bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut Microbiota of Drosophila subobscura Contributes to Its Heat Tolerance and Is Sensitive to Transient Thermal Stress
Authors: Jaramillo Angélica , Castañeda Luis E.
Published: May 2021

The gut microbiota can contribute to host physiology leading to an increase of resistance to abiotic stress conditions. For instance, temperature has profound effects on ectotherms, and the role of the gut microbiota on the thermal tolerance of ectotherms is a matter of recent research. However, most of these studies have been focused on single static temperatures instead of evaluating thermal tolerance in a wide range of stressful temperatures. Additionally, there is evidence supporting that the gut microbiota is sensitive to environmental temperature, which induces changes in its composition and diversity. These studies have evaluated the effects of thermal acclimation (>2 weeks) on the gut microbiota, but we know little about the impact of transient thermal stress on the composition and diversity of the gut microbiota. Thus, we investigated the role of the gut microbiota on the heat tolerance of Drosophila subobscura by measuring the heat tolerance of conventional and axenic flies exposed to different heat stressful temperatures (35, 36, 37, and 38°C) and estimating the heat tolerance landscape for both microbiota treatments. Conventional flies exposed to mild heat conditions exhibited higher thermal tolerance than axenic flies, whereas at higher stressful temperatures there were no differences between axenic and conventional flies. We also assessed the impact of transient heat stress on the taxonomical abundance, diversity, and community structure of the gut microbiota, comparing non-stressed flies (exposed to 21°C) and heat-stressed flies (exposed to 34°C) from both sexes. Bacterial diversity indices, bacterial abundances, and community structure changed between non-stressed and heat-stressed flies, and this response was sex-dependent. In general, our findings provide evidence that the gut microbiota influences heat tolerance and that heat stress modifies the gut microbiota at the taxonomical and structural levels. These results demonstrate that the gut microbiota contributes to heat tolerance and is also highly sensitive to transient heat stress, which could have important consequences on host fitness, population risk extinction, and the vulnerability of ectotherms to current and future climatic conditions.
Sustained Neutralizing Antibodies 6 Months Following Infection in 376 Japanese COVID-19 Survivors
Authors: Goto Atsushi , Go Hirofumi , Miyakawa Kei , Yamaoka Yutaro , Ohtake Norihisa , Kubo Sousuke , Jeremiah Sundararaj Stanleyraj , Mihara Takahiro , Senuki Kotaro , Miyazaki Tomoyuki , Ikeda Satoshi , Ogura Takashi , Kato Hideaki , Matsuba Ikuro , Sanno Naoko , Miyakawa Masaaki , Ozaki Haruo , Kikuoka Masakazu , Ohashi Yasuo , Ryo Akihide , Yamanaka Takeharu
Published: May 2021

Objective: There is scarce evidence regarding the long-term persistence of neutralizing antibodies among coronavirus disease 2019 (COVID-19) survivors. This study determined neutralizing antibody titers (NT50) and antibodies against spike protein (SP) or nucleocapsid protein (NP) antigens approximately 6 months after the diagnosis of COVID-19.

Methods: COVID-19 survivors in Japan were recruited. Serum samples and data related to patients’ characteristics and COVID-19 history were collected. NT50 and titers of antibodies against NP and SP antigens were measured at 20–32 weeks after the first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results. Factors associated with NT50 were identified using the multivariable linear regression and the correlations among NT50 and titers of immunoglobulin G (IgG) and total immunoglobulins (Igs) against NP and SP were assessed by Spearman’s correlation.

Results: Among 376 participants (median [range] days after testing positive for SARS-CoV-2, 180 (147–224); median [range] years of age, 50 (20–78); 188 [50%] male), most tested positive for NT50 (n = 367, 98%), SP-IgG (n = 344, 91%), SP-total Ig (n = 369, 98%), NP-IgG (n = 314, 84%), and NP-total Ig (n = 365, 97%). Regression analysis indicated that higher BMI, fever, and the requirement of mechanical ventilation or extracorporeal membrane oxygenation were significantly associated with higher NT50. Anti-SP antibodies correlated moderately with NT50 (Spearman’s correlation: 0.63 for SP IgG; 0.57 for SP-total Ig), while the correlation was weak for anti-NP antibodies (0.37 for NP IgG; 0.32 for NP-total Ig).

Conclusions: Most COVID-19 survivors had sustained neutralizing antibodies and tested positive for SP-total Ig and NP-total Ig approximately 6 months after infection.
ML-AdVInfect: A Machine-Learning Based Adenoviral Infection Predictor
Authors: Karabulut Onur Can , Karpuzcu Betül Asiye , Türk Erdem , Ibrahim Ahmad Hassan , Süzek Barış Ethem
Published: May 2021

