Frameless radiosurgery for intraocular metastatic tumor: Case report

AimThe aim of this case report is to describe the technique and response using frameless radiosurgery technique in intraocular metastases.BackgroundIntraocular metastases are the most common malignant lesion within the eye and its prevalence is probably underestimated. This is of great interest for oncologist as there are new treatment options with high rates of tumor control maintaining patient's quality of life.Case ReportWe report a case of a 54-year-old female with intraocular metastases from breast cancer using a frameless radiosurgery technique allowing organ preservation.ConclusionThe frameless robotic radiosurgery system is feasible and comfortable option for patients with intraocular metastases. Treatment planning and delivery requires an experienced interdisciplinary team.     

Ecomorphological patterns in the Blackcap Sylvia atricapilla: insular versus mainland populations

Capsule Blackcap Sylvia atricapilla populations from the Azores archipelago show morphological differences to continental birds which are consistent with the ‘Island Rule’.

Aims The morphology of insular vertebrates is usually the result of the evolution in their particular environment and leads to predictable morphological patterns, according to the Island Rule. We test the predictions of the Island Rule, using the Blackcap of the Azores archipelago as our model.

Methods We compared morphological variation (body size and wing shape) of populations from the nine islands of the Azores to continental birds, using multivariate indexes. Also, we looked at the relationship between these patterns and possible insular ecological drivers of morphological divergence.

Results Our findings are concordant with Island Rule predictions, as in general birds from the Azores are larger than continental populations, especially birds from the most distant islands. Wing shape also differs significantly, as Azorean Blackcaps tend to have rounder wings than continental birds with a migratory-like phenotype.

Conclusion Overall, we conclude that the observed morphological patterns in Blackcap in the Azores conform in general to the Island Rule predictions.     

Presidential Address—Some Reflections On The Nature Of Species

Background: Variation in the distribution and abundance of woody plants as consequence of disturbances such as fire may be explained by lineage age.

Aims: We tested whether lowland tropical tree lineages that colonise secondary forests are more late-diverging than clades from old-growth forests, and whether tree phylogenetic beta diversity from old-growth to secondary forests is higher in burned than non-burned secondary forests.

Methods: We sampled tree communities in old-growth forests and in secondary forests with distinct disturbance histories (burned and unburned). We calculated mean family age in each plot, and tested for differences among forest types using ANOVA. A phylogenetic fuzzy-weighting procedure was employed to generate a matrix describing the abundance of tree clades per plot, which was then analysed using a principal coordinate analysis.

Results: Most clades found in old-growth forests were underrepresented in secondary forests, which have been heavily colonised by a single species from a young lineage that is not found in old-growth forests. Phylogenetic beta diversity was higher between unburned secondary forests and old-growth forests than between burned secondary forests and old-growth forests.

Conclusions: The capacity of Neotropical trees to colonise secondary forests and persist after fire disturbance may be related to the age of distinct lineages.     

Effect of neighbour presence and soil volume on the growth of Andropogon gerardii Vitman

Background: Theory predicts that plants can reduce their fitness in the presence of neighbours by allocating resources to root growth, in order to pre-empt resource capture. A number of studies that have tested this idea have done so by using experiments where neighbour presence is confounded with soil volume.

Aims : To avoid confounding effects of neighbour presence and soil volume we adjusted these variables independently from one another.

Methods: We grew Andropogon gerardii with and without neighbours, holding soil volume available to each plant constant, and compared plant performance with a treatment where both neighbour presence and soil volume were varied. We also grew plants with a quarter of the soil volume but four times the nutrient concentration to determine if changes in plant growth in response to soil volume are caused by access different levels of soil resources.

Results: We found no evidence that plants adjust root growth to the presence of neighbour roots alone. We did, however, find a significant reduction in plant growth when soil volume was reduced. The reduction was overcome by increasing nutrient concentrations in the growth media.

Conclusions: Our results suggest the effects of soil volume on plant growth are mainly due to changes in nutrient availability.     

