bluuebunny/crossref_metadata_2025 huggingface dataset:
4543 Glucocorticoid Receptors are essential effectors of TGFβ signaling in Triple Negative Breast Cancer
Authors: Kerkvliet Carlos Jesus Perez , Dwyer Amy R , Diep Caroline , Oakley Robert , Liddle Christopher , Lange Carol A
Published: July 2020

OBJECTIVES/GOALS: The glucocorticoid receptor (GR) is a ubiquitous steroid hormone receptor that is emerging as a mediator of breast cancer metastasis. We aim to better understand the biology associated with phospho-GR species in TNBC and their contribution to tumor progression. METHODS/STUDY POPULATION: To better understand how p-S134 GR may impact TNBC cell biology, we probed GR regulation by soluble factors that are rich within the tumor microenvironment (TME), such as TGFβ. TNBC cells harboring endogenous wild-type or S134A-GR species were created by CRISPR/Cas knock-in and subjected to in vitro assays of advanced cancer behavior. RNA-Seq was employed to identify pS134-GR target genes that are uniquely regulated by TGFβ in the absence of exogenously added GR ligands. Direct regulation of selected TGFβ-induced pS134-GR target genes was validated accordingly. Bioinformatics tools were used to probe publicly available TNBC patient data sets for expression of a pS134-GR 24-gene signature. RESULTS/ANTICIPATED RESULTS: In the absence of GR ligands, GR is transcriptionally activated via p38-MAPK-dependent phosphorylation of Ser134 upon exposure of TNBC cells to TME-derived agents (TGFβ, HGF). The ligand-independent pS134-GR transcriptome primarily encompasses gene sets associated with TNBC cell survival and migration/invasion. Accordingly, pS134-GR was essential for TGFβ-induced TNBC cell migration, anchorage-independent growth in soft-agar, and tumorsphere formation, an in vitro readout of breast cancer stemness properties. Finally, a 24-gene pSer134-GR-dependent signature induced by TGFβ1 predicts shortened survival in breast cancer. We expect to find similar results using an in-house tissue microarray. DISCUSSION/SIGNIFICANCE OF IMPACT: Phospho-S134-GR is a critical downstream mediator of p38 MAPK signaling and TNBC migration, survival, and stemness properties. Our studies define GR as a required effector of TGFβ1 signaling and nominate pS134-GR as a biomarker of elevated risk of breast cancer dissemination.
4447 Leptin supplementation prevents the loss of hypoglycemia-induced glucagon release following exposure to six days of severe caloric restriction in mice
Authors: McDougal David H , DuVall Marina A. , Morrison Christopher D. , Moldovan Laura A. , Jariwala Rajvi
Published: July 2020

OBJECTIVES/GOALS: We have recently shown that mice exposed to six days of 60% caloric restriction acutely display reduced hypoglycemia-induced glucagon release following refeeding, and that this effect is concurrent with low leptin levels. The current study was conducted to ascertain if leptin treatment during caloric restriction would reverse this effect. METHODS/STUDY POPULATION: Three groups of mice were used, an ad libitum (Ad-lib) fed group and two caloric restriction (CR) groups, one of which received twice daily leptin injection (0.5-1μg/g; IP) and the other vehicle (saline) during their caloric restriction. CR mice were placed on 60% caloric restriction for 6 consecutive days. Ad lib mice were housed in an identical manner but fed ad libitum during this same period. Following 6 days of restriction, CR mice were given ad lib access to food for 16 h. After the 16 h period of refeeding, both CR and ad lib mice began a 6 h fast which was immediately followed by a hypoglycemic insulin tolerance test (ITT). ITTs consisted of a variable dose of insulin intended to achieve a blood glucose of ~45 mg/dL within 60 minutes, at which time blood was collected for glucagon and corticosterone assays. RESULTS/ANTICIPATED RESULTS: The mean blood glucose levels during the ITT at 45 and 60 minutes post injection across all three groups were 46.8 + 3.1 and 37.0 + 2.4, respectively. There were no significant differences in glucose levels between the three groups at these two time points. As expected, saline treated CR mice displayed significantly reduced serum glucagon levels in response to the ITT relative to Ad-lib mice (23.5 + 10.9 vs. 91.7 + 20.8 pg/mL, p = 0.009). In contrast, leptin-treated CR mice maintained their hypoglycemia-induced glucagon response to the ITT (78.0 + 16.8 pg/mL, p>0.99 vs. Ad-lib group). In addition, although corticosterone levels in saline treated CR mice were numerically lower than in Ad-lib mice, this difference was not statistically significance (3928 + 277 vs. 4571 + 178 pg/mL, p = 0.179). DISCUSSION/SIGNIFICANCE OF IMPACT: Diabetes patients on insulin therapy often develop impaired hypoglycemic counter-regulation which can lead to life-threatening hypoglycemic complications. Our results suggest that leptin may hold promise as a therapeutic intervention for the prevention of impaired hypoglycemic counter-regulation in persons with diabetes.
4007 Medroxyprogesterone Upregulates the Glucocorticoid Receptor in Female Long Evans Rats
Authors: Zimmerman Margaret , Ogola Benard , Lindsey Sarah
Published: July 2020

