bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA-sequencing and mass-spectrometry proteomic time-series analysis of T-cell differentiation identified multiple splice variants models that predicted validated protein biomarkers in inflammatory diseases
Authors: Magnusson Rasmus , Rundquist Olof , Kim Min Jung , Hellberg Sandra , Na Chan Hyun , Benson Mikael , Gomez-Cabrero David , Kockum Ingrid , Tegnér Jesper N. , Piehl Fredrik , Jagodic Maja , Mellergård Johan , Altafini Claudio , Ernerudh Jan , Jenmalm Maria C. , Nestor Colm E. , Kim Min-Sik , Gustafsson Mika
Published: August 2022

Profiling of mRNA expression is an important method to identify biomarkers but complicated by limited correlations between mRNA expression and protein abundance. We hypothesised that these correlations could be improved by mathematical models based on measuring splice variants and time delay in protein translation. We characterised time-series of primary human naïve CD4+ T cells during early T helper type 1 differentiation with RNA-sequencing and mass-spectrometry proteomics. We performed computational time-series analysis in this system and in two other key human and murine immune cell types. Linear mathematical mixed time delayed splice variant models were used to predict protein abundances, and the models were validated using out-of-sample predictions. Lastly, we re-analysed RNA-seq datasets to evaluate biomarker discovery in five T-cell associated diseases, further validating the findings for multiple sclerosis (MS) and asthma. The new models significantly out-performing models not including the usage of multiple splice variants and time delays, as shown in cross-validation tests. Our mathematical models provided more differentially expressed proteins between patients and controls in all five diseases. Moreover, analysis of these proteins in asthma and MS supported their relevance. One marker, sCD27, was validated in MS using two independent cohorts for evaluating response to treatment and disease prognosis. In summary, our splice variant and time delay models substantially improved the prediction of protein abundance from mRNA expression in three different immune cell types. The models provided valuable biomarker candidates, which were further validated in MS and asthma.
Transiently Nav1.8-expressing neurons are capable of sensing noxious stimuli in the brain
Authors: Tenza-Ferrer Helia , Collodetti Mélcar , Nicolau Eduardo de Souza , Birbrair Alexander , Magno Luiz Alexandre Viana , Romano-Silva Marco Aurélio
Published: August 2022

While current research highlights the role of Nav1. 8 sensory neurons from the peripheral nervous system, the anatomical and physiological characterization of encephalic Nav1.8 neurons remains unknown. Here, we use a Cre/fluorescent reporter mouse driven by the Nav1.8 gene promoter to reveal unexpected subpopulations of transiently-expressing Nav1.8 neurons within the limbic circuitry, a key mediator of the emotional component of pain. We observed that Nav1.8 neurons from the bed nuclei of the stria terminalis (BST), amygdala, and the periaqueductal gray (vPAG) are sensitive to noxious stimuli from an experimental model of chronic inflammatory pain. These findings identify a novel role for central Nav1.8 neurons in sensing nociception, which could be researched as a new approach to treating pain disorders.
Modelling the perception of music in brain network dynamics
Authors: Sawicki Jakub , Hartmann Lenz , Bader Rolf , Schöll Eckehard
Published: August 2022

We analyze the influence of music in a network of FitzHugh-Nagumo oscillators with empirical structural connectivity measured in healthy human subjects. We report an increase of coherence between the global dynamics in our network and the input signal induced by a specific music song. We show that the level of coherence depends crucially on the frequency band. We compare our results with experimental data, which also describe global neural synchronization between different brain regions in the gamma-band range in a time-dependent manner correlated with musical large-scale form, showing increased synchronization just before transitions between different parts in a musical piece (musical high-level events). The results also suggest a separation in musical form-related brain synchronization between high brain frequencies, associated with neocortical activity, and low frequencies in the range of dance movements, associated with interactivity between cortical and subcortical regions.
Assessing rheoencephalography dynamics through analysis of the interactions among brain and cardiac networks during general anesthesia
Authors: González Carmen , Garcia-Hernando Gabriel , Jensen Erik W. , Vallverdú-Ferrer Montserrat
Published: August 2022

