Improving microbial phylogeny with citizen science within a mass-market video game.

Citizen science video games are designed primarily for users already inclined to contribute to science, which severely limits their accessibility for an estimated community of 3 billion gamers worldwide. We created Borderlands Science (BLS), a citizen science activity that is seamlessly integrated within a popular commercial video game played by tens of millions of gamers. This integration is facilitated by a novel game-first design of citizen science games, in which the game design aspect has the highest priority, and a suitable task is then mapped to the game design. BLS crowdsources a multiple alignment task of 1 million 16S ribosomal RNA sequences obtained from human microbiome studies. Since its initial release on 7 April 2020, over 4 million players have solved more than 135 million science puzzles, a task unsolvable by a single individual. Leveraging these results, we show that our multiple sequence alignment simultaneously improves microbial phylogeny estimations and UniFrac effect sizes compared to state-of-the-art computational methods. This achievement demonstrates that hyper-gamified scientific tasks attract massive crowds of contributors and offers invaluable resources to the scientific community.

When online citizen science meets teaching: Storyfication of a science discovery game to teach, learn, and contribute to genomic research.

In the last decade, video games became a common vehicle for citizen science initiatives in life science, allowing participants to contribute to real scientific data analysis while learning about it. Since 2010, our scientific discovery game (SDG) Phylo enlists participants in comparative genomic data analysis. It is frequently used as a learning tool, but the activities were difficult to aggregate to build a coherent teaching activity. Here, we describe a strategy and series of recipes to facilitate the integration of SDGs in courses and implement this approach in Phylo. We developed new roles and functionalities enabling instructors to create assignments and monitor the progress of students. A story mode progressively introduces comparative genomics concepts, allowing users to learn and contribute to the analysis of real genomic sequences. Preliminary results from a user study suggest this framework may help to boost user motivation and clarify pedagogical objectives.

Complex AC Magnetic Susceptibility as a Tool for Exploring Nonlinear Magnetic Phenomena and Pinning Properties in Superconductors.

The versatile AC magnetic susceptibility technique offers a detailed insight into the complex electrodynamic phenomena in superconductors. In the present study, we outline the key effects related to the temperature, AC field amplitude and frequency variations of the fundamental and harmonic components for an investigation of the vortex dynamics in a flux-grown FeSe crystal. By means of higher harmonic (nonlinear) analysis, we have explored certain atypical, asymmetric features in the AC magnetic response. These effects were identified through the detection of an even (second) harmonic and an unusual temperature shift in the odd (third) harmonic, possibly due to the complex interactions related to the composite superconducting/magnetic morphology of the crystal. Using the high-frequency sensitivity of the third harmonic, the basic functional dependencies of the pinning activation energy, as the main mixed state parameter, were determined with the implementation of the Kim-Anderson Arrhenius relation in the framework of the collective creep theory.

High Pinning Force Values of a Fe(Se, Te) Single Crystal Presenting a Second Magnetization Peak Phenomenon.

The magnetization M of an Fe(Se, Te) single crystal has been measured as a function of temperature T and dc magnetic field H. The sample properties have been analyzed in the case of a magnetic field parallel to its largest face H||ab. From the M(T) measurement, the Tc of the sample and a magnetic background have been revealed. The superconducting hysteresis loops M(H) were between 2.5 K and 15 K showing a tilt due to the presence of a magnetic signal measured at T > Tc. From the M(H) curves, the critical current density Jc(H) has been extracted at different temperatures showing the presence of a second magnetization peak phenomenon. By extracting and fitting the Jc(T) curves at different fields, a pinning regime crossover has been identified and shown to be responsible for the origin of the second magnetization peak phenomenon. Then, the different kinds of pinning centers of the sample were investigated by means of Dew-Hughes analysis, showing that the pinning mechanism in the sample can be described in the framework of the collective pinning theory. Finally, the values of the pinning force density have been calculated at different temperatures and compared with the literature in order to understand if the sample is promising for high-current and high-power applications.

Successive Kinesin-5 Microtubule Crosslinking and Sliding Promote Fast, Irreversible Formation of a Stereotyped Bipolar Spindle.

