bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeated Sub-Concussive Impacts and the Negative Effects of Contact Sports on Cognition and Brain Integrity
Authors: Ntikas Michail , Binkofski Ferdinand , Shah N. Jon , Ietswaart Magdalena
Published: June 2022

Sports are yielding a wealth of benefits for cardiovascular fitness, for psychological resilience, and for cognition. The amount of practice, and the type of practiced sports, are of importance to obtain these benefits and avoid any side effects. This is especially important in the context of contact sports. Contact sports are not only known to be a major source of injuries of the musculoskeletal apparatus, they are also significantly related to concussion and sub-concussion. Sub-concussive head impacts accumulate throughout the active sports career, and thus can cause measurable deficits and changes to brain health. Emerging research in the area of cumulative sub-concussions in contact sports has revealed several associated markers of brain injury. For example, recent studies discovered that repeated headers in soccer not only cause measurable signs of cognitive impairment but are also related to a prolonged cortical silent period in transcranial magnetic stimulation measurements. Other cognitive and neuroimaging biomarkers are also pointing to adverse effects of heading. A range of fluid biomarkers completes the picture of cumulating effects of sub-concussive impacts. Those accumulating effects can cause significant cognitive impairment later in life of active contact sportswomen and men. The aim of this review is to highlight the current scientific evidence on the effects of repeated sub-concussive head impacts on contact sports athletes’ brains, identify the areas in need of further investigation, highlight the potential of advanced neuroscientific methods, and comment on the steps governing bodies have made to address this issue. We conclude that there are indeed neural and biofluid markers that can help better understand the effects of repeated sub-concussive head impacts and that some aspects of contact sports should be redefined, especially in situations where sub-concussive impacts and concussions can be minimized.
Lack of Functional P110δ Affects Expression of Activation Marker CD80 but Does Not Influence Functions of Neutrophils
Authors: Manda-Handzlik Aneta , Mroczek Agnieszka , Kuźmicka Weronika , Cieloch Adrianna , Homoncik Zuzanna , Muchowicz Angelika , Demkow Urszula , Wachowska Małgorzata
Published: June 2022

Neutrophils are specialized immune cells that are essential constituents of the innate immune response. They defend the organism against pathogens through various mechanisms. It was reported that phosphatidylinositols are key players in neutrophil functions, especially in the activity of class-I phosphoinositide 3-kinases (PI3Ks). P110δ, one of the PI3K subunits, is mostly expressed in immune cells, and its activity plays an important role in inflammatory responses. The aim of this study was to investigate the role of p110δ in neutrophil antimicrobial functions, activation status and cytokine production. To this end, we used bone marrow and splenic neutrophils isolated from a murine model expressing catalytically inactive p110δD910A/D910A. The level of phagocytosis and degranulation, the expressions of activation markers and cytokine production were determined by flow cytometry. ROS generation and NET release were assessed by fluorometry and fluorescent microscopy. We observed a significantly higher percentage of CD80-positive cells among the splenic granulocytes and found granulocytes subpopulations of differing phenotypes between WT and p110δD910A/D910A mice by multiparametric tSNE analysis. Moreover, we detected some differences in the expressions of activation markers, intracellular production of cytokines and bacterial killing. However, we did not observe any alterations in the selected neutrophil functions in p110δ mutant mice. Altogether, our data suggest that the catalytic p110 subunit(s), other than p110δ, is a key player in most neutrophil functions in mice. A follow-up study to correlate these in vitro results with in vivo observations is highly recommended.
Blocking ERK-DAPK1 Axis Attenuates Glutamate Excitotoxicity in Epilepsy
Authors: Gan Chen-Ling , Zou Yulian , Chen Dongmei , Shui Xindong , Hu Li , Li Ruomeng , Zhang Tao , Wang Junhao , Mei Yingxue , Wang Long , Zhang Mi , Tian Yuan , Gu Xi , Lee Tae Ho
Published: June 2022

Glutamate excitotoxicity induces neuronal cell death during epileptic seizures. Death-associated protein kinase 1 (DAPK1) expression is highly increased in the brains of epilepsy patients; however, the underlying mechanisms by which DAPK1 influences neuronal injury and its therapeutic effect on glutamate excitotoxicity have not been determined. We assessed multiple electroencephalograms and seizure grades and performed biochemical and cell death analyses with cellular and animal models. We applied small molecules and peptides and knocked out and mutated genes to evaluate the therapeutic efficacy of kainic acid (KA), an analog of glutamate-induced neuronal damage. KA administration increased DAPK1 activity by promoting its phosphorylation by activated extracellular signal-regulated kinase (ERK). DAPK1 activation increased seizure severity and neuronal cell death in mice. Selective ERK antagonist treatment, DAPK1 gene ablation, and uncoupling of DAPK1 and ERK peptides led to potent anti-seizure and anti-apoptotic effects in vitro and in vivo. Moreover, a DAPK1 phosphorylation-deficient mutant alleviated glutamate-induced neuronal apoptosis. These results provide novel insight into the pathogenesis of epilepsy and indicate that targeting DAPK1 may be a potential therapeutic strategy for treating epilepsy.
CX3CL1 Action on Microglia Protects from Diet-Induced Obesity by Restoring POMC Neuronal Excitability and Melanocortin System Activity Impaired by High-Fat Diet Feeding
Authors: Banerjee Jineta , Dorfman Mauricio D. , Fasnacht Rachael , Douglass John D. , Wyse-Jackson Alice C. , Barria Andres , Thaler Joshua P.
Published: June 2022

