bluuebunny/crossref_metadata_2025 huggingface dataset:
Getting in synch: Unpacking the role of parent–child synchrony in the development of internalizing and externalizing behaviors
Authors: Quiñones-Camacho Laura E. , Hoyniak Caroline P. , Wakschlag Lauren S. , Perlman Susan B.
Published: September 2021

While substantial research supports the role of parent–child interactions on the emergence of psychiatric symptoms, few studies have explored biological mechanisms for this association. The current study explored behavioral and neural parent–child synchronization during frustration and play as predictors of internalizing and externalizing behaviors across a span of 1.5 years. Parent–child dyads first came to the laboratory when the child was 4–5 years old and completed the Disruptive Behavior Diagnostic Observation Schedule: Biological Synchrony (DB-DOS: BioSync) task while functional near-infrared spectroscopy (fNIRS) data were recorded. Parents reported on their child's internalizing and externalizing behaviors using the Child Behavior Checklist (CBCL) four times over 1.5 years. Latent growth curve (LGC) modeling was conducted to assess neural and behavioral synchrony as predictors of internalizing and externalizing trajectories. Consistent with previous investigations in this age range, on average, internalizing and externalizing behaviors decreased over the four time points. Parent–child neural synchrony during a period of play predicted rate of change in internalizing but not externalizing behaviors such that higher parent–child neural synchrony was associated with a more rapid decrease in internalizing behaviors. Our results suggest that a parent–child dyad's ability to coordinate neural activation during positive interactions might serve as a protective mechanism in the context of internalizing behaviors.
Deep complex morphophysiological dormancy in seeds of Viburnum plicatum var. formosanum (Adoxaceae) from subtropical mountains
Authors: Chen Shun-Ying , Liu Chiung-Pin , Baskin Carol C. , Chien Ching-Te
Published: September 2021

Viburnum is a temperate-zone genus that also occurs in mountains of South America and Malesia, and seeds of many species have morphophysiological dormancy (MPD). Information on the level of MPD in seeds of species in various clades of Viburnum potentially would increase our understanding of the evolutionary relationships between the nine levels of MPD. Our aim was to determine the level of MPD in seeds of Viburnum plicatum var. formosanum that is endemic to mountains (1800–3000 m a.s.l.) in Taiwan and a member of the Lutescentia clade. The temperature requirements for embryo growth and root and shoot emergence and response of seeds to gibberellic acid (GA) were determined. No fresh seeds germinated during 16 weeks of incubation at 15/5, 20/10, 25/15, 30/20 or 25°C. Embryo growth and root emergence occurred during moist cold stratification at 5°C or at a temperature sequence of 15/5 to 5°C. During cold stratification, embryos length increased from 0.76 ± 0.06 to 3.40 ± 0.26 mm and the embryo length:seed length ratio from 0.20 ± 0.02 to 0.68 ± 0.07. In a temperature sequence simulating field conditions, embryos grew inside seeds at 5°C, roots emerged at 15/5°C and shoots emerged at 20/10°C. The optimum temperature for embryo growth was 5°C. Neither GA3 nor GA4 was effective in promoting root emergence. We conclude that seeds of V. plicatum var. formosanum have deep complex MPD, which is a first report for Viburnum. Dormancy release during the cool season at high elevations helps to ensure that seeds germinate at the beginning of the warm season.
Reimagining the Brown Body
Authors: Lim Wesley
Published: September 2021

William Forsythe’s screendanceAlignigung(2016) depicts two male dancers, one fair- and the other brown-skinned, in hyperflexible and intimate configurations that vacillate between object and human.Alignigungengages with an egalitarian ethos along the same lines as contact improvisation but further demonstrates an alternative masculinity through movement qualities by reimagining the stereotypical brown body.
Embodied Philology
Authors: Feldman Leah
Published: September 2021

A collaboration between actors and musicians of Tashkent, Uzbekistan, and Almaty, Kazakhstan, and local electronic musician and community activist Brother El of Chicago highlights the difficulties of translating embodied performances of race and ethnicity in a transnational post–Cold War context. In a comparative reading taking up a play by the Ilkhom Theatre of Tashkent alongside its citation in the Chicago collaboration, the framework of “embodied philology” exposes the limits of post–Cold War international political alignment.
Innovation in primary health care responses to COVID-19 in Sub-Saharan Africa
Authors: Ray Sunanda , Mash Robert
Published: September 2021

Background:

In May 2020, the African Journal of Primary Health Care and Family Medicine invited submissions on lessons learnt from responses to the COVID-19 pandemic from primary care providers in Africa. This included descriptions of innovations and good practices, the management of COVID-19 in district health services and responses of communities to the outbreak.

Aim:

To synthesise the lessons learnt from the COVID-19 pandemic in the Africa region.

Methods:

A thematic document analysis was conducted on twenty-seven short report publications from Botswana, Ghana, Nigeria, South Africa, Uganda and Zimbabwe. Findings: Eight major themes were derived from the data: community-based activities; screening and testing; reorganisation of health services; emergency care for COVID-19; maintenance of essential non-COVID-19 health services; caring for the vulnerable; use of information technology; and reframing training opportunities. Community health workers were a vital community resource, delivering medications and other supplies to homes, as well as following up on patients with chronic conditions. More investment in community partnerships and social mobilisation was proposed. Difficulties with procurement of test kits and turn-around times were constraints for most countries. Authors described how services were reorganised for focused COVID-19 activities, sometimes to the detriment of essential services and training of junior doctors. Innovations in use of internet technology for communication and remote consultations were explored. The contribution of family medicine principles in upholding the humanity of patients and their families, clear leadership and planning, multidisciplinary teamwork and continuity of care was emphasised even in the context of providing critical care.

