Sex Chromosome-Specific Regulation in the \u3ci\u3eDrosophila\u3c/i\u3e Male Germline But Little Evidence for Chromosomal Dosage Compensation or Meiotic Inactivation

The evolution of heteromorphic sex chromosomes (e.g., XY in males or ZW in females) has repeatedly elicited the evolution of two kinds of chromosome-specific regulation: dosage compensation—the equalization of X chromosome gene expression in males and females— and meiotic sex chromosome inactivation (MSCI)—the transcriptional silencing and heterochromatinization of the X during meiosis in the male (or Z in the female) germline. How the X chromosome is regulated in the Drosophila melanogaster male germline is unclear. Here we report three new findings concerning gene expression from the X in Drosophila testes. First, X chromosome-wide dosage compensation appears to be absent from most of the Drosophila male germline. Second, microarray analysis provides no evidence for X chromosome-specific inactivation during meiosis. Third, we confirm the previous discovery that the expression of transgene reporters driven by autosomal spermatogenesis-specific promoters is strongly reduced when inserted on the X chromosome versus the autosomes; but we show that this chromosomal difference in expression is established in premeiotic cells and persists in meiotic cells. The magnitude of the X-autosome difference in transgene expression cannot be explained by the absence of dosage compensation, suggesting that a previously unrecognized mechanism limits expression from the X during spermatogenesis in Drosophila. These findings help to resolve several previously conflicting reports and have implications for patterns of genome evolution and speciation in Drosophila

Sex Chromosome-Specific Regulation in the Drosophila Male Germline But Little Evidence for Chromosomal Dosage Compensation or Meiotic Inactivation

Suppression of X-linked transgene reporters versus normal expression of endogenous X-linked genes suggest a novel form of X chromosome-specific regulation in Drosophila testes, instead of sex chromosome dosage compensation or meiotic inactivation

Análise da interferência entre cilindros rígidos alinhados sujeitos a vibrações induzidas pelo escoamento

TCC (graduação) - Universidade Federal de Santa Catarina. Campus Joinville. Engenharia Naval.Com o desenvolvimento da indústria offshore de óleo e gás e a implementação de risers em suas operações, um melhor entendimento do fenômeno de vibração induzida pelo escoamento, ou Flow-Induced Vibration (FIV), envolvendo estruturas compostas por múltiplos cilindros se faz necessário, já que sistemas flutuantes em águas profundas podem conter um elevado número de risers de produção e sistemas de amarração em uma única plataforma. Neste contexto, experimentos foram conduzidos no Instituto de Pesquisas Tecnológicas (IPT) com dois cilindros rígidos semelhantes em tandem, ou seja, alinhados entre si e em relação ao escoamento. Ambos os cilindros foram montados em um suporte elástico permitindo a vibração em dois graus de liberdade, na direção transversal e longitudinal ao escoamento. Diferentes espaçamentos entre cilindros foram testados (2D; 2,5D; 3D; 4D; 6D; onde D corresponde ao diâmetro do cilindro). De maneira a permitir a excitação de toda a faixa de sincronização na direção transversal ao escoamento, as velocidades reduzidas empregadas variaram entre 3 a 13, o que é proporcional a números de Reynolds aproximadamente entre 3.〖10〗^3<Re<3.〖10〗^4. Os resultados mostrados no presente trabalho encontraram uma resposta qualitativamente similar entre o cilindro a montante e o cilindro isolado. O cilindro a jusante exibiu grandes amplitudes de resposta comparado ao cilindro a montante no ramo inferior de vibração. Por fim, a diferença de fase entre as oscilações transversais dos cilindros foi classificada de acordo com cinco padrões de fase, sendo que, os padrões de fase I e II mostraram respectivamente ter relação com os ramos inicial e superior de vibração para todos os casos.With the development of offshore oil field and deployment of riser pipes, a better understanding of the Flow-Induced Vibration (FIV) phenomenon involving multiples cylindrical structures it is necessary since actual deep-water floating systems can contain several numbers of production risers and many more mooring lines in a single platform. In this context, experiments were conducted at the Technological Research Institute (IPT) for two similar rigid cylinders in a tandem arrangement that means in-line between them and with the flow. Both cylinders were elastic mounted allowing two degrees of freedom, on the flow and cross-flow direction. Different spacing between cylinders was tested (2D; 2,5D; 3D; 4D; 6D; i.e. D corresponding to the cylinder diameter). In order to allow the excitation throughout the complete lock-in range in the crossflow direction, the reduced speeds ranged from 3 to 13, which correspond to Reynolds numbers approximately between 3.〖10〗^3<Re<3.〖10〗^4. The results shown in the present research found the upstream cylinder having a qualitatively similar response compared with the isolated cylinder. The downstream cylinder exhibited large response amplitudes compared to the upstream one in the lower branch of vibration. Lastly, the phase difference between transverse displacements of both cylinders was classified according to five phase patterns. The phase patterns I and II were shown respectively related to the initial and superior branches of vibration in all cases