Both hypothalamic microglial inflammation and melanocortin pathway dysfunction contribute to diet-induced obesity (DIO) pathogenesis. Previous studies involving models of altered microglial signaling demonstrate altered DIO susceptibility with corresponding POMC neuron cytological changes, suggesting a link between microglia and the melanocortin system. We addressed this hypothesis using the specific microglial silencing molecule, CX3CL1 (fractalkine), to determine whether reducing hypothalamic microglial activation can restore POMC/melanocortin signaling to protect against DIO. We performed metabolic analyses in high fat diet (HFD)-fed mice with targeted viral overexpression of CX3CL1 in the hypothalamus. Electrophysiologic recording in hypothalamic slices from POMC-MAPT-GFP mice was used to determine the effects of HFD feeding and microglial silencing via minocycline or CX3CL1 on GFP-labeled POMC neurons. Finally, mice with hypothalamic overexpression of CX3CL1 received central treatment with the melanocortin receptor antagonist SHU9119 to determine whether melanocortin signaling is required for the metabolic benefits of CX3CL1. Hypothalamic overexpression of CX3CL1 increased leptin sensitivity and POMC gene expression, while reducing weight gain in animals fed an HFD. In electrophysiological recordings from hypothalamic slice preparations, HFD feeding was associated with reduced POMC neuron excitability and increased amplitude of inhibitory postsynaptic currents. Microglial silencing using minocycline or CX3CL1 treatment reversed these HFD-induced changes in POMC neuron electrophysiologic properties. Correspondingly, blockade of melanocortin receptor signaling in vivo prevented both the acute and chronic reduction in food intake and body weight mediated by CX3CL1. Our results show that suppressing microglial activation during HFD feeding reduces DIO susceptibility via a mechanism involving increased POMC neuron excitability and melanocortin signaling.
Transcriptome Analysis Reveals the Regulatory Networks of Cytokinin in Promoting Floral Feminization in Castanea henryi
Authors: Wu Guo-Long , Zhu Zhou-Jun , Qiu Qi , Fan Xiao-Ming , Yuan De-Yi
Published: June 2022

Castanea henryi is a monoecious plant with a low female-to-male ratio, which limits its yield. The phytohormone cytokinin (CK) plays a crucial role in flower development, especially gynoecium development. Here, the feminizing effect of CK on the development of C. henryi was confirmed by the exogenous spraying of N-(2-chloro-4-pyridyl)-N’-phenylurea (CPPU). Spraying CPPU at 125 mg·L−1 thrice changed the male catkin into a pure female catkin, whereas at 5 mg·L−1 and 25 mg·L−1, only a part of the male catkin was transformed into a female catkin. A comparative transcriptome analysis of male catkins subjected to CPPU was performed to study the mechanism of the role of CKs in sex differentiation. Using Pearson’s correlation analysis between hormone content and hormone synthesis gene expression, four key genes, LOG1, LOG3, LOG7 and KO, were identified in the CK and GA synthesis pathways. Moreover, a hub gene in the crosstalk between JA and the other hormone signaling pathways, MYC2, was identified, and 15 flowering-related genes were significantly differentially expressed after CPPU treatment. These results suggest that CK interacts with other phytohormones to determine the sex of C. henryi, and CK may directly target floral organ recognition genes to control flower sex.
Effect of Photobiomodulation in Suppression of Oxidative Stress on Retinal Pigment Epithelium
Authors: Kim Jongmin , Won Jae Yon
Published: June 2022

As the world undergoes aging, the number of age-related diseases has increased. One of them is disease related to retinal pigment epithelium (RPE) degeneration, such as age-related macular degeneration, causing vision loss without physical damage in the ocular system. It is the leading cause of blindness, with no cure. Although the exact pathogenesis is still unknown, the research shows that oxidative stress is one of the risk factors. Various molecules have been reported as anti-oxidative materials; however, the disease has not yet been conquered. Here, we would like to introduce photobiomodulation (PBM). PBM is a non-invasive treatment based on red and near-infrared light and has been used to cure various diseases by regulating cellular functions. Furthermore, recent studies showed its antioxidant effect, and due to this reason, PBM is arising as a new treatment for ocular disease. In this study, we confirm the antioxidant effect of PBM in retinal pigment epithelium via an RPE model with hypoxia. The function of RPE is protected by PBM against damage from hypoxia. Furthermore, we observed the protective mechanism of PBM by its suppression effect on reactive oxygen species generation. These results indicate that PBM shows great potential to cure RPE degeneration to help patients with blindness.
A Bursaphelenchus xylophilus Effector, BxSCD3, Suppresses Plant Defense and Contributes to Virulence
Authors: Hu Long-Jiao , Wu Xiao-Qin , Wen Tong-Yue , Qiu Yi-Jun , Rui Lin , Zhang Yan , Ye Jian-Ren
Published: June 2022

