bluuebunny/crossref_metadata_2025 huggingface dataset:
Uso de metáfora publicitária nas aulas de Língua Portuguesa: desenvolvimento da consciência e competência comunicativa do aprendiz surdo
Authors: Mamedes Rosilene  Felix , Machado Adilma Gomes da Silva , Vanderley Juliana Soares , Silva Charlene de Lima Alexandre da , Aquino Maria das Graças da Silva , Formiga Christianne Nogueira Donato , Ribeiro Prisciane Pinto Fabricio , Santos Vanderson Douglas Tavares , Gabriel Rosenice de Lima
Published: January 2021

Este trabalho tem como objetivo relatar a experiência desenvolvida em uma turma do 9º ano de uma escola estadual, a partir do uso do gênero propaganda publicitária. A partir desse trabalho, foi possível desenvolver nos alunos surdos a consciência comunicativa para a comunicação, além de favorecer a ampliação do vocabulário da LIBRAS. Nesse sentido, usamos a metáfora publicitária nas aulas de língua portuguesa na perspectiva de desenvolver a consciência e competência comunicativa do aprendiz surdo para jovens surdos concluintes do 9ºano do ensino fundamental. A proposta foi desenvolvida na disciplina Língua Portuguesa como L2 para Surdos, com duração de 06h (referente a duas aulas com a duração de três horas cada aula), tendo como público-alvo alunos surdos do 9ºano do Fundamental II. Como objetivo para esta atividade elegemos: entender o processo de compreensão de metáforas na publicidade para o desenvolvimento da consciência e competência comunicativa do aprendiz surdo nas aulas de Língua Portuguesa como L2 na modalidade escrita. Como resultados apontamos o avanço dos discentes na comunicação em libras, bem como a expansão do vocabulário, além de possibilitar a interação junto aos demais alunos.
Ranavirus is widespread in Costa Rica and co-occurs with threatened amphibians
Authors: Whitfield SM , Alvarado-Barboza G , Abarca JG , Zumbado-Ulate H , Jimenez RR , Kerby J
Published: January 2021

Amphibians are globally threatened by emerging infectious diseases, and ranaviruses are among the most concerning pathogens to threaten species in the wild. We sampled for ranaviruses in wild amphibians at 8 sites in Costa Rica, spanning broad climatic zones and taxonomic associations. Seven of these sites are inhabited by highly threatened amphibian species that persist at low global population sizes after population declines due to amphibian chytridiomycosis. One of the surveyed sites is occupied by an introduced amphibian species, which is relatively rare in Central America but may be an important pathway for long-distance transport of ranaviruses. We detected ranavirus using quantitative polymerase chain reaction in 16.3% of the 243 individuals and among 5 of our 8 sites, but not at the site with the introduced species. Infection prevalence varied among species and sites, but not with mean annual temperature or mean annual precipitation. Infection intensity did not vary with species, site, temperature, or precipitation. Our results show that ranavirus infection is spatially widespread in Costa Rica, affecting a broad range of host species, and occurs across climatic zones—though we encountered no mortality or morbidity in our sampled species. Ranaviruses are known to cause intermittent mass mortality in amphibian populations, and the threatened species sampled here are likely vulnerable to population impacts from emerging ranaviruses. Therefore, we believe the potential impacts of ranaviruses on amphibian populations in tropical regions have likely been underestimated, and that they should be viewed as a potential major stressor to threatened amphibians in tropical regions.
Long-Term Efficacy and Safety of Conversion to Tacrolimus in Heart
Transplant Recipients with Ongoing or Recurrent Acute Cellular
Rejection
Authors: Skalická B , Málek I , Kubánek M , Vymětalová J , Kautzner J
Published: January 2021

Despite the widespread use of potent immunosuppressive drugs,
such as cyclosporin A and mycophenolate mofetil, ongoing and
recurrent cellular rejection remain a common problem after heart
transplantation. We aimed to describe the long-term effects of
conversion from cyclosporine A to tacrolimus in patients with
ongoing and recurrent cellular rejection. This was a single-centre
retrospective analysis of 17 heart transplant recipients who were
switched from cyclosporine A to tacrolimus due to ongoing
(5 patients) or recurrent cellular rejection (12 patients). We
studied long-term efficacy and safety of this approach. 167
endomyocardial biopsies were performed during a mean followup of 69.1±12.7 months. Thirteen biopsies (7.8 %) in eight
patients (47 %) revealed higher grades of acute cellular rejection
(Banff 2). However, they were not hemodynamically significant
and did not require intravenous antirejection therapy. The mean
rejection score was reduced significantly. Conversion to
tacrolimus was tolerated in 82 % pts without any significant side
effects during a long-term follow-up. In conclusion, the
conversion to tacrolimus in heart transplant recipients with
ongoing or recurrent acute cellular rejection was safe and
effective also during a long-term follow-up.
Despite Similar Reduction of Blood Pressure and Renal ANG II
and ET-1 Levels Aliskiren but not Losartan Normalizes Albuminuria
in Hypertensive Ren-2 Rats
Authors: Vaňourková Z , Kramer H J , Husková Z , Červenka L , Vaněčková I
Published: January 2021

