Australia''s oldest human remains: age of the Lake Mungo 3 skeleton

We have carried out a comprehensive ESR and U-series dating study on the Lake Mungo 3 (LM3) human skeleton. The isotopic Th/U and Pa/U ratios indicate that some minor uranium mobilization may have occurred in the past. Taking such effects into account, the best age estimate for the human skeleton is obtained through the combination of U-series and ESR analyses yielding 62,000+/-6000 years. This age is in close agreement with OSL age estimates on the sediment into which the skeleton was buried of 61,000+/-2000 years. Furthermore, we obtained a U-series age of 81,000+/-21,000 years for the calcitic matrix that was precipitated on the bones after burial. All age results are considerably older than the previously assumed age of LM3 and demonstrate the necessity for directly dating hominid remains. We conclude that the Lake Mungo 3 burial documents the earliest known human presence on the Australian continent. The age implies that people who were skeletally within the range of the present Australian indigenous population colonized the continent during or before oxygen isotope stage 4 (57,000-71,000 years).     

Mechanisms of platelet activating factor-induced aggregation and secretion in human platelets

The role of TXA2 in PAF-induced aggregation and secretion of human platelets is unclear. We have studied the relationship between aggregation, synthesis of TXA2 and release of 5-HT during the time course of aggregation induced by PAF and collagen. For PAF-induced aggregation there was strong aggregation and secretion with minimal production of TXA2 in contrast to collagen in which a surge in TXA2 synthesis preceded both aggregation and secretion. To determine the role of calcium flux in PAF-induced aggregation we have similarly studied the temporal relationships between aggregation, secretion and TXA2 synthesis for calcium ionophore A23187 induced aggregation but found these to be distinctly different from those determined for PAF. A method for measuring absolute amounts of 5HT released from platelets in small volumes of plasma is described. We conclude that TXA2 is not important in the mechanism of PAF induced aggregation and that an increase in the level of intraplatelet calcium per se is not sufficient to explain the mediation of PAF-induced aggregation.     

Chemonucleolysis for relief of sciatica due to a herniated intervertebral disc.

Chemonucleolysis is the nonoperative chemical removal of displaced lumbar disc material. The enzyme chymopapain, which has a wide margin of safety between its effective therapeutic and toxic doses, is effective in the management of sciatica due to a herniated intervertebral disc. The patient will have leg pain as the dominant symptom and a 50% reduction in straight-leg raising with or without bowstring discomfort and crossover pain. Neurologic symptoms and signs are usual, as are abnormal results of contrast studies, which will verify the level of involvement. In 220 randomly selected patients who met criteria for the diagnosis of sciatica due to a herniated intervertebral disc and did not have psychogenic or nonorganic spinal pain, a spinal stenosis or a history of a previous, unsuccessful operation to relieve the sciatica, chemonucleolysis had a success rate of 80%. The only complications were a severe anaphylactic reaction in two patients and lesser, delayed reactions in five others. All of the reactions were successfully treated. Of the 45 patients in whom chemonucleolysis was unsuccessful, 38 underwent a laminectomy. In 3 of the 38 the results of chemonucleolysis were initially good, but later the disc herniation recurred; thus, the long-term treatment failure rate was 1.4%.     

A kinetic study of the genetic control of hemopoietic progenitor cells assayed in culture and in vivo

The kinetics of growth of bone marrow cells from normal or genetically anemic mice (Sl/Sl^d and W/W^v) were studied in irradiated normal and genetically anemic hosts. The parameters followed included total cellularity, the number of peroxidase positive cells, and the number of cells capable of forming colonies in vivo (CFU-S) or in culture (CFU-C). The results of these experiments demonstrate that W and Sl defects alter the growth of CFU-C and peroxidase-positive cells to a modest degree; that the defects are more obvious when studied in spleen rather than in bone marrow; and that there is no additivity of W and Sl defects. Nineteen irradiated recipients of marrow from W/W^v mice were studied after three to six months. Of these, 18 showed host-type erythrocytes, while in one mouse the erythrocytes had the size distribution of W/W^v cells. This finding indicated that occasionally genetically defective stem cells may repopulate irradiated hosts.     

Local cerebral blood flow following the intrastriatal administration of vasoactive intestinal peptide or peptide histidine isoleucine in the rat

The effect of the intrastriatal microinjection of either vasoactive intestinal peptide (VIP) or a related peptide-peptide histidine isoleucine (PHI)-on local cerebral blood flow in the striatum was examined using iodo[14C]antipyrine quantitative autoradiography. In 37 rats, an injection needle was inserted into a chronically implanted guide cannula and 1 microliter of vehicle, VIP or PHI was injected into the striatum. Blood flow in sham controls was reduced by 15% in proximity to the injection site, when compared with blood flow in the contralateral uninjected control side (P less than 0.01). Similarly, following PHI administration (20 pmol), blood flow in the striatum was reduced by 14% when compared to that contralaterally (P less than 0.02). In contrast, following VIP administration (20 pmol), blood flow in proximity to the injection site was increased compared to flow in the contralateral striatum in 4/8 animals with the mean flow being elevated by 10% (n.s.) compared to blood flow contralaterally. VIP and PHI had similar effects on local cerebral glucose utilization in the caudate nucleus, their response being equivalent to that of sham animals. These experiments suggest that VIP and PHI have a differential influence on the microvasculature of the caudate nucleus, with VIP but not PHI mediating cerebrovascular dilation.     

