Differentiating core and co-opted mechanisms in calculation: The neuroimaging of calculation in aphasia

The role of language in exact calculation is the subject of debate. Some behavioral and functional neuroimaging investigations of healthy participants suggest that calculation requires language resources. However, there are also reports of individuals with severe aphasic language impairment who retain calculation ability. One possibility in resolving these discordant findings is that the neural basis of calculation has undergone significant reorganization in aphasic calculators. Using fMRI, we examined brain activations associated with exact addition and subtraction in two patients with severe agrammatic aphasia and retained calculation ability. Behavior and brain activations during two-digit addition and subtraction were compared to those of a group of 11 healthy, age-matched controls. Behavioral results confirmed that both patients retained calculation ability. Imaging findings revealed individual differences in processing, but also a similar activation pattern across patients and controls in bilateral parietal cortices. Patients differed from controls in small areas of increased activation in peri-lesional regions, a shift from left fronto-temporal activation to the contralateral region, and increased activations in bilateral superior parietal regions. Our results suggest that bilateral parietal cortex represents the core of the calculation network and, while healthy controls may recruit language resources to support calculation, these mechanisms are not mandatory in adult cognition.

Promoter analysis and immunolocalisation show that puroindoline genes are exclusively expressed in starchy endosperm cells of wheat grain

The purolindolines are small cysteine-rich proteins which are present in the grain of wheat. They have a major impact on the utilisation of the grain as they are the major determinants of grain texture, which affects both milling and baking properties. Bread and durum wheats were transformed with constructs comprising the promoter regions of the Puroindoline a (Pina) and Puroindoline b (Pinb) genes fused to the uidA (GUS) reporter gene. Nine lines showing 3:1 segregation for the transgene and comprising all transgene/species combinations were selected for detailed analysis of transgene expression during grain development. This showed that transgene expression occurred only in the starchy endosperm cells and was not observed in any other seed or vegetative tissues. The location of the puroindoline proteins in these cells was confirmed by tissue printing of developing grain, using a highly specific monoclonal antibody for detection and an antibody to the aleurone-localised 8S globulin as a control. This provides clear evidence that puroindolines are only synthesised and accumulated in the starchy endosperm cells of the wheat grain.

High-resolution provenance of desert dust deposited on Mt. Elbrus, Caucasus in 2009–2012 using snow pit and firn core records

The first record of dust deposition events on Mt. Elbrus, Caucasus Mountains derived from a snow pit and a shallow firn core is presented for the 2009–2012 period. A combination of isotopic analysis, SEVIRI red-greenblue composite imagery, MODIS atmospheric optical depth fields derived using the Deep Blue algorithm, air mass trajectories derived using the HYSPLIT model and analyses of meteorological data enabled identification of dust source regions with high temporal (hours) and spatial (ca. 20–100 km) resolution. Seventeen dust deposition events were detected; fourteen occurred in March–June, one in February and two in October. Four events originated in the Sahara, predominantly in northeastern Libya and eastern Algeria. Thirteen events originated in the Middle East, in the Syrian Desert and northern Mesopotamia, from a mixture of natural and anthropogenic sources. Dust transportation from Sahara was associated with vigorous Saharan depressions, strong surface winds in the source region and mid-tropospheric southwesterly flow with daily winds speeds of 20–30 m s−1 at 700 hPa level. Although these events were less frequent than those originating in the Middle East, they resulted in higher dust concentrations in snow. Dust transportation from the Middle East was associated with weaker depressions forming over the source region, high pressure centred over or extending towards the Caspian Sea and a weaker southerly or southeasterly flow towards the Caucasus Mountains with daily wind speeds of 12–18 m s−1 at 700 hPa level. Higher concentrations of nitrates and ammonium characterised dust from the Middle East deposited on Mt. Elbrus in 2009 indicating contribution of anthropogenic sources. The modal values of particle size distributions ranged between 1.98 µm and 4.16 µm. Most samples were characterised by modal values of 2.0– 2.8 µm with an average of 2.6 µm and there was no signifi- cant difference between dust from the Sahara and the Middle East.

