bluuebunny/crossref_metadata_2025 huggingface dataset:
PRE-SERVICE SCIENCE TEACHERS’ CONCEPTIONS OF THE "CONDUCTION OF HEAT IN SOLIDS"
Authors: Çoruhlu Tülay Şenel
Published: August 2021

There has been various researchers focus on “heat transfer". "Convection, radiation and conduction" discussed as mere elements of the wider object of analysis in these research. Given the lack of sufficient emphasis on conduction in solids, no cross age research conducted with pre-service science teachers supported by drawings, interviews, and open-ended questions could be found. Employing a cross-age design, this research determined pre-service science teachers' (PSTs’) conceptions in the "conduction of heat in solid". The sample group of the research consists of 257 PSTs (first year student-n=55; second year student-n=76, third year student-n=56, and fourth year student-n=70) selected from Department of Science Education in Fatih Faculty of Education at the Karadeniz Technical University in the city of Trabzon in Turkey. Conceptual understanding test and semi-structured interview were used in the data collection process. The test including two questions was administered to 257 PSTs from different years. Semi-structured interview including one question was conducted with 16 voluntary PSTs (4 students from each grade level). The research found that PSTs had difficulties in terms of describing and showing the movement of the particles of solid under the impact of heat. In the light of the findings, it can be suggested that animations should be used to the teaching of the movement of the particles under the impact of heat. Keywords: cross-age study, conduction of heat in solid, pre-service science teachers.
Translators of the Soul: Bingham Dai, Pow-Meng Yap, and the Making of Transcultural Psychoanalysis in the Asia Pacific
Authors: Chiang Howard
Published: August 2021

This essay argues that Asian psychoanalysts developed a new style of science, what I call transcultural reasoning, in the twentieth century. This conceptual innovation drew on the power of cultural narratives to elucidate the unconscious mind across different historical and geographical contexts. Focusing on the life and work of two experts in particular, Bingham Dai (1899–1996) and Pow-Meng Yap (1921–71), this article reconsiders the role of biography in the history of psychoanalysis and elucidates the importance of the Asia Pacific region to the transformation of mental health science in the twentieth century.
Short Tandem Repeats as a High-Resolution Marker for Capturing Recent Orangutan Population Evolution
Authors: Voicu Alina-Alexandra , Krützen Michael , Bilgin Sonay Tugce
Published: August 2021

The genus Pongo is ideal to study population genetics adaptation, given its remarkable phenotypic divergence and the highly contrasting environmental conditions it’s been exposed to. Studying its genetic variation bears the promise to reveal a motion picture of these great apes’ evolutionary and adaptive history, and also helps us expand our knowledge of the patterns of adaptation and evolution. In this work, we advance the understanding of the genetic variation among wild orangutans through a genome-wide study of short tandem repeats (STRs). Their elevated mutation rate makes STRs ideal markers for the study of recent evolution within a given population. Current technological and algorithmic advances have rendered their sequencing and discovery more accurate, therefore their potential can be finally leveraged in population genetics studies. To study patterns of population variation within the wild orangutan population, we genotyped the short tandem repeats in a population of 21 individuals spanning four Sumatran and Bornean (sub-) species and eight Southeast Asian regions. We studied the impact of sequencing depth on our ability to genotype STRs and found that the STR copy number changes function as a powerful marker, correctly capturing the demographic history of these populations, even the divergences as recent as 10 Kya. Moreover, gene ontology enrichments for genes close to STR variants are aligned with local adaptations in the two islands. Coupled with more advanced STR-compatible population models, and selection tests, genomic studies based on STRs will be able to reduce the gap caused by the missing heritability for species with recent adaptations.
CRISPR/Cas9-Mediated in vivo Genetic Correction in a Mouse Model of Hemophilia A
Authors: Luo Sanchuan , Li Zhongxiang , Dai Xin , Zhang Rui , Liang Zhibing , Li Wenzhou , Zeng Ming , Su Jinfeng , Wang Jun , Liang Xia , Wu Yong , Liang Desheng
Published: August 2021

Hemophilia A (HA), a common bleeding disorder caused by a deficiency of coagulation factor VIII (FVIII), has long been considered an attractive target for gene therapy studies. However, full-length F8 cDNA cannot be packaged efficiently by adeno-associated virus (AAV) vectors. As the second most prevalent mutation causing severe HA, F8 intron 1 inversion (Inv1) is caused by an intrachromosomal recombination, leaving the majority of F8 (exons 2–26) untranscribed. In theory, the truncated gene could be rescued by integrating a promoter and the coding sequence of exon 1. To test this strategy in vivo, we generated an HA mouse model by deleting the promoter region and exon 1 of F8. Donor DNA and CRISPR/SaCas9 were packaged into AAV vectors and injected into HA mice intravenously. After treatment, F8 expression was restored and activated partial thromboplastin time (aPTT) was shortened. We also compared two liver-specific promoters and two types of integrating donor vectors. When an active promoter was used, all of the treated mice survived the tail-clip challenge. This is the first report of an in vivo gene repair strategy with the potential to treat a recurrent mutation in HA patients.
S100 Calcium Binding Protein Family Members Associate With Poor Patient Outcome and Response to Proteasome Inhibition in Multiple Myeloma
Authors: Liu Minxia , Wang Yinyin , Miettinen Juho J. , Kumari Romika , Majumder Muntasir Mamun , Tierney Ciara , Bazou Despina , Parsons Alun , Suvela Minna , Lievonen Juha , Silvennoinen Raija , Anttila Pekka , Dowling Paul , O’Gorman Peter , Tang Jing , Heckman Caroline A.
Published: August 2021

