The outbreak of Zika virus (ZIKV) and associated fetal microcephaly mandates efforts to understand the molecular processes of infection. Related flaviviruses produce noncoding subgenomic flaviviral ...RNAs (sfRNAs) that are linked to pathogenicity in fetal mice. These viruses make sfRNAs by co-opting a cellular exonudease via structured RNAs called xrRNAs. We found that ZIKV-infected monkey and human epithelial cells, mouse neurons, and mosquito cells produce sfRNAs. The RNA structure that is responsible for ZIKV sfRNA production forms a complex fold that is likely found in many pathogenic flaviviruses. Mutations that disrupt the structure affect exonudease resistance in vitro and sfRNA formation during infection. The complete ZIKV xrRNA structure clarifies the mechanism of exonudease resistance and identifies features that may modulate function in diverse flaviviruses.
Grain sorghum is an important staple food crop grown globally while sweet sorghum is increasingly considered as a promising biofuel feedstock. Biofuels are the major economic products from the ...processing of large quantities of biomass, which is currently being utilized to make value-added products in the biorefinery approach. To date, these value-added products are typically commodity chemicals and waste materials used in agriculture. However, there are opportunities to generate high-value bioactive compounds from sorghum grain and biomass. Chronic diseases, such as cancers, are the top causes for morbidity and mortality in developed nations and are promoted by inflammation and oxidative stress. Globally, colorectal cancer results in approximately one-half million deaths annually. It is estimated that as much as 80% of colorectal cancer cases can be attributed to environmental and dietary factors. The sorghum grain and ligno-cellulosic biomass generated for biofuel production has been reported to be high in bioactive compounds, including phenolic acids and flavonoids, with antioxidant and anti-inflammatory properties. This review focuses on the bioactive compounds of grain and sweet sorghum (Sorghum bicolor L. Moench), for their anti-inflammatory, antioxidant, anti-colon cancer, and immune modulator functions. The review summarizes previous efforts to identify and quantify bioactive compounds in sorghum and documents their anti-cancer biological activities. Finally, this review discusses bioactive compound extraction methodologies and technologies as well as considerations for incorporating these technologies into current biorefining practices.
There is a growing interest in the utilization of sweet sorghum as a renewable resource for biofuels. During the biofuel production process, large quantities of biomass are generated, creating a rich ...source of bioactive compounds. However, knowledge of sweet sorghum stalk is lacking. We measured the phenolic content (Folin-Ciocalteu assay), antioxidant activity (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) assay), and phytochemical composition (LC-MS) in both the pith and dermal layer of the stalk. We further tested the antiproliferative (5-bromo-2'- deoxyuridine assay) and proapoptotic (terminal deoxynucleotidyl transferase dUTP nick end labeling assay) activities of these extracts using HCT116 cells and colon cancer stem cells (CCSCs) with and without the tumor suppressor gene p53. For the first time, we show that the dermal layer extract of sweet sorghum contains more of the 3-deoxyanthocyanidins apigeninidin and luteolinidin than the pith, and this is associated with more anticancer activity. Furthermore, luteolinidin suppressed CCSC proliferation more than apigeninidin. In addition to being renewable biofuel, sweet sorghum may also serve as a source of health-promoting compounds.
Alpha-synuclein (α-syn) is a highly conserved protein encoded by the SNCA gene and is expressed uniquely in neurons of both the central and peripheral nervous systems (CNS and PNS). α-Syn is known to ...cause sporadic and familial forms of Parkinson's disease (PD). However, the role for neuronal expression of α-syn in the first place remains unknown. We review and discuss recently published work that suggests a novel role for α-syn expression in neurons as a restriction factor that inhibits virus transmission from the PNS to the CNS. The potential new role for α-syn expression as a virus inhibitor may provide new approaches to understand the pathogenesis of PD and provide novel approaches to prevent and treat this common neurodegenerative disease.
: The human health benefits from consumption of cranberry products have been associated with the fruits’ unique flavonoid composition, including a complex profile of anthocyanins and ...proanthocyanidins. However, when processed by techniques such as pressing, canning, concentrating, or drying, a number of these natural components may be compromised or inactivated due to physical separation, thermal degradation, or oxidation. Fresh cranberries were compared to freeze‐dried berries and individual fruit tissues (skin and peeled fruit). Products examined included cranberry juices (commercial and prepared from concentrate), cranberry sauces (commercial and homemade), and sweetened‐dried cranberries (commercial). Freeze‐drying resulted in no detectable losses of anthocyanins or proanthocyanidins from cranberry fruits. Anthocyanins were localized in the skin. Proanthocyanins were higher in the skin than in the flesh, with the exception of procyanidin A‐2 dimer which was concentrated in the flesh. Anthocyanins were significantly higher in not‐from‐concentrate juice than in reconstituted juice from concentrate (8.3 mg and 4.2 mg/100 mL, respectively). Similarly, proanthocyanidins were markedly higher in not‐from‐concentrate juice compared to juice from concentrate (23.0 mg and 8.9 mg/100 mL, respectively). Homemade sauce contained far higher anthocyanins and proanthocyanidins (15.9 and 87.9 mg/100 g, respectively) than canned sauces processed with whole berries (9.6 and 54.4 mg/100 g, respectively) or jelled‐type (1.1 and 16 mg/100 g, respectively). Sweetened‐dried cranberries were quite low in anthocyanins (7.9 mg/100 g), but they still retained considerable proanthocyanidins (64.2 mg/100 g). Commercially processed products contained significantly lower levels of polyphenols as compared to fresh and home‐processed preparations. Anthocyanins were more sensitive to degradation than proanthocyanidins.