OBJECTIVES/GOALS: Estrogen monotherapy in postmenopausal women can reduce kidney function, while dual therapy combining estrogen with a progestin improves renal health. Using the female Long Evans rat as a novel animal model of postmenopausal cardiovascular disease, we found similar results where estrogen worsens renal health while co-administration of medroxyprogesterone acetate (MPA) was protective. MPA cross-activates glucocorticoid receptors (GR), which are targeted clinically for their anti-inflammatory actions. Therefore, our goal was to determine if estrogen monotherapy induces renal damage by increasing inflammation, while dual therapy with MPA opposes inflammation by cross-activating GR. METHODS/STUDY POPULATION: Female Long Evans rats underwent OVX at 11 months of age and received a subcutaneous implant containing E2, E2+MPA or vehicle for 40 days. RESULTS/ANTICIPATED RESULTS: Coadministration of MPA prevented the E2-induced increase in proteinuria (Veh: 0.27 ± 0.07; E2: 3.53 ± 1.16; E2 + MPA: 1.20 ± 0.58 mg/mg creatinine; P = 0.03) and decline in glomerular filtration rate (Veh: 0.51 ± 0.02; E2: 0.24 ± 0.05; E2+MPA: 0.39 ± 0.05 ml/min; P < 0.01). Co-administration of MPA significantly increased renal GR transcript levels compared with E2 alone (Veh: 0.96 ± 0.02; E2: 0.94 ± 0.10; E2+MPA: 1.24 ± 0.04 fold change; P < 0.01). Inflammatory marker COX 2 renal transcript levels were significantly reduced by a similar degree in both mono and dual therapies compared with vehicle (Veh: 1.07 ± 0.06; E2: 0.81 ± 0.04; E2+MPA: 0.81 ± 0.04 fold change; P < 0.01). Neither TNF-alpha and IL-6 mRNA nor urinary beta-microglobulin levels (Veh: 1.71 ± 0.31; E2: 2.88 ± 0.78; E2+MPA: 3.07 ± 1.15 mg/day; ns) were altered. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results show that the effect of E2 on renal pro-inflammatory markers was not altered by the addition of MPA despite the significant increase in renal GR levels. Therefore, the renoprotective effects of MPA in midlife hormone therapy may be independent of renal GR-mediated changes in the immune profile.
Creolised Confucianism: Syncretism and Confucian revivalism at the turn of the twentieth century in Java
Authors: Liu Oiyan
Published: July 2020

Confucian revivalism swept over China, the Straits Settlements and the Netherlands East Indies in the late nineteenth century. Rather than perceiving China as the single foundational centre for Confucian ideas, this article argues that pioneering Confucian revivalists who undertook to translate, interpret and spread Confucian knowledge in Java did not simply follow mainstream ideas that prevailed in China, or the lead of the Straits Settlements. Considered as the first Malay language translation of the ‘Great Learning’ and the ‘Doctrine of the Mean’, with accompanying commentaries, Yoe Tjai Siang and Tan Ging Tiong's Kitab Tai Hak–Tiong Iong (1900), contained an eclectic blend of Hokkien/Chinese, Malay, Javanese, Dutch/Christian and Arabic/Islamic concepts and vocabulary. Analysis of the translators’ aims and the work itself, shows that Java's peranakan Chinese initially developed a unique, creolised interpretation of Confucianism, while being connected to other reformers and revivalists in China and the Straits Settlements. As these connections and formal educational exchanges intensified, this creolised interpretation of Confucianism in Java would give way to a more orthodox version.
Expert knowledge assessment of threats and conservation strategies for breeding Hen Harrier and Short-eared Owl across Europe
Authors: FERNÁNDEZ-BELLON DARÍO , LUSBY JOHN , BOS JULES , SCHAUB TONIO , MCCARTHY ALAN , CARAVAGGI ANTHONY , IRWIN SANDRA , O’HALLORAN JOHN
Published: July 2020

Hen Harrier Circus cyaneus and Short-eared Owl Asio flammeus are open-country birds of prey with overlapping distributions. Although both species face similar conservation threats across their ranges, work to date has largely been undertaken at a national scale with few attempts to collate and assess factors relevant to their conservation at an international scale. Here we use an expert knowledge approach to evaluate the impact of conservation threats and the effectiveness of conservation strategies for each species across Europe. We report results of responses to a questionnaire from 23 Hen Harrier experts from nine countries and 12 Short-eared Owl experts from six countries. The majority of responses for both species reported declines in breeding numbers. The perceived impact of threats was broadly similar for both species: ecological factors (predation, extreme weather and prey availability), changes in land use (habitat loss and agricultural intensification) and indirect persecution (accidental nest destruction) were considered to be the greatest threats to breeding Hen Harrier and Short-eared Owl. Short-eared Owl experts also highlighted lack of knowledge and difficulties associated with monitoring as a major conservation challenge. Despite broad-scale similarities, geographical variation was also apparent in the perceived importance of conservation threats, with some threats (such as direct persecution, large-scale afforestation or habitat degradation) requiring country-specific actions. Implementation of different conservation strategies also varied between countries, with the designation of protected areas reported as the most widespread conservation strategy adopted, followed by species and habitat management. However, protected areas (including species-specific protected areas) were perceived to be less effective than active management of species and habitats. These findings highlight the overlap between the conservation requirements of these two species, and the need for collaborative international research and conservation approaches that prioritise pro-active conservation strategies subject to continued assessment and with specific conservation goals.
Macroeconomic Interventions and the Politics of Postwar Justice
Authors: Lai Daniela
Published: July 2020

This essay connects feminist political economy and critical/feminist transitional justice through the analysis of macroeconomic interventions in postwar Bosnia and Herzegovina. Previous contributions to Critical Perspectives have argued for the need to establish a dialogue and bring down divides between feminist security studies and political economy in feminist International Relations (Elias 2015; Chisolm and Stachowitsch 2017) and to look at the spaces where security and political economy intersect as a productive line of research (Sjoberg 2015). To build these connections, feminist scholars have stressed the importance of multidimensional concepts and questioned their unidimensional use whenever relevant. Security is certainly one of the concepts benefiting from a feminist critique that has opened up its meaning, with reference to its referent objects as well as its multiple dimensions (e.g., to include women's economic security alongside physical security; see Chisolm and Stachowitsch 2017; True 2015). Another concept that has been productively reframed as multidimensional by feminist scholars is violence (Bergeron, Cohn, and Duncanson 2017; Elias and Rai 2015; True 2012).
Leader Interpersonal Emotion Regulation and Follower Performance
Authors: Vasquez Cristian A. , Niven Karen , Madrid Hector P.
Published: July 2020

