bluuebunny/crossref_metadata_2025 huggingface dataset:
CUMHURİYET DÖNEMİ MİLLİ EĞİTİM ŞURALARININ VATANDAŞLIK EĞİTİMİ POLİTİKALARI BAĞLAMINDA İNCELENMESİ (1921-2021)
Authors: KARA İlyas , TOKMAK Ahmet , ÖZTÜRK Mehmet Baki
Published: October 2023

Bu araştırmada Cumhuriyet Dönemi vatandaşlık eğitimi politikaları bağlamında Milli Eğitim Şuralarının incelenmesi (1921-2021) amaçlanmıştır. Bu doğrultuda 1921-1926 yılları arasında faaliyet gösteren Heyet-i İlmiyenin çalışmaları ile 1939-2021 yılları arasında gerçekleştirilen Milli Eğitim Şûralarında alınan kararlar ve bu şûralara ait dokümanlar incelenmiştir. Vatandaşlık eğitimi politikaları dönemin siyasal özellikleriyle ilişkilendirilmiştir. Araştırma nitel bir çalışma olup çalışmada doküman analizi yöntemi kullanılmıştır. Araştırma sonucunda Kurtuluş Savaşı kazanıldıktan ve Cumhuriyet kurulduktan sonra eğitim-öğretim aracılığıyla Cumhuriyet’i özümsemiş, Cumhuriyetçi, demokratik ve laik vatandaşların yetiştirilmesinin amaçlandığı, millet olma bilincinin ve vatan sevgisinin ön plana çıktığı sonucuna varılmıştır. Tek Parti döneminde vatandaşlık eğitiminin genel olarak haktan çok vazife odaklı ve görev vurgulu olduğu, gerektiğinde bireysel çıkarlardan toplumun genel menfaatleri için vazgeçebilen, milliyetçi ve vatansever bireyler yetiştirmeyi amaçladığı görülmüştür. Bu dönemde her ne kadar cumhuriyetçi ulus meydana getirme projesi devam etse de daha çok evrensel, ulus-üstü, aydınlanmacı, modernist ve kültür-üstü kişilik kurmaya çalışıldığı tespit edilmiştir. Demokrat Partinin eğitimi şekillendiren siyasi anlayışının batıcılık ve geleneksellik şeklinde iki temel prensibe dayandığı saptanmıştır. Bu dönemdeki vatandaşlık eğitiminin de bu doğrultuda verildiği görülmüştür. 1960-1980 yılları arasında siyasal ve sosyal açıdan oldukça çalkantılı bir dönem yaşandığı, 1970’li yıllarda yaşanan şiddet ve anarşi olaylarının milli iradeyi yok sayan 12 Eylül askeri darbesi ile sonuçlandığı tespit edilmiştir. Darbe yönetiminin ilk hedefinin, aşırı derecede politize olmuş toplumu politikadan uzaklaştırarak siyasal ve toplumsal istikrarı sağlamak olduğu görülmüştür. Dönemin vatandaşlık eğitimi politikaları da bu doğrultuda gelişmiştir. Okullarda din eğitiminin verilmesi yasal bir zorunluluk haline getirilmiştir. Devlet bu gibi uygulamalarla din eğitimini teşvik etmiştir. 2002 yılı sonrasında değeler eğitimi, din eğitimi ve vatandaşlık eğitimi önemsenmiş ve bu konular Milli Eğitim Şuralarında sıklıkla konuşulmuştur.
INDONESIAN FLIGHT ATTENDANTS’ PERCEPTIONS OF DIALECT VARIETIES
Authors: Andayani Widya , Damanik Sisila Fitriani , Hutasuhut Mahmud Layan , Anshari Rudi
Published: October 2023

This research was aimed to examine flight attendants’ perceptions of dialect varieties in Indonesia. The researchers concerned in flight attendants' perceptions of various dialects used by partners, as well as passengers' attitudes toward the flight attendants' dialect. This research was conducted by using qualitative method. The participantswere 2 flight attendants which have different background cultures yet work in one aviation. In this research, direct quotations were presented unaltered. Each direct quotation is followed by a descriptive abbreviation noting the source of the quotation. The participants  answered some questions that was given. Interviews were conducted using Whatsapp application  because it was impossible to do face-to-face interviews with the participants in COVID-19 pandemic. Each interview took 30 to 40 minutes. Interviews were taped with a voice note feature on Whatsapp. The results revealed that each flight attendant saw the dialect variations in partners as an interesting thing to respect as long as the partner communicated well and politely, the passenger understood and got the point. In terms of the passengers' reactions to the flight attendants' dialect, there were possitive and negative from the passengers.
Expertise, disagreement, and trust in vaccine science and policy. The importance of transparency in a world of experts
Authors: Giubilini Alberto , Gur-Arie Rachel , Jamrozik Euzebiusz
Published: October 2023

We discuss the relationship between expertise, expert authority, and trust in the case of vaccine research and policy, with a particular focus on COVID-19 vaccines. We argue that expert authority is not merely an epistemic notion, but entails being trusted by the relevant public and is valuable if it is accompanied by expert trustworthiness. Trustworthiness requires, among other things, being transparent, acknowledging uncertainty and expert disagreement (e.g., around vaccines’ effectiveness and safety), being willing to revise views in response to new evidence, and being clear about the values that underpin expert recommendations. We explore how failure to acknowledge expert disagreement and uncertainty can undermine trust in vaccination and public health experts, using expert recommendations around COVID-19 vaccines as a case study.
Prevalence of the scuticociliate Orchitophrya stellarum in seastars from the Pacific and Atlantic oceans
Authors: Goggin CL , Leung TLF , Byrne M , Murphy NE , Koen T
Published: October 2023

