bluuebunny/crossref_metadata_2025 huggingface dataset:
Extended Amygdala Neuropeptide Circuitry of Emotional Arousal: Waking Up on the Wrong Side of the Bed Nuclei of Stria Terminalis
Authors: Giardino William J. , Pomrenze Matthew B.
Published: February 2021

Sleep is fundamental to life, and poor sleep quality is linked to the suboptimal function of the neural circuits that process and respond to emotional stimuli. Wakefulness (“arousal”) is chiefly regulated by circadian and homeostatic forces, but affective mood states also strongly impact the balance between sleep and wake. Considering the bidirectional relationships between sleep/wake changes and emotional dynamics, we use the term “emotional arousal” as a representative characteristic of the profound overlap between brain pathways that: (1) modulate wakefulness; (2) interpret emotional information; and (3) calibrate motivated behaviors. Interestingly, many emotional arousal circuits communicate using specialized signaling molecules called neuropeptides to broadly modify neural network activities. One major neuropeptide-enriched brain region that is critical for emotional processing and has been recently implicated in sleep regulation is the bed nuclei of stria terminalis (BNST), a core component of the extended amygdala (an anatomical term that also includes the central and medial amygdalae, nucleus accumbens shell, and transition zones betwixt). The BNST encompasses an astonishing diversity of cell types that differ across many features including spatial organization, molecular signature, biological sex and hormonal milieu, synaptic input, axonal output, neurophysiological communication mode, and functional role. Given this tremendous complexity, comprehensive elucidation of the BNST neuropeptide circuit mechanisms underlying emotional arousal presents an ambitious set of challenges. In this review, we describe how rigorous investigation of these unresolved questions may reveal key insights to enhancing psychiatric treatments and global psychological wellbeing.
Identification of Barriers to Access Endovascular Treatment for Acute Ischemic Stroke in the Health Care System of Mexico: Results From a National Survey Among Endovascular Neurologists
Authors: Gongora-Rivera Fernando , Gonzalez-Aquines Alejandro , Marquez-Romero Juan Manuel ,   Neurological Endovascular Therapy – Mexican Group (NET-MX Group)
Published: February 2021

Background: Providing endovascular treatment (EVT) access for acute ischemic stroke (AIS) is a challenge in Latin America. Even though the Mexican Endovascular Reperfusion Registry (MERR) and the RESILIENT trial have demonstrated the feasibility of EVT of AIS in Latin America, the MERR has uncovered potential challenges to delivering EVT to AIS patients.

Aim: To identify the perceived barriers to access EVT for AIS in Mexico.

Methods: We surveyed endovascular neurologists in Mexico. The survey addressed the situation of thrombectomy in the country and the infrastructure and resources available in the participants' institutions. The questionnaire inquired about costs, barriers, and challenges to accessing EVT for AIS, emphasizing the prices and availability of medical devices needed for EVT.

Results: We analyzed data from 21 hospitals. The most extreme identified barriers to access EVT were the lack of health coverage for EVT in the National Health System, the cost of the medical supplies for EVT, and inadequate knowledge of stroke symptoms in the general population. The median cost for EVT was USD 20,000 (IQR 7,500–20,000). From this amount, 60% (IQR 50–70%) corresponded to the costs involved with medical devices. EVT carried additional out-of-pocket costs in 90% of the hospitals, and in 57%, the costs exceed USD $10,000.

Conclusion: Efforts at all government levels and society are required to tackle these barriers. An increase in and efficient use of public funding for EVT coverage and the deployment of continuous and targeted stroke education campaigns could reduce inequities in EVT access in Mexico.
Functional Gait Can Be Affected by Noise: Effects of Age and Cognitive Function: A Pilot Study
Authors: Buyle Margot , Azoidou Viktoria , Pavlou Marousa , Van Rompaey Vincent , Bamiou Doris-Eva
Published: February 2021

Background: The ageing process may degrade an individual's balance control, hearing capacity, and cognitive function. Older adults perform worse on simultaneously executed balance and secondary tasks (i.e., dual-task performance) than younger adults and may be more vulnerable to auditory distraction.

Aim: The purpose of this study was to determine the effect of passive listening on functional gait in healthy older vs. younger adults, and to investigate the effect of age, functional gait, hearing ability and cognitive functioning on dual-task performance.

Methods: Twenty young and 20 older healthy adults were recruited. Functional gait (Functional Gait Assessment in silent and noisy condition), hearing function (audiogram; Speech in Babble test), and cognitive ability (Cambridge Neuropsychological Test Automated Battery) were measured.

Results: Overall, a significant difference between functional gait performance in silent vs. noisy conditions was found (p = 0.022), with no significant difference in dual-task cost between the two groups (p = 0.11). Correlations were found between increasing age, worse functional gait performance, poorer hearing capacity and lower performance on cognitive function tasks. Interestingly, worse performance on attention tasks appeared to be associated with a worse functional gait performance in the noisy condition.

