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UDP-Galactose 4′-Epimerase Activities toward UDP-Gal and UDP-GalNAc Play Different Roles in the Development of
In both humans and Drosophila melanogaster, UDP-galactose 4′-epimerase (GALE) catalyzes two distinct reactions, interconverting UDP-galactose (UDP-gal) and UDP-glucose (UDP-glc) in the final step of the Leloir pathway of galactose metabolism, and also interconverting UDP-N-acetylgalactosamine (UDP-galNAc) and UDP-N-acetylglucosamine (UDP-glcNAc). All four of these UDP-sugars serve as vital substrates for glycosylation in metazoans. Partial loss of GALE in humans results in the spectrum disorder epimerase deficiency galactosemia; partial loss of GALE in Drosophila melanogaster also results in galactose-sensitivity, and complete loss in Drosophila is embryonic lethal. However, whether these outcomes in both humans and flies result from loss of one GALE activity, the other, or both has remained unknown. To address this question, we uncoupled the two activities in a Drosophila model, effectively replacing the endogenous dGALE with prokaryotic transgenes, one of which (Escherichia coli GALE) efficiently interconverts only UDP-gal/UDP-glc, and the other of which (Plesiomonas shigelloides wbgU) efficiently interconverts only UDP-galNAc/UDP-glcNAc. Our results demonstrate that both UDP-gal and UDP-galNAc activities of dGALE are required for Drosophila survival, although distinct roles for each activity can be seen in specific windows of developmental time or in response to a galactose challenge. By extension, these data also suggest that both activities might play distinct and essential roles in humans.
Published in the journal:
. PLoS Genet 8(5): e32767. doi:10.1371/journal.pgen.1002721
Category: Research Article
doi: 10.1371/journal.pgen.1002721
In both humans and Drosophila melanogaster, UDP-galactose 4′-epimerase (GALE) catalyzes two distinct reactions, interconverting UDP-galactose (UDP-gal) and UDP-glucose (UDP-glc) in the final step of the Leloir pathway of galactose metabolism, and also interconverting UDP-N-acetylgalactosamine (UDP-galNAc) and UDP-N-acetylglucosamine (UDP-glcNAc). All four of these UDP-sugars serve as vital substrates for glycosylation in metazoans. Partial loss of GALE in humans results in the spectrum disorder epimerase deficiency galactosemia; partial loss of GALE in Drosophila melanogaster also results in galactose-sensitivity, and complete loss in Drosophila is embryonic lethal. However, whether these outcomes in both humans and flies result from loss of one GALE activity, the other, or both has remained unknown. To address this question, we uncoupled the two activities in a Drosophila model, effectively replacing the endogenous dGALE with prokaryotic transgenes, one of which (Escherichia coli GALE) efficiently interconverts only UDP-gal/UDP-glc, and the other of which (Plesiomonas shigelloides wbgU) efficiently interconverts only UDP-galNAc/UDP-glcNAc. Our results demonstrate that both UDP-gal and UDP-galNAc activities of dGALE are required for Drosophila survival, although distinct roles for each activity can be seen in specific windows of developmental time or in response to a galactose challenge. By extension, these data also suggest that both activities might play distinct and essential roles in humans.
Galactose is an essential component of glycoproteins and glycolipids in metazoans, and as a constituent monosaccharide of the milk sugar, lactose, also serves as a key nutrient for mammalian infants. Galactose is also found in notable quantities in some fruits, vegetables, and legumes. Galactose is both synthesized and catabolized in all species via the Leloir pathway, which is highly conserved across branches of the evolutionary tree [1].
The reactions of the Leloir pathway are catalyzed by the sequential activities of three enzymes: (1) galactokinase (GALK) which phosphorylates alpha-D-galactose to form galactose-1-phosphate (gal-1P), (2) galactose-1-phosphate uridylyltransferase (GALT), which transfers uridine monophosphate (UMP) from uridine diphosphoglucose (UDP-glc) to gal-1P, forming UDP-galactose (UDP-gal) and releasing glucose-1-phosphate (glc-1P), which can proceed to phosphoglucomutase and the glycolytic pathway, and (3) UDP-galactose 4′-epimerase (GALE) which interconverts UDP-gal and UDP-glc [1]. In addition to a role in the Leloir pathway, metazoan GALE enzymes also interconvert UDP-N-acetylgalactosamine (UDP-galNAc) and UDP-N-acetylglucosamine (UDP-glcNAc) (Figure 1). Because it catalyzes reversible reactions, GALE therefore not only contributes to the catabolism of dietary galactose, but also enables the endogenous biosynthesis of both UDP-gal and UDP-galNAc [2], [3] when exogenous sources are limited.
Deficiency in any of the three Leloir enzymes in humans results in a form of the metabolic disorder galactosemia, although the symptoms and clinical severity differ according to which enzyme is impaired and the extent of the impairment. Profound loss of hGALE results in generalized epimerase-deficiency galactosemia, an autosomal recessive and potentially severe disorder. To date, however, no patient has been reported with complete loss of GALE, and even the most severely affected demonstrate at least 5% residual enzyme activity [4]. Previous studies have indicated that different patient mutations impair hGALE to different extents [5]–[9]. Further, while some mutations impair both GALE activities similarly, others do not. For example, the hGALE allele V94M, which leads to severe epimerase-deficiency galactosemia in the homozygous state, encodes an enzyme that retains ∼5% residual activity toward UDP-gal but ∼25% residual activity toward UDP-galNAc [8], [9]. Disparities such as this have raised the question of whether the pathophysiology of epimerase deficiency galactosemia results from the loss of GALE activity toward UDP-gal/UDP-glc, or toward UDP-galNAc/UDP-glcNAc, or both.
To address this question, we applied a Drosophila melanogaster model of GALE deficiency [10]. Using this model, we have previously established that GALE is essential in Drosophila; animals completely lacking endogenous dGALE succumb as embryos, and conditional loss of dGALE in larvae results in death within two to four days of knockdown. Finally, partial loss of dGALE leads to galactose sensitivity in larvae, and transgenic expression of human GALE (hGALE) rescues each of these negative outcomes [7].
Here we have applied our transgenic Drosophila model to uncouple and examine the individual roles of GALE separately. Toward that end, we generated flies that lacked endogenous dGALE and expressed either of two prokaryotic transgenes, one encoding E. coli GALE (eGALE) which exhibits an approximately 8,000-fold substrate preference for UDP-gal/UDP-glc over UDP-galNAc/UDP-glcNAc [11], and the other encoding P. shigelloides wbgU, which exhibits an approximately 2,000-fold substrate preference for UDP-galNAc/UDP-glcNAc over UDP-gal/UDP-glc [12]. By expressing these prokaryotic transgenes individually or in combination in dGALE-deficient Drosophila we determined that both GALE activities are required for survival of embryos and larvae. We also found that restoration of one activity or the other in later development rescued some phenotypes. Combined, these results provide insight into the varied roles of dGALE in Drosophila development and homeostasis, and by extension, suggest that hGALE may play similarly complex and essential roles in humans.
The Drosophila GALE enzyme efficiently interconverts both UDP-gal/UDP-glc and UDP-galNAc/UDP-glcNAc
Human and other mammalian GALE enzymes efficiently interconvert both UDP-gal/UDP-glc and UDP-galNAc/UDP-glcNAc (e.g. [13]–[15]). Previously, we reported that Drosophila GALE interconverts the first of these substrate pairs (UDP-gal/UDP-glc) [10], but did not address whether dGALE could also interconvert the second. Here we demonstrate that dGALE from wild-type adult flies efficiently interconverts both substrate sets (left most bar, Figure 2). Of note, while purified human GALE [15] and dGALE each interconvert both UDP-gal/UDP-glc and UDP-galNAc/UDP-glcNAc, the apparent specific activity of both human and fly enzymes toward UDP-gal is significantly higher than toward UDP-galNAc.
eGALE and wbgU transgenes enable the expression of individual GALE activities in Drosophila
To generate flies with epimerase activity toward only UDP-gal/UDP-glc or only UDP-galNAc/UDP-glcNAc, we created transgenic lines expressing eGALE (UAS-eGALE) or wbgU (UAS-wbgU), respectively, each in a conditionally dGALE-impaired background. Each of these prokaryotic GALE genes has been demonstrated previously to encode epimerase activity toward only one of the two sets of epimer pairs (e.g. [11], [12]). To minimize background, activities of the encoded eGALE and WbgU enzymes toward UDP-gal and UDP-galNAc were assayed in flies knocked down for endogenous dGALE; results for the transgenes that demonstrated activities closest to those seen in wild-type Drosophila, eGALE62A and wbgU19A, are presented in Figure 2. As expected, lysates from dGALE knockdown flies expressing the eGALE transgene demonstrated strong activity toward UDP-gal, but not UDP-galNAc, and lysates from dGALE knockdown flies expressing the wbgU transgene demonstrated strong activity toward UDP-galNAc, but not UDP-gal. As a control we also tested lysates from dGALE knockdown flies expressing a human GALE transgene; as expected, those samples demonstrated very strong activity toward both substrates.
Both eGALE and wbgU transgene activities are required, in combination, to rescue viability of dGALE–deficient Drosophila
Previously, we created and characterized two dGALE-deficient alleles, dGALEf00624.4 and dGALEΔy, which allowed us to demonstrate that GALE is essential for survival in Drosophila [10]. To examine the requirement for the two different epimerase activities separately, we set up crosses which allowed for the expression of eGALE or wbgU, individually or in combination, driven by Act5C-GAL4 in an otherwise dGALE-deficient background (dGALEf00624.4/dGALEΔy). Table 1 shows the observed to expected ratios of surviving transgenic offspring that eclosed from these crosses. As presented in Table 1, neither eGALE alone nor wbgU alone was sufficient to rescue survival of the dGALE-deficient animals; however, expression of both eGALE and wbgU, in combination, was sufficient. These results demonstrate that GALE activities toward both UDP-gal and UDP-galNAc are essential for survival of D. melanogaster. To rule out the possibility that rescue with eGALE plus wbgU in combination occurred not because both GALE activities are essential but rather because neither individual transgene expressed sufficient enzyme, we also tested additional eGALE and wbgU transgenes that individually demonstrated higher levels of expression; none was sufficient to rescue (data not shown). Of note, there also was no apparent over-expression phenotype; for example, animals expressing either eGALE or wbgU in addition to endogenous dGALE, and animals dramatically over-expressing human GALE, remained viable, fertile, and appeared morphologically normal (data not shown).
Different requirements for GALE activities at different stages of Drosophila development
Previously, we described an approach that achieves conditional knockdown of dGALE in Drosophila using a UAS-RNAidGALE transgene (12030-R2, National Institute of Genetics Fly Stock Center, Mishima, Shizuoka, Japan) in combination with a temperature sensitive allele of yeast GAL80 (GAL80ts) ([10] and Figure 3A). Using this system, we found that dGALE is required from embryogenesis through pupation, and that loss of dGALE during pupation leads to defects in fecundity and perhaps also a shortened life span [10].
