Publications by authors named "Bolanos L"

We report the discovery of an imidazopyridine series of IRAK1/4/pan-FLT3 kinase inhibitors. Optimization of this series has produced compound which displays potent and selective inhibition of IRAK1, IRAK4, FLT3, and all mutant forms of FLT3, as well as good in vitro ADME and pharmacokinetic properties. In a mouse xenograft model of AML, produces survival prolongation equal to that of Gilteritinib, the leading marketed FLT3 inhibitor currently used to treat AML.

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Marine viruses are key players of ocean biogeochemistry, profoundly influencing microbial community ecology and evolution. Despite their importance, few studies have explored continuous inter-seasonal viral metagenomic time series in marine environments. Viral dynamics are complex, influenced by multiple factors such as host population dynamics and environmental conditions.

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Article Synopsis
  • A novel model simulating microbial processes in a 1 mL three-dimensional cube addresses gaps in existing ecosystem models by resolving individual microbes and their interactions at a 50 µm resolution.
  • Key findings reveal that copiotrophic bacteria largely depend on eukaryotic phytoplankton for carbon, while oligotrophic bacteria rely on cyanobacterial exudates, highlighting distinct growth and substrate patterns in aquatic environments.
  • The study also shows that attached bacteria lower carbon flux efficiency compared to free-living ones, indicating the importance of attachment and chemotaxis in optimizing bacteria's carbon acquisition in marine ecosystems.
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Viral outbreaks are a constant threat to aquaculture, limiting production for better global food security. A lack of diagnostic testing and monitoring in resource-limited areas hinders the capacity to respond rapidly to disease outbreaks and to prevent viral pathogens becoming endemic in fisheries productive waters. Recent developments in diagnostic testing for emerging viruses, however, offers a solution for rapid monitoring of viral outbreaks.

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Ocean spring phytoplankton blooms are dynamic periods important to global primary production. We document vertical patterns of a diverse suite of eukaryotic algae, the prasinophytes, in the North Atlantic Subtropical Gyre with monthly sampling over four years at the Bermuda Atlantic Time-series Study site. Water column structure was used to delineate seasonal stability periods more ecologically relevant than seasons defined by calendar dates.

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Dominant microorganisms of the Sargasso Sea are key drivers of the global carbon cycle. However, associated viruses that shape microbial community structure and function are not well characterised. Here, we combined short and long read sequencing to survey Sargasso Sea phage communities in virus- and cellular fractions at viral maximum (80 m) and mesopelagic (200 m) depths.

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TNF receptor associated factor 6 (TRAF6) is an E3 ubiquitin ligase that has been implicated in myeloid malignancies. Although altered TRAF6 expression is observed in human acute myeloid leukemia (AML), its role in the AML pathogenesis remains elusive. In this study, we showed that the loss of TRAF6 in AML cells significantly impairs leukemic function in vitro and in vivo, indicating its functional importance in AML subsets.

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The skin of fish contains a diverse microbiota that has symbiotic functions with the host, facilitating pathogen exclusion, immune system priming, and nutrient degradation. The composition of fish skin microbiomes varies across species and in response to a variety of stressors, however, there has been no systematic analysis across these studies to evaluate how these factors shape fish skin microbiomes. Here, we examined 1922 fish skin microbiomes from 36 studies that included 98 species and nine rearing conditions to investigate associations between fish skin microbiome, fish species, and water physiochemical factors.

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Traumatic brain injury (TBI) is the leading cause of death in young people and can cause cognitive and motor dysfunction and disruptions in functional connectivity between brain regions. In human TBI patients and rodent models of TBI, functional connectivity is decreased after injury. Recovery of connectivity after TBI is associated with improved cognition and memory, suggesting an important link between connectivity and functional outcome.

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Oxygen minimum zones (OMZs) are expanding due to increased sea surface temperatures, subsequent increased oxygen demand through respiration, reduced oxygen solubility, and thermal stratification driven in part by anthropogenic climate change. Devil's Hole, Bermuda is a model ecosystem to study OMZ microbial biogeochemistry because the formation and subsequent overturn of the suboxic zone occur annually. During thermally driven stratification, suboxic conditions develop, with organic matter and nutrients accumulating at depth.

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We present a cost-effective, compact foot-print, and open-source Raspberry Pi-based widefield imaging system. The compact nature allows the system to be used for close-proximity dual-brain cortical mesoscale functional-imaging to simultaneously observe activity in two head-fixed animals in a staged social touch-like interaction. We provide all schematics, code, and protocols for a rail system where head-fixed mice are brought together to a distance where the macrovibrissae of each mouse make contact.

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SAR11 bacteria dominate the surface ocean and are major players in converting fixed carbon back to atmospheric carbon dioxide. The SAR11 clade is comprised of niche-specialized ecotypes that display distinctive spatiotemporal transitions. We analyzed SAR11 ecotype seasonality in two long-term 16S rRNA amplicon time series representing different North Atlantic regimes: the Sargasso Sea (subtropical ocean-gyre; BATS) and the temperate coastal Western English Channel (WEC).