The relationship between angiotensin II (ANG II) and endothelin1 (ET-1) is known to be complex; both peptides can initiate and
potentiate the gene expression of each other. This pilot study
investigated the effects of the AT1 receptor blocker losartan or
the direct renin inhibitor aliskiren on mean arterial pressure
(MAP) and albuminuria and the renal ANG II and ET-1 levels.
3-month-old male Ren-2 transgenic rats (TGR) were treated
either with losartan (5 mg kg-1 day-1) or aliskiren (10 mg kg-1 day1
) for 10 weeks. At the end of the experiment, rats were
decapitated and cortical and papillary parts of kidneys were
separated. Plasma and tissue ANG II levels were measured by
RIA and tissue ET-1 concentrations by ELISA. In all four groups
of animals ET-1 levels were lowest in renal cortex and more than
100-fold higher in the papilla. Cortical and papillary ET-1
concentrations in untreated TGR significantly exceeded those of
control HanSD rats and were significantly depressed by both
drugs. In both strains, papillary ANG II concentrations were
moderately but significantly higher than cortical ANG II, TGR
exhibited higher ANG II levels both in cortex and papilla as
compared to control HanSD rats. Aliskiren and losartan at the
doses used depressed similarly the levels of ANG II in cortex and
papilla and reduced ET-1 significantly in the renal cortex and
papilla below control levels in HanSD rats. Albuminuria, which
was more than twice as high in TGR as in HanSD rats, was
normalized with aliskiren and reduced by 28 % with losartan,
although MAP was reduced to a similar degree by both drugs.
Despite similar reductions of MAP and renal ET-1 and ANG II
levels aliskiren appears to be more effective than losartan, at the
doses used, in reducing albuminuria in heterozygous
hypertensive Ren-2 rats.
PENGGUNAAN MEDIA KARTU DALAM MENINGKATKAN KETERAMPILAN MEMBACA PERMULAAN SISWA
Authors: Rosimasnita Rosimasnita
Published: January 2021

This research is motivated by the fact that there are still many students who are not fluent in reading the beginning and are not able to understand teacher instructions in learning. Through this research, it is hoped that it can improve students' skills in starting reading using word card media. This research is a classroom action research conducted in grade 2 SDN 21 Mandau. . The number of research subjects was 21 students with 12 male students and 9 female students. The data were obtained through reading tests and observations of students' learning activities. The results of the study in the first cycle showed that on average, the classical students had reading skills of 68.88 with 13 people who were able to reach the KKM, meaning that 61.90% of the students had classically reached the predetermined KKM. In cycle II, the average of students' pre-reading skills became 77.46 with the total number of students completing 18 people with a percentage of 85.71%. Based on the results of this study it can be concluded that the beginning reading skills of grade 2 SDN 21 Mandau students have increased through the use of word cards.
Hydrogen-Based Reduction Ironmaking Process and Conversion Technology
Authors: Yi Sang-Ho , Lee Woon-Jae , Lee Young-Seok , Kim Wan-Ho
Published: January 2021

This study analyzed the current state of technical development of the BF-based process, to determine ways to reduce carbon consumption. The technical features of the hydrogen reduction ironmaking process were also examined as a decarbonized ironmaking method, and related issues that should be considered when converting to hydrogen reduction are discussed. The coal rate consumed by the reduction reaction in the coal-based BF process should be less than 50%. The heat requirement for indirect reduction in hydrogen reduction is higher than that of CO reduction, since hydrogen reduction is endothermic. The BF-based integrated steel mill is an energy independent process, since coal is used for the reduction of iron ore and melting, and the by-product gases evolved from the BF process are utilized for reheating the furnace, the power plant, and steam production. For hydrogen reduction, only green hydrogen should be used for the reduction of iron ore, and the power required to melt the iron and for the downstream rolling process will have to be provided from the external grid. Therefore, to convert to hydrogen reduction, green power should be supplied from an external infrastructure system of the steel industry. It will be necessary to discuss an optimized pathway for the step-by-step replacement of current coal-based facilities, and to reach agreement on the socio-economic industrial transition to hydrogen reduction steel.
WATERFRONT SEBAGAI MODAL SOSIAL EKONOMI MASYARAKAT DI TEPIAN SUNGAI KAPUAS
Authors: Ramadhan Iwan , Dewantara Jagad Aditya , Efriani Efriani , Olendo Yudhistira Oscar , Bafadal Muhammad Fachrurrozi
Published: January 2021

Tujuan dalam penelitian ini adalah untuk mengetahui dampak pembangunan Waterfront City sebagai modal sosial ekonomi dalam fenomena perubahan yang signifikan terhadap masyarakat, terutama masyarakat sekitaran tepian Sungai Kapuas. Adapun metode yang digunakan pada penelitian ini adalah metode deskriptif kualitatif dengan pendekatan studi fenomenologis. Hasil yang didapat pada penelitian ini adalah, upaya yang dilakukan untuk merespon kerja sama dan partisipasi adalah bentuk kemampuan adaptasi masyakarat sekitaran Waterfront City. Kemudian dikembangkan lebih lanjut dengan upaya memobilisasi sumber daya yang menjadi tambahan pendapatan masyarakat sekitar. Adanya jaringan informal yang semakin meningkat di Kawasan Waterfront City yaitu jaringan kekeluargaan, ditandai dengan adanya prinsip saling gotong royong atau tolong menolong diantara sesama masyarakat, norma yang berlaku pada masyarakat sekitaran Sungai Kapuas khususnya di Kawasan Waterfront City banyak yang bersifat lisan, saling bertoleransi diantara sesama dan mudah untuk saling membantu, karena tidak ada yang menjadi penguasa bagi masyarakat di sana. Solidaritas sangat tinggi, mereka sudah mulai memahami bagaimana rasa persatuan dan kesatuan berjalan dengan baik dan saling menguntungkan antar sesama, serta harmonis dan solid. Sebelum pembangunan Waterfront City, kondisi sosial ekonomi masyarakat sekitar masih dikatakan cukup rendah dan hanya biasa-biasa saja. Sesudah pembangunan Waterfront City, kondisi sosial ekonomi masyarakat sekitar mengalami perubahan akibat pembangunan tersebut, baik di bidang sosial maupun ekonominya. Dampak setelah pembangunan ini tidak hanya dampak positif, tetapi juga berdampak negatif. Adapun dampak positifnya yaitu meningkatnya penghasilan masyarakat sekitar tepian Sungai Kapuas dari usaha berjualan, sedangkan dampak negatifnya yaitu banyaknya sampah yang berserakan meskipun sudah disediakan tempat pembuangan sampah.
PERAN FILOSOFI BUDAYA BATAK TOBA DALAM DUNIA PENDIDIKAN
Authors: Hutahaean Agnes Novianti Permata Sari , Agustina Winarti
Published: January 2021

