bluuebunny/crossref_metadata_2025 huggingface dataset:
Is gentamicin a viable therapeutic option for treating resistant Neisseria gonorrhoeae in New South Wales?
Authors: Armstrong Benjamin H , Limnios Athena , Lewis David A , Hogan Tiffany , Kundu Ratan , Ray Sanghamitra , Shoushtari Masoud , El Nasser Jasmin , Driscoll Tim , Lahra Monica M
Published: February 2021

The key issues with Neisseria gonorrhoeae infections, in Australia and elsewhere, are coincident increases in disease rates and in antimicrobial resistance (AMR), although these factors have not been shown to be correlated. Despite advances in diagnosis, control of this disease remains elusive, and incidence in Australia continues to increase. Of the Australian jurisdictions, New South Wales (NSW) has the highest N. gonorrhoeae notifications, and over the five-year period 2015–2019, notifications in NSW have increased above the national average (by 116% versus 85%, respectively).
Gonococcal disease control is reliant on effective antibiotic regimens. However, escalating AMR in N. gonorrhoeae is a global health priority, as the collateral injury of untreated infections has substantive impacts on sexual and newborn health. Currently, our first-line therapy for gonorrhoea is also our last line, with no ideal alternative identified. Despite some limitations, gentamicin is licensed and readily available in Australia, and is proposed for treatment of resistant N. gonorrhoeae in national guidelines; however, supportive published microbiological data are lacking.
Analysis of gonococcal resistance patterns within Australia for the period 1991–2019, including 35,000 clinical isolates from NSW, illustrates the establishment and spread of population-level resistance to all contemporaneous therapies. An analysis of gentamicin susceptibility on 2,768 N. gonorrhoeae clinical isolates from NSW, for the period 2015–2020, demonstrates that the median minimum inhibitory concentration (MIC) for gentamicin in NSW has remained low, at 4.0 mg/L, and resistance was not detected in any isolate. There has been no demonstration of MIC drift over time (p = 0.91, Kruskal-Wallis test), nor differences in MIC distributions according to patients’ sex or site of specimen collection.
This is the first large-scale evaluation of gentamicin susceptibility in N. gonorrhoeae in Australia. No gentamicin resistance was detected in clinical isolates, 2015–2020, hence this is likely to be an available treatment option for resistant gonococcal infections in NSW.
THE CHANGES IN CRIMINAL TRIAL PROCEEDINGS DURING COVID-19: CHALLENGES AND PROBLEMS
Authors: Santosa Dewa Gede Giri
Published: February 2021

COVID-19 pandemic forced the Supreme Court of the Republic of Indonesia to make several adjustments to the courts system of all in Indonesia, one of which was the adjustment of criminal procedural law in criminal trial proceedings. Some regulations were made related to the criminal trial proceedings in Indonesia to adjust to government policies that limit physical interaction between people. However, those regulations made by the Supreme Court also comes with challenges and problems in its implementation. This research was made using the normative legal research method, in purpose to find the changes made in the criminal trial proceedings in Indonesia due to the COVID-19 pandemic and also the challenges and problems encountered in its implementation. Through this research, several things that should be addressed for the change in the criminal trial proceedings amid the COVID-19 pandemic in Indonesia will not only accommodate the principle of expediency, but also the principles of justice and legal certainty .
ЗАСТОСУВАННЯ МОБІЛЬНОГО ДОДАТКА SSUQUESTIONNAIRE-M ДЛЯ КОНТРОЛЮ ЗНАНЬ СТУДЕНТІВ ІНЖЕНЕРНИХ СПЕЦІАЛЬНОСТЕЙ
Authors: Алєксєєв Олександр Миколайович , Маландій Тетяна Юріївна , Требухов Дмитро Вікторович
Published: February 2021

У статті розглянуто сучасні тенденції використання мобільних пристроїв для тестового контролю знань. Проведено аналіз ринку програмних продуктів, які призначені для створення мобільних додатків. За основу аналізу прийнято рівень комп'ютерної грамотності, який потрібен під час використання розглянутих програмних продуктів для розроблення мобільних додатків. З цієї класифікаційної ознаки виділено три групи програмних засобів із такими вимогами до компетенцій проєктувальників мобільних пристроїв: 1) повинні мати професійні навички програмування; 2) не вимагається знання мов програмування; 3) з уміннями проєктувати на базі вебінтерфейсу. Відзначено, що різноманітність представлених на ринку програмних продуктів і закладені в них функції надають можливість викладачам створювати якісні додатки для проведення тестового контролю знань студентів інженерних спеціальностей на мобільних пристроях. Зроблено припущення, що впровадження мобільних пристроїв у навчальний процес для проведення контрольних заходів буде успішнішим, якщо враховувати специфіку практичних занять з професійної та практичної підготовки студентів, майбутніх інженерів. Особливістю цих занять є те, що в якості вихідних даних і результатів виконання навчальних завдань часто використовуються графічні зображення. Після закінчення практичних занять студенти інженерних спеціальностей зобов'язані знати конструкцію складних технічних пристроїв і навчитися ними користуватися. Тому для проведення контролю знань треба передбачити використання в тесті завдань з графічними ілюстраціями, зокрема із зображеннями великого розміру. Важливо проводити контроль знань у навчальних лабораторіях і виробничих приміщеннях, де мають проходити практичні заняття, але там не завжди є можливість забезпечення доступу до мобільного зв'язку.Описано мобільний додаток SSUquestionnaire-m, який надає можливість врахувати зазначені в статті особливості інженерної освіти та охопити контрольними заходами всіх студентів, які присутні на занятті. Водночас не потрібно переходити на суміщені технології мобільного контролю та, обмежуючись можливістю користуватися лише мобільними пристроями студентів, проводити всі контрольні заходи в одну сесію.
Efeito do agente carreador na obtenção e caracterização do suco da laranja (citrus sinensis) por atomização
Authors: Almeida Thais Cartaxo de , Silva Veruscka Araújo , Ferreira Heber Sivini
Published: February 2021

