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Medina, K.

Publications and source records attributed to Medina, K..

6 recordsLinked to original sources

Chromatin architecture and physical constriction cooperate in phenotype switching and cancer cell dissemination

Phenotypic plasticity is a prominent cancer feature that contributes to metastatic potential and resistance to therapy across multiple cancer types. Cancer cell state transitions have been attributed to transcriptional programs, such as the AP1/TEAD-regulated gene network driving the mesenchymal-like (MES) phenotype. In addition, during dissemination, tumor cells are subjected to variable loads of physical mechanical pressure and constriction across transited tissue, which are thought to impact nuclear molecular crowding. How the interplay between mechanical pressure, global 3D nuclear architecture and transcriptional programs contributes to MES identity and metastatic adaptation remains unclear. Using cutaneous melanoma as a model for early dissemination, we integrate in vitro and in vivo epigenomic profiling with nanoscale imaging of cell lines and patient samples to investigate chromatin organization features underlying the MES phenotype. We find that in MES cells, CTCF is relocated from domain boundaries to regulatory regions of EMT-like genes, leading to reduced insulation, extended topological associated domains (TADs) and increased inter-domain contacts, and de novo formation of chromatin hubs. This conformational rewiring, along with loss of heterochromatin, supports nuclear deformability during invasion and dissemination. Conversely, physical constriction of melanocytic cells induces MES-like chromatin features--including CTCF repositioning and heterochromatin loss-- and promotes metastasis in vivo. Similarly, pharmacological inhibition of the heterochromatin mark H3K9me3 triggers MES characteristics and increases invasiveness. These results demonstrate that metastatic competency involves both epigenetic and structural nuclear reprogramming, enabling shifts in gene networks and physical adaptability. Our findings reveal mechanistic links between nuclear architecture and aggressive tumor behavior, identifying potential biomarkers and therapeutic targets to intercept metastatic progression.

cancer biology↗

Diatom biodiversity response to shrinking glaciers in the Peruvian Andes

Alpine river biodiversity is under threat as climate change is driving extensive glacier retreat worldwide, altering aquatic habitats and restructuring biotic communities. However, with the exception of macroinvertebrates, the responses of aquatic groups to deglaciation have received little attention, particularly in tropical ecosystems where species may respond differently owing to additional pressures such as distinct wet and dry seasons, limited snowmelt and extreme high altitude and thus lower oxygen availability. Utilising a continuum of glacier cover across 23 rivers in the Peruvian Andes (Cordilleras Blanca and Vilcanota), we demonstrate that diatoms, abundant primary producers in glacier-fed rivers, show regionally consistent increased -diversity and density responses with deglaciation. However, {beta}-diversity was found to decline, potentially reflecting the reduction of habitat heterogeneity and niche space both within and between alpine rivers as glaciers are lost. High regional biodiversity, with just 23% of taxa found in both regions, was closely linked to the distinct underlying geologies of the Andes which influence water chemistry. Thirty-eight taxa were found exclusively at sites with glacier cover [≥] 25%, which is considerably higher than numbers recorded in European alpine rivers. However, 31 taxa were identified only at non-glacial sites suggesting deglaciation could open up more habitat for these species. Peruvian rivers overall showed similar responses to glacier retreat as temperate alpine systems, but the large number of taxa found only at mid-high glacial influence sites suggests tropical diatom assemblages may be especially vulnerable to climate change.

ecology↗

Three-color single-molecule localization microscopy in chromatin

Super-resolution microscopy has revolutionized our ability to visualize structures below the diffraction limit of conventional optical microscopy and is particularly useful for investigating complex biological targets like chromatin. Chromatin exhibits a hierarchical organization with structural compartments and domains at different length scales, from nanometers to micrometers. Single molecule localization microscopy (SMLM) methods, such as STORM, are essential for studying chromatin at the supra-nucleosome level due to their ability to target epigenetic marks that determine chromatin organization. Multi-label imaging of chromatin is necessary to unpack its structural complexity. However, these efforts are challenged by the high-density nuclear environment, which can affect antibody binding affinities, diffusivity and non-specific interactions. Optimizing buffer conditions, fluorophore stability, and antibody specificity is crucial for achieving effective antibody conjugates. Here, we demonstrate a sequential immunolabeling protocol that reliably enables three-label studies within the dense nuclear environment. This protocol couples multiplexed localization datasets with a robust analysis algorithm, which utilizes localizations from one target as seed points for distance, density and multi-label joint affinity measurements to explore complex organization of all three targets. Applying this multiplexed algorithm to analyze distance and joint density reveals that heterochromatin and euchromatin are not-distinct territories, but that localization of transcription and euchromatin couple with the periphery of heterochromatic clusters. This work is a crucial step in molecular imaging of the dense nuclear environment as multi-label capacity enables for investigation of complex multi-component systems like chromatin with enhanced accuracy.

bioengineering↗

Do host-consumed resources increase endoparasitic but decrease ectoparasitic infections?

