bluuebunny/crossref_metadata_2025 huggingface dataset:
Panel Stochastic Frontier Analysis with Dependent Error Terms
Authors: EL MEHDİ Rachida , HAFNER Christian M.
Published: December 2021

In presence of panel data, technical efficiency is used to compare the performances of Decision-Making Units (DMUs). The novelty of this paper is the consideration of the dependence between the two error terms in the case of panel data and the introduction of time effect models in the Stochastic Frontier Analysis (SFA). Hence, our SFA model considers the balanced panel case, several models describing the evolution of the inefficiency over time and the dependence between the two error terms. The inefficiency and noise terms being dependent, a copula function which reflects the dependence between them is included in their joint density. The model is estimated by maximum likelihood and the Akaike Information Criterion (AIC) is used for model selection. Moreover, a likelihood ratio test is performed for the nested models. A bootstrap algorithm is proposed for statistical inference on the Technical Efficiency (TE) measures. Results for Moroccan policy of the production and sales of drinking water from 2001 to 2007 identify the most and least efficient provinces, and a generally positive trend of estimated TE measures.
Nutrient status, hydrogen peroxide content and peroxidase activity of arbuscular mycorrhizal plants of Melilotus albus grown in diesel-contaminated substrate
Authors: Hernández-Ortega Herminia Alejandra , Ferrera-Cerrato Ronald , López-Delgado Humberto Antonio , Sánchez-Rangel Juan Carlos , Alarcón Alejandro
Published: December 2021

Background: Petroleum hydrocarbons affect plant growth, but little is known about physiological responses of mycorrhizal plants facing diesel contamination.
Objective: To evaluate the effects of arbuscular mycorrhizal fungi (AMF) on the nutritional status, peroxidase activity (POX), and hydrogen peroxide content (H2O2) in leaves of Melilotus albus planted under diesel-contaminated sand (7500 mg kg-1).
Methods: A 2x2 factorial experiment was set in a completely randomized design, under greenhouse conditions for 35 days. Seedlings were pre-inoculated with AMF and transplanted to sand with or without diesel, including non-AMF plants.
Results and conclusions: Diesel contamination impaired plant growth; AMF plants had similar growth than non-AMF plants at diesel-contamination, but low nutrient content. Protein content decreased due to diesel in non-AMF plants, but this content was low in AMF plants regardless diesel contamination. Diesel increased POX; whereas AMF plants with or without diesel had higher POX than non-AMF plants. The H2O2 content in AMF plants with or without diesel was low than non-AMF plants. Diesel contamination diminished AMF-colonization, but AMF dissipate more diesel hydrocarbons (>40%). Overall, AMF alleviated the toxic effects of diesel on plants.
Improved growth of bell pepper (Capsicum annuum) plants by inoculating arbuscular mycorrhizal fungi and beneficial rhizobacteria
Authors: Angulo-Castro Azareel , Ferrera-Cerrato Ronald , Alarcón Alejandro , Almaraz-Suárez Juan José , Delgadillo-Martínez Julián , Jiménez-Fernández Maribel , García-Barradas Oscar
Published: December 2021

Background: Plant growth promoting rhizobacteria (PGPR) and arbuscular mycorrhizal fungi (AMF) are an alternative for sustainable management of pepper crops.
Objective: To investigate the beneficial effects of PGPR and AMF inoculation on the growth of bell pepper plants.
Methods: Two PGPR strains were used (Pseudomonas tolaasii P61 and Bacillus pumilus R44) as well as their mixture, and an uninoculated control. In addition, bacterial treatments were combined with an AMF-consortium (Funneliformis aff. geosporum and Claroideoglomus sp.). A 4×2 factorial experiment [four levels for the bacterial inoculation and two levels of AMF-inoculation (non-AMF and AMF)] was performed with eight treatments, at greenhouse conditions for 80 days after inoculation. AMF inoculation was done at sowing and PGPR after 15 days of seedling emergence.
Results and Conclusions: Uninoculated control showed lower growth responses than plants inoculated with PGPR and AMF, alone or in combination. Overall, inoculation of the strain P61 or the combination of R44+AMF increased plant growth. AMF improved the photochemical efficiency of PSII in comparison to either control plants or plants inoculated with R44 or with the bacterial mix. Both PGPR and AMF improved growth and vigor of bell pepper plants.
Influencia de las propiedades edáficas en la abundancia de esporas y colonización de hongos micorrízicos arbusculares en banano en dos temporadas del año
Authors: Carrillo  Aguilar Dulce Guadalupe , Hernández Ortega Herminia Alejandra , Franco Ramírez Alicia , Vallejo Jiménez Benjamín , Guzmán González Salvador , Manzo Sánchez Gilberto , Sánchez Rangel Juan Carlos
Published: December 2021

