Miracle-dz/UniFAR-FTUs huggingface dataset:
High Throughput and Mechanistic Analysis of the HRD Motif of Src Protein Tyrosine Kinase

Protein tyrosine kinases (PTK) play essential roles in cell signal transduction pathways. PTKs are associated with numerous diseases and promote oncogenic cell signal transduction in unregulated forms. Thus PTKs represent a large group of potential targets for anticancer drug discovery. Src was the first identified oncogene and has been intensively studied for decades. The work described in this dissertation studied the structure-function relationships of Src, to build a knowledge base for the function of conserved residues in the kinase domain. To accomplish this, the first focus of this dissertation was to develop a high throughput screening method to identify kinase functionalities regarding catalytic activity and substrate specificity. The developed method utilizes a bacterial screen system and detects phosphotyrosine in cell lysate by a high throughput manner. Combining the developed functional screening with a rational mutation library, functional mutants can be identified for further analysis. This in vivo strategy was validated by model PTKs and could be universally applied to study kinase catalytic activity and substrate specificity. A successful application of the developed method on the study of the conserved HRD motif in Src led to a more comprehensive understanding of the role of HRD in the kinase function. The second focus of the dissertation was to study the regulatory function of the arginine (R385) in the HRD motif of Src, since R385 was found unnecessary for catalysis in the first part of this dissertation. The effect of R385 mutation on the key regulatory mechanisms of Src and binding affinity towards PTK inhibitors was examined. First, autophosphorylation of Tyr416 in Src activates this enzyme, and overrides the negative regulation by Csk that phosphorylates Src on Tyr527. However, mutation of R385 to other residues abolished this override. The presence of the arginine prevents the transition of the active Src to inactivated Src. Second, type II inhibitors bind to the inactive conformation of Abl but not to Src even through Src and Abl are structurally very similar. Mutation of R385 greatly increased the affinity of Src towards type II inhibitors, but had no effect on type I inhibitor binding, which targets the active conformation. All together, when induced by Csk phosphorylation or PTK inhibitors that target the inactive conformation of kinase domain, R385 behaves as an energy barrier in the conformational transition from active to inactive conformation. The replacement of the R385 by any other amino acid made the transition much easier. R385 is the first identified residue among protein tyrosine kinases, that controls conformational transitions. This study sheds light on the fundamental mechanism of regulatory conformational changes and provides more insight on design and development of PTK inhibitors.
Prescribed Fire Decreases Lichen and Bryophyte Biomass and Alters Functional Group Composition in Pacific Northwest Prairies

Abstract The reintroduction of fire to Pacific Northwest prairies has been useful for removing non-native shrubs and supporting habitat for fire-adapted plant and animal species. However, very little is known about the influence of fire on prairie bryophyte and lichen communities. In this study, we investigated the effects of fire on ground-dwelling bryophytes and lichens by estimating standing biomass, cover, mat depth and functional group diversity in burned and unburned plots at five prairie sites located in the south Puget Sound bioregion of Washington State. After accounting for differences among sites, the bryophyte and lichen ground layer in burned plots had about 18% the biomass and about 60% the cover of unburned plots. All ground layer functional groups had lower average biomass in burned plots, except for ephemeral mosses, which had greater biomass. Forage lichens and nitrogen-fixing lichens were absent from all five burned plots. Of particular concern are the regionally rare, state-listed reindeer forage lichens (Cladonia ciliata var. ciliata, Cladonia ciliata var. tenuis and Cladonia portentosa ssp. pacifica), which occur at three of the five prairies we surveyed. Our results indicate that some lichen populations could be extirpated from these sites if they are not considered in prescribed burn management plans. We suggest some options that could maintain ground layer integrity while balancing other management objectives in the south Puget Sound prairies.
Pengaruh Attitude, Subjective Norms dan Perceived Behavioral Control terhadap Intensi Kepemilikan Kartu Kredit Syariah

