bluuebunny/crossref_metadata_2025 huggingface dataset:
The N-terminal region of Jaw1 has a role to inhibit the formation of organized smooth endoplasmic reticulum as an intrinsically disordered region
Authors: Kozono Takuma , Sato Hiroyuki , Okumura Wataru , Jogano Chifuyu , Tamura-Nakano Miwa , Kawamura Yuki I. , Rohrer Jack , Tonozuka Takashi , Nishikawa Atsushi
Published: January 2021

Jaw1/LRMP is a type II integral membrane protein that is localized at the endoplasmic reticulum (ER) and outer nuclear membrane. We previously reported that a function of Jaw1 is to maintain the nuclear shape as a KASH protein via its carboxyl terminal region, a component of linker of nucleoskeleton and cytoskeleton complex in the oligomeric state. Although the oligomerization of some KASH proteins via the cytosolic regions serves to stabilize protein-protein interactions, the issue of how the oligomerization of Jaw1 is regulated is not completely understood. Therefore, we focused on three distinct regions on the cytosolic face of Jaw1: the N-terminal region, the coiled-coil domain and the stem region, in terms of oligomerization. A co-immunoprecipitation assay showed that its coiled-coil domain is a candidate for the oligomerization site. Furthermore, our data indicated that the N-terminal region prevents the aberrant oligomerization of Jaw1 as an intrinsically disordered region (IDR). Importantly, the ectopic expression of an N-terminal region deleted mutant caused the formation of organized smooth ER (OSER), structures such as nuclear karmellae and whorls, in B16F10 cells. Furthermore, this OSER interfered with the localization of the oligomer and interactors such as the type III inositol 1,4,5-triphosphate receptor (IP3R3) and SUN2. In summary, the N-terminal region of Jaw1 inhibits the formation of OSER as an IDR to maintain the homeostatic localization of interactors on the ER membrane.
Integrated mRNA and miRNA expression profile analysis of female and male gonads in Hyriopsis cumingii
Authors: Wang Ya-Yu , Duan Sheng-Hua , Wang Gui-Ling , Li Jia-Le
Published: January 2021

Hyriopsis cumingiiis an important species for freshwater pearl cultivation in China. In terms of pearl production, males have larger pearls and better glossiness than females, but there are few reports focusing on the sex ofH. cumingii. In this study, six mRNA and six microRNA (miRNA) libraries were prepared from ovaries and testes. Additionally, 28,502 differentially expressed genes (DEGs) and 32 differentially expressed miRNAs (DEMs) were identified. Compared with testis, 14,360 mRNAs and 20 miRNAs were up-regulated in ovary, 14,142 mRNAs and 12 miRNAs were down-regulated. In DEGs, the known genes related to sex determinism and/or differentiation were also identified, such asDMRT1,SOX9,SF1for males,FOXL2for females, and other potentially significant candidate genes. Three sex-related pathways have also been identified, which are Wnt, Notch, and TGF-beta. In 32 DEMs, the three miRNAs (miR-9-5p, miR-92, miR-184) were paid more attention, they predicted 28 target genes, which may also be candidates for sex-related miRNAs and genes. Differential miRNAs target genes analysis reveals the pathway associated with oocyte meiosis and spermatogenesis. Overall, the findings of the study provide significant insights to enhance our understanding of sex differentiation and/or sex determination mechanisms forH. cumingii.
ROCK inhibition reduces morphological and functional damage to rod synapses after retinal injury
Authors: Halász Éva , Zarbin Marco A. , Davidow Amy L. , Frishman Laura J. , Gombkoto Peter , Townes-Anderson Ellen
Published: January 2021

Retinal detachment (RD) causes damage, including disjunction, of the rod photoreceptor-bipolar synapse, which disrupts vision and may contribute to the poor visual recovery observed after retinal reattachment surgery. We created a model of iatrogenic RD in adult female pigs to study damage to the rod-bipolar synapse after injury and the ability of a highly specific Rho-kinase (ROCK) inhibitor to preserve synaptic structure and function. This model mimics procedures used in humans when viral vectors or cells are injected subretinally for treatment of retinal disease. Synaptic disjunction by retraction of rod spherules, quantified by image analysis of confocal sections, was present 2 h after detachment and remained 2 days later even though the retina had spontaneously reattached by then. Moreover, spherule retraction occurred in attached retina 1–2 cms from detached retina. Synaptic damage was significantly reduced by ROCK inhibition in detached retina whether injected subretinally or intravitreally. Dark-adapted full-field electroretinograms were recorded in reattached retinas to assess rod-specific function. Reduction in synaptic injury correlated with increases in rod-driven responses in drug-treated eyes. Thus, ROCK inhibition helps prevent synaptic damage and improves functional outcomes after retinal injury and may be a useful adjunctive treatment in iatrogenic RD and other retinal degenerative diseases.
Long-term surgical outcomes of primary retropupillary iris claw intraocular lens implantation for the treatment of intraocular lens dislocation
Authors: Choi Eun Young , Lee Chul Hee , Kang Hyun Goo , Han Jae Yong , Byeon Suk Ho , Kim Sung Soo , Koh Hyoung Jun , Kim Min
Published: January 2021

