bluuebunny/crossref_metadata_2025 huggingface dataset:
Langbiangia, a new genus of Gesneriaceae endemic to Langbiang Plateau, southern Vietnam and a taxonomic endeavor to achieve key targets of the post-2020 global biodiversity framework
Authors: Luu Hong Truong , Hsieh Chia-Lun , Chuang Chia-Rong , Chen Cheng-Wei , Tran Ngoc Toan , Vu Ngoc Long , Chung Kuo-Fang
Published: May 2023

Situated in the southern end of the Annamite Mountain Range, Langbiang Plateau is a major biodiversity hotspot of southern Vietnam known for high species diversity and endemicity. To achieve effective conservation, parts of the plateau were designated as the Langbiang Biosphere Reserve, an UNESCO World Network aiming to improve relationships between inhabitants and their environments. Amongst the rich endemic flora of the plateau are three gesneriads ascribed to Primulina, a calciphilous genus with high species diversity in the vast limestone karsts stretching from southern China to northern Vietnam. However, a recent phylogenetic study questioned the generic placement of the Langbiang Primulina, corroborating with observations on the geographical distribution, habitat preference, and phyllotaxy of the three species. Based on phylogenetic analyses of nuclear ITS and plastid trnL-F DNA sequences of a comprehensive sampling covering nearly all genera of the Old World Gesneriaceae, we demonstrate that the three Langbiang Primulina species form a fully supported clade distantly related to other Primulina. As this clade is biogeographically, ecologically, morphologically, and phylogenetically distinct worthy of generic recognition, we propose to name it Langbiangia gen. nov. to highlight the rich and unique biodiversity of the Langbiang Plateau. By means of this taxonomic endeavor, we are hoping to raise the conservation awareness of this biodiversity heritage of southern Vietnam and promote the importance of Langbiang Biosphere Reserve that is crucial for achieving action-oriented global targets of the post-2020 global biodiversity framework (GBF) of the UN Convention on Biological Diversity (CBD)—effective conservation and management of at least 30% of biodiverse terrestrial, inland water, and costal and marine areas by 2030—that has been agreed at the COP15 in Montréal in December 2022.
Digital transformation, industrial structure change, and economic growth motivation: An empirical analysis based on manufacturing industry in Yangtze River Delta
Authors: Zheng Xuefeng , Zhang Xiufan , Fan Decheng
Published: May 2023

China is in a critical stage of economic growth mode transformation. The digital transformation of the manufacturing industry may create new impetus and new models for economic growth. Taking the manufacturing industry of 25 prefecture-level cities in the Yangtze River Delta region as the research object, we explore the digital transformation process of the manufacturing industry and verifies its theoretical mechanism of promoting economic growth through the industrial structure. A panel model based on the improved Feder two-sector model and a multiple mediating effect model are established to explore the dynamic mechanism of manufacturing digital transformation to promote economic growth through industrial restructuring. The results show that the digital transformation of the manufacturing industry in the Yangtze River Delta region of China is relatively high, and the speed of digital transformation has been accelerating in recent years. The digital transformation of the manufacturing industry can promote the change in industrial structure and form a new driving force for economic growth. The key is to improve the level of industrial structure and extend the length of the industrial chain. Based on these, we propose measures to promote the transformation and upgrading of industrial structure for the sustainable development of China’s economy.
Analysis of the interval between submission and publication in genetics journals
Authors: Zimmer Rafael Leal , Mancuso Aline Castello Branco , Matte Ursula , Ashton-Prolla Patricia
Published: May 2023

One of the main factors that attracts authors to choose a journal is the time interval between submission and publication, which varies between journals and subject matter. Here, we evaluated the time intervals between submission and publication according to journal impact factor and continent of author’s affiliation, considering articles with authors from single or multiple continents. Altogether, 72 journals indexed in the Web of Science database within the subject matter “Genetics and Heredity”, divided by impact factor into four quartiles and randomly selected were analyzed for time intervals from article submission to publication. Data from a total of 46,349 articles published from 2016 to 2020 were collected and analyzed considering the following time intervals: submission to acceptance (SA), acceptance to publication (AP) and submission to publication (SP). The median of the quartiles for the SP interval was 166 (IQR [118–225]) days for Q1, 147 (IQR [103–206]) days for Q2, 161 (IQR [116–226]) days for Q3 and 137 (IQR [69–264]) days for Q4, showing a significant difference among quartiles (p < 0.001). In Q4, median interval of time was shorter in interval SA but longer in interval AP, and overall, articles in Q4 had the shortest interval of time in SP. A potential association of the median time interval and authors’ continent was analysed and no significant difference was observed between articles with authors from single versus multiple continents or between continents in articles with authors from only one continent. However, in journals from Q4, time from submission to publication was longer for articles with authors from North America and Europe than from other continents, although the difference was not significant. Finally, articles of authors from the African continent had the smallest representation in journals from Q1-Q3 and articles from Oceania were underrepresented in group Q4. The study provides a global analysis of the total time required for submission, acceptance and publication in journals in the field of genetics and heredity. Our results may contribute in the development of strategies to expedite the process of scientific publishing in the field, and to promote equity in knowledge production and dissemination for researchers from all continents.
Barley systematics and taxonomy foreseen by seed morphometric variation
Authors: Jeanty Angèle , Bouby Laurent , Bonhomme Vincent , Balfourier François , Debiton Clément , Dham Camille , Ivorra Sarah , Ros Jérôme , Evin Allowen
Published: May 2023

