La caracara (cherimoya) Ramesh, Divya
Latin American Literary Review,
11/2019, Volume:
46, Issue:
92
Journal Article
Peer reviewed
Open access
A writer is the sum and extension of what she has had the privilege to read. A chance encounter, years ago, with Derek Sheffield’s “She Gathers Rocks” (The Georgia Review, 2016), inspired this poem ...now. Here, Divya tries to capture the stories of another kind of parent, of another kind of family—relevant and important in our present times.
Endurance exercise is an effective therapeutic intervention with substantial pro-healthspan effects. Male Drosophila respond to a ramped daily program of exercise by inducing conserved physiological ...responses similar to those seen in mice and humans. Female flies respond to an exercise stimulus but do not experience the adaptive training response seen in males. Here, we use female flies as a model to demonstrate that differences in exercise response are mediated by differences in neuronal activity. The activity of octopaminergic neurons is specifically required to induce the conserved cellular and physiological changes seen following endurance training. Furthermore, either intermittent, scheduled activation of octopaminergic neurons or octopamine feeding is able to fully substitute for exercise, conferring a suite of pro-healthspan benefits to sedentary Drosophila. These experiments indicate that octopamine is a critical mediator of adaptation to endurance exercise in Drosophila.
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•Exercise adaptations in Drosophila are sexually dimorphic•Octopamine (OA) is necessary and sufficient for exercise adaptation in Drosophila•Stimulation of OA-ergic neurons fully mimics exercise in sedentary flies
Chronic exercise causes stereotypical adaptations in muscle and adipose tissue of Drosophila. Sujkowski et al. show that these adaptations require the activity of octopaminergic neurons. Differences in octopaminergic activity control sexual dimorphism in exercise response. Both octopamine feeding and stimulation of octopaminergic neurons can substitute for endurance exercise.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Locomotion and mobility have been studied extensively in
Drosophila melanogaster
but less is known about the locomotor capacity of other
Drosophila
species, while the response to chronic exercise in ...other species has yet to be examined. We have shown that adult male
D. melanogaster
adapt to exercise training with improved running endurance, climbing speed, and flight ability compared to unexercised flies. Here, we examine baseline mobility of
D. sechellia
,
D. simulans
, and
D. virilis
, and their response to chronic exercise training. We found significant interspecific differences in mobility and in the response to exercise. Although there is a significant sex difference in exercise adaptations in
D. melanogaster
, intraspecific analysis reveals few sex differences in other
Drosophila
species. As octopamine has been shown to be important for exercise adaptations in
D. melanogaster,
we also asked if any observed differences could be attributed to baseline octopamine levels. We find that octopamine and tyramine levels have the same rank order as baseline climbing speed and endurance in males, but do not predict the response to chronic exercise in males or females. Future research should focus on determining the mechanisms responsible for the inter- and intraspecific differences in mobility and the response to exercise.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Extracellular vesicles (EVs) are lipid-bound vesicles produced into the extracellular space by cells. Apoptotic bodies (ApoBD), microvesicles (MVs), and exosomes are examples of EVs, which act as ...essential regulators in cell-cell communication in both normal and diseased conditions. Natural cargo molecules such as miRNA, messenger RNA, and proteins are carried by
EVs and transferred to nearby cells or distant cells through the process of circulation. Different signalling cascades are then influenced by these functionally active molecules. The information to be delivered to the target cells depends on the substances within the
EVs that also includes synthesis method.
EVs have attracted interest as potential delivery vehicles for therapies due to their features such as improved circulation stability, biocompatibility, reduced immunogenicity, and toxicity. Therefore,
EVs are being regarded as potent carriers of therapeutics that can be used as a therapeutic agent for diseases like cancer. This review focuses on the exosome-mediated drug delivery to cancer cells and the advantages and challenges of using exosomes as a carrier molecule.
