bluuebunny/crossref_metadata_2025 huggingface dataset:
Overdosage of HNF1B Gene Associated With Annular Pancreas Detected in Neonate Patients With 17q12 Duplication
Authors: Xiao Feifan , Liu Xiuyun , Lu Yulan , Wu Bingbing , Liu Renchao , Liu Bo , Yan Kai , Chen Huiyao , Cheng Guoqiang , Wang Laishuan , Ni Qi , Li Gang , Zhang Ping , Peng Xiaomin , Cao Yun , Shen Chun , Wang Huijun , Zhou Wenhao
Published: May 2021

The annular pancreas (AP) is a congenital anomaly of the pancreas that can cause acute abdominal pain and vomiting after birth. However, the genetic cause of AP is still unknown, and no study has reported AP in patients with 17q12 duplication. This study retrospectively analyzed the next-generation sequencing (NGS) data of individuals from January 2016 to June 2020 for 17q12 duplication. To identify the function of the key gene ofHNF1Bin the 17q12 duplication region, humanHNF1BmRNA was microinjected into LiPan zebrafish transgenic embryos. A total of 19 cases of 17q12 duplication were confirmed. AP was diagnosed during exploratory laparotomy in four patients (21.1%). The other common features of 17q12 duplication included intellectual disability (50%), gross motor delay (50%), and seizures/epilepsy (31.58%). The ratio of the abnormal pancreas in zebrafish was significantly higher in theHNF1Boverexpression models. In conclusion, we first reported AP in patients with duplication of the 17q12 region, resulting in the phenotype of 17q12 duplication syndrome. Furthermore, our zebrafish studies verified the role of theHNF1Bgene in pancreatic development.
The Associations of Serum IL-37 With the Severity and Prognosis in Patients With Community-Acquired Pneumonia: A Retrospective Cohort Study
Authors: Wang Jia-Le , Chen Xue , Xu Yi , Chen Yue-Xin , Wang Jing , Liu Yu-Lu , Song Hai-Tao , Fei Jun , Zhao Hui , Fu Lin
Published: May 2021

Background

Recent evidences suggested that IL-37 may participate in the pathophysiology of community-acquired pneumonia (CAP). Nevertheless, its exact biological role was unknown. The objective of this study was to determine the associations of serum IL-37 with the severity and prognosis in CAP patients based on a retrospective cohort study.

Methods

The whole of 120 healthy subjects and 240 CAP patients were summoned. Peripheral blood was collected and IL-37 was detected using ELISA.

Results

Serum IL-37 was obviously decreased in CAP patients on admission. In addition, serum IL-37 was gradually decreased in parallel with CAP severity scores. Correlative analysis revealed that serum IL-37 was negatively associated with CAP severity scores and inflammatory cytokines. Further logistical regression found that reduction of serum IL-37 augmented the severity of CAP patients. Moreover, the follow-up research was performed in CAP patients. Serum lower IL-37 on admission prolonged the hospital stay in CAP patients. Serum IL-37 combination with PSI and CURB-65 had a stronger predictive capacity for death than IL-37 and CAP severity score alone in CAP patients.

Conclusion

There are remarkably negative correlations between serum IL-37 with the severity and prognosis in CAP patients. Serum IL-37 on admission prolongs the hospital stay, demonstrating that IL-37 may involve in the process of CAP. Serum IL-37 may be regarded as a biomarker for diagnosis and prognosis for CAP patients.
Mechanisms of Macrophage Plasticity in the Tumor Environment: Manipulating Activation State to Improve Outcomes
Authors: Ricketts Tiffany Davia , Prieto-Dominguez Nestor , Gowda Pramod Sreerama , Ubil Eric
Published: May 2021

Macrophages are a specialized class of innate immune cells with multifaceted roles in modulation of the inflammatory response, homeostasis, and wound healing. While developmentally derived or originating from circulating monocytes, naïve macrophages can adopt a spectrum of context-dependent activation states ranging from pro-inflammatory (classically activated, M1) to pro-wound healing (alternatively activated, M2). Tumors are known to exploit macrophage polarization states to foster a tumor-permissive milieu, particularly by skewing macrophages toward a pro-tumor (M2) phenotype. These pro-tumoral macrophages can support cancer progression by several mechanisms including immune suppression, growth factor production, promotion of angiogenesis and tissue remodeling. By preventing the adoption of this pro-tumor phenotype or reprogramming these macrophages to a more pro-inflammatory state, it may be possible to inhibit tumor growth. Here, we describe types of tumor-derived signaling that facilitate macrophage reprogramming, including paracrine signaling and activation of innate immune checkpoints. We also describe intervention strategies targeting macrophage plasticity to limit disease progression and address their implications in cancer chemo- and immunotherapy.
Longitudinal Analysis of COVID-19 Patients Shows Age-Associated T Cell Changes Independent of Ongoing Ill-Health
Authors: Townsend Liam , Dyer Adam H. , Naughton Aifric , Kiersey Rachel , Holden Dean , Gardiner Mary , Dowds Joanne , O’Brien Kate , Bannan Ciaran , Nadarajan Parthiban , Dunne Jean , Martin-Loeches Ignacio , Fallon Padraic G. , Bergin Colm , O’Farrelly Cliona , Cheallaigh Cliona Ni , Bourke Nollaig M. , Conlon Niall
Published: May 2021

Objectives

The immunological and inflammatory changes following acute COVID-19 are hugely variable. Persistent clinical symptoms following resolution of initial infection, termed long COVID, are also hugely variable, but association with immunological changes has not been described. We investigate changing immunological parameters in convalescent COVID-19 and interrogate their potential relationships with persistent symptoms.