Conclusion: Passive listening to multi-talker babble noise can affect functional gait in both young and older adults. This effect could result from the cognitive load of the babble noise, due to the engagement of attention networks by the unattended speech.
Measuring Vestibular Contributions to Age-Related Balance Impairment: A Review
Authors: Wagner Andrew R. , Akinsola Olaoluwa , Chaudhari Ajit M. W. , Bigelow Kimberly E. , Merfeld Daniel M.
Published: February 2021

Aging is associated with progressive declines in both the vestibular and human balance systems. While vestibular lesions certainly contribute to imbalance, the specific contributions of age-related vestibular declines to age-related balance impairment is poorly understood. This gap in knowledge results from the absence of a standardized method for measuring age-related changes to the vestibular balance pathways. The purpose of this manuscript is to provide an overview of the existing body of literature as it pertains to the methods currently used to infer vestibular contributions to age-related imbalance.
Massive Cerebral Infarction Following Facial Injection of Autologous Fat: A Case Report and Review of the Literature
Authors: Qian Huan , Ling Yuxiao , Zhang Mengwen , Lenahan Cameron , Wang Chen , Zheng Zhe , Shao Anwen , Zhang Jianmin
Published: February 2021

Facial fat grafting techniques often offer impressive surgical results. However, fatal complications, such as irreversible cerebral ischemia, blindness, and hemiplegia are associated with them. We have presented a case report of a patient who presented with a massive cerebral infarction, a serious complication of facial autologous fat injection. The patient was a 28-year-old female who experienced motor dysfunction of the left extremities, which was accompanied with loss of consciousness immediately following fat grafting for facial augmentation. Imaging studies suggested that the patient had a large cerebral infarction on the right frontal, temporal, and parietal lobes due to complete occlusion of her right external carotid artery. Emergency decompressive craniectomy was completed in addition to multiple follow-up medical treatments. The patient recovered after 4 months with reduced motor function in her left upper extremity. This report further summarizes published cases of massive cerebral ischemia after facial injection of autologous fat, as well as lists high-risk facial areas and critical warnings.
Isoquercetin Improves Inflammatory Response in Rats Following Ischemic Stroke
Authors: Shi Yunwei , Chen Xinyi , Liu Jiaxing , Fan Xingjuan , Jin Ying , Gu Jingxiao , Liang Jiale , Liang Xinmiao , Wang Caiping
Published: February 2021

Inflammatory response contributes to brain injury after ischemia and reperfusion (I/R). Our previous literature has shown isoquercetin plays an important role in protecting against cerebral I/R injury. The present study was conducted to further investigate the effect of isoquercetin on inflammation-induced neuronal injury in I/R rats with the involvement of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and inhibitor of NF-κB (I-κB)/nuclear factor-kappa B (NF-κB) signaling pathway mediated by Toll-like receptor 4 (TLR4) and C5a receptor 1 (C5aR1). In vivo middle cerebral artery occlusion and reperfusion (MCAO/R) rat model and in vitro oxygen-glucose deprivation and reperfusion (OGD/R) neuron model were used. MCAO/R induced neurological deficits, cell apoptosis, and release of cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in ischemic brain in rats. Simultaneously, the expression of TLR4 and C5aR1 was significantly up-regulated in both MCAO/R rats and OGD/R neurons, accompanied with the inhibition of cAMP/PKA signaling and activation of I-κB/NF-κB signaling in the cortex of MCAO/R rats. Over-expression of C5aR1 in neurons induced decrease of cell viability, exerting similar effects with OGD/R injury. Isoquercetin acted as a neuroprotective agent against I/R brain injury to suppress inflammatory response and improve cell recovery by inhibiting TLR4 and C5aR1 expression, promoting cAMP/PKA activation, and inhibiting I-κB/NF-κB activation and Caspase 3 expression. TLR4 and C5aR1 contributed to inflammation and apoptosis via activating cAMP/PKA/I-κB/NF-κB signaling during cerebral I/R, suggesting that this signaling pathway may be a potent therapeutic target in ischemic stroke. Isoquercetin was identified as a neuroprotective agent, which maybe a promising therapeutic agent used for the treatment of ischemic stroke and related diseases.
Maternal Diabetes-Induced Suppression of Oxytocin Receptor Contributes to Social Deficits in Offspring
Authors: Liu Jianbo , Liang Yujie , Jiang Xing , Xu Jianchang , Sun Yumeng , Wang Zichen , Lin Ling , Niu Yanbin , Song Shiqi , Zhang Huawei , Xue Zhenpeng , Lu Jianping , Yao Paul
Published: February 2021

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by impaired skills in social interaction and communication in addition to restricted and repetitive behaviors. Many different factors may contribute to ASD development; in particular, oxytocin receptor (OXTR) deficiency has been reported to be associated with ASD, although the detailed mechanism has remained largely unknown. Epidemiological study has shown that maternal diabetes is associated with ASD development. In this study, we aim to investigate the potential role of OXTR on maternal diabetes-mediated social deficits in offspring. Our in vitro study of human neuron progenitor cells showed that hyperglycemia induces OXTR suppression and that this suppression remains during subsequent normoglycemia. Further investigation showed that OXTR suppression is due to hyperglycemia-induced persistent oxidative stress and epigenetic methylation in addition to the subsequent dissociation of estrogen receptor β (ERβ) from the OXTR promoter. Furthermore, our in vivo mouse study showed that maternal diabetes induces OXTR suppression; prenatal OXTR deficiency mimics and potentiates maternal diabetes-mediated anxiety-like behaviors, while there is less of an effect on autism-like behaviors. Additionally, postnatal infusion of OXTR partly, while infusion of ERβ completely, reverses maternal diabetes-induced social deficits. We conclude that OXTR may be an important factor for ASD development and that maternal diabetes-induced suppression of oxytocin receptor contributes to social deficits in offspring.
Astrocytic and Oligodendrocytic P2X7 Receptors Determine Neuronal Functions in the CNS
Authors: Zhao Ya-Fei , Tang Yong , Illes Peter
Published: February 2021

