bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive analysis of the history of DFT based on the bibliometric method RPYS
Authors: Haunschild Robin , Barth Andreas , French Bernie
Published: November 2019

This bibliometric study aims at providing a comprehensive analysis of the history of density functional theory (DFT) from a perspective of chemistry by using reference publication year spectroscopy (RPYS). 114,138 publications with their 4,412,152 non-distinct cited references are analyzed. The RPYS analysis revealed three different groups of seminal papers which researchers in DFT have drawn from: (i) some long-known experimental studies from the 19th century about physical and chemical phenomena were referenced rather frequently in contemporary DFT publications. (ii) Fundamental quantum-chemical papers from the time period 1900–1950 which predate DFT form another group of seminal papers. (iii) Finally, various very frequently employed DFT approximations, basis sets, and other techniques (e.g., implicit descriptions of solvents) constitute another group of seminal papers. The earliest cited reference we found was published in 1806. The references to papers published in the 19th century mainly served the purpose of referring to long-known physical and chemical phenomena which were used to test if DFT approximations deliver correct results (e.g., Van der Waals interactions). The foundational papers of DFT by Hohenberg and Kohn as well as Kohn and Sham do not seem to be affected by obliteration by incorporation as they appear as pronounced peaks in our RPYS analysis. Since the 1990s, only very few pronounced peaks occur as most years were referenced nearly equally often. Exceptions are 1993 and 1996 due to seminal papers by Axel Becke, John P. Perdew and co-workers, and Georg Kresse and co-workers.
CRISPRa-mediated FOXP3 gene upregulation in mammalian cells
Authors: Forstnerič Vida , Oven Irena , Ogorevc Jernej , Lainšček Duško , Praznik Arne , Lebar Tina , Jerala Roman , Horvat Simon
Published: November 2019

Background

Forkhead box P3+ (FOXP3+) regulatory T cells (Tregs) are a subset of lymphocytes, critical for the maintenance of immune homeostasis. Loss-of-function mutations of the FOXP3 gene in animal models and humans results in loss of differentiation potential into Treg cells and are responsible for several immune-mediated inflammatory diseases. Strategies of increasing FOXP3 expression represent a potential approach to increase the pool of Tregs within the lymphocyte population and may be employed in therapies of diverse autoimmune conditions. In the present study, a dCas9 CRISPR-based method was systematically employed to achieve upregulation and sustained high expression of endogenous FOXP3 in HEK293 and human Jurkat T cell lines through targeting of the core promotor, three known regulatory regions of the FOXP3 gene (CNS1–3), and two additional regions selected through extensive bioinformatics analysis (Cage1 and Cage2).

Results

Using an activator-domain fusion based dCas9 transcription activator, robust upregulation of FOXP3 was achieved, and an optimal combination of single guide RNAs was selected, which exerted an additive effect on FOXP3 gene upregulation. Simultaneous targeting of FOXP3 and EOS, a transcription factor known to act in concert with FOXP3 in initiating a Treg phenotype, resulted in upregulation of FOXP3 downstream genes CD25 and TNFR2. When compared to ectopic expression of FOXP3 via plasmid electroporation, upregulation of endogenous FOXP3 via the Cas9-based method resulted in prolonged expression of FOXP3 in Jurkat cells.

Conclusions

Transfection of both HEK293 and Jurkat cells with dCas9-activators showed that regulatory regions downstream and upstream of FOXP3 promoter can be very potent transcription inducers in comparison to targeting the core promoter. While introduction of genes by conventional methods of gene therapy may involve a risk of insertional mutagenesis due to viral integration into the genome, transient up- or down-regulation of transcription by a CRISPR–dCas9 approach may resolve this safety concern. dCas9-based systems provide great promise in DNA footprint-free phenotype perturbations (perturbation without the risk of DNA damage) to drive development of transcription modulation-based therapies.
λ-Analogues of Stirling polynomials of the first kind and their applications
Authors: Kim Taekyun , Kim Dae San , Kim Han Young , Pyo Sung-Soo
Published: November 2019

Recently, λ-analogues of Stirling numbers of the first kind were studied. In this paper, we introduce, as natural extensions of these numbers, λ-Stirling polynomials of the first kind and r-truncated λ-Stirling polynomials of the first kind. We give recurrence relations, explicit expressions, some identities, and connections with other special polynomials for those polynomials. Further, as applications, we show that both of them appear in an expression of the probability mass function of a suitable discrete random variable, constructed from λ-logarithmic and negative λ-binomial distributions.
Robust adaptive synchronization of complex network with bounded disturbances
Authors: Xu Chengjie , Su Housheng , Liu Chen , Zhang Guohua
Published: November 2019

In this paper, we investigate distributed robust adaptive synchronization for complex networked systems with bounded disturbances. We propose both average synchronization protocol and leader-following synchronization protocol based on adaptive control and variable structure control strategies. The synchronization conditions do not require any global information except a connection assumption under the adaptive control method. Furthermore, the external disturbances are attenuated effectively. Finally, we present numerical simulations to illustrate the theoretical findings.
Impulsive boundary value problems containing Caputo fractional derivative of a function with respect to another function
Authors: Promsakon Chanon , Suntonsinsoungvon Eakachai , Ntouyas Sotiris K. , Tariboon Jessada
Published: November 2019

