Core PCP mutations affect short-time mechanical properties but not tissue morphogenesis in the Drosophila pupal wing.

How morphogenetic movements are robustly coordinated in space and time is a fundamental open question in biology. We study this question using the wing of Drosophila melanogaster, an epithelial tissue that undergoes large-scale tissue flows during pupal stages. Previously, we showed that pupal wing morphogenesis involves both cellular behaviors that allow relaxation of mechanical tissue stress, as well as cellular behaviors that appear to be actively patterned (Etournay et al., 2015). Here, we show that these active cellular behaviors are not guided by the core planar cell polarity (PCP) pathway, a conserved signaling system that guides tissue development in many other contexts. We find no significant phenotype on the cellular dynamics underlying pupal morphogenesis in mutants of core PCP. Furthermore, using laser ablation experiments, coupled with a rheological model to describe the dynamics of the response to laser ablation, we conclude that while core PCP mutations affect the fast timescale response to laser ablation they do not significantly affect overall tissue mechanics. In conclusion, our work shows that cellular dynamics and tissue shape changes during Drosophila pupal wing morphogenesis do not require core PCP as an orientational guiding cue.

Self-organized patterning of cell morphology via mechanosensitive feedback.

Tissue organization is often characterized by specific patterns of cell morphology. How such patterns emerge in developing tissues is a fundamental open question. Here, we investigate the emergence of tissue-scale patterns of cell shape and mechanical tissue stress in the Drosophila wing imaginal disc during larval development. Using quantitative analysis of the cellular dynamics, we reveal a pattern of radially oriented cell rearrangements that is coupled to the buildup of tangential cell elongation. Developing a laser ablation method, we map tissue stresses and extract key parameters of tissue mechanics. We present a continuum theory showing that this pattern of cell morphology and tissue stress can arise via self-organization of a mechanical feedback that couples cell polarity to active cell rearrangements. The predictions of this model are supported by knockdown of MyoVI, a component of mechanosensitive feedback. Our work reveals a mechanism for the emergence of cellular patterns in morphogenesis.

During development, carefully choreographed cell movements ensure the creation of a healthy organism. To determine their identity and place across a tissue, cells can read gradients of far-reaching signaling molecules called morphogens; in addition, physical forces can play a part in helping cells acquire the right size and shape. Indeed, cells are tightly attached to their neighbors through connections linked to internal components. Structures or proteins inside the cells can pull on these junctions to generate forces that change the physical features of a cell. However, it is poorly understood how these forces create patterns of cell size and shape across a tissue. Here, Dye, Popovic et al. combined experiments with physical models to examine how cells acquire these physical characteristics across the developing wing of fruit fly larvae. This revealed that cells pushing and pulling on one another create forces that trigger internal biochemical reorganization ­ for instance, force-generating structures become asymmetrical. In turn, the cells exert additional forces on their neighbors, setting up a positive feedback loop which results in cells adopting the right size and shape across the organ. As such, cells in the fly wing can spontaneously self-organize through the interplay of mechanical and biochemical signals, without the need for pre-existing morphogen gradients. A refined understanding of how physical forces shape cells and organs would help to grasp how defects can emerge during development. This knowledge would also allow scientists to better grow tissues and organs in the laboratory, both for theoretical research and regenerative medicine.

Instrument-based screening for amblyopia risk factors in a primary care setting in children aged 18 to 30 months.

Amblyopia is the leading cause of vision impairment in children, and its early detection can avoid irreversible consequences for a child's visual ability. In this prospective study, to detect amblyopia risk factors, we examined patients aged 18 to 30 months in primary care settings. Patients were referred to an ophthalmologist for confirmation. The main aims were to detect amblyogenic risk factors and to assess the usefulness of a photoscreener in such settings. Out of 453 patients, 42 (9.3%) presented visual alterations according to the photoscreener, with astigmatism being the most common. The instrument had good sensitivity (89%) and specificity (91%), with a positive predictive value of 76% and a negative predictive value of 96%. Overall, 38% of the patients required follow-up, and 47% needed glasses. The automated screening device allowed these children to be diagnosed at an early stage.Conclusions: The use of a photoscreener to screen 2-year-old children in primary care settings was helpful and accurate. What is Known: • Early detection of amblyopic risk factors is important to avoid vision defects. However, it is very difficult to measure visual acuity using visual charts in children younger than 4 years old. What is New: • Instrument-based screening in children aged 18 to 30 months allows excellent detection of early amblyopia risk factors in primary care settings.