Intense Simulation-Based Surgical Education for Manual Small-Incision Cataract Surgery: The Ophthalmic Learning and Improvement Initiative in Cataract Surgery Randomized Clinical Trial in Kenya, Tanzania, Uganda, and Zimbabwe.

Importance: Cataracts account for 40% of cases of blindness globally, with surgery the only treatment. Objective: To determine whether adding simulation-based cataract surgical training to conventional training results in improved acquisition of surgical skills among trainees. Design, Setting, and Participants: A multicenter, investigator-masked, parallel-group, randomized clinical educational-intervention trial was conducted at 5 university hospital training institutions in Kenya, Tanzania, Uganda, and Zimbabwe from October 1, 2017, to September 30, 2019, with a follow-up of 15 months. Fifty-two trainee ophthalmologists were assessed for eligibility (required no prior cataract surgery as primary surgeon); 50 were recruited and randomized. Those assessing outcomes of surgical competency were masked to group assignment. Analysis was performed on an intention-to-treat basis. Interventions: The intervention group received a 5-day simulation-based cataract surgical training course, in addition to standard surgical training. The control group received standard training only, without a placebo intervention; however, those in the control group received the intervention training after the initial 12-month follow-up period. Main Outcomes and Measures: The primary outcome measure was overall surgical competency at 3 months, which was assessed with a validated competency assessment rubric. Secondary outcomes included surgical competence at 1 year and quantity and outcomes (including visual acuity and posterior capsule rupture) of cataract surgical procedures performed during a 1-year period. Results: Among the 50 participants (26 women [52.0%]; mean [SD] age, 32.3 [4.6] years), 25 were randomized to the intervention group, and 25 were randomized to the control group, with 1 dropout. Forty-nine participants were included in the final intention-to-treat analysis. Baseline characteristics were balanced. The participants in the intervention group had higher scores at 3 months compared with the participants in the control group, after adjusting for baseline assessment rubric score. The participants in the intervention group were estimated to have scores 16.6 points (out of 40) higher (95% CI, 14.4-18.7; P < .001) at 3 months than the participants in the control group. The participants in the intervention group performed a mean of 21.5 cataract surgical procedures in the year after the training, while the participants in the control group performed a mean of 8.5 cataract surgical procedures (mean difference, 13.0; 95% CI, 3.9-22.2; P < .001). Posterior capsule rupture rates (an important complication) were 7.8% (42 of 537) for the intervention group and 26.6% (54 of 203) for the control group (difference, 18.8%; 95% CI, 12.3%-25.3%; P < .001). Conclusions and Relevance: This randomized clinical trial provides evidence that intense simulation-based cataract surgical education facilitates the rapid acquisition of surgical competence and maximizes patient safety. Trial Registration: Pan-African Clinical Trial Registry, number PACTR201803002159198

