bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticipation Can Be More Common in Hereditary Spastic Paraplegia with SPAST Mutations Than It Appears
Authors: Hashemi Seyyed-Saleh , Hajati Reza , Davarzani Atefeh , Rohani Mohammad , DanaeeFard Fardad , Rahimi Bidgoli Mohammad Masoud , Fatehi Farzad , Kariminejad Ariana , Najmabadi Hossein , Nafissi Shahriar , Alavi Afagh
Published: August 2021

Background and objective:

Hereditary spastic paraplegia (HSP) is a heterogeneous neurodegenerative disorder with lower-limb spasticity and weakness. Different patterns of inheritance have been identified in HSP. Most autosomal-dominant HSPs (AD-HSPs) are associated with mutations of the SPAST gene (SPG4), leading to a pure form of HSP with variable age-at-onset (AAO). Anticipation, an earlier onset of disease, as well as aggravation of symptoms in successive generations, may be correlated to SPG4. Herein, we suggested that anticipation might be a relatively common finding in SPG4 families.

Methods:

Whole-exome sequencing was done on DNA of 14 unrelated Iranian AD-HSP probands. Data were analyzed, and candidate variants were PCR-amplified and sequenced by the Sanger method, subsequently checked in family members to co-segregation analysis. Multiplex ligation-dependent probe amplification (MLPA) was done for seven probands. Clinical features of the probands were recorded, and the probable anticipation was checked in these families. Other previous reported SPG4 families were investigated to anticipation.

Results:

Our findings showed that SPG4 was the common subtype of HSP; three families carried variants in the KIF5A, ATL1, and MFN2 genes, while five families harbored mutations in the SPAST gene. Clinical features of only SPG4 families indicated decreasing AAO in affected individuals of the successive generations, and this difference was significant (p-value <0.05).

Conclusion:

It seems SPAST will be the first candidate gene in families that manifests a pure form of AD-HSP and anticipation. Therefore, it may be a powerful situation of genotype–phenotype correlation. However, the underlying mechanism of anticipation in these families is not clear yet.
The Rise of the Contentious Right: Digitally Intermediated Linkage Strategies in Argentina and Brazil
Authors: Gold Tomás , Peña Alejandro M.
Published: August 2021

This article analyzes novel patterns of interaction between right-wing parties and protest movements during major contentious cycles in Argentina (2012–13) and Brazil (2013–16), which preceded the advent of the Cambiemos coalition in the former and the impeachment of Dilma Rousseff in the latter. Drawing on a dual process-tracing strategy and a wide range of data sources, this study shows that these interactions are central to understanding why and how right-wing parties leverage novel repertoires and resources from digital activists during contemporary protest cycles, a dynamic conceptualized as a new party linkage strategy through digital intermediation. The study traces its three-phase development in both countries, revealing how differences in institutional contexts and the strength of activist groups contributed to divergent trajectories of partisan opposition toward the end of the cycles, regarding both the subsequent reconfiguration of the right and the entry of digital activists into institutional arenas.
Collaboration and Its Political Functions
Authors: DIGESER P. E.
Published: August 2021

What functions does “collaboration” play in our moral and political practices and how did it come to play those roles? We use the term “collaboration” to identify a valued partnership, but it also names a morally compromised association and functions as a reason for blaming and punishing complicitous behavior. However, it has also played nefarious political roles: shoring up patriarchy, legitimizing ethnic cleansing, and bolstering a myth of national unity. “Collaboration” plays various roles because it is both ambiguous and vague. It is ambiguous in that there are multiple conceptions of collaboration, and it is vague because it contains borderline cases that are difficult, even impossible, to resolve. An exploration of “collaboration” combined with the history of its coming of age shows why its study is so vexing and how it functions in unexpected and disturbing ways.
Social environment perception and associations with overweight in the city of Porto Alegre, Brazil
Authors: Rosa Priscila Bárbara Zanini , Schuch Ilaine , Cunha Caroline Marques de Lima , Rodrigues Ylana Elias , Fanton Marcos , Canuto Raquel
Published: August 2021

The prevalence of overweight in Brazilian adults has grown in recent years. There is evidence indicating that environmental factors, especially social characteristics, may be involved in the aetiology of overweight, but few studies have investigated this association adequately. The main objective of this study was to identify residents’ perception of their social environment (social cohesion, security and violence) and assess its relationship with overweight in a central area of Porto Alegre, Brazil. The associations between socioeconomic characteristics and social environment perception were also explored. This cross-sectional study conducted in 2018–19 had 400 participants aged from 20 to 70 years living in low- and high-income areas of the city of Porto Alegre. Participants’ perception of social cohesion, security and violence were evaluated using a validated questionnaire. Participants’ body mass index (BMI) was measured, and those with a BMI ≥25 kg/m2 were considered to be overweight. Unadjusted and adjusted prevalence ratios (PRs) and 95% confidence intervals (95% CIs) were estimated through Poisson regression analysis; level of significance was 5%. The prevalence of overweight in the sample was 68.8% (95% CI 64.0–73.2). Individuals with a more positive social cohesion perception had a higher prevalence of overweight (PR 1.06; 95% CI: 1.00–1.12; p=0.02) than those with a less positive perception. Brown individuals also had a higher prevalence of overweight (PR: 1.08; 95% CI: 1.02–1.15; p=0.03) than those of other skin colour/race. No association was found between overweight and perception of security or violence. Therefore, social cohesion may be an important factor in overweight and the findings highlight the importance of considering social factors, and their perceptions, when planning actions for the prevention and control of overweight in a population.
The Trinity as social and constitutional: a rejoinder to Brian Leftow
Authors: HASKER WILLIAM
Published: August 2021