Cerebral blood flow (CBF) reflects the rate of delivery of arterial blood to the brain. Since no nutrients, oxygen or water can be stored in the cranial cavity due to space and pressure restrictions, a continuous perfusion of the brain is critical for survival. Anesthetic procedures are known to affect cerebral hemodynamics, but CBF is only monitored in critical patients due, among others, to the lack of a continuous and affordable bedside monitor for this purpose. A potential solution through bioelectrical impedance technology, also known as rheoencephalography (REG), is proposed, that could fill the existing gap for a low-cost and effective CBF monitoring tool. The underlying hypothesis is that REG signals carry information on CBF that might be recovered by means of the application of advanced signal processing techniques, allowing to track CBF alterations during anesthetic procedures. The analysis of REG signals was based on geometric features extracted from the time domain in the first place, since this is the standard processing strategy for this type of physiological data. Geometric features were tested to distinguish between different anesthetic depths, and they proved to be capable of tracking cerebral hemodynamic changes during anesthesia. Furthermore, an approach based on Poincaré plot features was proposed, where the reconstructed attractors form REG signals showed significant differences between different anesthetic states. This was a key finding, providing an alternative to standard processing of REG signals and supporting the hypothesis that REG signals do carry CBF information. Furthermore, the analysis of cerebral hemodynamics during anesthetic procedures was performed by means of studying causal relationships between global hemodynamics, cerebral hemodynamics and electroencephalogram (EEG) based-parameters. Interactions were detected during anesthetic drug infusion and patient positioning (Trendelenburg positioning and passive leg raise), providing evidence of the causal coupling between hemodynamics and brain activity. The provided alternative of REG signal processing confirmed the hypothesis that REG signals carry information on CBF. The simplicity of the technology, together with its low cost and easily interpretable outcomes, should provide a new opportunity for REG to reach standard clinical practice. Moreover, causal relationships among the hemodynamic physiological signals and brain activity were assessed, suggesting that the inclusion of REG information in depth of anesthesia monitors could be of valuable use to prevent unwanted CBF alterations during anesthetic procedures.
The independent and combined effects of single-child status and ideal lifestyle on clustered cardio-metabolic risk factors among Chinese children and adolescents
Authors: Dang Jiajia , Ma Ning , Liu Yunfei , Zhong Panliang , Shi Di , Cai Shan , Dong Yanhui , Zou Zhiyong , Ma Yinghua , Song Yi , Ma Jun
Published: August 2022

Background

Cardio-metabolic risk factors (CMRFs) represent the accumulation of metabolic abnormalities, significantly increasing the likelihood of cardiovascular diseases. Although studies assessed the independent association of single-child status and lifestyle risk factors with components of CMRFs or clustered CMRFs, little has been known about the combined effect of single-child status and lifestyles on clustered CMRFs as well as sex differences.

Materials and methods

Data was collected from a cross-sectional survey conducted in September 2013 in China. A total of 13,859 children and adolescents aged 7–18 years with blood samples were included. Anthropometric measurements and serum biochemical indexes were collected to assess clustered CMRFs, while questionnaires were used to obtain single-child status, lifestyle information, and characteristics of children and their parents. Mixed effect logistic regression was applied to analyze the independent and the combined effects of single-child status and ideal lifestyle category on clustered CMRFs.

Results

The prevalence of clustered CMRFs was 3.4%, with a higher prevalence in boys (4.0%) than girls (2.7%). Children and adolescents with clustered CMRFs had a higher proportion of single children (76.6 vs. 69.7%) and unfavorable lifestyles (62.1 vs. 29.2%) compared with their peers with non-clustered CMRFs. Both single children (OR = 1.67, 95% CI: 1.32–2.11) and unfavorable lifestyles (OR = 9.03, 95% CI: 6.26–13.02) were associated with an increased risk of clustered CMRFs. The risk of clustered CMRFs increased significantly (OR = 12.79, 95% CI: 6.67–24.52) when single children and an unfavorable lifestyle were combined, which was almost neutralized (OR = 1.33, 95% CI: 0.63–2.82) when single children adhered to a favorable lifestyle. However, no sex differences were observed in this study.

Conclusion

Single children with unfavorable lifestyles were associated with an obvious risk of clustered CMRFs, which might be partially offset by expanding family size (the number of siblings) or establishing a favorable lifestyle. A birth-friendly social environment as well as a family environment with a favorable lifestyle are encouraged in China.
A novel cuproptosis-related lncRNA nomogram to improve the prognosis prediction of gastric cancer
Authors: Feng Anqi , He Lingnan , Chen Tao , Xu Meidong
Published: August 2022

Background

Cuproptosis is a copper-triggered modality of mitochondrial cell death and cuproptosis process may play important roles in gastric cancer development. However, little is known about cuproptosis-related lncRNAs in gastric adenocarcinoma (STAD). This study is aimed to investigate the potential prognostic signatures of cuproptosis-related lncRNAs in STAD.

Methods

The Cancer Genome Atlas (TCGA) database were used to obtain gene expression profiles, clinicopathological, and OS information for STAD. Cuproptosis-related genes were collected based on previous studies and cuproptosis-related lncRNAs were screened out by co-expression analysis. The nomogram constructed by Cox regression analysis with the minimum absolute contraction and selection operator (lasso) algorithm. In addition, the potential response of ICB therapy and immune evasion incidence were estimated with Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Immune checkpoint expressions associated with risk scores were also analyzed. The correlation of immune checkpoint CD209 and HAVCR2 expressions associated with risk scores were experimentally testified by RT-qPCR, Western Blot, and IHC.

Results

Patients were classified into high-risk and low-risk groups based on the risk score calculated in this model. The Kaplan–Meier survival curve analysis revealed that the high-risk group was associated with poor prognosis. Multivariate Cox regression analysis suggested that this lncRNA prediction model was an independent risk factor affecting the OS rate. Furthermore, ROC curve indicates that the nomogram was superior to traditional clinicopathological features in predicting STAD prognosis. Finally, functional enrichment analysis and immune checkpoint investigation revealed that the nomogram is notably associated with cholesterol metabolism and immune functions, RT-qPCR and Western Blotting demonstrated the co-expression relationship of LINC01150 with CD209 and HAVCR2.

