An evolutionary conserved region (ECR) in the human dopamine receptor D4 gene supports reporter gene expression in primary cultures derived from the rat cortex

<p>Abstract</p> <p>Background</p> <p>Detecting functional variants contributing to diversity of behaviour is crucial for dissecting genetics of complex behaviours. At a molecular level, characterisation of variation in exons has been studied as they are easily identified in the current genome annotation although the functional consequences are less well understood; however, it has been difficult to prioritise regions of non-coding DNA in which genetic variation could also have significant functional consequences. Comparison of multiple vertebrate genomes has allowed the identification of non-coding evolutionary conserved regions (ECRs), in which the degree of conservation can be comparable with exonic regions suggesting functional significance.</p> <p>Results</p> <p>We identified ECRs at the dopamine receptor D4 gene locus, an important gene for human behaviours. The most conserved non-coding ECR (D4ECR1) supported high reporter gene expression in primary cultures derived from neonate rat frontal cortex. Computer aided analysis of the sequence of the D4ECR1 indicated the potential transcription factors that could modulate its function. D4ECR1 contained multiple consensus sequences for binding the transcription factor Sp1, a factor previously implicated in DRD4 expression. Co-transfection experiments demonstrated that overexpression of Sp1 significantly decreased the activity of the D4ECR1 <it>in vitro</it>.</p> <p>Conclusion</p> <p>Bioinformatic analysis complemented by functional analysis of the DRD4 gene locus has identified a) a strong enhancer that functions in neurons and b) a transcription factor that may modulate the function of that enhancer.</p

Baboon Feeding Ecology Informs the Dietary Niche of <i>Paranthropus boisei</i>

<div><p>Hominins are generally considered eclectic omnivores like baboons, but recent isotope studies call into question the generalist status of some hominins. <i>Paranthropus boisei</i> and <i>Australopithecus bahrelghazali</i> derived 75%–80% of their tissues’ δ¹³C from C₄ sources, i.e. mainly low-quality foods like grasses and sedges. Here I consider the energetics of <i>P. boisei</i> and the nutritional value of C₄ foods, taking into account scaling issues between the volume of food consumed and body mass, and <i>P. boisei</i>’s food preference as inferred from dento-cranial morphology. Underlying the models are empirical data for <i>Papio cynocephalus</i> dietary ecology. <i>Paranthropus boisei</i> only needed to spend some 37%–42% of its daily feeding time (conservative estimate) on C₄ sources to meet 80% of its daily requirements of calories, and all its requirements for protein. The energetic requirements of 2–4 times the basal metabolic rate (BMR) common to mammals could therefore have been met within a 6-hour feeding/foraging day. The findings highlight the high nutritional yield of many C₄ foods eaten by baboons (and presumably hominins), explain the evolutionary success of <i>P. boisei,</i> and indicate that <i>P. boisei</i> was probably a generalist like other hominins. The diet proposed is consistent with the species’ derived morphology and unique microwear textures. Finally, the results highlight the importance of baboon/hominin hand in food acquisition and preparation.</p></div

Illustration of the tensile stresses (σ) and resulting breakages in <i>P. boisei</i> teeth.

<p>Tensile stresses (σ) would occur when lateral loads are applied to a straight-walled tooth and the force vector is directed outside the dental tissue. Without decussating enamel, i.e. bundels of enamel prisms crossing over, transverse cracks initiated on the unloaded side will propagate through the tissue and will lead to catastrophic failure of the tooth. Cracks tend to travel along the protein-rich prism sheaths and are stopped by differently-oriented prisms. Such oblique/transverse breakages are frequently found in <i>P. boisei</i> teeth and are illustrated here in a sample of SEM pictures. Although these breaks may have occurred post mortem, they illustrate the plane of least resistance and thus allow an assessment of the loading conditions to which the tooth should not have been subjected <i>in vivo</i>. Images are not to scale and are for illustration only.</p

Changes in nutritional yield (<i>y</i>-axis) as a result of increasing food volume with body mass 28–59 kg (<i>z</i>-axis) at 10-minute increments of feeding on C₄ sources (<i>x</i>-axis) for yearling baboons (a) and yearling baboon with increased manipulatory capabilities m = 2, i.e. a doubling the efficiency (<i>B_j</i>) with which they process corms (b).

