| | Genetics: Feedforward loop for diversity
DNA-sequence analysis suggests that genetic mutations arise at elevated rates in genomes harbouring high levels of heterozygosity — the state in which the two copies of a genetic region contain sequence differences.
| Genetics of disease: Associations with depression
Two genetic regions associated with major depressive disorder have been revealed for the first time, through whole-genome sequencing of a population of Han Chinese women.
| Parasitology: CRISPR for Cryptosporidium
Study of the diarrhoea-causing pathogen Cryptosporidium has been hindered by a lack of genetic-modification and culture tools. A description of genome editing and propagation methods for the parasite changes this picture.
| Speed cells in the medial entorhinal cortex
On the basis of neural firing rates a specific class of neuron is identified in the medial entorhinal cortex that linearly encodes information on running speed in a context-independent manner and that is distinct from other functionally specific entorhinal neurons.
| Molecular basis of ligand recognition and transport by glucose transporters
The SLC2 family glucose transporters facilitate the transport of glucose and other monosaccharides across biological membranes; the X-ray crystal structure of human GLUT3 has been solved in outward-open and outward-occluded conformations and a model for how the membrane protein rearranges itself during a complete transport cycle has been proposed.
| Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy
Here the cis form of tau protein, which disrupts axonal microtubules and transport, spreads to other neurons, and leads to apoptosis in vitro and in vivo, is found to be produced by neurons immediately after traumatic brain injury (TBI); treating TBI mice with cis antibody blocks early production of cis tau, prevents tauopathy and spread and restores brain structural and functional outcomes, and may be further developed to treat TBI and to prevent neurodegeneration after injury.
| Comprehensive genomic profiles of small cell lung cancer
Genomic sequencing of 110 human small cell lung cancers identifies genomic signatures including nearly ubiquitous bi-allelic inactivation of TP53 and RB1, a role for NOTCH family genes, and somatic rearrangements that create an oncogenic version of TP73.
| Kinetochore-localized PP1–Sds22 couples chromosome segregation to polar relaxation
A study of division in proliferating animal cells points to the existence of a kinetochore-based signalling pathway, independent of furrow formation, centrosomes and microtubules, that couples chromosome segregation to cell division.
| Metabolic rescue in pluripotent cells from patients with mtDNA disease
Mutations in mitochondrial (mt)DNA are associated with severe disorders for which treatment is currently limited; this study shows that mtDNA mutations can be genetically corrected and normal metabolic function restored in cells derived from patients with mtDNA disease and reprogrammed to pluripotency through factor-mediated reprogramming or via a somatic cell nuclear transfer approach.
| A zeolite family with expanding structural complexity and embedded isoreticular structures
The complex structure of zeolite ZSM-25 is determined and a family of related structures are identified by using electron diffraction to uncover the structural 'coding' within them; this enabled the synthesis of two more-complex zeolites in the family.
| Genetic compensation induced by deleterious mutations but not gene knockdowns
Zebrafish embryos injected with egfl7 morpholino exhibit severe vascular defects but egfl7 mutants do not show any obvious phenotypes, illustrating the power of comparing mutants and morphants to identify modifier genes.
| Transcriptional control of autophagy–lysosome function drives pancreatic cancer metabolism
The MiT/TFE family of transcription factors is found to coordinate constitutive activation of autophagy and lysosome biogenesis to drive the metabolic programming and malignant growth of pancreatic cancer.
| Energetic coupling between plastids and mitochondria drives CO2 assimilation in diatoms
Diatoms optimize their photosynthetic efficiency via extensive energetic exchanges between plastids and mitochondria.
| Parent–progeny sequencing indicates higher mutation rates in heterozygotes
Mutation rates vary within genomes; here, by calling mutation events directly using a parent–offspring sequencing strategy in Arabidopsis, replicated in the rice and honey bee genomes, mutation rates are found to be higher in heterozygotes and in proximity to crossover events.
| Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum
Cryptosporidium is an important cause of diarrhoeal disease in young children but until now it has been difficult to study; here, the parasite is genetically modified, paving the way for in-depth investigation and the development of effective treatments.
| Sparse whole-genome sequencing identifies two loci for major depressive disorder
Genomic analysis of 5,303 Chinese women with recurrent major depressive disorder (MDD) enables the identification and replication of two genome-wide significant loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene; the other in an intron of the LHPP gene.
| Mechanism of phospho-ubiquitin-induced PARKIN activation
This study provides insights into conformational changes that lead to phospho-ubiquitin-induced PARKIN activation and how PARKIN is recruited to phospho-ubiquitin chains on mitochondria; the crystal structure of PARKIN in complex with phospho-ubiquitin also indicates that the pocket within PARKIN where phospho-ubiquitin binds carries amino acid residues that are mutated in patients with autosomal-recessive juvenile Parkinsonism.
| | | | | Noncoding RNAs in Endocrinology
Noncoding RNAs have important roles in the development and regulation of the endocrine system. This web collection on noncoding RNAs in endocrinology highlights current and future applications of noncoding RNAs as diagnostic and prognostic biomarkers and as therapeutic targets for personalized management of patients with a wide range of endocrine diseases.
Access the collection online. | | | | | | | | | | | | | Volcanic–plutonic parity and the differentiation of the continental crust
A global geochemical data set of volcanic and plutonic rocks indicates that differentiation trends from primitive basaltic to felsic compositions for volcanic versus plutonic samples are generally indistinguishable in subduction-zone settings, but are divergent in continental rifts.
C. Brenhin Keller, Blair Schoene, Melanie Barboni et al. | Progesterone receptor modulates ERα action in breast cancer
Progesterones, oestrogens and their receptors (PR, ERα and ERβ) are essential in normal breast development and homeostasis, as well as in breast cancer; here it is shown that PR controls ERα function by redirecting where ERα binds to the chromatin, acting as a proliferative brake in ERα+ breast tumours.
Hisham Mohammed, I. Alasdair Russell, Rory Stark et al. | Receptor-mediated exopolysaccharide perception controls bacterial infection
This paper describes the discovery of the exopolysaccharide receptor (Epr3) in plants, and shows that its expression is induced upon perception of the bacterial Nod factors; the EPR3 receptor recognizes exopolysaccharides on the surface of rhizobia, thus controlling the symbiotic infection of the roots of legumes.
Y. Kawaharada, S. Kelly, M. Wibroe Nielsen et al. | | Rapidly rotating second-generation progenitors for the 'blue hook' stars of ω Centauri
The observed range of luminosities of the extremely hot 'blue hook' stars of the globular cluster ω Centauri is successfully explained by a model in which the progenitors of these stars are second-generation helium-rich stars characterized by a range of rotation rates arising during the cluster's very early evolution.
Marco Tailo, Francesca D'Antona, Enrico Vesperini et al. | Laboratory confirmation of C60+ as the carrier of two diffuse interstellar bands
Laboratory measurements of the gas-phase spectrum of C60+ confirm that the diffuse interstellar bands observed at 9,632 ångströms and 9,577 ångströms arise as a result of C60+ in the interstellar medium.
E. K. Campbell, M. Holz, D. Gerlich et al. | Quantum-dot-in-perovskite solids
Organohalide perovskites and preformed colloidal quantum dots are combined in the solution phase to produce epitaxially aligned 'dots-in-a-matrix' crystals that have both the excellent electrical transport properties of the perovskite matrix and the high radiative efficiency of the quantum dots.
Zhijun Ning, Xiwen Gong, Riccardo Comin et al. | Nanotubes mediate niche–stem-cell signalling in the Drosophila testis
Drosophila male germline stem cells form previously unrecognized structures, microtubule-based nanotubes, which extend into the hub, a major niche component, to mediate the niche–stem-cell signalling.
Mayu Inaba, Michael Buszczak, Yukiko M. Yamashita | Supramolecular assemblies underpin turnover of outer membrane proteins in bacteria
Fluorescent labelling is used to show that in E. coli, outer membrane protein (OMP) turnover is passive and binary in nature, and OMPs cluster to form islands in which diffusion of individual proteins is restricted owing to lateral interactions with other OMPs; new OMPs are inserted mostly at mid-cell, meaning that old OMP islands are displaced to the poles of growing cells.
Patrice Rassam, Nikki A. Copeland, Oliver Birkholz et al. | Structural and functional features of central nervous system lymphatic vessels
The central nervous system undergoes constant immune surveillance, but the route that immune cells take to exit the brain has been unclear as it had been thought to lack a classical lymphatic drainage system; here functional lymphatic vessels able to carry both fluid and immune cells from the cerebrospinal fluid are shown to be located in the brain meninges.
Antoine Louveau, Igor Smirnov, Timothy J. Keyes et al. | HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation
Apolipoprotein-M-bound sphingosine-1-phosphate (S1P) is found to restrain the generation of new lymphocytes—and, consequently, adaptive immune responses—by activating the S1P1 receptor on bone marrow lymphocyte progenitors in mice.
Victoria A. Blaho, Sylvain Galvani, Eric Engelbrecht et al. | Conversion of abiraterone to D4A drives anti-tumour activity in prostate cancer
The drug abiraterone is converted to Δ4-abiraterone (D4A) in mice and patients with prostate cancer, which has more potent anti-tumour activity and may lead to more effective therapies.
Zhenfei Li, Andrew C. Bishop, Mohammad Alyamani et al. | Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment
Novel hotspot mutant p53 gain-of-function mouse model shows that tumours depend on its sustained expression, and genetic and pharmacological approaches reveal mutant p53 as an actionable cancer drug target.
E. M. Alexandrova, A. R. Yallowitz, D. Li et al. | A noisy linear map underlies oscillations in cell size and gene expression in bacteria
Quantification of single-cell growth over long periods of time in E. coli shows transient oscillations in cell size, with periods stretching across more than ten generations; a noisy negative feedback on cell-size control is proposed in which cells with a small initial size tend to divide later than cells with a large initial size with implications for the genetic and physiological processes required.
Yu Tanouchi, Anand Pai, Heungwon Park et al. | Intersecting transcription networks constrain gene regulatory evolution
Epistatic interactions, whereby a mutation's effect is contingent on another mutation, have been shown to constrain evolution within single proteins, and how such interactions arise in gene regulatory networks has remained unclear; here the appearance of pheromone-response regulator binding sites in the regulatory DNA of the a-specific genes of Saccharomyces cerevisiae are shown to have required specific changes in a second pathway during the evolution from its common ancestor with Candida albicans.
Trevor R. Sorrells, Lauren N. Booth, Brian B. Tuch et al. | Structural basis for retroviral integration into nucleosomes
Retroviruses such as HIV rely on the intasome, a tetramer of integrase protein bound to the viral DNA ends interacting with host chromatin, for integration into the host genome; the structure of the intasome as it interacts with a nucleosome is now solved, giving insight into the integration process.
Daniel P. Maskell, Ludovic Renault, Erik Serrao et al. | | | | |
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