Marine Actinobacteria are emerging as an unexplored source for natural product discovery. Eighty-seven deep-sea coral reef invertebrates were collected during an oceanographic expedition at the submarine Avilés Canyon (Asturias, Spain) in a range of 1500 to 4700 m depth. From these, 18 cultivable bioactive Actinobacteria were isolated, mainly from corals, phylum Cnidaria, and some specimens of phyla Echinodermata, Porifera, Annelida, Arthropoda, Mollusca and Sipuncula. As determined by 16S rRNA sequencing and phylogenetic analyses, all isolates belong to the phylum Actinobacteria, mainly to the Streptomyces genus and also to Micromonospora, Pseudonocardia and Myceligenerans. Production of bioactive compounds of pharmacological interest was investigated by high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) techniques and subsequent database comparison. Results reveal that deep-sea isolated Actinobacteria display a wide repertoire of secondary metabolite production with a high chemical diversity. Most identified products (both diffusible and volatiles) are known by their contrasted antibiotic or antitumor activities. Bioassays with ethyl acetate extracts from isolates displayed strong antibiotic activities against a panel of important resistant clinical pathogens, including Gram-positive and Gram-negative bacteria, as well as fungi, all of them isolated at two main hospitals (HUCA and Cabueñes) from the same geographical region. The identity of the active extracts components of these producing Actinobacteria is currently being investigated, given its potential for the discovery of pharmaceuticals and other products of biotechnological interest.

family of macrolide antibiotics known as nargenicins, 30 which exhibit antimicrobial activity mainly against Staph-31 ylococcus aureus. Nargenicins and branimycins have a tricyclic 32 structure with either a 9-or 10-membered lactone ring and 33 contain a unique ether bridge. In 1977, the first members of the 34 nargenicin family were isolated by Pfizer and Upjohn after the 35 aerobic fermentation of Nocardia argentinensis ATCC 31306. 36 This family of compounds and their antibacterial activity were 37 later patented, 1 and the structure of one of them, nargenicin 38 A1, was elucidated.2 Although it showed antibacterial activity in 39 vitro, this was restricted to Gram-positive bacteria, particularly 40 methicillin-resistant S. aureus (MRSA). It was also described 41 that nargenicin A1 induces cell differentiation and can be used, 42 therefore, as a possible treatment for neoplastic diseases. 43The first branimycin (1) was isolated in 1998 from the 44 Actinomycete GW 60/1571 and its structure determined by the 45

This paper tackles the flexible job-shop scheduling problem with uncertain processing times. The uncertainty in processing times is represented by means of fuzzy numbers, hence the name fuzzy flexible job-shop scheduling. We propose an effective genetic algorithm hybridised with tabu search and heuristic seeding to minimise the total time needed to complete all jobs, known as makespan. To build a high-quality and diverse set of initial solutions we introduce a heuristic method which benefits from the flexible nature of the problem. This initial population will be the starting point for the genetic algorithm, which then applies tabu search to every generated chromosome. The tabu search algorithm relies on a neighbourhood structure that is proposed and analysed in this paper; in particular, some interesting properties are proved, such as feasibility and connectivity. Additionally, we incorporate a filtering mechanism to reduce the neighbourhood size and a method that allows to speed-up the evaluation of new chromosomes. To assess the performance of the resulting method and compare it with the state-of-the-art, we present an extensive computational study on a benchmark with 205 instances, considering both deterministic and fuzzy instances to enhance the significance of the study. The results of these experiments clearly show that not only does the hybrid algorithm benefit from the synergy among its components but it is also quite competitive with the state-of-the-art when solving both crisp and fuzzy instances, providing new best-known solutions for a number of these test instances. Genetic Tabu AbstractThis paper tackles the flexible job-shop scheduling problem with uncertain processing times. The uncertainty in processing times is represented by means of fuzzy numbers, hence the name fuzzy flexible job-shop scheduling. We propose an effective genetic algorithm hybridised with tabu search and heuristic seeding to minimise the total time needed to complete all jobs, known as makespan. To build a high-quality and diverse set of initial solutions we introduce a heuristic method which benefits from the flexible nature of the problem. This initial population will be the starting point for the genetic algorithm, which then applies tabu search to every generated chromosome. The tabu search algorithm relies on a neighbourhood structure that is proposed and analysed in this paper; in particular, some interesting properties are proved, such as feasibility and connectivity. Additionally, we incorporate a filtering mechanism to reduce the neighbourhood size and a method that allows to speed-up the evaluation of new chromosomes. To assess the performance of the resulting method and compare it with the state-of-the-art, we present an extensive computational study on a benchmark with 205 instances, considering both deterministic and fuzzy instances to enhance the significance of the study. The results of these experiments clearly show that not only does the hybrid algorithm benefit from the synergy among its component...