Antecedentes: Las propiedades edáficas influyen en la abundancia de esporas y en la colonización de hongos micorrízicos arbusculares, sin embargo, existen pocos estudios de las propiedades que tienen mayor impacto sobre la micorriza arbuscular en época de sequía y de lluvia en cultivos de banano.
Objetivos: Determinar la influencia de las propiedades edáficas en la abundancia de esporas y en la colonización de hongos micorrízicos en plantaciones de banano en dos temporadas del año.
Métodos: Se colectó suelo y raíces de banano en Tecomán, Colima, y se determinó la influencia de las propiedades edáficas en la abundancia de esporas y colonización de hongos micorrízicos mediante un análisis de componentes principales.
Resultados y conclusiones: Los valores más altos de abundancia de esporas (1700 esporas/100 g de suelo) y colonización por hongos micorrízicos (63.3 %) se encontraron en época de lluvias y de sequía, respectivamente. Se identificaron 23 morfotipos de los géneros Claroideoglomus, Acaulospora, Rhizophagus, Racocetra, Funneliformis y Glomus, siendo este último el más común. Las propiedades edáficas que promueven o reducen la abundancia de esporas y colonización de HMA difieren en cada temporada, siendo mayor el número de factores que influyen en la abundancia de esporas.
Conocimiento micológico tradicional en dos comunidades aledañas al Parque Nacional Lagunas de Montebello, Chiapas, México
Authors: Ramírez-Terrazo Amaranta , Montoya Adriana , Kong Alejandro
Published: December 2021

Antecedentes: El Parque Nacional Lagunas de Montebello es un Área Natural Protegida con alta diversidad biológica y cultural. En el territorio habitan pobladores Chuj y Tojolabales, y son ellos quienes utilizan los hongos. Se tiene poca información sobre el conocimiento maya de los hongos en la zona.

Objetivo: Describir el conocimiento tradicional sobre los hongos en Antelá y Tziscao, Municipio de La Trinitaria.

Métodos: Se realizaron entrevistas dirigidas a los habitantes de ambas comunidades, salidas a diferentes zonas de vegetación para la recolección de hongos y se llevó a cabo la determinación taxonómica de los ejemplares recolectados.

Resultados y conclusiones: En la comunidad de Antelá se conocen 16 especies de hongos y 18 nombres en Tojolabal. En Tziscao conocen 15 especies y 21 nombres en Chuj. Se obtuvo información sobre diferentes aspectos del conocimiento tradicional de los hongos. Hay aspectos de éste (ej. concepto y origen de los hongos, factores para fructificar) que se comparten con otras regiones del país, en la zona se utilizan pocos hongos comparando con los datos de diversidad registrados. Se utilizan hongos tanto de ambientes conservados como de zonas perturbadas. Se recolectó una especie no descrita de hongo (Lactarius aff. deliciosus) conocida localmente como K’anchaya.
Diversidad de hongos micorrizógenos arbusculares en monocultivo de trigo en Michoacán, México
Authors: Mendoza-Churape Juan , Apáez-Barrios Patricio , Raya-Montaño Yurixhi Atenea , Pedraza-Santos Martha Elena , Aguirre-Paleo Salvador , Vargas-Sandoval Margarita , Lara-Chávez Ma. Blanca Nieves
Published: December 2021

Antecedentes: En México el trigo es considerado un grano básico, en 2019 se sembraron 526,449 ha, con producción de 3,121,601 t de grano. Las prácticas agrícolas como labranza, fertilización y falta de rotación de cultivos afectan la composición de la comunidad de hongos micorrizógenos arbusculares (HMA).
Objetivo: Determinar la diversidad e identificar taxonómicamente las especies de HMA en monocultivo de trigo con altas dosis de fertilización inorgánica.
Métodos: El estudio se ubicó en José Sixto Verduzco, Michoacán, México. Las muestras de suelo se recolectaron del horizonte superior (0-15 cm de profundidad) en cultivos de trigo de invierno durante marzo 2018. Las esporas se aislaron de muestras de 30 g y se identificaron morfológicamente. La diversidad se calculó usando el índice de Shannon-Wiener.
Resultados y Conclusiones: Se encontraron nueve especies, ocho de ellas fueron identificadas a nivel de especie: Claroideoglomus etunicatum, Diversispora spurca, Entrophospora infrequens, Funneliformis mosseae, Rhizophagus intraradices, Sclerocystis sinuosa, Septoglomus constrictum y Sieverdingia tortuosa. Funneliformis mosseae exhibió la mayor abundancia relativa (50 %). Las muestras de suelo agrícola con monocultivo de trigo presentaron baja diversidad de HMA (1.59) y alta frecuencia de una sola especie, limitando así los efectos ventajosos que estos microorganismos ejercen sobre los cultivos.
Evaluation of environmental heterogeneity and its effect on arbuscular mycorrhizal interaction in coastal dunes
Authors: Solís-Rodríguez Uriel Ramón Jakuosi , Guadarrama Patricia , Hernández-Cuevas Laura , Salinas-Peba Luis , Ramos-Zapata José
Published: December 2021

Background: Coastal dune scrub vegetation is established on a substrate that favors biodiversity, but this is currently restricted to small patches.
Objective: To determine the status of the arbuscular mycorrhizal fungi (AMF) in this vegetation under different anthropogenic pressures and to propose actions addressing its conservation and restoration.
Methods: Plant and fungal community was characterized through taxonomic identification of the AMF and determination of their percentage of viability, number of infective propagules (NIP) and percentage of mycorrhizal colonization. Three contrasting sites were identified in the Ría Lagartos Biosphere Reserve: C = Conserved, IPS = Intermediate perturbation by the salt industry and HPA = high perturbation of anthropogenic origin. In each site, fine roots were collected from 12 common species and compound soil samples were taken.
Results and conclusions: Eight AMF species were identified, in IPS, the highest values were presented in terms of percentage of colonization 55.43 ± 6.5, NIP = 142.07 ± 91.2 and viability = 27.6 ± 15.21 % while, in HPA, a higher number of healthy spores were found 43.6 ± 11.5/50 g. Infective propagules are an indicator of a “healthy ecosystem” and were found at a higher proportion in the conserved site.
Explant Analysis of Utah Electrode Arrays Implanted in Human Cortex for Brain-Computer-Interfaces
Authors: Woeppel Kevin , Hughes Christopher , Herrera Angelica J. , Eles James R. , Tyler-Kabara Elizabeth C. , Gaunt Robert A. , Collinger Jennifer L. , Cui Xinyan Tracy
Published: December 2021

