Volatile compounds of grosella (Phyllanthus acidus [L.] Skeels) fruit

Phyllanthus acidus (L.) Skeels es un árbol tropical pequeño, que alcanza hasta 12 m, que produce frutas grasosas de color amarillo claro en abundancia en las ramas, los que son comestibles y de sabor ácido. Esta especie es uno de los pocos miembros de la familia Euphorbiaceae que produce frutas comestibles. La pulpa ácida es usada como saborizante y para hacer jaleas. Los constituyentes volátiles de la fruta madura se aislaron por destilación-extracción simultáneas utilizando éter dietílico como disolvente y se analizaron por cromatografía de gases con detector de llama de hidrógeno y cromatografía de gases acoplada a espectrometría de masas. Se identificaron 77 compuestos volátiles agrupados en: 45 terpenos, 18 ésteres, siete ácidos, cuatro aldehídos, dos fenoles y un alcohol, de los cuales 66 se encontraron por primera vez en la grosella. La concentración total de compuestos volátiles fue de 109 mg/kg de fruta fresca. De acuerdo con las clases de compuestos, los terpenos (100,1 mg/kg) y los ácidos (6,7 mg/kg) dominaron el perfil cuantitativo en las frutas, mientras que los terpenos y los ésteres lo hicieron cualitativamente. En el grupo de los terpenos se identificaron varios monoterpenos y sesquiterpenos, siendo los más representativos el epi-α-muurolol (32,9 mg/kg) y el α-cadinol (22,1 mg/kg). El ácido hexadecanoico (3,8 mg/kg) fue el compuesto mayoritario en los ácidos

Physical and functional interaction between the dopamine transporter and the synaptic vesicle protein synaptogyrin-3.

Uptake through the dopamine transporter (DAT) represents the primary mechanism used to terminate dopaminergic transmission in brain. Although it is well known that dopamine (DA) taken up by the transporter is used to replenish synaptic vesicle stores for subsequent release, the molecular details of this mechanism are not completely understood. Here, we identified the synaptic vesicle protein synaptogyrin-3 as a DAT interacting protein using the split ubiquitin system. This interaction was confirmed through coimmunoprecipitation experiments using heterologous cell lines and mouse brain. DAT and synaptogyrin-3 colocalized at presynaptic terminals from mouse striatum. Using fluorescence resonance energy transfer microscopy, we show that both proteins interact in live neurons. Pull-down assays with GST (glutathione S-transferase) proteins revealed that the cytoplasmic N termini of both DAT and synaptogyrin-3 are sufficient for this interaction. Furthermore, the N terminus of DAT is capable of binding purified synaptic vesicles from brain tissue. Functional assays revealed that synaptogyrin-3 expression correlated with DAT activity in PC12 and MN9D cells, but not in the non-neuronal HEK-293 cells. These changes were not attributed to changes in transporter cell surface levels or to direct effect of the protein-protein interaction. Instead, the synaptogyrin-3 effect on DAT activity was abolished in the presence of the vesicular monoamine transporter-2 (VMAT2) inhibitor reserpine, suggesting a dependence on the vesicular DA storage system. Finally, we provide evidence for a biochemical complex involving DAT, synaptogyrin-3, and VMAT2. Collectively, our data identify a novel interaction between DAT and synaptogyrin-3 and suggest a physical and functional link between DAT and the vesicular DA system

Propuesta de un algoritmo para evaluar la causalidad de eventos adversos en los Ensayos Clínicos de Vacunas.

En el transcurso de los ensayos clínicos usualmente se designa a una comisión, la cual se encarga de evaluar la causalidad de los eventos adversos que se reportan y transcriben en los cuadernos de recogida de datos. Para llegar a contestar la pregunta de: ¿si una vacuna que se está estudiando ha causado un evento adverso?, los decisores pueden tomar diferentes caminos, por lo que obviamente la conclusión final podría variar mucho y la evaluación deficiente puede generar conclusiones erróneas, lo que confirma la necesidad de disponer de un procedimiento para definir las categorías que se utilizarán para analizar y clasificar la relación de causalidad. Una forma de contestar a la pregunta es mediante la construcción de un algoritmo. En relación con los ensayos clínicos no encontramos en la literatura un algoritmo que sea el "patrón clave" para establecer o descartar la causalidad, sin embargo es factible diseñarlo partiendo de la metodología internacional utilizada poscomercialización, lo cual fue el propósito de este trabajo. Se diseñó una primera propuesta que fue analizada individual y colectivamente por el grupo multidisciplinario de la Gerencia Médica del Instituto Finlay. Finalmente se aprobó por consenso el algoritmo que puede ser útil para aplicar en los ensayos clínicos dentro y fuera de la institución