P2X7 receptors are members of the ATP-gated cationic channel family with a preferential localization at the microglial cells, the resident macrophages of the brain. However, these receptors are also present at neuroglia (astrocytes, oligodendrocytes) although at a considerably lower density. They mediate necrosis/apoptosis by the release of pro-inflammatory cytokines/chemokines, reactive oxygen species (ROS) as well as the excitotoxic (glio)transmitters glutamate and ATP. Besides mediating cell damage i.e., superimposed upon chronic neurodegenerative processes in Alzheimer’s Disease, Parkinson’s Disease, multiple sclerosis, and amyotrophic lateral sclerosis, they may also participate in neuroglial signaling to neurons under conditions of high ATP concentrations during any other form of neuroinflammation/neurodegeneration. It is a pertinent open question whether P2X7Rs are localized on neurons, or whether only neuroglia/microglia possess this receptor-type causing indirect effects by releasing the above-mentioned signaling molecules. We suggest as based on molecular biology and functional evidence that neurons are devoid of P2X7Rs although the existence of neuronal P2X7Rs cannot be excluded with absolute certainty.
MicroRNAs Expression Patterns Predict Tumor Mutational Burden in Colorectal Cancer
Authors: Huang Jiahao , Liu Haizhou , Zhao Yang , Luo Tao , Liu Jungang , Liu Junjie , Pan Xiaoyan , Tang Weizhong
Published: February 2021

Background

Tumor mutational burden (TMB) could be a measure of response to immune checkpoint inhibitors therapy for patients with colorectal cancer (CRC). MicroRNAs (miRNAs) participate in anticancer immune responses. In the present study, we determined miRNA expression patterns in patients with CRC and built a signature that predicts TMB.

Methods

Next generation sequencing (NGS) on formalin-fixed paraffin-embedded samples from CRC patients was performed to measure TMB levels. We used datasets from The Cancer Genome Atlas to compare miRNA expression patterns in samples with high and low TMB from patients with CRC. We created an miRNA-based signature index using the selection operator (LASSO) and least absolute shrinkage method from the training set. We used an independent test set as internal validation. We used real-time polymerase chain reaction (RT-PCR) to validate the miRNA-based signature classifier.

Results

Twenty-seven samples from CRC patients underwent NGS to determine the TMB level. We identified four miRNA candidates in the training set for predicting TMB (N = 311). We used the test set (N = 204) for internal validation. The four-miRNA-based signature classifier was an accurate predictor of TMB, with accuracy 0.963 in the training set. In the test set, it was 0.902; and it was 0.946 in the total set. The classifier was superior to microsatellite instability (MSI) for predicting TMB in TCGA dataset. In the validation cohort, MSI status more positively correlated with TMB levels than did the classifier. Validation from RT-qPCR showed good target discrimination of the classifier for TMB prediction.

Conclusion

To our knowledge, this is the first miRNA-based signature classifier validated using high quality clinical data to accurately predict TMB level in patients with CRC.
CTHRC1 Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Kidney Renal Papillary Cell Carcinoma and Kidney Renal Clear Cell Carcinoma
Authors: Zhou Fenfang , Shen Dexin , Xiong Yaoyi , Cheng Songtao , Xu Huimin , Wang Gang , Qian Kaiyu , Ju Lingao , Zhang Xinhua
Published: February 2021

Kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) are the most common RCC types. RCC has high immune infiltration levels, and immunotherapy is currently one of the most promising treatments for RCC. Collagen triple helix repeat containing 1 (CTHRC1) is an extracellular matrix protein that regulates tumor invasion and modulates the tumor microenvironment. However, the association of CTHRC1 with the prognosis and tumor-infiltrating lymphocytes of KIRP and KIRC has not been reported. We examined the CTHRC1 expression differences in multiple tumor tissues and normal tissues via exploring TIMER, Oncomine, and UALCAN databases. Then, we searched the Kaplan-Meier plotter database to evaluate the correlation of CTHRC1 mRNA level with clinical outcomes. Subsequently, the TIMER platform and TISIDB website were chosen to assess the correlation of CTHRC1 with tumor immune cell infiltration level. We further explored the causes of aberrant CTHRC1 expression in tumorigenesis. We found that CTHRC1 level was significantly elevated in KIRP and KIRC tissues relative to normal tissues. CTHRC1 expression associates with tumor stage, histology, lymph node metastasis, and poor clinical prognosis in KIRP. The CTHRC1 level correlates to tumor grade, stage, nodal metastasis, and worse survival prognosis. Additionally, CTHRC1 is positively related to different tumor-infiltrating immune cells in KIRP and KIRC. Moreover, CTHRC1 was closely correlated with the gene markers of diverse immune cells. Also, high CTHRC1 expression predicted a worse prognosis in KIRP and KIRC based on immune cells. Copy number variations (CNV) and DNA methylation might contribute to the abnormal upregulation of CTHRC1 in KIRP and KIRC. In conclusion, CTHRC1 can serve as a biomarker to predict the prognosis and immune infiltration in KIRP and KIRC.
Phytoradiotherapy: An Integrative Approach to Cancer Treatment by Combining Radiotherapy With Phytomedicines
Authors: Alfonzetti Tyler , Yasmin-Karim Sayeda , Ngwa Wilfred , Avery Stephen
Published: February 2021