Bursaphelenchus xylophilus is the most economically important species of migratory plant-parasitic nematodes (PPNs) and causes severe damage to forestry in China. The successful infection of B. xylophilus relies on the secretion of a repertoire of effector proteins. The effectors, which suppress the host pine immune response, are key to the facilitation of B. xylophilus parasitism. An exhaustive list of candidate effectors of B. xylophilus was predicted, but not all have been identified and characterized. Here, an effector, named BxSCD3, has been implicated in the suppression of host immunity. BxSCD3 could suppress pathogen-associated molecular patterns (PAMPs) PsXEG1- and INF1-triggered cell death when it was secreted into the intracellular space in Nicotiana benthamiana. BxSCD3 was highly up-regulated in the early infection stages of B. xylophilus. BxSCD3 does not affect B. xylophilus reproduction, either at the mycophagous stage or the phytophagous stage, but it contributes to the virulence of B. xylophilus. Moreover, BxSCD3 significantly influenced the relative expression levels of defense-related (PR) genes PtPR-3 and PtPR-6 in Pinus thunbergii in the early infection stage. These results suggest that BxSCD3 is an important toxic factor and plays a key role in the interaction between B. xylophilus and host pine.
Dysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse Model
Authors: Ferrer Isidro , Andrés-Benito Pol , Ausín Karina , Cartas-Cejudo Paz , Lachén-Montes Mercedes , del Rio José Antonio , Fernández-Irigoyen Joaquín , Santamaría Enrique
Published: June 2022

Altered protein phosphorylation is a major pathologic modification in tauopathies and Alzheimer’s disease (AD) linked to abnormal tau fibrillar deposits in neurofibrillary tangles (NFTs) and pre-tangles and β-amyloid deposits in AD. hTau transgenic mice, which express 3R and less 4R human tau with no mutations in a murine knock-out background, show increased tau deposition in neurons but not NFTs and pre-tangles at the age of nine months. Label-free (phospho)proteomics and SWATH-MS identified 2065 proteins in hTau and wild-type (WT) mice. Only six proteins showed increased levels in hTau; no proteins were down-regulated. Increased tau phosphorylation in hTau was detected at Ser199, Ser202, Ser214, Ser396, Ser400, Thr403, Ser404, Ser413, Ser416, Ser422, Ser491, and Ser494, in addition to Thr181, Thr231, Ser396/Ser404, but not at Ser202/Thr205. In addition, 4578 phosphopeptides (corresponding to 1622 phosphoproteins) were identified in hTau and WT mice; 64 proteins were differentially phosphorylated in hTau. Sixty proteins were grouped into components of membranes, membrane signaling, synapses, vesicles, cytoskeleton, DNA/RNA/protein metabolism, ubiquitin/proteasome system, cholesterol and lipid metabolism, and cell signaling. These results showed that over-expression of human tau without pre-tangle and NFT formation preferentially triggers an imbalance in the phosphorylation profile of specific proteins involved in the cytoskeletal–membrane-signaling axis.
Eliminating Synaptic Ribbons from Rods and Cones Halves the Releasable Vesicle Pool and Slows Down Replenishment
Authors: Mesnard Chris S. , Barta Cody L. , Sladek Asia L. , Zenisek David , Thoreson Wallace B.
Published: June 2022

Glutamate release from rod and cone photoreceptor cells involves presynaptic ribbons composed largely of the protein RIBEYE. To examine roles of ribbons in rods and cones, we studied mice in which GCamP3 replaced the B-domain of RIBEYE. We discovered that ribbons were absent from rods and cones of both knock-in mice possessing GCamP3 and conditional RIBEYE knockout mice. The mice lacking ribbons showed reduced temporal resolution and contrast sensitivity assessed with optomotor reflexes. ERG recordings showed 50% reduction in scotopic and photopic b-waves. The readily releasable pool (RRP) of vesicles in rods and cones measured using glutamate transporter anion currents (IA(glu)) was also halved. We also studied the release from cones by stimulating them optogenetically with ChannelRhodopsin2 (ChR2) while recording postsynaptic currents in horizontal cells. Recovery of the release from paired pulse depression was twofold slower in the rods and cones lacking ribbons. The release from rods at −40 mV in darkness involves regularly spaced multivesicular fusion events. While the regular pattern of release remained in the rods lacking ribbons, the number of vesicles comprising each multivesicular event was halved. Our results support conclusions that synaptic ribbons in rods and cones expand the RRP, speed up vesicle replenishment, and augment some forms of multivesicular release. Slower replenishment and a smaller RRP in photoreceptors lacking ribbons may contribute to diminished temporal frequency responses and weaker contrast sensitivity.
Strategies to Counteract Oxidative Stress and Inflammation in Chronic-Degenerative Diseases
Authors: Prata Cecilia , Maraldi Tullia , Angeloni Cristina
Published: June 2022

The great increase in life expectancy is linked to the necessity of counteracting chronic-degenerative diseases, e [...]
Contribution of Cancer-Targeting Drugs toward Faster Clinical Application
Authors: Yoon Sungpil , Kim Hyung Sik
Published: June 2022

With advances in cancer-targeting therapeutic strategies, cancer cells have developed drug resistance [...]
RtcB2-PrfH Operon Protects E. coli ATCC25922 Strain from Colicin E3 Toxin
Authors: Maviza Tinashe P. , Zarechenskaia Anastasiia S. , Burmistrova Nadezhda R. , Tchoub Andrey S. , Dontsova Olga A. , Sergiev Petr V. , Osterman Ilya A.
Published: June 2022