This study aims to reveal how the influence of religiosity, attitudes, subjective norms and perceptions of behavioral control over the intention of ownership of credit cards sharia. This study uses a quantitative approach. The sampling technique uses convenience sampling. Sample used 150 respondents in DKI Jakarta Province Data collection techniques using questionnaires with closed questions to assess the influence of religiosity, attitudes, subjective norms and perceptions of behavioral control over the intention of ownership of sharia credit card Analysis method using SEM and with LISREL tool. The results of this study indicate that religiosity, attitudes, subjective norms and perceptions of behavioral control have a positive relationship or influence on the intention of ownership of sharia credit cards. And also religiosity has an indirect effect on the intention of ownership of credit card sharia. Keywords: Religiosity, Sharia credit card, TPB
Effect of the Stage of Ripening on the Nutrients, Anti-nutrients and Functional Properties of Flours Made from Whole Plantain Fruit

The study was carried out in collaboration between authors UEI, SEN and EBU. Author UEI designed the study. The three authors carried out the experimentation and gathered the initial data. Authors UEI and SEN managed the literature searches. Author UEI wrote the protocol and the first draft while author SEN performed the statistical analysis. The three authors read and approved the finial manuscript. plantains were washed, steam blanched (100°C for 10 min), cooled, sliced, oven dried (60°C), milled and sieved to obtain the flour used for analysis. Results: The results revealed that all the parameters analyzed varied with ripening stages. Protein, carbohydrate, Na, and Fe in the flours decreased from 6.39%, 86.73%, 28.14mg/100g, and 2.45 mg/100 g at unripe stage to 5.98%, 85.69%, 27.96 mg/100 g and 2.38 mg/100 g at fully ripe stage. Conversely, fat, ash, crude fibre, K, Ca, Mg and Zn increased from 0.70%, 2.57%, 3.61%, 476.09 mg/100 g, 148.52 mg/100 g, 121.32 mg/100 g and 3.60 mg/100 g in unripe plantain flour to 1.16%, 3.43%, 3.74%, 481.21 mg/100 g, 149.58 mg/100 g, 124.11 mg/100 g and 3.66 mg/100 g, respectively in fully ripe flour. All the anti-nutrients decreased significantly ( P = .05) with ripening. Bulk density, water and oil absorption capacities as well as swelling index decreased while foaming capacity increased with stages of ripening. Conclusion: Production of flours of high nutrients and low anti-nutrients from unpeeled plantain at various stages of ripening would ensure efficient utilization of plantain fruit with no waste generation and should be exploited.
The Prevalence of Neisseria gonoroheae among Iranian Women by Phenotyping and Genotyping Methods

Sexually transmitted disease (STD) consist of Neisseria gonoroheae, Chlamydia trachomatis, Syphilis and Trichomonyasis are a major public health concern. The prevalence of these organisms are increasing level because of homosexuality, migration and resistance to antibacterial agents and also usage of high technique for diagnosis of infection, according to WHO information 88 million people from 448 million which infected with STD, is Neisseria gonoroheae, whereas, Iran as a developing country have not complete prevalence information about Neisseria gonoroheae. In this study it has been tried to estimate the prevalence of Neisseria among Iranian women with phenotypin and genotyping methods. 300 specimens were enrolled in the present investigation which collected from women with genital problems. Dacron swab samples were cultured in chocolate agar in 37°C with 5-10% CO2 for 24-48 hours. Gram staining, oxidase and carbohydrate utilization tests were used to identify the isolated species. Extraction of DNA of all isolates recognize as Neisseria gonoroheae. PCR for amplification of 390 bp fragment of CPPB plasmid for confirmation of isolates were performed. From 300 specimens, 7 isolates recognize as Neisseria gonoroheae with culture and PCR methods. It means N. gonorrhoeae was detected in 2.6% cases which enrolled in this study. The study revealed that although primary report found no prevalence of gonorrohea in Iran but other study revealed different prevalence of bacteria in Iran, even in the recent studies, the results are very near to this result with consideration that gonoccocal infection have different sequelle in young age or pregnant women so it is very important that with culture or PCR methods, screening of bacteria should be done.
Genome-wide polygenic score to identify a monogenic risk-equivalent for coronary disease