Differences in clinical presentation of primary open-angle glaucoma between African and European populations

PURPOSE: Primary open‐angle glaucoma (POAG) has been reported to occur more frequently in Africans, and to follow a more severe course compared to Europeans. We aimed to describe characteristics of POAG presentation and treatment across three ethnic groups from Africa and one from Europe. METHODS: We ascertained 151 POAG patients from South African Coloured (SAC) and 94 South African Black (SAB) ethnicity from a university hospital in South Africa. In Tanzania, 310 patients were recruited from a university hospital and a referral hospital. In the Netherlands, 241 patients of European ancestry were included. All patients were over 35 years old and had undergone an extensive ophthalmic examination. Patients were diagnosed according to the ISGEO criteria. A biogeographic ancestry analysis was performed to estimate the proportion of genetic African ancestry (GAA). RESULTS: The biogeographic ancestry analysis showed that the median proportion of GAA was 97.6% in Tanzanian, 100% in SAB, 34.2% in SAC and 1.5% in Dutch participants. Clinical characteristics at presentation for Tanzanians, SAB, SAC and Dutch participants, respectively: mean age: 63, 57, 66, 70 years (p < 0.001); visual acuity in the worse eye: 1.78, 1.78, 0.3, 0.3 LogMAR (p < 0.001); maximum intraocular pressure of both eyes: 36, 34, 29, 29 mmHg (p (anova)  < 0.001); maximum vertical cup to disc ratio (VCDR) of both eyes: 0.90, 0.90, 0.84, 0.83 (p < 0.001); mean central corneal thickness: 506, 487, 511, 528 μm (p < 0.001). Fourteen percent of Tanzanian patients presented with blindness (<3/60 Snellen) in the better eye in contrast to only 1% in the Dutch. CONCLUSION: In this multi‐ethnic comparative study, Sub‐Saharan Africans present at a younger age with lower visual acuity, higher IOP, larger VCDR, than SAC and Dutch participants. This indicates the more progressive and destructive course in Sub‐Saharan Africans

Application of pharmacogenomics and bioinformatics to exemplify the utility of human <i>ex vivo</i> organoculture models in the field of precision medicine

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response

Parallelized computational 3D video microscopy of freely moving organisms at multiple gigapixels per second

To study the behavior of freely moving model organisms such as zebrafish (Danio rerio) and fruit flies (Drosophila) across multiple spatial scales, it would be ideal to use a light microscope that can resolve 3D information over a wide field of view (FOV) at high speed and high spatial resolution. However, it is challenging to design an optical instrument to achieve all of these properties simultaneously. Existing techniques for large-FOV microscopic imaging and for 3D image measurement typically require many sequential image snapshots, thus compromising speed and throughput. Here, we present 3D-RAPID, a computational microscope based on a synchronized array of 54 cameras that can capture high-speed 3D topographic videos over a 135-cm^2 area, achieving up to 230 frames per second at throughputs exceeding 5 gigapixels (GPs) per second. 3D-RAPID features a 3D reconstruction algorithm that, for each synchronized temporal snapshot, simultaneously fuses all 54 images seamlessly into a globally-consistent composite that includes a coregistered 3D height map. The self-supervised 3D reconstruction algorithm itself trains a spatiotemporally-compressed convolutional neural network (CNN) that maps raw photometric images to 3D topography, using stereo overlap redundancy and ray-propagation physics as the only supervision mechanism. As a result, our end-to-end 3D reconstruction algorithm is robust to generalization errors and scales to arbitrarily long videos from arbitrarily sized camera arrays. The scalable hardware and software design of 3D-RAPID addresses a longstanding problem in the field of behavioral imaging, enabling parallelized 3D observation of large collections of freely moving organisms at high spatiotemporal throughputs, which we demonstrate in ants (Pogonomyrmex barbatus), fruit flies, and zebrafish larvae