ABCB1 and ABCG2 work together at the blood–brain barrier (BBB) to limit brain distribution of dual ABCB1/ABCG2 substrates. In this pilot study we used positron emission tomography (PET) to assess ...brain distribution of two model ABCB1/ABCG2 substrates (11Celacridar and 11Ctariquidar) in healthy subjects without (c.421CC) or with (c.421CA) the ABCG2 single‐nucleotide polymorphism (SNP) c.421C>A. Subjects underwent PET scans under conditions when ABCB1 and ABCG2 were functional and during ABCB1 inhibition with high‐dose tariquidar. In contrast to the ABCB1‐selective substrate (R)‐11Cverapamil, 11Celacridar and 11Ctariquidar showed only moderate increases in brain distribution during ABCB1 inhibition. This provides evidence for a functional interplay between ABCB1 and ABCG2 at the human BBB and suggests that both ABCB1 and ABCG2 need to be inhibited to achieve substantial increases in brain distribution of dual ABCB1/ABCG2 substrates. During ABCB1 inhibition c.421CA subjects had significantly higher increases in 11Ctariquidar brain distribution than c.421CC subjects, pointing to impaired cerebral ABCG2 function.
Putative Late Ordovician land Plants Salamon, Mariusz A.; Gerrienne, Philippe; Steemans, Philippe ...
New phytologist,
June 2018, Letnik:
218, Številka:
4
Journal Article, Web Resource
Recenzirano
Odprti dostop
The colonization of early terrestrial ecosystems by embryophytes (i.e. land plants) irreversibly changed global biogeochemical cycles (Berner & Kothavala, 2001; Berner et al., 2007; Song et al., ...2012). However, when and how the process of plant terrestrialization took place is still intensely debated (Kenrick & Crane, 1997; Kenrick et al., 2012; Edwards et al., 2014; Edwards & Kenrick, 2015). Current knowledge suggests that the earliest land plants evolved from charophycean green algae (Karol et al., 2001) most probably during Early-Middle Ordovician times (Rubinstein et al., 2010; and references cited therein). They were represented by small nonvascular bryophyte-like organisms (Edwards & Wellman, 2001; Wellman et al., 2003; Kenrick et al., 2012). The oldest fossil evidence from dispersed spores of presumable bryophytic nature is known from a Middle Ordovician locality (c. 470 million years ago (Ma), Rubinstein et al., 2010; Fig. 1) from Argentina (Gondwana palaeocontinent). The dispersed spore fossil record also suggests that the first radiation of vascular plants probably occurred during Late Ordovician times (c. 450 Ma, Steemans et al., 2009). However, unequivocal macrofossils of vascular plants appear much later, during mid-Silurian (c. 430 Ma, Edwards et al., 1992). This macrofossil evidence comes from the fossil-genus Cooksonia, an early polysporangiophyte (i.e. a plant with bifurcating axes and more than one sporangium), which is considered the earliest vascular land plant (Edwards et al., 1992; Fig. 1). Further advances in knowledge about the origin and early dispersion of polysporangiophytes are needed for a better understanding of the initial plant diversification. Unfortunately, unravelling the initial steps of polysporangiophyte evolution is hindered by gaps in the fossil record of the earliest plants as well as by limitations of inference based on molecular clocks (Kenrick et al., 2012; Edwards & Kenrick, 2015).
Abstract The predation-driven Mesozoic marine revolution (MMR) is believed to have induced a dramatic change in the bathymetric distribution of many shallow marine invertebrates since the late ...Mesozoic. For instance, stalked crinoids – isocrinids (Isocrinida) have undergone a striking decline in shallow-sea environments and today they are restricted to deep-sea settings (below 100 m depth). However, the timing and synchronicity of this shift are a matter of debate. A delayed onset of MMR and/or shifts to a retrograde, low-predation community structure during the Paleogene in the Southern Ocean were invoked. In particular, recent data from the Southern Hemisphere suggest that the environmental restriction of isocrinids to the deep-sea settings may have occurred at the end of the Eocene around Antarctica and Australia, and later in the early Miocene in New Zealand. Here, we report the anomalous occurrence of the isocrinids in shallow nearshore marine facies from the middle Miocene of Poland (Northern Hemisphere, Central Paratethys). Thus, globally, this is the youngest record of shallow-sea stalked crinoids. This finding suggests that some relict stalked crinoids may have been able to live in the shallow-water environments by the middle Miocene, and further confirms that the depth restriction of isocrinids to offshore environments was not synchronous on a global scale.