We aimed to investigate the efficacy and safety of primary retropupillary iris claw intraocular lens (R-IOL) implantation in patients with complete intraocular lens (IOL) dislocation. In this single-center retrospective case series, we reviewed the medical records of patients who underwent R-IOL implantation surgery with pars plana vitrectomy for the treatment of IOL dislocation between September 2014 and July 2019. The primary outcome was change in visual acuity (VA) up to 24 months postoperatively. The secondary outcomes included changes in intraocular pressure (IOP), refractive errors, and endothelial cell count (ECC) over the same period. Data of 103 eyes (98 patients) were analyzed. The mean uncorrected VA was significantly improved at one month postoperatively (− 0.69 logMAR, P < 0.001), compared to the preoperative value. IOP (− 2.3 mmHg, P = 0.008) and ECC (− 333.4 cells/mm2, P = 0.027) significantly decreased one month post-surgery and remained stable thereafter. Postoperative mean spherical equivalents were similar to the prediction error throughout the follow-up period. IOP elevation (n = 8, 7.8%), cystoid macular edema (n = 4, 3.9%), and dislocation of the R-IOL (n = 10, 9.7%) were managed successfully. Overall, primary R-IOL implantation with pars plana vitrectomy is effective and safe for correcting IOL dislocation due to various causes.
Anti-proliferative and anti-migratory properties of coffee diterpenes kahweol acetate and cafestol in human renal cancer cells
Authors: Makino Tomoyuki , Izumi Kouji , Hiratsuka Kaoru , Kano Hiroshi , Shimada Takashi , Nakano Taito , Kadomoto Suguru , Naito Renato , Iwamoto Hiroaki , Yaegashi Hiroshi , Shigehara Kazuyoshi , Kadono Yoshifumi , Nakata Hiroki , Saito Yohei , Nakagawa-Goto Kyoko , Sakai Norihiko , Iwata Yasunori , Wada Takashi , Mizokami Atsushi
Published: January 2021

Despite improvements in systemic therapy options for renal cancer, it remains one of the most drug-resistant malignancies. Interestingly, reports have shown that kahweol and cafestol, natural diterpenes extracted from coffee beans, exhibit anti-cancer activity. However, the multiple potential pharmacological actions of both have yet to be fully understood. This study therefore investigated the effects of kahweol acetate and cafestol on human renal cancer ACHN and Caki-1 cells. Accordingly, the combination of kahweol acetate and cafestol administration synergistically inhibited cell proliferation and migration by inducing apoptosis and inhibiting epithelial–mesenchymal transition. Mechanistic dissection revealed that kahweol acetate and cafestol inhibited Akt and ERK phosphorylation. Moreover, kahweol acetate and cafestol downregulated the expression of not only C–C chemokine receptors 2, 5, and 6 but also programmed death-ligand 1, indicating their effects on the tumor microenvironment. Thus, kahweol acetate and cafestol may be novel therapeutic candidates for renal cancer considering that they exert multiple pharmacological effects.
Alkali metal doping of black phosphorus monolayer for ultrasensitive capture and detection of nitrogen dioxide
Authors: Marjani Azam , Ghambarian Mehdi , Ghashghaee Mohammad
Published: January 2021

Black phosphorus nanostructures have recently sparked substantial research interest for the rational development of novel chemosensors and nanodevices. For the first time, the influence of alkali metal doping of black phosphorus monolayer (BP) on its capabilities for nitrogen dioxide (NO2) capture and monitoring is discussed. Four different nanostructures including BP, Li-BP, Na-BP, and K-BP were evaluated; it was found that the adsorption configuration on Li-BP was different from others such that the NO2 molecule preferred a vertical stabilization rather than a parallel configuration with respect to the surface. The efficiency for the detection increased in the sequence of Na-BP < BP < K-BP < Li-BP, with the most significant improvement of + 95.2% in the case of Li doping. The Na-BP demonstrated the most compelling capacity (54 times higher than BP) for NO2 capture and catalysis (− 24.36 kcal/mol at HSE06/TZVP). Furthermore, the K-doped device was appropriate for both nitrogen dioxide adsorption and sensing while also providing the highest work function sensitivity (55.4%), which was much higher than that of BP (10.4%).
Selection and characterisation of Affimers specific for CEA recognition
Authors: Shamsuddin Shazana Hilda , Jayne David G. , Tomlinson Darren C. , McPherson Michael J. , Millner Paul A.
Published: January 2021

Carcinoembryonic antigen (CEA) is the only blood based protein biomarker at present, used for preoperative screening of advanced colorectal cancer (CRC) patients to determine the appropriate curative treatments and post-surveillance screening for tumour recurrence. Current diagnostics for CRC detection have several limitations and development of a highly sensitive, specific and rapid diagnostic device is required. The majority of such devices developed to date are antibody-based and suffer from shortcomings including multimeric binding, cost and difficulties in mass production. To circumvent antibody-derived limitations, the present study focused on the development of Affimer proteins as a novel alternative binding reagent for CEA detection. Here, we describe the selection, from a phage display library, of Affimers specific to CEA protein. Characterization of three anti-CEA Affimers reveal that these bind specifically and selectively to protein epitopes of CEA from cell culture lysate and on fixed cells. Kinetic binding analysis by SPR show that the Affimers bind to CEA with high affinity and within the nM range. Therefore, they have substantial potential for used as novel affinity reagents in diagnostic imaging, targeted CRC therapy, affinity purification and biosensor applications.
A case control study examining the feasibility of using eye tracking perimetry to differentiate patients with glaucoma from healthy controls
Authors: Tatham Andrew J. , Murray Ian C. , McTrusty Alice D. , Cameron Lorraine A. , Perperidis Antonios , Brash Harry M. , Fleck Brian W. , Minns Robert A.
Published: January 2021

