bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calcium based siRNA coating: a novel approach for knockdown of HER2 gene in MCF-7 cells using gold nanoparticles
Authors: Sami Abdul , Naqvi S.M. Saqalan , Qayyum Mazhar , Raza Rao Abida , Sabitaliyevich Uteuliyev Yerzhan , Ahmad M. Sheeraz 
Published: October 2020

Surface functionalization of nanoparticles (NPs) for therapeutic siRNA delivery into cancer cells has gained interest. The present study was designed for surface functionalization of gold nanoparticles (AuNPs) for efficient siRNA delivery and knockdown in cancer cells. In order to achieve this objective, AuNPs were coated with HER2-siRNA in the presence of 11-mercaptoundecanoic acid (11-MUA), calcium chloride (CaCl2) and polyethyleneimine (PEI) in alternate charge bearing successive layers. MCF-7 cells were cultured and transfected with fabricated assembly of AuNPs. Cytotoxicity analysis revealed that the half inhibitory concentration (IC50) for the formulation was 45.35 nM . Total RNA was isolated from transfected cells, reverse transcribed into complementary DNA (cDNA) and real-time polymerase chain reaction (RT-PCR) was performed. The RT-PCR based delta-delta Ct analysis in treated cells revealed a significant 18.94 times decrease (p<0.001) in the expression of HER2 gene standardized with ACTB housekeeping gene as compared to untreated cells, which makes this formulation a potent approach for siRNA delivery and gene knockout.
β-Adrenergic Receptors/Epac Signaling Increases the Size of the Readily Releasable Pool of Synaptic Vesicles Required for Parallel Fiber LTP
Authors: Martín Ricardo , García-Font Nuria , Suárez-Pinilla Alberto Samuel , Bartolomé-Martín David , Ferrero José Javier , Luján Rafael , Torres Magdalena , Sánchez-Prieto José 
Published: October 2020

The second messenger cAMP is an important determinant of synaptic plasticity that is associated with enhanced neurotransmitter release. Long-term potentiation (LTP) at parallel fiber (PF)–Purkinje cell (PC) synapses depends on a Ca2+-induced increase in presynaptic cAMP that is mediated by Ca2+-sensitive adenylyl cyclases. However, the upstream signaling and the downstream targets of cAMP involved in these events remain poorly understood. It is unclear whether cAMP generated by β-adrenergic receptors (βARs) is required for PF–PC LTP, although noradrenergic varicosities are apposed in PF–PC contacts. Guanine nucleotide exchange proteins directly activated by cAMP [Epac proteins (Epac 1-2)] are alternative cAMP targets to protein kinase A (PKA) and Epac2 is abundant in the cerebellum. However, whether Epac proteins participate in PF–PC LTP is not known. Immunoelectron microscopy demonstrated that βARs are expressed in PF boutons. Moreover, activation of these receptors through their agonist isoproterenol potentiated synaptic transmission in cerebellar slices from mice of either sex, an effect that was insensitive to the PKA inhibitors (H-89, KT270) but that was blocked by the Epac inhibitor ESI 05. Interestingly, prior activation of these βARs occluded PF–PC LTP, while the β1AR antagonist metoprolol blocked PF–PC LTP, which was also absent inEpac2−/−mice. PF–PC LTP is associated with an increase in the size of the readily releasable pool (RRP) of synaptic vesicles, consistent with the isoproterenol-induced increase in vesicle docking in cerebellar slices. Thus, the βAR-mediated modulation of the release machinery and the subsequent increase in the size of the RRP contributes to PF–PC LTP.SIGNIFICANCE STATEMENTG-protein-coupled receptors modulate the release machinery, causing long-lasting changes in synaptic transmission that influence synaptic plasticity. Nevertheless, the mechanisms underlying synaptic responses to β-adrenergic receptor (βAR) activation remain poorly understood. An increase in the number of synaptic vesicles primed for exocytosis accounts for the potentiation of neurotransmitter release driven by βARs. This effect is not mediated by the canonical protein kinase A pathway but rather, through direct activation of the guanine nucleotide exchange protein Epac by cAMP. Interestingly, this βAR signaling via Epac is involved in long term potentiation at cerebellar granule cell-to-Purkinje cell synapses. Thus, the pharmacological activation of βARs modulates synaptic plasticity and opens therapeutic opportunities to control this phenomenon.
4E-BP1 Protects Neurons from Misfolded Protein Stress and Parkinson's Disease Toxicity by Inducing the Mitochondrial Unfolded Protein Response
Authors: Dastidar Somasish Ghosh , Pham Michael T. , Mitchell Matthew B. , Yeom Steven G. , Jordan Sarah , Chang Angela , Sopher Bryce L. , La Spada Albert R. 
Published: October 2020

