bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid court resilience and the selection of cases
Authors: Vagias Michail
Published: September 2020

The article explores the extent to which the resilience of hybrid courts is impacted by their selection of cases. It proceeds from the observation that the cases pursued by hybrid institutions are the result of choice under constraints. The article examines the identity of the case-choosers and the relevance of such choices for the internal and external resilience of hybrid courts. The research reveals the need to distinguish between case selection by the drafters and case selection by court authorities in the context of each institution and the tensions between these two sets of practices. These tensions are examined in the context of four hybrid institutions. The Office of the Prosecutor at the Special Court for Sierra Leone enjoyed a relatively broad measure of discretion in terms of case selection. However, the Extraordinary African Chambers, the Cambodia Chambers and the Kosovo Specialist Chambers seem to have been established with specific accused in mind. The article argues that resilience considerations are probably relevant in instances of case selection by the court officers, albeit they are context sensitive and may vary over time. Case selection prior to the establishment of a court and/or by political stakeholders, on the other hand, is ill-suited for analysis using internal resilience and arguably fall outside its scope of application. For these cases, the research argues that the discussion requires re-orientation with emphasis shifted to concepts such as contribution to national reconciliation as opposed to resistance to external pressure.
Epidemiological profile and transmission dynamics of COVID-19 in the Philippines
Authors: Haw N. J. L. , Uy J. , Sy K. T. L. , Abrigo M. R. M.
Published: September 2020

The Philippines confirmed local transmission of COVID-19 on 7 March 2020. We described the characteristics and epidemiological time-to-event distributions for laboratory-confirmed cases in the Philippines recorded up to 29 April 2020 and followed until 22 May 2020. The median age of 8212 cases was 46 years (IQR 32–61), with 46.2% being female and 68.8% living in the National Capital Region. Health care workers represented 24.7% of all detected infections. Mean length of hospitalisation for those who were discharged or died were 16.00 days (95% CI 15.48–16.54) and 7.27 days (95% CI 6.59–8.24). Mean duration of illness was 26.66 days (95% CI 26.06–27.28) and 12.61 days (95% CI 11.88–13.37) for those who recovered or died. Mean serial interval was 6.90 days (95% CI 5.81–8.41). Epidemic doubling time prior to the enhanced community quarantine (ECQ; 11 February and 19 March) was 4.86 days (95% CI 4.67–5.07) and the reproductive number was 2.41 (95% CI 2.33–2.48). During the ECQ (20 March to 9 April), doubling time was 12.97 days (95% CI 12.57–13.39) and the reproductive number was 0.89 (95% CI 0.78–1.02).
The effectiveness of Virkon® S disinfectant against an invasive insect and implications for Antarctic biosecurity practices
Authors: Bartlett Jesamine C. , Radcliffe Richard James , Convey Pete , Hughes Kevin A. , Hayward Scott A.L.
Published: September 2020

The flightless midge Eretmoptera murphyi is thought to be continuing its invasion of Signy Island via the treads of personnel boots. Current boot-wash biosecurity protocols in the Antarctic region rely on microbial biocides, primarily Virkon® S. As pesticides have limited approval for use in the Antarctic Treaty area, we investigated the efficacy of Virkon® S in controlling the spread of E. murphyi using boot-wash simulations and maximum threshold exposures. We found that E. murphyi tolerates over 8 h of submergence in 1% Virkon® S. Higher concentrations increased effectiveness, but larvae still exhibited > 50% survival after 5 h in 10% Virkon® S. Salt and hot water treatments (without Virkon® S) were explored as possible alternatives. Salt water proved ineffective, with mortality only in first-instar larvae across multi-day exposures. Larvae experienced 100% mortality when exposed for 10 s to 50°C water, but they showed complete survival at 45°C. Given that current boot-wash protocols alone are an ineffective control of this invasive insect, we advocate hot water (> 50°C) to remove soil, followed by Virkon® S as a microbial biocide on ‘clean’ boots. Implications for the spread of invasive invertebrates as a result of increased human activity in the Antarctic region are discussed.
Early-life adversities and adult attachment in depression and alexithymia
Authors: Kajanoja Jani , Karukivi Max , Scheinin Noora M. , Ahrnberg Hanna , Karlsson Linnea , Karlsson Hasse
Published: September 2020

Alexithymia is a personality construct characterized by difficulties in identifying and verbalizing feelings, a restricted imagination, and an externally oriented thinking style. As alexithymia shows marked overlap with depression, its independent nature as a personality construct is still being debated. The etiology of alexithymia is unknown, although childhood emotional neglect and attachment formation are thought to play important roles. In the FinnBrain Birth Cohort Study, experiences of early-life adversities (EA) and childhood maltreatment (CM) were studied in a sample of 2,604 men and women. The overlap and differences between depression and alexithymia were investigated by comparing their associations with EA types and adult attachment style. Alexithymia was specifically associated with childhood emotional neglect (odds ratio (OR) 3.8, p < .001), whereas depression was related to several types of EA. In depression co-occurring with alexithymia, there was a higher prevalence of emotional neglect (81.3% vs. 54.4%, p < .001), attachment anxiety (t = 2.38, p = .018), and attachment avoidance (t = 4.03, p < .001). Early-life adversities were markedly different in the alexithymia group compared to those suffering from depression, or healthy controls. Depression with concurrent alexithymia may represent a distinct subtype, specifically associated with childhood experiences of emotional neglect, and increased attachment insecurity compared to non-alexithymic depression.
The change in social norms in the Mafia's territories: the anti-racket movement of Addiopizzo
Authors: Lipari Francesca , Andrighetto Giulia
Published: September 2020