In the bid to survive and thrive in an environmental setting, bacterial species constantly interact and compete for resources and space in the microbial ecosystem. Thus, they have adapted to use various antibiotics and toxins to fight their rivals. Simultaneously, they have evolved an ability to withstand weapons that are directed against them. Several bacteria harbor colicinogenic plasmids which encode toxins that impair the translational apparatus. One of them, colicin E3 ribotoxin, mediates cleavage of the 16S rRNA in the decoding center of the ribosome. In order to thrive upon deployment of such ribotoxins, competing bacteria may have evolved counter-conflict mechanisms to prevent their demise. A recent study demonstrated the role of PrfH and the RtcB2 module in rescuing a damaged ribosome and the subsequent re-ligation of the cleaved 16S rRNA by colicin E3 in vitro. The rtcB2-prfH genes coexist as gene neighbors in an operon that is sporadically spread among different bacteria. In the current study, we report that the RtcB2-PrfH module confers resistance to colicin E3 toxicity in E. coli ATCC25922 cells in vivo. We demonstrated that the viability of E. coli ATCC25922 strain that is devoid of rtcB2 and prfH genes is impaired upon action of colicin E3, in contrast to the parental strain which has intact rtcB2 and prfH genes. Complementation of the rtcB2 and prfH gene knockout with a high copy number-plasmid (encoding either rtcB2 alone or both rtcB2-prfH operon) restored resistance to colicin E3. These results highlight a counter-conflict system that may have evolved to thwart colicin E3 activity.
Immunomodulation of Melanoma by Chemo-Thermo-Immunotherapy Using Conjugates of Melanogenesis Substrate NPrCAP and Magnetite Nanoparticles: A Review
Authors: Tamura Yasuaki , Ito Akira , Wakamatsu Kazumasa , Kamiya Takafumi , Torigoe Toshihiko , Honda Hiroyuki , Yamashita Toshiharu , Uhara Hisashi , Ito Shosuke , Jimbow Kowichi
Published: June 2022

A major advance in drug discovery and targeted therapy directed at cancer cells may be achieved by the exploitation and immunomodulation of their unique biological properties. This review summarizes our efforts to develop novel chemo-thermo-immunotherapy (CTI therapy) by conjugating a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP: amine analog of tyrosine), with magnetite nanoparticles (MNP). In our approach, NPrCAP provides a unique drug delivery system (DDS) because of its selective incorporation into melanoma cells. It also functions as a melanoma-targeted therapeutic drug because of its production of highly reactive free radicals (melanoma-targeted chemotherapy). Moreover, the utilization of MNP is a platform to develop thermo-immunotherapy because of heat shock protein (HSP) expression upon heat generation in MNP by exposure to an alternating magnetic field (AMF). This comprehensive review covers experimental in vivo and in vitro mouse melanoma models and preliminary clinical trials with a limited number of advanced melanoma patients. We also discuss the future directions of CTI therapy.
Antagonistic Pharmacological Interaction between Sirtuin Inhibitor Cambinol and Paclitaxel in Triple-Negative Breast Cancer Cell Lines: An Isobolographic Analysis
Authors: Wawruszak Anna , Luszczki Jarogniew , Okon Estera , Czerwonka Arkadiusz , Stepulak Andrzej
Published: June 2022

Breast cancer (BC) is a heterogeneous disease with different intrinsic subtypes. The most aggressive subtype of BC–triple-negative breast cancer (TNBC) is characterized by high heterogeneity and metastasis rate, poor prognosis and lack of therapeutic targets due to the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Targeted therapies have been approved for many other cancers and even other subtypes of BC, but treatment options for TNBC are still mainly limited to chemotherapy. Therefore, new, more effective treatment regimens are needed. Combined chemotherapy with two or more active agents is considered a promising anti-neoplasm tool in order to achieve better therapeutic response and reduce therapy-related adverse effects. The study demonstrated an antagonistic effect commonly used in TNBC therapy cytostatic drug-paclitaxel (PAX) and sirtuin inhibitor: cambinol (CAM) in BT-549, MDA-MB-468 and HCC1937 TNBC cell lines. The type of pharmacological interaction was determined by a precise and rigorous pharmacodynamic method-isobolographic analysis. The cytotoxic and anti-proliferative effects of CAM used alone or combined with PAX were determined utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-bromo-2′-deoxyuridine (BrdU) assays, respectively. Induction of apoptosis in TNBC cell lines after PAX and CAM treatment applied individually or in combination was determined by flow cytometry (FACS) as a number of cells with active caspase-3. It has been observed that both agents used separately inhibit cell proliferation and induce apoptosis; however, applying them in combination ameliorated antiproliferative and pro-apoptotic effects in all analyzed TNBC cell lines. Our results demonstrate that CAM and PAX used in combination act antagonistically, limiting anti-cancer efficacy and showing the importance of preclinical testing.
The Antitumor Effect of Cinnamaldehyde Derivative CB-PIC in Hepatocellular Carcinoma Cells via Inhibition of Pyruvate and STAT3 Signaling
Authors: Kim Hyungjin , Lee Hyo-Jung , Sim Deok Yong , Park Ji Eon , Ahn Chi-Hoon , Park Su-Yeon , Jang Eungyeong , Kim Bonglee , Kim Sung-Hoon
Published: June 2022