Radiotherapy (RT) is an effective method of cancer treatment, but like any other method of cancer treatment, there are inherent limitations. While technological advances and a growing understanding of its biological effects have improved its results dramatically, the use of RT is still limited to certain patient populations and by normal tissue toxicities. The harmful side effects of treating patients with radiation can offset its therapy benefits, limiting its use in certain cases. Phyto, or plant-based, medicines offer a way to add to radiation treatment, while also protecting patients from its toxic side effects. Phytomedicines such as cannabinoids (CBD) and bitter melon extract have demonstrated therapeutic properties, including the ability to activate apoptotic death in cancer cells, diminish tumor progression, and generally decrease the incidence of several cancer types. In addition, herbal drugs have been shown to be powerful antioxidants with the ability to decrease toxicity of RT without the adverse side effects found in synthetic drugs. Furthermore, a number of phytomedicines have been shown to mitigate hypoxic conditions within the tumor microenvironment, creating a more radiosensitive disease and preventing tumorigenesis. The purpose of this article is to examine the merits and demerits of employing phytomedicines during RT. Results from studies that have tested the effects of combining radiotherapy with supplemental herbal treatment are discussed along with perspectives on where additional research is needed to advance “Phytoradiotherapy”. Overall, experimental evidence points to the fact that phytomedicines have significant potential to enhance RT, with need for cross-disciplinary collaborations to establish optimal dosing combinations with evidence-base for clinical translation.
Game of Bones: How Myeloma Manipulates Its Microenvironment
Authors: Moser-Katz Tyler , Joseph Nisha S. , Dhodapkar Madhav V. , Lee Kelvin P. , Boise Lawrence H.
Published: February 2021

Multiple myeloma is a clonal disease of long-lived plasma cells and is the second most common hematological cancer behind Non-Hodgkin’s Lymphoma. Malignant transformation of plasma cells imparts the ability to proliferate, causing harmful lesions in patients. In advanced stages myeloma cells become independent of their bone marrow microenvironment and form extramedullary disease. Plasma cells depend on a rich array of signals from neighboring cells within the bone marrow for survival which myeloma cells exploit for growth and proliferation. Recent evidence suggests, however, that both the myeloma cells and the microenvironment have undergone alterations as early as during precursor stages of the disease. There are no current therapies routinely used for treating myeloma in early stages, and while recent therapeutic efforts have improved patients’ median survival, most will eventually relapse. This is due to mutations in myeloma cells that not only allow them to utilize its bone marrow niche but also facilitate autocrine pro-survival signaling loops for further progression. This review will discuss the stages of myeloma cell progression and how myeloma cells progress within and outside of the bone marrow microenvironment.
Neonatal Encephalopathy Is Associated With Altered IL-8 and GM-CSF Which Correlates With Outcomes
Authors: Sweetman Deirdre U. , Strickland Tammy , Melo Ashanty M. , Kelly Lynne A. , Onwuneme Chike , Watson William R. , Murphy John F. A. , Slevin Marie , Donoghue Veronica , O'Neill Amanda , Molloy Eleanor J.
Published: February 2021

Aim: To investigate the relationship between cytokines associated with innate immune cell activation and brain injury and outcome in infants with NE compared to neonatal controls.

Methods: Serum and CSF biomarkers associated with activated neutrophils and monocytes [Interleukin-8 (IL-8) and Granulocyte-Macrophage-Colony-Stimulating-Factor (GM-CSF)] were serially measured using duplex immunoassays on days 1, 3 and 7 in term newborns with NE and controls. Results were compared to grade of encephalopathy, seizures, MRI brain imaging, mortality and Bayley Score of Infant and Toddler Development (Bayley-III) at 2 years of age.

Results: Ninety-four infants had serum samples collected with 34 CSF samples. NE Grade II/III was significantly associated with elevated on day 2 serum IL-8. Mortality was best predicted by elevated day 1 IL-8. GM-CSF was initially elevated on day 1 and abnormal MRI imaging was associated with decreased day 2 GM-CSF. Elevated GM-CSF at day of life 6–7 correlated negatively with composite cognitive, language and motor Bayley-III scores at 2 years.

Conclusion: Moderate or severe NE and mortality was associated with elevated IL-8. Day 2 GM-CSF could predict abnormal MRI results in NE and Bayley-III. Therefore, these cytokines are altered in NE and may predict early outcomes and further implicate inflammatory processes in NE.
Acute Kidney Injury and Pediatric Bone Health
Authors: Hegde Anisha , Denburg Michelle R. , Glenn Dorey A.
Published: February 2021

Acute kidney injury (AKI) has been associated with deleterious impacts on a variety of body systems. While AKI is often accompanied by dysregulation of mineral metabolism—including alterations in calcium, phosphate, vitamin D, parathyroid hormone, fibroblast growth factor 23, and klotho—its direct effects on the skeletal system of children and adolescents remain largely unexplored. In this review, the pathophysiology of dysregulated mineral metabolism in AKI and its potential effects on skeletal health are discussed, including data associating AKI with fracture risk.
The Effect of Initial Oxygen Exposure on Diaphragm Activity in Preterm Infants at Birth
Authors: van Leuteren Ruud W. , Scholten Anouk W. J. , Dekker Janneke , Martherus Tessa , de Jongh Frans H. , van Kaam Anton H. , te Pas Arjan B. , Hutten Jeroen
Published: February 2021

Background: The initial FiO2 that should be used for the stabilization of preterm infants in the delivery room (DR) is still a matter of debate as both hypoxia and hyperoxia should be prevented. A recent randomized controlled trial showed that preterm infants [gestational age (GA) < 30 weeks] stabilized with an initial high FiO2 (1.0) had a significantly higher breathing effort than infants stabilized with a low FiO2 (0.3). As the diaphragm is the main respiratory muscle in these infants, we aimed to describe the effects of the initial FiO2 on diaphragm activity.