Conclusions:

The community-orientated primary care approach was emphasised as well as long-term benefits of technological innovations. The pandemic exposed the need to deliver on governmental commitments to strengthening primary health care and universal health coverage.
The Expression of Cultural Identity in Mosque Architecture in Brunei Darussalam
Authors: Lopes Rui Oliveira , Hasnan Nuriskandar bin Mohd
Published: September 2021

The mosque connotes a place of prostration towards Allah. As a sacred space, mosque designs use great detail to respect specific ceremonial functions and some requirements outlined in the Quran, but accommodate diverse styles and construction materials that several traditional and cultural factors determine. As early as the seventh century, as Islam spread across the Mediterranean, North Africa, East Asia, and Southeast Asia, the mosque remained a quintessential Islamic building for local Muslim communities. Consequently, mosque architecture presents diverse styles and forms. It does not follow a normative design form besides having an essential hall to accommodate the congregation and visibly indicating the qibla. This paper explores mosque architecture designs in Brunei Darussalam to analyse expressions of cultural identity and constructions of a collective identity. Since the 1950s, mosque architecture in Brunei has distinguished itself by amalgamating designs that culturally significant historical exchanges within and beyond the Malay world dictated. The paper argues that specific governmental, social, cultural and economic contexts necessarily inform the built environment and, particularly, that of religious architecture, resulting in the development of autochthon styles.
Developments in the Rorschach Assessment of Disordered Thinking and	Communication
Authors: Kleiger James H. , Mihura Joni L.
Published: September 2021

Abstract. In its first 100 years, the Rorschach has been heralded as a valuable method for investigating disturbances in thought organization and reasoning. It has survived periods of intense scrutiny and criticism, as contemporary researchers continued to demonstrate the empirical validity of the Rorschach as a measure of disordered thinking ( Mihura et al., 2013 ). It is fitting to mark the centenary of Rorschach’s “experiment” by summarizing contemporary contributions of the Rorschach Performance Assessment System (R-PAS) and reviewing the empirical and conceptual bases for using the inkblots to assess disordered thinking and communication.
The Rorschach and Trauma – An Update
Authors: Kaser-Boyd Nancy
Published: September 2021

Abstract. Early research on trauma employing the Rorschach found it to be an ideal instrument, with its red, black, gray, and vibrant colors, to elicit trauma content. Two patterns of Rorschach responses emerged: the constricted pattern, where the evaluee kept to a form-based, avoidant approach to the blot, as if defending against the memories of the trauma, and a flooded pattern, where morbid and aggressive images paralleled that of psychosis. The Rorschach as an instrument continues to demonstrate high sensitivity to the experience of trauma, and research since 2005 has added complexity and additional validation for the use of the Rorschach in the evaluation of the effects of trauma.
Identifying and Characterizing Subsurface Tropical Instability Waves in the Atlantic Ocean in Simulations and Observations
Authors: Specht Mia Sophie , Jungclaus Johann , Bader Jürgen
Published: September 2021

Recent observations in the Pacific Ocean suggest that, apart from tropical instability waves (TIWs) at the surface, there also exist subsurface tropical instability waves (subTIWs), which can alter vertical mixing. However, the extent to which subTIWs impact mixing and heat flux is still unknown. Moreover, studies on subTIWs have been conducted exclusively in the Pacific. Here, we show the presence of subTIWs in the Atlantic for the first time, using mooring observations. Analyzing 16 years of simulations of a comprehensive, global, high‐resolution ocean model, we characterize subTIWs in the Atlantic with regard to their spatial and temporal variability and investigate their influence on vertical mixing. We find subTIWs in the Atlantic between 40 and 90 m depth in both the model and observations. Furthermore, the model results reveal that unlike TIWs, subTIWs frequently also occur south of the Equator in the Atlantic Ocean. We show that subTIWs induce an oscillating multilayer shear structure, suggesting subTIWs to destabilize the mean flow and thereby induce mixing. This is strongest north of the Equator, where both TIWs and subTIWs act simultaneously. We conclude that despite similar characteristics, TIWs and subTIWs are distinct waves which both impact mixing and heat flux within the thermocline. Therefore, future studies of thermocline dynamics in the tropical oceans should not only consider TIWs but also take into account the effect of subTIWs, particularly in the subTIW dominated region south of the Equator.
Satellite Constraints on the Latitudinal Distribution and Temperature Sensitivity of Wetland Methane Emissions
Authors: Ma Shuang , Worden John R. , Bloom A. Anthony , Zhang Yuzhong , Poulter Benjamin , Cusworth Daniel H. , Yin Yi , Pandey Sudhanshu , Maasakkers Joannes D. , Lu Xiao , Shen Lu , Sheng Jianxiong , Frankenberg Christian , Miller Charles E. , Jacob Daniel J.
Published: September 2021

