bluuebunny/crossref_metadata_2025 huggingface dataset:
TACE Plus Lenvatinib Versus TACE Plus Sorafenib for Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Prospective Cohort Study
Authors: Yang Biao , Jie Luo , Yang Ting , Chen Mingyang , Gao Yuemei , Zhang Tian , Zhang Yuzu , Wu Hao , Liao Zhengyin
Published: December 2021

Background and Objectives

This study aimed to compare the efficacy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S) to TACE plus lenvatinib (TACE-L) for the treatment of HCC with portal vein tumor thrombus (PVTT).

Methods

This cohort study recruited patients from September 2017 to September 2020. A total of 59 and 57 consecutive patients were treated with TACE-L and TACE-S, respectively.

Results

Before propensity score matching (PSM), comparing TACE-L to TACE-S, the median overall survival (OS) time was 16.4 months and 12.7 months, respectively [hazard ratio (HR) 1.34; 95% confidence interval (CI): 0.81–2.20; p = 0.25]. The median progression-free survival (PFS) time was 8.4 months and 7.43 months, respectively (HR 1.54; 95% CI: 0.98–2.41; p = 0.081). After PSM, the median OS time was 18.97 months and 10.77 months, respectively (HR 2.21; 95% CI: 1.12–4.38; p = 0.022); the median PFS time was 10.6 months (95% CI: 6.6–18.0 months) and 5.4 months (95% CI: 4.2–8.1 months), respectively (HR 2.62; 95% CI: 1.43–4.80; p = 0.002). After PSM, the overall response rate (ORR) was 66.8% vs. 33.3% [odds ratio (OR) 0.85; 1.05–6.90; p = 0.037].

Conclusion

Both TACE-L and TACE-S are safe, well-tolerated treatments for HCC with PVTT. In HCC with PVTT, TACE-L was significantly superior to TACE-S with respect to OS, PFS, and ORR. A larger-scale randomized clinical trial is needed.
Total Flavone of Abelmoschus manihot Ameliorates TNBS-Induced Colonic Fibrosis by Regulating Th17/Treg Balance and Reducing Extracellular Matrix
Authors: Qiao Lichao , Fang Lei , Zhu Junyi , Xiang Yu , Xu Haixia , Sun Xueliang , Chen Hongjin , Yang Bolin
Published: December 2021

Background and Aims: Surgery remains the major available strategy in inflammatory bowel disease (IBD) fibrotic strictures because no available drugs have sufficient prevention and treatment in this complication. This study aimed to evaluate the efficacy of the total flavone of Abelmoschus manihot L. Medic (TFA) on the development of colonic fibrosis in mice and its possible mechanism.

Methods: The 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic colonic inflammation-associated fibrosis mice were used to evaluate anti-fibrosis of TFA using macroscopic, histological, immunohistochemical analyses, ELISA, Masson staining, Verhoeff’s von Gieson staining, transcription-quantitative polymerase chain reaction, and immunoblot analysis.

Results: Oral administration of TFA attenuated body weight loss, reduced colon length shortening, lowered the morphological damage index score, and notably ameliorated the inflammatory response. TFA downregulated proinflammatory cytokines IL-6, IL-17, TNF-α, IFN-γ productions, and increased the levels of anti-inflammatory cytokine IL-10 and TGF-β. The histological severity of the colonic fibrosis was also notably improved by the TFA treatment and associated with a significant reduction in the colonic expression of col1a2, col3a2, and hydroxyproline. TFA inhibits α-SMA, TGF-β, vimentin, TIMP-1 expression, increasing MMPs, thereby inhibiting activated intestinal mesenchymal cells and extracellular matrix (ECM) deposition.

Conclusion: Together, we herein provide the evidence to support that TFA may restore the imbalance of Th17/Treg and decrease the generation of ECM. This may be a potential mechanism by which TFA protects the intestine under inflammatory conditions and acts as a therapeutic agent for the treatment of intestinal fibrosis in Crohn’s disease.
Molecular and Clinical Aspects of COVID-19 Vaccines and Other Therapeutic Interventions Apropos Emerging Variants of Concern
Authors: Islam Khursheed Ul , A-Elgadir Thoraya Mohamed Elhassan , Afaq Sarah , Ahmad Tanveer , Iqbal Jawed
Published: December 2021

Coronavirus disease 2019 (COVID-19) has overwhelmed the healthcare and economy of the world, with emerging new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posing an everlasting threat to humanity. While most COVID-19 vaccines provide adequate protective immunological response against the original SARS-CoV-2 variant, there is a pressing need to understand their biological and clinical responses. Recent evidence suggests that some of the new variants of SARS-CoV-2 evade the protection conferred by the existing vaccines, which may impede the ongoing efforts to expedite the vaccination programs worldwide. These concerns have also highlighted the importance of a pan-COVID-19 vaccine, which is currently in the making. Thus, it is imperative to have a better molecular and clinical understanding of the various COVID-19 vaccines and their immunological trajectory against any emerging variant of concerns (VOCs) in particular to break this vicious cycle. Furthermore, other treatment regimens based on cellular therapies and monoclonal antibodies should be explored systematically as an alternative and readily available option considering the possibility of the emergence of more virulent SARS-CoV-2 mutants. In this review, we shed light on the various molecular mechanisms and clinical responses of COVID-19 vaccines. Importantly, we review the recent findings of their long-term immune protection and efficacy against emerging VOCs. Considering that other targeted and effective treatments will complement vaccine therapy, we provide a comprehensive understanding of the role of cell-based therapies, monoclonal antibodies, and immunomodulatory agents as alternative and readily available treatment modalities against any emerging SARS-CoV-2 variant.
Differential Effects of Treatment Strategies in Individuals With Chronic Ocular Surface Pain With a Neuropathic Component
Authors: Patel Sneh , Mittal Rhiya , Felix Elizabeth R. , Sarantopoulos Konstantinos D. , Levitt Roy C. , Galor Anat
Published: December 2021