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Introducción: Las implicaciones clínicas y epidemiológicas de las respuestas inmunitarias anormales observadas en la COVID-19 en el cribado de la infección tuberculosa latente (ITL) no están claras. Método: Revisamos los resultados de QuantiFERON TB Gold Plus (QFT-Plus) desde julio de 2016 hasta octubre de 2021 (36.709 pacientes) en Asturias (España). También estudiamos una cohorte de noventa pacientes hospitalizados con neumonía COVID-19 sospechada/confirmada y un grupo de pacientes ancianos hospitalizados con COVID-19 que se sometieron a pruebas seriadas de QFT-Plus y perfiles inmunitarios. Resultados: La tasa de resultados indeterminados QFT-Plus pasó de 1,4% (julio de 2016 a noviembre de 2019) a 4,2% durante la pandemia COVID-19. La evolución del número de casos con respuesta de interferon-gamma (IFN-gamma) baja/muy baja en el tubo mitógeno de QFT-Plus era paralela a la actividad de la enfermedad y al número de muertes por COVID-19 registradas en nuestra región a lo largo de la pandemia (desde marzo de 2020 a octubre de 2021). El porcentaje de pacientes QFT-plus positivo no cambió significativamente antes y durante la pandemia (13,9% vs. 12,2%). Cuarenta y nueve pacientes de la cohorte con neumonía COVID-19 sospechada/confirmada (54,4%) tenían una respuesta de IFN-gamma baja/muy baja al mitógeno, 22 de ellos (24,4%) tenían neumonía grave y crítica. Ninguno recibió inmunosupresores antes de la prueba. Los hallazgos radiológicos anormales (P = 0,01), pero no la gravedad del COVID-19, se asociaron con una respuesta baja al mitógeno. El perfil inmunológico mostró una reducción de las células T-CD8 + y una correlación directa entre el número de células T-EMRA-CD8 + y la respuesta de IFN-gamma en el tubo mitógeno (P = 0,03). Conclusión: Las respuestas bajas de IFN-gamma al mitógeno en QFT-Plus ocurren a menudo en la neumonía por COVID-19, y se asocia con un número bajo de un subconjunto de células T-CD8 + efectoras, sin embargo no parece afectar la detección de ITL. Esta anomalía parece ser paralela a la dinámica de la COVID-19 a nivel poblacional y a su mortalidad.

Our study provides an alert regarding the transmission of rifampin-susceptible strains of Mycobacterium tuberculosis with a silent substitution in codon 514 of rpoB. Among 1,450 cases, we identified 12 isolates sharing this mutation and related restriction fragment length polymorphism (RFLP) types. The mutation impaired hybridization with the wild-type probes in three independent commercial assays, which could lead to misassignment of resistance.

Xpert CT values and smear status were strongly associated. However, diagnostic accuracy at set cut-off CT values of 27.7 or 31.8 would not replace smear microscopy. How CT values compare with smear microscopy in predicting infectiousness remains to be seen.

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