bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal and annual fluctuations of deer populations estimated by a Bayesian state–space model
Authors: Mizuki Inoue , Itô Hiroki , Yamasaki Michimasa , Fukumoto Shigeru , Okamoto Yuuki , Katsuki Masaya , Fukushima Keitaro , Sakai Masaru , Sakaguchi Shota , Fujiki Daisuke , Nakagawa Hikaru , Ishihara Masae , Takayanagi Atsushi
Published: November 2019

Deer overabundance is a contributing factor in the degradation of plant communities and ecosystems worldwide. The management and conservation of the deer-affected ecosystems requires us to urgently grasp deer population trends and to identify the factors that affect them. In this study, we developed a Bayesian state–space model to estimate the population dynamics of sika deer (Cervus nippon) in a cool-temperate forest in Japan, where wolves (Canis lupus hodophilax) are extinct. The model was based on field data collected from block count surveys, road count surveys by vehicles, mortality surveys during the winter, and nuisance control for 12 years (2007–2018). We clarified the seasonal and annual fluctuation of the deer population. We found two peaks of deer abundance (2007 and 2010) over 12 years. In 2011 the estimated deer abundance decreased drastically and has remained at a low level then. The deer population increased from spring to autumn and decreased from autumn to winter in most years. The seasonal fluctuation we detected could reflect the seasonal migration pattern of deer and the population recruitment through fawn births in early summer. In our model, snowfall accumulation, which can be a lethal factor for deer, may have slightly affected their mortality during the winter. Although we could not detect a direct effect of snow on population dynamics, snowfall decrease due to global warming may decelerate the winter migration of deer; subsequently, deer staying on-site may intensively forage evergreen perennial plants during the winter season. The nuisance control affected population dynamics. Even in wildlife protection areas and national parks where hunting is regulated, nuisance control could be effective in buffering the effect of deer browsing on forest ecosystems.
Real-time measurement of E2:ERα transcriptional activity in living cells
Authors: Cipolletti Manuela , Leone Stefano , Bartoloni Stefania , Busonero Claudia , Acconcia Filippo
Published: November 2019

Kinetic analyses of diverse physiological processes have the potential to unveil new aspects of the molecular regulation of cell biology at temporal levels. 17β-estradiol (E2) regulates diverse physiological effects by binding to the estrogen receptor α (ERα), which primarily works as a transcription factor. Although many molecular details of the modulation of ERα transcriptional activity have been discovered including the impact of receptor plasma membrane localization and its relative E2-evoked signalling, the knowledge of real-time ERα transcriptional dynamics in living cells is lacking. Here, we report the generation of MCF-7 and HeLa cells stably expressing a modified luciferase under the control of an E2-sensitive promoter, which activity can be continuously monitored in living cells and show that E2 induces a linear increase in ERα transcriptional activity. Ligand-independent (e.g., epidermal growth factor) receptor activation was also detected in a time-dependent manner. Kinetic profiles of ERα transcriptional activity measured in the presence of both receptor antagonists and inhibitors of ERα plasma membrane localization reveals a biphasic dynamic of receptor behaviour underlying novel aspects of receptor-regulated transcriptional effects. Finally, analysis of the rate of the dose-dependent E2 induction of ERα transcriptional activity demonstrates that low doses of E2 induce an effect identical to that determined by high concentrations of E2 as a function of the duration of hormone administration. Overall, we present the characterization of sensitive stable cell lines where to study the kinetic of E2 transcriptional signaling and to identify new aspects of ERα function in different physiological or pathophysiological conditions.
Introduced species dominate different responses of grassland communities to climate change on serpentine and nonserpentine soils
Authors: Braasch Joseph E , Johnson Maria A , Harrison Susan P , Dlugosch Katrina M
Published: November 2019

Introduced species are a common feature of modern plant communities and experience environmental challenges alongside native species. Changes to the environment may reveal distinct species-environment relationships for native and introduced components of plant communities. Extreme environmental change, such as drought, is predicted to result in declines in native species and increased opportunities for invasion, but empirical support for these ideas remains mixed. We tested for differences in the response of native and invaded species to environmental changes by analyzing a longterm dataset of species abundance in California grasslands collected during a period of severe drought. Sampling sites included a combination of stressful serpentine soils, which are resilient against invasion and maintain diverse native species assemblages, and more benign nonserpentine soils, which are heavily invaded and harbor low levels of native species cover. We found a significant correlation between sampling year and species composition for nonserpentine sites, but not for serpentine sites. These patterns were repeated when only introduced species were included in the analysis but no pattern of change was found for native species. The species most strongly associated with directional change on nonserpentine soils were three invasive Eurasian grasses, Bromus hordaceus, Taeniatherium caput-medusae, and Avena fatua. Differences in species composition on both serpentine and nonserpentine soils were significantly correlated with specific leaf area, a trait which has been linked to drought tolerance in these communities, although changes in abundance for the three Eurasian grasses most strongly associated with change did not consistently follow this pattern. Our analyses indicate relatively stable native community composition and strong directional change in introduced species composition, contradicting predictions for how native and introduced species will respond to environmental shifts, but supporting the hypothesis that native and invading species groups have important functional differences that shape their relationships to the environment.
The conserved and divergent roles of Prdm3 and Prdm16 in zebrafish and mouse craniofacial development
Authors: Shull Lomeli , Sen Rwik , Menzel Johannes , Artinger Kristin Bruk
Published: November 2019