Practical Application: As cranberry juices and other products are increasingly consumed for their recognized health benefits (including prophylaxis against urinary tract infection), it is relevant to consider how various degrees of commercial and home processing can alter innate levels of the biologically active flavonoids (especially anthocyanins and proanthocyanidins) characteristic to the intact fruits.
West Nile virus (WNV) is a (+) sense, single-stranded RNA virus in the
genus. WNV RNA possesses an
GpppN
5' cap with 2'-
-methylation that mimics host mRNAs preventing innate immune detection and ...allowing the virus to translate its RNA genome through the utilization of cap-dependent translation initiation effectors in a wide variety of host species. Our prior work established the requirement of the host mammalian target of rapamycin complex 1 (mTORC1) for optimal WNV growth and protein expression; yet, the roles of the downstream effectors of mTORC1 in WNV translation are unknown. In this study, we utilize gene deletion mutants in the ribosomal protein kinase called S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein (4EBP) pathways downstream of mTORC1 to define the role of mTOR-dependent translation initiation signals in WNV gene expression and growth. We now show that WNV growth and protein expression are dependent on mTORC1 mediated-regulation of the eukaryotic translation initiation factor 4E-binding protein/eukaryotic translation initiation factor 4E-binding protein (4EBP/eIF4E) interaction and eukaryotic initiation factor 4F (eIF4F) complex formation to support viral growth and viral protein expression. We also show that the canonical signals of mTORC1 activation including ribosomal protein s6 (rpS6) and S6K phosphorylation are not required for WNV growth in these same conditions. Our data suggest that the mTORC1/4EBP/eIF4E signaling axis is activated to support the translation of the WNV genome.
•We develop and test a time-efficient epoch method for spin sense determination.•We apply our method to 21 Flora-region asteroids.•We use the spin sense distribution to constrain Flora spin–orbit ...evolution models.•We measure the SDSS colors of several large inner main belt asteroids.
The Flora asteroid family’s size and location on the inner edge of the main belt make it a likely source of NEOs and terrestrial planet impactors; however, reliable determination of Flora membership is inhibited by the family’s age and the presence of a high density of background objects. Dykhuis et al. (Dykhuis et al. 2014. Icarus 243, 111–128) identified the Flora family as the product of a 950-My-old collision dispersed in semimajor axis as a result of the Yarkovsky effect, and defined the family’s membership and extent in orbital parameter space. The observed preponderance of prograde rotators at semimajor axes greater than that of (8) Flora is consistent with the predictions of the single-collision Yarkovsky dispersion model.
Here we extend the available rotational property data for the Flora family via a survey of 21 Flora-region asteroids, using a time-efficient modification of the “epoch method” to determine prograde/retrograde spin sense. Five of the survey asteroids are shown to be prograde; five are shown to be retrograde; six are shown to have spin axes in or near their orbital planes; and five represent other cases for which spin axis information was not determined. The high-semimajor axis component of the Flora family is found to have only prograde and in-plane rotators, consistent with model predictions of Yarkovsky dispersion. Moreover, we confirm a wide range of ecliptic latitudes of the spin axes among these prograde rotators, consistent with models of family evolution in which a significant fraction of the members are captured in spin–orbit resonance. Near the “center” of the family (near the semimajor axis location of (8) Flora), the spin directions are mixed, with a slight preference for retrograde rotators, placing constraints on the efficiency of YORP-cycle spin reorientation for the family.
In addition to our spin sense survey, we also report new measurements of the Sloan colors of a number of large inner main belt asteroids.
•Sweet sorghum (SS) is a rich source of bioactive 3-deoxyanthocyanidins.•Dermal and seed head (SH) phenolics were most potent apoptotic agents.•Dermal and SH induced apoptosis were p53-dependent and ...partially p53-dependent, respectively.•SS bioactives targeted Wnt/β-catenin signalling pathway proteins.
The extracts from sweet sorghum stalk were previously shown to eliminate human colon cancer stem cells (CCSC) in a partial p53-dependent fashion. However, the underlying mechanisms remain unknown. In this study, we transfected CCSC with shRNA against p53 and treated with sweet sorghum phenolics extracted from different plant components. While all sweet sorghum components demonstrated anti-proliferative and pro-apoptotic effects in CCSC, phenolics extracted from the dermal layer and seed head were more potent in eliminating CCSC by elevating caspase 3/7 activity, poly ADP-ribose polymerase cleavage, and DNA fragmentation in a p53-dependent and partial p53-dependent manner, respectively. These effects were associated with decreases in β-catenin, cyclin D1, cMyc, and survivin protein levels. These results suggest that the anti-proliferative and pro-apoptotic effects of sweet sorghum extracts against CCSC are potentially via suppression of Wnt/β-catenin signalling in a p53-dependent (dermal layer) and partial p53-dependent (seed head) manner.