Social norms pervade society and when they conflict with legal norms, the former undermine the latter making them ineffective. In this study, we propose that the extortion racket in Sicily has turned into a social norm and this is why recent top-down interventions have failed in stalling this socially undesirable activity. One exception is represented by Addiopizzo, a grass root movement that uses non-legal means to fight the racket phenomenon in Sicily. During the last 15 years, Addiopizzo was able to produce an effective reduction in the payment of protection money in the Sicilian city of Palermo by triggering, we suggest, among other things, a process of change in social norms. Acknowledging the importance of a change in social norms to achieve social change allows us to link the theory of institutions as ‘rules’ with the theory of institutions as ‘equilibria’.
Converging paths: bounded rationality, practice theory and the study of change in historical international relations
Authors: Bruneau Quentin
Published: September 2020

Bounded rationality and practice theory have both become popular theories of action for major strands of work in constructivist and rationalist International Relations (IR). Based on this observation, I make two arguments. The first is that although they underpin what are generally seen as opposed theoretical camps in IR, bounded rationality and practice theory share two fundamental assumptions. They both accept that how agents process information and make decisions depends on where they are situated in social space, and where they stand in historical time. In turn, these shared assumptions imply that they agree on the existence of a common type of change: change in terms of how groups of people process information and make decisions over time. My second argument is that by studying this type of change, it is possible to shed new light on major transformations of international relations, and that one way of engaging in this type of research is to study international practitioners' education over substantial time periods. With these arguments, this article makes a methodological contribution to the study of change in historical international relations and charts a practical course for pluralist dialogue in IR.
Experimental verification of super-compact ultra-wideband (UWB) polarization and incident angle-independent metamaterial absorber
Authors: Kaur Manpreet , Singh Hari Shankar
Published: September 2020

In this paper, a super-compact ultra-wideband (UWB) metamaterial absorber (MMA) is presented. The absorber design consists of an inverted L-shaped structure and a diagonal rectangular-shaped structure. The capacitive coupling between these two structures not only provides UWB nature but also provides a super-compact absorber design. The dimension of the unit cell arrangement is 5 × 5 mm2 and printed on a low-cost FR-4 substrate of thickness 1.54 mm (0.061λlowest). The design absorber provides more than 97% absorptivity from 12 to 21 GHz for normal incidence electromagnetic (EM) wave. However, the proposed MMA has a full width at half maximum absorption bandwidth of 11.71 GHz from 10.34 to 22.05 GHz. Moreover, the surface current distributions have been analyzed to understand the absorption mechanism of the MMA. The stability of the proposed design is validated with different incident angles (for TE and TM modes) and different polarization angles. Finally, the absorber design is fabricated and verified experimentally. Furthermore, the UWB frequency range, high absorption, ease in design and fabrication, and cost-effective make it suitable for different quality applications in stealth technology, thermal imaging, radar detection, antenna systems, and other EM devices.
Exercise induced leg pain due to endofibrosis of external iliac artery
Authors: Gähwiler Roman , Hirschmüller Anja , Grumann Thorsten , Isaak Andrej , Thalhammer Christoph
Published: September 2020

Summary: Due to monotonous movement patterns, muscular hypertrophy, and increased cardiac output peripheral vasculature of athletes are subject to extreme stresses during athletic performance. Individuals suffering from exercise induced non-traumatic lower leg pain may display underlying vascular pathology such as external iliac artery endofibrosis. Therefore, it is essential in the course of to discriminate vascular from non-vascular findings and prime the correct diagnostic path within the course of clinical examination. In this regard, interdisciplinary thinking and profound knowledge in exercise-associated pathologies of the musculoskeletal, nervous and vascular system is indispensable. Consequently, provocation testing displays an indispensable diagnostic tool and has to be continued until symptoms occur, or complete exhaustion is attained. Finally, selective assessment of conservative and surgical treatment options, as well as its ethical evaluation, are of major importance in order to protect, preserve and promote the health and physical integrity of our patients who are keen to perform.
Aerts Receives 2019 Gilbert F. White Distinguished Award
Authors:   AGU
Published: September 2020

Jeroen Aerts received the 2019 Gilbert F. White Distinguished Award at AGU’s Fall Meeting 2019, held 9–13 December in San Francisco, Calif. The award “recognizes the honoree’s original contributions to the basic knowledge of natural hazards or disaster risks.”
An era of single-cell genomics consortia
Authors: Ando Yoshinari , Kwon Andrew Tae-Jun , Shin Jay W.
Published: September 2020

The human body consists of 37 trillion single cells represented by over 50 organs that are stitched together to make us who we are, yet we still have very little understanding about the basic units of our body: what cell types and states make up our organs both compositionally and spatially. Previous efforts to profile a wide range of human cell types have been attempted by the FANTOM and GTEx consortia. Now, with the advancement in genomic technologies, profiling the human body at single-cell resolution is possible and will generate an unprecedented wealth of data that will accelerate basic and clinical research with tangible applications to future medicine. To date, several major organs have been profiled, but the challenges lie in ways to integrate single-cell genomics data in a meaningful way. In recent years, several consortia have begun to introduce harmonization and equity in data collection and analysis. Herein, we introduce existing and nascent single-cell genomics consortia, and present benefits to necessitate single-cell genomic consortia in a regional environment to achieve the universal human cell reference dataset.
Experimental evolution reveals nitrate tolerance mechanisms in Desulfovibrio vulgaris
Authors: Wu Bo , Liu Feifei , Zhou Aifen , Li Juan , Shu Longfei , Kempher Megan L , Yang Xueqin , Ning Daliang , Pan Feiyan , Zane Grant M , Wall Judy D , Van Nostrand Joy D , Juneau Philippe , Chen Shouwen , Yan Qingyun , Zhou Jizhong , He Zhili
Published: September 2020

