bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial Hsp90 Facilitates the Degradation of Aggregation-Prone Hsp70–Hsp40 Substrates
Authors: Fauvet Bruno , Finka Andrija , Castanié-Cornet Marie-Pierre , Cirinesi Anne-Marie , Genevaux Pierre , Quadroni Manfredo , Goloubinoff Pierre
Published: April 2021

In eukaryotes, the 90-kDa heat shock proteins (Hsp90s) are profusely studied chaperones that, together with 70-kDa heat shock proteins (Hsp70s), control protein homeostasis. In bacteria, however, the function of Hsp90 (HtpG) and its collaboration with Hsp70 (DnaK) remains poorly characterized. To uncover physiological processes that depend on HtpG and DnaK, we performed comparative quantitative proteomic analyses of insoluble and total protein fractions from unstressed wild-type (WT) Escherichia coli and from knockout mutants ΔdnaKdnaJ (ΔKJ), ΔhtpG (ΔG), and ΔdnaKdnaJΔhtpG (ΔKJG). Whereas the ΔG mutant showed no detectable proteomic differences with wild-type, ΔKJ expressed more chaperones, proteases and ribosomes and expressed dramatically less metabolic and respiratory enzymes. Unexpectedly, we found that the triple mutant ΔKJG showed higher levels of metabolic and respiratory enzymes than ΔKJ, suggesting that bacterial Hsp90 mediates the degradation of aggregation-prone Hsp70–Hsp40 substrates. Further in vivo experiments suggest that such Hsp90-mediated degradation possibly occurs through the HslUV protease.
Lower Plasma Total Testosterone Levels Were Associated With Steeper Decline in Brain Glucose Metabolism in Non-demented Older Men
Authors: Wang Xiwu , Lv Zhaoting , Wu Qian , Liu Huitao , Gu Yanrou , Ye Teng
Published: April 2021

Objective

There is growing evidence that testosterone may be implicated in the pathogenesis of Alzheimer’s disease (AD). We aimed to examine the relationship between plasma total testosterone levels and change in brain glucose metabolism over time among non-demented older people.

Methods

The association of plasma total testosterone levels with change in brain glucose metabolism among non-demented older people was investigated cross-sectionally and longitudinally. Given a significant difference in levels of plasma total testosterone between gender, we performed our analysis in a sex-stratified way. At baseline, 228 non-demented older people were included: 152 males and 76 females.

Results

In the cross-sectional analysis, no significant relationship between plasma total testosterone levels and brain glucose metabolism was found in males or females. In the longitudinal analysis, we found a significant association of plasma total testosterone levels with change in brain glucose metabolism over time in males, but not in females. More specifically, in males, higher levels of total testosterone in plasma at baseline were associated with slower decline in brain glucose metabolism.

Conclusion

We found that higher levels of total testosterone in plasma at baseline were associated with slower decline in brain glucose metabolism in males without dementia, indicating that testosterone may have beneficial effects on brain function.
The Benefits of High-Intensity Interval Training on Cognition and Blood Pressure in Older Adults With Hypertension and Subjective Cognitive Decline: Results From the Heart & Mind Study
Authors: Boa Sorte Silva Narlon C. , Petrella Andrea F. M. , Christopher Nathan , Marriott Catherine F. S. , Gill Dawn P. , Owen Adrian M. , Petrella Robert J.
Published: April 2021

Background: The impact of exercise on cognition in older adults with hypertension and subjective cognitive decline (SCD) is unclear.

Objectives: We determined the influence of high-intensity interval training (HIIT) combined with mind-motor training on cognition and systolic blood pressure (BP) in older adults with hypertension and SCD.

Methods: We randomized 128 community-dwelling older adults [age mean (SD): 71.1 (6.7), 47.7% females] with history of hypertension and SCD to either HIIT or a moderate-intensity continuous training (MCT) group. Both groups received 15 min of mind-motor training followed by 45 min of either HIIT or MCT. Participants exercised in total 60 min/day, 3 days/week for 6 months. We assessed changes in global cognitive functioning (GCF), Trail-Making Test (TMT), systolic and diastolic BP, and cardiorespiratory fitness.

Results: Participants in both groups improved diastolic BP [F(1, 87.32) = 4.392, p = 0.039], with greatest effect within the HIIT group [estimated mean change (95% CI): −2.64 mmHg, (−4.79 to −0.48), p = 0.017], but no between-group differences were noted (p = 0.17). Both groups also improved cardiorespiratory fitness [F(1, 69) = 34.795, p < 0.001], and TMT A [F(1, 81.51) = 26.871, p < 0.001] and B [F(1, 79.49) = 23.107, p < 0.001]. There were, however, no within- or between-group differences in GCF and systolic BP at follow-up.

Conclusion: Despite improvements in cardiorespiratory fitness, exercise of high- or moderate-intensity, combined with mind-motor training, did not improve GCF or systolic BP in individuals with hypertension and SCD.