Conclusion

A novel cuproptosis-related lncRNAs signature impacts on the prognosis and immunological features of GC.
Case report: New subtype of gastric adenocarcinoma arising from an H. pylori infection-negative stomach: Foveolar epithelium and mucous neck cell-mixed type adenocarcinoma
Authors: Liu Xuemei , Wu Xinglong , Zhu Jiaxing , Yagi Kazuyoshi , Ajioka Yoichi , Terai Shuji , Mizuno Kenichi , Li Hongping , Tuo Biguang , Di Lianjun
Published: August 2022

The characteristics of Helicobacter pylori (H. pylori) infection-negative gastric cancer have not been well documented because of its rarity, despite several types of H. pylori infection-negative gastric cancers being reported. In this report, we describe a case of early gastric cancer that developed without H. pylori infection with characteristic magnifying narrow-band imaging and novel histological findings. The difficulty in making an accurate diagnosis and differential diagnosis is highlighted, with the goal of providing more clinical experience for the diagnosis of H. pylori infection-negative gastric cancer.
Molecular subtypes, clinical significance, and tumor immune landscape of angiogenesis-related genes in ovarian cancer
Authors: Tang Haixia , Shan Jingsong , Liu Juan , Wang Xuehai , Wang Fengxu , Han Suping , Zhao Xinyuan , Wang Jinxiu
Published: August 2022

Angiogenesis is a physiological process, where new blood vessels are formed from pre-existing vessels through the mechanism called sprouting. It plays a significant role in supporting tumor growth and is expected to provide novel therapeutic ideas for treating tumors that are resistant to conventional therapies. We investigated the expression pattern of angiogenesis-related genes (ARGs) in ovarian cancer (OV) from public databases, in which the patients could be classified into two differential ARG clusters. It was observed that patients in ARGcluster B would have a better prognosis but lower immune cell infiltration levels in the tumor microenvironment. Then ARG score was computed based on differentially expressed genes via cox analysis, which exhibited a strong correlation to copy number variation, immunophenoscore, tumor mutation load, and chemosensitivity. In addition, according to the median risk score, patients were separated into two risk subgroups, of which the low-risk group had a better prognosis, increased immunogenicity, and stronger immunotherapy efficacy. Furthermore, we constructed a prognostic nomogram and demonstrated its predictive value. These findings help us better understand the role of ARGs in OV and offer new perspectives for clinical prognosis and personalized treatment.
The effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in critically ill patients with acute kidney injury: An observational study using the MIMIC database
Authors: Zhu Xu , Xue Jing , Liu Zheng , Dai Wenjie , Xiang Jingsha , Xu Hui , Zhou Qiaoling , Zhou Quan , Wei Xinran , Chen Wenhang
Published: August 2022

Background: The safety of prescribing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) during acute kidney injury (AKI) remains unclear. We aimed to investigate the associations of ACEI/ARB therapy in AKI with the risk of mortality, acute kidney disease (AKD), and hyperkalemia.

Methods: We conducted a retrospective monocentric study, which included patients in Massachusetts between 2008 and 2019 from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching was performed for the endpoint analysis. The association between ACEI/ARB therapy and mortality was assessed using Cox proportional hazards regression models. Logistic regression was used to assess the risk of AKD and hyperkalemia.

Results: Among the 19,074 individuals with AKI admitted to the intensive care unit (ICU), 3,244 (17.0%) received ACEI/ARBs, while 15,830 (83.0%) did not. In the propensity score-matched sample of 6,358 individuals, we found a decreased risk of mortality in those who received ACEI/ARBs compared to those who did not (hazard ratio [HR] for ICU mortality: 0.34, 95% confidence interval [CI]: 0.27–0.42); HR for in-hospital mortality: 0.47, 95% CI: 0.39–0.56; HR for 30-day mortality: 0.47, 95% CI: 0.40–0.56; HR for 180-day mortality: 0.53, 95% CI: 0.45–0.62). However, the use of ACEI/ARBs was associated with a higher risk of AKD (risk ratio [RR]: 1.81; 95% CI: 1.55–2.12). There was no significant association between ACEI/ARBs and an increased risk of hyperkalemia (RR: 1.21; 95% CI: 0.96–1.51).

