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Jingshu Xu et al. did a comprehensive post-mortem proteomics analysis across six brain regions obtained from Alzheimer’s disease patients and controls. With this spatial proteomics approach, they identified new disease-related pathways and a gradient of protein expression changes that correlates with the pathology of the affected regions.
Kim and Audet present a model-free, iterative search algorithm that optimizes serum-free formulations used to expand human hematopoietic cells. This method automatically identifies serum-free formulations that support cell expansions as effectively as the serum-containing conditions, demonstrating its utility.
Fatemeh Dorri et al. present MuClone, a method for simultaneous detection and classification of mutations across multiple tumor samples derived from one patient. They show that clonal information improves sensitivity in detecting somatic mutations.
Jaindra Tirpathi et al. report a strategy for inactivating endogenous banana streak virus sequences in the plantain B genome using CRISPR/Cas9. They show that three-quarters of edited plants had no viral symptoms under stress conditions, providing an improved B genome germplasm for plantain and banana breeding.
Takehara et al. show that Clostridium perfringens alpha-toxin impairs granulocyte colony-stimulating factor receptor-mediated granulocyte production while enhancing host inflammation. This study identifies dual mechanisms, whereby bacterial toxin simultaneously cripples and overstimulates host immunity to its demise.
Aleksandr Zenin et al. present a genome-wide association study and genetic risk model for human healthspan, the length of morbidity-free life. They identify 12 loci associated with healthspan and osbserve genetic correlations between healthspan and life-history and lifestyle traits, such as obesity and smoking.
Hadas Nevenzal, Meirav Noach-Hirsh et al. present a method for direct detection and analysis of tyrosine autophosphorylation using integrated microfluidics and arrays. They show that their method can be applied to soluble and transmembrane tyrosine kinases as well as to membranes in vitro.
Lars Maerz et al. show that pharmacological inhibition of cholesterol synthesis in zebrafish embryos leads to organ malformations and dysfunctions in cilium formation and signaling. These findings together with alterations to the cilia transition zone suggest an important role of cholesterol in cilia biogenesis and function.
Hideyuki Doi and Helmut Hillebrand investigate how the sequence of species immigration affects food-chain length and whether the effect depends on productivity. Using a microcosm experiment including a copepod predator, ciliate species, and bacteria, they find that food chains are longest when the top predator is added last and that high productivity reduces food-chain length.
Cristina de la Malla et al. show that an individual with extensive lesions to the ventral visual pathway can accurately judge the velocity at which an object moves despite not being able to correctly identify the object in question. This findings support a role of the dorsal visual pathway in judging velocity irrespective of perceptual processing.
Jeannine Diesch et al. report the changes in rDNA chromatin state associated with cell transition into malignancy. They show that a specific transcription factor regulates this transition by altering rDNA chromatin, resulting in the reorganization of contacts between rDNA and the genome.
Zhang, Hou, Xu, Srinivas et al. report the mechanism of colistin resistance imparted by MCR-4, which has a distinct catalytic domain but employs a similar ping-pong catalysis mechanism to that used by the well-studied MCR-1. This study provides further insights into the bacterial resistance to colistin, the last-resort antibiotic.
Saori Noguchi et al. demonstrate the role of Beclin 1 for recycling endosome during skin development, using keratinocyte-specific Beclin 1-knockout mice. This study suggests that a key autophagy player Beclin 1 is also important for skin formation by ensuring a proper localization of integrins.
Chengju Xiao et al. find that acute tobacco smoke exaggerates inflammation in recently wounded mouse corneas, thereby impairing wound repair. They show that the effect of tobacco smoke is mediated by activation of the sympathetic nervous system.
Hidenori Hashimura et al. show that cAMP-mediated signaling changes from propagating waves to a steady state at a multicellular stage of amoeba Dictyostelium discoideum. This study suggests that cAMP oscillation is not required for collective cell migration despite its importance at a unicellular stage.
Alexandra Murschhauser et al. present a high-throughput microscopy method for the analysis of single-cell longitudinal data using fluorescent markers. They apply the method to cancer cell lines exposed to cytotoxic nanoparticles and find that 58 nm PS-NH2 nanoparticles induce a lysosomal pathway and, at high doses, lead to cell death via a mitochondrial pathway.
Tomoyuki Murano et al. showed that neural hyperexcitation increases the expression of immaturity related genes. These changes in gene expression are shared among different neuropsychiatric and neurological conditions, hinting at their potential role as biomarkers.
Michal Olszewski et al. demonstrate the collaboration of Cdc48 and the 26S proteasome in degrading ubiquitinated, well-folded proteins that lack unstructured segments. This study suggests that Cdc48 creates flexible initiation regions in compact substrates for their proteasome-mediated degradation.
Akihisa Shinozawa, Ryoko Otake et al. report on an ancient subclass of the SNF1-related protein kinase 2 family involved in ABA signaling, which protect moss from drought stress. They propose that this signaling module evolved in early land plants to regulate dehydration-response.
Billing et al. clarify mechanisms ensuring reliable cytokine signaling despite variable expression and activation of signaling proteins in cells. Limited activation of signaling proteins either by feedback inhibition or low cytokine doses, and STAT3 serine phosphorylation timely orchestrate robustness and capacity of IL-6-induced signaling.