Broadening Participation: 21st Century Opportunities for Amateurs in Biology Research.

The modern field of biology has its roots in the curiosity and skill of amateur researchers and has never been purely the domain of professionals. Today, professionals and amateurs contribute to biology research, working both together and independently. Well-targeted and holistic investment in amateur biology research could bring a range of benefits that, in addition to positive societal benefits, may help to address the considerable challenges facing our planet in the 21st century. We highlight how recent advances in amateur biology have been facilitated by innovations in digital infrastructure as well as the development of community biology laboratories, launched over the last decade, and we provide recommendations for how individuals can support the integration of amateurs into biology research. The benefits of investment in amateur biology research could be many-fold, however, without a clear consideration of equity, efforts to promote amateur biology could exacerbate structural inequalities around access to and benefits from STEM. The future of the field of biology relies on integrating a diversity of perspectives and approaches-amateur biology researchers have an important role to play.

Profile-QSAR 2.0: Kinase Virtual Screening Accuracy Comparable to Four-Concentration IC50s for Realistically Novel Compounds.

While conventional random forest regression (RFR) virtual screening models appear to have excellent accuracy on random held-out test sets, they prove lacking in actual practice. Analysis of 18 historical virtual screens showed that random test sets are far more similar to their training sets than are the compounds project teams actually order. A new, cluster-based "realistic" training/test set split, which mirrors the chemical novelty of real-life virtual screens, recapitulates the poor predictive power of RFR models in real projects. The original Profile-QSAR (pQSAR) method greatly broadened the domain of applicability over conventional models by using as independent variables a profile of activity predictions from all historical assays in a large protein family. However, the accuracy still fell short of experiment on realistic test sets. The improved "pQSAR 2.0" method replaces probabilities of activity from naïve Bayes categorical models at several thresholds with predicted IC50s from RFR models. Unexpectedly, the high accuracy also requires removing the RFR model for the actual assay of interest from the independent variable profile. With these improvements, pQSAR 2.0 activity predictions are now statistically comparable to medium-throughput four-concentration IC50 measurements even on the realistic test set. Beyond the yes/no activity predictions from a typical high-throughput screen (HTS) or conventional virtual screen, these semiquantitative IC50 predictions allow for predicted potency, ligand efficiency, lipophilic efficiency, and selectivity against antitargets, greatly facilitating hitlist triaging and enabling virtual screening panels such as toxicity panels and overall promiscuity predictions.

Role of B-1 cells in the immune response against an antigen encapsulated into phosphatidylcholine-containing liposomes.

B-1 lymphocytes comprise a unique subset of B cells that differ phenotypically, ontogenetically and functionally from conventional B-2 cells. A frequent specificity of the antibody repertoire of peritoneal B-1 cells is phosphatidylcholine. Liposomes containing phosphatidylcholine have been studied as adjuvants and their interaction with dendritic cells and macrophages has been demonstrated. However, the role of B-1 cells in the adjuvanticity of liposomes composed of phosphatidylcholine has not been explored. In the present work, we studied the contribution of B-1 cells to the humoral response against ovalbumin (OVA) encapsulated into dipalmitoylphosphatidylcholine (DPPC) and cholesterol-containing liposomes. BALB/X-linked immunodeficient (xid) mice, which are deficient in B-1 cells, showed quantitative and qualitative differences in the anti-OVA antibody response compared with wild-type animals after immunization with these liposomes. The OVA-specific immune response was significantly increased in the BALB/xid mice when reconstituted with B-1 cells from naive BALB/c mice. Our results indicate the internalization of DPPC-containing liposomes by these cells and their migration from the peritoneal cavity to the spleen. Phosphatidylcholine significantly contributed to the immunogenicity of liposomes, as DPPC-containing liposomes more effectively stimulated the anti-OVA response compared with vesicles composed of dipalmitoylphosphatidylglycerol. In conclusion, we present evidence for a cognate interaction between B-1 cells and phosphatidylcholine liposomes, modulating the immune response to encapsulated antigens. This provides a novel targeting approach to assess the role of B-1 cells in humoral immunity.