The Body-QoL: Measuring Patient Reported Outcomes in Body Contouring Surgery Patients

Artículo de publicación SCOPUSBackground This study aimed to design a new patientreported outcome (PRO) instrument to measure patient satisfaction after body-contouring procedures such as liposculpture, abdominoplasty, body-lift, thigh-lift, and arm-lift. Methods Phase 1a involved an extensive literature review, 16 in-depth patient interviews, and expert focus groups with 5 plastic surgeons to develop a conceptual framework for the outcomes deemed important for body image and preliminary PRO instruments. In phase 1b, the preliminary instrument was tested with a second independent sample of 29 patients with whom simple interviews were additionally performed. In the second sample, scale reliability was calculated. Results In phase 1a, the domains identified for the conceptual framework included clothing and body image, sexual and affective life, self-image and self-esteem, social relationships, and physical symptoms. In phase 1b, the scale internal consistency was 91.5 %. Conclusions When psychometric evaluation is completed, the Body-Shape-Related Quality of Life instrument and its subscales will provide a reliable tool for plastic surgeons, researchers, and patients to use in measuring the impact and effectiveness of body-contouring procedures from the patient’s perspective. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-

Gene Acquisition by a Distinct Phyletic Group within Streptococcus pneumoniae Promotes Adhesion to the Ocular Epithelium

ABSTRACT Streptococcus pneumoniae (pneumococcus) displays broad tissue tropism and infects multiple body sites in the human host. However, infections of the conjunctiva are limited to strains within a distinct phyletic group with multilocus sequence types ST448, ST344, ST1186, ST1270, and ST2315. In this study, we sequenced the genomes of six pneumococcal strains isolated from eye infections. The conjunctivitis isolates are grouped in a distinct phyletic group together with a subset of nasopharyngeal isolates. The keratitis (infection of the cornea) and endophthalmitis (infection of the vitreous body) isolates are grouped with the remainder of pneumococcal strains. Phenotypic characterization is consistent with morphological differences associated with the distinct phyletic group. Specifically, isolates from the distinct phyletic group form aggregates in planktonic cultures and chain-like structures in biofilms grown on abiotic surfaces. To begin to investigate the association between genotype and epidemiology, we focused on a predicted surface-exposed adhesin (SspB) encoded exclusively by this distinct phyletic group. Phylogenetic analysis of the gene encoding SspB in the context of a streptococcal species tree suggests that sspB was acquired by lateral gene transfer from Streptococcus suis. Furthermore, an sspB deletion mutant displays decreased adherence to cultured cells from the ocular epithelium compared to the isogenic wild-type and complemented strains. Together these findings suggest that acquisition of genes from outside the species has contributed to pneumococcal tissue tropism by enhancing the ability of a subset of strains to infect the ocular epithelium causing conjunctivitis. IMPORTANCE Changes in the gene content of pathogens can modify their ability to colonize and/or survive in different body sites in the human host. In this study, we investigate a gene acquisition event and its role in the pathogenesis of Streptococccus pneumoniae (pneumococcus). Our findings suggest that the gene encoding the predicted surface protein SspB has been transferred from Streptococcus suis (a distantly related streptococcal species) into a distinct set of pneumococcal strains. This group of strains distinguishes itself from the remainder of pneumococcal strains by extensive differences in genomic composition and by the ability to cause conjunctivitis. We find that the presence of sspB increases adherence of pneumococcus to the ocular epithelium. Thus, our data support the hypothesis that a subset of pneumococcal strains has gained genes from neighboring species that enhance their ability to colonize the epithelium of the eye, thus expanding into a new niche

Dysregulation of FOXO1 (Forkhead Box O1 Protein) Drives Calcification in Arterial Calcification due to Deficiency of CD73 and Is Present in Peripheral Artery Disease