Since its Neolithic domestication in the Fertile Crescent, barley has spread to all continents and represents a major cereal in many modern agrarian systems. Current barley diversity includes thousands of varieties divided into four main categories corresponding to 2-row and 6-row subspecies and naked and hulled types, each of them with winter and spring varieties. This diversity is associated to different uses and allow cultivation in diverse environments. We used a large dataset of 58 varieties of French origin, (1) to assess the taxonomic signal in barley grain measurements comparing 2-row and 6-row subspecies, and naked and hulled types; (2) to test the impact of the sowing period and interannual variation on the grains size and shape; (3) to investigate the existence of morphological differences between winter and spring types; and finally (4) to contrast the relationship between the morphometric and genetic proximity. Size and shape of 1980 modern barley caryopses were quantified through elliptic Fourier Transforms and traditional size measurements. Our results indicate that barley grains record morphological diversity of the ear (89.3% classification accuracy between 2-row/6-row subspecies; 85.2% between hulled and naked type), sowing time of the grains (from 65.6% to 73.3% within barley groups), and environmental conditions during its cultivation and varietal diversity. This study opens perspectives for studying archaeological barley seeds and tracing the barley diversity and evolution since the Neolithic.
DYRK1A inhibitors leucettines and TGF-β inhibitor additively stimulate insulin production in beta cells, organoids, and isolated mouse islets
Authors: Pucelik Barbara , Barzowska Agata , Czarna Anna
Published: May 2023

The decreased β-cell mass and impaired β-cell functionality are the primary causes of diabetes mellitus (DM). Nevertheless, the underlying molecular mechanisms by which β-cell growth and function are controlled are not fully understood. In this work, we show that leucettines, known to be DYRK1A kinase inhibitors, can improve glucose-stimulated insulin secretion (GSIS) in rodent β-cells and isolated islets, as well as in hiPSC-derived β-cells islets. We confirm that DYRK1A is expressed in murine insulinoma cells MIN6. In addition, we found that treatment with selected leucettines stimulates proliferation of β-cells and promotes MIN6 cell cycle progression to the G2/M phase. This effect is also confirmed by increased levels of cyclin D1, which is highly responsive to proliferative signals. Among other leucettines, leucettine L43 had a negligible impact on β-cell proliferation, but markedly impair GSIS. However, leucettine L41, in combination with LY364947, a, a potent and selective TGF-β type-I receptor, significantly promotes GSIS in various cellular diabetic models, including MIN6 and INS1E cells in 2D and 3D culture, iPSC-derived β-cell islets derived from iPSC, and isolated mouse islets, by increased insulin secretion and decreased glucagon level. Our findings confirm an important role of DYRK1A inhibitors as modulators of β-cells function and suggested a new potential target for antidiabetic therapy. Moreover, we show in detail that leucettine derivatives represent promising antidiabetic agents and are worth further evaluation, especiallyin vivo.
Trends in depression risk before and during the COVID-19 pandemic
Authors: Villas-Boas Sofia B. , White Justin S. , Kaplan Scott , Hsia Renee Y.
Published: May 2023

Using 11 years of the U.S. Centers for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System survey data set for 2011 to 2021, we track the evolution of depression risk for U.S. states and territories before and during the COVID-19 pandemic. We use these data in conjunction with unemployment and COVID case data by state and by year to describe changes in the prevalence of self-reported diagnosis with a depressive disorder over time and especially after the onset of COVID in 2020 and 2021. We further investigate heterogeneous associations of depression risk by demographic characteristics. Regression analyses of these associations adjust for state-specific and period-specific factors using state and year-fixed effects. First, we find that depression risk had been increasing in the US in years preceding the pandemic. Second, we find no significant average changes in depression risk at the onset of COVID in 2020 relative to previous trends, but estimate a 3% increase in average depression risk in 2021. Importantly, we find meaningful variation in terms of changes in depression risk during the pandemic across demographic subgroups.
PIK3CA mutations in breast cancer: A Tunisian series
Authors: Ben Rekaya Mariem , Sassi Farah , Saied Essya , Bel Haj Kacem Linda , Mansouri Nada , Zarrouk Sinda , Azouz Saifeddine , Rammeh Soumaya
Published: May 2023

Background

The aim of this study was to analyze PIK3CA mutations in exons 9 and 20 in breast cancers (BCs) and their association with clinicopathological characteristics.

Methods

Mutational analysis of PIK3CA exon 9 and 20 was performed by Sanger sequencing in 54 primary BCs of Tunisian women. The associations of PIK3CA mutations with clinicopathological characteristics were analyzed.

