Genotypic and Phenotypic Study of Antiviral Resistance Mutations in Refractory Cytomegalovirus Infection.

BACKGROUND: This study describes the genotypic and phenotypic characterization of novel human cytomegalovirus (HCMV) genetic variants of a cohort of 94 clinically resistant HCMV patients. METHODS AND RESULTS: Antiviral-resistant mutations were detected in the UL97, UL54, and UL56 target genes of 25 of 94 (26.6%) patients. The genotype-phenotype correlation study resolved the status of 5 uncharacterized UL54 deoxyribonucleic acid polymerase (G441S, A543V, F460S, R512C, A928T) and 2 UL56 terminase (F345L, P800L) mutations found in clinical isolates. A928T conferred high, triple resistance to ganciclovir, foscarnet, and cidofovir, and A543V had 10-fold reduced susceptibility to cidofovir. Viral growth assays showed G441S, A543V, F345L, and P800L impaired viral growth capacities compared with wild-type AD169 HCMV. Three-dimensional modeling predicted A543V and A928T phenotypes but not R512C, reinforcing the need for individual characterization of mutations by recombinant phenotyping. CONCLUSIONS: Extending mutation databases is crucial to optimize treatments and to improve the assessment of patients with resistant/refractory HCMV infection.

Portobelamides A and B and Caciqueamide, Cytotoxic Peptidic Natural Products from a Caldora sp. Marine Cyanobacterium.

Three new compounds, portobelamides A and B (1 and 2), 3-amino-2-methyl-7-octynoic acid (AMOYA) and hydroxyisovaleric acid (Hiva) containing cyclic depsipeptides, and one long chain lipopeptide caciqueamide (3), were isolated from a field-collection of a Caldora sp. marine cyanobacterium obtained from Panama as part of the Panama International Cooperative Biodiversity Group Program. Their planar structures were elucidated through analysis of 2D NMR and MS data, especially high resolution (HR) MS2/MS3 fragmentation methods. The absolute configurations of compounds 1 and 2 were deduced by traditional hydrolysis, derivative formation, and chromatographic analyses compared with standards. Portobelamide A (1) showed good cytotoxicity against H-460 human lung cancer cells (33% survival at 0.9 µM).

Evaluating Nitrogen-Containing Biosynthetic Products Produced by Saltwater Culturing of Several California Littoral Zone Gram-Negative Bacteria.

The biosynthetic potential of marine-sediment-derived Gram-negative bacteria is poorly understood. Sampling of California near-shore marine environments afforded isolation of numerous Gram-negative bacteria in the Proteobacteria and Bacteriodetes phyla, which were grown in the laboratory to provide extracts whose metabolites were identified by comparative analyses of LC-mass spectrometry and MSn data. Overall, we developed an assemblage of seven bacterial strains grown in five different media types designed to coax out unique secondary metabolite production as a function of varying culture conditions. The changes in metabolite production patterns were tracked using the GNPS MS2 fragmentation pattern analysis tool. A variety of nitrogen-rich metabolites were visualized from the different strains grown in different media, and strikingly, all of the strains examined produced the same new, proton-atom-deficient compound, 1-methyl-4-methylthio-ß-carboline (1), C13H12N2S. Scale-up liquid culture of Achromobacter spanius (order: Burkholderiales; class: Betaproteobacteria) provided material for the final structure elucidation. The methods successfully combined in this work should stimulate future studies of molecules from marine-derived Gram-negative bacteria.

Salinipostins A-K, long-chain bicyclic phosphotriesters as a potent and selective antimalarial chemotype.

Despite significant advances in antimalarial chemotherapy over the past 30 years, development of resistance to frontline drugs remains a significant challenge that limits efforts to eradicate the disease. We now report the discovery of a new class of antimalarials, salinipostins A-K, with low nanomolar potencies and high selectivity indices against mammalian cells (salinipostin A: Plasmodium falciparum EC50 50 nM, HEK293T cytotoxicity EC50 > 50 µM). These compounds were isolated from a marine-derived Salinospora sp. bacterium and contain a bicyclic phosphotriester core structure, which is a rare motif among natural products. This scaffold differs significantly from the structures of known antimalarial compounds and represents a new lead structure for the development of therapeutic targets in malaria. Examination of the growth stage specificity of salinipostin A indicates that it exhibits growth stage-specific effects that differ from compounds that inhibit heme polymerization, while resistance selection experiments were unable to identify parasite populations that exhibited significant resistance against this compound class.

