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Summary Background The role of endoplasmic reticulum (ER) stress response in mental illness is not well understood. Human studies and animal models of depression show elevated brain ER stress response. In addition, some ER stress associated disorders (e.g. cardiovascular disease) show higher rates of depression compared to the general population, raising the possibility that ER stress response contributes to depression risk. It remains unknown, however, if ER stress response is present among individuals suffering from other stress-related mental illness, and whether such a response would be evident in a non-clinical sample. This study tests for systemic changes in ER stress response associated with Major Depressive Disorder (MDD) or post-traumatic stress disorder (PTSD) among community-dwelling individuals. Methods We analyzed expression of BiP , EDEM1 , CHOP , and XBP1 , the major indicators of ER stress response, with real-time PCR in leukocyte-derived RNA samples from 86 participants of the Detroit Neighborhood Health Study. Participants were selected based on the presence of either past year MDD or past year PTSD; controls were age and sex matched. Results Relative to controls, MDD is associated with a 1.34-fold increase in BiP ( P = 0.004), 1.35-fold increase in EDEM1 ( P = 0.001), 1.68-fold increase in CHOP ( P = 0.002), and 1.60-fold increase in XBP1 ( P = 0.004). These results remained significant after correction for multiple testing. In contrast, PTSD is associated with a 1.27-fold increase in EDEM1 expression only ( P = 0.027), a result that is attenuated to non-significance following adjustment for multiple testing; however, a subsample of participants with past month PTSD showed elevated expression of BiP and EDEM1 (uncorrected P value 0.049 and 0.017, respectively). Conclusions These data indicate systemic and persistent activation of the ER stress response pathway in MDD among community-dwelling individuals. Systemic activation of the ER stress response may also occur in PTSD among persons with more recent symptoms.

Forward and reverse genetics now allow researchers to understand embryonic and postnatal gene function in a broad range of species. Although some genetic mutations cause obvious morphological change, other mutations can be more subtle and, without adequate observation and quantification, might be overlooked. For the increasing number of genetic model organisms examined by the growing field of phenomics, standardized but sensitive methods for quantitative analysis need to be incorporated into routine practice to effectively acquire and analyze ever-increasing quantities of phenotypic data. In this study, we present platform-independent parameters for the use of microscopic x-ray computed tomography (microCT) for phenotyping species-specific skeletal morphology of a variety of different genetic model organisms. We show that microCT is suitable for phenotypic characterization for prenatal and postnatal specimens across multiple species.

The base of the cranium (i.e. the basioccipital, the sphenoid and the temporal bones) is of particular interest because it undergoes significant morphological change within the hominin clade, and because basicranial morphology features in several hominin species diagnoses. We use a parsimony analysis of published cranial and dental data to predict the cranial base morphology expected in the hypothetical last common ancestor of the Pan–Homo clade. We also predict the primitive condition of the cranial base for the hominin clade, and document the evolution of the cranial base within the major subclades within the hominin clade. This analysis suggests that cranial base morphology has continued to evolve in the hominin clade, both before and after the emergence of the genus Homo.

The skeletal remains of a diminutive small-brained hominin found in Late Pleistocene cave deposits on the island of Flores, Indonesia were assigned to a new species, Homo floresiensis [Brown P, et al. (2004) A new small-bodied hominin from the Late Pleistocene of Flores, Indonesia. Nature 431: 1055–1061]. A dramatically different interpretation is that this material belongs not to a novel hominin taxon but to a population of small-bodied modern humans affected, or unaffected, by microcephaly. The debate has primarily focused on the size and shape of the endocranial cavity of the type specimen, LB1, with less attention being paid to the morphological evidence provided by the rest of the LB1 cranium and postcranium, and no study thus far has addressed the problem of how scaling would affect shape comparisons between a diminutive cranium like LB1 and the much larger crania of modern humans. We show that whether or not the effects of its small cranial size are accounted for, the external cranial morphology of the LB1 cranium cannot be accommodated within a large global sample of normal modern human crania. Instead, the shape of LB1, which is shown by multivariate analysis to differ significantly from that of modern humans, is similar to that of Homo erectus sensu lato , and, to a lesser extent, Homo habilis . Our results are consistent with hypotheses that suggest the Liang Bua specimens represent a diminutive population closely related to either early H. erectus s. l. from East Africa and/or Dmanisi or to H. habilis .

The human brain excels in its capacity for phenotypic plasticity and response to experience. The objective of this study is to investigate the evolutionary history of human brain plasticity. We pre...

Forward and reverse genetics now enable researchers to understand embryonic and postnatal gene functioning in a wide range of species. Some genetic mutations cause obvious morphological change, whereas other mutations can lead to more subtle phenotypes and might be overlooked without adequate observations and quantifications. Due to the increase in number of genetic model organisms examined by the growing field of phenomics, standardized but sensitive methods for quantitative analysis are increasingly necessary in the everyday practice of analyzing ever-increasing quantities of phenotypic data. In this chapter, we have presented platform-independent parameters for the use of microscopic X-ray computed tomography (microCT) for phenotyping species-specific skeletal morphology of a variety of different genetic model organisms.