To explore the feasibility of using Saccadic Vector Optokinetic Perimetry (SVOP) to differentiate glaucomatous and healthy eyes. A prospective case–control study was performed using a convenience sample recruited from a single university glaucoma clinic and a group of healthy controls. SVOP and standard automated perimetry (SAP) was performed with testing order randomised. The reference standard was a diagnosis of glaucoma based a comprehensive ophthalmic examination and abnormality on standard automated perimetry (SAP). The index test was SVOP. 31 patients with glaucoma and 24 healthy subjects were included. Mean SAP mean deviation (MD) in those with glaucoma was − 8.7 ± 7.4 dB, with mean SAP and SVOP sensitivities of 23.3 ± 0.9 dB and 22.1 ± 4.3 dB respectively. Participants with glaucoma were significantly older. On average, SAP sensitivity was 1.2 ± 1.4 dB higher than SVOP (95% limits of agreement = − 1.6 to 4.0 dB). SVOP sensitivity had good ability to differentiate healthy and glaucomatous eyes with a 95% CI for area under the curve (AUC) of 0.84 to 0.96, similar to the performance of SAP sensitivity (95% CI 0.86 to 0.97, P = 0.60). For 80% specificity, SVOP had a 95% CI sensitivity of 75.7% to 94.8% compared to 77.8% to 96.0% for SAP. SVOP took considerably longer to perform (514 ± 54 s compared to 267 ± 76 s for SAP). Eye tracking perimetry may be useful for detection of glaucoma but further studies are needed to evaluate SVOP within its intended sphere of use, using an appropriate design and independent reference standard.
Nanodiamond surface chemistry controls assembly of polypyrrole and generation of photovoltage
Authors: Miliaieva Daria , Matunova Petra , Cermak Jan , Stehlik Stepan , Cernescu Adrian , Remes Zdenek , Stenclova Pavla , Muller Martin , Rezek Bohuslav
Published: January 2021

Nanoscale composite of detonation nanodiamond (DND) and polypyrrole (PPy) as a representative of organic light-harvesting polymers is explored for energy generation, using nanodiamond as an inorganic electron acceptor. We present a technology for the composite layer-by-layer synthesis that is suitable for solar cell fabrication. The formation, pronounced material interaction, and photovoltaic properties of DND-PPy composites are characterized down to nanoscale by atomic force microscopy, infrared spectroscopy, Kelvin probe, and electronic transport measurements. The data show that DNDs with different surface terminations (hydrogenated, oxidized, poly-functional) assemble PPy oligomers in different ways. This leads to composites with different optoelectronic properties. Tight material interaction results in significantly enhanced photovoltage and broadband (1–3.5 eV) optical absorption in DND/PPy composites compared to pristine materials. Combination of both oxygen and hydrogen functional groups on the nanodiamond surface appears to be the most favorable for the optoelectronic effects. Theoretical DFT calculations corroborate the experimental data. Test solar cells demonstrate the functionality of the concept.
Performance of Azure-winged magpies in Aesop’s fable paradigm
Authors: Zhang Yigui , Yu Cong , Chen Lixin , Li Zhongqiu
Published: January 2021

In this study, the improved Aesop’s fable paradigm—a series of experiments originally used to test whether some animals understand the causality associated with water replacement—was used to explore the cognitive ability of Azure-winged magpies (Cyanopica cyanus). Experimental results on causal cue tasks showed that the Azure-winged magpies prefer water-filled tubes over sand-filled tubes, heavy objects over light objects, and solid objects over hollow objects. However, they failed to notice the diameter and water level of the tubes. They also failed to pass the counterintuitive U-shaped tube task in arbitrary cue tasks. Our results demonstrated that Azure-winged magpies have a certain cognitive ability but not an understanding of causality, a characteristic comparable to that of other corvids. Moreover, Azure-winged magpies exhibited the ability of training transfer and analogical problem solving from the perspective of cognitive psychology. We believe that object-bias has little effect on Azure-winged magpies in this study. We can conclude that the Azure-winged magpies partially completed the tasks by trial-and-error learning.
A natural language processing approach for identifying temporal disease onset information from mental healthcare text
Authors: Viani Natalia , Botelle Riley , Kerwin Jack , Yin Lucia , Patel Rashmi , Stewart Robert , Velupillai Sumithra
Published: January 2021

Receiving timely and appropriate treatment is crucial for better health outcomes, and research on the contribution of specific variables is essential. In the mental health domain, an important research variable is the date of psychosis symptom onset, as longer delays in treatment are associated with worse intervention outcomes. The growing adoption of electronic health records (EHRs) within mental health services provides an invaluable opportunity to study this problem at scale retrospectively. However, disease onset information is often only available in open text fields, requiring natural language processing (NLP) techniques for automated analyses. Since this variable can be documented at different points during a patient’s care, NLP methods that model clinical and temporal associations are needed. We address the identification of psychosis onset by: 1) manually annotating a corpus of mental health EHRs with disease onset mentions, 2) modelling the underlying NLP problem as a paragraph classification approach, and 3) combining multiple onset paragraphs at the patient level to generate a ranked list of likely disease onset dates. For 22/31 test patients (71%) the correct onset date was found among the top-3 NLP predictions. The proposed approach was also applied at scale, allowing an onset date to be estimated for 2483 patients.
Global variation of seismic energy release with oceanic lithosphere age
Authors: Pinzón Nicolás , Vargas Carlos A.
Published: January 2021

