Disentangling Early Stone Age palimpsests: determining the functional independence of hominid- and carnivore-derived portions of archaeofaunas

Determining the extent to which hominid- and carnivore-derived components of fossil bone palimpsests formed independently of each other can provide valuable information to paleoanthropologists interested in reconstructing the foraging adaptations of hominids. Because stone tool cutmarks, hammerstone percussion marks, and carnivore tooth marks are usually only imparted on bone during nutrient extraction from a carcass, these bone surface modifications are particularly amenable to the types of analyses that might meet this goal. This study compares the percentage of limb bone specimens that preserve evidence of both hominid- and carnivore-imparted bone damage from actualistic control samples and several Plio-Pleistocene archaeofaunas, including new data from Swartkrans Member 3 (South Africa). We argue that this procedure, which elucidates the degree of hominid-carnivore independence in assemblage formation, will allow researchers to extract for focused analyses high integrity components (hominid and carnivore) from presumably low integrity sites. Comparisons suggest that the hominid- and carnivore-derived components from sites in Olduvai Gorge Bed II (Tanzania), the ST Site Complex at Peninj (Tanzania), and Swartkrans Member 3 formed largely independent of each other, while data from the FLK 22 Zinjanthropus (FLK Zinj) site (Olduvai Gorge Bed I) indicate significant interdependence in assemblage formation. This contrast suggests that some Early Stone Age assemblages (e.g., the Olduvai Gorge Bed II sites, the Peninj ST Site Complex, and Swartkrans Member 3) are probably more useful than others (e.g., FLK Zinj) for assessing the maximal carcass-acquiring abilities of early hominids; in such assemblages as those in the former set, sole hominid-contribution is more confidently discerned and isolated for analysis than in assemblages such as FLK Zinj.     

Molecular comparison of monocot and dicot U1 and U2 snRNAs

To elucidate differences between the pre-mRNA splicing components in monocots and dicots, we have cloned and characterized several U1 and U2 snRNA sequence variants expressed in wheat seedling nuclei. Primer extension sequencing on wheat and pea snRNA populations has demonstrated that two 5'-terminal nucleotides found in most other U1 snRNAs are missing/modified in many plant U1 snRNAs. Comparison of the wheat U1 and U2 snRNA variants with their counterparts expressed in pea nuclei has defined regions of structural divergence between monocot and dicot U1 and U2 snRNAs. The U1 and U2 snRNA sequences involved in RNA:RNA interaction with pre-mRNAs are absolutely conserved. Significant differences occur between wheat and pea U1 snRNAs in stem I and II structures implicated in the binding of U1-specific proteins suggesting that the monocot and dicot U1-specific snRNP proteins differ in their binding specificities. Stem III structures, which are required in mammalian systems for splicing complex formation but not for U1-specific protein binding, differ more extensively than stems I, II, or IV. In U2 snRNAs, the sequence differences between these two species are primarily localized in stem III and in stem IV which has been implicated in snRNP protein binding. These differences suggest that monocot and dicot U1 and U2 snRNPs represent distinct entities that may have monocot- and dicot-specific snRNP protein variants associated with each snRNA.     

Food insecurity among Inuit preschoolers: Nunavut Inuit Child Health Survey, 2007–2008

Background

Food security (i.e., a condition in which all people, at all times, have physical and economic access to sufficient, safe and nutritious food to meet their dietary needs and food preferences for an active and healthy life) has been noted to be lower in indigenous communities in Canada. We investigated the prevalence of inadequate food security, or food insecurity, among Inuit households with preschool children.

Methods

We conducted a cross-sectional survey of the health status of 388 randomly selected Inuit children aged three to five years in 16 Nunavut communities during the period from 2007 to 2008. From the survey data, we classified levels of food insecurity specifically among children. We also classified levels of overall food insecurity of the household of each child. We calculated the weighted prevalence of levels of child food insecurity and of household food insecurity.

Results

Nearly 70% of Inuit preschoolers resided in households rated as food insecure (69.6%; 95% confidence interval [CI] 64.7%–74.6%). Overall, 31.0% of children were moderately food insecure, and 25.1% were severely food insecure, with a weighted prevalence of child food insecurity of 56.1% (95% CI 51.0%–61.3%). Primary care-givers in households in which children were severely food insecure reported experiencing times in the past year when their children skipped meals (75.8%), went hungry (90.4%) or did not eat for a whole day (60.1%). Primary caregivers in households in which children were moderately food insecure reported experiencing times in the past year when they worried food would run out (85.1%), when they fed their children less expensive food (95.1%) and when their children did not eat enough because there was no money for food (64.3%).