Batak Toba ethnic group has a cultural philosophy in guiding their lives. To achieve this philosophy, they carry out education because they are aware of education constituting the rung to achieve the philosophy. This study aims to examine the philosophy of Toba Bataknese culture to shape the mindset of the Batak Toba ethnic group about the importance of education. The study design is qualitative one with the descriptive approach. The techniques of collection data are carried out through library research as a literature material that can present data and be accompanied with supporting document constituting an important reference in this study. The result of the study shows that the cultural philosophy of the Batak Toba ethnic group is intended to the power and the effort to achieve sahala ownership and understanding on rajawi man. The Content of sahala includes hagabeon (having children), hasangapon (honor achieved through education, and experience), and hamoraon (wealth). And the concept of a Rajawi man is a freedom of self-development, freedom to build a vision and to pursue life ambitions. The values of hagabeon, hasangapon, hamoraon and life ambition can be achieved by undergoing education in order to form a good mindset and to gain knowledge. So, it is unsurprising that the education on ethnic Batak is quite developing and advanced.
Both Hypoxia-Inducible Factor 1 and MAPK Signaling Pathway Attenuate PI3K/AKT via Suppression of Reactive Oxygen Species in Human Pluripotent Stem Cells
Authors: Fojtík Petr , Beckerová Deborah , Holomková Katerina , Šenfluk Martin , Rotrekl Vladimir
Published: January 2021

Mild hypoxia (5% O2) as well as FGFR1-induced activation of phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT) and MAPK signaling pathways markedly support pluripotency in human pluripotent stem cells (hPSCs). This study demonstrates that the pluripotency-promoting PI3K/AKT signaling pathway is surprisingly attenuated in mild hypoxia compared to the 21% O2 environment. Hypoxia is known to be associated with lower levels of reactive oxygen species (ROS), which are recognized as intracellular second messengers capable of upregulating the PI3K/AKT signaling pathway. Our data denote that ROS downregulation results in pluripotency upregulation and PI3K/AKT attenuation in a hypoxia-inducible factor 1 (HIF-1)-dependent manner in hPSCs. Using specific MAPK inhibitors, we show that the MAPK pathway also downregulates ROS and therefore attenuates the PI3K/AKT signaling—this represents a novel interaction between these signaling pathways. This inhibition of ROS initiated by MEK1/2–ERK1/2 may serve as a negative feedback loop from the MAPK pathway toward FGFR1 and PI3K/AKT activation. We further describe the molecular mechanism resulting in PI3K/AKT upregulation in hPSCs—ROS inhibit the PI3K's primary antagonist PTEN and upregulate FGFR1 phosphorylation. These novel regulatory circuits utilizing ROS as second messengers may contribute to the development of enhanced cultivation and differentiation protocols for hPSCs. Since the PI3K/AKT pathway often undergoes an oncogenic transformation, our data could also provide new insights into the regulation of cancer stem cell signaling.
Low Dose BMP2-Doped Calcium Phosphate Graft Promotes Bone Defect Healing in a Large Animal Model
Authors: Liu Tie , Fang Wen , Wu Gang , Li Yining , Pathak Janak L. , Liu Yuelian
Published: January 2021

Background: Bone grafts are in high demand due to the increase in the cases of bone defects mainly caused by trauma, old age, and disease-related bone damages. Tissue-engineered calcium phosphate (CaP) biomaterials match the major inorganic contents of bone, thereby could be the potential bone graft substitute. However, CaP-bone grafts lack the osteoinductivity that is vital for effective bone regeneration. In this study, we aimed to test the bone defect healing potential of biomimetically fabricated low dose BMP2-doped CaP (BMP2.BioCaP) grafts in a large animal model.

Methods: Low dose BMP2 was doped internally (BMP2-int.BioCaP) or on the surface of CaP (BMP2-sur.BioCaP) grafts during the fabrication process. Our previous study showed the robust bone regenerative potential of BMP2-int.BioCaP and BMP2-sur.BioCaP grafts in the rat ectopic model. In this study, we investigated the bone defect healing potential of BMP2.BioCaP grafts in sheep humerus/femoral defects, as well as compared with that of autologous bone graft and clinically used deproteinized bovine bone (DBB) xenograft.

Results: Different ways of BMP2 doping did not affect the surface morphology and degradation properties of the graft materials. Micro-CT and histology results showed robustly higher bone defect-healing potential of the BMP2.BioCaP grafts compared to clinically used DBB grafts. The bone defect healing potential of BMP2.BioCaP grafts was as effective as that of the autologous bone graft. Although, BMP2-int.BioCaP doped half the amount of BMP2 compared to BMP2-sur.BioCaP, its' bone defect healing potential was even robust. The BMP2.BioCaP grafts showed less immunogenicity compared to BioCaP or DBB grafts. The volume density of blood vessel-like and bone marrow-like structures in both BMP2.BioCaP graft groups were in a similar extent to the autologous group. Meticulous observation of higher magnification histological images showed active bone regeneration and remodeling during bone defect healing in BMP2.BioCaP graft groups.

