Homochiral Metal-Organic Frameworks for Enantioselective Separations in Liquid Chromatography

Selective separation of enantiomers is a substantial challenge for the pharmaceutical industry. Chromatography on chiral stationary phases is the standard method, but at a very high cost for industrial-scale purification owing to the high cost of the chiral stationary phases. Typically, these materials are poorly robust, expensive to manufacture and often too specific for a single desired substrate, lacking desirable versatility across different chiral analytes. Here we disclose a porous, robust homochiral metal-organic framework (MOF), TAMOF-1, built from copper(II) and an affordable linker prepared from natural L-histidine. TAMOF-1 has shown to be able to separate a variety of model racemic mixtures, including drugs, in a wide range of solvents of different polarity, outperforming several commercial chiral columns for HPLC separations. Although not exploited in the present article, it is worthy to mention that the preparation of this new material is scalable to the multikilogram scale, opening unprecedented possibilities for low-energy chiral separation at the industrial scale

A Deep Catalogue of Protein-Coding Variation in 983,578 Individuals

Rare coding variants that substantially affect function provide insights into the biology of a gene1-3. However, ascertaining the frequency of such variants requires large sample sizes4-8. Here we present a catalogue of human protein-coding variation, derived from exome sequencing of 983,578 individuals across diverse populations. In total, 23% of the Regeneron Genetics Center Million Exome (RGC-ME) data come from individuals of African, East Asian, Indigenous American, Middle Eastern and South Asian ancestry. The catalogue includes more than 10.4 million missense and 1.1 million predicted loss-of-function (pLOF) variants. We identify individuals with rare biallelic pLOF variants in 4,848 genes, 1,751 of which have not been previously reported. From precise quantitative estimates of selection against heterozygous loss of function (LOF), we identify 3,988 LOF-intolerant genes, including 86 that were previously assessed as tolerant and 1,153 that lack established disease annotation. We also define regions of missense depletion at high resolution. Notably, 1,482 genes have regions that are depleted of missense variants despite being tolerant of pLOF variants. Finally, we estimate that 3% of individuals have a clinically actionable genetic variant, and that 11,773 variants reported in ClinVar with unknown significance are likely to be deleterious cryptic splice sites. To facilitate variant interpretation and genetics-informed precision medicine, we make this resource of coding variation from the RGC-ME dataset publicly accessible through a variant allele frequency browser

Identification and characterization of antibacterial compound(s) of cockroaches (Periplaneta americana)

Infectious diseases remain a significant threat to human health, contributing to more than 17 million deaths, annually. With the worsening trends of drug resistance, there is a need for newer and more powerful antimicrobial agents. We hypothesized that animals living in polluted environments are potential source of antimicrobials. Under polluted milieus, organisms such as cockroaches encounter different types of microbes, including superbugs. Such creatures survive the onslaught of superbugs and are able to ward off disease by producing antimicrobial substances. Here, we characterized antibacterial properties in extracts of various body organs of cockroaches (Periplaneta americana) and showed potent antibacterial activity in crude brain extract against methicillin-resistant Staphylococcus aureus and neuropathogenic E. coli K1. The size-exclusion spin columns revealed that the active compound(s) are less than 10 kDa in molecular mass. Using cytotoxicity assays, it was observed that pre-treatment of bacteria with lysates inhibited bacteria-mediated host cell cytotoxicity. Using spectra obtained with LC-MS on Agilent 1290 infinity liquid chromatograph, coupled with an Agilent 6460 triple quadruple mass spectrometer, tissues lysates were analyzed. Among hundreds of compounds, only a few homologous compounds were identified that contained isoquinoline group, chromene derivatives, thiazine groups, imidazoles, pyrrole containing analogs, sulfonamides, furanones, flavanones, and known to possess broad-spectrum antimicrobial properties, and possess anti-inflammatory, anti-tumour, and analgesic properties. Further identification, characterization and functional studies using individual compounds can act as a breakthrough in developing novel therapeutics against various pathogens including superbugs

