Repurposing bioenergetic modulators against protozoan parasites responsible for tropical diseases

Malaria, leishmaniasis and trypanosomiasis are arthropod-borne, parasitic diseases that constitute a major global health problem. They are generally found in developing countries, where lack of access to preventive tools and treatment hinders their management. Because these parasites share an increased demand on glucose consumption with most cancer cells, six compounds used in anti-tumoral research were selected to be tested as antiparasitic agents in in vitro models of Leishmania infantum, Trypanosoma brucei, T. cruzi, and Plasmodium falciparum: dichloroacetic acid (DCA), 3-bromopyruvic acid (3BP), 2-deoxy-D-glucose (2DG), lonidamine (LND), metformin (MET), and sirolimus (SIR). No parasite-killing activity was found in L. infantum promastigotes, whereas DCA and 3BP reduced the burden of intra-macrophagic amastigotes. For T. brucei all selected compounds, but 2DG, decreased parasite survival. DCA, 2DG, LND and MET showed parasite-killing activity in T. cruzi. Finally, anti-plasmodial activity was found for DCA, 2DG, LND, MET and SIR. These results reinforce the hypothesis that drugs with proven efficacy in the treatment of cancer by interfering with ATP production, proliferation, and survival cell strategies might be useful in treating threatening parasitic diseases and provide new opportunities for their repurposing.info:eu-repo/semantics/publishedVersio

MARINE INFLUENCE DURING LATE EOCENE IN EASTERN AND SOUTH EASTERN COLOMBIA

Durante el Eoceno Tardío en las Cuencas Subandinas de Colombia tuvo lugar la depositación de uno de los más importantes reservorios del país: la Formación Mirador. Diversos modelos deposicionales reconocen un ambiente típicamente fluvial para su base, y ambientes más transicionales para su tope. Sin embargo, la presencia de una influencia marina en el tope del Mirador es aún discutida, y la distribución geográfica de este probable evento es desconocida. Con el objeto de establecer la paleogeografía de esta ingresión marina se analizaron palinológicamente 77 pozos y 3 secciones ubicados en el Oriente de Colombia. La influencia marina en los sedimentos se estableció determinando la Paleosalinidad asociada mediante un Índice de Salinidad (SI), que describe la relación entre palinomorfos marinos y continentales. La ingresión marina está registrada en dos áreas: la primera, en la Cordillera Oriental y el Piedemonte Llanero Central; y la segunda, en la cuenca del Putumayo. El comportamiento de la paleosalinidad sugiere que al Sur, en la Cuenca del Putumayo, la ingresión marina invadió el territorio Colombiano en sentido S-N a través de la costa Ecuatoriana. Sin embargo, cómo ingresó a la Cordillera Oriental y al sector central del Piedemonte no es claro, y los modelos paleogeográficos propuestos no lo explican satisfactoriamente. Un nuevo modelo paleogeográfico para el Eoceno Tardío deberá ser planteado.   Palabras Claves: Eoceno Tardío; Palinología; Índice de Salinidad; Influencia Marina; Formación Mirador          During Late Eocene in the Colombian Subandean basins one of the most important oil bearing Rocks in Colombia was deposited: The Mirador Formation. Most of the depositional models proposed recognize a typically fluvial environment for the Mirador´s base and transitional environments for its top. These models disagree about a probable Marine Influence in the Mirador´s Top, and the geographical distribution of this event remains unknown. In order to determine the paleogeography of this event, 77 wells and 3 sections were palynologically analyzed. The presence of the marine influence in the sediments was determined using a Salinity Index (SI) which describes the reverse relationship between continental and marine palynomorphs. Marine Influence was recognized in two areas: the first one, in the Eastern Cordillera and the Central-Eastern Foothills; and the second one, in the Putumayo Basin. Paleosalinity patterns suggest that in the Putumayo Basin the marine ingression flooded in to the Colombian territory in a South-North direction, through the Ecuatorian Coast. How the Marine Ingression flooded into the Eastern Cordillera and Central-Eastern Foothills is not clear, and paleogeographical models proposed can not explain it. A new paleogeographical model for the Colombian Late Eocene considering this event must be proposed.   Key Words: Late Eocene; Palynology; Salinity Index; Marine Influence; Mirador Formation &nbsp

