to assess nutritional status, the levels of nutritional status, determinants of undernutrition, and nutritional interventions employed for adolescents with HIV on Anti-Retroviral Therapy follow-up in Low- and Middle-Income countries.

Methods

Established methods were used to systematically identify and retrieve studies published in five databases between January 2000 to May 2021, and citation searching. Quality was appraised and findings were synthesized using narrative analysis and meta-analysis.

Result

Body Mass Index is the major indicator of nutritional status. The pooled prevalence of stunting, wasting, and overweight were 28.0%, 17.0%, and 5.0%, respectively. Adolescent males are 1.85 and 2.55 times more likely than adolescent females to suffer from both stunting and wasting at AOR = 1.85 (95%:1.47, 2.31) and AOR = 2.55 (95%: 1.88, 3.48), respectively. Similarly, adolescents with a history of opportunistic infections were 2.97 times more likely to be stunted than uninfected adolescents, AOR = 2.97 (95%:1.73, 5.12). One single intervention study found significant improvements in anthropometric status after nutritional supplementation.

Conclusion and recommendation

The few studies that have been conducted on nutritional status in adolescents living with HIV in low- and middle-income countries indicate that stunting and wasting are common in this population. Avoiding opportunistic infections is an important protective factor but the review highlighted the generally inadequate and fragmented nature of nutritional screening and support programs. Development of comprehensive and integrated systems for nutritional assessment and intervention services during ART follow-up should be prioritized to improve adolescent clinical outcomes and survival.
Mediastinal lymphadenopathy in sarcoidosis: Can diffusion MRI play a role in its evaluation?
Authors: Sabri Youssriah Yahia , Mahmoud Naglaa Mahmoud Mohamed , Abd El–Mageed Mohammed Raafat , Onsy Marwa Mohammed Mohammed , Mohamed Sabah Ahmed , Onsy Mahmoud Mohamed Mohamed , Khairy Mostafa Ahmed
Published: March 2023

Background

Sarcoidosis is a multisystem disease defined by non-caseous epithelioid cell granulomas that can affect virtually all organs. Lung, mediastinal and hilar lymph node involvement is prevalent, occurring in around 90% of the patients, and is responsible for the majority of the morbidity and mortality related to the disorder. Sarcoidosis is one of the differential diagnoses of the benign mediastinal lymphadenopathy. This research aimed to detect the diagnostic value of magnetic resonance imaging (MRI) diffusion in evaluation of mediastinal lymphadenopathy in sarcoid patients.

Results

This cross study involved a total of 30 patients known to have sarcoidosis: 6 males and 24 females aged between 18 and 50 years (with a mean age 38.97 ± 8.67); all of them presented with mediastinal lymphadenopathy. For all patients, each lymph node group was evaluated for the average size and average ADC value. The mean ADC measured was (1.76 ± 0.28) × 10−3 mm2/s. Eight patients showed concurrent activity with poor response to the treatment, and they showed different ADC values with one of them showing low ADC with pattern of diffusion restriction displaying mean ADC value of 1.28 × 10−3 mm2/s.

Conclusions

Diffusion-weighted MRI is an established imaging technique that could be utilized to evaluate mediastinal lymphadenopathy in sarcoidosis as the benign counterpart of mediastinal lymphadenopathy.
Salt and subsalt structure recovery — An envelope-based waveform inversion with local angle domain illumination compensation and L-BFGS
Authors: Luo Jingrui , Zhou Huamin , Wu Ru-Shan , Huang Xingguo
Published: March 2023

Correct subsalt structure recovery is important for subsalt reservoir exploration. However, high-precision subsalt structure retrieval using full-waveform inversion (FWI) is difficult, which is caused by the shielding from the salt body and the depth of the target. To obtain correct subsalt structures, techniques that can effectively work with deep targets are desired. In addition, the correct recovery of the salt body is critical for the recovery of the subsalt structure. However, the salt body recovery itself is also challenging in FWI, especially when a reasonable starting model is not available. We consider the recovery of the salt structure and subsalt structure. A local angle domain illumination-compensated direct envelope inversion with the local resolution function is developed to provide a large-scale background salt structure with an enhanced and more balanced recovery of the salt body in the deep part. Then, FWI with angle domain illumination compensation is used to improve the recovery of the salt and subsalt structures. To further enhance the quality of the inversion, model updating with the L-BFGS method is embedded into the whole process. Numerical examples with the SEG/EAGE salt model and the Sigsbee model demonstrate that the proposed method could retrieve the salt structure as well as the subsalt structure effectively with high precision starting from a linear initial model.
Local Recurrence After Breast-Conserving Therapy in Patients With Multiple Ipsilateral Breast Cancer: Results From ACOSOG Z11102 (Alliance)
Authors: Boughey Judy C. , Rosenkranz Kari M. , Ballman Karla V. , McCall Linda , Haffty Bruce G. , Cuttino Laurie W. , Kubicky Charlotte D. , Le-Petross Huong T. , Giuliano Armando E. , Van Zee Kimberly J. , Hunt Kelly K. , Hahn Olwen M. , Carey Lisa A. , Partridge Ann H.
Published: March 2023