Background: Dysfunction at the ocular system via nociceptive or neuropathic mechanisms can lead to chronic ocular pain. While many studies have reported on responses to treatment for nociceptive pain, fewer have focused on neuropathic ocular pain. This retrospective study assessed clinical responses to pain treatment modalities in individuals with neuropathic component ocular surface pain.

Methods: 101 individuals seen at the University of Miami Oculofacial Pain Clinic from January 2015 to August 2021 with ≥3 months of clinically diagnosed neuropathic pain were included. Patients were subcategorized (postsurgical, post-traumatic, migraine-like, and laterality) and self-reported treatment outcomes were assessed (no change, mild, moderate, or marked improvement). One-way ANOVA (analysis of variance) was used to examine relationships between follow up time and number of treatments attempted with pain improvement, and multivariable logistic regression was used to assess which modalities led to pain improvement.

Results: The mean age was 55 years, and most patients were female (64.4%) and non-Hispanic (68.3%). Migraine-like pain (40.6%) was most common, followed by postsurgical (26.7%), post-traumatic (16.8%) and unilateral pain (15.8%). The most common oral therapies were α2δ ligands (48.5%), the m common topical therapies were autologous serum tears (20.8%) and topical corticosteroids (19.8%), and the most common adjuvant was periocular nerve block (24.8%). Oral therapies reduced pain in post-traumatic (81.2%), migraine-like (73%), and unilateral (72.7%) patients, but only in a minority of postsurgical (38.5%) patients. Similarly, topicals improved pain in post-traumatic (66.7%), migraine-like (78.6%), and unilateral (70%) compared to postsurgical (43.7%) patients. Non-oral/topical adjuvants reduced pain in postsurgical (54.5%), post-traumatic (71.4%), and migraine-like patients (73.3%) only. Multivariable analyses indicated migraine-like pain improved with concomitant oral α2δ ligands and adjuvant therapies, while postsurgical pain improved with topical anti-inflammatories. Those with no improvement in pain had a shorter mean follow-up (266.25 ± 262.56 days) than those with mild (396.65 ± 283.44), moderate (652 ± 413.92), or marked improvement (837.93 ± 709.35) (p < 0.005). Identical patterns were noted for number of attempted medications.

Conclusion: Patients with migraine-like pain frequently experienced pain improvement, while postsurgical patients had the lowest response rates. Patients with a longer follow-up and who tried more therapies experienced more significant relief, suggesting multiple trials were necessary for pain reduction.
Mitochondrial Targeting Therapeutics: Promising Role of Natural Products in Non-alcoholic Fatty Liver Disease
Authors: Xu Jingqi , Shen Jiayan , Yuan Ruolan , Jia Bona , Zhang Yiwen , Wang Sijian , Zhang Yi , Liu Mengyang , Wang Tao
Published: December 2021

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide, and its prevalence is still growing rapidly. However, the efficient therapies for this liver disease are still limited. Mitochondrial dysfunction has been proven to be closely associated with NAFLD. The mitochondrial injury caused reactive oxygen species (ROS) production, and oxidative stress can aggravate the hepatic lipid accumulation, inflammation, and fibrosis. which contribute to the pathogenesis and progression of NAFLD. Therefore, pharmacological therapies that target mitochondria could be a promising way for the NAFLD intervention. Recently, natural products targeting mitochondria have been extensively studied and have shown promising pharmacological activity. In this review, the recent research progress on therapeutic effects of natural-product-derived compounds that target mitochondria and combat NAFLD was summarized, aiming to provide new potential therapeutic lead compounds and reference for the innovative drug development and clinical treatment of NAFLD.
Approaches to Decrease Hyperglycemia by Targeting Impaired Hepatic Glucose Homeostasis Using Medicinal Plants
Authors: Mata-Torres Gerardo , Andrade-Cetto Adolfo , Espinoza-Hernández Fernanda
Published: December 2021