ObjectiveThe recessive disease arterial calcification due to deficiency of CD73 (ACDC) presents with extensive nonatherosclerotic medial layer calcification in lower extremity arteries. Lack of CD73 induces a concomitant increase in TNAP (tissue nonspecific alkaline phosphatase; ALPL), a key enzyme in ectopic mineralization. Our aim was to investigate how loss of CD73 activity leads to increased ALPL expression and calcification in CD73-deficient patients and assess whether this mechanism may apply to peripheral artery disease calcification. Approach and Results: We previously developed a patient-specific disease model using ACDC primary dermal fibroblasts that recapitulates the calcification phenotype in vitro. We found that lack of CD73-mediated adenosine signaling reduced cAMP production and resulted in increased activation of AKT. The AKT/mTOR (mammalian target of rapamycin) axis blocks autophagy and inducing autophagy prevented calcification; however, we did not observe autophagy defects in ACDC cells. In silico analysis identified a putative FOXO1 (forkhead box O1 protein) binding site in the human ALPL promoter. Exogenous AMP induced FOXO1 nuclear localization in ACDC but not in control cells, and this was prevented with a cAMP analogue or activation of A2a/2b adenosine receptors. Inhibiting FOXO1 reduced ALPL expression and TNAP activity and prevented calcification. Mutating the FOXO1 binding site reduced ALPL promoter activation. Importantly, we provide evidence that non-ACDC calcified femoropopliteal arteries exhibit decreased CD73 and increased FOXO1 levels compared with control arteries.ConclusionsThese data show that lack of CD73-mediated cAMP signaling promotes expression of the human ALPL gene via a FOXO1-dependent mechanism. Decreased CD73 and increased FOXO1 was also observed in more common peripheral artery disease calcification

The Houts Farm: a porción of Edinburg

For nearly a century the Houts and Kaml families contributed to the story of Edinburg and South Texas agriculture. Both the Houts and Kaml families of German descent arrived in the Rio Grande Valley of Texas in the 1920s and participated in the growing agricultural business opportunities in the Magic Valley. These two families were joined together in marriage in 1955 when Eugene Houts married Marilyn Kaml. Today, the Houts farm is still in business but has diversified to keep up with the changing agricultural environment. This book not only describes progression of their farming family business but has demonstrated that three millennia earlier, their ancestors had left their mark on what is today the Houts farm. It is our sincere hope that this study as well as earlier studies will preserve our region\u27s complex and nuanced story.https://scholarworks.utrgv.edu/chapspublications/1009/thumbnail.jp

Unbiased compound screening identifies unexpected drug sensitivities and novel treatment options for gastrointestinal stromal tumors

Most gastrointestinal stromal tumors (GISTs) are caused by oncogenic KIT or PDGFRA activation, and the small molecule kinase inhibitor imatinib mesylate is an effective first-line therapy for metastatic or unresectable GIST. However, complete remissions are rare and most patients ultimately develop resistance, mostly due to secondary mutations in the driver oncogenic kinase. Hence there is a need for novel treatment options to delay failure of primary treatment and restore tumor control in patients who progress under therapy with targeted agents. Historic data suggest that GISTs do not respond to classical chemotherapy, but systematic unbiased screening has not been performed. In screening a compound library enriched for FDA-approved chemotherapeutic agents (NCI Approved Oncology Drugs Set II), we discovered that GIST cells display high sensitivity to transcriptional inhibitors and topoisomerase II inhibitors. Mechanistically, these compounds exploited the cells' dependency on continuous KIT expression and/or intrinsic DNA damage response defects, explaining their activity in GIST. Mithramycin A, an indirect inhibitor of the SP1 transcription factor, and mitoxantrone, a topoisomerase II inhibitor, exerted significant antitumor effects in mouse xenograft models of human GIST. Moreover, these compounds were active in patient-derived imatinib-resistant primary GIST cells, achieving efficacy at clinically relevant concentrations. Taken together, our findings reveal that GIST cells have an unexpectedly high and specific sensitivity to certain types of FDA-approved chemotherapeutic agents, with immediate implications for encouraging their clinical exploration.status: publishe