First Isolation of Leishmania from Northern Thailand: Case Report,Identification as Leishmania martiniquensis and Phylogenetic Position within the Leishmania enriettii Complex

Since 1996, there have been several case reports of autochthonous visceral leishmaniasis in Thailand. Here we report a case in a 52-year-old Thai male from northern Thailand, who presented with subacute fever, huge splenomegaly and pancytopenia. Bone marrow aspiration revealed numerous amastigotes within macrophages. Isolation of Leishmania LSCM1 into culture and DNA sequence analysis (ribosomal RNA ITS-1 and large subunit of RNA polymerase II) revealed the parasites to be members of the Leishmania enriettii complex, and apparently identical to L. martiniquensis previously reported from the Caribbean island of Martinique. This is the first report of visceral leishmaniasis caused by L. martiniquensis from the region. Moreover, the majority of parasites previously identified as “L. siamensis” also appear to be L. martiniquensis.     

Sample size and power for the weighted log-rank test and Kaplan-Meier based tests with allowance for nonproportional hazards

Asymptotic distributions under alternative hypotheses and their corresponding sample size and power equations are derived for nonparametric test statistics commonly used to compare two survival curves. Test statistics include the weighted log-rank test and the Wald test for difference in (or ratio of) Kaplan-Meier survival probability, percentile survival, and restricted mean survival time. Accrual, survival, and loss to follow-up are allowed to follow any arbitrary continuous distribution. We show that Schoenfeld's equation—often used by practitioners to calculate the required number of events for the unweighted log-rank test—can be inaccurate even when the proportional hazards (PH) assumption holds. In fact, it can mislead one to believe that 1:1 is the optimal randomization ratio (RR), when actually power can be gained by assigning more patients to the active arm. Meaningful improvements to Schoenfeld's equation are made. The present theory should be useful in designing clinical trials, particularly in immuno-oncology where nonproportional hazards are frequently encountered. We illustrate the application of our theory with an example exploring optimal RR under PH and a second example examining the impact of delayed treatment effect. A companion R package npsurvSS is available for download on CRAN.     

Contribution of dogs to white-tailed deer hunting success

Dogs (Canis familiaris) are used in hunting white-tailed deer (Odocoileus virginianus) in 10 North American jurisdictions. Although the practice is longstanding and controversial, the effects of dogs on the outcome of the hunt have rarely been studied. We evaluated the influence of dogs on recreational hunting of white-tailed deer based on long-term data from southeastern Ontario, Canada. Over 25 years, annual surveys of hunters were used to collect data on hunting effort and deer harvest from approximately 85 camps, roughly half of which had dogs. We investigated the relationship between harvest and 3 treatments (i.e., 0 dogs, 1 dog, and ≥2 dogs in camp), interactions with weather and deer density, and effects of neighboring camps. Dogs enhanced hunter success. We found no difference in deer encounter rates but, per unit effort, camps with ≥2 dogs harvested 0.013 (26%) more deer per hunter-day, missed 0.010 (23%) more deer per hunter-day, and wounded 0.002 (40%) more deer per hunter-day than camps without dogs. Conversely, camps without dogs saw, without shooting at, 0.033 (23%) more deer per hunter-day than camps with ≥2 dogs. These results are consistent with the idea that hunters with dogs are less selective. Hunters with dogs harvested more fawns per unit effort, but we found no difference in the harvest rate of older female deer. More precipitation, greater wind speed, lower temperatures and greater deer density improved harvest success but had no differential effect among dog treatments. Hunter success at camps with ≥2 dogs was less when neighboring camps also had ≥2 dogs. Because antlerless deer quotas are the principal means to control populations, increasing use of hunting dogs is unlikely to have substantial effects in managing overabundant deer. © 2012 The Wildlife Society.     

Fingerprinting facies of the Tuff IF marker,with implications for early hominin palaeoecology,Olduvai Gorge,Tanzania