Despite several new therapeutic options, multiple myeloma (MM) patients experience multiple relapses and inevitably become refractory to treatment. Insights into drug resistance mechanisms may lead to the development of novel treatment strategies. The S100 family is comprised of 21 calcium binding protein members with 17 S100 genes located in the 1q21 region, which is commonly amplified in MM. Dysregulated expression of S100 family members is associated with tumor initiation, progression and inflammation. However, the relationship between the S100 family and MM pathogenesis and drug response is unknown. In this study, the roles of S100 members were systematically studied at the copy number, transcriptional and protein level with patients’ survival and drug response. Copy number analysis revealed a predominant pattern of gains occurring in S100 genes clustering in the 1q21 locus. In general, gains of genes encoding S100 family members associated with worse patient survival. However, S100 gene copy number and S100 gene expression did not necessarily correlate, and high expression of S100A4 associated with poor patient survival. Furthermore, integrated analysis of S100 gene expression and ex vivo drug sensitivity data showed significant negative correlation between expression of S100 family members (S100A8, S100A9, and S100A12) and sensitivity to some drugs used in current MM treatment, including proteasome inhibitors (bortezomib, carfilzomib, and ixazomib) and histone deacetylase inhibitor panobinostat. Combined proteomic and pharmacological data exhibited significant negative association of S100 members (S100A4, S100A8, and S100A9) with proteasome inhibitors and panobinostat. Clinically, the higher expression of S100A4 and S100A10 were significantly linked to shorter progression free survival in patients receiving carfilzomib-based therapy. The results indicate an association and highlight the potential functional importance of S100 members on chromosome 1q21 in the development of MM and resistance to established myeloma drugs, including proteasome inhibitors.
Defect Engineering in Metal‒Organic Frameworks as Futuristic Options for Purification of Pollutants in an Aqueous Environment
Authors: Cao Yuhua , Mi Xin , Li Xiang , Wang Bo
Published: August 2021

Clean water scarcity is becoming an increasingly important worldwide issue. The water treatment industry is demanding the development of novel effective materials. Defect engineering in nanoparticles is among the most revolutionary of technologies. Because of their high surface area, structural diversity, and tailorable ability, Metal‒Organic Frameworks (MOFs) can be used for a variety of purposes including separation, storage, sensing, drug delivery, and many other issues. The application in wastewater treatment associated with water stable MOF‒based materials has been an emerging research topic in recent decades. Defect engineering is a sophisticated technique used to manufacture defects and to change the geometric framework of target compounds. Since MOFs have a series of designable structures and active sites, tailoring properties in MOFs by defect engineering is a novel concept. Defect engineering can excavate hidden active sites in MOFs, which can lead to better performance in many fields. Therefore, this technology will open new opportunities in water purification processes. However, there has been little effort to comprehensively discuss this topic. In this review, we provide an overview of the development of defect engineered MOFs for water purification processes. Furthermore, we discuss the potential applications of defect engineered materials.
MicroRNAs hsa-miR-618 and hsa-miR-297 Might Modulate the Pleiotropic Effects Exerted by Statins in Endothelial Cells Through the Inhibition of ROCK2 Kinase: in-silico Approach
Authors: Leal Karla , Saavedra Kathleen , Rebolledo Camilo , Salazar Luis A.
Published: August 2021

Several studies show that statin therapy improves endothelial function by cholesterol-independent mechanisms called “pleiotropic effects.” These are due to the inhibition of the RhoA/ROCK kinase pathway, its inhibition being an attractive atheroprotective treatment. In addition, recent work has shown that microRNAs, posttranscriptional regulators of gene expression, can affect the response of statins and their efficacy. For this reason, the objective of this study was to identify by bioinformatic analysis possible new microRNAs that could modulate the pleiotropic effects exerted by statins through the inhibition of ROCK kinases. A bioinformatic study was performed in which the differential expression of miRNAs in endothelial cells was compared under two conditions: Control and treated with simvastatin at 10 μM for 24 h, using a microarray. Seven miRNAs were differentially expressed, three up and four down. Within the up group, the miRNAs hsa-miR-618 and hsa-miR-297 present as a predicted target to ROCK2 kinase. Also, functional and enriched pathway analysis showed an association with mechanisms associated with atheroprotective effects. This work shows an in-silico approach of how posttranscriptional regulation mediated by miRNAs could modulate the pleiotropic effects exerted by statins on endothelial cells, through the inhibition of ROCK2 kinase and its effects.
Association Between Echocardiographic Non-invasive Myocardial Work Indices and Myocardial Fibrosis in Patients With Dilated Cardiomyopathy
Authors: Cui Cunying , Li Yanan , Liu Yuanyuan , Huang Danqing , Hu Yanbin , Wang Ying , Ma Lijia , Liu Lin
Published: August 2021

Objectives: To analyze the association between global myocardial work indices evaluated by non-invasive left ventricular (LV) pressure-strain loop (PSL) and LV myocardial fibrosis in patients with dilated cardiomyopathy (DCM).

Methods: A total of 57 patients with DCM were included in this prospective study. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE) and global longitudinal strain (GLS) were measured using LVPSL. LV volumes and LV ejection fraction (LVEF) were evaluated using cardiac magnetic resonance imaging (CMRI), LV myocardial fibrosis was estimated at CMRI by qualitative assessment of late gadolinium enhancement (LGE). According to the CMRI, the studied population was divided into two groups, namely: patients without LGE (LGE-) and patients with LGE (LGE+).