Despite a wide array of published actualistic studies on echinoderm taphonomy the detailed pattern of decay and disarticulation of their skeletons is still not well understood. Here we provide ...results of tumbling experiments using a rotating barrel filled with artificial seawater and medium-sized quartz sand to mimic physical forces experienced by echinoderms during transportation in high-energy conditions. In particular, we determined semi-quantitatively transportation-induced rates and patterns of damage and disintegration of freshly killed ophiuroid, asteroid and crinoid skeletons that were not allowed to decay initially. Our experiments showed that echinoderm specimens disintegrated in a characteristic sequence toward an increase of the degree of disarticulation, abrasion and roundness or thinness of echinoderm ossicles. The sequence of disintegration in crinoids began with the partial disintegration of distal arms after 2h (a time equivalent to ~1km of transport). The initial split of ophiuroid and asteroid arms and crinoid cirri occurred after 24h (~12km) and complete destruction of the asteroid mouth and ophiuroid disk area occurred after 72h (~36km). The duration of transport necessary to promote initial fragmentation in asteroid and ophiuroid arms and crinoid cirri into isolated ossicles was 120h (~60km). The complete disarticulation of crinoid, ophiuroid and asteroid arms and crinoid cirri occurred after 312h (~156km) and 408h (~204km), respectively. Although it has been argued that the quality of preservation can be a poor index of post-mortem transport, echinoderms allowed limited initial decay in the presence of rapid and relatively constant physical disturbance, an approximation of the distance of transport can be made.
Our data demonstrate that articulated ossicles can remain for several days, sufficient time for long (even a few hundredkm) transportation. This finding illustrates that articulated echinoderm remains do not necessarily imply low energy and highlights the importance of a reliable discrimination of autochthonous and allochthonous components of fossil echinoderm assemblages. Application of, in particular, isolated fossil echinoderm ossicles in e.g. paleoenvironmental and paleoecological reconstructions may lead to serious misinterpretations and should be supplemented by observations of abrasion traces.
•Patterns of damage and disintegration of echinoderm skeleton were determined.•Echinoderm skeletons can withstand considerable physical disturbance and transport.•Care has to be taken when using articulated ossicles in paleoenvironmental studies.
Crinoids were among the most abundant marine benthic animals throughout the Palaeozoic, but their body size evolution has received little attention. Here, we compiled a comprehensive database on ...crinoid calyx biovolumes throughout the Palaeozoic. A model comparison approach revealed contrasting and complex patterns in body size dynamics between the two major crinoid clades (Camerata and Pentacrinoidea). Interestingly, two major drops in mean body size at around two mass extinction events (during the late Ordovician and the late Devonian respectively) are observed, which is reminiscent of current patterns of shrinking body size of a wide range of organisms as a result of climate change. The context of some trends (marked declines during extinctions) suggests the cardinal role of abiotic factors (dramatic climate change associated with extinctions) on crinoid body size evolution; however, other patterns (two intervals with either relative stability or steady size increase in periods between mass extinctions) are more consistent with biotic drivers.
Background
The disease phase in localized scleroderma (LoS) is commonly assessed by clinical investigation using the LoS cutaneous assessment tool (LoSCAT). There is a need for more objective methods ...for assessing the degree of activity/inflammation in LoS. The aim of our work was to evaluate the correlation between severity of the LoS lesions scored using LoSCAT and the degree of hyperthermia observed with infrared thermography (IRT).
Materials and methods
The LoS lesions were examined using the LoSCAT and IRT independently by two examiners. The average temperature (Tavg) of the LoS lesional dermis were measured in the area of each lesion with the highest score for erythema (ER), skin thickness (ST), dermal atrophy (DAT) and subcutaneous atrophy (SAT). Measurements were compared to the contralateral healthy skin. The difference of the Tavg (ΔTavg) was calculated between each lesion and its normal control.