In this paper, we study the existence and uniqueness for a new class of impulsive fractional boundary value problems with separated boundary conditions containing the Caputo fractional derivative of a function with respect to another function. The existence of solutions is established by using the Leray–Schauder nonlinear alternative, and the uniqueness result is proved via Banach’s contraction mapping principle. Some examples are also constructed to demonstrate the application of main results.
Unidirectional animal-to-human transmission of methicillin-resistant Staphylococcus aureus ST398 in pig farming; evidence from a surveillance study in southern Italy
Authors: Pirolo Mattia , Visaggio Daniela , Gioffrè Angela , Artuso Irene , Gherardi Monica , Pavia Grazia , Samele Pasquale , Ciambrone Lucia , Di Natale Rossella , Spatari Giovanna , Casalinuovo Francesco , Visca Paolo
Published: November 2019

Background

Livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) belonging to clonal complex 398 is recognized as an occupational hazard for workers employed in intensive animal husbandry, especially in the swine-breeding chain. In this study, we compared the prevalence and epidemiological type of MRSA isolates from swine and farm workers in a large area of southern Italy.

Methods

Between January and March 2018, 88 workers from 32 farms where we had previously performed a survey for MRSA colonization of farmed pigs, were sampled by nasal swabbing. A follow-up investigation was conducted on seven workers 1 year after primary screening. MRSA isolates were characterized by MLST, spa and SCCmec typing, and tested for susceptibility to 15 antimicrobials. Epidemiological correlations between human and swine MRSA isolates were supported by Rep-MP3 and RAPD PCR fingerprinting, and whole-genome sequencing.

Results

The overall colonization rate of MRSA in swine farm workers was 21.6%, being significantly higher in intensive farms and in workers with direct animal contact. All human MRSA isolates were multi-drug resistant, belonged to the ST398 livestock clade, and did not carry Panton-Valentine leukocidin and enterotoxin genes. Notably, 94.1% of human MRSA isolates belonged to the same epidemiological type as swine MRSA isolates from the corresponding farm. Persistent MRSA carriage was documented in some workers 1 year after primary sampling.

Conclusions

We report a high prevalence of MRSA among swine farm workers, with higher colonization rates associated with intensive breeding and animal exposure. Our findings suggest unidirectional animal-to-human transmission of LA-MRSA and denote the high zoonotic transmissibility of the ST398 livestock clade.
Common polymorphic inversions at 17q21.31 and 8p23.1 associate with cancer prognosis
Authors: Ruiz-Arenas Carlos , Cáceres Alejandro , Moreno Victor , González Juan R.
Published: November 2019

Background

Chromosomal inversions are structural genetic variants where a chromosome segment changes its orientation. While sporadic de novo inversions are known genetic risk factors for cancer susceptibility, it is unknown if common polymorphic inversions are also associated with the prognosis of common tumors, as they have been linked to other complex diseases. We studied the association of two well-characterized human inversions at 17q21.31 and 8p23.1 with the prognosis of lung, liver, breast, colorectal, and stomach cancers.

Results

Using data from The Cancer Genome Atlas (TCGA), we observed that inv8p23.1 was associated with overall survival in breast cancer and that inv17q21.31 was associated with overall survival in stomach cancer. In the meta-analysis of two independent studies, inv17q21.31 heterozygosity was significantly associated with colorectal disease-free survival. We found that the association was mediated by the de-methylation of cg08283464 and cg03999934, also linked to lower disease-free survival.

Conclusions

Our results suggest that chromosomal inversions are important genetic factors of tumor prognosis, likely affecting changes in methylation patterns.
Effect of nicotine 6 mg gum on urges to smoke, a randomized clinical trial
Authors: Hansson Anna , Rasmussen Thomas , Perfekt Roland , Hall Elin , Kraiczi Holger
Published: November 2019

Background

Ability to manage urges to smoke is fundamental to maximizing the chances of success in smoking cessation. Previous studies have linked a higher dose of nicotine in nicotine replacement therapy to a higher success rate for smoking cessation. Thus, this study was performed to compare relief of urges to smoke, up until 5 h following treatment with a new 6 mg nicotine gum versus currently marketed 4 mg nicotine gum.

Methods

This was a randomized crossover clinical study. Following 12 h of abstinence from smoking, either one 6 mg or one 4 mg nicotine gum was given to 240 healthy adult smokers. Thereafter, urges to smoke were scored on a 100 mm Visual Analogue Scale repeatedly over 5 h.

Results

The reductions in urges to smoke over the first 1 and 3 h after administration were statistically significantly greater with 6 mg than 4 mg gum, (p < 0.005). A 50% reduction in perceived urges to smoke was reached in 9.4 min with 6 mg gum compared to 16.2 min with 4 mg gum (median values). The median duration of a 50% or more reduction in VAS urges to smoke score was 111 min with the 6 mg gum, versus 74 min for the 4 mg gum.

Conclusion

This study provides evidence that the 6 mg nicotine gum provided a greater reduction, faster and longer relief of urges to smoke than the 4 mg nicotine gum.