Methods

We performed paired immunophenotyping at initial SARS-CoV-2 infection and convalescence (n=40, median 68 days) and validated findings in 71 further patients at median 101 days convalescence. Results were compared to 40 pre-pandemic controls. Fatigue and exercise tolerance were assessed as cardinal features of long COVID using the Chalder Fatigue Scale and 6-minute-walk test. The relationships between these clinical outcomes and convalescent immunological results were investigated.

Results

We identify persistent expansion of intermediate monocytes, effector CD8+, activated CD4+ and CD8+ T cells, and reduced naïve CD4+ and CD8+ T cells at 68 days, with activated CD8+ T cells remaining increased at 101 days. Patients >60 years also demonstrate reduced naïve CD4+ and CD8+ T cells and expanded activated CD4+ T cells at 101 days. Ill-health, fatigue, and reduced exercise tolerance were common in this cohort. These symptoms were not associated with immune cell populations or circulating inflammatory cytokines.

Conclusion

We demonstrate myeloid recovery but persistent T cell abnormalities in convalescent COVID-19 patients more than three months after initial infection. These changes are more marked with age and are independent of ongoing subjective ill-health, fatigue and reduced exercise tolerance.
Identification, Selection and Immune Assessment of Liver Stage CD8 T Cell Epitopes From Plasmodium falciparum
Authors: Tucker Kenneth D. , Schanen Brian C. , Phares Timothy W. , Sassano Emily , Terry Frances E. , Hindocha Pooja , Moise Leonard , Kotraiah Vinayaka , Martin William D. , De Groot Anne S. , Drake Donald R. , Gutierrez Gabriel M. , Noe Amy R.
Published: May 2021

Immunization with radiation-attenuated sporozoites (RAS) has been shown to protect against malaria infection, primarily through CD8 T cell responses, but protection is limited based on parasite strain. Therefore, while CD8 T cells are an ideal effector population target for liver stage malaria vaccine development strategies, such strategies must incorporate conserved epitopes that cover a large range of class I human leukocyte antigen (HLA) supertypes to elicit cross-strain immunity across the target population. This approach requires identifying and characterizing a wide range of CD8 T cell epitopes for incorporation into a vaccine such that coverage across a large range of class I HLA alleles is attained. Accordingly, we devised an experimental framework to identify CD8 T cell epitopes from novel and minimally characterized antigens found at the pre-erythrocytic stage of parasite development. Through in silico analysis we selected conservedP. falciparumproteins, usingP. vivaxorthologues to establish stringent conservation parameters, predicted to have a high number of T cell epitopes across a set of six class I HLA alleles representative of major supertypes. Using the decision framework, five proteins were selected based on the density and number of predicted epitopes. Selected epitopes were synthesized as peptides and evaluated for binding to the class I HLA allelesin vitroto verify in silico binding predictions, and subsequently for stimulation of human T cells using the Modular IMmune In-vitro Construct (MIMIC®) technology to verify immunogenicity. By combining the in silico tools with theex vivohigh throughput MIMIC platform, we identified 15 novel CD8 T cell epitopes capable of stimulating an immune response in alleles across the class I HLA panel. We recommend these epitopes should be evaluated in appropriatein vivohumanized immune system models to determine their protective efficacy for potential inclusion in future vaccines.
Citizen Science Driven Big Data Collection Requires Improved and Inclusive Societal Engagement
Authors: Dalby Oliver , Sinha Isadora , Unsworth Richard K. F. , McKenzie Len J. , Jones Benjamin L. , Cullen-Unsworth Leanne C.
Published: May 2021

Marine ecosystems are in a state of crisis worldwide due to anthropogenic stressors, exacerbated by generally diminished ocean literacy. In other sectors, big data and technological advances are opening our horizons towards improved knowledge and understanding. In the marine environment the opportunities afforded by big data and new technologies are limited by a lack of available empirical data on habitats, species, and their ecology. This limits our ability to manage these systems due to poor understanding of the processes driving loss and recovery. For improved chances of achieving sustainable marine systems, detailed local data is required that can be connected regionally and globally. Citizen Science (CS) is a potential tool for monitoring and conserving marine ecosystems, particularly in the case of shallow nearshore habitats, however, limited understanding exists as to the effectiveness of CS programmes in engaging the general public or their capacity to collect marine big data. This study aims to understand and identify pathways for improved engagement of citizen scientists. We investigated the motivations and barriers to engagement of participants in CS using two major global seagrass CS programmes. Programme participants were primarily researchers in seagrass science or similar fields which speak to a more general problem of exclusivity across CS. Altruistic motivations were demonstrated, whilst deterrence was associated with poor project organisation and a lack of awareness of specified systems and associated CS projects. Knowledge of seagrass ecosystems from existing participants was high and gains because of participation consequently minimal. For marine CS projects to support big data, we need to expand and diversify their current user base. We suggest enhanced outreach to stakeholders using cooperatively identified ecological questions, for example situated within the context of maintaining local ecosystem services. Dissemination of information should be completed with a variety of media types and should stress the potential for knowledge transfer, novel social interactions, and stewardship of local environments. Although our research confirms the potential for CS to foster enhanced collection of big data for improved marine conservation and management, we illustrate the need to improve and expand approaches to user engagement to reach required data targets.
The Need for Social Considerations in SDG 14
Authors: Haward Marcus , Haas Bianca
Published: May 2021

