bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenic Hydrogel? A Novel-Entrapment Neuropathy Model Induced by Ultrasound-Guided Perineural Injections
Authors: Hsiao Ming-Yen , Wu Ya-Wen , Chen Wen-Shiang , Lin Yu-Ling , Kuo Po-Ling , Wu Chueh-Hung
Published: March 2021

Entrapment neuropathy (EN) is a prevalent and debilitative condition caused by a complex pathogenesis that involves a chronic compression–edema–ischemia cascade and perineural adhesion that results in excessive shear stress during motion. Despite decades of research, an easily accessible and surgery-free animal model mimicking the mixed etiology is currently lacking, thus limiting our understanding of the disease and the development of effective therapies. In this proof-of-concept study, we used ultrasound-guided perineural injection of a methoxy poly(ethylene glycol)-b-Poly(lactide-co-glycoilide) carboxylic acid (mPEG-PLGA-BOX) hydrogel near the rat’s sciatic nerve to induce EN, as confirmed sonographically, electrophysiologically, and histologically. The nerve that was injected with hydrogel appeared unevenly contoured and swollen proximally with slowed nerve conduction velocities across the injected segments, thus showing the compressive features of EN. Histology showed perineural cellular infiltration, deposition of irregular collagen fibers, and a possible early demyelination process, thus indicating the existence of adhesions. The novel method provides a surgery-free and cost-effective way to establish a small-animal model of EN that has mixed compression and adhesion features, thus facilitating the additional elucidation of the pathophysiology of EN and the search for promising treatments.
Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment
Authors: Terlikowska Katarzyna M. , Dobrzycka Bożena , Terlikowski Sławomir J.
Published: March 2021

Our increased understanding of tumour biology gained over the last few years has led to the development of targeted molecular therapies, e.g., vascular endothelial growth factor A (VEGF-A) antagonists, poly[ADP-ribose] polymerase 1 (PARP1) inhibitors in hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 mutants), increasing survival and improving the quality of life. However, the majority of ovarian cancer (OC) patients still do not have access to targeted molecular therapies that would be capable of controlling their disease, especially resistant or relapsed. Chimeric antigen receptors (CARs) are recombinant receptor constructs located on T lymphocytes or other immune cells that change its specificity and functions. Therefore, in a search for a successful solid tumour therapy using CARs the specific cell surface antigens identification is crucial. Numerous in vitro and in vivo studies, as well as studies on humans, prove that targeting overexpressed molecules, such as mucin 16 (MUC16), annexin 2 (ANXA2), receptor tyrosine-protein kinase erbB-2 (HER2/neu) causes high tumour cells toxicity and decreased tumour burden. CARs are well tolerated, side effects are minimal and they inhibit disease progression. However, as OC is heterogenic in its nature with high mutation diversity and overexpression of different receptors, there is a need to consider an individual approach to treat this type of cancer. In this publication, we would like to present the history and status of therapies involving the CAR T cells in treatment of OC tumours, suggest potential T cell-intrinsic determinants of response and resistance as well as present extrinsic factors impacting the success of this approach.
Mechanisms Underlying Connexin Hemichannel Activation in Disease
Authors: Van Campenhout Raf , Gomes Ana Rita , De Groof Timo W.M. , Muyldermans Serge , Devoogdt Nick , Vinken Mathieu
Published: March 2021

Gap junctions and connexin hemichannels mediate intercellular and extracellular communication, respectively. While gap junctions are seen as the “good guys” by controlling homeostasis, connexin hemichannels are considered as the “bad guys”, as their activation is associated with the onset and dissemination of disease. Open connexin hemichannels indeed mediate the transport of messengers between the cytosol and extracellular environment and, by doing so, fuel inflammation and cell death in a plethora of diseases. The present mini-review discusses the mechanisms involved in the activation of connexin hemichannels during pathology.
Recent Progress on Biodegradable Tissue Engineering Scaffolds Prepared by Thermally-Induced Phase Separation (TIPS)
Authors: Zeinali Reza , del Valle Luis J. , Torras Joan , Puiggalí Jordi
Published: March 2021

Porous biodegradable scaffolds provide a physical substrate for cells allowing them to attach, proliferate and guide the formation of new tissues. A variety of techniques have been developed to fabricate tissue engineering (TE) scaffolds, among them the most relevant is the thermally-induced phase separation (TIPS). This technique has been widely used in recent years to fabricate three-dimensional (3D) TE scaffolds. Low production cost, simple experimental procedure and easy processability together with the capability to produce highly porous scaffolds with controllable architecture justify the popularity of TIPS. This paper provides a general overview of the TIPS methodology applied for the preparation of 3D porous TE scaffolds. The recent advances in the fabrication of porous scaffolds through this technique, in terms of technology and material selection, have been reviewed. In addition, how properties can be effectively modified to serve as ideal substrates for specific target cells has been specifically addressed. Additionally, examples are offered with respect to changes of TIPS procedure parameters, the combination of TIPS with other techniques and innovations in polymer or filler selection.
Structural Basis for the Function of the C-Terminal Proton Release Pathway in the Calcium Pump
Authors: Espinoza-Fonseca L. Michel
Published: March 2021

