bluuebunny/crossref_metadata_2025 huggingface dataset:
Kepemimpinan dan Peranan Tokoh Adat dalam Pembangunan di Kabupaten Kampar Provinsi Riau
Authors: Mashuri Mashuri , Putra Afriadi
Published: January 2022

Penelitian ini dilaksanakan di Kabupaten Kampar Provinsi Riau. Permasalahan yang ingin dijawab dalam penelitian ini adalah bagaimana kepemimpinan dan peranan tokoh adat “Ninik Mamak” dalam pembangunan kabupaten Kampar. Penelitian ini membutuhkan data primer dan data sekunder berupa observasi, wawancara, penyebaran kuesioner, dokumen dan data terkait kepemimpinan dan peran Ninik Mamak dalam pembangunan kabupaten Kampar. Adapun hasil kajian yang dilakukan terhadap kepemimpinan dan peranan Ninik Mamak dalam pembangunan kabupaten Kampar adalah,  pertama sebagai tempat bertanya masyarakat dan anak kemenakan; kedua  memberikan dukungan dan informasi tentang program pemerintah. Meskipun dalam prakteknya peranan Ninik Mamak dalam pembangunan daerah terkadang masih kurang, padahal Ninik Mamak mendapatkan insentif rutin dari pemerintah daerah kabupaten Kampar.
KOMUNIKASI PENYADARAN KRITIS : PENDAMPINGAN KOMUNITAS WARGA PERKOTAAN UNTUK PENGOLAHAN SAMPAH
Authors: Sidharta Veranus , Arlena Wenny Maya , Wahyono Eko , Wihard Doddy
Published: January 2022

Masih adanya paradigma masyarakat terhadap sampah yang menganggap sampah merupakan barang tidak berguna dan perlu dibuang menambah jumlah penumpukan sampah semakin meningkat dari waktu ke waktu. Merubah paradigma masyarakat terhadap sampah perlu adanya  edukasi dan pemahaman terkait adanya manfaat yang dihasilkan dari sampah dalam suatu pengelolaan yang baik sehingga dapat tercipta kesadaran kritis serta partisipasi dalam penanganan sampah. Pengelolaan sampah melalui penyadaran kritis masyarakat akan membangun sistem sosial masyarakat terhadap perilaku dan perubahan sosial. Penelitian ini bertujuan memberikan solusi yang dapat menjadi kontribusi dalam strategi pendampingan dalam pengelolaan sampah. Kesimpulannya pengelolaan sampah di perkotaan memerlukan partisipasi yang aktif dari masyarakat. Keaktifan masyarakat ini mampu di dorong oleh aktor lokal yang memiliki keteladanan dan daya juang dalam mengelola sampah.
EFEKTIVITAS MUSIC VIDEO (MV) TERHADAP PENGUBAHAN PERILAKU SISWA PAUD MENGENAI PERILAKU HIDUP BERSIH DAN SEHAT (PHBS)
Authors: Mahdalena Vina , Handayani Lusia
Published: January 2022

Dalam perkembangan kasus Covid-19 di Indonesia, wilayah DKI Jakarta dan Jawa Timur menjadi penyumbang tertinggi yang menjadikan semua area dalam provinsi ini dikategori sebagai zona merah. Bagaimana kemudian memfasilitasi media sosialisasi yang paling efektif untuk meningkatkan pengetahuan siswa mengenai PHBS khususnya cuci tangan pakai sabun? Dalam penelitian ini kami berusaha untuk membuat eksperimen dengan menggunakan dua kelompok, satu kelompok perlakuan dengan music video (MV) dan satu kelompok kontrol dengan poster. Hasil penelitian menunjukkan baik poster dan video musik memiliki efektivitas yang tinggi dalam mengubah perilaku siswa mengenai PHBS mencuci tangan. Hasil uji tes akhir tidak menunjukkan adanya perbedaan yang nyata pada kedua media tersebut walaupun pada video musik memiliki skor yang lebih tinggi daripada media poster. Saran yang dapat diberikan tim peneliti untuk pemerintah dalam memberikan kampanye program gerakan masyarakat adalah memaksimalkan pemanfaatan media baik visual maupun audio visual seperti video musik yang semakin mudah untuk dirancang dan didesain sesuai dengan responden atau target sasaran.
PINK1 Alleviates Cognitive Impairments via Attenuating Pathological Tau Aggregation in a Mouse Model of Tauopathy
Authors: Jiang Xing Jun , Wu Yan Qing , Ma Rong , Chang Yan Min , Li Lu Lu , Zhu Jia Hui , Liu Gong Ping , Li Gang
Published: January 2022

As a primary cause of dementia and death in older people, Alzheimer’s disease (AD) has become a common problem and challenge worldwide. Abnormal accumulation of tau proteins in the brain is a hallmark pathology of AD and is closely related to the clinical progression and severity of cognitive deficits. Here, we found that overexpression of phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) effectively promoted the degradation of tau, thereby rescuing neuron loss, synaptic damage, and cognitive impairments in a mouse model of tauopathy with AAV-full-length human Tau (hTau) injected into the hippocampal CA1 area (hTau mice). Overexpression of PINK1 activated autophagy, and chloroquine but not MG132 reversed the PINK1-induced decrease in human Tau levels and cognitive improvement in hTau mice. Furthermore, PINK1 also ameliorated mitochondrial dysfunction induced by hTau. Taken together, our data revealed that PINK1 overexpression promoted degradation of abnormal accumulated tau via the autophagy–lysosome pathway, indicating that PINK1 may be a potential target for AD treatment.
Natural Killer Cells Regulate Pulmonary Macrophages Polarization in Host Defense Against Chlamydial Respiratory Infection
Authors: Zhao Lei , Li Jing , Zhou Xiaoqing , Pan Qianqian , Zhao Weiming , Yang Xi , Wang Hong
Published: January 2022