Methods: In a subgroup of infants from the original bi-center randomized controlled trial diaphragm activity was measured with transcutaneous electromyography of the diaphragm (dEMG), using three skin electrodes that were placed directly after birth. Diaphragm activity was compared in the first 5 min after birth. From the dEMG respiratory waveform several outcome measures were determined for comparison of the groups: average peak- and tonic inspiratory activity (dEMGpeak and dEMGton, respectively), inspiratory amplitude (dEMGamp), area under the curve (dEMGAUC) and the respiratory rate (RR).

Results: Thirty-one infants were included in this subgroup, of which 29 could be analyzed [n = 15 (median GA 28.4 weeks) and n = 14 (median GA 27.9 weeks) for the 100 and 30% oxygen group, respectively]. Tonic diaphragm activity was significantly higher in the high FiO2-group (4.3 ± 2.1 μV vs. 2.9 ± 1.1 μV; p = 0.047). The other dEMG-parameters (dEMGpeak, dEMGamp, dEMGAUC) showed consistently higher values in the high FiO2 group, but did not reach statistical significance. Average RR showed similar values in both groups (34 ± 9 vs. 32 ± 10 breaths/min for the high and low oxygen group, respectively).

Conclusion: Preterm infants stabilized with an initial high FiO2 showed significantly more tonic diaphragm activity and an overall trend toward a higher level of diaphragm activity than those stabilized with an initial low FiO2. These results confirm that a high initial FiO2 after birth stimulates breathing effort, which can be objectified with dEMG.
Higher ETV5 Expression Associates With Poor 5-Florouracil-Based Adjuvant Therapy Response in Colon Cancer
Authors: Giri Anil K.
Published: February 2021

Discovery of markers predictive for 5-Fluorouracil (5-FU)-based adjuvant chemotherapy (adjCTX) response in patients with locally advanced stage II and III colon cancer (CC) is necessary for precise identification of potential therapy responders. PEA3 subfamily of ETS transcription factors (ETV1, ETV4, and ETV5) are upregulated in multiple cancers including colon cancers. However, the underlying epigenetic mechanism regulating their overexpression as well as their role in predicting therapy response in colon cancer are largely unexplored. In this study, using gene expression and methylation data from The Cancer Genome Atlas (TCGA) project, we showed that promoter DNA methylation negatively correlates with ETV4 expression (ρ = −0.17, p = 5.6 × 10–3) and positively correlates with ETV5 expression (ρ = 0.22, p = 1.43 × 10–4) in colon cancer tissue. Further, our analysis in 1,482 colon cancer patients from five different cohorts revealed that higher ETV5 expression associates with shorter relapse-free survival (RFS) of adjCTX treated colon cancer patients (Hazard ratio = 2.09–5.43, p = 0.004–0.01). The present study suggests ETV5 expression as a strong predictive biomarker for 5-FU-based adjCTX response in stage II/III CC patients.
QTL Mapping for Seed Germination Response to Drought Stress in Brassica napus
Authors: Gad Mahmoud , Chao Hongbo , Li Huaixin , Zhao Weiguo , Lu Guangyuan , Li Maoteng
Published: February 2021

Drought stress is one of the most environmental abiotic stresses affecting seed germination and crop growth. In the present study, the genetic characteristics of seed germination under drought stress in a Brassica napus double haploid population were analyzed. Five germination-related indexes, including germination percentage (GP), root length (RL), shoot length (SL), fresh weight (FW), and root-to-shoot length ratio (R/S) under control and drought stress, were calculated, and the drought stress index (DSI), including DSI-GP, DSI-RL, DSI-SL, DSI-FW, and DSI-R/S, was determined using the quantitative trait loci (QTLs) analysis based on high-density genetic linkage map. The phenotypic analysis indicated that the R/S is an effective morphological trait in the determination of drought tolerance in the seedling stage. Thirty-nine identified QTLs were observed for these traits and then integrated into 36 consensus QTLs, in which 18 QTLs were found to affect the DSI of four traits (GP, RL, SL, and R/S). Based on the co-linearity between genetic and physical maps of B. napus, 256 candidate genes were detected, and 128 genes have single-nucleotidepolymorphisms/insertion–deletion (SNP/InDel) variations between two parents, some of which were associated with the drought stress tolerance (for example, BnaC03g32780D, BnaC03g37030D, and BnaC09g27300D). The present results laid insights into drought tolerance and its genetic bases in B. napus.
Localization, Gene Expression, and Functions of Glutamine Synthetase Isozymes in Wheat Grain (Triticum aestivum L.)
Authors: Wei Yihao , Xiong Shuping , Zhang Zhiyong , Meng Xiaodan , Wang Lulu , Zhang Xiaojiao , Yu Meiqin , Yu Haidong , Wang Xiaochun , Ma Xinming
Published: February 2021