Though cinnamaldehyde derivative (CB-PIC), a major compound of cinnamon, is known to have anticancer activity, its underlying mechanism is not fully understood. In the present study, the anticancer mechanism of CB-PIC was investigated in human hepatocellular carcinoma cells (HCCs) in association with signal transducer and activator of transcription 3 (STAT3) signaling. CB-PIC exerted cytotoxicity in HepG2 and Huh7 cells. CB-PIC increased the sub G1 population and attenuated the expression of pro-poly (ADP-ribose) polymerase (PARP) and pro-Caspase3 in HepG2 and Huh7 cells. Interestingly, CB-PIC significantly abrogated the expression of a glycolytic enzyme pyruvate kinase M2 (PKM2) in HepG2 cells more than in LNCaP, A549, and HCT-116 cells. Consistently, CB-PIC reduced the expression of hexokinase 2 (HK2) and PKM2, along with a reduced production of lactate in HepG2 and Huh7 cells. Notably, CB-PIC suppressed the phosphorylation of STAT3 in HepG2 and Huh7 cells and conversely STAT3 depletion enhanced the capacity of CB-PIC to suppress the expression of HK2, PKM2, and pro-caspase3 and to reduce the viability in Huh7 cells. Furthermore, CB-PIC activated the phosphorylation of AMPK and ERK and suppressed expression of IL-6 as STAT3-related genes in HepG2 and Huh7 cells. Conversely, pyruvate treatment reversed the inhibitory effect of CB-PIC on p-STAT3, HK2, PKM2, and pro-PARP in Huh7 cells. Overall, there findings suggest that CB-PIC exerts an apoptotic effect via inhibition of the Warburg effect mediated by p-STAT3 and pyruvate signaling.
Fe3O4 Nanozymes Improve Neuroblast Differentiation and Blood-Brain Barrier Integrity of the Hippocampal Dentate Gyrus in D-Galactose-Induced Aged Mice
Authors: Xia Zihao , Gao Manman , Sheng Peng , Shen Mengmeng , Zhao Lin , Gao Lizeng , Yan Bingchun
Published: June 2022

Aging is a process associated with blood–brain barrier (BBB) damage and the reduction in neurogenesis, and is the greatest known risk factor for neurodegenerative disorders. However, the effects of Fe3O4 nanozymes on neurogenesis have rarely been studied. This study examined the effects of Fe3O4 nanozymes on neuronal differentiation in the dentate gyrus (DG) and BBB integrity of D-galactose-induced aged mice. Long-term treatment with Fe3O4 nanozymes (10 μg/mL diluted in ddH2O daily) markedly increased the doublecortin (DCX) immunoreactivity and decreased BBB injury induced by D-galactose treatment. In addition, the decreases in the levels of antioxidant proteins including superoxide dismutase (SOD) and catalase as well as autophagy-related proteins such as Becin-1, LC3II/I, and Atg7 induced by D-galactose treatment were significantly ameliorated by Fe3O4 nanozymes in the DG of the mouse hippocampus. Furthermore, Fe3O4 nanozyme treatment showed an inhibitory effect against apoptosis in the hippocampus. In conclusion, Fe3O4 nanozymes can relieve neuroblast damage and promote neuroblast differentiation in the hippocampal DG by regulating oxidative stress, apoptosis, and autophagy.
Retinal Proteomic Analysis in a Mouse Model of Endotoxin-Induced Uveitis Using Data-Independent Acquisition-Based Mass Spectrometry
Authors: Zhang Jing , Wu Jiangmei , Lu Daqian , To Chi-Ho , Lam Thomas Chuen , Lin Bin
Published: June 2022

Uveitis is a group of sight-threatening ocular inflammatory diseases, potentially leading to permanent vision loss in patients. However, it remains largely unknown how uveitis causes retinal malfunction and vision loss. Endotoxin-induced uveitis (EIU) in rodents is a good animal model to study uveitis and associated acute retinal inflammation. To understand the pathogenic mechanism of uveitis and screen potential targets for treatment, we analyzed the retinal proteomic profile of the EIU mouse model using a data-independent acquisition-based mass spectrometry (SWATH-MS). After systemic LPS administration, we observed activation of microglial cells accompanied with the elevation of pro-inflammatory mediators and visual function declines. In total, we observed 79 upregulated and 90 downregulated differentially expressed proteins (DEPs). Among the DEPs, we found that histone family members (histone H1, H2A, H2B) and blood proteins including haptoglobin (HP), hemopexin (HPX), and fibrinogen gamma chain (FGG) were dramatically increased in EIU groups relative to those in control groups. We identified phototransduction and synaptic vesicle cycle as the top two significant KEGG pathways. Moreover, canonical pathway analysis on DEPs using Ingenuity Pathway Analysis revealed top three most significant enriched pathways related to acute phase response signaling, synaptogenesis signaling, and eif2 signaling. We further confirmed upregulation of several DEPs associated with the acute phase response signaling including HP, HPX, and FGG in LPS-treated retinas by qPCR and Western blot. In summary, this study serves as the first report to detect retinal proteome changes in the EIU model. The study provides several potential candidates for exploring the mechanism and novel therapeutic targets for uveitis and other retinal inflammatory diseases.
5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence Imaging for Tumor Detection: Recent Advances and Challenges
Authors: Harada Yoshinori , Murayama Yasutoshi , Takamatsu Tetsuro , Otsuji Eigo , Tanaka Hideo
Published: June 2022

5-Aminolevulinic acid (5-ALA) is a natural amino acid and a precursor of heme and chlorophyll. Exogenously administered 5-ALA is metabolized into protoporphyrin IX (PpIX). PpIX accumulates in cancer cells because of the low activity of ferrochelatase, an enzyme that metabolizes PpIX to heme. High expression of 5-ALA influx transporters, such as peptide transporters 1/2, in cancer cells also enhances PpIX production. Because PpIX radiates red fluorescence when excited with blue/violet light, 5-ALA has been used for the visualization of various tumors. 5-ALA photodynamic diagnosis (PDD) has been shown to improve the tumor removal rate in high-grade gliomas and non-muscular invasive bladder cancers. However, 5-ALA PDD remains a challenge as a diagnostic method because tissue autofluorescence interferes with PpIX signals in cases where tumors emit only weak signals, and non-tumorous lesions, such as inflammatory sites, tend to emit PpIX fluorescence. Here, we review the current outline of 5-ALA PDD and strategies for improving its diagnostic applicability for tumor detection, focusing on optical techniques and 5-ALA metabolic pathways in both viable and necrotic tumor tissues.
Prion Pathogenesis Revealed in a Series of the Special Issues “Prions and Prion Diseases”
Authors: Sakaguchi Suehiro
Published: June 2022