PURPOSE

Breast-conserving therapy (BCT) is the preferred treatment for unifocal breast cancer (BC). The oncologic safety of BCT for multiple ipsilateral breast cancer (MIBC) has not been demonstrated in a prospective study. ACOSOG Z11102 (Alliance) is a phase II, single-arm, prospective trial designed to evaluate oncologic outcomes in patients undergoing BCT for MIBC.

PATIENTS AND METHODS

Women age 40 years and older with two to three foci of biopsy-proven cN0-1 BC were eligible. Patients underwent lumpectomies with negative margins followed by whole breast radiation with boost to all lumpectomy beds. The primary end point was cumulative incidence of local recurrence (LR) at 5 years with an a priori rate of clinical acceptability of <8%.

RESULTS

Among 270 women enrolled between November 2012 and August 2016, there were 204 eligible patients who underwent protocol-directed BCT. The median age was 61 years (range, 40-87 years). At a median follow-up of 66.4 months (range, 1.3-90.6 months), six patients developed LR for an estimated 5-year cumulative incidence of LR of 3.1% (95% CI, 1.3 to 6.4). Patient age, number of sites of preoperative biopsy–proven BC, estrogen receptor status and human epidermal growth factor receptor 2 status, and pathologic T and N categories were not associated with LR risk. Exploratory analysis showed that the 5-year LR rate in patients without preoperative magnetic resonance imaging (MRI; n = 15) was 22.6% compared with 1.7% in patients with a preoperative MRI (n = 189; P = .002).

CONCLUSION

The Z11102 clinical trial demonstrates that breast-conserving surgery with adjuvant radiation that includes lumpectomy site boosts yields an acceptably low 5-year LR rate for MIBC. This evidence supports BCT as a reasonable surgical option for women with two to three ipsilateral foci, particularly among patients with disease evaluated with preoperative breast MRI.
Evaluation of In-Die Compression Data for a Deeper Understanding of Altered Excipient Properties upon Temperature Rise
Authors: Grumann Hanna Dorothea , Klinken Stefan , Kleinebudde Peter
Published: March 2023

The thermodynamic analysis of tablet formation includes the thermal and mechanical analysis during compression. The aim of this study was to evaluate alterations of force–displacement data upon temperature rise as an indicator for changed excipient properties. The tablet press was equipped with a thermally controlled die to imitate the heat evolution from tableting on an industrial scale. Six predominantly ductile polymers with a comparably low glass transition temperature were tableted at temperatures ranging from 22-70°C. Lactose served as a brittle reference with a high melting point. The energy analysis included the net and recovery work during compression, from which the plasticity factor was calculated. The respective results were compared to the changes in compressibility obtained via Heckel analysis. Elevated temperatures reduced the necessary work for plastic deformation for the ductile polymers, which was reflected in decreasing values for the net work of compaction and the plasticity factor. The recovery work slightly increased for the maximum tableting temperature. Lactose showed no response to temperature variations. Changes in the net work of compaction showed a linear correlation to the changes in yield pressure, which could be correlated to the glass transition temperature of a material. It is therefore possible to detect material alterations directly from the compression data, if the glass transition temperature of a material is sufficiently low.

Graphical Abstract
Gram-Negative Bacteria and Lipopolysaccharides as Risk Factors for the Occurrence of Diabetic Foot
Authors: Zhang Shili , Li Shuxian , Huang Jiali , Ding Xinyi , Qiu Yan , Luo Xiangrong , Meng Jianfu , Hu YanJun , Zhou Hao , Fan Hongying , Cao Ying , Gao Fang , Xue Yaoming , Zou Mengchen
Published: March 2023

Context

Imbalance of the skin microbial community could impair skin immune homeostasis and thus trigger skin lesions. Dysbiosis of skin microbiome may be involved in the early pathogenesis of diabetic foot (DF). However, the potential mechanism remains unclear.