Separation of duplicated spindle poles is the first step in forming the mitotic spindle. Kinesin-5 crosslinks and slides anti-parallel microtubules (MTs), but it is unclear how these two activities contribute to the first steps in spindle formation. In this study, we report that in monopolar spindles, the duplicated spindle poles snap apart in a fast and irreversible step that produces a nascent bipolar spindle. Using mutations in Kinesin-5 that inhibit microtubule sliding, we show that the fast, irreversible pole separation is primarily driven by microtubule crosslinking. Electron tomography revealed microtubule pairs in monopolar spindles have short overlaps that intersect at high angles and are unsuited for ensemble Kinesin-5 sliding. However, maximal extension of a subset of anti-parallel microtubule pairs approaches the length of nascent bipolar spindles and is consistent with a Kinesin-5 crosslinking-driven transition. Nonetheless, microtubule sliding by Kinesin-5 contributes to stabilizing the nascent spindle and setting its stereotyped equilibrium length.

Application of Immobilized Enzymes in Food Industry.

Enzymes are macromolecular biocatalysts, widely used in food industry. In applications, enzymes are often immobilized on inert and insoluble carriers, which increase their efficiency due to multiple reusability. The properties of immobilized enzymes depend on the immobilization method and the carrier type. The choice of the carrier usually concerns the biocompatibility, chemical and thermal stability, insolubility under reaction conditions, capability of easy regeneration and reusability, as well as cost efficiency. In this review, we provide an overview of various carriers for enzyme immobilization, with the primary focus on food industry.

Storage, visualization, and navigation of 3D genomics data.

The field of 3D genomics grew at increasing rates in the last decade. The volume and complexity of 2D and 3D data produced is progressively outpacing the capacities of the technology previously used for distributing genome sequences. The emergence of new technologies provides also novel opportunities for the development of innovative approaches. In this paper, we review the state-of-the-art computing technology, as well as the solutions adopted by the platforms currently available.

U.S. Dental Specialty Residents' Expectations and Anticipated Benefits of Academic Employment.

The aims of this study were to assess features of an academic career that dental specialty residents, as a group and by gender, find most attractive and to identify what determines their expectations for responsibilities and professional growth in academic employment. In November 2013, an invitation to participate in the study along with a link to an online survey was sent to the 407 U.S. program directors of six of the dental specialties (endodontics, oral and maxillofacial surgery, pediatric dentistry, periodontics, prosthodontics, and orthodontics), asking them to forward the survey to their residents. A total of 287 residents responded (112 [41.3%] female and 159 [58.7%] male) out of 4,400 enrolled in these specialty training programs (6.5% response rate). The female respondents were significantly more interested in joining academia than were the male respondents (female 48%; male 31.5%; p<0.005). Respondents of both genders were attracted to academic dentistry by opportunities for intellectual and professional stimulation, but the lifestyle of academicians was significantly more important for the female respondents. The most important feature of a successful academic career for the female respondents was the ability to have a good balance between career and personal life. While opportunity to conduct research was a positive feature for all residents interested in academia and both male and female respondents agreed strongly on the need for collaboration between faculty members for productive research, male respondents agreed significantly more than female respondents that faculty members should conduct independent research. Faculty members' feedback about academic employment were a significantly positive influence on those planning an academic career compared to those planning to enter private practice. This study found that the female and male residents differed in their expectations of responsibilities and professional growth in academic employment. These results may be useful for academic dental institutions and organizations when developing faculty recruitment and retention programs.

Clinical significance of immediate mandibular lateral translation: A systematic review.