Seguimiento de un brote de infección en tejido blando causado por Mycobacterium abscessus posterior a la mesoterapia en Venezuela / Follow-up on an outbreak in Venezuela of soft-tissue infection due to Mycobacterium abscessus associated with Mesotherapy

Introducción Las infecciones de la piel y los tejidos blandos causadas por micobacterias no tuberculosas (MNT) se han asociado a procedimientos como inyecciones, liposucción, cirugía plástica y acupuntura. Estudiamos un brote de infección en tejidos blandos, debido a MNT posterior a mesoterapia, un procedimiento cosmético que consiste en inyectar una mezcla de sustancias para reducir hipotéticamente el tejido adiposo localizado. Métodos Se entrevistó a pacientes con lesiones en la piel, con antecedentes de mesoterapia, que acudieron al Departamento de Dermatología del Hospital Público de la Ciudad de Barinas, Venezuela, en el período comprendido entre noviembre de 2004 y febrero de 2005. Se tomaron muestras clínicas y ambientales para el aislamiento de micobacterias. Resultados Las entrevistas revelaron que 68 pacientes se infectaron con MNT. Todos recibieron tratamiento en el mismo centro estético, a cargo del mismo terapeuta y con el mismo producto. De las muestras de 5 pacientes se aisló Mycobacterium abscessus. Ninguna de las soluciones utilizadas en la mesoterapia estuvo disponible para el análisis, pero se aisló M. abscessus de una muestra del ambiente tomada en el centro cosmético. La tipificación de las cepas con técnicas basadas en PCR (ERIC-PCR, BOXA1R y RAPD) mostró que los aislados de los pacientes fueron indistinguibles entre sí, pero diferentes del aislado del medio ambiente del centro. Conclusión Lo más probable es que este brote se haya causado por un producto contaminado utilizado en la mesoterapia y no por una micobacteria del ambiente del centro. Hacemos énfasis en la importancia de un mejor control microbiológico de estos productos. Este brote, que afectó al menos a 68 pacientes, es en nuestro conocimiento el más grande descrito en la literatura médica posterior a mesoterapia (AU)

Introduction Skin and soft tissue infections caused by nontuberculous mycobacteria (NMT) are reported to be associated with injections, liposuction, plastic surgery, and acupuncture. Herein, we describe an outbreak of soft tissue infection due to NMT following mesotherapy, a cosmetic procedure involving injection of poorly defined mixtures alleged to reduce local adiposity. Methods Patients with skin lesions and a history of mesotherapy treatment, who visited the dermatology department of the public hospital in Barinas, Venezuela, from November 2004 to February 2005 were interviewed. Clinical and environmental samples were taken for mycobacteria isolation. Results The interviews revealed that 68 patients who had been treated for cosmetic purposes at the same clinic by the same therapist had received injections with the same product and were infected with NMT. Clinical specimens from 5 patients grew Mycobacterium abscessus. No mesotherapy solution was available for analysis but M. abscessus was isolated from an environmental sample in the clinic. PCR-based strain typing techniques (ERIC-PCR, BOXA1R and RAPD) showed that the patient's isolates were undistinguishable from each other but different from the environmental isolate. Conclusions This outbreak was likely caused by a contaminated injectable mesotherapy product and not by mycobacteria from the clinic environment. We emphasize the importance of better microbiological control of these products. To our knowledge, this outbreak, which affected at least 68 patients, appears to be the largest ever associated with mesotherapy and described in the literature (AU)

[Follow-up on an outbreak in Venezuela of soft-tissue infection due to Mycobacterium abscessus associated with Mesotherapy]. / Seguimiento de un brote de infección en tejido blando causado por Mycobacterium abscessus posterior a la mesoterapia en Venezuela.

INTRODUCTION: Skin and soft tissue infections caused by nontuberculous mycobacteria (NMT) are reported to be associated with injections, liposuction, plastic surgery, and acupuncture. Herein, we describe an outbreak of soft tissue infection due to NMT following mesotherapy, a cosmetic procedure involving injection of poorly defined mixtures alleged to reduce local adiposity. METHODS: Patients with skin lesions and a history of mesotherapy treatment, who visited the dermatology department of the public hospital in Barinas, Venezuela, from November 2004 to February 2005 were interviewed. Clinical and environmental samples were taken for mycobacteria isolation. RESULTS: The interviews revealed that 68 patients who had been treated for cosmetic purposes at the same clinic by the same therapist had received injections with the same product and were infected with NMT. Clinical specimens from 5 patients grew Mycobacterium abscessus. No mesotherapy solution was available for analysis but M. abscessus was isolated from an environmental sample in the clinic. PCR-based strain typing techniques (ERIC-PCR, BOXA1R and RAPD) showed that the patient's isolates were undistinguishable from each other but different from the environmental isolate. CONCLUSIONS: This outbreak was likely caused by a contaminated injectable mesotherapy product and not by mycobacteria from the clinic environment. We emphasize the importance of better microbiological control of these products. To our knowledge, this outbreak, which affected at least 68 patients, appears to be the largest ever associated with mesotherapy and described in the literature.