Elevated nitrate in the environment inhibits sulfate reduction by important microorganisms of sulfate-reducing bacteria (SRB). Several SRB may respire nitrate to survive under elevated nitrate, but how SRB that lack nitrate reductase survive to elevated nitrate remains elusive. To understand nitrate adaptation mechanisms, we evolved 12 populations of a model SRB (i.e., Desulfovibrio vulgaris Hildenborough, DvH) under elevated NaNO3 for 1000 generations, analyzed growth and acquired mutations, and linked their genotypes with phenotypes. Nitrate-evolved (EN) populations significantly (p < 0.05) increased nitrate tolerance, and whole-genome resequencing identified 119 new mutations in 44 genes of 12 EN populations, among which six functional gene groups were discovered with high mutation frequencies at the population level. We observed a high frequency of nonsense or frameshift mutations in nitrosative stress response genes (NSR: DVU2543, DVU2547, and DVU2548), nitrogen regulatory protein C family genes (NRC: DVU2394-2396, DVU2402, and DVU2405), and nitrate cluster (DVU0246-0249 and DVU0251). Mutagenesis analysis confirmed that loss-of-functions of NRC and NSR increased nitrate tolerance. Also, functional gene groups involved in fatty acid synthesis, iron regulation, and two-component system (LytR/LytS) known to be responsive to multiple stresses, had a high frequency of missense mutations. Mutations in those gene groups could increase nitrate tolerance through regulating energy metabolism, barring entry of nitrate into cells, altering cell membrane characteristics, or conferring growth advantages at the stationary phase. This study advances our understanding of nitrate tolerance mechanisms and has important implications for linking genotypes with phenotypes in DvH.
Overactivated sonic hedgehog signaling aggravates intrauterine adhesion via inhibiting autophagy in endometrial stromal cells
Authors: Wei Cheng , Pan Yibin , Zhang Yinli , Dai Yongdong , Jiang Lingling , Shi Libing , Yang Weijie , Xu Shiqian , Zhang Yingyi , Xu Wenzhi , Zhang Yanling , Lin Xiaona , Zhang Songying
Published: September 2020

Autophagy can be dynamically induced in response to stresses and is an essential, ubiquitous intracellular recycling system that impacts the fate of damaged resident cells, thereby influencing wound healing. Endometrial fibrosis is a form of abnormal wound healing that causes intrauterine adhesion (IUA) and infertility. We previously demonstrated that overactivated sonic hedgehog (SHH) signaling exacerbated endometrial fibrosis, but the role of autophagy in this process is still unknown. Here, we report that impaired autophagy participates in SHH pathway-induced endometrial fibrosis. Endometrial stroma-myofibroblast transition accompanied by autophagy dysfunction was present in both endometrial biopsies of IUA patients and Amhr2cre/+R26-SmoM2+/− (AM2) transgenic mouse. Mechanistically, SHH pathway negatively regulated autophagy through pAKT-mTORC1 in a human endometrial stromal cell line (T-HESCs). Furthermore, SHH pathway-mediated fibrosis was partly counteracted by autophagy modulation in both T-HESCs and the murine IUA model. Specifically, the impact of SHH pathway inhibition (GANT61) was reversed by the pharmacological autophagy inhibitor chloroquine (CQ) or RNA interference of autophagy-related gene ATG5 or ATG7. Similar results were obtained from the murine IUA model treated with GANT61 and CQ. Moreover, promoting autophagy with rapamycin reduced fibrosis in the AM2 IUA model to baseline levels. In summary, defective autophagy is involved in SHH pathway-driven endometrial fibrosis, suggesting a potential novel molecular target for IUA treatment.
Checkpoint regulator B7x is epigenetically regulated by HDAC3 and mediates resistance to HDAC inhibitors by reprogramming the tumor immune environment in colorectal cancer
Authors: Li Yuxin , Liu Yao , Zhao Na , Yang Xiaojun , Li Yaqing , Zhai Fangzheng , Zang Xingxing , Cui Wei
Published: September 2020

