Historical genetic links among similar populations can be difficult to establish. Identity by descent (IBD) analyses find genomic blocks that represent direct genealogical relationships among individuals. However, this method has rarely been applied to ancient genomes because IBD stretches are progressively fragmented by recombination and thus not recognizable after few tens of generations. To explore such genealogical relationships, we estimated long IBD blocks among modern Europeans, generating networks to uncover the genetic structures. We found that Basques, Sardinians, Icelanders and Orcadians form, each of them, highly intraconnected sub-clusters in a European network, indicating dense genealogical links within small, isolated populations. We also exposed individual genealogical links -such as the connection between one Basque and one Icelandic individual- that cannot be uncovered with other, widely used population genetics methods such as PCA or ADMIXTURE. Moreover, using ancient DNA technology we sequenced a Late Medieval individual (Barcelona, Spain) to high genomic coverage and identified IBD blocks shared between her and modern Europeans. The Medieval IBD blocks are statistically overrepresented only in modern Spaniards, which is the geographically closest population. This approach can be used to produce a fine-scale reflection of shared ancestry across different populations of the world, offering a direct genetic link from the past to the present.The adult human central nervous system (CNS) has very limited regenerative capability, and injury at the cellular and molecular level cannot be studied in vivo. Modelling neural damage in human systems is crucial to identifying species-specific responses to injury and potentially neurotoxic compounds leading to development of more effective neuroprotective agents. Hence we developed human neural stem cell (hNSC) 3-dimensional (3D) cultures and tested their potential for modelling neural insults, including hypoxic-ischaemic and Ca2+-dependent injury. Standard 3D conditions for rodent cells support neuroblastoma lines used as human CNS models, but not hNSCs, but in all cases changes in culture architecture alter gene expression. Importantly, response to damage differs in 2D and 3D cultures and this is not due to reduced drug accessibility. Together, this study highlights the impact of culture cytoarchitecture on hNSC phenotype and damage response, indicating that 3D models may be better predictors of in vivo response to damage and compound toxicity.Elderly patients with type 2 diabetes (T2DM) are more prone to developing diabetic kidney disease (DKD). Patients with DKD can develop albuminuria, and some studies have suggested an association between metabolic syndrome and albuminuria. The prevalence of both metabolic syndrome and albuminuria increases with age. We evaluated the association of these risk factors with worsening renal function and albuminuria progression in 460 T2DM patients with a mean age of 72 years. During the 5-year follow-up period, progression of albuminuria and worsening of renal function were observed in 97 (21.2%) and 23 (5.1%) patients, respectively. After adjusting for confounding factors, the group with metabolic syndrome had a higher multivariable-adjusted hazard ratio (HR) for worsening renal function (P = 0.038) and albuminuria progression (P = 0.039) than the group without metabolic syndrome. When patients were divided into four groups according to the presence of metabolic syndrome and/or albuminuria, the HR gradually increased. The group with both albuminuria and metabolic syndrome exhibited the highest cumulative incidence of worsening renal function (P = 0.003). When we redefined metabolic syndrome to exclude the blood pressure (BP) component, similar results were obtained. We concluded that the presence of metabolic syndrome independently predicts the progression of renal disease in elderly patients with T2DM. The use of both metabolic syndrome and albuminuria provides a better risk stratification model for DKD progression than albuminuria alone.Metastatic progression is the leading cause of mortality in breast cancer. Invasive tumor cells develop invadopodia to travel through basement membranes and the interstitial matrix. Substantial efforts have been made to characterize invadopodia molecular composition. However, their full molecular identity is still missing due to the difficulty in isolating them. To fill this gap, we developed a non-hypothesis driven proteomic approach based on the BioID proximity biotinylation technology, using the invadopodia-specific protein Tks5α fused to the promiscuous biotin ligase BirA* as bait. In invasive breast cancer cells, Tks5α fusion concentrated to invadopodia and selectively biotinylated invadopodia components, in contrast to a fusion which lacked the membrane-targeting PX domain (Tks5β). Biotinylated proteins were isolated by affinity capture and identified by mass spectrometry. We identified known invadopodia components, revealing the pertinence of our strategy. Furthermore, we observed that Tks5 newly identified close neighbors belonged to a biologically relevant network centered on actin cytoskeleton organization. Analysis of Tks5β interactome demonstrated that some partners bound Tks5 before its recruitment to invadopodia. Thus, the present strategy allowed us to identify novel Tks5 partners that were not identified by traditional approaches and could help get a more comprehensive picture of invadopodia molecular landscape.We evaluated the potential effects of ATO in different pediatric SHH-MB cell lines (ONS-76 TP53-wild type; DAOY and UW402 TP53-mutated). MB cell lines molecular subgroup was confirmed and TP53 mutations were validated. Cell viability, clonogenicity and apoptosis were evaluated after ATO treatment at different concentrations (1-16 µM) alone or combined with irradiation doses (0.5, 1, 2 and 4 Gy). Rad51 and Ku86 proteins were evaluated by WB. ATO treatment reduced cell viability for all SHH-MB cell lines. Significant