bluuebunny/crossref_metadata_2025 huggingface dataset:
Pemanfaatan Panel Surya Sebagai Smart Street Lighting di Desa Banjarejo, Kec. Pakis, Kab. Malang
Authors: Hakim Lukman , Prasetyo Budi Eko , Wiharya Chandra , Santoso Asfari Hariz , Ridzki Imron
Published: July 2021

Permasalahan lampu PJU konvensional secara umum yang dihadapi oleh masyarakat pedesaan, yaitu beban yang harus ditanggung oleh masyarakat untuk membayar rekening, selain itu sering terjadi kelalaian untuk menyalakan dan mematikannya. Artikel ini membahas mengenai pemasngan smart PJU yang memanfaatkan pansel surya sebagai sumber utamanya. Secara teknis, penggunaan LDR dan PIR sangat membantu masyarakat untuk menyalakan dan mematikan lampu PJU, dan hasil pengukuran lampu smart PJU panel surya yang menggunakan lampu jenis LED 6 watt dipasang pada ketinggian 4meter dari permukaan jalan didapatkan nilai rata-rata kuat cahaya E sebesr 11.86 lux. Disisi ekonomisnya, masyarakat dapat menghemat energi selama 1 bulan (30 hari) sebesar 21.6kWh dengan total nilai rupiah sebesar Rp. 31,205.52.
Unraveling Subcellular and Ultrastructural Changes During Vitrification of Human Spermatozoa: Effect of a Mitochondria-Targeted Antioxidant and a Permeable Cryoprotectant
Authors: Kumar Pradeep , Wang Mengying , Isachenko Evgenia , Rahimi Gohar , Mallmann Peter , Wang Wanxue , Brandenstein Melanie von , Isachenko Vladimir
Published: July 2021

Mitochondria-targeted antioxidants have great potential to counterbalance the generated reactive oxygen species (ROS) because they cross the inner membrane of the mitochondria. Still, their use was not reported in vitrified human spermatozoa. Our laboratory has successfully vitrified spermatozoa without the use of permeable cryoprotectants, but subcellular-level evidence was missing. Therefore, this study aimed to improve spermatozoa vitrification using a mitochondria-targeted antioxidant (mitoquinone, MitoQ), reveal ultrastructural changes in the spermatozoa due to the use of a permeable cryoprotectant, and report alterations of functional proteins during the spermatozoa vitrification process. For this, each of 20 swim-up-prepared ejaculates was divided into seven aliquots and diluted with a vitrification medium supplemented with varying concentrations of MitoQ (0.02 and 0.2 μM), glycerol (1, 4, and 6%), and a combination of MitoQ and glycerol. All aliquots were vitrified by the aseptic capillary method developed in our laboratory. The spermatozoa function assays revealed that the addition of either MitoQ (0.02 μM), glycerol (1%), or a combination of MitoQ (0.02 μM) and glycerol (1%) in the vitrification medium results in better or equivalent spermatozoa quality relative to the control. Transmission electron microscopy revealed that MitoQ protects the spermatozoa from undergoing ultrastructural alterations, but glycerol induced ultrastructural alterations during the vitrification process. Next, we performed label-free quantitative proteomics and identified 1,759 proteins, of which 69, 60, 90, and 81 were altered in the basal medium, 0.02 μM MitoQ, 1% glycerol, and Mito-glycerol groups, respectively. Actin, tubulins, and outer dense fiber proteins were not affected during the vitrification process. Some of the identified ubiquitinating enzymes were affected during spermatozoa vitrification. Only a few proteins responsible for phosphorylation were altered during vitrification. Similarly, several proteins involved in spermatozoa–egg fusion and fertilization (IZUMO1 and Tektin) were not affected during the vitrification process. In conclusion, MitoQ attenuates the vitrification-induced ultrastructural changes and alterations in the key proteins involved in spermatozoa functions and fertilization.
Astrocyte-Neuron Signaling in Synaptogenesis
Authors: Shan Lili , Zhang Tongran , Fan Kevin , Cai Weibo , Liu Huisheng
Published: July 2021

Astrocytes are the key component of the central nervous system (CNS), serving as pivotal regulators of neuronal synapse formation and maturation through their ability to dynamically and bidirectionally communicate with synapses throughout life. In the past 20 years, numerous astrocyte-derived molecules promoting synaptogenesis have been discovered. However, our understanding of the cell biological basis underlying intra-neuron processes and astrocyte-mediated synaptogenesis is still in its infancy. Here, we provide a comprehensive overview of the various ways astrocytes talk to neurons, and highlight astrocytes’ heterogeneity that allow them to displays regional-specific capabilities in boosting synaptogenesis. Finally, we conclude with promises and future directions on how organoids generated from human induced pluripotent stem cells (hiPSCs) effectively address the signaling pathways astrocytes employ in synaptic development.
The Roles of MicroRNAs in Tendon Healing and Regeneration
Authors: Ding Lingli , Wang Min , Qin Shengnan , Xu Liangliang
Published: July 2021