NK cells and pulmonary macrophages both are important components of innate immunity. The interaction between NK cells and pulmonary macrophages during chlamydial infection is poorly understood. In this study, we explored the effect of NK cells on regulation of pulmonary macrophage function during chlamydial respiratory infection. We found that NK depletion led to polarization of pulmonary macrophages from M1 to M2 phenotype, and it is related to reduced miR-155 expression in lung macrophage. Using adoptive transfer approach, we found that the recipients receiving lung macrophages isolated fromC. muridarum-infected NK-cell-depleted mice exhibited an increased bacterial load and severe inflammation in the lung upon chlamydial challenge infection when compared with the recipients of lung macrophages from infected isotype control antibody treated mice. Herein, the effects of NK cells on macrophage polarization were examinedin vitro. We found that NK cells from chlamydial-infected mice (iNK) significantly induced M1 polarization compared to that from uninfected mice (uNK). Inhibition of miR-155 expression in macrophages reduced M1 polarization induced by iNK, while miR-155 over-expression enhanced it. Furthermore, neutralization of IFN-γ in the coculture system decreased the expression of miR-155 by macrophages, and resulted in weakened M1 polarization. The data indicates that NK cells promote M1 polarization through up-regulation of miR-155 in macrophages by producing IFN-γ during chlamydial infection, and NK-regulated macrophage polarization is functionally relevant to host defense against the infection.
A Computer-Assisted Writing Tool for an Extended Variety of Leichte Sprache (Easy-to-Read German)
Authors: Harbusch Karin , Steinmetz Ina
Published: January 2022

Leichte Sprache (LS; easy-to-read German) defines a variety of German characterized by simplified syntactic constructions and a small vocabulary. It provides barrier-free information for a wide spectrum of people with cognitive impairments, learning difficulties, and/or a low level of literacy in the German language. The levels of difficulty of a range of syntactic constructions were systematically evaluated with LS readers as part of the recent LeiSA project (Bock, 2019). That study identified a number of constructions that were evaluated as being easy to comprehend but which fell beyond the definition of LS. We therefore want to broaden the scope of LS to include further constructions that LS readers can easily manage and that they might find useful for putting their thoughts into words. For constructions not considered in the LeiSA study, we performed a comparative treebank study of constructions attested to in a collection of 245 LS documents from a variety of sources. Employing the treebanks TüBa-D/S (also called VERBMOBIL) and TüBa-D/Z, we compared the frequency of such constructions in those texts with their incidence in spoken and written German sources produced without the explicit goal of facilitating comprehensibility. The resulting extension is called Extended Leichte Sprache (ELS). To date, text in LS has generally been produced by authors proficient in standard German. In order to enable text production by LS readers themselves, we developed a computational linguistic system, dubbed ExtendedEasyTalk. This system supports LS readers in formulating grammatically correct and semantically coherent texts covering constructions in ELS. This paper outlines the principal components: (1) a natural-language paraphrase generator that supports fast and correct text production while taking readership-design aspects into account, and (2) explicit coherence specifications based on Rhetorical Structure Theory (RST) to express the communicative function of sentences. The system’s writing-workshop mode controls the options in (1) and (2). Mandatory questions generated by the system aim to teach the user when and how to consider audience-design concepts. Accordingly, users are trained in text production in a similar way to elementary school students, who also tend to omit audience-design cues. Importantly, we illustrate in this paper how to make the dialogues of these components intuitive and easy to use to avoid overtaxing the user. We also report the results of our evaluation of the software with different user groups.
Machine Learning for Clinical Decision-Making: Challenges and Opportunities in Cardiovascular Imaging
Authors: Sanchez-Martinez Sergio , Camara Oscar , Piella Gemma , Cikes Maja , González-Ballester Miguel Ángel , Miron Marius , Vellido Alfredo , Gómez Emilia , Fraser Alan G. , Bijnens Bart
Published: January 2022

The use of machine learning (ML) approaches to target clinical problems is called to revolutionize clinical decision-making in cardiology. The success of these tools is dependent on the understanding of the intrinsic processes being used during the conventional pathway by which clinicians make decisions. In a parallelism with this pathway, ML can have an impact at four levels: for data acquisition, predominantly by extracting standardized, high-quality information with the smallest possible learning curve; for feature extraction, by discharging healthcare practitioners from performing tedious measurements on raw data; for interpretation, by digesting complex, heterogeneous data in order to augment the understanding of the patient status; and for decision support, by leveraging the previous steps to predict clinical outcomes, response to treatment or to recommend a specific intervention. This paper discusses the state-of-the-art, as well as the current clinical status and challenges associated with the two later tasks of interpretation and decision support, together with the challenges related to the learning process, the auditability/traceability, the system infrastructure and the integration within clinical processes in cardiovascular imaging.
Multivariate GWAS of Structural Dental Anomalies and Dental Caries in a Multi-Ethnic Cohort
Authors: Alotaibi Rasha N. , Howe Brian J. , Moreno Uribe Lina M. , Valencia Ramirez Consuelo , Restrepo Claudia , Deleyiannis Frederic W. B. , Padilla Carmencita , Orioli Ieda M. , Buxó Carmen J. , Hecht Jacqueline T. , Wehby George L. , Neiswanger Katherine , Murray Jeffrey C. , Shaffer John R. , Weinberg Seth M. , Marazita Mary L.
Published: January 2022