Trial registration

EudraCT Number: 2010–023268-42. Study was first entered in EudraCT 2011-02-23.
Blood brain barrier leakage is not a consistent feature of white matter lesions in CADASIL
Authors: Rajani Rikesh M. , Ratelade Julien , Domenga-Denier Valérie , Hase Yoshiki , Kalimo Hannu , Kalaria Raj N. , Joutel Anne
Published: November 2019

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic paradigm of small vessel disease (SVD) caused by NOTCH3 mutations that stereotypically lead to the vascular accumulation of NOTCH3 around smooth muscle cells and pericytes. White matter (WM) lesions (WMLs) are the earliest and most frequent abnormalities, and can be associated with lacunar infarcts and enlarged perivascular spaces (ePVS). The prevailing view is that blood brain barrier (BBB) leakage, possibly mediated by pericyte deficiency, plays a pivotal role in the formation of WMLs. Herein, we investigated the involvement of BBB leakage and pericyte loss in CADASIL WMLs. Using post-mortem brain tissue from 12 CADASIL patients and 10 age-matched controls, we found that WMLs are heterogeneous, and that BBB leakage reflects the heterogeneity. Specifically, while fibrinogen extravasation was significantly increased in WMLs surrounding ePVS and lacunes, levels of fibrinogen leakage were comparable in WMLs without other pathology (“pure” WMLs) to those seen in the normal appearing WM of patients and controls. In a mouse model of CADASIL, which develops WMLs but no lacunes or ePVS, we detected no extravasation of endogenous fibrinogen, nor of injected small or large tracers in WMLs. Moreover, there was no evidence of pericyte coverage modification in any type of WML in either CADASIL patients or mice. These data together indicate that WMLs in CADASIL encompass distinct classes of WM changes and argue against the prevailing hypothesis that pericyte coverage loss and BBB leakage are the primary drivers of WMLs. Our results also have important implications for the interpretation of studies on the BBB in living patients, which may misinterpret evidence of BBB leakage within WM hyperintensities as suggesting a BBB related mechanism for all WMLs, when in fact this may only apply to a subset of these lesions.
Discovery and material study of the missing feet part from Magritte’s L’évidence éternelle of 1954
Authors: Defeyt Catherine , Vandepitte Francisca , Herens Elodie , Strivay David
Published: November 2019

One of the two missing canvases from L’évidence éternelle of 1954, the one of the feet, has been discovered beneath a small woman portrait painted in 1958, La toile de Pénélope. Indeed, the underlying woman’s feet revealed through the IRR and XRR images leave little doubt about the identity of the hidden composition. All the more so as the canvas dimensions perfectly match with the format ascribed to the feet part in the diagram Magritte made of the 1954 variant of L’évidence éternelle. This paper presents the main results of the material study conducted on La toile de Pénélope by means of non-invasive and complementary imaging and analytical techniques. Furthermore, it proposes a virtual colorized reconstruction of the hidden picture, built on the basis of the XRR and IRR images, the elemental information provided by the MA-XRF analysis, the Raman results and the microscope examination of the painting surface.
Analyzing the influence of correlation length in permeability on convective systems in heterogeneous aquifers using entropy production
Authors: Niederau Jan , Wellmann J. Florian , Börsing Nele
Published: November 2019

Hydrothermal convection in porous geothermal reservoir systems can be seen as a double-edged sword. On the one hand, regions of upflow in convective systems can increase the geothermal energy potential of the reservoir; on the other hand, convection introduces uncertainty, because it can be difficult to locate these regions of upflow. Several predictive criteria, such as the Rayleigh number, exist to estimate whether convection might occur under certain conditions. As such, it is of interest which factors influence locations of upwelling regions and how these factors can be determined. We use the thermodynamic measure entropy production to describe the influence of spatially heterogeneous permeability on a hydrothermal convection pattern in a 2D model of a hot sedimentary aquifer system in the Perth Basin, Western Australia. To this end, we set up a Monte Carlo study with multiple ensembles. Each ensemble contains several hundred realizations of spatially heterogeneous permeability. The ensembles only differ in the horizontal spatial continuity (i.e., correlation length) of permeability. The entropy production of the simulated ensembles shows that the convection patterns in our models drastically change with the introduction and increase of a finite, lateral correlation length in permeability. An initial decrease of the average entropy production number with increasing lateral correlation length shows that fewer ensemble members show convection. When neglecting the purely conductive ensembles in our analysis, no significant change in the number of convection cells is seen for lateral correlation lengths larger than 2000 m. The result suggests that the strength of convective heat transfer is not sensitive to changes in lateral correlation length beyond a specific factor. It does, however, change strongly compared to simulations with a homogeneous permeability field. As such, while the uncertainty in spatial continuity of permeability may not strongly influence the convective heat transfer, our findings show that it is important to consider spatial heterogeneity and continuity of permeability when simulating convective heat transfer in an aquifer.
An uppermost haze layer above 100 km found over Venus by the SOIR instrument onboard Venus Express
Authors: Takagi Seiko , Mahieux Arnaud , Wilquet Valérie , Robert Séverine , Vandaele Ann Carine , Iwagami Naomoto
Published: November 2019

The Solar Occultation in the InfraRed (SOIR) instrument onboard Venus Express was designed to measure the Venusian atmospheric transmission at high altitudes (65–220 km) in the infrared range (2.2–4.3 μm) with a high spectral resolution. In this work, we investigate the optical properties of Venus’s haze layer above 90 km using SOIR solar occultation observations. Vertical and latitudinal profiles of the extinction coefficient, optical thickness, and mixing ratio of aerosols are retrieved. One of the most remarkable results is that the aerosol mixing ratio tends to increase with altitude above 90 km at both high and low latitudes. We speculate how aerosols could be produced at such high altitudes.
Paleomagnetic study of basaltic rocks from Baengnyeong Island, Korea: efficiency of the Tsunakawa–Shaw paleointensity determination on non-SD-bearing materials and implication for the early Pliocene geomagnetic field intensity
Authors: Ahn Hyeon-Seon , Yamamoto Yuhji
Published: November 2019