The calcium pump (sarco/endoplasmic reticulum Ca2+-ATPase, SERCA) plays a major role in calcium homeostasis in muscle cells by clearing cytosolic Ca2+ during muscle relaxation. Active Ca2+ transport by SERCA involves the structural transition from a low-Ca2+ affinity E2 state toward a high-Ca2+ affinity E1 state of the pump. This structural transition is accompanied by the countertransport of protons to stabilize the negative charge and maintain the structural integrity of the transport sites and partially compensate for the positive charges of the two Ca2+ ions passing through the membrane. X-ray crystallography studies have suggested that a hydrated pore located at the C-terminal domain of SERCA serves as a conduit for proton countertransport, but the existence and function of this pathway have not yet been fully characterized. We used atomistic simulations to demonstrate that in the protonated E2 state and the absence of initially bound water molecules, the C-terminal pore becomes hydrated in the nanosecond timescale. Hydration of the C-terminal pore is accompanied by the formation of water wires that connect the transport sites with the cytosol. Water wires are known as ubiquitous proton-transport devices in biological systems, thus supporting the notion that the C-terminal domain serves as a conduit for proton release. Additional simulations showed that the release of a single proton from the transport sites induces bending of transmembrane helix M5 and the interaction between residues Arg762 and Ser915. These structural changes create a physical barrier against full hydration of the pore and prevent the formation of hydrogen-bonded water wires once proton transport has occurred through this pore. Together, these findings support the notion that the C-terminal proton release pathway is a functional element of SERCA and also provide a mechanistic model for its operation in the catalytic cycle of the pump.
Molecular Insights into Inflorescence Meristem Specification for Yield Potential in Cereal Crops
Authors: Wang Chengyu , Yang Xiujuan , Li Gang
Published: March 2021

Flowering plants develop new organs throughout their life cycle. The vegetative shoot apical meristem (SAM) generates leaf whorls, branches and stems, whereas the reproductive SAM, called the inflorescence meristem (IM), forms florets arranged on a stem or an axis. In cereal crops, the inflorescence producing grains from fertilized florets makes the major yield contribution, which is determined by the numbers and structures of branches, spikelets and florets within the inflorescence. The developmental progression largely depends on the activity of IM. The proper regulations of IM size, specification and termination are outcomes of complex interactions between promoting and restricting factors/signals. Here, we focus on recent advances in molecular mechanisms underlying potential pathways of IM identification, maintenance and differentiation in cereal crops, including rice (Oryza sativa), maize (Zea mays), wheat (Triticum aestivum), and barley (Hordeum vulgare), highlighting the researches that have facilitated grain yield by, for example, modifying the number of inflorescence branches. Combinatorial functions of key regulators and crosstalk in IM determinacy and specification are summarized. This review delivers the knowledge to crop breeding applications aiming to the improvements in yield performance and productivity.
Yersiniabactin Siderophore of Crohn’s Disease-Associated Adherent-Invasive Escherichia coli Is Involved in Autophagy Activation in Host Cells
Authors: Dalmasso Guillaume , Nguyen Hang Thi Thu , Faïs Tiphanie , Massier Sébastien , Chevarin Caroline , Vazeille Emilie , Barnich Nicolas , Delmas Julien , Bonnet Richard
Published: March 2021

Background: Adherent-invasive Escherichia coli (AIEC) have been implicated in the etiology of Crohn’s disease. The AIEC reference strain LF82 possesses a pathogenicity island similar to the high pathogenicity island of Yersinia spp., which encodes the yersiniabactin siderophore required for iron uptake and growth of the bacteria in iron-restricted environment. Here, we investigated the role of yersiniabactin during AIEC infection. Methods: Intestinal epithelial T84 cells and CEABAC10 transgenic mice were infected with LF82 or its mutants deficient in yersiniabactin expression. Autophagy was assessed by Western blot analysis for p62 and LC3-II expression. Results: Loss of yersiniabactin decreased the growth of LF82 in competitive conditions, reducing the ability of LF82 to adhere to and invade T84 cells and to colonize the intestinal tract of CEABAC10 mice. However, yersiniabactin deficiency increased LF82 intracellular replication. Mechanistically, a functional yersiniabactin is necessary for LF82-induced expression of HIF-1α, which is implicated in autophagy activation in infected cells. Conclusion: Our study highlights a novel role for yersiniabactin siderophore in AIEC–host interaction. Indeed, yersiniabactin, which is an advantage for AIEC to growth in a competitive environment, could be a disadvantage for the bacteria as it activates autophagy, a key host defense mechanism, leading to bacterial clearance.
Berberine Delays Onset of Collagen-Induced Arthritis through T Cell Suppression
Authors: Vita Alexandra A. , Aljobaily Hend , Lyons David O. , Pullen Nicholas A.
Published: March 2021

There is evidence that berberine (BBR), a clinically relevant plant compound, ameliorates clinically apparent collagen-induced arthritis (CIA) in vivo. However, to date, there are no studies involving the use of BBR which explore its prophylactic potential in this model of rheumatoid arthritis (RA). The aim of this study was to determine if prophylactic BBR use during the preclinical phase of collagen-induced arthritis would delay arthritic symptom onset, and to characterize the cellular mechanism underlying such an effect. DBA/1J mice were injected with an emulsion of bovine type II collagen (CII) and complete Freund’s adjuvant (day 0) and a booster injection of CII in incomplete Freund’s adjuvant (day 18) to induce arthritis. Mice were then given i.p. injections of 1 mg/kg/day of BBR or PBS (vehicle with 0.01% DMSO) from days 0 to 28, were left untreated (CIA control), or were in a non-arthritic control group (n = 15 per group). Incidence of arthritis in BBR-treated mice was 50%, compared to 90% in both the CIA and PBS controls. Populations of B and T cells from the spleens and draining lymph nodes of mice were examined on day 14 (n = 5 per group) and day 28 (n = 10 per group). BBR-treated mice had significantly reduced populations of CD4+Th and CD4+CXCR5+ Tfh cells, and an increased proportion of Foxp3+ Treg at days 14 and 28, as well as reduced expression of co-stimulatory molecules CD28 and CD154 at both endpoints. The effect seen on T cell populations and co-stimulatory molecule expression in BBR-treated mice was not mirrored in CD19+ B cells. Additionally, BBR-treated mice experienced reduced anti-CII IgG2a and anti-CII total IgG serum concentrations. These results indicate a potential role for BBR as a prophylactic supplement for RA, and that its effect may be mediated specifically through T cell suppression. However, the cellular effector involved raises concern for BBR prophylactic use in the context of vaccine efficacy and other primary adaptive immune responses.
The Mitogen-Activated Protein Kinase PlMAPK2 Is Involved in Zoosporogenesis and Pathogenicity of Peronophythoralitchii
Authors: Huang Jiamin , Xi Pinggen , Deng Yizhen , Huang Weixiong , Wang Jingrui , Zhao Qingqing , Yang Wensheng , Li Wen , Situ Junjian , Jiang Liqun , Guan Tianfang , Li Minhui , Jiang Zide , Kong Guanghui
Published: March 2021