Results: The LGE+ group presented with increased age, LV end systolic volume (LVESV) index and reduced GWI, GCW, GWE, GLS, CMRI-derived LVEF (LVEFCMRI), the differences between the two groups were statistically significant (P < 0.05). After correcting for age and LVESV index, LVEFCMRI, GLS, GWI, GCW, and GWE retained independent associations with LV myocardial fibrosis. According to receiver operating characteristics (ROC) analysis, LVEFCMRI, and GCW showed larger AUC and higher accuracy, sensitivity, and specificity than GLS, the accuracy of predicting LV myocardial fibrosis ranged from high to low as: LVEFCMRI, GCW, GWE, GWI, and GLS.

Conclusions: LVEFCMRI, GWI, GCW, GWE, and GLS remained significant predictors of LV myocardial fibrosis. LVEFCMRI, and GCW appeared to better predict LV myocardial fibrosis compared with GLS.
Effects of Combined High-Protein Diet and Exercise Intervention on Cardiometabolic Health in Middle-Aged Obese Adults: A Randomized Controlled Trial
Authors: Chen Chiao-Nan , Hsu Kuo-Jen , Chien Kuei-Yu , Chen Jeu-Jung
Published: August 2021

Background: Obesity is the main risk factor of cardiovascular diseases (CVD) and metabolic diseases. The middle-aged population is the age group with the highest prevalence of obesity. Thus, improving cardiometabolic health is important to prevent CVD and metabolic diseases in middle-aged obese adults. The aim of this study was to examine the effects of exercise alone or in combination with a high-protein diet on markers of cardiometabolic health in middle-aged adults with obesity.

Methods: Sixty-nine middle-aged adults with obesity were assigned randomly to the control group (C; n = 23), exercise group (E; n = 23), or exercise combined with high-protein diet group (EP; n = 23). Individuals in the E and EP groups received supervised exercise training and individuals in the EP group received high-protein diet intervention. Body composition (assessed by dual-energy X-ray absorptiometry), oral glucose tolerance test (OGTT), lipid profiles, and inflammatory markers were determined before and after 12 weeks of intervention. Insulin sensitivity index (ISI0,120) was calculated from values of fasting and 2-h insulin and glucose concentration of OGTT. Insulin-peak-time during the OGTT was recorded to reflect β-cell function. Analysis of covariance with baseline values as covariates was used to examine the effects of the intervention. The significant level was set at 0.05.

Results: After 12 weeks of intervention, the E group had a greater percentage of individuals with early insulin-peak-time during the OGTT than that in the C and EP groups (p = 0.031). EP group had lower total cholesterol and triglycerides than that in the C group (p = 0.046 and 0.014, respectively). Within-group comparisons showed that the 2-h glucose of OGTT and C-reactive protein decreased in the EP group (p = 0.013 and 0.008, respectively) but not in the E and C groups; insulin sensitivity improved in the EP group (p = 0.016) and had a trend to improve in the E group (p = 0.052); and abdominal fat mass and total body fat mass decreased in both intervention groups (p < 0.05).

Conclusion: Combined high-protein diet and exercise intervention significantly decreased fat mass and improved lipid profiles, insulin sensitivity, glucose tolerance, and inflammation in middle-aged adults with obesity.

Clinical Trial Registration: Thai Clinical Trials Registry, TCTR20180913003, 13-09-2018.
Case Report: The Neuromusclar Triad of Immune Checkpoint Inhibitors: A Case Report of Myositis, Myocarditis, and Myasthenia Gravis Overlap Following Toripalimab Treatment
Authors: Luo Yue-Bei , Tang Weiting , Zeng Qiuming , Duan Weiwei , Li Shuyu , Yang Xiaosu , Bi Fangfang
Published: August 2021

The neuromuscular adverse events of immune checkpoint inhibitor (ICI) treatment include myositis, polymyalgia rheumatica, myocarditis, and myasthenia syndrome. We report a 47-year old female presenting with external ophthalmoplegia, generalized muscle weakness, and third-degree atrioventricular block 4 weeks after toripalimab treatment for metastatic thymoma. Creatine kinase was elevated to 25,200 U/l and cardiac troponin I to 2.796 ng/ml. Autoantibody profiling shows positive anti-ryanodine receptor and anti-acetylcholine receptor antibodies and negative myositis specific antibodies. Repetitive nerve stimulation did not reveal decrement of compound muscle action potentials. Pulse methylprednisolone and immunoglobulin infusion, together with temporary pacemaker insertion normalized her muscle enzyme levels and cardiac rhythm. This is the first report of overlaping neuromuscular adverse event of toripalimab.
rGO/Silk Fibroin-Modified Nanofibrous Patches Prevent Ventricular Remodeling via Yap/Taz-TGFβ1/Smads Signaling After Myocardial Infarction in Rats
Authors: Feng Yanjing , Zhao Guoxu , Xu Min , Xing Xin , Yang Lijun , Ma Yao , Qi Mengyao , Zhang Xiaohui , Gao Dengfeng
Published: August 2021

Objective: After acute myocardial infarction (AMI), the loss of cardiomyocytes and dysregulation of extracellular matrix homeostasis results in impaired cardiac function and eventually heart failure. Cardiac patches have emerged as a potential therapeutic strategy for AMI. In this study, we fabricated and produced reduced graphene oxide (rGO)/silk fibroin-modified nanofibrous biomaterials as a cardiac patch to repair rat heart tissue after AMI and investigated the potential role of rGO/silk patch on reducing myocardial fibrosis and improving cardiac function in the infarcted rats.