The top of Tuff IF marks the upper boundary of the Plio-/Pleistocene Bed I succession exposed in Olduvai Gorge, NE Tanzania, a tephrostratigraphic interval that is well known for remarkable Oldowan archaeological and vertebrate fossil assemblages, including early hominins. Geochemically, Tuff IF is characterized by a relatively consistent silica-undersaturated trachytic to phonolitic composition that relates both in terms of numerical ages (1.79 Ma) and compositional constraints to Olmoti volcano, located 22–38 km E of Olduvai Gorge.Measured Tuff IF sections are characterized by a thick unwelded pyroclastic flow in proximal settings and a succession of surges and ashfalls that interfingers with fluvio-lacustrine deposits of the Olduvai Basin in the medial to distal settings. Only in those areas with a relatively low topographic gradient, in distal reaches and beyond the toe of an Olmoti-sourced volcaniclastic fan, did the Tuff IF marker develop a typical threefold subdivision comprising: (1) primary surges and minor fallout, (2) reworked pumice units as lateral correlatives of proximally emplaced pyroclastic flows and (3) a succession of mass flows in conjunction with aeolian and fluvially reworked units.The pyroclastic marker unit is thus highly heterogeneous with regard to its vertical and lateral facies architecture and this has immediate effects on its preservation potential and in situ burial of fossils and stone artifacts. Even though the volcanically-related environmental perturbations were probably more severe at the eastern lake margin, the evidence for at least temporary freshwater sources and trees suggests environments conducive to hominin activities, but not during emplacement of Tuff IF pyroclastic flows and surges. This inference is supported by the presence of rich Oldowan stone artifact assemblages immediately preceding and following the deposition of Tuff IF, but only extremely sparse archaeological traces from one site in Tuff IF, restricted to the upper, fluvially reworked portion of Tuff IF.Tuff IF facies record the maximum of a regressive (drying) cycle that correlates with regional marine arid indicators. An ecological crisis covering ～ 2000–3500 a of time during Tuff IF deposition resulted not only from the lethal effects of explosive volcanism but also from its coincidence with a pronounced period of climate induced drought. These combined effects appear to have made at least the eastern basin uninhabitable by hominins and other vertebrates for most of the time during which Tuff IF accumulated.     

Smchd1-dependent and -independent pathways determine developmental dynamics of CpG island methylation on the inactive x chromosome

X chromosome inactivation involves multiple levels of chromatin modification, established progressively and in a stepwise manner during early development. The chromosomal protein Smchd1 was recently shown to play an important role in DNA methylation of CpG islands (CGIs), a late step in the X inactivation?pathway that is required for long-term maintenance of gene silencing. Here we show that inactive X chromosome (Xi) CGI methylation can occur via either Smchd1-dependent or -independent pathways. Smchd1-dependent CGI methylation, the primary pathway, is acquired gradually over an extended period, whereas Smchd1-independent CGI methylation occurs rapidly after the onset of X inactivation. The de novo methyltransferase Dnmt3b is required for methylation of both classes of CGI, whereas Dnmt3a and Dnmt3L are dispensable. Xi CGIs methylated by these distinct pathways differ with respect to their sequence characteristics and immediate chromosomal environment. We discuss the implications of these results for understanding CGI methylation during development.     

Nonapeptides and social behavior in fishes

The nonapeptide hormones arginine vasotocin and isotocin play important roles in mediating social behaviors in fishes. Studies in a diverse range of species demonstrate variation in vasotocin neuronal phenotypes across within and between sexes and species as well as effects of hormone administration on aggressive and sexual behaviors. However, patterns vary considerably across species and a general explanatory model for the role of vasotocin in teleost sociosexual behaviors has proven elusive. We review these findings, examine potential explanations for the lack of agreement across studies, and propose a model based on the parvocellular AVT neurons primarily mediating social approach and subordinance functions while the magnocellular and gigantocellular AVT neurons mediate courtship and aggressive behaviors. Isotocin neuronal phenotypes and effects on behavior are relatively unstudied, but research to date suggests this will be a fruitful line of inquiry. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.     

Wound healing potential of ethanolic extract of Kalanchoe pinnata Lam. leaf--a preliminary study

The extract of K. pinnata was evaluated for its wound healing activity by using excision wound model in rats. On day 11, animals treated with the ethanolic leaf extract exhibited 86.33% reduction in the wound area, compared to petroleum jelly treated control (69.36%) and the mupirocin treated standard (85.49%). The hydroxyproline content of extract treated animals was higher, as compared to control and the standard groups. Histological analysis was also consistent with the proposal that K. pinnata leaf extract exhibits significant wound healing potential. The increased rate of wound contraction and hydroxyproline content in the extract treated animals supports the claims made by traditional healers of the benefits obtained from the medicinal use of K. pinnata.     

In vivo Imaging and Therapeutic Treatments in an Orthotopic Mouse Model of Ovarian Cancer

Human cancer and response to therapy is better represented in orthotopic animal models. This paper describes the development of an orthotopic mouse model of ovarian cancer, treatment of cancer via oral delivery of drugs, and monitoring of tumor cell behavior in response to drug treatment in real time using in vivo imaging system. In this orthotopic model, ovarian tumor cells expressing luciferase are applied topically by injecting them directly into the mouse bursa where each ovary is enclosed. Upon injection of D-luciferin, a substrate of firefly luciferase, luciferase-expressing cells generate bioluminescence signals. This signal is detected by the in vivo imaging system and allows for a non-invasive means of monitoring tumor growth, distribution, and regression in individual animals. Drug administration via oral gavage allows for a maximum dosing volume of 10 mL/kg body weight to be delivered directly to the stomach and closely resembles delivery of drugs in clinical treatments. Therefore, techniques described here, development of an orthotopic mouse model of ovarian cancer, oral delivery of drugs, and in vivo imaging, are useful for better understanding of human ovarian cancer and treatment and will improve targeting this disease.Download video file.^{(89M, mp4)}