The first hominin from the early Pleistocene paleocave of Haasgat, South Africa.

Haasgat is a primate-rich fossil locality in the northeastern part of the Fossil Hominid Sites of South Africa UNESCO World Heritage Site. Here we report the first hominin identified from Haasgat, a partial maxillary molar (HGT 500), that was recovered from an ex situ calcified sediment block sampled from the locality. The in situ fossil bearing deposits of the Haasgat paleokarstic deposits are estimated to date to slightly older than 1.95 Ma based on magnetobiostratigraphy. This places the hominin specimen at a critical time period in South Africa that marks the last occurrence of Australopithecus around 1.98 Ma and the first evidence of Paranthropus and Homo in the region between ∼2.0 and 1.8 Ma. A comprehensive morphological evaluation of the Haasgat hominin molar was conducted against the current South African catalogue of hominin dental remains and imaging analyses using micro-CT, electron and confocal microscopy. The preserved occlusal morphology is most similar to Australopithecus africanus or early Homo specimens but different from Paranthropus. Occlusal linear enamel thickness measured from micro-CT scans provides an average of ∼2.0 mm consistent with Australopithecus and early Homo. Analysis of the enamel microstructure suggests an estimated periodicity of 7-9 days. Hunter-Schreger bands appear long and straight as in some Paranthropus, but contrast with this genus in the short shape of the striae of Retzius. Taken together, these data suggests that the maxillary fragment recovered from Haasgat best fits within the Australopithecus-early Homo hypodigms to the exclusion of the genus Paranthropus. At ∼1.95 Ma this specimen would either represent another example of late occurring Australopithecus or one of the earliest examples of Homo in the region. While the identification of this first hominin specimen from Haasgat is not unexpected given the composition of other South African penecontemporaneous site deposits, it represents one of the few hominin localities in the topographically-distinct northern World Heritage Site. When coupled with the substantial differences in the mammalian faunal communities between the northern localities (e.g., Haasgat, Gondolin) and well-sampled Bloubank Valley sites (e.g., Sterkfontein, Swartkrans, Kromdraai), the recovery of the HGT 500 specimen highlights the potential for further research at the Haasgat locality for understanding the distribution and interactions of hominin populations across the landscape, ecosystems and fossil mammalian communities of early Pleistocene South Africa. Such contextual data from sites like Haasgat is critical for understanding the transition in hominin representation at ∼2 Ma sites in the region from Australopithecus to Paranthropus and early Homo.

The history and composition of the Raymond A. Dart Collection of Human Skeletons at the University of the Witwatersrand, Johannesburg, South Africa.

The Raymond A. Dart Collection of Human Skeletons (Dart Collection) is housed in the School of Anatomical Sciences at the University of the Witwatersrand, Johannesburg, South Africa, and comprises one of the largest documented cadaver-derived human skeletal assemblages in the world. This collection originated in the early 1920s as a result of the efforts of Raymond Dart and continues to grow. The skeletons included represent varied indigenous and immigrant populations from southern Africa, Europe and Asia. This contribution documents the history of the collection and provides an updated inventory and demographic assessment of this valuable research collection. According to a recent inventory the Dart Collection currently comprises 2,605 skeletons representing individuals from regional SA African (76%), White (15%), Coloured (4%) and Indian (0.3%) populations. A large proportion of the skeletons (71%) represent males. The recorded ages at death range from the first year to over 100 years of age, but the majority of individuals died between the ages of 20 and 70. The Dart Collection has been affected by collection procedures based on availability. All of the cadavers collected before 1958, and large proportions subsequently, were derived from unclaimed bodies in regional South African hospitals. Some details of documentation (age at death, population group) are estimates and some aspects of the collection demographics (sex ratios) do not closely reflect any living South African population. Our inventory and analysis of the Dart Collection is aimed to assist researchers planning research on the materials from this collection.

Post-hospitalization treatment adherence of schizophrenic patients: gender differences in skill acquisition.

A cohort of acutely ill, hospitalized patients with chronic psychotic disorders participated in a study of a manualized community reintegration skills training program. Initial data analyses revealed that skill levels improved significantly over the course of treatment, and that higher post-training skill levels were associated with better post-discharge functioning for the group as a whole. Post-discharge treatment adherence rates were dramatically better in females, and analyses were conducted to determine the role of gender. Males and females had different predictors of post-training skill level and post-discharge treatment adherence. In males, who as a group were at higher risk for poor post-discharge outcome, there was a positive association between post-training skill level and post-discharge treatment adherence. Females, on the other hand, showed good post-discharge treatment adherence regardless of post-training skill or symptom levels. This report is consistent with prior studies suggesting that male and female individuals with schizophrenia show differential patterns of social skill, skill improvement, and social adjustment.

Training hospitalized patients with schizophrenia in community reintegration skills.

OBJECTIVE: The study examined the effectiveness of the Community Re-Entry Program, a brief, time-limited skills training module designed to help acutely ill inpatients become engaged in community-based treatment programs. METHODS: Of 84 consecutive admissions to a chronic psychotic disorders unit, 44 completed assessments and attended the Community Re-Entry Program. The program consists of 16 daily small-group therapy sessions that engage the patient in efforts to define discharge readiness, identify symptoms and medication effects, and assist with discharge planning. Skill levels and positive and negative symptoms were assessed on admission and on completion of training, and a subsample of patients received two-week postdischarge follow-up assessments. RESULTS: From admission to discharge, positive symptoms diminished substantially, negative symptoms diminished to a lesser but statistically significant degree, and skill levels increased significantly. Posttraining skill level was predicted by pretraining skill level and level of participation in the skills training module. Patients' symptom levels did not predict participation in the program or skill acquisition. Skill level at discharge was also more predictive of two-week postdischarge community adjustment than were symptom levels. CONCLUSIONS: Although further controlled studies are required to fully establish the efficacy of the Community Re-Entry Program, these data suggest that brief, focused skills training may play an important role in augmenting optimal pharmacotherapy for hospitalized patients with chronic psychotic disorders.