Adenoviruses (AdVs) constitute a diverse family with many pathogenic types that infect a broad range of hosts. Understanding the pathogenesis of adenoviral infections is not only clinically relevant but also important to elucidate the potential use of AdVs as vectors in therapeutic applications. For an adenoviral infection to occur, attachment of the viral ligand to a cellular receptor on the host organism is a prerequisite and, in this sense, it is a criterion to decide whether an adenoviral infection can potentially happen. The interaction between any virus and its corresponding host organism is a specific kind of protein-protein interaction (PPI) and several experimental techniques, including high-throughput methods are being used in exploring such interactions. As a result, there has been accumulating data on virus-host interactions including a significant portion reported at publicly available bioinformatics resources. There is not, however, a computational model to integrate and interpret the existing data to draw out concise decisions, such as whether an infection happens or not. In this study, accepting the cellular entry of AdV as a decisive parameter for infectivity, we have developed a machine learning, more precisely support vector machine (SVM), based methodology to predict whether adenoviral infection can take place in a given host. For this purpose, we used the sequence data of the known receptors of AdVs, we identified sets of adenoviral ligands and their respective host species, and eventually, we have constructed a comprehensive adenovirus–host interaction dataset. Then, we committed interaction predictions through publicly available virus-host PPI tools and constructed an AdV infection predictor model using SVM with RBF kernel, with the overall sensitivity, specificity, and AUC of 0.88 ± 0.011, 0.83 ± 0.064, and 0.86 ± 0.030, respectively. ML-AdVInfect is the first of its kind as an effective predictor to screen the infection capacity along with anticipating any cross-species shifts. We anticipate our approach led to ML-AdVInfect can be adapted in making predictions for other viral infections.
The Role of PI3K Inhibition in the Treatment of Breast Cancer, Alone or Combined With Immune Checkpoint Inhibitors
Authors: Zhang Zhizhu , Richmond Ann
Published: May 2021

Dysregulation of phosphoinositide 3-kinase (PI3K) signaling is highly implicated in tumorigenesis, disease progression, and the development of resistance to the current standard of care treatments in breast cancer patients. This review discusses the role of PI3K pathway in breast cancer and evaluates the clinical development of PI3K inhibitors in both early and metastatic breast cancer settings. Further, this review examines the evidence for the potential synergistic benefit for the combination treatment of PI3K inhibition and immunotherapy in breast cancer treatment.
Adhesion of Helicobacter Species to the Human Gastric Mucosa: A Deep Look Into Glycans Role
Authors: Matos Rita , Amorim Irina , Magalhães Ana , Haesebrouck Freddy , Gärtner Fátima , Reis Celso A.
Published: May 2021

Helicobacter species infections may be associated with the development of gastric disorders, such as gastritis, peptic ulcers, intestinal metaplasia, dysplasia and gastric carcinoma. Binding of these bacteria to the gastric mucosa occurs through the recognition of specific glycan receptors expressed by the host epithelial cells. This review addresses the state of the art knowledge on these host glycan structures and the bacterial adhesins involved in Helicobacter spp. adhesion to gastric mucosa colonization. Glycans are expressed on every cell surface and they are crucial for several biological processes, including protein folding, cell signaling and recognition, and host-pathogen interactions. Helicobacter pylori is the most predominant gastric Helicobacter species in humans. The adhesion of this bacterium to glycan epitopes present on the gastric epithelial surface is a crucial step for a successful colonization. Major adhesins essential for colonization and infection are the blood-group antigen-binding adhesin (BabA) which mediates the interaction with fucosylated H-type 1 and Lewis B glycans, and the sialic acid-binding adhesin (SabA) which recognizes the sialyl-Lewis A and X glycan antigens. Since not every H. pylori strain expresses functional BabA or SabA adhesins, other bacterial proteins are most probably also involved in this adhesion process, including LabA (LacdiNAc-binding adhesin), which binds to the LacdiNAc motif on MUC5AC mucin. Besides H. pylori, several other gastric non-Helicobacter pylori Helicobacters (NHPH), mainly associated with pigs (H. suis) and pets (H. felis, H. bizzozeronii, H. salomonis, and H. heilmannii), may also colonize the human stomach and cause gastric disease, including gastritis, peptic ulcers and mucosa-associated lymphoid tissue (MALT) lymphoma. These NHPH lack homologous to the major known adhesins involved in colonization of the human stomach. In humans, NHPH infection rate is much lower than in the natural hosts. Differences in the glycosylation profile between gastric human and animal mucins acting as glycan receptors for NHPH-associated adhesins, may be involved. The identification and characterization of the key molecules involved in the adhesion of gastric Helicobacter species to the gastric mucosa is important to understand the colonization and infection strategies displayed by different members of this genus.
Macrophage Plasticity and Atherosclerosis Therapy
Authors: Lin Ping , Ji Hong-Hai , Li Yan-Jie , Guo Shou-Dong
Published: May 2021

Atherosclerosis is a chronic disease starting with the entry of monocytes into the subendothelium and the subsequent differentiation into macrophages. Macrophages are the major immune cells in atherosclerotic plaques and are involved in the dynamic progression of atherosclerotic plaques. The biological properties of atherosclerotic plaque macrophages determine lesion size, composition, and stability. The heterogenicity and plasticity of atherosclerotic macrophages have been a hotspot in recent years. Studies demonstrated that lipids, cytokines, chemokines, and other molecules in the atherosclerotic plaque microenvironment regulate macrophage phenotype, contributing to the switch of macrophages toward a pro- or anti-atherosclerosis state. Of note, M1/M2 classification is oversimplified and only represent two extreme states of macrophages. Moreover, M2 macrophages in atherosclerosis are not always protective. Understanding the phenotypic diversity and functions of macrophages can disclose their roles in atherosclerotic plaques. Given that lipid-lowering therapy cannot completely retard the progression of atherosclerosis, macrophages with high heterogeneity and plasticity raise the hope for atherosclerosis regression. This review will focus on the macrophage phenotypic diversity, its role in the progression of the dynamic atherosclerotic plaque, and finally discuss the possibility of treating atherosclerosis by targeting macrophage microenvironment.
Mitochondrial Fusion Protein Mfn2 and Its Role in Heart Failure
Authors: Chen Lei , Liu Bilin , Qin Yuan , Li Anqi , Gao Meng , Liu Hanyu , Gong Guohua
Published: May 2021