Wetland methane (CH4) emissions comprise about one‐third of the global CH4 source. The latitudinal distribution and climate sensitivity of wetland CH4 fluxes are the key determinants of the global CH4‐climate feedback. However, large differences exist between bottom‐up estimates, informed by ground‐based flux measurements, and top‐down estimates derived from spaceborne total column CH4. Despite the extensive coverage of satellite CH4 concentration observations, challenges remain with using top‐down estimates to test bottom‐up models, mainly because of the uncertainties in the satellite retrievals, the model representation errors, the variable prior emissions, and the confounding role of the posterior error covariance structures. Here, we use satellite‐based top‐down CH4 flux estimates (2010–2012) to test and refine 42 bottom‐up estimates of wetland emissions that use a range of hypothesized wetland extents and process controls. Our comparison between bottom‐up models and satellite‐based fluxes innovatively accounts for cross‐correlations and spatial uncertainties typically found in top‐down inverse estimates, such that only the information from satellite observations and the atmospheric transport model is kept as a constraint. We present a satellite‐constrained wetland CH4 ensemble product derived from assembling the highest‐performance bottom‐up models, which estimates global wetland CH4 emissions of 148 (117–189, 5th–95th percentile) Tg CH4 yr−1. We find that tropical wetland emissions contribute 72% (63%–85%) to the global wetland total. We also find that a lower‐than‐expected temperature sensitivity agrees better with atmospheric CH4 measurements. Overall, our approach demonstrates the potential for using satellites to quantitatively refine bottom‐up wetland CH4 emission estimates, their latitudinal distributions, and their sensitivity to climate.
Climate Feedback From Wetland Emissions of Methane May Necessitate Greater Anthropogenic Reductions
Authors: Thompson Rona L.
Published: September 2021

Key Points

Reducing methane emissions is key to limiting warming to 1.5 or 2.0°C in emission pathways to 2050

The climate response of wetland methane emissions is an important uncertainty in how much anthropogenic emissions will need to be reduced

Atmospheric observations and inverse modeling are crucial to monitoring emission reduction measures and changes in wetland emissions
Horizontal Movement of Polar Mesospheric Clouds Observed From the Himawari‐8 Geostationary Meteorological Satellite
Authors: Hozumi Yuta , Tsuda Takuo T. , Hosokawa Keisuke , Ando Yoshiaki , Suzuki Hidehiko , Murata Takeshi , Nakamura Takuji
Published: September 2021

The horizontal movement of polar mesospheric clouds (PMCs) is examined with data from Geostationary‐Earth‐Orbit (GEO) meteorological satellite Himawari‐8 using a cloud tracking technique. While previous PMC observations from the ground and Low‐Earth‐Orbit satellites have a limitation on local time coverage or field of view, observations from the GEO satellite provide a great opportunity to study the PMC variability with entire local time coverage and a wide field of view. A pattern matching technique is applied to PMC data from the Advanced Himawari Imagers (AHIs) onboard Himawari‐8, and the horizontal movement of PMC along the transverse direction to the line of sight is derived. At the center of field of view of AHI, the tracking velocity represents the zonal movement of PMCs around the latitude of 81.3°N and the longitude of 140.7°E. The horizontal movement shows large oscillations with amplitudes of 10–30 m/s and spectral peaks at periods of 12, 14.8, and 24 h. The mean zonal velocity for the northern summer season of 2018 is about 8 m/s in the westward direction. The characteristics of the tracking winds resemble those of horizontal wind reported by previous studies. This indicates that the horizontal movements of PMC observed by Himawari‐8 are mainly subjected to wind advection.
Latitudinal and Seasonal Asymmetries of the Helium Bulge in the Martian Upper Atmosphere
Authors: Gupta Neha , Rao N. V. , Bougher S. , Elrod M. K.
Published: September 2021

In the present study, we investigate the characteristics of helium (He) bulges in the Martian upper atmosphere using He densities and winds measured by the Neutral Gas and Ion Mass Spectrometer (NGIMS) aboard the Mars Atmosphere and Volatile EvolutioN (MAVEN) spacecraft. The observations are compared with those predicted by the Mars Global Ionosphere Thermosphere Model (M‐GITM). The results of the present study show that the nightside He bulge is a persistent feature of the Martian upper atmosphere in all seasons. The He densities inside the bulges are 1–2 orders of magnitude greater than those on the dayside. In solstices, the bulges are observed in the winter polar region which is in accordance with the model predictions. In equinoxes, however, the bulges are observed to extend from mid‐latitudes into the southern polar regions (>60°S), which is contrary to the model predictions at mid‐latitudes. These anomalous bulges are predominantly observed in the northern spring equinox and are 10–30 × greater than the modeled ones. During the autumnal equinox, the observed winds depart from the modeled winds. Furthermore, the observed winds point to the southern polar regions where the bulges are observed. Thus, the results of the present study indicate that in equinoxes the regions of local vertical advection, that are responsible for the formation of the bulges, are displaced toward the southern polar regions. The results of the present study point to the need of a larger wind database from NGIMS in southern polar region, particularly during equinoxes.
Inhibiting BCKDK in triple negative breast cancer suppresses protein translation, impairs mitochondrial function, and potentiates doxorubicin cytotoxicity
Authors: Biswas Dipsikha , Slade Logan , Duffley Luke , Mueller Neil , Dao Khoi Thien , Mercer Angella , Pakkiriswami Shanmugasundaram , El Hiani Yassine , Kienesberger Petra C. , Pulinilkunnil Thomas
Published: September 2021