Image-based 384-well high-throughput screening method for the discovery of skyllamycins A to C as biofilm inhibitors and inducers of biofilm detachment in Pseudomonas aeruginosa.

To date, most antibiotics have primarily been developed to target bacteria in the planktonic state. However, biofilm formation allows bacteria to develop tolerance to antibiotics and provides a mechanism to evade innate immune systems. Therefore, there is a significant need to identify small molecules to prevent biofilm formation and, more importantly, to disperse or eradicate preattached biofilms, which are a major source of bacterial persistence in nosocomial infections. We now present a modular high-throughput 384-well image-based screening platform to identify Pseudomonas aeruginosa biofilm inhibitors and dispersal agents. Biofilm coverage measurements were accomplished using non-z-stack epifluorescence microscopy to image a constitutively expressing green fluorescent protein (GFP)-tagged strain of P. aeruginosa and quantified using an automated image analysis script. Using the redox-sensitive dye XTT, bacterial cellular metabolic activity was measured in conjunction with biofilm coverage to differentiate between classical antibiotics and nonantibiotic biofilm inhibitors/dispersers. By measuring biofilm coverage and cellular activity, this screen identifies compounds that eradicate biofilms through mechanisms that are disparate from traditional antibiotic-mediated biofilm clearance. Screening of 312 natural-product prefractions identified the cyclic depsipeptide natural products skyllamycins B and C as nonantibiotic biofilm inhibitors with 50% effective concentrations (EC50s) of 30 and 60 µM, respectively. Codosing experiments of skyllamycin B and azithromycin, an antibiotic unable to clear preattached biofilms, demonstrated that, in combination, these compounds were able to eliminate surface-associated biofilms and depress cellular metabolic activity. The skyllamycins represent the first known class of cyclic depsipeptide biofilm inhibitors/dispersers.

ShetlandsUAVmetry: unmanned aerial vehicle-based photogrammetric dataset for Antarctic environmental research.

The study of the functioning and responses of Antarctica to the current climate change scenario is a priority and a challenge for the scientific community aiming to predict and mitigate impacts at a regional and global scale. Due to the difficulty of obtaining aerial data in such extreme, remote, and difficult-to-reach region of the planet, the development of remote sensing techniques with Unmanned Aerial Vehicles (UAVs) has revolutionized polar research. ShetlandsUAVmetry comprises original datasets collected by UAVs during the Spanish Antarctic Campaign 2021-2022 (January to March 2022), along with the photogrammetric products resulting from their processing. It includes data recorded during twenty-eight distinct UAV flights at various study sites on Deception and Livingston islands (South Shetland Islands, Antarctica) and consists of a total of 15,691 high-resolution optical RGB captures. In addition, this dataset is accompanied by additional associated files that facilitate its use and accessibility. It is publicly accessible and can be downloaded from the figshare data repository.

A first estimation of the role of penguin guano on copper cycling and organic speciation in Antarctic coastal waters.