Tendons connect the muscle abdomen of skeletal muscles to the bone, which transmits the force generated by the muscle abdomen contraction and pulls the bone into motion. Tendon injury is a common clinical condition occurring in certain populations, such as repeated tendon strains in athletes. And it can lead to substantial pain and loss of motor function, in severe cases, significant disability. Tendon healing and regeneration have attracted growing interests. Some treatments including growth factors, stem cell therapies and rehabilitation programs have been tried to improve tendon healing. However, the basic cellular biology and pathology of tendons are still not fully understood, and the management of tendon injury remains a considerable challenge. Regulating gene expression at post-transcriptional level, microRNA (miRNA) has been increasingly recognized as essential regulators in the biological processes of tendon healing and regeneration. A wide range of miRNAs in tendon injury have been shown to play vital roles in maintaining and regulating its physiological function, as well as regulating the tenogenic differentiation potential of stem cells. In this review, we show the summary of the latest information on the role of miRNAs in tendon healing and regeneration, and also discuss potentials for miRNA-directed diagnosis and therapy in tendon injuries and tendinopathy, which may provide new theoretical foundation for tenogenesis and tendon healing.
Cancel (Out) Emissions? The Envisaged Role of Carbon Dioxide Removal Technologies in Long-Term National Climate Strategies
Authors: Buylova Alexandra , Fridahl Mathias , Nasiritousi Naghmeh , Reischl Gunilla
Published: July 2021

Carbon dioxide removal (CDR) increasingly features in climate scenarios that hold global warming well below 2°C by 2100. Given the continuous gap between climate mitigation pledges and the emission pathways that are aligned with achieving the temperature goals of the Paris Agreement, we would expect countries to promote CDR in their long-term planning to achieve mid-century targets. Yet, countries may not consider it their responsibility to contribute to the global response to climate change using CDR. Thus, a study of the respective country's long-term climate plans is both timely and vital. Such a study could reveal the pledged collective ambition, the contribution of CDR to the pledged ambition, and how the envisaged role of CDR is described by the different countries. This paper explores the long-term low emission development strategies (LT-LEDS) of countries in order to map the role of CDR in addressing climate change. We also supplement our examination of strategies with the opinions of climate experts. Based on an inductive coding of the material and a literature review, the analytical focus of the analysis includes CDR targets and planning, types of CDR, barriers and opportunities to CDR implementation, as well as international cooperation. Our study of 25 national LT-LEDS submitted to the UN or to the EU, as well as 23 interviews with climate experts, shows that national plans for CDR vary substantially across countries and are generally lacking in detail. The findings also demonstrate that CDR is perceived to be necessary and desirable for achieving mid-century climate goals, but also reveal variation in the intended role of CDR. We use an interpretive approach to outline three possible visions of CDR in climate action: as a panacea, as a necessary fallback and as a chimera. We conclude by discussing what our findings of the envisaged roles of CDR in addressing climate change mean for climate governance. This research thereby contributes to the literature on governing CDR with new comprehensive insights into the long-term climate strategies of countries.
Long Term Rescue of the TSH Receptor Knock-Out Mouse – Thyroid Stem Cell Transplantation Restores Thyroid Function
Authors: Latif Rauf , Ma Risheng , Morshed Syed A. , Tokat Bengu , Davies Terry F.
Published: July 2021

The synergistic activation of transcription factors can lead to thyroid progenitor cell speciation. We have previously shown in vitro that mouse or human stem cells, expressing the transcription factors NKx2-1 and Pax8, can differentiate into thyroid neo-follicular structures (TFS). We now show that syngeneic mouse TFS when implanted into hypothyroid TSH receptor knockout (TSHR-KO) mice can ameliorate the hypothyroid state for an extended period. ES cells derived from heterozygous TSHR-KO blastocysts were stably transfected with Nkx2-1-GFP and Pax8-mcherry constructs and purified into 91.8% double positive cells by flow cytometry. After 5 days of activin A treatment these double positive cells were then induced to differentiate into neo-follicles in Matrigel for 21 days in the presence of 500μU/mL of TSH. Differentiated TFS expressing thyroglobulin mRNA were implanted under the kidney capsule of 4-6 weeks old TSHR-KO mice (n=5) as well as hind limb muscle (n=2) and anterior chamber of one eye (n=2). Five of the mice tested after 4 weeks were all rendered euthyroid and all mice remained euthyroid at 20 weeks post implantation. The serum T4 fully recovered (pre-bleed 0.62 ± 0.03 to 8.40 ± 0.57 µg/dL) and the previously elevated TSH became normal or suppressed (pre-bleed 391 ± 7.6 to 4.34 ± 1.25 ng/dL) at the end of the 20 week observation period. The final histology obtained from the implanted kidney tissues showed only rudimentary thyroid follicular structures but which stained positive for thyroglobulin expression. The presence of only rudimentary structures at the site of implant on these extended animals suggested possible migration of cells from the site of implant or an inability of TFCs to maintain proper follicular morphology in these external sites for extended periods. However, there were no signs of tumor formation and no immune infiltration. These preliminary studies show that TSHR-KO mice are a useful model for orthotropic implantation of functional thyroid cells without the need for thyroidectomy, radioiodine ablation or anti thyroid drug control of thyroid function. This approach is also proof of principle that thyroid cells derived from mouse ES cells are capable of surviving as functional neo-follicles in vivo for an extended period of 20 weeks.
Investigation of the S-Shaped Current–Voltage Curve in High Open-Circuit Voltage Ruddlesden–Popper Perovskite Solar Cells
Authors: Zhong Hong , Zhou Renlai , Wu Xiaoqing , Lin Xiaoyun , Wang Ya , Li Qian , Zhou Hang
Published: July 2021