Finding the statistical intensity signatures of the Earth’s magnetic field over geologic time has helped understanding of the evolution of the Earth’s interior and its interactions with other integral parts of Earth systems. However, this has been often hampered by a paucity of absolute paleointensity (API) data, which are difficult to obtain primarily because of non-ideal magnetic behaviors of natural materials. Here, we present new API determination data with paleodirectional and rock magnetic analyses from basaltic rocks probably aged ~ 4‒5 Ma in Baengnyeong Island, Korea. Paleodirectional analysis obtained an overall mean direction of D = 347.3° and I = 38.3° (α95 = 4.9°, k = 113.4) corresponding to a virtual geomagnetic pole at 342.1° E and 70.2° N. Comprehensive rock magnetic analyses identified Ti-poor titanomagnetite with, in part, multi-domain (MD) particles as a main carrier of remanent magnetization. The Tsunakawa–Shaw (TS) method yielded 12 qualified API estimates with a high success rate, efficiently removing possible MD influences, and resulted in a mean value of 13.1 μT with good precision (1.7 μT, standard deviation). The Thellier method of the IZZI protocol with pTRM checks, coupled with the use of a bootstrap approach instead of the “conventional best-fitting” in API determination, gave 6.6‒19.7 μT as a 95% confidence interval of its mean API estimate, which supports the reliability of our TS-derived API mean estimate; but it is not considered in the final mean value because of the relatively large uncertainty. The virtual dipole moment corresponding to the TS-derived API mean, 2.9 (± 0.4) × 1022 Am2, is somewhat lower than the expectations of the past few Myr averages. Combined with a global API database, our new data implies a larger dispersion in the dipole moment during the early Pliocene than previously inferred. This also suggests that the issue of whether the early Pliocene average dipole strength was moderately high (> 5 × 1022 Am2) or consistent (4‒5 × 1022 Am2) should be discussed further.
Viability and collagen secretion by fibroblasts on titanium surfaces with different acid-etching protocols
Authors: de Souza Vilton Zimmermann , Manfro Rafael , Joly Júlio César , Elias Carlos Nelson , Peruzzo Daiane Cristina , Napimoga Marcelo Henrique , Martinez Elizabeth Ferreira
Published: November 2019

Background

From the consolidation of surface treatments of dental implants and knowledge on the cellular mechanisms of osseointegration, studies have highlighted the importance of a connective tissue seal against the implant to prevent contamination from the oral environment and consequent biofilm formation.

Objective

This in vitro study aimed to evaluate whether different titanium surface treatments using acid solutions promoted an increase in collagen secretion, proliferation, and viability of fibroblasts.

Material and methods

Commercially pure grade-4 titanium disks (6 × 2 mm) were treated with different acid solutions (hydrochloric, nitric, and sulfuric) for 20 and 60 min, respectively, obtaining mean surface roughness of 0.1 to 0.15 μm and 0.5 to 0.7 μm. Human fibroblasts were seeded onto different surfaces and assessed after 24 h, 48 h, and 72 h for cell proliferation and viability using Trypan blue staining and MTT, respectively, as well as the secretion of type I collagen on to such surfaces using ELISA. Machined titanium surfaces were used as controls. Data were statistically analyzed using one-way ANOVA and Fisher's LSD test for multiple comparisons, adopting a significance level of 5%.

Results

No significant difference was observed in cell proliferation for the different surfaces analyzed. Cell viability was significantly lower on the machined surface, after 48 h, when compared to the groups treated with acid for 20 or 60 min, which did not differ from each other. The expression of type I collagen was lowest on the acid-treated surfaces.

Conclusion

The results showed that the acid treatment proposed did not promote fibroblast proliferation and viability nor favor type I collagen synthesis.
The Training and Development of Elite Sprint Performance: an Integration of Scientific and Best Practice Literature
Authors: Haugen Thomas , Seiler Stephen , Sandbakk Øyvind , Tønnessen Espen
Published: November 2019

Despite a voluminous body of research devoted to sprint training, our understanding of the training process leading to a world-class sprint performance is limited. The objective of this review is to integrate scientific and best practice literature regarding the training and development of elite sprint performance. Sprint performance is heavily dependent upon genetic traits, and the annual within-athlete performance differences are lower than the typical variation, the smallest worthwhile change, and the influence of external conditions such as wind, monitoring methodologies, etc. Still, key underlying determinants (e.g., power, technique, and sprint-specific endurance) are trainable. In this review, we describe how well-known training principles (progression, specificity, variation/periodization, and individualization) and varying training methods (e.g., sprinting/running, technical training, strength/power, plyometric training) are used in a sprint training context. Indeed, there is a considerable gap between science and best practice in how training principles and methods are applied. While the vast majority of sprint-related studies are performed on young team sport athletes and focus on brief sprints with maximal intensity and short recoveries, elite sprinters perform sprinting/running over a broad range of distances and with varying intensity and recovery periods. Within best practice, there is a stronger link between choice of training component (i.e., modality, duration, intensity, recovery, session rate) and the intended purpose of the training session compared with the “one-size-fits-all” approach in scientific literature. This review provides a point of departure for scientists and practitioners regarding the training and development of elite sprint performance and can serve as a position statement for outlining state-of-the-art sprint training recommendations and for generation of new hypotheses to be tested in future research.
Development of the duodenal, ileal, jejunal and caecal microbiota in chickens
Authors: Glendinning Laura , Watson Kellie A. , Watson Mick
Published: November 2019

Background

The chicken intestinal microbiota plays a large role in chicken health and productivity and a greater understanding of its development may lead to interventions to improve chicken nutrition, disease resistance and welfare.