Objective

To investigate the dynamic composition and function of the foot skin microbiome with risk stratification for DF and assess whether dysbiosis of the skin microbiome induces diabetic skin lesions.

Methods

We enrolled 90 consecutive subjects who were divided into 5 groups based on DF risk stratification: very low, low, moderate, and high risk for ulcers and a healthy control group. Integrated analysis of 16S ribosomal RNA and metagenomic sequencing of cotton swab samples was applied to identify the foot skin microbiome composition and functions in subjects. Then a mouse model of microbiota transplantation was used to evaluate the effects of the skin microbiome on diabetic skin lesions.

Results

The results demonstrated that, with the progression of diabetic complications, the proportion of gram-negative bacteria in plantar skin increased. At the species level, metagenome sequencing analyses showed Moraxella osloensis to be a representative core strain in the high-risk group. The major microbial metabolites affecting diabetic skin lesions were increased amino acid metabolites, and antibiotic resistance genes in microorganisms were abundant. Skin microbiota from high-risk patients induced more inflammatory cell infiltration, similar to the lipopolysaccharide (LPS)-stimulated response, which was inhibited by Toll-like receptor 4 (TLR4) antagonists.

Conclusions

The skin microbiome in patients with diabetes undergoes dynamic changes at taxonomic and functional levels with the progression of diabetic complications. The increase in gram-negative bacteria on the skin surface through LPS-TLR4 signal transduction could induce inflammatory response in early diabetic skin lesions.
Syndrome of Inappropriate Antidiuresis: From Pathophysiology to Management
Authors: Warren Annabelle M , Grossmann Mathis , Christ-Crain Mirjam , Russell Nicholas
Published: March 2023

Hyponatremia is the most common electrolyte disorder, affecting more than 15% of patients in the hospital. Syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause of hypotonic hyponatremia, mediated by nonosmotic release of arginine vasopressin (AVP, previously known as antidiuretic hormone), which acts on the renal V2 receptors to promote water retention. There are a variety of underlying causes of SIAD, including malignancy, pulmonary pathology, and central nervous system pathology. In clinical practice, the etiology of hyponatremia is frequently multifactorial and the management approach may need to evolve during treatment of a single episode. It is therefore important to regularly reassess clinical status and biochemistry, while remaining alert to potential underlying etiological factors that may become more apparent during the course of treatment. In the absence of severe symptoms requiring urgent intervention, fluid restriction (FR) is widely endorsed as the first-line treatment for SIAD in current guidelines, but there is considerable controversy regarding second-line therapy in instances where FR is unsuccessful, which occurs in around half of cases. We review the epidemiology, pathophysiology, and differential diagnosis of SIAD, and summarize recent evidence for therapeutic options beyond FR, with a focus on tolvaptan, urea, and sodium-glucose cotransporter 2 inhibitors.
Foxn1 overexpression promotes thymic epithelial progenitor cell proliferation and mTEC maintenance, but does not prevent thymic involution
Authors: Li Jie , Wachsmuth Lucas P. , Xiao Shiyun , Condie Brian G. , Manley Nancy R.
Published: March 2023

The transcription factor FOXN1 is essential for fetal thymic epithelial cell (TEC) differentiation and proliferation. Postnatally, Foxn1 levels vary widely between TEC subsets, from low/undetectable in putative TEC progenitors to highest in differentiated TEC subsets. Correct Foxn1 expression is required to maintain the postnatal microenvironment; premature downregulation of Foxn1 causes a rapid involution-like phenotype, and transgenic overexpression can cause thymic hyperplasia and/or delayed involution. We investigated a K5.Foxn1 transgene that drives overexpression in mouse TECs, but causes neither hyperplasia nor delay or prevention of aging-related involution. Similarly, this transgene cannot rescue thymus size in Foxn1lacZ/lacZ mice, which undergo premature involution as a result of reduced Foxn1 levels. However, TEC differentiation and cortico-medullary organization are maintained with aging in both K5.Foxn1 and Foxn1lacZ/lacZ mice. Analysis of candidate TEC markers showed co-expression of progenitor and differentiation markers as well as increased proliferation in Plet1+ TECs associated with Foxn1 expression. These results demonstrate that the functions of FOXN1 in promoting TEC proliferation and differentiation are separable and context dependent, and suggest that modulating Foxn1 levels can regulate the balance of proliferation and differentiation in TEC progenitors.
A compound PCP scheme underlies sequential rosettes-based cell intercalation
Authors: Xu Yichi , Cheng Yunsheng , Chen Allison T. , Bao Zhirong
Published: March 2023