The formation of the craniofacial skeleton is a highly dynamic process that requires proper orchestration of various cellular processes in cranial neural crest cell (cNCC) development, including cell migration, proliferation, differentiation, polarity and cell death. Alterations that occur during cNCC development result in congenital birth defects and craniofacial abnormalities such as cleft lip with or without cleft palate. While the gene regulatory networks facilitating neural crest development have been extensively studied, the epigenetic mechanisms by which these pathways are activated or repressed in a temporal and spatially regulated manner remain largely unknown. Chromatin modifers can precisely modify gene expression through a variety of mechanisms including histone modifications such as methylation. Here, we investigated the role of two members of the PRDM (Positive regulatory domain) histone methyltransferase family, Prdm3 and Prdm16 in craniofacial development using genetic models in zebrafish and mice. Loss of prdm3 or prdm16 in zebrafish causes craniofacial defects including hypoplasia of the craniofacial cartilage elements, undefined posterior ceratobranchials, and decreased mineralization of the parasphenoid. In mice, while conditional loss of Prdm3 in the early embryo proper causes mid-gestation lethality, loss of Prdm16 caused craniofacial defects including anterior mandibular hypoplasia, clefting in the secondary palate and severe middle ear defects. In zebrafish, prdm3 and prdm16 compensate for each other as well as a third Prdm family member, prdm1a. Combinatorial loss of prdm1a, prdm3, and prdm16 alleles results in severe hypoplasia of the anterior cartilage elements, abnormal formation of the jaw joint, complete loss of the posterior ceratobranchials, and clefting of the ethmoid plate. We further determined that loss of prdm3 and prdm16 reduces methylation of histone 3 lysine 9 (repression) and histone 3 lysine 4 (activation) in zebrafish. In mice, loss of Prdm16 significantly decreased histone 3 lysine 9 methylation in the palatal shelves but surprisingly did not change histone 3 lysine 4 methylation. Taken together, Prdm3 and Prdm16 play an important role in craniofacial development by maintaining temporal and spatial regulation of gene regulatory networks necessary for proper cNCC development and these functions are both conserved and divergent across vertebrates.
Inhibition of both mutant and wild-type RAS-GTP in KRAS G12C colorectal cancer through cotreatment with G12C and EGFR inhibitors
Authors: McFall Thomas , Trogdon Michael , Sisk-Hackworth Laura , Stites Edward C.
Published: November 2019

The combination of KRAS G12C inhibitors with EGFR inhibitors has reproducibly been shown to be beneficial. Here, we reveal a new benefit of this combination: it effectively inhibits both wild-type and mutant RAS. A role for WT RAS inhibition has not previously been reported for this important combination of targeted therapies. We believe that targeting both mutant and wild-type RAS helps explain why this combination of inhibitors is effective.
MiR‐29c protects against inflammation and apoptosis in Parkinson's disease model in vivo and in vitro by targeting SP1
Authors: Wang Ruili , Yang Ying , Wang Hui , He Ya , Li Chen
Published: November 2019

MicroRNAs (miRNAs) have been shown to have complicated implications in the pathogenesis of Parkinson's disease (PD). However, the role of miR‐29c and the underlying mechanism in the development of PD remain not well understood. In this work, the MPTP‐treated mice or MPP+‐intoxicated SH‐SY5Y cells were established as an in vivo or in vitro PD model. Then the specific agomir of miR‐29c was employed to examine its biological function on PD progress. We found that miR‐29c was down‐expressed but SP1 was high‐expressed in substantia nigra pars compacta (SNpc) of MPTP‐induced PD mice. Overexpression of miR‐29c attenuated dopaminergic neuron loss and α‐synuclein accumulation in SNpc of PD mice. Furthermore, the increments of pro‐inflammatory cytokines (TNF‐α, IL‐1β and IL‐6) and TUNEL‐positive apoptotic cells in MPTP‐treated mice were ameliorated by miR‐29c. Similarly, in SH‐SY5Y cell models of PD, we also found that miR‐29c inhibited inflammatory cytokine production, reduced apoptotic rate and suppressed pro‐apoptotic regulator activity. In addition, the increased expression of SP1 in PD models was found to be inhibited by miR‐29c. Luciferase reporter assay confirmed that SP1 was complementary with miR‐29c. Knockdown of SP1 with siRNA restored α‐synuclein accumulation, inflammation and apoptosis in MPP+‐induced SH‐SY5Y cells. Collectively, this current work presents that miR‐29c may directly target SP1 to protect against the neuroinflammatory and apoptotic responses in PD, providing a potential biomarker for PD diagnosis and treatment.
The loss of NMDAR‐dependent LTD following cannabinoid self‐administration is restored by positive allosteric modulation of CB1 receptors
Authors: Neuhofer Daniela , Spencer Sade M. , Chioma Vivian C. , Beloate Lauren N. , Schwartz Danielle , Kalivas Peter W.
Published: November 2019

