Cyclic olefin homopolymer-based microfluidics for protein crystallization and in situ X-ray diffraction

A cyclic olefin homopolymer-based microfluidics system has been established for protein crystallization and in situ X-ray diffraction

A New Population of High-z, Dusty Lyα Emitters and Blobs Discovered by WISE: Feedback Caught in the Act?

By combining data from the NASA Wide-field Infrared Survey Explorer (WISE) mission with optical spectroscopy from the W. M. Keck telescope, we discover a mid-IR color criterion that yields a 78% success rate in identifying rare, typically radio-quiet, 1.6 ≾ z ≾ 4.6 dusty Lyα emitters (LAEs). Of these, at least 37% have emission extended on scales of 30-100 kpc and are considered Lyα "blobs" (LABs). The objects have a surface density of only ~0.1 deg^(–2), making them rare enough that they have been largely missed in deep, small area surveys. We measured spectroscopic redshifts for 92 of these galaxies, and find that the LAEs (LABs) have a median redshift of 2.3 (2.5). The WISE photometry coupled with data from Herschel (Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA) reveals that these galaxies are in the Hyper Luminous IR galaxy regime (L IR ≳ 10^(13)-10^(14) L_☉) and have warm colors. They are typically more luminous and warmer than other dusty, z ~ 2 populations such as submillimeter-selected galaxies and dust-obscured galaxies. These traits are commonly associated with the dust being illuminated by intense active galactic nucleus activity. We hypothesize that the combination of spatially extended Lyα, large amounts of warm IR-luminous dust, and rarity (implying a short-lived phase) can be explained if the galaxies are undergoing brief, intense "feedback" transforming them from an extreme dusty starburst/QSO into a mature galaxy

OrthoDB v8: update of the hierarchical catalog of orthologs and the underlying free software

Orthology, refining the concept of homology, is the cornerstone of evolutionary comparative studies. With the ever-increasing availability of genomic data, inference of orthology has become instrumental for generating hypotheses about gene functions crucial to many studies. This update of the OrthoDB hierarchical catalog of orthologs (http://www.orthodb.org) covers 3027 complete genomes, including the most comprehensive set of 87 arthropods, 61 vertebrates, 227 fungi and 2627 bacteria (sampling the most complete and representative genomes from over 11,000 available). In addition to the most extensive integration of functional annotations from UniProt, InterPro, GO, OMIM, model organism phenotypes and COG functional categories, OrthoDB uniquely provides evolutionary annotations including rates of ortholog sequence divergence, copy-number profiles, sibling groups and gene architectures. We re-designed the entirety of the OrthoDB website from the underlying technology to the user interface, enabling the user to specify species of interest and to select the relevant orthology level by the NCBI taxonomy. The text searches allow use of complex logic with various identifiers of genes, proteins, domains, ontologies or annotation keywords and phrases. Gene copy-number profiles can also be queried. This release comes with the freely available underlying ortholog clustering pipeline (http://www.orthodb.org/software

E119D Neuraminidase Mutation Conferring Pan-Resistance to Neuraminidase Inhibitors in an A(H1N1)pdm09 Isolate From a Stem-Cell Transplant Recipient

Background. An influenza A(H1N1)pdm09 infection was diagnosed in a hematopoietic stem cell transplant recipient during conditioning regimen. He was treated with oral oseltamivir, later combined with intravenous zanamivir. The H275Y neuraminidase (NA) mutation was first detected, and an E119D NA mutation was identified during zanamivir therapy. Methods. Recombinant wild-type (WT) E119D and E119D/H275Y A(H1N1)pdm09 NA variants were generated by reverse genetics. Susceptibility to NA inhibitors (NAIs) was evaluated with a fluorometric assay using the 2′-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid (MUNANA) substrate. Susceptibility to favipiravir (T-705) was assessed using plaque reduction assays. The NA affinity and velocity values were determined with NA enzymatic studies. Results. We identified an influenza A(H1N1)pdm09 E119D mutant that exhibited a marked increase in the 50% inhibitory concentrations against all tested NAIs (827-, 25-, 286-, and 702-fold for zanamivir, oseltamivir, peramivir, and laninamivir, respectively). The double E119D/H275Y mutation further increased oseltamivir and peramivir 50% inhibitory concentrations by 790- and >5000-fold, respectively, compared with the WT. The mutant viruses remained susceptible to favipiravir. The NA affinity and velocity values of the E119D variant decreased by 8.1-fold and 4.5-fold, respectively, compared with the WT. Conclusions. The actual emergence of a single NA mutation conferring pan-NAI resistance in the clinical setting reinforces the pressing need to develop new anti-influenza strategie

A New Population of High Redshift, Dusty Lyman-Alpha Emitters and Blobs Discovered by WISE