Variations in Mid Ocean Ridge seismicity with age provide a new tool to understand the thermal evolution of the oceanic lithosphere. The sum of seismic energy released by earthquakes during a time, and for an area, is proportional to its lithospheric age. Asthenospheric temperatures emerge on ridge centers with new crust resulting in high seismic activity; thus, the energy released sum is highest on the young lithosphere and decreases with age. We propose a general model that relates the systematic variation of seismic energy released with the lithospheric age. Our analysis evaluates the main physical factors involved in the changes of energy released sum with the oceanic lithosphere age in MOR systems of different spreading rates. These observations are substantiated based on three cross-sections of the East Pacific Rise, six sections in the Mid Atlantic Ridge, and three profiles in the Central Indian Ridge. Our global model provides an additional tool for understanding tectonic processes, including the effects of seismicity and mid-plate volcanism, and a better understanding of the thermal evolution for the young oceanic lithosphere.
An in vivo model allowing continuous observation of human vascular formation in the same animal over time
Authors: Tsukada Yohei , Muramatsu Fumitaka , Hayashi Yumiko , Inagaki Chiaki , Su Hang , Iba Tomohiro , Kidoya Hiroyasu , Takakura Nobuyuki
Published: January 2021

Angiogenesis contributes to numerous pathological conditions. Understanding the molecular mechanisms of angiogenesis will offer new therapeutic opportunities. Several experimental in vivo models that better represent the pathological conditions have been generated for this purpose in mice, but it is difficult to translate results from mouse to human blood vessels. To understand human vascular biology and translate findings into human research, we need human blood vessel models to replicate human vascular physiology. Here, we show that human tumor tissue transplantation into a cranial window enables engraftment of human blood vessels in mice. An in vivo imaging technique using two-photon microscopy allows continuous observation of human blood vessels until at least 49 days after tumor transplantation. These human blood vessels make connections with mouse blood vessels as shown by the finding that lectin injected into the mouse tail vein reaches the human blood vessels. Finally, this model revealed that formation and/or maintenance of human blood vessels depends on VEGFR2 signaling. This approach represents a useful tool to study molecular mechanisms of human blood vessel formation and to test effects of drugs that target human blood vessels in vivo to show proof of concept in a preclinical model.
Integrated structured light architectures
Authors: Lemons Randy , Liu Wei , Frisch Josef C. , Fry Alan , Robinson Joseph , Smith Steve R. , Carbajo Sergio
Published: January 2021

The structural versatility of light underpins an outstanding collection of optical phenomena where both geometrical and topological states of light can dictate how matter will respond or display. Light possesses multiple degrees of freedom such as amplitude, and linear, spin angular, and orbital angular momenta, but the ability to adaptively engineer the spatio-temporal distribution of all these characteristics is primarily curtailed by technologies used to impose any desired structure to light. We demonstrate a laser architecture based on coherent beam combination offering integrated spatio-temporal field control and programmability, thereby presenting unique opportunities for generating light by design to exploit its topology.
Dual size-exclusion chromatography for efficient isolation of extracellular vesicles from bone marrow derived human plasma
Authors: Jung Jik-Han , Back Woojin , Yoon Junyong , Han Hyeonjeong , Kang Ka-Won , Choi Byeonghyeon , Jeong Hyesun , Park Jaena , Shin Hyunku , Hur Woojune , Choi Yeonho , Hong Sunghoi , Kim Hyun Koo , Park Yong , Park Ji-Ho
Published: January 2021

Isolation of pure extracellular vesicles (EVs), especially from blood, has been a major challenge in the field of EV research. The presence of lipoproteins and soluble proteins often hinders the isolation of high purity EVs upon utilization of conventional separation methods. To circumvent such problems, we designed a single-step dual size-exclusion chromatography (dSEC) column for effective isolation of highly pure EVs from bone marrow derived human plasma. With an aim to select appropriate column design parameters, we analyzed the physiochemical properties of the major substances in bone marrow derived plasma, which include EVs, lipoproteins, and soluble proteins. Based on these findings, we devised a novel dSEC column with two different types of porous beads sequentially stacked each other for efficient separation of EVs from other contaminants. The newly developed dSEC columns exhibited better performance in isolating highly pure EVs from AML plasma in comparison to conventional isolation methods.
Basiliximab impairs regulatory T cell (TREG) function and could affect the short-term graft acceptance in children with heart transplantation
Authors: López-Abente Jacobo , Martínez-Bonet Marta , Bernaldo-de-Quirós Esther , Camino Manuela , Gil Nuria , Panadero Esther , Gil-Jaurena Juan Miguel , Clemente Maribel , Urschel Simon , West Lori , Pion Marjorie , Correa-Rocha Rafael
Published: January 2021

CD25, the alpha chain of the IL-2 receptor, is expressed on activated effector T cells that mediate immune graft damage. Induction immunosuppression is commonly used in solid organ transplantation and can include antibodies blocking CD25. However, regulatory T cells (Tregs) also rely on CD25 for their proliferation, survival, and regulatory function. Therefore, CD25-blockade may compromise Treg protective role against rejection. We analysed in vitro the effect of basiliximab (BXM) on the viability, phenotype, proliferation and cytokine production of Treg cells. We also evaluated in vivo the effect of BXM on Treg in thymectomized heart transplant children receiving BXM in comparison to patients not receiving induction therapy. Our results show that BXM reduces Treg counts and function in vitro by affecting their proliferation, Foxp3 expression, and IL-10 secretion capacity. In pediatric heart-transplant patients, we observed decreased Treg counts and a diminished Treg/Teff ratio in BXM-treated patients up to 6-month after treatment, recovering baseline values at the end of the 12-month follow up period. These results reveal that the use of BXM could produce detrimental effects on Tregs, and support the evidence suggesting that BXM induction could impair the protective role of Tregs in the period of highest incidence of acute graft rejection.
Targeted disruption of pi–pi stacking in Malaysian banana lectin reduces mitogenicity while preserving antiviral activity
Authors: Covés-Datson Evelyn M. , King Steven R. , Legendre Maureen , Swanson Michael D. , Gupta Auroni , Claes Sandra , Meagher Jennifer L. , Boonen Arnaud , Zhang Lihong , Kalveram Birte , Raglow Zoe , Freiberg Alexander N. , Prichard Mark , Stuckey Jeanne A. , Schols Dominique , Markovitz David M.
Published: January 2021