Decline of protein quality control in neurons contributes to age-related neurodegenerative disorders caused by misfolded proteins. 4E-BP1 is a key node in the regulation of protein synthesis, as activated 4E-BP1 represses global protein translation. Overexpression of 4E-BP1 mediates the benefits of dietary restriction and can counter metabolic stress, and 4E-BP1 disinhibition on mTORC1 repression may be neuroprotective; however, whether 4E-BP1 overexpression is neuroprotective in mammalian neurons is yet to be fully explored. To address this question, we generated 4E-BP1-overexpressing transgenic mice and confirmed marked reductions in protein translation in 4E-BP1-overexpressing primary neurons. After documenting that 4E-BP1-overexpressing neurons are resistant to proteotoxic stress elicited by brefeldin A treatment, we exposed primary neurons to three different Parkinson's disease (PD)-linked toxins (rotenone, maneb, or paraquat) and documented significant protection in neurons from newborn male and female4E-BP1-OEtransgenic mice. We observed 4E-BP1-dependent upregulation of genes encoding proteins that comprise the mitochondrial unfolded protein response, and noted 4E-BP1 overexpression required activation of the mitochondrial unfolded protein response for neuroprotection against rotenone toxicity. We also tested whether 4E-BP1 could prevent α-synuclein neurotoxicity by treating 4E-BP1-overexpressing primary neurons with α-synuclein preformed fibrils, and we observed marked reductions in α-synuclein aggregation and neurotoxicity, thus validating that 4E-BP1 is a powerful suppressor of PD-linked pathogenic insults. Our results indicate that increasing 4E-BP1 expression or enhancing 4E-BP1 activation can robustly induce the mitochondrial unfolded protein response and thus could be an appealing strategy for treating a variety of neurodegenerative diseases, including especially PD.SIGNIFICANCE STATEMENTIn neurodegenerative disease, misfolded proteins accumulate and overwhelm normal systems of homeostasis and quality control. One mechanism for improving protein quality control is to reduce protein translation. Here we investigated whether neuronal overexpression of 4E-BP1, a key repressor of protein translation, can protect against misfolded protein stress and toxicities linked to Parkinson's disease, and found that 4E-BP1 overexpression prevented cell death in neurons treated with brefeldin A, rotenone, maneb, paraquat, or preformed fibrils of α-synuclein. When we sought the basis for 4E-BP1 neuroprotection, we discovered that 4E-BP1 activation promoted the mitochondrial unfolded protein response. Our findings highlight 4E-BP1 as a therapeutic target in neurodegenerative disease and underscore the importance of the mitochondrial unfolded protein response in neuroprotection against various insults.
Dopamine-Dependent QR2 Pathway Activation in CA1 Interneurons Enhances Novel Memory Formation
Authors: Gould Nathaniel L. , Sharma Vijendra , Hleihil Mohammad , Kolatt Chandran Sailendrakumar , David Orit , Edry Efrat , Rosenblum Kobi 
Published: October 2020