Sustainable Development Goal 14 acknowledges the need for action to achieve a sustainable future for our ocean. Many initiatives are working on ocean-related issues; however, social problems are often overlooked. In this article, we argue that to achieve a sustainable ocean, social aspects need to be considered. We explore the link between SDG 14 and SDG 8 as labor and working conditions on fishing vessels receive increasing attention. Regional Fisheries Management Organizations have the mandate to manage fisheries at the high seas, therefore, we argue that these organizations need to act on, and implement, resolutions and measures, addressing labor standards. Labor conditions related to the fishing sector have not received the level of scholarly attention that they deserve, thus more research is needed.
Integrative Description of Cryptic Tigriopus Species From Korea Using MALDI-TOF MS and DNA Barcoding
Authors: Yeom Jisu , Park Nayeon , Jeong Raehyuk , Lee Wonchoel
Published: May 2021

MALDI Time-of-Flight Mass Spectrometry (MALDI-TOF MS) provides a fast and reliable alternative method for species-level identification of pathogens and various metazoans. Compared to the commonly used mitochondrial cytochromecoxidase subunit I (mtCOI) barcoding, advantages of MALDI-TOF MS are rapid species identifications and low costs. In this study, we used MALDI-TOF MS to determine whether spectra patterns of different species can be used for species identification. We obtained a total of 138 spectra from individual specimens ofTigriopus, which were subsequently used for various cluster analyses. Our findings revealed these spectra form three clear clusters with high AU value support. This study validates the viability of MALDI-TOF MS as a methodology for higher-resolution species identification, allowing detection of cryptic species of harpacticoida. In addition, we propose a new species,Tigriopus koreanussp. nov. by utilizing integrative methods such as morphological comparison, mtCOI barcoding, and MALDI-TOF MS.
Site Characteristics More Than Vegetation Type Influence Food Web Structure of Intertidal Salt Marshes
Authors: Lafage Denis , Carpentier Alexandre , Duhamel Sylvain , Dupuy Christine , Feunteun Eric , Lesourd Sandric , Pétillon Julien
Published: May 2021

Salt marshes are under increasing anthropogenic pressures that have been reported to affect the diet of fish (e.g., change in prey composition and availability), eventually resulting in alterations in their nursery function. Most studies in Europe are based on fish gut content analysis, which only reflect a small proportion of pressures to salt marshes, and do not necessarily reflect long-term disturbances. In this study, we investigated the impact of salt-marsh vegetation type on trophic network structures (i.e., fish diet and trophic position). Primary producers (particulate organic matter, microphytobenthos, and dominant terrestrial plants), potential aquatic and terrestrial prey, and fish of two dominant species (sea bass and thinlip mullet) were sampled during the summer of 2010 in four creeks from two sites from Western France (the Mont-Saint-Michel Bay and the Seine Estuary). Analysis was undertaken using C and N stable-isotope compositions. Tested response variables (diet and trophic position) suggested a dominant site effect and a weaker effect of surrounding vegetation type. Site effect was attributed to differences in anthropogenic nitrogen inputs (with a steep increase in the Mont-Saint-Michel Bay) and tidal regime between the two bays, with more marine signatures associated with a higher frequency and duration of tidal flooding events in the Seine Estuary. A second hypothesis is that invasiveElytrigia acuta, which has recently replaced typical salt-marsh vegetation in Mont-Saint-Michel Bay, negatively impacted the native salt-marshes nursery function by modifying the access to terrestrial prey on this site. The trophic position of the sea bass and the thinlip mullet was unchanged by local salt-marsh vegetation, and considered consistent with their diet. This study highlights the relevance of stable-isotopes analyses for assessing long-term and integrative effects of changes in vegetation resulting from human disturbances in salt marshes.
Analysis of Anomalous Dynamic Responses of Fiber Metal Laminates Under Pulse Loading
Authors: Zhai Hongbo , Zhu Jianwei , Mao Boyong , Liu Wenyang
Published: May 2021

Composed of metallic layers and composite plies, fiber metal laminates (FMLs) combine inherent advantages of metals and composites. The phenomenon of anomalous response behavior, in which the permanent deformation is in the opposite direction to the incoming pressure wave, has been discovered in dynamic responses of monolithic plate subjected to impulsive loading. In this study, dynamic responses of FML plates of various configurations are examined and compared against the responses of a monolithic plate using finite element analysis. It is found that under the load condition in which an anomalous dynamic behavior of an aluminum plate is observed, FMLs oscillate a few cycles before resting on permanent deformation, and the laminate thickness strongly affects the final deflection, which could be in the counter-intuitive direction or near the initial position of zero deflection depending on configuration and specification of FMLs. In addition, interaction of damage accumulation with deflection responses is investigated. The findings of this study can be useful for optimal design of FMLs intended for usage under extreme loadings.
Applications of Bioinspired Reversible Dry and Wet Adhesives: A Review
Authors: Kang Minsu , Sun Kahyun , Seong Minho , Hwang Insol , Jang Hyejin , Park Seongjin , Choi Geonjun , Lee Sang-Hyeon , Kim Jaeil , Jeong Hoon Eui
Published: May 2021