As part of a study to investigate the use of the scuticociliate Orchitophrya stellarum as a biological control for the invasive seastar Asterias amurensis in Australia, we collected prevalence data for O. stellarum from 3 seastar species (A. amurensis, A. rubens, Pisaster ochraceus) between 1996 and 1999 from the Pacific (Australia, Japan, Korea, Canada) and Atlantic (France, Netherlands, Canada) oceans. In the Pacific Ocean, for the first time, we found O. stellarum in male A. amurensis in Korea and female A. amurensis in Japan. The parasite was not detected in the invasive A. amurensis from Australia. There was no significant difference between size of infected and uninfected male seastars, nor a correlation between biased sex ratio and parasite prevalence in populations in the Pacific or Atlantic oceans. Therefore, unlike other studies, we found size and sex ratio in seastar populations in the field are unreliable indicators of parasite impacts. Regular monitoring of infected seastar populations in the field would be useful to better understand how sex ratio varies with parasite prevalence. We recommend laboratory studies under controlled conditions to determine the effect of O. stellarum on seastar populations.
Case of congenital complete neck fistula patient in adulthood
Authors: Kosminskaya A. R. , Bykova A. A. , Drobyshev A. Yu. , Egorova E. A. , Pilnikov V. G. , Khon E. M.
Published: October 2023

Currently, the prevalence of congenital pathology in the form of cysts and fistulas is more often manifested at a young age, less often in adults. Complete congenital neck fistulas are extremely rare. In this regard, the problem of primary differential diagnostics remains relevant.
Application of the real-time PCR-method for the determination of periodontopathogens
Authors: Jafarov E. M. , Edisherashvili U. B. , Choniashvili M. Z. , Taimazova D. T. , Dolgalev A. A.
Published: October 2023

The etiological factor of periodontal diseases is the presence of periodontopathogens, under the condition of an imbalance with commensals, they begin to have a pathological effect. With a decrease in the number of periodontopathogens in the biofilm, it is possible to restore the balance and prevent periodontal diseases or their transition to the stage of remission. To date, the most informative and accessible diagnostic method for determining periodontopathogens is real-time PCR.
Provision of specialized medical care to patients in a modern inpatient polyclinic complex
Authors: Khelminskaya N. M. , Zavgorodnev K. D. , Posadskaya A. V. , Kravets V. I. , Eremin D. A. , Kravets A. V.
Published: October 2023

The article is devoted to the analysis of medical and economic standards of medical rehabilitation of patients with complicated and un[1]complicated fractures of the mandible. The structure of therapeutic measures for the treatment of fractures of the mandible in the hospital, complications of fractures of the mandible were studied. The results of the analysis of medical documentation of 550 patients with fractures of the mandible and their complications who sought medical help in Maxillofacial hospital for war veterans, Pirogov City Clinical Hospital №1 for the period from 2006 to 2021 are presented.
PERCEIVED BEHAVIORAL CONTROL, ATTITUDE AND PERCEPTION OF SECURITY AS DETERMINANTS OF PUBLIC INTEREST IN USING FINTECH P2P
Authors: Hikmah Hikmah , Sunargo Sunargo , Wangdra Yvonne
Published: October 2023

Peer-to-peer lending is the sole financial service provided in the form of transactions conducted online. Peer to Peer Lending currently offers a variety of loans, including those for businesses, health care, and education,  that the general public may access online so that lengthy approval processes are not necessary. The purpose of this study is to understand perceived behavioral control, attitude, and perceived risk as factors affecting how the general public uses fintech peer-to-peer lending. According to this study, all of the sub district that are present in Kota Batam are populous. data collection methodology using kuesioner. By using Jacob Cohen's book, there are 204 responses in this essay. The respondents to this study were people who had used peer-to-peer lending to make loans. Purposive sampling is the method of sampling that is employed. SEM is the analytical technique employed with the Smart PLS 3.0 program. According to the study's findings, perceived behavioral control, attitude, and perception of security all significantly and positively influence interest in batam City residents. Perceived behavioral control also significantly and positively influences interest in Batam City residents.
NEW MEDIA AS INTERNET MARKETING COMMUNICATIONS IN RETAIL COMPANY
Authors: Purwanti Angel , Reza Ana , Musa Umar , Nurhadi Zikri Fahrul , Triyadi Agus
Published: October 2023

A franchise company is PT. Indomarco Prismatama, better known as Indomaret, with the assistance of more than 500 distributors, Indomaret has developed a minimarket business with 16,000 locations, a full product inventory, 60% company-owned stores, and 40% franchise-owned stores. Both physical and online marketing initiatives are part of Indomaret's marketing plan. The expansion of the market for Indomaret products is the aim of this marketing strategy. The marketing strategy has been modified to meet market demands because of the existence of the internet, and Indomaret's success cannot be separated from the marketing strategy. This study attempts to understand and analyze the Internet Marketing Communication strategy used by Indomaret Batam to manage its business. In this form of research, a qualitative descriptive methodology is employed. Interviews were employed to acquire data and study of the literature. Data collection, data reduction, data display and conclusions, and a credibility and transferability test are the four processes in a Miles and Huberman data analysis. The study's findings revealed the three methods of online marketing communication they employed: (1) applications, such as Indomaret's klik Indomaret, I-Saku, and Indomaret Point; (2) social media platforms including Instagram, Youtube, Facebook, and Twitter; and (3) websites. Indomaret. The emergence of new media includes these three forms of communication. Indomaret can shape its target audience both offline and online thanks to these three new media genres that produce digital natives.
THE INFLUENCE OF DISCIPLINE AND LEADERSHIP ON THE PERFORMANCE EMPLOYEES OF BADAN PENGUSAHAAN (BP) BATAM
Authors: Dompak Timbul , Epriadi Dedi
Published: October 2023

