Showing papers by "Daniel L. Segal published in 2011"

Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models.

Abstract: An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of β-amyloid polypeptide (Aβ) play a key role in Alzheimer's disease (AD) pathology. Specifically, 56 kDa oligomeric species were shown to be correlated with impaired cognitive function in AD model mice. Several reports have documented the inhibition of Aβ plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Aβ oligomerization remains an unmet challenge. Here we identify a natural substance, based on cinnamon extract (CEppt), which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells. When administered to an AD fly model, CEppt rectified their reduced longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in their brain. Furthermore, oral administration of CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques and improvement in cognitive behavior. Our results present a novel prophylactic approach for inhibition of toxic oligomeric Aβ species formation in AD through the utilization of a compound that is currently in use in human diet.

Symbiotic bacteria are responsible for diet-induced mating preference in Drosophila melanogaster, providing support for the hologenome concept of evolution

Abstract: Diet-induced mating preference in Drosophila melanogaster results from amplification of the commensal bacterium Lactobacillus plantarum, providing a new role for gut microbiota and support for the hologenome concept of evolution. When the flies were treated with antibiotics prior to changing their diet, mating preference did not occur. These data also indicate that other potentially beneficial bacteria could be irreversibly lost by antibiotic treatment and that their replacement could provide a health benefit. We suggest that D. melanogaster can be a useful model organism to study the activities of gut microbiota and their interaction with the immune system.

Clinical Syndromes, Personality Disorders, and Neurocognitive Differences in Male and Female Inmates

Abstract: This study examined clinical syndromes, personality disorders, and neurocognitive problems in adult male (n = 523) and female inmates (n = 523) and a sample of unincarcerated adult women (n = 523). Inmates were administered the Coolidge Correctional Inventory (CCI), and the unincarcerated sample was given an identical test, the Coolidge Axis II Inventory. Although there were significant differences between the two inmate groups on a majority of the 32 CCI scales, only two scales achieved a medium effect size. The two inmate groups were found to be highly similar in a comparison of ranked personality disorder prevalence rates. Consistent with previous literature, male inmates had a significantly higher prevalence of antisocial personality disorder than female inmates (24% vs. 18%). Female inmates had double the prevalence of male inmates on the borderline and histrionic personality disorder scales. Female inmates also reported significantly more general neuropsychological dysfunction, specifically memory problems and neurosomatic symptoms, than male inmates. Female inmates also reported significantly higher levels of anxiety, depression, symptoms of schizophrenia, post-traumatic stress disorder, attention deficit hyperactivity disorder, and depersonalization than male inmates. Overall, the findings support previous research of high levels of psychological and neuropsychological problems in inmates, regardless of gender, and reinforces the need for comprehensive mental health screening of offender populations. Copyright © 2011 John Wiley & Sons, Ltd.

Bacteria-induced sexual isolation in Drosophila

Abstract: Commensal bacteria can induce sexual isolation between populations of Drosophila. This phenomenon has implications for speciation, and raises questions about its behavioral and developmental mechanisms, which are not yet known. In this Extra View, we discuss related work by others, bearing directly on these issues, and we speculate about how bacteria might influence fly behavior.There are many reports of interaction between Drosophila and their microbiota that significantly impacts mating preferences. Sexual isolation can be enhanced or reduced by altering the culture media, or the microbiota inhabiting those media. More dramatically, the endoparasite Wolbachia has induced strong mate preferences in some instances. While a sudden, ecologically induced shift in mating preferences falls far short of the changes required for speciation, it might be a first step in that direction.We hypothesize that bacteria-induced sexual isolation is caused by chemosensory cues. In our experiments, bacteria altered the prof...

EHD2 mediates trafficking from the plasma membrane by modulating Rac1 activity

Abstract: EHDs [EH (Eps15 homology)-domain-containing proteins] participate in different stages of endocytosis. EHD2 is a plasma-membrane-associated EHD which regulates trafficking from the plasma membrane and recycling. EHD2 has a role in nucleotide-dependent membrane remodelling and its ATP-binding domain is involved in dimerization, which creates a membrane-binding region. Nucleotide binding is important for association of EHD2 with the plasma membrane, since a nucleotide-free mutant (EHD2 T72A) failed to associate. To elucidate the possible function of EHD2 during endocytic trafficking, we attempted to unravel proteins that interact with EHD2, using the yeast two-hybrid system. A novel interaction was found between EHD2 and Nek3 [NIMA (never in mitosis in Aspergillus nidulans)-related kinase 3], a serine/threonine kinase. EHD2 was also found in association with Vav1, a Nek3-regulated GEF (guanine-nucleotide-exchange factor) for Rho GTPases. Since Vav1 regulates Rac1 activity and promotes actin polymerization, the impact of overexpression of EHD2 on Rac1 activity was tested. The results indicated that wt (wild-type) EHD2, but not its P-loop mutants, reduced Rac1 activity. The inhibitory effect of EHD2 overexpression was partially rescued by co-expression of Rac1 as measured using a cholera toxin trafficking assay. The results of the present study strongly indicate that EHD2 regulates trafficking from the plasma membrane by controlling Rac1 activity.