As an evolutionarily conserved pathway, mitogen-activated protein kinase (MAPK) cascades function as the key signal transducers that convey information by protein phosphorylation. Here we identified PlMAPK2 as one of 14 predicted MAPKs encoding genes in the plant pathogenic oomycete Peronophythora litchii. PlMAPK2 is conserved in P.litchii and Phytophthora species. We found that PlMAPK2 was up-regulated in sporangium, zoospore, cyst, cyst germination and early stage of infection. We generated PlMAPK2 knockout mutants using the CRISPR/Cas9 method. Compared with wild-type strain, the PlMAPK2 mutants showed no significant difference in vegetative growth, oospore production and sensitivity to various abiotic stresses. However, the sporangium release was severely impaired. We further found that the cleavage of the cytoplasm into uninucleate zoospores was disrupted in the PlMAPK2 mutants, and this developmental phenotype was accompanied by reduction in the transcription levels of PlMAD1 and PlMYB1 genes. Meanwhile, the PlMAPK2 mutants exhibited lower laccase activity and reduced virulence to lychee leaves. Overall, this study identified a MAPK that is critical for zoosporogenesis by regulating the sporangial cleavage and pathogenicity of P.litchii, likely by regulating laccase activity.
Products of Docosahexaenoate Oxidation as Contributors to Photosensitising Properties of Retinal Lipofuscin
Authors: Różanowska Małgorzata B. , Pawlak Anna , Różanowski Bartosz
Published: March 2021

Retinal lipofuscin which accumulates with age in the retinal pigment epithelium (RPE) is subjected to daily exposures to high fluxes of visible light and exhibits potent photosensitising properties; however, the molecules responsible for its photoreactivity remain unknown. Here, we demonstrate that autooxidation of docosahexaenoate (DHE) leads to the formation of products absorbing, in addition to UVB and UVA light, also visible light. The products of DHE oxidation exhibit potent photosensitising properties similar to photosensitising properties of lipofuscin, including generation of an excited triplet state with similar characteristics as the lipofuscin triplet state, and photosensitised formation of singlet oxygen and superoxide. The quantum yields of singlet oxygen and superoxide generation by oxidised DHE photoexcited with visible light are 2.4- and 3.6-fold higher, respectively, than for lipofuscin, which is consistent with the fact that lipofuscin contains some chromophores which do contribute to the absorption of light but not so much to its photosensitising properties. Importantly, the wavelength dependence of photooxidation induced by DHE oxidation products normalised to equal numbers of incident photons is also similar to that of lipofuscin—it steeply increases with decreasing wavelength. Altogether, our results demonstrate that products of DHE oxidation include potent photosensitiser(s) which are likely to contribute to lipofuscin photoreactivity.
Molecular and Immunological Identification of Low Allergenic Fruits among Old and New Apple Varieties
Authors: Siekierzynska Aleksandra , Piasecka-Kwiatkowska Dorota , Litwinczuk Wojciech , Burzynska Marta , Myszka Aleksander , Karpinski Pawel , Zygala Elzbieta , Piorecki Narcyz , Springer Ewa , Sozanski Tomasz
Published: March 2021

About 50–70% of patients allergic to birch pollen suffer from sensitization after apple ingestion. Apple allergenicity was established in only few varieties. Studies were performed on apple fruits of 21 traditional and nine modern varieties organically, intensively, or integratively produced. The aim of the study was to assess whether the factors like cultivation method, maturity stage, genotype, or type of tissue place an impact on the allergenic potential of apples. To answer these questions, we used semiquantitative real-time PCR, ELISA, and immunoblotting. Apple allergen genes present divergent expression across apple cultivars. Expression of the Mal d 1.06A correlates with the Mal d 1 level and is affected by the cultivation method and maturity of the fruit. The content of the main allergen Mal d 1 varied widely across cultivars. Interestingly, in our study, the Gala variety presented a low Mal d 1 concentration regardless of the cultivation method. Based on the Mal d 1.06A expression, the Mal d 1 protein content, and the immunoreactivity assay, the Kandil Sinap, Kosztela, Rumianka from Alma-Ata, Kantówka Gdańska, Reinette Coulon, and Gala cultivars emerged as potentially hypoallergenic apple cultivars. Our study allowed distinguishing between potentially low, medium, and highly allergenic varieties.
Genome-wide Identification and Characterization of FCS-Like Zinc Finger (FLZ) Family Genes in Maize (Zea mays) and Functional Analysis of ZmFLZ25 in Plant Abscisic Acid Response
Authors: Chen Shunquan , Li Xibao , Yang Chao , Yan Wei , Liu Chuanliang , Tang Xiaoyan , Gao Caiji
Published: March 2021

