Permian scorpions from the Petrified Forest of Chemnitz, Germany

Background: Paleozoic scorpions (Arachnida: Scorpiones) have been widely documented from the Carboniferous Period; which hosts a remarkable assemblage of more than sixty species including both putative stem- and crown-group fossils. By contrast the succeeding Permian Period is almost completely devoid of records, which are currently restricted to a trace fossil from the early Permian of New Mexico, USA and some limb fragments from the late Permian of the Vologda Region, Russia. Results: ?Opsieobuthus tungeri sp. nov. from the Petrified Forest of Chemnitz, Germany represents the first complete body fossils of scorpions from the Permian. Explosive volcanism preserved these remarkable specimens in situ as part of the palaeosol horizon and bedrock of the Petrified Forest, immediately beneath the Zeisigwald tuff horizon. This dates to the early Permian (Sakmarian) or ca. 291 Ma. Intriguingly, the specimens were obtained from a palaeosol horizon with a compacted network of different-sized woody roots and thus have been preserved in situ in their likely life position, even within their original burrows. Differences in the structure of the comb-like pectines in the two fossils offer evidence for sexual dimorphism, and permit further inferences about the ecology and perhaps even the reproductive biology of these animals. Conclusions: As putative members of a Coal Measures genus, these fossils suggest that at least some Carboniferous scorpion lineages extended their range further into the Permian. This contributes towards a picture of scorpion evolution in which both basal and derived (orthostern) forms coexisted for quite some time; probably from the end of the Carboniferous through to at least the mid Triassic

Overexpression of CD97 in Intestinal Epithelial Cells of Transgenic Mice Attenuates Colitis by Strengthening Adherens Junctions

The adhesion G-protein-coupled receptor CD97 is present in normal colonic enterocytes but overexpressed in colorectal carcinoma. To investigate the function of CD97 in colorectal carcinogenesis, transgenic Tg(villin-CD97) mice overexpressing CD97 in enterocytes were generated and subjected to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated tumorigenesis. Unexpectedly, we found a CD97 cDNA copy number-dependent reduction of DSS-induced colitis in Tg compared to wild-type (WT) mice that was confirmed by applying a simple DSS protocol. Ultrastructural analysis revealed that overexpression of CD97 strengthened lateral cell-cell contacts between enterocytes, which, in contrast, were weakened in CD97 knockout (Ko) mice. Transepithelial resistance was not altered in Tg and Ko mice, indicating that tight junctions were not affected. In Tg murine and normal human colonic enterocytes as well as in colorectal cell lines CD97 was localized preferentially in E-cadherin-based adherens junctions. CD97 overexpression upregulated membrane-bound but not cytoplasmic or nuclear β-catenin and reduced phospho-β-catenin, labeled for degradation. This was associated with inactivation of glycogen synthase kinase-3β (GSK-3β) and activation of Akt. In summary, CD97 increases the structural integrity of enterocytic adherens junctions by increasing and stabilizing junctional β-catenin, thereby regulating intestinal epithelial strength and attenuating experimental colitis

SNAI1 expression and the mesenchymal phenotype: an immunohistochemical study performed on 46 cases of oral squamous cell carcinoma

Abstract Background SNAI1 can initiate epithelial-mesenchymal transition (EMT), leading to loss of epithelial characteristics and, in cancer, to invasion and metastasis. We hypothesized that SNAI1 reactivation occurs in oral squamous cell carcinoma (OSCC) where it might also be associated with focal adhesion kinase (FAK) expression and p63 loss. Methods Immunohistochemistry was performed on 46 tumors and 26 corresponding lymph node metastases. Full tissue sections were examined to account for rare and focal expression. Clinical outcome data were collected and analyzed. Results SNAI1-positivity (nuclear, ≥ 5% tumor cells) was observed in 10 tumors and 5 metastases (n = 12 patients). Individual SNAI1(+) tumor cells were seen in primary tumors of 30 patients. High level SNAI1 expression (>10% tumor cells) was rare, but significantly associated with poor outcome. Two cases displayed a sarcomatoid component as part of the primary tumor with SNAI1(+)/FAK(+)/E-cadherin(-)/p63(-) phenotype, but disparate phenotypes in corresponding metastases. All cases had variable SNAI1(+) stroma. A mesenchymal-like immunoprofile in primary tumors characterized by E-cadherin loss (n = 29, 63%) or high cytoplasmic FAK expression (n = 10, 22%) was associated with N(+) status and tumor recurrence/new primary, respectively. Conclusions SNAI1 is expressed, although at low levels, in a substantial proportion of OSCC. High levels of SNAI1 may herald a poor prognosis and circumscribed SNAI1 expression can indicate the presence of a sarcomatoid component. Absence of p63 in this context does not exclude squamous tumor origin. Additional EMT inducers may contribute to a mesenchymal-like phenotype and OSCC progression