The formation of memory for a novel experience is a critical cognitive capacity. The ability to form novel memories is sensitive to age-related pathologies and disease, to which prolonged metabolic stress is a major contributing factor. Presently, we describe a dopamine-dependent redox modulation pathway within the hippocampus of male mice that promotes memory consolidation. Namely, following novel information acquisition, quinone reductase 2 (QR2) is suppressed by miRNA-182 (miR-182) in the CA1 region of the hippocampus via dopamine D1 receptor (D1R) activation, a process largely facilitated by locus coeruleus activity. This pathway activation reduces ROS generated by QR2 enzymatic activity, a process that alters the intrinsic properties of CA1 interneurons 3 h following learning, in a form of oxidative eustress. Interestingly, novel experience decreases QR2 expression predominately in inhibitory interneurons. Additionally, we find that in aged animals this newly described QR2 pathway is chronically under activated, resulting in miR-182 underexpression and QR2 overexpression. This leads to accumulative oxidative stress, which can be seen in CA1 via increased levels of oxidized, inactivated potassium channel Kv2.1, which undergoes disulfide bridge oligomerization. This newly described interneuron-specific molecular pathway lies alongside the known mRNA translation-dependent processes necessary for long-term memory formation, entrained by dopamine in CA1. It is a process crucial for the distinguishing features of novel memory, and points to a promising new target for memory enhancement in aging and age-dependent diseases.SIGNIFICANCE STATEMENTOne way in which evolution dictates which sensory information will stabilize as an internal representation, relies on information novelty. Dopamine is a central neuromodulator involved in this process in the mammalian hippocampus. Here, we describe for the first time a dopamine D1 receptor-dependent quinone reductase 2 pathway in interneurons. This is a targeted redox event necessary to delineate a novel experience to a robust long-term internal representation. Activation of this pathway alone can explain the effect novelty has on “flashbulb” memories, and it can become dysfunctional with age and diseases, such as Alzheimer's disease.
Inactivation of the GATA Cofactor ZFPM1 Results in Abnormal Development of Dorsal Raphe Serotonergic Neuron Subtypes and Increased Anxiety-Like Behavior
Authors: Tikker Laura , Casarotto Plinio , Singh Parul , Biojone Caroline , Piepponen T. Petteri , Estartús Nuri , Seelbach Anna , Sridharan Ravindran , Laukkanen Liina , Castrén Eero , Partanen Juha 
Published: October 2020

Serotonergic neurons in the dorsal raphe (DR) nucleus are associated with several psychiatric disorders including depression and anxiety disorders, which often have a neurodevelopmental component. During embryonic development, GATA transcription factors GATA2 and GATA3 operate as serotonergic neuron fate selectors and regulate the differentiation of serotonergic neuron subtypes of DR. Here, we analyzed the requirement of GATA cofactor ZFPM1 in the development of serotonergic neurons usingZfpm1conditional mouse mutants. Our results demonstrated that, unlike the GATA factors, ZFPM1 is not essential for the early differentiation of serotonergic precursors in the embryonic rhombomere 1. In contrast, in perinatal and adult male and femaleZfpm1mutants, a lateral subpopulation of DR neurons (ventrolateral part of the DR) was lost, whereas the number of serotonergic neurons in a medial subpopulation (dorsal region of the medial DR) had increased. Additionally, adult male and femaleZfpm1mutants had reduced serotonin concentration in rostral brain areas and displayed increased anxiety-like behavior. Interestingly, femaleZfpm1mutant mice showed elevated contextual fear memory that was abolished with chronic fluoxetine treatment. Altogether, these results demonstrate the importance of ZFPM1 for the development of DR serotonergic neuron subtypes involved in mood regulation. It also suggests that the neuronal fate selector function of GATAs is modulated by their cofactors to refine the differentiation of neuronal subtypes.SIGNIFICANCE STATEMENTPredisposition to anxiety disorders has both a neurodevelopmental and a genetic basis. One of the brainstem nuclei involved in the regulation of anxiety is the dorsal raphe, which contains different subtypes of serotonergic neurons. We show that inactivation of a transcriptional cofactor ZFPM1 in mice results in a developmental failure of laterally located dorsal raphe serotonergic neurons and changes in serotonergic innervation of rostral brain regions. This leads to elevated anxiety-like behavior and contextual fear memory, alleviated by chronic fluoxetine treatment. Our work contributes to understanding the neurodevelopmental mechanisms that may be disturbed in the anxiety disorder.
Geochemistry of Basaltic Merbabu Volcanic Rocks, Central Java, Indonesia
Authors: Mulyaningsih Sri , Shaban Godang 
Published: October 2020