Mitofusin 2 (Mfn2) is a transmembrane GTPase located on the mitochondrial outer membrane that contributes to mitochondrial network regulation. It is an essential multifunctional protein that participates in various biological processes under physical and pathological conditions, including mitochondrial fusion, reticulum–mitochondria contacts, mitochondrial quality control, and apoptosis. Mfn2 dysfunctions have been found to contribute to cardiovascular diseases, such as ischemia-reperfusion injury, heart failure, and dilated cardiomyopathy. Here, this review mainly focuses on what is known about the structure and function of Mfn2 and its crucial role in heart failure.
Increased Added Sugar Consumption Is Common in Parkinson's Disease
Authors: Palavra Natalie C. , Lubomski Michal , Flood Victoria M. , Davis Ryan L. , Sue Carolyn M.
Published: May 2021

Objectives: There is limited information about the dietary habits of patients with Parkinson's Disease (PD), or associations of diet with clinical PD features. We report on nutritional intake in an Australian PD cohort.

Methods: 103 PD patients and 81 healthy controls (HCs) completed a validated, semi-quantitative food frequency questionnaire. Food and nutrient intake was quantified, with consideration of micronutrients and macronutrients (energy, protein, carbohydrate, fat, fibre, and added sugar). Participants also completed PD-validated non-motor symptom questionnaires to determine any relationships between dietary intake and clinical disease features.

Results: Mean daily energy intake did not differ considerably between PD patients and HCs (11,131 kJ/day vs. 10,188 kJ/day, p = 0.241). However, PD patients reported greater total carbohydrate intake (279 g/day vs. 232 g/day, p = 0.034). This was largely attributable to increased daily sugar intake (153 g/day vs. 119 g/day, p = 0.003) and in particular free sugars (61 g/day vs. 41 g/day, p = 0.001). PD patients who (1) experienced chronic pain, (2) were depressed, or (3) reported an impulse control disorder, consumed more total sugars than HCs (all p < 0.05). Increased sugar consumption was associated with an increase in non-motor symptoms, including poorer quality of life, increased constipation severity and greater daily levodopa dose requirement.

Conclusions: We provide clinically important insights into the dietary habits of PD patients that may inform simple dietary modifications that could alleviate disease symptoms and severity. The results of this study support clinician led promotion of healthy eating and careful management of patient nutrition as part of routine care.
Lipidomic and Transcriptomic Analysis of the Longissimus Muscle of Luchuan and Duroc Pigs
Authors: Zhang Zhiwang , Liao Qichao , Sun Yu , Pan Tingli , Liu Siqi , Miao Weiwei , Li Yixing , Zhou Lei , Xu Gaoxiao
Published: May 2021

Meat is an essential food, and pork is the largest consumer meat product in China and the world. Intramuscular fat has always been the basis for people to select and judge meat products. Therefore, we selected the Duroc, a western lean pig breed, and the Luchuan, a Chinese obese pig breed, as models, and used the longissimus dorsi muscle for lipidomics testing and transcriptomics sequencing. The purpose of the study was to determine the differences in intramuscular fat between the two breeds and identify the reasons for the differences. We found that the intramuscular fat content of Luchuan pigs was significantly higher than that of Duroc pigs. The triglycerides and diglycerides related to flavor were higher in Luchuan pigs compared to Duroc pigs. This phenotype may be caused by the difference in the expression of key genes in the glycerolipid metabolism signaling pathway.
The Long-Term Recovery of Parotid Glands in Nasopharyngeal Carcinoma Treated by Intensity-Modulated Radiotherapy
Authors: Tasaka Shun , Jingu Keiichi , Takahashi Noriyoshi , Umezawa Rei , Yamamoto Takaya , Ishikawa Yojiro , Takeda Kazuya , Suzuki Yu , Kadoya Noriyuki
Published: May 2021

Background

Xerostomia is one of the most common adverse events of radiotherapy in head and neck cancer patients. There have been many reports on functional changes of the parotid gland after radiation therapy, but there have been few reports on the volume of the parotid gland and its relationship with oral quality of life (QOL) and even fewer reports on longitudinal change of the parotid gland volume. The purpose of this study was to evaluate the long-term change of the parotid gland volume after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma and the relationship between parotid irradiation dose and xerostomia symptoms.

Methods

We retrospectively analyzed 26 patients with nasopharyngeal cancer treated by IMRT. Longitudinal changes of parotid gland volumes after IMRT were evaluated on CT images. The parotid gland volumes in each period were converted to the ratio to parotid gland volumes before radiotherapy (relative parotid volume). Dunnett’s test was used to evaluate the longitudinal changes in relative parotid volumes at 0-6, 7-18, 19-30, 31-42, 43-54 and 55-66 months after IMRT. We assessed xerostomia 3 years or more after IMRT by measuring the degree of oral moisture using a moisture-checking device (Mucus, Life Co., Ltd.) and oral QOL evaluation by GOHAI (General Oral Health Assessment Index).