A laranja (Citrus sinensis) é o fruto cítrico de origem asiática com sabor variando do doce ao levemente ácido e rico em ácido ascórbico (vitamina C), além de outros nutrientes sendo o Brasil o maior produtor mundial da fruta. A perecíbilidade pode ser contornada por meio de um secador spray dryer, que produz um pó padronizado e estável com facilidade de transporte e armazenamento. O presente estudo buscou analisar o efeito do uso de maltodextrina como agente carreador em diferentes concentrações e do uso de diferentes temperaturas do ar de entrada na obtenção do suco de laranja em pó através da secagem em spray dryer observando a conservação de suas propriedades físico-químicas. Foram realizadas as analises físico-químicas com o pó produzido e com uma amostra comercial para comparação. O processo de secagem se mostrou viável com rendimentos em torno de 66%, as propriedades do suco reidratado foram conservadas em sua maioria apresentando uma caracterização eficaz em relação ao produto similar comercial.
Adsorção do corante básico Verde Malaquita via carvão ativado a partir do caroço de açaí
Authors: Sousa Antonio Almir Oliveira de , Oliveira Thalia Silva , Azevedo Luiz Eduardo Chaves de , Nobre João Rodrigo Coimbra , Stefanelli Wilson Fernando Rodrigues , Costa Thiago Antônio Paixão de Sousa , Silva João Paulo Sousa da , Barral Ana Vitoria Silva
Published: February 2021

Os corantes sintéticos são amplamente utilizados nos diversos seguimentos industriais, gerando um potencial poluente aos corpos hídricos. Desta forma, existindo grande necessidade de realizar-se tratamento adequado desse tipo de efluente, este estudo observou a eficiência na remoção do corante Verde Malaquita utilizando como adsorvente o Carvão Ativado (CA) produzido a partir do caroço de açaí (Euterpe oleracea), resíduo comumente gerado na região Amazônica. Na produção do CA foram utilizados dois agentes ativantes, Ácido Fosfórico (H3PO4), sendo denominado de CAG-A e o Hidróxido de sódio (NaOH), sendo denominado de CAG-B. A caracterização do CA foi realizada através das análises FTIR, ATG/ATD, área BET, e MEV/EDS. Para determinação da capacidade de adsorção bem como estudar e entender os mecanismos e etapas controladoras do processo de adsorção, os dados experimentais foram ajustados aos modelos matemáticos de Langmuir e Freundlich e aos modelos cinéticos de Pseudo-Primeira Ordem, Pseudo-Segunda Ordem e Difusão Intrapartícula. As análises para caracterização dos CA’s indicaram a presença de grupos funcionais ácidos, carregando negativamente a superfície de CAG-A e CAG-B, favorecendo o processo de adsorção, uma vez que o adsorbato deste estudo é um corante catiônico. Os dados experimentais tanto pra CAG-A como para CAG-B melhor se ajustaram à isoterma de Freundlich, bem como também, o modelo cinético de Pseudo-Segunda Ordem teve melhor ajuste em ambos os carvões. A adsorção do Verde Malaquita em CAG-A e CAG-B mostrou-se eficiente para os CA’s, obtendo-se valores de qmax = 113,9 mg/g e 668,88 mg/g respectivamente.
TUNING DARI PENGENDALI SUHU PADA OUTLET FURNACE-3 DI PPSDM MIGAS, CEPU
Authors: Azizah Nofiatul , Munawaroh Siti Iffah , Mufid Mufid , Suhadno Afdal , Subur Muh.
Published: February 2021

Furnace-3 di PPSDM Migas Cepu berfungsi untuk memanaskan crude oil sebelum masuk ke evaporator.  Penelitian ini dilakukan karena tidak pernah dilakukan tuning terhadap pengendali suhu pada outlet furnace.  Tujuan dilakukannya penelitian ini adalah untuk menentukan nilai parameter baru (Kp, τI dan τD untuk  Temperature Indicator Controller dan Kp dan τI untuk Pressure Indicator Controller) dengan menggunakan berbagai metode diantaranya metode Ziegler-Nichols, Chien-Servo, dan Astrom and Hagglund-Regulator serta  menentukan hasil analisis terbaik diantara metode tersebut. Penelitian dilakukan dengan menganalisis  pengendali suhu pada outlet Furnace-3 di PPSDM Migas Cepu dan tuning menggunakan berbagai metode yang  disimulasikan dengan Simulink matlab. Nilai parameter baru (Kp, τI dan τD) Temperature Indicator Controller  dari metode Ziegler-Nichols adalah 924, 10 dan 2.5, dari metode Chien-Servo adalah 462, 77 dan 2.5, dan dari  metode Astrom and Hagglund-Regulator adalah 723.8, 10 dan 2.5. Nilai parameter baru (Kp dan τI) Pressure  Indicator Controller dari metode Ziegler-Nichols adalah 54 dan 16.65, dari metode Chien-Servo adalah 21 dan  3.51, dan dari metode Astrom and Hagglund-Regulator 42 dan 11.5. Nilai parameter baru pressure indicator  controller yang paling optimal adalah parameter dari metode Chien-Servo, sedangkan nilai parameter baru (Kp,  τI dan τD) temperature indicator controller yang paling optimal adalah 75, 0.85 dan 2.8.
PEMANFAATAN FLY ASH SEBAGAI MATERIAL ADSORBEN UNTUK MENURUNKAN KANDUNGAN LOGAM FE PADA LIMBAH CAIR DI UNIT WASTE WATER TREATMENT PLANT PT POMI
Authors: Wardani Avielia Putri , Maulidz Safirda Dwi , Takwanto Anang , Yulianto Erwan
Published: February 2021