Brian Leftow continues to argue against my use of the constitution relation in explaining the Trinity. I consider his arguments, and have a bit more to say about Leftow's own formulation of trinitarian doctrine.
Using INTEGRATE-HTA for the assessment of videorasterstereography in idiopathic scoliosis
Authors: Buchberger Barbara , Wasem Jürgen , Spiller Ljuba
Published: August 2021

Objective

For the assessment of videorasterstereography compared with radiography for monitoring idiopathic scoliosis, new tools given by the INTEGRATE-HTA methodology were included within the frame set by the authority. In contrast to the usual linear approach by covering the single domains' safety and efficacy, costs, and ethical, legal, socio-cultural and organizational issues (ELSOI) separately, the methodology is based on the assumption of interactions of different aspects of the domains. From the very beginning, these interactions are captured systematically using various tools and are repeatedly discussed with stakeholders.

Methods

Relevant databases were systematically searched for studies and question catalogues were processed in order to be able to search for specific aspects in orienting bibliographic research. An initial logic model was developed and successively expanded. A synoptic table showing multiple mapping of aspects to domains, a complexity checklist, and a semantic complex highlighting the socio-cultural impact of the disease were newly developed.

Results

Four diagnostic studies with high risk of bias were included. For the clinical outcome, Cobb angle standard deviations up to 8.2 degrees and average measurement differences up to 8.8 degrees were determined. These differences in measurement accuracy correspond to those observed for purely radiographic measurements in other studies. In addition to freedom from radiation as the greatest advantage, there were clear arguments in favor of videorasterstereography when considering ELSOI, for example less harm.

Conclusions

Using INTEGRATE-HTA contributes to identify interactions between domains and to significantly expand the perspective on a technology. It improves patient-centered understanding and facilitates discussions.
Strategies for Maintaining Friendship in Dementia
Authors: Genoe M. Rebecca , Fortune Darla , Whyte Colleen
Published: August 2021

Although friendship is vital in later life, particularly amongst people who are living with dementia, little is known about how friendships are sustained following a diagnosis. Some research suggests that, because of dementia-related stigma, friendships dissolve following diagnosis; however, other researchers have shown that friendships can persist in dementia. The purpose of this article is to explore strategies that people with dementia and their friends (i.e., those who have been friends for at least 2 years) utilize to sustain their friendships. Following a constructivist approach, we interviewed people living with dementia, friends, and family members to better understand how friendships are maintained after a diagnosis of dementia. Data were analyzed using thematic analysis. An overarching theme, adapting to change, was generated. Participants adapted in several ways, including: (1) prioritizing friendship, (2) shifting ways of thinking about our friend/ship, and (3) addressing changes through practical strategies. These strategies helped maintain mutually beneficial, reciprocal friendships that were able to withstand changes that accompany a diagnosis of dementia.
Displaced peoples and the continued legacy of the Pacific War: Korean repatriation and the danger element
Authors: Caprio Mark E.
Published: August 2021

The battles of the Pacific War formally ended between mid-August and early September, 1945. However, the declarations of peace and surrender ceremonies that occurred during this time did not end informal battles across the Asian continent. Renegade Japanese military personnel refused to lay down their arms and repatriate quietly to their country. Some combed the waters between Japan and Korea in search of returnees attempting to repatriate with financial and material means in excess of that which the United States military governments allowed. Others sought to disrupt the occupation process by patrolling the streets of Korean cities and engaging in illegal and often violent activities. Koreans also caused problems by joining the Japanese in their postwar adventures or by harassing Japanese preparing to return to Japan and the Korean sympathizers who attempted to help them. Reportage of such actions appeared in the G-2 Periodic Report, which kept a daily record of such actions. These documents today open windows into the chaotic situation that the postwar era brought to Japanese and Koreans. Primarily through these reports, this paper sees the postwar belligerence that continued beyond official declarations of cease fire and peace in 1945 as kindling that sparked the broader conflicts of the late 1940s, and evolved to all-out war from the summer of 1950.
What's eating North America's edible insect industry? An examination of psychological, cultural and regulatory barriers
Authors: Li Christl , Cash Sean B. , Lesnik Julie , Griffin Timothy S. , Mason Joel , Blackstone Nicole Tichenor
Published: August 2021

Although research has demonstrated the positive nutritional value and environmental benefits associated with edible insect consumption, several factors challenge the growth and development of the edible insect industry for human consumption in the US and Canada. Cultural and psychological factors account for much of the aversion US and Canadian consumers display. The absence of specific regulation also constitutes a structural barrier to more widespread production and sale of edible insects. Compared to the US, the European Union has a more developed edible insect industry and has enacted legislation that removes some of the barriers. As consumer awareness of the putative health benefits of edible insects increases, more comprehensive regulations may emerge to keep pace with the growth of this industry. Overall, a multi-disciplinary approach that addresses both benefits and barriers to consumption is needed to facilitate a robust market for edible insects in the US and Canada.
The Limpopo Low‐Level Jet: Mean Climatology and Role in Water Vapor Transport
Authors: Spavins‐Hicks Zachary D. , Washington Richard , Munday Callum
Published: August 2021