Clinical Trial Registration:ClinicalTrials.gov (NCT03545958).
Nasal Delivery of D-Penicillamine Hydrogel Upregulates a Disintegrin and Metalloprotease 10 Expression via Melatonin Receptor 1 in Alzheimer’s Disease Models
Authors: Zhong Manli , Kou Hejia , Zhao Pu , Zheng Wei , Xu He , Zhang Xiaoyu , Lan Wang , Guo Chuang , Wang Tao , Guo Feng , Wang Zhanyou , Gao Huiling
Published: April 2021

Alzheimer’s disease (AD) is a type of neurodegenerative disease that is associated with the accumulation of amyloid plaques. Increasing non-amyloidogenic processing and/or manipulating amyloid precursor protein signaling could reduce AD amyloid pathology and cognitive impairment. D-penicillamine (D-Pen) is a water-soluble metal chelator and can reduce the aggregation of amyloid-β (Aβ) with metals in vitro. However, the potential mechanism of D-Pen for treating neurodegenerative disorders remains unexplored. In here, a novel type of chitosan-based hydrogel to carry D-Pen was designed and the D-Pen-CS/β-glycerophosphate hydrogel were characterized by scanning electron microscopy and HPLC. Behavior tests investigated the learning and memory levels of APP/PS1 mice treated through the D-Pen hydrogel nasal delivery. In vivo and in vitro findings showed that nasal delivery of D-Pen-CS/β-GP hydrogel had properly chelated metal ions that reduced Aβ deposition. Furthermore, D-Pen mainly regulated A disintegrin and metalloprotease 10 (ADAM10) expression via melatonin receptor 1 (MTNR1α) and the downstream PKA/ERK/CREB pathway. The present data demonstrated D-Pen significantly improved the cognitive ability of APP/PS1 mice and reduced Aβ generation through activating ADAM10 and accelerating non-amyloidogenic processing. Hence, these findings indicate the potential of D-Pen as a promising agent for treating AD.
Striatal Dopamine Transporter Function Is Facilitated by Converging Biology of α-Synuclein and Cholesterol
Authors: Threlfell Sarah , Mohammadi Amir Saeid , Ryan Brent J. , Connor-Robson Natalie , Platt Nicola J. , Anand Rishi , Serres Florence , Sharp Trevor , Bengoa-Vergniory Nora , Wade-Martins Richard , Ewing Andrew , Cragg Stephanie J. , Brimblecombe Katherine R.
Published: April 2021

Striatal dopamine transporters (DAT) powerfully regulate dopamine signaling, and can contribute risk to degeneration in Parkinson’s disease (PD). DATs can interact with the neuronal protein α-synuclein, which is associated with the etiology and molecular pathology of idiopathic and familial PD. Here, we tested whether DAT function in governing dopamine (DA) uptake and release is modified in a human-α-synuclein-overexpressing (SNCA-OVX) transgenic mouse model of early PD. Using fast-scan cyclic voltammetry (FCV) in ex vivo acute striatal slices to detect DA release, and biochemical assays, we show that several aspects of DAT function are promoted in SNCA-OVX mice. Compared to background control α-synuclein-null mice (Snca-null), the SNCA-OVX mice have elevated DA uptake rates, and more pronounced effects of DAT inhibitors on evoked extracellular DA concentrations ([DA]o) and on short-term plasticity (STP) in DA release, indicating DATs play a greater role in limiting DA release and in driving STP. We found that DAT membrane levels and radioligand binding sites correlated with α-synuclein level. Furthermore, DAT function in Snca-null and SNCA-OVX mice could also be promoted by applying cholesterol, and using Tof-SIMS we found genotype-differences in striatal lipids, with lower striatal cholesterol in SNCA-OVX mice. An inhibitor of cholesterol efflux transporter ABCA1 or a cholesterol chelator in SNCA-OVX mice reduced the effects of DAT-inhibitors on evoked [DA]o. Together these data indicate that human α-synuclein in a mouse model of PD promotes striatal DAT function, in a manner supported by extracellular cholesterol, suggesting converging biology of α-synuclein and cholesterol that regulates DAT function and could impact DA function and PD pathophysiology.
Integrating Structural and Functional Interhemispheric Brain Connectivity of Gait Freezing in Parkinson's Disease
Authors: Jin Chaoyang , Qi Shouliang , Teng Yueyang , Li Chen , Yao Yudong , Ruan Xiuhang , Wei Xinhua
Published: April 2021

Freezing of gait (FOG) has devastating consequences for patients with Parkinson's disease (PD), but the underlying pathophysiological mechanism is unclear. This was investigated in the present study by integrated structural and functional connectivity analyses of PD patients with or without FOG (PD FOG+ and PD FOG–, respectively) and healthy control (HC) subjects. We performed resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging of 24 PD FOG+ patients, 37 PD FOG– patients, and 24 HCs. Tract-based spatial statistics was applied to identify white matter (WM) abnormalities across the whole brain. Fractional anisotropy (FA) and mean diffusivity (MD) of abnormal WM areas were compared among groups, and correlations between these parameters and clinical severity as determined by FOG Questionnaire (FOGQ) score were analyzed. Voxel-mirrored homotopic connectivity (VMHC) was calculated to identify brain regions with abnormal interhemispheric connectivity. Structural and functional measures were integrated by calculating correlations between VMHC and FOGQ score and between FA, MD, and VMHC. The results showed that PD FOG+ and PD FOG– patients had decreased FA in the corpus callosum (CC), cingulum (hippocampus), and superior longitudinal fasciculus and increased MD in the CC, internal capsule, corona radiata, superior longitudinal fasciculus, and thalamus. PD FOG+ patients had more WM abnormalities than PD FOG– patients. FA and MD differed significantly among the splenium, body, and genu of the CC in all three groups (P < 0.05). The decreased FA in the CC was positively correlated with FOGQ score. PD FOG+ patients showed decreased VMHC in the post-central gyrus (PCG), pre-central gyrus, and parietal inferior margin. In PD FOG+ patients, VMHC in the PCG was negatively correlated with FOGQ score but positively correlated with FA in CC. Thus, FOG is associated with impaired interhemispheric brain connectivity measured by FA, MD, and VMHC, which are related to clinical FOG severity. These results demonstrate that integrating structural and functional MRI data can provide new insight into the pathophysiological mechanism of FOG in PD.
Balloon-Assisted Coils Embolization for Ophthalmic Segment Aneurysms of the Internal Carotid Artery
Authors: Chaohui Liang , Yu Zhang Guang , Kai Hou
Published: April 2021

Objective: To explore the role of balloon-assisted coils technique for ophthalmic segment aneurysms (OSAS).