Liver plays a pivotal role in maintaining blood glucose levels through complex processes which involve the disposal, storage, and endogenous production of this carbohydrate. Insulin is the hormone responsible for regulating hepatic glucose production and glucose storage as glycogen, thus abnormalities in its function lead to hyperglycemia in obese or diabetic patients because of higher production rates and lower capacity to store glucose. In this context, two different but complementary therapeutic approaches can be highlighted to avoid the hyperglycemia generated by the hepatic insulin resistance: 1) enhancing insulin function by inhibiting the protein tyrosine phosphatase 1B, one of the main enzymes that disrupt the insulin signal, and 2) direct regulation of key enzymes involved in hepatic glucose production and glycogen synthesis/breakdown. It is recognized that medicinal plants are a valuable source of molecules with special properties and a wide range of scaffolds that can improve hepatic glucose metabolism. Some molecules, especially phenolic compounds and terpenoids, exhibit a powerful inhibitory capacity on protein tyrosine phosphatase 1B and decrease the expression or activity of the key enzymes involved in the gluconeogenic pathway, such as phosphoenolpyruvate carboxykinase or glucose 6-phosphatase. This review shed light on the progress made in the past 7 years in medicinal plants capable of improving hepatic glucose homeostasis through the two proposed approaches. We suggest that Coreopsis tinctoria, Lithocarpus polystachyus, and Panax ginseng can be good candidates for developing herbal medicines or phytomedicines that target inhibition of hepatic glucose output as they can modulate the activity of PTP-1B, the expression of gluconeogenic enzymes, and the glycogen content.
Bright Soliton and Bright–Dark Soliton Pair in an Er-Doped Fiber Laser Mode-Locked Based on In2Se3 Saturable Absorber
Authors: Wei Qin , Han Xile , Zhang Huanian , Li Chonghui , Zhang Chao , Man Baoyuan
Published: December 2021

The output power in ultrafast fiber lasers is usually limited due to the lack of a versatile saturable absorber with high damage threshold and large modulation depth. Here we proposed a more efficient strategy to improve the output energy of erbium-doped fiber laser based on indium selenide (In2Se3) prepared by using the physical vapor deposition (PVD) method. Finally, stable mode-locked bright pulses and triple-wavelength dark–bright pulse pair generation were obtained successfully by adjusting the polarization state. The average output power and pulse energy were 172.4 mW/101 nJ and 171.3 mW/100 nJ, which are significantly improved compared with the previous work. These data demonstrate that the PVD-In2Se3 can be a feasible nonlinear photonic material for high-power fiber lasers, which will pave a fresh avenue for the high-power fiber laser.
A Nickelate Renaissance
Authors: Mitchell J. F.
Published: December 2021

The 2019 discovery of high temperature superconductivity in layered nickelate films, Nd1-xSrNiO2, has galvanized a community that has been studying nickelates for more than 30 years both as cuprate analogs and in their own right. On the surface, infinite layer nickelates, and their multilayer analogs, should be promising candidates based on our understanding of cuprates: square planar coordination and a parent d9 configuration that places a single hole in a dx2-y2 planar orbital makes nickelates seem poised for superconductivity. But creating crystals and films of sufficient quality of this d9 configuration in Ni1+ has proven to be a synthetic challenge, only recently overcome. These crystalline specimens are opening windows that shed new light on the cuprate-nickelate analogy and reveal nuances that leave the relationship between cuprates and nickelates very much an area open to debate. This Perspective gives a qualitative, phenomenological account of these newly discovered superconductors and multilayer members of the infinite layer nickelate family. The focus is on our current understanding of electronic and magnetic properties of these materials as well as some future opportunities, explored from the viewpoint of synthetic challenges and some suggested developments in materials discovery and growth to make further progress in this rejuvenated field.
STXBP1 Syndrome Is Characterized by Inhibition-Dominated Dynamics of Resting-State EEG
Authors: Houtman Simon J. , Lammertse Hanna C. A. , van Berkel Annemiek A. , Balagura Ganna , Gardella Elena , Ramautar Jennifer R. , Reale Chiara , Møller Rikke S. , Zara Federico , Striano Pasquale , Misra-Isrie Mala , van Haelst Mieke M. , Engelen Marc , van Zuijen Titia L. , Mansvelder Huibert D. , Verhage Matthijs , Bruining Hilgo , Linkenkaer-Hansen Klaus
Published: December 2021

STXBP1 syndrome is a rare neurodevelopmental disorder caused by heterozygous variants in the STXBP1 gene and is characterized by psychomotor delay, early-onset developmental delay, and epileptic encephalopathy. Pathogenic STXBP1 variants are thought to alter excitation-inhibition (E/I) balance at the synaptic level, which could impact neuronal network dynamics; however, this has not been investigated yet. Here, we present the first EEG study of patients with STXBP1 syndrome to quantify the impact of the synaptic E/I dysregulation on ongoing brain activity. We used high-frequency-resolution analyses of classical and recently developed methods known to be sensitive to E/I balance. EEG was recorded during eyes-open rest in children with STXBP1 syndrome (n = 14) and age-matched typically developing children (n = 50). Brain-wide abnormalities were observed in each of the four resting-state measures assessed here: (i) slowing of activity and increased low-frequency power in the range 1.75–4.63 Hz, (ii) increased long-range temporal correlations in the 11–18 Hz range, (iii) a decrease of our recently introduced measure of functional E/I ratio in a similar frequency range (12–24 Hz), and (iv) a larger exponent of the 1/f-like aperiodic component of the power spectrum. Overall, these findings indicate that large-scale brain activity in STXBP1 syndrome exhibits inhibition-dominated dynamics, which may be compensatory to counteract local circuitry imbalances expected to shift E/I balance toward excitation, as observed in preclinical models. We argue that quantitative EEG investigations in STXBP1 and other neurodevelopmental disorders are a crucial step to understand large-scale functional consequences of synaptic E/I perturbations.
Influence of Axial Load and a 45-Degree Flexion Head Position on Cervical Spinal Stiffness in Healthy Young Adults
Authors: Hofstetter Léonie , Häusler Melanie , Schweinhardt Petra , Heggli Ursula , Bron Denis , Swanenburg Jaap
Published: December 2021

Background: Neck pain is a major cause of disability worldwide. Poor neck posture such as using a smartphone or work-related additional cervical axial load, such headgear of aviators, can cause neck pain. This study aimed at investigating the role of head posture or additional axial load on spinal stiffness, a proxy measure to assess cervical motor control.