Bioinspired adhesives that emulate the unique dry and wet adhesion mechanisms of living systems have been actively explored over the past two decades. Synthetic bioinspired adhesives that have recently been developed exhibit versatile smart adhesion capabilities, including controllable adhesion strength, active adhesion control, no residue remaining on the surface, and robust and reversible adhesion to diverse dry and wet surfaces. Owing to these advantages, bioinspired adhesives have been applied to various engineering domains. This review summarizes recent efforts that have been undertaken in the application of synthetic dry and wet adhesives, mainly focusing on grippers, robots, and wearable sensors. Moreover, future directions and challenges toward the next generation of bioinspired adhesives for advanced industrial applications are described.
Health Issues and Immunological Assessment Related to Wuhan's COVID-19 Survivors: A Multicenter Follow-Up Study
Authors: Mei Qi , Wang Fei , Yang Yang , Hu Guangyuan , Guo Suihuai , Zhang Qing , Bryant Amy , Zhang Lingjie , Kurts Christian , Wei Li , Yuan Xianglin , Li Jian
Published: May 2021

Background: Currently, a large number of hospitalized coronavirus infectious disease-2019 (COVID-19) patients have met the clinical discharge criteria and have been discharged. Little is known about the sequelae and herd immunity, two important factors influencing the life quality and safety of COVID-19 survivors.

Methods: Discharged COVID-19 patients from four medical facilities in Wuhan, China, were followed in order to record and investigate possible post-COVID-19 sequelae and herd immunity. After hospital discharge, patients reported to Fangcang shelter hospitals for an initial 14-day period of mandatory clinical monitoring. After release from these shelter hospitals, patients returned home for self-quarantine. Real-time quantitative PCR (RT-qPCR) was used for severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) detection. Colloidal gold-based immunochromatographic strip assay (ICGSA) was used for anti-SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody testing. The data for this study are derived from case reports, medical records, and self-reports.

Results: A total of 3,677 COVID-19 survivors [median age = 59 years, interquartile range (IQR) = 47–68, range = 10–98; 55.5% female] who were released from four hospitals in Wuhan, China, between January 18 and March 29, 2020 were followed for a median of 144 days (IQR = 135–157). During follow-up, 976 (26.5%) patients had at least one post-COVID-19 sequela. The incidence of post-COVID-19 sequelae among elderly COVID-19 survivors (age ≥60 years) was slightly increased compared to that of young COVID-19 survivors (age <60 years; relative risk = 1.05, 95% CI = 1.02–1.10, p = 0.007). During follow-up, a dramatic reduction of anti-SARS-CoV-2 IgG (88.0%, 95% CI = 84.2–90.4) and IgM (93.2%, 95% CI = 88.5–96.4) antibodies was observed. Among these COVID-19 survivors, 1.2% (n = 45) retested positive for SARS-CoV-2 and 1.0% (n = 37) died during follow-up. Of those who died during follow-up, 70.3% were male and all were negative for both IgG and IgM, except for one person who was IgG-positive.

Conclusions: Our study documents significant post-COVID-19 sequelae that impair functions of multiple organ systems in COVID-19 survivors, suggesting that the long-term effects of this disease will negatively impact survivors' quality of life, continue to strain health care systems, and result in extended periods of lost productivity. Furthermore, female gender and anti-SARS-CoV-2 immunity may play an essential role in the survival after COVID-19 infection.
PD-L1 in Cytological Samples: A Review and a Practical Approach
Authors: Tejerina Eva , García Tobar Laura , Echeveste José I. , de Andrea Carlos E. , Vigliar Elena , Lozano María D.
Published: May 2021

With a growing number of predictive biomarkers needed to manage patients with non-small cell lung cancer (NSCLC), there has been a paradigm shift in care and handling of diagnostic samples. Among the various testing methods, immunohistochemistry (IHC) is the most cost- effective and widely available. Furthermore, over the past decade immunotherapy has emerged as one of the most promising cancer treatments. In this scenario IHC is the most used testing method available for PDL-1/PD1 immunotherapy. Several monoclonal antibodies targeting programmed death 1 (PD-1)/programmed death ligand-1 (PD-L1) pathways have been integrated into standard-of-care treatments of a wide range of cancer types, once provided evidence of PD-L1 expression in tumor cells by immunohistochemistry (IHC). Since currently available PD-L1 assays have been developed on formalin-fixed paraffin embedded (FFPE) histological specimens, a growing body of research is being dedicated to confirm the feasibility of applying PDL-1 assays also to cytological samples. Albeit promising results have been reported, several important issues still need to be addressed. Among these are the type of cytological samples, pre-analytical issues, cyto-histological correlation, and inter-observer agreement. This review briefly summarizes the knowledge of the role of cytopathology in the analysis of PD-L1 by immunocytochemistry (ICC) and future directions of cytopathology in the immunotherapy setting.
Phytochemical Moieties From Indian Traditional Medicine for Targeting Dual Hotspots on SARS-CoV-2 Spike Protein: An Integrative in-silico Approach
Authors: Umashankar V. , Deshpande Sanjay H. , Hegde Harsha V. , Singh Ishwar , Chattopadhyay Debprasad
Published: May 2021