We report our investigation on the S-shaped current–voltage characteristics in a hot-casting–processed (BA)2 (MA)3Pb4I13 Ruddlesden–Popper (RP) perovskite solar cell. The two-dimensional perovskite solar cells are fabricated with NiOx as the hole transport layer (HTL), which leads to significantly high open-circuit voltage (Voc). The champion device shows a Voc of 1.21 V and a short current density (Jsc) of 17.14 mA/cm2, leading to an overall power conversion efficiency (PCE) of 13.7%. Although the PCE is much higher than the control device fabricated on PEDOT:PSS, a significant S-shaped current–voltage behavior is observed in these NiOx-based devices. It is found that the S-shaped current–voltage behavior is related to the lower dimensional phase distribution and crystallinity at the bottom interface of the RP perovskite layer, and the S-shaped distortion is less severe after the device ageing test.
The Effect of Animal Bipedal Posture on Perceived Cuteness, Fear, and Willingness to Protect Them
Authors: Prokop Pavol , Zvaríková Martina , Zvarík Milan , Pazda Adam , Fedor Peter
Published: July 2021

Human–animal relationships have long been the subject of controversy because they are shaped by several cultural, inter-individual, and evolutionary factors. Understanding these relationships, however, is important to optimize conservation efforts. There is agreement that perceived similarity between animals and humans is associated with more positive attitudes. The human–animal similarity could be caused by phylogenetic closeness. We hypothesized that the bipedal posture of an animal may be perceived as a cue of phenotypic similarity with humans. We examined this topic by comparing perceived cuteness, fear, and willingness to protect animals differing in body posture, body size, and phylogenetic closeness with humans on a sample ofN= 349 Slovak participants. We found that the bipedal posture enhanced perceived cuteness, but this effect was most pronounced in small-bodied animals, particularly those with direct eye contact. Phylogenetically close and small-bodied species (e.g., small mammals) received greater conservation support than phylogenetically distant species (e.g., invertebrates). However, anthropomorphic-looking animals received greater conservation support, suggesting that pictures of animals that more closely resemble humans can be used in conservation campaigns.
Systematic Prediction of Antifungal Drug Synergy by Chemogenomic Screening in Saccharomyces cerevisiae
Authors: Gaikani Hamid , Smith Andrew M. , Lee Anna Y. , Giaever Guri , Nislow Corey
Published: July 2021

Since the earliest days of using natural remedies, combining therapies for disease treatment has been standard practice. Combination treatments exhibit synergistic effects, broadly defined as a greater-than-additive effect of two or more therapeutic agents. Clinicians often use their experience and expertise to tailor such combinations to maximize the therapeutic effect. Although understanding and predicting biophysical underpinnings of synergy have benefitted from high-throughput screening and computational studies, one challenge is how to best design and analyze the results of synergy studies, especially because the number of possible combinations to test quickly becomes unmanageable. Nevertheless, the benefits of such studies are clear—by combining multiple drugs in the treatment of infectious disease and cancer, for instance, one can lessen host toxicity and simultaneously reduce the likelihood of resistance to treatment. This study introduces a new approach to characterize drug synergy, in which we extend the widely validated chemogenomic HIP–HOP assay to drug combinations; this assay involves parallel screening of comprehensive collections of barcoded deletion mutants. We identify a class of “combination-specific sensitive strains” that introduces mechanisms for the synergies we observe and further suggest focused follow-up studies.
Truck Parking Occupancy Prediction: XGBoost-LSTM Model Fusion
Authors: Gutmann Sebastian , Maget Christoph , Spangler Matthias , Bogenberger Klaus
Published: July 2021

For haul truck drivers it is becoming increasingly difficult to find appropriate parking at the end of a shift. Proper, legal, and safe overnight parking spots are crucial for truck drivers in order for them to be able to comply with Hours of Service regulation, reduce fatigue, and improve road safety. The lack of parking spaces affects the backbone of the economy because 70% of all United States domestic freight shipments (in terms of value) are transported by trucks. Many research projects provide real-time truck parking occupancy information at a given stop. However, truck drivers ultimately need to know whether parking spots will be available at a downstream stop at their expected arrival time. We propose a machine-learning-based model that is capable of accurately predicting occupancy 30, 60, 90, and 120 min ahead. The model is based on the fusion of Extreme Gradient Boosting (XGBoost) and Long Short-Term Memory (LSTM) with the help of a feed-forward neural network. Our results show that prediction of truck parking occupancy can be achieved with small errors. Root mean square error metrics are 2.1, 2.9, 3.5, and 4.1 trucks for the four different horizons, respectively. The unique feature of our proposed model is that it requires only historic occupancy data. Thus, any truck occupancy detection system could also provide forecasts by implementing our model.
Novel Reclassification of Adult Diabetes Is Useful to Distinguish Stages of β-Cell Function Linked to the Risk of Vascular Complications: The DOLCE Study From Northern Ukraine
Authors: Fedotkina Olena , Sulaieva Oksana , Ozgumus Turkuler , Cherviakova Liubov , Khalimon Nadiya , Svietleisha Tetiana , Buldenko Tetiana , Ahlqvist Emma , Asplund Olof , Groop Leif , Nilsson Peter M. , Lyssenko Valeriya
Published: July 2021

Background

Presently, persons with diabetes are classified as having type 1 (T1D) or type 2 diabetes (T2D) based on clinical diagnosis. However, adult patients exhibit diverse clinical representations and this makes treatment approaches challenging to personalize. A recent Scandinavian study proposed a novel classification of adult diabetes into five clusters based on disease pathophysiology and risk of vascular complications. The current study aimed to characterize new subgroups of adult diabetes using this strategy in a defined population from northern Ukraine.

Methods

We analyzed 2,140 patients with established diabetes from the DOLCE study (n= 887 with new-onset diabetes andn= 1,253 with long duration). We used the k-means approach to perform clustering analyses using BMI, age at onset of diabetes, HbA1c, insulin secretion (HOMA2-B), and insulin resistance (HOMA2-IR) indices and glutamic acid decarboxylase antibodies (GADA) levels. Risks of macro- (myocardial infarction or stroke) and microvascular [retinopathy, chronic kidney disease (CKD) and neuropathy] complications and associations of genetic variants with specific clusters were studied using logistic regression adjusted for age, sex, and diabetes duration.