Abstract. Interpersonal emotion regulation (IER) refers to the actions of influencing other people’s feelings. We apply this construct to the context of leadership to determine whether leader IER may explain followers’ performance. Drawing on emotions-as-social-information theory, we argue that leader strategies to improve or worsen followers’ feelings would be related to followers’ affect and thereby to their performance. We tested these proposals using a multisource field study involving 31 leaders and 157 followers. Results from multilevel modeling supported a mediation model in which leaders’ attempts to improve their followers’ feelings enhance followers’ task performance via the followers’ experience of positive affect. In contrast, leaders’ use of affect-worsening actions was associated with the experience of followers’ negative affect, but not related to task performance. These findings contribute by expanding knowledge on the affective underpinnings of the leader–follower relationship and informing the development of leadership interventions aimed to foster employee performance.
Weathering Environmental Change Through Advances in AI
Authors: McGovern Amy , Bostrom Ann , Ebert-Uphoff Imme , He Ruoying , Thorncroft Chris , Tissot Philippe , Boukabara Sid , Demuth Julie , Gagne II David , Hickey Jason , Williams John
Published: July 2020

Developing trustworthy artificial intelligence for weather and ocean forecasting, as well as for long-term environmental sustainability, requires integrating collaborative efforts from many sources.
Geoengineered Ocean Vertical Water Exchange Can Accelerate Global Deoxygenation
Authors: Feng Ellias Yuming , Su Bei , Oschlies Andreas
Published: July 2020

Ocean deoxygenation is a threat to marine ecosystems. We evaluated the potential of two ocean intervention technologies, that is, “artificial downwelling (AD)” and “artificial upwelling (AU),” for remedying the expansion of Oxygen Deficient Zones (ODZs). The model‐based assessment simulated AD and AU implementations for 80 years along the eastern Pacific ODZ. When AD was simulated by pumping surface seawater to the 178–457 m‐depth range of the ODZ, vertically integrated oxygen increased by up to 4.5% in the deployment region. Pumping water from 457 m depth to the surface (i.e., AU), where it can equilibrate with the atmosphere, increased the vertically integrated oxygen by 1.03%. However, both simulated AD and AU increased biological production via enhanced nutrient supply to the sea surface, resulting in enhanced export production and subsequent aerobic remineralization also outside of the actual implementation region, and an ultimate net decline of global oceanic oxygen.
The Sources of Uncertainty in the Projection of Global Land Monsoon Precipitation
Authors: Zhou Tianjun , Lu Jingwen , Zhang Wenxia , Chen Ziming
Published: July 2020

Policy makers need reliable future climate projection for adaptation purposes. A clear separation of sources of uncertainty also helps narrow the projection uncertainty. However, it remains unclear for monsoon precipitation projections. Here we quantified the contributions of internal variability, model uncertainty, and scenario uncertainty to the ensemble spread of global land monsoon precipitation projections using Coupled Model Intercomparison Project Phase 5 (CMIP5) models and single‐model initial‐condition large ensembles (SMILEs). For mean precipitation, model uncertainty (contributing ~90%) dominates the projection uncertainty, while the contribution of internal variability (scenario uncertainty) decreases (increases) with time. The source of uncertainty for extreme precipitation differs from that of mean precipitation mainly in long‐term projection, with the contribution of scenario uncertainty comparable to model uncertainty. Reducing model uncertainty can effectively narrow the monsoon precipitation projection. The internal variability estimates differ slightly among models and methods, the uncertainty partitioning is robust in middle‐long term.
Raindrop Signature from Microwave Radiometer Over Deserts
Authors: You Yalei , Joseph Munchak S. , Ferraro Ralph , Mohr Karen , Peters‐Lidard Christa , Prigent Catherine , Ringerud Sarah , Rudlosky Scott , Wang Heshun , Norouzi Hamidreza , Prakash Satya
Published: July 2020

Rainfall estimates from spaceborne microwave radiometers form the foundation of global precipitation data sets. Since the beginning of the satellite microwave rainfall estimation era in the 1980s, the primary signature leveraged over land for these estimates has been the brightness temperature (TB) depression due to ice particle scattering. Contrary to this practice, time series analyses based on observations from two spaceborne radars and two spaceborne radiometers reveal a TB increase at H19 due to raindrop emission as the primary cloud particle signature over desert terrain. Low surface emissivity supports the use of liquid raindrop emission as the primary signature over desert surfaces. In these regions, the surface rain rate better correlates with the liquid raindrop emission signal than with the scattering induced by ice further aloft, suggesting a new potential for improving rainfall estimation over deserts by exploiting the liquid raindrop emission signature.
Downward Continuation and Transformation of Total‐Field Magnetic Anomalies Into Magnetic Gradient Tensors Between Arbitrary Surfaces Using Multilayer Equivalent Sources
Authors: Zuo Boxin , Hu Xiangyun , Leão‐Santos Marcelo , Wang Lizhe , Cai Yi
Published: July 2020