Results

In this study we examine the duodenal, jejunal, ileal and caecal microbiota of chickens from day of hatch to 5 weeks of age (day 1, 3, 7, 14 and week 5). DNA was extracted from intestinal content samples and the V4 region of the 16S rRNA gene was amplified and sequenced. We identified significant differences in microbial community composition, diversity and richness between samples taken from different locations within the chicken intestinal tract. We also characterised the development of the microbiota at each intestinal site over time.

Conclusions

Our study builds upon existing literature to further characterise the development of the chicken intestinal microbiota.
Molecular Evolution of IDH Wild-Type Glioblastomas Treated With Standard of Care Affects Survival and Design of Precision Medicine Trials: A Report From the EORTC 1542 Study
Authors: Draaisma Kaspar , Chatzipli Aikaterini , Taphoorn Martin , Kerkhof Melissa , Weyerbrock Astrid , Sanson Marc , Hoeben Ann , Lukacova Slávka , Lombardi Giuseppe , Leenstra Sieger , Hanse Monique , Fleischeuer Ruth , Watts Colin , McAbee Joseph , Angelopoulos Nicos , Gorlia Thierry , Golfinopoulos Vassilis , Kros Johan M. , Verhaak Roel G.W. , Bours Vincent , van den Bent Martin J. , McDermott Ultan , Robe Pierre A. , French Pim J.
Published: November 2019

PURPOSE

Precision medicine trials in glioblastoma (GBM) are often conducted at tumor recurrence. However, second surgeries for recurrent GBM are not routinely performed, and therefore, molecular data for trial inclusion are predominantly derived from the primary sample. This study aims to establish whether molecular targets change during tumor progression and, if so, whether this affects precision medicine trial design.

MATERIALS AND METHODS

We collected 186 pairs of primary-recurrent GBM samples from patients receiving chemoradiotherapy with temozolomide and sequenced approximately 300 cancer genes. MGMT, TERT, and EGFRvIII status was individually determined.

RESULTS

The molecular profile of our cohort was identical to that of other GBM cohorts ( IDH wild-type [WT], 95%; EGFR amplified, approximately 50%), indicating that patients amenable to second surgery do not represent a specific molecular subtype. Molecular events in IDH WT GBMs were stable in approximately 80% of events, but changes in mutation status were observed for all examined genes (range, approximately 90% and 60% for TERT and EGFR mutations, respectively), and such changes strongly affected targeted trial size and design. A similar pattern of GBM driver instability was observed within MGMT promoter–methylated tumors. MGMT promoter methylation status remained prognostic at tumor recurrence. The observation that hypermutation at GBM recurrence was rare (8%) and not correlated with outcome was relevant for immunotherapy-based treatments.

CONCLUSION

This large cohort of matched primary and recurrent IDH WT tumors establishes the frequency of GBM driver instability after chemoradiotherapy with temozolomide. This allows per gene or pathway calculation of trial size at tumor recurrence, using molecular data of the primary tumor only. We also identify genes for which repeat surgery is necessary because of low mutation retention rate.
Ghrelin Receptor Signaling Is Not Required for Glucocorticoid-Induced Obesity in Male Mice
Authors: Hay Rebecca E , Edwards Alex , Klein Marianne , Hyland Lindsay , MacDonald David , Karatsoreos Ilia , Hill Matthew N , Abizaid Alfonso
Published: November 2019

Chronically elevated levels of glucocorticoids increase food intake, weight gain, and adiposity. Similarly, ghrelin, a gut-secreted hormone, is also associated with weight gain, adiposity, and increased feeding. Here we sought to determine if corticosterone-induced metabolic and behavioral changes require functional ghrelin receptors (GHSR). To do this, we treated male C57BL mice with chronic corticosterone (CORT) mixed in their drinking water for 28 days. Half of these mice received the GHSR antagonist JMV2959 via osmotic minipumps while treated with CORT. In a second experiment, we gave the same CORT protocol to mice with a targeted mutation to the GHSR or their wild-type littermates. As expected, CORT treatment increased food intake, weight gain, and adiposity, but contrary to expectations, mice treated with a GHSR receptor antagonist or GHSR knockout (KO) mice did not show attenuated food intake, weight gain, or adiposity in response to CORT. Similarly, the effects of CORT on the liver were the same or more pronounced in GHSR antagonist-treated and GHSR KO mice. Treatment with JMV2959 did attenuate the effects of chronic CORT on glycemic regulation as determined by the glucose tolerance test. Finally, disruption of GHSR signaling resulted in behavioral responses associated with social withdrawal, potentially due to neuroprotective effects of GHSR activation. In all, we propose that blocking GHSR signaling helps to moderate glucose concentrations when CORT levels are high, but blocking GHSR signaling does not prevent increased food intake, weight gain, or increased adiposity produced by chronic CORT.
Chinese Uhuru
Authors: Cook Alexander C.
Published: November 2019