Interpretation

We observed a high prevalence of household food insecurity, with a substantial proportion of children with severely food insecure status. Interventions are needed to ensure a healthy start in life for Inuit preschoolers.According to the 1996 World Food Summit, food security exists when “all people, at all times, have physical and economic access to sufficient, safe and nutritious food to meet their dietary needs and food preferences for an active and healthy life.”¹ Food security is essential for public health² and important for child development. Suboptimal food security, or food insecurity, has deleterious effects on children’s academic performance and psychosocial development.^3,4 In Canada, food insecurity is higher in the three territories than in the provinces.⁵ According to limited data, a high degree of food insecurity exists among Inuit in particular.^6,7 Further, in most remote communities, the cost of food is at least double that in southern Canadian cities.⁸We assessed the prevalence of food insecurity among Inuit preschool-aged children.     

Gene expression profiling of early intervertebral disc degeneration reveals a down-regulation of canonical Wnt signaling and caveolin-1 expression: implications for development of regenerative strategies

Introduction

Early degeneration of the intervertebral disc (IVD) involves a change in cellular differentiation from notochordal cells (NCs) in the nucleus pulposus (NP) to chondrocyte-like cells (CLCs). The purpose of this study was to investigate the gene expression profiles involved in this process using NP tissue from non-chondrodystrophic and chondrodystrophic dogs, a species with naturally occurring IVD degeneration.

Methods

Dual channel DNA microarrays were used to compare 1) healthy NP tissue containing only NCs (NC-rich), 2) NP tissue with a mixed population of NCs and CLCs (Mixed), and 3) NP tissue containing solely CLCs (CLC-rich) in both non-chondrodystrophic and chondrodystrophic dogs. Based on previous reports and the findings of the microarray analyses, canonical Wnt signaling was further evaluated using qPCR of relevant Wnt target genes. We hypothesized that caveolin-1, a regulator of Wnt signaling that showed significant changes in gene expression in the microarray analyses, played a significant role in early IVD degeneration. Caveolin-1 expression was investigated in IVD tissue sections and in cultured NCs. To investigate the significance of Caveolin-1 in IVD health and degeneration, the NP of 3-month-old Caveolin-1 knock-out mice was histopathologically evaluated and compared with the NP of wild-type mice of the same age.

Results

Early IVD degeneration involved significant changes in numerous pathways, including Wnt/β-catenin signaling. With regard to Wnt/β-catenin signaling, axin2 gene expression was significantly higher in chondrodystrophic dogs compared with non-chondrodystrophic dogs. IVD degeneration involved significant down-regulation of axin2 gene expression. IVD degeneration involved significant down-regulation in Caveolin-1 gene and protein expression. NCs showed abundant caveolin-1 expression in vivo and in vitro, whereas CLCs did not. The NP of wild-type mice was rich in viable NCs, whereas the NP of Caveolin-1 knock-out mice contained chondroid-like matrix with mainly apoptotic, small, rounded cells.

Conclusions

Early IVD degeneration involves down-regulation of canonical Wnt signaling and Caveolin-1 expression, which appears to be essential to the physiology and preservation of NCs. Therefore, Caveolin-1 may be regarded an exciting target for developing strategies for IVD regeneration.     

Hypertriglyceridemic-waist phenotype and glucose intolerance among Canadian Inuit: the International Polar Year Inuit Health Survey for Adults 2007�C2008

Background

Inuit have not experienced an epidemic in type 2 diabetes mellitus, and it has been speculated that they may be protected from obesity’s metabolic consequences. We conducted a population-based screening for diabetes among Inuit in the Canadian Arctic and evaluated the association of visceral adiposity with diabetes.

Methods

A total of 36 communities participated in the International Polar Year Inuit Health Survey. Of the 2796 Inuit households approached, 1901 (68%) participated, with 2595 participants. Households were randomly selected, and adult residents were invited to participate. Assessments included anthropometry and fasting plasma lipids and glucose, and, because of survey logistics, only 32% of participants underwent a 75 g oral glucose tolerance test. We calculated weighted prevalence estimates of metabolic risk factors for all participants.

Results

Participants’ mean age was 43.3 years; 35% were obese, 43.8% had an at-risk waist, and 25% had an elevated triglyceride level. Diabetes was identified in 12.2% of participants aged 50 years and older and in 1.9% of those younger than 50 years. A hypertriglyceridemic-waist phenotype was a strong predictor of diabetes (odds ratio [OR] 8.6, 95% confidence interval [CI] 2.1–34.6) in analyses adjusted for age, sex, region, family history of diabetes, education and use of lipid-lowering medications.