Cu is a vital micronutrient, but free Cu ions (Cu2+) in seawater, even at subnanomolar concentrations, can impede phytoplankton growth. Natural Cu complexation with organic ligands regulates Cu acquisition and, in most instances, reduces Cu2+ concentrations below toxic thresholds. Along the Antarctic coast, the sources and sinks of Cu and its associated ligands remain poorly defined. Despite the high productivity in the area, there are no studies on the role of trophic transfer in Cu cycling. This study explores penguin guano release of Cu and Cu ligands and its potential in neutralizing copper toxicity along the Antarctic coast. We collected guano in a Chinstrap penguin nesting location in the West coast of Deception Island and extracted its components into aqueous solution imitating natural processes. Copper concentration in guano was 0.4 mg (dry weight g)-1 constituting a potential toxic threat and showed biomagnification with respect to krill. Surface seawater samples collected from various locations varying in penguin activity, were analyzed to assess the potential influence of guano on the area. Visual examination and elevated levels of Al suggested that a substantial portion of guano was lithogenic. Consequently, only a modest 16 % of the total Cu present in guano could be extracted using mechanical methods. Notably, the concentrations of the extracted organic ligands were approximately 23 times higher than the concentrations of the extracted Cu. This significant presence of ligands effectively nullifies any potential toxicity that could have arisen from free Cu2+ ions. Guano ligands' conditional stability constants were lower than those in surface seawater suggesting phytoplankton exudation was the main ligand source in the area. Overall, guano acts as a key node for Cu cycling in coastal Antarctic waters but its deleterious potential is neutralized by ligands from krill digestion and the high background concentration of phytoplankton exudates.

The contribution of penguin guano to the Southern Ocean iron pool.

Iron plays a crucial role in the high-nutrient, low-chlorophyll Southern Ocean regions, promoting phytoplankton growth and enhancing atmospheric carbon sequestration. In this area, iron-rich Antarctic krill (Euphausia superba) and baleen whale species, which are among their main predators, play a large role in the recycling of iron. However, penguins have received limited attention despite their representing the largest seabird biomass in the southern polar region. Here, we use breeding site guano volumes estimated from drone images, deep learning-powered penguin census, and guano chemical composition to assess the iron export to the Antarctic waters from one of the most abundant penguin species, the Chinstrap penguin (Pygoscelis antarcticus). Our results show that these seabirds are a relevant contributor to the iron remobilization pool in the Southern Ocean. With an average guano concentration of 3 mg iron g-1, we estimate that the Chinstrap penguin population is recycling 521 tonnes iron yr-1, representing the current iron contribution half of the amount these penguins were able to recycle four decades ago, as they have declined by more than 50% since then.

Mapping dinoflagellate blooms (Noctiluca and Alexandrium) in aquaculture production areas in the NW Iberian Peninsula with the Sentinel-2/3 satellites.

The Galician Rías (northwestern Spain) are periodically affected by harmful algal blooms (HABs), mostly dinoflagellates, which pose a challenge to aquaculture activities due to the accumulation of biotoxins in shellfish. Typically, reddish blooms in the Rías are associated with non-toxic species like Noctiluca scintillans, with a few exceptions such as Alexandrium minutum, a producer of paralytic shellfish toxins (PST). Here, a useful approach is presented for monitoring reddish blooms through satellite imagery based on three case studies, two of them belonged to monospecific blooms of red Noctiluca scintillans, and the third to a bloom of Alexandrium spp. dominated by A. tamarense. In every case, a propulsive index was evaluated using Sentinel-2A/B satellites, which provide high spatial and spectral resolutions, combined with adequate atmospheric and sunglint correction by using the ACOLITE and C2RCC processors. This approach offers a simple and feasible method to accurately and timely map blooms of red N. scintillans and Alexandrium spp. in the study area, useful to detect the distribution of reddish blooms with synoptic observations for monitoring and aquaculture management purposes. Conversely, Sentinel-3A/B satellites with a relatively coarser spatial resolution, lacking adequate visualization and mapping of the extent of small blooms, did not accurately detect bloom footprints in the coastal bay region, although this sensor displays a set of suitable multispectral bands.

Use of a real-time remote monitoring network (RTRM) to characterize the Guadalquivir estuary (Spain).

