Evaluating environmental and ecological landscape characteristics relevant to urban resilience across gradients of land-sharing-sparing and urbanity

Within urban landscape planning, debate continues around the relative merits of land-sparing (compaction) and land-sharing (sprawl) scenarios. Using part of Greater Manchester (UK) as a case-study, we present a landscape approach to mapping green infrastructure and variation in social-ecological-environmental conditions as a function of land sparing and sharing. We do so for the landscape as a whole as well as for areas of high and low urbanity. Results imply potential trade-offs between land-sparing-sharing scenarios relevant to characteristics critical to urban resilience such as landscape connectivity and diversity, air quality, surface temperature, and access to green space. These trade-offs may be particularly complex due to the parallel influence of patch attributes such as land-cover and size and imply that both ecological restoration and spatial planning have a role to play in reconciling tensions between land-sparing and sharing strategies

The level of BMP4 signaling is critical for the regulation of distinct T-box gene expression domains and growth along the dorso-ventral axis of the optic cup

BACKGROUND: Polarised gene expression is thought to lead to the graded distribution of signaling molecules providing a patterning mechanism across the embryonic eye. Bone morphogenetic protein 4 (Bmp4) is expressed in the dorsal optic vesicle as it transforms into the optic cup. Bmp4 deletions in human and mouse result in failure of eye development, but little attempt has been made to investigate mammalian targets of BMP4 signaling. In chick, retroviral gene overexpression studies indicate that Bmp4 activates the dorsally expressed Tbx5 gene, which represses ventrally expressed cVax. It is not known whether the Tbx5 related genes, Tbx2 and Tbx3, are BMP4 targets in the mammalian retina and whether BMP4 acts at a distance from its site of expression. Although it is established that Drosophila Dpp (homologue of vertebrate Bmp4) acts as a morphogen, there is little evidence that BMP4 gradients are interpreted to create domains of BMP4 target gene expression in the mouse. RESULTS: Our data show that the level of BMP4 signaling is critical for the regulation of distinct Tbx2, Tbx3, Tbx5 and Vax2 gene expression domains along the dorso-ventral axis of the mouse optic cup. BMP4 signaling gradients were manipulated in whole mouse embryo cultures during optic cup development, by implantation of beads soaked in BMP4, or the BMP antagonist Noggin, to provide a local signaling source. Tbx2, Tbx3 and Tbx5, showed a differential response to alterations in the level of BMP4 along the entire dorso-ventral axis of the optic cup, suggesting that BMP4 acts across a distance. Increased levels of BMP4 caused expansion of Tbx2 and Tbx3, but not Tbx5, into the ventral retina and repression of the ventral marker Vax2. Conversely, Noggin abolished Tbx5 expression but only shifted Tbx2 expression dorsally. Increased levels of BMP4 signaling caused decreased proliferation, reduced retinal volume and altered the shape of the optic cup. CONCLUSION: Our findings suggest the existence of a dorsal-high, ventral-low BMP4 signaling gradient across which distinct domains of Tbx2, Tbx3, Tbx5 and Vax2 transcription factor gene expression are set up. Furthermore we show that the correct level of BMP4 signaling is critical for normal growth of the mammalian embryonic eye

Production of hybrid granitic magma at the advancing front of basaltic underplating: Inferences from the Sesia Magmatic System (south-western Alps, Italy)

The Permian Sesia Magmatic System of the southwestern Alps displays the plumbing system beneath a Permian caldera, including a deep crustal gabbroic complex, upper crustal granite plutons and a bimodal volcanic field dominated by rhyolitic tuff filling the caldera. Isotopic compositions of the deep crustal gabbro overlap those of coeval andesitic basalts, whereas granites define a distinct, more radiogenic cluster (Sri 480.708 and 0.710, respectively). AFC computations starting from the best mafic candidate for a starting melt show that Nd and Sr isotopic compositions and trace elements of andesitic basalts may be modeled by reactive bulk assimilation of 4830% of partially depleted crust and 4815%\u201330% gabbro fractionation. Trace elements of the deep crustal gabbro cumulates require a further 4860% fractionation of the andesitic basalt and loss of 4840% of silica-rich residual melt. The composition of the granite plutons is consistent with a mixture of relatively constant proportions of residual melt delivered from the gabbro and anatectic melt. Chemical and field evidence leads to a conceptual modelwhich links the production of the two granitic components to the evolution of theMafic Complex. During the growth of the Mafic Complex, progressive incorporation of packages of crustal rocks resulted in a roughly steady state rate of assimilation. Anatectic granite originates in the hot zone of melting crust located above the advancing mafic intrusion. Upward segregation of anatectic melts facilitates the assimilation of the partially depleted restite by stoping. At each cycle of mafic intrusion and incorporation, residual and anatectic melts are produced in roughly constant proportions, because the amount of anatectic melt produced at the roof is a function of volume and latent heat of crystallization of the underplated mafic melt which in turn produces proportional amounts of hybrid gabbro cumulates and residualmelt. Such a process can explain the restricted range in isotopic compositions of most rhyolitic and granitic rocks of the Permo-Carboniferous province of Europe and elsewhere