Results

Fifteen exon 9 and exon 20 PIK3CA variants were identified in 33/54 cases (61%). PIK3CA mutations including pathogenic (class 5/Tier I) or likely pathogenic (class 4/Tier II) occurred in 24/54 cases (44%): 17/24 cases (71%) in exon 9, 5/24 cases (21%) in exon 20 and 2/24 cases (8%) in both exons. Of these 24 cases, 18 (75%) carried at least one of the three hot spot mutations: E545K (in 8 cases), H1047R (in 4 cases), E542K (in 3 cases), E545K/E542K (in one case), E545K/H1047R (in one case) and P539R/H1047R (in one case). Pathogenic PIK3CA mutations were associated with negative lymph node status (p = 0.027). Age distribution, histological SBR tumor grading, estrogen and progesterone receptors, human epidermal growth factor receptor 2, and molecular classification were not correlated with PIK3CA mutations (p > 0.05).

Conclusion

The frequency of somatic PIK3CA mutations in BCs of Tunisian women is slightly higher than that of BCs of Caucasian women and more observed in exon 9 than in exon 20. PIK3CA mutated status is associated with negative lymph node status. These data need to be confirmed in larger series.
Phenopacket-tools: Building and validating GA4GH Phenopackets
Authors: Danis Daniel , Jacobsen Julius O. B. , Wagner Alex H. , Groza Tudor , Beckwith Martha A. , Rekerle Lauren , Carmody Leigh C. , Reese Justin , Hegde Harshad , Ladewig Markus S. , Seitz Berthold , Munoz-Torres Monica , Harris Nomi L. , Rambla Jordi , Baudis Michael , Mungall Christopher J. , Haendel Melissa A. , Robinson Peter N.
Published: May 2023

The Global Alliance for Genomics and Health (GA4GH) is a standards-setting organization that is developing a suite of coordinated standards for genomics. The GA4GH Phenopacket Schema is a standard for sharing disease and phenotype information that characterizes an individual person or biosample. The Phenopacket Schema is flexible and can represent clinical data for any kind of human disease including rare disease, complex disease, and cancer. It also allows consortia or databases to apply additional constraints to ensure uniform data collection for specific goals. We present phenopacket-tools, an open-source Java library and command-line application for construction, conversion, and validation of phenopackets. Phenopacket-tools simplifies construction of phenopackets by providing concise builders, programmatic shortcuts, and predefined building blocks (ontology classes) for concepts such as anatomical organs, age of onset, biospecimen type, and clinical modifiers. Phenopacket-tools can be used to validate the syntax and semantics of phenopackets as well as to assess adherence to additional user-defined requirements. The documentation includes examples showing how to use the Java library and the command-line tool to create and validate phenopackets. We demonstrate how to create, convert, and validate phenopackets using the library or the command-line application. Source code, API documentation, comprehensive user guide and a tutorial can be found at https://github.com/phenopackets/phenopacket-tools. The library can be installed from the public Maven Central artifact repository and the application is available as a standalone archive. The phenopacket-tools library helps developers implement and standardize the collection and exchange of phenotypic and other clinical data for use in phenotype-driven genomic diagnostics, translational research, and precision medicine applications.
Racial/ethnic disparities for leukemias in Puerto Rico and the United States of America, 2015–2019
Authors: Alvarado Ortiz Mariela , Suárez Ramos Tonatiuh , Torres Cintrón Carlos R. , Zavala Zegarra Diego , Tortolero Luna Guillermo , Ortiz-Ortiz Karen J. , Castaneda-Avila Maira A.
Published: May 2023

Background

Leukemia is a cancer of the early-forming cells. Over the past decade, leukemia racial/ethnic disparities have been documented in the United States of America (USA). Although the Puerto Rican population in the USA represents the second-largest Hispanic population in the nation, most of the existing studies do not include Puerto Rico. We compared the incidence and mortality rates for leukemia and its subtypes in Puerto Rico and four racial/ethnic groups in the USA.

Methods

We used data from the Puerto Rico Central Cancer Registry and the Surveillance, Epidemiology, and End Results Program (2015–2019). The racial/ethnic groups studied were non-Hispanic whites (NHW), non-Hispanic blacks (NHB), Hispanics (USH), and Asian/Pacific Islanders (NHAPI) living in the USA and the Puerto Rico population. We calculated the incidence and mortality rates. The relative risk of developing or dying due to leukemia was also calculated.

Results

Compared with Puerto Rico, NHW [standardized incidence rate (SIR) = 1.47; 95%CI = 1.40–1.53; standardized mortality rates (SMR) = 1.55; 95%CI = 1.45–1.65)] and NHB (SIR = 1.09; 95%CI = 1.04–1.15; SMR = 1.27; 95%CI = 1.19–1.35) had higher incidence and mortality rates; but lower than the NHAPI (SIR = 0.78; 95%CI = 0.74–0.82; SMR = 0.83; 95%CI = 0.77–0.89); and similar to USH. However, we found differences among leukemia subtypes. For example, NHAPI and USH had lower risk of developing chronic leukemias than Puerto Rico. We found a lower risk to develop acute lymphocytic leukemia in NHB than in Puerto Rico.