Lectins, carbohydrate-binding proteins, have been regarded as potential antiviral agents, as some can bind glycans on viral surface glycoproteins and inactivate their functions. However, clinical development of lectins has been stalled by the mitogenicity of many of these proteins, which is the ability to stimulate deleterious proliferation, especially of immune cells. We previously demonstrated that the mitogenic and antiviral activities of a lectin (banana lectin, BanLec) can be separated via a single amino acid mutation, histidine to threonine at position 84 (H84T), within the third Greek key. The resulting lectin, H84T BanLec, is virtually non-mitogenic but retains antiviral activity. Decreased mitogenicity was associated with disruption of pi–pi stacking between two aromatic amino acids. To examine whether we could provide further proof-of-principle of the ability to separate these two distinct lectin functions, we identified another lectin, Malaysian banana lectin (Malay BanLec), with similar structural features as BanLec, including pi–pi stacking, but with only 63% amino acid identity, and showed that it is both mitogenic and potently antiviral. We then engineered an F84T mutation expected to disrupt pi–pi stacking, analogous to H84T. As predicted, F84T Malay BanLec (F84T) was less mitogenic than wild type. However, F84T maintained strong antiviral activity and inhibited replication of HIV, Ebola, and other viruses. The F84T mutation disrupted pi–pi stacking without disrupting the overall lectin structure. These findings show that pi–pi stacking in the third Greek key is a conserved mitogenic motif in these two jacalin-related lectins BanLec and Malay BanLec, and further highlight the potential to rationally engineer antiviral lectins for therapeutic purposes.
Longitudinal saliva omics responses to immune perturbation: a case study
Authors: Mias George I. , Singh Vikas Vikram , Rogers Lavida R. K. , Xue Shuyue , Zheng Minzhang , Domanskyi Sergii , Kanada Masamitsu , Piermarocchi Carlo , He Jin
Published: January 2021

Saliva omics has immense potential for non-invasive diagnostics, including monitoring very young or elderly populations, or individuals in remote locations. In this study, multiple saliva omics from an individual were monitored over three periods (100 timepoints) involving: (1) hourly sampling over 24 h without intervention, (2) hourly sampling over 24 h including immune system activation using the standard 23-valent pneumococcal polysaccharide vaccine, (3) daily sampling for 33 days profiling the post-vaccination response. At each timepoint total saliva transcriptome and proteome, and small RNA from salivary extracellular vesicles were profiled, including mRNA, miRNA, piRNA and bacterial RNA. The two 24-h periods were used in a paired analysis to remove daily variation and reveal vaccination responses. Over 18,000 omics longitudinal series had statistically significant temporal trends compared to a healthy baseline. Various immune response and regulation pathways were activated following vaccination, including interferon and cytokine signaling, and MHC antigen presentation. Immune response timeframes were concordant with innate and adaptive immunity development, and coincided with vaccination and reported fever. Overall, mRNA results appeared more specific and sensitive (timewise) to vaccination compared to other omics. The results suggest saliva omics can be consistently assessed for non-invasive personalized monitoring and immune response diagnostics.
Preliminary indoor evidences of microplastic effects on freshwater benthic macroinvertebrates
Authors: Gallitelli Luca , Cera Alessandra , Cesarini Giulia , Pietrelli Loris , Scalici Massimiliano
Published: January 2021

Plastics are to date considered one of the main detrimental drivers for the health of aquatic ecosystems, both in marine and inland waters. Regarding the latter habitat, it seems surprising how the plastic effects on benthic invertebrates are neglected since macroinvertebrates have a long tradition in the water quality assessment activities. In this context, we propose timely indoor observations on the exposure of caddisfly Odontocerum albicorne and mayfly Ephemera danica to various microplastic polymers (ABS, PET, PP, PS, PVDF). Three different experimental designs were performed on caddisflies and mayflies by exposing their larvae to natural and microplastic substrates. Our findings highlighted how microplastics affected both caddisflies in rebuilding its own case (after having removed the natural one) and mayflies burrowing. Particularly, all caddisflies rebuilt cases using the microplastic polymers provided instead of natural items only. Moreover, we provide the first evidence that mayflies burrow mainly in microplastic substrates rather than in natural ones. Our research highlights that macroinvertebrate larvae would use naturally occurring microplastics and this could be of particular concern in freshwaters with high contamination by plastics. Indeed, larvae appear to not necessarily perceive microplastics as a direct stressor. Further studies ought to be conducted to understand the chronic perturbation on larvae fitness and for example, on drift behaviour. Also, further investigations are needed to understand the potentialities of using plastics by benthic macroinvertebrates.
Sequential dual-drug delivery of BMP-2 and alendronate from hydroxyapatite-collagen scaffolds for enhanced bone regeneration
Authors: Lee Dongtak , Wufuer Maierdanjiang , Kim Insu , Choi Tae Hyun , Kim Byung Jun , Jung Hyo Gi , Jeon Byoungjun , Lee Gyudo , Jeon Ok Hee , Chang Hak , Yoon Dae Sung
Published: January 2021

