Repeated horizontal gene transfer of GALactose metabolism genes violates Dollo’s law of irreversible loss

Dollo’s law posits that evolutionary losses are irreversible, thereby narrowing the potential paths of evolutionary change. While phenotypic reversals to ancestral states have been observed, little is known about their underlying genetic causes. The genomes of budding yeasts have been shaped by extensive reductive evolution, such as reduced genome sizes and the losses of metabolic capabilities. However, the extent and mechanisms of trait reacquisition after gene loss in yeasts have not been thoroughly studied. Here, through phylogenomic analyses, we reconstructed the evolutionary history of the yeast galactose utilization pathway and observed widespread and repeated losses of the ability to utilize galactose, which occurred concurrently with the losses of GALactose (GAL) utilization genes. Unexpectedly, we detected multiple galactose-utilizing lineages that were deeply embedded within clades that underwent ancient losses of galactose utilization. We show that at least two, and possibly three, lineages reacquired the GAL pathway via yeast-to-yeast horizontal gene transfer. Our results show how trait reacquisition can occur tens of millions of years after an initial loss via horizontal gene transfer from distant relatives. These findings demonstrate that the losses of complex traits and even whole pathways are not always evolutionary dead-ends, highlighting how reversals to ancestral states can occur.     

Design,synthesis, and evaluation of a selective chemosensor for leucine-rich repeat kinase 2

We describe the design, synthesis, and evaluation of a selective activity probe for leucine-rich repeat kinase 2 (LRRK2), a possible molecular target for the treatment of Parkinson’s disease. Our optimal chemosensor design, termed Nictide-S2, incorporates a phosphorylation-sensitive sulfonamido-oxine fluorophore at an engineered cysteine within the substrate sequence. This design allows for the direct, real-time analysis of LRRK2 kinase activity with a detection limit of 2.5 nM. Under optimized conditions, we measured a Z′ factor of 0.7 demonstrating the potential utility of this assay for inhibitor screening. Off-target kinases capable of phosphorylating Nictide-S2 are identified and an optimized inhibitor cocktail for suppressing background signal is provided. The resulting chemosensor could be utilized to identify LRRK2 inhibitors as well as selectively report on LRRK2 activity in the presence of off-target kinases.     

Competition between two aquatic detritivorous isopods – a laboratory study

The role of adult faeces in juvenile nutrition of two isopod species, Proasellus coxalis s.l. and Asellus aquaticus (L.), with similar trophic strategies and different reproductive output, has been studied in laboratory. Our aim was to consider the possible competitive mechanisms occurring at the beginning of the species coexistence using allopatric populations in single and mixed species experiments. Two series of competition experiments were performed. In the first, adult specimens were used for breeding and feeding trials. Both population dynamics and the percentage of ovigerous females and juveniles were evaluated during 10 months. Adult densities and juvenile percentage of A.aquaticus were lower in the presence of P. coxalis s.l. than when alone. At the end of the breeding experiments the dietary preferences of adults on a set of fungally conditioned leaf discs were not different among treatments. In the second series of experiments, the influence of coexistence on the feeding rates of young asellids and the relative importance of faeces and decaying plant material in their diet were investigated. Individual consumption by wild juveniles in multiple-choice laboratory experiments was measured by radioisotopes (^{32 2}P). Juveniles of P. coxalis s.l. showed the highest ingestion rates. In co-occurrence, contrary to A.aquaticus, they were able to further increase feeding on parental faeces. The role of parental faeces in the diet of the two species juveniles and the competitive dominance of P. coxalis s.l. are discussed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Dwellings and workspaces at Strandvägen, 5600–5000 cal. BC

This paper describes identified workspaces and the manufacture of slotted bone points at the Late Mesolithic settlement Strandvägen in Motala, in eastern central Sweden. Several dwellings were documented, Dwelling 1 being typically round-oval in shape 9 × 5.5 meters, with a floor area covering 49.5 m². Radiocarbon dates fall between approximately 5600-5200 cal BC. A combined archaeological record, with lithics and bone artefacts as well as analyses of the osteological assemblage has shown that slotted bone tools with mounted lithic inserts have been produced adjacent of the dwelling. The spatial distribution of bone flakes, microblades, processed resin and slotted artefacts testify to a clearly and delimited craft area near the shoreline of the river Motala Ström. Analyses of the finds, e.g. birch bark resin and prepared bone preforms by direct percussion, also help in reconstructing the stages of manufacturing composite projectile points in this part of Eurasia.     