FCS-like zinc finger family proteins (FLZs), a class of plant-specific scaffold of SnRK1 complex, are involved in the regulation of various aspects of plant growth and stress responses. Most information of FLZ family genes was obtained from the studies in Arabidopsis thaliana, whereas little is known about the potential functions of FLZs in crop plants. In this study, 37 maize FLZ (ZmFLZ) genes were identified to be asymmetrically distributed on 10 chromosomes and can be divided into three subfamilies. Protein interaction and subcellular localization assays demonstrated that eight typical ZmFLZs interacted and partially co-localized with ZmKIN10, the catalytic α-subunit of the SnRK1 complex in maize leaf mesophyll cells. Expression profile analysis revealed that several ZmFLZs were differentially expressed across various tissues and actively responded to diverse abiotic stresses. In addition, ectopic overexpression of ZmFLZ25 in Arabidopsis conferred hypersensitivity to exogenous abscisic acid (ABA) and triggered higher expression of ABA-induced genes, pointing to the positive regulatory role of ZmFLZ25 in plant ABA signaling, a scenario further evidenced by the interactions between ZmFLZ25 and ABA receptors. In summary, these data provide the most comprehensive information on FLZ family genes in maize, and shed light on the biological function of ZmFLZ25 in plant ABA signaling.
Differential Response of Grapevine to Infection with ‘Candidatus Phytoplasma solani’ in Early and Late Growing Season through Complex Regulation of mRNA and Small RNA Transcriptomes
Authors: Dermastia Marina , Škrlj Blaž , Strah Rebeka , Anžič Barbara , Tomaž Špela , Križnik Maja , Schönhuber Christina , Riedle-Bauer Monika , Ramšak Živa , Petek Marko , Kladnik Aleš , Lavrač Nada , Gruden Kristina , Roitsch Thomas , Brader Günter , Pompe-Novak Maruša
Published: March 2021

Bois noir is the most widespread phytoplasma grapevine disease in Europe. It is associated with ‘Candidatus Phytoplasma solani’, but molecular interactions between the causal pathogen and its host plant are not well understood. In this work, we combined the analysis of high-throughput RNA-Seq and sRNA-Seq data with interaction network analysis for finding new cross-talks among pathways involved in infection of grapevine cv. Zweigelt with ‘Ca. P. solani’ in early and late growing seasons. While the early growing season was very dynamic at the transcriptional level in asymptomatic grapevines, the regulation at the level of small RNAs was more pronounced later in the season when symptoms developed in infected grapevines. Most differentially expressed small RNAs were associated with biotic stress. Our study also exposes the less-studied role of hormones in disease development and shows that hormonal balance was already perturbed before symptoms development in infected grapevines. Analysis at the level of communities of genes and mRNA-microRNA interaction networks revealed several new genes (e.g., expansins and cryptdin) that have not been associated with phytoplasma pathogenicity previously. These novel actors may present a new reference framework for research and diagnostics of phytoplasma diseases of grapevine.
Withholding of M-CSF Supplement Reprograms Macrophages to M2-Like via Endogenous CSF-1 Activation
Authors: Chen Yu-Chih , Lai Yin-Siew , Hsuuw Yan-Der , Chang Ko-Tung
Published: March 2021

Macrophage colony-stimulating factor (M-CSF or CSF-1) is known to have a broad range of actions on myeloid cells maturation, including the regulation of macrophage differentiation, proliferation and survival. Macrophages generated by M-CSF stimulus have been proposed to be alternatively activated or M2 phenotype. M-CSF is commonly overexpressed by tumors and is also known to enhance tumor growth and aggressiveness via stimulating pro-tumor activities of tumor-associated macrophages (TAMs). Currently, inhibition of CSF-1/CSF-1R interaction by therapeutic antibody to deplete TAMs and their pro-tumor functions is becoming a prevalent strategy in cancer therapy. However, its antitumor activity shows a limited single-agent effect. Therefore, macrophages in response to M-CSF interruption are pending for further investigation. To achieve this study, bone marrow derived macrophages were generated in vitro by M-CSF stimulation for 7 days and then continuously grown until day 21 in M-CSF absence. A selective pressure for cell survival was initiated after withdrawal of M-CSF. The surviving cells were more prone to M2-like phenotype, even after receiving interleukin-4 (IL-4) stimulation. The transcriptome analysis unveiled that endogenous CSF-1 level was dramatically up-regulated and numerous genes downstream to CSF-1 covering tumor necrosis factor (TNF), ras-related protein 1 (Rap1) and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway were significantly modulated, especially for proliferation, migration and adhesion. Moreover, the phenomenal increase of miR-21-5p and genes related to pro-tumor activity were observed in parallel. In summary, withholding of CSF-1/CSF-1R interaction would rather augment than suspend the M-CSF-driven pro-tumor activities of M2 macrophages in a long run.
Switching Ion Binding Selectivity of Thiacalix[4]arene Monocrowns at Liquid–Liquid and 2D-Confined Interfaces
Authors: Muravev Anton , Yakupov Ayrat , Gerasimova Tatiana , Nugmanov Ramil , Trushina Ekaterina , Babaeva Olga , Nizameeva Guliya , Syakaev Viktor , Katsyuba Sergey , Selektor Sofiya , Solovieva Svetlana , Antipin Igor
Published: March 2021