The temporal variability of hydrological variables in the Guadalquivir estuary was examined during three years through a real-time remote monitoring network (RTRM). The network was developed with the aim of studying the influence of hydrodynamical and hydrological features within the estuary on the functioning of the pelagic ecosystem. Completing this data-gathering network, monthly cruises were performed in order to measure biogeochemical variables that are indicative of the trophic status of the aquatic environment. The results showed that several sources of physical forcing, such as wind, tide-associated currents and river discharge were responsible for the spatio-temporal patterns of dissolved oxygen, salinity and turbidity in the estuary. The analysis was conducted under tidal and flood regime, which allowed us to identify river discharge as the main forcing agent of the hydrology inside the estuary. In particular, episodes of elevated turbidity detected by the network, together with episodes of low salinity and dissolved oxygen were closely related to the increase in water supply from a dam located upstream. The network installed provided accurate data that can be rapidly used for research or educational applications and by policy-makers or agencies in charge of the management of the coastal area.

Water quality monitoring with Sentinel-2 and Landsat-8 satellites during the 2021 volcanic eruption in La Palma (Canary Islands).

In this study, seawater quality was monitored with high-resolution satellite imagery during the 2021 volcanic eruption (September-December) on La Palma Island (Spain), the longest recorded in the history of the island, and the most destructive in the last century in Europe. The Sentinel-2A/B twin satellites and Landsat-8 satellite were jointly used as an optical constellation, which allowed us to successfully characterize the short- and medium-term evolution of the new lava delta and subsequent impact on the seawater. Robust atmospheric and sunglint correction approaches were applied to thoroughly quantify the environmental changes caused on the adjacent coastal waters. The cloud and volcanic ash coverage remained very high over the coast during the event, so restricted information with 14 images (45% of the total scenes) was retrieved from the multi-sensor approach. Nevertheless, the availability of pre-, syn-, and post-eruption satellite products allowed us to map and detect the main water quality variations in the marine environment. On the one hand, during the eruption, a change in the properties of the water quality was observed, with a markedly increased turbidity on the western side of the island near the new lava delta due to the deposition of volcanic ash and material. On the other hand, chlorophyll-a concentration did not significantly increase, algal blooms were not observed, and oligotrophic conditions were not swiftly altered towards eutrophic conditions. This information offered an excellent opportunity to characterize the emplacement of the new lava delta and its impact on the marine environment in La Palma. The present multi-sensor strategy is an excellent opportunity to highlight the potential of remote sensing technology as a relevant and powerful tool for future hazard monitoring and assessment during catastrophes and for a better interpretation of their impact on the marine environment.

Assessment of UL56 Mutations before Letermovir Therapy in Refractory Cytomegalovirus Transplant Recipients.

De novo mutations in the UL56 terminase subunit and its associated phenotypes were studied in the context of cytomegalovirus (CMV) transplant recipients clinically resistant to DNA-polymerase inhibitors, naive to letermovir. R246C was the only UL56 variant detected by standard and deep sequencing, located within the letermovir-resistance-associated region (residues 230-370). R246C emerged in 2/80 transplant recipients (1 hematopoietic and 1 heart) since first cytomegalovirus replication and responded transiently to various alternative antiviral treatments in vivo. Recombinant phenotyping showed R246C conferred an advanced viral fitness and was sensitive to ganciclovir, cidofovir, foscarnet, maribavir, and letermovir. These results demonstrate a low rate (2.5%) of natural occurring polymorphisms within the letermovir-resistant-associated region before its administration. Identification of high replicative capacity variants in patients not responding to treatment or experiencing relapses could be helpful to guide further therapy and dosing of antiviral molecules. IMPORTANCE We provide comprehensive data on the clinical correlates of both CMV genotypic follow-up by standard and deep sequencing and the clinical outcomes, as well as recombinant phenotypic results of this novel mutation. Our study emphasizes that the clinical follow-up in combination with genotypic and phenotypic studies is essential for the assessment and optimization of patients experiencing HCMV relapses or not responding to antiviral therapy. This information may be important for other researchers and clinicians working in the field to improve the care of transplant patients since drug-resistant CMV infections are an important emerging problem even with the new antiviral development.

Highlights of marine invertebrate-derived biosynthetic products: their biomedical potential and possible production by microbial associants.