Mobile elements drive recombination hotspots in the core genome of Staphylococcus aureus

Horizontal gene transfer is an important driver of bacterial evolution, but genetic exchange in the core genome of clonal species, including the major pathogen Staphylococcus aureus, is incompletely understood. Here we reveal widespread homologous recombination in S. aureus at the species level, in contrast to its near-complete absence between closely related strains. We discover a patchwork of hotspots and coldspots at fine scales falling against a backdrop of broad-scale trends in rate variation. Over megabases, homoplasy rates fluctuate 1.9-fold, peaking towards the origin-of-replication. Over kilobases, we find core recombination hotspots of up to 2.5-fold enrichment situated near fault lines in the genome associated with mobile elements. The strongest hotspots include regions flanking conjugative transposon ICE6013, the staphylococcal cassette chromosome (SCC) and genomic island νSaα. Mobile element-driven core genome transfer represents an opportunity for adaptation and challenges our understanding of the recombination landscape in predominantly clonal pathogens, with important implications for genotype–phenotype mapping.

A benchmark-driven modelling approach for evaluating deployment choices on a multi-core architecture

The complexity of current and emerging architectures provides users with options about how best to use the available resources, but makes predicting performance challenging. In this work a benchmark-driven model is developed for a simple shallow water code on a Cray XE6 system, to explore how deployment choices such as domain decomposition and core affinity affect performance. The resource sharing present in modern multi-core architectures adds various levels of heterogeneity to the system. Shared resources often includes cache, memory, network controllers and in some cases floating point units (as in the AMD Bulldozer), which mean that the access time depends on the mapping of application tasks, and the core's location within the system. Heterogeneity further increases with the use of hardware-accelerators such as GPUs and the Intel Xeon Phi, where many specialist cores are attached to general-purpose cores. This trend for shared resources and non-uniform cores is expected to continue into the exascale era. The complexity of these systems means that various runtime scenarios are possible, and it has been found that under-populating nodes, altering the domain decomposition and non-standard task to core mappings can dramatically alter performance. To find this out, however, is often a process of trial and error. To better inform this process, a performance model was developed for a simple regular grid-based kernel code, shallow. The code comprises two distinct types of work, loop-based array updates and nearest-neighbour halo-exchanges. Separate performance models were developed for each part, both based on a similar methodology. Application specific benchmarks were run to measure performance for different problem sizes under different execution scenarios. These results were then fed into a performance model that derives resource usage for a given deployment scenario, with interpolation between results as necessary.

Eemian and Holocene sea-surface conditions in the southern Black Sea: organic-walled dinoflagellate cyst record from core 22-GC3/3

In order to compare the sea-surface conditions in the Black Sea during the Holocene and Eemian, sapropelic parts of marine core 22-GC3 (42°13.53′N/36°29.55′E, 838 m water depth) were studied for organic-walled dinoflagellate cyst content. The record shows a change from freshwater/brackish assemblages (Pyxidinopsis psilata, Spiniferites cruciformis, and Caspidinium rugosum) to more marine assemblages (Lingulodinium machaerophorum and Spiniferites ramosus complex) during each interglacial, due to the inflow of saline Mediterranean water. The lacustrine–marine transitions in 22-GC3 occurred at ~ 8.3 cal kyr BP during the early Holocene and ~ 128 kyr BP during the early Eemian, slightly later compared to the onset of interglacial conditions on the adjacent land. Dinoflagellate cyst assemblages reveal higher sea-surface salinity (~ 28–30) (e.g. Spiniferites pachydermus, Bitectatodinium tepikiense, and Spiniferites mirabilis) around ~ 126.5–121 kyr BP in comparison to the Holocene (~ 15–20) as well as relatively high sea-surface temperature (e.g. Tuberculodinium vancampoae, S. pachydermus, and S. mirabilis) especially at ~ 127.6–125.3 kyr BP. Establishment of high sea-surface salinity during the Eemian correlates very well with reconstructed relatively high global sea-level and is explained as a combined effect of increased Mediterranean supply and high temperatures at the beginning of the last interglacial. The observed changes in the dinocyst record highlight the importance of nutrients for the composition of the Eemian and Holocene dinocyst assemblages.

Apples and cardiovascular health: is the gut microbiota a core consideration?

