bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth rates and persistence of annual and perennial clovers
Authors: Olykan Sonya , Lucas Richard , Hunter Stuart , Moot Derrick
Published: February 2022

This study quantified the temporal productivity of monocultures of four annual and two perennial clover species in a summer dry environment at Lincoln University, Canterbury, New Zealand. Clovers were ungrazed in the first year to enable natural re-establishment of the annuals, but grazed in the second year.

In 2019 clover cultivar affected (P<0.001) yield in early spring (24th September) with ‘Viper’ balansa (Trifolium michelianum) producing 5.0 t DM/ha compared (P<0.05) with 3.5 t for ‘Arrotas’ arrowleaf (T. vesiculosum), 3.2 t for ‘Antas’ and ‘Woogenellup’ sub clovers (T. subterraneum), 1.6 t for ‘Kopu’ white clover (T. repens) and 1.2 t for ‘Relish’ red clover (T. pratense). ‘Arrotas’ grew 111 kg DM/ha/d from 14th to 28th August, ‘Viper’ grew 123 kg DM/ha/d from 28th August to 24th September and then 183 kg DM/d to 9th October.

After a dry autumn in 2020, ‘Kopu’ white and ‘Relish’ red persisted, but only sub clovers ‘Napier’ and ‘Woogenellup’ successfully re-established. By 17th September, accumulated dry matter yield (t) differed with ‘Woogenellup’ sub (4.3) and ‘Relish’ red (3.7) producing more than ‘Kopu’ white  (2.8) and ‘Napier’ sub (2.2). ‘Woogenellup’ sub clover grew at 72 kg/ha/day from 20th August to 17th September, which was more than twice the rate of the other clovers (~30 kg/ha/day). These four clovers continued to provide grazable herbage through the second year.

In 2020 the re-establishment of arrowleaf, balansa and Persian (T. resupinatum) clovers was poor, and each yielded <0.5 t/ha by 17th September, with their plots dominated by weeds. These results confirm monocultures of top flowering annual clovers are productive in their first year but poor re-establishment may occur in their second year. They may therefore be best suited as one-year specialised crops for grazing or conserved feed.

The earlier growth profiles of the annual compared with perennial clovers suggests there is potential to increase their use in summer dry environments to meet early spring feed requirements of ewes and lambs.
Developing genomic selection for dry matter yield in white clover
Authors: Griffiths Andrew , Ehoche Grace , Arojju Sai , Larking Anna , Jauregui Ruy , Cousins Greig , O'Connor Jessica , Jahufer Zulfi
Published: February 2022

Genomic selection (GS) integrates DNA marker and trait data to develop a model that enables prediction of trait performance (genomic-estimated breeding values; GEBVs) based on genotype data alone. GS has been shown to improve the efficiency and effectiveness of breeding programmes, especially for complex traits such dry matter yield (DMY). DMY data were generated from a training population of 200 white clover half-sibling (HS) families assessed in multi-location field trials for two years. We generated a GS prediction model after integrating genotyping-by-sequencing marker data from parents of the HS families with the HS DMY data. We then compared two selection strategies: a conventional method where individuals were chosen randomly from the phenotypically top-ranked HS families (HSP); and another where GEBVs were used to select the best individual from the top-ranked HS families (APWFGS). The mean predicted DMY GEBVs of the selected plants, as well as the predicted response to selection, were compared with those of the base population. This study showed that, compared with conventional selection (HSP), incorporating genomic selection (APWGSHS) is predicted to double the increase in DMY and response to selection relative to the base population. Synthetic populations based on these selections have been generated and will be tested in a field trial to determine empirically the impact of genomic selection for a complex trait.
Quantification and mitigation of nitrogen leaching in a maize silage cropping system
Authors: Tsimba Rowland , Gunn Tania , Densley Raewyn , Williams Ian , Edmeades Greg , Millar Jamie
Published: February 2022

Nitrogen (N) leaching is a major source of groundwater contamination. We used a series of lysimeters and suction cups to measure total N leaching losses in a high N maize crop system on a long-term maize paddock in the Waikato.

The goal of the study was to 1) quantify N leaching losses under maize silage, 2) determine the effectiveness of a cut-and-carry annual ryegrass catch crop (RG) in mitigating N leaching losses and 3) determine an appropriate depth for measuring N leaching losses under maize.

At least 200 kg/ha more fertiliser N than calculated plant requirements was applied to the maize crop to ensure surplus soil N after maize.

Nitrogen leaching losses were measured in a maize-RG and maize-fallow rotation over two seasons (October 2018 - September 2020). Less than 10 % of N leaching losses occurred during the maize growing season. This is likely due to evapotranspiration exceeding rainfall in summer.

The greatest leaching losses were observed in the maize-fallow rotation, averaging 60 kg N/ha and 88 kg N/ha for the 2018/19 and 2019/20 seasons. This was despite 2020 winter  being drier than 2019. The greater 2019/20 leaching losses can be attributed to a greater soil N concentration (+15 mg N/L) in 2020.

The importance of catch crops as a N leaching mitigation tool after maize was evident over the two years, resulting in leaching reductions >85% in the maize-RG than the maize–fallow plots. The catch crop removed >200 kg N/ha from the soil, significantly reducing the soil N concentration, which appear to be the main driver of leaching losses in our study. Additionally, RG also increased gravimetric soil water content by 7.3 % in the top 30 cm.