Prion diseases are a group of devastating neurodegenerative disorders, which include Creutzfeldt–Jakob disease (CJD) in humans, and scrapie and bovine spongiform encephalopathy (BSE) in animals [...]
Hepatic Macrophage Abundance and Phenotype in Aging and Liver Iron Accumulation
Authors: Bloomer Steven A.
Published: June 2022

Liver macrophages serve important roles in iron homeostasis through phagocytosis of effete erythrocytes and the export of iron into the circulation. Conversely, intracellular iron can alter macrophage phenotype. Aging increases hepatic macrophage number and nonparenchymal iron, yet it is unknown whether age-related iron accumulation alters macrophage number or phenotype. To evaluate macrophages in a physiological model of iron loading that mimicked biological aging, young (6 mo) Fischer 344 rats were given one injection of iron dextran (15 mg/kg), and macrophage number and phenotype were evaluated via immunohistochemistry. A separate group of old (24 mo) rats was treated with 200 mg/kg deferoxamine every 12 h for 4 days. Iron administration to young rats resulted in iron concentrations that matched the values and pattern of tissue iron deposition observed in aged animals; however, iron did not alter macrophage number or phenotype. Aging resulted in significantly greater numbers of M1 (CD68+) and M2 (CD163+) macrophages in the liver, but neither macrophage number nor phenotype were affected by deferoxamine. Double-staining experiments demonstrated that both M1 (iNOS+) and M2 (CD163+) macrophages contained hemosiderin, suggesting that macrophages of both phenotypes stored iron. These results also suggest that age-related conditions other than iron excess are responsible for the accumulation of hepatic macrophages with aging.
A Mouse-Based Method to Monitor Wheat Allergens in Novel Wheat Lines and Varieties Created by Crossbreeding: Proof-of-Concept Using Durum and A. tauschii Wheats
Authors: Jorgensen Rick , Raghunath Rajsri , Gao Haoran , Olson Eric , Ng Perry K. W. , Gangur Venu
Published: June 2022

Wheat allergies are potentially life-threatening because of the high risk of anaphylaxis. Wheats belong to four genotypes represented in thousands of lines and varieties. Monitoring changes to wheat allergens is critical to prevent inadvertent ntroduction of hyper-allergenic varieties via breeding. However, validated methods for this purpose are unavailable at present. As a proof-of-concept study, we tested the hypothesis that salt-soluble wheat allergens in our mouse model will be identical to those reported for humans. Groups of Balb/cJ mice were rendered allergic to durum wheat salt-soluble protein extract (SSPE). Using blood from allergic mice, a mini hyper-IgE plasma bank was created and used in optimizing an IgE Western blotting (IEWB) to identify IgE binding allergens. The LC-MS/MS was used to sequence the allergenic bands. An ancient Aegilops tauschii wheat was grown in our greenhouse and extracted SSPE. Using the optimized IEWB method followed by sequencing, the cross-reacting allergens in A. tauschii wheat were identified. Database analysis showed all but 2 of the durum wheat allergens and all A. tauschii wheat allergens identified in this model had been reported as human allergens. Thus, this model may be used to identify and monitor potential changes to salt-soluble wheat allergens caused by breeding.
Characterization of the Secretome of a Specific Cell Expressing Mutant Methionyl-tRNA Synthetase in Co-Culture Using Click Chemistry
Authors: Shin Sungho , Lee Seonjeong , Choi Sunyoung , Park Narae , Kwon Yumi , Jeong Jaehoon , Ju Shinyeong , Chang Yunsil , Park Kangsik , Ha Chulwon , Lee Cheolju
Published: June 2022

Co-culture system, in which two or more distinct cell types are cultured together, is advantageous in that it can mimic the environment of the in vivo niche of the cells. In this study, we presented a strategy to analyze the secretome of a specific cell type under the co-culture condition in serum-supplemented media. For the cell-specific secretome analysis, we expressed the mouse mutant methionyl-tRNA synthetase for the incorporation of the non-canonical amino acid, azidonorleucine into the newly synthesized proteins in cells of which the secretome is targeted. The azidonorleucine-tagged secretome could be enriched, based on click chemistry, and distinguished from any other contaminating proteins, either from the cell culture media or the other cells co-cultured with the cells of interest. In order to have more reliable true-positive identifications of cell-specific secretory bodies, we established criteria to exclude any identified human peptide matched to bovine proteins. As a result, we identified a maximum of 719 secreted proteins in the secretome analysis under this co-culture condition. Last, we applied this platform to profile the secretome of mesenchymal stem cells and predicted its therapeutic potential on osteoarthritis based on secretome analysis.
Immobilization of Lathyrus cicera Amine Oxidase on Magnetic Microparticles for Biocatalytic Applications
Authors: Di Fabio Elisa , Iazzetti Antonia , Incocciati Alessio , Caseli Valentina , Fabrizi Giancarlo , Boffi Alberto , Bonamore Alessandra , Macone Alberto
Published: June 2022