HDAC inhibitors are efficacious for treating lymphoma, but display limited efficacy in treating solid tumors. Here, we investigated the relationship between HDAC inhibitor resistance and the tumor immune environment in colorectal cancer. Our data indicated that among the investigated immune factors, B7x expression was enhanced in HDAC inhibitor-resistant colorectal cancer models in vitro and in vivo. In addition, gene manipulation results demonstrated that xenograft mice with tumors derived from a B7x-overexpressing CT-26 colorectal cancer cell line were resistant to HDAC inhibitor treatment. Notably, we found that there is a negative relationship between HDAC and B7x expression in both colorectal cancer cell lines and patients’ tumors. Furthermore, our data indicated that elevated expression of B7x was related to a poor prognosis in colorectal tumor patients. Interestingly, treatment with a specific inhibitor or siRNA of HDAC3, but not HDAC2, 6, and 8, resulted in obvious upregulation of B7x expression in colorectal cancer cells. In addition, our data showed that a cell line with high HDAC3 expression and low B7x expression had decreased enrichment of acetylated histone H3 in the promoter region of the gene encoding B7x. This pattern was reversed by addition of HDAC3 inhibitors. Mechanistically, we found that HDAC3 regulated B7x transcription by promoting the binding of the transcription activator C/EBP-α with the B7x promoter region. Importantly, our data indicated that an antibody neutralizing B7x augmented the response to HDAC inhibitor in the colorectal cancer xenograft model and the lung metastasis model by increasing the ratios of both CD4-positive and CD8-positive T cells. In summary, we demonstrated a role of B7x in HDAC inhibitor resistance and identified the mechanism that dysregulates B7x in colorectal cancer. Our work provides a novel strategy to overcome HDAC inhibitor resistance.
CDK9 activity is critical for maintaining MDM4 overexpression in tumor cells
Authors: Štětková Monika , Growková Kateřina , Fojtík Petr , Valčíková Barbora , Palušová Veronika , Verlande Amandine , Jorda Radek , Kryštof Vladimír , Hejret Václav , Alexiou Panagiotis , Rotrekl Vladimír , Uldrijan Stjepan
Published: September 2020

The identification of the essential role of cyclin-dependent kinases (CDKs) in the control of cell division has prompted the development of small-molecule CDK inhibitors as anticancer drugs. For many of these compounds, the precise mechanism of action in individual tumor types remains unclear as they simultaneously target different classes of CDKs – enzymes controlling the cell cycle progression as well as CDKs involved in the regulation of transcription. CDK inhibitors are also capable of activating p53 tumor suppressor in tumor cells retaining wild-type p53 gene by modulating MDM2 levels and activity. In the current study, we link, for the first time, CDK activity to the overexpression of the MDM4 (MDMX) oncogene in cancer cells. Small-molecule drugs targeting the CDK9 kinase, dinaciclib, flavopiridol, roscovitine, AT-7519, SNS-032, and DRB, diminished MDM4 levels and activated p53 in A375 melanoma and MCF7 breast carcinoma cells with only a limited effect on MDM2. These results suggest that MDM4, rather than MDM2, could be the primary transcriptional target of pharmacological CDK inhibitors in the p53 pathway. CDK9 inhibitor atuveciclib downregulated MDM4 and enhanced p53 activity induced by nutlin-3a, an inhibitor of p53-MDM2 interaction, and synergized with nutlin-3a in killing A375 melanoma cells. Furthermore, we found that human pluripotent stem cell lines express significant levels of MDM4, which are also maintained by CDK9 activity. In summary, we show that CDK9 activity is essential for the maintenance of high levels of MDM4 in human cells, and drugs targeting CDK9 might restore p53 tumor suppressor function in malignancies overexpressing MDM4.
Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells
Authors: Zheng Jieling , Wang Baiyao , Zheng Rong , Zhang Jian , Huang Chunyue , Zheng Ronghui , Huang Zhong , Qiu Wenze , Liu Mengzhong , Yang Kaijun , Mao Zixu , Ji Aimin , Yuan Yawei
Published: September 2020

Radiotherapy is one of the standard treatments for glioma patients; however, its clinical efficacy is limited by radioresistance. We identified a mechanism of such resistance mediated by linc-RA1 (radioresistance-associated long intergenic noncoding RNA 1). Linc-RA1 was upregulated in radioresistant glioma cells and glioma tissue samples, compared with radiosensitive cells and nontumor tissues. Linc-RA1 was associated with inferior overall survival and advanced clinical stage of glioma. Linc-RA1 promoted glioma radioresistance in vitro and in vivo. Mechanistically, linc-RA1 stabilized the level of H2B K120 monoubiquitination (H2Bub1) by combining with H2B and inhibiting the interaction between H2Bub1 and ubiquitin-specific protease 44 (USP44), which inhibited autophagy, thus contributing to glioma radioresistance. These results reveal that linc-RA1-mediated autophagy is a key mechanism of radioresistance and is an actionable target for improving radiotherapy efficacy in patients with glioma.
c-myc regulates the sensitivity of breast cancer cells to palbociclib via c-myc/miR-29b-3p/CDK6 axis
Authors: Ji Wenfei , Zhang Wenwen , Wang Xin , Shi Yaqin , Yang Fang , Xie Hui , Zhou Wenbin , Wang Shui , Guan Xiaoxiang
Published: September 2020