MARINE INFLUENCE DURING LATE EOCENE IN EASTERN AND SOUTH EASTERN COLOMBIA

Durante el Eoceno Tardío en las Cuencas Subandinas de Colombia tuvo lugar la depositación de uno de los más importantes reservorios del país: la Formación Mirador. Diversos modelos deposicionales reconocen un ambiente típicamente fluvial para su base, y ambientes más transicionales para su tope. Sin embargo, la presencia de una influencia marina en el tope del Mirador es aún discutida, y la distribución geográfica de este probable evento es desconocida. Con el objeto de establecer la paleogeografía de esta ingresión marina se analizaron palinológicamente 77 pozos y 3 secciones ubicados en el Oriente de Colombia. La influencia marina en los sedimentos se estableció determinando la Paleosalinidad asociada mediante un Índice de Salinidad (SI), que describe la relación entre palinomorfos marinos y continentales. La ingresión marina está registrada en dos áreas: la primera, en la Cordillera Oriental y el Piedemonte Llanero Central; y la segunda, en la cuenca del Putumayo. El comportamiento de la paleosalinidad sugiere que al Sur, en la Cuenca del Putumayo, la ingresión marina invadió el territorio Colombiano en sentido S-N a través de la costa Ecuatoriana. Sin embargo, cómo ingresó a la Cordillera Oriental y al sector central del Piedemonte no es claro, y los modelos paleogeográficos propuestos no lo explican satisfactoriamente. Un nuevo modelo paleogeográfico para el Eoceno Tardío deberá ser planteado.   Palabras Claves: Eoceno Tardío; Palinología; Índice de Salinidad; Influencia Marina; Formación Mirador          During Late Eocene in the Colombian Subandean basins one of the most important oil bearing Rocks in Colombia was deposited: The Mirador Formation. Most of the depositional models proposed recognize a typically fluvial environment for the Mirador´s base and transitional environments for its top. These models disagree about a probable Marine Influence in the Mirador´s Top, and the geographical distribution of this event remains unknown. In order to determine the paleogeography of this event, 77 wells and 3 sections were palynologically analyzed. The presence of the marine influence in the sediments was determined using a Salinity Index (SI) which describes the reverse relationship between continental and marine palynomorphs. Marine Influence was recognized in two areas: the first one, in the Eastern Cordillera and the Central-Eastern Foothills; and the second one, in the Putumayo Basin. Paleosalinity patterns suggest that in the Putumayo Basin the marine ingression flooded in to the Colombian territory in a South-North direction, through the Ecuatorian Coast. How the Marine Ingression flooded into the Eastern Cordillera and Central-Eastern Foothills is not clear, and paleogeographical models proposed can not explain it. A new paleogeographical model for the Colombian Late Eocene considering this event must be proposed.   Key Words: Late Eocene; Palynology; Salinity Index; Marine Influence; Mirador Formation &nbsp

Validation Techniques for Sensor Data in Mobile Health Applications

Mobile applications have become a must in every user's smart device, and many of these applications make use of the device sensors' to achieve its goal. Nevertheless, it remains fairly unknown to the user to which extent the data the applications use can be relied upon and, therefore, to which extent the output of a given application is trustworthy or not. To help developers and researchers and to provide a common ground of data validation algorithms and techniques, this paper presents a review of the most commonly used data validation algorithms, along with its usage scenarios, and proposes a classification for these algorithms. This paper also discusses the process of achieving statistical significance and trust for the desired output

A simple and effective 1D-element discrete-based method for computational bone remodeling