When N leaching was measured at 70 cm, losses in fallow plots were almost three times higher than the 41.6 kg N/ha recorded at the 120 cm soil depth, our default maize rooting depth. 

A similar amount of isotopic 15N (1.2 %) was observed in maize grain at maturity when 15N was inserted to 60 cm or 120 cm soil depth. This was greater than the background values obtained when standard urea was applied to the plots (0.37 %), indicating 15N interception at depth.  

It is speculated that provided fertiliser rates match crop N demand and catch crops are used, N leaching losses in maize crops should be much lower than values reported here, irrespective of soil type and season.
Legumes are the key to increasing productivity at “Inverary”, a summer moist hill / high country farm in mid-Canterbury
Authors: Smith Malcolm , Moot Derrick , Lucas Richard , Chapman John
Published: February 2022

About half the 4250 ha of Inverary is undevelopedmountain land above 750 m a.s.l. There are 300 haof river flats, where lucerne and winter feed cropsare grown, and 300 ha conventional grass/cloverpastures. Limited areas of clover/plantain and winterfeed crops have been established at ~700 m a.s.l. oneasy rolling country. The 1600 ha of steep country,dominated by browntop, gives low spring and highsummer production that is difficult to manage. In2009, there were no lucerne or legume rich pastures.The legume emphasis increased animal productivitythrough improved lambing and lamb weight sold perewe. Total lamb meat production lifted from 230,113kg in 2009 to 245,039 kg in 2020, despite 1000 fewerewes. The current sheep to cattle ratio is 60:40 with13,000 stock units being wintered. Pre-development,a major shortage of nutritious forage in early springwas compounded by difficulty controlling reproductivegrass in summer and autumn. In 2016, total productionof legume dominant pastures was 40% more than sowngrass/clover pastures with limited nitrogen fertiliser(15 vs. 11 t DM/ha/year). In early spring, legumeshad higher growth rates of conventional grass/cloverpastures (90 vs. 44 kg DM/ha/day), whereas browntopdominant hill pastures grew 10 kg DM/ha/d and 5 tDM/ha/yr.
The Cosmopolitan Wife: (Self-)erasure and (Self-)empowerment of Isabel Burton and her Neo-Victorian Representations
Authors: Mieszkowski Sylvia
Published: February 2022

Isabel Burton, née Arundell, was a model cosmopolitan wife to her famous explorer husband Richard Francis Burton for thirty years. Yet, two pieces of twenty-first-century neo-Victorian Burton-biofiction –  The Collector of Worlds by Iliya Troyanov and The Strange Affair of Spring-Heeled Jack by Mark Hodder – write her clean out of their core narratives. Having explored these conspicuous absences, my article turns to the historical Lady Burton's life writing, focussing on The Life of Captain Sir Richard F. Burton, in which she narrativizes the couple's transnational lives. Two of its stylistic devices are discussed in detail – paratexts and the peculiar use of first-person narration – in order to trace in them a double-gesture by which Isabel Burton combines self-erasure with self-empowerment. The detailed analysis of six paratexts, as theorized by Philippe Lejeune and Gérard Genette, supports the claim that Isabel, from the text's fringe, constructs for herself a role that combines elements of the scribe, editor/curator, narrator and author. Looping back to the neo-Victorian biofictional texts, I propose that, in Life, the historical Isabel Burton fuses self-erasure (which Troyanov picks up) with self-empowerment (which Hodder picks up), to forge a female writerly identity compatible with her self-fashioning as the wife/widow of a Victorian transnational cosmopolitan.
Becoming the Apocalypse: Global Climate Change and a Tragic Swerve in Deleuze's Logic of Sense
Authors: Phillips Chas.
Published: February 2022

In this article, I argue that the dominant approaches to climate change impede a meaningful set of political interventions that might be galvanised in the face of destructive transformations in the climate. If one overemphasises the possibility of unexpected turns of events, the ability to build and pursue a political agenda is undermined. If, however, one overemphasises humanity's mastery over the course of events, deliberate interventions will falter when the unexpected occurs. Using Lewis Carroll to illustrate the former and Sophocles’ depiction of Theban sovereigns to illustrate the latter, I propose a Deleuzian-inspired middle ground: thinking through climate change as a Deleuzian ‘event’ described in The Logic of Sense provides a novel set of strategies for becoming alongside the changing climate. As resources, I call on both Sophocles and Lucretius to provide an account of the world that is marked by predictable events and occasional swerves in the normal course of things. Ultimately, I argue Deleuze's Event captures creative potentiality but insists on a degree of predictability and agentic influence. By drawing on the Event, the goal is to mitigate the dangers involved with the masterful agent in Oedipus as well as the nihilism that results from being at the whim of the fates – both of which preclude meaningful action in the face of climate change. Rather than ignoring, denying, or controlling the outcome of widespread transformation, I propose creatively participating in the metamorphosis.
The Risk Factors for Exposure to Covid-19 in Diabetes Patients in the Johar Baru Health Centre Work Area
Authors: Prabawati Dewi , Setiyowati Yovita
Published: February 2022