Methods: Clinical data of 30 patients with OSAS were reviewed between December 2017 and December 2018. OSAS were defined as arising from the internal carotid artery (ICA), reaching from the distal dural ring to the origin of the posterior communicating artery. OSAS were classified into four types based on the angiographic findings. The balloon-assisted coils technique was used for the embolization of aneurysms. The duration of balloon inflation cycles, as well as difficulty and complications during the embolization procedure, were recorded. The immediate angiographic results were evaluated according to the Raymond scale. Clinical results were evaluated based on the MRS score. Follow-ups were performed at 18 months post-embolization by DSA or MRA at our institution.

Results: Thirty-two aneurysms in 30 patients were detected by digital subtraction angiography (DSA), which included 30 unruptured and two ruptured cases. The patients with ruptured aneurysms were grade II status according to the Hunt-Hess scale. Three cases were type A, nine cases were type B, 17 cases were type C, and three cases were type D. According to aneurysm size, there were 19 cases of small, 11 cases of medium, two cases of large aneurysm. Thirty-two aneurysms were successfully embolized in 30 patients by balloon-assisted coils technique. The ophthalmic artery could be protected by an engorged balloon in the procedure, especially for type A aneurysms. Considering that type D aneurysm arises from the side-wall of the artery and near to tortuous ICA siphon, the balloon catheter was inflated to stabilize the microcatheter allowing for overinflation when necessary. The average duration of balloon dilatation was 4 min, and the average time was 2.5 times. Raymond class was one in 28 aneurysms and two in four aneurysms according to the immediate post-embolization angiographic results. All the patients achieved good clinical effects, except for one patient who presented with brain ischemia resulting in dizziness and contralateral limb weakness for 10 h due to prolonged temporary clamping of the responsible ICA. The follow-up angiography results were satisfactory at 18 months post-embolization.

Conclusion: OSAS endovascular treatment with balloon-assisted coils has different advantages in a different classification. The technique is safe, effective, and relatively inexpensive, especially for small and medium OSAS.
Roles of Neuropeptides, VIP and AVP, in the Mammalian Central Circadian Clock
Authors: Ono Daisuke , Honma Ken-ichi , Honma Sato
Published: April 2021

In mammals, the central circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Individual SCN cells exhibit intrinsic oscillations, and their circadian period and robustness are different cell by cell in the absence of cellular coupling, indicating that cellular coupling is important for coherent circadian rhythms in the SCN. Several neuropeptides such as arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) are expressed in the SCN, where these neuropeptides function as synchronizers and are important for entrainment to environmental light and for determining the circadian period. These neuropeptides are also related to developmental changes of the circadian system of the SCN. Transcription factors are required for the formation of neuropeptide-related neuronal networks. Although VIP is critical for synchrony of circadian rhythms in the neonatal SCN, it is not required for synchrony in the embryonic SCN. During postnatal development, the clock genes cryptochrome (Cry)1 and Cry2 are involved in the maturation of cellular networks, and AVP is involved in SCN networks. This mini-review focuses on the functional roles of neuropeptides in the SCN based on recent findings in the literature.
Prognostic Significance of Autophagy-Relevant Gene Markers in Colorectal Cancer
Authors: He Qinglian , Li Ziqi , Yin Jinbao , Li Yuling , Yin Yuting , Lei Xue , Zhu Wei
Published: April 2021

Background

Colorectal cancer (CRC) is a common malignant solid tumor with an extremely low survival rate after relapse. Previous investigations have shown that autophagy possesses a crucial function in tumors. However, there is no consensus on the value of autophagy-associated genes in predicting the prognosis of CRC patients. This work screens autophagy-related markers and signaling pathways that may participate in the development of CRC, and establishes a prognostic model of CRC based on autophagy-associated genes.

Methods

Gene transcripts from the TCGA database and autophagy-associated gene data from the GeneCards database were used to obtain expression levels of autophagy-associated genes, followed by Wilcox tests to screen for autophagy-related differentially expressed genes. Then, 11 key autophagy-associated genes were identified through univariate and multivariate Cox proportional hazard regression analysis and used to establish prognostic models. Additionally, immunohistochemical and CRC cell line data were used to evaluate the results of our three autophagy-associated genes EPHB2, NOL3, and SNAI1 in TCGA. Based on the multivariate Cox analysis, risk scores were calculated and used to classify samples into high-risk and low-risk groups. Kaplan-Meier survival analysis, risk profiling, and independent prognosis analysis were carried out. Receiver operating characteristic analysis was performed to estimate the specificity and sensitivity of the prognostic model. Finally, GSEA, GO, and KEGG analysis were performed to identify the relevant signaling pathways.