SARS-CoV-2 infection across the world has led to immense turbulence in the treatment modality, thus demanding a swift drug discovery process. Spike protein of SARS-CoV-2 binds to ACE2 receptor of human to initiate host invasion. Plethora of studies demonstrate the inhibition of Spike-ACE2 interactions to impair infection. The ancient Indian traditional medicine has been of great interest of Virologists worldwide to decipher potential antivirals. Hence, in this study, phytochemicals (1,952 compounds) from eight potential medicinal plants used in Indian traditional medicine were meticulously collated, based on their usage in respiratory disorders, along with immunomodulatory and anti-viral potential from contemporary literature. Further, these compounds were virtually screened against Receptor Binding Domain (RBD) of Spike protein. The potential compounds from each plant were prioritized based on the binding affinity, key hotspot interactions at ACE2 binding region and glycosylation sites. Finally, the potential hits in complex with spike protein were subjected to Molecular Dynamics simulation (450 ns), to infer the stability of complex formation. Among the compounds screened, Tellimagrandin-II (binding energy of −8.2 kcal/mol and binding free energy of −32.08 kcal/mol) fromSyzygium aromaticumL. and O-Demethyl-demethoxy-curcumin (binding energy of −8.0 kcal/mol and binding free energy of −12.48 kcal/mol) fromCurcuma longaL. were found to be highly potential due to their higher binding affinity and significant binding free energy (MM-PBSA), along with favorable ADMET properties and stable intermolecular interactions with hotspots (including the ASN343 glycosylation site). The proposed hits are highly promising, as these are resultant of stringentin silicocheckpoints, traditionally used, and are documented through contemporary literature. Hence, could serve as promising leads for subsequent experimental validations.
Effect of Water Chemistry, Land Use Patterns, and Geographic Distances on the Spatial Distribution of Bacterioplankton Communities in an Anthropogenically Disturbed Riverine Ecosystem
Authors: Zhao Jun , Peng Wang , Ding Mingjun , Nie Minghua , Huang Gaoxiang
Published: May 2021

The spatial distribution of bacterioplankton communities in rivers is driven by multiple environmental factors, including local and regional factors. Local environmental condition is associated with effect of river water chemistry (through species sorting); ecological process in region is associated with effects of land use and geography. Here, we investigated variation in bacterioplankton communities (free-living, between 0.22 and 5 μm) in an anthropogenically disturbed river using high-throughput DNA sequencing of community 16S rRNA genes in order to investigate the importance of water chemistry, land use patterns, and geographic distance. Among environmental factors, sulfate (SO42–), manganese (Mn), and iron (Fe) concentrations were the water chemistry parameters that best explained bacterioplankton community variation. In addition, forest and freshwater areas were the land use patterns that best explained bacterioplankton community variation. Furthermore, cumulative dendritic distance was the geographic distance parameter that best explained bacterial community variation. Variation partitioning analysis revealed that water chemistry, land use patterns, and geographic distances strongly shaped bacterioplankton communities. In particular, the direct influence of land use was prominent, which alone contributed to the highest proportion of variation (26.2% in wet season communities and 36.5% in dry season communities). These results suggest that the mechanisms of species sorting and mass effects together control bacterioplankton communities, although mass effects exhibited higher contributions to community variation than species sorting. Given the importance of allochthonous bacteria input from various land use activities (i.e., mass effects), these results provide new insights into the environmental factors and determinant mechanisms that shape riverine ecosystem communities.
Contributions of Genetic Evolution to Zika Virus Emergence
Authors: Hung Su-Jhen , Huang Sheng-Wen
Published: May 2021

Mosquito-borne Zika virus (ZIKV) was considered an obscure virus causing only mild or self-limited symptoms until the explosive outbreaks in French Polynesia in 2013–2014 and in the Americas in 2015–2016, resulting in more than 700,000 cases of the disease, with occasional miscarriage and severe congenital birth defects, such as intrauterine growth restriction, fetal microcephaly, and other neurodevelopmental malformations. In this review, we summarized the evolution of ZIKV from a mundane virus to an epidemic virus. ZIKV has acquired a panel of amino acid substitutions during evolution when the virus spread from Africa, Asia, Pacific, through to the Americas. Robust occurrence of mutations in the evolution of ZIKV has increased its epidemic potential. Here we discussed the contributions of these evolutionary mutations to the enhancement of viral pathogenicity and host-mosquito transmission. We further explored the potential hypotheses for the increase in ZIKV activity in recent decades. Through this review, we also explored the hypotheses for the occurrence of the recent ZIKV epidemics and highlighted the potential roles of various factors including pathogen-, host-, vector-related, and environmental factors, which may have synergistically contributed to the ZIKV epidemics.
Lysosome Sensing Is a Key Mechanism in Leishmania Intracellular Development
Authors: Zilberstein Dan
Published: May 2021