Aims: The study aims to analyse the risk factors for exposure to Covid-19 in Diabetes Mellitus (DM) Patients in the Johar Baru Health Centre work area.
Design: This research was an observational analytic with a cross-sectional design. 146 DM patients were selected using the purposive sampling technique as respondents. Four instruments were employed in this study, they were The Perceived Stress Scale, modified Diabetes Self-management Questionnaire, Self-assessment form from the Ministry of Health to measure the risk of exposure to Covid-19, and The Covid-19 Preventive Behaviour Questionnaire, which was compiled based on a literature study and tested for validity and reliability.
Methods: This research is a quantitative descriptive research.
Results : Using Kendal's Tau B statistics, the risk of being exposed to Covid-19 was found to have a significant relationship to the length of suffering from DM, comorbidities, stress levels, self-management, and Covid-19 preventive behaviour with a p-value <0.05. The multiple linear regression test found that the risk of being exposed to Covid-19 was influenced by the variable duration of suffering from DM, stress level, and Covid preventive behaviour (p-value < 0.05) with the results of Cox and Snell R = 0.382 indicating that the independent variable contributes 38.2%.
Conclusions: DM patients were in high risk for exposure Covid 19, thus they need to control stress levels and carry out Covid preventive behaviour by prioritizing optimal health procedures to prevent the risk of being exposed to Covid-19.
Learning for Job: A Study on Dual TVET System in the Context of Nepal
Authors: Rijal Nimananda
Published: February 2022

Learning for Job is a concept of learning by doing, learning by imitation, and learning by innovation, these three aspects affect the pedagogy of technical education. Therefore this TVET is a complex process that is directly linked to fulfilling the day-to-day requirement of the production in the industrial setup. A market competency is required for the job, therefore to solve this problem, a dual TVET system should come in with proper planning and investment in Nepal. The research found out, the people who are aware of the TVET and market competency, have rated 85% with a 4.20 mean of the respondent, Trainees should have employment almost 95 percent; this indicates the success of the program.
Kualitas Hidup Orang Tua dengan Anak Disabilitas
Authors: Nurasa Indri , Mareti Silvia
Published: February 2022

Anak dengan disabilitas memiliki kebutuhan fisik dan psikis yang lebih banyak dari pada anak tanpa disabilitas. Hal ini akan mempengaruhi respon orang tua. Kondisi orang tua dalam menghadapi anak dengan disabilitas juga akan mempengaruhi kualitas hidup orang tua. Tujuan: Menganalisis kualitas hidup orang tua dengan anak disabilitas. Metode: Menggunakan deskriptif kuantitatif dengan pendekatan cross sectional. Jumlah sampel sebanyak 122 responden dengan menggunakan teknik total sampling. Hasil: Domain kualitas hidup dengan nilai rerata tertinggi adalah domain hubungan sosial (64,80) disusul dengan domain yang memiliki nilai yang sama besarnya yaitu psikologis (63,07), dan lingkungan (62,98), sedangkan domain terendah adalah kesehatan fisik (54,24). Kesimpulan: Nilai median Q1 kualitas hidup orang tua secara umum adalah 4 yang berarti baik, dan nilai median Q2 adalah 4 yang bermakna memuaskan.
Role of Th17 Cytokines in Airway Remodeling in Asthma and Therapy Perspectives
Authors: Margelidon-Cozzolino Victor , Tsicopoulos Anne , Chenivesse Cécile , de Nadai Patricia
Published: February 2022

Airway remodeling is a frequent pathological feature of severe asthma leading to permanent airway obstruction in up to 50% of cases and to respiratory disability. Although structural changes related to airway remodeling are well-characterized, immunological processes triggering and maintaining this phenomenon are still poorly understood. As a consequence, no biotherapy targeting cytokines are currently efficient to treat airway remodeling and only bronchial thermoplasty may have an effect on bronchial nerves and smooth muscles with uncertain clinical relevance. Th17 cytokines, including interleukin (IL)-17 and IL-22, play a role in neutrophilic inflammation in severe asthma and may be involved in airway remodeling. Indeed, IL-17 is increased in sputum from severe asthmatic patients, induces the expression of “profibrotic” cytokines by epithelial, endothelial cells and fibroblasts, and provokes human airway smooth muscle cell migration in in vitro studies. IL-22 is also increased in asthmatic samples, promotes myofibroblast differentiation, epithelial-mesenchymal transition and proliferation and migration of smooth muscle cells in vitro. Accordingly, we also found high levels of IL-17 and IL-22 in a mouse model of dog-allergen induced asthma characterized by a strong airway remodeling. Clinical trials found no effect of therapy targeting IL-17 in an unselected population of asthmatic patients but showed a potential benefit in a sub-population of patients exhibiting a high level of airway reversibility, suggesting a potential role on airway remodeling. Anti-IL-22 therapies have not been evaluated in asthma yet but were demonstrated efficient in severe atopic dermatitis including an effect on skin remodeling. In this review, we will address the role of Th17 cytokines in airway remodeling through data from in vitro, in vivo and translational studies, and examine the potential place of Th17-targeting therapies in the treatment of asthma with airway remodeling.
Introgression of the Aedes aegypti Red-Eye Genetic Sexing Strains Into Different Genomic Backgrounds for Sterile Insect Technique Applications
Authors: Augustinos Antonios A. , Nikolouli Katerina , Duran de la Fuente Lucia , Misbah-ul-Haq Muhammad , Carvalho Danilo O. , Bourtzis Kostas
Published: February 2022