Identification of individuals at increased genetic risk for a complex disorder such as coronary disease can facilitate treatments or enhanced screening strategies. A rare monogenic mutation associated with increased cholesterol is present in ~1:250 carriers and confers an up to 4-fold increase in coronary risk when compared with non-carriers. Although individual common polymorphisms have modest predictive capacity, their cumulative impact can be aggregated into a polygenic score. Here, we develop a new, genome-wide polygenic score that aggregates information from 6.6 million common polymorphisms and show that this score can similarly identify individuals with a 4-fold increased risk for coronary disease. In >400,000 participants from UK Biobank, the score conforms to a normal distribution and those in the top 2.5% of the distribution are at 4-fold increased risk compared to the remaining 97.5%. Similar patterns are observed with genome-wide polygenic scores for two additional diseases – breast cancer and severe obesity. One Sentence Summary A genome-wide polygenic score identifies 2.5% of the population born with a 4-fold increased risk for coronary artery disease.
p-Menthenols chemotype of Cymbopogon distans from India: composition, antibacterial and antifungal activity of the essential oil against pathogens

Abstract Cymbopogon distans (Nees. ex. Steud.) W. Watson (family: Poaceae) is a perennial aromatic grass widely distributed in tropical and subtropical zones of north-western Himalaya. The essential oil of C. distans has industrial potential for aromatherapy, fragrances and for natural aroma isolates. In view of chemotypic variations and industrial potential of the essential oil of C. distans, the present study was carried out to investigate the variability in chemical composition of p-menthenols chemotype of the C. distans harvested in different seasons during annual growth, and to evaluate the antimicrobial potential of its essential oil against pathogenic bacterial and fungal strains. The major constituents identified in essential oil of C. distans were cis-p-menth-2-en-1-ol (24.5–26.7%), δ-2-carene (19.9–28.2%), cis-piperitol (10.9–23.6%), trans-p-menth-2-en-1-ol (8.4–13.3%) and trans-piperitol (5.4–7.3%). The essential oil showed antagonist activity against nine bacterial strains (MIC: 250–1000 μg/mL) and three fungal strains (MIC: 130–530 μg/mL). Results revealed that the essential oil of C. distans possessed >50.0% of p-menthenols viz., cis-p-menth-2-en-1-ol, trans-p-menth-2-en-1-ol, cis-piperitol and trans-piperitol as major constituents, with a significant antimicrobial potential for pathogenic microbial strains.
Effects of concentrates rich in by-products on growth performance, carcass characteristics and meat quality traits of light lambs

The effects of feeding concentrates with alternative ingredients to cereal and soybean meal on growth performance, carcass characteristics and meat quality traits of feedlot lambs were studied. A total of 105 non-castrated male lambs were randomly assigned to one of three treatments (5 replicates per treatment): Control (CON, similar to commercial concentrates), Camelina (CAM, where camelina meal replaced 50% of the crude protein from the soybean meal in the CON concentrate), and Fibrous (FIB, concentrate without cereals and soybean meal, with camelina meal in addition to several by-products, and 20% less energy). The CAM treatment performed as well as the CON one. The FIB treatment increased feed conversion rate and tended to improve the redness and the oxidative stability. The CAM and FIB were economically more favourable. We found that a concentrate for feedlot lambs based on alternative ingredients, including several by-products, could be a feasible alternative to typical cereal-soybean meal-based concentrates.
Nutritional assessment of different parts of Moringa oleifera Lamm collected from Central India.

Moringa is especially promising as a food source in the tropics. This rapidly-growing tree is a perennial softwood tree with timber of low quality, but for centuries has been advocated for traditional medicinal and industrial uses. All parts of the Moringa tree are edible and have long been consumed by humans. However, all the plant parts of Moringa oleifera from Central India have not been investigated for their nutritive values. The present study showcases a comprehensive investigation on different plant parts of Moringa oleifera collected from Jabalpur. All the parts have good amount of nutritionally important minerals and were devoid of toxic heavy metals, making them suitable as a source of nutrition for both human and animals.
DROSHA associates to DNA damage sites and is required for DNA repair

