critical pathway
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2021 ◽  
Vol 4 (4) ◽  
pp. 135-144
Author(s):  
Ferdinand D. Anabo

Household income diversification is a critical pathway to improve the living standard of agricultural households. It is the process by which households actively seek to increase the number of income-generating activities. This study sought to describe the prevalence and patterns of income diversification among agricultural households and to identify the factors related to the degree of income diversification. The study applied a quantitative research design using a cross-sectional survey from the Philippine Statistics Authority. The fractional response regression model was used to determine the factors affecting income diversification. Results revealed that most of the household samples have two income sources. Most come from agricultural labor, crop farming, and gardening. Factors related to income diversification are sex, age, education, family size, being married, agricultural income, access to credit, cash support, access to electricity and water, access to information and communication, and vehicle ownership.


2021 ◽  
Author(s):  
Nicolas Millet ◽  
Norma Veronica Solis ◽  
Diane Aquilar ◽  
Michail S. Lionakis ◽  
Robert T. Wheeler ◽  
...  

During infection the host relies on pattern-recognition receptors to sense invading fungal pathogens to launch immune defense mechanisms. While fungal recognition and immune effector responses are organ and cell type specific, during disseminated candidiasis myeloid cells exacerbate collateral tissue damage. However, the complex interplay between protective antifungal immunity and immunopathology remains incompletely understood. The β-glucan receptor ephrin type-A 2 receptor (EphA2) is required to initiate mucosal inflammatory responses during oral Candida infection. Here we report that Epha2 promotes renal immunopathology during disseminated candidiasis. EphA2 deficiency leads to reduced renal inflammation and injury. Comprehensive analyses reveal that EphA2 limits IL-23 secretion in dendritic cells, while IL-23 signaling prevents ferroptotic myeloid cell death during infection. Further, ferroptosis aggravates inflammation during infection, while at the same time reducing the fungal killing capacity of macrophages. Thus, we identify ferroptotic cell death as a critical pathway of Candida-mediated renal immunopathology that opens a new avenue to tackle Candida infection and inflammation.


Geofluids ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Bin Liu ◽  
Li Yang ◽  
Jiangxin Chen ◽  
Leonardo Azevedo ◽  
Tonggang Han

Pipe structures are considered as fluid conduits beneath cold seeps. These structures have been observed in many geological settings and are widely accepted as the most critical pathway for fluid migration. One of such pipe structures in the Haima cold seep region is investigated herein. The pipe structure extends from below the BSR and reaches the seafloor. It is characterized by a string of events with short and strong seismic amplitudes, similar to the string of bead reflections (SBRs) associated with small-scale caves in carbonate reservoirs. This leads to the hypothesis that multiple small-scale bodies exist within the pipe structure. We test this hypothesis by analysis of diffraction waves and numerical seismic modeling. Travel time pattern analysis indicates that the diffractors within the pipe structure caused the rich diffraction waves on the shot records, and the reversed polarity indicates that the diffractors have a lower impedance than the surrounding sediments. These low-impedance bodies are interpreted as gas pockets within the pipe structures. Based on these interpretations, a conceptual model is proposed to describe the fluid migration process within the pipe. Briefly, we propose that gas pockets within the pipe structure could be analogue to the magma chambers located beneath volcanoes and this may provide a new insight into how gases migrate through the pipe structure and reach the seafloor.


2021 ◽  
Author(s):  
Yusuke Fujioka ◽  
Kaori Kawai ◽  
Kuniyuki Endo ◽  
Minaka Ishibashi ◽  
Nobuyuki Iwade ◽  
...  

Psychosocial stress can impact feeding behavior outcomes. Although many studies have examined alterations to food intake, little is known about how stress affects feeding behavior patterns. To determine the impact of psychological stress on feeding behavior patterns, mice were subjected to various psychosocial stressors (social isolation, intermittent high-fat-diet, or physical restraint) prior to timed observations in a feeding arena that incorporated multiple bait loci. In addition, in vivo microdialysis was used to assess the effects of stressors on the reward system by measuring dopamine levels in the nucleus accumbens (NAcc) shell. Impaired feeding behavior patterns characterized by significant deviations in bait selection (i.e. fixated feeding) and prolonged periods of eating (i.e. protracted feeding) were observed in stressed mice relative to non-stressed controls. In addition to clear behavioral effects, the stressors also negatively impacted dopamine levels at the nucleus accumbens shell. Normalization of dopamine reversed the fixated feeding behavior, whereas specifically inhibiting neuronal activity in the dopaminergic neurons of the ventral tegmental area that project to the nucleus accumbens shell caused similar impairments in feeding. Given that the deviations were not consistently accompanied by changes in the amount of bait consumed, body weight, or metabolic factors, the qualitative effects of psychosocial stressors on feeding behavior likely reflect perturbations to a critical pathway in the mesolimbic dopamine system. These findings provide compelling evidence that aberrations in feeding behavior patterns can be developed as sensitive biomarkers of psychosocial stress and possibly a prodromal state of neuropsychiatric diseases.