Interpretation

Metabolic risk factors were prevalent among Inuit. Our results suggest that Inuit are not protected from the metabolic consequences of obesity, and that their rate of diabetes prevalence is now comparable to that observed in the general Canadian population. Assessment of waist circumference and fasting triglyceride levels could represent an efficient means for identifying Inuit at high risk for diabetes.Indigenous people across the Arctic continue to undergo cultural transitions that affect all dimensions of life, with implications for emerging obesity and changes in patterns of disease burden.^1–3 A high prevalence of obesity among Canadian Inuit has been noted,^3,4 and yet studies have suggested that the metabolic consequences of obesity may not be as severe among Inuit as they are in predominantly Caucasian or First Nations populations.^4–6 Conversely, the prevalence of type 2 diabetes mellitus, which was noted to be rare among Inuit in early studies,^7,8 now matches or exceeds that of predominately Caucasian comparison populations in Alaska and Greenland.^9–11 However, in Canada, available reports suggest that diabetes prevalence among Inuit remains below that of the general Canadian population.^3,12Given the rapid changes in the Arctic and a lack of comprehensive and uniform screening assessments, we used the International Polar Year Inuit Health Survey for Adults 2007–2008 to assess the current prevalence of glycemia and the toll of age and adiposity on glycemia in this population. However, adiposity is heterogeneous, and simple measures of body mass index (BMI) in kg/m² and waist circumference do not measure visceral adiposity (or intra-abdominal adipose tissue), which is considered more deleterious than subcutaneous fat.¹³ Therefore, we evaluated the “hypertriglyceridemic-waist” phenotype (i.e., the presence of both an at-risk waist circumference and an elevated triglyceride level) as a proxy indicator of visceral fat.^13–15     

A statistical framework for the interpretation of mtDNA mixtures: forensic and medical applications

Background

Mitochondrial DNA (mtDNA) variation is commonly analyzed in a wide range of different biomedical applications. Cases where more than one individual contribute to a stain genotyped from some biological material give rise to a mixture. Most forensic mixture cases are analyzed using autosomal markers. In rape cases, Y-chromosome markers typically add useful information. However, there are important cases where autosomal and Y-chromosome markers fail to provide useful profiles. In some instances, usually involving small amounts or degraded DNA, mtDNA may be the only useful genetic evidence available. Mitochondrial DNA mixtures also arise in studies dealing with the role of mtDNA variation in tumorigenesis. Such mixtures may be generated by the tumor, but they could also originate in vitro due to inadvertent contamination or a sample mix-up.

Methods/Principal Findings

We present the statistical methods needed for mixture interpretation and emphasize the modifications required for the more well-known methods based on conventional markers to generalize to mtDNA mixtures. Two scenarios are considered. Firstly, only categorical mtDNA data is assumed available, that is, the variants contributing to the mixture. Secondly, quantitative data (peak heights or areas) on the allelic variants are also accessible. In cases where quantitative information is available in addition to allele designation, it is possible to extract more precise information by using regression models. More precisely, using quantitative information may lead to a unique solution in cases where the qualitative approach points to several possibilities. Importantly, these methods also apply to clinical cases where contamination is a potential alternative explanation for the data.

Conclusions/Significance

We argue that clinical and forensic scientists should give greater consideration to mtDNA for mixture interpretation. The results and examples show that the analysis of mtDNA mixtures contributes substantially to forensic casework and may also clarify erroneous claims made in clinical genetics regarding tumorigenesis.     

Pharmacological or genetic blockade of the dopamine D3 receptor increases cell proliferation in the hippocampus of adult mice

Dopamine plays an important role in cellular processes controlling the functional and structural plasticity of neurons, as well as their generation and proliferation, both in the developing and the adult brain. The precise roles of individual dopamine receptors subtypes in adult neurogenesis remain poorly defined, although D3 receptors are known to be involved in neurogenesis in the subventricular zone. By contrast, very few studies have addressed the influence of dopamine and D3 receptors upon neurogenesis in the subgranular zone of the hippocampus, an issue addressed herein employing constitutive D3 receptor knockout mice, or chronic exposure to the preferential D3 receptor antagonist, S33138. D3 receptor knockout mice revealed increased baseline levels of cell proliferation and ongoing neurogenesis, as measured both using Ki‐67 and doublecortin, whereas there was no difference in cell survival as measured by BrdU (5‐bromo‐2′‐deoxyuridine). Chronic administration of S33138 was shown to be functionally active in enhancing levels of the plasticity‐related molecule, delta‐FosB, in the D3 receptor‐rich nucleus accumbens. In accordance with the stimulated neurogenesis seen in D3 receptor knockout mice, S33138 increased proliferation in wild‐type mice. These observations suggest that D3 receptors exert a tonic, constitutive inhibitory influence upon adult hippocampal neurogenesis.     

Molecular mechanisms that distinguish TFIID housekeeping from regulatable SAGA promoters

An important distinction is frequently made between constitutively expressed housekeeping genes versus regulated genes. Although generally characterized by different DNA elements, chromatin architecture and cofactors, it is not known to what degree promoter classes strictly follow regulatability rules and which molecular mechanisms dictate such differences. We show that SAGA‐dominated/TATA‐box promoters are more responsive to changes in the amount of activator, even compared to TFIID/TATA‐like promoters that depend on the same activator Hsf1. Regulatability is therefore an inherent property of promoter class. Further analyses show that SAGA/TATA‐box promoters are more dynamic because TATA‐binding protein recruitment through SAGA is susceptible to removal by Mot1. In addition, the nucleosome configuration upon activator depletion shifts on SAGA/TATA‐box promoters and seems less amenable to preinitiation complex formation. The results explain the fundamental difference between housekeeping and regulatable genes, revealing an additional facet of combinatorial control: an activator can elicit a different response dependent on core promoter class.