Coral reefs are among the most productive marine ecosystems and are the source of a large group of structurally unique biosynthetic products. Annual reviews of marine natural products continue to illustrate that the most prolific source of bioactive compounds consist of coral reef invertebrates-sponges, ascidians, mollusks, and bryozoans. This account examines recent milestone developments pertaining to compounds from invertebrates designated as therapeutic leads for biomedical discovery. The focus is on the secondary metabolites, their inspirational structural scaffolds and the possible role of micro-organism associants in their biosynthesis. Also important are the increasing concerns regarding the collection of reef invertebrates for the discovery process. The case examples considered here will be useful to insure that future research to unearth bioactive invertebrate-derived compounds will be carried out in a sustainable and environmentally conscious fashion. Our account begins with some observations pertaining to the natural history of these organisms. Many still believe that a serious obstacle to the ultimate development of a marine natural product isolated from coral reef invertebrates is the problem of compound supply. Recent achievements through total synthesis can now be drawn on to forcefully cast this myth aside. The tools of semisynthesis of complex natural products or insights from SAR efforts to simplify an active pharmacophore are at hand and demand discussion. Equally exciting is the prospect that invertebrate-associated micro-organisms may represent the next frontier to accelerate the development of high priority therapeutic candidates. Currently in the United States there are two FDA approved marine-derived therapeutic drugs and two others that are often cited as being marine-inspired. This record will be examined first followed by an analysis of a dozen of our favorite examples of coral reef invertebrate natural products having therapeutic potential. The record of using complex scaffolds of marine invertebrate products as the starting point for development will be reviewed by considering eight case examples. The potential promise of developing invertebrate-derived micro-organisms as the starting point for further exploration of therapeutically relevant structures is considered. Also significant is the circumstance that there are some 14 sponge-derived compounds that are available to facilitate fundamental biological investigations.

Monitoring cyanoHABs and water quality in Laguna Lake (Philippines) with Sentinel-2 satellites during the 2020 Pacific typhoon season.

Laguna Lake, the largest freshwater lake in the Philippines, is permanently subject to nutrient-driven eutrophication and pollution and experiences harmful algal blooms (cyanoHABs) periodically with serious socio-economic implications. The aim of this study is to evaluate the suitability of the Sentinel-2 imagery of the European Commission's Copernicus Earth Observation programme for lake monitoring during the 2020 Pacific typhoon season (September-November 2020). The Case-2 Regional CoastColour processor is used to atmospherically correct Level 1 data and generate water quality parameters, such as chlorophyll-a (Chl-a) and total suspended matter (TSM) at 10 m. Results show that Super Typhoon Goni and Typhoon Vamco delivered high suspended sediment loads to the reservoir at concentrations above 170 g/m3 compared to pre-storm situations (0-35 g/m3). The typhoons also affect Chl-a, with a mean concentration of 10 mg/m3 and 30 mg/m3 for pre- and post-typhoons, respectively. In addition, the normalized difference chlorophyll index (NDCI) is used in the Google Earth Engine platform for near-real time monitoring of cyanoHABs at 20 m spatial resolution. Satellite maps are key for detecting the distribution of the blooms due to the patchiness of the green algae species, which usually form scum and elongated slicks in the lake. Maximum records of bloom detection during the study period occur in the Central Bay, one of the lake sections with major aquaculture and fisheries activities. The Sentinel-2 mission improves synoptic mapping of cyanoHABs and enables trends in their extent and severity to be documented. These available methods provide an essential tool for rapid detection after extreme events and for regular water quality monitoring, which will assist and benefit the cost-effective management of Laguna Lake.

Applications of unmanned aerial vehicles in Antarctic environmental research.

Antarctica plays a fundamental role in the Earth's climate, oceanic circulation and global ecosystem. It is a priority and a scientific challenge to understand its functioning and responses under different scenarios of global warming. However, extreme environmental conditions, seasonality and isolation hampers the efforts to achieve a comprehensive understanding of the physical, biological, chemical and geological processes taking place in Antarctica. Here we present unmanned aerial vehicles (UAVs) as feasible, rapid and accurate tools for environmental and wildlife research in Antarctica. UAV surveys were carried out on Deception Island (South Shetland Islands) using visible, multispectral and thermal sensors, and a water sampling device to develop precise thematic ecological maps, detect anomalous thermal zones, identify and census wildlife, build 3D images of geometrically complex geological formations, and sample dissolved chemicals (< 0.22 µm) waters from inaccessible or protected areas.