Palbociclib, a CDK4/6 inhibitor, has been granted accelerated approval by US FDA for hormone receptor-positive HER2-negative metastatic breast cancer. To determine potential biomarkers of palbociclib sensitivity to assist in patient selection and clinical development, we investigated the effects of palbociclib in a panel of molecularly characterized breast cancer cell lines. We quantified palbociclib sensitivity and c-myc expression in 11 breast cancer cell lines, 124 breast cancer samples, and The Cancer Genome Atlas database. We found non-TNBC subtypes were more sensitive to palbociclib than TNBC. Activation of c-myc led to differential palbociclib sensitivities, and further inhibition of c-myc enhanced palbociclib sensitivity. Moreover, we identified for the first time a c-myc/miR-29b-3p/CDK6 axis in breast cancer that could be responsible for c-myc-induced palbociclib insensitivity, in which c-myc activation resulted in downregulation of miR-29b-3p, further activated CDK6 and inhibited cell-cycle arrest at G1 phase. Moreover, downregulated (inactived) c-myc-induced oncogenic addiction could increase palbociclib efficacy, using both Xenograft model and patient-derived tumor xenograft (PDTX) model. Our finding extends the concept of combined blockade of the CDK4/6 and c-myc signaling pathways to increase palbociclib sensitivity, making c-myc a promising biomarker for palbociclib sensitivity in breast cancer.
Identification of UBAP1 mutations in juvenile hereditary spastic paraplegia in the 100,000 Genomes Project
Authors: Bourinaris Thomas , Smedley Damian , Cipriani Valentina , Sheikh Isabella , Athanasiou-Fragkouli Alkyoni , Chinnery Patrick , Morris Huw , Real Raquel , Harrison Victoria , Reid Evan , Wood Nicholas ,   Genomics England Research Consortium, Vandrovcova Jana , Houlden Henry , Tucci Arianna
Published: September 2020

Hereditary spastic paraplegia (HSP) is a group of heterogeneous inherited degenerative disorders characterized by lower limb spasticity. Fifty percent of HSP patients remain yet genetically undiagnosed. The 100,000 Genomes Project (100KGP) is a large UK-wide initiative to provide genetic diagnosis to previously undiagnosed patients and families with rare conditions. Over 400 HSP families were recruited to the 100KGP. In order to obtain genetic diagnoses, gene-based burden testing was carried out for rare, predicted pathogenic variants using candidate variants from the Exomiser analysis of the genome sequencing data. A significant gene-disease association was identified for UBAP1 and HSP. Three protein truncating variants were identified in 13 patients from 7 families. All patients presented with juvenile form of pure HSP, with median age at onset 10 years, showing autosomal dominant inheritance or de novo occurrence. Additional clinical features included parkinsonism and learning difficulties, but their association with UBAP1 needs to be established.
House mouse Mus musculus dispersal in East Eurasia inferred from 98 newly determined complete mitochondrial genome sequences
Authors: Li Yue , Fujiwara Kazumichi , Osada Naoki , Kawai Yosuke , Takada Toyoyuki , Kryukov Alexey P. , Abe Kuniya , Yonekawa Hiromichi , Shiroishi Toshihiko , Moriwaki Kazuo , Saitou Naruya , Suzuki Hitoshi
Published: September 2020

The Eurasian house mouseMus musculusis useful for tracing prehistorical human movement related to the spread of farming. We determined whole mitochondrial DNA (mtDNA) sequences (ca. 16,000 bp) of 98 wild-derived individuals of two subspecies,M.m.musculus(MUS) andM.m.castaneus(CAS). We revealed directional dispersals reaching as far as the Japanese Archipelago from their homelands. Our phylogenetic analysis indicated that the eastward movement of MUS was characterised by five step-wise regional extension events: (1) broad spatial expansion into eastern Europe and the western part of western China, (2) dispersal to the eastern part of western China, (3) dispersal to northern China, (4) dispersal to the Korean Peninsula and (5) colonisation and expansion in the Japanese Archipelago. These events were estimated to have occurred during the last 2000–18,000 years. The dispersal of CAS was characterised by three events: initial divergences (ca. 7000–9000 years ago) of haplogroups in northernmost China and the eastern coast of India, followed by two population expansion events that likely originated from the Yangtze River basin to broad areas of South and Southeast Asia, including Sri Lanka, Bangladesh and Indonesia (ca. 4000–6000 years ago) and to Yunnan, southern China and the Japanese Archipelago (ca. 2000–3500). This study provides a solid framework for the spatiotemporal movement of the human-associated organisms in Holocene Eastern Eurasia using whole mtDNA sequences, reliable evolutionary rates and accurate branching patterns. The information obtained here contributes to the analysis of a variety of animals and plants associated with prehistoric human migration.
Effectiveness of protected areas in conserving tropical forest birds
Authors: Cazalis Victor , Princé Karine , Mihoub Jean-Baptiste , Kelly Joseph , Butchart Stuart H. M. , Rodrigues Ana S. L.
Published: September 2020

Protected areas (PAs) are the cornerstones of global biodiversity conservation efforts, but to fulfil this role they must be effective at conserving the ecosystems and species that occur within their boundaries. Adequate monitoring datasets that allow comparing biodiversity between protected and unprotected sites are lacking in tropical regions. Here we use the largest citizen science biodiversity dataset – eBird – to quantify the extent to which protected areas in eight tropical forest biodiversity hotspots are effective at retaining bird diversity. We find generally positive effects of protection on the diversity of bird species that are forest-dependent, endemic to the hotspots, or threatened or Near Threatened, but not on overall bird species richness. Furthermore, we show that in most of the hotspots examined this benefit is driven by protected areas preventing both forest loss and degradation. Our results provide evidence that, on average, protected areas contribute measurably to conserving bird species in some of the world’s most diverse and threatened terrestrial ecosystems.
Climate action requires new accounting guidance and governance frameworks to manage carbon in shelf seas
Authors: Luisetti Tiziana , Ferrini Silvia , Grilli Gaetano , Jickells Timothy D. , Kennedy Hilary , Kröger Silke , Lorenzoni Irene , Milligan Ben , van der Molen Johan , Parker Ruth , Pryce Tim , Turner R. Kerry , Tyllianakis Emmanouil
Published: September 2020

