Thermal stress induces glycolytic beige fat formation via a myogenic state.

Environmental cues profoundly affect cellular plasticity in multicellular organisms. For instance, exercise promotes a glycolytic-to-oxidative fibre-type switch in skeletal muscle, and cold acclimation induces beige adipocyte biogenesis in adipose tissue. However, the molecular mechanisms by which physiological or pathological cues evoke developmental plasticity remain incompletely understood. Here we report a type of beige adipocyte that has a critical role in chronic cold adaptation in the absence of β-adrenergic receptor signalling. This beige fat is distinct from conventional beige fat with respect to developmental origin and regulation, and displays enhanced glucose oxidation. We therefore refer to it as glycolytic beige fat. Mechanistically, we identify GA-binding protein α as a regulator of glycolytic beige adipocyte differentiation through a myogenic intermediate. Our study reveals a non-canonical adaptive mechanism by which thermal stress induces progenitor cell plasticity and recruits a distinct form of thermogenic cell that is required for energy homeostasis and survival

Construction and in vivo assembly of a catalytically proficient and hyperthermostable de novo enzyme

Although catalytic mechanisms in natural enzymes are well understood, achieving the diverse palette of reaction chemistries in re-engineered native proteins has proved challenging. Wholesale modification of natural enzymes is potentially compromised by their intrinsic complexity, which often obscures the underlying principles governing biocatalytic efficiency. The maquette approach can circumvent this complexity by combining a robust de novo designed chassis with a design process that avoids atomistic mimicry of natural proteins. Here, we apply this method to the construction of a highly efficient, promiscuous, and thermostable artificial enzyme that catalyzes a diverse array of substrate oxidations coupled to the reduction of H2O2. The maquette exhibits kinetics that match and even surpass those of certain natural peroxidases, retains its activity at elevated temperature and in the presence of organic solvents, and provides a simple platform for interrogating catalytic intermediates common to natural heme-containing enzymes

Engendering harm: a critique of sex selection for 'family balancing'

The most benign rationale for sex-selection is deemed to be “family balancing.” On this view, provided the sex-distribution of an existing offspring group is “unbalanced,” one may legitimately use reproductive technologies to select the sex of the next child. I present four novel concerns with granting “family balancing” as a justification for sex-selection: (a) families or family subsets should not be subject to medicalization; (b) sex selection for “family balancing” entrenches heteronormativity, inflicting harm in at least three specific ways; (c) the logic of affirmative action is appropriated; (d) the moral mandate of reproductive autonomy is misused. I conclude that the harms caused by “family balancing” are sufficiently substantive to over-ride any claim arising from a supposed right to sex selection as an instantiation of procreative autonomy

Microtubule sliding activity of a kinesin-8 promotes spindle assembly and spindle length control

Molecular motors play critical roles in the formation of mitotic spindles, either through controlling the stability of individual microtubules, or by cross-linking and sliding microtubule arrays. Kinesin-8 motors are best known for their regulatory roles in controlling microtubule dynamics. They contain microtubule-destabilizing activities, and restrict spindle length in a wide variety of cell types and organisms. Here, we report for the first time on an anti-parallel microtubule-sliding activity of the budding yeast kinesin-8, Kip3. The in vivo importance of this sliding activity was established through the identification of complementary Kip3 mutants that separate the sliding activity and microtubule destabilizing activity. In conjunction with kinesin-5/Cin8, the sliding activity of Kip3 promotes bipolar spindle assembly and the maintenance of genome stability. We propose a “slide-disassemble” model where Kip3’s sliding and destabilizing activity balance during pre-anaphase. This facilitates normal spindle assembly. However, Kip3’s destabilizing activity dominates in late anaphase, inhibiting spindle elongation and ultimately promoting spindle disassembly

Temperature Modulates Coccolithophorid Sensitivity of Growth, Photosynthesis and Calcification to Increasing Seawater pCO2

Increasing atmospheric CO2 concentrations are expected to impact pelagic ecosystem functioning in the near future by driving ocean warming and acidification. While numerous studies have investigated impacts of rising temperature and seawater acidification on planktonic organisms separately, little is presently known on their combined effects. To test for possible synergistic effects we exposed two coccolithophore species, Emiliania huxleyi and Gephyrocapsa oceanica, to a CO2 gradient ranging from ,0.5–250 mmol kg21 (i.e. ,20–6000 matm pCO2) at three different temperatures (i.e. 10, 15, 20uC for E. huxleyi and 15, 20, 25uC for G. oceanica). Both species showed CO2-dependent optimum-curve responses for growth, photosynthesis and calcification rates at all temperatures. Increased temperature generally enhanced growth and production rates and modified sensitivities of metabolic processes to increasing CO2. CO2 optimum concentrations for growth, calcification, and organic carbon fixation rates were only marginally influenced from low to intermediate temperatures. However, there was a clear optimum shift towards higher CO2 concentrations from intermediate to high temperatures in both species. Our results demonstrate that the CO2 concentration where optimum growth, calcification and carbon fixation rates occur is modulated by temperature. Thus, the response of a coccolithophore strain to ocean acidification at a given temperature can be negative, neutral or positive depending on that strain’s temperature optimum. This emphasizes that the cellular responses of coccolithophores to ocean acidification can only be judged accurately when interpreted in the proper eco-physiological context of a given strain or species. Addressing the synergistic effects of changing carbonate chemistry and temperature is an essential step when assessing the success of coccolithophores in the future ocean

Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells

Bacterial type II CRISPR-Cas9 systems have been widely adapted for RNA-guided genome editing and transcription regulation in eukaryotic cells, yet their in vivo target specificity is poorly understood. Here we mapped genome-wide binding sites of a catalytically inactive Cas9 (dCas9) from Streptococcus pyogenes loaded with single guide RNAs (sgRNAs) in mouse embryonic stem cells (mESCs). Each of the four sgRNAs we tested targets dCas9 to between tens and thousands of genomic sites, frequently characterized by a 5-nucleotide seed region in the sgRNA and an NGG protospacer adjacent motif (PAM). Chromatin inaccessibility decreases dCas9 binding to other sites with matching seed sequences; thus 70% of off-target sites are associated with genes. Targeted sequencing of 295 dCas9 binding sites in mESCs transfected with catalytically active Cas9 identified only one site mutated above background levels. We propose a two-state model for Cas9 binding and cleavage, in which a seed match triggers binding but extensive pairing with target DNA is required for cleavage.National Institutes of Health (U.S.) (Grant RO1-GM34277)National Institutes of Health (U.S.) (Grant R01-CA133404)National Cancer Institute (U.S.) (Grant PO1-CA42063)National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051)National Institutes of Health (U.S.) (Director's Pioneer Award 1DP1-MH100706)Damon Runyon Cancer Research FoundationKinship Foundation. Searle Scholars ProgramSimons Foundatio

Managing invasive species in cities:A decision support framework applied to Cape Town

It has been suggested that existing frameworks for guiding management of invasive species in rural areas and protected areas are inadequate for dealing with invasions in urban settings. A framework for selecting appropriate goals for managing invasive species in urban areas was developed by Gaertner et al. in 2016. This framework groups species into three management approaches (control priority, active engagement, and tolerance) depending on their real or perceived benefits and their potential to generate negative impacts.This study tests the practical application of the framework using the example of Cape Town. We assess the suitability of the framework to support decision-making for managing invasive species in urban ecosystems using a questionnaire-based survey of members of the public, and an e-mail-based survey and a workshop with invasion biology researchers and managers. Specifically, we (1) determine the differences in perceptions regarding the benefits and impacts of invasive species between the public, managers and researchers; (2) investigate how consistently managers and researchers group invasive species into the three management categories; and (3) identify, with the help of managers and researchers, issues linked to the framework and give suggestions to overcome the identified issues.We found no clear pattern in the perceptions of the public, managers and researchers regarding perceived benefits and negative impacts. Instead, the answers were widely scattered among all groups for most of the species that were considered. However, using the framework leads to a higher consistency among managers in placing the species into management categories, compared to invasive species grouping without guidance of the framework.We conclude that decision-support frameworks can assist managers in placing invasive species into management categories. However, even more specific guidelines on the use of invasive species management frameworks in urban areas are needed

Assessing the complex sponge microbiota: core, variable and species-specific bacterial communities in marine sponges

Marine sponges are well known for their associations with highly diverse, yet very specific and often highly similar microbiota. The aim of this study was to identify potential bacterial sub-populations in relation to sponge phylogeny and sampling sites and to define the core bacterial community. 16S ribosomal RNA gene amplicon pyrosequencing was applied to 32 sponge species from eight locations around the world's oceans, thereby generating 2567 operational taxonomic units (OTUs at the 97% sequence similarity level) in total and up to 364 different OTUs per sponge species. The taxonomic richness detected in this study comprised 25 bacterial phyla with Proteobacteria, Chloroflexi and Poribacteria being most diverse in sponges. Among these phyla were nine candidate phyla, six of them found for the first time in sponges. Similarity comparison of bacterial communities revealed no correlation with host phylogeny but a tropical sub-population in that tropical sponges have more similar bacterial communities to each other than to subtropical sponges. A minimal core bacterial community consisting of very few OTUs (97%, 95% and 90%) was found. These microbes have a global distribution and are probably acquired via environmental transmission. In contrast, a large species-specific bacterial community was detected, which is represented by OTUs present in only a single sponge species. The species-specific bacterial community is probably mainly vertically transmitted. It is proposed that different sponges contain different bacterial species, however, these bacteria are still closely related to each other explaining the observed similarity of bacterial communities in sponges in this and previous studies. This global analysis represents the most comprehensive study of bacterial symbionts in sponges to date and provides novel insights into the complex structure of these unique associations

The SAMI Galaxy Survey: instrument specification and target selection

The SAMI Galaxy Survey will observe 3400 galaxies with the Sydney-AAO Multi- object Integral-field spectrograph (SAMI) on the Anglo-Australian Telescope (AAT) in a 3-year survey which began in 2013. We present the throughput of the SAMI system, the science basis and specifications for the target selection, the survey observation plan and the combined properties of the selected galaxies. The survey includes four volume-limited galaxy samples based on cuts in a proxy for stellar mass, along with low-stellar-mass dwarf galaxies all selected from the Galaxy And Mass Assembly (GAMA) survey. The GAMA regions were selected because of the vast array of ancillary data available, including ultraviolet through to radio bands. These fields are on the celestial equator at 9, 12, and 14.5 hours, and cover a total of 144 square degrees (in GAMA-I). Higher density environments are also included with the addition of eight clusters. The clusters have spectroscopy from 2dFGRS and SDSS and photometry in regions covered by the Sloan Digital Sky Survey (SDSS) and/or VLT Survey Telescope/ATLAS. The aim is to cover a broad range in stellar mass and environment, and therefore the primary survey targets cover redshifts 0.004 < z < 0.095, magnitudes rpet < 19.4, stellar masses 107– 1012M⊙, and environments from isolated field galaxies through groups to clusters of _ 1015M⊙