We report a new technique to select 1.6<z<4.6 dusty Lyman-alpha emitters (LAEs), over a third of which are `blobs' (LABs) with emission extended on scales of 30-100kpc. Combining data from the NASA Wide-field Infrared Survey Explorer (WISE) mission with optical spectroscopy from the W.M. Keck telescope, we present a color criteria that yields a 78% success rate in identifying rare, dusty LAEs of which at least 37% are LABs. The objects have a surface density of only ~0.1 per square degree, making them rare enough that they have been largely missed in narrow surveys. We measured spectroscopic redshifts for 92 of these WISE-selected, typically radio-quiet galaxies and find that the LAEs (LABs) have a median redshift of 2.3 (2.5). The WISE photometry coupled with data from Herschel reveals that these galaxies have extreme far-infrared luminosities (L_IR>10^{13-14}L_sun) and warm colors, typically larger than submillimeter-selected galaxies (SMGs) and dust-obscured galaxies (DOGs). These traits are commonly associated with the dust being energized by intense AGN activity. We hypothesize that the combination of spatially extended Lyman-alpha, large amounts of warm IR-luminous dust, and rarity (implying a short-lived phase) can be explained if the galaxies are undergoing strong `feedback' transforming them from an extreme dusty starburst to a QSO.Comment: Submitted to ApJ Letters, 6 pages, 4 figures. Comments welcom

The First Hyper-luminous Infrared Galaxy Discovered by WISE

We report the discovery by the Wide-field Infrared Survey Explorer (WISE) of the z = 2.452 source WISE J181417.29+341224.9, the first hyperluminous source found in the WISE survey. WISE 1814+3412 is also the prototype for an all-sky sample of ~1000 extremely luminous "W1W2-dropouts" (sources faint or undetected by WISE at 3.4 and 4.6 μm and well detected at 12 or 22 μm). The WISE data and a 350 μm detection give a minimum bolometric luminosity of 3.7 × 10^(13) L_☉, with ~10^(14) L_☉ plausible. Follow-up images reveal four nearby sources: a QSO and two Lyman break galaxies (LBGs) at z = 2.45, and an M dwarf star. The brighter LBG dominates the bolometric emission. Gravitational lensing is unlikely given the source locations and their different spectra and colors. The dominant LBG spectrum indicates a star formation rate ~300 M_☉ yr^(–1), accounting for ≲ 10% of the bolometric luminosity. Strong 22 μm emission relative to 350 μm implies that warm dust contributes significantly to the luminosity, while cooler dust normally associated with starbursts is constrained by an upper limit at 1.1 mm. Radio emission is ~10 times above the far-infrared/radio correlation, indicating an active galactic nucleus (AGN) is present. An obscured AGN combined with starburst and evolved stellar components can account for the observations. If the black hole mass follows the local M BH-bulge mass relation, the implied Eddington ratio is ≳ 4. WISE 1814+3412 may be a heavily obscured object where the peak AGN activity occurred prior to the peak era of star formation

A New Population of High-z, Dusty Lyman-alpha Emitters and Blobs Discovered by WISE: Feedback Caught in the Act?

By combining data from the NASA Wide-field Infrared Survey Explorer (WISE) mission with optical spectroscopy from the W. M. Keck telescope, we discover a mid-IR color criterion that yields a 78% success rate in identifying rare, typically radio-quiet, 1.6 approx. 10(exp 13)-10(exp 14) Solar L) and have warm colors. They are typically more luminous and warmer than other dusty, z approx.. 2 populations such as submillimeter-selected galaxies and dust-obscured galaxies. These traits are commonly associated with the dust being illuminated by intense active galactic nucleus activity. We hypothesize that the combination of spatially extended Ly-alpha, large amounts of warm IR-luminous dust, and rarity (implying a short-lived phase) can be explained if the galaxies are undergoing brief, intense "feedback" transforming them from an extreme dusty starburst/QSO into a mature galaxy

What do changing weather and climate shocks and stresses mean for the UK food system?

In light of the publication of Henry Dimbleby’s National Food Strategy (www.nationalfoodstrategy. org/) and the COP26 climate meeting in Glasgow, it is timely to consider the impacts of weather and climate extremes on the UK food system. Climate change-driven changes in extreme weather events are one of the highest-risk future shocks to the UK food system [1], underlining the importance of preparedness across the food chain [2]. Here, we identify major knowledge gaps in the primary impacts of extreme weather and climate change across the UK’s food system, its functioning and their interactions to provide information to support adaptation and resilience planning. Research tends to focus on individual food system activities rather than taking a systematic approach [3, 4]. How- ever, strong evidence exists about the impacts of long- term climate trends and extremes [5] on primary food production [6]. The major knowledge gaps therefore concern post-primary production dimensions [4], notably food system activities between the ‘farm-gate’ and consumption—which are the core focus of this paper (supplementary material S1 available online at stacks.iop.org/ERL/17/051001/mmedia). These constitute major economic and social dimensions but are often the ‘missing middle’ in food system discus- sions. We use the UK food system as an illustrative case study, and consider both global and domestic risks and implications. We present methods, tools and frameworks for systemic analysis of climate impacts on food systems, consider the funding landscape, and highlight priorities for future research

Dementia: beyond disorders of mood

This editorial will present the growing argument in the research literature that mood disorders, as defined by psychiatric diagnostic criteria, do not well serve individuals with dementia. This is important because anxiety and depression are our most used and most influential ways of understanding a highly prevalent and personally important experience in dementia: emotion. As such, there is a need to review how the disorders are currently conceptualised since they may have limited applicability for individuals with dementia, and consider what alternatives there might be. Agitation is offered as a lesson in how imprecise descriptions of behaviour can exclude the internal world of people with dementia. In our research to explore how the emotional experiences of individuals with dementia are understood, we consider what might lie beyond disorders of mood

Growth control of the eukaryote cell: a systems biology study in yeast.

BACKGROUND: Cell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking. RESULTS: Metabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth. CONCLUSION: This work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are