Results

The relative parotid volumes during radiotherapy and at 0-6, 7-18, 19-30, 31-42, 43-54 and 55-66 months after IMRT were 75.2 ± 14.3%, 67.2 ± 11.4%, 68.5 ± 15.9%, 72.4 ± 14.8%, 73.0 ± 13.8%, 76.2 ± 17.5%, and 77.1% ± 17.3%, respectively. The parotid volume had recovered significantly at 43-54 and 55-66 months after IMRT, especially in parotids receiving less than 40 Gy as the mean dose. The mean irradiated dose for bilateral parotids showed negative correlations with oral QOL score and oral moisture after a long period.

Conclusions

The parotid volume recovered gradually but had not reached a plateau even 3 years after radiotherapy, especially in parotids receiving less than 40 Gy as the mean dose.
Predictive Validity of the Bayley-III Cognitive Scores at 6 Months for Cognitive Outcomes at 24 Months in Very-Low-Birth-Weight Infants
Authors: Liu Tzu-Yu , Chang Jui-Hsing , Peng Chun-Chih , Hsu Chyong-Hsin , Jim Wai-Tim , Lin Jia-Ying , Chen Chia-Huei , Li Sung-Tse , Chang Hung-Yang
Published: May 2021

Purpose:To assess the predictive validity of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive scores at 6 months of corrected age (CA) for cognitive outcomes at 24 months of CA in very-low-birth-weight (VLBW) infants and investigate the predictors of change in cognitive outcomes.

Methods:We retrospectively evaluated VLBW children enrolled in the Taiwan Premature Infant Follow-up Network between 2010 and 2015 and completed the Bayley-III at CA of 6 and 24 months. The predictive validity of the cognitive performance at 6-month CA for the cognitive outcomes at 24-month CA was analyzed. The positive and negative predictive factors were also evaluated using logistic regression. Cut-off scores of <70 and <85 were used to identify lower functioning groups based on the Bayley-III definition.

Results:A total of 2,972 VLBW children, born with a mean weight of 1116.4 ± 257.5 g and mean gestational age of 29.0 ± 2.8 weeks, were evaluated. A cognitive score of <70 at 6-month CA had a positive predictive value (PPV) of 27.4% (95% confidence interval [CI]: 19.2–35.7%) for a cognitive score of <70 at 24-month CA, while the negative predictive value (NPV) was 97.3% (95% CI: 96.7–97.9%). A cut-off score of 85 had a PPV of 33.6% (95% CI: 28.1–39.0%) and an NPV of 87.7% (95% CI: 86.4–88.9%). Abnormal muscle tone at 6 months was a risk factor for cognitive function decline at 24 months for both Bayley-III cognitive cut-off scores: scores of 70 (adjusted odds ratio [AOR]: 2.8; 95% CI: 1.5–5.5) and 85 (AOR: 2.6; 95% CI: 1.6–4.1). Lower maternal socioeconomic status was associated with a worsening of the cognitive function in infants at 24 months who scored ≥85 at 6 months (AOR: 1.6; 95% CI: 1.2–2.0).

Conclusion:Subnormal Bayley-III cognitive scores at 6-month CA were not predictive of subnormal cognitive function at 24-month CA. In children with normal cognition during early infancy, abnormal muscle tone and lower maternal socioeconomic status may influence the cognitive developing process; this highlighted the importance of early identification of high risk infants and complete preterm infant-associated public health policies to promote an improved neurodevelopmental outcome.
Notoginsenoside R1 Improves Cerebral Ischemia/Reperfusion Injury by Promoting Neurogenesis via the BDNF/Akt/CREB Pathway
Authors: Zhu Ting , Wang Lei , Xie Weijie , Meng Xiangbao , Feng Yicheng , Sun Guibo , Sun Xiaobo
Published: May 2021

Notoginsenoside R1 (R1), a major component isolated from P. notoginseng, is a phytoestrogen that exerts many neuroprotective effects in a rat model of ischemic stroke. However, its long-term effects on neurogenesis and neurological restoration after ischemic stroke have not been investigated. The aim of this study was to evaluate the effects of R1 on neurogenesis and long-term functional recovery after ischemic stroke. We used male Sprague-Dawley rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). R1 was administered by intraperitoneal (i.p.) injection immediately postischemia. We showed that R1 significantly decreased infarct volume and neuronal loss, restored neurological function, and stimulated neurogenesis and oligodendrogenesis in rats subjected to MCAO/R. More importantly, R1 promoted neuronal proliferation in PC12 cells in vitro. The proneurogenic effects of R1 were associated with the activation of Akt/cAMP responsive element-binding protein, as shown by the R1-induced increase in brain-derived neurotrophic factor (BDNF) expression, and with the activation of neurological function, which was partially eliminated by selective inhibitors of BDNF and PI3K. We demonstrated that R1 is a promising compound that exerts neuroprotective and proneurogenic effects, possibly via the activation of BDNF/Akt/CREB signaling. These findings offer insight into exploring new mechanisms in long-term functional recovery after R1 treatment of ischemic stroke.
Insular Pharmacopoeias: Ethnobotanical Characteristics of Medicinal Plants Used on the Adriatic Islands
Authors: Łuczaj Łukasz , Jug-Dujaković Marija , Dolina Katija , Jeričević Mirjana , Vitasović-Kosić Ivana
Published: May 2021