Glutamine synthetase (GS) plays a major role in plant nitrogen metabolism, but the roles of individual GS isoforms in grains are unknown. Here, the localization and expression of individual TaGS isozymes in wheat grain were probed with TaGS isoenzyme-specific antibodies, and the nitrogen metabolism of grain during the grain filling stage were investigated. Immunofluorescence revealed that TaGS1;1, TaGS1;3, and TaGS2 were expressed in different regions of the embryo. In grain transporting tissues, TaGS1;2 was localized in vascular bundle; TaGS1;2 and TaGS1;1 were in chalaza and placentochalaza; TaGS1;1 and TaGS1;3 were in endosperm transfer cells; and TaGS1;3 and TaGS2 were in aleurone layer. GS exhibited maximum activity and expression at 8 days after flowering (DAF) with peak glutamine content in grains; from then, NH4+ increased largely from NO3- reduction, glutamate dehydrogenase (GDH) aminating activity increased continuously, and the activities of GS and glutamate synthase (GOGAT) decreased, while only TaGS1;3 kept a stable expression in different TaGS isozymes. Hence, GS-GOGAT cycle and GDH play different roles in NH4+ assimilation of grain in different stages of grain development; TaGS1;3, located in aleurone layer and endosperm transfer cells, plays a key role in Gln into endosperm for gluten synthesis. At 30 DAF, grain amino acids are mainly transported from maternal phloem.
Effect of Engineered Nickel Oxide Nanoparticle on Reactive Oxygen Species–Nitric Oxide Interplay in the Roots of Allium cepa L.
Authors: Manna Indrani , Sahoo Saikat , Bandyopadhyay Maumita
Published: February 2021

Scientists anxiously follow instances of heavy metals augmenting in the environment and undergoing bioaccumulation and trace their biomagnification across food webs, wary of their potent toxicity on biological entities. Engineered nanoparticles supplement natural pools of respective heavy metals and can mimic their effects, exerting toxicity at higher concentrations. Thus, a thorough understanding of the underlying mechanism of this precarious interaction is mandatory. Most urban and industrial environments contain considerable quantities of nickel oxide nanoparticles. These in excess can cause considerable damage to plant metabolism through a significant increase in cellular reactive oxygen species and perturbation of its cross-talk with the reactive nitrogen species. In the present work, the authors have demonstrated how the intrusion of nickel oxide nanoparticles (NiO-NP) affected the exposed roots of Allium cepa: starting with disruption of cell membranes, before being interiorized within cell organelles, effectively disrupting cellular homeostasis and survival. A major shift in the reactive oxygen species (ROS) and nitric oxide (NO) equanimity was also observed, unleashing major altercations in several crucial biochemical profiles. Altered antioxidant contents and upregulation of stress-responsive genes, namely, Catalase, Ascorbate peroxidase, Superoxide dismutase, and Rubisco activase, showing on average 50–250% rise across NiO-NP concentrations tested, also entailed increased cellular hydrogen peroxide contents, with tandem rise in cellular NO. Increased NO content was evinced from altered concentrations of nitric oxide synthase and nitrate reductase, along with NADPH oxidase, when compared with the negative control. Though initially showing a dose-dependent concomitant rise, a significant decrease of NO was observed at higher concentrations of NiO-NP, while cellular ROS continued to increase. Modified K/Na ratios, with increased proline concentrations and GABA contents, all hallmarks of cellular stress, correlated with ROS–NO perturbations. Detailed studies showed that NiO-NP concentration had a significant role in inducing toxicity, perturbing the fine balance of ROS–NO, which turned lethal for the cell at higher dosages of the ENP precipitating in the accumulation of stress markers and an inevitable shutdown of cellular mechanisms.
Why Variation in Flower Color May Help Reproductive Success in the Endangered Australian Orchid Caladenia fulva
Authors: Basist Georgia , Dyer Adrian G. , Garcia Jair E. , Raleigh Ruth E. , Lawrie Ann C.
Published: February 2021

Caladenia fulvaG.W. Carr (Tawny Spider-orchid) is a terrestrial Australian endangered orchid confined to contiguous reserves in open woodland in Victoria, Australia. Natural recruitment is poor and no confirmed pollinator has been observed in the last 30 years. Polymorphic variation in flower color complicates plans for artificial pollination, seed collection andex situpropagation for augmentation or re-introduction. DNA sequencing showed that there was no distinction among color variants in the nuclear ribosomal internal transcribed spacer (ITS) region and the chloroplast trnT-trnF and matK regions. Also, authentic specimens of bothC. fulvaandCaladenia reticulatafrom the reserves clustered along with these variants, suggesting free interbreeding. Artificial cross-pollinationin situand assessment of seed viability further suggested that no fertility barriers existed among color variants. Natural fruit set was 15% of the population and was proportional to numbers of the different flower colors but varied with orchid patch within the population. Color modeling on spectral data suggested that a hymenopteran pollinator could discriminate visually among color variants. The similarity in fruiting success, however, suggests that flower color polymorphism may avoid pollinator habituation to specific non-rewarding flower colors. The retention of large brightly colored flowers suggests thatC. fulvahas maintained attractiveness to foraging insects rather than evolving to match a scarce unreliable hymenopteran sexual pollinator. These results suggest thatC. fulvashould be recognized as encompassing plants with these multiple flower colors, and artificial pollination should use all variants to conserve the biodiversity of the extant population.
Interaction Between Sex and Cardiac Interoceptive Accuracy in Measures of Induced Pain
Authors: Ferentzi Eszter , Geiger Mattis , Mai-Lippold Sandra A. , Köteles Ferenc , Montag Christian , Pollatos Olga
Published: February 2021