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

The seeds of divergence: the economy of French North America, 1688 to 1760

Generally, Canada has been ignored in the literature on the colonial origins of divergence with most of the attention going to the United States. Late nineteenth century estimates of income per capita show that Canada was relatively poorer than the United States and that within Canada, the French and Catholic population of Quebec was considerably poorer. Was this gap long standing? Some evidence has been advanced for earlier periods, but it is quite limited and not well-suited for comparison with other societies. This thesis aims to contribute both to Canadian economic history and to comparative work on inequality across nations during the early modern period. With the use of novel prices and wages from Quebec—which was then the largest settlement in Canada and under French rule—a price index, a series of real wages and a measurement of Gross Domestic Product (GDP) are constructed. They are used to shed light both on the course of economic development until the French were defeated by the British in 1760 and on standards of living in that colony relative to the mother country, France, as well as the American colonies. The work is divided into three components. The first component relates to the construction of a price index. The absence of such an index has been a thorn in the side of Canadian historians as it has limited the ability of historians to obtain real values of wages, output and living standards. This index shows that prices did not follow any trend and remained at a stable level. However, there were episodes of wide swings—mostly due to wars and the monetary experiment of playing card money. The creation of this index lays the foundation of the next component. The second component constructs a standardized real wage series in the form of welfare ratios (a consumption basket divided by nominal wage rate multiplied by length of work year) to compare Canada with France, England and Colonial America. Two measures are derived. The first relies on a “bare bones” definition of consumption with a large share of land-intensive goods. This measure indicates that Canada was poorer than England and Colonial America and not appreciably richer than France. However, this measure overestimates the relative position of Canada to the Old World because of the strong presence of land-intensive goods. A second measure is created using a “respectable” definition of consumption in which the basket includes a larger share of manufactured goods and capital-intensive goods. This second basket better reflects differences in living standards since the abundance of land in Canada (and Colonial America) made it easy to achieve bare subsistence, but the scarcity of capital and skilled labor made the consumption of luxuries and manufactured goods (clothing, lighting, imported goods) highly expensive. With this measure, the advantage of New France over France evaporates and turns slightly negative. In comparison with Britain and Colonial America, the gap widens appreciably. This element is the most important for future research. By showing a reversal because of a shift to a different type of basket, it shows that Old World and New World comparisons are very sensitive to how we measure the cost of living. Furthermore, there are no sustained improvements in living standards over the period regardless of the measure used. Gaps in living standards observed later in the nineteenth century existed as far back as the seventeenth century. In a wider American perspective that includes the Spanish colonies, Canada fares better. The third component computes a new series for Gross Domestic Product (GDP). This is to avoid problems associated with using real wages in the form of welfare ratios which assume a constant labor supply. This assumption is hard to defend in the case of Colonial Canada as there were many signs of increasing industriousness during the eighteenth and nineteenth centuries. The GDP series suggest no long-run trend in living standards (from 1688 to circa 1765). The long peace era of 1713 to 1740 was marked by modest economic growth which offset a steady decline that had started in 1688, but by 1760 (as a result of constant warfare) living standards had sunk below their 1688 levels. These developments are accompanied by observations that suggest that other indicators of living standard declined. The flat-lining of incomes is accompanied by substantial increases in the amount of time worked, rising mortality and rising infant mortality. In addition, comparisons of incomes with the American colonies confirm the results obtained with wages— Canada was considerably poorer. At the end, a long conclusion is provides an exploratory discussion of why Canada would have diverged early on. In structural terms, it is argued that the French colony was plagued by the problem of a small population which prohibited the existence of scale effects. In combination with the fact that it was dispersed throughout the territory, the small population of New France limited the scope for specialization and economies of scale. However, this problem was in part created, and in part aggravated, by institutional factors like seigneurial tenure. The colonial origins of French America’s divergence from the rest of North America are thus partly institutional

Evolution of reproductive strategies in dictyopteran insects—clues from ovipositor morphology of extinct roachoids

Dictyoptera, which comprises cockroaches, termites and mantids, is a quite successful group of insects in evolutionary terms with a long fossil record—roachoid insects were already abundant 315 million years ago in the Carboniferous forests. One of the most remarkable autapomorphies of extant dictyopterans, and possibly a major factor for their persisting success, is the ability to produce oothecae. Despite the robustness of this sort of egg package, fossils of oothecae are very rare, the oldest direct evidences being from the Cretaceous Crato Formation in Brazil (115 mya). The ability to produce oothecae is presumably linked to a specific ovipositor morphology, including a significant length reduction. Hence, ovipositor morphology can indirectly inform about the reproductive strategy of a species. Herein we describe the ovipositor morphology of various fossil forms of dictyopteran insects. Early fossil roachoids, in contrast to the modern forms, possessed a very long and prominent ovipositor, reminiscent of the ovipositor in orthopterans (Ensifera), indicating that these forms laid individual, rather small eggs into a substrate. We present examples from different fossil deposits, which show the entire range of ovipositor morphologies, from very long forms over forms with ovipositors partly reduced in length to modern-appearing morphologies. Most remarkably, different shapes of ovipositors seem to be present in roachoids in the fauna of the 115 million years old Crato Formation—species with long prominent ovipositors co-existed with species with a reduced short and broad ovipositor. Additionally, females that carry oothecae attached to their abdomen indicate a third type of ovipositor: a further reduced ovipositor as seen in modern forms, which already allowed the internal production of oothecae