Results

A total of 301 autophagy-related genes were differentially expressed in CRC. The areas under the 1-year, 3-year, and 5-year receiver operating characteristic curves of the autophagy-based prognostic model for CRC were 0.764, 0.751, and 0.729, respectively. GSEA analysis of the model showed significant enrichment in several tumor-relevant pathways and cellular protective biological processes. The expression of EPHB2, IL-13, MAP2, RPN2, and TRAF5 was correlated with microsatellite instability (MSI), while the expression of IL-13, RPN2, and TRAF5 was related to tumor mutation burden (TMB). GO analysis showed that the 11 target autophagy genes were chiefly enriched in mRNA processing, RNA splicing, and regulation of the mRNA metabolic process. KEGG analysis showed enrichment mainly in spliceosomes. We constructed a prognostic risk assessment model based on 11 autophagy-related genes in CRC.

Conclusion

A prognostic risk assessment model based on 11 autophagy-associated genes was constructed in CRC. The new model suggests directions and ideas for evaluating prognosis and provides guidance to choose better treatment strategies for CRC.
Being a Myeloproliferative Patient in COVID-19 Era: The Mytico Study
Authors: Cavalca Fabrizio , Renso Rossella , Zambrotta Giovanni Paolo Maria , Gambacorti-Passerini Carlo , Elli Elena Maria
Published: April 2021

Introduction

The Coronavirus disease 2019 (COVID-19) pandemic and the resulting social distancing, determined a reduction in access to care and limitations of individual freedom, with a consequent strong impact on quality of life (QoL), anxiety levels and medical management of onco-hematological people. In particular, in the case of patients with chronic myeloproliferative neoplasm (MPN), concern about SARS-CoV-2 infection added to the burden of symptoms (BS) which already weights on the QoL of these patients. We designed a cross-sectional survey in order to investigate the impact of the COVID-19 pandemic on status of anxiety, BS and QoL in MPN patients.

Methods

We analyzed the anxiety levels using the Zung Self-Rating Anxiety Scale (SAS); BS modifications were studied using the 18 items of the Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF].

Results

132 people answered to the survey: 27 (20.4%) patients achieved a moderate to marked anxiety index value: this group described a greater worsening of symptoms than the rest of the cohort (p <0.0001). Women showed a higher level of anxiety than men (p = 0.01). A trend for lower level of anxiety was reported by patients who performed habitual physical activity (p = 0.06). A total of 98 (74.2%) patients described worsening of their symptoms during the quarantine period; 94 (71.2%) patients had postponed appointments or visits: they showed a significant worsening of their BS (p =0.01).

Conclusion

This study first showed that the COVID-19 quarantine had a significant negative impact on the level of anxiety and BS in MPN patients. We identified female gender, absence of physical activity, the need for frequent visit to the hospital and the absence of a direct access to healthcare staff as the main factors associated to a higher anxiety index and worst BS.
Angiotensin AT2 Receptor is Anti-inflammatory and Reno-Protective in Lipopolysaccharide Mice Model: Role of IL-10
Authors: Fatima Naureen , Patel Sanket , Hussain Tahir
Published: April 2021

Acute kidney injury (AKI) due to endotoxemic insult is predicted by the infiltration of neutrophils, monocytes and macrophages, and the release of pro-and anti-inflammatory cytokines to the site of injury. Earlier, we have demonstrated the role of angiotensin-II type 2 receptor (AT2R) stimulation in reno-protection in lipopolysaccharide (LPS)-induced inflammation and AKI in C57BL6/NHsd mice. Moreover, AT2R activation has been shown to increase the anti-inflammatory cytokine interleukin-10 (IL-10), its role in AT2R-mediated anti-inflammation and reno-protection is unknown. To address this question, in the present study mice were treated with the AT2R agonist C21 (0.3 mg/kg, intraperitoneally), LPS (5 mg/kg, intraperitoneally), or LPS with C21 pre-treatment with or without neutralizing IL-10 antibody. Treatment with C21 alone caused an increase in the plasma and kidney IL-10 levels, which peaks at 2-h, and returned to baseline at 6-h. The C21-induced IL-10 increase was blocked by the AT2R antagonist PD123319 suggesting AT2R’s involvement. LPS treatment caused a profound increase in tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the LPS-induced increase in these cytokines was attenuated by the C21 pre-treatment (1-h prior LPS) both in the plasma and kidney. Neutralizing IL-10 antibody treatment abrogated the C21-lowering of TNF-α and IL-6 in the kidney but not in the plasma. Similar results as related to the cytokines profiles in all the groups were also observed in the heart and spleen. The alteration in early cytokine profile prompted us to measure the markers of renal function (blood urea nitogen and urinary creatinine) in order to analyze the effect of IL-10 neutralization. However, it was too early to observe changes in renal function. Therefore, the renal function and injury markers were again measured at 24 h. Treatment with neutralizing IL-10 antibody attenuated the C21-mediated improvement in indices of the kidney function, but not the biomarkers of renal injury (kidney injury molecule-1 and neutrophil-gelatinase associated lipocalin). Collectively, our data suggest that the involvement of IL-10 in AT2R-mediated anti-inflammation and reno-protection against LPS is complex, mediating the renal cytokine profile and kidney filtration function, but not the plasma cytokine profile and renal injury markers.
Harnessing the ECM Microenvironment to Ameliorate Mesenchymal Stromal Cell-Based Therapy in Chronic Lung Diseases
Authors: Elowsson Rendin Linda , Löfdahl Anna , Kadefors Måns , Söderlund Zackarias , Tykesson Emil , Rolandsson Enes Sara , Wigén Jenny , Westergren-Thorsson Gunilla
Published: April 2021