Phagolysosomes of macrophages are the niche where the parasitic protozoan Leishmania resides and causes human leishmaniasis. During infection, this organism encounters dramatic environmental changes. These include heat shock (from 26°C in the vector to 33°C or 37°C in the host, for cutaneous and visceral species, respectively) and acidic pH typical to the lysosome and nutrient availability. Leishmania cells developed ways to sense the lysosome-specific environment (acidic pH and body temperature) as means of recognition and, subsequently, initiation of differentiation into the intracellular form. Recent studies have indicated that protein kinase A plays a role as the gatekeeper that enables differentiation initiation. This review provides an update on the lysosome signaling pathway-mediated Leishmania intracellular development.
Microbial Community Succession and Its Environment Driving Factors During Initial Fermentation of Maotai-Flavor Baijiu
Authors: Hao Fei , Tan Yuwei , Lv Xibin , Chen Liangqiang , Yang Fan , Wang Heyu , Du Hai , Wang Li , Xu Yan
Published: May 2021

The microbial composition and environmental factors can take a great influence on community succession during the solid-state fermentation (SSF) of Maotai-flavor Baijiu. In this paper, high-throughput sequencing was used to reveal the dominant microorganisms and the evolution process of microbial community structure in the initial fermentation of Maotai-flavor Baijiu. The correlation analysis was carried out for the relationship between physicochemical factors and fermented microbes. The results showed that microorganisms were obviously enriched and the diversity of bacteria and fungi showed a downward trend during the heap fermentation process of Maotai-flavor Baijiu. However, the diversity of fungi in the pit fermentation process increased. Generally, Lactobacillus, Pichia, and Saccharomyces were the dominant microorganisms in the initial fermentation of Maotai-flavor Baijiu. According to the redundancy analysis, we found that reducing sugar was the key driving factor for microbial succession in the heap fermentation, while acidity, alcohol, and temperature were the main driving forces in pit fermentation. This study revealed the microbial succession and its related environmental factors in the initial fermentation of Maotai-flavor Baijiu, which will enrich our knowledge of the mechanism of solid-state liquor fermentation.
MLH1 Deficiency Down-Regulates TLR4 Expression in Sporadic Colorectal Cancer
Authors: Scarpa Melania , Ruffolo Cesare , Kotsafti Andromachi , Canal Fabio , Erroi Francesca , Basato Silvia , Dall’Agnese Lucia , Fiorot Alain , Pozza Anna , Brun Paola , Bassi Nicolò , Dei Tos Angelo , Castoro Carlo , Castagliuolo Ignazio , Scarpa Marco
Published: May 2021

Patients with mismatch repair (MMR)-deficient colorectal cancer (CRC) have a more favorable prognosis than patients with tumors with intact MMR. In order to obtain further insights on the reasons for this different outcome, we investigated the interplay between MMR genes and TLR4/MyD88 signaling. The cancer genome atlas (TCGA) databases were selected to predict the differential expression of TLR4 in colon cancer and its correlation with MMR genes. Moreover, the expression of MMR genes and TLR4 was evaluated by immunohistochemistry in 113 CRC samples and a cohort of 63 patients was used to assess TLR4 mRNA expression and MLH1 epigenetic silencing status. In vitro, the effect of MLH1 knockdown on TLR4 expression was quantified by Real Time PCR. TLR4 expression resulted dependent on MMR status and directly correlated to MLH1 expression. In vitro, MLH1 silencing decreased TLR4 expression. These observations may reflect the better prognosis and the chemoresistance of patients with CRC and MMR defects.
MicroRNAs and tRNA-Derived Small Fragments: Key Messengers in Nuclear–Mitochondrial Communication
Authors: Meseguer Salvador
Published: May 2021

Mitochondria are not only important as energy suppliers in cells but also participate in other biological processes essential for cell growth and survival. They arose from α-proteobacterial predecessors through endosymbiosis and evolved transferring a large part of their genome to the host cell nucleus. Such a symbiotic relationship has been reinforced over time through increasingly complex signaling mechanisms between the host cell and mitochondria. So far, we do not have a complete view of the mechanisms that allow the mitochondria to communicate their functional status to the nucleus and trigger adaptive and compensatory responses. Recent findings place two classes of small non-coding RNAs (sncRNAs), microRNAs (miRNAs), and tRNA-derived small fragments, in such a scenario, acting as key pieces in the mitochondria–nucleus cross-talk. This review highlights the emerging roles and the interrelation of these sncRNAs in different signaling pathways between mitochondria and the host cell. Moreover, we describe in what way alterations of these complex regulatory mechanisms involving sncRNAs lead to diseases associated with mitochondrial dysfunction. In turn, these discoveries provide novel prognostic biomarker candidates and/or potential therapeutic targets.
A Glimpse of “Dicer Biology” Through the Structural and Functional Perspective
Authors: Paturi Sneha , Deshmukh Mandar V.
Published: May 2021