Aedes aegyptiis an invasive mosquito species and major vector of human arboviruses. A wide variety of control methods have been employed to combat mosquito populations. One of them is the sterile insect technique (SIT) that has recently attracted considerable research efforts due to its proven record of success and the absence of harmful environmental footprints. The efficiency and cost-effectiveness of SIT is significantly enhanced by male-only releases. For mosquito SIT, male-only releases are ideally needed since females bite, blood-feed and transmit the pathogens.Ae. aegyptigenetic sexing strains (GSS) have recently become available and are based on eye colour mutations that were chosen as selectable markers. These genetic sexing strains were developed through classical genetics and it was shown to be subjected to genetic recombination, a phenomenon that is not suppressed in males as is the case in many Diptera. The genetic stability of these GSS was strengthened by the induction and isolation of radiation-induced inversions. In this study, we used the red eye mutation and the inversion Inv35 line of theAe. aegyptired-eye GSS s and introgressed them in six different genomic backgrounds to develop GSS with the respective local genomic backgrounds. Our goal was to assess whether the recombination frequencies in the strains with and without the inversion are affected by the different genomic backgrounds. In all cases the recombination events were suppressed in all Inv35 GSS strains, thus indicating that the genomic background does not negatively affect the inversion result. Absence of any effect that could be ascribed to genetic differences, enables the introgression of the key elements of the GSS into the local genomic background prior to release to the target areas. Maintaining the local background increases the chances for successful matings between released males and wild females and addresses potential regulatory concerns regarding biosafety and biosecurity.
Microbial Biocontainment Systems for Clinical, Agricultural, and Industrial Applications
Authors: Pantoja Angles Aaron , Valle-Pérez Alexander U. , Hauser Charlotte , Mahfouz Magdy M.
Published: February 2022

Many applications of synthetic biology require biological systems in engineered microbes to be delivered into diverse environments, such as for in situ bioremediation, biosensing, and applications in medicine and agriculture. To avoid harming the target system (whether that is a farm field or the human gut), such applications require microbial biocontainment systems (MBSs) that inhibit the proliferation of engineered microbes. In the past decade, diverse molecular strategies have been implemented to develop MBSs that tightly control the proliferation of engineered microbes; this has enabled medical, industrial, and agricultural applications in which biological processes can be executed in situ. The customization of MBSs also facilitate the integration of sensing modules for which different compounds can be produced and delivered upon changes in environmental conditions. These achievements have accelerated the generation of novel microbial systems capable of responding to external stimuli with limited interference from the environment. In this review, we provide an overview of the current approaches used for MBSs, with a specific focus on applications that have an immediate impact on multiple fields.
TCR-Induced Tyrosine Phosphorylation at Tyr270 of SUMO Protease SENP1 by Lck Modulates SENP1 Enzyme Activity and Specificity
Authors: Li Yun-Yi , Cen Haohua , Gong Bei-Ni , Mai Siqi , Wang Qi-Long , Mou Sisi , Li Yingqiu
Published: February 2022

Small ubiquitin-like modifier (SUMO) modification plays an important regulatory role in T cell receptor (TCR) signaling transduction. SUMO-specific proteases (SENPs) have dual-enzyme activities; they can both process SUMO precursors as endopeptidases and participate in SUMO deconjugation as isopeptidases. It remains unclear how the SUMO system, especially SENP1, is regulated by TCR signaling. Here, we show that Lck phosphorylates tyrosine 270 (Y270) of SENP1 upon TCR stimulation, indicating that SENP1 is a substrate of Lck. In vitro endopeptidase activity analysis showed that mutating SENP1 Y270 to either phenylalanine (F) to mimic the phosphorylation-defective state or to glutamate (E) to mimic the negative charge of tyrosine phosphorylation in the enzyme microenvironment did not change its endopeptidase activity towards pre-SUMO1. However, SENP1 Y270E but not Y270F mutation exhibited decreased endopeptidase activity towards pre-SUMO3. Through in vivo isopeptidase activity analysis by rescue expression of SENP1 and its Y270 mutants in a SENP1 CRISPR knockout T cell line, we found that SENP1 Y270F downregulated its isopeptidase activity towards both SUMO1 and SUMO2/3 conjugation by reducing SENP1 binding with sumoylated targets. While overexpression of SENP1 inhibited TCR-induced IL-2 production, overexpression of SENP1 Y270F enhanced it instead. In summary, TCR-induced Y270 phosphorylation of SENP1 may promote its isopeptidase activity and specifically decrease its endopeptidase activity against pre-SUMO3, which finely tunes activation of T cells.
The Diverse Roles of Histone Demethylase KDM4B in Normal and Cancer Development and Progression
Authors: Wang Zhongze , Cai Huarui , Zhao Erhu , Cui Hongjuan
Published: February 2022

Histone methylation status is an important process associated with cell growth, survival, differentiation and gene expression in human diseases. As a member of the KDM4 family, KDM4B specifically targets H1.4K26, H3K9, H3K36, and H4K20, which affects both histone methylation and gene expression. Therefore, KDM4B is often regarded as a key intermediate protein in cellular pathways that plays an important role in growth and development as well as organ differentiation. However, KDM4B is broadly defined as an oncoprotein that plays key roles in processes related to tumorigenesis, including cell proliferation, cell survival, metastasis and so on. In this review, we discuss the diverse roles of KDM4B in contributing to cancer progression and normal developmental processes. Furthermore, we focus on recent studies highlighting the oncogenic functions of KDM4B in various kinds of cancers, which may be a novel therapeutic target for cancer treatment. We also provide a relatively complete report of the progress of research related to KDM4B inhibitors and discuss their potential as therapeutic agents for overcoming cancer.
Dissecting the Crosstalk Between Nrf2 and NF-κB Response Pathways in Drug-Induced Toxicity
Authors: Gao Wen , Guo Lin , Yang Yan , Wang Yu , Xia Shuang , Gong Hui , Zhang Bi-Kui , Yan Miao
Published: February 2022