It is known that the cell environment such as biomechanical properties and extracellular matrix (ECM) composition dictate cell behaviour including migration, proliferation, and differentiation. Important constituents of the microenvironment, including ECM molecules such as proteoglycans and glycosaminoglycans (GAGs), determine events in both embryogenesis and repair of the adult lung. Mesenchymal stromal/stem cells (MSC) have been shown to have immunomodulatory properties and may be potent actors regulating tissue remodelling and regenerative cell responses upon lung injury. Using MSC in cell-based therapy holds promise for treatment of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). However, so far clinical trials with MSCs in COPD have not had a significant impact on disease amelioration nor on IPF, where low cell survival rate and pulmonary retention time are major hurdles to overcome. Research shows that the microenvironment has a profound impact on transplanted MSCs. In our studies on acellular lung tissue slices (lung scaffolds) from IPF patients versus healthy individuals, we see a profound effect on cellular activity, where healthy cells cultured in diseased lung scaffolds adapt and produce proteins further promoting a diseased environment, whereas cells on healthy scaffolds sustain a healthy proteomic profile. Therefore, modulating the environmental context for cell-based therapy may be a potent way to improve treatment using MSCs. In this review, we will describe the importance of the microenvironment for cell-based therapy in chronic lung diseases, how MSC-ECM interactions can affect therapeutic output and describe current progress in the field of cell-based therapy.
Curcumin Derivative Cur20 Attenuated Cerebral Ischemic Injury by Antioxidant Effect and HIF-1α/VEGF/TFEB-Activated Angiogenesis
Authors: Zhang Runfang , Zhao Tingkui , Zheng Beibei , Zhang Yun , Li Xiaohui , Zhang Feng , Cen Juan , Duan Shaofeng
Published: April 2021

In this paper, a curcumin derivative Cur20 was synthesized for better hydrolytic stability, which showed a higher angiogenic effect on zebrafish model than curcumin. In order to reveal the potential effects on neuroprotection, a mouse model of vascular dementia (VaD) induced by permanent right common carotid artery occlusion (rUCCAO) was established. After two weeks of curcumin administration, the cognitive function of mice was detected by Morris water maze and Y maze. The alteration on oxidative injuries and morphological damage were also analyzed by reactive oxygen species, superoxide dismutase, GSH, malondialdehyde tests, and Nissl stain on cortex/hippocampus. The angiogenesis and related signal factors were evaluated as well. The results showed that Cur20 significantly attenuated the cognitive dysfunction and histopathological changes of the VaD mice with enhanced antioxidant system and angiogenesis. In addition, primary rat brain microvessel endothelial cells (rBMECs) with oxygen glucose deprivation (OGD) were applied to further verify the possible mechanisms of Cur20-induced angiogenesis. The results demonstrated that the proliferation effect and the activation of pro-angiogenesis factors such as HIF-1α, VEGF, and TFEB might contribute to the protection of ischemic injury. Based on the above, our conclusion is that Cur20 can be considered as a promising therapeutic strategy for VaD.
Inflammation Pharmacological Reaction and YMDD Mutational Patterns in Lamivudine Therapeutics Hepatitis B Virus
Authors: Liu Hongcan , Wan Zemin , She Lanhui , Zhu Yajuan , Cai Zhiliang , Wu Bin , Zhuang Qizhen , Ke Peifeng , Wu Xinzhong , Li Zhuo , Huang Xianzhang
Published: April 2021

Background/Aims: Emergence of tyrosine-methionine-aspartate-aspartate (YMDD) motif in reverse transcriptase is a serious problem in chronic hepatitis B(CHB) patients after Lamivudine (LAM) therapy. However, the relationship between inflammation pharmacological reaction and YMDD mutational patterns of CHB has not been well-characterized. The aim of this study was to investigate the inflammation pharmacological reaction and different YMDD mutants patterns of CHB patients.

Methods: We investigated the inflammation pharmacological reaction and YMDD mutational patterns through biochemical, serological and virological detection among 83 CHB patients, including 25 YMDD mutants, 25 under detection, and 33 control patients without YMDD mutants.

Results: Prevalence of YMDD mutation patterns is different. Among 25 YMDD mutants patients, YIDD was the dominant mutation (72%), followed YVDD (16%) and the hybrid YIDD + YVDD (12%). The time course during the YMDD mutations was also different. 52.4% patients developed the mutation less than 12 months after the LAM therapy. Serum hepatitis B virus (HBV) DNA level in patients with YMDD mutants were significantly higher than that in control and negative groups. Serum HbsAg and HbeAg in patients with YMDD mutants were also higher than those in control and negative groups, despite no significant difference was found forserum HbeAb. ALT and AST levels were also significantly higher in mutants group.