The Adriatic islands in Croatia, usually divided into two archipelagos – the Kvarner and Dalmatian islands – is one of the largest groups of islands in Europe. Over 40 islands are still inhabited. Unfortunately the traditional use of medicinal plants was never properly documented there. Our data comes from 343 interviews carried out in 36 islands, including the 15 largest islands of the archipelago. The medicinal plants are mainly used to make herbal infusions or decoctions, occasionally medicinal liqueurs, syrups, compresses, or juices squeezed out of raw plants. We recorded the use of 146 taxa, among them 131 with at least one medicinal purpose and 15 only for tea. The frequency curve of use is relatively steep – several plants are used very frequently and most are reported only by one or two informants, which can be explained both by the large geographical spread of the area, and even more so by the devolution of local knowledge and disappearance of gathering practices due to specialization in tourism, modernization and depopulation. Most of the gathered plants already occur in ancient and medieval herbals and are a part of the pan-Mediterranean pharmacopoeia.
BYHWD Alleviates Inflammatory Response by NIK-Mediated Repression of the Noncanonical NF-κB Pathway During ICH Recovery
Authors: Xiao Wei , He Zehui , Luo Weikang , Feng Dandan , Wang Yang , Tang Tao , Yang Ali , Luo Jiekun
Published: May 2021

Intracerebral hemorrhage (ICH) is a life-threatening type of stroke that lacks effective treatments. The inflammatory response following ICH is a vital response that affects brain repair and organism recovery. The nuclear factor κB (NF-κB) signaling pathway is considered one of the most important inflammatory response pathways and one of its response pathways, the noncanonical NF-κB signaling pathway, is known to be associated with persistent effect and chronic inflammation. NF-κB–inducing kinase (NIK) via the noncanonical NF-κB signaling plays a key role in controlling inflammation. Here, we investigated potential effects of the traditional Chinese medicine formula Buyang Huanwu Decoction (BYHWD) on inflammatory response in a rat model of ICH recovery by inhibiting the NIK-mediated the noncanonical NF-κB signaling pathway. In the first part, rats were randomly divided into three groups: the sham group, the ICH group, and the BYHWD group. ICH was induced in rats by injecting collagenase (type VII) into the right globus pallidus of rats' brain. For the BYHWD group, rats were administered BYHWD (4.36 g/kg) once a day by intragastric administration until they were sacrificed. Neurological function was evaluated in rats by a modified neurological severity score (mNSS), the corner turn test, and the foot-fault test. The cerebral edema showed the degree of inflammatory response by sacrificed brain water content. Western blot and real-time quantitative reverse transcription PCR tested the activity of inflammatory response and noncanonical NF-κB signaling. In the second part, siRNA treatment and assessment of inflammation level as well as alterations in the noncanonical NF-κB signaling were performed to determine whether the effect of BYHWD on inflammatory response was mediated by suppression of NIK via the noncanonical NF-κB signaling pathway. We show that BYHWD treated rats exhibited: (i) better health conditions and better neural functional recovery; (ii) decreased inflammatory cytokine and the edema; (iii) reduced expression of NIK, a key protein in unregulated the noncanonical NF-κB signaling pathways; (iv) when compared with pretreated rats with NIK targeting (NIK siRNAs), showed the same effect of inhibiting the pathway and decreased inflammatory cytokine. BYHWD can attenuate the inflammatory response during ICH recovery in rats by inhibiting the NIK-mediated noncanonical NF-κB signaling pathway.
Dynamic Susceptibilities in Dense Soft Athermal Spheres Under a Finite-Rate Shear
Authors: Oyama Norihiro , Kawasaki Takeshi , Saitoh Kuniyasu
Published: May 2021

The mechanical responses of dense packings of soft athermal spheres under a finite-rate shear are studied by means of molecular dynamics simulations. We investigate the volume fraction and shear rate dependence of the fluctuations in the shear stress and the interparticle contact number. In particular, we quantify them by defining the susceptibility as the ratio of the global to local fluctuations. The obtained susceptibilities form ridges on the volume fraction-shear rate plane, which are reminiscent of the Widom lines around the critical point in an equilibrium phase transition.
XIAP Knockdown in Alcohol-Associated Liver Disease Models Exhibits Divergent in vitro and in vivo Phenotypes Owing to a Potential Zonal Inhibitory Role of SMAC
Authors: He Li , Sehrawat Tejasav S. , Verma Vikas K. , Navarro-Corcuera Amaia , Sidhu Guneet , Mauer Amy , Luo Xin , Katsumi Tomohiro , Chen Jingbiao , Shah Soni , Arab Juan Pablo , Cao Sheng , Kashkar Hamid , Gores Gregory J. , Malhi Harmeet , Shah Vijay H.
Published: May 2021