Diverged composition and regulation of the Trypanosoma brucei origin recognition complex that mediates DNA replication initiation

Initiation of DNA replication depends upon recognition of genomic sites, termed origins, by AAA+ ATPases. In prokaryotes a single factor binds each origin, whereas in eukaryotes this role is played by a six-protein origin recognition complex (ORC). Why eukaryotes evolved a multisubunit initiator, and the roles of each component, remains unclear. In Trypanosoma brucei, an ancient unicellular eukaryote, only one ORC-related initiator, TbORC1/CDC6, has been identified by sequence homology. Here we show that three TbORC1/CDC6-interacting factors also act in T. brucei nuclear DNA replication and demonstrate that TbORC1/CDC6 interacts in a high molecular complex in which a diverged Orc4 homologue and one replicative helicase subunit can also be found. Analysing the subcellular localization of four TbORC1/CDC6-interacting factors during the cell cycle reveals that one factor, TbORC1B, is not a static constituent of ORC but displays S-phase restricted nuclear localization and expression, suggesting it positively regulates replication. This work shows that ORC architecture and regulation are diverged features of DNA replication initiation in T. brucei, providing new insight into this key stage of eukaryotic genome copying.     

Interpersonal psychotherapy delivered by nonspecialists for depression and posttraumatic stress disorder among Kenyan HIV–positive women affected by gender-based violence: Randomized controlled trial

BackgroundHIV–positive women suffer a high burden of mental disorders due in part to gender-based violence (GBV). Comorbid depression and posttraumatic stress disorder (PTSD) are typical psychiatric consequences of GBV. Despite attention to the HIV-GBV syndemic, few HIV clinics offer formal mental healthcare. This problem is acute in sub-Saharan Africa, where the world’s majority of HIV–positive women live and prevalence of GBV is high.Methods and findingsWe conducted a randomized controlled trial at an HIV clinic in Kisumu, Kenya. GBV-affected HIV–positive women with both major depressive disorder (MDD) and PTSD were randomized to 12 sessions of interpersonal psychotherapy (IPT) plus treatment as usual (TAU) or Wait List+TAU. Nonspecialists were trained to deliver IPT inside the clinic. After 3 months, participants were reassessed, and those assigned to Wait List+TAU were given IPT. The primary outcomes were diagnosis of MDD and PTSD (Mini International Neuropsychiatric Interview) at 3 months. Secondary outcomes included symptom measures of depression and PTSD, intimate partner violence (IPV), and disability. A total of 256 participants enrolled between May 2015 and July 2016. At baseline, the mean age of the women in this study was 37 years; 61% reported physical IPV in the past week; 91% reported 2 or more lifetime traumatic events and monthly income was 18USD. Multilevel mixed-effects logistic regression showed that participants randomized to IPT+TAU had lower odds of MDD (odds ratio [OR] 0.26, 95% CI [0.11 to 0.60], p = 0.002) and lower odds of PTSD (OR 0.35, [0.14 to 0.86], p = 0.02) than controls. IPT+TAU participants had lower odds of MDD-PTSD comorbidity than controls (OR 0.36, 95% CI [0.15 to 0.90], p = 0.03). Linear mixed models were used to assess secondary outcomes: IPT+TAU participants had reduced disability (−6.9 [−12.2, −1.5], p = 0.01), and nonsignificantly reduced work absenteeism (−3.35 [−6.83, 0.14], p = 0.06); partnered IPT+TAU participants had a reduction of IPV (−2.79 [−5.42, −0.16], p = 0.04). Gains were maintained across 6-month follow-up. Treatment group differences were observed only at month 3, the time point at which the groups differed in IPT status (before cross over). Study limitations included 35% attrition inclusive of follow-up assessments, generalizability to populations not in HIV care, and data not collected on TAU resources accessed.ConclusionsIPT for MDD and PTSD delivered by nonspecialists in the context of HIV care yielded significant improvements in HIV–positive women’s mental health, functioning, and GBV (IPV) exposure, compared to controls.Trial registrationClinical Trials Identifier {"type":"clinical-trial","attrs":{"text":"NCT02320799","term_id":"NCT02320799"}}NCT02320799.

Susan Meffert and co-workers evaluate interpersonal psychotherapy for treatment of psychiatric disorders in women with HIV infection in Kenya.     

Fun in facets: A flexible new tool for population genomics in R

The landscape of analytical tools for population genomics continues to evolve. However, these tools are scattered across programming languages, making them largely inaccessible for many biologists. In this issue of Molecular Ecology Resources, Hemstrom and Jones, 2022 (Mol Ecol Resour; 962) introduce a new R package, snpR. This package combines a large number of existing analyses, to provide a one-stop shop for population genomics. F-statistics, admixture analyses, effective population size inferences, genome-wide association studies (GWAS), and parentage analyses are all implemented natively within the package. A variety of third-party software can also be run without leaving the R environment. The authors pay particular attention to data structure – avoiding redundancy – and allowing analyses to be run across multiple sample or single-nucleotide polymorphism (SNP) groupings. Because of its great accessibility and wide range of analyses, snpR has the potential to become a favourite within the Molecular Ecology community.