Ichnotaxonomy and trackmaker assignment of tetrapod tracks and swimming traces from the Middle Permian Hornburg Formation of Saxony-Anhalt (Germany)

Here we describe new material of tetrapod tracks and swimming traces from the Konberg quarry, a tracksite of the late middle Permian Hornburg Formation in Saxony-Anhalt, central Germany. A relatively well-preserved trackway and several isolated imprints are assigned to Capitosauroides isp. Among others, toe proportions in the manus and pes footprints of the newly described specimens and the long, proximal and detached pedal digit V imprint are similar to the type ichnospecies Capitosauroides bernburgensis from the Early Triassic of Bernburg, Saxony-Anhalt. In these features the new Konberg material differs from other ichnotaxa, such as Amphisauropus and Varanopus, which may look similar in their relative length of the sole, digit proportions and/or in the digit tip imprint morphology. The comparatively large manus imprint, which is wider than long, the relative length and shape of the sole impression, the digit proportions that are indicative for a more ectaxonic manus a more mesaxonic pes, the low pace angulation and the low imprint-size-normalized stride length in the Konberg track type are distinct from C. bernburgensis. It shares, however, a certain similarity with recently described material of Capitosauroides from middle-late Permian tracksites. These observations are in agreement with the results of a multivariate analysis including Capitosauroides and morphologically similar ichnotaxa. Our findings would justify the erection of a new ichnospecies if more trackways with a similar or slightly better preservation were at hand. Hornburg Formation material previously assigned to Amphisauropus is herein considered as indetermined tetrapod tracks, whereas the oc-currence of Dromopus isp. is confirmed. This reassignment shortens the stratigraphic range of the ichnogenus Amphisauropus,which appears to be restricted to the early Permian, since younger occurrences are questionable. In agreement with the attribution of Capitosauroides to eutheriodont producers, we regard the Konberg material assigned to this ichnogenus as tracks of small and possibly semi-aquatic therapsids. Abundant tetrapod swimming traces that co-occur with Capitosauroides isp. on the same bedding planes are interpreted as having been made by the same group of producers. The subaquatic traces often consist of short parallel claw mark sets. In agreement with a derived amniote producer group, they indicate propulsion by parasagittal limb movement rather than axial undulation

Improved blattoid insect and conchostracan zonation for the Late Carboniferous, Pennsylvanian, of Euramerica

For the biostratigraphy of mixed continental-marine and purely continental sections in the palaeotropical belt of Euramerica, 9 insect and 8 conchostracan zones are newly defined or improved. These zones encompass the time interval from the Early Pennsylvanian (middle Bashkirian) up into the early Permian (early Asselian) of the Euramercian biotic province. They are linked as much as possible to the marine Standard Global Chronostrigraphic Scale by common occurrences of insects and/or conchostracans with conodonts in mixed marine-continental sections as well as by the thus far available and reliable radioisotopic ages of associated volcanic rocks. This insect and conchostracan zonation is an alternative tool to the well-established macro-plant biostratigraphy of the Pennsylvanian. In contrast to the latter, only single specimens of insects or conchostracans, even if more rare than plant remains, allow biostratigraphic dating with a similar high temporal resolution

An Image Mapping Approach to U-Pb LA-ICP-MS Carbonate Dating and Applications to Direct Dating of Carbonate Sedimentation

We present a new approach to laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) U‐Pb dating of carbonates based on selection and pooling of pixels from 2‐D elemental and isotopic ratio maps. This image mapping technique is particularly useful for targeting subdomains in samples with complex geological histories. Key major and trace elements that are sensitive to detrital components, postformational fluid ingress, mineralogical changes, or diagenetic overprinting are measured along with the Pb and U isotopic data. Laser sampling is undertaken along successive linear rasters that are compiled into maps using the Monocle add‐on for Iolite, with one pixel in the map corresponding to one time slice of the time‐resolved signal. These element, element ratio, and isotope ratio maps can be overlain over photomicrographs or scanning electron microscopy images to spatially link compositional data to textural and structural features. The pixels corresponding to likely homogeneous age domains can be isolated by applying appropriate selection criteria (e.g., Th < 0.3 ppm, Mg/Ca < 0.004) and pooled into pseudo‐analyses using a proxy for the parent/daughter ratio (e.g., 207Pb/235U, 238U/208Pb) to retrieve the largest possible spread of the data points on isochron diagrams. The approach is best suited for analytical setups capable of rapidly or simultaneously scanning over a large mass range and can yield a precision of ±1% or better on quadrupole instruments depending on U concentration, 238U/204Pb, and age of the sample. The sample‐specific filtering criteria for selection and rejection of data and their rationale can be reported, resulting in more transparency with regard to data processing