Using Copernicus Sentinel-2 and Sentinel-3 data to monitor harmful algal blooms in Southern Chile during the COVID-19 lockdown.

During the southern summer of 2020, large phytoplankton blooms were detected using satellite technology in Chile (western Patagonia), where intensive salmonid aquaculture is carried out. Some harvesting sites recorded massive fish mortalities, which were associated with the presence of the dinoflagellate species Cochlodinium sp. The bloom included other phytoplankton species, as Lepidodinium chlorophorum, which persistently changed the colour of the ocean to green. These blooms coincided with the government-managed emergency lockdown due to the COVID-19 pandemic. Local in situ sampling was slowed down. However, imagery from the Copernicus programme allowed operational monitoring. This study shows the benefits of both Sentinel-3 and Sentinel-2 satellites in terms of their spectral, spatial and temporal capabilities for improved algal bloom monitoring. These novel tools, which can foster optimal decision-making, are available for delivering early alerts in situations of natural catastrophes and blockages, such as those occurred during the global COVID-19 lockdown.

New capabilities of Sentinel-2A/B satellites combined with in situ data for monitoring small harmful algal blooms in complex coastal waters.

The increased frequency of harmful algal blooms (HABs) is a major environmental concern worldwide, resulting not only in increased treatment costs for drinking water but also in impacts on tourism, commercial fishing and aquaculture and risks to human and animal health. Traditional strategies with ship-based approaches based on field sampling and laboratory analysis have been adopted to assess HABs. However, these methods are labour intensive and costly and do not provide synoptic views of the bloom conditions. Here, we show that the Sentinel-2 twin satellite mission of the Copernicus programme, in combination with in situ data, is a powerful tool that can offer valuable spatiotemporal information about a bloom of the dinoflagellate Lingulodinium polyedra that occurred on the SW Iberian Peninsula. Using the robust ACOLITE atmospheric correction processor combined with the normalized difference chlorophyll index (NDCI), the enhanced mapping of small blooms can be performed at a 10 m spatial resolution, revealing surface patches and a heterogeneous distribution. This research also demonstrates the improved capabilities of Sentinel-2 compared to those of Landsat-8 and Sentinel-3 for continuous monitoring. The Sentinel-3 and Sentinel-2 missions provide ecosystem observations that allow the environmental community and water managers to evaluate changes in water quality and bloom distribution and that facilitate field-based measurements. Therefore, the value added by the Copernicus products in terms of frequency and synoptic observations is of paramount importance for ecological and management purposes at regional and national scales.

Biomimetic synthesis of the shimalactones.

A biomimetic synthesis of shimalactone A and B is described. Its key features are an unprecedented acid-catalyzed cyclization of a dienyl beta-ketolactone and a Stille coupling/8pi-6pi electrocyclization cascade to create the oxabicyclo[2.2.1]heptane and bicyclo[4.2.0]octadiene, respectively. The synthesis is convergent and void of protecting groups.

Funciones ejecutivas de jóvenes que han infringido la ley: una revisión sistemática / Executive functions of juvenile offenders: a systematic review / Funções executivas dos delinquentes juvenis: uma revisão sistemática

Se propone una revisión sistemática que indaga en profundidad sobre el desempeño de jóvenes que han infringido la ley en mediciones de funciones ejecutivas. Una vez revisadas más de 1500 fuentes bibliográficas, se extrajeron 64 publicaciones que cumplieron los criterios de inclusión establecidos. Se evaluó que la enorme mayoría de las investigaciones revisadas constatan déficits específicos en funcionamiento ejecutivo entre jóvenes que han infringido la ley, elemento fundamental en la comprensión del origen del comportamiento delictual y la reincidencia, así como antecedente importante sobre la capacidad de respuesta de los atendidos, en el momento de impulsar acciones interventivas en el marco de programas de medida y sanción en justicia juvenil. Junto con lo anterior, se vincularán los resultados de la síntesis cualitativa con elementos teóricos, al igual que con un abordaje práctico sobre las herramientas de medición que podrían utilizarse en países de habla hispana. Finalmente, los resultados dan cuenta de la urgencia de implementar prácticas más informadas sobre neurodiversidad, así como la necesidad de disponer de planteles profesionales efectivamente interdisciplinarios en los sistemas de justicia juvenil.