Penelitian ini dilakukan dengan memanfaatkan abu terbang batubara teraktivasi dan antrasit sebagai adsorben  ion logam berat. Tujuan dari penelitian ini adalah untuk mengetahui pengaruh konsentrasi NaOH, suhu aktivasi  fisika dan interaksi antara NaOH dengan suhu aktivasi fisika terhadap penurunan kandungan logam Fe pada  limbah cair di PT POMI, serta untuk mengetahui pengaruh jenis adsorben terhadap penurunan kandungan  logam Fe pada limbah cair PT POMI. Penelitian ini dimulai dengan mengaktivasi abu terbang, dengan 2 metode,  yang pertama metode kimia dalam suasana basa menggunakan kosentrasi NaOH 1 M, kosentrasi NaOH 2 M,  kosentrasi NaOH 3 M dan yang kedua metode fisika menggunakan variabel suhu 100°C, 120°C, 140°C dan 160°C  selama 1 jam. Abu terbang yang telah diaktivasi dan antrasit (tanpa aktivasi) kemudian digunakan sebagai  adsorben limbah cair PT POMI. Hasil adsorpsi diuji dengan AAS untuk mengetahui penurunan kandungan  logamnya. Hasil penelitian menunjukkan bahwa penurunan kandungan logam Fe paling baik sebesar 4,459 ppm  pada penggunaan larutan NaOH 3 M dengan suhu 160°C dari konsentrasi awal sebelum adsorpsi sebesar 4,46  ppm menjadi 0,001 ppm. Sedangkan hasil adsorpsi menggunakan adsorben antrasit penurunan kandungan  logam Fe pada limbah cair sebesar 2,31 ppm dengan persentase penurunan sebesar 51,84%. Hal tersebut telah  memenuhi standar syarat kandungan logam yang ada di PT POMI yaitu maksimal 3 ppm.
Genetic Code Expansion of Vibrio natriegens
Authors: Ozer Eden , Alfonta Lital
Published: February 2021

Escherichia coli has been considered as the most used model bacteria in the majority of studies for several decades. However, a new, faster chassis for synthetic biology is emerging in the form of the fast-growing gram-negative bacterium Vibrio natriegens. Different methodologies, well established in E. coli, are currently being adapted for V. natriegens in the hope to enable a much faster platform for general molecular biology studies. Amongst the vast technologies available for E. coli, genetic code expansion, the incorporation of unnatural amino acids into proteins, serves as a robust tool for protein engineering and biorthogonal modifications. Here we designed and adapted the genetic code expansion methodology for V. natriegens and demonstrate an unnatural amino acid incorporation into a protein for the first time in this organism.
A Novel Molecular Method for Simultaneous Identification of Vibrio parahaemolyticus 57 K-Serogroups Using Probe Melting Curve Analysis
Authors: Lu Linying , Li Minxu , Li Yinghui , Jiang Min , Jiang Yixiang , Shi Xiaolu , Zuo Le , Wang Lei , Bian Shengzhe , Qiu Yaqun , Cai Rui , Liao Yiqun , Li Qingge , Li Liqiang , Hu Qinghua
Published: February 2021

The serotyping of Vibrio parahaemolyticus, which is crucial to the surveillance and detection of outbreaks of vibriosis infection, has been widely used in many countries. In this study, we developed a molecular assay, named multiplex ligation reaction based on probe melting curve analysis (MLMA), for simultaneous identification of V. parahaemolyticus 57 K-serogroups. Based on the previous genomes of 418 strains including 39 K-serogroups and the 18 K-serogroups sequences from public databases, we obtained 57 K-serogroups specific gene sequences for designing primers and probes. The developed MLMA assay for identifying the V. parahaemolyticus 57 K-serogroups showed high reproducibility, with the intra- and inter-assay standard deviations and coefficients of variation of no more than 1°C and 1%, respectively. The limit of detection for all gene targets ranged from 0.1 to 1.0 ng/µl. We validated the MLMA assay with a double-blind test identifying 595 V. parahaemolyticus isolates using conventional serotyping methods for comparison. The results showed the kappa value between the MLMA assay and the traditional serological method was 0.936 and that there was a 96.97% consistency rate with conventional serotyping methods for all detected isolates. Additionally, five rare K-serogroups were identified using the MLMA assay, as well as 18 strains that could not be identified using the traditional serotyping method. Thus, the MLMA assay provides a rapid, robust, and promising tool for the molecular serotyping of V. parahaemolyticus K-serogroups and has the potential application to the detection of outbreaks and surveillance of V. parahaemolyticus infection.
Dynamic Alterations of Oral Microbiota Related to Halitosis in Preschool Children
Authors: Zhang Yu , Zhu Ce , Cao Guizhi , Zhan Jingyu , Feng Xiping , Chen Xi
Published: February 2021

Objective

This longitudinal study was aimed to evaluate the dynamic shift in oral microbiota during the process of halitosis progression among preschool children.

Methods

The oral examinations, questionnaires and tongue coating specimens were collected at the baseline and 12-month follow-up. All children were oral healthy at the enrollment. At the 12-month follow-up, children who developed halitosis were included to the halitosis group (n = 10). While children who matched the age, gender, kindergarten and without halitosis were included to the control group (n = 10). 16S rRNA gene sequencing was used to reveal the shift of the tongue coating microbiome in these children during the 12- month period with the Human Oral Microbiome Database.