Conclusions: Illuminating inflammation pharmacological reaction and YMDD mutational patterns of CHB during pathological process may have implications for future therapy in YMDD mutation patients. This may have impact on the choice of treatment strategies for lamivudine-resistant HBV.
Th17 Cells in Depression: Are They Crucial for the Antidepressant Effect of Ketamine?
Authors: Cui Meiying , Dai Wanlin , Kong Jing , Chen Hongzhi
Published: April 2021

Background: Major depressive disorder is associated with inflammation and immune processes. Depressive symptoms correlate with inflammatory markers and alterations in the immune system including cytokine levels and immune cell function. Th17 cells are a T cell subset which exerts proinflammatory effects. Th17 cell accumulation and Th17/Treg imbalances have been reported to be critical in the pathophysiology of major depressive disorder and depressive-like behaviors in animal models. Th17 cells are thought to interfere with glutamate signaling, dopamine production, and other immune processes. Ketamine is a newly characterized antidepressant medication which has proved to be effective in rapidly reducing depressive symptoms. However, the mechanisms behind these antidepressant effects have not been fully elucidated.

Method: Literature about Th17 cells and their role in depression and the antidepressant effect of ketamine are reviewed, with the possible interaction networks discussed.

Result: The immune-modulating role of Th17 cells may participate in the antidepressant effect of ketamine.

Conclusion: As Th17 cells play multiple roles in depression, it is important to explore the mechanisms of action of ketamine on Th17 cells and Th17/Treg cell balance. This provides new perspectives for strengthening the antidepressant effect of ketamine while reducing its side effects and adverse reactions.
Trilobatin, a Component from Lithocarpus polystachyrus Rehd., Increases Longevity in C. elegans Through Activating SKN1/SIRT3/DAF16 Signaling Pathway
Authors: Li Na , Li Xi , Shi Yan-Ling , Gao Jian-Mei , He Yu-Qi , Li Fei , Shi Jing-Shan , Gong Qi-Hai
Published: April 2021

Trilobatin (TLB) is an effective component from Lithocarpus polystachyrus Rehd. Our previous study revealed that TLB protected against oxidative injury in neuronal cells by AMPK/Nrf2/SIRT3 signaling pathway. However, whether TLB can delay aging remains still a mystery. Therefore, the present study was designed to investigate the possible longevity-enhancing effect of TLB, and further to explore its underlying mechanism in Caenorhabditis elegans (C. elegans). The results showed that TLB exerted beneficial effects on C. elegans, as evidenced by survival rate, body movement assay and pharynx-pumping assay. Furthermore, TLB not only significantly decreased ROS and MDA levels, but also increased anti-oxidant enzyme activities including CAT and SOD, as well as its subtypes SOD2 andSOD3, but not affect SOD1 activity, as evidenced by heat and oxidative stress resistance assays. Whereas, the anti-oxidative effects of TLB were almost abolished in SKN1, Sir2.3, and DAF16 mutant C. elegans. Moreover, TLB augmented the fluorescence intensity of DAF16: GFP, SKN1:GFP, GST4:GFP mutants, indicating that TLB increased the contents of SKN1, SIRT3 and DAF16 due to fluorescence intensity of these mutants, which were indicative of these proteins. In addition, TLB markedly increased the protein expressions of SKN1, SIRT3 and DAF16 as evidenced by ELISA assay. However, its longevity-enhancing effect were abolished in DAF16, Sir2.3, SKN1, SOD2, SOD3, and GST4 mutant C. elegans than those of non-TLB treated controls. In conclusion, TLB effectively prolongs lifespan of C. elegans, through regulating redox homeostasis, which is, at least partially, mediated by SKN1/SIRT3/DAF16 signaling pathway.
Essential Roles of the Linker Sequence Between Tetratricopeptide Repeat Motifs of Ethylene Overproduction 1 in Ethylene Biosynthesis
Authors: An Chuanjing , Gao Yuefang
Published: April 2021

Ethylene Overproduction 1 (ETO1) is a negative regulator of ethylene biosynthesis. However, the regulation mechanism of ETO1 remains largely unclear. Here, a novel eto1 allele (eto1-16) was isolated with typical triple phenotypes due to an amino acid substitution of G480C in the uncharacterized linker sequence between the TPR1 and TPR2 motifs. Further genetic and biochemical experiments confirmed the eto1-16 mutation site. Sequence analysis revealed that G480 is conserved not only in two paralogs, EOL1 and EOL2, in Arabidopsis, but also in the homologous protein in other species. The glycine mutations (eto1-11, eto1-12, and eto1-16) do not influence the mRNA abundance of ETO1, which is reflected by the mRNA secondary structure similar to that of WT. According to the protein-protein interaction analysis, the abnormal root phenotype of eto1-16 might be caused by the disruption of the interaction with type 2 1-aminocyclopropane-1-carboxylic acid (ACC) synthases (ACSs) proteins. Overall, these data suggest that the linker sequence between tetratricopeptide repeat (TPR) motifs and the glycine in TPR motifs or the linker region are essential for ETO1 to bind with downstream mediators, which strengthens our knowledge of ETO1 regulation in balancing ACSs.
Cicer turcicum: A New Cicer Species and Its Potential to Improve Chickpea
Authors: Toker Cengiz , Berger Jens , Eker Tuba , Sari Duygu , Sari Hatice , Gokturk Ramazan Suleyman , Kahraman Abdullah , Aydin Bilal , von Wettberg Eric J.
Published: April 2021