This is an Accepted Manuscript of an article published by Taylor & Francis Group in Computer Methods in Biomechanics and Biomedical Engineering on 2022, available online at: http://www.tandfonline.com/10.1080/10255842.2021.1943370.In-silico models applied to bone remodeling are widely used to investigate bone mechanics, bone diseases, bone-implant interactions, and also the effect of treatments of bone pathologies. This paper proposes a new methodology to solve the bone remodeling problem using one-dimensional (1D) elements to discretize trabecular structures more efficiently for 2D and 3D domains. An Euler integration scheme is coupled with the momentum equations to obtain the evolution of material density at each step. For the simulations, the equations were solved by using the finite element method, and two benchmark tests were solved varying mesh parameters. Proximal femur and calcaneus bone were selected as study cases given the vast research available on the topology of these bones, and compared with the anatomical features of trabecular bone reported in the literature. The presented methodology has proven to be efficient in optimizing topologies of lattice structures; It can predict the trend of formation patterns of the main trabecular groups from two different cancellous bones (femur and calcaneus) using domains set up by discrete elements as a starting point. Preliminary results confirm that the proposed approach is suitable and useful in bone remodeling problems leading to a considerable computational cost reduction. Characteristics similar to those encountered in topological optimization (TO) algorithms were identified in the benchmark tests as well, showing the viability of the proposed approach in other applications such as bio-inspired design.Peer ReviewedPostprint (author's final draft

Manual lymphatic drainage therapy in patients with breast cancer related lymphoedema

<p>Abstract</p> <p>Background</p> <p>Lymphoedema is a common and troublesome condition that develops following breast cancer treatment. The aim of this study is to analyze the effectiveness of Manual Lymphatic Drainage in the treatment of postmastectomy lymphoedema in order to reduce the volume of lymphoedema and evaluate the improvement of the concomitant symptomatology.</p> <p>Methods</p> <p>A randomized, controlled clinical trial in 58 women with post-mastectomy lymphoedema. The control group includes 29 patients with standard treatment (skin care, exercise and compression measures, bandages for one month and, subsequently, compression garnments). The experimental group includes 29 patients with standard treatment plus Manual Lymphatic Drainage. The therapy will be administered daily for four weeks and the patient's condition will be assessed one, three and six months after treatment.</p> <p>The primary outcome parameter is volume reduction of the affected arm after treatment, expressed as a percentage. Secondary outcome parameters include: duration of lymphoedema reduction and improvement of the concomitant symptomatology (degree of pain, sensation of swelling and functional limitation in the affected extremity, subjective feeling of being physically less atractive and less feminine, difficulty looking at oneself naked and dissatisfaction with the corporal image).</p> <p>Discussion</p> <p>The results of this study will provide information on the effectiveness of Manual Lymphatic Drainage and its impact on the quality of life and physical limitations of these patients.</p> <p>Trial registration</p> <p>ClinicalTrials (NCT): <a href="http://www.clinicaltrials.gov/ct2/show/NCT01152099">NCT01152099</a></p

Ectoparasite activity during incubation increases microbial growth on avian eggs

We thank Estefanía López for lab work, and Tomás Pérez-Contreras and Emilio Pagani-Núñez for facilitating collection of some of the flies used in manipulations. We also thank Ángela Martínez-García for help with management of ARISA data and Natalia Juárez and Deseada Parejo for the pictures of owls and roller clutches, respectively. We appreciate the comments provided by Dr. Adèle Mennerat and five anonymous referees on earlier versions of the manuscript.All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.While direct detrimental effects of parasites on hosts are relatively well documented, other more subtle but potentially important effects of parasitism are yet unexplored. Biological activity of ectoparasites, apart from skin injuries and blood-feeding, often results in blood remains, or parasite faeces that accumulate and modify the host environment. In this way, ectoparasite activities and remains may increase nutrient availability that may favour colonization and growth of microorganisms including potential pathogens. Here, by the experimental addition of hematophagous flies (Carnus hemapterus, a common ectoparasite of birds) to nests of spotless starlings Sturnus unicolor during incubation, we explore this possible side effect of parasitism which has rarely, if ever, been investigated. Results show that faeces and blood remains from parasitic flies on spotless starling eggshells at the end of incubation were more abundant in experimental than in control nests. Moreover, eggshell bacterial loads of different groups of cultivable bacteria including potential pathogens, as well as species richness of bacteria in terms of Operational Taxonomic Units (OTUs), were also higher in experimental nests. Finally, we also found evidence of a link between eggshell bacterial loads and increased embryo mortality, which provides indirect support for a bacterial-mediated negative effect of ectoparasitism on host offspring. Trans-shell bacterial infection might be one of the main causes of embryo death and, consequently, this hitherto unnoticed indirect effect of ectoparasitism might be widespread in nature and could affect our understanding of ecology and evolution of host-parasite interactionsFinancial support was provided by Spanish Ministerio de Economía y Competitividad and FEDER (CGL2013-48193-C3-1-P, CGL2013-48193-C3-2-P), by JAE programme to DMG and MRR, and by Juan de la Cierva and Ramón y Cajal programmes to GT. All procedures were conducted under licence from the Environmental Department of the Regional Government of Andalucía, Spain (reference SGYB/FOA/AFR)

