Selective Labeling and Identification of the Tumor Cell Proteome of Pancreatic Cancer In Vivo

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers. Dissecting the tumor cell proteome from that of the non-tumor cells in the PDAC tumor bulk is critical for tumorigenesis studies, biomarker discovery, and development of therapeutics. However, investigating the tumor cell proteome has proven evasive due to the tumor’s extremely complex cellular composition. To circumvent this technical barrier, we have combined bioorthogonal noncanonical amino acid tagging (BONCAT) and data-independent acquisition mass spectrometry (DIA-MS) in an orthotopic PDAC model to specifically identify the tumor cell proteome in vivo. Utilizing the tumor cell-specific expression of a mutant tRNA synthetase transgene, this approach provides tumor cells with the exclusive ability to incorporate an azide-bearing methionine analogue into newly synthesized proteins. The azide-tagged tumor cell proteome is subsequently enriched and purified via a bioorthogonal reaction and then identified and quantified using DIA-MS. Applying this workflow to the orthotopic PDAC model, we have identified thousands of proteins expressed by the tumor cells. Furthermore, by comparing the tumor cell and tumor bulk proteomes, we showed that the approach can distinctly differentiate proteins produced by tumor cells from those of non-tumor cells within the tumor microenvironment. Our study, for the first time, reveals the tumor cell proteome of PDAC under physiological conditions, providing broad applications for tumorigenesis, therapeutics, and biomarker studies in various human cancers

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Electrospinning with polymer melts - state of the art and future perspectives

It is broadly valued by the biomaterials community that electrospinning from both the solution and melt is a technologically attractive method to process polymeric and composite materials; yet the number of publications reported in the current scientific literature regards the two methods has an estimated ratio of 1 to 400. Among the many reasons for the currently limited research output in melt electrospinning (MES) is that the fabrication of a well-designed melt-based electrospinning devices is technologically and scientifically more challenging than assembling a laboratory-scaled bench top solution electrospinning (SES) machine. Interestingly, the traditional polymer science-rooted MES community has for the most part published studies using micron-diameter fibers; however, the biomaterials community prefers scaffold-processing technologies that allow the fabrication of submicron architectures. From a manufacturing point of view and compared to other fiber forming processes, less operational volatility is induced, as MES is a solvent-free process. Additionally to this key aspect and from a users’ safety perspective, no further concerns exist in regards to toxicity. If controlled appropriately, the charged polymer jet, which is formed during MES can be accurately directed to the collector without instabilities. Through the application of MES in a direct writing mode, i.e., the implementation of moving stages in two dimensions (X and Y), the resulting process can be considered as a new class of three-dimensional (3D) printing. This article reviews MES research from a polymer processing and machine design point of view. It concludes postulating that the emergence of the progressive, innovative, and creative MES technology will increasingly supersede the conventionally used SES until it becomes successfully established within the biomaterials community

Functionality of redox-active crysteines is required for restriction of retroviral replication by SAMHD1

Open access article. Creative Commons 4.0 International License (CC BY 4.0) appliesSAMHD1 is a dNTP triphosphohydrolase (dNTPase)that impairs retroviral replication in a subset of non-cycling immune cells. Here we show that SAMHD1is a redox-sensitive enzyme and identify threeredox-active cysteines within the protein: C341,C350, and C522. The three cysteines reside nearone another and the allosteric nucleotide bindingsite. Mutations C341S and C522S abolish the abilityof SAMHD1 to restrict HIV replication, whereas theC350S mutant remains restriction competent. TheC522S mutation makes the protein resistant to inhibi-tion by hydrogen peroxide but has no effect onthe tetramerization-dependent dNTPase activity ofSAMHD1in vitroor on the ability of SAMHD1 todeplete cellular dNTPs. Our results reveal that enzy-matic activation of SAMHD1 via nucleotide-depen-dent tetramerization is not sufficient for the estab-lishment of the antiviral state and that retroviralrestriction depends on the ability of the protein to un-dergo redox transformations.Ye

Voces de la gestión territorial. Estrategias complementarias para la conservación de la biodiversidad en Colombia

Colombia es un país con una alta riqueza biológica y cultural, tan diverso en su territorio como en las estrategias de conservación que en él se implementan. Sin embargo, muchas de estas estrategias no se han dado a conocer lo suficiente, lo que hace difícil su articulación a los procesos de gestión y ordenamiento del territorio. Existen algunos avances en su identificación como los ejercicios que se han realizado en los sistemas regionales de áreas protegidas para recopilar la información sobre estrategias complementarias de conservación en sus jurisdicciones, la articulación que realizan organizaciones privadas para identificar las iniciativas de conservación voluntaria por parte de la sociedad civil y el trabajo realizado por comunidades campesinas, indígenas y afrodescendientes para visibilizar sus áreas de conservación. Este libro, por lo tanto, tiene como objetivo visibilizar experiencias de conservación y gestión de la biodiversidad, diferentes a las áreas protegidas, teniendo en cuenta que el Convenio de Diversidad Biológica a través de la Meta Aichi 11 introduce el concepto de otras medidas efectivas de conservación basadas en áreas (OMEC) o áreas conservadas como instrumentos para lograr sistemas de conservación más completos, representativos y efectivamente gestionados (UNEP CDB, 2010). Esperamos sea un aporte para llenar un vacío de conocimiento acerca de dichas estrategias, mostrando sus principales características, los diferentes tipos de gobernanza con los que cuentan, sus mecanismos de implementación, fortalezas y debilidades, aprendizajes y cómo estos pueden ser aplicados a la gestión de la biodiversidad en el territorio.Servicios ecosistémicosGobernanzaManejo de territoriosDeforestación de bosquesPérdida y degradaciónEcosistemasComunidades localesConservación de la biodiversida

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study (vol 46, pg 2021, 2022)

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Global attitudes in the management of acute appendicitis during COVID-19 pandemic: ACIE Appy Study

Background: Surgical strategies are being adapted to face the COVID-19 pandemic. Recommendations on the management of acute appendicitis have been based on expert opinion, but very little evidence is available. This study addressed that dearth with a snapshot of worldwide approaches to appendicitis. Methods: The Association of Italian Surgeons in Europe designed an online survey to assess the current attitude of surgeons globally regarding the management of patients with acute appendicitis during the pandemic. Questions were divided into baseline information, hospital organization and screening, personal protective equipment, management and surgical approach, and patient presentation before versus during the pandemic. Results: Of 744 answers, 709 (from 66 countries) were complete and were included in the analysis. Most hospitals were treating both patients with and those without COVID. There was variation in screening indications and modality used, with chest X-ray plus molecular testing (PCR) being the commonest (19\ub78 per cent). Conservative management of complicated and uncomplicated appendicitis was used by 6\ub76 and 2\ub74 per cent respectively before, but 23\ub77 and 5\ub73 per cent, during the pandemic (both P < 0\ub7001). One-third changed their approach from laparoscopic to open surgery owing to the popular (but evidence-lacking) advice from expert groups during the initial phase of the pandemic. No agreement on how to filter surgical smoke plume during laparoscopy was identified. There was an overall reduction in the number of patients admitted with appendicitis and one-third felt that patients who did present had more severe appendicitis than they usually observe. Conclusion: Conservative management of mild appendicitis has been possible during the pandemic. The fact that some surgeons switched to open appendicectomy may reflect the poor guidelines that emanated in the early phase of SARS-CoV-2