Brain-computer interfaces are being developed to restore movement for people living with paralysis due to injury or disease. Although the therapeutic potential is great, long-term stability of the interface is critical for widespread clinical implementation. While many factors can affect recording and stimulation performance including electrode material stability and host tissue reaction, these factors have not been investigated in human implants. In this clinical study, we sought to characterize the material integrity and biological tissue encapsulation via explant analysis in an effort to identify factors that influence electrophysiological performance. We examined a total of six Utah arrays explanted from two human participants involved in intracortical BCI studies. Two platinum (Pt) arrays were implanted for 980 days in one participant (P1) and two Pt and two iridium oxide (IrOx) arrays were implanted for 182 days in the second participant (P2). We observed that the recording quality followed a similar trend in all six arrays with an initial increase in peak-to-peak voltage during the first 30–40 days and gradual decline thereafter in P1. Using optical and two-photon microscopy we observed a higher degree of tissue encapsulation on both arrays implanted for longer durations in participant P1. We then used scanning electron microscopy and energy dispersive X-ray spectroscopy to assess material degradation. All measures of material degradation for the Pt arrays were found to be more prominent in the participant with a longer implantation time. Two IrOx arrays were subjected to brief survey stimulations, and one of these arrays showed loss of iridium from most of the stimulated sites. Recording performance appeared to be unaffected by this loss of iridium, suggesting that the adhesion of IrOx coating may have been compromised by the stimulation, but the metal layer did not detach until or after array removal. In summary, both tissue encapsulation and material degradation were more pronounced in the arrays that were implanted for a longer duration. Additionally, these arrays also had lower signal amplitude and impedance. New biomaterial strategies that minimize fibrotic encapsulation and enhance material stability should be developed to achieve high quality recording and stimulation for longer implantation periods.
In-vitro and In-Vivo Assessment of 4D Flow MRI Reynolds Stress Mapping for Pulsatile Blood Flow
Authors: Ha Hojin , Huh Hyung Kyu , Park Kyung Jin , Dyverfeldt Petter , Ebbers Tino , Kim Dae-Hee , Yang Dong Hyun
Published: December 2021

Imaging hemodynamics play an important role in the diagnosis of abnormal blood flow due to vascular and valvular diseases as well as in monitoring the recovery of normal blood flow after surgical or interventional treatment. Recently, characterization of turbulent blood flow using 4D flow magnetic resonance imaging (MRI) has been demonstrated by utilizing the changes in signal magnitude depending on intravoxel spin distribution. The imaging sequence was extended with a six-directional icosahedral (ICOSA6) flow-encoding to characterize all elements of the Reynolds stress tensor (RST) in turbulent blood flow. In the present study, we aimed to demonstrate the feasibility of full RST analysis using ICOSA6 4D flow MRI under physiological conditions. First, the turbulence analysis was performed through in vitro experiments with a physiological pulsatile flow condition. Second, a total of 12 normal subjects and one patient with severe aortic stenosis were analyzed using the same sequence. The in-vitro study showed that total turbulent kinetic energy (TKE) was less affected by the signal-to-noise ratio (SNR), however, maximum principal turbulence shear stress (MPTSS) and total turbulence production (TP) had a noise-induced bias. Smaller degree of the bias was observed for TP compared to MPTSS. In-vivo study showed that the subject-variability on turbulence quantification was relatively low for the consistent scan protocol. The in vivo demonstration of the stenosis patient showed that the turbulence analysis could clearly distinguish the difference in all turbulence parameters as they were at least an order of magnitude larger than those from the normal subjects.
Estrogen Receptor α Signaling in Osteoblasts is Required for Mechanotransduction in Bone Fracture Healing
Authors: Steppe Lena , Krüger Benjamin Thilo , Tschaffon Miriam Eva Angelica , Fischer Verena , Tuckermann Jan , Ignatius Anita , Haffner-Luntzer Melanie
Published: December 2021

Biomechanical stimulation by whole-body low-magnitude high-frequency vibration (LMHFV) has demonstrated to provoke anabolic effects on bone metabolism in both non-osteoporotic and osteoporotic animals and humans. However, preclinical studies reported that vibration improved fracture healing and bone formation in osteoporotic, ovariectomized (OVX) mice representing an estrogen-deficient hormonal status, but impaired bone regeneration in skeletally healthy non-OVX mice. These effects were abolished in general estrogen receptor α (ERα)-knockout (KO) mice. However, it remains to be elucidated which cell types in the fracture callus are targeted by LMHFV during bone healing. To answer this question, we generated osteoblast lineage-specific ERα-KO mice that were subjected to ovariectomy, femur osteotomy and subsequent vibration. We found that the ERα specifically on osteoblastic lineage cells facilitated the vibration-induced effects on fracture healing, because in osteoblast lineage-specific ERα-KO (ERαfl/fl; Runx2Cre) mice the negative effects in non-OVX mice were abolished, whereas the positive effects of vibration in OVX mice were reversed. To gain greater mechanistic insights, the influence of vibration on murine and human osteogenic cells was investigated in vitro by whole genome array analysis and qPCR. The results suggested that particularly canonical WNT and Cox2/PGE2 signaling is involved in the mechanotransduction of LMHFV under estrogen-deficient conditions. In conclusion, our study demonstrates a critical role of the osteoblast lineage-specific ERα in LMHFV-induced effects on fracture healing and provides further insights into the molecular mechanism behind these effects.
Evaluation of Bi-Layer Silk Fibroin Grafts for Penile Tunica Albuginea Repair in a Rabbit Corporoplasty Model
Authors: Gundogdu Gokhan , Okhunov Zhamshid , Starek Stephanie , Veneri Faith , Orabi Hazem , Holzman Sarah A. , Sullivan Maryrose P. , Khoury Antoine E. , Mauney Joshua R.
Published: December 2021