Glutamatergic plasticity in the nucleus accumbens core (NAcore) is a key neuronal process in appetitive learning and contributes to pathologies such as drug addiction. Understanding how this plasticity factors into cannabis addiction and relapse has been hampered by the lack of a rodent model of cannabis self‐administration. We used intravenous self‐administration of two constituents of cannabis, Δ9‐tetrahydrocannabinol (THC) and cannabidiol (CBD) to examine how contingent cannabis use and cue‐induced cannabinoid‐seeking alters glutamatergic neurotransmission and synaptic plasticity in NAcore. NMDA receptor (NMDAR)–dependent long‐term depression (LTD) in the NAcore was lost after cannabinoid, but not sucrose self‐administration. Surprisingly, when rats underwent cue‐induced cannabinoid seeking, LTD was restored. Loss of LTD was accompanied by desensitization of cannabinoid receptor 1 (CB1R). CB1R are positioned to regulate synaptic plasticity by being expressed on glutamatergic terminals and negatively regulating presynaptic excitability and glutamate release. Supporting this possibility, LTD was restored by promoting CB1R signaling with the CB1 positive allosteric modulator GAT211. These data implicate NAcore CB1R as critical regulators of metaplasticity induced by cannabis self‐administration and the cues predicting cannabis availability.
Investigating causality between liability to ADHD and substance use, and liability to substance use and ADHD risk, using Mendelian randomization
Authors: Treur Jorien L. , Demontis Ditte , Smith George Davey , Sallis Hannah , Richardson Tom G. , Wiers Reinout W. , Børglum Anders D. , Verweij Karin J.H. , Munafò Marcus R.
Published: November 2019

Attention‐deficit hyperactivity disorder (ADHD) has consistently been associated with substance use, but the nature of this association is not fully understood. To inform intervention development and public health messages, a vital question is whether there are causal pathways from ADHD to substance use and/or vice versa. We applied bidirectional Mendelian randomization, using summary‐level data from the largest available genome‐wide association studies (GWAS) on ADHD, smoking (initiation, cigarettes per day, cessation, and a compound measure of lifetime smoking), alcohol use (drinks per week, alcohol problems, and alcohol dependence), cannabis use (initiation), and coffee consumption (cups per day). Genetic variants robustly associated with the “exposure” were selected as instruments and identified in the “outcome” GWAS. Effect estimates from individual genetic variants were combined with inverse‐variance weighted regression and five sensitivity analyses (weighted median, weighted mode, MR‐Egger, generalized summary data–based MR, and Steiger filtering). We found evidence that liability to ADHD increases likelihood of smoking initiation and heaviness of smoking among smokers, decreases likelihood of smoking cessation, and increases likelihood of cannabis initiation. There was weak evidence that liability to ADHD increases alcohol dependence risk but not drinks per week or alcohol problems. In the other direction, there was weak evidence that smoking initiation increases ADHD risk, but follow‐up analyses suggested a high probability of horizontal pleiotropy. There was no clear evidence of causal pathways between ADHD and coffee consumption. Our findings corroborate epidemiological evidence, suggesting causal pathways from liability to ADHD to smoking, cannabis use, and, tentatively, alcohol dependence. Further work is needed to explore the exact mechanisms mediating these causal effects.
Aspirin and N‐acetylcysteine co‐administration markedly inhibit chronic ethanol intake and block relapse binge drinking: Role of neuroinflammation‐oxidative stress self‐perpetuation
Authors: Israel Yedy , Quintanilla María Elena , Ezquer Fernando , Morales Paola , Santapau Daniela , Berríos‐Cárcamo Pablo , Ezquer Marcelo , Olivares Belen , Herrera‐Marschitz Mario
Published: November 2019

Chronic alcohol intake leads to neuroinflammation and cell injury, proposed to result in alterations that perpetuate alcohol intake and cued relapse. Studies show that brain oxidative stress is consistently associated with alcohol‐induced neuroinflammation, and literature implies that oxidative stress and neuroinflammation perpetuate each other. In line with a self‐perpetuating mechanism, it is hypothesized that inhibition of either oxidative stress or neuroinflammation could reduce chronic alcohol intake and relapse. The present study conducted on alcohol‐preferring rats shows that chronic ethanol intake was inhibited by 50% to 55% by the oral administration of low doses of either the antioxidant N‐acetylcysteine (40 mg/kg/d) or the anti‐inflammatory aspirin (ASA; 15 mg/kg/d), while the co‐administration of both dugs led to a 70% to 75% (P < .001) inhibition of chronic alcohol intake. Following chronic alcohol intake, a prolonged alcohol deprivation, and subsequent alcohol re‐access, relapse drinking resulted in blood alcohol levels of 95 to 100 mg/dL in 60 minutes, which were reduced by 60% by either N‐acetylcysteine or aspirin and by 85% by the co‐administration of both drugs (blood alcohol: 10 to 15 mg/dL; P < .001). Alcohol intake either on the chronic phase or following deprivation and re‐access led to a 50% reduction of cortical glutamate transporter GLT‐1 levels, while aspirin administration fully returned GLT‐1 to normal levels. N‐acetylcysteine administration did not alter GLT‐1 levels, while N‐acetylcysteine may activate the cystine/glutamate transport xCT, presynaptically inhibiting relapse. Overall, the study suggests that a neuroinflammation/oxidative stress self‐perpetuation cycle maintains chronic alcohol intake and relapse drinking. The co‐administration of anti‐inflammatory and antioxidant agents may have translational value in alcohol‐use disorders.
What agricultural and food policies do U.S. consumers prefer? A best–worst scaling approach
Authors: Caputo Vincenzina , Lusk Jayson L.
Published: November 2019