Conclusions: ACEI/ARB treatment during an episode of AKI may decrease all-cause mortality, but increases the risk of AKD. Future randomized controlled trials are warranted to validate these findings.
Effects of Periplaneta americana extracts on the growth and proliferation of cutaneous interstitial cells in cutaneous-wound healing
Authors: Liang Zheng , Han Guiqi , Luo Zecheng , Li Baojie , Liu Wentao , Shen Chongyang
Published: August 2022

Cutaneous-wound healing requires a coordinated reaction of multiple cells, including interstitial cells. Impaired recovery of cutaneous wounds can lead to various adverse health outcomes. Kangfuxin (KFX), an extract obtained from Periplaneta americana, is beneficial in cutaneous-wound healing. In this study, we isolated dermal cells from suckling mice and established a mouse model of cutaneous injury to evaluate the therapeutic effects of KFX. Cell biology experiments indicated that treatment with KFX improved cell proliferation and migration and also repaired cutaneous wounds in the animal model. Activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway was the core molecular mechanism of KFX. Our study provides a theoretical and practical basis for the clinical application of KFX in cutaneous-wound healing.
Improved pharmacokinetics of tenofovir ester prodrugs strengthened the inhibition of HBV replication and the rebalance of hepatocellular metabolism in preclinical models
Authors: Hong Xiaodan , Cai Zuhuan , Zhou Fang , Jin Xiaoliang , Wang Guangji , Ouyang Bingchen , Zhang Jingwei
Published: August 2022

Tenofovir (TFV) ester prodrugs, a class of nucleotide analogs (NAs), are the first-line clinical anti-hepatitis B virus (HBV) drugs with potent antiviral efficacy, low resistance rate and high safety. In this work, three marketed TFV ester drugs, tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF) and tenofovir amibufenamide fumarate (TMF), were used as probes to investigate the relationships among prodrug structures, pharmacokinetic characteristics, metabolic activations, pharmacological responses and to reveal the key factors of TFV ester prodrug design. The results indicated that TMF and TAF exhibited significantly stronger inhibition of HBV DNA replication than did TDF in HBV-positive HepG2.2.15 cells. The anti-HBV activity of TMF was slightly stronger than TAF after 9 days of treatment (EC50 7.29 ± 0.71 nM vs. 12.17 ± 0.56 nM). Similar results were observed in the HBV decline period post drug administration to the HBV transgenic mouse model, although these three TFV prodrugs finally achieved the same anti-HBV effect after 42 days treatments. Furthermore, TFV ester prodrugs showed a correcting effect on disordered host hepatic biochemical metabolism, including TCA cycle, glycolysis, pentose phosphate pathway, purine/pyrimidine metabolism, amino acid metabolism, ketone body metabolism and phospholipid metabolism. The callback effects of the three TFV ester prodrugs were ranked as TMF > TAF > TDF. These advantages of TMF were believed to be attributed to its greater bioavailability in preclinical animals (SD rats, C57BL/6 mice and beagle dogs) and better target loading, especially in terms of the higher hepatic level of the pharmacologically active metabolite TFV-DP, which was tightly related to anti-HBV efficacy. Further analysis indicated that stability in intestinal fluid determined the actual amount of TFV prodrug at the absorption site, and hepatic/intestinal stability determined the maintenance amount of prodrug in circulation, both of which influenced the oral bioavailability of TFV prodrugs. In conclusion, our research revealed that improved pharmacokinetics of TFV ester prodrugs (especially intestinal stability) strengthened the inhibition of HBV replication and the rebalance of hepatocellular metabolism, which provides new insights and a basis for the design, modification and evaluation of new TFV prodrugs in the future.
A novel necroptosis-related lncRNAs signature effectively predicts the prognosis for osteosarcoma and is associated with immunity
Authors: Liu Binfeng , Feng Chengyao , Liu Zhongyue , Tu Chao , Li Zhihong
Published: August 2022

Background: Necroptosis is closely related to tumorigenesis and development. Accumulating evidence has revealed that long non-coding RNAs (lncRNAs) are also central players in osteosarcoma (OS). However, the role of necroptosis-related lncRNAs in OS remains unclear. In the present study, we aim to craft a prognostic signature based on necroptosis-related lncRNAs to improve the OS prognosis prediction.

Methods: The signature based on necroptosis-related lncRNAs was discovered using univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis. The prognosis efficiency of the signature was then estimated by employing various bioinformatics methods. Subsequently, immunological analysis and Gene Set Enrichment Analysis (GSEA) were used to explore the association between necroptosis-related lncRNAs with clinical outcomes and immune status. More importantly, several necroptosis-related lncRNAs were validated with RT-qPCR.

Results: Consequently, a novel prognosis signature was successfully constructed based on eight necroptosis-related lncRNAs. Meanwhile, the novel necroptosis-related lncRNAs model could distribute OS patients into two risk groups with a stable and accurate predictive ability. Additionally, the GSEA and immune analysis revealed that the necroptosis-related lncRNAs signature affects the development and prognosis of OS by regulating the immune status. The necroptosis-related lncRNA signature was closely correlated with multiple anticancer agent susceptibility. Moreover, the RT-qPCR results indicated several necroptosis-related lncRNAs were significantly differently expressed in osteosarcoma and osteoblast cell lines.