Methods: The posterior-to-anterior cervical spinal stiffness of 49 young healthy male military employees [mean (SD) age 20 ± 1 years] was measured in two head positions: neutral and 45-degree flexed head position and two loading conditions: with and without additional 3 kg axial load. Each test condition comprised three trials. Measurements were taken at three cervical locations, i.e., spinous processes C2 and C7 and mid-cervical (MC).

Results: Cervical spinal stiffness measurements showed good reliability in all test conditions. There was a significant three-way interaction between location × head position × load [F(2, 576) = 9.305, p < 0.001]. Significant two-way interactions were found between measurement locations × loading [F(2, 576) = 15.688, p < 0.001] and measurement locations × head position [F(2, 576) = 9.263, p < 0.001]. There was no significant interaction between loading × head position [F(1, 576) = 0.692, p = 0.406]. Post hoc analysis showed reduction of stiffness in all three measurement locations in flexion position. There was a decrease in stiffness in C2 with loading, increase in stiffness in C7 and no change in MC.

Discussion: A flexed head posture leading to decreased stiffness of the cervical spine might contribute to neck pain, especially if the posture is prolonged and static, such as is the case with smartphone users. Regarding the additional load, stiffness decreased high cervical and increased low cervical. There was no change mid cervical. The lower spinal stiffness at the high cervical spine might be caused by capsular ligament laxity due to the buckling effect. At the lower cervical spine, the buckling effect seems to be less dominant, because the proximity to the ribs and sternum provide additional stiffness.
Lipid Transport in Brown Adipocyte Thermogenesis
Authors: Wade Gina , McGahee Ayren , Ntambi James M. , Simcox Judith
Published: December 2021

Non-shivering thermogenesis is an energy demanding process that primarily occurs in brown and beige adipose tissue. Beyond regulating body temperature, these thermogenic adipocytes regulate systemic glucose and lipid homeostasis. Historically, research on thermogenic adipocytes has focused on glycolytic metabolism due to the discovery of active brown adipose tissue in adult humans through glucose uptake imaging. The importance of lipids in non-shivering thermogenesis has more recently been appreciated. Uptake of circulating lipids into thermogenic adipocytes is necessary for body temperature regulation and whole-body lipid homeostasis. A wide array of circulating lipids contribute to thermogenic potential including free fatty acids, triglycerides, and acylcarnitines. This review will summarize the mechanisms and regulation of lipid uptake into brown adipose tissue including protein-mediated uptake, lipoprotein lipase activity, endocytosis, vesicle packaging, and lipid chaperones. We will also address existing gaps in knowledge for cold induced lipid uptake into thermogenic adipose tissue.
Remarkable Sensitivity of Young Honey Bee Workers to Multiple Non-photic, Non-thermal, Forager Cues That Synchronize Their Daily Activity Rhythms
Authors: Siehler Oliver , Wang Shuo , Bloch Guy
Published: December 2021

Honey bees live in colonies containing tens of thousands of workers that coordinate their activities to produce efficient colony-level behavior. In free-foraging colonies, nest bees are entrained to the forager daily phase of activity even when experiencing conflicting light-dark illumination regime, but little is known on the cues mediating this potent social synchronization. We monitored locomotor activity in an array of individually caged bees in which we manipulated the contact with neighbour bees. We used circular statistics and coupling function analyses to estimate the degree of social synchronization. We found that young bees in cages connected to cages housing foragers showed stronger rhythms, better synchronization with each other, higher coupling strength, and a phase more similar to that of the foragers compared to similar bees in unconnected cages. These findings suggest that close distance contacts are sufficient for social synchronization or that cage connection facilitated the propagation of time-giving social cues. Coupling strength was higher for bees placed on the same tray compared with bees at a similar distance but on a different tray, consistent with the hypothesis that substrate borne vibrations mediate phase synchronization. Additional manipulation of the contact between cages showed that social synchronization is better among bees in cages connected with tube with a single mesh partition compared to sealed tubes consistent with the notion that volatile cues act additively to substrate borne vibrations. These findings are consistent with self-organization models for social synchronization of activity rhythms and suggest that the circadian system of honey bees evolved remarkable sensitivity to non-photic, non-thermal, time giving entraining cues enabling them to tightly coordinate their behavior in the dark and constant physical environment of their nests.
The Changes of KCNQ5 Expression and Potassium Microenvironment in the Retina of Myopic Guinea Pigs
Authors: Yang Qin , Tan Qing Qing , Lan Chang Jun , Lv Bo Zhen , Zhou Gui Mei , Zhong Wei Qi , Gu Zhi Ming , Mao Yu Mei , Liao Xuan
Published: December 2021