Conclusion: The robust bone regenerative potential of BMP2.BioCaP grafts in the ectopic model and in-situ bone defects in small and large animals warrant the pre-clinical studies on large animal critical-sized segmental bone defects.
Thyroid Hormones Interaction With Immune Response, Inflammation and Non-thyroidal Illness Syndrome
Authors: De Luca Roberto , Davis Paul J. , Lin Hung-Yun , Gionfra Fabio , Percario Zulema A. , Affabris Elisabetta , Pedersen Jens Z. , Marchese Cinzia , Trivedi Pankaj , Anastasiadou Eleni , Negro Roberto , Incerpi Sandra
Published: January 2021

The interdependence between thyroid hormones (THs), namely, thyroxine and triiodothyronine, and immune system is nowadays well-recognized, although not yet fully explored. Synthesis, conversion to a bioactive form, and release of THs in the circulation are events tightly supervised by the hypothalamic–pituitary–thyroid (HPT) axis. Newly synthesized THs induce leukocyte proliferation, migration, release of cytokines, and antibody production, triggering an immune response against either sterile or microbial insults. However, chronic patho-physiological alterations of the immune system, such as infection and inflammation, affect HPT axis and, as a direct consequence, THs mechanism of action. Herein, we revise the bidirectional crosstalk between THs and immune cells, required for the proper immune system feedback response among diverse circumstances. Available circulating THs do traffic in two distinct ways depending on the metabolic condition. Mechanistically, internalized THs form a stable complex with their specific receptors, which, upon direct or indirect binding to DNA, triggers a genomic response by activating transcriptional factors, such as those belonging to the Wnt/β-catenin pathway. Alternatively, THs engage integrin αvβ3 receptor on cell membrane and trigger a non-genomic response, which can also signal to the nucleus. In addition, we highlight THs-dependent inflammasome complex modulation and describe new crucial pathways involved in microRNA regulation by THs, in physiological and patho-physiological conditions, which modify the HPT axis and THs performances. Finally, we focus on the non-thyroidal illness syndrome in which the HPT axis is altered and, in turn, affects circulating levels of active THs as reported in viral infections, particularly in immunocompromised patients infected with human immunodeficiency virus.
Nuclear Factor-κB Activating Protein Plays an Oncogenic Role in Neuroblastoma Tumorigenesis and Recurrence Through the Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathway
Authors: Liu Jun , Zhang Mingyu , Kan Ying , Wang Wei , Liu Jie , Gong Jianhua , Yang Jigang
Published: January 2021

Nuclear factor-κB activating protein (NKAP) is a conserved nuclear protein that acts as an oncogene in various cancers and is associated with a poor prognosis. This study aimed to investigate the role of NKAP in neuroblastoma (NB) progression and recurrence. We compared NKAP gene expression between 89 recurrence and 134 non-recurrence patients with NB by utilizing the ArrayExpress database. The relationship between NKAP expression and clinicopathological features was evaluated by correlation analysis. We knocked down NKAP expression in NB1 and SK-N-SH cells by small interfering RNA transfection to verify its role in tumor proliferation, apoptosis, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. NKAP gene expression in NB tissues was significantly overexpressed in the recurrence group compared with the non-recurrence group, and NKAP was enriched in the PI3K/AKT pathway. Correlation analysis revealed NKAP expression was correlated with chromosome 11q deletion in patients with NB. Knockdown of NKAP expression significantly inhibited the proliferation and promoted the apoptosis of NB1 and SK-N-SH cells. Moreover, we found that small interfering NKAP significantly reduced p-PI3K and p-AKT expression. NKAP knockdown played an oncogenic role in NB by inhibiting PI3K/AKT signaling pathway activations both in vitro and in vivo. Our research revealed that NKAP mediates NB cells by inhibited proliferation and promoted apoptosis through activating the PI3K/AKT signaling pathways, and the expression of NKAP may act as a novel biomarker for predicting recurrence and chromosome 11q deletion in patients with NB.
Alterations in Chromatin Structure and Function in the Microglia
Authors: Fujita Yuki , Yamashita Toshihide
Published: January 2021

Microglia are resident immune cells in the central nervous system (CNS). Microglia exhibit diversity in their morphology, density, electrophysiological properties, and gene expression profiles, and play various roles in neural development and adulthood in both physiological and pathological conditions. Recent transcriptomic analysis using bulk and single-cell RNA-seq has revealed that microglia can shift their gene expression profiles in various contexts, such as developmental stages, aging, and disease progression in the CNS, suggesting that the heterogeneity of microglia may be associated with their distinct functions. Epigenetic changes, including histone modifications and DNA methylation, coordinate gene expression, thereby contributing to the regulation of cellular state. In this review, we summarize the current knowledge regarding the epigenetic mechanisms underlying spatiotemporal and functional diversity of microglia that are altered in response to developmental stages and disease conditions. We also discuss how this knowledge may lead to advances in therapeutic approaches for diseases.
Mst1 Knockout Alleviates Mitochondrial Fission and Mitigates Left Ventricular Remodeling in the Development of Diabetic Cardiomyopathy
Authors: Feng Xinyu , Wang Shanjie , Yang Xingjun , Lin Jie , Man Wanrong , Dong Yuan , Zhang Yan , Zhao Zhijing , Wang Haichang , Sun Dongdong
Published: January 2021