Conclusions

Our study provides a better understanding of leukemia’s racial/ethnic disparities and fills a knowledge gap by examining the incidence and mortality rates in Puerto Rico. Future studies are needed to better understand the factors influencing the differences found in the incidence and mortality of leukemia among different racial/ethnic groups.
Persistence of SARS-CoV-2 RNA shedding and infectivity in immunized population: Prospective study along different epidemiological periods in Argentina
Authors: Theaux Clara , Martin Yamila , Montoto Piazza Luciana , Wenk Gretel , Notaristefano Guillermo , Miño Laura , Sevilla María Eugenia , Aprea Valeria , Claps Aldana , Nabaes Jodar Mercedes , Acuña Dolores , Salvatori Melina , Álvarez Laura , Langan María Eugenia , Turk Gabriela , Del Olmo Ricardo , Viegas Mariana , Bruno Miriam , Bokser Vivian
Published: May 2023

During the pandemic of COVID-19, numerous waves of infections affected the two hemispheres with different impacts on each country. Throughout these waves, and with the emergence of new variants, health systems and scientists have tried to provide real-time responses to the complex biology of SARS-CoV-2, dealing with different clinical presentations, biological characteristics, and clinical impact of these variants. In this context, knowing the extent period in which an infected individual releases infectious viral particles has important implications for public health. This work aimed to investigate viral RNA shedding and infectivity of SARS-CoV-2 beyond 10 days after symptom onset (SO). A prospective multicenter study was performed between July/2021 and February/2022 on 116 immunized strategic personnel with COVID-19 diagnosed by RT-qPCR, with asymptomatic (7%), mild (91%) or moderate disease (2%). At the time of diagnosis, 70% had 2 doses of vaccines, 26% had 2 plus a booster, and 4% had one dose. After day 10 from SO, sequential nasopharyngeal swabs were taken to perform RT-qPCR, viral isolation, and S gene sequencing when possible. Viral sequences were obtained in 98 samples: 43% were Delta, 16% Lambda, 15% Gamma, 25% Omicron (BA.1) and 1% Non-VOC/VOI, in accordance with the main circulating variants at each moment. SARS-CoV-2 RNA was detected 10 days post SO in 57% of the subjects. Omicron was significantly less persistent. Noteworthy, infective viruses could not be isolated in any of the samples. In conclusion, a 10-days isolation period was useful to prevent further infections, and proved valid for the variants studied. Recently, even shorter periods have been applied, as the Omicron variant is prevalent, and worldwide population is largely vaccinated. In the future, facing the possible emergence of new variants and considering immunological status, a return to 10 days may be necessary.
Characteristics of Carbapenem-resistant Klebsiella pneumoniae in sewage from a tertiary hospital in Jilin Province, China
Authors: Liu Mingwei , Zheng Lin , Zhu Lingwei , Lu Gejin , Guo Hongru , Guan Jiayao , Jing Jie , Sun Shiwen , Wang Ying , Wang Zixian , Sun Yang , Ji Xue , Jiang Bowen , Liu Jun , Zhang Wenhui , Guo Xuejun
Published: May 2023

Background

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is a serious problem in hospitals worldwide. We monitored a tertiary hospital in Changchun, Jilin Province, China, and found that CRKP was the major species among the carbapenem-resistant isolates in sewage. Subsequently, we evaluated the drug susceptibility, resistance genes, virulence genes, outer pore membrane protein-related genes (OmpK35 & OmpK 36), multi-locus sequence typing and replicons, biofilm formation capabilities, and resistance to chlorine-containing disinfectants among KP isolates. Identification of drug sensitivity, multiple resistance profiles were observed including 77 (82.80%) multidrug resistant (MDR), 16 (17.20%) extensive drug resistant (XDR). Some antibiotic resistance genes were detected, the most prevalent carbapenemase gene was blaKPC, and 16 resistance genes were associated with other antibiotics. In addition, 3 (3.23%) CRKP isolates demonstrated loss of OmpK-35 and 2 (2.15%) demonstrated loss of OmpK-36. In the detection of multi-locus sequence typing (MLST), 11 ST11 isolates carried virulence genes. The most common replicon type was IncFII. Biofilm-forming capabilities were demonstrated by 68.8% of the isolates, all of which were resistant to chlorine-containing disinfectants. The results of the study showed that antibiotic-resistant isolates, especially CRKP, could resist disinfectants in hospital wastewater, and improper treatment of hospital wastewater may lead to the spread of drug-resistant bacteria and their genes. Thus, these bacteria must be eliminated before being discharged into the municipal sewage system.
Prediction of concrete strength using response surface function modified depth neural network
Authors: Chen Xiaohong , Zhang Yueyue , Ge Pei
Published: May 2023

In order to overcome the discreteness of input data and training data in deep neural network (DNN), the multivariable response surface function was used to revise input data and training data in this paper. The loss function based on the data on the response surface was derived, DNN based on multivariable response surface function (MRSF-DNN) was established. MRSF-DNN model of recycled brick aggregate concrete compressive strength was established, in which coarse aggregate volume content, fine aggregate volume content and water cement ratio are influencing factors. Furthermore, the predictive analysis and extended analysis of MRSF-DNN model were carried out. The results show that: MRSF-DNN model had high prediction accuracy, the correlation coefficient between the real values and the forecast values was 0.9882, the relative error was between -0.5% and 1%. Furthermore, MRSF-DNN had more stable prediction ability and stronger generalization ability than DNN.
Hemodynamical consequences and tolerance of sustained ventricular tachycardia
Authors: Delasnerie Hubert , Biendel Caroline , Elbaz Meyer , Mandel Franck , Beneyto Maxime , Domain Guillaume , Voglimacci-Stephanopoli Quentin , Mondoly Pierre , Delmas Clement , Bongard Vanina , Rollin Anne , Maury Philippe
Published: May 2023

Aims

Factors underlying clinical tolerance and hemodynamic consequences of monomorphic sustained ventricular tachycardia (VT) need to be clarified.