KCNQ5 is suggestively associated with myopia, but its specific role in the myopic process has not been studied further. The aim of this study was to investigate the expression of potassium channel gene KCNQ5 and the changes of K+ microenvironment within the retina of form deprivation myopia (FDM) guinea pigs. A total of 60 guinea pigs were randomly divided into the normal control (NC) group, the self-control (SC) group, and the form-deprivation (FD) group for different treatments. Molecular assays and immunohistochemistry (IHC) were conducted to measure the expression and distribution of KCNQ5-related gene and protein in the retina. We determined the K+ concentration in the retina. In addition, the possible effects of form deprivation on potassium ionic currents and the pharmacological sensitivity of KCNQ5 activator Retigabine and inhibitor XE991 to the M-current in RPE cells were investigated using the patch-clamp technique. As a result, FD eyes exhibited more myopic refraction and longer AL. The mRNA and protein levels of KCNQ5 significantly decreased in the FD eyes, but the K+ concentration increased. In addition, the M-type K+ current [IK(M)] density decreased in FD RPE cells, and were activated or inhibited in a concentration-dependent manner due to the addition of Retigabine or XE991. Overall, KCNQ5 was significantly downregulated in the retina of FD guinea pigs, which may be associated with the increasing K+ concentration, decreasing IK(M) density, and elongating ocular axis. It suggested that KCNQ5 may play a role in the process of myopia, and the intervention of potassium channels may contribute to the prevention and control of myopia.
Platelet Deposition Onto Vascular Wall Regulated by Electrical Signal
Authors: Wang Mingyan , Zhang Wei , Qi Zhi
Published: December 2021

Platelets deposition at the site of vascular injury is a key event for the arrest of bleeding and for subsequent vascular repair. Therefore, the regulation of platelet deposition onto the injured site during the process of platelet plug formation is an important event. Herein, we showed that electrical signal could regulate the deposition of platelets onto the injured site. On the one hand, the area of platelet deposition was reduced when the cathode of the applied electric field was placed at the injured site beforehand, while it was increased when the anode was at the site. On the other hand, if a cathode was placed at the injured site after the injury, the electrical signal could remove the outer layer of the deposited platelets. Furthermore, an electric field could drive rapid platelet deposition onto the blood vessel wall at the site beneath the anode even in uninjured blood vessels. Platelet deposition could thus be manipulated by externally applied electric field, which might provide a mechanism to drive platelet deposition onto the wall of blood vessels.
Brachialis Muscle Activity Can Be Measured With Surface Electromyography: A Comparative Study Using Surface and Fine-Wire Electrodes
Authors: Date Shota , Kurumadani Hiroshi , Nakashima Yuko , Ishii Yosuke , Ueda Akio , Kurauchi Kazuya , Sunagawa Toru
Published: December 2021

Muscle activities of the elbow flexors, especially the brachialis muscle (BR), have been measured with intramuscular electromyography (EMG) using the fine-wire electrodes. It remains unclear whether BR activity can be assessed using surface EMG. The purpose of this study was to compare the EMG patterns of the BR activity recorded during elbow flexion using surface and fine-wire electrodes and to determine whether surface EMG can accurately measure the BR activity. Six healthy men were asked to perform two tasks—a maximum isometric voluntary contractions (MVICs) task and an isotonic elbow-flexion task without lifting any weight. The surface and intramuscular EMG were simultaneously recorded from the BR and the long and short heads of the biceps brachii muscle (BBLH and BBSH, respectively). The locations of the muscles were identified and marked under ultrasonographic guidance. The peak cross-correlation coefficients between the EMG signals during the MVICs task were calculated. For the isotonic elbow-flexion task, the EMG patterns for activities of each muscle were compared between the surface and the fine-wire electrodes. All cross-correlation coefficients between the surface EMG signals from the muscles were lower than 0.3. Furthermore, the EMG patterns of the BR activity were not significantly different between the surface and the fine-wire electrodes. The BR has different EMG pattern from the BBLH and the BBSH. The BR activity, conventionally measured with intramuscular EMG, can be accurately accessed with surface EMG during elbow flexion performed without lifting any weight, independent from the BBLH and BBSH activities.
Comparative Analysis of Neuropeptides in Homologous Interneurons and Prohormone Annotation in Nudipleuran Sea Slugs
Authors: Lee Colin A. , Romanova Elena V. , Southey Bruce R. , Gillette Rhanor , Sweedler Jonathan V.
Published: December 2021

Despite substantial research on neuronal circuits in nudipleuran gastropods, few peptides have been implicated in nudipleuran behavior. In this study, we expanded the understanding of peptides in this clade, using three species with well-studied nervous systems, Hermissenda crassicornis, Melibe leonina, and Pleurobranchaea californica. For each species, we performed sequence homology analysis of de novo transcriptome predictions to identify homologs to 34 of 36 prohormones previously characterized in the gastropods Aplysia californica and Lymnaea stagnalis. We then used single-cell mass spectrometry to characterize peptide profiles in homologous feeding interneurons: the multifunctional ventral white cell (VWC) in P. californica and the small cardioactive peptide B large buccal (SLB) cells in H. crassicornis and M. leonina. The neurons produced overlapping, but not identical, peptide profiles. The H. crassicornis SLB cells expressed peptides from homologs to the FMRFamide (FMRFa), small cardioactive peptide (SCP), LFRFamide (LFRFa), and feeding circuit activating peptides prohormones. The M. leonina SLB cells expressed peptides from homologs to the FMRFa, SCP, LFRFa, and MIP-related peptides prohormones. The VWC, previously shown to express peptides from the FMRFa and QNFLa (a homolog of A. californica pedal peptide 4) prohormones, was shown to also contain SCP peptides. Thus, each neuron expressed peptides from the FMRFa and SCP families, the H. crassicornis and M. leonina SLB cells expressed peptides from the LFRFa family, and each neuron contained peptides from a prohormone not found in the others. These data suggest each neuron performs complex co-transmission, which potentially facilitates a multifunctional role in feeding. Additionally, the unique feeding characteristics of each species may relate, in part, to differences in the peptide profiles of these neurons. These data add chemical insight to enhance our understanding of the neuronal basis of behavior in nudipleurans and other gastropods.
Earthworms Modulate Impacts of Soil Heterogeneity on Plant Growth at Different Spatial Scales
Authors: Adomako Michael Opoku , Xue Wei , Roiloa Sergio , Zhang Qian , Du Dao-Lin , Yu Fei-Hai
Published: December 2021