2021 ◽  
Author(s):  
Sonia Thapa ◽  
Rafiq A. Rather ◽  
Shashank K. Singh ◽  
Madhulika Bhagat

Oncogene addiction, a term first coined by Bernard Weinstein in 2000, refers to a condition where a tumor cell, despite harboring a multitude of genetic alterations, depends on a single oncogenic pathway or oncoprotein for sustained proliferation and survival. Several lines of evidence from mammalian cell culture models, genetically modified mice models, and human intervention trials of targeted drugs have revealed that many tumors, if not all, rely on oncogene addiction for sustained proliferation and survival. Oncogene addiction strongly impacts the therapeutic response of tumors to acute oncoprotein inhibition. An important implication of oncogene addiction is that inhibiting this critical pathway, on which cancer cells become dependent, can cause selective and specific cell death in cancer cells while sparing normal surrounding cells that are not oncogene addicted. However, the mechanism by which cancer cells become dependent on a single pathway or activated oncoprotein is not precisely understood in most cases. Thus, a better understanding of oncogene addiction may provide a rationale for improving current cancer therapies and help develop novel therapeutic strategies for the management of cancer.


2021 ◽  
Author(s):  
Qiming Li ◽  
Gang Deng ◽  
Yunlei He ◽  
Jiafeng Yang

Abstract Purpose: To perform network pharmacological analysis so as to identify and screen the active ingredients of Jianpi Yiqi Formula; find its core target and explore its mechanism in the treatment of idiopathic thrombocytopenic purpura (ITP). Materials and Methods: A network pharmacology approach was used to inquire and screen the active ingredients from the Traditional Chinese Medicine System Pharmacology (TCMSP) database for potential active compounds that are commonly contained in the Jianpi Yiqi formula. The Swiss Target Prediction database was used for the prediction of the active ingredient's target of the action; the genecard database was used to search for target genes associated with ITP and to screen for target genes, in which the drug target was intersected with the disease target. Protein interaction network was constructed using string database software for GO and KEGG analysis to construct the "component/target/pathway" pharmacology network of Jianpi Yiqi granules therapy for ITP. Cytoscape 3.7.2 software was harnessed to visualize and integrate this network. The Virtua Drug web-based pharmacology website ( https://www.dockingserver.com ) was used to validate the regulatory relationship between key active compounds and critical pathway molecular signals by molecular docking. Results: Two key active ingredients, quercetin, and kaempferol, were selected from hundreds of herbal ingredients referenced in online pharmacological studies. Molecular docking analysis revealed that quercetin and kaempferol could stably bind PI3K/AKT and exert inhibitory effects, respectively. It was also speculated that PI3K/AKT/mTOR pathway might be the critical pathway for the pharmacokinetic mechanism of Jianpi Yiqi Granules. Conclusion: The present study suggests the multi-component effect characteristic of the treatment of ITP with Jianpi Yiqi granules, thus providing a theoretical basis for the clinical use of Jianpi Yiqi formula.


Author(s):  
Maud J. F. Landers ◽  
Stephan P. L. Meesters ◽  
Martine van Zandvoort ◽  
Wouter de Baene ◽  
Geert-Jan M. Rutten

AbstractFocal white matter lesions can cause cognitive impairments due to disconnections within or between networks. There is some preliminary evidence that there are specific hubs and fiber pathways that should be spared during surgery to retain cognitive performance. A tract potentially involved in important higher-level cognitive processes is the frontal aslant tract. It roughly connects the posterior parts of the inferior frontal gyrus and the superior frontal gyrus. Functionally, the left frontal aslant tract has been associated with speech and the right tract with executive functions. However, there currently is insufficient knowledge about the right frontal aslant tract’s exact functional importance. The aim of this study was to investigate the role of the right frontal aslant tract in executive functions via a lesion-symptom approach. We retrospectively examined 72 patients with frontal glial tumors and correlated measures from tractography (distance between tract and tumor, and structural integrity of the tract) with cognitive test performances. The results indicated involvement of the right frontal aslant tract in shifting attention and letter fluency. This involvement was not found for the left tract. Although this study was exploratory, these converging findings contribute to a better understanding of the functional frontal subcortical anatomy. Shifting attention and letter fluency are important for healthy cognitive functioning, and when impaired they may greatly influence a patient’s wellbeing. Further research is needed to assess whether or not damage to the right frontal aslant tract causes permanent cognitive impairments, and consequently identifies this tract as a critical pathway that should be taken into account during neurosurgical procedures.