Alcohol-associated liver disease (ALD) has been recognized as the most common cause of advanced liver disease worldwide, though mechanisms of pathogenesis remain incompletely understood. The X-linked inhibitor of apoptosis (XIAP) protein was originally described as an anti-apoptotic protein that directly binds and inhibits caspases-3, 7, and 9. Here, we investigated the function of XIAP in hepatocytes in vitro using gain and loss-of-function approaches. We noted an XIAP-dependent increase in caspase activation as well as increased inflammatory markers and pro-inflammatory EV release from hepatocytes in vitro. Primary hepatocytes (PMH) from XiapAlb.Cre and XiaploxP mice exhibited higher cell death but surprisingly, lower expression of inflammation markers. Conditioned media from these isolated Xiap deleted PMH further decrease inflammation in bone marrow-derived macrophages. Also, interestingly, when administered an ethanol plus Fas-agonist-Jo2 model and an ethanol plus CCl4 model, these animals failed to develop an exacerbated disease phenotype in vivo. Of note, neither XiapAlb.Cre nor XiapAAV8.Cre mice presented with aggravated liver injury, hepatocyte apoptosis, liver steatosis, or fibrosis. Since therapeutics targeting XIAP are currently in clinical trials and caspase-induced death is very important for development of ALD, we sought to explore the potential basis of this unexpected lack of effect. We utilized scRNA-seq and spatially reconstructed hepatocyte transcriptome data from human liver tissue and observed that XIAP was significantly zonated, along with its endogenous inhibitor second mitochondria-derived activator of caspases (SMAC) in periportal region. This contrasted with pericentral zonation of other IAPs including cIAP1 and Apollon as well as caspases 3, 7, and 9. Thus providing a potential explanation for compensation of the effect of Xiap deletion by other IAPs. In conclusion, our findings implicate a potential zonallydependent role for SMAC that prevented development of a phenotype in XIAP knockout mice in ALD models. Targeting SMAC may also be important in addition to current efforts of targeting XIAP in treatment of ALD.
Floral UV Features of Plant Species From a Neotropical Savanna
Authors: Tunes Priscila , Camargo Maria Gabriela Gutierrez , Guimarães Elza
Published: May 2021

Despite the wide interest in flower colours, only after the end of the nineteenth-century studies started to comprise floral UV reflection, which is invisible to humans but visible to the major groups of pollinators. Many flowers and inflorescences display colour patterns, an important signal for pollinators, promoted by the presence of at least two different colours within flowers or inflorescences, including colours in the UV waveband. For Neotropical savanna plant species, we characterised floral UV features using UV-photography and reflectance measurements. We tested (i) whether floral UV features were constrained by their shared ancestry, (ii) whether floral UV features were associated with pollinators, and (iii) whether floral UV features were associated with floral traits mediating these interactions, including floral resource, type of attraction unit and presence/absence of non-UV colour patterns. Of 80 plant species, ca. 70% were UV-patternless, most of them UV-absorbing. Approximately 30% presented one of three types of UV-patterns: bullseye, contrasting corolla markings oriented toward floral resources or contrasting reproductive structures, which were all considered as floral guides. Floral UV features were phylogenetically constrained and were associated with pollinators, floral resources and attraction unit, but not with non-UV colour patterns. UV-patternless flowers were associated with most of the pollination systems, while UV-patterned flowers were mainly associated with bee-pollination. UV-absorbing flowers comprised the only category with hawkmoth- and butterfly-pollinated flowers, and a high percentage of hummingbird-pollinated species. Nocturnal pollinated species were also commonly UV-absorbing, except for one UV-reflecting bat-pollinated species and one beetle-pollinated species with UV-reflecting stigmas. All types of floral UV features were associated with nectar; however, flowers with contrasting reproductive structures were mainly associated with pollen. There was an association between UV-absorbing species and the presence of inflorescences and intermediate attraction units. Our results evince that phylogenetic relatedness can constraint floral UV features’ diversification, but combinations of evolutionary and ecological processes may be expected in this scenario.
Towards Understanding Afghanistan Pea Symbiotic Phenotype Through the Molecular Modeling of the Interaction Between LykX-Sym10 Receptor Heterodimer and Nod Factors
Authors: Solovev Yaroslav V. , Igolkina Anna A. , Kuliaev Pavel O. , Sulima Anton S. , Zhukov Vladimir A. , Porozov Yuri B. , Pidko Evgeny A. , Andronov Evgeny E.
Published: May 2021

The difference in symbiotic specificity between peas of Afghanistan and European phenotypes was investigated using molecular modeling. Considering segregating amino acid polymorphism, we examined interactions of pea LykX-Sym10 receptor heterodimers with four forms of Nodulation factor (NF) that varied in natural decorations (acetylation and length of the glucosamine chain). First, we showed the stability of the LykX-Sym10 dimer during molecular dynamics (MD) in solvent and in the presence of a membrane. Then, four NFs were separately docked to one European and two Afghanistan dimers, and the results of these interactions were in line with corresponding pea symbiotic phenotypes. The European variant of the LykX-Sym10 dimer effectively interacts with both acetylated and non-acetylated forms of NF, while the Afghanistan variants successfully interact with the acetylated form only. We additionally demonstrated that the length of the NF glucosamine chain contributes to controlling the effectiveness of the symbiotic interaction. The obtained results support a recent hypothesis that the LykX gene is a suitable candidate for the unidentified Sym2 allele, the determinant of pea specificity toward Rhizobium leguminosarum bv. viciae strains producing NFs with or without an acetylation decoration. The developed modeling methodology demonstrated its power in multiple searches for genetic determinants, when experimental detection of such determinants has proven extremely difficult.
Progress and Prospects of Mycorrhizal Fungal Diversity in Orchids
Authors: Li Taiqiang , Yang Wenke , Wu Shimao , Selosse Marc-André , Gao Jiangyun
Published: May 2021