The disruption of mitochondrial dynamics is responsible for the development of diabetic cardiomyopathy (DCM). However, the mechanisms that regulate the balance of mitochondrial fission and fusion are not well-understood. Wild-type, Mst1 transgenic and Mst1 knockout mice were induced with experimental diabetes by streptozotocin injection. In addition, primary neonatal cardiomyocytes were isolated and cultured to simulate diabetes to explore the mechanisms. Echocardiograms and hemodynamic measurements revealed that Mst1 knockout alleviated left ventricular remodeling and cardiac dysfunction in diabetic mice. Mst1 knockdown significantly decreased the number of TUNEL-positive cardiomyocytes subjected to high-glucose (HG) medium culture. Immunofluorescence study indicated that Mst1 overexpression enhanced, while Mst1 knockdown mitigated mitochondrial fission in DCM. Mst1 participated in the regulation of mitochondrial fission by upregulating the expression of Drp1, activating Drp1S616 phosphorylation and Drp1S637 dephosphorylation, as well as promoting Drp1 recruitment to the mitochondria. Furthermore, Drp1 knockdown abolished the effects of Mst1 on mitochondrial fission, mitochondrial membrane potential and mitochondrial dysfunction in cardiomyocytes subjected to HG treatment. These results indicated that Mst1 knockout inhibits mitochondrial fission and alleviates left ventricular remodeling thus prevents the development of DCM.
Plastin 3 in X-Linked Osteoporosis: Imbalance of Ca2+-Dependent Regulation Is Equivalent to Protein Loss
Authors: Schwebach Christopher L. , Kudryashova Elena , Kudryashov Dmitri S.
Published: January 2021

Osteogenesis imperfecta is a genetic disorder disrupting bone development and remodeling. The primary causes of osteogenesis imperfecta are pathogenic variants of collagen and collagen processing genes. However, recently variants of the actin bundling protein plastin 3 have been identified as another source of osteogenesis imperfecta. Plastin 3 is a highly conserved protein involved in several important cellular structures and processes and is controlled by intracellular Ca2+which potently inhibits its actin-bundling activity. The precise mechanisms by which plastin 3 causes osteogenesis imperfecta remain unclear, but recent advances have contributed to our understanding of bone development and the actin cytoskeleton. Here, we review the link between plastin 3 and osteogenesis imperfecta highlightingin vitrostudies and emphasizing the importance of Ca2+regulation in the localization and functionality of plastin 3.
FKBP25 Regulates Meiotic Apparatus During Mouse Oocyte Maturation
Authors: Wang Danni , Sun Hongzheng , Zhang Jiaqi , Huang Zhenyue , Li Congyang , Han Longsen , Xin Yongan , Tang Shoubin , Ge Juan , Wang Qiang
Published: January 2021

FK506 binding proteins 25 (FKBP25) has been shown to function in ribosome biogenesis, chromatin organization, and microtubule stability in mitosis. However, the role of FKBP25 in oocyte maturation has not been investigated. Here, we report that oocytes with FKBP25 depletion display abnormal spindle assembly and chromosomes alignment, with defective kinetochore-microtubule attachment. Consistent with this finding, aneuploidy incidence is also elevated in oocytes depleted of FKBP25. Importantly, FKBP25 protein level in old oocytes is significantly reduced, and ectopic expression of FKBP25 could partly rescue the aging-associated meiotic defects. In addition, by employing site-specific mutagenesis, we identify that serine 163 is a major, if not unique, phosphorylation site modulating the action of FKBP25 on meiotic maturation. In summary, our data indicate that FKBP25 is a pivotal factor for determining oocyte quality, and may mediate the effects of maternal aging on female reproduction.
Decoding Genetics of Congenital Heart Disease Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs)
Authors: Lin Hui , McBride Kim L. , Garg Vidu , Zhao Ming-Tao
Published: January 2021

Congenital heart disease (CHD) is the most common cause of infant death associated with birth defects. Recent next-generation genome sequencing has uncovered novel genetic etiologies of CHD, from inherited andde novovariants to non-coding genetic variants. The next phase of understanding the genetic contributors of CHD will be the functional illustration and validation of this genome sequencing data in cellular and animal model systems. Human induced pluripotent stem cells (iPSCs) have opened up new horizons to investigate genetic mechanisms of CHD using clinically relevant and patient-specific cardiac cells such as cardiomyocytes, endothelial/endocardial cells, cardiac fibroblasts and vascular smooth muscle cells. Using cutting-edge CRISPR/Cas9 genome editing tools, a given genetic variant can be corrected in diseased iPSCs and introduced to healthy iPSCs to define the pathogenicity of the variant and molecular basis of CHD. In this review, we discuss the recent progress in genetics of CHD deciphered by large-scale genome sequencing and explore how genome-edited patient iPSCs are poised to decode the genetic etiologies of CHD by coupling with single-cell genomics and organoid technologies.
Regulation of Wnt Signaling Pathways at the Plasma Membrane and Their Misregulation in Cancer
Authors: Azbazdar Yagmur , Karabicici Mustafa , Erdal Esra , Ozhan Gunes
Published: January 2021