The clinical use of bioactive molecules in bone regeneration has been known to have side effects, which result from uncontrolled and supraphysiological doses. In this study, we demonstrated the synergistic effect of two bioactive molecules, bone morphogenic protein-2 (BMP-2) and alendronate (ALN), by releasing them in a sequential manner. Collagen-hydroxyapatite composite scaffolds functionalized using BMP-2 are loaded with biodegradable microspheres where ALN is encapsulated. The results indicate an initial release of BMP-2 for a few days, followed by the sequential release of ALN after two weeks. The composite scaffolds significantly increase osteogenic activity owing to the synergistic effect of BMP-2 and ALN. Enhanced bone regeneration was identified at eight weeks post-implantation in the rat 8-mm critical-sized defect. Our findings suggest that the sequential delivery of BMP-2 and ALN from the scaffolds results in a synergistic effect on bone regeneration, which is unprecedented. Therefore, such a system exhibits potential for the application of cell-free tissue engineering.
Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis
Authors: Shukla Pradeep K. , Meena Avtar S. , Dalal Kesha , Canelas Cherie , Samak Geetha , Pierre Joseph F. , Rao RadhaKrishna
Published: January 2021

Alcohol use disorders are associated with altered stress responses, but the impact of stress or stress hormones on alcohol-associated tissue injury remain unknown. We evaluated the effects of chronic restraint stress on alcohol-induced gut barrier dysfunction and liver damage in mice. To determine whether corticosterone is the stress hormone associated with the stress-induced effects, we evaluated the effect of chronic corticosterone treatment on alcoholic tissue injury at the Gut-Liver-Brain (GLB) axis. Chronic restraint stress synergized alcohol-induced epithelial tight junction disruption and mucosal barrier dysfunction in the mouse intestine. These effects of stress on the gut were reproduced by corticosterone treatment. Corticosterone synergized alcohol-induced expression of inflammatory cytokines and chemokines in the colonic mucosa, and it potentiated the alcohol-induced endotoxemia and systemic inflammation. Corticosterone also potentiated alcohol-induced liver damage and neuroinflammation. Metagenomic analyses of 16S RNA from fecal samples indicated that corticosterone modulates alcohol-induced changes in the diversity and abundance of gut microbiota. In Caco-2 cell monolayers, corticosterone dose-dependently potentiated ethanol and acetaldehyde-induced tight junction disruption and barrier dysfunction. These data indicate that chronic stress and corticosterone exacerbate alcohol-induced mucosal barrier dysfunction, endotoxemia, and systemic alcohol responses. Corticosterone-mediated promotion of alcohol-induced intestinal epithelial barrier dysfunction and modulation of gut microbiota may play a crucial role in the mechanism of stress-induced promotion of alcohol-associated tissue injury at the GLB axis.
Transfer of oral bacteria to the fetus during late gestation
Authors: Yu Kevin , Rodriguez Michelle , Paul Zubin , Gordon Elizabeth , Gu Tongjun , Rice Kelly , Triplett Eric W. , Keller-Wood Maureen , Wood Charles E.
Published: January 2021

The fetus develops in a privileged environment, as the placenta serves as both a gateway for nutrients and a barrier for pathogen transfer to the fetus. Regardless, recent evidence suggests the presence of bacterial DNA in both placenta and fetus, and we have reported that DNA and protein from small numbers of bacteria gain access to the fetus from the maternal bloodstream. Other routes of environmental bacterial transfer from the mother to fetus remain unknown, as well as the physiological relevance of their presence. In these experiments, we examine multiple routes by which bacterial cellular components can enter the fetus and the fetal response to influx of bacterial DNA and protein. We inoculated maternal sheep with genetically-labeled S. aureus (Staphylococcus aureus) using three routes: intravenously, orally, and intra-vaginally. The inoculum did not produce sepsis or fever in the ewes, therefore mimicking incidental exposure to bacteria during pregnancy. 3–5 days post inoculation, we assessed the presence of bacterial components in the fetal tissues and analyzed fetal brain tissue to identify any alterations in gene expression. Our results demonstrate that components of bacteria that were introduced into the maternal mouth were detected in the fetal brain and that they stimulated changes in gene expression. We conclude that an oral route of transmission is relevant for transfer of bacterial cellular components to the fetus.
CircRNA_103765 acts as a proinflammatory factor via sponging miR-30 family in Crohn’s disease
Authors: Ye Yulan , Zhang Liping , Hu Tong , Yin Juan , Xu Lijuan , Pang Zhi , Chen Weichang
Published: January 2021