Understanding the interaction of ions with organic receptors in confined space is of fundamental importance and could advance nanoelectronics and sensor design. In this work, metal ion complexation of conformationally varied thiacalix[4]monocrowns bearing lower-rim hydroxy (type I), dodecyloxy (type II), or methoxy (type III) fragments was evaluated. At the liquid–liquid interface, alkylated thiacalixcrowns-5(6) selectively extract alkali metal ions according to the induced-fit concept, whereas crown-4 receptors were ineffective due to distortion of the crown-ether cavity, as predicted by quantum-chemical calculations. In type-I ligands, alkali-metal ion extraction by the solvent-accessible crown-ether cavity was prevented, which resulted in competitive Ag+ extraction by sulfide bridges. Surprisingly, amphiphilic type-I/II conjugates moderately extracted other metal ions, which was attributed to calixarene aggregation in salt aqueous phase and supported by dynamic light scattering measurements. Cation–monolayer interactions at the air–water interface were monitored by surface pressure/potential measurements and UV/visible reflection–absorption spectroscopy. Topology-varied selectivity was evidenced, towards Sr2+ (crown-4), K+ (crown-5), and Ag+ (crown-6) in type-I receptors and Na+ (crown-4), Ca2+ (crown-5), and Cs+ (crown-6) in type-II receptors. Nuclear magnetic resonance and electronic absorption spectroscopy revealed exocyclic coordination in type-I ligands and cation–π interactions in type-II ligands.
Tailoring Nano-Porous Surface of Aligned Electrospun Poly (L-Lactic Acid) Fibers for Nerve Tissue Engineering
Authors: Xuan Hongyun , Li Biyun , Xiong Feng , Wu Shuyuan , Zhang Zhuojun , Yang Yumin , Yuan Huihua
Published: March 2021

Despite the existence of many attempts at nerve tissue engineering, there is no ideal strategy to date for effectively treating defective peripheral nerve tissue. In the present study, well-aligned poly (L-lactic acid) (PLLA) nanofibers with varied nano-porous surface structures were designed within different ambient humidity levels using the stable jet electrospinning (SJES) technique. Nanofibers have the capacity to inhibit bacterial adhesion, especially with respect to Staphylococcus aureus (S. aureus). It was noteworthy to find that the large nano-porous fibers were less detrimentally affected by S. aureus than smaller fibers. Large nano-pores furthermore proved more conducive to the proliferation and differentiation of neural stem cells (NSCs), while small nano-pores were more beneficial to NSC migration. Thus, this study concluded that well-aligned fibers with varied nano-porous surface structures could reduce bacterial colonization and enhance cellular responses, which could be used as promising material in tissue engineering, especially for neuro-regeneration.
Fermented Gamma Aminobutyric Acid Improves Sleep Behaviors in Fruit Flies and Rodent Models
Authors: Jeong A-Hyun , Hwang Jisu , Jo Kyungae , Kim Singeun , Ahn Yejin , Suh Hyung Joo , Choi Hyeon-Son
Published: March 2021

The aim of this study was to investigate the effect of Lactobacillus brevis-fermented γ-aminobutyric acid (LB-GABA) on sleep behaviors in invertebrate and vertebrate models. In Drosophila melanogaster, LB-GABA-treated group showed an 8–9%-longer sleep duration than normal group did. LB-GABA-treated group also showed a 46.7% lower level of nighttime activity with a longer (11%) sleep duration under caffeine-induced arousal conditions. The LB-GABA-mediated inhibition of activity was confirmed as a reduction of total movement of flies using a video tracking system. In the pentobarbital-induced sleep test in mice, LB-GABA (100 mg/kg) shortened the time of onset of sleep by 32.2% and extended sleeping time by 59%. In addition, mRNA and protein level of GABAergic/Serotonergic neurotransmitters were upregulated following treatment with LB-GABA (2.0%). In particular, intestine- and brain-derived GABAA protein levels were increased by sevenfold and fivefold, respectively. The electroencephalography (EEG) analysis in rats showed that LB-GABA significantly increased non-rapid eye movement (NREM) (53%) with the increase in theta (θ, 59%) and delta (δ, 63%) waves, leading to longer sleep time (35%), under caffeine-induced insomnia conditions. LB-GABA showed a dose-dependent agonist activity on human GABAA receptor with a half-maximal effective concentration (EC50) of 3.44 µg/mL in human embryonic kidney 293 (HEK293) cells.
BrLETM2 Protein Modulates Anthocyanin Accumulation by Promoting ROS Production in Turnip (Brassica rapa subsp. rapa)
Authors: Song Hyon , Yang Jianfei , Mun Nam , Chen Bowei , Chen Yunzhu , Kim Pyol , Kawabata Saneyuki , Li Yuhua , Wang Yu
Published: March 2021

In ‘Tsuda’ turnip, the swollen root peel accumulates anthocyanin pigments in a light-dependent manner, but the mechanism is unclear. Here, mutant g120w which accumulated extremely low levels of anthocyanin after light exposure was identified. Segregation analysis showed that the anthocyanin-deficient phenotype was controlled by a single recessive gene. By using bulked-segregant analysis sequencing and CAPS marker-based genetic mapping analyses, a 21.6-kb region on chromosome A07 was mapped, in which a calcium-binding EF hand family protein named BrLETM2 was identified as the causal gene. RNA sequencing analysis showed that differentially expressed genes (DEGs) between wild type and g120w in light-exposed swollen root peels were enriched in anthocyanin biosynthetic process and reactive oxygen species (ROS) biosynthetic process GO term. Furthermore, nitroblue tetrazolium (NBT) staining showed that the ROS level decreased in g120w mutant. Anthocyanins induced by UV-A were abolished by the pre-treatment of seedlings with DPI (an inhibitor of nicotinamide adenine nucleoside phosphorylase (NADPH) oxidase) and decreased in g120w mutant. These results indicate that BrLETM2 modulates ROS signaling to promote anthocyanin accumulation in turnip under UV-A and provides new insight into the mechanism of how ROS and light regulate anthocyanin production.
Silver Nanoparticles from Oregano Leaves’ Extracts as Antimicrobial Components for Non-Infected Hydrogel Contact Lenses
Authors: Meretoudi Anastasia , Banti Christina N. , Raptis Panagiotis K. , Papachristodoulou Christina , Kourkoumelis Nikolaos , Ikiades Aris A. , Zoumpoulakis Panagiotis , Mavromoustakos Thomas , Hadjikakou Sotiris K.
Published: March 2021