Conclusion: In this summary, a novel prognostic signature integrating necroptosis-related lncRNAs was firstly constructed and could accurately predict the prognosis of OS. This study may increase the predicted value and guide the personalized chemotherapy treatment for OS.
Negative regulation of ATP-induced inflammasome activation and cytokine secretion by acute-phase proteins: A mini review
Authors: Richter Katrin , Amati Anca-Laura , Padberg Winfried , Grau Veronika
Published: August 2022

The expression of the acute-phase reactants C-reactive protein (CRP), α1-antitrypsin (AAT), and secretory leukocyte protease inhibitor (SLPI), is induced in response to inflammation by pro-inflammatory mediators, including interleukin-1β. It is conceivable that acute-phase proteins exert protective functions, when the integrity of an organism is challenged by pathogens or trauma, which result in uncontrolled release of endogenous damage-associated molecular patterns like Toll-like receptor agonists and ATP. Acute-phase proteins can enhance or down-modulate immunity against infections or protect the host against damage caused by over-shooting effector functions of the immune system. CRP is mainly regarded as a pro-inflammatory opsonizing agent that binds to bacteria and damaged host cells thereby contributing to their inactivation and elimination. AAT and SLPI are well known for their anti-protease activity, which protects the lung extracellular matrix against degradation by proteases that are released by activated neutrophil granulocytes. In addition, there is growing evidence, that CRP, AAT, and SLPI can control the biosynthesis, maturation, and secretion of pro-inflammatory cytokines. The purpose of this narrative mini review is to summarize these anti-inflammatory functions with a focus on the negative control of the ATP-induced, inflammasome-dependent secretion of interleukin-1β by monocytes. CRP-, AAT- and SLPI-mediated control of interleukin-1β release involves the activation of unconventional nicotinic acetylcholine receptors that inhibits the ionotropic function of the ATP receptor P2X7. Apart from other functions, CRP, AAT, and SLPI seem to be central elements of systemic negative feedback loops that protect the host against systemic hyperinflammation, barrier dysfunction, and death by multiple organ damage.
Upregulation of nuclear division cycle 80 contributes to therapeutic resistance via the promotion of autophagy-related protein-7-dependent autophagy in lung cancer
Authors: Chen Xi , He Qingchun , Zeng Shuangshuang , Xu Zhijie
Published: August 2022

Lung cancer remains the leading cause of malignant mortality worldwide. Hence, the discovery of novel targets that can improve therapeutic effects in lung cancer patients is an urgent need. In this study, we screened differentially expressed genes using isobaric tags for relative and absolute quantitation (iTRAQ) analysis and datasets from the cancer genome atlas database, and found that nuclear division cycle 80 (NDC80) might act as a novel prognostic indicator of lung cancer. The expression of NDC80 was significantly increased in lung cancer tissues, as compared to normal tissues, and high expression levels of NDC80 were correlated with unfavorable survival rates. Furthermore, an in vitro analysis showed that the stable knockdown of NDC80 decreased the cell viability and increased therapeutic sensitivity in two lung cancer cell lines, A549-IRR and H1246-IRR. Moreover, gene set enrichment analysis results showed that NDC80 was enriched in autophagy-related pathways. The downregulation of NDC80 inhibited the formation of autophagosomes, and reduced the expression of autophagy-related proteins such as LC3II, Beclin-1, and p62 in lung cancer cells. To further clarify the role of NDC80 as a downstream regulator of autophagy, we validated autophagic mediators through iTRAQ analysis and real-time polymerase chain reaction arrays. Autophagy-related protein7 (ATG7) was observed to be downregulated after the knockdown of NDC80 in lung cancer cells. Immunohistochemistry assay results revealed that both NDC80 and ATG7 were upregulated in an array of lung adenocarcinoma samples, compared to normal tissues, and the expression of NDC80 was identified to be positively associated with the levels of ATG7. Our findings suggest that NDC80 promotes the development of lung cancer by regulating autophagy, and might serve as a potential target for increasing the therapeutic sensitivity of lung cancer.
Dark solitons impinging on interfaces in a superfluid Fermi gas
Authors: Merckx Jannes , Tempere Jacques
Published: August 2022

Ultracold quantum gases in the superfluid regime exhibit solitons, localized excitations that require nonlinearity of the underlying field equation in order to preserve their shape as they propagate. Here, we investigate the behavior of solitons at an inhomogeneity: an interface that separates two different interaction regimes of a superfluid Fermi gas. It is known that the soliton properties depend on the interaction regime, but what happens as a soliton impinges on such an interface is not clear. Using an effective field theory to describe the superfluid Fermi gas, we reveal the nontrivial dynamics of such a collision. Whether the original soliton makes it through the interface depends on the amplitude of the soliton. Regardless of whether the original soliton is transmitted or not, there will always be a shock wave with a phonon train created behind the interface and reflected secondary solitons. The details of this dynamics depends strongly on the equation of state corresponding to underlying microscopic theory describing the superfluid Fermi gas, and we argue that these collisions are realistic experimental probes to test microscopic theories of pairing in ultracold Fermi gases.
The protective effect of the spleen in sickle cell patients. A comparative study between patients with asplenia/hyposplenism and hypersplenism
Authors: Peretz Sari , Livshits Leonid , Pretorius Etheresia , Makhro Asya , Bogdanova Anna , Gassmann Max , Koren Ariel , Levin Carina
Published: August 2022