The use of autologous tissue grafts for tunica albuginea repair in Peyronie’s disease and congenital chordee is often restricted by limited tissue availability and donor site morbidity, therefore new biomaterial options are needed. In this study, bi-layer silk fibroin (BLSF) scaffolds were investigated to support functional tissue regeneration of tunica albuginea in a rabbit corporoplasty model. Eighteen adult male, New Zealand white rabbits were randomized to nonsurgical controls (NSC, N = 3), or subjected to corporoplasty with BLSF grafts (N = 5); decellularized small intestinal submucosa (SIS) matrices (N = 5); or autologous tunica vaginalis (TV) flaps (N = 5). End-point evaluations were cavernosography, cavernosometry, histological, immunohistochemical, and histomorphometric assessments. Maximum intracorporal pressures (ICP) following papaverine-induced erection were similar between all groups. Eighty percent of rabbits repaired with BLSF scaffolds or TV flaps achieved full rigid erections, compared to 40% of SIS reconstructed animals. Five-minute peak erections were maintained in 60% of BLSF rabbits, compared to 20% of SIS and TV flap reconstructed rabbits. Graft perforation occurred in 60% of TV group at maximum ICP compared to 20% of BLSF cohort. Neotissues supported by SIS and BLSF scaffolds were composed of collagen type I and elastin fibers similar to NSC. SIS and TV flaps showed significantly elevated levels of corporal fibrosis relative to NSC with a corresponding decrease in corporal smooth muscle cells expressing contractile proteins. BLSF biomaterials represent emerging platforms for corporoplasty and produce superior functional and histological outcomes in comparison to TV flaps and SIS matrices for tunica albuginea repair.
Inhibition of Neovascularization and Inflammation in a Mouse Model of Corneal Alkali Burns Using Cationic Liposomal Tacrolimus
Authors: Lin Xueqi , Yu Xuewen , Chen Xiang , Sheng Siting , Wang Jingwen , Wang Ben , Xu Wen
Published: December 2021

Eye drops account for more than 90% of commercialized ophthalmic drugs. However, eye drops have certain shortcomings, such as short precorneal retention time and weak corneal penetration. The requirement of frequent instillation of eye drops also causes poor patient compliance, which may lead to further aggravation of the disease. We aimed to develop a cationic liposome formulation to increase the bioavailability of the therapeutic agent and solve the aforementioned problems. In the present study, we prepared cationic liposomal tacrolimus (FK506) with a surface potential of approximately +30 mV, which could bind to the negatively charged mucin layer of the ocular surface. Our results showed that the content of FK506 in the cornea was increased by 93.77, 120.30, 14.24, and 20.36 times at 5, 30, 60, and 90 min, respectively, in the FK506 liposome group (0.2 mg/ml) compared with the free drug group (0.2 mg/ml). Moreover, FITC-labeled FK506 liposomes significantly prolonged the ocular surface retention time to 50 min after a single dose. In addition, the results of the Cell Counting Kit-8 assay, live and dead cell assay, sodium fluorescein staining, and hematoxylin and eosin staining all indicated that FK506 liposomes had good biological compatibility in both human corneal epithelial cells and mouse eyeballs. Compared with the free drug at the same concentration, FK506 liposomes effectively inhibited vascular endothelial growth factor-induced green fluorescent protein-transduced human umbilical vein endothelial cell migration and tube formation in vitro. In a mouse corneal neovascularization model induced by alkali burns, FK506 liposomes (0.2 mg/ml) enhanced corneal epithelial recovery, inhibited corneal neovascularization, and reduced corneal inflammation, and its therapeutic effect was better than those of the commercial FK506 eye drops (1 mg/ml) and the free drug (0.2 mg/ml). Collectively, these results indicate that cationic FK506 liposomes could increase the efficacy of FK506 in the corneal neovascularization model. Therefore, cationic FK506 liposomes can be considered as a promising ocular drug delivery system.
N6-Methyladenosine Methyltransferase METTL3 Promotes Angiogenesis and Atherosclerosis by Upregulating the JAK2/STAT3 Pathway via m6A Reader IGF2BP1
Authors: Dong Guo , Yu Jiangbo , Shan Gaojun , Su Lide , Yu Nannan , Yang Shusen
Published: December 2021