A systematic review is proposed that investigates in depth the performance of young people who have broken the law in executive function measurements. After reviewing more than 1500 bibliographic sources, 64 publications that met the established inclusion criteria were extracted. It was evaluated that the vast majority of the research reviewed showed specific deficits in executive functioning among young people who have broken the law, a fundamental element in the understanding of the origin of delinquent behavior and recidivism, as well as an important antecedent on the response capacity of those served, at the time of promoting intervention actions in the framework of juvenile justice programs of measures and sanctions. Together with the above, the results of the qualitative synthesis will be linked to theoretical elements, as well as to a practical approach to measurement tools that could be used in Spanish-speaking countries. Finally, the results point to the urgency of implementing more informed practices on neurodiversity, as well as the need for effective interdisciplinary professional staffs in juvenile justice systems.

É proposta uma revisão sistemática que investiga em profundidade o desempenho dos jovens infratores em medidas de funções executivas. Após a revisão de mais de 1500 fontes de literatura, foram extraídas 64 publicações que preenchiam os critérios de inclusão estabelecidos. Foi avaliado que a grande maioria das pesquisas analisadas encontrou déficits específicos no funcionamento executivo entre os jovens que infringiram a lei, um elemento fundamental para entender a origem do comportamento delinqüente e da reincidência, assim como um antecedente importante sobre a capacidade de resposta dos que estão sob cuidados, no momento de promover ações de intervenção no âmbito de programas de medidas e sanções na justiça juvenil. Juntamente com o acima exposto, os resultados da síntese qualitativa estarão ligados a elementos teóricos, bem como a uma abordagem prática das ferramentas de medição que poderiam ser utilizadas nos países de língua espanhola. Finalmente, os resultados apontam para a urgência de implementar mais práticas informadas sobre a neurodiversidade, bem como a necessidade de uma equipe profissional interdisciplinar eficaz nos sistemas de justiça juvenil.

Kalkipyrone B, a marine cyanobacterial γ-pyrone possessing cytotoxic and anti-fungal activities.

Bioassay-guided fractionation of two marine cyanobacterial extracts using the H-460 human lung cancer cell line and the OVC-5 human ovarian cancer cell line led to the isolation of three related α-methoxy-ß, ß'-dimethyl-γ-pyrones each containing a modified alkyl chain, one of which was identified as the previously reported kalkipyrone and designated kalkipyrone A. The second compound was an analog designated kalkipyrone B. The third was identified as the recently reported yoshinone A, also isolated from a marine cyanobacterium. Kalkipyrone A and B were obtained from a field-collection of the cyanobacterium Leptolyngbya sp. from Fagasa Bay, American Samoa, while yoshinone A was isolated from a field-collection of cyanobacteria (cf. Schizothrix sp.) from Panama. One-dimensional and two-dimensional NMR experiments were used to determine the overall structures and relative configurations of the kalkipyrones, and the absolute configuration of kalkipyrone B was determined by (1)H NMR analysis of diastereomeric Mosher's esters. Kalkipyrone A showed good cytotoxicity to H-460 human lung cancer cells (EC50=0.9µM), while kalkipyrone B and yoshinone A were less active (EC50=9.0µM and >10µM, respectively). Both kalkipyrone A and B showed moderate toxicity to Saccharomyces cerevisiae ABC16-Monster strain (IC50=14.6 and 13.4µM, respectively), whereas yoshinone A was of low toxicity to this yeast strain (IC50=63.8µM).