Heritability: the link between development and the microevolution of molar tooth form

Abstract

The developmental gene expression, morphogenesis, and population variation in mammalian molar teeth has become increasingly well understood, providing a model system for synthesizing evolution and developmental genetics. In this study, we estimated additive genetic covariances in molar shape (G) using parent-offspring regression in Cryptotis parva, the Least Shrew. We found that crown shape had an overall h² value of 0.34 (±0.08), with higher heritabilities in molar cusps than notches. We compared the genetic covariances to phenotypic (P) and environmental (E) covariances, and to the covariances in crown features expected from the enamel knot developmental cascade (D). We found that G and D were not strongly correlated and that major axes of G (evolutionary lines of least resistance) are better predictors of evolutionary divergences in soricines than is D. We conclude that the enamel knot cascade does impose constraints on the evolution of molar shape, but that it is so permissive that the divergences among soricines (whose last common ancestor lived about 14 million years ago) do not fully explore its confines. Over tens of millions of years, G will be a better predictor of the major axes of evolution in molar shape than D.     

Multicellular dosimetric chain for molecular radiotherapy exemplified with dose simulations on 3D cell spheroids

PurposeAbsorbed radiation dose-response relationships are not clear in molecular radiotherapy (MRT). Here, we propose a voxel-based dose calculation system for multicellular dosimetry in MRT. We applied confocal microscope images of a spherical cell aggregate i.e. a spheroid, to examine the computation of dose distribution within a tissue from the distribution of radiopharmaceuticals.MethodsA confocal microscope Z-stack of a human hepatocellular carcinoma HepG2 spheroid was segmented using a support-vector machine algorithm and a watershed function. Heterogeneity in activity uptake was simulated by selecting a varying amount of the cell nuclei to contain ¹¹¹In, ¹²⁵I, or ¹⁷⁷Lu. Absorbed dose simulations were carried out using vxlPen, a software application based on the Monte Carlo code PENELOPE.ResultsWe developed a schema for radiopharmaceutical dosimetry. The schema utilizes a partially supervised segmentation method for cell-level image data together with a novel main program for voxel-based radiation dose simulations. We observed that for ¹⁷⁷Lu, radiation cross-fire enabled full dose coverage even if the radiopharmaceutical had accumulated to only 60% of the spheroid cells. This effect was not found with ¹¹¹In and ¹²⁵I. Using these Auger/internal conversion electron emitters seemed to guarantee that only the cells with a high enough activity uptake will accumulate a lethal amount of dose, while neighboring cells are spared.ConclusionsWe computed absorbed radiation dose distributions in a 3D-cultured cell spheroid with a novel multicellular dosimetric chain. Combined with pharmacological studies in different tissue models, our cell-level dosimetric calculation method can clarify dose-response relationships for radiopharmaceuticals used in MRT.     

Structures and energies of the radicals and anions generated from chlorpyrifos

The radicals and anions generated from chlorpyrifos by removing a hydrogen atom have been investigated using the hybrid density functional B3PW91 method. The results show that all the radicals have been classified as three groups and their stability order is methylene (radical 1, 3, 5, and 7) > methyl (radical 9, 11 and 13) > ring (15); the anions have the relative energetic order: methyl > methylene > ring. Moreover, some decomposition reactions are also reported. The large HOMO-LUMO gaps indicate that both radicals and anions are predicted to be high-kinetic stable molecules. We also find that radicals 9, 11 and 13 have the highest AEAs and anions 2, 4 and 6 have higher VDEs. Additionally, natural population analysis charges show that there is the lowest Δq (0.14) for the C7 and C9 atoms. We hope that our theoretical results may provide a reference for further experiment and practical application.     