Atherosclerosis (AS) is a life-threatening vascular disease. RNA N6-methyladenosine (m6A) modification level is dysregulated in multiple pathophysiologic processes including AS. In this text, the roles and molecular mechanisms of m6A writer METTL3 in AS progression were explored in vitro and in vivo. In the present study, cell proliferative, migratory, and tube formation capacities were assessed through CCK-8, Transwell migration, and tube formation assays, respectively. RNA m6A level was examined through a commercial kit. RNA and protein levels of genes were measured through RT-qPCR and western blot assays, respectively. VEGF secretion level was tested through ELISA assay. JAK2 mRNA stability was detected through actinomycin D assay. The relationship of METTL3, IGF2BP1, and JAK2 was investigated through bioinformatics analysis, MeRIP, RIP, RNA pull-down, and luciferase reporter assays. An AS mouse model was established to examine the effect of METTL3 knockdown on AS development in vivo. The angiogenetic activity was examined through chick chorioallantoic membrane assay in vivo. The results showed that METTL3 was highly expressed in ox-LDL-induced dysregulated HUVECs. METTL3 knockdown inhibited cell proliferation, migration, tube formation, and VEGF expression/secretion in ox-LDL-treated HUVECs, hampered AS process in vivo, and prevented in vivo angiogenesis of developing embryos. METTL3 positively regulated JAK2 expression and JAK2/STAT3 pathway in an m6A dependent manner in HUVECs. IGF2BP1 positively regulated JAK2 expression through directly binding to an m6A site within JAK2 mRNA in HUVECs. METTL3 knockdown weakened the interaction of JAK2 and IGF2BP1. METTL3 exerted its functions through JAK2/STAT3 pathway. In conclusion, METTL3 knockdown prevented AS progression by inhibiting JAK2/STAT3 pathway via IGF2BP1.
Human Telomerase RNA Protein Encoded by Telomerase RNA is Involved in Metabolic Responses
Authors: Shliapina Viktoriia , Koriagina Mariia , Vasilkova Daria , Govorun Vadim , Dontsova Olga , Rubtsova Maria
Published: December 2021

Cell proliferation is associated with increased energy and nutrients consumption. Metabolism switch from oxidative phosphorylation to glycolysis and telomerase activity are induced during stimulation of proliferation, such as tumorigenesis, immune cell activation, and stem cell differentiation, among others. Telomerase RNA is one of the core components of the telomerase complex and participates in survival mechanisms that are activated under stress conditions. Human telomerase RNA protein (hTERP) is encoded by telomerase RNA and has been recently shown to be involved in autophagy regulation. In this study, we demonstrated the role of hTERP in the modulation of signaling pathways regulating autophagy, protein biosynthesis, and cell proliferation. The AMPK signaling pathway was affected in cells deficient of hTERP and when hTERP was overexpressed. The appearance of hTERP is important for metabolism switching associated with the accelerated proliferation of cells in healthy and pathological processes. These findings demonstrate the connection between telomerase RNA biogenesis and function and signaling pathways.
A Novel Circular RNA CircRFX3 Serves as a Sponge for MicroRNA-587 in Promoting Glioblastoma Progression via Regulating PDIA3
Authors: Li Tong , Xu Jianguo , Liu Yi
Published: December 2021

An increasing number of studies have indicated that circular RNAs (circRNAs) participate in the progression of numerous tumors. However, the functions of circRNAs in glioblastoma (GBM) remain largely unknown. In this study, we focused on a novel circRNA (hsa_circRFX3_003) that was spliced from RFX3, which we named circRFX3. We confirmed that the expression of circRFX3 was substantially increased in GBM cell lines and clinical GBM tissues. The results of a series of overexpression and knockdown assays indicated that circRFX3 could boost the proliferation, invasion, and migration of GBM cells. By performing dual-luciferase reporter gene and RNA pull-down assays, we verified that circRFX3 could sponge microRNA-587 (miR-587) to exercise its function as a competing endogenous RNA (ceRNA) in the development of GBM. In addition, PDIA3 was proven to be a downstream target of miR-587 and to regulate the Wnt/β-catenin pathway. In conclusion, circRFX3 could act as a cancer-promoting circRNA to boost the development of GBM and regulate the miR-587/PDIA3/β-catenin axis. This study might provide a novel target for the treatment of GBM with molecular therapy.
Weight Loss in Cancer Patients Correlates With p38β MAPK Activation in Skeletal Muscle
Authors: Zhang Guohua , Anderson Lindsey J. , Gao Song , Sin Thomas K. , Zhang Zicheng , Wu Hongyu , Jafri Syed H. , Graf Solomon A. , Wu Peter C. , Dash Atreya , Garcia Jose M. , Li Yi-Ping
Published: December 2021

Unintentional weight loss, a first clinical sign of muscle wasting, is a major threat to cancer survival without a defined etiology. We previously identified in mice that p38β MAPK mediates cancer-induced muscle wasting by stimulating protein catabolism. However, whether this mechanism is relevant to humans is unknown. In this study, we recruited men with cancer and weight loss (CWL) or weight stable (CWS), and non-cancer controls (NCC), who were consented to rectus abdominis (RA) biopsy and blood sampling (n = 20/group). In the RA of both CWS and CWL, levels of activated p38β MAPK and its effectors in the catabolic pathways were higher than in NCC, with progressively higher active p38β MAPK detected in CWL. Remarkably, levels of active p38β MAPK correlated with weight loss. Plasma analysis for factors that activate p38β MAPK revealed higher levels in some cytokines as well as Hsp70 and Hsp90 in CWS and/or CWL. Thus, p38β MAPK appears a biomarker of weight loss in cancer patients.
Mutual Modulation Between Extracellular Vesicles and Mechanoenvironment in Bone Tumors
Authors: Urciuoli Enrica , Peruzzi Barbara
Published: December 2021