The RNA interference pathway (RNAi) is executed by two core enzymes, Dicer and Argonaute, for accomplishing a tailored transcriptional and post-transcriptional gene regulation. Dicer, an RNase III enzyme, initiates the RNAi pathway, plays a pivotal role in fighting infection against pathogens, and acts as a housekeeping enzyme for cellular homeostasis. Here, we review structure-based functional insights of Dicer and its domains present in a diverse group of organisms. Although Dicer and its domains are evolutionarily conserved from microsporidian parasites to humans, recent cryo-electron microscopy structures of Homo sapiens Dicer and Drosophila melanogaster Dicer-2 suggest characteristic variations in the mechanism of the dsRNA substrate recognition. Interestingly, the necessity for more than one functionally distinct Dicer paralogs in insects and plants compared with a single Dicer in other eukaryotic life forms implies Dicer’s role in the interplay of RNAi and other defense mechanisms. Based on the structural and mechanistic information obtained during the last decade, we aim to highlight the significance of key Dicer domains that are crucial to Dicer specific recognition and precise cleavage of dsRNA substrates. Further, the role of Dicer in the formation of Argonaute-based RNA-induced silencing complex (RISC) assembly formation, Dicer’s ability to regulate a complex protein interaction network, and its role in other cellular processes, as well as its therapeutic potentials, are emphasized.
The Universally Conserved ATPase YchF Regulates Translation of Leaderless mRNA in Response to Stress Conditions
Authors: Landwehr Victoria , Milanov Martin , Angebauer Larissa , Hong Jiang , Jüngert Gabriela , Hiersemenzel Anna , Siebler Ariane , Schmit Fränk , Öztürk Yavuz , Dannenmaier Stefan , Drepper Friedel , Warscheid Bettina , Koch Hans-Georg
Published: May 2021

The universally conserved P-loop GTPases control diverse cellular processes, like signal transduction, ribosome assembly, cell motility, and intracellular transport and translation. YchF belongs to the Obg-family of P-loop GTPases and is one of the least characterized member of this family. It is unique because it preferentially hydrolyses ATP rather than GTP, but its physiological role is largely unknown. Studies in different organisms including humans suggest a possible role of YchF in regulating the cellular adaptation to stress conditions. In the current study, we explored the role of YchF in the model organismEscherichia coli. By western blot and promoter fusion experiments, we demonstrate that YchF levels decrease during stress conditions or when cells enter stationary phase. The decline in YchF levels trigger increased stress resistance and cells lacking YchF are resistant to multiple stress conditions, like oxidative stress, replication stress, or translational stress. Byin vivosite directed cross-linking we demonstrate that YchF interacts with the translation initiation factor 3 (IF3) and with multiple ribosomal proteins at the surface of the small ribosomal subunit. The absence of YchF enhances the anti-association activity of IF3, stimulates the translation of leaderless mRNAs, and increases the resistance against the endoribonuclease MazF, which generates leaderless mRNAs during stress conditions. In summary, our data identify YchF as a stress-responsive regulator of leaderless mRNA translation.
Cox4i2 Triggers an Increase in Reactive Oxygen Species, Leading to Ferroptosis and Apoptosis in HHV7 Infected Schwann Cells
Authors: Chang Bowen , Guan Haochen , Wang Xueyi , Chen Zheng , Zhu Wanchun , Wei Xiangyu , Li Shiting
Published: May 2021

Emerging evidence suggests that reactive oxygen species (ROS) play a significant role in the pathogenesis of peripheral nerve damage. Our previous study indicated that human herpesvirus 7 (HHV7) induces Bell’s palsy. However, the specific mechanism underlying the effects of ROS in HHV7 infection-induced facial nerve damage is unknown. In this study, we established a rat FN model by inoculating an HHV7 virus solution. The facial grading score and LuxolFastBlue (LFB) staining were used to assess the success of the model. Using mRNA-sequencing analysis, we found that the expression of Complex IV Subunit 4 Isoform 2 (Cox4i2) increased in infected Schwann cells (SCs). Cox4i2 was suggested to increase COX activity, thereby promoting ROS production. The changes in the endogenous oxidant and antioxidant system were assessed, and the results showed that oxidative stress increased after HHV7 infection in vivo and in vitro. However, we found that oxidative injury was relieved after the transfection of shCox4i2 in HHV7-treated SCs by evaluating cell death, cell proliferation, and the ROS level as well as the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). Furthermore, we hypothesised that Cox4i2 loss would attenuate HHV7-induced ferroptosis and apoptosis, which are closely related to ROS in SCs. Our research illustrated that the knockdown of Cox4i2 suppresses HHV7-induced RSC96 cell ferroptosis as well as apoptosis via the ERK signalling pathway. Overall, several in vitro and in vivo methods were adopted in this study to reveal the new mechanism of ROS-induced and Cox4i2-mediated apoptosis and ferroptosis in HHV7 infected SCs.
How Do the Players Play? A Post-Genomic Analysis Paradigm to Understand Aquatic Ecosystem Processes
Authors: Reid Thomas , Bergsveinson Jordyn
Published: May 2021