Here we have expanded the GAL80tsconditional dGALE knockdown system to include different GAL4-dependent GALE transgenes and have applied this expanded system to test the ability of each transgene, or pair of transgenes, to compensate for the loss of endogenous dGALE. By using age-synchronized cohorts of animals and shifting from the permissive (18°C) to the restrictive temperature (28–29°C) at different times we also were able to test the ability of each GALE transgene, or pair of transgenes, to sustain survival and fecundity at different stages of development. At 18°C these animals expressed endogenous dGALE, but not their transgenes, and at 28–29°C these animals expressed their transgenes but not dGALE (Figure 3A). Specifically, we tested Drosophila that carried no GALE transgene, an eGALE transgene, a wbgU transgene, both eGALE and wbgU transgenes, or an hGALE transgene.
As expected from prior results ([10] and Table 1), animals expressing no GALE transgene succumbed when shifted to the restrictive temperature as larvae, while animals expressing either human GALE or both eGALE plus wbgU remained viable and fertile (Figure 3C). Surprisingly, expression of either eGALE or wbgU alone was also sufficient to rescue survival, albeit to a lesser extent. The fact that the individual prokaryotic transgenes were sufficient to rescue dGALE knockdown animals, but not animals genetically null for dGALE (Table 1), suggests that trace residual dGALE expression in the knockdown animals lowered the threshold of transgene function required for rescue.
Of note, while dGALE knockdown animals encoding either eGALE or wbgU remained viable following a shift to the restrictive temperature in early to mid-development (Figure 3C), these survivors were not entirely healthy. Specifically, these animals demonstrated either partial or complete loss of fecundity as adults. To test whether the degree of dGALE knockdown was comparable between males and females, and therefore not a confounding factor in differential outcome, we performed GALE and GALT enzyme assays on newly eclosed and three day old male and female knockdown adults that carried no GALE transgene and that had been switched to the restrictive temperature as early to mid-stage pupa. The degree of GALE knockdown in both males and females was profound and comparable (Figure 3B). As expected, the level of GALE activity was even lower in the older animals, presumably because any GALE synthesized prior to the temperature switch had three additional days to decay. Also as expected, GALT activity was normal and apparently unaffected by the dGALE knockdown in all samples tested (data not shown).
To examine fecundity, we collected and sequestered newly eclosed virgin female and male flies from each surviving cohort, crossed them to an equal number of wild-type flies of the opposite sex, and counted the numbers of viable offspring resulting from each cross. Crosses resulting in large numbers of viable offspring (>50) were scored as "normal fecundity". Crosses resulting in fewer than 10 viable offspring were scored as "reduced fecundity," and crosses resulting in no viable offspring were scored as "loss of fecundity" (Figure 3C). For example, when dGALE knockdown was initiated during early to mid-stage pupal development, animals of both sexes displayed diminished fecundity. Expression of eGALE alone, but not wbgU alone, rescued the male defect, whereas expression of both prokaryotic transgenes in combination, or hGALE alone, was required to rescue the female defect. These results indicate that GALE activity toward UDP-gal is both necessary and sufficient for male fecundity, but that GALE activities toward both UDP-gal and UDP-galNAc are required for female fecundity.
Galactose exposure of transgenic flies with late-onset dGALE knockdown reveals differential roles of GALE activities toward UDP-gal and UDP-galNAc
We have previously demonstrated that Drosophila expressing a hypomorphic allele of dGALE are viable but sensitive to galactose exposure [10]. To assess the roles of the two GALE activities in coping with environmental galactose, we collected adult flies in which dGALE knockdown coupled with hGALE, eGALE, wbgU, or eGALE plus wbgU transgene expression was initiated using the GAL80ts system during late larval or early-to-mid-pupal development. These animals were allowed to develop on a standard molasses-based food, and were then transferred as newly eclosed adults to food containing either 555 mM glucose as the sole sugar, or 555 mM glucose plus 175 mM galactose.
We assessed the lifespan of each cohort of animals on both foods; as a control, knockdown animals expressing no GALE transgene were also monitored (Figure 4). In the absence of galactose, all cohorts showed similar longevity profiles, although females (Figure 4C) showed greater variability than males (Figure 4A). In the presence of galactose, however, both males and females expressing either no GALE transgene, or only the wbgU transgene, demonstrated a dramatic reduction in life span (p<0.0001, Figure 4B and 4D). Females expressing eGALE alone exhibited a slight decrease in life span that was independent of diet. Animals expressing hGALE or eGALE+wbgU had lifespans comparable to control animals expressing endogenous dGALE, regardless of diet. These data implicate loss of UDP-gal activity as responsible for the galactose-dependent early demise of adult dGALE-impaired Drosophila.
Differentially GALE–impaired flies exposed to galactose demonstrate different metabolic abnormalities
As one approach to explore the pathophysiology underlying the different galactose-dependent outcomes observed in Drosophila deficient in GALE activity toward UDP-gal or UDP-galNAc we measured the levels of gal-1P, UDP-gal, and UDP-galNAc in lysates prepared from galactose-exposed third instar larvae expressing different GALE transgenes. As illustrated in Figure 5, galactose exposed animals deficient in both GALE activities (bars marked "KD" for knockdown) accumulated abnormally high levels of gal-1P (Figure 5A and 5D) and UDP-gal (Figure 5B and 5E). Animals deficient only in GALE activity toward UDP-gal (bars marked "wbgU" in Figure 5) also demonstrated elevated gal-1P (Figure 5A and 5D) and UDP-gal (Figure 5B and 5E). In contrast, galactose exposed larvae deficient only in GALE activity toward UDP-galNAc (bars marked "eGALE" in Figure 5C and 5F) demonstrated no extraordinary metabolic abnormalities, although, as expected, the absolute level of UDP-galNAc was diminished in these animals independent of diet relative to the "no knockdown" control (Figure 5C). Also as expected, animals expressing either hGALE or both eGALE plus wbgU demonstrated no clear metabolic abnormalities (Figure 5).
UDP-galactose 4′-epimerase (GALE) is an essential enzyme in Drosophila [10] and in humans [16], but until now the relative contributions of the two distinct GALE activities to development and galactose-tolerance has remained unclear. Understanding these roles has important implications regarding mechanism of galactose sensitivity, and may be applicable to diagnosis and prognosis in humans with epimerase-deficiency galactosemia. Our experiments described here exploit the genetic and biochemical facility of Drosophila melanogaster to test the consequences of losing each of the two GALE activities individually at different stages of development, or under different conditions of galactose exposure.
Our results demonstrate that developing animals require at least some GALE activity toward both epimer pairs, even in the absence of dietary galactose. Complete loss of either activity in embryos is lethal (Table 1). In animals with trace dGALE activity left by knockdown rather than genetic deletion or disruption, however, transgenic expression of either GALE activity alone is sufficient for rescue (Figure 3C). Further, in animals that expressed both GALE activities as larvae, knockdown of both activities during pupation is not lethal.
However, knockdown of either GALE activity in early development, or knockdown of both activities in later development has consequences. For example, loss of activity toward UDP-gal in larvae results in impaired fecundity of both males and females, while loss of activity toward UDP-galNAc in larvae results in impaired fecundity of females but not males. Individual loss of one activity or the other later in development also results in differential sensitivity to galactose. Specifically, both male and female flies deficient in GALE activity toward UDP-gal exhibit a markedly reduced lifespan when exposed to galactose; this effect is not seen in wild-type flies or in flies uniquely deficient in GALE activity toward UDP-galNAc.
These results support two important conclusions. First, the essential role of GALE in development and homeostasis of Drosophila extends beyond the Leloir pathway. Whether GALE activity toward UDP-galNAc is essential because of its presumed role in establishing and maintaining substrate pools for glycosylation, or for some other reason, remains unknown. Prior studies in GALE-deficient mammalian cells [17] showed that uridine supplementation could rescue growth and some metabolic abnormalities caused by galactose exposure, raising the possibility that depleted pools of uridine or uridine-derivatives might also be contributing factors. In the current study it is also unclear whether animals subjected to knockdown of one or both GALE activities later in development demonstrate a less severe outcome than those knocked down earlier in development because the products of GALE function, namely UDP-gal, UDP-glc, UDP-galNAc, and UDP-glcNAc, are less essential later in development, or rather because these UDP sugars have already accumulated to sufficient levels and can be recycled for use. Similarly, the differential sensitivities of male and female fecundity to loss of GALE activity later in development may reflect fundamental differences in male and female development, or alternatively may reflect differential sensitivity to loss; for example, eggs may require a more substantial pool of specific UDP-sugar substrates than sperm to give rise to a viable embryo.
Implications for mechanism
The disparate metabolic profiles observed in GALE-impaired flies exposed to galactose provide a window of insight into potential mechanisms behind the outcomes observed. For example, gal-1P accumulates to abnormal levels in animals missing GALE activity toward UDP-gal but not UDP-galNAc, and only those animals demonstrate substantially reduced lifespan when exposed to galactose as adults. This metabolic result is expected, since only GALE activity toward UDP-gal should impact the Leloir pathway, and this outcome result implies that gal-1P might contribute to the early demise of these animals. However, the gal-1P result also implies that the negative outcomes observed in Drosophila deficient in GALE activity toward UDP-galNAc, e.g. compromised survival in embryos and compromised fecundity in adult females, do not result from gal-1P accumulation. This is an important point because it challenges the common supposition that gal-1P underlies pathophysiology in both classic and epimerase deficiency galactosemias. Clearly there must be another basis for the negative outcomes observed in these animals. It is also interesting to note that while loss of GALE activity toward UDP-galNAc in developing animals has phenotypic consequences, at least for female fecundity, it does not appear to negatively impact the "global" level of UDP-galNAc in animals exposed to galactose. The explanation for this apparent disparity might involve subtle or tissue-specific differences below the threshold of detection of our experimental approach.