Pain perception is influenced by several factors, and among them, affect, sex, and perception of bodily signals are assumed to play a prominent role. The aim of the present study is to explore how sex, cardiac interoceptive accuracy, and the interaction of the latter two influence the perception of experimentally induced pain. We investigated a large sample of young adults (n= 159, 50.9% female, age: 23.45, SD = 3.767), assessing current positive and negative affective state with the Positive and Negative Affect Schedule (both involved as control variables), cardiac interoceptive accuracy with the mental heartbeat tracking task, and pain sensitivity with electrical stimulation on the back of the dominant hand, applying a repeated-measures staircase protocol. Males showed a significantly higher pain threshold and tolerance level than females, whereas cardiac interoceptive accuracy was not associated with pain sensitivity. The impact of sex × cardiac interoceptive accuracy interaction was significant for pain threshold only, while pain tolerance was predicted only by sex. According to these findings, the associations between pain sensitivity, cardiac IAc, and sex might be more complicated than it was supposed in previous studies. Interactions between factors impacting pain perception appear worthy of further investigation.
Case Report: Theory of Mind and Figurative Language in a Child With Agenesis of the Corpus Callosum
Authors: Melogno Sergio , Pinto Maria Antonietta , Scalisi Teresa Gloria , Badolato Fausto , Parisi Pasquale
Published: February 2021

In this case report, we studied Theory of Mind (ToM) and figurative language comprehension in a 7.2-year-old child, conventionally named RJ, with isolated and complete agenesis of the corpus callosum (ACC), a rare malformation due to the absence of the corpus callosum, the major tract connecting the two brain hemispheres. To study ToM, which is the capability to infer the other’s mental states, we used the classical false belief tasks, and to study figurative language, i.e., those linguistic usages involving non-literal meanings, we used tasks assessing metaphor and idiom comprehension. RJ’s intellectual level and his phonological, lexical, and grammatical abilities were all adequate. In both the ToM false belief tasks and novel sensory metaphor comprehension, RJ showed a delay of 3 years and a significant gap compared to a typically developing control group, while in idioms, his performance was at the border of average. These outcomes suggest that RJ has a specific pragmatic difficulty in all tasks where he must interpret the other’s communicative intention, as in ToM tasks and novel sensory metaphor comprehension. The outcomes also open up interesting insights into the relationships between ToM and figurative language in children with isolated and complete ACC.
Reach-to-Grasp: A Multisensory Experience
Authors: Betti Sonia , Castiello Umberto , Begliomini Chiara
Published: February 2021

The reach-to-grasp movement is ordinarily performed in everyday living activities and it represents a key behavior that allows humans to interact with their environment. Remarkably, it serves as an experimental test case for probing the multisensory architecture of goal-oriented actions. This review focuses on experimental evidence that enhances or modifies how we might conceptualize the “multisensory” substrates of prehension. We will review evidence suggesting that how reach-to-grasp movements are planned and executed is influenced by information coming from different sensory modalities such as vision, proprioception, audition, taste, and olfaction. The review closes with some considerations about the predominant role of the multisensory constituents in shaping prehensile behavior and how this might be important for future research developments, especially in the rehabilitative domain.
Identifying New/Emerging Psychoactive Substances at the Time of COVID-19; A Web-Based Approach
Authors: Catalani Valeria , Arillotta Davide , Corkery John Martin , Guirguis Amira , Vento Alessandro , Schifano Fabrizio
Published: February 2021

COVID-19-related disruptions of people and goods' circulation can affect drug markets, especially for new psychoactive substances (NPSs). Drug shortages could cause a change in available NPS, with the introduction of new, unknown, substances. The aims of the current research were to use a web crawler, NPSfinder®, to identify and categorize emerging NPS discussed on a range of drug enthusiasts/psychonauts' websites/fora at the time of the pandemic; social media for these identified NPS were screened as well. The NPSfinder® was used here to automatically scan 24/7 a list of psychonaut websites and NPS online resources. The NPSs identified in the time frame between January and August 2020 were searched in both the European Monitoring Center for Drugs and Drug Addictions (EMCDDA)/United Nations Office on Drugs and Crime (UNODC) databases and on social media (Facebook, Twitter, Instagram, Pinterest, and YouTube) as well, with a content qualitative analysis having been carried out on reddit.com. Of a total of 229 NPSs being discussed at the time of the pandemic, some 18 NPSs were identified for the first time by the NPSfinder®. These included six cathinones, six opioids, two synthetic cannabinoid receptor agonists (SCRAs), two phenylcyclohexylpiperidine (PCP)-like molecules, and two psychedelics. Of these NPSs, 10 were found to be previously unreported to either the UNODC or the EMCDDA. Of these 18 NPSs, opioids and cathinones were the most discussed on social media/reddit, with the highest number of threads associated. Current findings may support the use of both automated web crawlers and social listening approaches to identify emerging NPSs; the pandemic-related imposed restrictions may somehow influence the demand for specific NPS classes.
The Early Impact of the COVID-19 Lockdown on Stress and Addictive Behaviors in an Alcohol-Consuming Student Population in France
Authors: Flaudias Valentin , Zerhouni Oulmann , Pereira Bruno , Cherpitel Cheryl J. , Boudesseul Jordane , de Chazeron Ingrid , Romo Lucia , Guillaume Sébastien , Samalin Ludovic , Cabe Julien , Bègue Laurent , Gerbaud Laurent , Rolland Benjamin , Llorca Pierre-Michel , Naassila Mickael , Brousse Georges
Published: February 2021

Background: This study evaluated factors linked with perceived stress related to the COVID-19 pandemic and lockdown and addictive behaviors prior to and during lockdown in a sample of students who indicated engaging in alcohol consumption behaviors before lockdown.