Method: rGO/silk nanofibrous biomaterial was prepared by electrospinning and vacuum filtration. A rat model of AMI was used to investigate the ability of patches with rGO/silk to repair the injured heart in vivo. Echocardiography and stress–strain analysis of the left ventricular papillary muscles was used to assess the cardiac function and mechanical property of injured hearts treated with this cardiac patch. Masson's trichrome staining and immunohistochemical staining for Col1A1 was used to observe the degree of myocardial fibrosis at 28 days after patch implantation. The potential direct mechanism of the new patch to reduce myocardial fibrosis was explored in vitro and in vivo.

Results: Both echocardiography and histopathological staining demonstrated improved cardiac systolic function and ventricular remodeling after implantation of the rGO/silk patch. Additionally, cardiac fibrosis and myocardial stiffness of the infarcted area were improved with rGO/silk. On RNA-sequencing, the gene expression of matrix-regulated genes was altered in cardiofibroblasts treated with rGO. Western blot analysis revealed decreased expression of the Yap/Taz-TGFβ1/Smads signaling pathway in heart tissue of the rGO/silk patch group as compared with controls. Furthermore, the rGO directly effect on Col I and Col III expression and Yap/Taz-TGFβ1/Smads signaling was confirmed in isolated cardiofibroblasts in vitro.

Conclusion: This study suggested that rGO/silk improved cardiac function and reduced cardiac fibrosis in heart tissue after AMI. The mechanism of the anti-fibrosis effect may involve a direct regulation of rGO on Yap/Taz-TGFβ1/Smads signaling in cardiofibroblasts.
microRNA-377 Signaling Modulates Anticancer Drug-Induced Cardiotoxicity in Mice
Authors: Henderson John , Dubey Praveen K. , Patil Mallikarjun , Singh Sarojini , Dubey Shubham , Namakkal Soorappan Rajasekaran , Kannappan Ramaswamy , Sethu Palaniappan , Qin Gangjian , Zhang Jianyi , Krishnamurthy Prasanna
Published: August 2021

Doxorubicin (DOX, an anthracycline) is a widely used chemotherapy agent against various forms of cancer; however, it is also known to induce dose-dependent cardiotoxicity leading to adverse complications. Investigating the underlying molecular mechanisms and strategies to limit DOX-induced cardiotoxicity might have potential clinical implications. Our previous study has shown that expression of microRNA-377 (miR-377) increases in cardiomyocytes (CMs) after cardiac ischemia-reperfusion injury in mice, but its specific role in DOX-induced cardiotoxicity has not been elucidated. In the present study, we investigated the effect of anti-miR-377 on DOX-induced cardiac cell death, remodeling, and dysfunction. We evaluated the role of miR-377 in CM apoptosis, its target analysis by RNA sequencing, and we tested the effect of AAV9-anti-miR-377 on DOX-induced cardiotoxicity and mortality. DOX administration in mice increases miR-377 expression in the myocardium. miR-377 inhibition in cardiomyocyte cell line protects against DOX-induced cell death and oxidative stress. Furthermore, RNA sequencing and Gene Ontology (GO) analysis revealed alterations in a number of cell death/survival genes. Intriguingly, we observed accelerated mortality and enhanced myocardial remodeling in the mice pretreated with AAV9-anti-miR-377 followed by DOX administration as compared to the AAV9-scrambled-control-pretreated mice. Taken together, our data suggest that in vitro miR-377 inhibition protects against DOX-induced cardiomyocyte cell death. On the contrary, in vivo administration of AAV9-anti-miR-377 increases mortality in DOX-treated mice.
The Positive Influence of Inquiry-Based Learning Teacher Professional Learning and Industry Partnerships on Student Engagement With STEM
Authors: Attard Catherine , Berger Nathan , Mackenzie Erin
Published: August 2021

School teachers in science, technology, engineering and mathematics (STEM) face challenges in developing and maintaining high levels of student engagement and achievement in those disciplines. Consequently, declining numbers of students are electing these subjects beyond the compulsory years of schooling. A major factor in student engagement often is curriculum content being relevant to the lives of students outside the classroom. Two key ways teachers can enhance the real-world relevance of their lessons are inquiry-based learning and localising the curriculum to provide an authentic context for teaching and learning. In this paper, we report a qualitative study into the perceived influences of inquiry-based learning on student engagement, as facilitated through teacher professional learning in the context of two major infrastructure programs in Sydney, Australia. Semi-structured interviews and focus groups were conducted with primary and secondary teachers who participated in professional learning about inquiry-based pedagogies, as well as with their students who undertook inquiry-based learning projects based on the infrastructure programs in their local community. Inductive and deductive content analyses using Attard’s Framework for Engagement with STEM illustrated how the combination of teacher professional learning, student inquiry-based learning, and localised industry-school partnerships enhanced student engagement across operative, cognitive, and affective domains. Another significant finding was the extent to which professional learning as the vehicle for inquiry-based learning and industry connections enhanced teachers’ pedagogical relationships and pedagogical repertoires in ways not possible with more conventional approaches to industry-school partnerships.
Maternal Chronodisruption Throughout Pregnancy Impairs Glucose Homeostasis and Adipose Tissue Physiology in the Male Rat Offspring
Authors: Halabi Diego , Richter Hans G. , Mendez Natalia , Kähne Thilo , Spichiger Carlos , Salazar Esteban , Torres Fabiola , Vergara Karina , Seron-Ferre Maria , Torres-Farfan Claudia
Published: August 2021

