bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interplay of isoform 1N4R tau protein and amyloid-β peptide fragment 25–35 in reducing and non-reducing conditions
Authors: Mohammadi Fatemeh , Takalloo Zeinab , Rahmani Hossein , Nasiri Khalili Mohammad Ali , Khajeh Khosro , Riazi Gholamhossein , H. Sajedi Reza 
Published: August 2020

Abstract
Amyloid-β (Aβ) peptide and tau protein are two hallmark proteins in Alzheimer's disease (AD); however, the parameters, which mediate the abnormal aggregation of Aβ and tau, have not been fully discovered. Here, we have provided an optimum method to purify tau protein isoform 1N4R by using nickel-nitrilotriacetic acid agarose chromatography under denaturing condition. The biochemical and biophysical properties of the purified protein were further characterized using in vitro tau filament assembly, tubulin polymerization assay, circular dichroism (CD) spectroscopy and atomic force microscopy. Afterwards, we investigated the effect of tau protein on aggregation of Aβ (25–35) peptide using microscopic imaging and cell viability assay. Incubation of tau at physiologic and supra-physiologic concentrations with Aβ25–35 for 40 days under reducing and non-reducing conditions revealed formation of two types of aggregates with distinct morphologies and dimensions. In non-reducing condition, the co-incubated sample showed granular aggregates, while in reducing condition, they formed annular protofibrils. Results from cell viability assay revealed the increased cell viability for the co-incubated sample. Therefore, the disassembling action shown by tau protein on Aβ25–35 suggests the possibility that tau may have a protective role in preventing Aβ peptide from acquiring the cytotoxic, aggregated form against oxidative stress damages.
Developmental Biology of Forensically Important Beetle, Necrophila (Calosilpha) brunnicollis (Coleoptera: Silphidae)
Authors: Jakubec Pavel , Qubaiová Jarin , Novák Martin , Růžička Jan 
Published: August 2020

AbstractThe postmortem interval (PMI) estimation, in cases where the body was discovered in an advanced stage of decomposition, is predominantly based on entomological evidence. However, very few forensically important species are sufficiently known in detail to allow a practical application. One of them is the carrion beetle, Necrophila (Calosilpha) brunnicollis (Kraatz, 1877). Its development from egg to adulthood was studied under a range of ecologically relevant constant temperatures to find parameters of thermal summation models. Developmental sexual dimorphism and the presence of developmental rate isomorphy were investigated. Herein we present the lower developmental thresholds and sum of effective temperatures for all developmental stages of N. brunnicollis (egg, first–third larval instar, postfeeding stage, and pupae). We did not find any evidence of developmental sexual dimorphism nor was the presence of developmental rate isomorphy confirmed. Our results present the first thermal summation model of the East Asian carrion beetle that can be used for the PMI estimation.
Cobblestone Malformation in LAMA2 Congenital Muscular Dystrophy (MDC1A)
Authors: Jayakody Himali , Zarei Sanam , Nguyen Huy , Dalton Joline , Chen Kelly , Hudgins Louanne , Day John , Withrow Kara , Pandya Arti , Teasley Jean , Dobyns William B , Mathews Katherine D , Moore Steven A 
Published: August 2020

Abstract
Congenital muscular dystrophy type 1A (MDC1A) is caused by recessive variants in laminin α2 (LAMA2). Patients have been found to have white matter signal abnormalities on magnetic resonance imaging (MRI) but rarely structural brain abnormalities. We describe the autopsy neuropathology in a 17-year-old with white matter signal abnormalities on brain MRI. Dystrophic pathology was observed in skeletal muscle, and the sural nerve manifested a mild degree of segmental demyelination and remyelination. A diffuse, bilateral cobblestone appearance, and numerous points of fusion between adjacent gyri were apparent on gross examination of the cerebrum. Brain histopathology included focal disruptions of the glia limitans associated with abnormal cerebral cortical lamination or arrested cerebellar granule cell migration. Subcortical nodular heterotopia was present within the cerebellar hemispheres. Sampling of the centrum semiovale revealed no light microscopic evidence of leukoencephalopathy. Three additional MDC1A patients were diagnosed with cobblestone malformation on brain MRI. Unlike the autopsied patient whose brain had a symmetric distribution of cobblestone pathology, the latter patients had asymmetric involvement, most severe in the occipital lobes. These cases demonstrate that cobblestone malformation may be an important manifestation of the brain pathology in MDC1A and can be present even when patients have a structurally normal brain MRI.
NOTCH2NLC CGG Repeats Are Not Expanded and Skin Biopsy Was Negative in an Infantile Patient With Neuronal Intranuclear Inclusion Disease
Authors: Jedlickova Ivana , Pristoupilova Anna , Hulkova Helena , Vrbacka Alena , Stranecky Viktor , Hruba Eva , Jesina Pavel , Honzik Tomas , Hrdlicka Ivan , Fremuth Jiri , Pivovarcikova Kristyna , Bitar Ibrahim , Matej Radoslav , Kmoch Stanislav , Sikora Jakub 
Published: August 2020