Increasing evidence suggests that circular RNAs (circRNAs) play critical roles in various pathophysiological activities. However, the role of circRNAs in inflammatory bowel disease (IBD) remains unclear. Here we report the potential roles of hsa_circRNA_103765 in regulating cell apoptosis induced by TNF-α in Crohn’s disease (CD). We identify that CircRNA_103765 expression was significantly upregulated in peripheral blood mononuclear cells (PBMCs) of patients with active IBD. A positive correlation with TNF-α significantly enhanced circRNA_103765 expression in CD, which was significantly reversed by anti-TNF-α mAb (infliximab) treatment. In vitro experiments showed that TNF-α could induce the expression of circRNA_103765, which was cell apoptosis dependent, while silencing of circRNA_103765 could protect human intestinal epithelial cells (IECs) from TNF-α-induced apoptosis. In addition, circRNA_103765 acted as a molecular sponge to adsorb the miR-30 family and impair the negative regulation of Delta-like ligand 4 (DLL4). Collectively, CircRNA_103765 is a novel important regulator of the pathogenesis of IBD via sponging miR-30 family-mediated DLL4 expression changes. Blockade of circRNA_103765 could serve as a novel approach for the treatment of IBD patients.
A deep learning framework combined with word embedding to identify DNA replication origins
Authors: Wu Feng , Yang Runtao , Zhang Chengjin , Zhang Lina
Published: January 2021

The DNA replication influences the inheritance of genetic information in the DNA life cycle. As the distribution of replication origins (ORIs) is the major determinant to precisely regulate the replication process, the correct identification of ORIs is significant in giving an insightful understanding of DNA replication mechanisms and the regulatory mechanisms of genetic expressions. For eukaryotes in particular, multiple ORIs exist in each of their gene sequences to complete the replication in a reasonable period of time. To simplify the identification process of eukaryote’s ORIs, most of existing methods are developed by traditional machine learning algorithms, and target to the gene sequences with a fixed length. Consequently, the identification results are not satisfying, i.e. there is still great room for improvement. To break through the limitations in previous studies, this paper develops sequence segmentation methods, and employs the word embedding technique, ‘Word2vec’, to convert gene sequences into word vectors, thereby grasping the inner correlations of gene sequences with different lengths. Then, a deep learning framework to perform the ORI identification task is constructed by a convolutional neural network with an embedding layer. On the basis of the analysis of similarity reduction dimensionality diagram, Word2vec can effectively transform the inner relationship among words into numerical feature. For four species in this study, the best models are obtained with the overall accuracy of 0.975, 0.765, 0.885, 0.967, the Matthew’s correlation coefficient of 0.940, 0.530, 0.771, 0.934, and the AUC of 0.975, 0.800, 0.888, 0.981, which indicate that the proposed predictor has a stable ability and provide a high confidence coefficient to classify both of ORIs and non-ORIs. Compared with state-of-the-art methods, the proposed predictor can achieve ORI identification with significant improvement. It is therefore reasonable to anticipate that the proposed method will make a useful high throughput tool for genome analysis.
Renewable energy from biomass surplus resource: potential of power generation from rice straw in Vietnam
Authors: Cuong Tran Thien , Le Hoang Anh , Khai Nguyen Manh , Hung Pham Anh , Linh Le Thuy , Thanh Nguyen Viet , Tri Ngo Dang , Huan Nguyen Xuan
Published: January 2021

Biomass, one of the renewable resources, is expected to play an important role in the world’s energy future. In Asia, rice straw is an abundant agricultural surplus because rice is one of the leading staple food crops in the region. Often, rice straw is burned directly in the field via uncontrolled combustion methods that emit large amounts of short-lived air pollutants, greenhouse gases, and other pollutants. In Vietnam, the energy and environment protection sectors are facing great challenges because of rapid urbanisation and industrialisation. A national strategic choice is to exploit renewable energy, including biomass-derived energy, to achieve energy security and CO2 emission reduction. This study investigates the potential of rice straw as an energy source for power plants at a local scale in Vietnam using data derived from satellite Sentinel-1 images. The results show that Vietnam can produce 2,565 MW from rice straw, for which 24 out of 63 provinces have a potential capacity higher than 30 MW, and the Kien Giang province has the highest capacity (245 MW). The study also analyses limitations and obstacles overcoming which can promote the biomass energy sector in the country.
AITRL, an evolutionarily conserved plant specific transcription repressor regulates ABA response in Arabidopsis
Authors: Ma Yanxing , Tian Hainan , Lin Rao , Wang Wei , Zhang Na , Hussain Saddam , Yang Wenting , Zhang Chen , Zhou Ganghua , Wang Tianya , Wang Shucai
Published: January 2021

Expression of stress response genes can be regulated by abscisic acid (ABA) dependent and ABA independent pathways. Osmotic stresses promote ABA accumulation, therefore inducing the expression of stress response genes via ABA signaling. Whereas cold and heat stresses induce the expression of stress response genes via ABA independent pathway. ABA induced transcription repressors (AITRs) are a family of novel transcription factors that play a role in ABA signaling, and Drought response gene (DRG) has previously been shown to play a role in regulating plant response to drought and freezing stresses. We report here the identification of DRG as a novel transcription factor and a regulator of ABA response in Arabidopsis. We found that the expression of DRG was induced by ABA treatment. Homologs searching identified AITR5 as the most closely related Arabidopsis protein to DRG, and homologs of DRG, including the AITR-like (AITRL) proteins in bryophytes and gymnosperms, are specifically presented in embryophytes. Therefore we renamed DRG as AITRL. Protoplast transfection assays show that AITRL functioned as a transcription repressor. In seed germination and seedling greening assays, the aitrl mutants showed an increased sensitivity to ABA. By using qRT-PCR, we show that ABA responses of some ABA signaling component genes including some PYR1-likes (PYLs), PROTEIN PHOSPHATASE 2Cs (PP2Cs) and SUCROSE NONFERMENTING 1 (SNF1)-RELATED PROTEIN KINASES 2s (SnRK2s) were reduced in the aitrl mutants. Taken together, our results suggest that AITRLs are a family of novel transcription repressors evolutionally conserved in embryophytes, and AITRL regulates ABA response in Arabidopsis by affecting ABA response of some ABA signaling component genes.
Investigation of the selective color-changing mechanism of Dynastes tityus beetle (Coleoptera: Scarabaeidae)
Authors: Sun Jiyu , Wu Wei , Tian Limei , Li Wei , Zhang Fang , Wang Yueming
Published: January 2021