Methods

Intra-arterial pressures (IAP) during VT were collected in patients admitted for VT ablation and correlated to clinical, ECG and baseline echocardiographical parameters.

Results

114 VTs from 58 patients were included (median 67 years old, 81% ischemic heart disease, median left ventricular ejection fraction 30%). 61 VTs were untolerated needing immediate termination (54%). VT tolerance was tightly linked to the evolution of IAPs. Faster VT rates (p<0.0001), presence of resynchronization therapy (p = 0.008), previous anterior myocardial infarction (p = 0.009) and more marginally larger baseline QRS duration (p = 0.1) were independently associated with VT tolerance. Only an inferior myocardial infarction was more often present in patients with only tolerated VTs vs patients with only untolerated VTs in multivariate analysis (OR 3.7, 95% CI 1.4–1000, p = 0.03). In patients with both well-tolerated and untolerated VTs, a higher VT rate was the only variable independently associated with untolerated VT (p = 0.02). Two different patterns of hemodynamic profiles during VT could be observed: a regular 1:1 relationship between electrical (QRS) and mechanical (IAP) events or some dissociation between both. VT with the second pattern were more often untolerated compared to the first pattern (78% vs 29%, p<0.0001).

Conclusion

This study helps to explain the large variability in clinical tolerance during VT, which is clearly related to IAP. VT tolerance may be linked to resynchronization therapy, VT rate, baseline QRS duration and location of myocardial infarction.
A novel kinetic energy harvesting system for lifetime deployments of wildlife trackers
Authors: Gregersen Troels , Wild Timm A. , Havmøller Linnea Worsøe , Møller Peter Rask , Lenau Torben Anker , Wikelski Martin , Havmøller Rasmus Worsøe
Published: May 2023

Wildlife tracking devices are key in obtaining detailed insights on movement, animal migration, natal dispersal, home-ranges, resource use and group dynamics of free-roaming animals. Despite a wide use of such devices, tracking for entire lifetimes is still a considerable challenge for most animals, mainly due to technological limitations. Deploying battery powered wildlife tags on smaller animals is limited by the mass of the devices. Micro-sized devices with solar panels sometimes solve this challenge, however, nocturnal species or animals living under low light conditions render solar cells all but useless. For larger animals, where battery weight can be higher, battery longevity becomes the main challenge. Several studies have proposed solutions to these limitations, including harvesting thermal and kinetic energy on animals. However, these concepts are limited by size and weight. In this study, we used a small, lightweight kinetic energy harvesting unit as the power source for a custom wildlife tracking device to investigate its suitability for lifetime animal tracking. We integrated a Kinetron MSG32 microgenerator and a state-of-the-art lithium-ion capacitor (LIC) into a custom GPS-enabled tracking device that is capable of remotely transmitting data via the Sigfox ‘Internet of Things’ network. Prototypes were tested on domestic dog (n = 4), wild-roaming Exmoor pony (n = 1) and wisent (n = 1). One of the domestic dogs generated up to 10.04 joules of energy in a day, while the Exmoor pony and wisent generated on average 0.69 joules and 2.38 joules per day, respectively. Our results show a significant difference in energy generation between animal species and mounting method, but also highlight the potential for this technology to be a meaningful advancement in ecological research requiring lifetime tracking of animals. The design of the Kinefox is provided open source.
Distinct immune responses associated with vaccination status and protection outcomes after malaria challenge
Authors: Oyong Damian A. , Duffy Fergal J. , Neal Maxwell L. , Du Ying , Carnes Jason , Schwedhelm Katharine V. , Hertoghs Nina , Jun Seong-Hwan , Miller Helen , Aitchison John D. , De Rosa Stephen C. , Newell Evan W. , McElrath M Juliana , McDermott Suzanne M. , Stuart Kenneth D.
Published: May 2023

Understanding immune mechanisms that mediate malaria protection is critical for improving vaccine development. Vaccination with radiation-attenuated Plasmodium falciparum sporozoites (PfRAS) induces high level of sterilizing immunity against malaria and serves as a valuable tool for the study of protective mechanisms. To identify vaccine-induced and protection-associated responses during malarial infection, we performed transcriptome profiling of whole blood and in-depth cellular profiling of PBMCs from volunteers who received either PfRAS or noninfectious mosquito bites, followed by controlled human malaria infection (CHMI) challenge. In-depth single-cell profiling of cell subsets that respond to CHMI in mock-vaccinated individuals showed a predominantly inflammatory transcriptome response. Whole blood transcriptome analysis revealed that gene sets associated with type I and II interferon and NK cell responses were increased in prior to CHMI while T and B cell signatures were decreased as early as one day following CHMI in protected vaccinees. In contrast, non-protected vaccinees and mock-vaccinated individuals exhibited shared transcriptome changes after CHMI characterized by decreased innate cell signatures and inflammatory responses. Additionally, immunophenotyping data showed different induction profiles of vδ2+ γδ T cells, CD56+ CD8+ T effector memory (Tem) cells, and non-classical monocytes between protected vaccinees and individuals developing blood-stage parasitemia, following treatment and resolution of infection. Our data provide key insights in understanding immune mechanistic pathways of PfRAS-induced protection and infective CHMI. We demonstrate that vaccine-induced immune response is heterogenous between protected and non-protected vaccinees and that inducted-malaria protection by PfRAS is associated with early and rapid changes in interferon, NK cell and adaptive immune responses.