Wnt signaling is one of the key signaling pathways that govern numerous physiological activities such as growth, differentiation and migration during development and homeostasis. As pathway misregulation has been extensively linked to pathological processes including malignant tumors, a thorough understanding of pathway regulation is essential for development of effective therapeutic approaches. A prominent feature of cancer cells is that they significantly differ from healthy cells with respect to their plasma membrane composition and lipid organization. Here, we review the key role of membrane composition and lipid order in activation of Wnt signaling pathway by tightly regulating formation and interactions of the Wnt-receptor complex. We also discuss in detail how plasma membrane components, in particular the ligands, (co)receptors and extracellular or membrane-bound modulators, of Wnt pathways are affected in lung, colorectal, liver and breast cancers that have been associated with abnormal activation of Wnt signaling. Wnt-receptor complex components and their modulators are frequently misexpressed in these cancers and this appears to correlate with metastasis and cancer progression. Thus, composition and organization of the plasma membrane can be exploited to develop new anticancer drugs that are targeted in a highly specific manner to the Wnt-receptor complex, rendering a more effective therapeutic outcome possible.
Gut Microbiota Composition Changes in Constipated Women of Reproductive Age
Authors: Li Hongxia , Chen Jianwei , Ren Xiaojing , Yang Chuanli , Liu Shuai , Bai Xinshu , Shan Shuhua , Dong Xiushan
Published: January 2021

Background

Chronic constipation is one of the most prevalent functional gastrointestinal disorders, yet its etiology is multifactorial, and the pathophysiological mechanism is still unclear. Previous studies have shown that the gut microbiota of constipated patients differs from healthy controls; however, many discrepancies exist in the findings, and no clear link has been confirmed between chronic constipation and changes in the gut microbiota. Growing evidence indicates that age, gender, and hormone levels can affect the composition of gut microbiota. The aim of this study is to examine the overall changes in gut microbiota within a specific sub-population of patients, namely, constipated women of reproductive age.

Methods

We carried out a cross-sectional study comparing the fecal microbial composition of 30 healthy women and 29 constipated women using 16S rRNA gene sequencing. Only women of reproductive age were recruited to reduce the effects of age, gender, and hormone levels on the microbiome, and to prevent conflating the impact of these factors with the effects of constipation.

Results

There were obvious differences in the gut microbiota in constipated women of reproductive age compared with the healthy controls, manifesting mainly as a significant increase in the abundance of Bacteroides (p < 0.05) and a significant decrease in the abundance of Proteobacteria (p < 0.01). The overall composition of the gut microbiota in each group was different, which was reflected in the ratios of Firmicutes to Bacteroidetes (F/B), which was 1.52 in the constipated group vs. 2.21 in the healthy group. Additionally, there was a significant decrease in butyrate-producing bacteria, like Roseburia and Fusicatenibacter (p < 0.01).

Conclusion

The overall composition of the gut microbiota changed in constipated women of reproductive age, characterized by a loss in Proteobacteria and an increase in Bacteroidetes. Furthermore, the abundance of some butyrate-producing bacteria also reduced. These changes may reflect the unique interactions between host and some bacteria, or some bacterial metabolic products, which may be important targets for future studies to explore the pathogenesis of constipation.
Changes in the Ice-Front Position and Surface Elevation of Glaciar Pío XI, an Advancing Calving Glacier in the Southern Patagonia Icefield, From 2000–2018
Authors: Hata Shuntaro , Sugiyama Shin
Published: January 2021

Glaciar Pío XI has advanced and thickened over the past several decades in contrast to the generally retreating and thinning trends seen in other glaciers in the Southern Patagonia Icefield (SPI). To quantify recent changes in ice-front positions and glacier surface elevation over the ablation area of Glaciar Pío XI, we analyzed satellite data acquired from 2000 to 2018. Two major glacier termini, and most of the small outlet glaciers, showed advancing trends, including the largest advance (1,400 m), observed at the southern terminus during the study period. Surface elevation increased by 37.3 ± 0.4 m as a mean over the study area, and the rate of the increase accelerated by 135 ± 10% from Period 1 (2000–2007) to Period 2 (2007–2017/18). Elevation change during Period 1 was only slightly positive except for extraordinary thickening (∼20 m a−1) observed near the southern terminus and one of the outlet glacier fronts, whereas significant thickening (∼2.7 m a−1) occurred over the entire ablation area during Period 2. Satellite imagery showed an emergence of sedimentary mounds in front of the southern terminus, suggesting that reduction in frontal ablation and increasingly compressive flow regime are the main drivers of the recent rapid thickening and advance. Most likely, the influence of the sediment deposition on the southern terminus subsequently propagated to the northern terminus and upper reaches of the glacier. The rate of ice mass increase during the study period was 0.48 ± 0.03 Gt a−1, which corresponds to 4% of the total mass loss from the SPI from 2000 to 2015/16.
Integrative Analyses of Genes Associated With Osteoporosis in CD16+ Monocyte
Authors: Hu Bin , Kong Xiangan , Li Li , Dai Fang , Zhang Qiu , Shi Ruifeng
Published: January 2021

Background

Osteoporosis is a metabolic bone disease characterized by decreased bone mineral density and abnormal bone quality. Monocytes can secret cytokines for bone resorption, resulting in bone mass loss. However, the mechanism by which monocytes subpopulations lead to osteoporosis remains unclear. The aim of this study was to identify genes associated with osteoporosis in monocytes subsets.

Methods

Three microarray datasets including GSE7158 (transcription of low/high-peak bone mass), GSE101489 (transcription of CD16+/CD16− monocyte) and GSE93883 (miRNA expression profile of primary osteoporosis) were derived from the Gene Expression Omnibus (GEO) database and analyzed with GEO2R tool to identify differentially expressed genes (DEGs). Functional enrichment was analyzed using Metascape database and GSEA software. STRING was utilized for the Protein–Protein Interaction Network construct. The hub genes were screened out using the Cytoscape software. Related miRNAs were predicted in miRWalk, miRDB, and TargetScan databases.