The formation of sequential rosettes is a type of collective cell behavior recently discovered in the Caenorhabditis elegans embryo that mediates directional cell migration through sequential formation and resolution of multicellular rosettes involving the migrating cell and its neighboring cells along the way. Here, we show that a planar cell polarity (PCP)-based polarity scheme regulates sequential rosettes, which is distinct from the known mode of PCP regulation in multicellular rosettes during the process of convergent extension. Specifically, non-muscle myosin (NMY) localization and edge contraction are perpendicular to that of Van Gogh as opposed to colocalizing with Van Gogh. Further analyses suggest a two-component polarity scheme: one being the canonical PCP pathway with MIG-1/Frizzled and VANG-1/Van Gogh localized to the vertical edges, the other being MIG-1/Frizzled and NMY-2 localized to the midline/contracting edges. The NMY-2 localization and contraction of the midline edges also required LAT-1/Latrophilin, an adhesion G protein-coupled receptor that has not been shown to regulate multicellular rosettes. Our results establish a distinct mode of PCP-mediated cell intercalation and shed light on the versatile nature of the PCP pathway.
Next-generation plasmids for transgenesis in zebrafish and beyond
Authors: Kemmler Cassie L. , Moran Hannah R. , Murray Brooke F. , Scoresby Aaron , Klem John R. , Eckert Rachel L. , Lepovsky Elizabeth , Bertho Sylvain , Nieuwenhuize Susan , Burger Sibylle , D'Agati Gianluca , Betz Charles , Puller Ann-Christin , Felker Anastasia , Ditrychova Karolina , Bötschi Seraina , Affolter Markus , Rohner Nicolas , Lovely C. Ben , Kwan Kristen M. , Burger Alexa , Mosimann Christian
Published: March 2023

Transgenesis is an essential technique for any genetic model. Tol2-based transgenesis paired with Gateway-compatible vector collections has transformed zebrafish transgenesis with an accessible modular system. Here, we establish several next-generation transgenesis tools for zebrafish and other species to expand and enhance transgenic applications. To facilitate gene regulatory element testing, we generated Gateway middle entry vectors harboring the small mouse beta-globin minimal promoter coupled to several fluorophores, CreERT2 and Gal4. To extend the color spectrum for transgenic applications, we established middle entry vectors encoding the bright, blue-fluorescent protein mCerulean and mApple as an alternative red fluorophore. We present a series of p2A peptide-based 3′ vectors with different fluorophores and subcellular localizations to co-label cells expressing proteins of interest. Finally, we established Tol2 destination vectors carrying the zebrafish exorh promoter driving different fluorophores as a pineal gland-specific transgenesis marker that is active before hatching and through adulthood. exorh-based reporters and transgenesis markers also drive specific pineal gland expression in the eye-less cavefish (Astyanax). Together, our vectors provide versatile reagents for transgenesis applications in zebrafish, cavefish and other models.
Günümüz Türkiyesinde İranlı Göçmenlerin Sosyoekonomik Entegrasyonu
Authors: Ekhtiari Maryam , Aysan Mehmet Fatih
Published: March 2023