Triple-negative breast cancers (TNBCs) are characterized by poor survival, prognosis, and gradual resistance to cytotoxic chemotherapeutics, like doxorubicin (DOX). The clinical utility of DOX is limited by its cardiotoxic and chemoresistant effects that manifest over time. To induce chemoresistance, TNBC rewires oncogenic gene expression and cell signaling pathways. Recent studies have demonstrated that reprogramming of branched-chain amino acids (BCAAs) metabolism facilitates tumor growth and survival. Branched-chain ketoacid dehydrogenase kinase (BCKDK), a regulatory kinase of the rate-limiting enzyme of the BCAA catabolic pathway, is reported to activate RAS/RAF/MEK/ERK signaling to promote tumor cell proliferation. However, it remains unexplored if BCKDK action remodels TNBC proliferation and survival per se and influences susceptibility to DOX-induced genotoxic stress. TNBC cells treated with DOX exhibited reduced BCKDK expression and intracellular BCKAs. Genetic and pharmacological inhibition of BCKDK in TNBC cell lines also showed a similar reduction in intracellular and secreted BCKAs. BCKDK silencing in TNBC cells downregulated mitochondrial metabolism genes, reduced electron complex protein expression, oxygen consumption, and ATP production. Transcriptome analysis of BCKDK silenced cells confirmed dysregulation of mitochondrial metabolic networks and upregulation of the apoptotic signaling pathway. Furthermore, BCKDK inhibition with concurrent DOX treatment exacerbated apoptosis, caspase activity, and loss of TNBC proliferation. Inhibition of BCKDK in TNBC also upregulated sestrin 2 and concurrently decreased mTORC1 signaling and protein synthesis. Overall, loss of BCKDK action in TNBC remodels BCAA flux, reduces protein translation triggering cell death, ATP insufficiency, and susceptibility to genotoxic stress.
Blue food demand across geographic and temporal scales
Authors: Naylor Rosamond L. , Kishore Avinash , Sumaila U. Rashid , Issifu Ibrahim , Hunter Blaire P. , Belton Ben , Bush Simon R. , Cao Ling , Gelcich Stefan , Gephart Jessica A. , Golden Christopher D. , Jonell Malin , Koehn J. Zachary , Little David C. , Thilsted Shakuntala H. , Tigchelaar Michelle , Crona Beatrice
Published: September 2021

Numerous studies have focused on the need to expand production of ‘blue foods’, defined as aquatic foods captured or cultivated in marine and freshwater systems, to meet rising population- and income-driven demand. Here we analyze the roles of economic, demographic, and geographic factors and preferences in shaping blue food demand, using secondary data from FAO and The World Bank, parameters from published models, and case studies at national to sub-national scales. Our results show a weak cross-sectional relationship between per capita income and consumption globally when using an aggregate fish metric. Disaggregation by fish species group reveals distinct geographic patterns; for example, high consumption of freshwater fish in China and pelagic fish in Ghana and Peru where these fish are widely available, affordable, and traditionally eaten. We project a near doubling of global fish demand by mid-century assuming continued growth in aquaculture production and constant real prices for fish. Our study concludes that nutritional and environmental consequences of rising demand will depend on substitution among fish groups and other animal source foods in national diets.
Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells
Authors: Arsic Nikola , Slatter Tania , Gadea Gilles , Villain Etienne , Fournet Aurelie , Kazantseva Marina , Allemand Frédéric , Sibille Nathalie , Seveno Martial , de Rossi Sylvain , Mehta Sunali , Urbach Serge , Bourdon Jean-Christophe , Bernado Pau , Kajava Andrey V. , Braithwaite Antony , Roux Pierre
Published: September 2021

The p53 isoform, Δ133p53β, is critical in promoting cancer. Here we report that Δ133p53β activity is regulated through an aggregation-dependent mechanism. Δ133p53β aggregates were observed in cancer cells and tumour biopsies. The Δ133p53β aggregation depends on association with interacting partners including p63 family members or the CCT chaperone complex. Depletion of the CCT complex promotes accumulation of Δ133p53β aggregates and loss of Δ133p53β dependent cancer cell invasion. In contrast, association with p63 family members recruits Δ133p53β from aggregates increasing its intracellular mobility. Our study reveals novel mechanisms of cancer progression for p53 isoforms which are regulated through sequestration in aggregates and recruitment upon association with specific partners like p63 isoforms or CCT chaperone complex, that critically influence cancer cell features like EMT, migration and invasion.
C3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates
Authors: Schmitz Robin , Fitch Zachary W. , Schroder Paul M. , Choi Ashley Y. , Manook Miriam , Yoon Janghoon , Song Mingqing , Yi John S. , Khandelwal Sanjay , Arepally Gowthami M. , Farris Alton B. , Reis Edimara S. , Lambris John D. , Kwun Jean , Knechtle Stuart J.
Published: September 2021

Sensitized kidney transplant recipients experience high rates of antibody-mediated rejection due to the presence of donor-specific antibodies and immunologic memory. Here we show that transient peri-transplant treatment with the central complement component C3 inhibitor Cp40 significantly prolongs median allograft survival in a sensitized nonhuman primate model. Despite donor-specific antibody levels remaining high, fifty percent of Cp40-treated primates maintain normal kidney function beyond the last day of treatment. Interestingly, presence of antibodies of the IgM class associates with reduced median graft survival (8 vs. 40 days;p = 0.02). Cp40 does not alter lymphocyte depletion by rhesus-specific anti-thymocyte globulin, but inhibits lymphocyte activation and proliferation, resulting in reduced antibody-mediated injury and complement deposition. In summary, Cp40 prevents acute antibody-mediated rejection and prolongs graft survival in primates, and inhibits T and B cell activation and proliferation, suggesting an immunomodulatory effect beyond its direct impact on antibody-mediated injury.
A prostate-specific membrane antigen activated molecular rotor for real-time fluorescence imaging
Authors: Zhang Jingming , Rakhimbekova Anastasia , Duan Xiaojiang , Yin Qingqing , Foss Catherine A. , Fan Yan , Xu Yangyang , Li Xuesong , Cai Xuekang , Kutil Zsofia , Wang Pengyuan , Yang Zhi , Zhang Ning , Pomper Martin G. , Wang Yiguang , Bařinka Cyril , Yang Xing
Published: September 2021