decrease of clonogenic capacity and higher apoptosis rates were also observed after ATO exposure, being cell death more pronounced (>70%) for the SHH-MB TP53-mutated. Combined treatment of ATO with irradiation also reduced colonies formation in UW402 tumor cells, which was independent of DNA damage repair proteins Rad51 and Ku86. In silico analyses suggested that a set of genes from cell cycle and p53 pathways are differentially expressed in SHH tumor subtypes, suggesting that cell lines may respond to therapies according to the gene expression profiles. Herein, we showed ATO cytotoxicity in pediatric SHH cell lines, with marked radiosensitizing effect for the MB-SHH TP53-mutated cells. These results highlight the potential of ATO, alone or in combination with radiotherapy, supporting further clinical investigations.Lineage-specific genetic programs rely on cell-restricted super-enhancers, which are platforms for high-density transcription factor occupation. It is not known whether super-enhancers synergize specifically with their native promoters or provide autonomous and independent regulatory platforms. Here, we investigated the ability of the mammary Wap super-enhancer to activate the promoter of the juxtaposed and ubiquitously expressed Tbrg4 gene in the mouse mammary gland. The Wap super-enhancer was fused, alone or in combination with the Wap promoter, to the Tbrg4 gene. While the super-enhancer increased the expression of the Tbrg4 promoter five-fold, the combination of the super-enhancer and promoter resulted in 80-fold gene upregulation, demonstrating lineage-specific promoter-enhancer synergy. Employing ChIP-seq profiling to determine transcription factor binding and identify activating histone marks, we uncovered a chromatin platform that enables the high-level expression of the native promoter-enhancer but not the heterologous promoter. Taken together, our data reveal that lineage-specific enhancer-promoter synergy is critical for mammary gene regulation during pregnancy and lactation.An amendment to this paper has been published and can be accessed via a link at the top of the paper.BACKGROUND Whether sex differences exist in the inflammatory response after ST-elevation myocardial infarction (STEMI) remains to be elucidated. We studied leukocyte profiles and their prognostic value in men and women presenting with STEMI. METHODS From a total of 552 consecutive STEMI patients, blood samples were collected at hospital admission. Linear regression was used to assess the relationship between leukocyte profiles and enzymatic infarct size. Cox regression was used to assess the association between leukocyte profiles and one-year mortality. RESULTS Women presented with higher lymphocyte counts (2.3·109 cells/L (IQR 1.6-3.1) vs. 1.8·109 cells/L (IQR 1.4-2.5), p = 3.00 ∙ 10-4) and percentages (21.1% (IQR 14.4-28.1) vs. 17.1% (IQR 12.3-24.3), p = 0.004). Lymphocyte to monocyte ratio (LMR) was also higher in women (3.25 (IQR 2.56-4.5) vs. 2.68 (IQR 2.08-3.59), p = 7.28 ∙ 10-7). Higher LMR was associated with lower peak CK-MB (β = -0.27 (95% CI -0.50, -0.03), p = 0.026), lower peak troponin T (β = -0.45 (95% CI -0.77, -0.13), p = 0.006) and lower one-year mortality risk (HR 0.35 (95% CI 0.13, 0.96), p = 0.042). CONCLUSION At admission for STEMI, women present with higher lymphocyte count and LMR. Higher LMR is associated with smaller infarct size and decreased one-year mortality risk and could be used as a biomarker to predict outcome.There are currently many problems related to excessive fertilizer application, low fertilizer-use efficiency and lack of an agricultural labor force for cotton production in China. Therefore, the objective of this paper was to explain the optimal application time for once fertilization based on cotton nutrient accumulation of nitrogen, phosphorus and potassium to provide technical support for simplified fertilization management in cotton production. A 2 yr field experiment and a 1 yr pot experiment were conducted with fertilizer (225, 67.5, and 225 kg ha-1 of N, P2O5, and K2O, respectively) applied once at 0 (FT1), 5 (FT2), 10 (FT3), 15 (FT4), or 20 (FT5) d after the appearance of the first flower and a triple application (preplant 30%, first bloom 40%, and peak bloom 30%) as the conventional control (FT6). The results showed that FT1 exhibited the greatest nutrient accumulation speed for both the average (5.81, 1.22, and 5.74 kg ha-1 of N, P2O5, and K2O, respectively) and the maximum (6.31, 1.44, and 6.24 kg ha-1 of N, P2O5, and K2O, respectively) during the fast accumulation period. Moreover, among the different treatments, FT1 exhibited the greatest nutrient recovery and partial productivity. The results suggest that applying the minimum amount of fertilizer at the appearance of the first flower is optimal for maximizing nutrient utilization while minimizing environmental disturbance.The insect repellent IR3535 is one of the important alternative in the fight against mosquito-borne disease such as malaria, dengue, chikungunya, yellow fever and Zika. Using a multidisciplinary approach, we propose the development of an innovative insecticide-based vector control strategy using an unexplored property of IR3535. We have demonstrated that in insect neurosecretory cells, very low concentration of IR3535 induces intracellular calcium rise through cellular mechanisms involving orthosteric/allosteric sites of the M1-muscarinic receptor subtype, G protein βγ subunits, background potassium channel inhibition generating depolarization, which induces voltage-gated calcium channel activation. The resulting internal calcium concentration elevation increases nicotinic receptor sensitivity to the neonicotinoid insecticide thiacloprid. The synergistic interaction between IR3535 and thiacloprid contributes to significantly increase the efficacy of the treatment while reducing concentrations. In this context, IR3535, used as a synergistic agent, seems to promise a new approach in the optimization of the integrated vector management for vector control.