Abstract
Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disorder categorized into 3 phenotypic variants: infantile, juvenile, and adult. Four recent reports have linked NIID to CGG expansions in the NOTCH2NLC gene in adult NIID (aNIID) and several juvenile patients. Infantile NIID (iNIID) is an extremely rare neuropediatric condition. We present a 7-year-old male patient with severe progressive neurodegenerative disease that included cerebellar symptoms with cerebellar atrophy on brain MRI, psychomotor developmental regression, pseudobulbar syndrome, and polyneuropathy. The diagnosis of iNIID was established through a postmortem neuropathology work-up. We performed long-read sequencing of the critical NOTCH2NLC repeat motif and found no expansion in the patient. We also re-evaluated an antemortem skin biopsy that was collected when the patient was 2 years and 8 months old and did not identify the intranuclear inclusions. In our report, we highlight that the 2 methods (skin biopsy and CGG expansion testing in NOTCH2NLC) used to identify aNIID patients may provide negative results in iNIID patients.
Cellular and molecular insights on the regulation of innate immune responses to experimental aspergillosis in chicken and turkey poults
Authors: Vahsen Tobias , Zapata Laura , Guabiraba Rodrigo , Melloul Elise , Cordonnier Nathalie , Botterel Françoise , Guillot Jacques , Arné Pascal , Risco-Castillo Veronica 
Published: August 2020

AbstractAcross the world, many commercial poultry flocks and captive birds are threatened by infection with Aspergillus fumigatus. Susceptibility to aspergillosis varies among birds; among galliform birds specifically, morbidity and mortality rates seem to be greater in turkeys than in chickens. Little is known regarding the features of avian immune responses after inhalation of Aspergillus conidia, and to date, scarce information on inflammatory responses during aspergillosis exists. Thus, in the present study, we aimed to improve our understanding of the interactions between A. fumigatus and economically relevant galliform birds in terms of local innate immune responses. Intra-tracheal aerosolization of A. fumigatus conidia in turkey and chicken poults led to more severe clinical signs and lung lesions in turkeys, but leukocyte recovery from lung lavages was higher in chickens at 1dpi only. Interestingly, only chicken CD8+ T lymphocyte proportions increased after infection. Furthermore, the lungs of infected chickens showed an early upregulation of pro-inflammatory cytokines, including IL-1β, IFN-γ and IL-6, whereas in turkeys, most of these cytokines showed a downregulation or a delayed upregulation. These results confirmed the importance of an early pro-inflammatory response to ensure the development of an appropriate anti-fungal immunity to avoid Aspergillus dissemination in the respiratory tract. In conclusion, we show for the first time that differences in local innate immune responses between chickens and turkeys during aspergillosis may determine the outcome of the disease.
Returning radiation in strong gravity around black holes: reverberation from the accretion disc
Authors: Wilkins D R , García J A , Dauser T , Fabian A C 
Published: August 2020