Mao’s most famous statement about postcolonial struggle came in response to the Congo Crisis of the 1960s, yet China’s understanding of and involvement in that conflict has been largely ignored. Based on briefly declassified archival sources and long-forgotten cultural works, this essay examines the significance of China’s engagement in the heart of Africa. A close reading of the spoken-word drama War Drums on the Equator (1965) reveals the importance of mobilizing “subjugated knowledge” in asymmetrical conflict.
The Place-ness of the DMZ
Authors: Koh Dong-Yeon
Published: November 2019

During the last decade, the DMZ (demilitarized zone) has emerged as one of the most popular tourist attractions for both domestic and international travelers—despite continued conflicts over nuclear weapons under Jungun Kim’s administration as well as ongoing landmine problems. Inspired by Marc Augé’s theory of non-place, this essay critically examines the policy to create an eco-friendly image of the DMZ that became prevalent among public art projects such as Dreaming of Earth, proposed by sculptor Jaeeun Choi and renowned Japanese architect Shigeru Ban, and the construction of the Pyungwha Nuri Gil (Spread Peace Trail). The essay further analyzes the key examples from the 2015 Real DMZ Project, the annual art event, started in 2012, on the site of Cheorwon, that serve as alternatives to public art projects for domestic visitors and international travelers. I argue that Hayoun Kwon’s 489 Years, Jisun Shin’s Contemplating Landscape, and Youngjoo Cho’s DMG_Demilitarized Goddesses (all of the 2015 Real DMZ Project) challenge the DMZ’s allegedly safe and benign image. More important, Minouk Lim’s Monument 300 (2014) evolves from the audience’s process of finding imaginary traces left by the historical massacre inside the DMZ. The participatory nature of Lim’s Monument 300: Chasing Watermarks calls our attention not only to the forgotten history of the area but also to the changing and unsettled meanings of the site. Therefore, the essay treats the DMZ as a symbolic site through which one can explore how the historical and political significance of the Korean War and its ideological tensions have been consistently forged within postwar South Korean society, particularly for the last two decades.
Wrong Place, Right Time
Authors: Williams Evan Calder , Toscano Alberto
Published: November 2019

This essay critically approaches the use of “1968” as a periodizing category by contrasting historiographic and political debates on the event and aftermath of the French May with the spatial and temporal unevenness that attaches to Italy’s “long” 1968. We explore two interlocking dimensions of the latter: the reprise of the “Southern question” in the midst of this sociopolitical upheaval, on the one hand, and the potent if enigmatic image of an Italian “creeping May,” on the other. A political and historiographic reflection on the Italian case suggests the need to dislocate a linear, if punctuated, periodization of 1968, and to move toward an understanding of the crises and movements that cluster around this date through a framework anchored around the notion of rhythm conceived as the site of political and spatial unevenness.
A comparison of the bone and growth phenotype of mdx, mdx:Cmah−/− and mdx:Utrn
+/− murine models with the C57BL/10 wild-type mouse
Authors: Wood Claire L. , Suchacki Karla J. , van ’t Hof Rob , Cawthorn Will P. , Dillon Scott , Straub Volker , Wong Sze Choong , Ahmed Syed F. , Farquharson Colin
Published: November 2019

The muscular dystrophy X-linked (mdx) mouse is commonly used as a mouse model of Duchenne muscular dystrophy (DMD). Its phenotype is, however, mild, and other mouse models have been explored. The mdx:Cmah−/− mouse carries a human-like mutation in the Cmah gene and has a severe muscle phenotype, but its growth and bone development are unknown. In this study, we compared male mdx, mdx:Utrn+/−, mdx:Cmah−/− and wild-type (WT) mice at 3, 5 and 7 weeks of age to determine the suitability of the mdx:Cmah−/− mouse as a model for assessing growth and skeletal development in DMD. The mdx:Cmah−/− mice were lighter than WT mice at 3 weeks, but heavier at 7 weeks, and showed an increased growth rate at 5 weeks. Cortical bone fraction as assessed by micro-computed tomography was greater in both mdx and mdx:Cmah−/− mice versus WT mice at 7 weeks. Tissue mineral density was also higher in mdx:Cmah−/− mice at 3 and 7 weeks. Gene profiling of mdx:Cmah−/− bone identified increased expression of Igf1, Igf1r and Vegfa. Both the mdx and mdx:Cmah−/− mice showed an increased proportion of regulated bone marrow adipose tissue (BMAT) but a reduction in constitutive BMAT. The mdx:Cmah−/− mice show evidence of catch-up growth and more rapid bone development. This pattern does not mimic the typical DMD growth trajectory and therefore the utility of the mdx:Cmah−/− mouse for studying growth and skeletal development in DMD is limited. Further studies of this model may, however, shed light on the phenomenon of catch-up growth.