The DNA damage response (DDR) is the signaling cascade through which a cell recognizes DNA lesions, and promotes their resolution via the repair pathways of Non-Homologous End Joining (NHEJ), or Homologous Recombination (HR). We recently demonstrated that DROSHA boosts DDR signaling by processing damage-induced long non-coding RNAs into smaller DNA damage response RNAs (DDRNAs). However, the location at which DROSHA exerts its DDR functions, relative to sites of DNA damage, remains unknown. To investigate DROSHA’s localization during DDR activation, we used the DiVA cellular system, which allows the controlled induction of several DNA double strand breaks (DSBs) in the human genome. Indeed, by genome wide chromatin immunoprecipitation followed by next generation sequencing, we demonstrate that DROSHA associates with DSBs. In support of this, DSB-recruitment of DROSHA is detectable at the single-cell level by Proximity Ligation Assay between DROSHA and known DDR markers, and by DNA damage in situ ligation followed by Proximity Ligation Assay (DI-PLA), which demonstrates proximity of DROSHA to DNA ends. DROSHA recruitment occurs at both genic and inter-genic DSBs, suggesting that its recruitment is independent from ongoing transcription preceding damage generation. DROSHA’s recruitment to DNA lesions occurs throughout the cell cycle, and with a preference for NHEJ-prone DSBs. Consistently, inhibition of the HR pathway increases DROSHA recruitment, and DROSHA knock down strongly impairs NHEJ efficiency in a GFP-reporter cellular system for monitoring NHEJ DNA repair. Overall, these results demonstrate that DROSHA acts locally at sites of DNA damage to promote NHEJ DNA repair.
Site-specific transgenesis of the D. melanogaster Y-chromosome using CRISPR/Cas9

Despite the importance of Y-chromosomes in evolution and sex determination, their heterochromatic, repeat-rich nature makes them difficult to sequence and genetically manipulate, and therefore they generally remain poorly understood. For example, the D. melanogaster Y-chromosome, one of the best understood, is widely heterochromatic and composed mainly of highly repetitive sequences, with only a handful of expressed genes scattered throughout its length. Efforts to insert transgenes on this chromosome have thus far relied on either random insertion of transposons (sometimes harboring ‘landing sites’ for subsequent integrations) with limited success or on chromosomal translocations, thereby limiting the types of Y-chromosome related questions that could be explored. Here we describe a versatile approach to site-specifically insert transgenes on the Y-chromosome in D. melanogaster via CRISPR/Cas9-mediated HDR. We demonstrate the ability to insert, and detect expression from, fluorescently marked transgenic transgenes at two specific locations on the Y-chromosome, and we utilize these marked Y-chromosomes to detect and quantify rare chromosomal nondisjunction effects. Finally, we discuss how this Y-docking technique could be adapted to other insects to aid in the development of genetic control technologies for the management of insect disease vectors and pests.
Cytoskeletal changes during classical activation of macrophages in 2D and 3D environments

As effector cells of the innate immune response, macrophages are capable of recognizing and eliminating pathogens during inflammation. Macrophages achieve maximal immunological potential by undergoing cellular activation. Classical activation of macrophages (M1) with interferon-γ (IFNγ) and lipopolysaccharide (LPS) greatly enhances the immune response against intruding pathogens. We have previously revealed that stathmin association with microtubules (MTs) is considerably reduced in M1 macrophages using proteomics approaches. In this thesis, we demonstrate a LPS-dependent stathmin protein reduction in M1 macrophages. We also explored the functional roles of stathmin down-regulation by generating stable cell lines overexpressing stathmin-GFP. Stathmin-GFP overexpression impaired MT integrity and reduced activation-associated phenotypes. Furthermore, overexpressing stathmin-GFP inhibited complement receptor 3 (CR3)-mediated phagocytosis and cellular activation, implicating its pivotal inhibitory role in classical activation of macrophages. We next explored the role of the microenvironment in the classical activation of macrophages. Previous studies were predominately conducted on two-dimensional (2D) platforms. Consequently, we cultured
Comparison of Two Trap Types for Monitoring Bactrocera oleae (Rossi) (Diptera: Tephritidae) in Commercial Olive Groves of the Western Cape Province, South Africa

