Digit-only sauropod pes trackways from China - evidence of swimming or a preservational phenomenon?

For more than 70 years unusual sauropod trackways have played a pivotal role in debates about the swimming ability of sauropods. Most claims that sauropods could swim have been based on manus-only or manus-dominated trackways. However none of these incomplete trackways has been entirely convincing, and most have proved to be taphonomic artifacts, either undertracks or the result of differential depth of penetration of manus and pes tracks, but otherwise showed the typical pattern of normal walking trackways. Here we report an assemblage of unusual sauropod tracks from the Lower Cretaceous Hekou Group of Gansu Province, northern China, characterized by the preservation of only the pes claw traces, that we interpret as having been left by walking, not buoyant or swimming, individuals. They are interpreted as the result of animals moving on a soft mud-silt substrate, projecting their claws deeply to register their traces on an underlying sand layer where they gained more grip during progression. Other sauropod walking trackways on the same surface with both pes and manus traces preserved, were probably left earlier on relatively firm substrates that predated the deposition of soft mud and silt . Presently, there is no convincing evidence of swimming sauropods from their trackways, which is not to say that sauropods did not swim at all

Disease transmission models for public health decision making: toward an approach for designing intervention strategies for Schistosomiasis japonica.

Mathematical models of disease transmission processes can serve as platforms for integration of diverse data, including site-specific information, for the purpose of designing strategies for minimizing transmission. A model describing the transmission of schistosomiasis is adapted to incorporate field data typically developed in disease control efforts in the mountainous regions of Sichuan Province in China, with the object of exploring the feasibility of model-based control strategies. The model is studied using computer simulation methods. Mechanistically based models of this sort typically have a large number of parameters that pose challenges in reducing parametric uncertainty to levels that will produce predictions sufficiently precise to discriminate among competing control options. We describe here an approach to parameter estimation that uses a recently developed statistical procedure called Bayesian melding to sequentially reduce parametric uncertainty as field data are accumulated over several seasons. Preliminary results of applying the approach to a historical data set in southwestern Sichuan are promising. Moreover, technologic advances using the global positioning system, remote sensing, and geographic information systems promise cost-effective improvements in the nature and quality of field data. This, in turn, suggests that the utility of the modeling approach will increase over time

Uncovering the overlapping community structure of complex networks in nature and society

Many complex systems in nature and society can be described in terms of networks capturing the intricate web of connections among the units they are made of. A key question is how to interpret the global organization of such networks as the coexistence of their structural subunits (communities) associated with more highly interconnected parts. Identifying these a priori unknown building blocks (such as functionally related proteins, industrial sectors and groups of people) is crucial to the understanding of the structural and functional properties of networks. The existing deterministic methods used for large networks find separated communities, whereas most of the actual networks are made of highly overlapping cohesive groups of nodes. Here we introduce an approach to analysing the main statistical features of the interwoven sets of overlapping communities that makes a step towards uncovering the modular structure of complex systems. After defining a set of new characteristic quantities for the statistics of communities, we apply an efficient technique for exploring overlapping communities on a large scale. We find that overlaps are significant, and the distributions we introduce reveal universal features of networks. Our studies of collaboration, word-association and protein interaction graphs show that the web of communities has non-trivial correlations and specific scaling properties.Comment: The free academic research software, CFinder, used for the publication is available at the website of the publication: http://angel.elte.hu/clusterin

Recombination-mediated escape from primary CD8+ T cells in acute HIV-1 infection

Abstract Background A major immune evasion mechanism of HIV-1 is the accumulation of non-synonymous mutations in and around T cell epitopes, resulting in loss of T cell recognition and virus escape. Results Here we analyze primary CD8+ T cell responses and virus escape in a HLA B*81 expressing subject who was infected with two T/F viruses from a single donor. In addition to classic escape through non-synonymous mutation/s, we also observed rapid selection of multiple recombinant viruses that conferred escape from T cells specific for two epitopes in Nef. Conclusions Our study shows that recombination between multiple T/F viruses provide greater options for acute escape from CD8+ T cell responses than seen in cases of single T/F virus infection. This process may contribute to the rapid disease progression in patients infected by multiple T/F viruses

Clinical and genetic spectrum of a Chinese cohort with SCN4A gene mutations

Skeletal muscle sodium channelopathies due to SCN4A gene mutations have a broad clinical spectrum. However, each phenotype has been reported in few cases of Chinese origin. We present detailed phenotype and genotype data from a cohort of 40 cases with SCN4A gene mutations seen in neuromuscular diagnostic service in Huashan hospital, Fudan University. Cases were referred from 6 independent provinces from 2010 to 2018. A questionnaire covering demographics, precipitating factors, episodes of paralysis and myotonia was designed to collect the clinical information. Electrodiagnostic studies and muscle MRI were retrospectively analyzed. The clinical spectrum of patients included: 6 Hyperkalemic periodic paralysis (15%), 18 Hypokalemic periodic paralysis (45%), 7 sodium channel myotonia (17.5%), 4 paramyotonia congenita (10%) and 5 heterozygous asymptomatic mutation carriers (12.5%). Review of clinical information highlights a significant delay to diagnosis (median 15 years), reports of pain and myalgia in the majority of patients, male predominance, circadian rhythm and common precipitating factors. Electrodiagnostic studies revealed subclinical myotonic discharges and a positive long exercise test in asymptomatic carriers. Muscle MRI identified edema and fatty infiltration in gastrocnemius and soleus. A total of 13 reported and 2 novel SCN4A mutations were identified with most variants distributed in the transmembrane helix S4 to S6, with a hotspot mutation p.Arg675Gln accounting for 32.5% (13/40) of the cohort. Our study revealed a higher proportion of periodic paralysis in SCN4A-mutated patients compared with cohorts from England and the Netherlands. It also highlights the importance of electrodiagnostic studies in diagnosis and segregation studies