Compelling evidence in rats support the idea that gestational chronodisruption induces major changes in maternal circadian rhythms and fetal development and that these changes impact adult life at many physiological levels. Using a model of chronic photoperiod shifting throughout gestation (CPS), in which pregnant female rats (Sprague–Dawley strain; n = 16 per group) were exposed to lighting schedule manipulation every 3–4 days reversing the photoperiod completely or light/dark photoperiod (12/12; LD), we explored in the adult rat male offspring body weight gain, glucose homeostasis, adipose tissue content, adipose tissue response to norepinephrine (NE), and adipose tissue proteomic in the basal condition with standard diet (SD) and in response to high-fat diet (HFD). In adult CPS male (100–200 days old; n = 8 per group), we found increasing body weight, under SD and adiposity. Also, we found an increased response to intraperitoneal glucose (IGTT). After 12 weeks of HFD, white adipose tissue depots in CPS offspring were increased further, and higher IGTT and lower intraperitoneal insulin tolerance response were found, despite the lack of changes in food intake. In in vitro experiments, we observed that adipose tissue (WAT and BAT) glycerol response to NE from CPS offspring was decreased, and it was completely abolished by HFD. At the proteomic level, in CPS adipose tissue, 275 proteins displayed differential expression, compared with LD animals fed with a standard diet. Interestingly, CPS offspring and LD fed with HFD showed 20 proteins in common (2 upregulated and 18 downregulated). Based on these common proteins, the IPA analysis found that two functional pathways were significantly altered by CPS: network 1 (AKT/ERK) and network 2 (TNF/IL4; data are available via ProteomeXchange with identifier PXD026315). The present data show that gestational chronodisruption induced deleterious effects in adipose tissue recruitment and function, supporting the idea that adipose tissue function was programmed in utero by gestational chronodisruption, inducing deficient metabolic responses that persist into adulthood.
An In Vitro Study on Extracellular Vesicles From Adipose-Derived Mesenchymal Stem Cells in Protecting Stress Urinary Incontinence Through MicroRNA-93/F3 Axis
Authors: Wang Lu , Wang Yali , Xiang Yuancui , Ma Jinping , Zhang Hui , Dai Jingfang , Hou Yanan , Yang Yupei , Ma Jingru , Li Hongjuan
Published: August 2021

Since the potential roles of extracellular vesicles secreted by adipose-derived mesenchymal stem cells (ADSCs) are not well understood in collagen metabolism, the purpose of this research was to evaluate the effects of ADSCs-extracellular vesicles in stress urinary incontinence and the regulatory mechanism of delivered microRNA-93 (miR-93). ADSCs were isolated and cultured, and ADSCs-extracellular vesicles were extracted and identified. Stress urinary incontinence primary fibroblasts or satellite cells were treated with ADSCs-extracellular vesicles to detect the expression of Elastin, Collagen I, and Collagen III in fibroblasts and Pax7 and MyoD in satellite cells. After transfecting ADSCs with miR-93 mimics or inhibitors, extracellular vesicles were isolated and treated with stress urinary incontinence primary fibroblasts or satellite cells to observe cell function changes. The online prediction and luciferase activity assay confirmed the targeting relationship between miR-93 and coagulation factor III (F3). The rescue experiment verified the role of ADSCs-extracellular vesicles carrying miR-93 in stress urinary incontinence primary fibroblasts and satellite cells by targeting F3. ADSCs-extracellular vesicles treatment upregulated expression of Elastin, Collagen I, and Collagen III in stress urinary incontinence primary fibroblasts and expression of Pax7 and MyoD in stress urinary incontinence primary satellite cells. miR-93 expression was increased in stress urinary incontinence primary fibroblasts or satellite cells treated with ADSCs-extracellular vesicles. Extracellular vesicles secreted by ADSCs could deliver miR-93 to fibroblasts and then negatively regulate F3 expression; ADSCs-extracellular vesicles could reverse the effect of F3 on extracellular matrix remodeling in stress urinary incontinence fibroblasts. miR-93 expression was also increased in stress urinary incontinence primary satellite cells treated by ADSCs-extracellular vesicles. Extracellular vesicles secreted by ADSCs were delivered to satellite cells through miR-93, which directly targets F3 expression and upregulates Pax7 and MyoD expression in satellite cells. Our study indicates that miR-93 delivered by ADSCs-extracellular vesicles could regulate extracellular matrix remodeling of stress urinary incontinence fibroblasts and promote activation of stress urinary incontinence satellite cells through targeting F3.
IGF-I and IGFBP-1 in Relation to Body Composition and Physical Performance in Female Olympic Athletes
Authors: Eklund Emma , Hellberg Anton , Berglund Bo , Brismar Kerstin , Hirschberg Angelica Lindén
Published: August 2021

Introduction

Insulin- like growth factor-I (IGF-I) is an anabolic hormone that may affect athletic performance in female athletes, and insulin-like growth factor binding protein-1 (IGFBP-1) is an important regulator of bioactive IGF-I. There is limited knowledge of the role of endogenous IGF-I and IGFBP-1 for body composition and physical performance in female elite athletes.

Purpose

To examine IGF-I, age adjusted IGF-I (IGFSD), IGFBP-1 and insulin in female Olympic athletes compared with controls and different sport categories, and in relation to body composition and physical performance in the athletes.