Odontogenesis is a complex process, where disruption can result in dental anomalies and/or increase the risk of developing dental caries. Based on previous studies, certain dental anomalies tend to co-occur in patients, suggesting that these traits may share common genetic and etiological components. The main goal of this study was to implement a multivariate genome wide association study approach to identify genetic variants shared between correlated structural dental anomalies and dental caries. Our cohort (N = 3,579) was derived from the Pittsburgh Orofacial Clefts Study, where multiple dental traits were assessed in both the unaffected relatives of orofacial cleft (OFC) cases (n = 2,187) and unaffected controls (n = 1,392). We identified four multivariate patterns of correlated traits in this data: tooth agenesis, impaction, and rotation (AIR); enamel hypoplasia, displacement, and rotation (HDR); displacement, rotation, and mamelon (DRM); and dental caries, tooth agenesis and enamel hypoplasia (CAH). We analyzed each of these four models using genome-wide multivariate tests of association. No genome-wide statistically significant results were found, but we identified multiple suggestive association signals (P ≤ 10−5) near genes with known biological roles during tooth development, including ADAMTS9 and PRICKLE2 associated with AIR; GLIS3, WDR72, and ROR2 associated with HDR and DRM; ROBO2 associated with DRM; BMP7 associated with HDR; and ROBO1, SMAD2, and MSX2 associated with CAH. This is the first study to investigative genetic associations for multivariate patterns of correlated dental anomalies and dental caries. Further studies are needed to replicate these results in independent cohorts.
Glucocorticoid Receptor Antagonism Upregulates Somatostatin Receptor Subtype 2 Expression in ACTH-Producing Neuroendocrine Tumors: New Insight Based on the Selective Glucocorticoid Receptor Modulator Relacorilant
Authors: Pivonello Rosario , Munster Pamela N. , Terzolo Massimo , Ferrigno Rosario , Simeoli Chiara , Puglisi Soraya , Bali Utsav , Moraitis Andreas G.
Published: January 2022

Somatostatin exhibits an inhibitory effect on pituitary hormone secretion, including inhibition of growth hormone and adrenocorticotropic hormone (ACTH), and it can have antisecretory and antitumor effects on neuroendocrine tumors (NETs) that express somatostatin receptors. Although the precise mechanism remains unclear, the finding that glucocorticoids downregulate somatostatin receptor subtype 2 (SSTR2) expression has been used to explain the lack of efficacy of traditional SSTR2-targeting analogs in patients with ACTH-secreting NETs. Glucocorticoid receptor (GR) antagonism with mifepristone has been shown to reverse the glucocorticoid-induced downregulation of SSTR2; however, the effects of GR modulation on SSTR2 expression in ACTH-secreting NETs, particularly corticotroph pituitary tumors, are not well known. The current study presents new insight from in vitro data using the highly selective GR modulator relacorilant, showing that GR modulation can overcome dexamethasone-induced suppression of SSTR2 in the murine At-T20 cell line. Additional data presented from clinical case observations in patients with ACTH-secreting NETs suggest that upregulation of SSTR2 via GR modulation may re-sensitize tumors to endogenous somatostatin and/or somatostatin analogs. Clinical, laboratory, and imaging findings from 4 patients [2 ACTH-secreting bronchial tumors and 2 ACTH-secreting pituitary tumors (Cushing disease)] who were treated with relacorilant as part of two clinical studies (NCT02804750 and NCT02762981) are described. In the patients with ectopic ACTH secretion, SSTR2-based imaging (Octreoscan and 68Ga-DOTATATE positron emission tomography) performed before and after treatment with relacorilant showed increased radiotracer uptake by the tumor following treatment with relacorilant without change in tumor size at computed tomography. In the patients with Cushing disease who received relacorilant prior to scheduled pituitary surgery, magnetic resonance imaging after a 3-month course of relacorilant showed a reduction in tumor size. Based on these findings, we propose that GR modulation in patients with ACTH-secreting NETs upregulates previously suppressed SSTR2s, resulting in tumor-specific antisecretory and anti-proliferative effects. The effect of relacorilant on pituitary corticotroph tumors is being investigated in an ongoing phase 3 study (NCT03697109; EudraCT 2018-003096-35).
Sperm Storage Costs Determine Survival and Immunocompetence in Newly Mated Queens of the Leaf-Cutting Ant Atta colombica
Authors: Baer-Imhoof Barbara , den Boer Susanne P. A. , Boomsma Jacobus J. , Baer Boris
Published: January 2022

In the leaf-cutting ant Atta colombica, queens receive ejaculates from multiple males during one single mating event early in their lives. A queen’s fertility and fitness therefore depend on maximizing the number of sperm cells she can store and maintain inside her spermatheca. Previous studies implied significant physiological mating costs, either originating from energetic investments maximizing sperm survival, or from resolving sexual conflicts to terminate male-driven incapacitation of rival sperm via serine proteases found in seminal fluid. Here we conducted an artificial insemination experiment, which allowed us to distinguish between the effects of sperm and seminal fluid within the queen’s sexual tract on her survival and immunocompetence. We found significantly higher mortality in queens that we had inseminated with sperm, independently of whether seminal fluid was present or not. Additionally, after receiving sperm, heavier queens had a higher probability of survival compared to lightweight queens, and immunocompetence decreased disproportionally for queens that had lost weight during the experiment. These findings indicate that queens pay significant physiological costs for maintaining and storing sperm shortly after mating. On the other hand, the presence of seminal fluid within the queens’ sexual tract neither affected their survival nor their immunocompetence. This suggests that the energetic costs that queens incur shortly after mating are primarily due to investments in sperm maintenance and not costs of terminating conflicts between competing ejaculates. This outcome is consistent with the idea that sexually selected traits in social insects with permanent castes can evolve only when they do not affect survival or life-time fitness of queens in any significant way.
Welcome to the Dark Side: Partial Nighttime Illumination Affects Night-and Daytime Foraging Behavior of a Small Mammal
Authors: Hoffmann Julia , Hölker Franz , Eccard Jana A.
Published: January 2022

