Strategies for cancer gene-delivery improvement by non-viral vectors

Lack of selectivity together with severe side effects in conventional cancer treatment have afforded the devel- opment of new strategies based on gene therapy. Nowadays, gene therapy is employed through both viral and non-viral vectors. In spite of the high transfection activity of viral vectors, some drawbacks have pointed out to non-viral vectors as a safer alternative. To overcome low efficiency as well as other issues associated with the use of non-viral vectors, complexes formed by lipids and polymers with DNA, named lipoplexes and polyplexes respectively, have been modified in order to improve its features. Suitability of cancer gene therapy also requires the capacity to distinguish between normal and tumoral cells. This requirement has been solved by the addition of specific ligands that enable receptor binding and subsequent endocytosis. In this article we review the most recent approaches in structure modification of non-viral vectors through different methods comprising conjugation, addition of helper lipids or changes in design and synthesis as well as the strategy based on exploiting receptors that are usually overexpressed in malignancies. Such improvements confer specificity, efficient gene delivery, condensation, protection of DNA and low levels of toxicity avoiding off-target effects which turn into a potential tool to treat cancer

Electronic Descriptors for Supervised Spectroscopic Predictions

Spectroscopic properties of molecules holds great importance for the description of the molecular response under the effect of an UV/Vis electromagnetic radiation. Computationally expensive ab initio (e.g. MultiConfigurational SCF, Coupled Cluster) or TDDFT methods are commonly used by the quantum chemistry community to compute these properties. In this work, we propose a (supervised) Machine Learning approach to model the absorption spectra of organic molecules. Several supervised ML methods have been tested such as Kernel Ridge Regression (KRR), Multiperceptron Neural Networs (MLP) and Convolutional Neural Networks. The use of only geometrical descriptors (e.g. Coulomb Matrix) proved to be insufficient for an accurate training. Inspired on the TDDFT theory, we propose to use a set of electronic descriptors obtained from low-cost DFT methods: orbital energy differences, transition dipole moment between occupied and unoccupied Kohn-Sham orbitals and charge-transfer character of mono-excitations. We demonstrate that with this electronic descriptors and the use of Neural Networks we can predict not only a density of excited states, but also getting very good estimation of the absorption spectrum and charge-transfer character of the electronic excited states, reaching results close to the chemical accuracy (~2 kcal/mol or ~0.1eV)

A basic electro-topological descriptor for the prediction of organic molecule geometries by simple machine learning

This paper proposes a machine learning (ML) method to predict stable molecular geometries from their chemical composition. The method is useful for generating molecular conformations which may serve as initial geometries for saving time during expensive structure optimizations by quantum mechanical calculations of large molecules. Conformations are found by predicting the local arrangement around each atom in the molecule after trained from a database of previously optimized small molecules. It works by dividing each molecule in the database into minimal building blocks of different type. The algorithm is then trained to predict bond lengths and angles for each type of building block using an electro-topological fingerprint as descriptor. A conformation is then generated by joining the predicted blocks. Our model is able to give promising results for optimized molecular geometries from the basic knowledge of the chemical formula and connectivity. The method trends to reproduce interatomic distances within test blocks with RMSD under 0.05

Update on Dihydropteroate Synthase (DHPS) Mutations in Pneumocystis jirovecii

A Pneumocystis jirovecii is one of the most important microorganisms that cause pneumonia in immunosupressed individuals. The guideline for treatment and prophylaxis of Pneumocystis pneumonia (PcP) is the use of a combination of sulfa drug-containing trimethroprim and sulfamethoxazole. In the absence of a reliable method to culture Pneumocystis, molecular techniques have been developed to detect mutations in the dihydropteroate synthase gene, the target of sulfa drugs, where mutations are related to sulfa resistance in other microorganisms. The presence of dihydropteroate synthase (DHPS) mutations has been described at codon 55 and 57 and found almost around the world. In the current work, we analyzed the most common methods to identify these mutations, their geographical distribution around the world, and their clinical implications. In addition, we describe new emerging DHPS mutations. Other aspects, such as the possibility of transmitting Pneumocystis mutated organisms between susceptible patients is also described, as well as a brief summary of approaches to study these mutations in a heterologous expression system

Distribución altitudinal del género Charinus (Arachnida: Amblypygi: Charinidae) en América

La presente contribución aborda la distribución altitudinal de las especies de amblipígidos del género Charinus Simon, 1892 en las Américas, un aspecto no estudiado previamente. Para ello se analizaron 75 artículos de taxonomía y ecología del grupo. La mayoría (62%) de estas especies habitan a menos de 301 m s.n.m.; 24.0% habitan entre los 301 y 600 m y solamente cuatro especies (5.0%) han sido reportadas de localidades situadas entre los 1201 y 1920 m s.n.m., siendo esta última la cota de máxima altitud registrada para el género en este continente. En América del Sur se localizan todas las especies americanas con un rango de distribución altitudinal por encima de los 1000 m, aunque en este subcontinente solamente Ecuador y Perú disponen de suficiente información al respecto