The bone microenvironment homeostasis is guaranteed by the balanced and fine regulated bone matrix remodeling process. This equilibrium can be disrupted by cancer cells developed in the bone (primary bone cancers) or deriving from other tissues (bone metastatic lesions), through a mechanism by which they interfere with bone cells activities and alter the microenvironment both biochemically and mechanically. Among the factors secreted by cancer cells and by cancer-conditioned bone cells, extracellular vesicles (EVs) are described to exert pivotal roles in the establishment and the progression of bone cancers, by conveying tumorigenic signals targeting and transforming normal cells. Doing this, EVs are also responsible in modulating the production of proteins involved in regulating matrix stiffness and/or mechanotransduction process, thereby altering the bone mechanoenvironment. In turn, bone and cancer cells respond to deregulated matrix stiffness by modifying EV production and content, fueling the vicious cycle established in tumors. Here, we summarized the relationship between EVs and the mechanoenvironment during tumoral progression, with the final aim to provide some innovative perspectives in counteracting bone cancers.
Mechanisms of FA-Phagy, a New Form of Selective Autophagy/Organellophagy
Authors: Lu Jiayi , Linares Bernard , Xu Zhen , Rui Yan-Ning
Published: December 2021

Focal adhesions (FAs) are adhesive organelles that attach cells to the extracellular matrix and can mediate various biological functions in response to different environmental cues. Reduced FAs are often associated with enhanced cell migration and cancer metastasis. In addition, because FAs are essential for preserving vascular integrity, the loss of FAs leads to hemorrhages and is frequently observed in many vascular diseases such as intracranial aneurysms. For these reasons, FAs are an attractive therapeutic target for treating cancer or vascular diseases, two leading causes of death world-wide. FAs are controlled by both their formation and turnover. In comparison to the large body of literature detailing FA formation, the mechanisms of FA turnover are poorly understood. Recently, autophagy has emerged as a major mechanism to degrade FAs and stabilizing FAs by inhibiting autophagy has a beneficial effect on breast cancer metastasis, suggesting autophagy-mediated FA turnover is a promising drug target. Intriguingly, autophagy-mediated FA turnover is a selective process and the cargo receptors for recognizing FAs in this process are context-dependent, which ensures the degradation of specific cargo. This paper mainly reviews the cargo recognition mechanisms of FA-phagy (selective autophagy-mediated FA turnover) and its disease relevance. We seek to outline some new points of understanding that will facilitate further study of FA-phagy and precise therapeutic strategies for related diseases associated with aberrant FA functions.
Bilaterally Asymmetric Helical Myofibrils in Ascidian Tadpole Larvae
Authors: Matsuo Koichi , Tamura Ryota , Hotta Kohji , Okada Mayu , Takeuchi Akihisa , Wu Yanlin , Hashimoto Koh , Takano Hidekazu , Momose Atsushi , Nishino Atsuo
Published: December 2021

The locomotor system is highly bilateral at the macroscopic level. Homochirality of biological molecules is fully compatible with the bilateral body. However, whether and how single-handed cells contribute to the bilateral locomotor system is obscure. Here, exploiting the small number of cells in the swimming tadpole larva of the ascidian Ciona, we analyzed morphology of the tail at cellular and subcellular scales. Quantitative phase-contrast X-ray tomographic microscopy revealed a high-density midline structure ventral to the notochord in the tail. Muscle cell nuclei on each side of the notochord were roughly bilaterally aligned. However, fluorescence microscopy detected left-right asymmetry of myofibril inclination relative to the longitudinal axis of the tail. Zernike phase-contrast X-ray tomographic microscopy revealed the presence of left-handed helices of myofibrils in muscle cells on both sides. Therefore, the locomotor system of ascidian larvae harbors symmetry-breaking left-handed helical cells, while maintaining bilaterally symmetrical cell alignment. These results suggest that bilateral animals can override cellular homochirality to generate the bilateral locomotor systems at the supracellular scale.
Poly-Phthalocyanine–Doped Graphene Oxide Nanosheet Conjugates for Electrocatalytic Oxidation of Drug Residues
Authors: Chundu Prince , Dube Edith , Zinyama Ngceboyakwethu P. , Moyo Mambo , Shumba Munyaradzi
Published: December 2021

Donor and acceptor phthalocyanine molecules were copolymerized and linked to graphene oxide nanosheets through amidation to yield electrocatalytic platforms on glassy carbon electrodes. The platforms were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, UV/Vis spectroscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The fabricated electrochemical catalytic surfaces were then evaluated toward electrocatalytic detection of ascorbic acid and tryptophan. These were characterized by a wide linear dynamic range and low limits of detection and quantification of 2.13 and 7.12 µM for ascorbic acid and 1.65 and 5.5 µM for tryptophan, respectively. The catalytic rate constant was 1.86 × 104and 1.51 × 104 M−1s−1for ascorbic acid and tryptophan, respectively. The Gibbs energy for catalytic reactions was −17.45 and −14.83 kJ mol−1depicting a spontaneous reaction on the electrode surface. The sensor platform showed an impressive recovery when applied in real samples such as fresh cow milk, in the range 91.71–106.73% for both samples. The developed sensor therefore shows high potential for applicability for minute quantities of the analytes in real biological samples.
Structure of Simple Dipolar Water-Like Fluids: Primitive Model and Hard Tetrahedra
Authors: Nezbeda I.
Published: December 2021