Differences in natural light conditions caused by changes in moonlight are known to affect perceived predation risk in many nocturnal prey species. As artificial light at night (ALAN) is steadily increasing in space and intensity, it has the potential to change movement and foraging behavior of many species as it might increase perceived predation risk and mask natural light cycles. We investigated if partial nighttime illumination leads to changes in foraging behavior during the night and the subsequent day in a small mammal and whether these changes are related to animal personalities. We subjected bank voles to partial nighttime illumination in a foraging landscape under laboratory conditions and in large grassland enclosures under near natural conditions. We measured giving-up density of food in illuminated and dark artificial seed patches and video recorded the movement of animals. While animals reduced number of visits to illuminated seed patches at night, they increased visits to these patches at the following day compared to dark seed patches. Overall, bold individuals had lower giving-up densities than shy individuals but this difference increased at day in formerly illuminated seed patches. Small mammals thus showed carry-over effects on daytime foraging behavior due to ALAN, i.e., nocturnal illumination has the potential to affect intra- and interspecific interactions during both night and day with possible changes in personality structure within populations and altered predator-prey dynamics.
Promotor Hypomethylation Mediated Upregulation of miR-23b-3p Targets PTEN to Promote Bronchial Epithelial-Mesenchymal Transition in Chronic Asthma
Authors: Guo Yimin , Yuan Xiaoqing , Hong Luna , Wang Qiujie , Liu Shanying , Li Zhaolin , Huang Linjie , Jiang Shanping , Shi Jianting
Published: January 2022

Chronic asthma is characterized by airway inflammation and irreversible airway remodeling. Epithelial-mesenchymal transition (EMT) is a typical pathological change of airway remodeling. Our previous research demonstrated miR-23b inhibited airway smooth muscle proliferation while the function of miR-23b-3p has not been reported yet. Besides, miRNA is regulated by many factors, including DNA methylation. The function of miR-23b-3p and whether it is regulated by DNA methylation are worth exploring. Balb/c mice were given OVA sensitization to develop the asthmatic model. Expression of miR-23b-3p and EMT markers were measured by RT-qPCR, WB and immunohistochemistry (IHC). DNA methylation was detected by methylation-specific PCR (MSP) and the MassARRAY System. Asthmatic mice and TGF-β1-stimulated bronchial epithelial cells (BEAS-2B) showed EMT with increased miR-23b-3p. Overexpression of miR-23b-3p promoted EMT and migration, while inhibition of miR-23b-3p reversed these transitions. DNA methyltransferases were decreased in asthmatic mice. MSP and MassARRAY System detected the promotor of miR-23b showed DNA hypomethylation. DNA methyltransferase inhibitor 5’-AZA-CdZ increased the expression of miR-23b-3p. Meanwhile, PTEN was identified as a target gene of miR-23b-3p. Our results indicated that promotor hypomethylation mediated upregulation of miR-23b-3p targets PTEN to promote EMT in chronic asthma. miR-23b-3p and DNA methylation might be potential therapeutic targets for irreversible airway remodeling.
The GT1-TPS Structural Domain Protein From Haemonchus contortus Could Be Suppressive Antigen of Goat PBMCs
Authors: Wen Zhaohai , Aleem Muhammad Tahir , Aimulajiang Kalibixiati , Chen Cheng , Liang Meng , Song Xiaokai , Xu Lixin , Li Xiangrui , Yan Ruofeng
Published: January 2022

Trehalose phosphate synthase (TPS), a key enzyme in trehalose synthesis, is not present in mammals but critical to the viability of a wide range of lower organisms. However, almost nothing is known about the function of Hc-TPS (GT1-TPS structural domain protein from Haemonchus contortus). In this study, Hc-TPS gene was cloned and the recombinant protein (rHc-TPS) was expressed and purified. The quantitative real-time PCR (qPCR) results showed that Hc-TPS was transcribed at different stages of H. contortus, with higher levels of transcription at the molting and embryo stages. Immunofluorescence analysis showed that Hc-TPS was widely distributed in adults, but the expression was mainly localized on the mucosal surface of the intestine as well as in the embryos of female worms. The impacts of rHc-TPS on peripheral blood mononuclear cell (PBMC) proliferation, nitric oxide (NO) generation, transcriptional expression of cytokines, and related pathways were examined by co-incubating rHc-TPS with goat PBMCs. The results showed that rHc-TPS significantly inhibited PBMC proliferation and NO secretion in a dose-dependent manner. We also found that rHc-TPS activated the interleukin (IL)-10/signal transducer and activator of transcription 3/suppressor of cytokine signaling 3 (IL-10/STAT3/SOCS3) axis and significantly promoted SOCS3 expression, while inhibiting interferon-gamma (INF-γ), IL-4, IL-9, and IL-2 pathways. Our findings may contribute to understanding the immune evasion mechanism for the parasite during host–parasite interactions and also help to provide ideas for discovering new drug targets.
Modulation of Host Immune Response during Leishmania infantum Natural Infection: A Whole-Transcriptome Analysis of the Popliteal Lymph Nodes in Dogs
Authors: Sanz Carolina R. , Miró Guadalupe , Sevane Natalia , Reyes-Palomares Armando , Dunner Susana
Published: January 2022