Results

Total 368 DEGs from GSE7158 were screened out, which were mostly enriched in signaling, positive regulation of biological process and immune system process. The hub genes were clustered into two modules by PPI network analysis. We identified 15 overlapping DGEs between GSE101489 and GSE7158 microarray datasets. Moreover, all of them were up-regulated genes in both datasets. Then, nine key genes were screened out from above 15 overlapping DEGs using Cytoscape software. It is a remarkable fact that the nine genes were all in one hub gene module of GSE7158. Additionally, 183 target miRNAs were predicted according to the above nine DEGs. After cross-verification with miRNA express profile dataset for osteoporosis (GSE93883), 12 DEmiRNAs were selected. Finally, a miRNA-mRNA network was constructed with the nine key genes and 12 miRNAs, which were involved in osteoporosis.

Conclusion

Our analysis results constructed a gene expression framework in monocyte subsets for osteoporosis. This approach could provide a novel insight into osteoporosis.
Clinical Potential of Extracellular Vesicles in Type 2 Diabetes
Authors: Liu Jie , Sun Xin , Zhang Fu-Liang , Jin Hang , Yan Xiu-Li , Huang Shuo , Guo Zhen-Ni , Yang Yi
Published: January 2021

Type 2 diabetes (T2D) is a major public health disease which is increased in incidence and prevalence throughout the whole world. Insulin resistance (IR) in peripheral tissues and insufficient pancreatic β-cell mass and function have been recognized as primary mechanisms in the pathogenesis of T2D, while recently, systemic chronic inflammation resulting from obesity and a sedentary lifestyle has also gained considerable attention in T2D progression. Nowadays, accumulating evidence has revealed extracellular vesicles (EVs) as critical mediators promoting the pathogenesis of T2D. They can also be used in the diagnosis and treatment of T2D and its complications. In this review, we briefly introduce the basic concepts of EVs and their potential roles in the pathogenesis of T2D. Then, we discuss their diagnostic and therapeutic potentials in T2D and its complications, hoping to open new prospects for the management of T2D.
Calcaneal Ultrasound and Its Relation to Dietary and Lifestyle Factors, Anthropometry, and Vitamin D Deficiency in Young Medical Students
Authors: Jafri Lena , Majid Hafsa , Ahmed Sibtain , Naureen Ghazala , Khan Aysha Habib
Published: January 2021

Background

Bone quality and peak bone mass are greatly affected by lifestyle factors. The objective of the study was to investigate the relationships between anthropometry, dietary and caloric intake, body composition measurements, physical activity, and vitamin D status with quantitative ultrasound-based bone parameters among medical students.

Methods

Both male and female medical college students were included in this study. A detailed questionnaire was administered, collecting clinical, dietary, physical activity information, physical examination details, including body mass index (BMI). Body composition (total body fat, total body water, muscle mass, mean visceral fat mass, basal metabolic rate, bone mass using a bioelectrical impedance analyzer) and calcaneal heel ultrasound parameters were measured using an Osteosys Sonost-3000, Ultrasound Bone Densitometer were measured, respectively.

Results

In this cross-sectional study, 211 healthy students with a mean age of 20.1 ± 1.1 years, 51.7% (n = 109) were males. Majority (79.4%) of the young adults had vitamin D deficiency. The mean BMI, calcium intake, and vitamin D levels were 22.35 ± 3.43 kg/m2, 788.7 ± 364.8 mg/day, and 15.02 ± 8.63 ng/ml, respectively. Female subjects compared to males had statistically significantly lower daily energy intake, muscle mass, visceral fat mass, calcium intake, and vitamin D levels. In addition the median Z-scores in females [−1.40 (−0.57 to −1.82)] was significantly poorer than the male [−0.50 (0.20 to −1.3)] counterparts, p-value <0.001. Multiple regression analysis showed that overall body fat percent (p-value 0.016) and visceral fat percent (p-value 0.029) were the only significant negative predictors to the calcaneal bone quality index (BQI) values.

Conclusion

Adolescent lifestyle patterns can influence young adult bone strength. The young Pakistani females exhibited significantly lower dietary intakes and more inadequate bone parameters compared to males. Our data suggest that total body and visceral fat percent are the predominant negatively associated determinant of bone strength for this cohort. Calcaneal ultrasound can be utilized for mass screening of young adults for identification of low BMD.
Electroacupuncture Regulates Inguinal White Adipose Tissue Browning by Promoting Sirtuin-1-Dependent PPARγ Deacetylation and Mitochondrial Biogenesis
Authors: Tang Qianqian , Lu Mengjiang , Xu Bin , Wang Yaling , Lu Shengfeng , Yu Zhi , Jing Xinyue , Yuan Jinhong
Published: January 2021

Background

Previous studies had suggested that electroacupuncture (EA) can promote white adipose tissue (WAT) browning to counter obesity. But the mechanism was still not very clear.

Aim

In this study, we aim to study the effect of EA on promoting inguinal WAT (iWAT) browning and its possible mechanism.

Method

Three-week-old rats were randomly divided into a normal diet (ND) group and a high-fat diet (HFD) group. After 10 weeks, the HFD rats were grouped into HFD + EA group and HFD control group. Rats in the EA group were electro-acupunctured for 4 weeks on Tianshu (ST25) acupoint under gas anesthesia with isoflurane, while the rats in HFD group were under gas anesthesia only. Body weight and cumulative food intake were monitored, and H&E staining was performed to assess adipocyte area. The effect of EA on WAT was assessed by qPCR, immunoblotting, immunoprecipitation and Co-immunoprecipitation. Mitochondria were isolated from IWAT to observe the expression of mitochondrial transcription factor A (TFAM).