This article has an associated First Person interview with the first author of the paper.
The liquid nucleome – phase transitions in the nucleus at a glance
Authors: Strom Amy R. , Brangwynne Clifford P.
Published: November 2019

Cells organize membrane-less internal compartments through a process called liquid–liquid phase separation (LLPS) to create chemically distinct compartments, referred to as condensates, which emerge from interactions among biological macromolecules. These condensates include various cytoplasmic structures such as P-granules and stress granules. However, an even wider array of condensates subcompartmentalize the cell nucleus, forming liquid-like structures that range from nucleoli and Cajal bodies to nuclear speckles and gems. Phase separation provides a biophysical assembly mechanism underlying this non-covalent form of fluid compartmentalization and functionalization. In this Cell Science at a Glance article and the accompanying poster, we term these phase-separated liquids that organize the nucleus the liquid nucleome; we discuss examples of biological phase transitions in the nucleus, how the cell utilizes biophysical aspects of phase separation to form and regulate condensates, and suggest interpretations for the role of phase separation in nuclear organization and function.
In vivo force-length and activation dynamics of two distal rat hindlimb muscles in relation to gait and grade
Authors: Eng Carolyn M. , Konow Nicolai , Tijs Chris , Holt Natalie C. , Biewener Andrew A.
Published: November 2019

Muscle function changes to meet the varying mechanical demands of locomotion across different gait and grade conditions. A muscle's work output is determined by time-varying patterns of neuromuscular activation, muscle force and muscle length change, but how these patterns change under different conditions in small animals is not well-defined. Here we report the first integrated in vivo force-length and activation patterns in rats, a commonly used small animal model, to evaluate the dynamics of two distal hindlimb muscles (medial gastrocnemius, MG and plantaris, PL) across a range of gait (walk, trot, and gallop) and grade (level versus incline) conditions. We use these data to explore how the pattern of force production, muscle activation and muscle length changes across conditions in a small quadrupedal mammal. As hypothesized, we found that the rat muscles show limited fascicle strains during active force generation in stance across gaits and grades, indicating that these distal rat muscles generate force economically but perform little work, similar to patterns observed in larger animals during level locomotion. Additionally, given differences in fiber type composition and variation in motor unit recruitment across the gait and grade conditions examined here for these muscles, the in vivo force-length behavior and neuromuscular activation data reported here can be used to validate improved two-element Hill-type muscle models.
Temporal integration of conflicting directional cues in sound localization
Authors: Reichert Michael S. , Ronacher Bernhard
Published: November 2019

Sound localization is fundamental to hearing. In nature, sound degradation and noise erode directional cues and can generate conflicting directional perceptions across different subcomponents of sounds. Little is known about how sound localization is achieved in the face of conflicting directional cues in non-human animals, although this is relevant for many species in which sound localization in noisy conditions mediates mate finding or predator avoidance. We studied the effects of conflicting directional cues in male grasshoppers, Chorthippus biguttulus, which orient towards signaling females. We presented playbacks varying in the number and temporal position of song syllables providing directional cues in the form of either time or amplitude differences between two speakers. Males oriented towards the speaker broadcasting a greater number of leading or louder syllables. For a given number of syllables providing directional information, syllables with timing differences at the song's beginning were weighted most heavily, while syllables with intensity differences were weighted most heavily when they were in the middle of the song. When timing and intensity cues conflicted, the magnitude and temporal position of each cue determined their relative influence on lateralization, and males sometimes quickly corrected their directional responses. We discuss our findings with respect to similar results from humans.
The role of intestinal bacteria in ammonia detoxification ability of teleost fish
Authors: Turner Leah A. , Bucking Carol
Published: November 2019

Protein catabolism during digestion generates appreciable levels of ammonia in the gastrointestinal tract (GIT) lumen. Amelioration by the enterocyte, via enzymes such as glutamine synthetase (GS), glutamate dehydrogenase (GDH), and alanine and aspartate aminotransferases (ALT; AST), is found in teleost fish. Conservation of these enzymes across bacterial phyla suggests that the GIT microbiome could also contribute to ammonia detoxification by providing supplemental activity. Hence, the GIT microbiome, enzyme activities, and ammonia detoxification were investigated in two fish occupying dissimilar niches; the carnivorous rainbow darter and the algivorous central stoneroller. There was a strong effect of fish species on the activity levels of GS, GDH, AST, and ALT, as well as GIT lumen ammonia concentration, and bacterial composition of the GIT microbiome. Further, removal of the intestinal bacteria impacted intestinal activities of GS and ALT in the herbivorous fish but not the carnivore. The repeatability and robustness of this relationship was tested across field locations and years. Within an individual waterbody, there was no impact of sampling location on any of these factors. However, different waterbodies affected enzyme activities and luminal ammonia concentrations in both fish, while only the central stoneroller intestinal bacteria populations varied. Overall, a relationship between GIT bacteria, enzyme activity, and ammonia detoxification was observed in herbivorous fish while the carnivorous fish displayed a correlation between enzyme activity and ammonia detoxification alone that was independent of the GIT microbiome. This could suggest that carnivorous fish are less dependent on non-host mechanisms for ammonia regulation in the GIT.
A low-cost, open-source inertial movement GPS logger for eco-physiology applications
Authors: Fahlbusch James A. , Harrington Katie J.
Published: November 2019