STATEMENT OF PROBLEM: Immediate mandibular lateral translation (IMLT) has been widely described in theory, but its clinical significance in prosthodontics and restorative dentistry is not clear. PURPOSE: The purpose of this study was to systematically review the existing literature to identify the clinical significance of IMLT (immediate side shift). MATERIAL AND METHODS: An electronic search for articles in the English language literature was performed independently by multiple investigators using a systematic search process with the PubMed search engine. After applying predetermined inclusion and exclusion criteria, the final list of studies was analyzed to identify the clinical significance of IMLT. RESULTS: The initial electronic search yielded 858 titles. The systematic application of the inclusion and exclusion criteria eventually produced 23 studies addressing IMLT in 914 human participants. Eleven studies reported use of voluntary movements, 5 articles reported use of only induced movements, 2 studies reported use of both voluntary and induced movements, and 5 articles did not report the recording method. The amount of IMLT reported ranged from 0 to 3 mm with minimal clarity among authors on the exact description of IMLT. No studies reported on any clinical implication (harm or benefit to patients or clinicians) of incorporating IMLT in diagnosis and treatment planning. CONCLUSIONS: This systematic review did not identify any scientific evidence on the clinical implications of IMLT. Furthermore, there is a lack of clear terminology related to IMLT and the timing of the side shift, occurrence of IMLT on the working versus nonworking condyle, and induced versus noninduced methods of recording and measuring. Current scientific evidence does not support the need to include IMLT as a factor when prosthodontic or restorative treatment is planned and executed.

Distinct roles for antiparallel microtubule pairing and overlap during early spindle assembly.

During spindle assembly, microtubules may attach to kinetochores or pair to form antiparallel pairs or interpolar microtubules, which span the two spindle poles and contribute to mitotic pole separation and chromosome segregation. Events in the specification of the interpolar microtubules are poorly understood. Using three-dimensional electron tomography and analysis of spindle dynamical behavior in living cells, we investigated the process of spindle assembly. Unexpectedly, we found that the phosphorylation state of an evolutionarily conserved Cdk1 site (S360) in γ-tubulin is correlated with the number and organization of interpolar microtubules. Mimicking S360 phosphorylation (S360D) results in bipolar spindles with a normal number of microtubules but lacking interpolar microtubules. Inhibiting S360 phosphorylation (S360A) results in spindles with interpolar microtubules and high-angle, antiparallel microtubule pairs. The latter are also detected in wild-type spindles <1 µm in length, suggesting that high-angle microtubule pairing represents an intermediate step in interpolar microtubule formation. Correlation of spindle architecture with dynamical behavior suggests that microtubule pairing is sufficient to separate the spindle poles, whereas interpolar microtubules maintain the velocity of pole displacement during early spindle assembly. Our findings suggest that the number of interpolar microtubules formed during spindle assembly is controlled in part through activities at the spindle poles.

Clathrin- and Arp2/3-independent endocytosis in the fungal pathogen Candida albicans.

UNLABELLED: Clathrin-mediated endocytosis (CME) is conserved among eukaryotes and has been extensively analyzed at a molecular level. Here, we present an analysis of CME in the human fungal pathogen Candida albicans that shows the same modular structure as those in other fungi and mammalian cells. Intriguingly, C. albicans is perfectly viable in the absence of Arp2/3, an essential component of CME in other systems. In C. albicans, Arp2/3 function remains essential for CME as all 15 proteins tested that participate in CME, including clathrin, lose their characteristic dynamics observed in wild-type (WT) cells. However, since arp2/3 cells are still able to endocytose lipids and fluid-phase markers, but not the Ste2 and Mup1 plasma membrane proteins, there must be an alternate clathrin-independent pathway we term Arp2/3-independent endocytosis (AIE). Characterization of AIE shows that endocytosis in arp2 mutants relies on actin cables and other Arp2/3-independent actin structures, as inhibition of actin functions prevented cargo uptake in arp2/3 mutants. Transmission electron microscopy (TEM) showed that arp2/3 mutants still formed invaginating tubules, cell structures whose proper functions are believed to heavily rely on Arp2/3. Finally, Prk1 and Sjl2, two proteins involved in patch disassembly during CME, were not correctly localized to sites of endocytosis in arp2 mutants, implying a role of Arp2/3 in CME patch disassembly. Overall, C. albicans contains an alternative endocytic pathway (AIE) that relies on actin cable function to permit clathrin-independent endocytosis (CIE) and provides a system to further explore alternate endocytic routes that likely exist in fungal species. IMPORTANCE: There is a well-established process of endocytosis that is generally used by eukaryotic cells termed clathrin-mediated endocytosis (CME). Although the details are somewhat different between lower and higher eukaryotes, CME appears to be the dominant endocytic process in all eukaryotes. While fungi such as Saccharomyces cerevisiae have proven excellent models for dissecting the molecular details of endocytosis, loss of CME is so detrimental that it has been difficult to study alternate pathways functioning in its absence. Although the fungal pathogen Candida albicans has a CME pathway that functions similarly to that of S. cerevisiae, inactivation of this pathway does not compromise growth of yeast-form C. albicans. In these cells, lipids and fluid-phase molecules are still endocytosed in an actin-dependent manner, but membrane proteins are not. Thus, C. albicans provides a powerful model for the analysis of CME-independent endocytosis in lower eukaryotes.