Surgery is an efficient way to treat localized prostate cancer (PCa), however, it is challenging to demarcate rapidly and accurately the tumor boundary intraoperatively, as existing tumor detection methods are seldom performed in real-time. To overcome those limitations, we develop a fluorescent molecular rotor that specifically targets the prostate-specific membrane antigen (PSMA), an established marker for PCa. The probes have picomolar affinity (IC50 = 63-118 pM) for PSMA and generate virtually instantaneous onset of robust fluorescent signal proportional to the concentration of the PSMA-probe complex. In vitro and ex vivo experiments using PCa cell lines and clinical samples, respectively, indicate the utility of the probe for biomedical applications, including real-time monitoring of endocytosis and tumor staging. Experiments performed in a PCa xenograft model reveal suitability of the probe for imaging applications in vivo.
Spin/valley pumping of resident electrons in WSe2 and WS2 monolayers
Authors: Robert Cedric , Park Sangjun , Cadiz Fabian , Lombez Laurent , Ren Lei , Tornatzky Hans , Rowe Alistair , Paget Daniel , Sirotti Fausto , Yang Min , Van Tuan Dinh , Taniguchi Takashi , Urbaszek Bernhard , Watanabe Kenji , Amand Thierry , Dery Hanan , Marie Xavier
Published: September 2021

Monolayers of transition metal dichalcogenides are ideal materials to control both spin and valley degrees of freedom either electrically or optically. Nevertheless, optical excitation mostly generates excitons species with inherently short lifetime and spin/valley relaxation time. Here we demonstrate a very efficient spin/valley optical pumping of resident electrons in n-doped WSe2 and WS2 monolayers. We observe that, using a continuous wave laser and appropriate doping and excitation densities, negative trion doublet lines exhibit circular polarization of opposite sign and the photoluminescence intensity of the triplet trion is more than four times larger with circular excitation than with linear excitation. We interpret our results as a consequence of a large dynamic polarization of resident electrons using circular light.
Chlamydia evasion of neutrophil host defense results in NLRP3 dependent myeloid-mediated sterile inflammation through the purinergic P2X7 receptor
Authors: Yang Chunfu , Lei Lei , Collins John W. Marshall , Briones Michael , Ma Li , Sturdevant Gail L. , Su Hua , Kashyap Anuj K. , Dorward David , Bock Kevin W. , Moore Ian N. , Bonner Christine , Chen Chih-Yu , Martens Craig A. , Ricklefs Stacy , Yamamoto Masahiro , Takeda Kiyoshi , Iwakura Yoichiro , McClarty Grant , Caldwell Harlan D.
Published: September 2021

Chlamydia trachomatis infection causes severe inflammatory disease resulting in blindness and infertility. The pathophysiology of these diseases remains elusive but myeloid cell-associated inflammation has been implicated. Here we show NLRP3 inflammasome activation is essential for driving a macrophage-associated endometritis resulting in infertility by using a female mouse genital tract chlamydial infection model. We find the chlamydial parasitophorous vacuole protein CT135 triggers NLRP3 inflammasome activation via TLR2/MyD88 signaling as a pathogenic strategy to evade neutrophil host defense. Paradoxically, a consequence of CT135 mediated neutrophil killing results in a submucosal macrophage-associated endometritis driven by ATP/P2X7R induced NLRP3 inflammasome activation. Importantly, macrophage-associated immunopathology occurs independent of macrophage infection. We show chlamydial infection of neutrophils and epithelial cells produce elevated levels of extracellular ATP. We propose this source of ATP serves as a DAMP to activate submucosal macrophage NLRP3 inflammasome that drive damaging immunopathology. These findings offer a paradigm of sterile inflammation in infectious disease pathogenesis.
Magnetoelectric phase transition driven by interfacial-engineered Dzyaloshinskii-Moriya interaction
Authors: Liu Xin , Song Wenjie , Wu Mei , Yang Yuben , Yang Ying , Lu Peipei , Tian Yinhua , Sun Yuanwei , Lu Jingdi , Wang Jing , Yan Dayu , Shi Youguo , Sun Nian Xiang , Sun Young , Gao Peng , Shen Ka , Chai Guozhi , Kou Supeng , Nan Ce-Wen , Zhang Jinxing
Published: September 2021