Culture-independent and meta-omics sequencing methods have shed considerable light on the so-called “microbial dark matter” of Earth’s environmental microbiome, improving our understanding of phylogeny, the tree of life, and the vast functional diversity of microorganisms. This influx of sequence data has led to refined and reimagined hypotheses about the role and importance of microbial biomass, that paradoxically, sequencing approaches alone are unable to effectively test. Post-genomic approaches such as metabolomics are providing more sensitive and insightful data to unravel the fundamental operations and intricacies of microbial communities within aquatic systems. We assert that the implementation of integrated post-genomic approaches, specifically metabolomics and metatranscriptomics, is the new frontier of environmental microbiology and ecology, expanding conventional assessments toward a holistic systems biology understanding. Progressing beyond siloed phylogenetic assessments and cataloging of metabolites, toward integrated analysis of expression (metatranscriptomics) and activity (metabolomics) is the most effective approach to provide true insight into microbial contributions toward local and global ecosystem functions. This data in turn creates opportunity for improved regulatory guidelines, biomarker discovery and better integration of modeling frameworks. To that end, critical aquatic environmental issues related to climate change, such as ocean warming and acidification, contamination mitigation, and macro-organism health have reasonable opportunity of being addressed through such an integrative approach. Lastly, we argue that the “post-genomics” paradigm is well served to proactively address the systemic technical issues experienced throughout the genomics revolution and focus on collaborative assessment of field-wide experimental standards of sampling, bioinformatics and statistical treatments.
Dual Regulation of Phosphatidylserine Decarboxylase Expression by Envelope Stress Responses
Authors: Hassoun Yasmine , Bartoli Julia , Wahl Astrid , Viala Julie Pamela , Bouveret Emmanuelle
Published: May 2021

Bacteria adapt to versatile environments by modulating gene expression through a set of stress response regulators, alternative Sigma factors, or two-component systems. Among the central processes that must be finely tuned is membrane homeostasis, including synthesis of phospholipids (PL). However, few genetic regulations of this process have been reported. We have previously shown that the gene coding the first step of PL synthesis is regulated by σE and ppGpp, and that the BasRS (PmrAB) two component system controls the expression of the DgkA PL recycling enzyme. The gene coding for phosphatidylserine decarboxylase, the last step in phosphatidylethanolamine synthesis is another gene in the PL synthesis pathway susceptible of stress response regulation. Indeed, psd appears in transcriptome studies of the σE envelope stress Sigma factor and of the CpxAR two component system. Interestingly, this gene is presumably in operon with mscM coding for a miniconductance mechanosensitive channel. In this study, we dissected the promoter region of the psd-mscM operon and studied its regulation by σE and CpxR. By artificial activation of σE and CpxRA stress response pathways, using GFP transcriptional fusion and western-blot analysis of Psd and MscM enzyme production, we showed that the operon is under the control of two distinct promoters. One is activated by σE, the second is activated by CpxRA and also responsible for basal expression of the operon. The fact that the phosphatidylethanolamine synthesis pathway is controlled by envelope stress responses at both its first and last steps might be important for adaptation of the membrane to envelope perturbations.
New Faces of old Friends: Emerging new Roles of RNA-Binding Proteins in the DNA Double-Strand Break Response
Authors: Klaric Julie A. , Wüst Stas , Panier Stephanie
Published: May 2021

DNA double-strand breaks (DSBs) are highly cytotoxic DNA lesions. To protect genomic stability and ensure cell homeostasis, cells mount a complex signaling-based response that not only coordinates the repair of the broken DNA strand but also activates cell cycle checkpoints and, if necessary, induces cell death. The last decade has seen a flurry of studies that have identified RNA-binding proteins (RBPs) as novel regulators of the DSB response. While many of these RBPs have well-characterized roles in gene expression, it is becoming increasingly clear that they also have non-canonical functions in the DSB response that go well beyond transcription, splicing and mRNA processing. Here, we review the current understanding of how RBPs are integrated into the cellular response to DSBs and describe how these proteins directly participate in signal transduction, amplification and repair at damaged chromatin. In addition, we discuss the implications of an RBP-mediated DSB response for genome instability and age-associated diseases such as cancer and neurodegeneration.
Direct Communication Between Brains: A Systematic PRISMA Review of Brain-To-Brain Interface
Authors: Nam Chang S. , Traylor Zachary , Chen Mengyue , Jiang Xiaoning , Feng Wuwei , Chhatbar Pratik Yashvant
Published: May 2021

This paper aims to review the current state of brain-to-brain interface (B2BI) technology and its potential. B2BIs function via a brain-computer interface (BCI) to read a sender's brain activity and a computer-brain interface (CBI) to write a pattern to a receiving brain, transmitting information. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to systematically review current literature related to B2BI, resulting in 15 relevant publications. Experimental papers primarily used transcranial magnetic stimulation (tMS) for the CBI portion of their B2BI. Most targeted the visual cortex to produce phosphenes. In terms of study design, 73.3% (11) are unidirectional and 86.7% (13) use only a 1:1 collaboration model (subject to subject). Limitations are apparent, as the CBI method varied greatly between studies indicating no agreed upon neurostimulatory method for transmitting information. Furthermore, only 12.4% (2) studies are more complicated than a 1:1 model and few researchers studied direct bidirectional B2BI. These studies show B2BI can offer advances in human communication and collaboration, but more design and experiments are needed to prove potential. B2BIs may allow rehabilitation therapists to pass information mentally, activating a patient's brain to aid in stroke recovery and adding more complex bidirectionality may allow for increased behavioral synchronization between users. The field is very young, but applications of B2BI technology to neuroergonomics and human factors engineering clearly warrant more research.