Nrf2 and NF-κB are important regulators of the response to oxidative stress and inflammation in the body. Previous pharmacological and genetic studies have confirmed crosstalk between the two. The deficiency of Nrf2 elevates the expression of NF-κB, leading to increased production of inflammatory factors, while NF-κB can affect the expression of downstream target genes by regulating the transcription and activity of Nrf2. At the same time, many therapeutic drug-induced organ toxicities, including hepatotoxicity, nephrotoxicity, cardiotoxicity, pulmonary toxicity, dermal toxicity, and neurotoxicity, have received increasing attention from researchers in clinical practice. Drug-induced organ injury can destroy body function, reduce the patients’ quality of life, and even threaten the lives of patients. Therefore, it is urgent to find protective drugs to ameliorate drug-induced injury. There is substantial evidence that protective medications can alleviate drug-induced organ toxicity by modulating both Nrf2 and NF-κB signaling pathways. Thus, it has become increasingly important to explore the crosstalk mechanism between Nrf2 and NF-κB in drug-induced toxicity. In this review, we summarize the potential molecular mechanisms of Nrf2 and NF-κB pathways and the important effects on adverse effects including toxic reactions and look forward to finding protective drugs that can target the crosstalk between the two.
The Circular RNA CircCOL1A1 Functions as a miR-149-5p Sponge to Regulate the Formation of Superior-Quality Brush Hair via the CMTM3/AR Axis
Authors: Wang Jian , Wu Xi , Sun Xiaomei , Zhang Liuming , Wang Qiang , Qu Jingwen , Wang Yanhu , Li Yongjun
Published: February 2022

Superior-quality brush hair, also called Type III hair, can be obtained only from the cervical spine region of skin tissues of Yangtze River Delta white goats. The formation of superior-quality brush hair is controlled by a series of critical genes and related signaling pathways. Circular RNAs (circRNAs) are ubiquitous endogenous noncoding RNAs that regulate many biological and physiological processes in mammals. However, little is known about the potential regulatory role of circRNAs in superior-quality brush hair formation. Here, we analyzed circRNA sequencing data from cervical spine region skin tissues of normal-quality brush hair goats and superior-quality brush hair goats and then selected and identified the differentially expressed circRNA circCOL1A1. To investigate the regulatory role and mechanism of action of circCOL1A1, goat hair follicle stem cells (gHFSCs) were cultured and treated with a circCOL1A1 overexpression plasmid and small-interfering RNAs (siRNAs). Functional assays showed that circCOL1A1 knockdown promoted the proliferation and differentiation of gHFSCs cultured in vitro but inhibited stem cell apoptosis, whereas overexpression of circCOL1A1 suppressed stem cell proliferation and differentiation and induced apoptosis. Bioinformatics analysis combined with dual-luciferase reporter assays and RNA binding protein immunoprecipitation (RIP) verified that, mechanistically, circCOL1A1 could bind miR-149-5p directly and then relieve its inhibitory effect on CMTM3 to further control the CMTM3/AR axis. Collectively, our results reveal a novel regulatory pathway for the formation of superior-quality brush hair and indicate that circCOL1A1 plays a role in gHFSC growth and superior-quality brush hair formation by targeting the miR-149-5p/CMTM3/AR axis.
TI: NLRP3 Inflammasome-Dependent Pyroptosis in CNS Trauma: A Potential Therapeutic Target
Authors: Zhou Conghui , Zheng Jinfeng , Fan Yunpeng , Wu Junsong
Published: February 2022

Central nervous system (CNS) trauma, including traumatic brain injury (TBI) and traumatic spinal cord injury (SCI), is characterized by high morbidity, disability, and mortality. TBI and SCI have similar pathophysiological mechanisms and are often accompanied by serious inflammatory responses. Pyroptosis, an inflammation-dependent programmed cell death, is becoming a major problem in CNS post-traumatic injury. Notably, the pyrin domain containing 3 (NLRP3) inflammasome is a key protein in the pyroptosis signaling pathway. Therefore, underlying mechanism of the NLRP3 inflammasome in the development of CNS trauma has attracted much attention. In this review, we briefly summarize the molecular mechanisms of NLRP3 inflammasome in pyroptosis signaling pathway, including its prime and activation. Moreover, the dynamic expression pattern, and roles of the NLRP3 inflammasome in CNS post-traumatic injury are summarized. The therapeutic applications of NLRP3 inflammasome activation inhibitors are also discussed.
Oscillatory Behaviors of microRNA Networks: Emerging Roles in Retinal Development
Authors: Fishman Elizabeth S. , Han Jisoo S. , La Torre Anna
Published: February 2022

