188 research outputs found

    Tinklalaidės neformaliajame mokymesi: socialinių medijų naudojimas asmeninės mokymosi aplinkos, asmeninio mokymosi tinklo kūrimui

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    The use of second-generation web technology (WEB2) in education is emphasising the role of social media as educational sources. Researchers that are analysing personal learning environments (Schaffert, Kalz, 2009; Dabbagh, Kitsantas, 2012), personal learning networks (Couros, 2010) suggest the importance of social media, although this emphasis is attributed to the collaborative interaction of learners. To comprehensively assess the potential of podcasts as social media in the creation of personal learning environments, personal learning networks, the research described in this article does not restrict the definition of podcasts as the potential of collaboration provided by social media. In this article, attention is directed towards the potential of podcasts in the creation of personal learning environment and personal learning networks. By using integrated information behaviour module analysis to determine if the students of Lithuanian higher education institutions value the potential of informal learning provided by podcasts. To determine if these technologies are used for the formation of personal learning environments, personal learning networks, a discussion group research was conducted. During the research the analysis of participant podcast usage showed there is interaction between media content used for recreation and media content used for formal and informal learning. This means that the participants of the research use podcasts to create personal learning environments. On the other hand, this interaction is minimal, created only by the learners and reasoned by the search of educational podcasts. The analysis of the experiences of the discussion participants revealed that the collaborative interaction between learners involved in the research in searching, sharing and using podcasts in the process of learning is not intensive, it is typically fragmented. This allows to point out that the communities that use podcasts for informal learning are not forming. This shows that the potential of podcasts in creating a learning network is not fulfilled, and that podcasts don’t inspire participatory learning.Antrosios kartos saityno technologijų (WEB2) naudojimas mokymesi nurodo socialinių medijų kaip mokymosi šaltinių, išteklių reikšmės augimą. Šiame straipsnyje dėmesys atkreipiamas į tinklalaidžių potencialą besimokančiųjų asmeninės mokymosi aplinkos, asmeninio mokymosi tinklo kūrimui. Mokslininkai, analizuojantys asmeninę mokymosi aplinką (Schaffert, Kalz, 2009; Dabbagh, Kitsantas, 2012), asmeninius mokymosi tinklus (Couros, 2010), nurodo išskirtinę socialinių medijų svarbą. Tačiau toks socialinių medijų sureikšminimas siejamas su besimokančiųjų bendradarbiaujamosios sąveikos užtikrinimu. Šiame straipsnyje pristatomame tyrime siekiant visapusiškai įvertinti tinklalaidžių kaip socialinių medijų potencialą kuriant asmeninę mokymosi aplinką, asmeninį mokymosi tinklą, neapsiribota tik jų kaip socialinių medijų teikiamų bendradarbiavimo galimybių įvertinimu. Taikant integruoto informacinės elgsenos modelio tyrimo prieigą nustatant, kaip Lietuvos aukštųjų mokyklų studentai vertina tinklalaidžių neformaliojo savaiminio mokymosi potencialą: ar šios technologijos naudojamos asmeninei mokymosi aplinkai, asmeniniam mokymosi tinklui formuoti, buvo atliktas diskusijų grupių tyrimas. Tyrimo metu atlikta diskusijos dalyvių tinklalaidžių naudojimo analizė parodė, kad yra formuojama sąveika tarp pramogoms ir formaliajam bei neformaliajam mokymuisi naudojamo šių naujųjų medijų turinio. Tai reiškia, kad tyrimo dalyviai tinklalaides naudoja asmeninės mokymosi aplinkos kūrimui. Tačiau ši sąveika yra minimali, kuriama tik pačių besimokančiųjų, ji grindžiama mokymosi turinio tinklalaidžių saviieška. Diskusijos dalyvių patirčių analizė atskleidė, kad bendradarbiaujamoji sąveika tarp tyrime dalyvavusių besimokančiųjų ieškant, dalijantis, naudojant tinklalaides mokymuisi nėra intensyvi, jai būdingas fragmentiškumas. Tai leidžia pastebėti, kad neformaliojo mokymosi naudojant tinklalaides bendruomenės nesiformuoja. Tai rodo, kad tinklalaidžių potencialas neišnaudojamas dalyvaujamojo mokymosi tinklo kūrimui, tinklalaidės neinspiruoja dalyvaujamojo mokymosi