The outbreak of Zika virus (ZIKV) and associated fetal microcephaly mandates efforts to understand the molecular processes of infection. Related flaviviruses produce non-coding subgenomic flaviviral ...RNAs (sfRNAs) that are linked to pathogenicity in fetal mice. These viruses make sfRNAs by co-opting a cellular exoribonuclease using structured RNAs called xrRNAs. Here, we demonstrate that ZIKV infected monkey and human epithelial cells, mouse neurons, and mosquito cells produce sfRNAs. The RNA structure that is responsible for ZIKV sfRNA production forms a complex fold that is likely found in many pathogenic flaviviruses. Mutations that disrupt the structure affect exonuclease resistance
in vitro
and sfRNA formation during infection. The complete ZIKV xrRNA structure clarifies the mechanism of exonuclease resistance and identifies features that may modulate function in diverse flaviviruses.
Sorghum bicolor is the fifth most cultivated cereal crop worldwide. Varieties of S bicolor, known as grain sorghum, are cultivated for human food and animal feed. Certain varieties, known as sweet ...sorghum, concentrate sugar in the pith cells of the stalk and are cultivated for sugars and syrups. Recently, interest has grown in the use of sweet sorghum as a feedstock for biofuel production. This is due to reduced water requirements, shorter growing periods and reduced cultivation cost when compared to other feedstocks. Biofuel production of sweet sorghum generates large masses of biological wastes, comprised of stalks, leaves, leaf sheaths and seed heads. This biomass could serve as a potential reservoir for bioactive compounds for human health. Rich in phenolic acids and flavonoids, these parts of the sorghum plant have been used as a traditional medicine in African and Asian cultures for the treatment of various disease states, including cancer. Furthermore, recent studies have elucidated in vitro and in vivo antiinflammatory, antioxidant, and anticancer activities of the seed head, leaf and leaf sheath. Much less is known about the in vitro and in vivo bioactivities of the stalk components of sweet sorghum varieties. Here, the in vitro anticancer activity, and the in vivo antiinflammatory and antioxidant activity of sweet sorghum with a focus on the dermal layer, a component of sweet sorghum stalk, were investigated. It was hypothesized that the dermal layer contains phenolic compounds with antiproliferative, proapoptotic and antiinflammatory/antioxidant properties. Given the high rates of cancer incidence and mortality, as well as the close connection to a Western diet, in vitro colon cancer cell models and in vivo Western diet induced obesity and oxidative stress models were utilized for the purposes of this study. For in vitro studies, the colon cancer HCT116 cell line and colon cancer stem cells (CCSCs), and their p53 variants HCT116 p53 -/- and CCSCs p53 shRNA, were treated with different doses of phenolic rich extracts from the stalk components (pith and dermal layer), the leaves, and the seed head. Phenolic compounds are ubiquitous throughout the plant kingdom, consistently display bioactivity, and their antioxidant activity has been linked to the anticancer activity of phenolics. Total phenolics and antioxidant activities were determined by the Folin-Ciocalteu and 2,2`-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays, respectively. Individual phenolic compounds were identified by LC-MS analysis. Increased proliferation and suppressed apoptosis are two important hallmarks of cancer and are commonly targets of anticancer therapies. Given this, cancer cell proliferation was assessed with cell counting and BrdU assay, and apoptosis was assessed by Caspase 3/7 Glo, PARP cleavage and TUNEL assays. The colony formation assay was used as a measure of cell stemness in CCSCs. For in vivo studies of inflammation and oxidative stress, the murine Western/high-fat diet (HFD; 40% kcal fat) induced obesity and oxidative stress model was utilized. Male and female A/J mice were provided with HFD and low-fat diet control (LFD) for 10 weeks with and without 1% sweet sorghum stalk (dermal layer) extract (SS). During the treatment period, weekly measures of bodyweight, feed intake and water intake were collected. At the end of the study, dual energy X-ray absorptiometry (DEXA) was performed to assess adiposity. After treatment period, mice were sacrificed, vital organs weighed, and tissues and plasma collected for further analysis. It was demonstrated that the stalk (pith and dermal layer), leaf, and seed head contain phenolic and antioxidant compounds conferring anticancer properties in colon cancer stem cells, supporting the hypothesis. This activity was most prominent in the dermal layer and seed head. Furthermore these extracts were shown to act via decreasing β-catenin and β-catenin's prosurvival target genes. Additionally, we have demonstrated phenolic rich extract from dermal has in vivo antioxidant activities, and was well-tolerated in a high-fat diet mouse model of obesity and oxidative stress. More research is still needed to further elucidate the mechanisms through which sweet sorghum derived bioactive compounds favorably alter β-catenin levels in vitro and oxidative stress in vivo. Together this data suggests that sweet sorghum, an attractive source of fermentable sugars for biofuel production producing large quantities of biomass, is also an attractive reservoir of bioactive phenolic compounds with human health benefiting properties. (Abstract shortened by UMI.)
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