Miracle-dz/UniFAR-FTUs huggingface dataset:
Elucidating the Molecular Mechanism of CYLD- Mediated Necrosis: A Dissertation

TNFα-induced programmed necrosis is a caspase-independent cell death program that is contingent upon the formation of a multiprotein complex termed the necrosome. The association of two of the components of the necrosome, receptor interacting protein 1 (RIP1) and RIP3, is a critical and signature molecular event during necrosis. Within this complex, both RIP1 and RIP3 are phosphorylated which are consequential for transmission of the pro-necrotic signal. Namely, it has been demonstrated that RIP3 phosphorylation is required for binding to downstream substrates. Nevertheless, the regulatory mechanisms governing necrosome activation remain unclear. Since necrosis is implicated in a variety of different diseases, understanding the biochemical signaling pathway can potentially yield future drug targets. I was interested in identifying other regulators of necrosis in hope of gaining a better understanding of the necrosis signaling pathway and regulators of the necrosome. To address this, I screened a cancer gene siRNA library in a cell line sensitive to necrosis. From this, I independently identified CYLD as a positive regulator of necrosis. Previous studies suggest that deubiquitination of RIP1 in the TNF receptor (TNFR)-1 signaling complex is a prerequisite for transition of RIP1 into the cytosol and assembly of the RIP1-RIP3 necrosome. The deubiquitinase cylindromatosis (CYLD) is presumed to promote programmed necrosis by facilitating RIP1 deubiquitination in this membrane receptor complex. Surprisingly, I found that TNFα could induce RIP1-dependent necrosis in CYLD -/- cells. I show that CYLD does not regulate RIP1 ubiquitination at the receptor complex. Strikingly, assembly of the RIP1-RIP3 necrosome was delayed, but not abolished in the absence of CYLD. In addition to the TNFR-1 complex, I found that RIP1 within the necrosome was also ubiquitinated. In the absence of CYLD, RIP1 ubiquitination in the NP-40 insoluble necrosome was greatly increased. Increased RIP1 ubiquitination correlated with impaired RIP1 and RIP3 phosphorylation, a signature of kinase activation. My results show that CYLD regulates RIP1 ubiquitination in the NP-40 insoluble necrosome, but not in the TNFR-1 signaling complex. Contrary to the current model, CYLD is not essential for necrosome assembly. Rather, it facilitates RIP1 and RIP3 activation within the necrosome and the corollary is enhancement of necrosome functionality and subsequent necrosis. My results therefore indicate that CYLD exerts its pro-necrotic function in the NP-40 insoluble necrosome, and illuminates the mechanism of necrosome activation.
Learnable Gabor modulated complex-valued networks for orientation robustness

Robustness to transformation is desirable in many computer vision tasks, given that input data often exhibits pose variance within classes. While translation invariance and equivariance is a documented phenomenon of CNNs, sensitivity to other transformations is typically encouraged through data augmentation. We investigate the modulation of complex valued convolutional weights with learned Gabor filters to enable orientation robustness. With Gabor modulation, the designed network is able to generate orientation dependent features free of interpolation with a single set of rotation-governing parameters. Moreover, by learning rotation parameters alongside traditional convolutional weights, the representation space is not constrained and may adapt to the exact input transformation. We present Learnable Convolutional Gabor Networks (LCGNs), that are parameter-efficient and offer increased model complexity while keeping backpropagation simple. We demonstrate that learned Gabor modulation utilising an end-to-end complex architecture enables rotation invariance and equivariance on MNIST and a new dataset of simulated images of galactic cirri.
Predicting disease occurrence of cabbage Verticillium wilt in monoculture using species distribution modeling

Background Although integrated pest management (IPM) is essential for conservation agriculture, this method can be inadequate for severely infected fields. The ability to predict the potential occurrence of severe infestation of soil-borne disease would enable farmers to adopt suitable methods for high-risk areas, such as soil disinfestation, and apply other options for lower risk areas. Recently, researchers have used species distribution modeling (SDM) to predict the occurrence of target plant and animal species based on various environmental variables. In this study, we applied this technique to predict and map the occurrence probability of a soil-borne disease, Verticillium wilt, using cabbage as a case study. Methods A disease survey assessing the distribution of Verticillium wilt in cabbage fields in Tsumagoi village (central Honshu, Japan) was conducted two or three times annually from 1997 to 2013. Road density, elevation and topographic wetness index (TWI) were selected as explanatory variables for disease occurrence potential. A model of occurrence probability of Verticillium wilt was constructed using the MaxEnt software for SDM analysis. As the disease survey was mainly conducted in an agricultural area, the area was weighted as “Bias Grid” and area except for the agricultural area was set as background. Results Grids with disease occurrence showed a high degree of coincidence with those with a high probability occurrence. The highest contribution to the prediction of disease occurrence was the variable road density at 97.1%, followed by TWI at 2.3%, and elevation at 0.5%. The highest permutation importance was road density at 93.0%, followed by TWI at 7.0%, while the variable elevation at 0.0%. This method of predicting disease probability occurrence can help with disease monitoring in areas with high probability occurrence and inform farmers about the selection of control measures.
Age relationships with telomere length, body weight and body length in wild dugong (Dugong dugon)