Who acquires infection from whom and how? Disentangling multi-host and multi-mode transmission dynamics in the 'elimination' era

Multi-host infectious agents challenge our abilities to understand, predict and manage disease dynamics. Within this, many infectious agents are also able to use, simultaneously or sequentially, multiple modes of transmission. Furthermore, the relative importance of different host species and modes can itself be dynamic, with potential for switches and shifts in host range and/ or transmission mode in response to changing selective pressures, such as those imposed by disease control interventions. The epidemiology of such multi-host, multi-mode infectious agents thereby can involve a multi-faceted community of definitive and intermediate/secondary hosts or vectors, often together with infectious stages in the environment, all of which may represent potential targets, as well as specific challenges, particularly where disease elimination is proposed. Here, we explore, focusing on examples fromboth human and animal pathogen systems, why and how we should aim to disentangle and quantify the relative importance of multi-host multi-mode infectious agent transmission dynamics under contrasting conditions, and ultimately, how this can be used to help achieve efficient and effective disease control. This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'

Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

<p>Abstract</p> <p>Background</p> <p>Acetaminophen-cysteine adducts (APAP-CYS) are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose.</p> <p>Methods</p> <p>Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated). Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection.</p> <p>Results</p> <p>Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD) peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20) nmol/ml, Trial 2- 0.1 (0.09) nmol/ml and Trial 3- 0.3 (0.12) nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml). No subject had detectable APAP-CYS following exposure to a non-acetaminophen hepatotoxin.</p> <p>Conclusions</p> <p>Lower concentrations of APAP-CYS are detectable after exposure to therapeutic doses of acetaminophen and higher concentrations are detected after acute acetaminophen overdose and in patients with acetaminophen toxicity following repeated exposure.</p

Evaluating environmental and ecological landscape characteristics relevant to urban resilience across gradients of land-sharing-sparing and urbanity

Within urban landscape planning, debate continues around the relative merits of land-sparing (compaction) and land-sharing (sprawl) scenarios. Using part of Greater Manchester (UK) as a case-study, we present a landscape approach to mapping green infrastructure and variation in social-ecological-environmental conditions as a function of land sparing and sharing. We do so for the landscape as a whole as well as for areas of high and low urbanity. Results imply potential trade-offs between land-sparing-sharing scenarios relevant to characteristics critical to urban resilience such as landscape connectivity and diversity, air quality, surface temperature, and access to green space. These trade-offs may be particularly complex due to the parallel influence of patch attributes such as land-cover and size and imply that both ecological restoration and spatial planning have a role to play in reconciling tensions between land-sparing and sharing strategies

Nanosatellite experiments to enable future space-based QKD missions

We present a programme for establishing the space worthiness of highly-miniaturised, polarisation-entangled, photon pair sources using CubeSat nanosatellites. Once demonstrated, the photon pair sources can be deployed on more advanced satellites that are equipped with optical links to establish a global space-based quantum key distribution network. In doing so, this work will also bring experimental tests of the overlap between quantum and relativistic regimes closer to realisation

Functional polymorphisms in the P2X7 receptor gene are associated with stress fracture injury

Context: Military recruits and elite athletes are susceptible to stress fracture injuries. Genetic predisposition has been postulated to have a role in their development. The P2X7 receptor (P2X7R) gene, a key regulator of bone remodelling, is a genetic candidate that may contribute to stress fracture predisposition. Objective: To evaluate the putative contribution of P2X7R to stress fracture injury in two separate cohorts, military personnel and elite athletes. Methods: In 210 Israeli Defence Forces (IDF) military conscripts, stress fracture injury was diagnosed (n=43) based on symptoms and a positive bone scan. In a separate cohort of 518 elite athletes, self-reported medical imaging scan-certified stress fracture injuries were recorded (n=125). Non-stress fracture controls were identified from these cohorts who had a normal bone scan or no history or symptoms of stress fracture injury. Study participants were genotyped for functional SNPs within the P2X7R gene using proprietary fluorescence-based competitive allele-specific PCR assay. Pearson Chi-square (χ2) tests, corrected for multiple comparisons, were used to assess associations in genotype frequencies. Results: The variant allele of P2X7R SNP rs3751143 (Glu496Ala- loss of function) was associated with stress fracture injury, while the variant allele of rs1718119 (Ala348Thr- gain of function) was associated with a reduced occurrence of stress fracture injury in military conscripts (P<0.05). The association of the variant allele of rs3751143 with stress fractures was replicated in elite athletes (P<0.05), whereas the variant allele of rs1718119 was also associated with reduced multiple stress fracture cases in elite athletes (P<0.05). Conclusions: The association between independent P2X7R polymorphisms with stress fracture prevalence supports the role of a genetic predisposition in the development of stress fracture injury