Amine oxidases are enzymes belonging to the class of oxidoreductases that are widespread, from bacteria to humans. The amine oxidase from Lathyrus cicera has recently appeared in the landscape of biocatalysis, showing good potential in the green synthesis of aldehydes. This enzyme catalyzes the oxidative deamination of a wide range of primary amines into the corresponding aldehydes but its use as a biocatalyst is challenging due to the possible inactivation that might occur at high product concentrations. Here, we show that the enzyme’s performance can be greatly improved by immobilization on solid supports. The best results are achieved using amino-functionalized magnetic microparticles: the immobilized enzyme retains its activity, greatly improves its thermostability (4 h at 75 °C), and can be recycled up to 8 times with a set of aromatic ethylamines. After the last reaction cycle, the overall conversion is about 90% for all tested substrates, with an aldehyde production ranging between 100 and 270 mg depending on the substrate used. As a proof concept, one of the aldehydes thus produced was successfully used for the biomimetic synthesis of a non-natural benzylisoquinoline alkaloid.
Maintenance Management Model for Nonurban Road Network
Authors: Majstorović Ana , Jajac Nikša
Published: June 2022

Management of nonurban road network maintenance is a complex management process that requires the inclusion of many technical, economic, and other characteristics of the problem, as well as the continuous application of new knowledge and approaches, to maintenance management. To effectively manage the maintenance of the road network in conditions of limited financial resources, maintenance is examined through three interrelated management functions of planning: implementation, monitoring, and maintenance control. This paper includes an analysis of current and relevant papers on this topic. Based on the conducted analysis, the paper gives a theoretical framework and proposes a management model for road network maintenance between urban areas. This model supports the previously mentioned management functions using Multicriteria Decision-Making Methods. The AHP method and the TOPSIS method are engaged in the process of generating a priority road maintenance plan and Earned Value Analysis in maintenance monitoring and control. The AHP method is used to determine the criteria weight vector as a key role in defining the rank of alternatives and in identifying the optimal maintenance rank of nonurban roads using the TOPSIS method. All of the above aim to ensure the safe flow of traffic and the permanent preservation of the construction, traffic, and economic value of roads between urban areas.
Development of Soundness Diagnostic Model for Concrete Slab Using Bridge Inspection Data
Authors: Minami Takahiro , Fukuoka Tomotaka , Yoshikura Mai , Suwa Taiki , Fujiu Makoto
Published: June 2022

With the aging of bridges, the efficiency of periodic inspections has become a problem. As issues with the continuing close visual inspection of bridges are surfacing, remote imaging systems are expected to become a new inspection method that replaces close visual inspection. The objective of the study is to develop a classification model of countermeasure categories using the results of past periodic inspections of bridges conducted by skilled inspectors. Focusing on concrete slabs, a model was constructed to classify the countermeasure categories based on the characteristics of the damage maps by random forest classification. As a result, it was possible to classify two classes of countermeasure categories with a macro-average precision rate of about 88%. It became clear that the degree of crack development and the number of cracks are the most important factors in the classification of judgment categories.
Checked and Approved? Human Resources Managers’ Uses of Social Media for Cybervetting
Authors: Walrave Michel , Van Ouytsel Joris , Diederen Kay , Ponnet Koen
Published: June 2022

Human resource (HR) professionals who assess job candidates may engage in cybervetting, the collection and analysis of applicants’ personal information available on social network sites (SNS). This raises important questions about the privacy of job applicants. In this study, interviews were conducted with 24 HR professionals from profit and governmental organizations to examine how information found on SNS is used to screen job applicants. HR managers were found to check for possible mismatches between the online information and the experiences and competences claimed by candidates. Pictures of the job candidates’ spare time activities, drinking behavior, and physical appearance are seen as very informative. Pictures posted by job candidates’ connections are valued as more informative than those posted by the applicants themselves. Governmental organizations’ HR managers differ from profit-sector professionals by the fact that political views may play a role for the former. Finally, some HR professionals do not collect personal information about job candidates through social media, since they aim to respect a clear distinction between private life and work. They do not want to be influenced by information that has no relation with candidates’ qualifications. The study’s implications for theory and practice are also discussed.
A Combination of Alloy Modification and Heat Treatment Strategies toward Enhancing the Properties of LPBF Processed Hot Working Tool Steels (HWTS)
Authors: Raffeis Iris , Adjei-Kyeremeh Frank , Ewald Simon , Schleifenbaum Johannes Henrich , Bührig-Polaczek Andreas
Published: June 2022

Hot working tool steels (HWTS) are popular for industrial applications such as injection molding tools, and casting dies because of their high wear resistance, fatigue, strength, and toughness properties, even at elevated temperatures. Conventionally, they go through multi-stage heat treatments in order to attain targeted microstructures. Achieving such microstructures with a laser powder bed fusion (LPBF) process will require tailor-made process parameters since it is characterized by non-equilibrium conditions, non-uniform temperature distribution, and metastable phase formation. Recent advances in the LPBF qualification of 1.2343/4 HWTS have shown commendable results but are still fraught with the limitations of poor ductility or extra post-heat treatment steps. For the industrial competitiveness of LPBF HWTS, the enhancement of strength and ductility and elimination of post processing is critical. Therefore, minimizing retained austenite in the as-built samples through pre-heat treatment or alloying to reduce post heat treatments without sacrificing strength will be economically important for industry. In this work, 1.2343 HWTS and its modified form were LPBF printed both in the as-built, pre- and post-heat-treated conditions. The results are discussed based on the correlations of the powder properties with LPBF—part density, microstructure, and mechanical properties.
Epidemiological Characteristics of COVID-19 Inpatient Deaths during the First and Second Waves in Limpopo Province, South Africa
Authors: Tshitangano Takalani G. , Setati Musa E. , Mphekgwana Peter M. , Ramalivhana Naledzani J. , Matlala Sogo F.
Published: June 2022