Consumer welfare effects from policy changes are traditionally calculated using estimates of consumer preferences for the underlying goods and services affected. This conventional approach is indirect, does not consider preferences people may have for the policies themselves, and makes it difficult to easily compare relative preferability of a large set of policy options. In this paper, we use the best–worst scaling approach to determine consumers’ preferences for 13 policies. A nationwide survey of 1,056 U.S. consumers indicates the highest levels of support for investments in agricultural research and requirements of food and agricultural literacy standards in public education. Fat, calorie, and soda taxes are the least popular; fewer than one‐third of respondents are in favor of these three policies.
Global and local food value chains in Africa: A review
Authors: Feyaerts Hendrik , Van den Broeck Goedele , Maertens Miet
Published: November 2019

The rapid expansion of agrifood exports from low‐ and middle‐income countries and the contribution of global value chains to rural development are well‐documented in the literature. Also, studies on modernization of domestic food value chains in these countries are emerging. Yet, the linkages between global and local value chains are rarely studied. On the one hand, the development and expansion of global value chains may create competition with local value chains for land, labor, water, soil nutrients, and other resources. On the other hand, positive spillover effects, such as investment, technical or institutional spillovers, may occur and spur the development of local value chains. In this article, we put forward a conceptual discussion on the type of linkages between global and local value chains, and how these depend on crop and value chain characteristics. We review the empirical evidence on these linkages. Our focus is on Africa, where agrifood exports and global value chains evolved rapidly and where challenges remain to upgrade and increase efficiency in local food value chains.
Trade, policy, and food security
Authors: Smith Vincent H. , Glauber Joseph W.
Published: November 2019

Food insecurity is extensive throughout the world and hunger and malnutrition are expected to remain serious humanitarian and political concerns, both in the short term and for the foreseeable future, particularly in low income developing countries where many rural and urban households are both income and asset poor. In those countries, domestic agricultural production is expected to be especially vulnerable to the impacts of climate change over the next 30 years. Thus international markets for staple agricultural commodities, which have become increasingly important as sources of nutrition for both developing and developed countries over the past 60 years, are likely to become even more important in the future. Free trade policies allow countries to exploit their comparative advantages in economic activity, increasing average per capita incomes, longer term growth rates and a country's capacity to fund social safety nets for the poor. However, many countries abandoned those policies in favor of domestic protections in their efforts to mitigate the effects of short run food crises. The policy challenge is therefore to resolve the tension between optimal long run policies and short run initiatives to address food security concerns.
Prevalence of non‐alcoholic fatty liver and liver fibrosis in patients with moderate–severe psoriasis: A cross‐sectional cohort study
Authors: Magdaleno‐Tapial Jorge , Valenzuela‐Oñate Cristian , Ortiz‐Salvador José María , Martínez‐Doménech Álvaro , García‐Legaz‐Martínez Marta , Alonso‐Carpio Miriam , Tamarit‐García Juan José , Diago‐Madrid Moisés , Sánchez‐Carazo José Luis , Pérez‐Ferriols Amparo
Published: November 2019

Background/Objectives

Several studies have reported that non‐alcoholic fatty liver disease (NAFLD) is more frequent in patients with psoriasis, but few have reviewed the presence of liver fibrosis in those patients.

Methods

Cross‐sectional cohort, single‐centre study, continuously selecting all patients with moderate–severe psoriasis seen at the Psoriasis Unit of a Tertiary Hospital. The grade of liver steatosis was assessed using liver ultrasound, and the quantity of liver fibrosis was graded using a transitional vibration‐controlled elastography (Fibroscan®).

Results

A total of 71 patients (66.2% male) were included, with an average age of 46.6 years old. The maximum historical PASI average was 14.4 while the baseline PASI average at the time of the study was 2. A third (36%) of patients met the criteria for metabolic syndrome 52% of patients had steatosis; being male, having metabolic syndrome comorbidities, elevated AST/ALT enzymes, dyslipidemia and high initial PASI were significantly related. 14% of patients had moderate liver fibrosis (≥7.6 KPa). In 30% of them, no ultrasound liver steatosis was observed.

Conclusions

Elastography may be a useful tool along with ultrasound to evaluate liver disease in patients with psoriasis.
Peroxisome proliferator‐activated receptor alpha regulates the expression of the immune response mediators in the porcine endometrium during the estrous cycle and early pregnancy
Authors: Kunicka Zuzanna , Kurzyńska Aleksandra , Szydłowska Anna , Bogacka Iwona
Published: November 2019

Problem

Cytokines are immune response mediators that play an important role in the regulation of reproductive functions. An association between cytokines and peroxisome proliferator receptors (PPARs) has been reported in various tissues, including the endometrium. The present study aimed to evaluate the impact of PPARα ligands on the expression of nuclear factor kappa B (NF‐κB) and cytokines (interleukin [IL]‐1β, IL‐4, IL‐6, IL‐8, IL‐10, and LIF) in the porcine endometrium in different reproductive stages.

Methods of study

Endometrial slices were collected from gilts on days 10‐12 or 14‐16 of the estrous cycle and pregnancy. Endometrial tissue explants were incubated in vitro in the presence or absence of PPARα agonist WY‐14643 and antagonist MK886. Expression of mRNA and protein for NF‐ĸB and selected cytokines was evaluated by real‐time PCR and immunoblot.

Results

PPARα agonist WY‐14643 decreased the mRNA expression of NF‐κB in most of the analyzed stages (excluding days 10‐12 of the estrous cycle), but increased the expression of NF‐κB protein (excluding days 14‐16 of pregnancy). The WY‐14643 increased expression of IL‐1β and IL‐6 proteins, and the mRNA expression of IL‐8 and LIF, decreased IL‐4 expression, and did not affect the mRNA and protein expression of IL‐10.