Results

A remarkable shift in relative abundance of specific bacteria was observed prior to halitosis development. The principal coordinates and alpha diversity analyses revealed different shifting patterns of halitosis and the healthy participants’ microbiome structures and bacterial diversity over the 12-month follow-up. Both groups showed variable microbiota community structures before the onset of halitosis. Halitosis-enriched species Prevotella melaninogenica, Actinomyces sp._HMT_180 and Saccharibacteria TM7_G-1_bacterium_HMT_352 were finally selected as biomarkers in the halitosis-onset prediction model after screening, with a prediction accuracy of 91.7%.

Conclusions

The microbiome composition and relative abundance of the tongue coatings in the halitosis and control groups remarkably differed, even prior to the onset of the clinical manifestations of halitosis. The halitosis prediction model constructed on the basis of tongue coating microbiome biomarkers indicated the microbial shifts before the halitosis onset. Therefore, this can be considered for the timely detection and intervention of halitosis in children.
Metagenome Analysis of Intestinal Bacteria in Healthy People, Patients With Inflammatory Bowel Disease and Colorectal Cancer
Authors: Ma Yongshun , Zhang Yao , Jiang Houxiang , Xiang Shixin , Zhao Yueshui , Xiao Mintao , Du Fukuan , Ji Huijiao , Kaboli Parham Jabbarzadeh , Wu Xu , Li Mingxing , Wen Qinglian , Shen Jing , Yang Zhongming , Li Jing , Xiao Zhangang
Published: February 2021

Objectives

Several reports suggesting that the intestinal microbiome plays a key role in the development of inflammatory bowel disease (IBD) or colorectal cancer (CRC), but the changes of intestinal bacteria in healthy people, patients with IBD and CRC are not fully explained. The study aimed to investigate changes of intestinal bacteria in healthy subjects, patients with IBD, and patients with CRC.

Materials

We collected data from the European Nucleotide Archive on healthy people and patients with colorectal cancer with the study accession number PRJEB6070, PRJEB7774, PRJEB27928, PRJEB12449, and PRJEB10878, collected IBD patient data from the Integrated Human Microbiome Project from the Human Microbiome Project Data Portal. We performed metagenome-wide association studies on the fecal samples from 290 healthy subjects, 512 IBD patients, and 285 CRC patients. We used the metagenomics dataset to study bacterial community structure, relative abundance, functional prediction, differentially abundant bacteria, and co-occurrence networks.

Results

The bacterial community structure in both IBD and CRC was significantly different from healthy subjects. Our results showed that IBD patients had low intestinal bacterial diversity and CRC patients had high intestinal bacterial diversity compared to healthy subjects. At the phylum level, the relative abundance of Firmicutes in IBD decreased significantly, while the relative abundance of Bacteroidetes increased significantly. At the genus level, the relative abundance of Bacteroides in IBD was higher than in healthy people and CRC. Compared with healthy people and CRC, the main difference of intestinal bacteria in IBD patients was Bacteroidetes, and compared with healthy people and IBD, the main difference of intestinal bacteria in CRC patients was in Fusobacteria, Verrucomicrobia, and Proteobacteria. The main differences in the functional composition of intestinal bacteria in healthy people, IBD and CRC patients were L-homoserine and L-methionine biosynthesis, 5-aminoimidazole ribonucleotide biosynthesis II, L-methionine biosynthesis I, and superpathway of L-lysine, L-threonine, and L-methionine biosynthesis I. The results of stratified showed that the abundance of Firmicutes, Bacteroidetes, and Actinobacteria involved in metabolic pathways has significantly changed. Besides, the association network of intestinal bacteria in healthy people, IBD, and CRC patients has also changed.

Conclusions

In conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in IBD and CRC patients was significantly changed.
Higher-Order Chromatin Structures of Chromosomally Integrated HHV-6A Predict Integration Sites
Authors: Mariani Michael , Zimmerman Cosima , Rodriguez Princess , Hasenohr Ellie , Aimola Giulia , Gerrard Diana Lea , Richman Alyssa , Dest Andrea , Flamand Louis , Kaufer Benedikt , Frietze Seth
Published: February 2021

Human herpesvirus -6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of human chromosomes. Viral integration can occur in several cell types, including germinal cells, resulting in individuals that harbor the viral genome in every cell of their body. The integrated genome is efficiently silenced but can sporadically reactivate resulting in various clinical symptoms. To date, the integration mechanism and the subsequent silencing of HHV-6A/B genes remains poorly understood. Here we investigate the genome-wide chromatin contacts of the integrated HHV-6A in latently-infected cells. We show that HHV-6A becomes transcriptionally silent upon infection of these cells over the course of seven days. In addition, we established an HHV-6–specific 4C-seq approach, revealing that the HHV-6A 3D interactome is associated with quiescent chromatin states in cells harboring integrated virus. Furthermore, we observed that the majority of virus chromatin interactions occur toward the distal ends of specific human chromosomes. Exploiting this finding, we established a 4C-seq method that accurately detects the chromosomal integration sites. We further implement long-read minION sequencing in the 4C-seq assay and developed a method to identify HHV-6A/B integration sites in clinical samples.
Future Directions in Reducing Gastrointestinal Disorders in Children With ASD Using Fecal Microbiota Transplantation
Authors: Żebrowska Paulina , Łaczmańska Izabela , Łaczmański Łukasz
Published: February 2021