Dipolar versions of two qualitatively different types of simple short range model fluids which exhibit the phenomenon of hydrogen bonding and which could thus serve as a reference in equations of state for associating fluids have been considered: the primitive model of water descending from the TIP4P model and the fluid of hard tetrahedra. The hydrogen bonding structure exhibited by the latter model results from purely repulsive interactions whereas in the first model the “hydrogen bonding interaction” is explicitly incorporated in the model. Since the water molecules bear a strong dipole moment, the effect of the added dipole-dipole interaction on the structure of the two short-range models is therefore examined considering them both in the full and screened dipole-dipole modifications. It is found that the hydrogen bonding structure in the primitive model resulting from the site-site interactions is so strong that the additional dipole-dipole interaction has only a marginal effect on its structure and contributes thus only to the internal energy. On the contrary, even only a weak dipole-dipole interaction destroys the original hydrogen bonding structure of the hard tetrahedron fluid; to preserve it, a screened dipole-dipole interaction has to be used in the equation of state development.
A Fast and Easy-To-Go Method for the Preparation of Au Nanocluster and Its Application for Fe(III) Cation Sensing
Authors: Zhu Peibin , Chen Wen , Liu Liang
Published: December 2021

In this article, we reported the synthesis and characterization of gold nanoclusters (AuNCs) with a diameter of ∼2 nm. A simple method of microwave-assisted reaction was applied here, with L-cysteine as both reducing agent and stabilizer. The resulting AuNCs were analyzed by means of TEM, XPS, DLS, and IR. Their photophysical performance was then analyzed in detail, including UV-vis absorption, emission, quantum yield, and lifetime. Efficient red emission was observed from these AuNCs, originating from ligand-to-metal nanoparticle core charge transfer (LMNCT). This red emission was found quenchable by Fe(III) cations. The corresponding quenching curve and sensing performance were discussed. An effective working region of 0–80 μM with an LOD of 3.9 μM was finally observed. Their quenching mechanism was revealed as Fe(III) energy competing for the LMNCT process. The novelty and advancement of this work is the simple synthesis and impressive sensing performance, including wide working region, good linearity, and selectivity.
Click Pt(IV)-Carbohydrates Pro-Drugs for Treatment of Osteosarcoma
Authors: Moynihan Eoin , Bassi Giada , Ruffini Andrea , Panseri Silvia , Montesi Monica , Velasco-Torrijos Trinidad , Montagner Diego
Published: December 2021

The selectivity vs. cancer cells has always been a major challenge for chemotherapeutic agents and in particular for cisplatin, one of the most important anticancer drugs for the treatment of several types of tumors. One strategy to overtake this challenge is to modify the coordination sphere of the metallic center with specific vectors whose receptors are overexpressed in the tumoral cell membrane, such as monosaccharides. In this paper, we report the synthesis of four novel glyco-modified Pt(IV) pro-drugs, based on cisplatin scaffold, and their biological activity against osteosarcoma (OS), a malignant tumor affecting in particular adolescents and young adults. The sugar moiety and the Pt scaffold are linked exploiting the Copper Azide Alkyne Cycloaddition (CUAAC) reaction, which has become the flagship of click chemistry due to its versatility and mild conditions. Cytotoxicity and drug uptake on three different OS cell lines as well as CSCs (Cancer Stem Cell) are described.
Characteristics of Fecal Microbiota and Machine Learning Strategy for Fecal Invasive Biomarkers in Pediatric Inflammatory Bowel Disease
Authors: Wang Xinqiong , Xiao Yuan , Xu Xu , Guo Li , Yu Yi , Li Na , Xu Chundi
Published: December 2021

Background

Early diagnosis and treatment of pediatric Inflammatory bowel disease (PIBD) is challenging due to the complexity of the disease and lack of disease specific biomarkers. The novel machine learning (ML) technique may be a useful tool to provide a new route for the identification of early biomarkers for the diagnosis of PIBD.

Methods

In total, 66 treatment naive PIBD patients and 27 healthy controls were enrolled as an exploration cohort. Fecal microbiome profiling using 16S rRNA gene sequencing was performed. The correlation between microbiota and inflammatory and nutritional markers was evaluated using Spearman’s correlation. A random forest model was used to set up an ML approach for the diagnosis of PIBD using 1902 markers. A validation cohort including 14 PIBD and 48 irritable bowel syndrome (IBS) was enrolled to further evaluate the sensitivity and accuracy of the model.

Result

Compared with healthy subjects, PIBD patients showed a significantly lower diversity of the gut microbiome. The increased Escherichia-Shigella and Enterococcus were positively correlated with inflammatory markers and negatively correlated with nutrition markers, which indicated a more severe disease. A diagnostic ML model was successfully set up for differential diagnosis of PIBD integrating the top 11 OTUs. This diagnostic model showed outstanding performance at differentiating IBD from IBS in an independent validation cohort.