Conclusion

The obtained results demonstrate that PPARα is involved in the regulation of NF‐κB and cytokine expression in the porcine endometrium. PPARα ligands exert a varied influence on immune system components, which could be attributed to differences in the receptivity of porcine endometrial tissue during the reproductive cycle.
Self‐reported mental health and cortisol activity at 27‐28 years of age in individuals born with very low birthweight
Authors: Leijon Ingemar , Bladh Marie , Finnström Orvar , Gäddlin Per‐Olof , Nelson Nina , Hammar Mats , Theodorsson Elvar , Sydsjö Gunilla
Published: November 2019

Aim

To assess mental health outcomes of very low birthweight (VLBW, <1500 g) subjects to adulthood and to examine salivary cortisol and hair cortisol levels and their relation to birth characteristics and mental health.

Methods

A Swedish regional cohort of 56 VLBW subjects and 55 full‐term controls were assessed at the ages 27‐28 with adult self‐reported scales and the mean of 2 days diurnal salivary cortisol and hair cortisol. The cohorts had been assessed at 15 years of age with youth self‐reported scales.

Results

There were no differences between the groups in youth self‐reported scales and adult self‐reported scores. The 24 participating VLBW girls scored lower on youth self‐reported scales externalising and total problem scores than the control girls. In adulthood, the 21 participating VLBW women had significantly higher morning concentrations of salivary cortisol than control women, P = .014. No significant associations were found between cortisol concentrations and adult self‐reported scales internalising, externalising and total scores.

Conclusion

Self‐reported mental health in VLBW subjects was comparable with normal birthweight controls indicating a satisfying transition from adolescence to adulthood. VLBW females had higher morning salivary cortisol concentrations, suggesting a gender difference. We found no correlations between cortisol and mental health.
Influence of grinding on the preservation of starch grains from rice
Authors: Li W. , Pagán‐Jiménez J. R. , Tsoraki C. , Yao L. , Van Gijn A.
Published: November 2019

China is a major centre for rice domestication, where starch grain analysis has been widely applied to archaeological grinding tools to gain information about plant use by ancient Chinese societies. However, few rice starch grains have been identified to date. To understand this apparent scarcity of starch grains from rice, dry‐ and wet‐grinding experiments with stone tools were carried out on four types of cereals: rice (Oryza sativa L.), foxtail millet (Setaria italica), Job's tears (Coix lacryma‐jobi L.) and barley (Hordeum vulgare L.). The results reveal that dry‐grinding produces significant damage to starches to the point where they may be undetected in archaeological samples, while wet‐grinding causes only slight morphological changes to the starch grains. Moreover, rice starch grains have the most substantial alterations from dry‐grinding, possibly impeding their identification. These findings provide a possible means to explain the relative scarcity of rice starch grains recovered from archaeological grinding tools, which it is suggested was caused by the use of the dry‐grinding technique. Therefore, it is suggested that rice starch grains have been likely underrepresented in the archaeological record, and previous interpretations of starch analyses need to be reconsidered.
Elevated lead exposure in Roman occupants of Londinium: New evidence from the archaeological record
Authors: Scott S. R. , Shafer M. M. , Smith K. E. , Overdier J. T. , Cunliffe B. , Stafford T. W. , Farrell P. M.
Published: November 2019

The evolution of metallurgical practices over several millennia has resulted in human exposures to a diverse variety of toxic elements. These exposures were not just confined to the metalworkers, but in many cases broadly impacted the larger community and society. The role of lead in Roman civilization is particularly fascinating, where the available evidence of lead use in a myriad of applications by Roman civilization suggests the potential for elevated exposures. The present paper addresses the hypothesis that because of these practices, Roman occupants of ancient Londinium (43–410 ad) were exposed to levels of lead that far exceeded exposures in the preceding populations of Iron Age Britain (700 bc–43 ad). The elemental content and stable lead and strontium isotopic signatures of 30 femora from three Londinium cemeteries and radiocarbon‐dated representative burials were examined and the results then compared with 70 femora dating to the pre‐Roman Iron Age from the well‐known Iron Age hillfort of Danebury, Hampshire, and from three cemeteries in East Yorkshire. Extensive efforts were directed at the minimization of sediment and soil contamination, the assessment of contamination from burial artefacts and a careful review of the burial context of specimens. Data for lead and 20 additional trace and major elements were obtained by magnetic sector inductively coupled plasma mass spectrometry (ICPMS), after acid dissolution of pre‐cleaned bone cores. Lead isotope ratios in the bone core digests (and burial soils) were measured by multi‐collector ICPMS. It was found that concentrations of lead in the Roman/Londinium‐era femora were > 70‐fold greater than those from pre‐Roman populations. This was confirmed by femoral data obtained from the analysis of a pre‐Roman burial from the early first century bc found adjacent to the Southern Cemetery. Several major and trace element metrics for diagenesis demonstrate that levels of lead in the bone are robust indicators of human exposure during life. Lead isotope data for the Roman population are consistent with previously identified widespread lead pollution. The pre‐Roman populations contain lead isotopic compositions consistent with highly localized, minor sources of lead. Together, these data provide unequivocal confirmation that the Romans in Londinium were exposed to elevated lead levels. Elevated blood lead levels would have resulted, negatively affecting their health and possibly contributing to declining birth rates.
Microanalytical study of copper ores from the Chalcolithic settlement of São Pedro (Portugal): Copper production in the south‐western Iberian Peninsula
Authors: Valério P. , Cardoso I. P. , Santiago M. , Araújo M. F. , Alves L. C. , Gonçalves M. A. , Mataloto R.
Published: November 2019