Research on the use of fecal microbiota transplantation (FMT) in the treatment of disorders related to digestive system ailments in children with autism spectrum disorders (ASDs) is a new attempt in a therapeutic approach. There are very little scientific evidences available on this emerging alternative method. However, it appears to be interesting not only because of its primary outcome, relieving the gastrointestinal (GI) symptoms, but also secondary therapeutic effect of alleviating autistic behavioral symptoms. FMT seems to be also promising method in the treatment of another group of pediatric patients, children with inflammatory bowel disease (IBD). The aim of this study is to discuss the potential use of FMT and modified protocols (MTT, microbiota transfer therapy) in the treatment of GI disorders in ASD children supported by reports on another disease, IBD concerning pediatric patients. Due to the few reports of the use of FMT in the treatment of children, these two patients groups were selected, although suffering from distant health conditions: neurodevelopmental disorder and gastrointestinal tract diseases, because of the the fact that they seem related in aspects of the presence of GI symptoms, disturbed intestinal microbiota, unexplained etiology of the condition and age range of patients. Although the outcomes for all are promising, this type of therapy is still an under-researched topic, studies in the group of pediatric patients are sparse, also there is a high risk of transmission of infectious and noninfectious elements during the procedure and no long-term effects on global health are known. For those reasons all obtained results should be taken with a great caution. However, in the context of future therapeutic directions for GI observed in neurodevelopmental disorders and neurodegenerative diseases, the topic seems worthy of attention.
Theileria annulata Subtelomere-Encoded Variable Secreted Protein-TA05575 Binds to Bovine RBMX2
Authors: Li Zhi , Liu Junlong , Zhao Shuaiyang , Ma Quanying , Liu Aihong , Li Youquan , Guan Guiquan , Luo Jianxun , Yin Hong
Published: February 2021

Tropical theileriosis is the disease caused by tick-transmitted apicomplexan parasite Theileria annulata, which has ability to transform bovine leukocytes, including B cells, macrophage cells, and dendritic cells. The T. annulata transformed cells are characterized as uncontrolled proliferation and shared some cancer-like phenotypes. The mechanism of the transformation by T. annulata is still not understood well. In previous reports, the subtelomere-encoded variable secreted proteins (SVSP) of T. parva were considered to contribute to phenotypic changes of the host cell, but the role of SVSP of T. annulata in host-pathogen relationship remains unknown. In the present study, a member of SVSP family, TA05575 of T. annulata was selected as the target molecule to analyze its expression profiles in different life cycle stages of T. annulata by qPCR and investigate its subcellular distribution of different passages of T. annulata transformed cells using confocal experiments. From the results, the transcription level of TA05575 at schizont stage was significantly higher than the other two life stages of T. annulata, and the protein of TA05575 was mainly distributed in nucleus of T. annulata infected cells. In addition, the potential proteins of host cells interacting with TA05575 were screened by Yeast-two hybrid system. The results of Co-IP experiment confirmed that TA05575 interacted with RBMX2-like protein that participated in transcription regulation of cells. In addition, a novel BiFC assay and flow cytometry were carried out, and the results further revealed that TA05575-RBMX2-like pair was directly interacted in cell context. Moreover, this interacting pair was found to distribute in intracellular compartments of HEK293T cells by using confocal microscopy. The results of the present study suggest that TA05575 may contribute for cells transformation due its distribution. According to the function of RBMX2, the interaction of TA05575 and RMMX2-like will provide a new information to further understand the mechanisms of cells transformation by T. annulata.
Acquiring Syntactic Variability: The Production of Wh-Questions in Children and Adults Speaking Akan
Authors: Omane Paul Okyere , Höhle Barbara
Published: February 2021

This paper investigates the predictions of the Derivational Complexity Hypothesis by studying the acquisition of wh-questions in 4- and 5-year-old Akan-speaking children in an experimental approach using an elicited production and an elicited imitation task. Akan has two types of wh-question structures (wh-in-situ and wh-ex-situ questions), which allows an investigation of children’s acquisition of these two question structures and their preferences for one or the other. Our results show that adults prefer to use wh-ex-situ questions over wh-in-situ questions. The results from the children show that both age groups have the two question structures in their linguistic repertoire. However, they differ in their preferences in usage in the elicited production task: while the 5-year-olds preferred the wh-in-situ structure over the wh-ex-situ structure, the 4-year-olds showed a selective preference for the wh-in-situ structure in who-questions. These findings suggest a developmental change in wh-question preferences in Akan-learning children between 4 and 5 years of age with a so far unobserved u-shaped developmental pattern. In the elicited imitation task, all groups showed a strong tendency to maintain the structure of in-situ and ex-situ questions in repeating grammatical questions. When repairing ungrammatical ex-situ questions, structural changes to grammatical in-situ questions were hardly observed but the insertion of missing morphemes while keeping the ex-situ structure. Together, our findings provide only partial support for the Derivational Complexity Hypothesis.
Early Miocene Exhumation of High-Pressure Rocks in the Himalaya: A Response to Reduced India-Asia Convergence Velocity
Authors: Maiti Giridas , Mandal Nibir
Published: February 2021