Pre-culturing islets with mesenchymal stromal cells using a direct contact configuration is beneficial for transplantation outcome in diabetic mice

Background aimsWe recently showed that co-transplantation of mesenchymal stromal cells (MSCs) improves islet function and revascularization in vivo. Pre-transplant islet culture is associated with the loss of islet cells. MSCs may enhance islet cell survival or function by direct cell contact mechanisms and soluble mediators. We investigated the capacity of MSCs to improve islet cell survival or β-cell function in vitro using direct and indirect contact islet-MSC configurations. We also investigated whether pre-culturing islets with MSCs improves islet transplantation outcome.MethodsThe effect of pre-culturing islets with MSCs on islet function in vitro was investigated by measuring glucose-stimulated insulin secretion. The endothelial cell density of fresh islets and islets cultured with or without MSCs was determined by immunohistochemistry. The efficacy of transplanted islets was tested in vivo using a syngeneic streptozotocin-diabetic minimal islet mass model. Graft function was investigated by monitoring blood glucose concentrations.ResultsIndirect islet-MSC co-culture configurations did not improve islet function in vitro. Pre-culturing islets using a direct contact MSC monolayer configuration improved glucose-stimulated insulin secretion in vitro, which correlated with superior islet graft function in vivo. MSC pre-culture had no effect on islet endothelial cell number in vitro or in vivo.ConclusionsPre-culturing islets with MSCs using a direct contact configuration maintains functional β-cell mass in vitro and the capacity of cultured islets to reverse hyperglycemia in diabetic mice.     

视网膜周边视野人工成像研究

目的 对于中心视力受损的人群，新型人工视觉系统可以将简化后的图像投射到视网膜上黄斑区以外的区域，从而帮助他们利用周边视觉感知信息。本文探究周边视野的感知特征，为植入式光学人工视觉系统的图形编码设计提供依据。方法 设计了探索周边视野感知特征的实验环境，向被试施加符号、数字、汉字的图案刺激，并控制刺激的大小、颜色组合、偏离角度、运动情况。用图形化的方法分析感知能力与各变量的关系。结果 周边视野的感知能力随偏离角度增大而下降，其趋势分为两个阶段，且受颜色组合、大小的影响明显。结论 研究结果提供了感知识别率较高的变量组合，为人工视觉系统的光学投影、眼内光学植入装置、特殊通信彩色符号编码开发等“人机结合”新技术提供重要的实验依据。     

microRNA signatures in peripheral blood fail to detect acute cellular rejection after liver transplantation

Objective: We investigated whether microRNA signatures in whole blood samples are associated with acute cellular rejection (ACR) after liver transplantation.

Materials and methods: Blood samples were collected using Paxgene technology and analyzed by microarrays and quantitative real-time polymerase chain reaction (qRT-PCR).

Results: microRNA signatures failed to distinguish between 19 patients with ACR and 16 controls. Let-7b-5p and let-7c were upregulated in a subgroup of patients with ACR during the 6th and 7th postoperative days but failed in an independent validation of 20 patients.

Conclusion: microRNA signatures in whole blood processed by Paxgene technology are not suited for the detection of ACR after liver transplantation.     

Accelerating multiple replica molecular dynamics simulations using the Intel® Xeon Phi™ coprocessor

We investigate the performance increase provided by the Intel^® Xeon Phi? coprocessor in multiple replica molecular dynamics applications using a novel parallelisation scheme. The benefits of the proposed parallelisation scheme are demonstrated by glycine in water, a system of significant interest in the crystallisation simulation community. The molecular dynamics (MD) engine consists of initially serial LAMMPS and NAMD subroutines, and is subsequently modified and parallelised using a heterogeneous programming model, where each MPI rank is paired with a unique Intel^® Xeon Phi? coprocessor and CPU socket. The MD engine is parallelised using an OpenMP atom domain decomposition algorithm on the Intel^® Xeon Phi? coprocessor and OpenMP task parallelism on the host CPU socket. Using nodes with two Intel^® Xeon Phi? coprocessors, one per socket, we demonstrate that a factor of five reduction in the required computational resources is achieved per replica with the coprocessor, when compared against employing the standard spatial domain decomposition algorithm with no accelerator. Furthermore, the proposed parallelisation scheme achieves ideal weak scaling with respect to the number of employed MPI ranks (replicas). The Intel^® Xeon Phi? coprocessor not only allows us to the increase performance output per socket by a factor of five, when compared against no accelerators, but also significantly reduces the parallelisation complexity necessary to achieve this performance, as the Intel^® Xeon Phi? coprocessor operates using the simple OpenMP programming language.     