This study aims to investigate the effects of discipline and leadership on the performance employees of Badan Pengusahaan (BP) Batam. By giving respondents questionnaires, this study uses quantitative methods. 100 people make up the research sample. The research yielded the following conclusions: (1) There is a partial influence of discipline on employee performance, as shown by a t-count value of (7.351) > t-table (1.984), (2) There is a partial influence of leadership on employee performance, as shown by a t-count value of (3.632) > t-table (1.984), and (3) There is a simultaneous influence of discipline and leadership on employee performance, as shown by an F-count (126.347) > F-table (3.09).
DIGITAL MARKETING POTENTIAL IN INDONESIA
Authors: Alfonsius Alfonsius
Published: October 2023

One of the impacts of the Covid-19 pandemic is the sluggishness of the business and economic world. Therefore, marketers or business actors need to find alternative solutions to market goods or services to consumers. This research aims to examine the potential of digital marketing so that business people can use it to survive. The research method used in this study is qualitative with a descriptive approach. The Covid-19 pandemic has required business actors to shift their marketing, promotion, and transaction strategies from traditional to digital. The results of this study recommend entrepreneurs develop digital marketing as a very effective option for reaching their target consumers.
Factors affecting customer satisfaction at Ahass Motorcycle Workshop in Bantul Area
Authors: Farhan Fikri , Murgiyanti Murgiyanti , Zalzalah Guruh Ghifar
Published: October 2023

in the Bantul area of Yogyakarta. Service quality, facilities, and product quality are hypothesized to influence customer satisfaction. This study uses quantitative methods. The primary data is collected through questionnaires to 160 consumers who have used repair or replacement services for their motorcycle parts at the AHASS repair shop in the Bantul area of Yogyakarta. The data in this study were processed using the SPSS analysis tool with multiple linear regression techniques. The results showed that service quality, facilities, and product quality positively and significantly affected customer satisfaction.
COMPANY EXTERNAL INFLUENCE ON SHARE PRICE CONSUMER GOODS INDUSTRY SECTOR
Authors: Efriyenti Dian , Azmiana Risca , Prima Argo Putra , Poniman Poniman
Published: October 2023

In order to gain from their stock investments, investors frequently attempt to pay close attention to fluctuations in stock prices on a planned basis. The purpose of this study is to ascertain how inflation and interest rates affect stock prices at publicly traded consumer products companies on the Indonesia Stock Exchange. Purposive sampling was utilized as the sampling method in this study, and 10 companies were eligible to participate. The F test results indicate a substantial effect, which means that both inflation and interest rates simultaneously affect stock prices in a way that makes it possible to examine the regression model used in this study. The results, partially using the t test, indicate.
Pembinaan Literasi Media pada Pelajar SMA Ananda Kota Batam dalam Pencegahan Disinformasi di Era New Normal
Authors: Cindoswari Ageng , Kundori Kundori , Handayani Nurma Dhona , Patimah Nenti Siti , Yansyah Tedy , Framana Qori , Rusli Gustama Putra , Porang Alfian Juanda Putra
Published: October 2023

Media literacy education as a form of effort to prevent the negative side of globalization which cannot be stopped is very important to do because it is not only because of the needs of today's information society, but also UNESCO's international mandate for all countries in the world. Media literacy education is highly recommended to be carried out in formal institutions/organizations or in the school environment. SMA Ananda is one of the educational institutions in the city of Batam that requires assistance regarding media literacy, especially for students. This training is carried out with the aim of providing (1). Knowledge of students in the city of Batam about the benefits and uses of the internet, (2). Knowledge of students in the city of Batam regarding media literacy (3). Skills for students regarding the spread of disinformation in the new normal era. This coaching will be carried out using lecture, discussion, and practice methods with a duration of 1 hour per session for 4 meetings involving 3 assistants alternately and on a scheduled basis. This coaching will be given to students at Ananda High School in Batam City, totaling around 20-30 people which will be held in the January-December 2021 range.
Pendidikan Adalah Faktor Penentu Daya Saing Bangsa
Authors: Sanga Laurensius Dihe , Wangdra Yvonne
Published: October 2023

The reality of the education system in Indonesia is continually evolving. This article aims to explore the relationship between education and national, even international, competitiveness. Indonesia's national competitiveness has fluctuated over the years. By examining various data, is there an educational factor that determines the nation's competitive position? Through the analysis of various documents and articles, including journals and books, it becomes evident that education is one of the key pillars of a nation's competitiveness. The author gathered material through library research and employed descriptive analysis. The author's findings indicate that education is a critical endeavor for a nation to enhance the quality of its human resources. Therefore, improving the quality and equity of education is essential because it is through education that individuals can become highly competitive and quality-driven individuals.
Protein quality assessment with a loss function designed for high-quality decoys
Authors: Roy Soumyadip , Ben-Hur Asa
Published: October 2023

Motivation: The prediction of a protein 3D structure is essential for understanding protein function, drug discovery, and disease mechanisms; with the advent of methods like AlphaFold that are capable of producing very high-quality decoys, ensuring the quality of those decoys can provide further confidence in the accuracy of their predictions.