Conclusion

The diagnosis penal based on the ML of the gut microbiome may be a favorable tool for the precise diagnosis and treatment of PIBD. A study of the relationship between disease status and the microbiome was an effective way to clarify the pathogenesis of PIBD.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Membrane (M) and Spike (S) Proteins Antagonize Host Type I Interferon Response
Authors: Zhang Qi , Chen Zhiqiang , Huang Chenxiao , Sun Jiuyuan , Xue Minfei , Feng Tingting , Pan Wen , Wang Kezhen , Dai Jianfeng
Published: December 2021

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide and has infected more than 250 million people. A typical feature of COVID-19 is the lack of type I interferon (IFN-I)-mediated antiviral immunity in patients. However, the detailed molecular mechanisms by which SARS-CoV-2 evades the IFN-I-mediated antiviral response remain elusive. Here, we performed a comprehensive screening and identified a set of SARS-CoV-2 proteins that antagonize the IFN-I response. Subsequently, we characterized the mechanisms of two viral proteins antagonize IFN-I production and downstream signaling. SARS-CoV-2 membrane protein binds to importin karyopherin subunit alpha-6 (KPNA6) to inhibit interferon regulatory factor 3(IRF3) nuclear translocation. Further, the spike protein interacts with signal transducer and activator of transcription 1 (STAT1) to block its association with Janus kinase 1 (JAK1). This study increases our understanding of SARS-CoV-2 pathogenesis and suggests novel therapeutic targets for the treatment of COVID-19.
Oral Colonization by Entamoeba gingivalis and Trichomonas tenax: A PCR-Based Study in Health, Gingivitis, and Periodontitis
Authors: Yaseen Alaa , Mahafzah Azmi , Dababseh Deema , Taim Duaa , Hamdan Ahmad A. , Al-Fraihat Esraa , Hassona Yazan , Şahin Gülşen Özkaya , Santi-Rocca Julien , Sallam Malik
Published: December 2021

Background

The etiology of periodontitis remains unclear, as is the place of gingivitis in its pathophysiology. A few studies linked the colonization by oral parasites (Entamoeba gingivalis and Trichomonas tenax) to periodontal disease and its severity. The aim of the current study was to estimate the prevalence of these oral parasites among healthy individuals, and in patients with gingivitis and periodontitis in Jordan.

Methods

The study was conducted during July 2019–December 2019. Samples were composed of saliva and periodontal material including dental plaque sampled with probes. The detection of oral parasites was done using conventional polymerase chain reaction (PCR).

Results

The total number of study participants was 237: healthy (n=94), gingivitis (n=53) and periodontitis (n=90). The prevalence of E. gingivalis was 88.9% among the periodontitis patients, 84.9% among the gingivitis patients and 47.9% in the healthy group. For T. tenax, the prevalence was 25.6% among the periodontitis patients, 5.7% among the gingivitis patients and 3.2% in the heathy group. Positivity for E. gingivalis was significantly correlated with the presence of periodontal disease compared to the healthy group with odds ratio (OR) of 6.6. Periodontal disease was also correlated with lower monthly income (OR=8.2), lack of dental care (OR=4.8), and history of diabetes mellitus (OR=4.5). Colonization by E. gingivalis was correlated with gingivitis (OR=6.1) compared to the healthy group. Colonization by E. gingivalis and T. tenax were significantly correlated with periodontitis (OR=6.4 for E. gingivalis, and OR=4.7, for T. tenax) compared to the healthy group. T. tenax was only detected among individuals with generalized periodontal disease compared to its total absence among those with localized disease (19.6% vs. 0.0%; p=0.039). The co-infection rate by the two oral parasites was 11.0%.

Conclusions

The higher prevalence of human oral parasites in periodontal disease compared to healthy individuals appears to be more than a mere marker for the disease and might also be associated with disease severity and potential for progression. Thus, the dogmatic view of E. gingivalis and T. tenax as commensals needs to be re-evaluated and their contribution to pathophysiology of periodontal diseases cannot be neglected.
Empowering Skepticism: Neuroethics Engagement with Tibetan Buddhist Monastics
Authors: Specker Sullivan Laura
Published: December 2021

Neuroethics has been incorporated into neuroscience training through the Science for Monks program since 2016. In this article, I describe this in-progress effort and I consider how the program has changed since this first year to develop into a pilot program in community-engaged participatory research with the monastic community. The current goals of the project are to train the monastics in social science research skills as a means of empowering them to harness their deep knowledge of ethics and to bring it to bear on ethical challenges in neuroscience, neurology, and neurotechnology.
Are Bumblebees Relevant Models for Understanding Wild Bee Decline?
Authors: Ghisbain Guillaume
Published: December 2021

The unsustainable use of ecosystems by human societies has put global biodiversity in peril. Bees are, in this context, a popular example of a highly diversified group of pollinators whose collapse is a major concern given the invaluable ecosystem services they provide. Amongst them, bumblebees (Bombus) have increasingly drawn the attention of scientists due to their dramatic population declines globally. This regression has converted them into popular conservation entities, making them the second most studied group of bees worldwide. However, in addition to have become relevant models in the fields of ecology, evolution and biogeography, bumblebees have also been used as models for studying wild bee decline and conservation worldwide. Integrating evidence from the comparative ecology and resilience of bumblebees and wild bees, I discuss the relevance of usingBombusas radars for wild bee decline worldwide. Responses of bumblebees to environmental changes are generally not comparable with those of wild bees because of their relatively long activity period, their inherent sensitivity to high temperatures, their relatively generalist diet breadth and many aspects arising from their eusocial behavior. Moreover, important differences in the available historical data between bumblebees and other bees make comparisons of conservation status even more arduous. Overall, these results reinforce the need for conservation actions that consider a higher level of understanding of ecological diversity in wild bees, highlight the need for an updated and more extensive sampling of these organisms, and emphasize that more caution is required when extrapolating trends from model species.