Copper ores recovered at the third millennium bce settlement of São Pedro, Portugal, were characterized by micro‐Raman spectroscopy, micro‐energy dispersive X‐ray spectrometry (micro‐EDXRF) and micro‐particle‐induced X‐ray emission spectrometry (micro‐PIXE). The collection shows the common presence of secondary copper minerals (malachite, pseudomalachite and libethenite) combined with iron oxyhydroxides (hematite and goethite), while arsenic‐rich minerals are absent and, therefore, can be excluded as the source of arsenical copper. Overall, these copper ores suggest a primitive technology involving the exploitation of the superficial zone of ore bodies and reliant on the fortuitous finding of arsenic‐rich sources to produce the arsenical copper alloy frequently present among metallic collections of the Iberian Peninsula.
Leftovers: The presence of manufacture‐derived aquatic lipids in Alaskan pottery
Authors: Admiraal M. , Lucquin A. , Drieu L. , Casale S. , Jordan P. D. , Craig O. E.
Published: November 2019

Lipids preserved within the walls of ancient pottery vessels are routinely analysed to reveal their original contents. The provenience of aquatic lipids in pottery is generally connected to vessel function (e.g., for cooking or storing fish, shellfish and aquatic mammals). However, ethnographic reports from early historic Alaska mention the use of aquatic oils for waterproofing low‐fired pottery. Results of lipid residue studies on Alaskan pottery reflect an exclusive function of pottery to process aquatic resources. However, can one be sure these residues are the product of vessel function and not a remnant of the manufacturing process? The study presents the results of an experiment where the preservation of aquatic lipids during the firing process at different temperatures was measured. It was found that nearly all lipids were removed at firing temperatures of ≥ 400°C. Petrographic analysis of Alaskan pottery samples indicates that firing temperatures were generally > 550°C but < 800°C. The contribution of pre‐firing manufacture‐derived lipids to samples fired at these temperatures may be regarded as negligible. While the possible presence of aquatic lipids from post‐firing surface treatments cannot be excluded, such treatments appear unnecessary for well‐fired pottery.
Stable isotope analysis of the Inca mummy from Nevado de Chuscha (Salta, Argentina)*
Authors: Killian Galván V. A. , Tessone A. , Valenzuela L. O. , Sharp Z. D. , Panarello H. O.
Published: November 2019

This paper presents the carbon (13C/12C), nitrogen (15N/14N), oxygen (18O/16O), hydrogen (2H/1H) and sulfur (34S/32S) stable isotope values measured in the hair of a female individual from north‐western Argentina. The analysis of segments of this tissue allows for the recording of the diet and migratory changes with a short time resolution. The sample is from a mummified young female individual discovered in Chuscha mount, Salta province. It was found at more than 5000 masl, in a mountain sanctuary of the Inca expansion (capacochas). The paper discusses the paleodiet and mobility patterns of this individual in the period before her death, focusing on the isotopic variations in a limited time scale. The results indicate that the individual moved from a different region to the place where she was sacrificed. Furthermore, in the last year the individual was alive, a shift in the isotopic composition of the food consumed is detected: a variation in the importance of C4 over C3 resources is evident. The results are compared with the isotopic estimations for other children and young people recovered in archaeological contexts associated with capacochas to infer variability in the geographical trajectories covered during their last months of life.
Geoarchaeology and spatial distributions of the ‘Coche Quemado' obsidian source in north‐western Patagonia
Authors: Salgán M. L. , De La Paz Pompei M. , Diéguez S. , Glascock M. D. , Neme G. , Gil A.
Published: November 2019

In north‐western Patagonia, obsidian was used during the entire Holocene, and its importance increased with time. Recent fieldwork discovered a new obsidian source located in the Río Grande, which was called ‘Coche Quemado' (CQ). The results indicate that the CQ source has a different geochemical signal than all other sources in the region. Its use is spatially restricted to piedmont and, to a lesser extent, the plains. Chronologically, CQ was exploited in the middle and late Holocene, and its use accounts for a range of spatial distribution between 150 and 200 km.
Connections and disconnections between family and religion: A family geography of Guangzhou Muslim immigrants
Authors: Yang Rong , Xue Desheng , Liu Chen
Published: November 2019

This paper explores how Muslim immigrants negotiate their family practices and religious identities in secular Guangzhou, a global city in south China, drawing on an in‐depth qualitative analysis. It provides a lens for better understanding the interrelationship between family practices, transnational mobility, and religious values spatially in the Chinese context. The key arguments of this research suggest that transnational mobility plays important roles in making, remaking, and unmaking of connections between family and religion. Moreover, both family spaces and religious spaces are dynamic and on the move. As an empirical study on family and religion in the Chinese context, this research can not only be read as a contribution to family and religious geographies in an everyday setting, but also one of the first everyday geography studies of Islam and Muslims in globalised China.
Statistical inference for net benefit measures in biomarker validation studies
Authors: Marsh Tracey L. , Janes Holly , Pepe Margaret S.
Published: November 2019

