Community differentiation and kinship among Europe's first farmers

Community differentiation is a fundamental topic of the social sciences, and its prehistoric origins in Europe are typically assumed to lie among the complex, densely populated societies that developed millennia after their Neolithic predecessors. Here we present the earliest, statistically significant evidence for such differentiation among the first farmers of Neolithic Europe. By using strontium isotopic data from more than 300 early Neolithic human skeletons, we find significantly less variance in geographic signatures among males than we find among females, and less variance among burials with ground stone adzes than burials without such adzes. From this, in context with other available evidence, we infer differential land use in early Neolithic central Europe within a patrilocal kinship system.     

Leukopenic chronic T cell leukemia mimicking hairy cell leukemia: association with human retroviruses

We report two cases of a T cell lymphoproliferative disease not previously described, with cytologic and clinical features similar to those associated with Galton's "prolymphocytic" leukemia (PL). Our patients, like those with Galton's PL, had massive splenomegaly and minimal or absent hepatomegaly and lymphadenopathy. In contrast, however, our patients had leukopenia, as well as low percentages of leukemic cells in the peripheral blood and in the bone marrow. In splenic imprints, the nuclear chromatin pattern of most of the leukemic cells was intermediate between those of mature lymphocytes and those of lymphoblasts, and the nuclei contained single, centrally located, conspicuous nucleoli. In sections of the spleen, the leukemic cells diffusely infiltrated the red pulp in a pattern strikingly similar to that of hairy cell leukemia; however, when the leukemic cells were studied cytochemically, the cytoplasmic acid phosphatase positivity was punctate and tartrate-sensitive. The leukemic cells were sheep erythrocyte rosette-positive and expressed T cell-associated antigens. Initially, both patients responded well to therapeutic splenectomy. One patient received combination chemotherapy after splenectomy and is alive and well 24 months after diagnosis. The other patient was in complete clinical remission for one year after splenectomy and received chemotherapy at relapse. He died, however, 23 months after splenectomy, with disseminated disease. IgG antibody titers against human T lymphotropic virus type I (HTLV-I) were detected in one patient and against HTLV-II in the other. The leukemia in these patients represents a distinct clinicopathologic entity within the spectrum of peripheral T cell lymphoproliferative diseases that includes Galton's PL of T cell derivation, T cell chronic lymphocytic leukemia, T cell hairy cell leukemia, and adult T cell leukemia/lymphoma.     

Ultrastructure of epithelial cells in human periodontal ligament explants

The ultrastructure of epithelial rests of Malessez from explants of human periodontal membrane has been described. They differ from the resting cells seen in vivo in areas of the epithelial-connective tissue junction, in their abundance of cytoplasm and increased number of lateral cell processes, by the marked alterations in number, arrangement, and morphology of organelles and inclusions; evidence of pinocytotic or reverse pinocytotic processes, and random areas of apatite formation. These findings provide further proof that the cell rests may remain viable upon completion of root formation. Apparently they are able to respond to environmental stimuli through an alteration in their enzymatic and protein synthesizing machinery. The arrangement of the organelles in cultured epithelial rests suggests protein utilization by the cells themselves and possibly also as a contribution to continuing alterations of their surrounding basement lamina.     

Psychometric evaluation of the Psychotic Symptom Rating Scales

Background

The aims of this study were to examine the psychometric properties of a German version of the Psychotic Symptom Rating Scales (PSYRATS) in a sample of patients with schizophrenic spectrum disorders and affective disorders with delusions and to validate subscales of the PSYRATS with other ratings of psychotic symptoms.

Sampling and methods

Two hundred patients with schizophrenic spectrum disorder and affective disorders with delusions were examined. Psychometric properties of the PSYRATS items and scales were determined, and the scores of the PSYRATS scales and subscales were compared to the Positive and Negative Syndrome Scale (PANSS) and other ratings of psychotic symptoms.

Results

The PSYRATS items and scales were found to have excellent interrater reliability. Two factors for the delusions scale (DS) and 4 factors of the auditory hallucinations scale were found. Subscales of the DS and auditory hallucinations scale were replicated by factor analysis, and the validity of the subscales was supported.