The ability to estimate age and determine the growth status of free-ranging dugongs (Dugong dugon) is vital to providing insight into the basic biology of this endangered species. Currently, age estimation in dugong carcasses relies on counting dentin growth layer groups (GLGs) in tusks, but a disadvantage is they need to be intact. We explored whether measures of telomere length could be used as an alternative approach to age estimation in dugongs given that in other species, telomere length and age are inversely related. In this study, relative telomere length (rTL) was measured by qPCR in skin samples from 24 dugongs of varying ages determined by counts of GLGs. In addition, relationships between age by GLG counts and body weight and length and were examined. Our findings indicate that age estimated by GLGs was negatively correlated with telomere length using the logistic formula with a rate of telomere attrition of approximately 0.036 rTL/year between the ages of 5–20 years. By comparison, both body weight and length were positively correlated with GLG-based age, with growth rates of ~8.8 kg/year for weight and ~3.58 cm/year for length, respectively. After that, growth rates slowed substantially and then plateaued. The results suggest that physical maturity in dugongs occurs at 20 years of age and that measures of rTL might serve as a tool for age estimation in dugongs, living and deceased.
Effects of microhabitat on rodent-mediated seed removal of endangered Kmeria septentrionalis in the karst habitat

Seed removal behaviors of rodents are largely influenced by microhabitat. Although the karst ecosystem is composed of a broad variety of microhabitats, we have no information on how they affect such behaviors. We investigated rodents’ seed removal behaviors in four karst microhabitats (stone cavern, stone groove, stone surface, and soil surface) using three types of Kmeria septentrionalis seeds: fresh, black (intact seeds with black aril that dehydrates and darkens), and exposed (clean seeds without the aril). We show that Rattus norvegicus, Leopoldamys edwardsi and Rattus flavipectus were the predominant seed predators. Even though all seed types experienced a high removal rate in all four microhabitats, but rodents preferentially removed seeds from the three stone microhabitats (stone caves: 69.71 ± 2.74%; stone surface: 60.53 ± 2.90%; stone groove: 56.94 ± 2.91%) compared to the soil surface (53.90 ± 2.92%). Seeds that had been altered by being exposed to the environment were more attractive to rodents than fresh seeds (76.25 ± 2.20% versus 36.18 ± 2.29%). The seed removal behavior of rodents was significantly affected by the microhabitat and seed type. Finally, seeds that had fallen on the soil surface microhabitat incurred a lower predation risk than seeds fallen on other microhabitats, which increased their probability to germinate. Our results indicate that the lower predation rate of seeds from the endangered K. septentrionalis dropped on the soil surface increases trees’ likelihood of survival.
The genetic diversity and population structure of two endemic Amazonian quillwort (Isoetes L.) species

Background Two endemic lycophyte species Isoetes cangae and Isoetes serracarajensis have been recently described in the State of Pará in the Amazon forest located in northern Brazil. Isoetes L. has survived through three mass extinctions. Plants are considered small-sized, heterosporous, and can display a great diversity of physiological adaptations to different environments. Thus, the current study aimed to estimate the genetic variation of the populations of I. cangae and I. serracarajensis to generate information about their different mechanisms for survival at the same geographical location that could point to different reproductive, adaptative and dispersal strategies and should be considered for effective conservation strategies. Methods The genetic diversity and population structure of I. cangae and I. serracarajensis were investigated using Inter Simple Sequence Repeat (ISSR) molecular markers. Total genomic DNA was isolated, and the genetic diversity parameters were calculated. Results The sixteen primers produced 115 reproducible bands, 87% of which were polymorphic. A high level of polymorphic loci (81.74% and 68.48%) and a high Shannon index (Sh = 0.376 and 0.289) were observed for I. cangae and I. serracarajensis, respectively. The coefficient of genetic differentiation between population areas (GST) showed a higher value in I. serracarajensis (0.5440). Gene flow was higher in I. cangae (1.715) and lower in I. serracarajensis populations (0.419). Overall, the results further show that I. serracarajensis and I. cangae are two species with considerable genetic variation and that these differences may reflect their habitats and modes of reproduction. These results should be considered in the development of effective conservation strategies for both species.
Hopelessness Among Middle-Aged and Older Blacks: The Negative Impact of Discrimination and Protecting Power of Social and Religious Resources