DOI: 10.17014/ijog.7.2.161-178The studied area is located along the hiking track of Kajor - Selo, the south flank of Merbabu Volcano, Central Java, Indonesia. Olivine basalt and augite-rich basalt compose the volcanic rocks. A geochemical study recognizes these basalts which tend to originate from the product of tholeiitic magma, in terms of transitional enriched mantle source. It is interpreted to have been formed as primary magma that mixed later with higher degrees of partial melting with a mantle wedge. Both fl uid and melt were derived from the mixing of lower active continental margin and subducting oceanic slab. This study also shows general trends of increasing incompatible elements, i.e. Rb, Ba, Pb2+, and Sr as LIL trace elements and Th, U, Nb, Ce, Zr, Hf, Nb, and Ta as HFS element comparing to basaltic andesites exposed at Thekelan, they show decreasing compatible of MgO, Fe2O3*, Al2O3, CaO, TiO2, Ni, Sr, and Ba in line with increasing SiO2. It was fractional crystallization process, shown by the slightly wide variation of Rb/Zr and La/Sm that indicates random crustal contamination.
South goes East. Zuid-Afrikaanse literatuur bij Volk & Welt
Authors: Zajas Pawel 
Published: October 2020

The paper analyses the transfer of South African literature to the German Democratic Republic. In its historiographic/methodological dimension it presents findings on the statistics of (South) African literature(s) translations in the Verlag Volk und Welt (the major East German publisher in the area of contemporary world literature), and on the place of literary translations in the East German foreign cultural policy, as well as in the socialist solidarity discourse of the Socialist Unity Party of Germany (SED) and the antiapartheid movement. Furthermore, findings are presented on the publisher-internal selection criteria applied to South African literature, based on the archival data from the Bundesarchiv in Berlin (i.e. applications for a print permit and internal/external reviews), on issues around the transformation and adaptation of literature translated in the realm of the East German Weltliteratur, and on the transfer of South African literature from the GDR, based on the English language series Seven Seas Books. Lastly, the function of this alternative canon, framed within the so-called ‘minor transnationalism’, is spelled out.
ASETABULUM KIRIKLARINDA ORTA DÖNEM KONSERVATİF VE CERRAHİ TEDAVİ SONUÇLARIMIZ
Authors: DİNÇER Recep , ATAY Tolga , BURÇ Halil , BAYKAL Yakup Barbaros , KIRDEMİR Vecihi 
Published: October 2020

