•Genome sequence of the 4-androstene-3,17-dione (AD) producer strain ‘M. neoaurum’ NRRL B-3805 (formerly Mycobacterium sp. NRRL B-3805).•Sequence of B-3805 was nearly identical to that of VKM ...Ac-1815D, but the detected differences determine its higher AD and lower ADD production.•These genome data permit the species-level identification of the strain using three marker sequences as Mycobacterium neoaurum.
Microbial bioconversion of sterols into high value steroid precursors, such as 4-androstene-3,17-dione (AD), is an industrial challenge. Genes and enzymes involved in sterol degradation have been proposed, although the complete pathway is not yet known. The genome sequencing of the AD producer strain ‘Mycobacterium neoaurum’ NRRL B-3805 (formerly Mycobacterium sp. NRRL B-3805) will serve to elucidate the critical steps for industrial processes and will provide the basis for further genetic engineering. The genome comprises a circular chromosome (5 421 338bp), is devoid of plasmids and contains 4844 protein-coding genes.
Presentamos aquí tres inscripciones romanas, inéditas y presumiblemente procedentes del territorio de la actual provincia de Córdoba, dos de ellas registradas en el segundo volumen de la ...autobiografía de Carlos Castilla del Pino titulada Casa del Olivo. Las dos primeras son de carácter funerario y, al menos la segunda, se acomoda en tipología y contenido a los parámetros usuales de la epigrafía funeraria de la antigua Colonia Patricia Corduba; por el contrario, la tercera, fragmentada, corresponde a un epígrafe de carácter métrico
En este trabajo se quiere demostrar la existencia de conubium como derecho inherente a la condición latina provincial. Para ello se detiene principalmente en el análisis de la lex Minicia de liberis ...y en la propuesta realizada por G. Luraschi respecto a la datación y destinatarios de dicha ley. Se analiza asimismo la carta del emperador Domiciano recogida al final de la lex Irnitana por cuanto que esta carta, junto con la lex Minicia son utilizados con frecuencia para negar que los latinos provinciales disfrutasen del derecho de conubium. Se defiende finalmente la datación tradicional de la lex Minicia en un momento anterior a la guerra Social y por tanto la necesidad de desvincular sus restricciones del estudio de la latinidad de época imperial.
Dimethyl fumarate is a cytoprotective and immunomodulatory drug used in the treatment of multiple sclerosis. We performed a bibliometric study examining the characteristics and trends of the top 100 ...cited articles that include dimethyl fumarate in the title. On 21 September 2020 we carried out an electronic search in the Web of Science (WOS), seeking articles that include the following terms within the title: dimethyl fumarate, BG-12, or Tecfidera. To focus our investigation on original research, we refined the search to include only articles, early access, others, case report, and clinical trials. We obtained a total of 1115 items, which were cited 7169 times, had a citation density of 6.43 citations/item, and an h-index of 40. Around 2010, there was a jump in the number of published articles per year, rising from 5 articles/year up to 12 articles/year. We sorted all the items by the number of citations and selected the top 100 most cited (T100). The T100 had 4164 citations, with a density of 37 citations/year and contained 16 classic research articles. They were published between 1961 and 2018; the years 2010-2018 amassed nearly 80% of the T100. We noted 17 research areas with articles in the T100. Of these, the number one ranking went to neurosciences/neurology with 39 articles, and chemistry ranked second on the T100 list with 14 items. We noticed that the percentage of articles belonging to different journals changed depending on the time period. Chemistry held the highest number of papers during 1961-2000, while pharmacology andneurosciences/neurology led the 2001-2018 interval. A total of 478 authors from 145 institutions and 25 countries were included in the T100 ranking. The paper by Gold R et al. was the most successful with 14 articles, 1.823 citations and a density of 140.23 citations/year. The biotechnological company Biogen led the T100 list with 20 articles. With 59 published articles, the USA was the leading country in publications. We concluded that this study analyzed the use of and research on dimethyl fumarate from a different perspective, which will allow the readership (expert or not) to understand the relevance of classic and recent literature on this topic.