Low-viscosity channel flow, originating from a melt-weakened mid-crustal layer, is one of the most popular tectonic models to explain the exhumation of deep-seated rocks in the Greater Himalayan Sequence (GHS). The driving mechanism of such channel flow, generally attributed to focused erosion in the mountain front, is still debated, and yet to be resolved. Moreover, the channel flow model cannot explain eclogites in the GHS. In this study, we present a new two-dimensional thermo-mechanical numerical model, based on lubrication dynamics to demonstrate the exhumation process of deep crustal rocks in GHS. The model suggests that a dynamic-pressure drop in the Himalayan wedge, following a large reduction in the India-Asia convergence velocity (15 cm/yr at 50 Ma to nearly 5 cm/yr at ∼22 Ma) localized a fully developed extrusion zone, which controlled the pressure-temperature-time (P-T-t) path of GHS rocks. We show that the wedge extrusion, originated in the lower crust (∼60 km), was initially bounded by two oppositely directed ductile shear zones: the South Tibetan Detachment systems (STDS) at the top and the Higher Himalayan Discontinuity (HHD) at the bottom. With time the bottom shear boundary of the extrusion zone underwent a southward migration, forming the Main Central Thrust (MCT) at ∼17 Ma. Our model successfully reproduces two apparently major paradoxical observations in the Himalaya: syn-convergence extension and inverted metamorphic isograds. Model peak P (10–17 kb) and T (700–820°C) and the exhumation P-T-t path estimated from several Lagrangian points, traveling through the extrusion zone, are largely compatible with the petrological observations in the GHS. The model results account for the observed asymmetric P-T distribution between the MCT and STDS, showing peak P-T values close to the MCT. The lubrication dynamics proposed in this article sheds light on the fast exhumation event (>1 cm/yr) in the most active phase of crustal extrusion (22-17 Ma), followed by a slowed-down event. Finally, our model explains why the extrusion zone became weak in the last 8-10 Ma in the history of India-Asia collision.
Investigation of the Molecular Mechanisms of Antioxidant Damage and Immune Response Downregulation in Liver of Coilia nasus Under Starvation Stress
Authors: Wang Meiyao , Xu Gangchun , Tang Yongkai , Su Shengyan , Wang Yinping , Zhu Zhixiang
Published: February 2021

Commercial fishing of estuarine tapertail anchovy (Coilia nasus), an important anadromous fish species in the Yangtze River of China, has been prohibited due to the serious damage overfishing has caused to the wild population. Research regarding the energy metabolism is important for migratory fish to ensure the continuation of their existence. In this study, we performed, for the first time, a comparative transcriptome analysis of the liver of C. nasus subjected to long-term starvation stress. The results indicated that the damaging effects involved downregulation of the antioxidant capacity and immune response. The positive response to starvation involved upregulation of the anti-allergy and anticancer capacity, which supports the function of starvation in cancer inhibition, as has also been determined for human beings. This study revealed regulatory pathways, differentially expressed genes (DEGs), and mechanisms leading to damage of the liver in C. nasus affected by starvation. This research contributes information for the further study of the energy metabolism mechanism of C. nasus and provides a theoretical reference for starvation metabolism research of other fish species and even human beings.
Dietary Fiber Is Essential to Maintain Intestinal Size, L-Cell Secretion, and Intestinal Integrity in Mice
Authors: Hunt Jenna Elizabeth , Hartmann Bolette , Schoonjans Kristina , Holst Jens Juul , Kissow Hannelouise
Published: February 2021

Dietary fiber has been linked to improved gut health, yet the mechanisms behind this association remain poorly understood. One proposed mechanism is through its influence on the secretion of gut hormones, including glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2). We aimed to: 1) investigate the impact of a fiber deficient diet on the intestinal morphological homeostasis; 2) evaluate L-cell secretion; and 3) to ascertain the role of GLP-1, GLP-2 and Takeda G protein-receptor-5 (TGR5) signaling in the response using GLP-1 receptor, GLP-2 receptor and TGR5 knockout mice. Female C57BL/6JRj mice (n = 8) either received a standard chow diet or were switched to a crude fiber-deficient diet for a short (21 days) and long (112 days) study period. Subsequent identical experiments were performed in GLP-1 receptor, GLP-2 receptor and TGR5 knockout mice. The removal of fiber from the diet for 21 days resulted in a decrease in small intestinal weight (p < 0.01) and a corresponding decrease in intestinal crypt depth in the duodenum, jejunum and ileum (p < 0.001, p < 0.05, and p < 0.01, respectively). Additionally, colon weight was decreased (p < 0.01). These changes were associated with a decrease in extractable GLP-1, GLP-2 and PYY in the colon (p < 0.05, p < 0.01, and p < 0.01). However, we could not show that the fiber-dependent size decrease was dependent on GLP-1 receptor, GLP-2 receptor or TGR5 signaling. Intestinal permeability was increased following the removal of fiber for 112 days. In conclusion, our study highlights the importance of dietary fiber to maintain intestinal weight, colonic L-cell secretion and intestinal integrity.
The Effect of Activity, Energy Use, and Species Identity on Environmental DNA Shedding of Freshwater Fish
Authors: Thalinger Bettina , Rieder Andreas , Teuffenbach Anna , Pütz Yannick , Schwerte Thorsten , Wanzenböck Josef , Traugott Michael
Published: February 2021

The quantitative measurement of environmental DNA (eDNA) from field-collected water samples is gaining importance for the monitoring of fish communities and populations. The interpretation of these signal strengths depends, among other factors, on the amount of target eDNA shed into the water. However, shedding rates are presumably associated with species-specific traits such as physiology and behavior. Although such differences between juvenile and adult fish have been previously detected, the general impact of movement and energy use in a resting state on eDNA release into the surrounding water remains hardly addressed. In an aquarium experiment, we compared eDNA shedding between seven fish species occurring in European freshwaters. The investigated salmonids, cyprinids, and sculpin exhibit distinct adaptions to microhabitats, diets, and either solitary or schooling behavior. The fish were housed in aquaria with constant water flow and their activity was measured by snapshots taken every 30 s. Water samples for eDNA analysis were taken every 3 h and energy use was determined in an intermittent flow respirometer. After controlling for the effect of fish mass, our results demonstrate a positive correlation between target eDNA quantities as measured with digital PCR, fish activity, and energy use, as well as species-specific differences. For cyprinids, the model based on data from individual fish was only partly transferable to groups, which showed lower activity and higher energy use. Our findings highlight the importance of fish physiology and behavior for the comparative interpretation of taxon-specific eDNA quantities. Species traits should therefore be incorporated into eDNA-based monitoring and conservation efforts.
Inhibition of Arginase 1 Liberates Potent T Cell Immunostimulatory Activity of Human Neutrophil Granulocytes
Authors: Vonwirth Verena , Bülbül Yagmur , Werner Anke , Echchannaoui Hakim , Windschmitt Johannes , Habermeier Alice , Ioannidis Sonia , Shin Niu , Conradi Roland , Bros Matthias , Tenzer Stefan , Theobald Matthias , Closs Ellen Ildicho , Munder Markus
Published: February 2021