An Improved Synthesis of N6-(6-Aminohexyl)FAD

Abstract

We report an improved synthesis of N ⁶-(6-aminohexyl)FAD (1) using an efficient one-pot conversion of inosine to the N-trifluoroacetyl protected N ⁶-(6-aminohexyl)adenosine 3. The 5′-O-phosphorylated AMP derivative 4, activated as the imidazolide, was coupled with commercial sodium riboflavin phosphate by using 18-crown-6 in DMF.     

A Dodecapeptide Selected by Phage Display as a Potential Theranostic Probe for Colon Cancers

AimColon cancer is one of the leading causes of cancer-related mortality. However, specific biomarkers for its diagnosis or treatment are not established well.MethodsWe developed a colon-cancer specific peptide probe using phage display libraries. We validated the specificity of this probe to colon cancer cells with immunohistochemical staining and FACS analysis using one normal cell and five colon cancer cell lines.ResultsThis peptide probe maintained binding affinity even after serum incubation. For therapeutic applications, this peptide probe was conjugated to hematoporphyrin, a photosensitizer, which showed a significantly enhanced cellular uptake and high photodynamic effect to kill tumor cells. As another application, we made a nanoparticle modified from the peptide probe. It efficiently delivered SN-38, an anticancer drug, into tumor cells, and its tumor-targeting ability was observed in vivo after intravenous injection to the same xenograft model.ConclusionThe noble dodecapeptide probe can be a promising candidate for both colon tumor diagnosis and targeted drug delivery.     

创伤弧菌毒力相关因子的全基因组关联分析研究

【目的】创伤弧菌是致死率最高的弧菌物种,但目前尚无在全基因组层面挖掘毒力相关因子的研究。本研究以创伤弧菌分离来源(临床和环境)作为不同表型,通过与260株基因组序列进行关联分析,挖掘毒力相关因子,从而进一步了解创伤弧菌致病因素。【方法】对139株创伤弧菌分离株进行高通量测序,获取其全基因组序列;与公共数据库已公开发表的121株基因组整合,使用pyseer软件进行全基因组关联分析,对与不同分离来源显著相关的基因进行注释和解读。【结果】共发现11个基因与临床分离株显著相关,其中9个是本研究新发现的创伤弧菌潜在毒力相关因子。【结论】本研究使用群体基因组学和统计遗传学方法,在全基因组范围扫描挖掘了创伤弧菌毒力相关因子,为深入揭示该物种致病机制、设计新的疫苗和治疗靶点提供了重要依据。     

Sulfolobus acidocaldarius DNA聚合酶IV跨越损伤合成能力的酶学特征

[目的]以嗜酸嗜热硫化叶菌Sulfolobus acidocaldarius的DNA聚合酶IV （Saci_0554）为例,表征其跨越模板上损伤碱基的DNA合成效果。[方法]将DNA聚合酶IV （SacpolIV）在大肠杆菌中进行重组表达,经亲和层析纯化得到SacpolIV蛋白;利用人工合成的带有不同损伤的寡核苷酸片段作为模板DNA,用尿素变性聚丙烯酰胺凝胶电泳技术,鉴定SacpolIV在体外跨越各种损伤碱基进行跨损伤合成的催化能力。[结果]SacpolIV重组蛋白能够不同程度地跨越嘌呤和嘧啶损伤,跨越能力的高低取决于损伤碱基与正常碱基形成氢键的能力。本研究还发现,SacpolIV能够在DNA链中掺入核糖核苷酸,但掺入核糖核苷酸的效率低于脱氧核糖核苷酸。[结论]本研究证实SacpolIV具有很强的跨越损伤合成能力,能够跨越多种氢键配对能力减弱的损伤碱基,为其在细胞内的跨越损伤合成功能提供了生化证据。     