Results

Severe autoimmune diabetes (SAID, 11 and 6%) and severe insulin-deficient diabetes (SIDD, 25 and 14%) clusters were twice as prevalent in patients with long-term as compared to those with new-onset diabetes. Patients with long duration in both SAID and SIDD clusters had highest risks of proliferative retinopathy, and elevated risks of CKD. Long-term insulin-resistant obese diabetes 1 (IROD1) subgroup had elevated risks of CKD, while insulin-resistant obese diabetes 2 (IROD2) cluster exhibited the highest HOMA2-B, lowest HbA1c, and lower prevalence of all microvascular complications as compared to all other clusters. Genetic analyses of IROD2 subgroup identified reduced frequency of the risk alleles in theTCF7L2gene as compared to all other clusters, cumulatively and individually (p= 0.0001).

Conclusion

The novel reclassification algorithm of patients with adult diabetes was reproducible in this population from northern Ukraine. It may be beneficial for the patients in the SIDD subgroup to initiate earlier insulin treatment or other anti-diabetic modalities to preserve β-cell function. Long-term diabetes cases with preserved β-cell function and lower risk for microvascular complications represent an interesting subgroup of patients for further investigations of protective mechanisms.
Biomarker Categorization in Transcriptomic Meta-Analysis by Concordant Patterns With Application to Pan-Cancer Studies
Authors: Ye Zhenyao , Ke Hongjie , Chen Shuo , Cruz-Cano Raul , He Xin , Zhang Jing , Dorgan Joanne , Milton Donald K. , Ma Tianzhou
Published: July 2021

With the increasing availability and dropping cost of high-throughput technology in recent years, many-omics datasets have accumulated in the public domain. Combining multiple transcriptomic studies on related hypothesis via meta-analysis can improve statistical power and reproducibility over single studies. For differential expression (DE) analysis, biomarker categorization by DE pattern across studies is a natural but critical task following biomarker detection to help explain between study heterogeneity and classify biomarkers into categories with potentially related functionality. In this paper, we propose a novel meta-analysis method to categorize biomarkers by simultaneously considering the concordant pattern and the biological and statistical significance across studies. Biomarkers with the same DE pattern can be analyzed together in downstream pathway enrichment analysis. In the presence of different types of transcripts (e.g., mRNA, miRNA, and lncRNA, etc.), integrative analysis including miRNA/lncRNA target enrichment analysis and miRNA-mRNA and lncRNA-mRNA causal regulatory network analysis can be conducted jointly on all the transcripts of the same category. We applied our method to two Pan-cancer transcriptomic study examples with single or multiple types of transcripts available. Targeted downstream analysis identified categories of biomarkers with unique functionality and regulatory relationships that motivate new hypothesis in Pan-cancer analysis.
Integrated Genome and Transcriptome Sequencing to Solve a Neuromuscular Puzzle: Miyoshi Muscular Dystrophy and Early Onset Primary Dystonia in Siblings of the Same Family
Authors: Zhu Feng , Zhang Fengxiao , Hu Lizhi , Liu Haowen , Li Yahua
Published: July 2021

Background

Neuromuscular disorders (NMD), many of which are hereditary, affect muscular function. Due to advances in high-throughput sequencing technologies, the diagnosis of hereditary NMDs has dramatically improved in recent years.

Methods and Results

In this study, we report an family with two siblings exhibiting two different NMD, Miyoshi muscular dystrophy (MMD) and early onset primary dystonia (EOPD). Whole exome sequencing (WES) identified a novel monoallelic frameshift deletion mutation (dysferlin: c.4404delC/p.I1469Sfs∗17) in the Dysferlin gene in the index patient who suffered from MMD. This deletion was inherited from his unaffected father and was carried by his younger sister with EOPD. However, immunostaining staining revealed an absence of dysferlin expression in the proband’s muscle tissue and thus suggested the presence of the second underlying mutant allele in dysferlin. Using integrated RNA sequencing (RNA-seq) and whole genome sequencing (WGS) of muscle tissue, a novel deep intronic mutation in dysferlin (dysferlin: c.5341-415A > G) was discovered in the index patient. This mutation caused aberrant mRNA splicing and inclusion of an additional pseudoexon (PE) which we termed PE48.1. This PE was inherited from his unaffected mother. PE48.1 inclusion altered the Dysferlin sequence, causing premature termination of translation.

Conclusion

Using integrated genome and transcriptome sequencing, we discovered hereditary MMD and EOPD affecting two siblings of same family. Our results added further weight to the combined use of RNA-seq and WGS as an important method for detection of deep intronic gene mutations, and suggest that integrated sequencing assays are an effective strategy for the diagnosis of hereditary NMDs.
U5 snRNA Interactions With Exons Ensure Splicing Precision
Authors: Artemyeva-Isman Olga V. , Porter Andrew C. G.
Published: July 2021