The equivalent source method offers a potential means for continuing and manipulating magnetic data between arbitrary surfaces. However, it ultimately suffers from a limited continuation distance and significant errors, which restrict its applicability in practice. To address this problem, we reformulate the equivalent source method with a partial differential equation framework. A multilayer equivalent susceptibility method is innovatively derived based on this approach. The location of equivalent sources is designed for adaptive estimation through the inverse procedure. We introduce nonlinear optimization, regularization, and constraining technologies in inversion to improve the stability and accuracy of the solution. Synthetic, real airborne, and ground data are tested in experiments. The results show that the new method significantly improves the capability and accuracy of the downward continuation and transformation of irregularly located data between arbitrary undulating surfaces.
Can the Madden‐Julian Oscillation Affect the Antarctic Total Column Ozone?
Authors: Yang Chengyun , Smith Anne K. , Li Tao , Kinnison Douglas E. , Li Jianghanyang , Dou Xiankang
Published: July 2020

The effect of the Madden‐Julian Oscillation (MJO) on springtime Antarctic ozone variations is revealed for the first time from multi‐satellite reanalysis and model simulations. Twenty to 30 days after MJO Phase 8 (P8), Antarctic total column ozone (TCO) anomalies significantly decrease by up to −15 DU, associated with a wave‐1 response at around 60°S. After MJO P8, MJO‐related geopotential height anomalies in the southern hemispheric (SH) Indian Ocean emanate from subtropics to polar regions, leading to suppressed upward and poleward propagation of planetary waves (PWs) and weakened Brewer‐Dobson circulation in the SH stratosphere. This in turn results in less ozone transport from midlatitudes into the polar region and thus a negative polar TCO response. Dynamical transport plays a dominant role in modulating the Antarctic TCO after MJO P8. The magnitude of transient changes due to chemical processes is relatively weak than that caused by dynamical transport.
Current concepts in tumour-derived organoids
Authors: Porter Ross J. , Murray Graeme I. , McLean Mairi H.
Published: July 2020

Cancer comprises a collection of highly proliferative and heterogeneous cells growing within an adaptive and evolving tumour microenvironment. Cancer survival rates have significantly improved following decades of cancer research. However, many experimental and preclinical studies do not translate to the bedside, reflecting the challenges of modelling the complexities and multicellular basis of human disease. Organoids are novel, complex, three-dimensional ex vivo tissue cultures that are derived from embryonic stem cells, induced pluripotent stem cells or tissue-resident progenitor cells, and represent a near-physiological model for studying cancer. Organoids develop by self-organisation, and can accurately represent the diverse genetic, cellular and pathophysiological hallmarks of cancer. In addition, co-culture methods and the ability to genetically manipulate these organoids have widened their utility in cancer research. Organoids thus offer a new and exciting platform for studying cancer and directing personalised therapies. This review aims to highlight how organoids are shaping the future of cancer research.
Integrating single-cell RNA-sequencing and functional assays to decipher mammary cell states and lineage hierarchies
Authors: Regan Joseph L. , Smalley Matthew J.
Published: July 2020

The identification and molecular characterization of cellular hierarchies in complex tissues is key to understanding both normal cellular homeostasis and tumorigenesis. The mammary epithelium is a heterogeneous tissue consisting of two main cellular compartments, an outer basal layer containing myoepithelial cells and an inner luminal layer consisting of estrogen receptor-negative (ER−) ductal cells and secretory alveolar cells (in the fully functional differentiated tissue) and hormone-responsive estrogen receptor-positive (ER+) cells. Recent publications have used single-cell RNA-sequencing (scRNA-seq) analysis to decipher epithelial cell differentiation hierarchies in human and murine mammary glands, and reported the identification of new cell types and states based on the expression of the luminal progenitor cell marker KIT (c-Kit). These studies allow for comprehensive and unbiased analysis of the different cell types that constitute a heterogeneous tissue. Here we discuss scRNA-seq studies in the context of previous research in which mammary epithelial cell populations were molecularly and functionally characterized, and identified c-Kit+ progenitors and cell states analogous to those reported in the recent scRNA-seq studies.
Spatiotemporal DNA methylome dynamics of the developing mouse fetus
Authors: He Yupeng , Hariharan Manoj , Gorkin David U. , Dickel Diane E. , Luo Chongyuan , Castanon Rosa G. , Nery Joseph R. , Lee Ah Young , Zhao Yuan , Huang Hui , Williams Brian A. , Trout Diane , Amrhein Henry , Fang Rongxin , Chen Huaming , Li Bin , Visel Axel , Pennacchio Len A. , Ren Bing , Ecker Joseph R.
Published: July 2020

Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited1,2. Here, as part of the mouse Encyclopedia of DNA Elements (ENCODE) project, we profiled 168 methylomes from 12 mouse tissues or organs at 9 developmental stages from embryogenesis to adulthood. We identified 1,808,810 genomic regions that showed variations in CG methylation by comparing the methylomes of different tissues or organs from different developmental stages. These DNA elements predominantly lose CG methylation during fetal development, whereas the trend is reversed after birth. During late stages of fetal development, non-CG methylation accumulated within the bodies of key developmental transcription factor genes, coinciding with their transcriptional repression. Integration of genome-wide DNA methylation, histone modification and chromatin accessibility data enabled us to predict 461,141 putative developmental tissue-specific enhancers, the human orthologues of which were enriched for disease-associated genetic variants. These spatiotemporal epigenome maps provide a resource for studies of gene regulation during tissue or organ progression, and a starting point for investigating regulatory elements that are involved in human developmental disorders.
First evidence of microbial wood degradation in the coastal waters of the Antarctic
Authors: Björdal Charlotte G. , Dayton Paul K.
Published: July 2020