Kuzey Amerika ve Batı Avrupa hedefli göçlerde yaşanan zorluklar ile komşu ülkedeki fırsatlar, son yıllarda birçok İranlı için Türkiye’yi yeni “hedef ülke” konumuna getirmiştir. Bu araştırma, Türkiye’de yaşayan İranlı göçmenler ile uluslararası koruma başvurusunda bulunmuş İranlıların göç deneyimlerini, Türkiye’ye entegrasyonlarında karşılaştıkları zorlukları, sosyal, ekonomik ve kültürel faktörleri de dikkate alarak incelemektedir. Araştırmanın temel amacı; İranlıların Türkiye’yi hedef ülke olarak seçme nedenleri ile ülkeye yerleşme ve entegrasyon süreçlerini analiz etmektir. Bu amacı gerçekleştirmek için çalışmada, Türkiye’nin farklı illerinde yaşayan 41 İranlı ile yarı yapılandırılmış görüşmeler gerçekleştirilmiştir. Nitel bulgular, coğrafi ve kültürel yakınlığı nedeniyle Türkiye’nin İranlılar için en iyi varış ülkelerinden biri olduğunu ve bu yakınlıkların İranlıların Türkiye’ye daha kolay entegre olabilmelerine imkân sağladığını göstermektedir. Ancak göçmenlerin yeni topluma entegre olma konusunda ciddi zorluklarla karşılaştıkları da görülmektedir. Bu zorluklar, işgücü piyasasına dâhil olmanın önündeki engellerden sağlık hizmetlerine erişime kadar uzanmaktadır. Ayrıca İranlı göçmenlerin günlük yaşamları ve gelecek planları, Türkiye’nin göçmenlere yönelik sürekli değişen uygulamalarından da etkilenmektedir. Bu araştırma, göç yönetimindeki karar vericilere İranlı göçmenlerin sosyoekonomik entegrasyonundaki engelleri azaltmak için stratejiler sunmaktadır.
Bir Unutuluş Serüveni: İslamcılık, Post-İslamcılık ve Siyasal Üzerine Notlar
Authors: Sakarya Sümeyye
Published: March 2023

İslamcılığın sonu veya post-İslamcılık iddiaları, 1990’ların başından beri İslamcılığın en popüler yorumu oldu. Bu yorumlar bir yandan İslamcılık çalışmalarının temel araçlarını sağlarken diğer yandan da öne sürülen her alternatif İslamcılık okumasının ilk muhatabını da oluşturdu. Ancak otuz yıl sonra bile her fırsatta post İslamcılardan ziyade İslamcıların sonunu ilan etmeleri, bu iddiaların İslamcılığı yorumlamadaki başarısızlığını göstermektedir. İslamcılığın daha derin ve kapsamlı bir okumasının imkânlarını sorgulamayı ve sunmayı amaçlayan bu makale, öncelikle Asef Bayat’ın ve büyük ölçüde de Olivier Roy’un kavramsallaştırmaları üzerinden bu iddiaları sunmakta ardından da değerlendirmektedir. Bu değerlendirme, bahsedilen iddiaların, varolanşeyler, kurallar, gelenekler, düzenlemeler ve kurumlar gibi ontik (siyaset) şeylere odaklanarak varoluş koşullarını ve anlaşılabilirliği ilgilendiren ontolojik (politik) olanı unuttuğunu iddia etmektedir. Son olarak bu unutuluşu literatürün ana sorunu olarak belirleyen makale, Salman Sayyid’in İslamcılık kavramsallaştırmasını Heidegger ile diyaloğa sokarak ontolojik (politik) bir çalışma için araçlar önermektedir. Bu anlamda makale, bir deneyim olarak İslamcılığın analizini sunmaktan ziyade böyle bir analizin çerçevesini geliştirmeye çalışmaktadır.
Evaluating Target Audience Surveillance on Instagram in the Context of Public Relations Practices
Authors: Bekman Müge
Published: March 2023

The relationship between public relations and surveillance is a form of communication that reveals the interactions between today’s surveillance practices and companies’ sales strategies. The purpose of this article is to examine the relationships between demographic factors and individuals’ Instagram attitudes and behaviors. The article also looks at the relationships among levels of corporate trust, the sharing of private information on Instagram, individuals’ motivation to log in, the time spent daily on Instagram, and the number of accounts followed. Two-way ANOVA and post hoc tests have been used to examine with respect to demographics the differences between levels of institutional trust and levels at which relatively private information is sent. The relationships among level of institutional trust, level at which relatively private information is posted, motivation to log on, time spent daily on Instagram, and number of accounts followed have been examined using discriminant analysis. Individuals’ beliefs about protecting personal information and preventing unauthorized access have been determined to differ according to age group. Likewise, the level at which individuals post relatively private information on Instagram varies by age group. Also, a significant difference has been found for individuals’ level of institutional trust with their education and income levels. A significant relationship has been found for individuals’ institutional trust levels with their individual posting levels, motivation to log on, and time spent daily on Instagram. As a result, this study contributes to institutions that carry out public relations activities on Instagram and their target audiences with regard to recognizing their trust levels toward Instagram and institutions and their behaviors on Instagram.
Alternative conceptions of COVID-19 and post-COVID-19 assumed by Basic Education pre-service teachers. A case study for Universidad Técnica del Norte, Ecuador
Authors: Guerra-Reyes Frank , Naranjo-Toro Miguel , Basantes-Andrade Andrea , Guerra-Dávila Eric
Published: March 2023