In the landscape of colorectal cancer treatment, classical chemotherapeutic agents such as 5-fluorouracil, capecitabine, irinotecan, oxaliplatin, trifluridine, and tipiracil have historically played ...a pivotal role. This study presents a comprehensive bibliometric analysis of the top 100 most influential articles focusing on these classic chemotherapy drugs in the management of colorectal cancer. With this, we shed light on their current importance, despite the emergence of new therapeutic targets and treatments in the field of oncology. Systematically evaluating research outputs, this analysis reveals a prevalence of co-authorship among institutions, countries (led by the United States, China, and Europe), and researchers highlighting the global and collaborative nature of efforts in research, utilization, and development of these drugs. Three thematic axes lead the research: pharmacogenetics, the development of new pharmaceutical forms, and the use of adjuvants. This research serves as a foundation for future endeavors, aiding researchers, clinicians, and policymakers in making informed decisions about the direction of research and development in the dynamic field of colorectal cancer therapy.
Feed restriction during the early life of ewe lambs (F0) triggers the transfer of epigenetic marks to the next generation, thus impairing the reproductive performance of F1. However, the effects of ...this factor on milk production and composition, including its abundance in regulatory miRNA (many of which are contained in exosomes, small vesicles of endocytic origin that play a role in the modulation of immune response of the offspring) has not been tested so far. Therefore, in this study, the replacement ewe lambs (F0) obtained in a previous project (a group of ewes fed milk replacer ad libitum –ADL– vs. a group of ewes restricted –RES– to 62.5 % the intake level of milk replacer during the suckling period) were raised under similar post-weaning conditions and mated to obtain the progeny (F1). The F1 female lambs were also mated to obtain F2. Milk production was recorded during the peak lactation period of F1, and milk samples were obtained for each gland (udder half) separately to measure chemical composition, somatic cell counts (SCC), and bacteria counts. Moreover, exosomes were also isolated from the milk of each gland separately to obtain the miRNAome following a Next Generation Sequencing approach. No significant differences were found in either milk production of F1, chemical composition of milk (fat, protein, lactase), or bacteriology (colony forming units, CFU). However, SCC was reduced significantly in milk samples of F1-RES dairy sheep, whereas the abundance of five miRNAs was also modified. Thus, oar-miR-150, oar-miR-221, oar-miR-23a, oar-miR-27a, oar-miR-376c were all down modulated in F1-RES when compared to F1-ADL. Most of these miRNAs have been found to play a role in biological functions such as development, apoptosis, muscle differentiation, reproduction, or milk production. However, the exosomes extracted from the milk of these sheep (F1-RES) did not affect the production of IL-9 and IL-2 cytokines after in vitro culture with CaCo-2 cells. This study reveals that nutritional programming events such as feed restriction may drive the abundance of not only SCC but also some milk's bioactive components such as miRNAs, although it is not clear if these changes may modulate the immune response at the intestinal level of the offspring.
•Feed restriction of ewes (F0) causes nutritional programming of the offspring (F1).•The somatic cell counts of the F1 milk is reduced by this event.•The miRNAome of the F1 milk exosomes is also affected by this circumstance.•The expression of cytokines by Caco-2 cells is not altered by these changes.
One of the major drawbacks of current treatments for neglected tropical diseases is the low safety of the drugs used and the emergence of resistance. Leishmaniasis is a group of neglected diseases ...caused by protozoa of the trypanosomatidae family that lacks preventive vaccines and whose pharmacological treatments are scarce and unsafe. Combination therapy is a strategy that could solve the above-mentioned problems, due to the participation of several mechanisms of action and the reduction in the amount of drug necessary to obtain the therapeutic effect. In addition, this approach also increases the odds of finding an effective drug following the repurposing strategy. From the previous screening of two collections of repositioning drugs, we found that pyrvinium pamoate had a potent leishmanicidal effect. For this reason, we decided to combine it separately with two clinically used leishmanicidal drugs, miltefosine and paromomycin. These combinations were tested in axenic amastigotes of 'Leishmania infantum' obtained from bone marrow cells and in intramacrophagic amastigotes obtained from primary cultures of splenic cells, both cell types coming from experimentally infected mice. Some of the combinations showed synergistic behavior, especially in the case of the combination of pyrvinium pamoate with paromomycin, and exhibited low cytotoxicity and good tolerability on intestinal murine organoids, which reveal the potential of these combinations for the treatment of leishmaniasis.