Low‐level jets (LLJs) are well established as critical features of regional climates globally. However, across sub‐Saharan Africa, LLJs have received relatively little attention, in part due to a lack of data. Utilizing high‐resolution reanalysis data, this paper develops the first climatology of a neglected feature of the southern African circulation – the Limpopo LLJ – and investigates its role in delivering water vapor to the continental interior. We demonstrate that the LLJ has a clear diurnal cycle and is a regular feature of the circulation throughout the year, forming on 80.9% of days. The pressure gradient between southern Mozambique and the continental interior acts as a first‐order control on the annual cycle of jet strength, which peaks in October, achieving average maximum windspeeds of 15.8 m.s−1 at the core. Water vapor transport follows the same clear diurnal cycle, with at least 72% occurring over 18:00–08:00, and is closely related to jet strength: On average the strongest jet events advect 1.04 × 1012 kg (1.02 × 1012 kg) more moisture each night than the weakest in October‐December (January‐March). Strong jet events are typically linked to ridging anticyclones along the east coast of South Africa and are associated with increased rainfall in central and southern Botswana and northern South Africa the following day.
Surviving Invasion: Regaining Native Fish Resilience Following Fish Invasions in a Modified Floodplain Landscape
Authors: Pingram M. A. , Collier K. J. , Williams A. K. , David B. O. , Garrett‐Walker J. , Górski K. , Özkundakci D. , Ryan E. F.
Published: August 2021

Floodplain ecosystems are focal points for human settlement, and consequently are often subjected to extensive modification and infrastructure development. Establishment of non‐native species in floodscapes presents a range of challenges when they become problematic and drive changes in native aquatic communities and ecosystems. These non‐native species are often tolerant of reduced water and habitat quality, conferring a competitive advantage over native species. The coupled effects of invasive alien species, landscape modification and floodscape hydrological control collectively reduce ecological resilience, creating feedback loops that reinforce negative effects on native fish. The regulated lower Waikato River floodplain is a New Zealand hotspot for fish introductions, with their proliferation exacerbating the effects of agricultural development, urban expansion, and flood control infrastructure. We argue that the resilience of native fish assemblages to these pressures can be improved through utilizing a series of complementary measures, including enhanced catchment management, strategic alterations to the location, design, and operation of floodplain infrastructure (e.g., gates, pumpstations, and stopbanks), habitat restoration for native fish, and targeted management of invasive species. These measures will need to consider the likely persistence of invasive alien fish, however, to limit their expansion in the face of a changing climate. Although knowledge and implementation gaps exist, tying these strands together presents an opportunity to enhance the resilience of native fisheries into the future. Key to success will be re‐thinking floodplain management to include ecosystem services, and this will require ongoing commitment and cooperation amongst all stakeholders to address knowledge gaps and enable effective implementation.
Ensemble Drought Exposure Projection for Multifactorial Interactive Effects of Climate Change and Population Dynamics: Application to the Pearl River Basin
Authors: Duan Ruixin , Huang Guohe , Zhou Xiong , Li Yongping , Tian Chuyin
Published: August 2021

With a changing climate, drought has become a common natural disaster. In our study, population exposure to drought over the Pearl River Basin (PRB) under climate change is investigated. Drought frequency is evaluated through the Standardized Precipitation Evapotranspiration Index (SPEI). The data needed for SPEI calculation are obtained based on the ensemble of multiple global climate model (GCM) outputs. Population exposure to drought for the future is assessed by combining drought frequency under two emission scenarios (RCP4.5 and RCP8.5) with three downscaled population scenarios (SSP1, SSP2, and SSP3). Moreover, the main contribution (and their interactions) of GCM, RCP, and SSP to the sources of uncertainty on population exposure projections is explored through multilevel factorial analysis. Results indicate that the temperature and precipitation would continually increase for the future, and the increase in drought frequency is more substantial during the 2080s than in the 2050s. Meanwhile, population exposure to drought accounts for 21.60% of the total population in 1976–2005 over the PRB area. During the 2050s, it would decrease to 11.98–12.28% under RCP4.5 and 14.15–14.40% under RCP8.5, respectively. By the 2080s, population exposure would slightly reduce under RCP4.5 and increase to 28.86–29.44% under RCP8.5. GCM is the primary uncertainty source of drought exposure in the 2050s, with contribution rates of 72.41%, 57.47%, 51.10%, and 78.71% to the four responses. In comparison, by the 2080s, RCP is the primary contributing factor, with contribution rates of 53.91%, 44.92%, 64.20%, and 48.00%, respectively.
Past and Future Climate Variability Uncertainties in the Global Carbon Budget Using the MPI Grand Ensemble
Authors: Loughran T. F. , Boysen L. , Bastos A. , Hartung K. , Havermann F. , Li H. , Nabel J. E. M. S. , Obermeier W. A. , Pongratz J.
Published: August 2021