The efficacy of two commercially available traps used for monitoring Bactrocera oleae (Rossi) (olive fruit fly) were tested in the Western Cape Province, South Africa. We compared the efficacy of yellow Delta traps and yellow Bucket traps, baited with Olive Fruit Fly lure, which attracts both B. oleae males and females. Traps were tested in 20 commercial olive groves, at three locations during autumn (March–May) in 2013. The yellow Delta traps caught significantly more B. oleae than the yellow Bucket traps, as well as significantly more B. oleae males than females. Ceratitis capitata (Wiedemann) and Bactrocera biguttula (Bezzi) were also trapped during the study. For both species, yellow Delta traps caught significantly more individuals than yellow Bucket traps. This study showed that yellow Delta traps performed better than yellow Bucket traps, in monitoring B. oleae activity in commercial olive groves during autumn, prior to harvest
Diet-related differences in craniodental morphology between captive-reared and wild coyotes, Canis latrans (Carnivora: Canidae)

In mammals, skull loading incurred during feeding and prey capture shapes craniodental morphology as a result of bone plasticity, but the degree to which skull form is influenced by mechanical loading is poorly understood. Here, we tested how craniodental morphology is affected by differences in diet and age between wild and captive-reared coyotes (Canis latrans) raised on a relatively soft diet lacking bone. For both samples, we quantified tooth wear, external skull dimensions and frontal sinus morphology. Skull dimensions were similar between both populations, but captive coyotes had significantly broader zygomatic widths and palates, and lesser tooth wear and tooth fracture. However, differences observed between captive and wild coyotes are less than those observed in larger, more hypercarnivorous carnivorans. Frontal sinus volume did not differ significantly between populations, but was significantly correlated with external cranial dimensions in wild, but not captive coyotes. We hypothesize that greater mechanical demands of a wild diet, as evidenced by greater tooth wear, resulted in a stronger correlation between frontal sinus form and external skull form in wild coyotes. In captive coyotes, reduced skull loading because of a softer diet reduces constraints on cranial morphology and results in less covariation between internal and external cranial morphology.
Nutrient Status of Aprioct (Prunus armeniaca L.) Orchards of District Kargil, Ladakh

Apricot (Prunus armeniaca L.) belongs to family Rosaceae. It is grown mostly in the temperate regions of the world e.g. Western and Central Asia, Europe, North Western Himalaya and Western Tibet. It is probably a native of Western China. In India, it is cultivated in Jammu and Kashmir, Himachal Pradesh and hills of Uttar Pradesh. In Jammu and Kashmir State, about 3030 hectare area covered under this fruit. Ladakh is named as International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 7 Number 06 (2018) Journal homepage: http://www.ijcmas. com
Investigating resting-state functional connectivity in health and epilepsy using magnetonencephalography

It is now widely accepted that different areas of the brain are functionally connected even in the absence of explicit task demands, the so-called 'resting-state'. Differences in resting-state connectivity between groups are increasingly used as a marker of pathology in a number of neurological diseases and neuropsychiatric disorders. However, in order for a specific pattern of functional connectivity to represent a valid biomarker, it must be proven to be stable and reliably measurable in the absence of disease or disorder. Further, much is still unknown about the biological basis and purpose of resting-state activity, that may help to elucidate the functional relevance in patient groups. Magnetoencephalography (MEG) is a technique that is well suited to the study of resting-state connectivity because it provides a direct inference of synchronised neuronal activity. In chapter two of this thesis, the test-retest repeatability of two different approaches to assessing functional coupling of brain areas using MEG is examined. Having established a preferential analysis pipeline, chapter three compares frequency band-limited MEG connectivity with functional connectivity derived from BOLD-fMRI data. The connectivity pipeline is then used for two different applications. First, the approach is combined with pharmacological intervention in healthy subjects in order to investigate the role of AMPA receptors in the glutamate system on the MEG signal and functional connectivity (chapter four). The final experimental chapter focuses on comparing functional connectivity in a group of generalised epilepsy patients with age- and gender-matched healthy control subjects. Taken together, the results of this thesis have implications for the study of functional connectivity in the resting-state using MEG, particularly the sensitivity of the technique to microscale as well as macroscale changes