El presente artículo pretende demostrar la existencia de la condición latina y la necesidad de su introducción en el análisis onomástico referido a las ciudades del Occidente del Imperio, limitado ...habitualmente a la identificación de población romana o peregrina. El análisis de la onomástica de los ediles de Andelo podría indicar la condición latina de estos magistrados.This article aims to demonstrate the existence of the Latin condition and the need for its implementation in the onomastic analysis of the cities of the Western Empire, which is usually limited to identifying cives Romani or peregrini. The onomastic analysis of Andelo aediles could indicate the Latin condition of these magistrates.
Visceral leishmaniasis is a neglected vector-borne tropical disease caused by
and
that is endemic not only in East African countries, but also in Asia, regions of South America and the Mediterranean ...Basin. For the pharmacological control of this disease, there is a limited number of old and, in general, poorly adherent drugs, with a multitude of adverse effects and low oral bioavailability, which favor the emergence of resistant pathogens. Pentavalent antimonials are the first-line drugs, but due to their misuse, resistant
strains have emerged worldwide. Although these drugs have saved many lives, it is recommended to reduce their use as much as possible and replace them with novel and more friendly drugs. From a commercial collection of anti-infective drugs, we have recently identified nifuratel-a nitrofurantoin used against vaginal infections-as a promising repurposing drug against a mouse model of visceral leishmaniasis. In the present work, we have tested combinations of miltefosine-the only oral drug currently used against leishmaniasis-with nifuratel in different proportions, both in axenic amastigotes from bone marrow and in intracellular amastigotes from infected Balb/c mouse spleen macrophages, finding a potent synergy in both cases. In vivo evaluation of oral miltefosine/nifuratel combinations using a bioimaging platform has revealed the potential of these combinations for the treatment of this disease.
Natalizumab is being used in recurrent multiple sclerosis despite its history of market withdrawal due to lethal cases. We have carried out a bibliometric analysis of this drug from 1999 to February ...2020 in order to assess the real impact of the use natalizumab with the goal to identify the key articles that sustain the current knowledge on the therapeutic possibilities of this compound. We have extracted from the Web of Science the top 100 most cited records (T100) and tabulated data on the journal, authors, publication year, number of citations, countries and institutions of publication, T100-records, citation density and citations per record of the works. The 100 most cited articles were selected from a total of 32,507 citations out of 2817 publications with an h-number of 74, 11.54 citations/publication, and a density of 1544.79 citations/year. Citations ranged from 63 of the paper placed in the 100th position (T100) to 1940 of the paper in the first position (T1). T2 was cited 888 times, and the difference in the number of citations between T1 and T2 was higher than that between T2 and T10. T1, T2 and T3 are clinical trials. When articles are arranged by institution and nationality having more than 10 T100 articles, biotechnology company Biogen and the USA, respectively, lead the ranking, but we also find that 8 out of 10 are academic European institutions. A co-authorship analysis reveals an intense collaborative activity between countries and institutions. We conclude that the clinical and academic communities have shown a sustained interest in natalizumab for the therapy of recurrent multiple sclerosis over the last 20 years.
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•Bibliometric analysis of Natalizumab (1999–2019) to assess the real impact of the use of this drug.•Identify the key articles that sustain the current knowledge on the therapeutic possibilities of natalizumab.•Identify the collaborative activity between countries and institutions.
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