ABSTRACT
We study reflected X-ray emission that returns to the accretion disc in the strong gravitational fields around black holes using General Relativistic ray-tracing and radiative transfer calculations. Reflected X-rays that are produced when the inner regions of the disc are illuminated by the corona are subject to strong gravitational light bending, causing up to 47 per cent of the reflected emission to be returned to the disc around a rapidly spinning black hole, depending upon the scale height of the corona. The iron Kα line is enhanced relative to the continuum by 25 per cent, and the Compton hump by up to a factor of 3. Additional light traveltime between primary and secondary reflections increases the reverberation time lag measured in the iron K band by 49 per cent, while the soft X-ray lag is increased by 25 per cent and the Compton hump response time is increased by 60 per cent. Measured samples of X-ray reverberation lags are shown to be consistent with X-rays returning to the accretion disc in strong gravity. Understanding the effects of returning radiation is important in interpreting reverberation observations to probe black holes. Reflected X-rays returning to the disc can be uniquely identified by blueshifted returning iron K line photons that are Compton scattered from the inner disc, producing excess, delayed emission in the 3.5–4.5 keV energy range that will be detectable with forthcoming X-ray observatories, representing a unique test of General Relativity in the strong field limit.
Genomic Consequences of Long-Term Population Decline in Brown Eared Pheasant
Authors: Wang Pengcheng , Burley John T , Liu Yang , Chang Jiang , Chen De , Lu Qi , Li Shou-Hsien , Zhou Xuming , Edwards Scott , Zhang Zhengwang 
Published: August 2020

Abstract
Population genetic theory and empirical evidence indicate that deleterious alleles can be purged in small populations. However, this viewpoint remains controversial. It is unclear whether natural selection is powerful enough to purge deleterious mutations when wild populations continue to decline. Pheasants are terrestrial birds facing a long-term risk of extinction as a result of anthropogenic perturbations and exploitation. Nevertheless, there are scant genomics resources available for conservation management and planning. Here, we analyzed comparative population genomic data for the three extant isolated populations of Brown eared pheasant (Crossoptilon mantchuricum) in China. We showed that C. mantchuricum has low genome-wide diversity and a contracting effective population size because of persistent declines over the past 100,000 years. We compared genome-wide variation in C. mantchuricum with that of its closely related sister species, the Blue eared pheasant (C. auritum) for which the conservation concern is low. There were detrimental genetic consequences across all C. mantchuricum genomes including extended runs of homozygous sequences, slow rates of linkage disequilibrium decay, excessive loss-of-function mutations, and loss of adaptive genetic diversity at the major histocompatibility complex region. To the best of our knowledge, this study is the first to perform a comprehensive conservation genomic analysis on this threatened pheasant species. Moreover, we demonstrated that natural selection may not suffice to purge deleterious mutations in wild populations undergoing long-term decline. The findings of this study could facilitate conservation planning for threatened species and help recover their population size.
Decorin production by the human decidua: role in decidual cell maturation
Authors: Halari C D , Nandi P , Jeyarajah M J , Renaud S J , Lala P K 
Published: August 2020

AbstractDecidualization involves the proliferation and differentiation of fibroblast-like endometrial stromal cells into epithelioid-shaped and secretory ‘decidual’ cells in response to steroid hormones. Human decidual cells produce insulin-like growth factor-binding protein-1 and prolactin (PRL), two well-recognized markers of decidual cell maturation and a proteoglycan decorin (DCN). We reported that DCN restrains the human trophoblast renewal, migration, invasion and endovascular differentiation needed for uterine arterial remodeling during normal pregnancy. DCN overproduction by the decidua is associated with a hypo-invasive placenta and a serious pregnancy disorder, pre-eclampsia (PE). Furthermore, elevated maternal plasma DCN levels during the second trimester is a predictive biomarker of PE. While these paracrine roles of decidua-derived DCN on trophoblast physiology and pathology have been well-defined, it remains unknown whether DCN plays any autocrine role in decidual cell development. The objectives of this study were to examine: the kinetics of DCN production during decidualization of human endometrial stromal cells; gestational age-related changes in DCN production by the first trimester decidua; and a possible autocrine role of DCN on decidual cell maturation. We found that DCN production is enhanced during decidualization of both primary and immortalized human endometrial stromal cells in vitro and during early gestation in decidual samples tested ex vivo, and that it is important for endometrial stromal cell maturation into a decidual phenotype. Decorin-depleted human endometrial stromal cells exposed to decidualizing stimuli failed to mature fully, as evidenced by fibroblastoid morphology, reduced insulin-like growth factor-binding protein-1 and PRL expression, and reduction in cellular ploidy. We identified heart and neural crest derivatives-expressed protein 2, and progesterone receptor as potential downstream mediators of DCN effects.
eIF4G-driven translation initiation of downstream ORFs in mammalian cells
Authors: Nobuta Risa , Machida Kodai , Sato Misaki , Hashimoto Satoshi , Toriumi Yasuhito , Nakajima Shizuka , Suto Daiki , Imataka Hiroaki , Inada Toshifumi 
Published: August 2020