Orchids form mycorrhizal symbioses with fungi in natural habitats that affect their seed germination, protocorm growth, and adult nutrition. An increasing number of studies indicates how orchids gain mineral nutrients and sometime even organic compounds from interactions with orchid mycorrhizal fungi (OMF). Thus, OMF exhibit a high diversity and play a key role in the life cycle of orchids. In recent years, the high-throughput molecular identification of fungi has broadly extended our understanding of OMF diversity, revealing it to be a dynamic outcome co-regulated by environmental filtering, dispersal restrictions, spatiotemporal scales, biogeographic history, as well as the distribution, selection, and phylogenetic spectrum width of host orchids. Most of the results show congruent emerging patterns. Although it is still difficult to extend them to all orchid species or geographical areas, to a certain extent they follow the “everything is everywhere, but the environment selects” rule. This review provides an extensive understanding of the diversity and ecological dynamics of orchid-fungal association. Moreover, it promotes the conservation of resources and the regeneration of rare or endangered orchids. We provide a comprehensive overview, systematically describing six fields of research on orchid-fungal diversity: the research methods of orchid-fungal interactions, the primer selection in high-throughput sequencing, the fungal diversity and specificity in orchids, the difference and adaptability of OMF in different habitats, the comparison of OMF in orchid roots and soil, and the spatiotemporal variation patterns of OMF. Further, we highlight certain shortcomings of current research methodologies and propose perspectives for future studies. This review emphasizes the need for more information on the four main ecological processes: dispersal, selection, ecological drift, and diversification, as well as their interactions, in the study of orchid-fungal interactions and OMF community structure.
How Mycorrhizal Associations Influence Orchid Distribution and Population Dynamics
Authors: Li Taiqiang , Wu Shimao , Yang Wenke , Selosse Marc-André , Gao Jiangyun
Published: May 2021

Orchid distribution and population dynamics are influenced by a variety of ecological factors and the formation of holobionts, which play key roles in colonization and ecological community construction. Seed germination, seedling establishment, reproduction, and survival of orchid species are strongly dependent on orchid mycorrhizal fungi (OMF), with mycorrhizal cheating increasingly observed in photosynthetic orchids. Therefore, changes in the composition and abundance of OMF can have profound effects on orchid distribution and fitness. Network analysis is an important tool for the study of interactions between plants, microbes, and the environment, because of the insights that it can provide into the interactions and coexistence patterns among species. Here, we provide a comprehensive overview, systematically describing the current research status of the effects of OMF on orchid distribution and dynamics, phylogenetic signals in orchid–OMF interactions, and OMF networks. We argue that orchid–OMF associations exhibit complementary and specific effects that are highly adapted to their environment. Such specificity of associations may affect the niche breadth of orchid species and act as a stabilizing force in plant–microbe coevolution. We postulate that network analysis is required to elucidate the functions of fungal partners beyond their effects on germination and growth. Such studies may lend insight into the microbial ecology of orchids and provide a scientific basis for the protection of orchids under natural conditions in an efficient and cost-effective manner.
Qualitative and Quantitative Analysis on Flavonoid Distribution in Different Floral Parts of 42 Hemerocallis Accessions
Authors: Li Sen , Cui Huliang , Wang Jinyao , Hou Feifan , Xiong Xiong , Kang Xiuping , Xing Guoming
Published: May 2021

The Hemerocallis accessions is widely consumed as nutritious vegetable and traditional medicine in eastern Asia and used as an ornamental flower worldwide. Compared with most other horticultural products, its flower is richer in polyphenols, flavonoids, carotenoids, and anthocyanins. Therefore, the flower has strong antioxidant activity that inhibits cancer cell proliferation, which could used for health and pharmaceutical purposes. The flavonoids composition and distribution in the flowers, and the content varied between different accssions is still unclear. In this context, eight flavonols, two flavones, and two anthocyanins were determined in Hemerocallis flower by high-performance liquid chromatography (HPLC) coupled with photodiode array and mass spectrometric detectors. Rutin was the most abundant flavonols and cyanidin 3,5-glucoside and cyanidin 3-rutinoside were the major anthocyanins in Hemerocallis tepals, resulting in flower petal coloration, and their content in the petal was higher than that of the sepal. Hierarchical cluster analysis grouped the 42 accessions into four groups, and they were significantly different (p < 0.05) from each other in the ten significant compounds by One-way ANOVA. Overall, the qualitative and quantitative analysis of flavonoid constituents in six floral parts of 42 Hemerocallis accessions were elucidated, which could be helpful for the food and pharmaceutical industries, and lay the foundation for the Hemerocallis flower color research.
Implementing the Refugee Resettlement Process: Diverging Objectives, Interdependencies and Power Relations
Authors: Schneider Hanna
Published: May 2021

Refugee resettlement is implemented by many different national and international stakeholders who operate in different locations and on the basis of sometimes diverging objectives. The implementation of the resettlement process has thus been characterized as multi-level governance, with resettlement stakeholders coordinating and negotiating the selection of refugees for resettlement. Still, literature on the implementation of refugee resettlement has remained very limited and has mainly focused on one specific stakeholder or stage of the process. In addition, a common conceptualization of the different stages is currently missing in academic literature. To address this research gap, the article proposes a common terminology of all stages of the resettlement process. Highlighting the diversity of resettlement programs, the article relies on a comparative case study of the German resettlement and humanitarian admission programs from Jordan and Turkey. By drawing on the concept of multi-level governance, the article examines diverging objectives and interdependencies between resettlement stakeholders, such as UNHCR and resettlement countries. As a result, the article argues that the increasing emphasis on national selection criteria by resettlement countries, including Germany, puts resettlement countries even more in the center of decision-making authority–in contrast to a diffusion of power that characterizes multi-level governance.
Challenging Climate Strikers' Youthfulness: The Evolution of the Generational Gap in Environmental Attitudes Since 1999
Authors: Lorenzini Jasmine , Monsch Gian-Andrea , Rosset Jan
Published: May 2021