Nueva especie del género Charinus (Amblypygi; Charinidae) del Cusco, Perú

Se describe una especie nueva del género Charinus Simon, 1892, procedente del distrito Santa Teresa (1436 –1511 m de altitud), en La Convención, Cusco, Perú, la cual es la tercera para dicha región y la quinta para este país sudamericano. Su aspecto general y los gonópodos de la hembra son muy parecidos a los de Charinus longitarsus Armas & Palomino-Cardenas, 2016 y C. yanatile Palomino-Cardenas & Armas, 2022, también del Cusco; pero se diferencia de ambas por presentar en la distitibia del cuarto par de patas 16 tricobotrios, en lugar de 14; además, C. longitarsus posee 30 tarsómeros en las patas I (43 en la especie nueva); mientras que en C. yanatile, el tubérculo ocular es más grande y el tarsómero 1 del primer par de patas es más largo que los dos siguientes juntos (en la especie nueva es más corto). También se enmienda la descripción de los gonópodos femeninos de C. longitarsus y se incluye una clave taxonómica para la identificación de las especies peruanas de Charinus. Publicación registrada en Zoobank/ZooBank article registered: LSID urn:lsid:zoobank.org:pub:F00CAB9F-4562-466E-93AD-9C07AB977721 Acto nomenclatural/nomenclatural act: Charinus castilloae Armas & Palomino-Cárdenas, 2023 LSID urn:lsid:zoobank.org:act:4AC454B0-1DCB-46D4-8379-4876E28E684

A Case Study of Malignant Edema in Postpartum Mediterranean Buffaloes (Bubalus bubalis)

The paper describes for the first time four cases of postparturient malignant edema in water buffaloes due to Clostridium septicum (Cl. septicum). The study was carried out on four primiparous buffaloes that showed swelling of perineal and perivulvar areas, fever and agalactia a few hours after calving. Two of them died within 20 hours after calving. The other two developed edema in the skeletal muscles of one leg and were treated with sulfadiazine-trimethoprim for 10 days. The clinical signs completely resolved. Culture and molecular investigations identified the pathogen isolated from exudate taken from the vulva as Cl. septicum. The isolate showed multi-drug resistance. In the management of infection due to Cl. septicum, timely diagnosis and the chirurgic curettage, associated with a broad-spectrum antibiotic therapy, were found to be sufficient for the survival and recovery of the infected animals

The optical counterpart of the bright X-ray transient Swift J1745-26

We present a 30-day monitoring campaign of the optical counterpart of the bright X-ray transient Swift J1745-26, starting only 19 minutes after the discovery of the source. We observe the system peaking at i' ~17.6 on day 6 (MJD 56192) to then decay at a rate of ~0.04 mag/day. We show that the optical peak occurs at least 3 days later than the hard X-ray (15-50 keV) flux peak. Our measurements result in an outburst amplitude greater than 4.3 magnitudes, which favours an orbital period < 21 h and a companion star with a spectral type later than ~ A0. Spectroscopic observations taken with the GTC-10.4 m telescope reveal a broad (FWHM ~ 1100 km/s), double-peaked H_alpha emission line from which we constrain the radial velocity semi-amplitude of the donor to be K_2 > 250 km/s. The breadth of the line and the observed optical and X-ray fluxes suggest that Swift J1745-26 is a new black hole candidate located closer than ~7 kpc.Comment: 5 pages, 4 figures, accepted for publication in MNRA

Proteases in parasite organisms

Las proteasas tienen gran importancia en la biología y Fisiología de los seres vivos, por lo que no resulta extraño que estas enzimas hayan sido encontradas en diferentes organismos parásitos implicadas en una gran variedad de procesos propios del parásito, con las procesos de nutrición o de muda y desarrollo así como en las interacciones con el hospedador al invadir sus tejidos digerir sus proteínas o evadir su respuesta inmune (Mc Kerrow 1989) los últimos trabajos apuntan a la posibilidad de utilizar estas enzimas en el control de las parasitosis tanto como fuente de antígenos útiles para la realización de técnicas inmunodiagnósticas como material inmunógeno aplicable en inmunoprofilaxis como blancos de acción de nuevos fármacos antiparasitarios (Song y Chapeil 1993 Williams y Cooms 1995 Armas et al 1995a). Por todo ellos ya que posiblemente el mayor conocimiento de estas enzimas contribuirá a un mejor control de las parasitosis a continuación pasaremos a realizar una revisión bibliográfica de lo realizado al respecto en las últimos años siguiendo una ordenación en cuanto a su estructura química.Proteases have been implicated in the most important biological and physiological processes of the living organisms although is not rare thing to find them implicated in a variety of activities of the parasite (nutrition or exchysement and growth) as interactions with the host (invading their tissues degrading their proteins or avoiding its immune response) (Mc Kerrow 1989). Recent works propose the possibility of using these enzymes in the control of the parasites, as antigens for making immunodiagnosis or immunoprophylaxis as well as new targets from alternative antiparasitic treatment (Song and Chapeil 1993 Williams and Cooms 1995 Armas et al 1995a). The present revision was made according to the chemical structure of the enzymes.Facultad de Ciencias Veterinaria