Serotonergic medications for sexual obsessions, sexual addictions, and paraphilias.

BACKGROUND: Paraphilias and related disorders have recently been thought of as sexual addictions. However, it has also been argued that these disorders are sexual compulsions. The question arises as to whether these disorders and obsessive compulsive disorder respond in the same way to pharmacotherapy. METHOD: We retrospectively reviewed outcome in 13 patients who presented with sexual symptoms and were treated with serotonin reuptake blockers. Symptoms were divided into paraphilias, nonparaphilic sexual addictions, and sexual obsessions. RESULTS: Paraphilias had the least improvement, while sexual obsessions had the best response to medication. CONCLUSION: Paraphilias and related disorders may be less responsive than sexual obsessions or compulsions to serotonin reuptake blockers. Perhaps paraphilias and related disorders are on the impulsive rather than the compulsive end of the spectrum of obsessive compulsive disorders. Controlled trials are, however, necessary to replicate these preliminary findings.

A molecular defect in virally transformed muscle cells that cannot cluster acetylcholine receptors.

Muscle cells infected at the permissive temperature with temperature-sensitive mutants of Rous sarcoma virus and shifted to the non-permissive temperature form myotubes that are unable to cluster acetylcholine receptors (Anthony, D. T., S. M. Schuetze, and L. L. Rubin. 1984. Proc. Natl. Acad. Sci. USA. 81:2265-2269). Work described in this paper demonstrates that the virally-infected cells are missing a 37-kD peptide which reacts with an anti-tropomyosin antiserum. Using a monoclonal antibody specific for the missing peptide, we show that this tropomyosin is absent from fibroblasts and is distinct from smooth muscle tropomyosins. It is also different from the two previously identified striated muscle myofibrillar tropomyosins (alpha and beta). We suggest that, in normal muscle, this novel, non-myofibrillar, tropomyosin-like molecule is an important component of a cytoskeletal network necessary for cluster formation.

Neural regulation of properties of the nicotinic acetylcholine receptor.

During nerve-muscle synapse formation, acetylcholine receptors become localized and modified to allow efficient transfer of information from nerve to muscle. In this paper we summarize our studies on two aspects of receptor modulation--their concentration at synaptic sites and their ability to desensitize in response to prolonged application of agonist. We demonstrate that receptor localization is a complex event which extensively reorganizes the structure of the junctional region. This allows the subsequent influences of contraction to be exerted differently in junctional and extrajunctional regions. We indicate that increases in muscle cell Ca2+ appear to mediate some of the effects of muscle contraction and suggest how regulation of Ca2+ levels may specify junctional and extrajunctional differences. Finally, we discuss the role of receptor phosphorylation in determining the rate of desensitization.

Regulation of nicotinic acetylcholine receptor phosphorylation in rat myotubes by forskolin and cAMP.

The nicotinic acetylcholine receptor (AcChoR) from rat myotubes prelabeled in culture with [32P]orthophosphate was isolated by acetylcholine affinity chromatography followed by immunoaffinity chromatography. Under basal conditions, the nicotinic AcChoR was shown to be phosphorylated in situ on the beta and delta subunits. Regulation of AcChoR phosphorylation by cAMP-dependent protein kinase was explored by the addition of forskolin or cAMP analogues to prelabeled cell cultures. Forskolin, an activator of adenylate cyclase, stimulated the phosphorylation of the delta subunit 20-fold over basal phosphorylation and induced phosphorylation of the alpha subunit. The effect of forskolin was dose dependent with a half-maximal response at 8 microM in the presence of 35 microM Ro 20-1724, a phosphodiesterase inhibitor. Stimulation of delta subunit phosphorylation was almost maximal within 5 min, whereas stimulation of alpha subunit phosphorylation was not maximal until 45 min after forskolin treatment. Stimulation of AcChoR phosphorylation by 8-benzylthioadenosine 3',5'-cyclic monophosphate was identical to that obtained by forskolin. Two-dimensional thermolytic phosphopeptide maps of the delta subunit revealed a single major phosphopeptide. These results correlate closely with the observed effects of forskolin on AcChoR desensitization in muscle and suggest that cAMP-dependent phosphorylation of the delta subunit increases the rate of AcChoR desensitization in rat myotubes.

Transformation by Rous sarcoma virus prevents acetylcholine receptor clustering on cultured chicken muscle fibers.

Acetylcholine receptors aggregate in the membrane of cultured chicken myotubes; the process of receptor clustering can be stimulated by exogenous factors that we, among others, have begun to characterize. Chicken myoblasts transformed by temperature-sensitive mutants of Rous sarcoma virus, such as tsNY68, fuse to form multinucleated myotubes at 42 degrees C, the nonpermissive temperature for transformation. However, tsNY68-infected myotubes do not cluster acetylcholine receptors at 42 degrees C, even in the presence of active clustering agents. This phenomenon is not merely a result of viral infection, since myotubes infected with a transformation-deficient viral mutant, td107A, behave like noninfected myotubes with respect to receptor clustering; thus, the effects of tsNY68 on the clustering process must be mediated by the src gene product. These experiments may provide a method of identifying essential elements of acetylcholine receptor clusters.