Results: In this work, we describe Qϵ, a graph convolutional network (GCN) that utilizes a minimal set of atom and residue features as inputs to predict the global distance test total score (GDTTS) and local distance difference test (lDDT) score of a decoy. To improve the model’s performance, we introduce a novel loss function based on the ϵ-insensitive loss function used for SVM regression. This loss function is specifically designed for evaluating the characteristics of the quality assessment problem and provides predictions with improved accuracy over standard loss functions used for this task. Despite using only a minimal set of features, it matches the performance of recent state-of-the-art methods like DeepUMQA.

Availability: The code for Qϵ is available at https://github.com/soumyadip1997/qepsilon.
Targeted control of supporting pathways in paclitaxel biosynthesis with CRISPR-guided methylation
Authors: Brzycki Newton Cassandra , Young Eric M. , Roberts Susan C.
Published: October 2023

Introduction: Plant cell culture biomanufacturing is rapidly becoming an effective strategy for production of high-value plant natural products, such as therapeutic proteins and small molecules, vaccine adjuvants, and nutraceuticals. Many of these plant natural products are synthesized from diverse molecular building blocks sourced from different metabolic pathways. Even so, engineering approaches for increasing plant natural product biosynthesis have typically focused on the core biosynthetic pathway rather than the supporting pathways.

Methods: Here, we use both CRISPR-guided DNA methylation and chemical inhibitors to control flux through the phenylpropanoid pathway in Taxus chinensis, which contributes a phenylalanine derivative to the biosynthesis of paclitaxel (Taxol), a potent anticancer drug. To inhibit PAL, the first committed step in phenylpropanoid biosynthesis, we knocked down expression of PAL in Taxus chinensis plant cell cultures using a CRISPR-guided plant DNA methyltransferase (NtDRM). For chemical inhibition of downstream steps in the pathway, we treated Taxus chinensis plant cell cultures with piperonylic acid and caffeic acid, which inhibit the second and third committed steps in phenylpropanoid biosynthesis: cinnamate 4-hydroxylase (C4H) and 4-coumaroyl-CoA ligase (4CL), respectively.

Results: Knockdown of PAL through CRISPR-guided DNA methylation resulted in a profound 25-fold increase in paclitaxel accumulation. Further, through the synergistic action of both chemical inhibitors and precursor feeding of exogenous phenylalanine, we achieve a 3.5-fold increase in paclitaxel biosynthesis and a similar reduction in production of total flavonoids and phenolics. We also observed perturbations to both activity and expression of PAL, illustrating the complex transcriptional co-regulation of these first three pathway steps.

Discussion: These results highlight the importance of controlling the metabolic flux of supporting pathways in natural product biosynthesis and pioneers CRISPR-guided methylation as an effective method for metabolic engineering in plant cell cultures. Ultimately, this work demonstrates a powerful method for rewiring plant cell culture systems into next-generation chassis for production of societally valuable compounds.
The developments of cyan emitting phosphors to fulfill the cyan emission gap of white-LEDs
Authors: Khan Noor Zamin , Khan Sayed Ali , Chen Weilong , Padhiar Muhammad Amin , Abbas Muhammad Tahir , Ullah Zakir , Runowski Marcin , Xu Xin , Zheng Ren-Kui
Published: October 2023

Future generations of solid-state lighting (SSL) will prioritize the development of innovative luminescent materials with superior characteristics. The phosphors converted into white light-emitting diodes (white LEDs) often have a blue-green cavity. Cyan-emitting phosphor fills the spectral gap and produces “full-visible-spectrum lighting.” Full-visible spectrum lighting is beneficial for several purposes, such as light therapy, plant growth, and promoting an active and healthy lifestyle. The design of cyan garnet-type phosphors, like Ca2LuHf2Al3O12 (CLHAO), has recently been the subject of interest. This review study reports a useful cyan-emitting phosphor based on CLHAO composition with a garnet structure to have a cyan-to-green emitting color with good energy transfer. It could be employed as cyan filler in warm-white LED manufacturing. Due to its stability, ability to dope with various ions suitable for their desired qualities, and ease of synthesis, this garnet-like compound is a great host material for rare-earth ions. The development of CLHAO cyan-emitting phosphors has exceptionally high luminescence, resulting in high CRI and warm-white LEDs, making them a viable desire for LED manufacturing. The development of CLHAO cyan-emitting phosphors with diverse synthesis techniques, along with their properties and applications in white LEDs, are extensively covered in this review paper.
No risk, no fun…ctioning? Perceived climate risks, but not nature connectedness or self-efficacy predict climate anxiety
Authors: Reese Gerhard , Rueff Maria , Wullenkord Marlis C.
Published: October 2023