Leishmania infantum, the etiological agent of canine leishmaniosis (CanL) in Europe, was responsible of the largest outbreak of human leishmaniosis in Spain. The parasite infects and survives within myeloid lineage cells, causing a potentially fatal disease if left untreated. The only treatment option relies on chemotherapy, although immunotherapy strategies are being considered as novel approaches to prevent progression of the disease. To this aim, a deeper characterization of the molecular mechanisms behind the immunopathogenesis of leishmaniosis is necessary. Thus, we evaluated, for the first time, the host immune response during L. infantum infection through transcriptome sequencing of the popliteal lymph nodes aspirates of dogs with CanL. Differential expression and weighted gene co-expression network analyses were performed, resulting in the identification of 5,461 differentially expressed genes (DEGs) and four key modules in sick dogs, compared to controls. As expected, defense response was the highest enriched biological process in the DEGs, with six genes related to immune response against pathogens (CHI3L1, SLPI, ACOD1, CCL5, MPO, BPI) included among the ten most expressed genes; and two of the key co-expression modules were associated with regulation of immune response, which also positively correlated with clinical stage and blood monocyte concentration. In particular, sick dogs displayed significant changes in the expression of Th1, Th2, Th17 and Tr1 cytokines (e. g. TNF-α, IFN-γ, IL-21, IL-17, IL-15), markers of T cell and NK cell exhaustion (e. g. LAG3, CD244, Blimp-1, JUN), and B cell, monocyte and macrophage disrupted functionality (e. g. CD40LG, MAPK4, IL-1R, NLRP3, BCMA). In addition, we found an overexpression of XBP1 and some other genes involved in endoplasmic reticulum stress and the IRE1 branch of the unfolded protein response, as well as one co-expression module associated with these processes, which could be induced by L. infantum to prevent host cell apoptosis and modulate inflammation-induced lymphangiogenesis at lymph nodes. Moreover, 21 lncRNAs were differentially expressed in sick dogs, and one key co-expression module was associated with chromatin organization, suggesting that epigenetic mechanisms could also contribute to dampening host immune response during natural L. infantum infection in the lymph nodes of dogs suffering from clinical leishmaniosis.
The Structure and Immune Regulatory Implications of the Ubiquitin-Like Tandem Domain Within an Avian 2’-5’ Oligoadenylate Synthetase-Like Protein
Authors: Shepard Justin D. , Freitas Brendan T. , Rodriguez Sergio E. , Scholte Florine E. M. , Baker Kailee , Hutchison Madelyn R. , Longo Jaron E. , Miller Holden C. , O’Boyle Brady M. , Tandon Aarushi , Zhao Peng , Grimsey Neil J. , Wells Lance , Bergeron Éric , Pegan Scott D.
Published: January 2022

Post-translational modification of host and viral proteins by ubiquitin and ubiquitin-like proteins plays a key role in a host’s ability to mount an effective immune response. Avian species lack a ubiquitin-like protein found in mammals and other non-avian reptiles; interferon stimulated gene product 15 (ISG15). ISG15 serves as a messenger molecule and can be conjugated to both host and viral proteins leading them to be stabilized, degraded, or sequestered. Structurally, ISG15 is comprised of a tandem ubiquitin-like domain (Ubl), which serves as the motif for post-translational modification. The 2’-5’ oligoadenylate synthetase-like proteins (OASL) also encode two Ubl domains in series near its C-terminus which binds OASL to retinoic acid inducible gene-I (RIG-I). This protein-protein interaction increases the sensitivity of RIG-I and results in an enhanced production of type 1 interferons and a robust immune response. Unlike human and other mammalian OASL homologues, avian OASLs terminate their tandem Ubl domains with the same LRLRGG motif found in ubiquitin and ISG15, a motif required for their conjugation to proteins. Chickens, however, lack RIG-I, raising the question of structural and functional characteristics of chicken OASL (chOASL). By investigating chOASL, the evolutionary history of viruses with deubiquitinases can be explored and drivers of species specificity for these viruses may be uncovered. Here we show that the chOASL tandem Ubl domains shares structural characteristics with mammalian ISG15, and that chOASL can oligomerize and conjugate to itself. In addition, the ISG15-like features of avian OASLs and how they impact interactions with viral deubiquitinases and deISGylases are explored.
Dysregulated TP53 Among PTSD Patients Leads to Downregulation of miRNA let-7a and Promotes an Inflammatory Th17 Phenotype
Authors: Busbee Philip B. , Bam Marpe , Yang Xiaoming , Abdulla Osama A. , Zhou Juhua , Ginsberg Jay Paul (Jack) , Aiello Allison E. , Uddin Monica , Nagarkatti Mitzi , Nagarkatti Prakash S.
Published: January 2022