Open-source technology has been increasingly used for developing low-cost animal-borne bio-loggers, however, a gap remains for a bio-logger that records both inertial movement and GPS positions. We address this need with the Tapered Wings Logger (TWLogger), an archival bio-logger that records high-resolution (e.g. 50-Hz) tri-axial accelerometry and magnetometry, temperature, and GPS. The TWLogger can be built for 90 USD, accepts user-defined sampling parameters, and with a 500-mAh battery weighs 25-g. We provide publicly available build instructions and custom analysis scripts. Bench tests recorded 50-Hz inertial movement and 2-min GPS for 31.8 ± 2.2 h (mean±SD, n=6) with GPS accuracy within 10.9±13.6 m. Field deployments on a medium-sized bird of prey in the wild achieved similar results (n=13). The customizable TWLogger has wide-ranging application across systems and thus offers a practical solution for eco-physiology applications.
Extremity CT and ultrasound in the assessment of ankle injuries: occult fractures and ligament injuries
Authors: Allen Georgina M , Wilson David J , Bullock Stuart A. , Watson Marion
Published: November 2019

Objective:

To assess the rates of fractures and ligament injuries in patients with an acute ankle injury and a normal radiographic examination, and to consider the most appropriate examination protocol.

Methods:

Patients with an acute ankle injury who presented to the John Radcliffe Hospital Emergency Department with a normal radiographic examination were eligible for the study. They were invited to receive a cone beam CT and ultrasound examination at a local radiology department within 5 days of their ankle injury.

Results:

Of the 100 patients recruited to the study, 19 patients were found to have major fractures and 42 patients had small avulsion fractures. Additionally, 42 patients had ankle effusions and there were a large number of soft tissue injuries. There were 83 acute injuries of the anterior talofibular ligament, 19 of the anterior tibiofibular ligaments, 26 of the calcaneofibular ligament, 39 of the deltoid ligament complex, 21 of the talonavicular ligament, 14 of the spring ligament and 3 of the calcaneocuboid ligament.

Conclusion:

Conventional radiographic examination misses significant fractures of the foot and ankle and the presence of an ankle effusion does not relate to the severity of injury. Ultrasound is a useful imaging technique that can supplement clinical practice, but it is unlikely to replace current protocols alone. Cone beam CT is an appropriate alternative to plain radiography, being more sensitive in detecting fractures and delivering a similar dose of radiation. However, neither CT or ultrasound examination can detect all avulsion fractures. Simple anterior process fractures of the calcaneus are associated with talonavicular ligament injuries and the medial ligaments are injured in almost 50% of cases when there is a lateral ligament injury.

Advances in knowledge:

Fractures in the foot and ankle are detected more precisely with cone beam CT compared to radiographs. Cone beam CT delivers similar doses of to conventional radiographs which is around 10% of that resulting from conventional CT. Ultrasound examination is an effective assessment tool to detect ligamentous injuries. The absence of an ankle effusion does not exclude a major fracture.
Fear not: recent advances in understanding the neural basis of fear memories and implications for treatment development
Authors: Milton Amy L.
Published: November 2019

Fear is a highly adaptive emotion that has evolved to promote survival and reproductive fitness. However, maladaptive expression of fear can lead to debilitating stressor-related and anxiety disorders such as post-traumatic stress disorder. Although the neural basis of fear has been extensively researched for several decades, recent technological advances in pharmacogenetics and optogenetics have allowed greater resolution in understanding the neural circuits that underlie fear. Alongside conceptual advances in the understanding of fear memory, this increased knowledge has clarified mechanisms for some currently available therapies for post-traumatic stress disorder and has identified new potential treatment targets.
PRESERVATION OF THE ENVIRONMENT: the possibilities of society and law The Collection of Materials of the Summer School-2018
Authors: Авхадеев Владислав , Avkhadeev Vladislav , Bagautdinova Sania , Bagautdinova Sania , Боголюбов Сергей , Bogolyubov Syergyey , Ecker Daniela , Ecker Daniela , Golovanona Natalia , Golovanona Natalia , Ismailova Larisa , Ismailova Larisa , Хлуденева Наталья , Khludeneva Natalya , Кичигин Николай , Kichigin Nikolay , Лещенков Феликс , Leshchenkov Feliks , Помазанский Андрей , Pomazanskiy Andrey , Пономарев Михаил , Ponomarev Mikhail , Попова Анна , Popova Anna , Путило Наталья , Putilo Natalya , Sarkisyan Gor , Sarkisyan Gor , Shcherbak Stanislaw , Shcherbak Stanislaw , Шрам Валерий , Shram Valeriy , Shulga Sergej , Shulga Sergej , Шуплецова Юлия , Shupletsova Yuliya , Сиваков Дмитрий , Sivakov Dmitriy , Solntsev Alexander , Solntsev Alexander , Цомартова Фатима , Tsomartova Fatima , Волкова Наталья , Volkova Natalya , Журавлева Оксана , Zhuravleva Oksana
Published: November 2019

The best way to ensure environmental protection is to organize rational use of all types of natural resources: land, soil, mineral resources, forests, other vegetation, surface and groundwater, wildlife objects, protection of atmospheric air and near-Earth space, with the help of law and wide public involvement.
This monograph is the result of a discussion of environmental protection issues in the framework of the International Summer School, held at the Institute of Legislation and Comparative Law under the Government of the Russian Federation «The preservation of the environment: the opportunities of society, the possibilities of law» (August–September 2018, Moscow, Russia), which was held with the participation of the German academic exchange service (DAAD).
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