Strongly correlated oxides with a broken symmetry could exhibit various phase transitions, such as superconductivity, magnetism and ferroelectricity. Construction of superlattices using these materials is effective to design crystal symmetries at atomic scale for emergent orderings and phases. Here, antiferromagnetic Ruddlesden-Popper Sr2IrO4 and perovskite paraelectric (ferroelectric) SrTiO3 (BaTiO3) are selected to epitaxially fabricate superlattices for symmetry engineering. An emergent magnetoelectric phase transition is achieved in Sr2IrO4/SrTiO3 superlattices with artificially designed ferroelectricity, where an observable interfacial Dzyaloshinskii-Moriya interaction driven by non-equivalent interface is considered as the microscopic origin. By further increasing the polarization namely interfacial Dzyaloshinskii-Moriya interaction via replacing SrTiO3 with BaTiO3, the transition temperature can be enhanced from 46 K to 203 K, accompanying a pronounced magnetoelectric coefficient of ~495 mV/cm·Oe. This interfacial engineering of Dzyaloshinskii-Moriya interaction provides a strategy to design quantum phases and orderings in correlated electron systems.
A deep-learning framework for multi-level peptide–protein interaction prediction
Authors: Lei Yipin , Li Shuya , Liu Ziyi , Wan Fangping , Tian Tingzhong , Li Shao , Zhao Dan , Zeng Jianyang
Published: September 2021

Peptide-protein interactions are involved in various fundamental cellular functions and their identification is crucial for designing efficacious peptide therapeutics. Recently, a number of computational methods have been developed to predict peptide-protein interactions. However, most of the existing prediction approaches heavily depend on high-resolution structure data. Here, we present a deep learning framework for multi-level peptide-protein interaction prediction, called CAMP, including binary peptide-protein interaction prediction and corresponding peptide binding residue identification. Comprehensive evaluation demonstrated that CAMP can successfully capture the binary interactions between peptides and proteins and identify the binding residues along the peptides involved in the interactions. In addition, CAMP outperformed other state-of-the-art methods on binary peptide-protein interaction prediction. CAMP can serve as a useful tool in peptide-protein interaction prediction and identification of important binding residues in the peptides, which can thus facilitate the peptide drug discovery process.
Analysis of 427 genomes reveals moso bamboo population structure and genetic basis of property traits
Authors: Zhao Hansheng , Sun Shuai , Ding Yulong , Wang Yue , Yue Xianghua , Du Xiao , Wei Qiang , Fan Guangyi , Sun Huayu , Lou Yongfeng , Yang Huanming , Wang Jian , Xu Xun , Li Lichao , Yang Kebin , Xu Hao , Wang Jiongliang , Zhu Chenglei , Wang Sining , Shan Xuemeng , Hou Yinguang , Wang Yu , Fei Benhua , Liu Xin , Jiang Zehui , Gao Zhimin
Published: September 2021

Moso bamboo (Phyllostachys edulis) is an economically and ecologically important nontimber forestry species. Further development of this species as a sustainable bamboo resource has been hindered by a lack of population genome information. Here, we report a moso bamboo genomic variation atlas of 5.45 million single-nucleotide polymorphisms (SNPs) from whole-genome resequencing of 427 individuals covering 15 representative geographic areas. We uncover low genetic diversity, high genotype heterozygosity, and genes under balancing selection underlying moso bamboo population adaptation. We infer its demographic history with one bottleneck and its recently small population without a rebound. We define five phylogenetic groups and infer that one group probably originated by a single-origin event from East China. Finally, we conduct genome-wide association analysis of nine important property-related traits to identify candidate genes, many of which are involved in cell wall, carbohydrate metabolism, and environmental adaptation. These results provide a foundation and resources for understanding moso bamboo evolution and the genetic mechanisms of agriculturally important traits.
Strong and ductile Fe-24Mn-3Cr alloy resistant against erosion-corrosion
Authors: Jeong Yeong Jae , Kim Si On , Park Jin Sung , Lee Jae Won , Hwang Joong-Ki , Lee Soon Gi , Choi Jong Kyo , Kim Sung Jin
Published: September 2021

The ternary-based Fe-24Mn-3Cr alloy has superior mechanical properties based on an attractive combination of high strength and ductility, with long-term environmental stability in highly corrosive environments compared to conventional ferritic steel alloys. This study reports that the environmental instability caused by the rapid electrochemical corrosion kinetics on the surface of conventional high Mn-bearing ferrous alloys could be overcome by a combination of high Mn–low Cr-balanced Fe and their synergistic interactions. In contrast to Cr-free Mn-bearing alloys, the high Mn–low Cr-bearing alloy showed comparatively lower corrosion kinetic parameters, without a continuously increasing trend, and higher polarization resistance according to electrochemical polarization and impedance spectroscopy measurements. Moreover, the rate of degradation caused by erosion–corrosion synergistic interaction under erosion–corrosion dynamic flow conditions was the lowest in the high Mn–low Cr-bearing alloy. These surface-inhibiting characteristics of the alloy were attributed primarily to the formation of a bilayer scale structure consisting of inner α-Fe2−xCrxO3/outer FexMn3−xO4on the surface.
Usefulness analysis of the 2018 ASCO/IDSA guideline for outpatient management of fever and neutropenia in adults treated for malignancy
Authors: Hwang Soyoon , Kwon Ki Tae , Kim Yoonjung , Bae Sohyun , Chang Hyun-Ha , Kim Shin-Woo , Yoo Seung Soo , Nam Su Youn , Baek Jin Ho
Published: September 2021