    The cost of promiscuity: sexual transmission of Nosema microsporidian parasites in polyandrous honey bees

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    Multiple mating (and insemination) by females with different males, polyandry, is widespread across animals, due to material and/or genetic benefits for females. It reaches particularly high levels in some social insects, in which queens can produce significantly fitter colonies by being polyandrous. It is therefore a paradox that two thirds of eusocial hymenopteran insects appear to be exclusively monandrous, in spite of the fitness benefits that polyandry could provide. One possible cost of polyandry could be sexually transmitted parasites, but evidence for these in social insects is extremely limited. Here we show that two different species of Nosema microsporidian parasites can transmit sexually in the honey bee Apis mellifera. Honey bee males that are infected by the parasite have Nosema spores in their semen, and queens artificially inseminated with either Nosema spores or the semen of Nosema-infected males became infected by the parasite. The emergent and more virulent N. ceranae achieved much higher rates of infection following insemination than did N. apis. The results provide the first quantitative evidence of a sexually transmitted disease (STD) in social insects, indicating that STDs may represent a potential cost of polyandry in social insects

    Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg

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    Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 μg contain equal amounts of lactose per carrier. However, 150 μg has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 μg and 300 μg), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD ≤5 μm irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter <3 μm is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 μg. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez Breezhaler®, and confirm the good practice to make two separate inhalations from the same dose

    Domain architecture evolution of pattern-recognition receptors

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    In animals, the innate immune system is the first line of defense against invading microorganisms, and the pattern-recognition receptors (PRRs) are the key components of this system, detecting microbial invasion and initiating innate immune defenses. Two families of PRRs, the intracellular NOD-like receptors (NLRs) and the transmembrane Toll-like receptors (TLRs), are of particular interest because of their roles in a number of diseases. Understanding the evolutionary history of these families and their pattern of evolutionary changes may lead to new insights into the functioning of this critical system. We found that the evolution of both NLR and TLR families included massive species-specific expansions and domain shuffling in various lineages, which resulted in the same domain architectures evolving independently within different lineages in a process that fits the definition of parallel evolution. This observation illustrates both the dynamics of the innate immune system and the effects of “combinatorially constrained” evolution, where existence of the limited numbers of functionally relevant domains constrains the choices of domain architectures for new members in the family, resulting in the emergence of independently evolved proteins with identical domain architectures, often mistaken for orthologs

    Probing the Mutational Interplay between Primary and Promiscuous Protein Functions: A Computational-Experimental Approach

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    Protein promiscuity is of considerable interest due its role in adaptive metabolic plasticity, its fundamental connection with molecular evolution and also because of its biotechnological applications. Current views on the relation between primary and promiscuous protein activities stem largely from laboratory evolution experiments aimed at increasing promiscuous activity levels. Here, on the other hand, we attempt to assess the main features of the simultaneous modulation of the primary and promiscuous functions during the course of natural evolution. The computational/experimental approach we propose for this task involves the following steps: a function-targeted, statistical coupling analysis of evolutionary data is used to determine a set of positions likely linked to the recruitment of a promiscuous activity for a new function; a combinatorial library of mutations on this set of positions is prepared and screened for both, the primary and the promiscuous activities; a partial-least-squares reconstruction of the full combinatorial space is carried out; finally, an approximation to the Pareto set of variants with optimal primary/promiscuous activities is derived. Application of the approach to the emergence of folding catalysis in thioredoxin scaffolds reveals an unanticipated scenario: diverse patterns of primary/promiscuous activity modulation are possible, including a moderate (but likely significant in a biological context) simultaneous enhancement of both activities. We show that this scenario can be most simply explained on the basis of the conformational diversity hypothesis, although alternative interpretations cannot be ruled out. Overall, the results reported may help clarify the mechanisms of the evolution of new functions. From a different viewpoint, the partial-least-squares-reconstruction/Pareto-set-prediction approach we have introduced provides the computational basis for an efficient directed-evolution protocol aimed at the simultaneous enhancement of several protein features and should therefore open new possibilities in the engineering of multi-functional enzymes

    An Atlas of the Thioredoxin Fold Class Reveals the Complexity of Function-Enabling Adaptations