Revista de Vertebrados de la Estación Biológica de Doñana

Tiempo y orden de aparición de las escamas en el salmón del Atlántico (Salmo salar)Estudios sobre el sapo corredor (Bufo calamita) en el sur de España.III. ReproducciónInfluencia de las carecterísticas del medio acuático sobre las poblaciones de larvas de anfibios en lala Reserva Biológica de Doñana(Huelva, EspañaDieta de la cigüeñuela (Himantopus himantopus) en las salinas del estuario del GuadianaOrientación y selección del lugar del nido en el gorrión moruno (Passer hispaniolensis)la avifauna de las Vegas Bajas del Guadianala reproducción de la malvasía (Oxyura leucocephala) en el sur de la provincia de Córdoba, España.La alimentación de la curruca cabecinegra (Sylvia melanocephala, Gmelin 1788) en olivares de la provincia de Jaén (otoño-invierno)Consideraciones sobre el efecto de los conejos y los grandes herbívoros en los pastizales de la Vera de DoñanaAnálisis factorial de las expresiones faciales del babuino sagrado (Papio hamadryas)Contaminación xenobiótica del Parque Nacionalde Doñana. II. Residuos de insecticidas organoclorados, bifenilos policlorados, (PGBs) y metales pesados en Falconiformes y StrigiformesTransferencia total y del y bioacumulación de mercurio y metilmercurio en ecosistemas del Parque Nacional de DoñanaNota sobre la alimentación de larvas de anfibios: I. Pleurodeles waltl en charcas temporaleNota sobre nuevas especies parasitada por el críalo (Clamator glandarius) en EspañaEstructura de la jerarquización en la predación de huevos y pichones en Spheniscus magellanicusPasser domesticus, nueva specie para Bolivia¿Están realmente subalimentados los cernícalos primilla en el valle del Guadalquivir durante el periodo no reproductor?.Nidificación del paiño común (Hydrobates pelagicus) en las Islas Canarias.Nuevos datos sobre la presencia del visón europeo (Mustela lutreola L.) en NavarraLa población de gamos del Parque Nacional de Doñana en 1979Puntualización a la nota "predacción de Falco peregrino y Falco subbuteo sobre quirópteros" de Aymerich y García de Castro aparecida en el vol. 9 de esta revista.Peer reviewe

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential

Introduction: Atezolizumab is a fully humanized, engineered monoclonal antibody that specifically targets PD-L1, key molecule in the cancer-immunity pathway. Atezolizumab is currently approved for the treatment of metastatic non-small-cell lung cancer and advanced urothelial carcinomas. Areas covered: In this review, we will present the available data supporting the efficacy of atezolizumab for the treatment of metastatic colorectal cancer (mCRC). We will also provide an update on the ongoing/future clinical trials evaluating the role of atezolizumab for the treatment of CRC in different settings (alone or in combination with other checkpoint inhibitors and/or targeted therapies). So far, a small subgroup of mCRC (those with deficiency in mismatch repair - dMMR) appears to benefit significantly from checkpoint inhibitors. As expected, further research is needed to develop biomarkers, effective therapeutic strategies and novel combinations to overcome immune escape resistance and achieve better responses with minimal toxicities. Expert opinion: Interim analyses from ongoing early-phase studies in mCRC have shown encouraging activity of atezolizumab in combination with chemotherapy and/or targeted therapies, especially with MEK inhibitor cobimetinib. Within the next few years, this PD-L1 checkpoint inhibitor will likely be included as one of the treatment options for CRC, at least for patients with dMMRGonzalo Tapia Rico and Timothy J. Pric

Adjuvant systemic treatment for high-risk resected non-cutaneous melanomas: What is the evidence?

Non-cutaneous melanomas (mucosal, uveal, leptomeningeal, unknown primaries) represent around 5-10 % of all melanoma diagnoses. Non-cutaneous melanomas demonstrate differences in tumour biology, generally present with more advanced stages and have an overall poorer prognosis compared to skin melanomas. The cornerstone of their treatment is surgery followed by radiotherapy in some cases. Unfortunately, in many of these patients their melanoma will recur. Adjuvant therapy for non-cutaneous melanomas remains controversial. To date, almost all of the tested adjuvant agents have failed to demonstrate any benefit; the two randomised positive trials were criticized for methodological reasons, small sample size and conflicting results. The aim of this review is to assess the current evidence on systemic adjuvant treatments for high-risk resected non-cutaneous melanomas. We also provide a summary table with the currently recruiting clinical trials in these settings and we discuss some strategies to improve trial design in this particularly niche area of oncology