There is now considerable scientific evidence that a diet rich in fruits and vegetables can improve human health and protect against chronic diseases. However, it is not clear whether different fruits and vegetables have distinct beneficial effects. Apples are among the most frequently consumed fruits and a rich source of polyphenols and fiber. A major proportion of the bioactive components in apples, including the high molecular weight polyphenols, escape absorption in the upper gastrointestinal tract and reach the large intestine relatively intact. There, they can be converted by the colonic microbiota to bioavailable and biologically active compounds with systemic effects, in addition to modulating microbial composition. Epidemiological studies have identified associations between frequent apple consumption and reduced risk of chronic diseases such as cardiovascular disease. Human and animal intervention studies demonstrate beneficial effects on lipid metabolism, vascular function and inflammation but only a few studies have attempted to link these mechanistically with the gut microbiota. This review will focus on the reciprocal interaction between apple components and the gut microbiota, the potential link to cardiovascular health and the possible mechanisms of action.

Briefing paper for universities on Core Maths

This briefing paper outlines the rationale for and development of the new Core Maths qualifications, the characteristics of Core Maths, and why Core Maths is important for higher education. It is part of a communication to university vice-chancellors from the Department for Business, Innovation and Skills (BIS) comprising this paper and a joint Ministerial letter from Jo Johnson, Minister of State for Universities and Science in BIS, and Nick Gibb, Minister of State for Schools in the Department for Education (DfE).

Promoting core maths - background, evidence, plans, opportunities, and challenges

This article discusses some of the issues relating to the promotion of Core Maths to students, parents, schools and colleges and their senior leadership teams, and also to employers and higher education (HE). Some challenges are highlighted, and addressed, with suggestions for ways forward to secure the future of Core Maths and widespread adoption by all stakeholders. A summary of the background reports that led to the introduction of Core Maths, and the related educational landscape prior to its introduction, is included.

The non-conservation of potential vorticity by a dynamical core compared with the effects of parametrized physical processes

Numerical models of the atmosphere combine a dynamical core, which approximates solutions to the adiabatic, frictionless governing equations for fluid dynamics, with tendencies arising from the parametrization of other physical processes. Since potential vorticity (PV) is conserved following fluid flow in adiabatic, frictionless circumstances, it is possible to isolate the effects of non-conservative processes by accumulating PV changes in an air-mass relative framework. This “PV tracer technique” is used to accumulate separately the effects on PV of each of the different non-conservative processes represented in a numerical model of the atmosphere. Dynamical cores are not exactly conservative because they introduce, explicitly or implicitly, some level of dissipation and adjustment of prognostic model variables which acts to modify PV. Here, the PV tracers technique is extended to diagnose the cumulative effect of the non-conservation of PV by a dynamical core and its characteristics relative to the PV modification by parametrized physical processes. Quantification using the Met Office Unified Model reveals that the magnitude of the non-conservation of PV by the dynamical core is comparable to those from physical processes. Moreover, the residual of the PV budget, when tracing the effects of the dynamical core and physical processes, is at least an order of magnitude smaller than the PV tracers associated with the most active physical processes. The implication of this work is that the non-conservation of PV by a dynamical core can be assessed in case studies with a full suite of physics parametrizations and directly compared with the PV modification by parametrized physical processes. The nonconservation of PV by the dynamical core is shown to move the position of the extratropical tropopause while the parametrized physical processes have a lesser effect at the tropopause level.

Characterisation of chicken riboflavin carrier protein gene structure and promoter regulation by estrogen

Estrogen is an important steroid hormone that mediates most of its effects on regulation of gene expression by binding to intracellular receptors. The consensus estrogen response element (ERE) is a 13 bp palindromic inverted repeat with a three nucleotide spacer. However, several reports suggest that many estrogen target genes are regulated by diverse elements, such as imperfect EREs and ERE half sites (ERE 1/2),which are either the proximal or the distal half of the palindrome. To gain more insight into ERE half site-mediated gene regulation, we used a region from the estrogen-regulated chicken riboflavin carrier protein (RCP) gene promoter that contains ERE half sites. Using moxestrol, an analogue of estrogen and transient transfection of deletion and mutation containing RCP promoter/reporter constructs in chicken hepatoma (LMH2A) cells, we identified an estrogen response unit (ERU) composed of two consensus ERE 1/2 sites and one non-consensus ERE 1/2 site. Mutation of any of these sites within this ERU abolishes moxestrol response. Further, the ERU is able to confer moxestrol responsiveness to a heterologous promoter. Interestingly, RCP promoter is regulated by moxestrol in estrogen responsive human MCF-7 cells, but not in other cell lines such as NIH3T3 and HepG2 despite estrogen receptor-alpha (ER-�) co transfection. Electrophoretic mobility shift assays (EMSAs) with promoter regions encompassing the half sites and nuclear extracts from LMH2A cells show the presence of a moxestrol-induced complex that is abolished by a polyclonal anti-ER� antibody. Surprisingly, estrogen receptor cannot bind to these promoter elements in isolation. Thus, there appears to be a definite requirement for some other factor(s) in addition to estrogen receptor, for the generation of a suitable response of this promoter to estrogen. Our studies therefore suggest a novel mechanism of gene regulation by estrogen, involving ERE half sites without direct binding of ER to the cognate elements.