Anisotropic Impurity-States, Quasiparticle Scattering and Nematic Transport in Underdoped Ca(Fe1-xCox)2As2

Iron-based high temperature superconductivity develops when the `parent' antiferromagnetic/orthorhombic phase is suppressed, typically by introduction of dopant atoms. But their impact on atomic-scale electronic structure, while in theory quite complex, is unknown experimentally. What is known is that a strong transport anisotropy with its resistivity maximum along the crystal b-axis, develops with increasing concentration of dopant atoms; this `nematicity' vanishes when the `parent' phase disappears near the maximum superconducting Tc. The interplay between the electronic structure surrounding each dopant atom, quasiparticle scattering therefrom, and the transport nematicity has therefore become a pivotal focus of research into these materials. Here, by directly visualizing the atomic-scale electronic structure, we show that substituting Co for Fe atoms in underdoped Ca(Fe1-xCox)2As2 generates a dense population of identical anisotropic impurity states. Each is ~8 Fe-Fe unit cells in length, and all are distributed randomly but aligned with the antiferromagnetic a-axis. By imaging their surrounding interference patterns, we further demonstrate that these impurity states scatter quasiparticles in a highly anisotropic manner, with the maximum scattering rate concentrated along the b-axis. These data provide direct support for the recent proposals that it is primarily anisotropic scattering by dopant-induced impurity states that generates the transport nematicity; they also yield simple explanations for the enhancement of the nematicity proportional to the dopant density and for the occurrence of the highest resistivity along the b-axis

Evolution of Th2 responses : Characterization of IL-4/13 in sea bass (Dicentrarchus labrax L.) and studies of expression and biological activity

Acknowledgements This research was funded by the European Commission under the 7th Framework Programme for Research and Technological Development (FP7) of the European Union (Grant Agreement 311993 TARGETFISH). T.W. received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland). MASTS is funded by the Scottish Funding Council (grant reference number HR09011) and contributing institutions.Peer reviewedPublisher PD

Expression of the α7 nicotinic acetylcholine receptor in human lung cells

BACKGROUND: We and others have shown that one of the mechanisms of growth regulation of small cell lung cancer cell lines and cultured pulmonary neuroendocrine cells is by the binding of agonists to the α7 neuronal nicotinic acetylcholine receptor. In addition, we have shown that the nicotine-derived carcinogenic nitrosamine, 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is a high affinity agonist for the α7 nicotinic acetylcholine receptor. In the present study, our goal was to determine the extent of α7 mRNA and protein expression in the human lung. METHODS: Experiments were done using reverse transcription polymerase chain reaction (RT-PCR), a nuclease protection assay and western blotting using membrane proteins. RESULTS: We detected mRNA for the neuronal nicotinic acetylcholine receptor α7 receptor in seven small cell lung cancer (SCLC) cell lines, in two pulmonary adenocarcinoma cell lines, in cultured normal human small airway epithelial cells (SAEC), one carcinoid cell line, three squamous cell lines and tissue samples from nine patients with various types of lung cancer. A nuclease protection assay showed prominent levels of α7 in the NCI-H82 SCLC cell line while α7 was not detected in SAEC, suggesting that α7 mRNA levels may be higher in SCLC compared to normal cells. Using a specific antibody to the α7 nicotinic receptor, protein expression of α7 was determined. All SCLC cell lines except NCI-H187 expressed protein for the α7 receptor. In the non-SCLC cells and normal cells that express the α7 nAChR mRNA, only in SAEC, A549 and NCI-H226 was expression of the α7 nicotinic receptor protein shown. When NCI-H69 SCLC cell line was exposed to 100 pm NNK, protein expression of the α7 receptor was increased at 60 and 150 min. CONCLUSION: Expression of mRNA for the neuronal nicotinic acetylcholine receptor α7 seems to be ubiquitously expressed in all human lung cancer cell lines tested (except for NCI-H441) as well as normal lung cells. The α7 nicotinic receptor protein is expressed in fewer cell lines, and the tobacco carcinogen NNK increases α7 nicotinic receptor protein levels

An experiment of the combined treatment of traditional Lei-huo-jiu therapy with Chinese medicine for the lacrimal gland of Sjögren’s syndrome

This experiment chooses nonobese diabetic (NOD) mouse as the animal model of Sjögren’s syndrome and investigates the morphologic changes, the expression of inflammatory factors and growth factors of this mouse’s lacrimal gland in response to a combined treatment of traditional Lei-huo-jiu therapy alone and in combination with Chinese medicine. The methods were to (1) use a morphological approach to directly observe pathological changes of the lacrimal gland in response to combined treatment and (2) to detect the level of tumor necrosis factor (TNF)-α, interleukin (IL)-1, and nuclear factor kappa B (NF-κB) in lacrimal gland tissue caused by the combined treatments using a immunohistochemical approach. There is a reduction of the mast cell’s degranulation and modulation of the level of cytokines in TNF-α, IL-1, and NF-κB in the combined therapy group. The combined treatment of traditional Lei-huo-jiu therapy with Chinese medicine can improve the pathological changes of the lacrimal gland tissue of the NOD mouse through modulating the level of TNF-α, IL-1, and NF-κB which results in improved tear secretion and function of the lacrimal gland

TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.

Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies