AMPK:a nutrient and energy sensor that maintains energy homeostasis

AMP-activated protein kinase (AMPK) is a crucial cellular energy sensor. Once activated by falling energy status, it promotes ATP production by increasing the activity or expression of proteins involved in catabolism while conserving ATP by switching off biosynthetic pathways. AMPK also regulates metabolic energy balance at the whole-body level. For example, it mediates the effects of agents acting on the hypothalamus that promote feeding and entrains circadian rhythms of metabolism and feeding behaviour. Finally, recent studies reveal that AMPK conserves ATP levels through the regulation of processes other than metabolism, such as the cell cycle and neuronal membrane excitability

Friedreich's Ataxia (GAA)n•(TTC)n Repeats Strongly Stimulate Mitotic Crossovers in Saccharomyces cerevisae

Expansions of trinucleotide GAA•TTC tracts are associated with the human disease Friedreich's ataxia, and long GAA•TTC tracts elevate genome instability in yeast. We show that tracts of (GAA)230•(TTC)230 stimulate mitotic crossovers in yeast about 10,000-fold relative to a “normal” DNA sequence; (GAA)n•(TTC)n tracts, however, do not significantly elevate meiotic recombination. Most of the mitotic crossovers are associated with a region of non-reciprocal transfer of information (gene conversion). The major class of recombination events stimulated by (GAA)n•(TTC)n tracts is a tract-associated double-strand break (DSB) that occurs in unreplicated chromosomes, likely in G1 of the cell cycle. These findings indicate that (GAA)n•(TTC)n tracts can be a potent source of loss of heterozygosity in yeast

Turning Males On: Activation of Male Courtship Behavior in Drosophila melanogaster

The innate sexual behaviors of Drosophila melanogaster males are an attractive system for elucidating how complex behavior patterns are generated. The potential for male sexual behavior in D. melanogaster is specified by the fruitless (fru) and doublesex (dsx) sex regulatory genes. We used the temperature-sensitive activator dTRPA1 to probe the roles of fruM- and dsx-expressing neurons in male courtship behaviors. Almost all steps of courtship, from courtship song to ejaculation, can be induced at very high levels through activation of either all fruM or all dsx neurons in solitary males. Detailed characterizations reveal different roles for fruM and dsx in male courtship. Surprisingly, the system for mate discrimination still works well when all dsx neurons are activated, but is impaired when all fruM neurons are activated. Most strikingly, we provide evidence for a fruM-independent courtship pathway that is primarily vision dependent

Progressive GAA·TTC Repeat Expansion in Human Cell Lines

Trinucleotide repeat expansion is the genetic basis for a sizeable group of inherited neurological and neuromuscular disorders. Friedreich ataxia (FRDA) is a relentlessly progressive neurodegenerative disorder caused by GAA·TTC repeat expansion in the first intron of the FXN gene. The expanded repeat reduces FXN mRNA expression and the length of the repeat tract is proportional to disease severity. Somatic expansion of the GAA·TTC repeat sequence in disease-relevant tissues is thought to contribute to the progression of disease severity during patient aging. Previous models of GAA·TTC instability have not been able to produce substantial levels of expansion within an experimentally useful time frame, which has limited our understanding of the molecular basis for this expansion. Here, we present a novel model for studying GAA·TTC expansion in human cells. In our model system, uninterrupted GAA·TTC repeat sequences display high levels of genomic instability, with an overall tendency towards progressive expansion. Using this model, we characterize the relationship between repeat length and expansion. We identify the interval between 88 and 176 repeats as being an important length threshold where expansion rates dramatically increase. We show that expansion levels are affected by both the purity and orientation of the repeat tract within the genomic context. We further demonstrate that GAA·TTC expansion in our model is independent of cell division. Using unique reporter constructs, we identify transcription through the repeat tract as a major contributor to GAA·TTC expansion. Our findings provide novel insight into the mechanisms responsible for GAA·TTC expansion in human cells

Dental metric standards for sex estimation in archaeological populations from Iran

Sex estimation of skeletal remains is one of the major components of forensic identification of unknown individuals. Teeth are a potential source of information on sex and are often recovered in archaeological or forensic contexts due to their post-mortem longevity. Currently there is limited data on dental sexual dimorphism of archaeological populations from Iran. This dissertation represents the first study to provide a dental sex estimation method for Iron Age populations. The current study was conducted on the skeletal remains of 143 adults from two Iron Age populations in close temporal and geographic proximity in the Solduz Valley (West Azerbaijan Province of Iran). 2D and 3D cervical mesiodistal and buccolingual and root volume measurements of maxillary and mandibular teeth were used to investigate the degree of sexual dimorphism in permanent dentition and to assess their applicability in sex estimation. In total 1327, 457, and 480 anterior and posterior teeth were used to collect 2D cervical, 3D cervical, and root volume measurements respectively. 2D cervical measurements were taken using Hillson-Fitzgerald dental calliper and 3D measurements were collected using CT images provided by Open Research Scan Archive (ORSA) - Penn Museum. 3D models of the teeth were created using manual segmentation in the Amira 6.01 software package. Since tooth density largely differs from crown to apex, root segmentation required two threshold levels: the segmentation of the root from the jaw and the segmentation of the crown from the root. Thresholds used for root segmentation were calculated using the half maximum height protocol of Spoor et al. (1993) for each skull, and thresholds used for crown segmentation were set visually for each tooth separately. Data was analysed using discriminant function analysis and posterior probabilities were calculated for all produced formulae where sex was previously assessed from morphological features of pelvis and skull. Bootstrapping was used to account for small sample sizes in the analysis. Statistical analysis was carried out using SPSS 23. The percentage of sexual dimorphism was also used to quantify the amount of sexual dimorphism in the sample. The results showed that incisors and canines were the most sexually dimorphic teeth, providing percentages of correct sex classification between 80% and 100% depending on the measurement used. Root volume measurement was shown to be the most sexually dimorphic variable providing an accuracy of over 90% in all functions. The present study provided the first dental metric standards for sex estimation using odontometric data in Iranian archaeological populations. Dental measurements, particularly root volume measurements, were found to be of value for sex assessment and the method presented here could be a useful tool for establishing accurate demographic data from skeletal remains of the Iron Age from Iran

Changing Lives and the Role of Income Support

This report presents the finding of a study to explore the nature and effects of changes in circumstances for Income Support claimants. The study involved a survey of claimants, depth interviews with claimants and Benefits Agency staff and secondary analysis of data from the Department of Social Security's Annual Statistical Enquiry

The new structure of child benefit A review

SIGLEAvailable from British Library Document Supply Centre- DSC:q93/09259 / BLDSC - British Library Document Supply CentreGBUnited Kingdo