Quantifying the anthropogenic fluxes of CO2 is important to understand the evolution of carbon sink capacities, on which the required strength of our mitigation efforts directly depends. For the historical period, the global carbon budget (GCB) can be compiled from observations and model simulations as is done annually in the Global Carbon Project's (GCP) carbon budgets. However, the historical budget only considers a single realization of the Earth system and cannot account for internal climate variability. Understanding the distribution of internal climate variability is critical for predicting the future carbon budget terms and uncertainties. We present here a decomposition of the GCB for the historical period and the RCP4.5 scenario using single‐model large ensemble simulations from the Max Planck Institute Grand Ensemble (MPI‐GE) to capture internal variability. We calculate uncertainty ranges for the natural sinks and anthropogenic emissions that arise from internal climate variability, and by using this distribution, we investigate the likelihood of historical fluxes with respect to plausible climate states. Our results show these likelihoods have substantial fluctuations due to internal variability, which are partially related to El Niño‐Southern Oscillation (ENSO). We find that the largest internal variability in the MPI‐GE stems from the natural land sink and its increasing carbon stocks over time. The allowable fossil fuel emissions consistent with 3 C warming may be between 9 and 18 Pg C yr−1. The MPI‐GE is generally consistent with GCP's global budgets with the notable exception of land‐use change emissions in recent decades, highlighting that human action is inconsistent with climate mitigation goals.
Small Shear Wave Splitting Delays Suggest Weak Anisotropy in Cratonic Mantle Lithosphere
Authors: Chen Xiaoran , Levin Vadim , Yuan Huaiyu
Published: August 2021

We use splitting in core‐refracted teleseismic shear waves (SKS, PKS, and similar) to investigate anisotropic properties of the upper mantle beneath the Superior craton in eastern North America and the Yilgarn craton in Western Australia. At four sites in each craton, we assemble extensive data sets that emphasize directional coverage, and use three different measurement methods to develop mutually consistent constraints on the nature of splitting and on the likely anisotropic properties that cause it. In both cratons, we see evidence of clear directional variation in both delays and fast polarization directions, as well as lateral differences between sites. Relatively small (0.3–0.8 s) amounts of splitting imply weak anisotropy within 150–220 km thick mantle lithosphere. Anisotropy in the asthenosphere likely contributes to splitting in North America where fast directions align with absolute plate motion, but not in Western Australia where fast polarizations and plate motion are nearly orthogonal.
Denitrification and Anammox Shift Nutrient Stoichiometry and the Phytoplankton Community Structure in the Benguela Upwelling System
Authors: Mashifane T. B.
Published: August 2021

A shift in nutrient stoichiometry and phytoplankton community structure due to denitrification and anammox is investigated using coupled physical‐biogeochemical model experiments in the northern Benguela. Denitrification depletes more dissolved inorganic nitrogen (DIN) than anammox, increasing phosphate accumulation and this creates a shift in nutrient stoichiometry. This decreases the nutrient stoichiometry to below the Redfield ratio with an effect on phytoplankton composition in the system. Flagellates dominate the community structure in the northern Benguela as compared to diatoms, picophytoplankton and large phytoplankton. Denitrification limits the growth of picophytoplankton resulting in a flagellate‐dominated community structure and diatom succession at depth. The phytoplankton community structure shift and succession correspond with a negative correlation between the phytoplankton groups, denitrification, anammox and DIN. The nutrient stoichiometry and a decline in phytoplankton concentrations from denitrification decrease Dissolved inorganic carbon (DIC) uptake more than gross primary production. Annual mean diatoms decline from denitrification is 0.012 Gg N , reducing DIC uptake by 2.793 Gg C  and resulting in an estimated gross primary production of 0.080 Gg N  in the northern Benguela. Anammox drives an estimated flagellates decline of 0.008 Gg N , a diatoms increase of 0.873 Gg N  and DIC uptake of up to 46.08 Gg C . The direct links between denitrification, anammox, DIC uptake and primary production as demonstrated in this study present considerable implications for the biological pump in the northern Benguela.
All‐Sky Aerosol Direct Radiative Effects at the ARM SGP Site
Authors: Balmes Kelly A. , Fu Qiang
Published: August 2021