Genetic resources of the genus Cicer L. are not only limited when compared to other important food legumes and major cereal crops but also, they include several endemic species with endangered status based on the criteria of the International Union for Conservation of Nature. The chief threats to endemic and endangered Cicer species are over-grazing and habitat change in their natural environments driven by climate changes. During a collection mission in east and south-east Anatolia (Turkey), a new Cicer species was discovered, proposed here as C. turcicum Toker, Berger & Gokturk. Here, we describe the morphological characteristics, images, and ecology of the species, and present preliminary evidence of its potential utility for chickpea improvement. C. turcicum is an annual species, endemic to southeast Anatolia and to date has only been located in a single population distant from any other known annual Cicer species. It belongs to section Cicer M. Pop. of the subgenus Pseudononis M. Pop. of the genus Cicer L. (Fabaceae) and on the basis of internal transcribed spacer (ITS) sequence similarity appears to be a sister species of C. reticulatum Ladiz. and C. echinospermum P.H. Davis, both of which are inter-fertile with domestic chickpea (C. arietinum L.). With the addition of C. turcicum, the genus Cicer now comprises 10 annual and 36 perennial species. As a preliminary evaluation of its potential for chickpea improvement two accessions of C. turcicum were field screened for reproductive heat tolerance and seeds were tested for bruchid resistance alongside a representative group of wild and domestic annual Cicer species. C. turcicum expressed the highest heat tolerance and similar bruchid resistance as C. judaicum Boiss. and C. pinnatifidum Juab. & Spach, neither of which are in the primary genepool of domestic chickpea. Given that C. arietinum and C. reticulatum returned the lowest and the second lowest tolerance and resistance scores, C. turcicum may hold much potential for chickpea improvement if its close relatedness supports interspecific hybridization with the cultigen. Crossing experiments are currently underway to explore this question.
The Motor Function Evaluation of College Students’ Physical Activity State From the Perspective of Educational Psychology
Authors: Ge Sha , Song Chao , Yao Wanxiang
Published: April 2021

College students have taken part in less and less physical activities as a result of the common static lifestyle in recent years, lowering the level of motor function. This phenomenon has been a source of concern for schools and the government, and it is necessary to take corresponding measures to change it. The general motor function level of Chinese college students is explored first based on artificial intelligence and the human–computer interaction technology. The Physical Activity Questionnaire for College Students is compiled by referring to the International Physical Activity Questionnaire, and 561 students from colleges in Tianjin province are assessed based on the functional movement screen (FMS). Spearman correlation and multivariate regression analysis (MRA) are used to analyze the correlation between the motor function and physical activity status. In terms of lunch break frequency, the proportion of students having one to two lunch breaks in a week is the highest (54.15%); in terms of the frequency of doing moderate physical exercise, the proportion of students doing moderate physical exercise for 1–2 days in a week is the highest (50.61%); in terms of the frequency of doing heavy physical exercise, the proportion of students doing heavy exercise for 1–2 days in a week is the highest (47.26%); in terms of the sedentary time, the proportion of students with sedentary time more than 5 h in a day is the highest (40.61%); in terms of eye use time, the proportion of students with 8–10 h eye use time in a day is the highest (43.61%). Besides, in terms of the FMS score, the proportion of students with 13–15 FMS is the highest (48.46%). The hurdle step (21.03%), straight knee lift (22.52%), and body rotation stability (18.31%) have a relatively low proportion among the three-point items. There is a positive correlation between motor function score with the time of moderate exercise and the time of heavy exercise (P < 0.05). College students generally have insufficient rest time, long eye use time, and long sitting time, leading to a low level of motor function, manifested by an asymmetry between both sides of the body and poor trunk stability. It is recommended to add hurdling steps, straight knee lifts, and body rotation stability tests to college physical education courses.
Resolving Conflicts Between People and Over Time in the Transformation Toward Sustainability: A Framework of Interdependent Conflicts
Authors: Majer Johann M. , Barth Matthias , Zhang Hong , van Treek Marie , Trötschel Roman
Published: April 2021

Transformative and mutually beneficial solutions require decision-makers to reconcile present- and future interests (i.e., intrapersonal conflicts over time) and to align them with those of other decision-makers (i.e., interpersonal conflicts between people). Despite the natural co-occurrence of intrapersonal and interpersonal conflicts in the transformation toward sustainability, both types of conflicts have been studied predominantly in isolation. In this conceptual article, we breathe new life into the traditional dialog between individual decision-making and negotiation research and address critical psychological barriers to the transformation toward sustainability. In particular, we argue that research on intrapersonal and interpersonal conflicts should be tightly integrated to provide a richer understanding of the interplay between these conflicts. We propose a novel, unifying framework of interdependent conflicts that systematically structures this interplay, and we analyze how complex interdependencies between the social (i.e., conflict between decision-makers) and temporal (i.e., conflict within a decision-maker) dimensions pose fundamental psychological barriers to mutually beneficial solutions. Since challenges to conflict resolution in the transformation toward sustainability emerge not only between individual decision-makers but also frequently between groups of decision-makers, we scale the framework up to the level of social groups and thereby provide an interdependent-conflicts perspective on the interplay between intra- and intergenerational conflicts. Overall, we propose simple, testable propositions, identify intervention approaches, and apply them to transition management. By analyzing the challenges faced by negotiating parties during interdependent conflicts and highlighting potential intervention approaches, we contribute to the transformation toward sustainability. Finally, we discuss implications of the framework and point to avenues for future research.
User Responses to a Humanoid Robot Observed in Real Life, Virtual Reality, 3D and 2D
Authors: Mara Martina , Stein Jan-Philipp , Latoschik Marc Erich , Lugrin Birgit , Schreiner Constanze , Hostettler Rafael , Appel Markus
Published: April 2021