The consequences of climate change are becoming increasingly visible. Recent research suggests that people may respond to climate change and its predicted consequences with a specific anxiety. Yet, little is known about potential antecedents of climate anxiety. The current study aimed to understand the contribution of climate risk perception to climate anxiety, along with nature-connectedness, self-efficacy, and political orientation. With a sample of 204 German adults, we assessed these constructs together with environmental policy support that may result from climate anxiety. Stronger risk perception and a left political orientation predicted climate anxiety. Self-efficacy and nature connectedness, however, were unrelated to climate anxiety. In line with previous studies, climate anxiety correlated positively with environmental policy support but did not predict environmental policy support when controlling for climate risk perception. We discuss results with regard to further developing the concept of climate anxiety and its dynamics and suggest directions for future research.
Continental subduction of Adria in the Apennines and relation with seismicity and hazard
Authors: Chiarabba C. , Menichelli I. , Bianchi I. , Giacomuzzi G. , De Gori P.
Published: October 2023

The subduction of continental lithosphere is a complex process because the buoyancy of the crust is higher than the oceanic and should resist sinking into the mantle. Anyway, studies on the Alpine-Himalayan collision system indicate that a large portion of the continental crust is subducted, while some material is accreted in the orogens. The Apennine is a perfect case for studying how such processes evolve, thanks to high quality seismic images that illuminate a critical depth range not commonly resolved in many collisional settings. In this paper, we show the structure of the Apennines orogen, as jointly revealed by seismicity and deep structure from regional and teleseismic tomography and receiver function profiles. The westward subducting Adria lithosphere is well defined along the orogen showing a mid-crustal delamination. Seismicity within the underthrusting lower crust and velocity anomalies in the mantle wedge highlight how the subduction evolution is entangled with the liberation of fluids. The eclogitization of subducted material enhances the fluid release into the wedge, the delamination and retreat of the Adria plate. This delamination/subduction generates a coupled compression and extension system that migrates eastward following the retreat of the lithosphere, with broad sets of normal faults that invert or interfere with pre-existing compressional structures all over the roof plate. The sparseness and non-ubiquity of intermediate depth earthquakes along the subduction panel suggest that the brittle response of the subducting crust is governed by its different composition and fluid content. Therefore, the lower crust composition appears essential in conditioning the evolution of continental subduction.
Elevated CO2 does not improve seedling performance in a naturally regenerated oak woodland exposed to biotic stressors
Authors: Mayoral Carolina , Ioni Susanna , Luna Estrella , Crowley Liam M. , Hayward Scott A. L. , Sadler Jon P. , MacKenzie A. Robert
Published: October 2023

Introduction

Insect herbivores and biotrophic pathogens are major stressors influencing natural regeneration in woodlands. Information on the effect of elevated CO2 (eCO2) on plant-insect-pathogen interactions under natural conditions is lacking.

Methods

We studied the effects of eCO2 on leaf-out phenology, as well as on levels of insect herbivory and powdery mildew (PM), i.e., reduction of leaf photosynthetic material. We then assessed the combined impacts of these biotic stressors and eCO2 on seedling photosynthesis and growth. A total of 92 naturally recruited and 114 potted seedlings of 5 temperate tree species (Quercus robur, Acer pseudoplatanus, Corylus avellana, Crataegus monogyna, and Ilex aquifolium) within a mature oak woodland were studied.

Results

We found that eCO2 advanced leaf-out phenology and was a significant explanatory variable for growth and physiological performance in potted seedlings. Potted oak seedlings experienced 11-fold higher tissue loss from insect herbivory than natural seedlings. The earliest leaf-flushing species, hawthorn, and the evergreen holly were resistant to insect attack and were not affected by PM. Oak was defoliated most but showed the highest regeneration capacity. Hazel was more resistant to PM infection than oak and sycamore. Despite being highly infected by PM, sycamore was less affected than oak. The more vigorous sycamore and oak seedlings suffered more severe PM disease.

Conclusion

No evidence emerged that eCO2 enhances natural regeneration under biotic stress for any of the species studied.
A novel cold-chain free VCG-based subunit vaccine protects against Chlamydia abortus-induced neonatal mortality in a pregnant mouse model
Authors: Richardson Shakyra , Bell Courtnee R. , Medhavi Fnu , Tanner Tayhlor , Lundy Stephanie , Omosun Yusuf , Igietseme Joseph U. , Eko Francis O.
Published: October 2023

Chlamydia abortus (Cab) causes spontaneous abortion and neonatal mortality in infected ruminants and pregnant women. Most Cab infections are asymptomatic, although they can be treated with antibiotics, signifying that control of these infections may require alternative strategies, including the use of effective vaccines. However, the limitations imposed by live attenuated and inactivated vaccines further suggest that employment of subunit vaccines may need to be considered. The efficacy of a newly generated Vibrio cholerae ghost (rVCG)-based subunit vaccine harboring the N-terminal portion of the Cab Pmp18D protein (rVCG-Pmp18.3) in preventing Cab-induced abortion or neonatal mortality was evaluated in pregnant mice. Mice were intranasally (IN) immunized and boosted twice, 2 weeks apart with the vaccine, and immunized and unimmunized mice were caged with males 4 weeks postimmunization. The mice were then infected either IN or transcervically (TC) 10 days after pregnancy, and the fertility rate was determined 7 days postpartum. Eight days after delivery, the mice were sacrificed, and Cab infectivity in the lungs and spleens was evaluated by culturing tissue homogenates in tissue culture. Our results demonstrated that the vaccine induced immune effectors that mediated complete clearance of infection in the lungs and significantly reduced Cab infectivity in the spleen following IN immunization. Vaccine immunization also afforded protection against Cab-induced upper genital tract pathology (uterine dilation). Furthermore, while there was no incidence of abortion in both immunized and unimmunized mice, immunized mice were completely protected against neonatal mortality compared to unimmunized infected controls, which lost a significant percentage of their litter 7 days postpartum. Our results establish the capability of the rVCG-Pmp18.3 vaccine to prevent infection in the lungs (mucosal) and spleen (systemic) and protect mice from Cab-induced tubal pathologies and neonatal mortality, a hallmark of Cab infection in ruminants. To advance the commercial potential of this vaccine, future studies will optimize the antigen dose and the number of vaccine doses required for protection of ruminants.
Effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 Omicron BA.2 infection in Guangdong, China: a cohort study
Authors: He Xiaofeng , Zeng Biao , Wang Ye , Pang Yulian , Zhang Meng , Hu Ting , Liang Yuanhao , Kang Min , Tang Shixing
Published: October 2023