CRISPR-Cas9系统与mazF介导的大片段删减法在酿酒酵母染色体大片段删减中的比较

【目的】比较CRISPR-Cas9系统与maz F法这两种酿酒酵母染色体大片段删减方法。【方法】分别用上述两种方法删减了酿酒酵母长度为26.5 kb的染色体大片段YKL072W-YKL061W,并比较了两种方法的转化效率、敲除成功率。【结果】利用CRISPR-Cas9系统平均得到5个转化子,但正确率为100%;maz F法得到约100个转化子,正确率略低于前者,为93%。【结论】两种方法均能高效删减酿酒酵母染色体大片段,CRISPR-Cas9系统正确率较高,操作简便省时;maz F法相对稳定,对目的基因无PAM位点要求。     

Correlation between the number of false positive variants and the quality of results using Ion Torrent PGM™ sequencing to screen BRCA genes

Introduction: Next Generation Sequencing (NGS) is cost-effective and a faster method to study genes, but its protocol is challenging.Objective: To analyze different adjustments to the protocol for screening the BRCA genes using Ion Torrent PGM sequencing and correlate the results with the number of false positive (FP) variants.Material and methods: We conducted a library preparation process and analyzed the number of FP InDels, the library concentration, the number of cycles in the target amplification step, the purity of the nucleic acid, the input, and the number of samples/Ion 314 chips in association with the results obtained by NGS.Results: We carried out 51 reactions and nine adjustments of protocols and observed eight FP InDels in homopolymer regions. No FP Single-Nucleotide Polymorphism variant was observed; 67.5% of protocol variables were jointly associated with the quality of the results obtained (p<0.05). The number of FP InDels decreased when the quality of results increased.Conclusion: The Ion AmpliSeq BRCA1/BRCA2 Community Panel had a better performance using four samples per Ion-314 chip instead of eight and the optimum number of cycles in the amplification step, even when using high-quality DNA, was 23. We observed better results with the manual equalization process and not using the Ion Library Equalizer kit. These adjustments provided a higher coverage of the variants and fewer artifacts (6.7-fold). Laboratories must perform internal validation because FP InDel variants can vary according to the quality of results while the NGS assay should be validated with Sanger.     

Measurement of the Girth of Coniferous Trees at Braemar in 1894

ABSTRACT

Background: Plant communities are usually characterised by species composition and abundance, but also underlie a multitude of complex interactions that we have only recently started unveiling. Yet, we are still far from understanding ecological and evolutionary processes shaping the network-level organisation of plant diversity, and to what extent these processes are specific to certain spatial scales or environments.

Aims: Understanding the systemic mechanisms of plant–plant network assembly and their consequences for diversity patterns.

Methods: We review recent methods and results of plant–plant networks.

Results: We synthetize how plant–plant networks can help us to: (a) assess how competition and facilitation may balance each other through the network; (b) analyse the role of plant–plant interactions beyond pairwise competition in structuring plant communities, and (c) forecast the ecological implications of complex species dependencies. We discuss pros and cons, assumptions and limitations of different approaches used for inferring plant–plant networks.

Conclusions: We propose novel opportunities for advancing plant ecology by using ecological networks that encompass different ecological levels and spatio-temporal scales, and incorporate more biological information. Embracing networks of interactions among plants can shed new light on mechanisms driving evolution and ecosystem functioning, helping us to mitigate diversity loss.     

Status and population trends of Starling Sturnus vulgaris in Great Britain

Capsule Starling populations have declined markedly since 1964, with the greatest declines in pastoral areas in the south and west of Britain.

Aims To establish the size of the Starling population and its recent decline in different habitats and regions.

Methods We use distance-based transect sampling to establish, for the first time, robust estimates of population size in different habitats and regions. We then analyse long-term trend data from two extensive monitoring schemes using generalized additive models to find correlates of the population decline.

Results The mean national breeding population of Starling over the period 1994–2000 was estimated at about 8.5 million birds, with a 95% confidence interval of 8.1–10.8 million. Most Starlings (36%) occur in southern Britain and densities are greatest in suburban habitats. Populations in both suburban areas and the wider countryside declined by over 50% between 1964 and 2000, being greatest in the south and west of Britain and in areas of livestock farming.

Conclusions Changes in pastoral farming practices are likely to account for at least some of the decline in the wider countryside, probably related to changes in food resources, though these are largely unquantified.