All‐sky aerosol direct radiative effect (DRE) was estimated for the first time at the Atmospheric Radiation Measurement Southern Great Plains site using multiyear ground‐based observations. The NASA Langley Fu‐Liou radiation model was employed. Observed inputs for the radiation model include aerosol and cloud vertical extinction profile from Raman lidar; spectral aerosol optical depth, single‐scattering albedo, and asymmetry factor from Aerosol Robotic Network; cloud water content profiles from radars; temperature and water vapor profiles from radiosondes; and surface shortwave spectral albedo from radiometers. A cloudy‐sky radiative closure experiment was performed. The relative mean differences between modeled and observed surface downwelling shortwave total fluxes were 6% (7%) for transparent (opaque) cloudy‐skies. The estimated annual mean all‐sky aerosol DRE is −2.130.54 W m−2 at the top of atmosphere (TOA) and −5.950.87 W m−2 at the surface, compared to −3.000.58 W m−2 and −6.851.00 W m−2, respectively, under clear‐sky conditions. The seasonal cycle of all‐sky aerosol DRE is similar to that of the clear‐sky, except with secondary influences of the clouds: The cloud radiative effect is strongest (most negative) in the spring, which reduces the all‐sky aerosol DRE. The relative uncertainties in all‐sky aerosol DRE due to measurement errors are generally comparable to those in clear‐sky conditions except for the aerosol single‐scattering albedo. The TOA all‐sky aerosol DRE relative uncertainty due to aerosol single‐scattering albedo uncertainty is larger than that in clear‐sky, leading to a larger total relative uncertainty. The measurement errors in cloud properties have small effects on the all‐sky aerosol DRE.
Cerebrospinal fluid flow cytometry distinguishes psychosis spectrum disorders from differential diagnoses
Authors: Räuber Saskia , Heming Michael , Repple Jonathan , Ruland Tillmann , Kuelby Rebecca , Schulte-Mecklenbeck Andreas , Gross Catharina C. , Arolt Volker , Baune Bernhard , Hahn Tim , Dannlowski Udo , Meuth Sven G. , Melzer Nico , Wiendl Heinz , Meyer zu Hörste Gerd
Published: August 2021

Psychotic disorders are common and disabling mental conditions. The relative importance of immune-related mechanisms in psychotic disorders remains subject of debate. Here, we present a large-scale retrospective study of blood and cerebrospinal fluid (CSF) immune cell profiles of psychosis spectrum patients. We performed basic CSF analysis and multi-dimensional flow cytometry of CSF and blood cells from 59 patients with primary psychotic disorders (F20, F22, F23, and F25) in comparison to inflammatory (49 RRMS and 16 NMDARE patients) and non-inflammatory controls (52 IIH patients). We replicated the known expansion of monocytes in the blood of psychosis spectrum patients, that we identified to preferentially affect classical monocytes. In the CSF, we found a relative shift from lymphocytes to monocytes, increased protein levels, and evidence of blood–brain barrier disruption in psychosis. In fact, these CSF features confidently distinguished autoimmune encephalitis from psychosis despite similar (initial) clinical features. We then constructed machine learning models incorporating blood and CSF parameters and demonstrated their superior ability to differentiate psychosis from non-inflammatory controls compared to individual parameters. Multi-dimensional and multi-compartment immune cell signatures can thus support the diagnosis of psychosis spectrum disorders with the potential to accelerate diagnosis and initiation of therapy.
FBP1 regulates proliferation, metastasis, and chemoresistance by participating in C-MYC/STAT3 signaling axis in ovarian cancer
Authors: Li Haoran , Qi Zihao , Niu Yongdong , Yang Yufei , Li Mengjiao , Pang Yangyang , Liu Mingming , Cheng Xi , Xu Midie , Wang Ziliang
Published: August 2021

Fructose-1,6-bisphosphatase (FBP1) is a rate-limiting enzyme in gluconeogenesis and an important tumor suppressor in human malignancies. Here, we aimed to investigate the expression profile of FBP1 in ovarian cancer, the molecular mechanisms that regulate FBP1 expression and to examine how the FBP1 regulatory axis contributes to tumorigenesis and progression in ovarian cancer. We showed that FBP1 expression was significantly decreased in ovarian cancer tissues compared with normal ovarian tissues, and low-FBP1 expression predicted poor prognosis in patients with ovarian cancer. The enhanced expression of FBP1 in ovarian cancer cell lines suppressed proliferation and 2-D/3-D invasion, reduced aerobic glycolysis, and sensitized cancer cells to cisplatin-induced apoptosis. Moreover, DNA methylation and C-MYC binding at the promoter inhibited FBP1 expression. Furthermore, through physical interactions with signal transducer and activator of transcription 3 (STAT3), FBP1 suppressed nuclear translocation of STAT3 and exerted its non-metabolic enzymatic activity to induce the dysfunction of STAT3. Thus, our study suggests that FBP1 may be a valuable prognostic predictor for ovarian cancer. C-MYC-dependent downregulation of FBP1 acted as a tumor suppressor via modulating STAT3, and the C-MYC/FBP1/STAT3 axis could be a therapeutic target.
The long shadow of socioeconomic deprivation over the modern management of acute myeloid leukemia: time to unravel the challenges
Authors: John M. Joseph , Kuriakose Philip , Smith Mark , Roman Eve , Tauro Sudhir
Published: August 2021

Biological and non-biological variables unrelated to acute myeloid leukemia (AML) preclude standard therapy in many settings, with “real world” patients under-represented in clinical trials and prognostic models. Here, using a case-based format, we illustrate the impact that socioeconomic and anthropogeographical constraints can have on optimally managing AML in 4 different healthcare systems. The granular details provided, emphasize the need for the development and targeting of socioeconomic interventions that are commensurate with the changing landscape of AML therapeutics, in order to avoid worsening the disparity in outcomes between patients with biologically similar disease.
A novel CDC25A/DYRK2 regulatory switch modulates cell cycle and survival
Authors: Lara-Chica Maribel , Correa-Sáez Alejandro , Jiménez-Izquierdo Rafael , Garrido-Rodríguez Martín , Ponce Francisco J. , Moreno Rita , Morrison Kimberley , Di Vona Chiara , Arató Krisztina , Jiménez-Jiménez Carla , Morrugares Rosario , Schmitz M. Lienhard , de la Luna Susana , de la Vega Laureano , Calzado Marco A.
Published: August 2021