Imperfect conservation of human pre-mRNA splice sites is necessary to produce alternative isoforms. This flexibility is combined with the precision of the message reading frame. Apart from intron-termini GU_AG and the branchpoint A, the most conserved are the exon-end guanine and +5G of the intron start. Association between these guanines cannot be explained solely by base-pairing with U1 snRNA in the early spliceosome complex. U6 succeeds U1 and pairs +5G in the pre-catalytic spliceosome, while U5 binds the exon end. Current U5 snRNA reconstructions by CryoEM cannot explain the conservation of the exon-end G. Conversely, human mutation analyses show that guanines of both exon termini can suppress splicing mutations. Our U5 hypothesis explains the mechanism of splicing precision and the role of these conserved guanines in the pre-catalytic spliceosome. We propose: (1) optimal binding register for human exons and U5—the exon junction positioned at U5Loop1 C39|C38; (2) common mechanism for base-pairing of human U5 snRNA with diverse exons and bacterial Ll.LtrB intron with new loci in retrotransposition—guided by base pair geometry; and (3) U5 plays a significant role in specific exon recognition in the pre-catalytic spliceosome. Statistical analyses showed increased U5 Watson–Crick pairs with the 5′exon in the absence of +5G at the intron start. In 5′exon positions −3 and −5, this effect is specific to U5 snRNA rather than U1 snRNA of the early spliceosome. Increased U5 Watson–Crick pairs with 3′exon position +1 coincide with substitutions of the conserved −3C at the intron 3′end. Based on mutation and X-ray evidence, we propose that −3C pairs with U2 G31 juxtaposing the branchpoint and the 3′intron end. The intron-termini pair, formed in the pre-catalytic spliceosome to be ready for transition after branching, and the early involvement of the 3′intron end ensure that the 3′exon contacts U5 in the pre-catalytic complex. We suggest that splicing precision is safeguarded cooperatively by U5, U6, and U2 snRNAs that stabilize the pre-catalytic complex by Watson–Crick base pairing. In addition, our new U5 model explains the splicing effect of exon-start +1G mutations: U5 Watson–Crick pairs with exon +2C/+3G strongly promote exon inclusion. We discuss potential applications for snRNA therapeutics and gene repair by reverse splicing.
Sarcopenia: What Is the Origin of This Aging-Induced Disorder?
Authors: Gustafsson Thomas , Ulfhake Brun
Published: July 2021

We here review the loss of muscle function and mass (sarcopenia) in the framework of human healthspan and lifespan, and mechanisms involved in aging. The rapidly changing composition of the human population will impact the incidence and the prevalence of aging-induced disorders such as sarcopenia and, henceforth, efforts to narrow the gap between healthspan and lifespan should have top priority. There are substantial knowledge gaps in our understanding of aging. Heritability is estimated to account for only 25% of lifespan length. However, as we push the expected lifespan at birth toward those that we consider long-lived, the genetics of aging may become increasingly important. Linkage studies of genetic polymorphisms to both the susceptibility and aggressiveness of sarcopenia are still missing. Such information is needed to shed light on the large variability in clinical outcomes between individuals and why some respond to interventions while others do not. We here make a case for the concept that sarcopenia has a neurogenic origin and that in manifest sarcopenia, nerve and myofibers enter into a vicious cycle that will escalate the disease progression. We point to gaps in knowledge, for example the crosstalk between the motor axon, terminal Schwann cell, and myofiber in the denervation processes that leads to a loss of motor units and muscle weakness. Further, we argue that the operational definition of sarcopenia should be complemented with dynamic metrics that, along with validated biomarkers, may facilitate early preclinical diagnosis of individuals vulnerable to develop advanced sarcopenia. We argue that preventive measures are likely to be more effective to counter act aging-induced disorders than efforts to treat manifest clinical conditions. To achieve compliance with a prescription of preventive measures that may be life-long, we need to identify reliable predictors to design rational and convincing interventions.
Innate Lymphoid Cells Activation and Transcriptomic Changes in Response to Human Dengue Infection
Authors: Poonpanichakul Tiraput , Chan-In Wilawan , Opasawatchai Anunya , Loison Fabien , Matangkasombut Oranart , Charoensawan Varodom , Matangkasombut Ponpan ,   DENFREE Thailand
Published: July 2021

Background

Dengue virus (DENV) infection has a global impact on public health. The clinical outcomes (of DENV) can vary from a flu-like illness called dengue fever (DF), to a more severe form, known as dengue hemorrhagic fever (DHF). The underlying innate immune mechanisms leading to protective or detrimental outcomes have not been fully elucidated. Helper innate lymphoid cells (hILCs), an innate lymphocyte recently discovered, functionally resemble T-helper cells and are important in inflammation and homeostasis. However, the role of hILCs in DENV infection had been unexplored.

Methods

We performed flow cytometry to investigate the frequency and phenotype of hILCs in peripheral blood mononuclear cells from DENV-infected patients of different disease severities (DF and DHF), and at different phases (febrile and convalescence) of infection. Intracellular cytokine staining of hILCs from DF and DHF were also evaluated by flow cytometry after ex vivo stimulation. Further, the hILCs were sorted and subjected to transcriptome analysis using RNA sequencing. Differential gene expression analysis was performed to compare the febrile and convalescent phase samples in DF and DHF. Selected differentially expressed genes were then validated by quantitative PCR.

Results

Phenotypic analysis showed marked activation of all three hILC subsets during the febrile phase as shown by higher CD69 expression when compared to paired convalescent samples, although the frequency of hILCs remained unchanged. Upon ex vivo stimulation, hILCs from febrile phase DHF produced significantly higher IFN-γ and IL-4 when compared to those of DF. Transcriptomic analysis showed unique hILCs gene expression in DF and DHF, suggesting that divergent functions of hILCs may be associated with different disease severities. Differential gene expression analysis indicated that hILCs function both in cytokine secretion and cytotoxicity during the febrile phase of DENV infection.