Humanoid robots (i.e., robots with a human-like body) are projected to be mass marketed in the future in several fields of application. Today, however, user evaluations of humanoid robots are often based on mediated depictions rather than actual observations or interactions with a robot, which holds true not least for scientific user studies. People can be confronted with robots in various modes of presentation, among them (1) 2D videos, (2) 3D, i.e., stereoscopic videos, (3) immersive Virtual Reality (VR), or (4) live on site. A systematic investigation into how such differential modes of presentation influence user perceptions of a robot is still lacking. Thus, the current study systematically compares the effects of different presentation modes with varying immersive potential on user evaluations of a humanoid service robot. Participants (N = 120) observed an interaction between a humanoid service robot and an actor either on 2D or 3D video, via a virtual reality headset (VR) or live. We found support for the expected effect of the presentation mode on perceived immediacy. Effects regarding the degree of human likeness that was attributed to the robot were mixed. The presentation mode had no influence on evaluations in terms of eeriness, likability, and purchase intentions. Implications for empirical research on humanoid robots and practice are discussed.
Synchronization and Coordination of Art Performances in Highly Competitive Contexts: Battle Scenes of Expert Breakdancers
Authors: Shimizu Daichi , Okada Takeshi
Published: April 2021

In the performing arts, such as music and dance performances, people actively interact with each other and show their exciting performances. Some studies have proposed that this interaction is a social origin of the performing arts. Some have further investigated this phenomenon based on the synchronization and coordination theory. Though the majority of these studies have focused on the collaborative context, several genres of the performing arts, such as jazz sessions and breakdance battles, have a competitive context. Several studies have suggested that, in this competitive context, performers actively interact with each other and construct some correspondence. Moreover, a few recent studies focusing on competitive conversations, such as debates, have shown that, compared to people's interactions in collaborative conversations, people in competitive contexts frequently coordinate their behaviors in complicated ways. However, the interaction and coordination among performers in these competitive contexts have not been sufficiently investigated. Therefore, we investigated the coordination of expert breakdancers in battle scenes and measured their rhythmic movements using a motion capture system. We calculated the relative phase of the rhythmic movements between two dancers to investigate their coordination. The results showed that the dancers' rhythmic movements tended to synchronize in an anti-phase fashion, which means that there were similarities as well as differences between the two dancers' rhythmic movements. Furthermore, this pattern of coordination changed dynamically as time elapsed, from an in-phase synchronization or leader-follower relationships to an anti-phase synchronization and then leader-follower relationships.
Can Yogic Breathing Techniques Like Simha Kriya and Isha Kriya Regulate COVID-19-Related Stress?
Authors: Rain Manjari , Subramaniam Balachundhar , Avti Pramod , Mahajan Pranay , Anand Akshay
Published: April 2021

The global impact of Coronavirus Disease 2019 (COVID-19) is tremendous on human life, not only affecting the physical and mental health of population but also impacting the economic system of countries and individual itself. The present situation demands prompt response toward COVID-19 by equipping the humans with strategies to overcome the infection and stress associated with it. These strategies must not only be limited to preventive and therapeutic measures, but also aim at improving immunity and mental health. This can be achieved by yogic breathing techniques. In this perspective, we emphasize the importance of yogic breathing,Simha KriyaandIsha kriya, the simple yet effective breathing techniques.
Investigating Behavioral Responses to Mirrors and the Mark Test in Adult Male Zebra Finches and House Crows
Authors: Parishar Pooja , Mohapatra Alok Nath , Iyengar Soumya
Published: April 2021

Earlier evidence suggests that besides humans, some species of mammals and birds demonstrate visual self-recognition, assessed by the controversial “mark” test. Whereas, there are high levels of inter-individual differences amongst a single species, some species such as macaques and pigeons which do not spontaneously demonstrate mirror self-recognition (MSR) can be trained to do so. We were surprised to discover that despite being widely used as a model system for avian research, the performance of zebra finches (Taenopygia guttata) on the mark test had not been studied earlier. Additionally, we studied the behavioral responses of another species of passerine songbirds (Indian house crows; Corvus splendens) to a mirror and the MSR mark test. Although a small number of adult male zebra finches appeared to display heightened responses toward the mark while observing their reflections, we could not rule out the possibility that these were a part of general grooming rather than specific to the mark. Furthermore, none of the house crows demonstrated mark-directed behavior or increased self-exploratory behaviors when facing mirrors. Our study suggests that self-directed behaviors need to be tested more rigorously in adult male zebra finches while facing their reflections and these findings need to be replicated in a larger population, given the high degree of variability in mirror-directed behaviors.
Numerosities and Other Magnitudes in the Brains: A Comparative View
Authors: Lorenzi Elena , Perrino Matilde , Vallortigara Giorgio
Published: April 2021

The ability to represent, discriminate, and perform arithmetic operations on discrete quantities (numerosities) has been documented in a variety of species of different taxonomic groups, both vertebrates and invertebrates. We do not know, however, to what extent similarity in behavioral data corresponds to basic similarity in underlying neural mechanisms. Here, we review evidence for magnitude representation, both discrete (countable) and continuous, following the sensory input path from primary sensory systems to associative pallial territories in the vertebrate brains. We also speculate on possible underlying mechanisms in invertebrate brains and on the role played by modeling with artificial neural networks. This may provide a general overview on the nervous system involvement in approximating quantity in different animal species, and a general theoretical framework to future comparative studies on the neurobiology of number cognition.