Trial Registration: ClinicalTrials.gov NCT01994525.
Intervention reducing malaria parasite load in vector mosquitoes: No impact on Plasmodium falciparum extrinsic incubation period and the survival of Anopheles gambiae
Authors: Guissou Edwige , Da Dari Frédéric , Hien Domombabele François de Sales , Yameogo Koudraogo Bienvenue , Yerbanga Serge Rakiswende , Ouédraogo Georges Anicet , Dabiré Kounbobr Roch , Lefèvre Thierry , Cohuet Anna
Published: May 2023

In the fight against malaria, transmission blocking interventions (TBIs) such as transmission blocking vaccines or drugs, are promising approaches to complement conventional tools. They aim to prevent the infection of vectors and thereby reduce the subsequent exposure of a human population to infectious mosquitoes. The effectiveness of these approaches has been shown to depend on the initial intensity of infection in mosquitoes, often measured as the mean number of oocysts resulting from an infectious blood meal in absence of intervention. In mosquitoes exposed to a high intensity of infection, current TBI candidates are expected to be ineffective at completely blocking infection but will decrease parasite load and therefore, potentially also affect key parameters of vector transmission. The present study investigated the consequences of changes in oocyst intensity on subsequent parasite development and mosquito survival. To address this, we experimentally produced different intensities of infection for Anopheles gambiae females from Burkina Faso by diluting gametocytes from three natural Plasmodium falciparum local isolates and used a newly developed non-destructive method based on the exploitation of mosquito sugar feeding to track parasite and mosquito life history traits throughout sporogonic development. Our results indicate the extrinsic incubation period (EIP) of P. falciparum and mosquito survival did not vary with parasite density but differed significantly between parasite isolates with estimated EIP50 of 16 (95% CI: 15–18), 14 (95% CI: 12–16) and 12 (95% CI: 12–13) days and median longevity of 25 (95% CI: 22–29), 15 (95% CI: 13–15) and 18 (95% CI: 17–19) days for the three isolates respectively. Our results here do not identify unintended consequences of the decrease of parasite loads in mosquitoes on the parasite incubation period or on mosquito survival, two key parameters of vectorial capacity, and hence support the use of transmission blocking strategies to control malaria.
Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2
Authors: Ma Yong , Li Pengbin , Hu Yunqi , Qiu Tianyi , Wang Lixiang , Lu Hongjie , Lv Kexin , Xu Mengxin , Zhuang Jiaxin , Liu Xue , He Suhua , He Bing , Liu Shuning , Liu Lin , Wang Yuanyuan , Yue Xinyu , Zhai Yanmei , Luo Wanyu , Mai Haoting , Kuang Yu , Chen Shifeng , Ye Feng , Zhou Na , Zhao Wenjing , Chen Jun , Chen Shoudeng , Xiong Xiaoli , Shi Mang , Pan Ji-An , Chen Yao-Qing
Published: May 2023

SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus’ evolution.
Integrated post-genomic cell wall analysis reveals floating biofilm formation associated with high expression of flocculins in the pathogen Pichia kudriavzevii
Authors: Alvarado María , Gómez-Navajas Jesús Alberto , Blázquez-Muñoz María Teresa , Gómez-Molero Emilia , Berbegal Carmen , Eraso Elena , Kramer Gertjan , De Groot Piet W. J.
Published: May 2023

The pathogenic yeast Pichia kudriavzevii, previously known as Candida krusei, is more distantly related to Candida albicans than clinically relevant CTG-clade Candida species. Its cell wall, a dynamic organelle that is the first point of interaction between pathogen and host, is relatively understudied, and its wall proteome remains unidentified to date. Here, we present an integrated study of the cell wall in P. kudriavzevii. Our comparative genomic studies and experimental data indicate that the general structure of the cell wall in P. kudriavzevii is similar to Saccharomyces cerevisiae and C. albicans and is comprised of β-1,3-glucan, β-1,6-glucan, chitin, and mannoproteins. However, some pronounced differences with C. albicans walls were observed, for instance, higher mannan and protein levels and altered protein mannosylation patterns. Further, despite absence of proteins with high sequence similarity to Candida adhesins, protein structure modeling identified eleven proteins related to flocculins/adhesins in S. cerevisiae or C. albicans. To obtain a proteomic comparison of biofilm and planktonic cells, P. kudriavzevii cells were grown to exponential phase and in static 24-h cultures. Interestingly, the 24-h static cultures of P. kudriavzevii yielded formation of floating biofilm (flor) rather than adherence to polystyrene at the bottom. The proteomic analysis of both conditions identified a total of 33 cell wall proteins. In line with a possible role in flor formation, increased abundance of flocculins, in particular Flo110, was observed in the floating biofilm compared to exponential cells. This study is the first to provide a detailed description of the cell wall in P. kudriavzevii including its cell wall proteome, and paves the way for further investigations on the importance of flor formation and flocculins in the pathogenesis of P. kudriavzevii.
Pathogenicity, tissue tropism and potential vertical transmission of SARSr-CoV-2 in Malayan pangolins
Authors: Liang Xianghui , Chen Xiaoyuan , Zhai Junqiong , Li Xiaobing , Zhang Xu , Zhang Zhipeng , Zhang Ping , Wang Xiao , Cui Xinyuan , Wang Hai , Zhou Niu , Chen Zu-Jin , Su Renwei , Zhou Fuqing , Holmes Edward C. , Irwin David M. , Chen Rui-Ai , He Qian , Wu Ya-Jiang , Wang Chen , Du Xue-Qing , Peng Shi-Ming , Xie Wei-Jun , Shan Fen , Li Wan-Ping , Dai Jun-Wei , Shen Xuejuan , Feng Yaoyu , Xiao Lihua , Chen Wu , Shen Yongyi
Published: May 2023

Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.
Identification of CDRH3 loops in the B cell receptor repertoire that can be engaged by candidate immunogens
Authors: Swanson Olivia , Martin Beem Joshua S. , Rhodes Brianna , Wang Avivah , Barr Maggie , Chen Haiyan , Parks Robert , Saunders Kevin O. , Haynes Barton F. , Wiehe Kevin , Azoitei Mihai L.
Published: May 2023

A major goal for the development of vaccines against rapidly mutating viruses, such as influenza or HIV, is to elicit antibodies with broad neutralization capacity. However, B cell precursors capable of maturing into broadly neutralizing antibodies (bnAbs) can be rare in the immune repertoire. Due to the stochastic nature of B cell receptor (BCR) rearrangement, a limited number of third heavy chain complementary determining region (CDRH3) sequences are identical between different individuals. Thus, in order to successfully engage broadly neutralizing antibody precursors that rely on their CDRH3 loop for antigen recognition, immunogens must be able to tolerate sequence diversity in the B cell receptor repertoire across an entire vaccinated population. Here, we present a combined experimental and computational approach to identify BCRs in the human repertoire with CDRH3 loops predicted to be engaged by a target immunogen. For a given antibody/antigen pair, deep mutational scanning was first used to measure the effect of CDRH3 loop substitution on binding. BCR sequences, isolated experimentally or generated in silico, were subsequently evaluated to identify CDRH3 loops expected to be bound by the candidate immunogen. We applied this method to characterize two HIV-1 germline-targeting immunogens and found differences in the frequencies with which they are expected to engage target B cells, thus illustrating how this approach can be used to evaluate candidate immunogens towards B cell precursors engagement and to inform immunogen optimization strategies for more effective vaccine design.
Cruelty and democracy: Understanding Lippmann’s gambit
Authors: Van Rythoven Eric
Published: May 2023

A paradox haunts Lippmann’s critique of democracy running through his early work in Public Opinion up through The Public Philosophy. Liberal democracies, despite their claim to securing space for human dignity and freedom, can be sites of incredible cruelty. From the racial prejudices cutting through American politics, to the way Americans treated adversaries during war, democracy appeared to do little to vitiate the human propensity to inflict suffering upon others. This article examines Lippmann’s understanding of cruelty as a recurring feature of democracy and how he grappled with the question of how to curb the democratic public’s worst impulses. I argue that while Lippmann offers an expansive understanding of cruelty his analysis continually gravitates towards the role of cruelty in democracy and how the existence of mobs and demagogues represent democracy’s ever-latent potential for cruelty. Exploring his thinking further, I suggest there are at least two distinct views on the origins and dynamics of cruelty in his work – what I designate ‘callous’ and ‘joyful’ cruelty – influenced by James and Freud respectively. Finally, I contend that recognizing the gravity Lippmann assigns to the problem of cruelty is important because it can help us understand his puzzling turn to natural law in The Public Philosophy. Here I suggest Lippmann’s turn to natural law should be read as a radical pragmatist gambit in which the myth of natural law is mobilized to create a ‘tradition of civility’ aimed at curbing democratic cruelty. When we attend to this side of Lippmann we see a version of him that is less a conservative reactionary and more an anxious critic desperate to ward off the darker impulses of democracy.
Lippmann’s triangular relationship on the crime scene: Pseudo-environments convicting the innocent
Authors: Blom Robin
Published: May 2023

Lippmann noted that analyses of public opinion must start ‘by recognizing the triangular relationship between the scene of action, the human picture of that scene, and the human response to that picture working itself out upon the scene of action’. This is certainly the case for crime scenes. The majority of the public will never be a victim of serious crime, and many people will not have close contact with law enforcement and the court system. Hence, much of what is learnt about crime is from exposure to news reports and depictions in popular media. Lippmann noted that crime is among the most important topics in terms of news output. Two case studies of persons who were initially convicted and later exonerated provide examples of how journalists report on eyewitness testimony when those eyewitness reports formed the main evidence for the prosecution. These case studies also provided opportunities to explore how pseudo-environments were developed by journalists to signify that the wrongfully convicted individuals were indeed guilty after such a jury verdict – without much, if any, reference to the possibility that those individuals were convicted based on witness misidentification.
Lippmann–Ortega: On the role of elites in a democracy
Authors: Simón Rodolfo Gutiérrez
Published: May 2023