Wood submerged in saline and oxygenated marine waters worldwide is efficiently degraded by crustaceans and molluscs. Nevertheless, in the cold coastal waters of the Antarctic, these degraders seem to be absent and no evidence of other wood-degrading organisms has been reported so far. Here we examine long-term exposed anthropogenic wood material (Douglas Fir) collected at the seafloor close to McMurdo station, Antarctica. We used light and scanning electron microscopy and demonstrate that two types of specialized lignocellulolytic microbes—soft rot fungi and tunnelling bacteria—are active and degrade wood in this extreme environment. Fungal decay dominates and hyphae penetrate the outer 2–4 mm of the wood surface. Decay rates observed are about two orders of magnitude lower than normal. The fungi and bacteria, as well as their respective cavities and tunnels, are slightly smaller than normal, which might represent an adaptation to the extreme cold environment. Our results establish that there is ongoing wood degradation also in the Antarctic, albeit at a vastly reduced rate compared to warmer environments. Historical shipwrecks resting on the seafloor are most likely still in good condition, although surface details such as wood carvings, tool marks, and paint slowly disintegrate due to microbial decay.
Global prevalence and distribution of vancomycin resistant, vancomycin intermediate and heterogeneously vancomycin intermediate Staphylococcus aureus clinical isolates: a systematic review and meta-analysis
Authors: Shariati Aref , Dadashi Masoud , Moghadam Majid Taati , van Belkum Alex , Yaslianifard Somayeh , Darban-Sarokhalil Davood
Published: July 2020

Vancomycin-resistantStaphylococcus aureus(VRSA), Vancomycin-intermediateS. aureus(VISA) and heterogeneous VISA (hVISA) are subject to vancomycin treatment failure. The aim of the present study was to determine their precise prevalence and investigate prevalence variability depending on different years and locations. Several international databases including Medline (PubMed), Embase and Web of Sciences were searched (data from 1997 to 2019) to identify studies that addressed the prevalence of VRSA, VISA and hVISA among human clinical isolates around the world. Subgroup analyses and meta-regression were conducted to indicate potential source of variation. Publication bias was assessed using Egger’s test. Statistical analyses were conducted using STATA software (version 14.0). Data analysis showed that VRSA, VISA and hVISA isolates were reported in 23, 50 and 82 studies, with an overall prevalence of 1.5% among 5855S. aureusisolates, 1.7% among 22,277 strains and 4.6% among 47,721 strains, respectively. The overall prevalence of VRSA, VISA, and hVISA before 2010 was 1.2%, 1.2%, and 4%, respectively, while their prevalence after this year has reached 2.4%, 4.3%, and 5.3%. The results of this study showed that the frequency of VRSA, VISA and hVISA after 2010 represent a 2.0, 3.6 and 1.3-fold increase over prior years. In a subgroup analysis of different strain origins, the highest frequency of VRSA (3.6%) and hVISA (5.2%) was encountered in the USA while VISA (2.1%) was more prevalent in Asia. Meta-regression analysis showed significant increasing of VISA prevalence in recent years (pvalue ≤ 0.05). Based on the results of case reports (which were not included in the calculations mentioned above), the numbers of VRSA, VISA and hVISA isolates were 12, 24 and 14, respectively, among different continents. Since the prevalence of VRSA, VISA and hVISA has been increasing in recent years (especially in the Asian and American continents), rigorous monitoring of vancomycin treatment, it’s the therapeutic response and the definition of appropriate control guidelines depending on geographical regions is highly recommended and essential to prevent the further spread of vancomycin-resistantS. aureus.
Long-term sustainability of biogas bubbles in sand
Authors: Hu Xiaoying , Li Dandan , Peng Erxing , Hou Zheng , Sheng Yu , Chou Yaling
Published: July 2020

Desaturation is a new method to mitigate liquefaction of sand. It aims to prevent liquefaction by generating gas/air in the pores of fully saturated sands, and biogas is one of the most suitable gas. In order to evaluate the long-term sustainability of biogas bubbles, a series sustainability test on biogas bubbles in pores of sand was conducted with a one-dimensional device under hydrostatic condition, hydraulic gradient flow condition and horizontal excitation condition. The variation trend of the retention of biogas bubbles in the pores of soil under the aforementioned conditions was analyzed. Test results indicated that after 72 weeks of monitoring sand samples, biogas bubbles existed stably in the pores of soil under hydrostatic conditions. In hydraulic gradient flow, the stability under upward seepage flow showed a similar trend to that of downward seepage flow. When the hydraulic gradient was constant, the degree of saturation increased in a certain period and finally remained constant. When the hydraulic gradient increased by 0.1, 0.2, 0.3, 0.4, and 0.5, the degrees of saturation increase were 0.8%, 11.5%, 0.5%, 0.1%, and 0%, respectively. After 41,200 cycles with different accelerations, the degree of saturation of the sample increased slightly, and the biogas bubbles basically remained stable.
Action sound–shape congruencies explain sound symbolism
Authors: Margiotoudi Konstantina , Pulvermüller Friedemann
Published: July 2020

Sound symbolism, the surprising semantic relationship between meaningless pseudowords (e.g., ‘maluma’, ‘takete’) and abstract (round vs. sharp) shapes, is a hitherto unexplained human-specific knowledge domain. Here we explore whether abstract sound symbolic links can be explained by those between the sounds and shapes of bodily actions. To this end, we asked human subjects to match pseudowords with abstract shapes and, in a different experimental block, the sounds of actions with the shapes of the trajectories of the actions causing these same sounds. Crucially, both conditions were also crossed. Our findings reveal concordant matching in the sound symbolic and action domains, and, importantly, significant correlations between them. We conclude that the sound symbolic knowledge interlinking speech sounds and abstract shapes is explained by audiovisual information immanent to action experience along with acoustic similarities between speech and action sounds. These results demonstrate a fundamental role of action knowledge for abstract sound symbolism, which may have been key to human symbol-manipulation ability.
Continuous scanning for Bragg coherent X-ray imaging
Authors: Li Ni , Dupraz Maxime , Wu Longfei , Leake Steven J. , Resta Andrea , Carnis Jérôme , Labat Stéphane , Almog Ehud , Rabkin Eugen , Favre-Nicolin Vincent , Picca Frédéric-Emmanuel , Berenguer Felisa , van de Poll Rim , Hofmann Jan P. , Vlad Alina , Thomas Olivier , Garreau Yves , Coati Alessandro , Richard Marie-Ingrid
Published: July 2020