Implications for patients
The implications of this work for patients with epimerase deficiency galactosemia are two-fold. First, these results demonstrate that both GALE activities are essential for health of flies, and possibly also people. To our knowledge clinical laboratories that test patient samples for GALE activity only test activity toward UDP-gal. While this practice is certainly understandable, given that mutations may impact the two GALE activities differently [18]–[20], the results presented here raise the possibility that rare patients with GALE deficiency limited to UDP-galNAc activity could be missed. Second, given the impact of GALE-loss on both male and female fecundity in flies, these results suggest that long-term studies of both male and female reproductive issues in epimerase-deficiency galactosemia patients might be warranted.
Materials and Methods
Drosophila stocks and maintenance
The Drosophila stocks used in this study are listed in Table S1. Stocks were maintained at 25°C on a molasses-based food that contained 43.5 g/l cornmeal, 17.5 g/l yeast extract, 8.75 g/l agar, 54.7 ml/l molasses, 10 mls propionic acid and 14.4 ml/l tegosept mold inhibitor (10% w/v in ethanol). For experiments in which the levels and types of sugar were to be varied, we used a glucose-based food [5.5 g/l agar, 40 g/l yeast, 90 g/l cornmeal, 100 g/l glucose, 10 ml/l propionic acid and 14.4 ml/l tegosept mold inhibitor (10% w/v in ethanol)] [21] supplemented with galactose, as indicated.
Generation of transgenic lines
UAS-eGALE and UAS-wbgU transgenes were generated by subcloning the eGALE and wbgU coding sequences, respectively, as EcoRI/XhoI fragments, into pUAST [22] using the EcoRI and XhoI sites in the pUAST polylinker region. The wbgU sequence was amplified from a plasmid generously provided by Peng George Wang (Ohio State University). Resulting plasmids were confirmed by sequence analysis. UAS-eGALE stocks were generated using standard transgenic techniques following injection of the transgene into embryos by the fly core of the Massachusetts General Hospital, Charlestown, MA. UAS-wbgU stocks were generated using standard transgenic techniques following injection of the transgene into embryos by Genetic Services, Inc., Cambridge, MA. Transformants were selected by the presence of the white gene within pUAST. Expression of functional eGALE or wbgU was confirmed by enzymatic assay of lysates from transformants.
GALK, GALT, and GALE (UDP-gal) enzyme assays
Lysates were prepared and assays for GALK, GALT and GALE with UDP-gal as the substrate were performed (n≥3) as described previously [10].
GALE assay conditions for activity toward UDP-galNAc
Activity was calculated from the conversion of UDP-galNAc to UDP-glcNAc. The initial reaction mixture concentrations were: 100 mM glycine pH 8.7, 1.6 mM UDP-galNAc and 0.5 mM NAD. Enzyme assays were performed as described in Sanders et al. [10] except for the following changes: To start each reaction, 7.5 µl of diluted protein and 5 µl of a cocktail of substrates and cofactors were combined. Reaction mixtures were incubated at 25°C for 30 minutes and then quenched by the addition of 112.5 µl of ice-cold high-performance liquid chromatography (HPLC)-grade water (Fisher). Lysates were diluted 1∶4, except for those prepared from animals with RNAi knockdown, which were undiluted, and those prepared from animals overexpressing hGALE or wbgU transgenes, which were diluted to a greater extent. Lysates from Act5C>hGALE22C animals were diluted 1∶60. Lysates from Act5C>wbgU19A animals were diluted 1∶20.
Determining requirement for GALE activities in development and homeostasis
Generation of animals in which GALE knockdown was initiated at 24-hour intervals throughout development was achieved as described previously [10]. A stock homozygous for both P{tubP-GAL80ts}10 and 12030R-2 was used in all crosses. These flies were then crossed to the appropriate genotypes to obtain offspring expressing various transgenes; for: no transgene, P{Act5C-GAL4}25FO1 ; +/T(2;3)TSTL, Tb, Hu; eGALE only, P{Act5C-GAL4}25FO1, UAS-eGALE62A/CyO; wbgU only, P{Act5C-GAL4}25FO1/CyO; P{Act5C-GAL4}25FO1/CyO ; UAS-wbgU19A/TM6B; eGALE plus wbgU, P{Act5C-GAL4}25FO1, UAS-eGALE62A/CyO ; UAS-wbgU19A/TM6B; hGALE, P{Act5C-GAL4}25FO1/CyO ; UAS-hGALE22C/TM6B. Adult flies eclosing from the vials were scored for the presence or absence of humeral and/or curly, as appropriate for each cross.
Measurement of life span
Animals in which dGALE knockdown with concurrent transgene expression was achieved throughout development were obtained as described above. These animals were maintained on standard molasses medium until eclosion. Within 24 hours after eclosion, approximately 20 virgin male or female flies were placed in fresh vials of food containing 555 mM glucose only or 555 mM glucose plus 175 mM galactose. Flies were transferred to fresh food every 2–3 days, and the number of dead flies in each vial was recorded every other day. Log rank and Wilcoxon tests were used for statistical analysis using the program JMP (http://www.jmp.com/).
Measuring metabolite accumulation in GALE–deficient larvae
Cohorts of newly hatched larvae raised at 18°C were transferred to vials of food containing either 555 mM glucose only or 555 mM glucose plus 175 mM galactose. The larvae were maintained at 18°C for one additional day, then transferred to 28°–29°C and allowed to develop for another four days prior to harvest. Metabolites were extracted and quantified as described previously [10], and were separated and quantified using a Dionex HPLC, as described previously [23] with the following changes: UDP-gal and UDP-galNAc were separated using a high salt isocratic procedure with a flow rate of 0.5 mL/min and buffer concentrations of 45% A and 55% B (0–61 min), followed by washing with a linear increase of B to 95% (61–80 min). For all samples, 20 µl were injected into a 25 µl injection loop. Ratios of the level of each metabolite on food containing galactose over the level on food containing glucose only were calculated, and 95% confidence intervals were determined using Fieller's theorem.
Supporting Information
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13. MaleyFMaleyGF 1959 The enzymatic conversion of glucosamine to galactosamine. Biochim Biophys Acta 31 577 578
14. PillerFHanlonMHHillRL 1983 Co-purification and characterization of UDP-glucose 4-epimerase and UDP-N-acetylglucosamine 4-epimerase from porcine submaxillary glands. J Biol Chem 258 10774 10778
15. SchulzJWatsonASandersRRossKThodenJ 2004 Determinants of function and substrate specificity in human UDP-galactose 4′-epimerase. J Biol Chem 279 32796 32803
16. Fridovich-KeilJBeanLHeMSchroerR 2011 Epimerase Deficiency Galactosemia. PagonRBirdTDolanCStephensK GeneReviews Seattle, (WA) University of Washington, Seattle
17. SchulzJRossKMalmstromKKriegerMFridovich-KeilJ 2005 Mediators of galactose sensitivity in UDP-galactose 4′-epimerase-impaired mammalian cells. J Biol Chem 280 13493 13502
18. OpenoKSchulzJVargasCOrtonCEpsteinM 2006 Epimerase-deficiency galactosemia is not a binary condition. Am J Hum Genet 78 89 102
19. WohlersTFridovich-KeilJL 2000 Studies of the V94M-substituted human UDP-galactose-4-epimerase enzyme associated with generalized epimerase-deficiency galactosemia. J Inher Metab Dis 23 713 729
20. WohlersTMChristacosNCHarremanMTFridovich-KeilJL 1999 Identification and Characterization of a Mutation, in the Human UDP Galactose-4-Epimerase Gene, Associated with Generalized Epimerase-Deficiency Galactosemia. Am J Hum Gen 64 462 470
21. HonjoKFTK 2005 Induction of cAMP response element-binding protein-dependent medium-term memory by appetitive gustatory reinforcement in Drosophila larvae. Journal of Neuroscience 25 7905 7913
22. BrandAHPerrimonN 1993 Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118 401 415
23. RossKLDavisCNFridovich-KeilJL 2004 Differential roles of the Leloir pathway enzymes and metabolites in defining galactose sensitivity in yeast. Mol Gen Metab 83 103 116
ŠtítkyGenetika Reprodukční medicína
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PLOS Genetics
2012 Číslo 5
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Tomuto tématu se dále věnují…
- Inactivation of a Novel FGF23 Regulator, FAM20C, Leads to Hypophosphatemic Rickets in Mice
- Genome-Wide Association of Pericardial Fat Identifies a Unique Locus for Ectopic Fat
- Slowing Replication in Preparation for Reduction
- An Essential Role for Katanin p80 and Microtubule Severing in Male Gamete Production
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Kemp Construction ensures that their portfolio, tenders, references, client relations, delivery and follow through remain professional and complete right through the building process.
"We were very pleased with the workmanship of Kemp Roofing in providing us with a new roof in the spring of 2009. We were particularly impressed with how attentive they were to ensure that the numerous perennial flowerbeds that surround our home were not harmed in the process of discarding the old shingles and hoisting the new shingles up. They went the extra mile that makes all the difference in providing excellent service, with little extras such as taking down the weather vane lantern on the garage, refurbishing and reinstalling it. Also, they were careful to replace deteriorated sheathing and fascia before re-shingling our backyard shed.
We would, without hesitation, recommend Kemp Roofing to anyone who values honest, professional, and skilled workmanship."
Luc and Eileen Saint-Martin
" We required a new roof on our home in 2008. I contacted Mr. Kevin Kemp in order to have our roof replaced. Mr. Kemp appraised the job in a very timely and professional manner. The work was very prorfessionally done both on the roof and the yard was left just as if no one was ever there. Quality workmanship, professional people, and affordable prices have made this experience a pleasant one. I would have no problem with using Kemp Roofing in the future or recommending them to others."
Mark and Sharon Virtue, Ottawa, ON
" Kemp Construction was able to maintain the established construction schedule and the quality of their workmanship was well above average. Most notable was Mr. Kevin Kemp's personal commitment to seeing this project successfully completed to both our satisfaction and the client's."
Cole+Associates Architects Inc., Ottawa, Ontario
" being committed to staying in the area Kemp Construction restored and updated our home as well as blending a major addition to the existing structure. We are pleased with the renovation and have recommended Kemp Construction to friends."
Allan and Diane Lumsden, Dows Lake, Ottawa Ontario
" We quickly forgot about moving to an apartment when my daughter and son-in-law suggested we build an addition onto their home. This was a solution that made sense. The great appeal was that it would allow closeness and mutual support. With Kevin and his team on board we were able to meet our goal to maximize the use of space and create a bright and airy self-sufficient residence. Also with his track record we knew quality workmanship was primary."
David and Natalie Crosby, Kanata, Ontario


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Football Manager 2014 match engine shown in new dev diary, watch here
Football Manager 2014 developer Sports Interactive has posted a new dev diary that shows the game's match engine in action.
The footage is pre-beta and shows matches as they unfold on the pitch. We're expecting more updates on Football Manager 2014 from the UK-based studio ahead of its October 31 launch. Stay tuned.
What do you think?


text: hard disk sentinel Archive Hard Disk Sentinel Pro 5.01.14 Build 9372 Beta Author: admin | Apr052018 Categories: Softwares No comments Hard Disk Sentinel Pro is a multi-OS hard disk drive monitoring application. Its goal is to find, test, diagnose and repair hard disk drive problems, display hard disk health, performance degradations and failures. Hard Disk Sentinel Pro gives complete textual description, tips and displays/reports the most comprehensive information about Continue Reading


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T-adapters for CAT5e (ethernet) applications
Are great cost saving devices that help to reduce the number of lines needed to connect two distant points. They ARE NOT splitters in the traditional sense. You CAN NOT use it to split a single port on a modem, computer, switch, router or hub. What they do allow you to do is connect 2 ports on a switch, hub or router to 2 different computers using a single Ethernet cable to bridge the two points.
It takes the initial two Ethernet connections from two PC's into the two female ports on the "T" adapter. The male Ethernet cable attached to the "T" adapter, connects to a wall plate/inline coupler/network panel. Then from the wall plate/inline coupler/network panel to the "T" adapter's male Ethernet cable and branches off to two female ports with Ethernet cables connected to and from the Router/Hub/Switch.
Bridges all jack pairs, compatible with any Jack wiring
Provides an additional 4-pair jack With the same wiring


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- You are in:
- Homepage >
- Entertainment >
- Music >
- Music news
Time to get serious
PJ Harvey is through with playing. The singer has judged that the time is now right to release songs about 'things that really matter'.
The singer-songwriter reportedly spent two years writing lyrics for Let England Shake, her forthcoming record and follow-up to 2007's White Chalk and last year's collaboration with John Parish, A Woman a Man Walked By.
Harvey said: 'I do feel at this stage of my life, it feels very important to give voice to the things that really matter. Things that I feel need to be said that aren't being said, and address the issues of the day.
'I think that it's only now that I've been writing for this period of years that I feel I can begin to tackle these things with language.'
But the singer was quick to add that she did not expect the album to be 'self-righteous' or 'dogmatic'.


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Axmouth United clearly suffering from rain lay-off as they go down again
PUBLISHED: 19:53 03 March 2014 | UPDATED: 19:54 03 March 2014
Awliscombe 2, Axmouth United 1
The long weather-enforced break certainly hasn't helped Axmouth in their Fresha League Division Four title challenge.
Having been beaten just once in 15-games before the rain forced a near total two-month wipe out of fixtures, United have returned to action and lost both games they have played!
They followed the previous weekends defeat at the hands of Lords XI with a narrow defeat in an East Devon derby at Awliscombe.
Having shaded the better of the first half they deservedly took the lead following sustained pressure although Scott Dyers opener was a result of a keeper mistake than power or placement of his shot.
More opportunities were spurned and they paid the price as Awliscombe equalised inside the last five minutes of the half.
After the break the game continued in similar fashion as Axmouth found the woodwork denying Asa Sandman giving them the lead and the home defence stood firm until a counter attack saw the Awls steal a winner with eight minutes remaining.
United boss Laurie Forino cut a disconsolate figure post match. He said: "It's a case of being frustrated and disappointed at the same time. I thought we did enough to get, at the very least, a point. Sadly we have come away empty handed. Awliscombe always put up strong opposition and it's usually a good game between the two sides as was this latest contest and we have to give them credit for taking their chances.
It's been a harsh return to action and we need to get back to winning ways to maintain our challenge. Hopefully we can pick ourselves up for the next game."
Next up for United is a meeting with a North Tawton side that has won both matches they have played since they too suffered a lengthy break from action.
Forino also explained why he hoes for a larger than average crowd to see his team in Saturday's home game. He said: "We are looking for a good turnout as one of our top fans-Jim Fossey has pledged to help our fundraising effort by running a sponsored lap or two of the pitch in a mankini after the game!"
If you value what this story gives you, please consider supporting the Midweek Herald. Click the link in the orange box above for details.


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There's one rather endearing detail disappointingly absent from the tourist websites, in-flight magazines and online reviews of Flinders Island. It's something visitors need to know about this haven of wallabies, lichen adorned sculptural granite and unnervingly pure turquoise water.Read More
King Island Racing, Festival of King Island and Long Table Festival are coming up in the next few months. Let us catch you up on all the details here.Read More


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On Thursday 17th March the Dance lady will be coming in to Playgroup.
Monthly Archives: March 2016
Walk on Tuesday 8th March
Thank You to Marie, Madison's Mummy, Bex, Jimi's Mummy and Ed, Isaac's Daddy for their help with the walk on Tuesday 08th March. We hope you all enjoyed it as much as we did!


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Cell: 858.414.9967
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Fax: 855.518.7437
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Karla is a native San Diegan who is passionate about meeting and helping others. She started in the mortgage industry in 2012, shortly after graduating from the University of California, Irvine (Zot! Zot!) with a degree in Business Economics.
She specializes in caring. That may sound silly, but when you think of banks and lending, there is often a negative assumption that the people there just don't care. That is not the case with Karla. She fully understands that discussing your finances and making the decision to become a homeowner is a big and personal step in one's life. She is fully on board to make the home loan process as painless as possible and is always willing to provide guidance and search for solutions.
Since joining the mortgage industry, she has had a hand in successfully originating and closing hundreds of loans. Her experience includes originating conventional, FHA, VA, jumbo, and other specialty loan products. Being able to be a part of someone's journey in buying their first home or to be able to find a way to save a homeowner hundreds of dollars a month on their mortgage gives Karla all the reason to stay in mortgage for years to come.
Branch Address: 404 Camino Del Rio S, Suite 602 San Diego, CA 92108
You'd love to own a vacation home (who wouldn't?!) but you're not sure if you can afford it, or even qualify, on...


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The energy of the new year is so good, isn't it? So refreshing and full of possibility.
Throw in the full moon energy, and the time feels ripe for clearing out, making plans, and entering a year of pulling in all that is good and right and uniquely you.
And there's so much beautiful work to be done!
I believe in measuring accomplishments and habits and goals by your own personal abilities and characteristics. No trying to shove a square peg into a round hole for me, thanks.
So usually, following a prescribed practice doesn't work so well for me.
Which is why, for many years, I've shied away from the whole "one word for your year" idea. ONE word? For a WHOLE YEAR? I'm much too dynamic and finicky an individual for all of that nonsense.
In fact, when I succeed at anything, it's because whatever I'm working on is flexible to my whims and inspirations. Like when I did 31 Days this past year...2017 was the only time I was able to accomplish it. Because my theme bent and flexed towards whatever I wanted to share each day.
But when I stopped to think about this one word thing for a minute, a word came to me in seconds.
And I was instantly sure of it.
When something happens without all of the wild analyzing I'm usually prone to, I know that I was actually still enough to hear guidance from something bigger than myself. And I cannot, and should not, ignore it.
So I looked at this teeny tiny, unassuming word to see how I felt about it.
That's it. Two letters.
It is perfect in its simplicity. But Up is anything but small.
Up is where the sky is blue, and the stars shine over us.
Up is where sunlight gives life to our world.
Up is where the birds fly, the wind and rain blow in, the leaves grow.
Up is where you go when your vibes are high and your heart is full of love.
Up is where you climb when you work hard (and smart.)
Up is where our life's expansion takes us - where we belong - where we exist beyond this human experience.
Up is where the number of our age naturally goes.
Up is hopefully, the direction of our bank accounts.
Up is the number of friends we collect in our lives.
Up is the amount of love we are surrounded by.
Up is increasing. Up is expanding. Up is big.
Up is the two-letter way of saying "live the bigger life."
And it's my perfectly perfect word for this year of stepping into purpose.
So, how about you?
Do you like the one word idea? Do you pick one? What's your word for this year?
Lay all of that sweet inspiration on me! ;)
Join the Enrychment Newsletter


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What type of UPS are you looking for?
We provide a complete range of Single-Phase and Three-Phase UPS products to ensure a constant supply of clean and reliable power for mission critical and industrial applications. In addition to our wide range of UPS systems, we offer project management, planning services for end-users and consultants, and comprehensive after-sales support services.


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Volunteer Administration: Professional Practice, 3rd Edition
Product description
If your organization engages volunteers, you already know the importance and value of what volunteers contribute a successful operation. Effectively managing, administering and deploying your volunteers can help you achieve your organization's mandate. Volunteer Administration: Professional Practice is the only book that addresses the full body of knowledge required by professional administration and management of volunteers.
Now in its Third Edition, this text has been revised to provide readers with a solid foundation, the most up-to-date information, and best practices for managing volunteers. Whether you run an all-volunteer group, not-for-profit, or public sector agency, you will find in this practice-oriented book, a comprehensive foundation for effective volunteer engagement.
- Introduces and helps to implement the best volunteer management competencies
- Examines many elements of the recently updated competency framework for volunteer management and administration:
- Plan for Strategic Volunteer Engagement
- Advocate for Volunteer Involvement
- Attract and Onboard a Volunteer Workforce
- Prepare Volunteers for their Roles
- Document Volunteer Involvement
- Manage Volunteer Performance and Impact
- Acknowledge, Celebrate and Sustain Volunteer Involvement
- Provides a solid theoretical framework and professional context on how to properly support volunteer engagement
- Supported by research, statistics, and perspectives from the leading lecturers, practitioners and academics in this field
- Provides proven approaches to practice from leading professionals in the field of volunteer administration
- Case studies provide practical examples which apply volunteer management and administration principles, and include discussion questions to test the reader's understanding
New in This Edition
- New chapter on Ethical Decision-Making
- Updated research and references and best practices in all chapters throughout the book
- Updated content on risk management
- Re-vamped chapter on data management
- Revised chapter on advocacy in volunteer administration
- New Appendices:
- Quality Improvement
- The Volunteer Program, Relationships and Community Impact
- Case-studies
Who Needs this Book
- Candidates seeking certification by the Council for Certification in Volunteer Administration (CCVA)
- Students taking volunteer administration courses offered by universities, colleges and continuing education programs
- Managers, coordinators and team leaders of volunteers at not-for-profit organizations and public agencies
- Lawyers with a charities or not-for-profit practices
- Libraries – to provide a resource for lawyers, students and professionals looking for an understanding of volunteer administration and management
Table of contents
Chapter 1: An Introduction to the Profession of Volunteer Administration (by Erin Spink)
Chapter 2: Terminology and Resources (by Jeffrey L. Brudney and Melissa A. Heinlein)
Chapter 3: Ethics – Concepts and Definitions (by Kathleen McCleskey)
Chapter 4: Ethical Decision-Making (by Cheryle N. Yallen)
Chapter 5: Strategic Management of Volunteer Programs (by F. Ellen Netting)
Chapter 6: Operational Planning and Management (by Allan B. Serafino)
Chapter 7: Volunteer Staffing and Development (by Diana L. Krywood and Milena M. Meneghetti)
Chapter 8: Sustaining Volunteer Involvement (by Mark A. Hager and Jeffrey L. Brudney)
Chapter 9: Financial Management (by Marianne Kerr)
Chapter 10: Data Management (by Norman A. Dolch and Pamela J. Sybert)
Chapter 11: Evaluation and Outcome Management (by R. Dale Safrit)
Chapter 12: Risk Management (by Melanie Lockwood Herman)
Chapter 13: Leadership for Nonprofit Organizations (by Paul Varella)
Chapter 14: Skills for Effective Organizational Involvement (by Melissa Eystad)
Chapter 15: Advocacy in Volunteer Administration (by Emilie Bromet-Bauer)
Chapter 16: A History of the Profession of Volunteer Administration (by Keith Seel and Sarah Jane Rehnborg)
Chapter 17: Community Collaboration and Alliances (by Anita Angelini)
Appendix 1: Quality Improvement (by Salvatore P. Alaimo)
Appendix 2: The Volunteer Program, Relationships and Community Impact (by Anita Angelini)
Appendix 3: Case Studies
Related products
Management of Nonprofit and Charitable Organizations in Canada, 4th EditionRelease date: March 21, 2018$125.00
New!PreorderOntario Landlord & Tenant Law Practice, 2021 EditionNew!Release date: November 30, 2020$157.00
New!PreorderCompetition and Antitrust Laws in Canada: Mergers, Joint Ventures and Competitor Collaborations, 3rd EditionNew!Release date: November 30, 2020$225.00


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Salsa Savings – Save money on Class Salsa Lesson registration
Salsa Savings – Save money on Class Salsa Lesson – Fall into salsa dancing this autumn. Take advantage of low price on Bachata Class Salsa courses.
Salsa Savings on Class Salsa Lesson registration
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Be aware that falling into Salsa Class Lessons, you might fall into someone's arms this autumn. Wouldn't it be nice?
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Uttaran 27th January 2014 Written Episode Update
Uttaran 27th January 2014 Written Episode, Uttaran 27th January 2014 Written Update
Epi begins with Ambika trying to take the bottle from Sankrant but it falls and breaks in the process. He loudly shouts at her to be in her limits. Next second he laughs it off. He holds Ambika's hand a little forcefully as he wants to dance with her. Everyone is watching it shocked as he tries to dance with her forcefully. she tries to move away from him while he holds onto the pallu of her saree which comes off a little. Everyone is shocked to see this. A chant is playing in the background. Akash takes off his hand while Meethi holds Ambika's pallu. Akash slaps Sankrant. Maiyya closes her eyes in pain while Ambika has a slight smile on her face. Meethi covers Ambika who has changed her expressions by now to tears. Akash warns Sankrant to stop it. Ambika tells him not to slap Sankrant. However way he is, he is my husband. Nani is amused. Both the brothers fought amongst each other. Looks like now the war between the brothers has started. The board of directors, Thakur family is dismayed to have seen all this. Everyone starts leaving and Ambika smirks to see the state of both the brothers.
Mukku cannot sleep as Vishnu's words keep echoing in her head. Vishnu picks up his pillow and is about to go but fills a glass of water to keep it by Mukta's side. she has turned her face the other side but holds onto his hand as he keeps the glass for her. Can we not forget what has happened? He replies he is not able to…even though he has been trying to. He takes her hand off his goes from there while she cries.
Akash is sad in his room as he recalls the fiasco that happened in the party because of which he had to slap his brother. He looks at his hand, makes a fist and starts hitting it at the wall / window. Meethi had just come there and runs off to stop him from doing this. Maiyya too has come upon hearing the noises. Meethi asks him not to hurt himself. He says I slapped my younger brother with the same hand. He is in tears. I was wrong. She denies. Someone had to stop him. Sankrant dint do it intentionally. You know he is such a nice person but his addiction for alcohol made him do so. It isn't so that he doesn't want to come out of it. He is trying his best by taking his medicine on time. We too have noticed the change in him. He only needs some time. We will have to make him understand with love, not anger. Akash dint like the way Sankrant behaved with Ambika because of which I had to (slap him in front of everyone). She tells him to forget everything that happened for his brother's sake. Go seek forgiveness from your brother. Everything will be fine trust me. She gestures him to go and he obliges. Maiyya stops Meethi from going out. Don't you think ever as to what's happening in my both son's lives all of a sudden? The brothers have fought for the first time. Who's playing this game? Meethi doesn't know who is doing all this. But I can tell you one thing that I wont let anyone create any kind of rift between both the brothers till I am in this home. A chant plays in the background followed by the voice of conch shell. She stops to tell him something else too. Anni always says you will row the same seeds which you have sown. Meethi leaves from there. Maiyya calls it a slap on her face and I haven't done anything. What's happening!
Sankrant is standing by the window of his room sadly recalling how his brother slapped him. ambika watches him with glee. You must be hurt. But what to do I cannot see anything beyond my revenge. She asks him about the slap. Just then Akash comes there. Ambika asks Sankrant to seek apology from Akash but Akash surprises both of them by saying that it is he who should be apologizing. Meethi joins them. sankrant cannot stop his tears. Akash seeks forgiveness from Sankrant by folding his hands but Sankrant asks him not to. I should be apologising. I embarrassed you in front of everyone. I am not worth being called your brother. Akash declines him being at fault. I forgot that my brother is trying to fight his weakness. I should have supported you, tried to understand you instead I hurt you in front of everyone. The brothers share an emotional hug. Meethi is happy while Ambika is not. Akash promises Sankrant he will get him out of this addiction. Meethi too offers to help him. We all will support you. She asks him about his medicines and he immediately shows it to her. I take it daily and Ambika too reminds me. ambika agrees. Meethi looks at the bottle and gets thinking as to why isn't the medicine showing its effect if Sankrant is continuously taking it. Ambika thinks, it isn't reacting as this is vitamin capsules and not the ones which you all are thinking it to be.
Mukku is reading some files but is lost. Yuvi was passing by but stops to look at her. he smiles seeing her and comes inside her cabin. He asks her if she is all right. She nods grimly. He asks her about his appointments. He is about to go but then asks her about the party. Did you wear that dress? What was your husband's reaction? Meethi answers that Mukta was looking fab in the party. A chant is playing in the background. Mukku is happily surprised to see her there while Yuvi is shocked to see her there. He remembers his first encounter with Meethi in the college and the way she had reacted. Next he remembers how Iccha had hurt him with a knife in order to save Mukta and he was sent to jail based on her testimony. He cannot forgive Iccha's face.
Mukku introduces Meethi to Yuvi and vice versa. Yuvi cannot look at her face as he is feeling a whole lot of emotions. She offers her hand for handshake while he is lost in thoughts. Meethi and Mukku watch it in surprise / confused. He closes his eyes in pain / anger. Meethi backs off. She says ma used to say that the people who don't look into your eye while talking are definitely hiding something. Yuvi stares at her and she notices the distant look in his eyes. He agrees. Maybe ma was right. He then corrects himself saying, your ma. That is the reason why your friend isn't looking in my eyes while talking. Meethi is confused while Mukku shakes her head. Yuvi excuses himself and walks out. Mukku invites her to sit. Meethi finds him strange. Don't know I feel like something is wrong. The way he walked out. What was his name? Mukku tells her – Yuvaan. Meethi repeats the name and then looks at the door. epi ends on her thinking face.
Precap: Meethi was coming to talk to Maiyya but stops as she hears her talking to Gomti. She dint leave any chance. She is my enemy. If it would have been Aatishgarh then I would have gotten her picked up at night and cut her into pieces leaving her in the jungle to be eaten by the wild animals. If nothing else will happen then will do that only. I will kill my DIL. I will end her. meethi is shocked.
Update Credit to: Pooja


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Ian Angus's new book of 'essential debates at the intersections of socialism and science' will be available soon. Here's what some early readers say about it.
Archive | March, 2017
John Bellamy Foster answers five questions about Marxism and ecology
Can Marxism strengthen our understanding of ecological crises? The author of Marx's Ecology replies to a critic on metabolic rift, sustainable human development, degrowth, population growth, and industrialism.
Global climate broke multiple records in 2016; Extreme conditions continue in 2017
World Meteorological Organization says 2016 made history, with a record global temperature, exceptionally low sea ice, and unabated sea level rise and ocean heat. Extreme weather and climate conditions continue in 2017.
Marx and Engels and the Red Chemist
Accounts of Marx and Engels's lives ignore Carl Schorlemmer's influence on their studies of the natural sciences. It is time to acknowledge his rightful place in the socialist tradition.
Carbon dioxide levels now rising at record speed
CO2 growth rate sets new record in 2015-16. Increase in the past ten years is 100 to 200 times as fast as the increase that ended the last ice age
The terrifying mathematics of the Anthropocene
For four billion years, one formula summarized global change. That has changed in just four decades, and if we don't act quickly, human civilization may not survive.
'Ecosocialism is more than a strategy, it's a project for civilization'
"Climate change is far more than a technological issue. It poses the fundamental question of a global alternative to this mode of production."
Countries on Trump's ban list face world's biggest humanitarian crisis since 1945
Twenty million people face imminent death from starvation and famine. Many more will suffer and die from disease. These are the people that Trump is targeting.
Heatwave frequency rises twice as fast in the poorest countries
New research proves that the countries least responsible for global warming, those least able to adapt, have already been hit much harder by deadly extremes than rich nations — and the gap is growing
Climate crisis: There is only one way out
Climate catastrophe can only be averted if people around the globe unite in the biggest, broadest, most effective global social movement the world has ever seen
Ecosocialist Bookshelf, March 2017
Three important new books on the growing global environmental crisis, and two that mark the 100th anniversary of the Russian Revolution … Peter Wadhams, Razmig Keucheyan, Orrin Pilkey, Neil Faulkner, Paul Le Blanc, David Mandel


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Make Your First Impression Count
Posted by Brit in Archaeology & Ancient History on September 24, 2018
Your personal statement is the first things Universities see, well read, about you. This means that whatever you choose to put in there, make it count. I was told some AMAZING tips that allowed me to get offers from all the Universities that I applied for. Tip No.1: Start with something powerful and thought-provoking. […]
Posted in Essay, Future, Studying, Uncategorized | Tagged amazing, archaeological site, archaeology, archaeology student, Ardnamurchan, avebury, camping, college, end of college, era, Erasmus, Erasmus Student Network, erasmus year abroad, essay, Europe, excavation, family, Fieldwork, friends, fun, future, grades, halls, history, holiday, home, job, Leicester, Malta, music, national trust, neolithic, personal, personal statement, places, revision, Roman, Scotland, sea, shopping, stargazing, statement, student, students, study, study abroad, summer, sun, tigers, tips, travel, ucas, universities, university, university accommodation, university of leicester, year abroad
My Visit to Marsaxlokk Fishing Village and Other Adventures
Posted by sra16 in Archaeology & Ancient History on June 29, 2016
I decided to spend my last Sunday in Malta at its famous fishing village, Marsaxlokk (pronounced: marsh-a-slock). Marsaxlokk is not only famous for its fish market on a Sunday, which has now evolved into a market selling everything from fish, fruit and veg to craft items and clothes, it is also famous for its harbour […]
Posted in Erasmus, Leisure, Study Abroad, Uncategorized | Tagged fishing, fishing boats, Malta, Maltese, market, Marsaxlokk, sea, Sliema, swim, trading, traditions, Valletta
The Triumphant Trio's Travels
Posted by sra16 in Archaeology & Ancient History on April 28, 2016
A few weeks ago I was lucky enough to be visited by two of my closest friend from Leicester. Andy and Harry, like myself, are on an Erasmus year abroad but in Bologna. I was very much looking forward to their visit and in the few days they were in Malta we saw a lot […]
Posted in Erasmus, Friends, Holiday, Leisure, Study Abroad, Uncategorized | Tagged Bologna, church, dome, Erasmus, erasmus year abroad, friends, Hagar Qim, history, island, Italy, Leicester, Lower Barrakka Gardens, Malta, Mdina, Mnajdra, Mosta, Mosta Rotunda, San Anton Gardens, San Anton Palace Gardens, sea, second world war, Sliema, sun, temples, Upper Barrakka Gardens, Valletta, year abroad
Work, Life, Study balance!
Posted by Mark in Archaeology & Ancient History on March 5, 2016
In the workplace we occasionally hear the phrase "work- life balance" usually concerning the lack of said balance! We however, have study to add to the mix and, it can be a bit of a balancing act! My own routine consists of study from 0530-0630 each morning. I call this the "golden hour" when I find […]
Posted in Career, Dissertation, Distance Learning, Employment, Erasmus, Essay, Exams, Friends, Future, Graduation, Holiday, Study Abroad | Tagged 2016, archaeology, archaeology student, Erasmus, essay, excavation, family, Fieldwork, friends, holiday, home, job, Leicester, sea, university of leicester | 3 Responses
An Indian Summer (or a November in Malta)
Posted by sra16 in Archaeology & Ancient History on November 30, 2015
Malta experienced its hottest November in 12 years and I was lucky enough to be here to bathe in the glory of the sun. Due to what I like to call an 'extended summer' this month I did a lot more sightseeing and photographing and though I would share some of my favourite Indian summer […]
Posted in Erasmus, Leisure, Study Abroad, Uncategorized | Tagged archaeology, Erasmus, fort, Fort St. Angelo, fortifications, fortified walls, grand harbour, Grand Harbour Malta, Malta, Malta hottest November in 12 years, Malta Indian Summer, Maritime museum, Mdina, Medina, mosaic, Rabat, Roman, Roman town house, sea, sun, sunrise
The Erasmus Student Network Boat Party (Malta)
Posted by sra16 in Archaeology & Ancient History on September 29, 2015
Saturday night brought an amazing experience in my new life in Malta, it was the first Erasmus Student Network (ESN) social of the academic year and what a way to start my new Erasmus year abroad by celebrating in style at a boat party! Before even moving into my accommodation I threw myself into the […]
Posted in Erasmus, Friends, Leisure, Societies, Study Abroad, Studying, Uncategorized | Tagged boat party, boat trip, bucket list, Erasmus, Erasmus Student Network, ESN, ESN Malta, Europe, Gozo, Malta, Mediterranean, music, party, sea, social, student union, study abroad bucket list, university of leicester, University of Leicester SU
My Study Abroad Bucket List
Posted by sra16 in Archaeology & Ancient History on September 20, 2015
As a going away present one of closest friends bought me the most adorable travel journal I have ever seen. I am not the kind of person who has ever kept a diary or journal and I don't tend to document my life. However, after receiving this beautiful gift I have decided to give it […]
Posted in Erasmus, Friends, Future, Leisure, Study Abroad, Uncategorized | Tagged bucket list, diary, erasmus year abroad, friends, journal, list, Malta, museum, postcard, sea, shopping, stargazing, study abroad, swim, the university of leicester, travel, travel journal, university


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Date: November 17th, 2020
Virtual Presentation
One of the most asked questions during challenging or uncertain times is, 'Who are the leaders of the future?' Never has that been more prevalent or appropriate than now.
At the Vancouver Business Journal we ask the community to help us answer that question through our annual Accomplished & Under 40 program. You know who these young achievers are. They are the rising stars in your companies, they sit on nonprofit boards with you and they are active in the community as coaches, mentors, volunteers and in neighborhood organizations. Professionally, those recognized in previous years have come from the ranks of small business owners, physicians, educators, marketers and public service.
Join us for this annual recognition luncheon as we highlight the brightest, young leaders in our community.
Nominations are now open for 2020! Submit your nomination here.
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Ruben Loftus-Cheek has enjoyed a productive season at Selhurst Park and the midfielder is
set to return to Stamford Bridge this summer.
Crystal Palace have benefited from the 22-year old's dynamism and he's helped the Eagles steer themselves clear of the relegation zone. As a result of his eye-catching performances in a Palace shirt, he is believed to be one of the club's top targets this summer.
Following their 2-0 win against already-relegated West Brom, Loftus-Cheek expressed his
gratification to everybody at the club, wishing them "all the best in the future".
A number of Crystal Palace fans are already imploring their side to splash the cash in order to ensure he returns to South London next year but the lure of playing at Stamford Bridge may persuade him to remain with Chelsea.
Born in Lewisham, Loftus-Cheek joined the club at the age of eight and enjoyed tremendous success playing for the club's youth team. According to a study by Betting.net, less than 0.5% of nine-year-olds at club academies become professional footballers, meaning Loftus-Cheek is one of a small group of players who have bucked the trend.
He has constantly improved and progressed with age and he has recently been rewarded with an England call-up. The survey also reveals that players from London stand a greater chance of progression than their counterparts in the South-West or East-Midlands.
He is unlikely to leave West London if he believes there is a chance of breaking into the first
team, although, with the future of manager Antonio Conte unclear, it may be a while until
any decision is made.
He found the back of the net on two occasions for Roy Hodgson's side and chipped in with
three Premier League assists. He also played at least one key pass per game and, despite
having an injury-hit campaign, he still managed to make 21 appearances.
The Palace manager admitted that "you don't replace the quality of players like Ruben Loftus-Cheek very easily" before explaining that the club will need to be patient and realistic with its approach to negotiations this summer.
He would provide a useful outlet for Chelsea next season as the club bids to return to the
UEFA Champions League and many Blues fans are keen to see an academy graduate feature regularly in the first team.
Loftus-Cheek has a decision to make this summer but he is likely to bide his time before deciding whether his future lies at Stamford Bridge or Selhurst Park.


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Unity 5 Is Out Now, Has Free No-Royalty "Personal Edition"
I'm at a Unity [official site] special event at GDC and I've had a donut for breakfast. Take everything I'm writing below with a pinch of the sugar rushing through my veins, but Unity have just announced that Unity 5 is available to download now and that there's a free, no-royalty Personal Edition for use by small companies.
There's a livestream of the event and more details below.
I am adding more details on what Unity 5 contains in between looking for some fruit.
For starters, there's a question over whether Unity have an answer to Epic MegaGames' announcement yesterday that the Unreal Engine would now be free (with a 5% royalty on games released using it). Unity 5 Professional's pricing is the same as Unity 4 – $75/month or $1500 with no royalty. However, they also announced Unity Personal Edition, which is free, with no royalties, and for use for companies with earnings below $100k.
That sounds good, though a larger coup is maybe that Unity CEO John Riccitiello then introduced Mike Capps to the stage, who was the long-time president of Epic (MegaGames). That's some top corporate trolling. Capps talked about Unity's graphics engine and how it now allows small teams to reach "high-end graphics". It's weird to think that small indie developers are basically repeating the graphics race that triple-A went through in the late '90s.
The second big thing is how Unity has been working with Oculus to put native-support for the virtual reality headset into Unity 5. An alpha for that has just launched. I have no idea what that means over the old plugin implementation, but Oculus Rift inventor Palmer Luckey seemed excited. And young. He's very young.
This is a developer-focused event, and the focus so far is on ways that Unity 5 can make development either easier or make games potentially prettier. The first example is a quicker-to-use lighting model, which one of Unity's founders demonstrated by building and lighting a scene live on stage. Then the developer of Republique talked about how Republique Remastered – the PC/Mac version of the iOS sneak-'em-up – was made within Unity 5. It seems that lots of lighting that was previously faked by being baked into the textures is now able to be rendered in real-time.
Hey look, screenshots of what Unity 5 can do.
Sexy curves/moustaches.
They're now bigging up Unity Ads, a service for monetizing mobile games. The example they give is Crossy Road, which apparently has made $3 million from its in-app adverts. This is definitely a developer-focused event.
The highlight of the event for me is i) the introducer pronouncing John Riccitiello's name wrong and ii) Riccitiello doing mouth sound effects when the first trailer's audio didn't work. I am not a game developer, YMMV.
Here's the livestream.


text: On 4 Apr 2012, at 14:46, Robert Neiman wrote: Troll v Richterbach <reply> are you sure you didn't mean 84 GV Ch Cobert's Trollstigen ROM OFA ============================================================================ POST is Copyrighted 2011. All material remains the property of the original author and of GSD Communication, Inc. NO REPRODUCTIONS or FORWARDS of any kind are permitted without prior permission of the original author AND of the Showgsd-l Management. ALL RIGHTS RESERVED. Each Author is responsible for the content of his/her post. This group and its administrators are not responsible for the comments or opinions expressed in any post. ALL PERSONS ARE ON NOTICE THAT THE FORWARDING, REPRODUCTION OR USE IN ANY MANNER OF ANY MATERIAL WHICH APPEARS ON SHOWGSD-L WITHOUT THE EXPRESS PERMISSION OF ALL PARTIES TO THE POST AND THE LIST MANAGEMENT IS EXPRESSLY FORBIDDEN, AND IS A VIOLATION OF LAW. VIOLATORS OF THIS PROHIBITION WILL BE PROSECUTED. For assistance, please contact the List Management at admin@xxxxxxxxxxx VISIT OUR WEBSITE - http://showgsd.org SUBSCRIPTION:http://showgsd.org/mail.html NATIONAL BLOG - http://gsdnational.blogspot.com/ ============================================================================


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Rep. Charlie Rangel said there's no reason for his Democratic colleague, Anthony Weiner, to resign, and that he could be an effective congressman "if the press gets off his back."
Rangel, who survived his own ethics investigation last year for improperly reporting his financial assets, said there's no reason for Weiner to step aside.
"Not one person has given any reason for a resignation," said Rangel. "The Constitution is abundantly clear" on describing appropriate conduct for Congress members.
"He wasn't going with prostitutes. He wasn't going out with little boys. He wasn't going into men's room with broad stances," Rangel said. "I mean, All of those I understand; I'm 80 years old. But high-tech stuff like this, I can't respond. But I know immoral sex when I hear it from other members, and no one has screamed for their resignation. So I don't know why they're selecting Anthony."
Rep. Carolyn Maloney, of Manhattan and Queens, was less supportive. She said she's not sure if she'd support him for re-election, since it's unclear who will be on the ballot.
And Assembly Speaker Sheldon Silver said he hadn't heard of any plans to re-draw Weiner's district out of existence, joking that the two seats New York must lose "could be two Republicans."
Silver, noting that the lines will are expected to be re-drawn by an independent for the first time, jokingly added, "I don't know what those professors are going to do."
This was all the reporters wanted to talk about, as one by one, elected official left a press conference this morning honoring Iranian bloggers for promoting democracy through the use of social media.
Weiner was originally scheduled to be among the attendees, but his name was removed once his problems with Twitter became known.


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We are open with safety measures in place, how can we help you?
Be one of the first to test drive the new MINI Countryman*. *Test drive subject to applicant status and availability.
MINI Electric has everything you'd expect – good looks, that unique go-kart handling – plus it's fully electric.


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All News
ORNL's Communications team works with news media seeking information about the laboratory. Media may use the resources listed below or send questions to email@example.com.
1 - 10 of 16 Results
A team led by Dan Jacobson of Oak Ridge National Laboratory used the Summit supercomputer at ORNL to analyze genes from cells in the lung fluid of nine COVID-19 patients compared with 40 control patients.
Scientists at ORNL used neutron scattering and supercomputing to better understand how an organic solvent and water work together to break down plant biomass, creating a pathway to significantly improve the production of renewable
A team of researchers has performed the first room-temperature X-ray measurements on the SARS-CoV-2 main protease — the enzyme that enables the virus to reproduce.
Scientists have tapped the immense power of the Summit supercomputer at Oak Ridge National Laboratory to comb through millions of medical journal articles to identify potential vaccines, drugs and effective measures that could suppress or stop the spread of COVID-19.
For the second year in a row, a team from the Department of Energy's Oak Ridge and Los Alamos national laboratories led a demonstration hosted by EPB, a community-based utility and telecommunications company serving Chattanooga, Tennessee.
The prospect of simulating a fusion plasma is a step closer to reality thanks to a new computational tool developed by scientists in fusion physics, computer science and mathematics at ORNL.
A novel approach developed by scientists at ORNL can scan massive datasets of large-scale satellite images to more accurately map infrastructure – such as buildings and roads – in hours versus days.
An international team of researchers has discovered the hydrogen atoms in a metal hydride material are much more tightly spaced than had been predicted for decades — a feature that could possibly facilitate superconductivity at or near room temperature and pressure.
The U.S. Department of Energy's Office of Science announced allocations of supercomputer access to 47 science projects for 2020.
Processes like manufacturing aircraft parts, analyzing data from doctors' notes and identifying national security threats may seem unrelated, but at the U.S. Department of Energy's Oak Ridge National Laboratory, artificial intelligence is improving all of these tasks.