Referral strategies based on risk scores and medical tests are commonly proposed. Direct assessment of their clinical utility requires implementing the strategy and is not possible in the early phases of biomarker research. Prior to late‐phase studies, net benefit measures can be used to assess the potential clinical impact of a proposed strategy. Validation studies, in which the biomarker defines a prespecified referral strategy, are a gold standard approach to evaluating biomarker potential. Uncertainty, quantified by a confidence interval, is important to consider when deciding whether a biomarker warrants an impact study, does not demonstrate clinical potential, or that more data are needed. We establish distribution theory for empirical estimators of net benefit and propose empirical estimators of variance. The primary results are for the most commonly employed estimators of net benefit: from cohort and unmatched case‐control samples, and for point estimates and net benefit curves. Novel estimators of net benefit under stratified two‐phase and categorically matched case‐control sampling are proposed and distribution theory developed. Results for common variants of net benefit and for estimation from right‐censored outcomes are also presented. We motivate and demonstrate the methodology with examples from lung cancer research and highlight its application to study design.
Prognostic impact of interim positron emission tomography in mantle cell lymphoma patients treated with frontline R‐CHOP
Authors: Jeon Young‐Woo , O Joo‐Hyun , Park Kyung‐Sin , Min Gi June , Park Sung‐Soo , Yoon Jae‐Ho , Eom Ki‐Seong , Min Chang‐Ki , Cho Seok‐Goo
Published: November 2019

Although 18F‐fluorodeoxyglucose positron emission tomography (18F‐FDG PET) is commonly used for initial staging and therapeutic response evaluation in aggressive lymphomas, its prognostic utility for mantle cell lymphoma (MCL) is controversial. Therefore, we retrospectively evaluated the correlations of interim PET (iPET) and end‐of‐treatment PET (ePET) response with survival outcomes in 89 consecutive advanced MCL patients treated with frontline R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone). iPET positivity was strongly associated with inferior five‐year overall survival (OS) [hazard ratio (HR) 7·84, P < 0·0001] and poor five‐year progression‐free survival (PFS) (HR 3·34, P < 0·0001). OS and PFS were more favourable in the order early metabolic responder (iPETneg → ePETneg), delayed responder (iPETpos → ePETneg), loss‐metabolic responder (iPETneg → ePETpos), and never‐metabolic responder (iPETpos → ePETpos). In the autologous haematopoietic stem cell transplantation (auto‐HSCT)‐fit subgroup, OS was more favourable in the order early metabolic responders, delayed metabolic responders, and non‐metabolic responders, with a marginal trend toward statistical significance (HR 3·41, P = 0·051), and PFS was significantly superior in early metabolic responders (HR 4·43, P = 0·002). In a group that was ineligible for auto‐HSCT, OS and PFS were significantly superior in early metabolic responders. Our results suggested that iPET is of prognostic value and an independent predictor of survival in MCL patients receiving frontline R‐CHOP. Therefore, prospective clinical trials of iPET‐guided treatment strategies for these patients are warranted.
Novel neuroactive steroid with hypnotic and T‐type calcium channel blocking properties exerts effective analgesia in a rodent model of post‐surgical pain
Authors: Joksimovic Sonja Lj. , Joksimovic Srdjan M. , Manzella Francesca M. , Asnake Betelehem , Orestes Peihan , Raol Yogendra H. , Krishnan Kathiresan , Covey Douglas F. , Jevtovic‐Todorovic Vesna , Todorovic Slobodan M.
Published: November 2019

Background and Purpose

Neuroactive steroid (3β,5β,17β)‐3‐hydroxyandrostane‐17‐carbonitrile (3β‐OH) is a novel hypnotic and voltage‐dependent blocker of T‐type calcium channels. Here, we examine its potential analgesic effects and adjuvant anaesthetic properties using a post‐surgical pain model in rodents.

Experimental Approach

Analgesic properties of 3β‐OH were investigated in thermal and mechanical nociceptive tests in sham or surgically incised rats and mice, with drug injected either systemically (intraperitoneal) or locally via intrathecal or intraplantar routes. Hypnotic properties of 3β‐OH and its use as an adjuvant anaesthetic in combination with isoflurane were investigated using behavioural experiments and in vivo EEG recordings in adolescent rats.

Key Results

A combination of 1% isoflurane with 3β‐OH (60 mg·kg−1, i.p.) induced suppression of cortical EEG and stronger thermal and mechanical anti‐hyperalgesia during 3 days post‐surgery, when compared to isoflurane alone and isoflurane with morphine. 3β‐OH exerted prominent enantioselective thermal and mechanical antinociception in healthy rats and reduced T‐channel‐dependent excitability of primary sensory neurons. Intrathecal injection of 3β‐OH alleviated mechanical hyperalgesia, while repeated intraplantar application alleviated both thermal and mechanical hyperalgesia in the rats after incision. Using mouse genetics, we found that CaV3.2 T‐calcium channels are important for anti‐hyperalgesic effect of 3β‐OH and are contributing to its hypnotic effect.

Conclusion and Implications

Our study identifies 3β‐OH as a novel analgesic for surgical procedures. 3β‐OH can be used to reduce T‐channel‐dependent excitability of peripheral sensory neurons as an adjuvant for induction and maintenance of general anaesthesia while improving analgesia and lowering the amount of volatile anaesthetic needed for surgery.
The double EMG distribution and trade elasticities
Authors: Sager Erick , Timoshenko Olga A.
Published: November 2019

Using Brazilian export data that, unlike many trade data sets, have a full record of small export sales, this paper reconsiders trade elasticities and the welfare gains from trade. Using the Brazilian data, this paper provides novel evidence on the properties of the distributions of log‐export sales and shows that the double exponentially modified Gaussian (EMG) distribution parsimoniously captures these properties. Using the double EMG distribution in a standard monopolistic competition model of trade, this paper demonstrates that data truncation, which is prevalent in many data sets, leads to an upward bias in measuring the partial elasticity of trade with respect to variable trade costs. This bias subsequently leads to the underestimation of the gains from trade by 1% to 9% depending on the extent of data truncation, a range that is commensurate with typical economic growth and large booms.
RNA‐binding protein NONO promotes breast cancer proliferation by post‐transcriptional regulation of SKP2 and E2F8
Authors: Iino Kaori , Mitobe Yuichi , Ikeda Kazuhiro , Takayama Ken‐ichi , Suzuki Takashi , Kawabata Hidetaka , Suzuki Yutaka , Horie‐Inoue Kuniko , Inoue Satoshi
Published: November 2019

The majority of breast cancers are primarily hormone‐sensitive and can be managed by endocrine therapy, although therapy‐resistant or hormone‐refractory cancers need alternative treatments. Recently, increasing attention is being paid to RNA‐binding proteins (RBP) in cancer pathophysiology. The precise role of RBP in breast cancer, however, remains to be clarified. We herein show that an RBP non‐POU domain‐containing octamer binding (NONO) plays a critical role in the pathophysiology of breast cancers regardless of their hormone dependency. Clinicopathological and immunohistochemical study of 127 breast cancer cases showed that NONO is a significant independent prognostic factor for breast cancer patients. Notably, siRNA‐mediated NONO knockdown substantially repressed the proliferation of both hormone‐sensitive MCF‐7 and hormone‐refractory MB‐MDA‐231 breast cancer cells. Integrative analysis combined with expression microarray and RIP‐sequencing (RNA immunoprecipitation‐sequencing) showed that NONO post‐transcriptionally regulates the expression of cell proliferation‐related genes by binding to their mRNAs, as exemplified by S‐phase‐associated kinase 2 and E2F transcription factor 8. Overall, these results suggest that NONO is a key regulator for breast cancer proliferation through the pre‐mRNA splicing of cell proliferation‐related genes and could be a potential new diagnostic and therapeutic target for advanced disease.
Unraveling the Relation Between Reading Comprehension and Print Exposure
Authors: Erbeli Florina , van Bergen Elsje , Hart Sara A.
Published: November 2019

The purpose of this study was to test the directionality of influence between reading comprehension (RC) and print exposure (PE), thereby estimating genetic and environmental effects of this relation. The sample consisted of 910 twins in fourth through ninth grades (Mage = 12.33 years, SD = 1.41) from the Florida Twin Project on Reading, Behavior, and Environment. Using direction‐of‐causation model in a twin design, results supported a direction of influence running from RC to PE. This relation was underpinned by genetic and environmental factors of RC as well as PE. Implications for reading education are discussed.
A fluorescent probe for the dual detection of mercury ions and thiols based on a simple coumarin derivative
Authors: Tao Pei , Chen Dongling , Xu Zhenxiang , Song Yanxi , Li Hongqi , Xian Chunying
Published: November 2019

A fluorescent probe based on a simple coumarin derivative could recognise mercury ions (Hg(ii)) and thiols selectively in aqueous solution. The addition of Hg(ii) induced a blue shift of the fluorescence emission band of the probe while the fluorescence was almost quenched by the addition of p‐toluenethiol or cysteine (Cys). The detection limit of the probe towards Hg(ii) and Cys was 8 µmol/L. The probe could be used for the detection of Hg(ii) and thiols by the naked eye under ultraviolet light irradiation.
Cooperative conservation: Seven ways to save the world
Authors: Curry Oliver S. , Hare Darragh , Hepburn Cameron , Johnson Dominic D. P. , Buhrmester Michael D. , Whitehouse Harvey , Macdonald David W.
Published: November 2019

The world faces serious environmental problems. To solve them we must work together. Fortunately, humans are a very cooperative species. We have faced a range of cooperative problems in the past, and have evolved and invented a range of cooperative solutions to them—kin altruism, mutualism, reciprocity, heroism, deference, fairness, and property rights. Here, we illustrate how each of these solutions can be pressed into the service of conservation goals. Unlocking this potential will require overcoming conservationists' current cycloptic focus on only one type of cooperative problem (the prisoner's dilemma) and one type of solution (reciprocity). Only then will policy makers be able draw on the full range of cooperative dispositions and design more systematic and effective environmental interventions.
Thin‐endoscope endoscopic submucosal dissection for early esophageal cancer with postoperative stricture
Authors: Muramoto Takashi , Sakai Eiji , Ohata Ken
Published: November 2019

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Promoting physiological closure of the fistula, not just full‐thickness suturing, is critical to heal a refractory gastric stump‐cutaneous fistula after esophagectomy
Authors: Jin Duochen , Peng Lei , Zhang Guoxin
Published: November 2019

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Useful endoscopic resection technique for large pedunculated lesions in the duodenum using thread‐traction method with a double‐channel endoscope
Authors: Ozeki Yuichiro , Hirasawa Kingo , Sato Chiko
Published: November 2019

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