Background: Almost at the end of 2022, the world is experiencing a relative calm after the rigors imposed by the COVID-19 pandemic. Knowing the ideas, feelings and procedures used by people in this type of unexpected events, which exceeded all established standards of educational and health actions, can help us be prepared for the possible occurrence of similar events. This study aims to determine the main alternative conceptions that pre-service teachers hold about the pandemic and the post-pandemic within the framework of the four basic pillars of Education.

Methods: A case study was conducted using an ethnographic approach. The unit of analysis was made up of 227 students from the major of Basic Education at Universidad Técnica del Norte. Two research instruments were used to collect the data: a test for verbal associations where participants can express themselves freely with hierarchical, substitution and connotative evocations; and Specialized Analytical Summary sheets to revise and organize specialized scientific texts. The data was analyzed using the IRaMuTeQ software.

Results: At first glance, what was expressed in the two contexts, both in the pandemic and in the post-pandemic, show a similar structure; however, a deeper analysis reveals different perspectives.

Conclusions: In the end, the alternative conceptions moved from expressing fear to tranquility.
Endothelin-1 as predictor of major adverse cardiovascular events in chronic coronary syndrome patients undergoing coronary intervention
Authors: Wasyanto Trisulo , Yasa Ahmad , Ayu Nimas
Published: March 2023

Background: Major adverse cardiovascular events (MACE) are predicted to be low in chronic coronary syndrome (CCS) patients who have undergone percutaneous coronary intervention (PCI). Endothelin-1 has been considered a pro inflammatory biomarker and                suggested as a novel prognostic indicator in CCS. The objective of this research was to prove endothelin- 1 as predictor of MACE within 1-year evaluation in CCS patients undergoing PCI.

Methods: This research was an analytic observational study with a cohort design. The participants were CCS patients who had undergone PCI. Endotelin-1 levels were checked before the patient underwent PCI. Occurrences of MACE were observed within 1 year. The comparison between normally distributed continuous data was performed with a T-test, and the Mann–Whitney test was used for not normally distributed data. A comparison between categorical data was performed with the Chi-square test. The cut-off point of endothelin-1 levels to predict MACE was analyzed by receiver operating characteristics (ROC).

Results: Participants in this study were 63 patients. Six patients experienced MACE within 1 year (9.5%) and 57 patients were included in the non-MACE group (90.5%). Mann Whitney T test showed there were significance differences in endothelin-1 levels from the two groups (p=0.022). The ROC curve showed cut off point the endothelin-1 is 4.07 ng/dl with a sensitivity of 83.3%, specificity of 75.4% and accuracy of 76.2%. Based on the area under curve (AUC) value and the accuracy of this study, endothelin-1 was able to detect MACE within 1 year of follow-up.

Conclusions: Endothelin-1 can be used as predictor of MACE within 1-year evaluation in CCS patients undergoing coronary intervention.
The genome sequence of the Brindled Pug, Eupithecia abbreviata (Stephens, 1831)
Authors: Boyes Douglas , Holland Peter W.H. ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: March 2023

We present a genome assembly from an individual female Eupithecia abbreviata (the Brindled Pug; Arthropoda; Insecta; Lepidoptera; Geometridae). The genome sequence is 383.4 megabases in span. Most of the assembly is scaffolded into 32 chromosomal pseudomolecules, including the assembled Z and W sex chromosomes. The mitochondrial genome has also been assembled and is 15.3 kilobases in length. Gene annotation of this assembly on Ensembl identified 16,676 protein coding genes.
Communication training based on movies
Authors: Tserekh S.G. , Ovchinnikov I.G.
Published: March 2023