The effectiveness of COVID-19 vaccines wanes over time and the emergence of the SARS-CoV-2 Omicron variant led to the accelerated expansion of efforts for booster vaccination. However, the effect and contribution of booster vaccination with inactivated COVID-19 vaccines remain to be evaluated. We conducted a retrospective close contacts cohort study to analyze the epidemiological characteristics and Omicron infection risk, and to evaluate the effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 infection, symptomatic COVID-19, and COVID-19 pneumonia during the outbreaks of Omicron BA.2 infection from 1 February to 31 July 2022 in Guangdong, China. A total of 46,547 close contacts were identified while 6.3% contracted Omicron BA.2 infection, 1.8% were asymptomatic infection, 4.1% developed mild COVID-19, and 0.3% had COVID-19 pneumonia. We found that females and individuals aged 0-17 or ≥ 60 years old were more prone to SARS-CoV-2 infection. The vaccinated individuals showed lower infection risk when compared with the unvaccinated people. The effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 was 28.6% (95% CI: 11.6%, 35.0%) and 39.6% (95% CI: 30.0, 47.9) among adults aged ≥ 18 years old, respectively when compared with full vaccination. Booster vaccination provided a moderate level of protection against SARS-CoV-2 infection (VE: 49.9%, 95% CI: 22.3%-67.7%) and symptomatic COVID-19 (VE: 62.6%, 95% CI: 36.2%-78.0%) among adults aged ≥ 60 years old. Moreover, the effectiveness of booster vaccination was 52.2% (95% CI: 21.3%, 70.9%) and 83.8% (95% CI: 28.1%, 96.3%) against COVID-19 pneumonia in adults aged ≥ 18 and ≥ 60 years old, respectively. The reduction of absolute risk rate of COVID-19 pneumonia in the booster vaccination group was 0·96% (95% CI: 0.33%, 1.11%), and the number needed to vaccinate to prevent one case of COVID-19 pneumonia was 104 (95% CI: 91, 303) in adults aged ≥ 60 years old. In summary, booster vaccination with inactivated COVID-19 vaccines provides a low level of protection against infection and symptomatic in adults of 18-59 years old, and a moderate level of protection in older adults of more than 60 years old, but a high level of protection against COVID-19 pneumonia in older adults.
Omicron subvariants illustrate reduced respiratory tissue penetration, cell damage and inflammatory responses in human airway epithelia
Authors: Zaderer Viktoria , Abd El Halim Hussam , Wyremblewsky Anna-Lena , Lupoli Gaia , Dächert Christopher , Muenchhoff Maximilian , Graf Alexander , Blum Helmut , Lass-Flörl Cornelia , Keppler Oliver T. , Huber Lukas A. , Posch Wilfried , Wilflingseder Doris
Published: October 2023

Introduction

To explore whether the reported lower pathogenicity in infected individuals of variant of concern (VoC) Omicron and its current subvariants compared to VoC Delta may be related to fundamental differences in the initial virus-tissue interaction, we assessed their ability to penetrate, replicate and cause damage in a human 3D respiratory model.

Methods

For this, we used TEER measurements, real-time PCR, LDH, cytokine and complex confocal imaging analyses.

Results and discussion

We observed that Delta readily penetrated deep into the respiratory epithelium and this was associated with major tissue destruction, high LDH activity, high viral loads and pronounced innate immune activation as observed by intrinsic C3 activation and IL-6 release at infection sites. In contrast, Omicron subvariants BA.5, BQ.1.1 and BF7 remained superficially in the mucosal layer resulting merely in outward-directed destruction of cells, maintenance of epithelial integrity, minimal LDH activity and low basolateral release of virus at infection sites, as well as significantly smaller areas of complement activation and lower IL-6 secretion. Interestingly, also within Omicron subvariants differences were observed with newer Omicron subvariants BQ.1.1 and BF.7 illustrating significantly reduced viral loads, IL-6 release and LDH activity compared to BA.5. Our data indicate that earliest interaction events after SARS-CoV-2 transmission may have a role in shaping disease severity.
Extracellular nicotinamide phosphoribosyltransferase: role in disease pathophysiology and as a biomarker
Authors: Semerena Elise , Nencioni Alessio , Masternak Krzysztof
Published: October 2023