Conclusions

Helper ILCs are activated in the febrile phase of DENV infection and display unique transcriptomic changes as well as cytokine production that correlate with severity. Targeting hILCs during early innate response to DENV might help shape subsequent immune responses and potentially lessen the disease severity in the future.
Comparison of Different Test Systems for the Detection of Antiphospholipid Antibodies in a Chinese Cohort
Authors: Hu Chaojun , Li Siting , Xie Zhijuan , You Hanxiao , Jiang Hui , Shi Yu , Qi Wanting , Zhao Jiuliang , Wang Qian , Tian Xinping , Li Mengtao , Zhao Yan , Zeng Xiaofeng
Published: July 2021

Background

Diagnosis of antiphospholipid syndrome (APS) is based on the positivity of laboratory criteria antiphospholipid antibodies (aPLs). Test results for aPLs could be contradictory among different detection methods as well as commercial manufacturers. This study aimed to assess and compare the diagnostic and analytic performances of four commercial assays prevalently used in China.

Methods

A total of 313 patients including 100 patients diagnosed with primary APS, 52 with APS secondary to SLE, 71 with SLE, and 90 health controls were recruited. Serum IgG, IgM, and IgA for aCL, and aβ2GPI antibodies were detected with two ELISA and two CLIA systems, and test system with the best diagnostic value was explored of its correlation with key clinical features.

Results

CLIA by YHLO Biotech Co. was considered as the system with the best predictive power, where 58.55 and 57.89% of APS patients were positive for aCL or aβ2GPI for at least one antibody (IgG or IgM or IgA). Overall, CLIA showed better performance characteristics than traditional ELISA test systems.

Conclusion

CLIA was considered as a better platform for aPL detection in APS diagnosis. A combination of other detection platforms could assist in differential diagnosis as well as in identifying high-risk patients.
Understanding the Gastrointestinal Protective Effects of Polyphenols using Foodomics-Based Approaches
Authors: Zhang Wenwen , Qi Suzhen , Xue Xiaofeng , Al Naggar Yahya , Wu Liming , Wang Kai
Published: July 2021

Plant polyphenols are rich sources of natural anti-oxidants and prebiotics. After ingestion, most polyphenols are absorbed in the intestine and interact with the gut microbiota and modulated metabolites produced by bacterial fermentation, such as short-chain fatty acids (SCFAs). Dietary polyphenols immunomodulatory role by regulating intestinal microorganisms, inhibiting the etiology and pathogenesis of various diseases including colon cancer, colorectal cancer, inflammatory bowel disease (IBD) and colitis. Foodomics is a novel high-throughput analysis approach widely applied in food and nutrition studies, incorporating genomics, transcriptomics, proteomics, metabolomics, and integrating multi-omics technologies. In this review, we present an overview of foodomics technologies for identifying active polyphenol components from natural foods, as well as a summary of the gastrointestinal protective effects of polyphenols based on foodomics approaches. Furthermore, we critically assess the limitations in applying foodomics technologies to investigate the protective effect of polyphenols on the gastrointestinal (GI) system. Finally, we outline future directions of foodomics techniques to investigate GI protective effects of polyphenols. Foodomics based on the combination of several analytical platforms and data processing for genomics, transcriptomics, proteomics and metabolomics studies, provides abundant data and a more comprehensive understanding of the interactions between polyphenols and the GI tract at the molecular level. This contribution provides a basis for further exploring the protective mechanisms of polyphenols on the GI system.
A Strong Synergy Between the Thiopeptide Bacteriocin Micrococcin P1 and Rifampicin Against MRSA in a Murine Skin Infection Model
Authors: Ovchinnikov Kirill V. , Kranjec Christian , Telke Amar , Kjos Morten , Thorstensen Tage , Scherer Siegfried , Carlsen Harald , Diep Dzung B.
Published: July 2021

Antibiotic-resistant bacterial pathogens have become a serious threat worldwide. One of these pathogens is methicillin-resistant Staphylococcus aureus (MRSA), a major cause of skin and soft tissue infections. In this study we identified a strain of Staphylococcus equorum producing a substance with high antimicrobial activity against many Gram-positive bacteria, including MRSA. By mass spectrometry and whole genome sequencing the antimicrobial substance was identified as the thiopeptide bacteriocin micrococcin P1 (MP1). Based on its properties we developed a one-step purification protocol resulting in high yield (15 mg/L) and high purity (98%) of MP1. For shorter incubation times (5-7 h) MP1 was very potent against MRSA but the inhibitory effect was overshadowed by resistance development during longer incubation time (24h or more). To overcome this problem a synergy study was performed with a number of commercially available antibiotics. Among the antibiotics tested, the combination of MP1 and rifampicin gave the best synergistic effect, with MIC values 25 and 60 times lower than for the individual drugs, respectively. To assess the therapeutic potential of the MP1-rifampicin combination, we used a murine skin infection model based on the use of the multidrug-resistant luciferase-tagged MRSA strain Xen31. As expected, neither of the single antimicrobials (MP1 or rifampicin) could eradicate Xen31 from the wounds. By contrary, the MP1-rifampicin combination was efficient not only to eradicate but also to prevent the recurrence of Xen31 infection. Furthermore, compared to fucidin cream, which is commonly used in skin infection treatments, MP1-rifampicin combination was superior in terms of preventing resistance development. Our results show that combining MP1, and probably other thiopeptides, with antibiotics can be a promising strategy to treat SSTIs caused by MRSA and likely many other Gram-positive bacteria.
Targeting TLR4 Signaling to Blunt Viral-Mediated Acute Lung Injury
Authors: Shirey Kari Ann , Blanco Jorge C. G. , Vogel Stefanie N.
Published: July 2021