Methods

Female athletes (n=103) and untrained controls (n=113) were included in this cross-sectional study. Body composition was established by dual-energy X-ray absorptiometry. Serum IGF-I and IGFBP-1 were analyzed by radioimmunoassay and IGFSD was calculated. Insulin was analyzed by electrochemiluminescence immunoassay. Athletes were offered to participate in standardized physical fitness tests.

Results

The athletes demonstrated significantly higher IGF-I, IGFSD and IGFBP-1 and lower insulin levels than controls (p<0.05, p<0.05, p<0.01, p<0.001 respectively). Power athletes had significantly higher IGFSD compared to both endurance and technical athletes (p<0.05, p<0.01, respectively). In athletes and controls combined, significant positive correlations were found between IGF variables and higher bone mineral density (BMD) and lean mass and lower fat percent. IGF-I was positively correlated with squat jump (rs = 0.28, p<0.05) and IGFBP-1 correlated positively with squats (rs =0.35, p<0.05).

Conclusion

We found higher IGF-I, IGFSD and IGFBP-1 in female athletes than controls, and the highest IGFSD in power athletes. IGF-I and IGFBP-1 were related to increased BMD and lean mass and lower fat percent, as well as were positively associated with physical fitness tests. Future studies are needed to elucidate if these results reflect adaptive responses to physical activity or genetic predisposition.
Afforestation With Different Tree Species Causes a Divergent Evolution of Soil Profiles and Properties
Authors: Morazzo German , Riestra Diego Rene , Leizica Emmanuel , Álvarez Lucila , Noellemeyer Elke
Published: August 2021

Land-use change and specifically a change in the type of vegetation cover affects soil morphology, chemistry, biology, and nutrient regimes. Numerous studies have documented that in land-use conversions from agricultural land to forest, or from plantations to restored natural savanna most soil attributes and functions undergo changes. The purpose of the present study was to evaluate the changes brought about by afforestation of degraded croplands and to understand the impact of forest vegetation on soil evolution in a semiarid region where soils originally co-evolved with a savanna biotope. We used long-term experiments (>40 years) of five tree species: Pinus halepensis (PH), Pinus halepensis inoculated with ecto-mycorrhiza at planting (PM), Pinus pinea (PP), Eucalyptus spp. (E), and Gleditsia triacanthos (G) and compared these to an agricultural soil (A) at the same site near Santa Rosa, La Pampa in the semiarid center of Argentina. Soil profiles were described, and samples taken for chemical and physical analyses of soil properties [organic matter (OM), pH, cation exchange capacity (CEC) and exchangeable cations, particle size distribution (texture), aggregate stability (MWD), bulk density (BD), porosity (TP), and water holding capacity (WHC)]. We found a strong effect of tree species on soil profile morphology, even taxonomy, and on all studied variables. PM and G had highest OM, CEC, neutral pH, higher TP, WHC, while PH, PP, and E had acid pH, lower base saturation, OM, TP, and WHC. The effect of tree species on the soil profile was noticeable a depth of about 40 cm, comprising the A and AC, but not the C horizons. The results showed that to obtain reasonable results of OM sequestration under forest systems, tree species should be chosen to include legumes to improve C/N stoichiometry for C fixation, or inoculation with mycorrhiza to promote microbial transformation of forest litter.
Identifying Breast Cancer-Related Genes Based on a Novel Computational Framework Involving KEGG Pathways and PPI Network Modularity
Authors: Zhang Yan , Xiang Ju , Tang Liang , Li Jianming , Lu Qingqing , Tian Geng , He Bin-Sheng , Yang Jialiang
Published: August 2021

Complex diseases, such as breast cancer, are often caused by mutations of multiple functional genes. Identifying disease-related genes is a critical and challenging task for unveiling the biological mechanisms behind these diseases. In this study, we develop a novel computational framework to analyze the network properties of the known breast cancer–associated genes, based on which we develop a random-walk-with-restart (RCRWR) algorithm to predict novel disease genes. Specifically, we first curated a set of breast cancer–associated genes from the Genome-Wide Association Studies catalog and Online Mendelian Inheritance in Man database and then studied the distribution of these genes on an integrated protein–protein interaction (PPI) network. We found that the breast cancer–associated genes are significantly closer to each other than random, which confirms the modularity property of disease genes in a PPI network as revealed by previous studies. We then retrieved PPI subnetworks spanning top breast cancer–associated KEGG pathways and found that the distribution of these genes on the subnetworks are non-random, suggesting that these KEGG pathways are activated non-uniformly. Taking advantage of the non-random distribution of breast cancer–associated genes, we developed an improved RCRWR algorithm to predict novel cancer genes, which integrates network reconstruction based on local random walk dynamics and subnetworks spanning KEGG pathways. Compared with the disease gene prediction without using the information from the KEGG pathways, this method has a better prediction performance on inferring breast cancer–associated genes, and the top predicted genes are better enriched on known breast cancer–associated gene ontologies. Finally, we performed a literature search on top predicted novel genes and found that most of them are supported by at least wet-lab experiments on cell lines. In summary, we propose a robust computational framework to prioritize novel breast cancer–associated genes, which could be used for further in vitro and in vivo experimental validation.
Integrative Transcriptomic, Lipidomic, and Metabolomic Analysis Reveals Potential Biomarkers of Basal and Luminal Muscle Invasive Bladder Cancer Subtypes
Authors: Feng Chao , Pan Lixin , Tang Shaomei , He Liangyu , Wang Xi , Tao Yuting , Xie Yuanliang , Lai Zhiyong , Tang Zhong , Wang Qiuyan , Li Tianyu
Published: August 2021