We explore the use of continuous scanning during data acquisition for Bragg coherent diffraction imaging, i.e., where the sample is in continuous motion. The fidelity of continuous scanning Bragg coherent diffraction imaging is demonstrated on a single Pt nanoparticle in a flow reactor at $$400\,^\circ \hbox {C}$$

400

∘

C

in an Ar-based gas flowed at 50 ml/min. We show a reduction of 30% in total scan time compared to conventional step-by-step scanning. The reconstructed Bragg electron density, phase, displacement and strain fields are in excellent agreement with the results obtained from conventional step-by-step scanning. Continuous scanning will allow to minimise sample instability under the beam and will become increasingly important at diffraction-limited storage ring light sources.
Pre-clinical studies of EC2629, a highly potent folate- receptor-targeted DNA crosslinking agent
Authors: Reddy Joseph A. , Nelson Melissa , Dircksen Christina , Vetzel Marilynn , Johnson Theresa , Cross Vicky , Westrick Elaine , Qi LongWu , Hahn Spencer , Santhapuram Hari Krishna , Parham Garth , Wang Kevin , Vaughn Jeremy F. , Felten Albert , Pugh Michael , Lu June , Klein Patrick , Vlahov Iontcho R. , Leamon Christopher P.
Published: July 2020

Folate receptor (FR)-targeted small molecule drug conjugates (SMDCs) have shown promising results in early stage clinical trials with microtubule destabilizing agents, such as vintafolide and EC1456. In our effort to develop FR-targeted SMDCs with varying mechanisms of action, we synthesized EC2629, a folate conjugate of a DNA crosslinking agent based on a novel DNA-alkylating moiety. This agent was found to be extremely potent with an in vitro IC50 ~ 100× lower than folate SMDCs constructed with various microtubule inhibitors. EC2629 treatment of nude mice bearing FR-positive KB human xenografts led to cures in 100% of the test animals with very low dose levels (300 nmol/kg) following a convenient once a week schedule. The observed activity was not accompanied by any noticeable weight loss (up to 20 weeks post end of dosing). Complete responses were also observed against FR-positive paclitaxel (KB-PR) and cisplatin (KB-CR) resistant models. When evaluated against FR-positive patient derived xenograft (PDX) models of ovarian (ST070), endometrial (ST040) and triple negative breast cancers (ST502, ST738), EC2629 showed significantly greater anti-tumor activity compared to their corresponding standard of care treatments. Taken together, these studies thus demonstrated that EC2629, with its distinct DNA reacting mechanism, may be useful in treating FR-positive tumors, including those that are classified as drug resistant.
Integrated bioinformatics analysis to decipher molecular mechanism of compound Kushen injection for esophageal cancer by combining WGCNA with network pharmacology
Authors: Zhou Wei , Wu Jiarui , Zhang Jingyuan , Liu Xinkui , Guo Siyu , Jia ShanShan , Zhang Xiaomeng , Zhu Yingli , Wang Miaomiao
Published: July 2020

Compound Kushen injection (CKI), a medicine in widespread clinical use in China, has proven therapeutic effects on cancer. However, few molecular mechanism analyses have been carried out. To address this problem, bioinformatics approaches combining weighted gene co-expression network analysis with network pharmacology methods were undertaken to elucidate the underlying molecular mechanisms of CKI in the treatment of esophageal cancer (ESCA). First, the key gene modules related to the clinical traits of ESCA were analysed by WCGNA. Based on the results, the hub genes related to CKI treatment for ESCA were explored through network pharmacology. Molecular docking simulation was performed to recognize the binding activity of hub genes with CKI compounds. The results showed that the potential hub targets, including EGFR, ErbB2, CCND1 and IGF1R, are therapeutic targets of CKI for the treatment of ESCA. Moreover, these targets were significantly enriched in many pathways related to cancer and signalling pathways, such as the PI3K-Akt signalling pathway and ErbB signalling pathway. In conclusion, this research partially highlighted the molecular mechanism of CKI in the treatment of ESCA, offering great potential in the identification of the effective compounds in CKI and biomarkers for ESCA treatment.
Plant endophytes promote growth and alleviate salt stress in Arabidopsis thaliana
Authors: Fan Di , Subramanian Sowmyalakshmi , Smith Donald L.
Published: July 2020