In 2019, youth took to the street to express their fears and ambitions in relation to climate change. Alongside, many adult and senior citizens expressed their solidarity. While the media present environmental issues as being generationally dividing, we know little about potential differences between generations in terms of environmental attitudes. In this paper, we analyze data collected in the framework of street demonstrations in Switzerland and longitudinal data collected in the Swiss population. Our analyses of survey data on climate strike demonstrators in Switzerland show that while the early demonstrations attracted mostly youth, the age composition of climate strike demonstrators became more diverse over time increasingly including members of different generations. Furthermore, we explore how age differences evolved over the last 20 years using the Swiss Household Panel data. Our analyses show that the share of individuals who favor the environment over the economy is greater among younger generations and that the climate strike generation stands out with the largest share of pro-environmental attitudes. However, all generations have moved in parallel over the last twenty years following a non-linear but generally upward trend illustrating that the political context affects all generations. Overall, our analyses contribute to understanding incremental changes in public attitudes in the environmental area and the role played by generational renewal in these regards.
Brain Activation of Patients With Obsessive-Compulsive Disorder During a Mental Rotation Task: A Functional MRI Study
Authors: Oh Sanghoon , Jung Wi Hoon , Kim Taekwan , Shim Geumsook , Kwon Jun Soo
Published: May 2021

Functional neuroimaging studies have implicated alterations in frontostriatal and frontoparietal circuits in obsessive-compulsive disorder (OCD) during various tasks. To date, however, brain activation for visuospatial function in conjunction with symptoms in OCD has not been comprehensively evaluated. To elucidate the relationship between neural activity, cognitive function, and obsessive-compulsive symptoms, we investigated regional brain activation during the performance of a visuospatial task in patients with OCD using functional magnetic resonance imaging (fMRI). Seventeen medication-free patients with OCD and 21 age-, sex-, and IQ-matched healthy controls participated in this study. Functional magnetic resonance imaging data were obtained while the subjects performed a mental rotation (MR) task. Brain activation during the task was compared between the two groups using a two-sample t-test. Voxel-wise whole-brain multiple regression analyses were also performed to examine the relationship between obsessive-compulsive symptom severity and neural activity during the task. The two groups did not differ in MR task performance. Both groups also showed similar task-related activation patterns in frontoparietal regions with no significant differences. Activation in the right dorsolateral prefrontal cortex in patients with OCD during the MR task was positively associated with their total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. This study identified the specific brain areas associated with the interaction between symptom severity and visuospatial cognitive function during an MR task in medication-free patients with OCD. These findings may serve as potential neuromodulation targets for OCD treatment.
Comparative Evaluation of the Cytotoxicity of Glyphosate-Based Herbicides and Glycine in L929 and Caco2 Cells
Authors: Truzzi Francesca , Mandrioli Daniele , Gnudi Federica , Scheepers Paul T. J. , Silbergeld Ellen K. , Belpoggi Fiorella , Dinelli Giovanni
Published: May 2021

Introduction: Glyphosate, an amino acid analog of glycine, is the most widely applied organophosphate pesticide worldwide and it is an active ingredient of all glyphosate-based herbicides (GBHs), including the formulation “Roundup. ” While glycine is an essential amino acid generally recognized safe, both epidemiological and toxicological in vivo and in vitro studies available in literature report conflicting findings on the toxicity of GBHs. In our earlier in vivo studies in Sprague–Dawley rats we observed that exposure to GBHs at doses of glyphosate of 1.75 mg/kg bw/day, induced different toxic effects relating to sexual development, endocrine system, and the alteration of the intestinal microbiome. In the present work, we aimed to comparatively test in in vitro models the cytotoxicity of glycine and GBHs.

Methods: We tested the cytotoxic effects of glycine, glyphosate, and its formulation Roundup Bioflow at different doses using MTT and Trypan Blue assays in human Caco2 and murine L929 cell lines.

Results: Statistically significant dose-related cytotoxic effects were observed in MTT and Trypan Blue assays in murine (L929) and human (Caco2) cells treated with glyphosate or Roundup Bioflow. No cytotoxic effects were observed for glycine. In L929, Roundup Bioflow treatment showed a mean IC50 value that was significantly lower than glyphosate in both MTT and Trypan Blue assays. In Caco2, Roundup Bioflow treatment showed a mean IC50 value that was significantly lower than glyphosate in the MTT assays, while a comparable IC50 was observed for glyphosate and Roundup Bioflow in Trypan Blue assays. IC50 for glycine could not be estimated because of the lack of cytotoxic effects of the substance.

Conclusion: Glyphosate and its formulation Roundup Bioflow, but not glycine, caused dose-related cytotoxic effects in in vitro human and murine models (Caco2 and L929). Our results showed that glycine and its analog glyphosate presented different cytotoxicity profiles. Glyphosate and Roundup Bioflow demonstrate cytotoxicity similar to other organophosphate pesticides (malathion, diazinon, and chlorpyriphos).