Conclusions

The German version of the PSYRATS is a reliable and valid assessment tool for delusions and hallucinations. The findings support the validity of the PSYRATS subscales. The DS is also applicable for patients with affective disorders.     

Genetic evidence for ubiquitin-specific proteases USP24 and USP40 as candidate genes for late-onset Parkinson disease

Linkage studies have defined susceptibility regions for late-onset Parkinson disease (PD) on chromosomes 1 and 2, but specific genetic variants have not been definitively identified. Here we report the results of a case-control study to identify disease-associated single nucleotide polymorphisms (SNPs) in these loci. In the initial phase of our study, we genotyped two putative functional SNPs in ubiquitin-specific protease 24 (USP24), a biological candidate gene within the chromosome 1 linkage region, and scanned the chromosome 2 linkage peak with 43 SNPs in a sample set of 224 PD cases and 186 matched controls. Both USP24 SNPs were significantly associated with disease risk (p = 0.0037 for rs1165222:T > C, p.Thr195ILe, and p = 0.037 for rs13312:C > G, a SNP in the 3'-untranslated region), and one marker, rs1048603:C > T, p.Arg1123Cys, in USP40 was significant from the chromosome 2 scan (p = 0.038). Further genotyping of the region surrounding these initial markers led us to identify 19 additional SNPs with strong disease association. In the second phase, we genotyped the 22 significant markers in an additional 110 cases and 162 controls, which together with part of the initial sample set (201 cases and 149 controls) constitute an expanded sample set of 311 age- and gender-matched case-control pairs. Twenty-one markers were significant in the expanded sample set (most significant allelic p-value: 0.0006 for rs287235:C > G on chromosome 1, and 0.005 for rs838552:T > C on chromosome 2), and six SNPs in USP24 remained significant after conservatively adjusting for testing 27 markers (pBonferroni = 0.017-0.049). It is unlikely that population stratification contributed to this finding, as population stratification was undetectable in our sample set using 78 null markers. Our data suggest that genetic variants in USP24 and USP40 affect the risk for late-onset PD, which is consistent with the predicted role of the ubiquitination pathway in PD etiology.     

Reduced structural connectivity of a major frontolimbic pathway in generalized anxiety disorder

CONTEXT Emotion regulation deficits figure prominently in generalized anxiety disorder (GAD) and in other anxiety and mood disorders. Research examining emotion regulation and top-down modulation has implicated reduced coupling of the amygdala with prefrontal cortex and anterior cingulate cortex, suggesting altered frontolimbic white matter connectivity in GAD. OBJECTIVES To investigate structural connectivity between ventral prefrontal cortex or anterior cingulate cortex areas and the amygdala in GAD and to assess associations with functional connectivity between those areas. DESIGN Participants underwent diffusion-tensor imaging and functional magnetic resonance imaging. SETTING University magnetic resonance imaging facility. PARTICIPANTS Forty-nine patients with GAD and 39 healthy volunteer control subjects, including a matched subset of 21 patients having GAD without comorbid Axis I diagnoses and 21 healthy volunteers matched for age, sex, and education. MAIN OUTCOME MEASURES The mean fractional anisotropy values in the left and right uncinate fasciculus, as measured by tract-based analysis for diffusion-tensor imaging data. RESULTS Lower mean fractional anisotropy values in the bilateral uncinate fasciculus indicated reduced frontolimbic structural connectivity in patients with GAD. This reduction in uncinate fasciculus integrity was most pronounced for patients without comorbidity and was not observed in other white matter tracts. Across all participants, higher fractional anisotropy values were associated with more negative functional coupling between the pregenual anterior cingulate cortex and the amygdala during the anticipation of aversion. CONCLUSIONS Reduced structural connectivity of a major frontolimbic pathway suggests a neural basis for emotion regulation deficits in GAD. The functional significance of these structural differences is underscored by decreased functional connectivity between the anterior cingulate cortex and the amygdala in individuals with reduced structural integrity of the uncinate fasciculus.