Myeloid cell arginase-mediated arginine depletion with consecutive inhibition of T cell functions is a key component of tumor immune escape. Both, granulocytic myeloid-derived suppressor cells (G-MDSC) and conventional mature human polymorphonuclear neutrophil granulocytes (PMN) express high levels of arginase 1 and can act as suppressor cells of adaptive anti-cancer immunity. Here we demonstrate that pharmacological inhibition of PMN-derived arginase 1 not only prevents the suppression of T cell functions but rather leads to a strong hyperactivation of T cells. Human PMN were incubated in cell culture medium in the absence or presence of an arginase inhibitor. T cells from healthy donors were then activated either polyclonally or in an antigen-specific manner in the supernatants of the PMN cultures at different PMN-T cell ratios. T cell proliferation was completely suppressed in these supernatants in the absence of an arginase inhibitor. Arginase inhibition led to a strong hyperinduction of T cell proliferation, which exceeded control activation conditions up to 25-fold. The hyperinduction was correlated with higher PMN-T cell ratios and was only apparent when PMN arginase activity was blocked sufficiently. The T cell stimulatory factor was liberated very early by PMN and was present in the < 3 kDa fraction of the PMN supernatants. Increased T cell production of specific proinflammatory cytokines by PMN supernatant in the presence of arginase inhibitor was apparent. Upon arginase inhibition, downregulation of important T cell membrane activation and costimulation proteins was completely prevented or de novo induction accelerated. Antigen-specific T cell cytotoxicity against tumor cells was enhanced by PMN supernatant itself and could be further increased by PMN arginase blockade. Finally, we analyzed anergic T cells from multiple myeloma patients and noticed a complete reversal of anergy and the induction of strong proliferation upon T cell activation in PMN supernatants by arginase inhibition. In summary, we discovered a potent PMN-mediated hyperactivation of human T cells, which is apparent only when PMN arginase-mediated arginine depletion is concurrently inhibited. Our findings are clearly relevant for the analysis and prevention of human tumor immune escape in conjunction with the application of arginase inhibitors already being developed clinically.
Peroxisome Proliferator-Activated Receptor-δ Deficiency in Microglia Results in Exacerbated Axonal Injury and Tissue Loss in Experimental Autoimmune Encephalomyelitis
Authors: Doroshenko Ellinore R. , Drohomyrecky Paulina C. , Gower Annette , Whetstone Heather , Cahill Lindsay S. , Ganguly Milan , Spring Shoshana , Yi Tae Joon , Sled John G. , Dunn Shannon E.
Published: February 2021

Peroxisome proliferator-activated receptor (PPAR)-δ is a nuclear receptor that functions to maintain metabolic homeostasis, regulate cell growth, and limit the development of excessive inflammation during immune responses. Previously, we reported that PPAR-δ-deficient mice develop a more severe clinical course of experimental autoimmune encephalomyelitis (EAE); however, it was difficult to delineate the role that microglia played in this disease phenotype since PPAR-δ-deficient mice exhibited a number of immune defects that enhanced CNS inflammation upstream of microglia activation. Here, we specifically investigated the role of PPAR-δ in microglia during EAE by using mice where excision of a floxed Ppard allele was driven by expression of a tamoxifen (TAM)-inducible CX3C chemokine receptor 1 promoter-Cre recombinase transgene (Cx3cr1CreERT2: Ppardfl/fl). We observed that by 30 days of TAM treatment, Cx3cr1CreERT2: Ppardfl/fl mice exhibited Cre-mediated deletion primarily in microglia and this was accompanied by efficient knockdown of Ppard expression in these cells. Upon induction of EAE, TAM-treated Cx3cr1CreERT2: Ppardfl/fl mice presented with an exacerbated course of disease compared to TAM-treated Ppardfl/fl controls. Histopathological and magnetic resonance (MR) studies on the spinal cord and brains of EAE mice revealed increased Iba-1 immunoreactivity, axonal injury and CNS tissue loss in the TAM-treated Cx3cr1CreERT2: Ppardfl/fl group compared to controls. In early EAE, a time when clinical scores and the infiltration of CD45+ leukocytes was equivalent between Cx3cr1CreERT2: Ppardfl/fl and Ppardfl/fl mice, Ppard-deficient microglia exhibited a more reactive phenotype as evidenced by a shorter maximum process length and lower expression of genes associated with a homeostatic microglia gene signature. In addition, Ppard-deficient microglia exhibited increased expression of genes associated with reactive oxygen species generation, phagocytosis and lipid clearance, M2-activation, and promotion of inflammation. Our results therefore suggest that PPAR-δ has an important role in microglia in limiting bystander tissue damage during neuroinflammation.
Antibodies Against the NH2-Terminus of the GluA Subunits Affect the AMPA-Evoked Releasing Activity: The Role of Complement
Authors: Cisani Francesca , Olivero Guendalina , Usai Cesare , Van Camp Gilles , Maccari Stefania , Morley-Fletcher Sara , Pittaluga Anna Maria
Published: February 2021

