Tasmanian Aborigines and DNA

The hyper-variable control region (HVI and HVII) of mitochondrial DNA (mtDNA) from Tasmanians with an unbroken, direct Tasmanian Aboriginal maternal lineage were DNA sequenced. The lineage dates back to the early 1800s, as evidenced by published family genealogies (Mollison 1978, Ryan 1981, Plomley 1966, 1971, 1987, 1990). Of the five distinct mtDNA haplotypes discovered, VI was found in living Tasmanian descendants traced back to a Port Phillip Aboriginal woman who lived with European sealers in Bass Strait. Haplotype T2 is two nucleotide transitions removed from 1/WD 2 of van Holst Pellekaan et al. 1998 and therefore related to this Australian mainland Aboriginal mtDNA haplotype. Vestiges of Tasmanian maternal mtDNA haplotypes from before white settlement, passing down through up to eight generations, still survive in Tasmania. The Tasmanian Aboriginal people are related and relatable to mainland Aboriginal people

Aboriginal Australian mitochondrial genome variation - An increased understanding of population antiquity and diversity

Aboriginal Australians represent one of the oldest continuous cultures outside Africa, with evidence indicating that their ancestors arrived in the ancient landmass of Sahul (present-day New Guinea and Australia) ∼55 thousand years ago. Genetic studies, though limited, have demonstrated both the uniqueness and antiquity of Aboriginal Australian genomes. We have further resolved known Aboriginal Australian mitochondrial haplogroups and discovered novel indigenous lineages by sequencing the mitogenomes of 127 contemporary Aboriginal Australians. In particular, the more common haplogroups observed in our dataset included M42a, M42c, S, P5 and P12, followed by rarer haplogroups M15, M16, N13, O, P3, P6 and P8. We propose some major phylogenetic rearrangements, such as in haplogroup P where we delinked P4a and P4b and redefined them as P4 (New Guinean) and P11 (Australian), respectively. Haplogroup P2b was identified as a novel clade potentially restricted to Torres Strait Islanders. Nearly all Aboriginal Australian mitochondrial haplogroups detected appear to be ancient, with no evidence of later introgression during the Holocene. Our findings greatly increase knowledge about the geographic distribution and phylogenetic structure of mitochondrial lineages that have survived in contemporary descendants of Australia's first settlers. © The Author(s) 2017

Translational Systems Biology of Inflammation

Inflammation is a complex, multi-scale biologic response to stress that is also required for repair and regeneration after injury. Despite the repository of detailed data about the cellular and molecular processes involved in inflammation, including some understanding of its pathophysiology, little progress has been made in treating the severe inflammatory syndrome of sepsis. To address the gap between basic science knowledge and therapy for sepsis, a community of biologists and physicians is using systems biology approaches in hopes of yielding basic insights into the biology of inflammation. “Systems biology” is a discipline that combines experimental discovery with mathematical modeling to aid in the understanding of the dynamic global organization and function of a biologic system (cell to organ to organism). We propose the term translational systems biology for the application of similar tools and engineering principles to biologic systems with the primary goal of optimizing clinical practice. We describe the efforts to use translational systems biology to develop an integrated framework to gain insight into the problem of acute inflammation. Progress in understanding inflammation using translational systems biology tools highlights the promise of this multidisciplinary field. Future advances in understanding complex medical problems are highly dependent on methodological advances and integration of the computational systems biology community with biologists and clinicians