Accounting guidelines exist for the recording of carbon flows in terrestrial and coastal ecosystems. Shelf sea sediments, while considered an important carbon store, have yet to receive comparable scrutiny. Here, we explore whether effective management of carbon stocks accumulating in shelf seas could contribute towards a nation’s greenhouse gas emissions reduction targets. We review the complexities of carbon transport and fate in shelf seas, and the geopolitical challenges of carbon accounting in climate governance because of the transboundary nature of carbon flows in the marine environment. New international accounting guidance and governance frameworks are needed to prompt climate action.
NEMF mutations that impair ribosome-associated quality control are associated with neuromuscular disease
Authors: Martin Paige B. , Kigoshi-Tansho Yu , Sher Roger B. , Ravenscroft Gianina , Stauffer Jennifer E. , Kumar Rajesh , Yonashiro Ryo , Müller Tina , Griffith Christopher , Allen William , Pehlivan Davut , Harel Tamar , Zenker Martin , Howting Denise , Schanze Denny , Faqeih Eissa A. , Almontashiri Naif A. M. , Maroofian Reza , Houlden Henry , Mazaheri Neda , Galehdari Hamid , Douglas Ganka , Posey Jennifer E. , Ryan Monique , Lupski James R. , Laing Nigel G. , Joazeiro Claudio A. P. , Cox Gregory A.
Published: September 2020

A hallmark of neurodegeneration is defective protein quality control. The E3 ligase Listerin (LTN1/Ltn1) acts in a specialized protein quality control pathway—Ribosome-associated Quality Control (RQC)—by mediating proteolytic targeting of incomplete polypeptides produced by ribosome stalling, and Ltn1 mutation leads to neurodegeneration in mice. Whether neurodegeneration results from defective RQC and whether defective RQC contributes to human disease have remained unknown. Here we show that three independently-generated mouse models with mutations in a different component of the RQC complex, NEMF/Rqc2, develop progressive motor neuron degeneration. Equivalent mutations in yeast Rqc2 selectively interfere with its ability to modify aberrant translation products with C-terminal tails which assist with RQC-mediated protein degradation, suggesting a pathomechanism. Finally, we identify NEMF mutations expected to interfere with function in patients from seven families presenting juvenile neuromuscular disease. These uncover NEMF’s role in translational homeostasis in the nervous system and implicate RQC dysfunction in causing neurodegeneration.
Effects of quercetin-conjugated with superparamagnetic iron oxide nanoparticles on learning and memory improvement through targeting microRNAs/NF-κB pathway
Authors: Ebrahimpour Shiva , Esmaeili Abolghasem , Dehghanian Fariba , Beheshti Siamak
Published: September 2020

Quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) have an ameliorative effect on diabetes-induced memory impairment. The current study aimed to compare the effect of quercetin (QC) and QCSPIONs on inflammation-related microRNAs and NF-κB signaling pathways in the hippocampus of diabetic rats. The expression levels of miR-146a, miR-9, NF-κB, and NF-κB-related downstream genes, including TNF-α, BACE1, AβPP, Bax, and Bcl-2 were measured using quantitative real-time PCR. To determine the NF-κB activity, immunohistochemical expression of NF-κB/p65 phosphorylation was employed. Computer simulated docking analysis also performed to find the QC target proteins involved in the NF-κB pathway. Results indicate that diabetes significantly upregulated the expression levels of miR-146a, miR-9, TNF-α, NF-κB, and subsequently AβPP, BACE1, and Bax. Expression analysis shows that QCSPIONs are more effective than pure QC in reducing the expression of miR-9. Interestingly, QCSPIONs reduce the pathological activity of NF-κB and subsequently normalize BACE1, AβPP, and the ratio of Bax/Bcl-2 expression better than pure QC. Comparative docking analyses also show the stronger binding affinity of QC to IKK and BACE1 proteins compared to specific inhibitors of each protein. In conclusion, our study suggests the potent efficacy of QCSPIONs as a promising drug delivery system in memory improvement through targeting the NF-κB pathway.
A correlation analysis of Light Microscopy and X-ray MicroCT imaging methods applied to archaeological plant remains’ morphological attributes visualization
Authors: Calo Cristina Marilin , Rizzutto Marcia A. , Carmello-Guerreiro Sandra M. , Dias Carlos S. B. , Watling Jennifer , Shock Myrtle P. , Zimpel Carlos A. , Furquim Laura P. , Pugliese Francisco , Neves Eduardo G.
Published: September 2020

In this work, several attributes of the internal morphology of drupaceous fruits found in the archaeological site Monte Castelo (Rondonia, Brazil) are analyzed by means of two different imaging methods. The aim is to explore similarities and differences in the visualization and analytical properties of the images obtained via High Resolution Light Microscopy and X-ray micro-computed tomography (X-ray MicroCT) methods. Both provide data about the three-layered pericarp (exo-, meso- and endocarp) of the studied exemplars, defined by cell differentiation, vascularisation, cellular contents, presence of sclerenchyma cells and secretory cavities. However, it is possible to identify a series of differences between the information that can be obtained through each of the methods. These variations are related to the definition of contours and fine details of some characteristics, their spatial distribution, size attributes, optical properties and material preservation. The results obtained from both imaging methods are complementary, contributing to a more exhaustive morphological study of the plant remains. X-ray MicroCT in phase-contrast mode represents a suitable non-destructive analytic technique when sample preservation is required.
The effects of anxiety and dual-task on upper limb motor control of chronic stroke survivors
Authors: Hejazi-Shirmard Mahnaz , Lajevardi Laleh , Rassafiani Mehdi , Taghizadeh Ghorban
Published: September 2020