Persistencia simultánea del conducto uraco y onfalomesentérico en un paciente adulto, reporte de caso / Simultaneous persistence of the urachus and vitelline ducts in an adult patient, case report / Persistência simultânea de úraco e do ducto onfalomesentérico em um paciente adulto: relato de caso

Introducción. La patología umbilical es un tema frecuente en el ámbito pediátrico, la presentación clínica de una fístula umbilical hace pensar en dos patologías mencionadas en la literatura de manera independiente; la primera es la persistencia del conducto onfalomesentérico y la segunda es la persistencia del remanente del uraco producto del fracaso en el cierre de las estructuras embrionarias. Su presencia en adultos es infrecuente y no existen datos estadísticos acerca de su presentación conjunta en población pediátrica o adulta, solo algunos pocos reportes de caso. El diagnóstico se basa principalmente en la sospecha clínica, depende en gran manera del examen físico al evidenciar secreción a través del ombligo al realizar esfuerzos o maniobras de Valsalva. Objetivo. Mostrar un caso infrecuente de la presentación simultánea del conducto de uraco y onfalomesentérico en un paciente adulto. Reporte de caso. Paciente femenina de 24 años de edad con antecedentes de infecciones urinarias y celulitis periumbilicales a repetición. Se sospecha un conducto persistente onfalomesentérico por lo que es sometida a un procedimiento quirúrgico en el que se encontró incidentalmente la persistencia simultánea del conducto onfalomesentérico y persistencia del uraco. Discusión. La persistencia del conducto onfalomesentérico o la persistencia del uraco de forma individual es poco frecuente en adultos, y es aún más raro la persistencia simultánea de ambos conductos; la presencia simultánea de ambos conductos es reportada principalmente en menores de dos años. Conclusiones. La persistencia de estos conductos es rara en adultos y representa un reto diagnóstico para el clínico. Cómo citar: Escudero-Sepúlveda AF, Cala-Duran JC, Belén Jurado MB, Pinasco-Gómez R, Tomasone SE, Roccuzzo C, Domínguez-Alvarado GA. Persistencia simultánea del conducto uraco y onfalomesentérico en un paciente adulto, reporte de caso. MedUNAB. 2020;23(2): 288-293. doi: 10.29375/01237047.3826.

Introduction. Umbilical pathology is a common topic in the pediatric sphere. The clinical presentation of an umbilical fistula leads to the consideration of two pathologies independently reported in literature. The first is a persistent vitelline duct and the second is a persistent urachal remnant as a result of the embryonic structures' failure to close. They are uncommon in adults and there are no statistical data about their presentation together in the pediatric or adult population, only very few case reports. The diagnosis is mainly based on clinical suspicion. It largely depends on a physical examination noting secretion through the navel when straining or performing Valsalva maneuvers. Objective. Show an uncommon case of the simultaneous presentation of the urachus and vitelline ducts in an adult patient. Case report. Female patient aged 24 years with a background of repeated urinary tract infections and periumbilical cellulitis. A persistent vitelline duct is suspected. Therefore, the patient is subject to a surgical procedure in which the simultaneous persistence of the vitelline duct and the urachus was found incidentally. Discussion. The persistence of the vitelline duct or the persistence of the urachus individually is uncommon in adults, and the simultaneous persistence of both ducts is even rarer. The simultaneous presence of both ducts is reported mainly in infants aged under two years. Conclusions. The persistence of these ducts is rare in adults and poses a diagnostic challenge for clinicians. Cómo citar: Escudero-Sepúlveda AF, Cala-Duran JC, Belén Jurado MB, Pinasco-Gómez R, Tomasone SE, Roccuzzo C, Domínguez-Alvarado GA. Persistencia simultánea del conducto uraco y onfalomesentérico en un paciente adulto, reporte de caso. MedUNAB. 2020;23(2): 288-293. doi: 10.29375/01237047.3826.