The monoacylglycerol lipase (MAGL) inhibitor 4-nitrophenyl 4-(dibenzod1,3dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) produces antinociceptive and anti-inflammatory effects. However, ...repeated administration of high-dose JZL184 (40 mg/kg) causes dependence, antinociceptive tolerance, cross-tolerance to the pharmacological effects of cannabinoid receptor agonists, and cannabinoid receptor type 1 (CB1) downregulation and desensitization. This functional CB1 receptor tolerance poses a hurdle in the development of MAGL inhibitors for therapeutic use. Consequently, the present study tested whether repeated administration of low-dose JZL184 maintains its antinociceptive actions in the chronic constriction injury of the sciatic nerve neuropathic pain model and protective effects in a model of nonsteroidal anti-inflammatory drug-induced gastric hemorrhages. Mice given daily injections of high-dose JZL184 (≥16 mg/kg) for 6 days displayed decreased CB1 receptor density and function in the brain, as assessed in (3)HSR141716A binding and CP55,940 (-)-cis-3-2-hydroxy-4-(1,1-dimethylheptyl)phenyl-trans-4-(3-hydroxypropyl) cyclohexanol-stimulated guanosine 5'-O-(3-(35)Sthio)triphosphate binding assays, respectively. In contrast, normal CB1 receptor expression and function were maintained following repeated administration of low-dose JZL184 (≤8 mg/kg). Likewise, the antinociceptive and gastroprotective effects of high-dose JZL184 underwent tolerance following repeated administration, but these effects were maintained following repeated low-dose JZL184 treatment. Consistent with these observations, repeated high-dose JZL184, but not repeated low-dose JZL184, elicited cross-tolerance to the common pharmacological effects of Δ(9)-tetrahydrocannabinol. This same pattern of effects was found in a rimonabant (5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide)-precipitated withdrawal model of cannabinoid dependence. Taken together, these results indicate that prolonged, partial MAGL inhibition maintains potentially beneficial antinociceptive and anti-inflammatory effects, without producing functional CB1 receptor tachyphylaxis/tolerance or cannabinoid dependence.
Prolonged exposure to drugs of abuse, such as cannabinoids and opioids, leads to pharmacological tolerance and receptor desensitization in the nervous system. We found that a similar form of ...functional antagonism was produced by sustained inactivation of monoacylglycerol lipase (MAGL), the principal degradative enzyme for the endocannabinoid 2-arachidonoylglycerol. After repeated administration, the MAGL inhibitor JZL184 lost its analgesic activity and produced cross-tolerance to cannabinoid receptor (CB1) agonists in mice, effects that were phenocopied by genetic disruption of Mgll (encoding MAGL). Chronic MAGL blockade also caused physical dependence, impaired endocannabinoid-dependent synaptic plasticity and desensitized brain CB1 receptors. These data contrast with blockade of fatty acid amide hydrolase, an enzyme that degrades the other major endocannabinoid anandamide, which produced sustained analgesia without impairing CB1 receptors. Thus, individual endocannabinoids generate distinct analgesic profiles that are either sustained or transitory and associated with agonism and functional antagonism of the brain cannabinoid system, respectively.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
BACKGROUND:A major research emphasis has been focused on defining the molecular changes that occur from acute to chronic pain to identify potential therapeutic targets for chronic pain. As the ...endocannabinoid system is dynamically involved in pain signaling, a plausible mechanism that may contribute to chronic pain vulnerability involves alterations in the amount of circulating endocannabinoids. Therefore, this study sought to examine cannabinoid type 1 (CNR1), type 2 (CNR2) receptors, fatty acid amide hydrolase (FAAH), and the vanilloid receptor (transient receptor potential cation channel subfamily V member 1 TRPV1) gene expression profiles among individuals with acute and chronic low back pain (cLBP) at their baseline visit. We also assessed associations among selected single nucleotide polymorphisms (SNPs) of FAAH and CNR2 and measures of somatosensory function and self-report pain measures.Using a previously established quantitative sensory testing protocol, we comprehensively assessed somatosensory parameters among 42 acute LBP, 42 cLBP, and 20 pain-free participants. Samples of whole blood were drawn to examine mRNA expression and isolate genomic DNA for genotyping.CNR2 mRNA was significantly upregulated in all LBP patients compared with controls. However, FAAH mRNA and TRPV1 mRNA were significantly upregulated in cLBP compared with controls. A significant association was observed between FAAH SNP genotype and self-report pain measures, mechanical and cold pain sensitivity among LBP participants. cLBP participants showed increased FAAH and TRPV1 mRNA expression compared with acute LBP patients and controls.Further research to characterize pain-associated somatosensory changes in the context of altered mRNA expression levels and SNP associations may provide insight on the molecular underpinnings of maladaptive chronic pain.