A broad repertoire of transcription factors and other genes display oscillatory patterns of expression, typically ranging from 30 min to 24 h. These oscillations are associated with a variety of biological processes, including the circadian cycle, somite segmentation, cell cycle, and metabolism. These rhythmic behaviors are often prompted by transcriptional feedback loops in which transcriptional activities are inhibited by their corresponding gene target products. Oscillatory transcriptional patterns have been proposed as a mechanism to drive biological clocks, the molecular machinery that transforms temporal information into accurate spatial patterning during development. Notably, several microRNAs (miRNAs) -small non-coding RNA molecules-have been recently shown to both exhibit rhythmic expression patterns and regulate oscillatory activities. Here, we discuss some of these new findings in the context of the developing retina. We propose that miRNA oscillations are a powerful mechanism to coordinate signaling pathways and gene expression, and that addressing the dynamic interplay between miRNA expression and their target genes could be key for a more complete understanding of many developmental processes.
Thin Film Electrodes for Anodic Stripping Voltammetry: A Mini-Review
Authors: Wygant Bryan R. , Lambert Timothy N.
Published: February 2022

Anodic stripping voltammetry (ASV) is a powerful electrochemical analytical technique that allows for the detection and quantification of a variety of metal ion species at very low concentrations in aqueous media. While early, traditional ASV measurements relied on macroscopic electrodes like Hg drop electrodes to provide surfaces suitable for plating/stripping, more recent work on the technique has replaced these electrodes with thin film metal electrodes generated in situ. Such electrodes are plated alongside the analyte species onto the surface of a primary electrode, producing a composite metal electrode from which the analyte(s) can then be stripped, identified, and quantified. In this minireview, we will explore the development and use of these unique electrodes in a variety of different applications. A number of metals (e.g., Hg, Bi, Sn, etc.) have shown promise as thin film ASV electrodes in both acidic and alkaline media, and frequently multiple metals in addition to the analyte of interest are deposited together to optimize the plating/stripping behavior, improving sensitivity. Due to the relatively simple nature of the measurement and its suitability for a wide range of pH, it has been used broadly: To measure toxic metals in the environment, characterize battery materials, and enable biological assays, among other applications. We will discuss these applications in greater detail, as well as provide perspective on future development and uses of these thin film electrodes in ASV measurements.
Room Temperature Phosphorescence Emission From Multi-States
Authors: Zhang Xiaofeng , Zhang Beibei , Luo Ji , Guo Song , Wei Chun , Gong Yongyang
Published: February 2022

Organic room temperature phosphorescence (RTP) materials have received considerable attention due to their fascinating photophysical properties. During the past decade, various organic luminogens exhibiting RTP emission in solid states were reported. However, the phosphorescence emission of organic compounds can hardly be observed in their solutions at room temperature. Herein, we reported two fluorene derivatives that can emit RTP in degassed organic solvents, polymer doped film, and crystalline states. Furthermore, those RTP luminogens emitted different colors with different phosphorescence lifetimes in multi-states. These results indicated that the phosphorescence performance can be adjusted flexibly in different condensed states. To our knowledge, this is the first example possessing diverse organic RTP at multi-states, including solution state.
Quadruple Target Evaluation of Diversity-Optimized Halogen-Enriched Fragments (HEFLibs) Reveals Substantial Ligand Efficiency for AP2-Associated Protein Kinase 1 (AAK1)
Authors: Dammann Marcel , Kramer Markus , Zimmermann Markus O. , Boeckler Frank M.
Published: February 2022

Fragment-based drug discovery is one of the most utilized approaches for the identification of novel weakly binding ligands, by efficiently covering a wide chemical space with rather few compounds and by allowing more diverse binding modes to be found. This approach has led to various clinical candidates and approved drugs. Halogen bonding, on the other hand, has gained traction in molecular design and lead optimization, but could offer additional benefits in early drug discovery. Screening halogen-enriched fragments (HEFLibs) could alleviate problems associated with the late introduction of such a highly geometry dependent interaction. Usually, the binding mode is then already dominated by other strong interactions. Due to the fewer competing interactions in fragments, the halogen bond should more often act as an anchor point for the binding mode. Previously, we proposed a fragment library with a focus on diverse binding modes that involve halogens for gaining initial affinity and selectivity. Herein, we demonstrate the applicability of these HEFLibs with a small set of diverse enzymes: the histone-lysine N-methyltransferase DOT1L, the indoleamine 2,3-dioxygenase 1 (IDO1), the AP2-associated protein kinase 1 (AAK1), and the calcium/calmodulin-dependent protein kinase type 1G (CAMK1G). We were able to identify various binding fragments via STD-NMR. Using ITC to verify these initial hits, we determined affinities for many of these fragments. The best binding fragments exhibit affinities in the one-digit micromolar range and ligand efficiencies up to 0.83 for AAK1. A small set of analogs was used to study structure-affinity relationships and hereby analyze the specific importance of each polar interaction. This data clearly suggests that the halogen bond is the most important interaction of fragment 9595 with AAK1.
Mechanochemical Strategies for the Preparation of SiO2-Supported AgAu Nanoalloy Catalysts
Authors: da Silva Rafael T. P. , Córdoba De Torresi Susana I. , de Oliveira Paulo F. M.
Published: February 2022