Post-traumatic stress disorder (PTSD) is a psychiatric disorder and patients diagnosed with PTSD often express other comorbid health issues, particularly autoimmune and inflammatory disorders. Our previous reports investigating peripheral blood mononuclear cells (PBMCs) from PTSD patients showed that these patients exhibit an increased inflammatory T helper (Th) cell phenotype and widespread downregulation of microRNAs (miRNAs), key molecules involved in post-transcriptional gene regulation. A combination of analyzing prior datasets on gene and miRNA expression of PBMCs from PTSD and Control samples, as well as experiments using primary PBMCs collected from human PTSD and Controls blood, was used to evaluate TP53 expression, DNA methylation, and miRNA modulation on Th17 development. In the current report, we note several downregulated miRNAs were linked to tumor protein 53 (TP53), also known as p53. Expression data from PBMCs revealed that compared to Controls, PTSD patients exhibited decreased TP53 which correlated with an increased inflammatory Th17 phenotype. Decreased expression of TP53 in the PTSD population was shown to be associated with an increase in DNA methylation in the TP53 promotor region. Lastly, the most significantly downregulated TP53-associated miRNA, let-7a, was shown to negatively regulate Th17 T cells. Let-7a modulation in activated CD4+ T cells was shown to influence Th17 development and function, via alterations in IL-6 and IL-17 production, respectively. Collectively, these studies reveal that PTSD patients could be susceptible to inflammation by epigenetic dysregulation of TP53, which alters the miRNA profile to favor a proinflammatory Th17 phenotype.
Cladobranchia (Gastropoda, Nudibranchia) as a Promising Model to Understand the Molecular Evolution of Photosymbiosis in Animals
Authors: Rola Marcellina , Frankenbach Silja , Bleidissel Sabrina , Sickinger Corinna , Donath Alexander , Frommlet Jörg C. , Greve Carola , Serôdio João , Preisfeld Angelika , Melo Clavijo Jenny , Christa Gregor
Published: January 2022

Symbiosis with photoautotrophic organisms has evolved in various species and even whole animal lineages, which allowed them to directly benefit from photosynthesis. This so-called photosymbiosis is best studied in cnidarians, which primarily establish symbioses with dinoflagellates from the family Symbiodiniaceae. In most other animals the mechanisms of establishing photosymbiosis, the physiological basis, and the evolution of a photosymbiotic life history remain poorly understood. Sea slugs belonging to the Cladobranchia (Gastropoda, Nudibranchia) are no exception, and are a rather neglected animal lineage in the research field of photosymbiosis. Yet, studying these sea slugs holds great potential to establish a unique photosymbiosis model, as they are the only known taxon that has evolved two different strategies to acquire their symbiont: either from cnidarian prey (thus becoming a secondary host) or directly out of the water column. The mechanisms for photobiont uptake and maintenance are unknown for these sea slugs, but might be similar to those of cnidarians. However, in terms of the evolution of photosymbiosis, Cladobranchia seem to share many commonalities with more closely related sea slugs belonging to the Sacoglossa, which only maintain the chloroplasts of the algae they feed on. Hence, Cladobranchia have the potential to shed light on the evolution of photosymbiosis in taxonomically divergent animals that also harbor photobionts of different evolutionary lineages.
Inter-Nesting Movements, Migratory Pathways, and Resident Foraging Areas of Green Sea Turtles (Chelonia mydas) Satellite-Tagged in Southwest Florida
Authors: Sloan Kelly A. , Addison David S. , Glinsky Andrew T. , Benscoter Allison M. , Hart Kristen M.
Published: January 2022

Globally, sea turtle research and conservation efforts are underway to identify important high-use areas where these imperiled individuals may be resident for weeks to months to years. In the southeastern Gulf of Mexico, recent telemetry studies highlighted post-nesting foraging sites for federally endangered green turtles (Chelonia mydas) around the Florida Keys. In order to delineate additional areas that may serve as inter-nesting, migratory, and foraging hotspots for reproductively active females nesting in peninsular southwest Florida, we satellite-tagged 14 green turtles that nested at two sites along the southeast Gulf of Mexico coastline between 2017 and 2019: Sanibel and Keewaydin Islands. Prior to this study, green turtles nesting in southwest Florida had not previously been tracked and their movements were unknown. We used switching state space modeling to show that an area off Cape Sable (Everglades), Florida Bay, and the Marquesas Keys are important foraging areas that support individuals that nest on southwest Florida mainland beaches. Turtles were tracked for 39–383 days, migrated for a mean of 4 days, and arrived at their respective foraging grounds in the months of July through September. Turtles remained resident in their respective foraging sites until tags failed, typically after several months, where they established mean home ranges (50% kernel density estimate) of 296 km2. Centroid locations for turtles at common foraging sites were 1.2–36.5 km apart. The area off southwest Florida Everglades appears to be a hotspot for these turtles during both inter-nesting and foraging; this location was also used by turtles that were previously satellite tagged in the Dry Tortugas after nesting. Further evaluation of this important habitat is warranted. Understanding where and when imperiled yet recovering green turtles forage and remain resident is key information for designing surveys of foraging resources and developing additional protection strategies intended to enhance population recovery trajectories.
Different Fish Meal and Fish Oil Dietary Levels in European Sea Bass: Welfare Implications After Acute Confinement Stress
Authors: Pelusio Nicole Francesca , Bonaldo Alessio , Gisbert Enric , Andree Karl B. , Esteban Maria Angeles , Dondi Francesco , Sabetti Maria Chiara , Gatta Pier Paolo , Parma Luca
Published: January 2022