Differential interaction of estrogen receptor and thyroid hormone receptor isoforms on the rat oxytocin receptor promoter leads to differences in transcriptional regulation

Both the estrogen receptor (ER) and thyroid hormone receptor (TR) are members of the nuclear receptor superfamily. Two isoforms of the ER, alpha and beta, exist. The TRalpha and beta isoforms are products of two distinct genes that are further differentially spliced to give TRalpha1 and alpha2, TRbeta1 and beta2. The TRs have been shown to interfere with ER-mediated transcription from both the consensus estrogen response element (ERE) and the rat preproenkephalin (PPE) promoter, possibly by competing with ER binding to the ERE or by squelching coactivators essential for ER-mediated transcription. The rat oxytocin receptor (OTR) gene is thought to be involved in several facets of reproductive and affiliative behaviors. 17beta-Estradiol-bound ERs upregulate the OTR gene in the ventromedial hypothalamus, a region critical for the induction of lordosis behavior in several species. We investigated the effects of the ligand-binding TR isoforms on the ER-mediated transcription from a physiological promoter of a behaviorally relevant gene such as the OTR. Only ERalpha could induce the OTR gene in two cell lines tested, the CV-1 and the SK-N-BE2C neuroblastoma cell lines. ERbeta was incapable of inducing the gene in either cell line. ERalpha is therefore not equivalent to ERbeta on this physiological promoter. Indeed, in the neural cell line, ERbeta can inhibit ERalpha-mediated induction from the OTR promoter. While the TRalpha1 isoform inhibited ERalpha-mediated induction in the neural cell line, the TRbeta1 isoform stimulated induction, thus demonstrating isoform specificity in the interaction. The use of a DNA-binding mutant, the TR P box mutant, showed that inhibition of ERalpha-mediated induction of the rat OTR gene promoter by the TRalpha1 isoform does not require DNA-binding ability. SRC-1 overexpression relieved TRalpha1-mediated inhibition in both cell lines, suggesting that squelching for coactivators is an important molecular mechanism in TRalpha-mediated inhibition. Such interactions between TR and ER isoforms on the rat OTR promoter provide a mechanism to achieve neuroendocrine integration.

Isoform specificity for oestrogen receptor and thyroid hormone receptor genes and their interactions on the NR2D gene promoter

Oestrogens are critical for the display of lordosis behaviour and, in recent years, have also been shown to be involved in synaptic plasticity. In the brain, the regulation of ionotropic glutamate receptors has consequences for excitatory neurotransmission. Oestrogen regulation of the N-methyl-d-aspartate receptor subunit 2D (NR2D) has generated considerable interest as a possible molecular mechanism by which synaptic plasticity can be modulated. Since more than one isoform of the oestrogen receptor (ER) exists in mammals, it is possible that oestrogen regulation via the ERalpha and ERbeta isoforms on the NR2D oestrogen response element (ERE) is not equivalent. In the kidney fibroblast (CV1) cell line, we show that in response to 17beta-oestradiol, only ERalpha, not ERbeta, could upregulate transcription from the ERE which is in the 3' untranslated region of the NR2D gene. When this ERE is in the 5' position, neither ERalpha nor ERbeta showed transactivation capacity. Thyroid hormone receptor (TR) modulation of ER mediated induction has been shown for other ER target genes, such as the preproenkephalin and oxytocin receptor genes. Since the various TR isoforms exhibit distinct roles, we hypothesized that TR modulation of ER induction may also be isoform specific. This is indeed the case. The TRalpha1 isoform stimulated ERalpha mediated induction from the 3'-ERE whereas the TRbeta1 isoform inhibited this induction. This study shows that isoforms of both the ER and TR have different transactivation properties. Such flexible regulation and crosstalk by nuclear receptor isoforms leads to different transcriptional outcomes and the combinatorial logic may aid neuroendocrine integration.