Soil heterogeneity (uneven distribution of soil nutrients and/or other properties) is ubiquitous in nature and can greatly affect plant growth. As earthworm activity can influence nutrient redistribution in the soil, we hypothesize that earthworms may alter the effect of soil heterogeneity on plant growth and this effect may depend on the scale of soil heterogeneity. To test these hypotheses, we grew the clonal grass Leymus chinensis in three soil treatments (heterogeneous large vs. heterogeneous small patch vs. homogeneous soil treatment) with or without earthworms [i.e., Eisenia fetida Savigny (Lumbricidae, epigeic redworm)]. In the heterogeneous treatments, the soil consisted of patches with and without 15N-labeled litter (referred to as high- and low-quality patches, respectively), and in the homogeneous treatment, the soil was an even mixture of the two types of soil patches. Biomass of L. chinensis was significantly higher in the high- than in the low-quality patches, showing the foraging response; this foraging response occurred at both scales and under both earthworm treatments. Compared to the homogeneous treatment, the heterogeneous large patch treatment increased biomass of L. chinensis without earthworms, but decreased it with earthworms. In contrast, biomass of L. chinensis in the heterogeneous small patch treatment did not differ from that in the homogeneous treatment, irrespective of earthworms. Belowground biomass was much greater in the heterogeneous small than in the heterogeneous large patch treatment without earthworms, but it did not differ between these two scale treatments with earthworms. In the heterogeneous treatments, soil 15N was greater in the high- than in the low-quality patches, but this effect became much weaker with than without earthworms, suggesting that earthworm activity homogenized the soil. We conclude that earthworms can change the impact of soil heterogeneity on plant growth via homogenizing the soil, and that this effect of earthworms varies with patch scale. Such scale-dependent interactive effects of soil heterogeneity and earthworms could be a potential mechanism modulating plant community structure and productivity.
Soybean GmMYB133 Inhibits Hypocotyl Elongation and Confers Salt Tolerance in Arabidopsis
Authors: Shan Binghui , Wang Wei , Cao Jinfeng , Xia Siqi , Li Ruihua , Bian Shaomin , Li Xuyan
Published: December 2021

REVEILLE (RVE) genes generally act as core circadian oscillators to regulate multiple developmental events and stress responses in plants. It is of importance to document their roles in crops for utilizing them to improve agronomic traits. Soybean is one of the most important crops worldwide. However, the knowledge regarding the functional roles of RVEs is extremely limited in soybean. In this study, the soybean gene GmMYB133 was shown to be homologous to the RVE8 clade genes of Arabidopsis. GmMYB133 displayed a non-rhythmical but salt-inducible expression pattern. Like AtRVE8, overexpression of GmMYB133 in Arabidopsis led to developmental defects such as short hypocotyl and late flowering. Seven light-responsive or auxin-associated genes including AtPIF4 were transcriptionally depressed by GmMYB133, suggesting that GmMYB133 might negatively regulate plant growth. Noticeably, the overexpression of GmMYB133 in Arabidopsis promoted seed germination and plant growth under salt stress, and the contents of chlorophylls and malondialdehyde (MDA) were also enhanced and decreased, respectively. Consistently, the expressions of four positive regulators responsive to salt tolerance were remarkably elevated by GmMYB133 overexpression, indicating that GmMYB133 might confer salt stress tolerance. Further observation showed that GmMYB133 overexpression perturbed the clock rhythm of AtPRR5, and yeast one-hybrid assay indicated that GmMYB133 could bind to the AtPRR5 promoter. Moreover, the retrieved ChIP-Seq data showed that AtPRR5 could directly target five clients including AtPIF4. Thus, a regulatory module GmMYB133-PRR5-PIF4 was proposed to regulate plant growth and salt stress tolerance. These findings laid a foundation to further address the functional roles of GmMYB133 and its regulatory mechanisms in soybean.
Rootstock-Mediated Genetic Variance in Cadmium Uptake by Juvenile Cacao (Theobroma cacao L.) Genotypes, and Its Effect on Growth and Physiology
Authors: Fernández-Paz Jessica , Cortés Andrés J. , Hernández-Varela Camila A. , Mejía-de-Tafur Maria Sara , Rodriguez-Medina Caren , Baligar Virupax C.
Published: December 2021