The cell division cycle 25A (CDC25A) phosphatase is a key regulator of cell cycle progression that acts on the phosphorylation status of Cyclin–Cyclin-dependent kinase complexes, with an emergent role in the DNA damage response and cell survival control. The regulation of CDC25A activity and its protein level is essential to control the cell cycle and maintain genomic integrity. Here we describe a novel ubiquitin/proteasome-mediated pathway negatively regulating CDC25A stability, dependent on its phosphorylation by the serine/threonine kinase DYRK2. DYRK2 phosphorylates CDC25A on at least 7 residues, resulting in its degradation independent of the known CDC25A E3 ubiquitin ligases. CDC25A in turn is able to control the phosphorylation of DYRK2 at several residues outside from its activation loop, thus affecting DYRK2 localization and activity. An inverse correlation between DYRK2 and CDC25A protein amounts was observed during cell cycle progression and in response to DNA damage, with CDC25A accumulation responding to the manipulation of DYRK2 levels or activity in either physiological scenario. Functional data show that the pro-survival activity of CDC25A and the pro-apoptotic activity of DYRK2 could be partly explained by the mutual regulation between both proteins. Moreover, DYRK2 modulation of CDC25A expression and/or activity contributes to the DYRK2 role in cell cycle regulation. Altogether, we provide evidence suggesting that DYRK2 and CDC25A mutually control their activity and stability by a feedback regulatory loop, with a relevant effect on the genotoxic stress pathway, apoptosis, and cell cycle regulation.
Integrated analysis of high-throughput sequencing data reveals the key role of LINC00467 in the invasion and metastasis of testicular germ cell tumors
Authors: Bo Hao , Zhu Fang , Liu Zhizhong , Deng Qi , Liu Guangmin , Li Ruixue , Zhu Wenbing , Tan Yueqiu , Liu Gang , Fan Jingyu , Fan Liqing
Published: August 2021

Long noncoding RNAs (lncRNAs) are involved in various physiological and pathological processes. However, the role of lncRNAs in testicular germ cell tumor (TGCT) has been rarely reported. Our purpose is to comprehensively survey the expression and function of lncRNAs in TGCT. In this study, we used RNA sequencing to construct the lncRNA expression profiles of 13 TGCT tissues and 4 paraneoplastic tissues to explore the function of lncRNAs in TGCT. The bioinformatics analysis showed that many lncRNAs are differentially expressed in TGCT. GO and KEGG enrichment analyses revealed that the differentially expressed lncRNAs participated in various biological processes associated with tumorigenesis incisandtransmanners. Further, we found that the expression of LINC00467 was positively correlated with the poor prognosis and pathological grade of TGCT using WGCNA analysis and GEPIA database data mining. In vitro experiments revealed that LNC00467 could promote the migration and invasion of TGCT cells by regulating the expression of AKT3 and influencing total AKT phosphorylation. Further analysis of TCGA data revealed that the expression was negatively correlated with the infiltration of immune cells and the response to PD1 immunotherapy. In summary, this study is the first to construct the expression profile of lncRNAs in TGCT. It is also the first study to identify the metastasis-promoting role of LNC00467, which can be used as a potential predictor of TGCT prognosis and immunotherapeutic response to provide a clinical reference for the treatment and diagnosis of TGCT metastasis.
Human sensorimotor organoids derived from healthy and amyotrophic lateral sclerosis stem cells form neuromuscular junctions
Authors: Pereira João D. , DuBreuil Daniel M. , Devlin Anna-Claire , Held Aaron , Sapir Yechiam , Berezovski Eugene , Hawrot James , Dorfman Katherine , Chander Vignesh , Wainger Brian J.
Published: August 2021

Human induced pluripotent stem cells (iPSC) hold promise for modeling diseases in individual human genetic backgrounds and thus for developing precision medicine. Here, we generate sensorimotor organoids containing physiologically functional neuromuscular junctions (NMJs) and apply the model to different subgroups of amyotrophic lateral sclerosis (ALS). Using a range of molecular, genomic, and physiological techniques, we identify and characterize motor neurons and skeletal muscle, along with sensory neurons, astrocytes, microglia, and vasculature. Organoid cultures derived from multiple human iPSC lines generated from individuals with ALS and isogenic lines edited to harbor familial ALS mutations show impairment at the level of the NMJ, as detected by both contraction and immunocytochemical measurements. The physiological resolution of the human NMJ synapse, combined with the generation of major cellular cohorts exerting autonomous and non-cell autonomous effects in motor and sensory diseases, may prove valuable to understand the pathophysiological mechanisms of ALS.
Whole-genome sequencing of Schistosoma mansoni reveals extensive diversity with limited selection despite mass drug administration
Authors: Berger Duncan J. , Crellen Thomas , Lamberton Poppy H. L. , Allan Fiona , Tracey Alan , Noonan Jennifer D. , Kabatereine Narcis B. , Tukahebwa Edridah M. , Adriko Moses , Holroyd Nancy , Webster Joanne P. , Berriman Matthew , Cotton James A.
Published: August 2021