Methods: Cross-sectional study. French students from four universities participated in this study, and 2,760 students reported alcohol use. During the first week of lockdown, students reported their perceived levels of stress regarding COVID-19. Substance use and addictive behaviors were reported before and during lockdown, and media exposure, demographical, living conditions, and environmental stressors were reported during lockdown.

Results: Women reported greater levels of stress (95% CI: 1.18 to 1.93, p < 0.001). Highly-stressed students also report less social support (95% CI: −1.04 to −0.39, p < 0.001) and were more likely to worry about the lockdown (95% CI: 0.27 to −0.65, p < 0.001). Alcohol-related problemswere more prevalent among the most stressed students (95% CI: 0.02 to 0.09, p = 0.004) as well as eating problems (95% CI: 0.04 to 0.36, p = 0.016) and problematic internet use (95% CI, 0.06 to 0.14, p < 0.001). Students reporting the highest levels of stress also indicated more compulsive eating during the previous seven days (95% CI, 0.21 to 1.19, p = 0.005).

Conclusions: The level of stress was strongly related to four categories of variables: (i) intrinsic characteristics, (ii) addictive behaviors before lockdown, (iii) lockdown-specific conditions, and (iv) addictive behaviors during the lockdown. Several variables linked to COVID-19 were not directly linked with perceived stress, while perceived stress was found to correlate with daily life organization-related uncertainty and anticipated consequences of lockdown. Importantly, social support seems to be a protective factor on high level of stress.
COVID-19 Stress and Addictive Social Media Use (SMU): Mediating Role of Active Use and Social Media Flow
Authors: Zhao Nan , Zhou Guangyu
Published: February 2021

The ongoing COVID-19 pandemic is likely to enhance the risk of addictive social media use (SMU) as people spend more time online maintaining connectivity when face-to-face communication is limited. Stress is assumed to be a critical predictor of addictive SMU. However, the mechanisms underlying the association between stress and addictive SMU in crises like the current COVID-19 situation remain unclear. The present study aimed to understand the relationship between COVID-19 stress and addictive SMU by examining the mediating role of active use and social media flow (i.e., an intensive, enjoyable experience generated by SMU that perpetuates media use behaviors). A sample of 512 Chinese college students (Mage = 22.12 years, SD = 2.47; 62.5% women) provided self-report data on COVID-19 stress and SMU variables (i.e., time, active use, flow, addictive behavior) via an online survey from March 24 to April 1, 2020. The results showed that COVID-19 stress was positively associated with tendencies toward addictive SMU. Path analyses revealed that this relationship was significantly serially mediated by active use and social media flow, with SMU time being controlled. Our findings suggest that individuals who experience more COVID-19 stress are at increased risk of addictive SMU that may be fostered by active use and flow experience. Specific attention should be paid to these high-risk populations and future interventions to reduce addictive SMU could consider targeting factors of both active use and social media flow.
Cell Populations Expressing Stemness-Associated Markers in Vascular Anomalies
Authors: Kilmister Ethan J. , Hansen Lauren , Davis Paul F. , Hall Sean R. R. , Tan Swee T.
Published: February 2021

Treatment of vascular anomalies (VAs) is mostly empirical and, in many instances unsatisfactory, as the pathogeneses of these heterogeneous conditions remain largely unknown. There is emerging evidence of the presence of cell populations expressing stemness-associated markers within many types of vascular tumors and vascular malformations. The presence of these populations in VAs is supported, in part, by the observed clinical effect of the mTOR inhibitor, sirolimus, that regulates differentiation of embryonic stem cells (ESCs). The discovery of the central role of the renin-angiotensin system (RAS) in regulating stem cells in infantile hemangioma (IH) provides a plausible explanation for its spontaneous and accelerated involution induced by β-blockers and ACE inhibitors. Recent work on targeting IH stem cells by inhibiting the transcription factor SOX18 using the stereoisomer R(+) propranolol, independent of β-adrenergic blockade, opens up exciting opportunities for novel treatment of IH without the β-adrenergic blockade-related side effects. Gene mutations have been identified in several VAs, involving mainly the PI3K/AKT/mTOR and/or the Ras/RAF/MEK/ERK pathways. Existing cancer therapies that target these pathways engenders the exciting possibility of repurposing these agents for challenging VAs, with early results demonstrating clinical efficacy. However, there are several shortcomings with this approach, including the treatment cost, side effects, emergence of treatment resistance and unknown long-term effects in young patients. The presence of populations expressing stemness-associated markers, including transcription factors involved in the generation of induced pluripotent stem cells (iPSCs), in different types of VAs, suggests the possible role of stem cell pathways in their pathogenesis. Components of the RAS are expressed by cell populations expressing stemness-associated markers in different types of VAs. The gene mutations affecting the PI3K/AKT/mTOR and/or the Ras/RAF/MEK/ERK pathways interact with different components of the RAS, which may influence cell populations expressing stemness-associated markers within VAs. The potential of targeting these populations by manipulating the RAS using repurposed, low-cost and commonly available oral medications, warrants further investigation. This review presents the accumulating evidence demonstrating the presence of stemness-associated markers in VAs, their expression of the RAS, and their interaction with gene mutations affecting the PI3K/AKT/mTOR and/or the Ras/RAF/MEK/ERK pathways, in the pathogenesis of VAs.