Silver-gold nanoalloys were prepared from their metal salts precursors through bottom-up mechanochemical synthesis, using one-pot or galvanic replacement reaction strategies. The nanostructures were prepared over amorphous SiO2 as an inert supporting material, facilitating their stabilization without the use of any stabilizing agent. The nanomaterials were extensively characterized, confirming the formation of the bimetallic nanostructures. The nanoalloys were tested as catalysts in the hydrogenation of 2-nitroaniline and exhibited up to 4-fold the rate constant and up to 37% increased conversion compared to the respective single metal nanoparticles. Our approach is advantageous to produce nanoparticles with clean surfaces with available catalytic sites, directly in the solid-state and in an environmentally friendly manner.
The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics
Authors: Ferreira Roberto Rodrigues , Waghabi Mariana Caldas , Bailly Sabine , Feige Jean-Jacques , Hasslocher-Moreno Alejandro M. , Saraiva Roberto M. , Araujo-Jorge Tania C.
Published: February 2022

The anti-inflammatory cytokine transforming growth factor beta (TGF-β) plays an important role in Chagas disease (CD), a potentially life-threatening illness caused by Trypanosoma cruzi. In this review we revisited clinical studies in CD patients combined with in vitro and in vivo experiments, presenting three main sections: an overview of epidemiological, economic, and clinical aspects of CD and the need for new biomarkers and treatment; a brief panorama of TGF-β roles and its intracellular signaling pathways, and an update of what is known about TGF-β and Chagas disease. In in vitro assays, TGF-β increases during T. cruzi infection and modulates heart cells invasion by the parasite fostering its intracellular parasite cycle. TGF-β modulates host immune response and inflammation, increases heart fibrosis, stimulates remodeling, and slows heart conduction via gap junction modulation. TGF-β signaling inhibitors reverts these effects opening a promising therapeutic approach in pre-clinical studies. CD patients with higher TGF-β1 serum level show a worse clinical outcome, implicating a predictive value of serum TGF-β as a surrogate biomarker of clinical relevance. Moreover, pre-clinical studies in chronic T. cruzi infected mice proved that inhibition of TGF-β pathway improved several cardiac electric parameters, reversed the loss of connexin-43 enriched intercellular plaques, reduced fibrosis of the cardiac tissue, restored GATA-6 and Tbox-5 transcription, supporting cardiac recovery. Finally, TGF-β polymorphisms indicate that CD immunogenetics is at the base of this phenomenon. We searched in a Brazilian population five single-nucleotide polymorphisms (-800 G>A rs1800468, -509 C>T rs1800469, +10 T>C rs1800470, +25 G>C rs1800471, and +263 C>T rs1800472), showing that CD patients frequently express the TGF-β1 gene genotypes CT and TT at position -509, as compared to noninfected persons; similar results were observed with genotypes TC and CC at codon +10 of the TGF-β1 gene, leading to the conclusion that 509 C>T and +10 T>C TGF-β1 polymorphisms are associated with Chagas disease susceptibility. Studies in genetically different populations susceptible to CD will help to gather new insights and encourage the use of TGF-β as a CD biomarker.
Use of Clinical Isolates to Establish Criteria for a Mouse Model of Latent Cryptococcus neoformans Infection
Authors: Ding Minna , Smith Kyle D. , Wiesner Darin L. , Nielsen Judith N. , Jackson Katrina M. , Nielsen Kirsten
Published: February 2022

The mechanisms of latency in the context ofC. neoformansinfection remain poorly understood. Two reasons for this gap in knowledge are: 1) the lack of standardized criteria for defining latent cryptococcosis in animal models and 2) limited genetic and immunological tools available for studying host parameters againstC. neoformansin non-murine models of persistent infection. In this study, we defined criteria required for latency inC. neoformansinfection models and used these criteria to develop a murine model of persistentC. neoformansinfection using clinical isolates. We analyzed infections with two clinicalC. neoformansstrains, UgCl223 and UgCl552, isolated from advanced HIV patients with cryptococcal meningitis. Our data show that the majority of C57BL/6 mice infected with the clinicalC. neoformansisolates had persistent, stable infections with low fungal burden, survived beyond 90 days-post infection, exhibited weight gain, had no clinical signs of disease, and had yeast cells contained within pulmonary granulomas with no generalized alveolar inflammation. Infected mice exhibited stable relative frequencies of pulmonary immune cells during the course of the infection. Upon CD4+ T-cell depletion, the CD4DTRmice had significantly increased lung and brain fungal burden that resulted in lethal infection, indicating that CD4+ T-cells are important for control of the pulmonary infection and to prevent dissemination. Cells expressing the Tbettranscription factor were the predominant activated CD4 T-cell subset in the lungs during the latent infection. These Tbet-expressing T-cells had decreased IFNγ production, which may have implications in the capacity of the cells to orchestrate the pulmonary immune response. Altogether, these results indicate that clinicalC. neoformansisolates can establish a persistent controlled infection that meets most criteria for latency; highlighting the utility of this new mouse model system for studies of host immune responses that controlC. neoformansinfections.
Interferon Alpha Induces Cellular Autophagy and Modulates Hepatitis B Virus Replication
Authors: Li Jia , Kemper Thekla , Broering Ruth , Chen Jieliang , Yuan Zhenghong , Wang Xueyu , Lu Mengji
Published: February 2022

