All together, the results confirmed the predisposition of the pyritic coal waste to bioleaching and the potential of endogenous microorganisms for efficient bioleaching at 48 °C. The good leaching yields open the perspective to optimize further and scale-up the bioleaching process.Skin integrity and function depends to a large extent on the composition of the extracellular matrix, which regulates tissue organization. Collagen XII is a homotrimer with short collagenous domains that confer binding to the surface of collagen I-containing fibrils and extended flexible arms, which bind to non-collagenous matrix components. Thereby, collagen XII helps to maintain collagen suprastructure and to absorb stress. Mutant or absent collagen XII leads to reduced muscle and bone strength and lax skin, whereas increased collagen XII amounts are observed in tumor stroma, scarring and fibrosis. This study aimed at uncovering in vivo mechanisms by which collagen XII may achieve these contrasting outcomes. We analyzed skin as a model tissue that contains abundant fibrils, composed of collagen I, III and V with collagen XII decorating their surface, and which is subject to mechanical stress. The impact of different collagen XII levels was investigated in collagen XII-deficient (Col12-KO) mice and in mice wnction. Together, these functions are pivotal for re-establishing homeostasis after injury.Acquired BRAF/MAPK/extracellular signal‒regulated kinase inhibitor resistance in melanoma results in a new transcriptional state associated with an increased risk of metastasis. In this study, we identified noncanonical ephrin receptor (Eph) EphA2 signaling as a driver of the resistance-associated metastatic state. We used mass spectrometry‒based proteomic and phenotypic assays to demonstrate that the expression of active noncanonical EphA2-S897E in melanoma cells led to a mesenchymal-to-amoeboid transition driven by Cdc42 activation. The induction of mesenchymal-to-amoeboid transition promoted melanoma cell invasion, survival under shear stress, adhesion to endothelial cells under continuous-flow conditions, increased permeability of endothelial cell monolayers, and stimulated melanoma transendothelial cell migration. In vivo, melanoma cells expressing EphA2-S897E or active Cdc42 showed superior lung retention after tail-vain injection. Analysis of BRAF inhibitor‒sensitive and ‒resistant melanoma cells demonstrated resistance to be associated with a mesenchymal-to-amoeboid transition switch, upregulation of Cdc42 activity, increased invasion, and transendothelial migration. The drug-resistant metastatic state was dependent on histone deacetylase 8 activity. Silencing of histone deacetylase 8 led to the inhibition of EphA2 and protein kinase B phosphorylation, reduced invasion, and impaired melanoma cell-endothelial cell interactions. In summary, we have demonstrated that the metastatic state associated with acquired BRAF inhibitor resistance is dependent on noncanonical EphA2 signaling, leading to increased melanoma-endothelial cell interactions and enhanced tumor dissemination.The coronavirus disease 2019 (COVID-19) pandemic is a grave public health crisis, causing massive disruption to daily life. Dermatology clinical trials in psoriasis, atopic dermatitis, and hidradenitis have been suspended, terminated, or otherwise disrupted. Clinical investigators need to embrace a COVID-19 new normal and adjust research procedures to mitigate the risk of transmitting severe acute respiratory syndrome coronavirus 2 and depleting personal protective equipment while maintaining scientific rigor.Slac2-b, also known as exophilin-5, is a Rab27b effector protein with a role in exosome transport and is encoded by the EXPH5 gene. We previously described biallelic loss-of-function mutations in EXPH5 in an autosomal recessive form of epidermolysis bullosa simplex. However, how the loss of Slac2-b expression leads to skin fragility and erosions is unknown. In this study, we demonstrate that keratinocytes (KCs) isolated from two different individuals with mutations in EXPH5 have significant defects in cell‒matrix adhesion. EXPH5-mutant KCs also showed increased perinuclear accumulation and significantly reduced trafficking of CD63+ vesicles. These phenotypes were also seen in Slac2-b‒deficient KCs. This was coincident with a reduction in Rab27a protein expression in Slac2-b‒mutant KCs as well as reduced secretion of extracellular vesicles containing extracellular matrix proteins. Live imaging analysis revealed a strong correlation between CD63+ vesicle trafficking to the plasma membrane and focal adhesion dynamics. These findings support a role for Slac2-b in regulating local focal adhesion dynamics to support effective KC adhesion and provide insight into the underlying pathophysiology of inherited skin blistering.Vitellogenin (vg) expression is consistently associated with variation in insect phenotypes, particularly egg-laying. Primitively eusocial species, such as eusocial sweat bees, have behaviourally totipotent castes, in which each female is capable of high levels of ovarian development. Few studies have investigated vg expression patterns in primitively eusocial insects, and only one study has focused on a primitively eusocial bee. Here we use a primitively eusocial sweat bee, Lasioglossum laevissimum, and Real Time quantitative PCR (RT-qPCR) to investigate the relationship between vg expression, castes, and variation in phenotypes associated with castes differences. selleck inhibitor These assays showed that females with high ovarian development had the highest levels of vg expression, and that vg expression levels reflected the reproductive status of females first and caste second. This is in contrast to vg expression patterns observed in advanced eusocial queens and workers, which differ in vg expression based on caste and have caste-specific vg expression patterns. Furthermore, future queens (gynes) do not have ovarian development and had similar vg expression levels to early spring foundresses, which do have ovarian development, supporting Vg’s function as a transporter of lipids and amino acids before diapause.