Control and elimination of the parasitic disease schistosomiasis relies on mass administration of praziquantel. Whilst these programmes reduce infection prevalence and intensity, their impact on parasite transmission and evolution is poorly understood. Here we examine the genomic impact of repeated mass drug administration onSchistosoma mansonipopulations with documented reduced praziquantel efficacy. We sequenced whole-genomes of 198S. mansonilarvae from 34 Ugandan children from regions with contrasting praziquantel exposure. Parasites infecting children from Lake Victoria, a transmission hotspot, form a diverse panmictic population. A single round of treatment did not reduce this diversity with no apparent population contraction caused by long-term praziquantel use. We find evidence of positive selection acting on members of gene families previously implicated in praziquantel action, but detect no high frequency functionally impactful variants. As efforts to eliminate schistosomiasis intensify, our study provides a foundation for genomic surveillance of this major human parasite.
A mechatronic shape display based on auxetic materials
Authors: Steed Anthony , Ofek Eyal , Sinclair Mike , Gonzalez-Franco Mar
Published: August 2021

Shape displays enable people to touch simulated surfaces. A common architecture of such devices uses a mechatronic pin-matrix. Besides their complexity and high cost, these matrix displays suffer from sharp edges due to the discreet representation which reduces their ability to render a large continuous surface when sliding the hand. We propose using an engineered auxetic material actuated by a smaller number of motors. The material bends in multiple directions, feeling smooth and rigid to touch. A prototype implementation uses nine actuators on a 220 mm square section of material. It can display a range of surface curvatures under the palm of a user without aliased edges. In this work we use an auxetic skeleton to provide rigidity on a soft material and demonstrate the potential of this class of surface through user experiments.
Long-life lithium-sulfur batteries with high areal capacity based on coaxial CNTs@TiN-TiO2 sponge
Authors: Zhang Hui , Ono Luis K. , Tong Guoqing , Liu Yuqiang , Qi Yabing
Published: August 2021

Rational design of heterostructures opens up new opportunities as an ideal catalyst system for lithium polysulfides conversion in lithium-sulfur battery. However, its traditional fabrication process is complex, which makes it difficult to reasonably control the content and distribution of each component. In this work, to rationally design the heterostructure, the atomic layer deposition is utilized to hybridize the TiO2-TiN heterostructure with the three-dimensional carbon nanotube sponge. Through optimizing the deposited thickness of TiO2 and TiN layers and adopting the annealing post-treatment, the derived coaxial sponge with uniform TiN-TiO2 heterostructure exhibits the best catalytic ability. The corresponding lithium-sulfur battery shows enhanced electrochemical performance with high specific capacity of 1289 mAh g−1 at 1 C and capacity retention of 85% after 500 cycles at 2 C. Furthermore, benefiting from the highly porous structure and interconnected conductive pathways from the sponge, its areal capacity reaches up to 21.5 mAh cm−2.
Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses
Authors: Ortega Natalia , Ribes Marta , Vidal Marta , Rubio Rocío , Aguilar Ruth , Williams Sarah , Barrios Diana , Alonso Selena , Hernández-Luis Pablo , Mitchell Robert A. , Jairoce Chenjerai , Cruz Angeline , Jimenez Alfons , Santano Rebeca , Méndez Susana , Lamoglia Montserrat , Rosell Neus , Llupià Anna , Puyol Laura , Chi Jordi , Melero Natalia Rodrigo , Parras Daniel , Serra Pau , Pradenas Edwards , Trinité Benjamin , Blanco Julià , Mayor Alfredo , Barroso Sonia , Varela Pilar , Vilella Anna , Trilla Antoni , Santamaria Pere , Carolis Carlo , Tortajada Marta , Izquierdo Luis , Angulo Ana , Engel Pablo , García-Basteiro Alberto L. , Moncunill Gemma , Dobaño Carlota
Published: August 2021

Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and the individual characteristics influencing it, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E, NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed up to 7 months (N = 578). Seroprevalence increases over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, are stable over time, except IgG to nucleocapsid antigen and IgM levels that wane. After the peak response, anti-spike antibody levels increase from ~150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. IgG and IgA to HCoV are significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.
Purple sulfur bacteria fix N2 via molybdenum-nitrogenase in a low molybdenum Proterozoic ocean analogue
Authors: Philippi Miriam , Kitzinger Katharina , Berg Jasmine S. , Tschitschko Bernhard , Kidane Abiel T. , Littmann Sten , Marchant Hannah K. , Storelli Nicola , Winkel Lenny H. E. , Schubert Carsten J. , Mohr Wiebke , Kuypers Marcel M. M.
Published: August 2021