Results
One hundred and four LoS lesions were examined in 40 adults. Thirty‐one lesions were erythematous, 26 were sclerotic, 35 presented as atrophy of the dermis and 11 as atrophy of the subcutaneous tissue. The sensitivity and specificity of IRT for detecting activity/inflammation were 80.7% and 86.3%, respectively. The positive predictive value was 71%, negative predictive value 91%. Statistically significant positive correlation was found between the ΔTavg and the clinical ER and DAT scores.
Conclusion
IRT may be a useful method for assessing erythematous LoS lesions and quantifying the degree of activity/inflammation. Knowing the patient, false positive results attributable to more severe degree of skin and subcutaneous fat atrophy can be easily recognized.
A rich assemblage of various types of bromalites from the lower Carnian "Konservat-Lagerstätte" from the Reingraben Shales in Polzberg (Northern Calcareous Alps, Lower Austria) is described for the ...first time in detail. They comprise large regurgitalites consisting of numerous entire shells of ammonoid Austrotrachyceras or their fragments and rare teuthid arm hooks, and buccal cartilage of Phragmoteuthis. Small coprolites composed mainly of fish remains were also found. The size, shape and co-occurrence with vertebrate skeletal remains imply that regurgitalites were likely produced by large durophagous fish (most likely by cartilaginous fish Acrodus). Coprolites, in turn, were likely produced by medium-sized piscivorous actinopterygians. Our findings are consistent with other lines of evidence suggesting that durophagous predation has been intense during the Triassic and that the so-called Mesozoic marine revolution has already started in the early Mesozoic.
Localized scleroderma (LoS) is a rare inflammatory skin disorder that affects the dermis and sometimes subcutaneous tissues. LoS can have very long periods of quiescence followed by reactivation, but ...the progression or activity of the disease is difficult to measure. To review the measuring tools used for the evaluation of LoS activity, to choose the most appropriate technique to facilitate progress towards properly assessing the disease, a systematic review of the literature was carried out using the PubMed MEDLINE. Sixty‐three studies describing groups of children, adults or both were reviewed and included in the analysis. Case reports were excluded. The analysed papers were published between June 1986 and February 2016. Data were extracted with a focus on instruments measuring the clinical signs of LoS, health‐related quality of life (HRQoL), laboratory tests and imaging techniques. Perusal of the literature confirmed that clinical characteristics of the lesions were used to identify activity and scoring systems that focused on a series of signs, and were initially validated in cases of childhood‐onset disease; however, there were no data concerning the adult‐onset form of the disease. Adult patients with LoS scored lower on HDLQI than those with paediatric‐onset LoS. No validated biological markers were available as correlative laboratory parameters of LoS activity. For infrared thermography, ultrasound and other imaging techniques, the features of active lesions were described, but were only useful with appropriate clinical correlation. Measuring tools have not been prospectively validated yet. Summarizing, scoring methods seem to provide the most adequate assessment of LoS and deserve to be further investigated. Combined imaging techniques create optimal conditions for the proper interpretation of the temperature at the skin surface, as well as the structure and vascularity of LoS lesions. Additional scores, musculoskeletal or neuroimaging techniques and laboratory parameters are needed for the specific disease subtypes to monitor extracutaneous manifestations.
Sea urchins are a major component of recent marine communities where they exert a key role as grazers and benthic predators. However, their impact on past marine organisms, such as crinoids, is hard ...to infer in the fossil record. Analysis of bite mark frequencies on crinoid columnals and comprehensive genus-level diversity data provide unique insights into the importance of sea urchin predation through geologic time. These data show that over the Mesozoic, predation intensity on crinoids, as measured by bite mark frequencies on columnals, changed in step with diversity of sea urchins. Moreover, Mesozoic diversity changes in the predatory sea urchins show a positive correlation with diversity of motile crinoids and a negative correlation with diversity of sessile crinoids, consistent with a crinoid motility representing an effective escape strategy. We contend that the Mesozoic diversity history of crinoids likely represents a macroevolutionary response to changes in sea urchin predation pressure and that it may have set the stage for the recent pattern of crinoid diversity in which motile forms greatly predominate and sessile forms are restricted to deep-water refugia.
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