To provide practical feeding management guidelines preceding a stressful episode during farming practices, European sea bass juveniles (initial weight: 72.3 g) were fed for 60-days different fish meal (FM) and fish oil (FO) dietary levels [high (30% FM, 15% FO, FM30/FO15), intermediate (20% FM, 7% FO, FM20/FO7), and low (10% FM, 3% FO, FM10/FO3)] in triplicate conditions. Fish were then fasted for 36 h and exposed to a 2-h acute crowding (80 kg m–3 biomass). Plasma biochemistry, skin mucus parameters and gene expression of stress and immune-related genes were performed before, at 2 and 24 h after crowding. At the end of the trial, the FM10/FO3 group showed lower final body weight, weight gain, and specific growth rate compared to the other treatments. Most of the plasma parameters were mainly affected by crowding condition rather than diet; however, after stress, lactate was higher in the FM30/FO15 group compared to the other treatments. Similarly, protease, antiprotease, peroxidase and lysozyme in skin mucus were mostly affected by crowding conditions, while fish fed FM10/FO3 displayed higher skin mucosal IgM and bactericidal activity against Vibrio anguillarum and V. harveyi. Most of the stress-related genes considered (hsp70 and gr-1 in the brain; hsp70, gr-1 and gr-2 in the head kidney), showed an overall expression pattern that increased over time after stress, in addition, hsp70 in the head kidney was also up-regulated in fish fed FM30/FO15 after stress. Higher plasmatic lactate together with the up-regulation of some stress-related transcripts suggest a higher reactivity to acute crowding of the stress-response mechanism in fish fed high FM and FO dietary levels. Otherwise, the higher skin mucosal IgM and bactericidal activity observed in fish fed FM10/FO3 dietary levels seems to indicate that acute crowding was able to activate a higher pro-inflammatory response in this treatment. Overall, the results of the present study seem to indicate that 10% FM and 3% FO dietary levels might affect stress and immune responses.
Ionic Liquid Additives in Water-Based Lubricants for Bearing Steel – Effect of Electrical Conductivity and pH on Surface Chemistry, Friction and Wear
Authors: Wijanarko W. , Khanmohammadi H. , Espallargas N.
Published: January 2022

Water-based lubricants have the potential to become the largest environmentally friendly lubricants in applications such as electric vehicles and the newly emerging green technologies of the future due to their inherent low viscosity and cooling properties. In order to be environmentally acceptable (EAL), both base lubricants and additives should comply with biodegradability, non-toxicity, and non-bioaccumulation requirements. Additives for water-based lubricants should ideally be polar and soluble in water and, at the same time, should not increase the electrical conductivity to critical levels for corrosion. However, most additives used in synthetic or mineral oils are non-polar. Ionic liquids have recently gained attention as lubricant additives due to their high polarity, making them highly surface-active (i.e. high tendency to adsorb on metal surfaces). However, they are seen as highly corrosive for many metal alloys. In this work, a water-glycol lubricant containing two different ionic liquids has been investigated as a potential green lubricant for a bearing steel AISI 52100 with accurate control on electrical conductivity and pH. The selected ionic liquids were tributylmethylphosphonium dimethylphosphate (PP) and 1-butyl-1-methylpyrrolidinium tris(pentafluoroethyl)trifluorophosphate (BMP). The tribological behaviour of the ionic liquids was compared with a well-known organic friction modifier, dodecanoic acid (C12). The ionic liquids showed lower friction and wear rate than the water-based lubricant alone. However, they showed higher friction than the lubricant formulated with C12, in which PP gave lower friction than BMP due to low pH. A detailed subsurface analysis of the wear track using scanning-transmission electron microscopy (STEM) showed that a thick oxide tribofilm was built on the wear track for both lubricants formulated with ionic liquids due to high electrical conductivity. This tribofilm gave beneficial effect on wear. Although PP and BMP gave thicker tribofilms than C12, it was not durable, resulting in cracking and detachment.
Functional Investigation of Plant Growth Promoting Rhizobacterial Communities in Sugarcane
Authors: Li Mingjia , Liu Ran , Li Yanjun , Wang Cunhu , Ma Wenjing , Zheng Lei , Zhang Kefei , Fu Xing , Li Xinxin , Su Yachun , Huang Guoqiang , Zhong Yongjia , Liao Hong
Published: January 2022

Plant microbiota are of great importance for host nutrition and health. As a C4 plant species with a high carbon fixation capacity, sugarcane also associates with beneficial microbes, though mechanisms underlying sugarcane root-associated community development remain unclear. Here, we identify microbes that are specifically enriched around sugarcane roots and report results of functional testing of potentially beneficial microbes propagating with sugarcane plants. First, we analyzed recruitment of microbes through analysis of 16S rDNA enrichment in greenhouse cultured sugarcane seedlings growing in field soil. Then, plant-associated microbes were isolated and assayed for beneficial activity, first in greenhouse experiments, followed by field trials for selected microbial strains. The promising beneficial microbe SRB-109, which quickly colonized both roots and shoots of sugarcane plants, significantly promoted sugarcane growth in field trials, nitrogen and potassium acquisition increasing by 35.68 and 28.35%, respectively. Taken together, this report demonstrates successful identification and utilization of beneficial plant-associated microbes in sugarcane production. Further development might facilitate incorporation of such growth-promoting microbial applications in large-scale sugarcane production, which may not only increase yields but also reduce fertilizer costs and runoff.
Transcriptomic Analysis Reveals Competitive Growth Advantage of Non-pigmented Serratia marcescens Mutants
Authors: Xiang Tingting , Zhou Wei , Xu Cailing , Xu Jing , Liu Rui , Wang Nuo , Xu Liang , Zhao Yu , Luo Minhui , Mo Xiaoxin , Mao Zeyang , Wan Yongji
Published: January 2022