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Inhibitors of anti-apoptotic BCL-2 family proteins in combination with chemotherapy and hypomethylating agents (HMA) are promising therapeutic approaches in acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). Alvocidib, a cyclin-dependent kinase 9 (CDK9) inhibitor and indirect transcriptional repressor of the anti-apoptotic factor MCL-1, has previously shown clinical activity in AML. Availability of biomarkers for response to the alvocidib + 5-azacytidine (5-AZA) could also extend the rationale of this treatment concept to high-risk MDS.

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Drought is among the main abiotic factors causing agronomical losses worldwide. To minimize its impact, several strategies have been proposed, including the use of plant growth-promoting bacteria (PGPBs), as they have demonstrated roles in counteracting abiotic stress. This aspect has been little explored in emergent crops such as quinoa, which has the potential to contribute to reducing food insecurity.

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The SAR11 clade are the most abundant members of surface marine bacterioplankton and a critical component of global biogeochemical cycles. Similarly, pelagiphages that infect SAR11 are ubiquitous and highly abundant in the oceans. Pelagiphages are predicted to shape SAR11 community structures and increase carbon turnover throughout the oceans.

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Dysregulation of innate immune signaling is a hallmark of hematologic malignancies. Recent therapeutic efforts to subvert aberrant innate immune signaling in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have focused on the kinase IRAK4. IRAK4 inhibitors have achieved promising, though moderate, responses in preclinical studies and clinical trials for MDS and AML.

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Tilapia farming is one of the most important sectors in aquaculture worldwide and of major importance to global food security. Infectious spleen and kidney necrosis virus (ISKNV) has been identified as an agent of high morbidity and mortality, threatening tilapia aquaculture. ISKNV was detected in Lake Volta, Ghana, in September 2018 and spread rapidly, with mortality rates between 60 and 90% and losses of more than 10 tonnes of fish per day.

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Quinoa is an Andean crop whose cultivation has been extended to many different parts of the world in the last decade. It shows a great capacity for adaptation to diverse climate conditions, including environmental stressors, and, moreover, the seeds are very nutritious in part due to their high protein content, which is rich in essential amino acids. They are gluten-free seeds and contain good amounts of other nutrients such as unsaturated fatty acids, vitamins, or minerals.

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On the eve of the 100th anniversary of Dr. Warington's discovery of boron (B) as a nutrient essential for higher plants, "" have struggled to demonstrate a role beyond its structural function in cell walls dimerizing pectin molecules of rhamnogalacturonan II (RGII). In this regard, B deficiency has been associated with a plethora of symptoms in plants that include macroscopic symptoms like growth arrest and cell death and biochemical or molecular symptoms that include changes in cell wall pore size, apoplast acidification, or a steep ROS production that leads to an oxidative burst.

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Atopic dermatitis (AD) is a common skin condition and is undertreated in children under 2 years, whom there are no specific guidelines for. We sought to understand barriers to AD treatment and primary care pediatricians' (PCPs) suggested solutions. We conducted semi-structured focus groups (n = 5) with PCPs (n = 17) on how the undertreatment of AD can be addressed.

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Background: Collective and discrete neural crest cell (NCC) migratory streams are crucial to vertebrate head patterning. However, the factors that confine NCC trajectories and promote collective cell migration remain unclear.

Results: Computational simulations predicted that confinement is required only along the initial one-third of the cranial NCC migratory pathway.

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Within the context of climate change and its impact on global food security, seed storage has become key, as it ensures long-term food and next-season seed preservation. Aiming at evaluating quality-related changes in quinoa seeds over storage time, different storage temperatures (-20, 4, 12, 25, and 37°C) and humidity conditions (use of silica gel or not) were studied and different seed nutritional parameters were evaluated at different points during a year of storage. Also, to determine if these variations could be conditioned by the genotype used, two quinoa cultivars were compared.

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Scorpions were among the first animals on land around 430 million years ago. Like many arachnids, scorpions have evolved complex venoms used to paralyze their prey and for self-defense. Here we sequenced and analyzed the metagenomic DNA from venom glands from Vaejovis smithi scorpions.

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Deep convective mixing of dissolved and suspended organic matter from the surface to depth can represent an important export pathway of the biological carbon pump. The seasonally oligotrophic Sargasso Sea experiences annual winter convective mixing to as deep as 300 m, providing a unique model system to examine dissolved organic matter (DOM) export and its subsequent compositional transformation by microbial oxidation. We analyzed biogeochemical and microbial parameters collected from the northwestern Sargasso Sea, including bulk dissolved organic carbon (DOC), total dissolved amino acids (TDAA), dissolved metabolites, bacterial abundance and production, and bacterial community structure, to assess the fate and compositional transformation of DOM by microbes on a seasonal time-scale in 2016-2017.

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