Plant growth promoting rhizobacteria (PGPR) are a functionally diverse group of microbes having immense potential as biostimulants and stress alleviators. Their exploitation in agro-ecosystems as an eco-friendly and cost-effective alternative to traditional chemical inputs may positively affect agricultural productivity and environmental sustainability. The present study describes selected rhizobacteria, from a range of origins, having plant growth promoting potential under controlled conditions. A total of 98 isolates (ectophytic or endophytic) from various crop and uncultivated plants were screened, out of which four endophytes (n, L, K and Y) from Phalaris arundinacea, Solanum dulcamara, Scorzoneroides autumnalis, and Glycine max, respectively, were selected in vitro for their vegetative growth stimulating effects on Arabidopsis thaliana Col-0 seedlings with regard to leaf surface area and shoot fresh weight. A 16S rRNA gene sequencing analysis of the strains indicated that these isolates belong to the genera Pseudomonas, Bacillus, Mucilaginibacter and Rhizobium. Strains were then further tested for their effects on abiotic stress alleviation under both Petri-plate and pot conditions. Results from Petri-dish assay indicated strains L, K and Y alleviated salt stress in Arabidopsis seedlings, while strains K and Y conferred increases in fresh weight and leaf area under osmotic stress. Results from subsequent in vivo trials indicated all the isolates, especially strains L, K and Y, distinctly increased A. thaliana growth under both normal and high salinity conditions, as compared to control plants. The activity of antioxidant enzymes (ascorbate peroxidase, catalase and peroxidase), proline content and total antioxidative capacity also differed in the inoculated A. thaliana plants. Furthermore, a study on spatial distribution of the four strains, using either conventional Petri-plate counts or GFP-tagged bacteria, indicated that all four strains were able to colonize the endosphere of A. thaliana root tissue. Thus, the study revealed that the four selected rhizobacteria are good candidates to be explored as plant growth stimulators, which also possess salt stress mitigating property, partially by regulating osmolytes and antioxidant enzymes. Moreover, the study is the first report of Scorzoneroides autumnalis (fall dandelion) and Solanum dulcamara (bittersweet) associated endophytes with PGP effects.
Incidence, reasons, and risk factors for 30-day readmission after lumbar spine surgery for degenerative spinal disease
Authors: Cho Pyung Goo , Kim Tae Hyun , Lee Hana , Ji Gyu Yeul , Park Sang Hyuk , Shin Dong Ah
Published: July 2020

This study investigated risk factors for 30-day readmission of discharged patients who had undergone lumbar spinal surgery. This retrospective, case–control study reviewed 3,933 patients discharged after elective spinal surgery for lumbar degenerative diseases from 2005 to 2012 at a university hospital. Of these patients, 102 were re-hospitalized within 30 days of discharge. Patient medical records were reviewed. The incidence of readmission within 30 days was 2.6%, and uncontrolled pain was the most common reason for readmission. In the univariate analysis, age, mental illness, the number of medical comorbidities, previous spinal surgery, fusion surgery, number of fusion levels, estimated blood loss, operation time, intensive care unit (ICU) admission, length of hospital stays, and total medical expenses were associated with a higher risk of readmission within 30 days. Multiple logistic regression analysis revealed that previous spinal surgery, operation time, ICU admission, length of hospital stays, and total medical expenses were independent risk factors for 30-day readmission. Independent risk factors for readmission were longer operation time, a previous spinal surgery, ICU admission, longer hospital stays, and higher medical expenses. Further studies controlling these risk factors could contribute to reducing readmission and thus improving the quality of care.
Confined transverse-electric graphene plasmons in negative refractive-index systems
Authors: Zhang Xinyan , Hu Hao , Lin Xiao , Shen Lian , Zhang Baile , Chen Hongsheng
Published: July 2020

Transverse electric graphene plasmons are generally weakly confined in the direction perpendicular to the graphene plane. They are featured by a skin depth δ, namely the penetration depth of their evanescent fields into the surrounding environment, much larger than the wavelength λ in free space (e.g., δ > 10λ). The weak spatial confinement of transverse electric graphene plasmons is now the key drawback that limits their practical applications. Here we report the skin depth of TE graphene plasmons can be largely decreased down to the subwavelength scale (e.g., δ < λ/10) in negative refractive-index environments. The underlying mechanism originates from the different existence conditions for TE graphene plasmons in negative and positive refractive-index environments. To be specific, their existence in negative (positive) refractive-index environments requires Im(σs) > 0 (Im(σs) < 0) and lies in the frequency range of ħω/μc < 1.667 (ħω/μc > 1.667), where σs and μc are the surface conductivity and chemical potential of monolayer graphene, respectively.
Exploitation of human mesenchymal stromal cell derived matrix towards the structural and functional restoration of the ocular surface
Authors: Yan Dan , Yan Chenxi , Yu Fei , Zhang Siyi , Chen Liangbo , Wu Nianxuan , Shao Chunyi , Yao Qinke , Sun Hao , Fu Yao
Published: July 2020

Decellularized matrix of ADMSCs is a promising conjunctival substitute with superb wound repairing property by promoting proliferation of conjunctival epithelial cells and restoring goblet cells without causing cosmetic differences.
In vitro and in vivo studies on ultrafine-grained biodegradable pure Mg, Mg–Ca alloy and Mg–Sr alloy processed by high-pressure torsion
Authors: Li Wenting , Liu Xiao , Zheng Yufeng , Wang Wenhao , Qiao Wei , Yeung Kelvin W. K. , Cheung Kenneth M. C. , Guan Shaokang , Kulyasova Olga B. , Valiev R. Z.
Published: July 2020

High-pressure torsion processing is an effective way to significantly refine the microstructure and consequently modify the mechanical properties, biodegradable behaviors and biocompatibility of pure Mg, Mg–1Ca and Mg–2Sr alloys.
Tumor microenvironment responsive supramolecular glyco-nanovesicles based on diselenium-bridged pillar[5]arene dimer for targeted chemotherapy
Authors: Wang Yang , Jin Ming , Chen Zelong , Hu Xianjun , Pu Liang , Pei Zhichao , Pei Yuxin
Published: July 2020

Supramolecular glyco-nanovesicles (SeSe-(P5)2⊃Man-NH3+) were successfully constructed via the self-assembly of a diselenium-bridged pillar[5]arene dimer and a mannose derivative, which exhibited tumor microenvironment-responsiveness and targetability.
A highly diastereoselective synthesis of deep molecular baskets
Authors: Lei Zhiquan , Gunther Michael J. , Liyana Gunawardana Vageesha W. , Pavlović Radoslav Z. , Xie Han , Zhu Xingrong , Keenan Mason , Riggs Alex , Badjić Jovica D.
Published: July 2020