Serratia marcescens is a common bacterium well-known for the red secondary metabolite prodigiosin. However, color mutants have long been described. Non-pigmented strains can be found to exist both naturally and under laboratory conditions. It is unclear why S. marcescens loses prodigiosin synthesis capacity in certain conditions. In the present study, we find that the spontaneous color mutants arise within a few generations (about five passages) and rapidly replace the wild-type parent cells (about 24 passages), which indicates a growth advantage of the former. Although, the loss of prodigiosin synthesis genes (pigA-N) is frequently reported as the major reason for pigment deficiency, it was unexpected that the whole gene cluster is completely preserved in the different color morphotypes. Comparative transcriptomic analysis indicates a dramatic variation at the transcriptional level. Most of the pig genes are significantly downregulated in the color morphotypes which directly lead to prodigiosin dyssynthesis. Besides, the transcriptional changes of several other genes have been noticed, of which transcriptional regulators, membrane proteins, and nearly all type VI secretion system (T6SS) components are generally downregulated, while both amino acid metabolite and transport systems are activated. In addition, we delete the transcription regulator slyA to generate a non-pigmented mutant. The ΔslyA strain loses prodigiosin synthesis capacity, but has a higher cell density, and surprisingly enhances the virulence as an entomopathogen. These data indicate that S. marcescens shuts down several high-cost systems and activates the amino acid degradation and transport pathways at the transcriptional level to obtain extra resources, which provides new insights into the competitive growth advantage of bacterial spontaneous color mutants.
Phenotypic and Transcriptomic Analyses Reveal the Cell Membrane Damage of Pseudomonas fragi Induced by Cinnamic Acid
Authors: Zhang Yuxiang , Wei Jianping , Guo Hong , Niu Chen , Yuan Yahong , Yue Tianli
Published: January 2022

Cinnamic acid (CA) is a safe and effective antimicrobial agent. The objective of this study was to reveal the antibacterial mechanism of CA against a food-derived Pseudomonas fragi 38-8, from the aspects of bacterial growth kinetics, cell membrane homeostasis, cell microstructure, and transcription. The minimum inhibitory concentration (MIC) of CA against P. fragi 38-8 was 0.25 mg/ml. CA retarded bacterial growth and induced a series of cell membrane changes. After CA treatment, cell membrane homeostasis was destroyed, which was evidenced by cell membrane depolarization, intracellular pH reduction, and intracellular ATPase activity decrease. Field emission scanning electron microscope (FESEM), transmission electron microscope (TEM), and confocal laser scanning fluorescence microscope (CLSM) realized the visualization of cell microstructure changes, showing cell death and morphological changes, such as cell rupture, shrinkage, and hollowness. RNA sequencing analysis further confirmed the effects of CA to the cell membrane, because of the significant enrichment of differentially expressed genes (DEGs) related to membrane. The results of the phenotype tests and RNA-seq both focused on cell membrane damage, which showed that CA exerted antibacterial effect mainly by acting on cell membrane.
Hypermethylated PCDHGB7 as a Biomarker for Early Detection of Endometrial Cancer in Endometrial Brush Samples and Cervical Scrapings
Authors: Yuan Jiangjing , Mao Zhanrui , Lu Qi , Xu Peng , Wang Chengyang , Xu Xiaona , Zhou Zhaowei , Zhang Tongsheng , Yu Wenqiang , Dong Shihua , Wang Yudong , Cheng Weiwei
Published: January 2022

Endometrial cancer (EC) is one of the most common gynecologic cancers in developed countries. Presently, it is imperative to develop a reliable, noninvasive, or minimally invasive detection method for EC. We explored the possibility of using DNA methylation marker from endometrial brush samples (with a “Tao brush”) and cervical scrapes (with a “Pap brush”) for early detection of EC. We analyzed the methylation data of EC and normal endometrial tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. An optimized methylation-sensitive restriction enzyme combined with real-time fluorescent quantitative PCR (MSRE-qPCR) was used for methylation detection. Included in the training set were 143 endometrial tissues, 103 Tao, and 109 Pap brush samples. The validation set included 110 Tao and 112 Pap brush samples.PCDHGB7was significantly hypermethylated in EC compared with normal endometrial tissues in the TCGA and GEO data sets (AUC >0.95), which was verified in clinical samples. In the Pap brush samples, the AUC was 0.86 with 80.65% sensitivity and 82.81% specificity, whereas the Tao brush samples exhibited higher specificity (95.31%). The combination of Tao and Pap brush samples significantly increased the sensitivity to 90.32%. In the validation set, the final model yielded a sensitivity of 98.61%, specificity of 60.53%, positive predictive value of 82.56%, and negative predictive value of 95.83%. These results demonstrate the potential application of the novel methylation marker, hypermethylatedPCDHGB7, in cervical scrapings and endometrial brush, which provides a viable, noninvasive, or minimally invasive method for early endometrial cancer detection across different clinical features and histologies to supplement current hysteroscopy diagnosis.
Electrophysiological Signatures of Numerosity Encoding in a Delayed Match-to-Sample Task
Authors: Fu Wanlu , Dolfi Serena , Decarli Gisella , Spironelli Chiara , Zorzi Marco
Published: January 2022

The number of elements in a small set of items is appraised in a fast and exact manner, a phenomenon called subitizing. In contrast, humans provide imprecise responses when comparing larger numerosities, with decreasing precision as the number of elements increases. Estimation is thought to rely on a dedicated system for the approximate representation of numerosity. While previous behavioral and neuroimaging studies associate subitizing to a domain-general system related to object tracking and identification, the nature of small numerosity processing is still debated. We investigated the neural processing of numerosity across subitizing and estimation ranges by examining electrophysiological activity during the memory retention period in a delayed numerical match-to-sample task. We also assessed potential differences in the neural signature of numerical magnitude in a fully non-symbolic or cross-format comparison. In line with behavioral performance, we observed modulation of parietal-occipital neural activity as a function of numerosity that differed in two ranges, with distinctive neural signatures of small numerosities showing clear similarities with those observed in visuospatial working memory tasks. We also found differences in neural activity related to numerical information in anticipation of single vs. cross-format comparison, suggesting a top-down modulation of numerical processing. Finally, behavioral results revealed enhanced performance in the mixed-format conditions and a significant correlation between task performance and symbolic mathematical skills. Overall, we provide evidence for distinct mechanisms related to small and large numerosity and differences in numerical encoding based on task demands.