Amaç
Deneyimli klinikler ve cerrahlar eklem uyumunun çok
önemli olduğu asetabuler bölgeye dair tecrübelerini
yayınlamaktadır. Biz de asetabulum kırığıyla başvuran
hastaların klinik tecrübelerimiz eşliğinde orta dönem
sonuçlarını sunmayı amaçladık.
Gereç ve Yöntem
Kliniğimize Ocak 2004-Mayıs 2013 tarihleri arasında
asetabulum kırığıyla başvuran 52 hastanın, kriterleri
taşıyan 37’si çalışmaya alındı. 10 hastaya konservatif,
27 hastaya cerrahi tedavi uygulandı. Cinsiyet dağılımı
28 erkek, 9 kadın şeklindeydi. Kırıkların 23’ü
sağ tarafta, 14’ü sol asetabulumu içermekteydi. Oluş
mekanizmalarına bakıldığında 16(%43,2) hasta araç
içi trafik kazası, 13(%35,1) hasta araç dışı trafik kazası,
6 hasta yüksekten düşme ve 2 hasta da üzerine
ağırlık düşmesi sonucu meydana gelmişti. 18 vakada
eşlik eden diğer ortopedik yaralanmalar mevcuttu.
Tüm hastalara Judet grafileri ve bilgisayarlı tomografi
çekildi.
Bulgular
Ortalama takip süresi 37 ay(12-108)’dı. Kırıkların 28’i
basit kırıklardan, 9’u kompleks kırıklardan oluşmaktaydı.
8(%21,6) hastada posterior kalça dislokasyonu
bulunmaktaydı. Acilde ilk değerlendirme sonrası tüm
hastaların kalçaları redükte edildi. Kırıkların oluş mekanizması
ve kırık tipi arasında bir ilişki saptanmadı(
p=0,456). Cerrahi uygulanan grupta 2, konservatif
grupta 1 olguda kırık sonrasında oluşan siyatik hasar
mevcuttu(p=0,440). 20 hastaya Kocher-Langenbeck
(%70,9), 3 hastaya İlioinguinal (%12,5), 2 hastaya Triradyat
(%8,3), 2 hastaya da kombine (%8,3) insizyon
uygulandı. Fonksiyonel sonuçlar Harris kalça skorlamasına
göre yapıldı; konservatif grupta 6(%60) hastada
mükemmel, 2(%20) hastada iyi, 2(%20) hastada
da kötü sonuç elde edildi(p=0,659). Cerrahi uygulanan
grupta klinik fonksiyonel sonuçları 10 hastada
mükemmel, 11 hastada iyi, 3 hastada orta ve 3 hastada
kötü olarak saptadık(p=0,665).
Sonuç
Kırık tipine uygun cerrahi planlama ile anatomik redüksiyon
uygun ve uyumlu hastalarda tatmin edici sonuçlar
ortaya çıkartır. Yalnız anatomik redüksiyonun
tek başına yeterli olmadığı, ilk gelişte dislokasyonun
olması, meydana gelen femur başı ve asetabulumdaki
kıkırdak hasarı ve siyatik sinir hasarı gibi komplikasyonların
da prospektif etkisinin olduğu unutulmamalıdır.
Predicting and Clustering Plant CLE Genes with a New Method Developed Specifically for Short Amino Acid Sequences
Authors: Zhang Zhe , Liu Lei , Kucukoglu Melis , Tian Dongdong , Larkin Robert M. , Shi Xueping , Zheng Bo 
Published: October 2020

Abstract
Background: The CLV3/ESR-RELATED (CLE) gene family encodes small secreted peptides (SSPs) and plays vital roles in plant growth and development by promoting cell-to-cell communication. The prediction and classification of CLE genes is challenging because of their low sequence similarity. Results: We developed a machine learning-aided method for predicting CLE genes by using a CLE motif-specific residual score matrix and a novel clustering method based on the Euclidean distance of 12 amino acid residues from the CLE motif in a site-weight dependent manner. In total, 2156 CLE candidates—including 627 novel candidates—were predicted from 69 plant species. The results from our CLE motif-based clustering are consistent with previous reports using the entire pre-propeptide. Characterization of CLE candidates provided systematic statistics on protein lengths, signal peptides, relative motif positions, amino acid compositions of different parts of the CLE precursor proteins, and decisive factors of CLE prediction. The approach taken here provides information on the evolution of the CLE gene family and provides evidence that the CLE and IDA/IDL genes share a common ancestor. Conclusions: Our new approach is applicable to SSPs or other proteins with short conserved domains and hence, provides a useful tool for gene prediction, classification and evolutionary analysis.
Magnitude of Turnover Intention and Associated Factors Among Nurses Working in Emergency Departments of Governmental Hospitals in Addis Ababa, Ethiopia: A cross sectional institutional based study.
Authors: Aniley Andualem Wubetie , Taye Biniyam , Girma Biruk 
Published: October 2020