Abstract
Comprehensive genome-wide analysis has revealed the presence of translational elements in the 3′ untranslated regions (UTRs) of human transcripts. However, the mechanisms by which translation is initiated in 3′ UTRs and the physiological function of their products remain unclear. This study showed that eIF4G drives the translation of various downstream open reading frames (dORFs) in 3′ UTRs. The 3′ UTR of GCH1, which encodes GTP cyclohydrolase 1, contains an internal ribosome entry site (IRES) that initiates the translation of dORFs. An in vitro reconstituted translation system showed that the IRES in the 3′ UTR of GCH1 required eIF4G and conventional translation initiation factors, except eIF4E, for AUG-initiated translation of dORFs. The 3′ UTR of GCH1-mediated translation was resistant to the mTOR inhibitor Torin 1, which inhibits cap-dependent initiation by increasing eIF4E-unbound eIF4G. eIF4G was also required for the activity of various elements, including polyU and poliovirus type 2, a short element thought to recruit ribosomes by base-pairing with 18S rRNA. These findings indicate that eIF4G mediates translation initiation of various ORFs in mammalian cells, suggesting that the 3′ UTRs of mRNAs may encode various products.
Isotopic evidence for size-based dietary shifts in the jellyfish Cyanea nozakii in the northern East China Sea
Authors: Wang Pengpeng , Zhang Fang , Liu Mengtan , Sun Song , Xian Haochen 
Published: August 2020

Abstract
Cyanea nozakii is a common bloom-forming Scyphomedusa in coastal waters of China. To understand the diet of this jellyfish and its trophic relationship with other zooplankton groups, stable isotope δ13C and δ15N values of C. nozakii in the bloom area within the northern East China Sea (ECS) in August 2017 were analyzed. We examined: first, the size-based variation in C. nozakii stable isotope values, second, the contributions of different food sources to the C. nozakii diet, and possible size-based dietary shifts in individual C. nozakii and, third, the contribution of gelatinous prey to the C. nozakii diet. Isotope values of differently sized C. nozakii ranged from −18.81 to −16.88‰ for δ13C and from 8.23 to 10.46‰ for δ15N. A significant change in δ15N values implies that the trophic position and the diet of C. nozakii changed as body size increased. The MixSIAR model indicated that C. nozakii underwent a dietary shift during growth, from a seston-dominant diet in smaller medusae to a zooplankton-dominant diet in larger medusae. Copepods were an important food source for C. nozakii, irrespective of size. The mean proportions of gelatinous zooplankton increased significantly in the C. nozakii diet with increasing C. nozakii diameter, suggesting that larger C. nozakii consumed more gelatinous prey. The diet of larger C. nozakii included 9.54% Nemopilema nomurai and 9.53% small medusae. The results suggest that intraguild predation among these jellyfish exist in the northern ECS.
Utility of direct 3D co-culture model for chondrogenic differentiation of mesenchymal stem cells on hyaluronan scaffold (Hyaff-11)
Authors: Deszcz Iwona , Lis-Nawara Anna , Grelewski Piotr , Dragan Szymon , Bar Julia 
Published: August 2020