Results

The body weight, WAT/body weight ratio and cumulative food consumption obviously decreased (P < 0.05) in the EA group. The expressions of brown adipose tissue (BAT) markers were increased in the iWAT of EA rats. Nevertheless, the mRNA expressions of WAT genes were suppressed by 4-week EA treatment. Moreover, EA increased the protein expressions of SIRT-1, PPARγ, PGC-1α, UCP1 and PRDM16 which trigger the molecular conversion of iWAT browning. The decrease of PPARγ acetylation was also found in EA group, indicating EA could advance WAT-browning through SIRT-1 dependent PPARγ deacetylation pathway. Besides, we found that EA could activate AMPK to further regulate PGC-1α-TFAM-UCP1 pathway to induce mitochondrial biogenesis.

Conclusion

In conclusion, EA can remodel WAT to BAT through inducing SIRT-1 dependent PPARγ deacetylation, and regulating PGC-1α-TFAM-UCP1 pathway to induce mitochondrial biogenesis. This may be one of the mechanisms by which EA affects weight loss.
Efficiency of Aerial Drones for Macrolitter Monitoring on Baltic Sea Beaches
Authors: Escobar-Sánchez Gabriela , Haseler Mirco , Oppelt Natascha , Schernewski Gerald
Published: January 2021

Marine litter is a global problem that requires soon management and design of mitigation strategies. Marine litter monitoring is an essential step to assess the abundances, distributions, sinks and hotspots of pollution as well as the effectiveness of mitigation measures. However, these need to be time and cost-efficient, fit for purpose and context, as well as provide a standardized methodology suitable for comparison among surveys. In Europe, the Marine Strategy Framework Directive (MSFD) provides a structure for the effective implementation of long-term monitoring. For beaches, the well-established 100 m OSPAR macrolitter monitoring exists. However, this method requires a high staff effort and suffers from a high spatio-temporal variability of the results. In this study, we test the potential of aerial drones or Unmanned Aerial Vehicles (UAVs) together with a Geographic Information System approach for semi-automatic classification of meso- (1–25 mm) and macrolitter (>25 mm) at four beaches of the southern Baltic Sea. Visual screening of drone images in recovery experiments (50 m2 areas) at 10 m height revealed an accuracy of 99%. The total accuracy of classification using object-based classification was 45–90% for the classification with four classes and 50–66% for the classification with six classes, depending on the algorithm and flight height used. On 100 m beach monitoring transects the accuracy was between 39–74% (4 classes) and 25–74% (6 classes), with very low kappa values, indicating that the GIS classification method cannot be regarded as a reliable method for the detection of litter in the Southern Baltic. In terms of cost-efficiency, the drone method showed high reproducibility and moderate accuracy, with much lower flexibility and quality of data than a comparable spatial-OSPAR method. Consequently, our results suggest that drone based monitoring cannot be recommended as a replacement or complement existing methods in southern Baltic beaches. However, drone monitoring could be useful at other sites and other methods for image analysis should be tested to explore this tool for fast-screening of non-accessible sites, fragile ecosystems, floating litter or heavily polluted beaches.
Forest Degradation and Inter-annual Tree Level Brazil Nut Production in the Peruvian Amazon
Authors: Jansen Merel , Guariguata Manuel R. , Chiriboga-Arroyo Fidel , Quaedvlieg Julia , Vargas Quispe Flor M. , Arroyo Quispe Eriks , García Roca Mishari R. , Corvera-Gomringer Ronald , Kettle Chris J.
Published: January 2021

Brazil nuts are an economically important non-timber forest product throughout the Amazon Basin, but the forests in which they grow are under threat of severe degradation by logging, road building, agricultural expansion, and forest fires. As a result, many Brazil nut trees grow within a mosaic of young secondary forest, primary forest remnants and agricultural fields. Little is known about the reproductive ecology and fruit production of Brazil nut in such degraded landscapes. Previous studies on Brazil nut productivity did not explicitly address forest degradation as a factor. In this study, we analyzed the extent to which Brazil nut fruit production is affected by the level of forest degradation. We collected 3 years of fruit production data of 126 Brazil nut trees occurring in degraded forest (the above-mentioned mosaics) and closed canopy (i.e., undegraded) forest in and around the Tambopata National Reserve in Madre de Dios, Peru. We analyzed the effect of forest degradation at two different levels: at the site type (i.e., degraded vs. undegraded forest) and the individual tree level (quantified as stand basal area and stem density around the individual Brazil nut trees). Stand basal area around the individual Brazil nut trees significantly positively influenced tree fruit production in all 3 years and stem density in year 2 and 3, with strongest effects in the 3rd year, and weakest effect in the 1st year, coinciding with an El Niño year. Trees in undegraded forest produced more fruits in the 2nd and 3rd year than trees in degraded forest (29.4% and 35.8% more, respectively), but not in the 1st year in which trees in undegraded forest produced 31.7% less fruits than trees in degraded forest. These within year effects were not significant, although the effects significantly differed between years. Our results show that forest degradation can affect Brazil nut fruit production, and suggest that the strength (and possibly the sign) of this effect might be different in (extreme) El Niño years. This illustrates the potential importance of restoring degraded forest to enhance resilience and protect the livelihoods of people depending on the Brazil nut trade.