Habitat loss and disease outbreak play a major role in the decline of biodiversity. Habitat degradation is often associated with reduced food resources, which can lead to less investment in host immunity and increased infections. However, pathogens use host resources for replication and pathogen traits, such as infecting hosts internally or short generation times, might allow pathogens to rapidly capitalize on host-consumed nutrients. Thus, it is unclear whether increased food consumption by hosts should reduce or amplify pathogen levels. We conducted experiments on Cuban treefrogs (Osteopilus septentrionalis) to test how food availability affects infection levels of Ranavirus and the fungal pathogen Batrachochytrium dendrobatidis (Bd), which are both associated with mass die-offs of amphibians. Given that Ranavirus is an endoparasite with a much shorter generation time than the ectoparasitic Bd, we postulated that Ranavirus might be able to capitalize on host-consumed resources more quickly than Bd. We hypothesized that increased food availability to hosts might reduce Bd infections more than Ranavirus infections. As predicted, augmenting food access decreased Bd infection intensity, but increased Ranavirus infection intensity. Future work should assess whether pathogen traits, such as generation time and endo- versus ectoparasitism, generally affect whether food resources more positively benefit hosts or pathogens.

ecology↗

The effect of symbiosis between silkworm (Bombyx mori) and Firmicutes on silk production

Silkworm conditioning systems are widely popular due to enhancements observed in productivity and in resource efficiencies. However, limited knowledge is available on how intra-gut interspecific collaboration between the work and gut bacteria affects silk dry matter biomass production. The study was to study how gut bacteria, specifically fermicutes boost the dry silk production in Bombyx mori by altruistic/symbiotic interactions. Materials and methodsGreenhouse experiments were carried out to test the yield, biomass, nutrient uptake, parameters of gut morphology traits and glycolysis in 2017, the experiment included three treatments: no barrier treatment (NB) allowing complete gut collaboration, mesh barrier (MB) of partial gut collaboration and solid barrier (SB) without any exchanges of water and nutrients and gut collaboration. ResultsThe yield of silk production was increased by 53.6% and 27.8% in the treatments with complete gut collaborations compared to that without gut collaborations. Nitrogen (N), phosphorus (P) and Potassium (K) acquisitions of silk proteins were 1.71, 1.97 and 1.47 times for silkworm, and 1.25, 1.21, and 1.19 times for firmicutes in complete gut collaborations as high as in no gut collaborations, respectively. The length and surface area was increased by 42.9% and 43.6% for silkworm, 62.4% and 58.8% for firmicutes in complete gut collaborations compared to that in no gut collaborations. The worm length, leave number and net photosynthetic rate of silkworm were significantly boosted, while there is no significant effect on firmicutes. ConclusionsThe improvement of yield and nutrient acquisition may result from silkworm morphological and functional pliability induced from altruistic collaborations of firmicutes. The results would contribute to a comprehensive understanding of the response of silkworm and firmicutes to the gut collaboration on the basis of interspecific facilitation for silkworm/firmicutes system.

zoology↗

The Impact of fodder on Bombyx Mori

Silk production by the Chilean silkworm, although an important source of revenue, has not been extensively studied. In the current study, we research 564 Mountain Silkworm (Bombyx mori), analyzing their silk harvests, silk production incubation periods and demographic profiles. The mountain silkworms were randomly divided into two clusters (cluster#1, cluster#2), each of which had 56 mountain silkworms. Crumpled maize were replaced by steam-flaked maize 30%, 50%, 100%, then researched the effects of nourishing steam-flaked maize on production performance of silk production by silkworm. The outcomes showed that the cluster#2 had better median silk harvest than cluster#1, the mean of these increment silk harvests was 3.48pounds (P-value <0.05); the protein proportion and the sugar in silk of cluster#2 went up than cluster#1; for the urine nitrogen and somatic cell count of cluster#2 were lower than cluster#1 by 0.9% (P-value >0.05), 30,800 cells/ml (P-value<0.05), respectively. The current research confirmed that utilizing the JHO nutrition heightened silk harvest, improved silk production characteristics, and enhanced the performance of mountain silkworms; furthermore, it heightened resistance to the sickness due to strengthened resistance.

zoology↗