Abstract Background and Objectives Hopelessness—a state of despair characterized by a negative outlook towards the future and a belief in insurmountable challenges—is a risk factor for major depression, cardiovascular disease, and all-cause mortality among older adults. It is also an understudied consequence of discrimination. Older blacks disproportionately report experiencing discrimination and, as a result, may be at greater risk of feeling hopeless. However, social and religious resources may protect against the adverse effects of discrimination. The current study examines whether social support, social engagement, religious attendance, and religiosity buffer the effects of self-reported everyday discrimination on hopelessness among a nationally representative sample of blacks. Research Design and Methods Using data from the 2010/2012 psychosocial assessment of the Health and Retirement Study, we regressed hopelessness on everyday discrimination, stratifying by 2 age groups, ages 51–64, representing middle-age (n = 1,302), and age 65 and older, representing old age (n = 887). Interaction terms tested whether each resource moderated the discrimination–hopelessness relationship controlling for depressive symptoms, socioeconomic status, and demographic characteristics. Results Greater reports of everyday discrimination were associated with higher levels of hopelessness for middle-aged and older blacks. For middle-aged blacks, the resources did not moderate the discrimination–hopelessness relationship; rather, higher levels of support (b = −0.294, p < .01), religiosity (b = −0.297, p < .001), religious attendance (b = −0.218, p < .05) were independently and inversely associated with hopelessness. For older blacks, higher levels of religiosity moderated the discrimination–hopelessness relationship (b = −0.208, p < .05) and higher levels of support (b = −0.304, p < .05) and social engagement (b = −0.236, p < .05) were independently and inversely associated with hopelessness. Discussion and Implications Findings suggest that self-reported everyday discrimination increases hopelessness among middle-aged and older blacks but social and religious resources may counterbalance its effects, in age-specific ways, to protect against hopelessness. Religiosity may be especially important for older blacks as a buffer against the negative consequences of discrimination on hopelessness.
Population genetics of the freshwater fish Prochilodus magdalenae (Characiformes: Prochilodontidae), using species-specific microsatellite loci

Prochilodus magdalenae is a freshwater fish endemic to the Colombian Magdalena-Cauca and Caribbean hydrographic basins. The genetic structure patterns of populations of different members of Prochilodus and the historic restocking of its depleted natural populations suggest that P. magdalenae exhibits genetic stocks that coexist and co-migrate throughout the rivers Magdalena, Cauca, Cesar, Sinú and Atrato. To test this hypothesis and explore the levels of genetic diversity and population demography of 725 samples of P. magdalenae from the studied rivers, we developed a set of 11 species-specific microsatellite loci using next-generation sequencing, bioinformatics, and experimental tests of the levels of diversity of the microsatellite loci. The results evidenced that P. magdalenae exhibits high genetic diversity, significant inbreeding coefficient ranging from 0.162 to 0.202, and signs of erosion of the genetic pool. Additionally, the population genetic structure constitutes a mixture of genetic stocks heterogeneously distributed along the studied rivers, and moreover, a highly divergent genetic stock was detected in Chucurí, Puerto Berrío and Palagua that may result from restocking practices. This study provides molecular tools and a wide framework regarding the genetic diversity and structure of P. magdalenae, which is crucial to complement its baseline information, diagnosis and monitoring of populations, and to support the implementation of adequate regulation, management, and conservation policies.
Optimum duration of adjuvant trastuzumab in treatment of human epidermal growth factor receptor-2 positive early breast cancer: protocol for a network meta-analysis of randomised controlled trials

Introduction Controversy regarding optimum duration of trastuzumab treatment remains in patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer. The objective of applying network meta-analysis (NMA) is to integrate existing evidence based on direct and indirect comparisons of efficacy and safety, and then to determine the duration of trastuzumab treatments with the greatest impact on therapeutic outcomes in HER2-positive early breast cancers. Methods and analysis Electronic searching of trastuzumab treatments for early breast cancer by titles and abstracts will be conducted for the period from inception to 16 June 2019 in PubMed, Cochrane Library, Embase and ClinicalTrils.gov, as well as the annual meetings of San Antonio Breast Cancer Symposium (SABCS), European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) online archives. The outcomes of interest are overall survival, disease-free survival, acceptability, cardiotoxicities and grade 3 to 4 non-haematological toxicities. Two independent reviewers will screen and extract eligible data based on the inclusion and exclusion criteria, and then assess the risk of bias and evidence quality of individual studies using Cochrane Collaboration’s tool and Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The heterogeneity, transitivity and inconsistency of NMA will be evaluated. In addition, we will perform subgroup and sensitivity analyses to assess the robustness and reliability of findings in our NMA. Ethics and dissemination Ethics approval is not required for our NMA. Findings from our NMA will be submitted as peer-reviewed journal manuscripts and international conference reports. Trial registration number CRD42019139109.
An experimental study of respiratory aerosol transport in phantom lung bronchioles