Nicotinamide phosphoribosyltransferase (NAMPT) plays a central role in mammalian cell metabolism by contributing to nicotinamide adenine dinucleotide biosynthesis. However, NAMPT activity is not limited to the intracellular compartment, as once secreted, the protein accomplishes diverse functions in the extracellular space. Extracellular NAMPT (eNAMPT, also called visfatin or pre-B-cell colony enhancing factor) has been shown to possess adipocytokine, pro-inflammatory, and pro-angiogenic activities. Numerous studies have reported the association between elevated levels of circulating eNAMPT and various inflammatory and metabolic disorders such as obesity, diabetes, atherosclerosis, arthritis, inflammatory bowel disease, lung injury and cancer. In this review, we summarize the current state of knowledge on eNAMPT biology, proposed roles in disease pathogenesis, and its potential as a disease biomarker. We also briefly discuss the emerging therapeutic approaches for eNAMPT inhibition.
Novel insight into cGAS-STING pathway in ischemic stroke: from pre- to post-disease
Authors: Ma Xiaoqi , Xin Dan , She Ruining , Liu Danhong , Ge Jinwen , Mei Zhigang
Published: October 2023

Ischemic stroke, a primary cause of disability and the second leading cause of mortality, has emerged as an urgent public health issue. Growing evidence suggests that the Cyclic GMP-AMP synthase (cGAS)- Stimulator of interferon genes (STING) pathway, a component of innate immunity, is closely associated with microglia activation, neuroinflammation, and regulated cell death in ischemic stroke. However, the mechanisms underlying this pathway remain inadequately understood. This article comprehensively reviews the existing literature on the cGAS-STING pathway and its multifaceted relationship with ischemic stroke. Initially, it examines how various risk factors and pre-disease mechanisms such as metabolic dysfunction and senescence (e.g., hypertension, hyperglycemia, hyperlipidemia) affect the cGAS-STING pathway in relation to ischemic stroke. Subsequently, we explore in depth the potential pathophysiological relationship between this pathway and oxidative stress, endoplasmic reticulum stress, neuroinflammation as well as regulated cell death including ferroptosis and PANoptosis following cerebral ischemia injury. Finally, it suggests that intervention targeting the cGAS-STING pathway may serve as promising therapeutic strategies for addressing neuroinflammation associated with ischemic stroke. Taken together, this review concludes that targeting the microglia cGAS-STING pathway may shed light on the exploration of new therapeutic strategies against ischemic stroke.
Single cell transcriptomics reveals cell type specific features of developmentally regulated responses to lipopolysaccharide between birth and 5 years
Authors: Read James F. , Serralha Michael , Armitage Jesse D. , Iqbal Muhammad Munir , Cruickshank Mark N. , Saxena Alka , Strickland Deborah H. , Waithman Jason , Holt Patrick G. , Bosco Anthony
Published: October 2023

Background

Human perinatal life is characterized by a period of extraordinary change during which newborns encounter abundant environmental stimuli and exposure to potential pathogens. To meet such challenges, the neonatal immune system is equipped with unique functional characteristics that adapt to changing conditions as development progresses across the early years of life, but the molecular characteristics of such adaptations remain poorly understood. The application of single cell genomics to birth cohorts provides an opportunity to investigate changes in gene expression programs elicited downstream of innate immune activation across early life at unprecedented resolution.

Methods

In this study, we performed single cell RNA-sequencing of mononuclear cells collected from matched birth cord blood and 5-year peripheral blood samples following stimulation (18hrs) with two well-characterized innate stimuli; lipopolysaccharide (LPS) and Polyinosinic:polycytidylic acid (Poly(I:C)).

Results

We found that the transcriptional response to LPS was constrained at birth and predominantly partitioned into classical proinflammatory gene upregulation primarily by monocytes and Interferon (IFN)-signaling gene upregulation by lymphocytes. Moreover, these responses featured substantial cell-to-cell communication which appeared markedly strengthened between birth and 5 years. In contrast, stimulation with Poly(I:C) induced a robust IFN-signalling response across all cell types identified at birth and 5 years. Analysis of gene regulatory networks revealed IRF1 and STAT1 were key drivers of the LPS-induced IFN-signaling response in lymphocytes with a potential developmental role for IRF7 regulation.

Conclusion

Additionally, we observed distinct activation trajectory endpoints for monocytes derived from LPS-treated cord and 5-year blood, which was not apparent among Poly(I:C)-induced monocytes. Taken together, our findings provide new insight into the gene regulatory landscape of immune cell function between birth and 5 years and point to regulatory mechanisms relevant to future investigation of infection susceptibility in early life.
Interactions between innate immunity and insulin signaling affect resistance to infection in insects
Authors: Darby Andrea M. , Lazzaro Brian P.
Published: October 2023

An active immune response is energetically demanding and requires reallocation of nutrients to support resistance to and tolerance of infection. Insulin signaling is a critical global regulator of metabolism and whole-body homeostasis in response to nutrient availability and energetic needs, including those required for mobilization of energy in support of the immune system. In this review, we share findings that demonstrate interactions between innate immune activity and insulin signaling primarily in the insect model Drosophila melanogaster as well as other insects like Bombyx mori and Anopheles mosquitos. These studies indicate that insulin signaling and innate immune activation have reciprocal effects on each other, but that those effects vary depending on the type of pathogen, route of infection, and nutritional status of the host. Future research will be required to further understand the detailed mechanisms by which innate immunity and insulin signaling activity impact each other.
The regulation of antiviral innate immunity through non-m6A RNA modifications
Authors: Shen Shenghai , Zhang Li-Sheng
Published: October 2023