Antibodies recognizing the amino-terminal domain of receptor subunit proteins modify the receptor efficiency to controlling transmitter release in isolated nerve endings (e.g., synaptosomes) indirectly confirming their presence in these particles but also allowing to speculate on their subunit composition. Western blot analysis and confocal microscopy unveiled the presence of the GluA1, GluA2, GluA3, and GluA4 receptor subunits in cortical synaptosomes. Functional studies confirmed the presence of presynaptic release-regulating AMPA autoreceptors in these terminals, whose activation releases [3H]D-aspartate ([3H]D-Asp, here used as a marker of glutamate) in a NBQX-dependent manner. The AMPA autoreceptors traffic in a constitutive manner, since entrapping synaptosomes with the pep2-SVKI peptide (which interferes with the GluA2-GRIP1/PICK1 interaction) amplified the AMPA-evoked releasing activity, while the inactive pep2-SVKE peptide was devoid of activity. Incubation of synaptosomes with antibodies recognizing the NH2 terminus of the GluA2 and the GluA3 subunits increased, although to a different extent, the GluA2 and 3 densities in synaptosomal membranes, also amplifying the AMPA-evoked glutamate release in a NBQX-dependent fashion. We then analyzed the releasing activity of complement (1:300) from both treated and untreated synaptosomes and found that the complement-induced overflow occurred in a DL-t-BOA-sensitive, NBQX-insensitive fashion. We hypothesized that anti-GluA/GluA complexes in neuronal membranes could trigger the classic pathway of activation of the complement, modifying its releasing activity. Accordingly, the complement-evoked release of [3H]D-Asp from antiGluA2 and anti-GluA3 antibody treated synaptosomes was significantly increased when compared to untreated terminals and facilitation was prevented by omitting the C1q component of the immunocomplex. Antibodies recognizing the NH2 terminus of the GluA1 or the GluA4 subunits failed to affect both the AMPA and the complement-evoked tritium overflow. Our results suggest the presence of GluA2/GluA3-containing release-regulating AMPA autoreceptors in cortical synaptosomes. Incubation of synaptosomes with commercial anti-GluA2 or anti-GluA3 antibodies amplifies the AMPA-evoked exocytosis of glutamate through a complement-independent pathway, involving an excessive insertion of AMPA autoreceptors in plasma membranes but also affects the complement-dependent releasing activity, by promoting the classic pathway of activation of the immunocomplex. Both events could be relevant to the development of autoimmune diseases typified by an overproduction of anti-GluA subunits.
Case Report: Refractory Autoimmune Gastritis Responsive to Abatacept in LRBA Deficiency
Authors: Boz Valentina , Valencic Erica , Girardelli Martina , Pin Alessia , Gàmez-Diaz Laura , Tommasini Alberto , Lega Sara , Bramuzzo Matteo
Published: February 2021

Primary immunodeficiency (PID) with immune dysregulation may present with early onset gastrointestinal autoimmune disorders. When gastrointestinal autoimmunity is associated with multiple extraintestinal immune system dysfunction the diagnosis of PID is straightforward. However, with the advent of next generation sequencing technologies, genetic defects in PID genes have been increasingly recognized even when a single or no extraintestinal signs of immune dysregulation are present. A genetic diagnosis is especially important considering the expanding armamentarium of therapies designed to inhibit specific molecular pathways. We describe a boy with early-onset severe, refractory autoimmune gastritis and biallelic mutations in the LRBA gene causing a premature STOP-codon who was successfully treated with CTLA4-Ig, abatacept, with long term clinical and endoscopic remission. The case underscores the importance to consider a monogenetic defect in early onset autoimmune disorders, since the availability of targeted treatments may significantly improve patient prognosis.
The Role of NKG2D in Vitiligo
Authors: Plaza-Rojas Lourdes , Guevara-Patiño José A.
Published: February 2021

Vitiligo is an acquired multifactorial disease that affects melanocytes and results in skin depigmentation. In this review, we examine the role of cells stress and self-reactive T cells responses. Given the canonical and non-canonical functions of NKG2D, such as authenticating stressed target and enhance TCR signaling, we examine how melanocyte stress leads to the expression of ligands that are recognized by the activating receptor NKG2D, and how its signaling results in the turning of T cells against self (melanocyte suicide by proxy). We also discuss how this initiation phase is followed by T cell perpetuation, as NKG2D signaling results in self-sustained long-lasting T cells, with improved cytolytic properties.
The Dynamic Immune Response of Yellow Catfish (Pelteobagrus fulvidraco) Infected With Edwardsiella ictaluri Presenting the Inflammation Process
Authors: Zhou Xu , Zhang Gui-Rong , Ji Wei , Shi Ze-Chao , Ma Xu-Fa , Luo Zun-Lan , Wei Kai-Jian
Published: February 2021

Edwardsiella ictaluri is a highly destructive pathogen in cultured yellow catfish, thus it was very necessary to study the immune response of yellow catfish against bacterial infection. In this study, RNA-Seq technology was used to study the immune response in two distinct tissues of yellow catfish at eight different time points (h) after E. ictaluri infection. The number of differentially expressed genes (DEGs) in the spleen and liver was low at 3 h and 6 h post-infection, respectively. Afterwards, the most number of DEGs in the spleen was detected at 72 h, while the number of DEGs in the liver maintained a high level from 24 h to 120 h. The GO and KEGG enrichment analyses of DEGs at different time points uncovered that cytokines were continuously transcribed at 6 h to 120 h; whereas the liver is the main organ that secretes the components of the complement system, and metabolic regulation was activated from 12 h to 120 h. Moreover, an overview of the inflammation response of yellow catfish was exhibited including pattern-recognition receptors, inflammatory cytokines, chemokines, complements, and inflammation-related signal pathways. The similar expression tendency of nine genes by qRT-PCR validated the accuracy of transcriptome analyses. The different transcriptomic profiles obtained from the spleen and liver will help to better understand the dynamic immune response of fish against bacterial infection, and will provide basic information for establishing effective measures to prevent and control diseases in fish.