The oregano leaves’ extract (ORLE) was used for the formation of silver nanoparticles (AgNPs(ORLE)). ORLE and AgNPs(ORLE) (2 mg/mL) were dispersed in polymer hydrogels to give the pHEMA@ORLE_2 and pHEMA@AgNPs(ORLE)_2 using hydroxyethyl–methacrylate (HEMA). The materials were characterized by X-ray fluorescence (XRF) spectroscopy, X-ray powder diffraction analysis (XRPD), thermogravimetric differential thermal analysis (TG-DTA), derivative thermogravimetry/differential scanning calorimetry (DTG/DSC), ultraviolet (UV-Vis), and attenuated total reflection mode (ATR-FTIR) spectroscopies in solid state and UV–Vis in solution. The crystallite size value, analyzed with XRPD, was determined at 20 nm. The antimicrobial activity of the materials was investigated against Gram-negative bacterial strains Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). The Gram-positive ones of the genus of Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus) are known to be involved in microbial keratitis by the means of inhibitory zone (IZ), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). The IZs, which developed upon incubation of P. aeruginosa, E. coli, S. epidermidis, and S. aureus with paper discs soaked in 2 mg/mL of AgNPs(ORLE), were 11.7 ± 0.7, 13.5 ± 1.9, 12.7 ± 1.7, and 14.3 ± 1.7 mm. When the same dose of ORLE was administrated, the IZs were 10.2 ± 0.7, 9.2 ± 0.5, 9.0 ± 0.0, and 9.0 ± 0.0 mm. The percent of bacterial viability when they were incubated over the polymeric hydrogel discs of pHEMA@AgNPs(ORLE)_2 was interestingly low (66.5, 88.3, 77.7, and 59.6%, respectively, against of P. aeruginosa, E. coli, S. epidermidis, and S. aureus) and those of pHEMA@ORLE_2 were 89.3, 88.1, 92.8, and 84.6%, respectively. Consequently, pHEMA@AgNPs(ORLE)_2 could be an efficient candidate toward the development of non-infectious contact lenses.
Pathological Relationship between Intracellular Superoxide Metabolism and p53 Signaling in Mice
Authors: Watanabe Kenji , Shibuya Shuichi , Ozawa Yusuke , Toda Toshihiko , Shimizu Takahiko
Published: March 2021

Intracellular superoxide dismutases (SODs) maintain tissue homeostasis via superoxide metabolism. We previously reported that intracellular reactive oxygen species (ROS), including superoxide accumulation caused by cytoplasmic SOD (SOD1) or mitochondrial SOD (SOD2) insufficiency, induced p53 activation in cells. SOD1 loss also induced several age-related pathological changes associated with increased oxidative molecules in mice. To evaluate the contribution of p53 activation for SOD1 knockout (KO) (Sod1−/−) mice, we generated SOD1 and p53 KO (double-knockout (DKO)) mice. DKO fibroblasts showed increased cell viability with decreased apoptosis compared with Sod1−/− fibroblasts. In vivo experiments revealed that p53 insufficiency was not a great contributor to aging-like tissue changes but accelerated tumorigenesis in Sod1−/− mice. Furthermore, p53 loss failed to improve dilated cardiomyopathy or the survival in heart-specific SOD2 conditional KO mice. These data indicated that p53 regulated ROS-mediated apoptotic cell death and tumorigenesis but not ROS-mediated tissue degeneration in SOD-deficient models.
Newly Isolated Animal Pathogen Corynebacterium silvaticum Is Cytotoxic to Human Epithelial Cells
Authors: Möller Jens , Busch Anne , Berens Christian , Hotzel Helmut , Burkovski Andreas
Published: March 2021

Corynebacterium silvaticum is a newly identified animal pathogen of forest animals such as roe deer and wild boars. The species is closely related to the emerging human pathogen Corynebacterium ulcerans and the widely distributed animal pathogen Corynebacterium pseudotuberculosis. In this study, Corynebacterium silvaticum strain W25 was characterized with respect to its interaction with human cell lines. Microscopy, measurement of transepithelial electric resistance and cytotoxicity assays revealed detrimental effects of C. silvaticum to different human epithelial cell lines and to an invertebrate animal model, Galleria mellonella larvae, comparable to diphtheria toxin-secreting C. ulcerans. Furthermore, the results obtained may indicate a considerable zoonotic potential of this newly identified species.
Low-Cost Automatic Weather Stations in the Internet of Things
Authors: Ioannou Konstantinos , Karampatzakis Dimitris , Amanatidis Petros , Aggelopoulos Vasileios , Karmiris Ilias
Published: March 2021