The charcoal trap: Miombo forests and the energy needs of people

<p>Abstract</p> <p>Background</p> <p>This study evaluates the carbon dioxide and other greenhouse gas fluxes to the atmosphere resulting from charcoal production in Zambia. It combines new biomass and flux data from a study, that was conducted in a <it>miombo </it>woodland within the Kataba Forest Reserve in the Western Province of Zambia, with data from other studies.</p> <p>Results</p> <p>The measurements at Kataba compared protected area (3 plots) with a highly disturbed plot outside the forest reserve and showed considerably reduced biomass after logging for charcoal production. The average aboveground biomass content of the reserve (Plots 2-4) was around 150 t ha^-1, while the disturbed plot only contained 24 t ha^-1. Soil carbon was not reduced significantly in the disturbed plot. Two years of eddy covariance measurements resulted in net ecosystem exchange values of -17 ± 31 g C m^-2y^-1, in the first and 90 ± 16 g C m^-2in the second year. Thus, on the basis of these two years of measurement, there is no evidence that the <it>miombo </it>woodland at Kataba represents a present-day carbon sink. At the country level, it is likely that deforestation for charcoal production currently leads to a per capita emission rate of 2 - 3 t CO₂y^-1. This is due to poor forest regeneration, although the resilience of <it>miombo </it>woodlands is high. Better post-harvest management could change this situation.</p> <p>Conclusions</p> <p>We argue that protection of <it>miombo </it>woodlands has to account for the energy demands of the population. The production at national scale that we estimated converts into 10,000 - 15,000 GWh y^-1of energy in the charcoal. The term "Charcoal Trap" we introduce, describes the fact that this energy supply has to be substituted when woodlands are protected. One possible solution, a shift in energy supply from charcoal to electricity, would reduce the pressure of forests but requires high investments into grid and power generation. Since Zambia currently cannot generate this money by itself, the country will remain locked in the charcoal trap such as many other of its African neighbours. The question arises whether and how money and technology transfer to increase regenerative electrical power generation should become part of a post-Kyoto process. Furthermore, better inventory data are urgently required to improve knowledge about the current state of the woodland usage and recovery. Net greenhouse gas emissions could be reduced substantially by improving the post-harvest management, charcoal production technology and/or providing alternative energy supply.</p

A Patient-Specific in silico Model of Inflammation and Healing Tested in Acute Vocal Fold Injury

The development of personalized medicine is a primary objective of the medical community and increasingly also of funding and registration agencies. Modeling is generally perceived as a key enabling tool to target this goal. Agent-Based Models (ABMs) have previously been used to simulate inflammation at various scales up to the whole-organism level. We extended this approach to the case of a novel, patient-specific ABM that we generated for vocal fold inflammation, with the ultimate goal of identifying individually optimized treatments. ABM simulations reproduced trajectories of inflammatory mediators in laryngeal secretions of individuals subjected to experimental phonotrauma up to 4 hrs post-injury, and predicted the levels of inflammatory mediators 24 hrs post-injury. Subject-specific simulations also predicted different outcomes from behavioral treatment regimens to which subjects had not been exposed. We propose that this translational application of computational modeling could be used to design patient-specific therapies for the larynx, and will serve as a paradigm for future extension to other clinical domains

The HIV-1 transmission bottleneck

It is well established that most new systemic infections of HIV-1 can be traced back to one or a limited number of founder viruses. Usually, these founders are more closely related to minor HIV-1 populations in the blood of the presumed donor than to more abundant lineages. This has led to the widely accepted idea that transmission selects for viral characteristics that facilitate crossing the mucosal barrier of the recipient’s genital tract, although the specific selective forces or advantages are not completely defined. However, there are other steps along the way to becoming a founder virus at which selection may occur. These steps include the transition from the donor’s general circulation to the genital tract compartment, survival within the transmission fluid, and establishment of a nascent stable local infection in the recipient’s genital tract. Finally, there is the possibility that important narrowing events may also occur during establishment of systemic infection. This is suggested by the surprising observation that the number of founder viruses detected after transmission in intravenous drug users is also limited. Although some of these steps may be heavily selective, others may result mostly in a stochastic narrowing of the available founder pool. Collectively, they shape the initial infection in each recipient

Leukemia-cell proliferation and disease progression in patients with early stage chronic lymphocytic leukemia

The clinical course of patients with recently diagnosed early stage chronic lymphocytic leukemia (CLL) is highly variable. We examined the relationship between CLL-cell birth rate and treatment-free survival (TFS) in 97 patients with recently diagnosed, Rai stage 0-II CLL in a blinded, prospective study, using in vivo 2H2O labeling. Birth rates ranged from 0.07 to 1.31% new cells per day. With median follow-up of 4.0 years, 33 subjects (34%) required treatment by NCI criteria. High-birth rate was observed in 44% of subjects and was significantly associated with shorter TFS, unmutated IGHV status and expression of ZAP70 and of CD38. In multivariable modeling considering age, gender, Rai stage, expression of ZAP70 or CD38, IGHV mutation status and FISH cytogenetics, only CLL-cell birth rate and IGHV mutation status met criteria for inclusion. Hazard ratios were 3.51 (P=0.002) for high-birth rate and 4.93 (P&lt;0.001) for unmutated IGHV. The association between elevated birth rate and shorter TFS was observed in subjects with either mutated or unmutated IGHVs, and the use of both markers was a better predictor of TFS than either parameter alone. Thus, an increased CLL birth rate in early stage disease is a strong predictor of disease progression and earlier treatment