В работе представлено применение способа расчета участка сопряжения железнодорожной насыпи земляного полотна с искусственными сооружениями с использованием математической модели взаимодействия подъездной насыпи на подходе к искусственным сооружением с целью определения наиболее эффективного способа укрепления насыпи земляного полотна. Для бесперебойной работы инфраструктуры железнодорожного сообщения, в первую очередь необходимо обеспечить надлежащее функционирование насыпи земляного полотна и искусственных сооружений (водопропускные трубы, мосты и путепроводы), что соответствует долгосрочной программе развития открытого акционерного общества «Российские железные дороги», утвержденной Правительством Российской Федерации от 19 марта 2019 г. N 466-Р. В зоне сопряжения неоднородных сооружений, а именно насыпи земляного полотна и искусственного сооружения возникают деформации (просадки) грунта, что приводит к изменению характера динамического воздействия нагрузки на искусственные сооружения (водопропускные трубы, мосты и путепроводы) и, как следствие, к просадкам и повреждениям насыпи. Для подтверждения математической модели, исследования эффективности укрепления земляного полотна подходной насыпи усиливающими сваями и определения осадки насыпи был разработан способ расчета, базирующаяся на основе программного комплекса Midas. Модель представляет собой укрепленный сваями грунтовый массив с расположенной в нем водопропускной трубой. Для моделирования применены реальные данные физико-механических характеристик грунтов насыпи земляного полотна и подстилающих слоев, приложена временная подвижная железнодорожная нагрузка С-14. Смоделированная нагрузка С-14 задана таким образом, чтобы была возможность определять любые перемещения (грунта, свай, водопропускной трубы и т.д.) в любой момент нагружения и расположения колесной пары от движущегося состава. В результате применения данного способа получены решения по эффективному применению укреплений насыпи земляного полотна при помощи свайного ряда в зависимости от климатических характеристик района (температурный режим местности), количества, расстановки и диаметра свай, типов грунта (связанный, несвязанный) и прочих условий.
Manifestation of solar wind corotating interaction regions in GCR intensity variations
Authors: Krainev Mikhail , Kalinin Mikhail , Bazilevskaya Galina , Svirzhevskaya Albina , Svirzhevsky Nikolay , Luo Xi , Aslam O.P.M. , Shen F. , Ngobeni M.D. , Potgieter M.S.
Published: March 2023

The regions of interaction between solar wind streams of different speed, known as corotating interaction regions, form an almost constantly existing structure of the inner heliosphere. Using observational data on the main characteristics of the heliosphere, important for GCR modulation, and the results of 3D MHD modeling of corotating interaction regions, and Monte Carlo simulation of recurrent GCR variations, we analyze the importance of the corotating interaction regions for longitude-averaged characteristics of the heliosphere and GCR propagation, and possible ways for simulating long-term GCR intensity variations with respect to the corotating interaction regions.
A relação entre atividade física e saúde: uma abordagem histórica e conceitual
Authors: Porto Luiz Guilherme Grossi , Azevedo Mario Renato , Molina Guilherme Eckhardt , Guedes Dartagnan Pinto , Nahas Markus Vinicius , Hallal Pedro Curi , Matsudo Victor Keihan Rodrigues
Published: March 2023

A partir de uma abordagem histórica, conceitual, crítica e didática, este ensaio teórico propõe uma reflexão sobre a relação entre atividade física (AF) e saúde e o desenvolvimento desta área de estudo, com um olhar especial sobre o Brasil. Apresenta-se revisão histórica a partir de grandes temas de pesquisa na área desde os anos 1950 e da evolução das recomendações de AF para a saúde. São abordadas definições conceituais e operacionais que passaram por atualizações recentes e que são cruciais na área. Faz-se destaque a instituições e documentos relevantes, além de reflexões sobre perspectivas e desafios futuros para a área. Por fim, destaca a necessidade da redução na distância entre a solidez do conhecimento já produzido sobre os benefícios da AF para a saúde e os desejados avanços no contexto da promoção da saúde, em especial na atenção primária à saúde.
Advantages of out-of-plane pulse compression gratings
Authors: Smith Dale L. , Erdogan Samuel L. , Erdogan Turan
Published: March 2023

Diffraction gratings for pulse compression generally perform best at
the Littrow angle, but reflection gratings require a nonzero deviation
angle to separate the incident and diffracted beams, so they cannot be
used at the Littrow angle. In this paper, we show both theoretically
and experimentally that most practical multilayer dielectric (MLD) and
gold reflection grating designs can be used with quite substantial
beam-deviation angles—as large as even 30°—by
mounting the grating out-of-plane and choosing the optimal
polarization. The impact of polarization when mounting out-of-plane is
explained and quantified.