Grafting typically offers a shortcut to breed tree orchards throughout a multidimensional space of traits. Despite an overwhelming spectrum of rootstock-mediated effects on scion traits observed across several species, the exact nature and mechanisms underlying the rootstock-mediated effects on scion traits in cacao (Theobroma cacaoL.) plants often remain overlooked. Therefore, we aimed to explicitly quantify rootstock-mediated genetic contributions in recombinant juvenile cacao plants across target traits, specifically cadmium (Cd) uptake, and its correlation with growth and physiological traits. Content of chloroplast pigments, fluorescence of chlorophylla, leaf gas exchange, nutrient uptake, and plant biomass were examined across ungrafted saplings and target rootstock × scion combinations in soils with contrasting levels of Cd. This panel considered a total of 320 progenies from open-pollinated half-sib families and reciprocal full-sib progenies (derived from controlled crosses between the reference genotypes IMC67 and PA121). Both family types were used as rootstocks in grafts with two commercial clones (ICS95 and CCN51) commonly grown in Colombia. A pedigree-based best linear unbiased prediction (A-BLUP) mixed model was implemented to quantify rootstock-mediated narrow-sense heritability (h2) for target traits. A Cd effect measured on rootstocks before grafting was observed in plant biomass, nutrient uptake, and content of chloroplast pigments. After grafting, damage to the Photosystem II (PSII) was also evident in some rootstock × scion combinations. Differences in the specific combining ability for Cd uptake were mostly detected in ungrafted rootstocks, or 2 months after grafting with the clonal CCN51 scion. Moderate rootstock effects (h2> 0.1) were detected before grafting for five growth traits, four nutrient uptake properties, and chlorophylls and carotenoids content (h2= 0.19, 95% CI 0.05–0.61,r= 0.7). Such rootstock effects faded (h2< 0.1) when rootstock genotypes were examined in soils without Cd, or 4 months after grafting. These results suggest a pervasive genetic conflict between the rootstock and the scion genotypes, involving the triple rootstock × scion × soil interaction when it refers to Cd and nutrient uptake, early growth, and photosynthetic process in juvenile cacao plants. Overall, deepening on these findings will harness early breeding schemes of cacao rootstock genotypes compatible with commercial clonal scions and adapted to soils enriched with toxic levels of Cd.
Chloroplast Ribosomes Interact With the Insertase Alb3 in the Thylakoid Membrane
Authors: Ackermann Bernd , Dünschede Beatrix , Pietzenuk Björn , Justesen Bo Højen , Krämer Ute , Hofmann Eckhard , Günther Pomorski Thomas , Schünemann Danja
Published: December 2021

Members of the Oxa1/YidC/Alb3 protein family are involved in the insertion, folding, and assembly of membrane proteins in mitochondria, bacteria, and chloroplasts. The thylakoid membrane protein Alb3 mediates the chloroplast signal recognition particle (cpSRP)-dependent posttranslational insertion of nuclear-encoded light harvesting chlorophyll a/b-binding proteins and participates in the biogenesis of plastid-encoded subunits of the photosynthetic complexes. These subunits are cotranslationally inserted into the thylakoid membrane, yet very little is known about the molecular mechanisms underlying docking of the ribosome-nascent chain complexes to the chloroplast SecY/Alb3 insertion machinery. Here, we show that nanodisc-embedded Alb3 interacts with ribosomes, while the homolog Alb4, also located in the thylakoid membrane, shows no ribosome binding. Alb3 contacts the ribosome with its C-terminal region and at least one additional binding site within its hydrophobic core region. Within the C-terminal region, two conserved motifs (motifs III and IV) are cooperatively required to enable the ribosome contact. Furthermore, our data suggest that the negatively charged C-terminus of the ribosomal subunit uL4c is involved in Alb3 binding. Phylogenetic analyses of uL4 demonstrate that this region newly evolved in the green lineage during the transition from aquatic to terrestrial life.
CRISPR/Cas9 Targeted Editing of Genes Associated With Fungal Susceptibility in Vitis vinifera L. cv. Thompson Seedless Using Geminivirus-Derived Replicons
Authors: Olivares Felipe , Loyola Rodrigo , Olmedo Blanca , Miccono María de los Ángeles , Aguirre Carlos , Vergara Ricardo , Riquelme Danae , Madrid Gabriela , Plantat Philippe , Mora Roxana , Espinoza Daniel , Prieto Humberto
Published: December 2021