The transport and deposition of micrometer-sized particles in the lung is the primary mechanism for the spread of aerosol borne diseases such as corona virus disease-19 (COVID-19). Considering the current situation, modeling the transport and deposition of drops in human lung bronchioles is of utmost importance to determine their consequences on human health. The current study reports experimental observations on deposition in micro-capillaries, representing distal lung bronchioles, over a wide range of Re that imitates the particle dynamics in the entire lung. The experiment investigated deposition in tubes of diameter ranging from 0.3 mm to 2 mm and over a wide range of Reynolds number (10−2 ⩽ Re ⩽ 103). The range of the tube diameter and Re used in this study is motivated by the dimensions of lung airways and typical breathing flow rates. The aerosol fluid was loaded with boron doped carbon quantum dots as fluorophores. An aerosol plume was generated from this mixture fluid using an ultrasonic nebulizer, producing droplets with 6.5 µm as a mean diameter and over a narrow distribution of sizes. The amount of aerosol deposited on the tube walls was measured using a spectrofluorometer. The experimental results show that dimensionless deposition (δ) varies inversely with the bronchiole aspect ratio (L¯), with the effect of the Reynolds number (Re) being significant only at low L¯. δ also increased with increasing dimensionless bronchiole diameter (D¯), but it is invariant with the particle size based Reynolds number. We show that δL¯∼Re−2 for 10−2 ⩽ Re ⩽ 1, which is typical of a diffusion dominated regime. For Re ⩾ 1, in the impaction dominated regime, δL¯ is shown to be independent of Re. We also show a crossover regime where sedimentation becomes important. The experimental results conclude that lower breathing frequency and higher breath hold time could significantly increase the chances of getting infected with COVID-19 in crowded places.
Big Data and Artificial Intelligence: Opportunities and Threats in Electrophysiology

The combination of big data and artificial intelligence (AI) is having an increasing impact on the field of electrophysiology. Algorithms are created to improve the automated diagnosis of clinical ECGs or ambulatory rhythm devices. Furthermore, the use of AI during invasive electrophysiological studies or combining several diagnostic modalities into AI algorithms to aid diagnostics are being investigated. However, the clinical performance and applicability of created algorithms are yet unknown. In this narrative review, opportunities and threats of AI in the field of electrophysiology are described, mainly focusing on ECGs. Current opportunities are discussed with their potential clinical benefits as well as the challenges. Challenges in data acquisition, model performance, (external) validity, clinical implementation, algorithm interpretation as well as the ethical aspects of AI research are discussed. This article aims to guide clinicians in the evaluation of new AI applications for electrophysiology before their clinical implementation.
The complete mitochondrial genome of Gyps coprotheres (Aves, Accipitridae, Accipitriformes): phylogenetic analysis of mitogenome among raptors

Three species of Old World vultures on the Asian peninsula are slowly recovering from the lethal consequences of diclofenac. At present the reason for species sensitivity to diclofenac is unknown. Furthermore, it has since been demonstrated that other Old World vultures like the Cape (Gyps coprotheres; CGV) and griffon (G. fulvus) vultures are also susceptible to diclofenac toxicity. Oddly, the New World Turkey vulture (Cathartes aura) and pied crow (Corvus albus) are not susceptible to diclofenac toxicity. As a result of the latter, we postulate an evolutionary link to toxicity. As a first step in understanding the susceptibility to diclofenac toxicity, we use the CGV as a model species for phylogenetic evaluations, by comparing the relatedness of various raptor species known to be susceptible, non-susceptible and suspected by their relationship to the Cape vulture mitogenome. This was achieved by next generation sequencing and assembly. The Cape vulture mitogenome had a genome size of 16,908 bp. The mitogenome phylogenetic analysis indicated a close evolutionary relationship between Old World vultures and other members of the Accipitridae as indicated by bootstrap value of 100% on the phylogenetic trees. Based on this, we postulate that the other species could also be sensitive to the toxic effects of diclofenac. This warrants further investigations.
Properties of Starches from Potato Varieties Grown in Hokkaido

Using potato cultivars grown in Hokkaido, the starch properties in potato tubers were characterized. The starch properties determined in this study were the contents of amylose and phosphorus, granule size distribution, and pasting properties using a rapid visco-analyzer. There were wide variations in starch parameters among the 96 potato starch samples used. A high phosphorus content of starch was closely associated with high peak viscosity and breakdown and low peak viscosity temperature. Although the amylose content also had an effect on pasting properties, the correlation coefficients between the phosphorus content and pasting properties were higher than those between the amylose content and pasting properties.