Automatic Weather Stations (AWS) are extensively used for gathering meteorological and climatic data. The World Meteorological Organization (WMO) provides publications with guidelines for the implementation, installation, and usages of these stations. Nowadays, in the new era of the Internet of Things, there is an ever-increasing necessity for the implementation of automatic observing systems that will provide scientists with the real-time data needed to design and apply proper environmental policy. In this paper, an extended review is performed regarding the technologies currently used for the implementation of Automatic Weather Stations. Furthermore, we also present the usage of new emerging technologies such as the Internet of Things, Edge Computing, Deep Learning, LPWAN, etc. in the implementation of future AWS-based observation systems. Finally, we present a case study and results from a testbed AWS (project AgroComp) developed by our research team. The results include test measurements from low-cost sensors installed on the unit and predictions provided by Deep Learning algorithms running locally.
Effectiveness of Push–Pull Systems to Fall Armyworm (Spodoptera frugiperda) Management in Maize Crops in Morelos, Mexico
Authors: Guera Ouorou Ganni Mariel , Castrejón-Ayala Federico , Robledo Norma , Jiménez-Pérez Alfredo , Sánchez-Rivera Georgina , Salazar-Marcial Lilia , Flores Moctezuma Hilda Elizabet
Published: March 2021

Chemical control is the main method used to combat fall armyworm in maize crops. However, its indiscriminate use usually leads to a more complex scenario characterized by loss of its effectiveness due to the development of resistance of the insect pest, emergence of secondary pests, and reduction of the populations of natural enemies. For this reason, efforts to develop strategies for agroecological pest management such as Push–Pull are increasingly growing. In this context, the present study was carried out to evaluate field effectiveness of Push–Pull systems for S. frugiperda management in maize crops in Morelos, Mexico. In a randomized block experiment, the incidence and severity of S. frugiperda, the development and yield of maize were evaluated in nine Push–Pull systems and a maize monoculture. The Push–Pull systems presented incidence/severity values lower than those of the monoculture. Morphological development and maize yield in the latter were lower than those of most Push–Pull systems. Mombasa—D. ambrosioides, Mulato II—T. erecta, Mulato II—C. juncea, Tanzania—T. erecta and Tanzania—D. ambrosioides systems presented higher yields than those of monocultures.
A Dynamic Energy Budget Approach for the Prediction of Development Times and Variability in Spodoptera frugiperda Rearing
Authors: Gergs Andre , Baden Christian U.
Published: March 2021

A major challenge in insect rearing is the need to provide certain life cycle stages at a given time for the initiation of experimental trials. The timing of delivery, organism quality, and variability directly affect the outcome of such trials. Development times and intraspecific variability are directly linked to the availability of food and to the ambient temperature. Varying temperature regimes is an approach to adapt development times to fulfill experimental needs without impairment of larval quality. However, current practices of temperature setting may lead to increased variability in terms of development times and the frequency of particular life stages at a given point in time. In this study, we analyzed how resource availability and ambient temperature may affect the larval development of the economically important noctuid species Spodoptera frugiperda by means of dynamic energy budget modeling. More specifically, we analyzed how rearing practices such as raising of temperatures may affect the variability in larval development. Overall, the presented modeling approach provides a support system for decisions that must be made for the timely delivery of larvae and reduction of variability.
Application of IDeS (Industrial Design Structure) to Sustainable Mobility: Case Study of an Innovative Bicycle
Authors: Frizziero Leonardo , Liverani Alfredo , Donnici Giampiero , Giuliano Ilaria , Picciariello Maria Grazia , Tucci Maria Luigia , Reimer Donald , Ali Ahad
Published: March 2021

The present study aims to validate a new research method called IDeS (industrial design structure) through the design of an electric bicycle for everyday city life. IDeS is the latest evolution of a combination of innovative and advanced systematic approaches that are used to set a new industrial project. The IDeS methodology is sequentially composed of quality function deployment (QFD), benchmarking (BM), top-flop analysis (TFA), stylistic design engineering (SDE), design for X, prototyping and testing, budgeting, and planning. The present work illustrates how to integrate the abovementioned design methods and achieve a convincing result. In going through the IDeS method step by step, we compare the different solutions on the market in order to understand which are the best performing products and to understand what is missing on the market. This method allowed us to design a bicycle that is as close as possible to the “ideal bike”, obtained with the top/flop analysis.
Emerging Technologies for the Energy Systems of the Future
Authors: Anvari-Moghaddam Amjad , Vahidinasab Vahid , Mohammadi-Ivatloo Behnam , Razzaghi Reza , Mohammadi Fazel
Published: March 2021

The way the world gets its energy is undergoing a rapid transition, driven by both the increased urgency of decarbonizing energy systems and the plummeting costs of renewable energy technologies [...]
Towards Privacy Paradigm Shift Due to the Pandemic: A Brief Perspective
Authors: Majeed Abdul , Lee Sungchang
Published: March 2021

With the advent of the pandemic (e.g., novel corona virus disease 2019 (COVID-19)), a tremendous amount of data about individuals are collected by the health authorities on daily basis for curbing the disease’s spread. The individuals’ data collection/processing at a massive scale for community well-being with the help of digital solutions (e.g., mobile apps for mobility and proximity analysis, contact tracing through credit card usage history, facial recognition through cameras, and crowd analysis using cellular networks data etc.) raise several privacy concerns. Furthermore, the privacy concerns that are arising mainly due to the fine-grained data collection has hindered the response to tackle this pandemic in many countries. Hence, acquiring/handling individuals data with privacy protection has become a vibrant area of research in these pandemic times. This paper explains the shift in privacy paradigm due to the pandemic (e.g., COVID-19) which involves more and detailed data collection about individuals including locations and demographics. We explain technical factors due to which the people’s privacy is at higher risk in the COVID-19 time. In addition, we discuss privacy concerns in different epidemic control measures (ECMs) (e.g., contact tracing, quarantine monitoring, and symptoms reporting etc.) employed by the health authorities to tackle this disease. Further, we provide an insight on the data management in the ECMs with privacy protection. Finally, the future prospects of the research in this area tacking into account the emerging technologies are discussed. Through this brief article, we aim to provide insights about the vulnerability to user’s privacy in pandemic times, likely privacy issues in different ECMs adopted by most countries around the world, how to preserve user’s privacy effectively in all phases of the ECMs considering relevant data in loop, and conceptual foundations of ECMs to fight with future pandemics in a privacy preserving manner.
Cardiac Catheterization Procedures in Patients with HIV: A Retrospective Analysis
Authors: Ebner Bertrand , Vincent Louis , Grant Jelani , Martinez Claudia
Published: March 2021