Not only does the Dynastes tityus beetle display a reversible color change controlled by differences in humidity, but also, the elytron scale can change color from yellow-green to deep-brown in specified shapes. The results obtained by focused ion beam-scanning electron microscopy (FIB-SEM), show that the epicuticle (EPI) is a permeable layer, and the exocuticle (EXO) is a three-dimensional photonic crystal. To investigate the mechanism of the reversible color change, experiments were conducted to determine the water contact angle, surface chemical composition, and optical reflectance, and the reflective spectrum was simulated. The water on the surface began to permeate into the elytron via the surface elemental composition and channels in the EPI. A structural unit (SU) in the EXO allows local color changes in varied shapes. The reflectance of both yellow-green and deep-brown elytra increases as the incidence angle increases from 0° to 60°. The microstructure and changes in the refractive index are the main factors that influence the process of reversible color change. According to the simulation, the lower reflectance causing the color change to deep-brown results from water infiltration, which increases light absorption. Meanwhile, the waxy layer has no effect on the reflection of light. This study lays the foundation to manufacture engineered photonic materials that undergo controllable changes in iridescent color.
Evaluation for pharmacokinetic exposure of cytotoxic anticancer drugs in elderly patients receiving (R-)CHOP therapy
Authors: Nakagawa Junichi , Takahata Takenori , Hyodo Rui , Chen Yu , Hasui Kengo , Sasaki Kota , Saito Kensuke , Ueno Kayo , Hosoi Kazuhiro , Terui Kazufumi , Sato Atsushi , Niioka Takenori
Published: January 2021

(R-)miniCHOP therapy, which delivers approximately half-doses of the (R-)CHOP regimen, has shown efficacy and safety in patients who are more than 80 years old. This study aimed to compare the area under the plasma concentration–time curves (AUCs) of vincristine (VCR), doxorubicin (DXR), and cyclophosphamide (CPA) between (R-)CHOP and (R-)miniCHOP regimens. The AUCs were compared between patients aged 65–79 years receiving (R-)CHOP therapy and those aged 80 years and older receiving (R-)miniCHOP therapy. Age was not an independent variable for predicting the dose-adjusted AUCs (AUC/Ds) of cytotoxic anticancer drugs. The median AUCs of DXR and CPA were significantly smaller in the (R-)miniCHOP group than in the (R-)CHOP group (168.7 vs. 257.9 ng h/mL,P = 0.003, and 219.9 vs. 301.7 µg h/mL,P = 0.020, respectively). The median AUCs of VCR showed the same trend but the difference was not significant (24.83 vs. 34.85 ng h/mL,P = 0.135). It is possible that the AUCs of VCR, DXR, and CPA in patients aged 80 years and older receiving (R-)miniCHOP therapy may be lower than those in patients 65–79 years old receiving (R-)CHOP therapy.
Pseudogymnoascus destructans growth in wood, soil and guano substrates
Authors: Urbina Jenny , Chestnut Tara , Allen Jennifer M. , Levi Taal
Published: January 2021

Understanding how a pathogen can grow on different substrates and how this growth impacts its dispersal are critical to understanding the risks and control of emerging infectious diseases. Pseudogymnoascus destructans (Pd) causes white-nose syndrome (WNS) in many bat species and can persist in, and transmit from, the environment. We experimentally evaluated Pd growth on common substrates to better understand mechanisms of pathogen persistence, transmission and viability. We inoculated autoclaved guano, fresh guano, soil, and wood with live Pd fungus and evaluated (1) whether Pd grows or persists on each (2) if spores of the fungus remain viable 4 months after inoculation on each substrate, and (3) whether detection and quantitation of Pd on swabs is sensitive to the choice to two commonly used DNA extraction kits. After inoculating each substrate with 460,000 Pd spores, we collected ~ 0.20 g of guano and soil, and swabs from wood every 16 days for 64 days to quantify pathogen load through time using real-time qPCR. We detected Pd on all substrates over the course of the experiment. We observed a tenfold increase in pathogen loads on autoclaved guano and persistence but not growth in fresh guano. Pathogen loads increased marginally on wood but declined ~ 60-fold in soil. After four months, apparently viable spores were harvested from all substrates but germination did not occur from fresh guano. We additionally found that detection and quantitation of Pd from swabs of wood surfaces is sensitive to the DNA extraction method. The commonly used PrepMan Ultra Reagent protocol yielded substantially less DNA than did the QIAGEN DNeasy Blood and Tissue Kit. Notably the PrepMan Ultra Reagent failed to detect Pd in many wood swabs that were detected by QIAGEN and were subsequently found to contain substantial live conidia. Our results indicate that Pd can persist or even grow on common environmental substrates with results dependent on whether microbial competitors have been eliminated. Although we observed clear rapid declines in Pd on soil, viable spores were harvested four months after inoculation. These results suggest that environmental substrates and guano can in general serve as infectious environmental reservoirs due to long-term persistence, and even growth, of live Pd. This should inform management interventions to sanitize or modify structures to reduce transmission risk as well early detection rapid response (EDRR) planning.