Respiratory viral infections have been a long-standing global burden ranging from seasonal recurrences to the unexpected pandemics. The yearly hospitalizations from seasonal viruses such as influenza can fluctuate greatly depending on the circulating strain(s) and the congruency with the predicted strains used for the yearly vaccine formulation, which often are not predicted accurately. While antiviral agents are available against influenza, efficacy is limited due to a temporal disconnect between the time of infection and symptom development and viral resistance. Uncontrolled, influenza infections can lead to a severe inflammatory response initiated by pathogen-associated molecular patterns (PAMPs) or host-derived danger-associated molecular patterns (DAMPs) that ultimately signal through pattern recognition receptors (PRRs). Overall, these pathogen-host interactions result in a local cytokine storm leading to acute lung injury (ALI) or the more severe acute respiratory distress syndrome (ARDS) with concomitant systemic involvement and more severe, life threatening consequences. In addition to traditional antiviral treatments, blocking the host’s innate immune response may provide a more viable approach to combat these infectious pathogens. The SARS-CoV-2 pandemic illustrates a critical need for novel treatments to counteract the ALI and ARDS that has caused the deaths of millions worldwide. This review will examine how antagonizing TLR4 signaling has been effective experimentally in ameliorating ALI and lethal infection in challenge models triggered not only by influenza, but also by other ALI-inducing viruses.
Mangrove Loss and Gain in a Densely Populated Urban Estuary: Lessons From the Guangdong-Hong Kong-Macao Greater Bay Area
Authors: Wang Heng , Peng Yisheng , Wang Chen , Wen Qingke , Xu Jinyong , Hu Zhan , Jia Xing , Zhao Xuemei , Lian Weihang , Temmerman Stijn , Wolf Judith , Bouma Tjeerd
Published: July 2021

Understanding the recent changes in mangrove adjacent to mega-cities is critical for conservation, management, and policymaking in coastal zones with fast population growth and global change. Here we investigated mangrove area changes in one of the world’s largest urban areas near the main estuaries in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA). Mangrove area changes are quantified for the period 1990–2018 by analyzing multiple sources of satellite images by classification algorithms. We found that estuarine mangrove area dynamics are driven by human actions and are contrasting between these two periods. (1) During 1990–2000, the estuarine mangrove area approximately decreased from 11.5 to 6.9 km2, among which the bulk part was transformed into aquaculture ponds (41.1%) and built-up area (29.9%). (2) During 2000–2018, the estuarine mangrove area rapidly increased to 18.3 km2 resulting from the protection and restoration efforts. Proportions of mangrove occurring in nature reserves increased from 37.5% in 1990 to >80% in the 2000s. Two major mangrove expansion ways, natural establishment (NE, in protected areas without any human interference) and human afforestation (HA) accounted almost equally (53.1 and 46.9%) for the gained estuarine mangrove area during 2010–2018. A future projection according to the current mangrove increasing rate suggests that all the low-lying land that is theoretically suitable for mangrove afforestation would be used up by 2060. Although afforestation has contributed to important gains in mangrove quantity, we highlight that it may also imply decreased habitat quality. It has resulted in a great occupation of high tidal mudflats and a loss of their valuable ecosystem services, and it may lead to spreading of non-native species, e.g., Sonneratia apetala, used in afforestation programs. Future restoration approaches should adopt more eco-friendly strategies, like reversing (abandoned) aquaculture ponds to native mangrove forests. Knowledge obtained from the GBA in this study may be also instrumental to ecological restorations for mangrove forests in other urbanized estuaries.
Contrasting Behaviors of 210Pb and 210Po in the Productive Shelf Water Versus the Oligotrophic Water
Authors: Seo Hojong , Joung DongJoo , Kim Guebuem
Published: July 2021

We measured the total, truly dissolved (<10 kDa), colloidal (10 kDa–0.2 μm), and particulate phases (>0.2 μm) of 210Pb and 210Po in the East China Sea (ECS) shelf water and the East Sea (Japan Sea). In order to examine the behaviors of 210Pb and 210Po in different marine environments, we compiled our results with previously reported data in the same region and in the northwestern Pacific Ocean (NWPO). The proportions of the truly dissolved, colloidal, and particulate phases in the shelf water were 32, 27, and 41% for 210Pb and 49, 32, and 19% for 210Po, respectively. Based on a steady-state scavenging model, 210Pb and 210Po showed higher (3.0 ± 0.6 year–1) and lower (0.3 ± 0.2 year–1) scavenging rates, respectively, in the shelf water than those in the NWPO and the East Sea. A non-steady-state model, accounting for the residence time of the shelf water, also showed twice more efficient removal rate of 210Pb in the shelf water than that in the NWPO and the East Sea. In contrast, there was the net input of 210Po in the shelf water relative to the large removal in the NWPO and the East Sea. The large proportions of total dissolved (truly dissolved + colloidal) 210Po (>80%) in the shelf water indicate active regeneration of 210Po from the sinking particles and the surface sediments. Our results suggest that the ECS shelf is the source for Po in the northwestern Pacific marginal seas, a proxy for sulfur group elements (S, Se, and Te), whereas it is the efficient sink for Pb, together with other particle-reactive trace elements.
Impact of 6-Month Exposure to Aerosols From Potential Modified Risk Tobacco Products Relative to Cigarette Smoke on the Rodent Gastrointestinal Tract
Authors: Battey James N. D. , Szostak Justyna , Phillips Blaine , Teng Charles , Tung Ching Keong , Lim Wei Ting , Yeo Ying Shan , Ouadi Sonia , Baumer Karine , Thomas Jerome , Martinis Jacopo , Sierro Nicolas , Ivanov Nikolai V. , Vanscheeuwijck Patrick , Peitsch Manuel C. , Hoeng Julia
Published: July 2021