More COVID-19 inpatient deaths occurred during the second wave when compared to the first wave in South Africa in both the public and private sectors. This study describes the characteristics of 969 COVID-19 inpatient deaths in the public sector of Limpopo Province during the first and second waves using population-based retrospective design. The results indicate that about 84% of deaths were aged 50+ years; 53.6% were females; 43% occurred in Capricorn district; 56% occurred in PUI wards; 64% had hypertension followed by diabetes mellitus; 88% manifested with shortness of breaths/respiratory distress on admission. The study concludes that as the average age among the population aged 60+ was greater among females than males, the increased death among females compared to males might be influenced by the older age of female inpatients during the first and second waves in Limpopo Province. Some COVID-19 inpatient deaths are possibly preventable if older women may be taken into consideration when planning prevention and management interventions in future pandemics.
The Pricing Model of Pension Benefit Guaranty Corporation Insurance with Regime-Switching Processes
Authors: Chen Ting-Fu , Lin Shih-Kuei , Chang An-Sing , Wang Wei-Hao
Published: June 2022

This paper aims to evaluate Pension Benefit Guaranty Corporation (PBGC) insurance values through regime-switching models. We separate periods of the economy with faster growth from those with slower growth to observe long-term trends in the economy. We derive a fair PBGC insurance pricing formula under distress termination and intervention termination using regime-switching processes. We set parameters by estimating the S&P 500 index and one-year treasury bills via expectation maximization particle swarm optimization (EM-PSO)-Gradient, which is an extension of the EM-Gradient method. Then, we conduct sensitivity analysis to investigate the impact of model parameters on insurance values. According to the maximum likelihood estimation results, the Akaike information criterion (AIC) and Bayesian information criterion (BIC) estimators show that the regime-switching process has better goodness of fit than the geometric Brownian motion. Scenario analysis also supports the adequacy of our pricing formula.
Location, Location, Location! Evaluating Space Use of Captive Aquatic Species—A Case Study with Elasmobranchs
Authors: Hart Alexis M. , Reynolds Zac , Troxell-Smith Sandra M.
Published: June 2022

The space use of captive animals has been reliably used as a tool to measure animal welfare in recent years. However, most analyses of space use focus primarily on terrestrial animals, with very little emphasis placed on the space use of aquatic animals. By comparing the space use of these animals to their natural histories and what would be expected of them physiologically, a general assessment of their overall welfare can be obtained. Using the Zoomonitor program, this study investigated the space use of five elasmobranch species housed in a captive aquatic environment: a blacktip reef shark (Carcharhinus melanopterus), a nurse shark (Ginglymostoma cirratum), a smooth dogfish (Musteluscanis), a bonnethead shark (Sphyrna tiburo), and a blacknose shark (Carcharhinus acronotus). The exhibit was delineated into five different zones: three represented the animal locations along the X/Y axis (‘Exhibit Use’), and two zones were related to the Z-axis (‘Depth Use’). The location of each individual on both the X/Y and Z axes was recorded during each observation. Heat maps generated from the Zoomonitor program were used in conjunction with the Spread of Participation Index (SPI) to interpret the data. It was found that while all the individuals used their given space differently, the Exhibit Use was relatively even overall (the SPI values ranged from 0.0378 to 0.367), while the Depth Use was more uneven (the SPI ranged from 0.679 to 0.922). These results mostly reflected what would be expected based on the species’ natural histories. However, for the smooth dogfish, the observed Exhibit Use and activity patterns revealed a mismatch between the anticipated and the actual results, leading to further interventions. As demonstrated here, space use results can be utilized to make positive changes to husbandry routines and enclosure designs for aquatic individuals; they are thus an important additional welfare measure to consider for aquatic species.
Physical Activity Behaviour in Solid Organ Transplant Recipients: Proposal of Theory-Driven Physical Activity Interventions
Authors: Leunis Sofie , Vandecruys Marieke , Cornelissen Véronique , Van Craenenbroeck Amaryllis H. , De Geest Sabina , Monbaliu Diethard , De Smet Stefan
Published: June 2022

Physical inactivity is highly prevalent after solid organ transplantation and leads to unfavourable outcomes. This review aimed to understand posttransplant physical activity behaviour and propose physical activity interventions. Michie’s Behavioural Change Wheel was applied, in which the Context and Implementation of Complex Interventions framework, the Capability-Opportunity-Motivation and Behaviour model, and the Theoretical Domains Framework were embedded. Various contextual factors were found to modulate physical activity behaviour. Promising strategies to promote long-term physical activity included (i) tailoring of physical activity programs to patients’ abilities and preferences; (ii) incitement of intrinsic and autonomous motivation to change; (iii) SMART goals setting (e.g., Specific, Measurable, Achievable, Realistic, Timebound), (iv) autonomy-supportive co-design of action plans; (v) foster new habit formation; (vi) self-monitoring of physical activity; (vii) follow-up opportunities for evaluation and adjustment; (viii) education of transplant recipients, healthcare providers, and the patients’ social network; (iv) improvement of self-efficacy through incremental successes, verbal persuasion, peer modelling, and awareness of exercise-related bodily signals; (x) providing physical activity opportunity within patients’ social and environmental setting; (xi) encouragement and support from patients’ social network and healthcare providers; and (xii) governmental action that alleviates financial barriers and restructures the physical environment to promote physical activity. These new insights may contribute to physical activity program development for transplantation recipients.