<p>Incremental steps are highlighted by shaded bands.</p

Summary diagram of the composition of diet eaten by a 34–49 kg hominin.

<p>In (a) the empirical data for yearling <i>Papio cynocephalus</i> are shown. In (b) the basic model shown in (a) is scaled up to account for larger body masses and feeding on all C₄ sources is increased until the target of approximately 9700 kJ is reached (i). Then, once the model has been scaled to larger body masses, only the time feeding for stolons, leaves, meristem and seeds is increased (ii.), or on leaves (iii) or corms (iv); feeding time on fruits and invertebrates was kept constant to the level of yearling baboons (ii–iv). In (c) the models outlined in (b) are repeated with improved manipulations skills for the processing of corms (m = 2). In (d) only C₄ food sources that are well-suited to be broken down by <i>P. boisei</i> dento-cranial morphology, i.e. hard, brittle or soft, are selected. The effects of manipulatory capabilities (m) were tested. The models shown in (e) are considered most appropriate for inferences about the feeding ecology of <i>P. boisei.</i> These are achieved when all C₄ sources are selected, but only feeding time on corms is increased beyond the time observed in yearling baboons. The total time available for feeding, including foraging, is assumed to be 50% of the day in all models, i.e. 360 minutes.</p

Change of ownership of a limited liability company

V diplomskem delu z naslovom »Sprememba lastništva družbe pri družbi z omejeno odgovornostjo« sem predstavila nasledstvo v lastništvu podjetja ter raziskala načine spremembe lastniške strukture pri družbi z omejeno odgovornostjo. V uvodnem poglavju sem najprej opredelila problem in področje raziskovanja ter namen, cilje in osnovne trditve raziskave. V nadaljevanju sem navedla predpostavke, omejitve in metode raziskave, ki sem jih uporabljala pri raziskovanju problema. V drugem poglavju sem se seznanila z nasledstvom v lastništvu podjetja, z dejavniki, ki vplivajo na prenos lastništva podjetja in s planiranjem nasledstva v lastništvu podjetja. Ugotovila sem, katere stopnje postopka zaposlovanja in izbire naslednikov je treba upoštevati za dosego uspešnega prenosa lastništva podjetja. Tretje poglavje je namenjeno opisu načinov spremembe lastniške strukture pri družbi z omejeno odgovornostjo. S pomočjo analize sem ugotovila, da lahko lastniško strukturo spremenimo preko brezplačnega prenosa poslovnega deleža, preko prodaje poslovnega deleža in preko statusnopravnega preoblikovanja družbe. V četrtem poglavju sem predstavila vpliv pravočasne in najugodnejše izbire načina spremembe lastniške strukture družbe na nadaljnji obstoj in delovanje podjetja pri naslednji generaciji. V zadnjem, petem in sklepnem poglavju sem povzela ključne ugotovitve in zaključila s predlogi izboljšav na področju spremembe lastniške strukture družbe.In the undergraduate thesis entitled "Change of ownership in a limited liability company", I presented the continuation and succession of companies and explored ways of changing ownership structure in a limited liability company. In the introductory chapter, the problem and research topic, goals, objectives and main statements are identified. In addition, the assumptions, limitations and methods of research that have been used are listed. In the second chapter, I became acquainted with the succession of the company, with factors that influence the transfer of ownership of the company and the importance of planning the inheritance. I have identified which stages of the recruitment process and which choice of successors have to be considered in order to achieve a successful transfer of the company. The third section is dedicated to description of modalities of changing ownership structure in a limited liability company. With the help of the analysis, I found out that the ownership structure can be changed through a free transfer, through a sale of the company and through a status transformation of the company. In the fourth chapter I have presented why is it important to start preparing for the change of ownership structure in advance and how the mode of transition can influence further existence of the company in the next generation. Finally, I have summarized the key findings and concluded with an affirmation of the thesis