Aging is characterized by extensive metabolic reprogramming. To identify metabolic pathways associated with aging, we analyzed age-dependent changes in the metabolomes of long-lived
. Among the ...metabolites that changed, levels of tyrosine were increased with age in long-lived flies. We demonstrate that the levels of enzymes in the tyrosine degradation pathway increase with age in wild-type flies. Whole-body and neuronal-specific downregulation of enzymes in the tyrosine degradation pathway significantly extends
lifespan, causes alterations of metabolites associated with increased lifespan, and upregulates the levels of tyrosine-derived neuromediators. Moreover, feeding wild-type flies with tyrosine increased their lifespan. Mechanistically, we show that suppression of ETC complex I drives the upregulation of enzymes in the tyrosine degradation pathway, an effect that can be rescued by tigecycline, an FDA-approved drug that specifically suppresses mitochondrial translation. In addition, tyrosine supplementation partially rescued lifespan of flies with ETC complex I suppression. Altogether, our study highlights the tyrosine degradation pathway as a regulator of longevity.
Thyroid cancer is a common endocrine malignancy with a significant increase in its incidence in the past three decades. Even though research has significantly aided the management of the disease, the ...progression towards advanced forms of cancers remains indeterminate. In order to investigate the current challenges in thyroid cancer studies, the present work employed systematic and interactive transcriptomic data to construct plausible protein-protein interaction networks to reveal the putative transcriptional control mechanisms in cancer. The data from 4 different datasets consisting of normal samples vs thyroid cancer samples were chosen. Hypoxia being a significant hallmark of cancer was predicted to have a functional role in the progression of cancer. Consequently, prognostic pathways involved in cancer in response to hypoxia were predicted in the present study. The genes from the datasets were intersected with the hypoxia hallmark gene set to detect the significantly differentially expressed genes which were deregulated under the influence of hypoxia. These genes were analyzed by bioinformatic tools and a high correlation was found between 12 significant genes (PLAUR, BGN, SDC2, DUSP1, FOS, EGFR, CP, PPARGC1A, CITED2, RORA, HSPA5 and ACKR3) indicating a significant association between them. Of all the genes PLAUR was found to be novel and it was significantly upregulated under the influence of hypoxia. The hub genes and their role as predicted biomarkers were also determined by ROC curve analysis. This may assist in further research towards understanding role of hypoxia in Thyroid cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The majority of women experience pain during breastfeeding initiation with few strategies to manage breast and nipple pain. In fact, women cite breast and nipple pain as among the most common reasons ...for breastfeeding cessation. To address this important issue, we developed a breastfeeding self‐management (BSM) intervention, based on the Individual and Family Self‐Management Theory Framework. In this framework, self‐management is conceptualized as a process in which women use knowledge, beliefs, and social facilitation to achieve breastfeeding goals. The purpose of this longitudinal pilot randomized controlled trial was to test the feasibility, acceptability, and preliminary efficacy of the BSM intervention with women initiating breastfeeding. Recruitment of 60 women intending to breastfeed occurred within 48 hr of delivery and women were randomized to either the intervention or usual care group. The BSM intervention group received BSM education modules that included information of how to manage breast and nipple pain and self‐management support through biweekly texting from the study nurse, and were asked to complete a daily breastfeeding journal. Primary outcomes measured at baseline, 1, 2, and 6 weeks will be used to (a) evaluate feasibility, acceptability, and preliminary efficacy of the BSM intervention, and (b) assess the influence of protective and risk factors of breastfeeding pain (including individual genetic polymorphisms related to pain sensitivity) on process variables for self‐management of breastfeeding and breastfeeding pain, and on proximal (breastfeeding pain severity and interference, breastfeeding frequency) and distal outcomes (breastfeeding exclusivity and duration and general well‐being).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
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