Muscle invasive bladder cancer (MIBC) is a heterogeneous disease with a high recurrence rate and poor clinical outcomes. Molecular subtype provides a new framework for the study of MIBC heterogeneity. Clinically, MIBC can be classified as basal and luminal subtypes; they display different clinical and pathological characteristics, but the molecular mechanism is still unclear. Lipidomic and metabolomic molecules have recently been considered to play an important role in the genesis and development of tumors, especially as potential biomarkers. Their different expression profiles in basal and luminal subtypes provide clues for the molecular mechanism of basal and luminal subtypes and the discovery of new biomarkers. Herein, we stratified MIBC patients into basal and luminal subtypes using a MIBC classifier based on transcriptome expression profiles. We qualitatively and quantitatively analyzed the lipids and metabolites of basal and luminal MIBC subtypes and identified their differential lipid and metabolite profiles. Our results suggest that free fatty acids (FFAs) and sulfatides (SLs), which are closely associated with immune and stromal cell types, can contribute to the diagnosis of basal and luminal subtypes of MIBC. Moreover, we showed that glycerophosphocholine (GCP)/imidazoles and nucleosides/imidazoles ratios can accurately distinguish the basal and luminal tumors. Overall, by integrating transcriptomic, lipidomic, and metabolomic data, our study reveals specific biomarkers to differentially diagnose basal and luminal MIBC subtypes and may provide a basis for precision therapy of MIBC.
Case Report: Identification of a Heterozygous XPA c.553C>T Mutation Causing Neurological Impairment in a Case of Xeroderma Pigmentosum Complementation Group A
Authors: García-Carmona Juan Antonio , Yousefzadeh Matthew J. , Alarcón-Soldevilla Fernando , Fages-Caravaca Eva , Kieu Tra L. , Witt Mariah A. , López-Ávila Ángel , Niedernhofer Laura J. , Pérez-Vicente José Antonio
Published: August 2021

We aimed to determine if an adolescent patient presenting with neurological impairment has xeroderma pigmentosum (XP). For this purpose, whole-exome sequencing was performed to assess mutations in XP genes. Dermal fibroblasts were established from a skin biopsy and XPA expression determined by immunoblotting. Nucleotide excision repair (NER) capacity was measured by detection of unscheduled DNA synthesis (UDS) in UVC-irradiated patient fibroblasts. Genetic analysis revealed two recessive mutations in XPA, one known c.682C>T, p.Arg228Ter, and the other c.553C>T, p.Gln185Ter, only two cases were reported. XPA protein was virtually undetectable in lysates from patient-derived fibroblast. The patient had significantly lower UV-induced UDS (3.03 ± 1.95%, p < 0.0001) compared with healthy controls (C5RO = 100 ± 12.2; C1UMN = 118 ± 5.87), indicating significant NER impairment. In conclusion, measurement of NER capacity is beneficial for the diagnosis of XP and in understanding the functional impact of novel mutations in XP genes. Our findings highlight the importance of neurologists considering XP in their differential diagnosis when evaluating patients with atypical neurodegeneration.
Prostaglandin E2 Signaling Mediates Oenocytoid Immune Cell Function and Lysis, Limiting Bacteria and Plasmodium Oocyst Survival in Anopheles gambiae
Authors: Kwon Hyeogsun , Hall David R. , Smith Ryan C.
Published: August 2021

Lipid-derived signaling molecules known as eicosanoids have integral roles in mediating immune and inflammatory processes across metazoans. This includes the function of prostaglandins and their cognate G protein-coupled receptors (GPCRs) to employ their immunological actions. In insects, prostaglandins have been implicated in the regulation of both cellular and humoral immune responses, yet in arthropods of medical importance, studies have been limited. Here, we describe a prostaglandin E2 receptor (AgPGE2R) in the mosquito Anopheles gambiae and demonstrate that its expression is most abundant in oenocytoid immune cell populations. Through the administration of prostaglandin E2 (PGE2) and AgPGE2R-silencing, we demonstrate that prostaglandin E2 signaling regulates a subset of prophenoloxidases (PPOs) and antimicrobial peptides (AMPs) that are strongly expressed in populations of oenocytoids. We demonstrate that PGE2 signaling via the AgPGE2R significantly limits both bacterial replication and Plasmodium oocyst survival. Additional experiments establish that PGE2 treatment increases phenoloxidase (PO) activity through the increased expression of PPO1 and PPO3, genes essential to anti-Plasmodium immune responses that promote oocyst killing. We also provide evidence that the mechanisms of PGE2 signaling are concentration-dependent, where high concentrations of PGE2 promote oenocytoid lysis, negating the protective effects of lower concentrations of PGE2 on anti-Plasmodium immunity. Taken together, our results provide new insights into the role of PGE2 signaling on immune cell function and its contributions to mosquito innate immunity that promote pathogen killing.
Experimental Models of Infectious Pulmonary Complications Following Hematopoietic Cell Transplantation
Authors: Zhou Xiaofeng , Moore Bethany B.
Published: August 2021