The RPH clasp assembly: a simple alternative to traditional designs.

One of the popular designs for the distal extension partial removable dental prosthesis is the RPI clasp assembly. A modification of the RPI clasp assembly is introduced. It incorporates a mesial rest (R), proximal plate (P), and a horizontal retentive arm (H-RPH). This clasp assembly provides benefits of the RPI clasp and can be used in clinical situations where the RPI clasp is contraindicated.

Microfluidic perfusion system for culturing and imaging yeast cell microarrays and rapidly exchanging media.

High resolution live cell microscopy is increasingly used to detect cellular dynamics in response to drugs and chemicals, but it depends on complex and expensive liquid handling devices that have limited its wider adoption. Here, we present a microfluidic perfusion system that is built without using specialized microfabrication infrastructure, simple to use because only a pipette is needed for liquid handling, and yet allows for rapid media exchange and simultaneous fluorescence microscopy imaging. Yeast cells may be introduced from a culture, or spotted as arrays on a coverslip, and are sandwiched with a 20 mum thick track-etched membrane. A second coverslip and a mesh with 120 mum porosity are placed on top, forming a microfluidic conduit for lateral flow of solutions by capillary effects. Solutions introduced through the inlet flow through the mesh and chemicals diffuse vertically across the membrane to the cells trapped below. Solutions are exchanged by adding a new sample to the inlet. Using this system, we studied the dynamic response of F-actin in living yeast expressing Sac6-EGFP-a protein associated with discrete F-actin structures called "patches"-to the drug latrunculin A, a well known inhibitor of actin polymerization. We observed that the patches disappeared in 85% of the cells within 5 min, and re-assembled in 45 min following exchange of the drug with media. The perfusion system presented here is a simple, inexpensive device suited for analysis of drug dose-response and regeneration of single cells and arrays of cells.

Prosthodontic complications in a prospective clinical trial of single-stage implants at 36 months.

PURPOSE: The present material reports on prosthodontic complications in a trial of 51 patients with prostheses supported by single-stage implants over a period of 36 months. MATERIALS AND METHODS: One hundred eighty-six single-stage implants were placed in 51 patients over a 3-year period in 2 carefully controlled prospective clinical trials. Nineteen of the patients (103 implants) were completely edentulous and restored with a maxillary complete denture and a mandibular fixed-detachable complete prosthesis. Single metal-ceramic crowns or fixed partial dentures were fabricated for the remaining 32 patients (83 implants). The fixed restorations were either screw-retained or cemented. RESULTS: All patients/implants were followed for a minimum of 3 years. Complications in the edentulous patients included fracture of denture teeth, fracture of the maxillary denture, and occlusal screw loosening. Occlusal screw loosening and loss of the resin composite access plug were the only complications observed in the patients treated with screw-retained restorations. No complications were found in the patients restored with cemented restorations on solid abutments. DISCUSSION: Problems with prostheses were very common in the completely edentulous patients (13 of 19 patients encountered complications), possibly a result of increased bite force or inadequate laboratory technique. Tooth fractures were seen more frequently in men than in women. Complications occurred in only 5 of the 32 partially edentulous patients. CONCLUSION: Complications were associated with laboratory-related procedures rather than the implant system itself.