Abstract
This study presents direct 2D and 3D co-culture model of mesenchymal stem cells (MSCs) line with chondrocytes isolated from patients with osteoarthritis (unaffected area). MSCs differentiation into chondrocytes after 14, 17 days was checked by estimation of collagen I, II, X, aggrecan expression using immunohistochemistry. Visualization, localization of cells on Hyaff-11 was performed using enzymatic technique and THUNDER Imaging Systems. Results showed, that MSCs/chondrocytes 3D co-culture induced suitable conditions for chondrocytes grow and MSCs differentiation than 2D monoculture. Despite that differentiated cells on Hyaff-11 expressed collagen X, they showed high collagen II (80%) and aggrecan (60%) expression with simultaneous decrease of collagen I expression (10%). The high concentration of differentiated cells on Hyaff-11, indicate that this structure has an impact on cells cooperation and communication. In conclusion, we suggest that high expression of collagen II and aggrecan in 3D co-culture model, indicate that cooperation between different subpopulations may have synergistic impact on MSCs chondrogenic potential. Revealed the high concentration and localization of cells growing in deeper layers of membrane in 3D co-culture, indicate that induced microenvironmental enhance cell migration within scaffold. Additionally, we suggest that co-culture model might be useful for construction a bioactive structure for cartilage tissue regeneration.
Preclinical study of a self-expanding pulmonary valve for the treatment of pulmonary valve disease
Authors: Kuang Dajun , Lei Yang , Yang Li , Wang Yunbing 
Published: August 2020

AbstractIn the past decade, balloon-expandable percutaneous pulmonary valves have been developed and applied in clinical practice. However, all the existing products of pulmonary artery interventional valves in the market have a straight structure design, and they require a preset support frame and balloon expansion. This shape design of the valve limits the application range. In addition, the age of the population with pulmonary artery disease is generally low, and the existing products cannot meet the needs of anti-calcification properties and valve material durability. In this study, through optimization of the support frame and leaflet design, a self-expanding pulmonary valve product with a double bell-shaped frame was designed to improve the match of the valve and the implantation site. A loading and deployment study showed that the biomaterial of the valve was not damaged after being compressed. Pulsatile flow and fatigue in vitro tests showed that the fabricated pulmonary valve met the hydrodynamic requirements after 2 × 108 accelerated fatigue cycles. The safety and efficacy of the pulmonary valve product were demonstrated in studies of pulmonary valve implantation in 11 pigs. Angiography and echocardiography showed that the pulmonary valves were implanted in a good position, and they had normal closure and acceptable valvular regurgitation. The 180 days’ implantation results showed that the calcium content was 0.31–1.39 mg/g in the anti-calcification treatment group, which was significantly lower than that in the control valve without anti-calcification treatment (16.69 mg/g). Our new interventional pulmonary valve product was ready for clinical trials and product registration.
Haste or Waste? Peer Pressure and Productivity in the Emergency Department
Authors: Silver David 
Published: August 2020

AbstractMotivated by wide cross-sectional variations in intensity of care that are unrelated to quality of care, researchers and policymakers commonly claim that healthcare providers waste considerable resources, engaging in so-called “flat-of-the-curve” medicine. A key yet elusive prediction of this hypothesis is that providers ought to be able to cut back on care without sacrificing quality. This article examines the effects of a particular form of provider cutbacks—those generated by physicians working in high-pressure peer group environments. Using expansive, time-stamped discharge data from 137 hospital-based emergency departments, I document that physicians systematically alter their pace and intensity of care across frequently shuffled peer groups. Peer groups that induce a physician to work faster also induce her to order fewer tests and spend less money. Contrary to the flat-of-the-curve hypothesis, these cutbacks lead to large reductions in quality of care. This evidence, paired with the fact that slower physicians do not produce better average outcomes, suggests that cross-physician differences in resource utilization reflect substantial differences in physician productivity within a hospital.
Marketing Mutual Funds
Authors: Roussanov Nikolai , Ruan Hongxun , Wei Yanhao 
Published: August 2020

Abstract
Marketing and distribution expenses are responsible for about one-third of the cost of active management in the mutual fund industry. Estimating a structural model with costly investor search and learning about fund skill, we find that marketing is nearly as important as performance and fees in determining fund size. Eliminating marketing substantially improves welfare: capital shifts toward cheaper funds and competition decreases fees; active funds shrink and capital allocation becomes more closely aligned with skill. Declining investor search costs imply a reduction in marketing expenses and management fees as well as a shift toward passive investing, as observed empirically.