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    The group of proteins that contain a thioredoxin (Trx) fold is huge and diverse. Assessment of the variation in catalytic machinery of Trx fold proteins is essential in providing a foundation for understanding their functional diversity and predicting the function of the many uncharacterized members of the class. The proteins of the Trx fold class retain common features—including variations on a dithiol CxxC active site motif—that lead to delivery of function. We use protein similarity networks to guide an analysis of how structural and sequence motifs track with catalytic function and taxonomic categories for 4,082 representative sequences spanning the known superfamilies of the Trx fold. Domain structure in the fold class is varied and modular, with 2.8% of sequences containing more than one Trx fold domain. Most member proteins are bacterial. The fold class exhibits many modifications to the CxxC active site motif—only 56.8% of proteins have both cysteines, and no functional groupings have absolute conservation of the expected catalytic motif. Only a small fraction of Trx fold sequences have been functionally characterized. This work provides a global view of the complex distribution of domains and catalytic machinery throughout the fold class, showing that each superfamily contains remnants of the CxxC active site. The unifying context provided by this work can guide the comparison of members of different Trx fold superfamilies to gain insight about their structure-function relationships, illustrated here with the thioredoxins and peroxiredoxins

    Perspectives on the use of transcriptomics to advance biofuels

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    As a field within the energy research sector, bioenergy is continuously expanding. Although much has been achieved and the yields of both ethanol and butanol have been improved, many avenues of research to further increase these yields still remain. This review covers current research related with transcriptomics and the application of this high-throughput analytical tool to engineer both microbes and plants with the penultimate goal being better biofuel production and yields. The initial focus is given to the responses of fermentative microbes during the fermentative production of acids, such as butyric acid, and solvents, including ethanol and butanol. As plants offer the greatest natural renewable source of fermentable sugars within the form of lignocellulose, the second focus area is the transcriptional responses of microbes when exposed to plant hydrolysates and lignin-related compounds. This is of particular importance as the acid/base hydrolysis methods commonly employed to make the plant-based cellulose available for enzymatic hydrolysis to sugars also generates significant amounts of lignin-derivatives that are inhibitory to fermentative bacteria and microbes. The article then transitions to transcriptional analyses of lignin-degrading organisms, such as Phanerochaete chrysosporium, as an alternative to acid/base hydrolysis. The final portion of this article will discuss recent transcriptome analyses of plants and, in particular, the genes involved in lignin production. The rationale behind these studies is to eventually reduce the lignin content present within these plants and, consequently, the amount of inhibitors generated during the acid/base hydrolysis of the lignocelluloses. All four of these topics represent key areas where transcriptomic research is currently being conducted to identify microbial genes and their responses to products and inhibitors as well as those related with lignin degradation/formation.clos

    Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

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    To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges

    Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

    Get PDF
    To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges

    More Than 1,001 Problems with Protein Domain Databases: Transmembrane Regions, Signal Peptides and the Issue of Sequence Homology

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    Large-scale genome sequencing gained general importance for life science because functional annotation of otherwise experimentally uncharacterized sequences is made possible by the theory of biomolecular sequence homology. Historically, the paradigm of similarity of protein sequences implying common structure, function and ancestry was generalized based on studies of globular domains. Having the same fold imposes strict conditions over the packing in the hydrophobic core requiring similarity of hydrophobic patterns. The implications of sequence similarity among non-globular protein segments have not been studied to the same extent; nevertheless, homology considerations are silently extended for them. This appears especially detrimental in the case of transmembrane helices (TMs) and signal peptides (SPs) where sequence similarity is necessarily a consequence of physical requirements rather than common ancestry. Thus, matching of SPs/TMs creates the illusion of matching hydrophobic cores. Therefore, inclusion of SPs/TMs into domain models can give rise to wrong annotations. More than 1001 domains among the 10,340 models of Pfam release 23 and 18 domains of SMART version 6 (out of 809) contain SP/TM regions. As expected, fragment-mode HMM searches generate promiscuous hits limited to solely the SP/TM part among clearly unrelated proteins. More worryingly, we show explicit examples that the scores of clearly false-positive hits, even in global-mode searches, can be elevated into the significance range just by matching the hydrophobic runs. In the PIR iProClass database v3.74 using conservative criteria, we find that at least between 2.1% and 13.6% of its annotated Pfam hits appear unjustified for a set of validated domain models. Thus, false-positive domain hits enforced by SP/TM regions can lead to dramatic annotation errors where the hit has nothing in common with the problematic domain model except the SP/TM region itself. We suggest a workflow of flagging problematic hits arising from SP/TM-containing models for critical reconsideration by annotation users
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