The effect of prism orientation and loading direction on contact stresses in prismatic enamel: implications for interpreting wear patterns

NoThe ability of prisms to effectively dissipate contact stress at the surface will influence wear rates in teeth. The aim of this investigation was to begin to quantify the effect of prism orientation on surface stresses. Seven finite element models of enamel microstructure were created, each model differing in the angulation of prism orientation with regard to the wear surface. For validation purposes, the mechanical behavior of the model was compared with published experimental data. In order to test the enamel under lateral loads, a compressed food particle was dragged across the surface from the dentino-enamel junction (DEJ) towards the outer enamel surface (OES). Under these conditions, tensile stresses in the enamel model increased with increases in the coefficient of friction. More importantly, stresses were found to be lowest in models in which the prisms approach the surface at lower angles (i.e., more obliquely cut prisms), and highest when the prisms approached the surface at 60° (i.e., less obliquely cut). Finally, the direction of travel of the simulated food particle was reversed, allowing comparison of the difference in behavior between trailing and leading edge enamels (i.e., when the food particle was dragged either towards or away from the DEJ). Stresses at the trailing edge were usually lower than stresses at the leading edge. Taken together with what is known about prism orientation in primate teeth, such findings imply greater wear resistance at the intercuspal region and less wear resistance at the lateral enamel at midcrown. Such findings appear to be supported by archeological evidence

Age Changes in Bone Microstructure - Do They Occur Uniformly?

NoAge estimations based on conventional multifactorial methods were compared with trends observed in the internal morphology of bones obtained from high-resolution µCT. Specifically, average trabecular thickness and number of trabeculae/mm transect were determined in the non-load-bearing capitate (hand) and the load-bearing navicular (foot). The µCT findings reveal age-related trends but - surprisingly - these correspond only loosely with the ages assigned by conventional ageing methods, and are also not in accordance with what would be predicted from biomechanical considerations: trabeculae tend to be thinner in the (habitually) load-bearing navicular than in the (habitually) non-load-bearing capitate. While the statistically significant correlation between trabecular thickness and number of trabeculae would suggest a compensatory mechanism between these two aspects of microanatomy, they are not correlated with the assigned ages and, importantly, may differ between sexes. Only in females is there an unequivocal trend towards trabecular thickness increase with age. These findings, although unexpected, can be reconciled with recent histological evidence and assumed average activity levels in historical populations. Conversely, changes in trabecular number are less clear-cut and may be due to the lack of very old individuals in the sample. Nevertheless, the trends observed for trabecular thickness, as well as for trabecular number, seem to imply that the higher incidence of osteoporosis in women could be explained from a structural point of view alone

Palaeoenvironmental reconstruction: evidence for seasonality at Allia Bay, Kenya, at 3.9 million years

NoIn an earlier study, stress lines in primate teeth were found to occur on a recurrent basis, probably corresponding to seasonal fluctuations in environmental parameters, such as food availability (Macho et al., J. Hum. Evol. 30 (1996) 57¿70). In the present study this approach was extended to the study of teeth of extant and extinct mammals, with the specific aim to determine the pattern of seasonality at the Australopithecus anamensis-bearing site at Allia Bay, Kenya. It was found that extant and extinct species, who share similar dietary/ecological adaptations, are comparable in their patterns of stress. Typical browsers/mixed feeders were found to exhibit three recurrent disturbances per year, whereas grazers usually only exhibit two. The average spacing between lines is also comparable between extant and extinct species. Hence, while the severity and predictability of the seasons probably fluctuated during crucial periods of hominin evolution, there is little doubt that all hominins lived in a seasonal environment. At Allia Bay, the pattern of stress lines found in mammals suggests that the environmental conditions in which A. anamensis lived may have been comparable to those found in the Masai Mara today

Jaw kinematics in South African Plio-Pleistocene hominins inferred from maxillary molar root morphology: implications for species identification

Max Planck Society FONDECYT (Chile) 11150175 FR-TAF3890 CGL2010-2086