This study was designed to investigate the effects of anxiety and dual-task on reach and grasp motor control in chronic stroke survivors compared with age- and sex-matched healthy subjects (HC). Reach and grasp kinematic data of 68 participants (high-anxiety stroke (HA-stroke), n = 17; low-anxiety stroke (LA-stroke), n = 17; low-anxiety HC, n = 17; and high-anxiety HC, n = 17) were recorded under single- and dual-task conditions. Inefficient reach and grasp of stroke participants, especially HA-stroke were found compared with the control groups under single- and dual-task conditions as evidenced by longer movement time (MT), lower and earlier peak velocity (PV) as well as delayed and smaller hand opening. The effects of dual-task on reach and grasp kinematic measures were similar between HCs and stroke participants (i.e., increased MT, decreased PV that occurred earlier, and delayed and decreased hand opening), with greater effect in stroke groups than HCs, and in HA-stroke group than LA-stroke group. The results indicate that performing a well-learned upper limb movement with concurrent cognitive task leads to decreased efficiency of motor control in chronic stroke survivors compared with HCs. HA-stroke participants were more adversely affected by challenging dual-task conditions, underlying importance of assessing anxiety and designing effective interventions for it in chronic stroke survivors.
Theoretical analysis of a circular hybrid plasmonic waveguide to design a hybrid plasmonic nano-antenna
Authors: Khodadadi Maryam , Nozhat Najmeh , Moshiri Seyyed Mohammad Mehdi
Published: September 2020

In this paper, a circular hybrid plasmonic waveguide-fed nano-antenna (CHPWFNA) has been introduced for operating at the standard telecommunication wavelength of 1,550 nm. For the first time, the dispersion relation of a circular hybrid plasmonic waveguide as the feed line of the proposed nano-antenna has been derived, analytically. To verify the accuracy of the analytical solution, two numerical techniques of finite element method (FEM) and finite-difference time-domain (FDTD) method have been used. Numerical results are well-matched with the theoretical ones. The characteristics of the CHPWFNA have been studied by two mentioned methods. The obtained realized gains (directivities) by the FDTD and FEM simulations are 9.03 dB (9.38 dBi) and 10.00 dB (10.32 dBi), respectively, at 1,550 nm wavelength. For on-chip point-to-point wireless link performance, the obtained quality factor by the FDTD method (FEM) is 63.97 (100). The obtained radiation characteristics and link performance reveal that at 1,550 nm, the proposed antenna has the best performance. Besides, the frequency bandwidth of the antenna (185–200 THz) covers the low-loss optical frequency range. Also, paying attention to the laser eye safety is so important. Consequently, the wavelength of 1,550 nm has been chosen as the target wavelength. Moreover, the array configuration has been studied and the directivity and realized gain have been obtained based on the array factor theory and numerical methods, which are agree with each other. The attained realized gain by the FDTD method (FEM) for the considered single row array, at 1,550 nm, is 11.20 dB (11.30 dB). There is a little difference between the numerical results due to the total mesh size, the grid size refinement and the relative error of the numerical methods convergence. Finally, as one of the most important challenges in fabrication is the gold surface quality, we have studied the effect of gold surface roughness and its pentagonal cross section on the antenna performance.
Semaphorin 3A controls enteric neuron connectivity and is inversely associated with synapsin 1 expression in Hirschsprung disease
Authors: Gonzales Jacques , Le Berre-Scoul Catherine , Dariel Anne , Bréhéret Paul , Neunlist Michel , Boudin Hélène
Published: September 2020

Most of the gut functions are controlled by the enteric nervous system (ENS), a complex network of enteric neurons located throughout the wall of the gastrointestinal tract. The formation of ENS connectivity during the perinatal period critically underlies the establishment of gastrointestinal motility, but the factors involved in this maturation process remain poorly characterized. Here, we examined the role of Semaphorin 3A (Sema3A) on ENS maturation and its potential implication in Hirschsprung disease (HSCR), a developmental disorder of the ENS with impaired colonic motility. We found that Sema3A and its receptor Neuropilin 1 (NRP1) are expressed in the rat gut during the early postnatal period. At the cellular level, NRP1 is expressed by enteric neurons, where it is particularly enriched at growth areas of developing axons. Treatment of primary ENS cultures and gut explants with Sema3A restricts axon elongation and synapse formation. Comparison of the ganglionic colon of HSCR patients to the colon of patients with anorectal malformation shows reduced expression of the synaptic molecule synapsin 1 in HSCR, which is inversely correlated with Sema3A expression. Our study identifies Sema3A as a critical regulator of ENS connectivity and provides a link between altered ENS connectivity and HSCR.
Network science characteristics of brain-derived neuronal cultures deciphered from quantitative phase imaging data
Authors: Yin Chenzhong , Xiao Xiongye , Balaban Valeriu , Kandel Mikhail E. , Lee Young Jae , Popescu Gabriel , Bogdan Paul
Published: September 2020