2021 ◽  
Author(s):  
Lauren C. Panzera ◽  
Ben Johnson ◽  
In Ha Cho ◽  
Michael M. Tamkun ◽  
Michael B. Hoppa

The endoplasmic reticulum (ER) forms a continuous and dynamic network throughout a neuron, extending from dendrites to axon terminals, and axonal ER dysfunction is implicated in several neurological disorders. In addition, tight junctions between the ER and plasma membrane (PM) are formed by several molecules including Kv2 channels, but the cellular functions of many ER-PM junctions remain unknown. Dynamic Ca2+ uptake into the ER during electrical activity plays an essential role in synaptic transmission as failure to allow rapid ER Ca2+ filling during stimulation activates stromal interaction molecule 1 (STIM1) and decreases both presynaptic Ca2+ influx and synaptic vesicle exocytosis. Our experiments demonstrate that Kv2.1 channels are necessary for enabling ER Ca2+ uptake during electrical activity as genetic depletion of Kv2.1 rendered both the somatic and axonal ER unable to accumulate Ca2+ during electrical stimulation. Moreover, our experiments show that the loss of Kv2.1 in the axon impairs synaptic vesicle fusion during stimulation via a mechanism unrelated to modulation of membrane voltage. Thus, our data demonstrate that the non-conducting role of Kv2.1 in forming stable junctions between the ER and PM via ER VAMP-associated protein (VAP) binding couples ER Ca2+ uptake with electrical activity. Our results further suggest that Kv2.1 has a critical function in neuronal cell biology for Ca2+-handling independent of voltage and reveals a novel and critical pathway for maintaining ER lumen Ca2+ levels and efficient neurotransmitter release. Taken together these findings reveal an essential non-classical role for both Kv2.1 and the ER-PM junctions in synaptic transmission.


2021 ◽  
Vol 38 (12) ◽  
Author(s):  
Li Su ◽  
Jicheng Zhang ◽  
Xinglong Zhang ◽  
Lei Zheng ◽  
Zhifa Zhu

AbstractGallbladder cancer (GBC), the most common malignancy in the biliary tract, is highly lethal malignant due to seldomly specific symptoms in the early stage of GBC. This study aimed to identify exosome-derived miRNAs mediated competing endogenous RNAs (ceRNA) participant in GBC tumorigenesis. A total of 159 differentially expressed miRNAs (DEMs) was identified as exosome-derived miRNAs, contains 34 upregulated exo-DEMs and 125 downregulated exo-DEMs based on the expression profiles in GBC clinical samples downloaded from the Gene Expression Omnibus database with the R package. Among them, 2 up-regulated exo-DEMs, hsa-miR-125a-3p and hsa-miR-4647, and 5 down-regulated exo-DEMs, including hsa-miR-29c-5p, hsa-miR-145a-5p, hsa-miR-192-5p, hsa-miR-194-5p, and hsa-miR-338-3p, were associated with the survival of GBC patients. Results of the gene set enrichment analysis showed that the cell cycle-related pathways were activated in GBC tumor tissues, mainly including cell cycle, M phase, and cell cycle checkpoints. Furthermore, the dysregulated ceRNA network was constructed based on the lncRNA-miRNA-mRNA interactions using miRDB, TargetScan, miRTarBase, miRcode, and starBase v2.0., consisting of 27 lncRNAs, 6 prognostic exo-DEMs, and 176 mRNAs. Together with prognostic exo-DEMs, the STEAP3-AS1/hsa-miR-192-5p/MAD2L1 axis was identified, suggesting lncRNA STEAP3-AS1, might as a sponge of exosome-derived hsa-miR-192-5p, modulates cell cycle progression via affecting MAD2L1 expression in GBC tumorigenesis. In addition, the biological functions of genes in the ceRNA network were also annotated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Our study promotes exploration of the molecular mechanisms associated with tumorigenesis and provide potential targets for GBC diagnosis and treatment.


2021 ◽  
Vol 35 (1) ◽  
pp. S39-S39
Author(s):  
Heeyoung Kim ◽  
Manki Ju ◽  
Jung Jun Lee ◽  
Sunyoung Son

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