Although the clinical practice guideline for outpatient management of febrile neutropenia (FN) in adults treated for malignancy was updated by the ASCO/IDSA in 2018, most patients with FN in our hospital have been hospitalized. We performed this study to analyze the usefulness of the guideline. The medical records of patients hospitalized for FN in Kyungpook National University Chilgok Hospital from May 2016 to April 2018 were retrospectively reviewed. The feasibility of candidates for outpatient management according to the guideline was evaluated based on the outcomes. A total of 114 patients were enrolled and categorized into two groups, low-risk (38.6%) and high-risk (61.4%). The proportion of feasible candidates for outpatient management was 70.2% and was higher in the low-risk than in the high-risk group (90.0% vs. 57.1%; P < 0.001). The low-risk group had no mortality, no resistance to oral amoxicillin/clavulanate or ciprofloxacin, a higher rate of successful empirical antibiotics, and lower rates of glycopeptide or carbapenem administration. A significant number of hospitalized cancer patients treated for FN after chemotherapy were found to be feasible candidates for outpatient management. The guideline can be a useful tool to reduce labor of healthcare workers and hospitalization costs.
Patient characteristics, treatment patterns, and outcomes of Rickettsial diseases among a commercially insured population in the United States, 2005–2017
Authors: Binder Alison M. , Armstrong Paige A.
Published: September 2021

Rickettsial diseases (RDs) are transmitted to humans by ectoparasites, including ticks and fleas. Symptoms range from mild febrile illness, to severe disease or death. Doxycycline is the treatment of choice for patients of all ages; early treatment based on clinical diagnosis is critical to prevent severe outcomes. We conducted a descriptive analysis using insurance claims data captured by IBM MarketScan® research databases to describe demographics, treatment patterns, and outcomes of patients diagnosed with RDs in the United States during 2005–2017. Overall, 14,830 patients had a RD diagnosis during 2005–2017; 7,517 (50.7%) spotted fever rickettsiosis (SFR), 4,571 ( 30.8%) ehrlichiosis, 1,362 (9.2%) typhus group rickettsiosis (TGR), and 1,193 (8.0%) other rickettsial diseases. Among all patients diagnosed, 53.1% received doxycycline. Prescription rates varied by diagnosis and age; 24.1% of TGR and 61.1% of SFR patients received doxycycline; 23.9% of persons < 8 years received doxycycline, compared with 47.7% for 8–17 years, and 55.4% for ≥ 18 years. RDs are frequently diagnosed in the outpatient population; however, providers prescribed the recommended treatment to about half of patients. Continued education of treatment recommendations is critical to prevent severe outcomes.
Towards reliable diagnostics of prostate cancer via breath
Authors: Maiti K. S. , Fill E. , Strittmatter F. , Volz Y. , Sroka R. , Apolonski A.
Published: September 2021

Early detection of cancer is a key ingredient for saving many lives. Unfortunately, cancers of the urogenital system are difficult to detect at early stage. The existing noninvasive diagnostics of prostate cancer (PCa) suffer from low accuracy (< 70%) even at advanced stages. In an attempt to improve the accuracy, a small breath study of 63 volunteers representing three groups: (1) of 19 healthy, (2) 28 with PCa, (3) with 8 kidney cancer (KC) and 8 bladder cancer (BC) was performed. Ultrabroadband mid-infrared Fourier absorption spectroscopy revealed eight spectral ranges (SRs) that differentiate the groups. The resulting accuracies of supervised analyses exceeded 95% for four SRs in distinguishing (1) vs (2), three for (1) vs (3) and four SRs for (1) vs (2) + (3). The SRs were then attributed to volatile metabolites. Their origin and involvement in urogenital carcinogenesis are discussed.
Functionally diverse heteromeric traps for ligands of the transforming growth factor-β superfamily
Authors: Kumar Ravindra , Grinberg Asya V. , Li Huiming , Kuo Tzu-Hsing , Sako Dianne , Krishnan Lavanya , Liharska Katia , Li Jia , Grenha Rosa , Maguire Michelle C. , Briscoe Steven D. , Pearsall R. Scott , Herrin Brantley R. , Suragani Rajasekhar N. V. S. , Castonguay Roselyne
Published: September 2021

Ligands of the transforming growth factor-β (TGF-β) superfamily are important targets for therapeutic intervention but present challenges because they signal combinatorially and exhibit overlapping activities in vivo. To obtain agents capable of sequestering multiple TGF-β superfamily ligands with novel selectivity, we generated soluble, heterodimeric ligand traps by pairing the extracellular domain (ECD) of the native activin receptor type IIB (ActRIIB) alternately with the ECDs of native type I receptors activin receptor-like kinase 4 (ALK4), ALK7, or ALK3. Systematic analysis of these heterodimeric constructs by surface plasmon resonance, and comparison with their homodimeric counterparts, revealed that each type I receptor partner confers a distinct ligand-binding profile to the heterodimeric construct. Additional characterization in cell-based reporter gene assays confirmed that the heterodimeric constructs possessed different profiles of signaling inhibition in vitro, which translated into altered patterns of pharmacological activity when constructs were administered systemically to wild-type mice. Our results detail a versatile platform for the modular recombination of naturally occurring receptor domains, giving rise to inhibitory ligand traps that could aid in defining the physiological roles of TGF-β ligand sets or be directed therapeutically to human diseases arising from dysregulated TGF-β superfamily signaling.
KCa channel blockers increase effectiveness of the EGF receptor TK inhibitor erlotinib in non-small cell lung cancer cells (A549)
Authors: Glaser Felix , Hundehege Petra , Bulk Etmar , Todesca Luca Matteo , Schimmelpfennig Sandra , Nass Elke , Budde Thomas , Meuth Sven G. , Schwab Albrecht
Published: September 2021