Introdução. A patologia umbilical é um tópico frequente no cenário pediátrico; a apresentação clínica de uma fístula umbilical faz pensar em duas patologias mencionadas na literatura de forma independente; a primeira é a persistência do ducto onfalomesentérico e a segunda é a persistência do úraco como resultado da falha no fechamento das estruturas embrionárias. É pouco frequente sua presença em adultos e não há dados estatísticos sobre sua apresentação conjunta em população pediátrica nem adulta, apenas alguns poucos relatos de caso. O diagnóstico baseia-se principalmente na suspeita clínica, dependendo em grande parte do exame físico ao evidenciar uma secreção pelo umbigo quando realizar esforço ou manobra de Valsalva. Objetivo. Mostrar um caso infrequente de apresentação simultânea do úraco e ducto onfalomesentérico em um paciente adulto. Relato de caso. Paciente do sexo feminino, 24 anos, com histórico de infecções urinárias e celulite periumbilical recorrentes. Suspeita-se de um ducto onfalomesentérico persistente, portanto ela é submetida a um procedimento cirúrgico no qual encontrou-se a persistência do ducto onfalomesentérico e a persistência de úraco simultaneamente. Discussão. A persistência do ducto onfalomesentérico e a persistência de úraco individualmente é rara em adultos, e a persistência simultânea de ambos os ductos é ainda mais rara; esta presença simultânea é relatada principalmente em crianças menores de dois anos de idade. Conclusão. A persistência desses ductos é rara em adultos e representa um desafio diagnóstico para o profissional de saúde clínico. Cómo citar: Escudero-Sepúlveda AF, Cala-Duran JC, Belén Jurado MB, Pinasco-Gómez R, Tomasone SE, Roccuzzo C, Domínguez-Alvarado GA. Persistencia simultánea del conducto uraco y onfalomesentérico en un paciente adulto, reporte de caso. MedUNAB. 2020;23(2): 288-293. doi: 10.29375/01237047.3826.

Epithelial Viscoelasticity Is Regulated by Mechanosensitive E-cadherin Turnover.

Studying how epithelia respond to mechanical stresses is key to understanding tissue shape changes during morphogenesis. Here, we study the viscoelastic properties of the Drosophila wing epithelium during pupal morphogenesis by quantifying mechanical stress and cell shape as a function of time. We find a delay of 8 h between maximal tissue stress and maximal cell elongation, indicating a viscoelastic deformation of the tissue. We show that this viscoelastic behavior emerges from the mechanosensitivity of endocytic E-cadherin turnover. The increase in E-cadherin turnover in response to stress is mediated by mechanosensitive relocalization of the E-cadherin binding protein p120-catenin (p120) from cell junctions to cytoplasm. Mechanosensitivity of E-cadherin turnover is lost in p120 mutant wings, where E-cadherin turnover is constitutively high. In this mutant, the relationship between mechanical stress and stress-dependent cell dynamics is altered. Cells in p120 mutant deform and undergo cell rearrangements oriented along the stress axis more rapidly in response to mechanical stress. These changes imply a lower viscosity of wing epithelium. Taken together, our findings reveal that p120-dependent mechanosensitive E-cadherin turnover regulates viscoelastic behavior of epithelial tissues.

Potential Distribution Map of Culicoides insignis (Diptera: Ceratopogonidae), Vector of Bluetongue Virus, in Northwestern Argentina.

Culicoides insignis Lutz is incriminated as a vector of bluetongue virus (BTV) to ruminants in America. In South America, almost all countries have serological evidence of BTV infections, but only four outbreaks of the disease have been reported. Although clinical diseases have never been cited in Argentina, viral activity has been detected in cattle. In this study, we developed a potential distribution map of Culicoides insignis populations in northwestern Argentina using Maximum Entropy Modeling (Maxent). For the analyses, information regarding both data of specimen collections between 2003 and 2013, and climatic and environmental variables was used. Variables selection was based on the ecological relevance in relation to Culicoides spp. biology and distribution in the area. The best Maxent model according to the Jackknife test included 53 C. insignis presence records and precipitation of the warmest quarter, altitude, and precipitation of the wettest month. Accuracy was evaluated by the area under the curve (AUC = 0.97). These results provide an important analytical resource of high potential for both the development of suitable control strategies and the assessment of disease transmission risk in the region.

Synthesis of polyhydroxy amino acids based on D- and L-alanine from D-glycero-D-gulo-heptono-1,4-lactone.

2-Amino-2,3-dideoxy-D-manno-heptonic acid (7) has been synthesized from 2,5,6,7-tetra-O-acetyl-3-deoxy-D-gluco-heptono-1,4-lactone (1), which was readily prepared from D-glycero-D-gulo-heptono-1,4-lactone. O-Deacetylation of 1 followed by treatment with 13:1 (v/v) 2,2-dimethoxypropane/acetone in the presence of p-toluenesulfonic acid gave methyl 3-deoxy-4,5:6,7-di-O-isopropylidene-D-gluco-heptonate (3) as a crystalline product (80% yield). The free hydroxyl group (OH-2) of 3 was mesylated and substituted by azide to give the corresponding azide derivative 5. Hydrogenolysis and further hydrolysis of the ester function of 5 afforded alpha-amino acid 7 (43% overall yield from 1). Compound 7 is an analog of L-alanine having a polyhydroxy chain attached to C-3. The diastereoisomer of 7 at C-2, 2-amino-2,3-dideoxy-D-gluco-heptonic acid (12) was also prepared from 3, by a route that involved 2,3-dideoxy-2-iodo derivative 8 as a key intermediate.