A novel synthetic method for obtaining multigram quantities of uniquely functionalized and deep molecular baskets is now available, clearing the way toward useful supramolecular materials.
Correction: Cryptand-imidazolium supported total synthesis of the lasso peptide BI-32169 and its d-enantiomer
Authors: Chen Ming , Wang Shuanglong , Yu Xihan
Published: July 2020

Correction for ‘Cryptand-imidazolium supported total synthesis of the lasso peptide BI-32169 and its d-enantiomer’ by Ming Chen et al., Chem. Commun., 2019, 55, 3323–3326, DOI: 10.1039/C8CC10301A.
Anticancer and antitrypanosomal activities of trinuclear ruthenium compounds with orthometalated phenazine ligands
Authors: da Silva Camila Fontes Neves , Chrispim Pedro Branco Hauch , Possato Bruna , Portapilla Gisele Bulhões , Rohrabaugh Thomas N. , Ramos Loyanne Carla Barbosa , Santana da Silva Roberto , de Albuquerque Sérgio , Turro Claudia , Nikolaou Sofia
Published: July 2020

Four metalo-intercalators ([Ru3(μ3-O)(μ2-OAc)5(L)(py)2]PF6, L = phenazines) present high DNA intercalation constants and high HSA affinity. They are active against melanoma cancer and T. Cruzi parasite.
Slow magnetic relaxation in cobalt N-heterocyclic carbene complexes
Authors: Saber Mohamed R. , Przyojski Jacob A. , Tonzetich Zachary J. , Dunbar Kim R.
Published: July 2020

The combined experimental and theoretical investigation of the magnetic properties of [Co(CH2SiMe3)2(IPr)] (1), [CoCl2(IMes)2] (2) revealed a large easy plane anisotropy for 1 and a moderate easy axis anisotropy for 2.
In situ organic solvent-free synthesis of a novel red emitting Mn4+ doped KRbGeF6 phosphor at the room temperature
Authors: Jia Yajun , Pan Yuexiao , Zhu Jiawen , Chen Xi'an , Wang Aiyin , Lian Hongzhou , Lin Jun
Published: July 2020

An efficient red emitting phosphor KRbGeF6 : Mn4+ was prepared by an in situ one-pot ion-exchange method at room temperature without organic solvents or HF.
Ductile cooling phase change material
Authors: Gogoi Pratahdeep , Li Zheng , Guo Zipeng , Khuje Saurabh , An Lu , Hu Yong , Chang Shuquan , Zhou Chi , Ren Shenqiang
Published: July 2020

The as-manufactured elastic and flexible hydrogels demonstrate a potential application in the ductile cooling phase-change medium.
Monitoring ligand-mediated helix 12 transitions within the human estrogen receptor α using bipartite tetracysteine display
Authors: Pokhrel Ranju , Tang Tang , Holub Justin M.
Published: July 2020

Fluorescent labeling coupled with bipartite tetracysteine display enables the surveillance of ligand-mediated helix 12 transitions within the estrogen receptor α ligand-binding domain.
Oxidative trimerization of indoles via water-assisted visible-light photoredox catalysis and the study of their anti-cancer activities
Authors: Cheng Li-Ting , Luo Sheng-Qi , Hong Bor-Cherng , Chen Chia-Ling , Li Wen-Shan , Lee Gene-Hsiang
Published: July 2020

The water-promoted visible-light photoreaction of indole was demonstrated, and the indolinones synthesized were evaluated for their anti-cancer activities.
The conjugation of rhodamine B enables carrier-free mitochondrial delivery of functional proteins
Authors: Shi Jiayuan , Zhao Dan , Li Xiang , Ding Feng , Tang Xuemei , Liu Nian , Huang Hua , Liu Changlin
Published: July 2020

Small molecule-guided mitochondrial carrier-free delivery and tumor suppression of functional proteins.
Photoisomerization of azobenzene units drives the photochemical reaction cycles of proteorhodopsin and bacteriorhodopsin analogues
Authors: Haque Shariful , Kikukawa Takashi , Tamaoki Nobuyuki
Published: July 2020

In this study we substituted the retinal units in proteorhodopsin (PR) and bacteriorhodopsin (BR) with azo chromophores to investigate the mechanism of photoinduced proton pumping in rhodopsins and potentially develop new artificial molecular pumps.
Polymer mask-weakening grain-boundary effect: towards high-performance organic thin-film transistors with mobility closing to 20 cm2 V−1 s−1
Authors: Ji Deyang , Li Jie , Chen Xiaosong , Li Lin , Li Liqiang , Hu Wenping
Published: July 2020

Polystyrene-based masks are fabricated to produce top-contact high-resolution (5 μm) electrodes. With this mask, the mobility of DPA-based thin-film transistors could reach 19.22 cm2 V−1 s−1, which is a new breakthrough for DPA thin-film transistors.
Highly biodegradable, thermostable eutectogels prepared by gelation of natural deep eutectic solvents using xanthan gum: preparation and characterization
Authors: Zeng Chaoxi , Zhao Haiyang , Wan Zheng , Xiao Qian , Xia Huiping , Guo Shiyin
Published: July 2020

Highly biodegradable, thermostable eutectogels prepared by gelation of natural deep eutectic solvents using xanthan gum are expected to be widely used in the fields of food, medicine and materials.
ZnO-embedded S-doped g-C3N4 heterojunction: mediator-free Z-scheme mechanism for enhanced charge separation and photocatalytic degradation
Authors: Kalisamy Periyathambi , Lallimathi Mathiazhagan , Suryamathi Mathiazhagan , Palanivel Baskaran , Venkatachalam Munusamy
Published: July 2020

We have developed the LED light active ZnO-embedded S-doped g-C3N4 (SCN) mediator free Z-scheme heterojunction photocatalyst for effective organic pollutant degradation.