Structural Basis for Inhibiting β-Amyloid Oligomerization by a Non-coded β-Breaker-Substituted Endomorphin Analogue

Abstract: The distribution of endomorphins (EM) 1 and 2 in the human brain inversely correlates with cerebral neurodegeneration in Alzheimer's disease (AD), implying a protective role. These endogenous opioid peptides incorporate aromatic residues and a β-breaker motif, as seen in several optimized inhibitors of Aβ aggregation. The activity of native endomorphins was studied, as well as the rationally designed analogue Aib-1, which includes a remarkably efficient β-breaker, α-aminoisobutyric acid (Aib). In vitro and GFP fusion protein assays showed that Aib-1 interacted with Aβ and markedly inhibited the formation of toxic oligomer and fibril growth. Moreover, Aib-1 prevented the toxicity of Aβ toward neuronal PC12 cells and markedly rectified reduced longevity of an AD fly model. Atomistic simulations and NMR-derived solution structures revealed that Aib-1 significantly reduced the propensity of Aβ to aggregate due to multimode interactions including aromatic, hydrophobic, and polar contacts. We suggest that hindering the self-assembly process by interfering with the aromatic core of amyloidogenic peptides may pave the way toward developing therapeutic agents to treat amyloid-associated diseases.

Assessment of Emotional and Personality Disorders in Older Adults

Abstract: Publisher Summary motions and personalities are multidimensional constructs that require appropriate measures for each dimension. No single method of assessment is consistently superior to any other in cognitively intact individuals. The psychological assessment of older adults is fraught with multiple age-related factors that contribute to its complexity and resulting challenges. The assessment of emotional and personality disorders has advanced considerably in the past two decades through the design and development of assessment instruments for older adults, and through an appreciation of the many factors that can contribute to the performance of older adults. The use of multiple methods has been strongly recommended as a means to ensure accurate, reliable, and valid information. Until the issue of age-related presentations of emotional and personality disorders is addressed, clinicians should be circumspect in their use of assessment instruments developed with young adults, and their application of the current diagnostic criteria. At the very least, clinicians might consider adopting a more dimensional approach to assessment that is more sensitive to the subsyndromal presentations of emotional disorders among older adults.

Modularity of CHIP/LDB transcription complexes regulates cell differentiation

Abstract: Transcription is the first step through which the cell operates, via its repertoire of transcription complexes, to direct cellular functions and cellular identity by generating the cell-specific transcriptome. The modularity of the composition of constituents of these complexes allows the cell to delicately regulate its transcriptome. In a recent study we have examined the effects of reducing the levels of specific transcription co-factors on the function of two competing transcription complexes, namely CHIP-AP and CHIP-PNR which regulate development of cells in the thorax of Drosophila. We found that changing the availability of these co-factors can shift the balance between these complexes leading to transition from utilization of CHIP-AP to CHIP-PNR. This is reflected in change in the expression profile of target genes, altering developmental cell fates. We propose that such a mechanism may operate in normal fly development. Transcription complexes analogous to CHIP-AP and CHIP-PNR exist in mammals and we discuss how such a shift in the balance between them may operate in normal mammalian development.

Retrospective Assessments of Childhood Psychopathology by Adults and Their Parents

Abstract: The present study compared retrospective personality and psychopathological assessments of adults about their childhood and adolescence with concurrent assessments by one of their parents. One-hundred three college stu-dents (Mage = 23.1 years) and one of their parents (Mage = 51.2 years) completed a retrospective version of the 200-item, parent-as-respondent, Coolidge Personality and Neuropsychological Inventory (R-CPNI). The median internal scale reliabilities (Cronbach’s α) for all 46 scales of the R-CPNI were substantial for the adult retrospec-tive (α = 0.78) and the parent retrospective versions (α = 0.79), and there was a strong correlation between the adult and parent retrospective scale reliabilities (r = 0.88). To evaluate group differences, t tests revealed that the parent means were significantly lower than the adult means on 45 of the 46 scales with mostly large effect sizes. Principal components analyses of the scales for both adult and parent retrospective versions were strongly and positively correlated (r = 0.88) for the total number of components extracted. These findings appear to support the contention that retrospective assessments tend to be reliable and valid and that parents’ retrospective recol-lections of their children’s psychopathology tend to be more positive than the retrospective reports by the adults. Based on these preliminary findings, it appears that the R-CPNI may provide a unique and interesting tool for the retrospective measurement of psychopathology.

Preliminary psychometric properties of a measure of Karen Horney's Tridimensional theory in children and adolescents.

Abstract: This study established the psychometric properties of a child and adolescent version of the Horney-Coolidge Tridimensional Inventory (HCTI), which assesses psychoanalyst Karen Horney's theory of neurotic types. Parents of 302 children (ages 5 to 17 years; median age = 12.0 years) completed the new 45-item version of the HCTI and the Coolidge Personality and Neuropsychological Inventory (CPNI) about their children. The three main scales (Compliance, Aggression, and Detachment) had good internal scale reliability and excellent test-retest reliability. Principal components analysis supported Horney's three dimensions and a six-component substructure. There was also sufficient construct validity with personality disorder scales from the CPNI with the three HCTI dimensions and their six components. The implications of the findings are discussed for Horneyan theory.