Abstract
Background: Turnover intention is a probability of an employee to leave the current institution within a certain period due to various factors. It is the strongest predictor of actual turnover expected to increase as the intention increases. Emergency Department (ED) nurses are especially vulnerable to high turnover because of their increased risk of developing burnout and compassion fatigue associated with the work environment. This study is aimes to assess nurses’ intention to leave emergency departments and associated factors at selected governmental hospitals in Addis Ababa, Ethiopia.Methods: Institutional based cross-sectional study was conducted on 102 nurses in three selected governmental hospitals, Addis Ababa from February 19 to March 31, 2018, using a structured pre-tested self-administered questionnaire. The logistic regression model was used and an adjusted odds ratio with a 95% confidence interval was calculated to identify associated factors.Result: A total of 102 respondents were involved with a response rate of 91.1%. Among them, 79 (77.5%) respondents had the intention to leave the current working unit of the emergency department or hospital. Significant predictive factors of nurses' intention to leave their institutions are educational status (adjusted odds ratio (OR) =4.700, 95% confidence interval (CI)=1.033- 50.772; p<0.048), monthly income of less than 3145 Birr (adjusted OR=6.05, 95% CI=1.056-34.641; p<0.043) and professional autonomy (adjusted OR=0.191, 95% CI=0.040- 0.908; p<0.037).Conclusion: More than 77% of the respondents have the intention to leave their current working place of the emergency unit. Educational status, monthly income, and autonomy were significantly associated with emergency nurses’ turnover intention in three governmental hospitals. Emergency leaders and hospital managers should have made efforts to enhance nurses' decision making for patient care activities and shared decision overwork or unit related activities.
Influences on Contraceptive Method Choice Among Adolescent Women across Urban Centers in Nigeria: A Qualitative Study
Authors: Sanchez Elynn Kann , McGuire Courtney , Calhoun Lisa M. , Hainsworth Gwyn , Speizer Ilene S. 
Published: October 2020

Abstract
Background: Despite calls to increase contraceptive use among adolescents and youth, large gaps still exist, creating an unmet need for family planning. Past research has focused on barriers to seeking a method. There is less understanding of the types of methods young women want and who and what influences these decisions. This study examines what method characteristics young Nigerian women prioritize when choosing a method to inform future family planning programming.Methods: In 2018, eight focus group discussions (FGD) were conducted in the Nigerian cities of Ilorin and Jos with 83 young women ages 15-24. Participants were identified by community contacts and separated into groups by religion and marital status. The discussion guide utilized a vignette structure to understand the participants’ perceptions on contraceptive behavior and attitudes and misconceptions surrounding different types of methods. The FGDs were undertaken and analyzed by collaborative teams from the University of Ibadan and the University of North Carolina-Chapel Hill. A thematic analysis of the transcripts was performed using Atlas.ti, including two rounds of coding, and multiple reviews by the research team.Results: The method characteristics associated with young women’s contraceptive decisions include: side effects, reliability, length of coverage, privacy, cost, and accessibility. Side effects, reliability, and privacy were described as negatively linked to short-acting methods whereas easy accessibility and low cost were positive characteristics of these methods. Long-acting methods were generally viewed as positive. Participants’ focus on side effects commonly resulted from concerns about the impact on future fertility. The characteristics prioritized by individuals change throughout their adolescence and as their marital status changes. Providers, peers, parents, and partners were all found to have an influence over method choice in different ways. The role of these influencers also changes over the adolescent years. Conclusion: This study demonstrates that programs should prioritize expanding method choice to increase the number of available options to ensure all young women can access a method that fits their desired method characteristics. Programming should ensure that medically accurate information is widely distributed to harness providers, peers, parents and partners as a resource for information about specific methods.