Evolution in Australasian Mangrove Forests: Multilocus Phylogenetic Analysis of the Gerygone Warblers (Aves: Acanthizidae)

The mangrove forests of Australasia have many endemic bird species but their evolution and radiation in those habitats has been little studied. One genus with several mangrove specialist species is Gerygone (Passeriformes: Acanthizidae). The phylogeny of the Acanthizidae is reasonably well understood but limited taxon sampling for Gerygone has constrained understanding of its evolution and historical biogeography in mangroves. Here we report on a phylogenetic analysis of Gerygone based on comprehensive taxon sampling and a multilocus dataset of thirteen loci spread across the avian genome (eleven nuclear and two mitochondrial loci). Since Gerygone includes three species restricted to Australia's coastal mangrove forests, we particularly sought to understand the biogeography of their evolution in that ecosystem. Analyses of individual loci, as well as of a concatenated dataset drawn from previous molecular studies indicates that the genus as currently defined is not monophyletic, and that the Grey Gerygone (G. cinerea) from New Guinea should be transferred to the genus Acanthiza. The multilocus approach has permitted the nuanced view of the group's evolution into mangrove ecosystems having occurred on multiple occasions, in three non-overlapping time frames, most likely first by the G. magnirostris lineage, and subsequently followed by those of G. tenebrosa and G. levigaster

Identification and Phylogenetic Analysis of Tityus pachyurus and Tityus obscurus Novel Putative Na+-Channel Scorpion Toxins

Background: Colombia and Brazil are affected by severe cases of scorpionism. In Colombia the most dangerous accidents are caused by Tityus pachyurus that is widely distributed around this country. In the Brazilian Amazonian region scorpion stings are a common event caused by Tityus obscurus. The main objective of this work was to perform the molecular cloning of the putative Na+-channel scorpion toxins (NaScTxs) from T. pachyurus and T. obscurus venom glands and to analyze their phylogenetic relationship with other known NaScTxs from Tityus species. Methodology/Principal Findings: cDNA libraries from venom glands of these two species were constructed and five nucleotide sequences from T. pachyurus were identified as putative modulators of Na+-channels, and were named Tpa4, Tpa5, Tpa6, Tpa7 and Tpa8; the latter being the first anti-insect excitatory b-class NaScTx in Tityus scorpion venom to be described. Fifteen sequences from T. obscurus were identified as putative NaScTxs, among which three had been previously described, and the others were named To4 to To15. The peptides Tpa4, Tpa5, Tpa6, To6, To7, To9, To10 and To14 are closely related to the a-class NaScTxs, whereas Tpa7, Tpa8, To4, To8, To12 and To15 sequences are more related to the b-class NaScTxs. To5 is possibly an arthropod specific toxin. To11 and To13 share sequence similarities with both a and b NaScTxs. By means of phylogenetic analysis using the Maximum Parsimony method and the known NaScTxs from Tityus species, these toxins were clustered into 14 distinct groups. Conclusions/Significance: This communication describes new putative NaScTxs from T. pachyurus and T. obscurus and their phylogenetic analysis. The results indicate clear geographic separation between scorpions of Tityus genus inhabiting the Amazonian and Mountain Andes regions and those distributed over the Southern of the Amazonian rainforest. Based on the consensus sequences for the different clusters, a new nomenclature for the NaScTxs is proposed