The post-transcriptional RNA modifications impact the dynamic regulation of gene expression in diverse biological and physiological processes. Host RNA modifications play an indispensable role in regulating innate immune responses against virus infection in mammals. Meanwhile, the viral RNAs can be deposited with RNA modifications to interfere with the host immune responses. The N6-methyladenosine (m6A) has boosted the recent emergence of RNA epigenetics, due to its high abundance and a transcriptome-wide widespread distribution in mammalian cells, proven to impact antiviral innate immunity. However, the other types of RNA modifications are also involved in regulating antiviral responses, and the functional roles of these non-m6A RNA modifications have not been comprehensively summarized. In this Review, we conclude the regulatory roles of 2’-O-methylation (Nm), 5-methylcytidine (m5C), adenosine-inosine editing (A-to-I editing), pseudouridine (Ψ), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N6,2’-O-dimethyladenosine (m6Am), and N4-acetylcytidine (ac4C) in antiviral innate immunity. We provide a systematic introduction to the biogenesis and functions of these non-m6A RNA modifications in viral RNA, host RNA, and during virus-host interactions, emphasizing the biological functions of RNA modification regulators in antiviral responses. Furthermore, we discussed the recent research progress in the development of antiviral drugs through non-m6A RNA modifications. Collectively, this Review conveys knowledge and inspiration to researchers in multiple disciplines, highlighting the challenges and future directions in RNA epitranscriptome, immunology, and virology.
Do costal erosion and urban development threat loggerhead sea turtle nesting? Implications for sandy beach management
Authors: Costa Leonardo Lopes , Bulhões Eduardo Manuel Rosa , Caetano João Pedro Almeida , Arueira Vitor Figueira , de Almeida Daniella Torres , Vieira Tatiane Bittar , Cardoso Leandro Jorge Telles , Zalmon Ilana Rosental
Published: October 2023

Nest beach selection by sea turtles at a regional scale may depend on upper shore environmental cues. Thus, the variability of sandy beach conditions, including coastal erosion rates and urban development can affect their nesting ecology. Almost half of worldwide sandy beaches are suffering from erosion and most of them are located in highly developed areas. This can lead to shore stretches with coastal squeeze and loss of habitat for beach-dependent species such as sea turtles. Understanding whether an endangered species, such as the loggerhead sea turtle Caretta caretta (Linnaeus, 1758), selects certain beaches to nest is the first step in devising mitigation strategies for human activities and climate change impacts. We predicted that the occurrence of loggerhead nests along 62 km of sandy beaches in southeastern Brazil is negatively related to higher urbanization levels and extreme erosion. A total of 731 nests of the loggerhead sea turtle were recorded in the 2022-2023 nesting season. Only 6% of those nests were found on beach sectors with severe and extreme erosion. The probability of laying a nest was negatively related to erosion rate. Also, approximately 50% of nests were found on low-urbanized beaches; thus, the higher the urbanization, the lower the probability of a turtle laying a nest. Nature-based solutions to recover the beach-dune system are recommended in order to mitigate coastal erosion where loggerheads are avoiding nesting. This should be coupled with management planning of the protected areas where nests are laid and must include nest relocation and monitoring as priority actions.
A human pilot study on positive electrostatic charge effects in solid tumors of the late-stage metastatic patients
Authors: Zandi Ashkan , Shojaeian Fatemeh , Abbasvandi Fereshteh , Faranoush Mohammad , Anbiaee Robab , Hoseinpour Parisa , Gilani Ali , Saghafi Mohammad , Zandi Afsoon , Hoseinyazdi Meisam , Davari Zahra , Miraghaie Seyyed Hossein , Tayebi Mahtab , Taheri Morteza Sanei , Ardestani S. Mehdi Samimi , Sheikhi Mobarakeh Zahra , Nikshoar Mohammad Reza , Enjavi Mohammad Hossein , Kordehlachin Yasin , Mousavi-kiasary S. M. Sadegh , Mamdouh Amir , Akbari Mohammad Esmaeil , Yunesian Masud , Abdolahad Mohammad
Published: October 2023

Background

Correlative interactions between electrical charges and cancer cells involve important unknown factors in cancer diagnosis and treatment. We previously reported the intrinsic suppressive effects of pure positive electrostatic charges (PEC) on the proliferation and metabolism of invasive cancer cells without any effect on normal cells in cell lines and animal models. The proposed mechanism was the suppression of pro-caspases 3 and 9 with an increase in Bax/Bcl2 ratio in exposed malignant cells and perturbation induced in the KRAS pathway of malignant cells by electrostatic charges due to the phosphate molecule electrostatic charge as the trigger of the pathway. This study aimed to examine PECs as a complementary treatment for patients with different types of solid metastatic tumors, who showed resistance to chemotherapy and radiotherapy.

Methods

In this study, solid metastatic tumors of the end-stage patients (n = 41) with various types of cancers were locally exposed to PEC for at least one course of 12 days. The patient’s signs and symptoms, the changes in their tumor size, and serum markers were followed up from 30 days before positive electrostatic charge treating (PECT) until 6 months after the study.

Results

Entirely, 36 patients completed the related follow-ups. Significant reduction in tumor sizes and cancer-associated enzymes as well as improvement in cancer-related signs and symptoms and patients’ lifestyles, without any side effects on other tissues or metabolisms of the body, were observed in more than 80% of the candidates.

Conclusion

PECT induced significant cancer remission in combination with other therapies. Therefore, this non-ionizing radiation would be a beneficial complementary therapy, with no observable side effects of ionizing radiotherapy, such as post-radiation inflammation.