The woody nature of grapevine (Vitis viniferaL.) has hindered the development of efficient gene editing strategies to improve this species. The lack of highly efficient gene transfer techniques, which, furthermore, are applied in multicellular explants such as somatic embryos, are additional technical handicaps to gene editing in the vine. The inclusion of geminivirus-based replicons in regular T-DNA vectors can enhance the expression of clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) elements, thus enabling the use of these multicellular explants as starting materials. In this study, we usedBean yellow dwarf virus(BeYDV)-derived replicon vectors to express the key components of CRISPR/Cas9 systemin vivoand evaluate their editing capability in individuals derived fromAgrobacterium-mediated gene transfer experiments of ‘Thompson Seedless’ somatic embryos. Preliminary assays using a BeYDV-derived vector forgreen fluorescent proteinreporter gene expression demonstrated marker visualization in embryos for up to 33 days post-infiltration. A universal BeYDV-based vector (pGMV-U) was assembled to produce all CRISPR/Cas9 components with up to four independent guide RNA (gRNA) expression cassettes. With a focus on fungal tolerance, we used gRNA pairs to address considerably large deletions of putative grape susceptibility genes, includingAUXIN INDUCED IN ROOT CULTURE 12(VviAIR12),SUGARS WILL EVENTUALLY BE EXPORTED TRANSPORTER 4(VviSWEET4),LESION INITIATION 2(VviLIN2), andDIMERIZATION PARTNER-E2F-LIKE 1(VviDEL1). The editing functionality of gRNA pairs in pGMV-U was evaluated by grapevine leaf agroinfiltration assays, thus enabling longer-term embryo transformations. These experiments allowed for the establishment of greenhouse individuals exhibiting a double-cut edited status for all targeted genes under different allele-editing conditions. After approximately 18 months, the edited grapevine plants were preliminary evaluated regarding its resistance toErysiphe necatorandBotrytis cinerea. Assays have shown that a transgene-freeVviDEL1double-cut edited line exhibits over 90% reduction in symptoms triggered by powdery mildew infection. These results point to the use of geminivirus-based replicons for gene editing in grapevine and other relevant fruit species.
The TSN1 Binding Protein RH31 Is a Component of Stress Granules and Participates in Regulation of Salt-Stress Tolerance in Arabidopsis
Authors: Liu Yanan , Liu Shijie , Shi Huiying , Ma Jingyue , Jing Meng , Han Yuzhen
Published: December 2021

Tudor staphylococcal nucleases (TSNs) are evolutionarily conserved RNA binding proteins, which include redundant TSN1 and TSN2 in Arabidopsis. It has been showed TSNs are the components of stress granules (SGs) and regulate plant growth under salt stress. In this study, we find a binding protein of TSN1, RH31, which is a DEAD-box RNA helicase (RH). Subcellular localization studies show that RH31 is mainly located in the nucleus, but under salinity, it translocates to the cytoplasm where it accumulates in cytoplasmic granules. After cycloheximide (CHX) treatment which can block the formation of SGs by interfering with mRNP homeostasis, these cytoplasmic granules disappeared. More importantly, RH31 co-localizes with SGs marker protein RBP47. RH31 deletion results in salt-hypersensitive phenotype, while RH31 overexpression causes more resistant to salt stress. In summary, we demonstrate that RH31, the TSN1 binding protein, is a component of plant SGs and participates in regulation of salt-stress tolerance in Arabidopsis.
Transcription Factor CitERF16 Is Involved in Citrus Fruit Sucrose Accumulation by Activating CitSWEET11d
Authors: Hu Xiaobo , Li Shaojia , Lin Xiahui , Fang Heting , Shi Yanna , Grierson Donald , Chen Kunsong
Published: December 2021

Sugars are the primary products of photosynthesis and play an important role in plant growth and development. They contribute to sweetness and flavor of fleshy fruits and are pivotal to fruit quality, and their translocation and allocation are mainly dependent on sugar transporters. Genome-wide characterization of Satsuma mandarin identified eighteen SWEET family members that encode transporters which facilitate diffusion of sugar across cell membranes. Analysis of the expression profiles in tissues of mandarin fruit at different developmental stages showed that CitSWEET11d transcripts were significantly correlated with sucrose accumulation. Further studies indicated that overexpression of CitSWEET11d in citrus callus and tomato fruit showed a higher sucrose level compared to wild-type, suggesting that CitSWEET11d could enhance sucrose accumulation. In addition, we identified an ERF transcription factor CitERF16 by yeast one-hybrid screening assay which could directly bind to the DRE cis-element on the promoter of CitSWEET11d. Overexpression of CitERF16 in citrus callus significantly induced CitSWEET11d expression and elevated sucrose content, suggesting that CitERF16 acts as a positive regulator to promote sucrose accumulation via trans-activation of CitSWEET11d expression.
Identifying and Shifting Disempowering Paradigms for Families of Children With Disability Through a System Informed Positive Psychology Approach
Authors: Mahmic Sylvana , Kern Margaret L. , Janson Annick
Published: December 2021

Despite the emergence of socio-ecological, strength-based, and capacity-building approaches, care for children with disability remains primarily grounded in a deficit-based perspective. Diagnoses and interventions primarily focus on what children and families cannot do, rather than what might be possible, often undermining the competence, mental health, and functioning of both the children and their families. We first critically examine typical approaches to disability care for families of young children, describe the importance of a systems-informed positive psychology (SIPP) approach to care, and identify the existence of two dominant paradigms, disability is a disadvantage and experts know best. Then, we present a case study investigating families’ experiences with these two paradigms and whether shifts to alternative perspectives could occur through participation in a SIPP-based program co-designed by professionals and families. Of program participants, nine parents and five early intervention professionals participated in two separate focus groups, and ten e-books were randomly selected for review. Thematic analysis of the e-books and focus group data identified two primary themes representing alternative perspectives that arose through the intervention: we will start with our strengths and we’ve got this. Participant comments indicated that they developed a greater sense of hope, empowerment, engagement, and wellbeing, enabled by embedding wellbeing concepts and practices in their routines and communications with their children. We suggest that benefits arose in part from the structure of the program and the development of wellbeing literacy in participants. While care needs to be taken in generalizing the results, the case study provides clear examples of shifts in perspectives that occurred and suggests that the incorporation of SIPP principles within early intervention approaches provides a potential pathway for shifting the problematic paradigms that dominate disability care.