Pulmonary infections remain a major cause of morbidity and mortality in hematopoietic cell transplantation (HCT) recipients. The prevalence and type of infection changes over time and is influenced by the course of immune reconstitution post-transplant. The interaction between pathogens and host immune responses is complex in HCT settings, since the conditioning regimens create periods of neutropenia and immunosuppressive drugs are often needed to prevent graft rejection and limit graft-versus-host disease (GVHD). Experimental murine models of transplantation are valuable tools for dissecting the procedure-related alterations to innate and adaptive immunity. Here we review mouse models of post-HCT infectious pulmonary complications, primarily focused on three groups of pathogens that frequently infect HCT recipients: bacteria (oftenP. aeruginosa), fungus (primarilyAspergillus fumigatus), and viruses (primarily herpesviruses). These mouse models have advanced our knowledge regarding how the conditioning and HCT process negatively impacts innate immunity and have provided new potential strategies of managing the infections. Studies using mouse models have also validated clinical observations suggesting that prior or occult infections are a potential etiology of noninfectious pulmonary complications post-HCT as well.
Occurrence of COVID-19 Symptoms During SARS-CoV-2 Infection Defines Waning of Humoral Immunity
Authors: Wu Jun , Liang Bo-Yun , Fang Yao-Hui , Wang Hua , Yang Xiao-Li , Shen Shu , Chen Liang-Kai , Li Su-Meng , Lu Si-Hong , Xiang Tian-Dan , Liu Jia , Le-Trilling Vu Thuy Khanh , Lu Meng-Ji , Yang Dong-Liang , Deng Fei , Dittmer Ulf , Trilling Mirko , Zheng Xin
Published: August 2021

Approximately half of the SARS-CoV-2 infections occur without apparent symptoms, raising questions regarding long-term humoral immunity in asymptomatic individuals. Plasma levels of immunoglobulin G (IgG) and M (IgM) against the viral spike or nucleoprotein were determined for 25,091 individuals enrolled in a surveillance program in Wuhan, China. We compared 405 asymptomatic individuals who mounted a detectable antibody response with 459 symptomatic COVID-19 patients. The well-defined duration of the SARS-CoV-2 endemic in Wuhan allowed a side-by-side comparison of antibody responses following symptomatic and asymptomatic infections without subsequent antigen re-exposure. IgM responses rapidly declined in both groups. However, both the prevalence and durability of IgG responses and neutralizing capacities correlated positively with symptoms. Regardless of sex, age, and body weight, asymptomatic individuals lost their SARS-CoV-2-specific IgG antibodies more often and rapidly than symptomatic patients did. These findings have important implications for immunity and favour immunization programs including individuals after asymptomatic infections.
Influence of Nutrition and Maternal Bonding on Postnatal Lung Development in the Newborn Pig
Authors: Schlosser-Brandenburg Josephine , Ebner Friederike , Klopfleisch Robert , Kühl Anja A. , Zentek Jürgen , Pieper Robert , Hartmann Susanne
Published: August 2021

Background

Microbial colonization and immune cell maturation coincide at mucosal sites and are decisive for postnatal lung development. How external factors influence neonatal pulmonary immune development is poorly understood.

Objective

To elucidate the impact of key determinants in early life, nutrition, and maternal bonding, on postnatal lung maturation in a human-relevant animal model. To investigate the underlying immunological changes of impaired lung maturation and study the mechanisms of conversion.

Methods

Newborn piglets were kept with or without isolation from their mothers and fed bovine milk-based infant formula or received milk of sow. Lung growth, histomorphology, respiratory immune responses, and lung microbiota were analyzed. Mother- and sow-milk-deprived piglets received maternal material or were reintroduced to the maternal environment at varying intervals to study options for reversal.

Results

Formula feeding combined with isolation of newborn piglets resulted in disturbed postnatal lung maturation. Reduced lung growth correlated with dampened IL-33 expression, impaired lung myeloid cell activation, and decreased Th1 differentiation, along with diminished richness and diversity of the lung microbiota. Transfer of bacteria-enriched maternal material reversed the negative effects on pulmonary immune maturation. Early (within 3 days) but not late (within 7 days) reintroduction to the mother allowed restoration of normal lung development.

Conclusion

Our findings reveal that lung growth, respiratory immunity, and microbial lung colonization in newborns depend on postnatal diet and maternal contact, and targeting these key regulators could promote lung development during this critical life stage.

Disturbances in natural diet and reduced maternal contact during the neonatal period impair postnatal lung maturation. In pediatrics, timely breast milk feeding and intensive maternal bonding represent valuable intervention measures to promote early postnatal lung development.
Corals and Sponges Under the Light of the Holobiont Concept: How Microbiomes Underpin Our Understanding of Marine Ecosystems
Authors: Stévenne Chloé , Micha Maud , Plumier Jean-Christophe , Roberty Stéphane
Published: August 2021

In the past 20 years, a new concept has slowly emerged and expanded to various domains of marine biology research: the holobiont. A holobiont describes the consortium formed by a eukaryotic host and its associated microorganisms including bacteria, archaea, protists, microalgae, fungi, and viruses. From coral reefs to the deep-sea, symbiotic relationships and host–microbiome interactions are omnipresent and central to the health of marine ecosystems. Studying marine organisms under the light of the holobiont is a new paradigm that impacts many aspects of marine sciences. This approach is an innovative way of understanding the complex functioning of marine organisms, their evolution, their ecological roles within their ecosystems, and their adaptation to face environmental changes. This review offers a broad insight into key concepts of holobiont studies and into the current knowledge of marine model holobionts. Firstly, the history of the holobiont concept and the expansion of its use from evolutionary sciences to other fields of marine biology will be discussed. Then, the ecology and physiology of marine holobionts will be investigated through the examples of corals and sponges. We will discuss the impacts of environmental change on organisms at the holobiont level and how microbiomes contribute to the resilience and/or vulnerability of their host in the face of environmental stressors. Finally, we will conclude with the development of new technologies, holistic approaches, and future prospects for conservation biology surrounding marine holobionts.