Sickle cell disease (SCD) is caused by a point mutation in the beta-globin gene. SCD is characterized by chronic hemolytic anemia, vaso-occlusive events leading to tissue ischemia, and progressive organ failure. Chronic inflammatory state is part of the pathophysiology of SCD. Patients with SCD have extremely variable phenotypes, from mild disease to severe complications including early age death. The spleen is commonly injured in SCD. Early splenic dysfunction and progressive spleen atrophy are common. Splenomegaly and hypersplenism can also occur with the loss of the crucial splenic function. Acute, life-threatening spleen-related complications in SCD are well studied. The association of laboratory parameters with the spleen status including hyposplenism, asplenia, and splenomegaly/hypersplenism, and their implication in vaso-occlusive crisis and long-term complications in SCD remain to be determined. We evaluated the association between the spleen status with clinical and laboratory parameters in 31 SCD patients: Group a) Patients with asplenia/hyposplenism (N = 22) (including auto-splenectomy and splenectomized patients) vs. Group b) patients with splenomegaly and or hypersplenism (N = 9). Laboratory studies included: Complete Blood Count, reticulocyte count, iron metabolism parameters, C Reactive Protein (CRP), Hb variant distribution, and D-dimer. Metabolic and morphological red blood cell (RBC) studies included: density gradient (by Percoll), glucose consumption, lactate release, and K+ leakage, fetal RBC (F-Cells) and F-Reticulocytes, annexinV+, CD71+, oxidative stress measured by GSH presence in RBC and finally Howell Jolly Bodies count were all analyzed by Flow Cytometry. Scanning electron microscopy analysis of RBC was also performed. Patients with asplenia/hyposplenism showed significantly higher WBC, platelet, Hematocrit, hemoglobin S, CRP, D-dimer, Gamma Glutamyl Transferase (GGT), cholesterol, transferrin, annexin V+ RBCs, CD71+ RBCs, together with a markedly lower F Reticulocyte levels in comparison with splenomegaly/hypersplenism patients. In summary, important differences were also found between the groups in the studied RBCs parameters. Further studies are required to elucidate the effect of the spleen including hyper and hypo-splenia on laboratory parameters and in clinical manifestations, vascular pathology, and long-term complications of SCD. The benefits and risks of splenectomy compared to chronic transfusion need to be evaluated in clinical trials and the standard approach managing hypersplenism in SCD patients should be re-evaluated.
Baseline of Physiological Body Temperature and Hematological Parameters in Captive Rousettus aegyptiacus and Eidolon helvum Fruit Bats
Authors: Rissmann Melanie , Friedrichs Virginia , Kley Nils , Straube Martin , Sadeghi Balal , Balkema-Buschmann Anne
Published: August 2022

The discovery of bats as reservoir hosts for a number of highly pathogenic zoonotic agents has led to an increasing interest of infectious disease research in experimental studies with bats. Therefore, we established breeding colonies of Rousettus aegyptiacus and Eidolon helvum fruit bats, which both have been identified as reservoir hosts for relevant zoonotic disease agents, such as Marburg virus and Lagos bat virus. Since 2013, individuals of both species have been recruited to the Friedrich-Loeffler-Institut (FLI) from zoological gardens in Europe, to where these species had been introduced from the wild several decades ago. The aviaries have been designed according to national recommendations published by the Federal Ministry of Agriculture. Under these conditions, both species have been reproducing for years. To better understand the physiology of these animals, and to generate baseline knowledge for infection experiments, we monitored the body core temperatures of R. aegyptiacus bats in the aviaries, and found a circadian variation between 34°C and 41.5°C. We also determined the hematological parameters of both species, and detected specific differences between both bat species. For values of clinical chemistry, no correlation to age or sex was observed. However, species-specific differences were detected since ALT, BUN and CREA were found to be significantly higher in R. aegyptiacus and GLU and TP were significantly higher in E. helvum bats. A higher hematocrit, hemoglobin and red blood cell level was observed in subadult R. aegyptiacus, with hemoglobin and red blood cells also being significantly increased compared to E. helvum. Lymphocytes were found to be the dominant white blood cells in both species and are higher in female E. helvum. Neutrophil granulocytes were significantly higher in E. helvum bats. This underlines the necessity to define baseline profiles for each bat species prior to their use in experimental challenge.
Serotonin modulation in the male Aedes aegypti ear influences hearing
Authors: Xu Yifeng Y. J. , Loh YuMin M. , Lee Tai-Ting , Ohashi Takuro S. , Su Matthew P. , Kamikouchi Azusa
Published: August 2022