Biological N2fixation was key to the expansion of life on early Earth. The N2-fixing microorganisms and the nitrogenase type used in the Proterozoic are unknown, although it has been proposed that the canonical molybdenum-nitrogenase was not used due to low molybdenum availability. We investigate N2fixation in Lake Cadagno, an analogue system to the sulfidic Proterozoic continental margins, using a combination of biogeochemical, molecular and single cell techniques. In Lake Cadagno, purple sulfur bacteria (PSB) are responsible for high N2fixation rates, to our knowledge providing the first direct evidence for PSB in situ N2fixation. Surprisingly, no alternative nitrogenases are detectable, and N2fixation is exclusively catalyzed by molybdenum-nitrogenase. Our results show that molybdenum-nitrogenase is functional at low molybdenum conditions in situ and that in contrast to previous beliefs, PSB may have driven N2fixation in the Proterozoic ocean.
Cell specific photoswitchable agonist for reversible control of endogenous dopamine receptors
Authors: Donthamsetti Prashant , Winter Nils , Hoagland Adam , Stanley Cherise , Visel Meike , Lammel Stephan , Trauner Dirk , Isacoff Ehud
Published: August 2021

Dopamine controls diverse behaviors and their dysregulation contributes to many disorders. Our ability to understand and manipulate the function of dopamine is limited by the heterogenous nature of dopaminergic projections, the diversity of neurons that are regulated by dopamine, the varying distribution of the five dopamine receptors (DARs), and the complex dynamics of dopamine release. In order to improve our ability to specifically modulate distinct DARs, here we develop a photo-pharmacological strategy using a Membrane anchored Photoswitchable orthogonal remotely tethered agonist for the Dopamine receptor (MP-D). Our design selectively targets D1R/D5R receptor subtypes, most potently D1R (MP-D1ago), as shown in HEK293T cells. In vivo, we targeted dorsal striatal medium spiny neurons where the photo-activation of MP-D1agoincreased movement initiation, although further work is required to assess the effects of MP-D1agoon neuronal function. Our method combines ligand and cell type-specificity with temporally precise and reversible activation of D1R to control specific aspects of movement. Our results provide a template for analyzing dopamine receptors.
A subduction influence on ocean ridge basalts outside the Pacific subduction shield
Authors: Yang A. Y. , Langmuir C. H. , Cai Y. , Michael P. , Goldstein S. L. , Chen Z.
Published: August 2021

The plate tectonic cycle produces chemically distinct mid-ocean ridge basalts and arc volcanics, with the latter enriched in elements such as Ba, Rb, Th, Sr and Pb and depleted in Nb owing to the water-rich flux from the subducted slab. Basalts from back-arc basins, with intermediate compositions, show that such a slab flux can be transported behind the volcanic front of the arc and incorporated into mantle flow. Hence it is puzzling why melts of subduction-modified mantle have rarely been recognized in mid-ocean ridge basalts. Here we report the first mid-ocean ridge basalt samples with distinct arc signatures, akin to back-arc basin basalts, from the Arctic Gakkel Ridge. A new high precision dataset for 576 Gakkel samples suggests a pervasive subduction influence in this region. This influence can also be identified in Atlantic and Indian mid-ocean ridge basalts but is nearly absent in Pacific mid-ocean ridge basalts. Such a hemispheric-scale upper mantle heterogeneity reflects subduction modification of the asthenospheric mantle which is incorporated into mantle flow, and whose geographical distribution is controlled dominantly by a “subduction shield” that has surrounded the Pacific Ocean for 180 Myr. Simple modeling suggests that a slab flux equivalent to ~13% of the output at arcs is incorporated into the convecting upper mantle.
Cortical neurons exhibit diverse myelination patterns that scale between mouse brain regions and regenerate after demyelination
Authors: Call Cody L. , Bergles Dwight E.
Published: August 2021

Axons in the cerebral cortex show a broad range of myelin coverage. Oligodendrocytes establish this pattern by selecting a cohort of axons for myelination; however, the distribution of myelin on distinct neurons and extent of internode replacement after demyelination remain to be defined. Here we show that myelination patterns of seven distinct neuron subtypes in somatosensory cortex are influenced by both axon diameter and neuronal identity. Preference for myelination of parvalbumin interneurons was preserved between cortical areas with varying myelin density, suggesting that regional differences in myelin abundance arises through local control of oligodendrogenesis. By imaging loss and regeneration of myelin sheaths in vivo we show that myelin distribution on individual axons was altered but overall myelin content on distinct neuron subtypes was restored. Our findings suggest that local changes in myelination are tolerated, allowing regenerated oligodendrocytes to restore myelin content on distinct neurons through opportunistic selection of axons.
High performance temperature difference triboelectric nanogenerator
Authors: Cheng Bolang , Xu Qi , Ding Yaqin , Bai Suo , Jia Xiaofeng , Yu Yangdianchen , Wen Juan , Qin Yong
Published: August 2021

Usually, high temperature decreases the output performance of triboelectric nanogenerator because of the dissipation of triboelectric charges through the thermionic emission. Here, a temperature difference triboelectric nanogenerator is designed and fabricated to enhance the electrical output performance in high temperature environment. As the hotter friction layer’s temperature of nanogenerator is 0 K to 145 K higher than the cooler part’s temperature, the output voltage, current, surface charge density and output power are increased 2.7, 2.2, 3.0 and 2.9 times, respectively (from 315 V, 9.1 μA, 19.6 μC m−2, 69 μW to 858 V, 20 μA, 58.8 μC m−2, 206.7 μW). With the further increase of temperature difference from 145 K to 219 K, the surface charge density and output performance gradually decrease. At the optimal temperature difference (145 K), the largest output current density is 443 μA cm−2, which is 26.6% larger than the reported record value (350 μA cm−2).