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While the streets outside the Stonewall Inn are set ablaze, a small Appalachian mining town goes through its own quieter turmoil. Anthropology Lesson explores the lives of "roommates" Thomas and Douglas during the summer of 1969. The men have spent the last 13 years building a life together, until an unexpected late-night visitor interrupts Douglas' first night home after a weekend away. As the play unfolds, the two men's lives are turned upside down while a principal, a mother, and a student all come to terms with their own sets of truths.
Winner of the 2018 SETC/Stage Rights Ready to Publish Award.
Anthropology Lesson is a story framed by a classroom of students and teachers who act as a contemporary Greek chorus. The play opens with a prologue where the classroom teaches the audience about the setting of the play— Grundy, Virginia, a small town in Appalachia in 1969.
Scene 1 opens in the home of Thomas and Douglas, where the action of the play takes place. Thomas welcomes Douglas home and invites Douglas' student Luke to stay for dinner. Luke and Douglas have just returned from a long drive across the state. At dinner, Douglas and Luke recount their experiences over the past few days, including Luke impressing a college baseball coach. We also learn just how much Luke means to Douglas as a student and vice versa.
After a transitional lesson from the "classroom," Scene 2 opens to reveal Thomas and Douglas later that same evening. As they clean up from dinner and catch each other up on the past few days, they show the audience just how clearly in love with each other they are and, more importantly, how settled and comfortable they are in Grundy. Luke unexpectedly returns to the home and "catches" Douglas and Thomas in a kiss. Luke grabs what he came back for and leaves for the night. Thomas and Douglas are confused about whether to be worried about Luke seeing their kiss. After a transition and lesson from the classroom, Scene 3 begins.
Scene 3 takes place the next evening with Thomas and Douglas having a quiet night at home. We learn that it is the week of July 4th and Thomas will get a day off. As they are discussing their plans for the holiday, there is a knock at their door— it's Luke. Luke reveals that he has gotten in a fight with his mother and needs a place to stay for the evening. Douglas has a soft spot in his heart for Luke and his family and agrees to let him stay the night in the guest room. Luke agrees to call his mom and patch things up the next morning.
Scene 4 takes place a couple of days later, and the radio lets the audience know that it is Independence Day. Thomas is enjoying a great holiday morning, cooking breakfast and listening to his favorite radio station. While getting ready for the morning, the town sheriff interrupts Thomas' breakfast preparations. The sheriff engages in some small talk and is clearly stalling for time, saying he is waiting for Douglas to wake up. The sheriff is taken aback and Thomas is unnerved as young Luke comes into the kitchen both in the underwear he has been sleeping in and completely unaware of the sheriff's presence. The sheriff has indeed made the visit to see if Luke had spent the last few evenings with Douglas and Thomas, and has come to bring him home to his mother. The scene closes as Luke reluctantly goes with the sheriff and leaves Thomas and Douglas wondering what has happened. (Although written as a full-length play in one act, the end of Scene 4 would be the ideal place to put an intermission, if desired).
In the next "classroom" lesson it is revealed that the audience is about to see the "Anthropology Lesson."
Scene 5 is a non-linear scene where Douglas' boss, the high school principal, is interviewing people about Luke and Douglas' student/teacher relationship. In this scene, we meet Luke's mom Dulce for the first time. She express concerns about Douglas and Thomas and calls them "peculiar," which the audience learns is a euphemism for "queer." The scene reveals that Douglas may be being judged for his actions being taken out of context. The principal's questions intensify and cause Luke to lose his temper in defense of his teacher Douglas. Throughout the questioning, Douglas sticks to the facts, while Thomas, Luke, and Dulce all reveal only part of the truth. The "classroom" doesn't really know how to react to the intensity of Scene 5, but offers a simple transition and lesson in preparation for Scene 6.
In Scene 6, Dulce has come to Thomas and Douglas' home to talk to Thomas. A couple of weeks have passed since the principal interviews, and Dulce believes that Douglas is about to be fired. In order to protect her relationship with her son, Dulce has come to suggest that Douglas resign before being fired. Thomas sees that this is a play to keep Dulce innocent in Luke's eyes. Thomas and Dulce have a rather intense exchange about the intention of Thomas and Douglas' kindness to her family. Dulce suggests that part of her insecurity is the judgment of the town about her poverty, and Thomas challenges that he is actually more of a victim of the town's judgment. Dulce wants her family to remain intact, and Thomas wants Douglas' dignity to be undamaged. It is clear that only one of them will get their way.
Scene 7 opens at the end of the summer. During the scene, we see that weeks have passed, Douglas has indeed been fired, and he is leaving town. Thomas and Douglas are spending their last morning at home before Douglas' departure. They are committed to staying together, but their relationship and standing in the community have both suffered because of this incident with Luke. They share tender moments before Thomas has to leave for work, and after he does, Luke pays one final visit to Douglas. The teacher and young man share their admiration for each other and the audience sees that the two have each benefited and grown because of the other. Douglas is touched by Luke's visit and kind words, but is also troubled by the fact that Luke might join the military rather than take a college scholarship. Luke is troubled by the fact that Douglas has decided to leave town, but is committed to keeping in touch with his mentor. As the scene and play end, Douglas and Luke part ways and Douglas has his final moments alone in the home he has loved. Curtain.
Characters:Thomas Hodges – Thomas is in his early thirties; when he isn't working at the coal mine, he enjoys a pastime in painting and his simple life at home with Douglas.
Douglas Walker – Douglas is a high school English teacher in his hometown of Grundy, Virginia who has settled into his life living with Thomas and being the teacher everyone loves.
Luke Robinson – Luke has spent a few weeks away from home before starting his senior year of high school at Grundy High School where he enjoys playing baseball for the school and community teams.
Radio Announcer – A voice actor who could be doubled with Dulce Robinson.
Sheriff Hollins – Sheriff Hollins is a friendly small-town sheriff who could be doubled with Andy Smith.
Andy Smith – Andy is the principal of Grundy High School and seems to know everyone in town.
Dulce Russell – Dulce is a single mom who works at the Piggly Wiggly and is raising Luke and two other siblings.
Teachers/Students 1, 2, 3, 4 & 5 – These characters provide a variety of functions in the storytelling, almost serving as a contemporary, educational Greek chorus. These parts could be doubled with the named characters.
Note: Creativity on the casting, blocking, and use of this ensemble is encouraged.
Setting: The action of the play takes place in a unit set which is the 1969 kitchen/living room of Thomas and Douglas' home.
Performance Royalties for AMATEUR and EDUCATIONAL Groups begin at $90.00 per performance for theaters under 150 seats, and rise depending on ticket prices and theater particulars. Please fill out an application for your personalized quote.
Performance Royalties for PROFESSIONAL Theaters will be quoted as a box office percentage, with a minimum guarantee based on ticket prices and theater particulars. Please fill out an application for your personalized quote.
An Authorized Materials/Rehearsal Package must be purchased from Stage Rights as a part of your licensing agreement (see Materials).
Billing responsibilities, pertinent copyright information, and playwrights' biographies are available in the show rider that comes with your license agreement.
An Authorized Materials/Rehearsal Package must be purchased from Stage Rights as a part of your licensing agreement. Your materials will be sent to you two months prior to your opening date, unless other arrangements have been made in advance with your Stage Rights Licensing Representative.
The Authorized Materials/Rehearsal Package for Anthropology Lesson consists of:
18 Production Scripts / $210.00 (shipping included)
Production Scripts for Plays are professionally printed and bound with a full-color cover.
You will have the option to purchase additional Production Scripts at a discounted rate when you complete your Licensing Agreement.
Official Logo Pack Now Included! To help you promote your show, Stage Rights now includes a logo pack with your license. The logo pack includes high resolution versions (both color and black and white) of our show logo. The logo is the portion of the artwork with the title of the show. The surrounding artwork is also available for an additional fee.
Optional Materials:
Stage Manager's Script – Printed on standard 8.5" x 11" 3-hole-punched paper, with the same page numbers and text as the Printed Production Scripts, but with more space on the page for notes and cues.


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July 25, 2018
Vulnerabilities, attacks, and breaches of connected devices highlight market need for secure IoT and validate the approach taken by the Afero next-generation IoT platform
Los Altos, California – Afero, the next-generation IoT platform company, confirmed that the recently discovered Bluetooth and DNS-Rebinding vulnerabilities do not affect IoT devices that are powered by the Afero Platform™. The vulnerabilities would allow a remote attacker to gain unauthenticated access to a device or manipulate the data traffic generated by the device.
Tracked as CVE-2018-5383, the vulnerability is related to both Bluetooth®and Bluetooth low energy (BLE) implementations, and reportedly affects firmware or operating system software drivers from vendors including Apple, Broadcom, Intel, Qualcomm, and possibly others.
Also in the news is a vulnerability that can be exploited to bypass a network's cybersecurity firewall. This would allow an attacker to gain insecure access to a connected device.
The Afero IoT Platform™ represents the most secure IoT platform in the industry since it provides always-encrypted always-authenticated data paths, secure device and service identities backed by hardware roots of trust, secure supply chain, and implements the full scope of security best practices.
"Security in IoT is not just an issue for companies, but also for consumers," said Joe Britt, CEO and co-founder of Afero. "Best practices in security must be designed in from the beginning, must go beyond securing data paths to include the entire supply chain, and must remain vigilant throughout the life of a connected device. That's what the Afero Platform provides."
In addition to being highly secure and simple for customers to use, Afero IoT connectivity has been proven to work beyond seven-plus-figure levels, allowing IoT innovators to prepare for the rapid growth the industry is known for.
Afero has built a strong set of partnerships across the IoT technology spectrum as it leads a new approach for end-to-end IoT with notable projects such as Kenmore and D-Link. Afero was named a 2016 Cool Vendor in the Internet of Things by Gartner, Inc.
About Afero
The Afero next-generation IoT platform accelerates time to market, provides hardened security from sensor to cloud and from factory to customers, simplifies onboarding to help maximize customer connections, and uses data ontology to streamline machine learning. The platform is supported by elastic, multi-cloud services that deliver reliability and responsiveness, and a new software engineering model that unifies embedded, mobile, and cloud development.
Afero has assembled world-class mobile, hardware, security, and cloud veterans from Google, Apple, Nest, Danger, Microsoft, Amazon, Twitter, and Netflix. To learn more about Afero, please visit www.afero.io.


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Tel: Tel:(732)-842-7773
Serious car crash → Brain injury → Truck accidents →
Mr. Moriarty has received the highest accolade by his peers for his superior trial work. His AV peer review rating with Martindale-Hubbell attests to his professional excellence, skill, and integrity. In addition, Mr. Moriarty is Certified by the Supreme Court of New Jersey as a Civil and Criminal Trial Attorney. There are over 85,000 practicing attorneys in the State New Jersey and only 43 of them are Certified by the Supreme Court of New Jersey as Trial Attorneys in both Civil and Criminal law.
Criminal defense is a significant part of Mr. Moriarty's practice, and many of his cases have received attention in print media, on television, and on the Internet. While he relishes his work on these complex trials, he has said that some of his most significant victories were those in which a client was being investigated for wrongdoing, but, thanks to his legal intervention, was never charged.
Mr. Moriarty also handles all types of traffic matters, concentrating heavily on Driving While Intoxicated (DWI) and other alcohol and/or drug-related offenses. He has lectured countless seminars and training courses involving criminal and DWI jurisprudence.
Mr. Moriarty is a former President of the Monmouth County Bar Association and Municipal prosecutor in several towns with more than 40 years of experience in criminal and personal injury law. Mr. Moriarty has served on the adjunct faculty of Rutgers Law School – Newark. Mr. Moriarty is one of the founding members of the Hayden Proctor Inns of Court.
Mr. Moriarty along with two of his sons Timothy & Kevin Moriarty are the three partners that make up The Moriarty Law Firm.