The aim of this article is to contrast the understanding of elites by José Ortega y Gasset and Walter Lippmann. Although they both agreed in not seeing a conflict between elitism and democracy, they differed in three aspects. First, while for Lippmann the elites are the insiders, those who have privileged access to political information, for Ortega the elites are a phenomenon that has more to do with the moral and the psychological (those ‘egregious men’ who make an effort, who do not get carried away) and are not limited to the political sphere, but include other fields, such as culture or the arts. Second, they also differ in their conception of public opinion: whereas for Lippmann public opinion is the images that outsiders form from the stereotypes created by insiders, for Ortega public opinion is that which is held by everyone and by no one in particular, the well-known, the taken-for-granted. The third difference refers to the relationship between insiders and outsiders: while Lippmann fears the separation between pundits and the passive mass audience, the relationship between Ortega’s ‘egregious men’ and the ‘mass-men’ must be dynamic: the first must lead well, by example, the second must let themselves be guided.
Parochialism, propaganda and Public Opinion: Reading Lippmann in Zuboff’s Age of Surveillance Capitalism
Authors: Durham Frank D.
Published: May 2023

By comparing the theoretical assessments of the effects of propaganda on liberal democratic discourse about the role of media in liberal democracy made by Walter Lippmann in Public Opinion in 1922 and Shoshana Zuboff in The Age of Surveillance Capitalism (2019) nearly a century later, this historically grounded article considers the two critics’ analyses of the threat posed by propaganda to the reproduction of free speech in a liberal democracy. The cross-century comparison of their respective critiques of media demonstrates the relevance of Lippmann’s ‘stereotype’ and his frustrated, but still useful, three-part dynamic of public opinion: journalism, the public and the government. For both scholars, the rehabilitation of the public ‘un-commons’ from domination by state and corporate-driven propaganda is paramount.
Not Exactly Lying: Fake News and Fake Journalism in American History, Andie Tucher (2022)
Authors: Nerone John
Published: May 2023

Review of: Not Exactly Lying: Fake News and Fake Journalism in American History, Andie Tucher (2022)

New York: Columbia University Press, 384 pp.,

ISBN 978-0-23118-635-3, p/bk, $28.00
СONTENT OF ALKALOIDS IN DIFFERENT ORGANS OF PEGANUM HARMALA L. DURING ONTOGENESIS
Authors: Kruglov Dmitriy Semenovich , Velichko Viktoriya Vladimirovna , Yusupbayeva Aidana Talaibekovna
Published: May 2023

Peganum garmala contains in its composition quinazoline (L-peganine (vasicin), pegamine, peganol, deoxypeganine, peganidin, etc.) and β-carboline (harmine, harman, harmaline, harmalol, etc.) alkaloids, which also cause different pharmacological activity harmala preparations. The accumulation of alkaloids depends on the stage of ontogenesis and differs in the aboveground and underground parts of the plant. The aim of the work is to determine the possibility of using various plant organs for the isolation of individual alkaloids. The study was conducted on the underground and aboveground organs of a plant collected on the territory and the Republic of Kyrgyzstan in the phases of vegetation, flowering and fruiting. Using thin-layer chromatography and spectrophotometry, it was found that the alkaloid peganine predominates in the aerial part of the plant. In the roots in the phase of vegetation and flowering, harmine predominates, while in the fruiting phase it is absent and only peganine is recorded. Quantitative determination of the content of both alkaloids was carried out by measuring the optical density at wavelengths characteristic of the extremums of peganine (266 nm) and harmine (315 nm). As a result, it was found that the content of peganin in the aboveground organs of the common harmala does not depend on the stage of ontogenesis. At the same time, the content of alkaloids in harmala roots decreases in ontogeny with a simultaneous change in the ratio of harmine and peganine – harmine predominates in the vegetation and flowering stages, and in the fruiting stage, its content decreases to a trace level with a simultaneous increase in the content of peganine.
INVESTIGATION OF CELANDINE EXTRACTS (CHELIDONIUM MAJUS L.) BY 1H NMR AND QNMR METHODS
Authors: Korotkikh Mikhail Olegovich , Romanenko Elena Petrovna , Tikhova Vera Dmitriyevna , Tkachev Aleksej Vasil'evich
Published: May 2023

The analysis of Celandine extracts (Chelidonium majus L.) by 1H NMR method makes it possible to identify the main alkaloids – derivatives of phenanthridine, protoberberin and protopin, and the use of the qNMR method provides information with satisfactory accuracy about the content of these alkaloids. The content of alkaloids determined in the composition of Celandine extracts by the qNMR method (0.35%) is 2 times lower than when using the spectrophotometric determination procedure described in the GF of the Russian Federation XIV (0.72%). The extraction results according to the methods given in the State Pharmacopoeia of the Russian Federation of the XIV edition and in the State Pharmacopoeia of the USSR of the IX edition give similar results: the same alkaloids are found in the extracts – chelidonin, stylopine and protopine, and the total content of alkaloids is 1.6-1.8 times less than when extracting the same raw material samples by the method insistence. When extracted by infusion, the main alkaloids in the extracts are dihydrosanguinarin, chelidonin, stylopine, berberine and coptisin.