Understanding the mechanisms by which neurons create or suppress connections to enable communication in brain-derived neuronal cultures can inform how learning, cognition and creative behavior emerge. While prior studies have shown that neuronal cultures possess self-organizing criticality properties, we further demonstrate that in vitro brain-derived neuronal cultures exhibit a self-optimization phenomenon. More precisely, we analyze the multiscale neural growth data obtained from label-free quantitative microscopic imaging experiments and reconstruct the in vitro neuronal culture networks (microscale) and neuronal culture cluster networks (mesoscale). We investigate the structure and evolution of neuronal culture networks and neuronal culture cluster networks by estimating the importance of each network node and their information flow. By analyzing the degree-, closeness-, and betweenness-centrality, the node-to-node degree distribution (informing on neuronal interconnection phenomena), the clustering coefficient/transitivity (assessing the “small-world” properties), and the multifractal spectrum, we demonstrate that murine neurons exhibit self-optimizing behavior over time with topological characteristics distinct from existing complex network models. The time-evolving interconnection among murine neurons optimizes the network information flow, network robustness, and self-organization degree. These findings have complex implications for modeling neuronal cultures and potentially on how to design biological inspired artificial intelligence.
Males and females exhibit distinct relationships between intervertebral disc degeneration and pain in a rat model
Authors: Mosley Grace E. , Wang Minghui , Nasser Philip , Lai Alon , Charen Daniel A. , Zhang Bin , Iatridis James C.
Published: September 2020

Back pain is linked to intervertebral disc (IVD) degeneration, but clinical studies show the relationship is complex. This study assessed whether males and females have distinct relationships between IVD degeneration and pain using an in vivo rat model. Forty-eight male and female Sprague–Dawley rats had lumbar IVD puncture or sham surgery. Six weeks after surgery, IVDs were evaluated by radiologic IVD height, histological grading, and biomechanical testing. Pain was assessed by von Frey assay and dorsal root ganglia (DRG) expression ofCalcaandTac1genes. Network analysis visualized which measures of IVD degeneration most related to pain by sex. In both females and males, annular puncture induced structural IVD degeneration, but functional biomechanical properties were similar to sham. Females and males had distinct differences in mechanical allodynia and DRG gene expression, even though sex differences in IVD measurements were limited. Network analysis also differed by sex, with more associations between annular puncture injury and pain in the male network. Sex differences exist in the interactions between IVD degeneration and pain. Limited correlation between measures of pain and IVD degeneration highlights the need to evaluate pain or nociception in IVD degeneration models to better understand nervous system involvement in discogenic pain.
Modeling transport of antibiotic resistant bacteria in aquatic environment using stochastic differential equations
Authors: Gothwal Ritu , Thatikonda Shashidhar
Published: September 2020

Contaminated sites are recognized as the “hotspot” for the development and spread of antibiotic resistance in environmental bacteria. It is very challenging to understand mechanism of development of antibiotic resistance in polluted environment in the presence of different anthropogenic pollutants. Uncertainties in the environmental processes adds complexity to the development of resistance. This study attempts to develop mathematical model by using stochastic partial differential equations for the transport of fluoroquinolone and its resistant bacteria in riverine environment. Poisson’s process is assumed for the diffusion approximation in the stochastic partial differential equations (SPDE). Sensitive analysis is performed to evaluate the parameters and variables for their influence over the model outcome. Based on their sensitivity, the model parameters and variables are chosen and classified into environmental, demographic, and anthropogenic categories to investigate the sources of stochasticity. Stochastic partial differential equations are formulated for the state variables in the model. This SPDE model is then applied to the 100 km stretch of river Musi (South India) and simulations are carried out to assess the impact of stochasticity in model variables on the resistant bacteria population in sediments. By employing the stochasticity in model variables and parameters we came to know that environmental and anthropogenic variations are not able to affect the resistance dynamics at all. Demographic variations are able to affect the distribution of resistant bacteria population uniformly with standard deviation between 0.087 and 0.084, however, is not significant to have any biological relevance to it. The outcome of the present study is helpful in simplifying the model for practical applications. This study is an ongoing effort to improve the model for the transport of antibiotics and transport of antibiotic resistant bacteria in polluted river. There is a wide gap between the knowledge of stochastic resistant bacterial growth dynamics and the knowledge of transport of antibiotic resistance in polluted aquatic environment, this study is one step towards filling up that gap.
Beta oscillations following performance feedback predict subsequent recall of task-relevant information
Authors: HajiHosseini Azadeh , Hutcherson Cendri A. , Holroyd Clay B.
Published: September 2020

Reward delivery in reinforcement learning tasks elicits increased beta power in the human EEG over frontal areas of the scalp but it is unclear whether these 20–30 Hz oscillations directly facilitate reward learning. We previously proposed that frontal beta is not specific to reward processing but rather reflects the role of prefrontal cortex in maintaining and transferring task-related information to other brain areas. To test this proposal, we had subjects perform a reinforcement learning task followed by a memory recall task in which subjects were asked to recall stimuli associated either with reward feedback (Reward Recall condition) or error feedback (Error Recall condition). We trained a classifier on post-feedback beta power in the Reward Recall condition to discriminate trials associated with reward feedback from those associated with error feedback and then tested the classifier on post-feedback beta power in the Error Recall condition. Crucially, the model classified error-related beta in the Error Recall condition as reward-related. The model also predicted stimulus recall from post-feedback beta power irrespective of feedback valence and task condition. These results indicate that post-feedback beta power is not specific to reward processing but rather reflects a more general task-related process.