Non-small cell lung cancer (NSCLC) has a poor prognosis with a 5 year survival rate of only ~ 10%. Important driver mutations underlying NSCLC affect the epidermal growth factor receptor (EGFR) causing the constitutive activation of its tyrosine kinase domain. There are efficient EGFR tyrosine kinase inhibitors (TKIs), but patients develop inevitably a resistance against these drugs. On the other hand, KCa3.1 channels contribute to NSCLC progression so that elevated KCa3.1 expression is a strong predictor of poor NSCLC patient prognosis. The present study tests whether blocking KCa3.1 channels increases the sensitivity of NSCLC cells towards the EGFR TKI erlotinib and overcomes drug resistance. mRNA expression of KCa3.1 channels in erlotinib-sensitive and -resistant NSCLC cells was analysed in datasets from Gene expression omnibus (GEO) and ArrayExpress. We assessed proliferation and migration of NSCLC cells. These (live cell-imaging) experiments were complemented by patch clamp experiments and Western blot analyses. We identified three out of four datasets comparing erlotinib-sensitive and -resistant NSCLC cells which revealed an altered expression of KCa3.1 mRNA in erlotinib-resistant NSCLC cells. Therefore, we evaluated the combined effect of erlotinib and the KCa3.1 channel inhibition with sencapoc. Erlotinib elicits a dose-dependent inhibition of migration and proliferation of NSCLC cells. The simultaneous application of the KCa3.1 channel blocker senicapoc increases the sensitivity towards a low dose of erlotinib (300 nmol/L) which by itself has no effect on migration and proliferation. Partial erlotinib resistance can be overcome by KCa3.1 channel blockade. The sensitivity towards erlotinib as well as the potentiating effect of KCa3.1 blockade is further increased by mimicking hypoxia. Our results suggest that KCa3.1 channel blockade may constitute a therapeutic concept for treating NSCLC and overcome EGFR TKI resistance. We propose that this is due to complementary mechanisms of action of both blockers.
Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma
Authors: Kułach Natalia , Pilny Ewelina , Cichoń Tomasz , Czapla Justyna , Jarosz-Biej Magdalena , Rusin Marek , Drzyzga Alina , Matuszczak Sybilla , Szala Stanisław , Smolarczyk Ryszard
Published: September 2021

Due to immunosuppressive properties and confirmed tropism towards cancer cells mesenchymal stromal cells (MSC) have been used in many trials. In our study we used these cells as carriers of IL-12 in the treatment of mice with primary and metastatic B16-F10 melanomas. IL-12 has confirmed anti-cancer activity, induces a strong immune response against cancer cells and acts as an anti-angiogenic agent. A major limitation of the use of IL-12 in therapy is its systemic toxicity. The aim of the work was to develop a system in which cytokine may be administered intravenously without toxic side effects. In this study MSC were used as carriers of the IL-12. We confirmed antitumor effectiveness of the cells secreting IL-12 (MSC/IL-12) in primary and metastatic murine melanoma models. We observed inhibition of tumor growth and a significant reduction in the number of metastases in mice after MSC/IL-12 administration. MSC/IL-12 decreased vascular density and increased the number of anticancer M1 macrophages and CD8+ cytotoxic T lymphocytes in tumors of treated mice. To summarize, we showed that MSC are an effective, safe carrier of IL-12 cytokine. Administered systemically they exert therapeutic properties of IL-12 cytokine without toxicity. Therapeutic effect may be a result of pleiotropic (proinflammatory and anti-angiogenic) properties of IL-12 released by modified MSC.
Localised labyrinthine patterns in ecosystems
Authors: Clerc M. G. , Echeverría-Alar S. , Tlidi M.
Published: September 2021

Self-organisation is a ubiquitous phenomenon in ecosystems. These systems can experience transitions from a uniform cover towards the formation of vegetation patterns as a result of symmetry-breaking instability. They can be either periodic or localised in space. Localised vegetation patterns consist of more or less circular spots or patches that can be either isolated or randomly distributed in space. We report on a striking patterning phenomenon consisting of localised vegetation labyrinths. This intriguing pattern is visible in satellite photographs taken in many territories of Africa and Australia. They consist of labyrinths which is spatially irregular pattern surrounded by either a homogeneous cover or a bare soil. The phenomenon is not specific to particular plants or soils. They are observed on strictly homogenous environmental conditions on flat landscapes, but they are also visible on hills. The spatial size of localized labyrinth ranges typically from a few hundred meters to ten kilometres. A simple modelling approach based on the interplay between short-range and long-range interactions governing plant communities or on the water dynamics explains the observations reported here.
Future intensification of extreme Aleutian low events and their climate impacts
Authors: Giamalaki K. , Beaulieu C. , Henson S. A. , Martin A. P. , Kassem H. , Faranda D.
Published: September 2021

Extreme Aleutian Low (AL) events have been associated with major ecosystem reorganisations and unusual weather patterns in the Pacific region, with serious socio-economic consequences. Yet, their future evolution and impacts on atmosphere–ocean interactions remain uncertain. Here, a large ensemble of historical and future runs from the Community Earth System Model is used to investigate the evolution of AL extremes. The frequency and persistence of AL extremes are quantified and their connection with climatic variables is examined. AL extremes become more frequent and persistent under the RCP8.5 scenario, associated with changes in precipitation and air temperature patterns over North America. Future changes in AL extremes also increase the variability of the sea surface temperature and net heat fluxes in the Kuroshio Extension, the most significant heat and energy flux region of the basin. The increased frequency and persistence of future AL extremes may potentially cause substantial changes in fisheries and ecosystems of the entire Pacific region as a knock-on effect.