With the advent of effective antiretroviral therapies, there has been a decrease in HIV-related mortality, but an increase in non-AIDS-related comorbidities including cardiovascular disease (CVD). We sought to investigate current status of cardiac catheterization (CC) procedures in people with HIV (PWH). This is a retrospective study done at a University Hospital in South Florida between 2017 and 2019. Medical records from 985 PWH indicated that CC was performed in 1.9% of the cases. Of the PWH who underwent CC, 68% were found to have obstructive coronary artery disease (CAD). Among obstructive CAD cases, PCI was performed in 77% and CABG in 21% of cases; 26% had a repeat procedure and 11% died from non-cardiac causes. When comparing PWH who had CC to those who did not, there was a significantly higher rate of statin use (63% vs. 25%, p < 0.015) and a higher prevalence of low ejection fraction (38% vs. 11%, p = 0.004) among those patients who underwent CC. However, there was no significant difference in the prevalence of hypertension (p = 0.13), HbA1c levels (p = 0.32), CD4 count (p = 0.45) nor in undetectable viral load status (p = 0.75) after controlling for age, sex and BMI. Despite the finding of traditional CVD risk factors among PWH, there were no differences in HIV-related factors among patients requiring CC, supporting the importance of optimization of traditional CVD risk factors in this population.
Pregnancy and Neonatal Outcomes after Transfer of Mosaic Embryos: A Review
Authors: Abhari Sina , Kawwass Jennifer F.
Published: March 2021

Preimplantation genetic testing for aneuploidy (PGT-A) seeks to identify embryos with a normal chromosome complement during in vitro fertilization (IVF). Transfer of one euploid embryo at a time maximizes the chance of implantation while minimizing the risk of multiple pregnancy. The emergence of new technologies including next generation sequencing (NGS) has led to increased diagnosis of embryonic mosaicism, suggesting the presence of karyotypically distinct cells within a single trophectoderm (TE). Clinical implications of embryonic mosaicism are important in both naturally conceived and IVF pregnancies. Although information regarding outcomes after mosaic embryo transfer (MET) is limited, more than 100 live births have now been documented with rather reassuring outcomes with no abnormal phenotype. Here, we aim to provide a summary of recent data regarding clinical and neonatal outcomes after transfer of mosaic embryos in IVF/PGT-A cycles.
Correlations of Host and Bacterial Characteristics with Clinical Parameters and Survival in Staphylococcus aureus Bacteremia
Authors: Wächter Hannah , Yörük Erdal , Becker Karsten , Görlich Dennis , Kahl Barbara C.
Published: March 2021

Staphylococcus aureus bacteremia (SAB) is a frequent, severe condition that occurs in patients of all age groups and affects clinical departments of all medical fields. It is associated with a high mortality rate of 20–30%. In this study, we analyzed patient mortality associated with SAB at our tertiary care university hospital, assessed the clinical management in terms of administered antimicrobial therapy, and determined which factors have an impact on the clinical course and outcome of patients with this disease. We collected clinical data and blood culture isolates of 178 patients diagnosed with SAB between May 2013 and July 2015. For this study, bacteria were cultured and analyzed concerning their phenotype, hemolysis activity, biofilm formation, nuclease activity, prevalence of toxin genes, spa and agr type. Overall mortality was 24.2% and 30-day mortality was 14.6%. Inadequate initial therapy was administered to 26.2% of patients and was associated with decreased survival (p = 0.041). Other factors associated with poor survival were patient age (p = 0.003), agr type 4 (p ≤ 0.001) and pathological leukocyte counts (p = 0.029 if elevated and p = 0.003 if lowered). The type of infection focus, spa clonal complex and enterotoxin genes seg and sei had an impact on severity of inflammation. Our results indicate that mortality and burden of disease posed by SAB are high at our university hospital.
Two Decades from the Introduction of Microdissection Testicular Sperm Extraction: How This Surgical Technique Has Improved the Management of NOA
Authors: Punjani Nahid , Kang Caroline , Schlegel Peter N.
Published: March 2021

The treatment of men with non-obstructive azoospermia (NOA) has improved greatly over the past two decades. This is in part due to the discovery of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), but also significantly due to improvements in surgical sperm retrieval methods, namely the development of microdissection testicular sperm extraction (mTESE). This procedure has revolutionized the field by allowing for identification of favorable seminiferous tubules while simultaneously limiting the amount of testicular tissue removed. Improving sperm retrieval rates is imperative in this cohort of infertile men as there are a limited number of factors that are predictive of successful sperm retrieval. Currently, sperm retrieval in NOA men remains dependent on surgeon experience, preoperative patient optimization and teamwork with laboratory personnel. In this review, we discuss the evolution of surgical sperm retrieval methods, review predictors of sperm retrieval success, compare and contrast the data of conventional versus mTESE, share tips for optimizing sperm retrieval outcomes, and discuss the future of sperm retrieval in men with NOA.