MaleAedes aegypti(Ae. aegypti) mosquitoes rely on hearing to identify conspecific females for mating, with the male attraction to the sound of flying females (“phonotaxis”) an important behavior in the initial courtship stage. Hearing thus represents a promising target for novel methods of mosquito control, and hearing behaviors (such as male phonotaxis) can be targetedviathe use of sound traps. These traps unfortunately have proven to be relatively ineffective during field deployment. Shifting the target from hearing behavior to hearing function could therefore offer a novel method of interfering withAe. aegyptimating. Numerous neurotransmitters, including serotonin (5-hydroxytryptamine, or 5-HT) and octopamine, are expressed in the male ear, with modulation of the latter proven to influence the mechanical responses of the ear to sound. The effect of serotonin modulation however remains underexplored despite its significant role in determining many key behaviors and biological processes of animals. Here we investigated the influence of serotonin on theAe. aegyptihearing function and behaviors. Using immunohistochemistry, we found significant expression of serotonin in the male and femaleAe. aegyptiears. In the male ear, presynaptic sites identifiedviaantibody labelling showed only partial overlap with serotonin. Next, we used RT-qPCR to identify and quantify the expression levels of three different serotonin receptor families (5-HT1, 5-HT2, and 5-HT7) in the mosquito heads and ears. Although all receptors were identified in the ears of both sexes, those from the 5-HT7family were significantly more expressed in the ears relative to the heads. We then thoracically injected serotonin-related compounds into the mosquitoes and found a significant, reversible effect of serotonin exposure on the male ear mechanical tuning frequency. Finally, oral administration of a serotonin-synthesis inhibitor altered male phonotaxis. The mosquito serotonergic system and its receptors thus represent interesting targets for novel methods of mosquito, and thus disease, control.
Inspiratory muscle strength training for lowering blood pressure and improving endothelial function in postmenopausal women: comparison with “standard of care” aerobic exercise
Authors: Craighead Daniel H. , Freeberg Kaitlin A. , McCarty Narissa P. , Rossman Matthew J. , Moreau Kerrie L. , You Zhiying , Chonchol Michel , Seals Douglas R.
Published: August 2022

Background: High blood pressure (BP), particularly systolic BP (SBP), is the major modifiable risk factor for cardiovascular diseases and related disorders of aging. SBP increases markedly with aging in women such that the prevalence of above-normal SBP (i.e., ≥120 mmHg) in postmenopausal women exceeds rates in age-matched men. This increase in SBP is associated with vascular endothelial dysfunction, mediated by excessive reactive oxygen species-induced oxidative stress and consequent reductions in nitric oxide bioavailability. Moderate-intensity aerobic exercise is a recommended lifestyle strategy for reducing SBP. However, adherence to aerobic exercise guidelines among postmenopausal women is low (<30%) and aerobic exercise does not consistently enhance endothelial function in estrogen-deficient postmenopausal women. High-resistance inspiratory muscle strength training (IMST) is a time-efficient, adherable lifestyle intervention that involves inhaling against resistance through a handheld device (30 breaths/day). Here, we present the protocol for a randomized controlled trial investigating the efficacy of 3 months of high-resistance IMST compared to guideline-based, “standard-of-care” aerobic exercise training for decreasing SBP and improving endothelial function in estrogen-deficient postmenopausal women with above-normal SBP (120–159 mmHg) at baseline (ClinicalTrials.gov Identifier: NCT05000515).

Methods: A randomized, single-blind, parallel-group design clinical trial will be conducted in 72 (36/group) estrogen-deficient postmenopausal women with above-normal SBP. Participants will complete baseline testing and then be randomized to either 3 months of high-resistance IMST (30 breaths/day, 6 days/week, 75% maximal inspiratory pressure) or moderate-intensity aerobic exercise training (brisk walking 25 min/day, 6 days/week, 40–60% heart rate reserve). Outcome measures will be assessed after 3 months of either intervention. Following end-intervention testing, participants will abstain from their assigned intervention for 6 weeks, after which BP and endothelial function will be assessed to evaluate the potential persistent effects of the intervention on the primary and secondary outcomes.

Discussion: This study is designed to compare the effectiveness of time-efficient, high-resistance IMST to guideline-based aerobic exercise training for lowering SBP and improving endothelial function, and interrogating potential mechanisms of action, in estrogen-deficient postmenopausal women.

Clinical Trial Registration:ClinicalTrials.gov, Identifier: NCT05000515.
A shoot derived long distance iron signal may act upstream of the IMA peptides in the regulation of Fe deficiency responses in Arabidopsis thaliana roots
Authors: García María José , Angulo Macarena , Romera Francisco Javier , Lucena Carlos , Pérez-Vicente Rafael
Published: August 2022

When plants suffer from Fe deficiency, they develop morphological and physiological responses, mainly in their roots, aimed to facilitate Fe mobilization and uptake. Once Fe has been acquired in sufficient quantity, the responses need to be switched off to avoid Fe toxicity and to conserve energy. Several hormones and signaling molecules, such as ethylene, auxin and nitric oxide, have been involved in the activation of Fe deficiency responses in Strategy I plants. These hormones and signaling molecules have almost no effect when applied to plants grown under Fe-sufficient conditions, which suggests the existence of a repressive signal related to the internal Fe content. The nature of this repressive signal is not known yet many experimental results suggest that is not related to the whole root Fe content but to some kind of Fe compound moving from leaves to roots through the phloem. After that, this signal has been named LOng-Distance Iron Signal (LODIS). Very recently, a novel family of small peptides, “IRON MAN” (IMA), has been identified as key components of the induction of Fe deficiency responses. However, the relationship between LODIS and IMA peptides is not known. The main objective of this work has been to clarify the relationship between both signals. For this, we have used Arabidopsis wild type (WT) Columbia and two of its mutants, opt3 and frd3, affected, either directly or indirectly, in the transport of Fe (LODIS) through the phloem. Both mutants present constitutive activation of Fe acquisition genes when grown in a Fe-sufficient medium despite the high accumulation of Fe in their roots. Arabidopsis WT Columbia plants and both mutants were treated with foliar application of Fe, and later on the expression of IMA and Fe acquisition genes was analyzed. The results obtained suggest that LODIS may act upstream of IMA peptides in the regulation of Fe deficiency responses in roots. The possible regulation of IMA peptides by ethylene has also been studied. Results obtained with ethylene precursors and inhibitors, and occurrence of ethylene-responsive cis-acting elements in the promoters of IMA genes, suggest that IMA peptides could also be regulated by ethylene.
Variations of wheat (Triticum aestivum L.) chromosomes caused by the 5A chromosomes with complex cytological structure
Authors: Zou Yang , Luo Jie , Tang Zongxiang , Fu Shulan
Published: August 2022