Cigarette smoking causes adverse health effects that might occur shortly after smoking initiation and lead to the development of inflammation and cardiorespiratory disease. Emerging studies have demonstrated the role of the intestinal microbiome in disease pathogenesis. The intestinal microbiome is susceptible to the influence of environmental factors such as smoking, and recent studies have indicated microbiome changes in smokers. Candidate modified risk tobacco products (CMRTP) are being developed to provide substitute products to lower smoking-related health risks in smokers who are unable or unwilling to quit. In this study, the ApoE–/– mouse model was used to investigate the impact of cigarette smoke (CS) from the reference cigarette 3R4F and aerosols from two CMRTPs based on the heat-not-burn principle [carbon-heated tobacco product 1.2 (CHTP 1.2) and tobacco heating system 2.2 (THS 2.2)] on the intestinal microbiome over a 6-month period. The effect of cessation or switching to CHTP 1.2 after 3 months of CS exposure was also assessed. Next-generation sequencing was used to evaluate the impact of CMRTP aerosols in comparison to CS on microbiome composition and gene expression in the digestive tract of mice. Our analyses highlighted significant gene dysregulation in response to 3R4F exposure at 4 and 6 months. The findings showed an increase in the abundance of Akkermansiaceae upon CS exposure, which was reversed upon cessation. Cessation resulted in a significant decrease in Akkemansiaceae abundance, whereas switching to CHTP 1.2 resulted in an increase in Lactobacillaceae abundance. These microbial changes could be important for understanding the effect of CS on gut function and its relevance to disease pathogenesis via the microbiome.
STAT3-Dependent Gene TRIM5γ Interacts With HBx Through a Zinc Binding Site on the BBox Domain
Authors: Song Hongxiao , Xu Fengchao , Pang Xiaoli , Xiao Qingfei , Wei Qi , Lei Bingxin , Li Xiaolu , Fan Xixi , Tan Guangyun
Published: July 2021

Owing to its broad-spectrum antivirus activities, interferon (IFN) is an important alternative agent for use in the treatment of hepatitis B virus (HBV)-infected patients; however, the mechanism involved in the inhibition of HBV infection and replication by IFN remains unclear. We previously reported that the induction of TRIM5γ is important in the IFN treatment of HBV patients as it promotes the degradation of the HBx protein, while the manner in which TRIM5γ is induced by IFN and how TRIM5γ interacts with HBx remain unestablished until date. Our present findings confirmed the TRIM5γ-HBx-DDB1 interactions in the HBV-infected Primary human hepatocytes (PHH), and we further found that STAT3, and not STAT1, was responsible for the induction of TRIM5γ upon IFN stimulation and that the zinc binding site His123 on the BBOX domain was a decisive site in the interaction between TRIM5γ BBOX and HBx. In addition, based on the BBOX domain, we detected a 7-amino acid peptide with the potential of promoting HBx degradation and inhibiting HBV replication. On the other hand, we noted that the TRIM5γ expression was inhibited by HBV in chronically HBV infected patients. Thus, our study identified the crucial role of STAT3 in the induction of TRIM5γ, as well as proposed a 7-amino acid, small peptide as a potential candidate for the development of therapeutic agents targeting HBx.
Selenium Yeast Dietary Supplement Affects Rumen Bacterial Population Dynamics and Fermentation Parameters of Tibetan Sheep (Ovis aries) in Alpine Meadow
Authors: Cui Xiongxiong , Wang Zhaofeng , Tan Yuhui , Chang Shenghua , Zheng Huiru , Wang Haiying , Yan Tianhai , Guru Tsedan , Hou Fujiang
Published: July 2021

Selenium (Se) deficiency is a widespread and seasonally chronic phenomenon observed in Tibetan sheep (Ovis aries) traditionally grazed on the Qinghai–Tibet Plateau (QTP). Effects of the dietary addition of Se-enriched yeast (SeY) on the bacterial community in sheep rumen and rumen fermentation were evaluated with the aim of gaining a better understanding of the rumen prokaryotic community. Twenty-four yearling Tibetan rams [initial average body weight (BW) of 31.0 ± 0.64 kg] were randomly divided into four treatment groups, namely, control (CK), low Se (L), medium Se (M), and high Se (H). Each group comprised six rams and was fed a basic diet of fresh forage cut from the alpine meadow, to which SeY was added at prescribed dose rates. This feed trial was conducted for over 35 days. On the final day, rumen fluid was collected using a transesophageal sampler for analyzing rumen pH, NH3-N content, volatile fatty acid (VFA) level, and the rumen microbial community. Our analyses showed that NH3-N, total VFA, and propionate concentrations in the M group were significantly higher than in the other groups (P < 0.05). Both the principal coordinates analysis (PCoA) and the analysis of similarities revealed that the bacterial population structure of rumen differed among the four groups. The predominant rumen bacterial phyla were found to be Bacteroidetes and Firmicutes, and the three dominant genera in all the samples across all treatments were Christensenellaceae R7 group, Rikenellaceae RC9 gut group, and Prevotella 1. The relative abundances of Prevotella 1, Rikenellaceae RC9 gut group, Ruminococcus 2, Lachnospiraceae XPB1014 group, Carnobacterium, and Hafnia-Obesumbacterium were found to differ significantly among the four treatment groups (P < 0.05). Moreover, Tax4fun metagenome estimation revealed that gene functions and metabolic pathways associated with carbohydrate and other amino acids were overexpressed in the rumen microbiota of SeY-supplemented sheep. To conclude, SeY significantly affects the abundance of rumen bacteria and ultimately affects the rumen microbial fermentation.