Hepatitis B virus (HBV) infection causes acute and chronic liver diseases, including severe hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Interferon alpha 2a (IFNα-2a) is commonly used for treating chronic HBV infection. However, its efficacy remains relatively low. Yet, the immunological and molecular mechanisms for successful IFNα-2a treatment remain elusive. One issue is whether the application of increasing IFNα doses may modulate cellular processes and HBV replication in hepatic cells. In the present study, we focused on the interaction of IFNα signaling with other cellular signaling pathways and the consequence for HBV replication. The results showed that with the concentration of 6000 U/ml IFNα-2a treatment downregulated the activity of not only the Akt/mTOR signaling but also the AMPK signaling. Additionally, IFNα-2a treatment increased the formation of the autophagosomes by blocking autophagic degradation. Furthermore, IFNα-2a treatment inhibited the Akt/mTOR signaling and initiated autophagy under low and high glucose concentrations. In reverse, inhibition of autophagy using 3-methyladenine (3-MA) and glucose concentrations influenced the expression of IFNα-2a-induced ISG15 and IFITM1. Despite of ISGs induction, HBV replication and gene expression in HepG2.2.15 cells, a cell model with continuous HBV replication, were slightly increased at high doses of IFNα-2a. In conclusion, our study indicates that IFNα-2a treatment may interfere with multiple intracellular signaling pathways, facilitate autophagy initiation, and block autophagic degradation, thereby resulting in slightly enhanced HBV replication.
Isolation of SARS-CoV-2 in Viral Cell Culture in Immunocompromised Patients With Persistently Positive RT-PCR Results
Authors: Sung Abby , Bailey Adam L. , Stewart Henry B. , McDonald David , Wallace Meghan A. , Peacock Kate , Miller Candace , Reske Kimberly A. , O’Neil Caroline A. , Fraser Victoria J. , Diamond Michael S. , Burnham Carey-Ann D. , Babcock Hilary M. , Kwon Jennie H.
Published: February 2022

Immunocompromised adults can have prolonged acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive RT-PCR results, long after the initial diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to determine if SARS-CoV-2 virus can be recovered in viral cell culture from immunocompromised adults with persistently positive SARS-CoV-2 RT-PCR tests. We obtained 20 remnant SARS-CoV-2 PCR positive nasopharyngeal swabs from 20 immunocompromised adults with a positive RT-PCR test ≥14 days after the initial positive test. The patients’ 2nd test samples underwent SARS-CoV-2 antigen testing, and culture with Vero-hACE2-TMPRSS2 cells. Viral RNA and cultivable virus were recovered from the cultured cells after qRT-PCR and plaque assays. Of 20 patients, 10 (50%) had a solid organ transplant and 5 (25%) had a hematologic malignancy. For most patients, RT-PCR Ct values increased over time. There were 2 patients with positive viral cell cultures; one patient had chronic lymphocytic leukemia treated with venetoclax and obinutuzumab who had a low viral titer of 27 PFU/mL. The second patient had marginal zone lymphoma treated with bendamustine and rituximab who had a high viral titer of 2 x 106 PFU/mL. Most samples collected ≥7 days after an initial positive SARS-CoV-2 RT-PCR had negative viral cell cultures. The 2 patients with positive viral cell cultures had hematologic malignancies treated with chemotherapy and B cell depleting therapy. One patient had a high concentration titer of cultivable virus. Further data are needed to determine risk factors for persistent viral shedding and methods to prevent SARS-CoV-2 transmission from immunocompromised hosts.
Prevalence, Serotype Distribution and Antimicrobial Resistance of Non-Typhoidal Salmonella in Hospitalized Patients in Conghua District of Guangzhou, China
Authors: Gong Baiyan , Li Hong , Feng Yulian , Zeng Shihan , Zhuo Zhenxu , Luo Jiajun , Chen Xiankai , Li Xiaoyan
Published: February 2022

Salmonella infection is a major public health concern worldwide, has contributed to an increased economic burden on the health systems. Non-typhoidal Salmonella (NTS) is a common cause of bacterial enteritis in humans, causing 93.8 million cases of gastroenteritis globally each year, with 155,000 deaths. Guangzhou city is situated in the south of China and has a sub-tropical climate, the heat and heavy rainfall helps the spread of NTS. However, no information of NTS infection is available in humans in Conghua District, the largest administrative district of Guangzhou. To understand the prevalence, serotype distribution, risk factors and drug resistance of NTS infection in humans in the survey area, an epidemiological investigation was conducted in hospitalized patients in Conghua District in Guangzhou, China. A total of 255 fecal specimens were collected from hospitalized patients (one each), with a questionnaire for each participant, and NTS infection was identified by culture, as well as serotypes confirmed by slide agglutination tests. An average prevalence of 20.39% (52/255) was observed and three serogroups were identified—serogroup B (n = 46), serogroup C1 (n = 4) and serogroup D1 (n = 2). Among them, Salmonella Typhimurium (n = 39) was the most common serotype. Children aged <3 years were observed to have a statistically higher prevalence of NTS infection than adults (25.15% versus 4.65%, P = 0.006); children with artificial feeding had a statistically higher prevalence than those with breastfeeding (30.77% versus 8.33%, P = 0.044). Antimicrobial resistance testing revealed that the majority of strains were resistant to ampicillin (92.16%), as well as 47.06% of all strains were multi-drug resistant. Therefore, it is necessary to continuous monitoring and rational use of antibiotics, which will be helpful to reduce the prevalence of resistant strains. These data will aid in making efficient control strategies to intervene with and prevent occurrence of salmonellosis.