To study the effects of structural alterations of chromosomes caused by tandem repeats on the meiotic recombination, the wheat (Triticum aestivum L.) 5A chromosomes with different structure from ten wheat cultivars were used to investigate their meiotic recombination using non-denaturing fluorescence in situ hybridization (ND-FISH) technology. Fifteen cross combinations were carried out and they were divided into seven F1 categories. The structural difference between the intercalary regions of the long arms of the two 5A chromosomes (5AL) in the F1 categories III, VI, and VII was greater than that in the categories I and II, subsequently, the recombination frequencies in the distal regions of the 5AL arm in the progenies from the three categories were significantly lower than that from the categories I and II. For the two 5A chromosomes in the F1 categories VI and VII, the structural differences in the distal regions of both of the two arms were greater than that in the categories IV and V. So, the recombination frequencies in the intercalary region of the 5AL arm in the progeny from the categories IV and V were higher than that in the progeny from the categories VI and VII. The breakage of 5A chromosome together with the 5A translocations and the breakage of some other chromosomes were observed in the progeny from the F1 categories V, VI, and VII. These chromosomal variations were not observed in the progenies from the other four F1 categories. In conclusion, the smaller structural difference between the 5A chromosomes in distal regions of the two arms resulted in a higher recombination frequency in interstitial region and vice versa. The 5A chromosome with complex cytological structure can be used to induce genetic variations of wheat genome.
Heavier Lies Her Crown: Gendered Patterns of Leader Emotional Labor and Their Downstream Effects
Authors: Vial Andrea C. , Cowgill Colleen M.
Published: August 2022

Women use power in more prosocial ways than men and they also engage in more emotional labor (i.e., self-regulate their emotions to respond and attend to the needs and emotions of other people in a way that advances organizational goals). However, these two constructs have not been previously connected. We propose that gendered emotional labor practices and pressures result in gender differences in the prosocial use of power. We integrate the literature on emotional labor with research on the psychology of power to articulate three routes through which this happens. First, women may be more adept than men at the intrapersonal and interpersonal processes entailed in emotional labor practices—a skill that they can apply at all hierarchical levels. Second, given women’s stronger internal motivation to perform emotional labor, they construe power in a more interdependent manner than men, which promotes a more prosocial use of power. As a result, female powerholders tend to behave in more prosocial ways. Third, when they have power, women encounter stronger external motivation to engage in emotional labor, which effectively constrains powerful women’s behaviors in a way that fosters a more prosocial use of power. We discuss how, by promoting prosocial behavior among powerholders, emotional labor can be beneficial for subordinates and organizations (e.g., increase employee well-being and organizational trust), while simultaneously creating costs for individual powerholders, which may reduce women’s likelihood of actually attaining and retaining power by (a) making high-power roles less appealing, (b) guiding women toward less prestigious and (c) more precarious leadership roles, (d) draining powerful women’s time and resources without equitable rewards, and (e) making it difficult for women to legitimize their power in the eyes of subordinates (especially men). Thus, emotional labor practices can help explain the underrepresentation of women in top leadership positions.
Perceived teacher autonomy support for adolescents’ reading achievement: The mediation roles of control-value appraisals and emotions
Authors: Wang Meishu , Hu Jie
Published: August 2022

Analyzing students’ internal cognitive-motivational appraisals and achievement emotions is of pivotal importance for educational outcomes and student individual wellbeing, yet little is shown about their associations with teacher autonomy support. This study investigates the relationship between perceived teacher autonomy support and reading achievement by addressing mediating influences of control and value-related constructs, i.e., reading self-efficacy, meaning in life, and reading enjoyment. Multiple mediation modeling was adopted to test the proposed model with carrying out a total of 12,058 students from 361 schools in China in the Programme for International Student Assessment (PISA) 2018 reading database. The results elucidated that student-perceived teacher autonomy support is significantly positively related to adolescents’ reading outcomes by fostering internal control and value appraisals and academic enjoyment. These current findings confirm the positive correlation between teacher autonomy support and adolescents’ motivational and emotional factors, providing significant practical implications for educators to adopt various teaching strategies to enhance adolescents’ self-efficacy, intrinsic values, and positive emotions.