Alterations and Mechanism of Gut Microbiota in Graves’ Disease and Hashimoto’s Thyroiditis

To explore the role of gut microbiota in Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Seventy fecal samples were collected, including 27 patients with GD, 27 with HT, and 16 samples from healthy volunteers. Chemiluminescence was used to detect thyroid function and autoantibodies (FT3, FT4, TSH, TRAb, TGAb, and TPOAb); thyroid ultrasound and 16S sequencing were used to analyze the bacteria in fecal samples; KEGG (Kyoto Encyclopedia of Genes and Genomes) and COG (Clusters of Orthologous Groups) were used to analyze the functional prediction and pathogenesis. The overall structure of gut microbiota in the GD and HT groups was significantly different from the healthy control group. Proteobacteria and Actinobacteria contents were the highest in the HT group. Compared to the control group, the GD and HT groups had a higher abundance of Erysipelotrichia, Cyanobacteria, and Ruminococcus_2 and lower levels of Bacillaceae and Megamonas. Further analysis of KEGG found that the “ABC transporter” metabolic pathway was highly correlated with the occurrence of GD and HT. COG analysis showed that the GD and HT groups were enriched in carbohydrate transport and metabolism compared to the healthy control group but not in amino acid transport and metabolism. Our data suggested that Bacillus, Blautia, and Ornithinimicrobium could be used as potential markers to distinguish GD and HT from the healthy population and that “ABC transporter” metabolic pathway may be involved in the pathogenesis of GD and HT.     

最大信息熵原理与群体遗传平衡

建立了用最大信息熵原理推导群体遗传平衡定律的统一数学模型,并给出了模型的统一解,此解正是Hardy-Weinberg定律所给出的平衡群体的基因型频率,说明当群体信息熵达到最大时,群体基因型频率不再变化,即达到“平衡”。这证明了最大熵分布就是Hardy-Weinberg平衡分布。Hardy-Weinberg平衡定律与最大信息熵原理的内在一致性说明,杂交和随机交配是一个不可逆过程,使群体基因型信息熵增大,无序性增,是选择和近亲交配使群体的信息熵降低,有序性增加,育种过程实际就是调节群体信息熵的过程。过程信息熵的含义是表示一个概率分布的不确定性,最大熵原理意味着在一定的约束条件,选择具有最大不确定性的分布,从而其分布是最为随机的。最大熵原理在信息,工程,天文,地理,图像处理,模式识别等自然科学和社会科学领域都有广泛的成功应用,本文从群体遗传学角度证明了这一原理具有普遍适用性。熵是描述系统状态的函数,而最大熵原理则表明了系统发展变化的趋势,系统的最终状态必然是熵增加至最大值的状态,对于任何系统都是如此。因此,群体遗传系统的平衡定律可以统一用最大熵原理进行判定和描述;任意群体的基因型信息熵在随机交配世代传递时有不断增加的趋势;在一定约束条件下基因型信息熵达到最大值时,就称之为达到遗传平衡。本文将信息论原理应用于群体遗传学研究,揭示了基因信息熵的生物学意义,并表明可以用信息学和控制论的原理和方法来研究群体遗传学问题。     

Lipids,lipid metabolism and Kaposi’s sarcoma-associated herpesvirus pathogenesis

Lipids are essential for mammalian cells to maintain many physiological functions. Emerging evidence has shown that cancer cells can develop specific alterations in lipid biosynthesis and metabolism to facilitate their survival and various malignant behaviors. To date, the precise role of cellular lipids and lipid metabolism in viral oncogenesis is still largely unclear with only a handful of literature covering this topic to implicate lipid metabolism in oncogenic virus associated pathogenesis. In this review, we focus on the role of lipid biosynthesis and metabolism in the pathogenesis of the Kaposi’s sarcoma-associated herpesvirus, a common causative factor for cancers arising in the immunocompromised settings.

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Tadpole-like Conformations of Huntingtin Exon 1 Are Characterized by Conformational Heterogeneity that Persists regardless of Polyglutamine Length

Soluble huntingtin exon 1 (Httex1) with expanded polyglutamine (polyQ) engenders neurotoxicity in Huntington's disease. To uncover the physical basis of this toxicity, we performed structural studies of soluble Httex1 for wild-type and mutant polyQ lengths. Nuclear magnetic resonance experiments show evidence for conformational rigidity across the polyQ region. In contrast, hydrogen–deuterium exchange shows absence of backbone amide protection, suggesting negligible persistence of hydrogen bonds. The seemingly conflicting results are explained by all-atom simulations, which show that Httex1 adopts tadpole-like structures with a globular head encompassing the N-terminal amphipathic and polyQ regions and the tail encompassing the C-terminal proline-rich region. The surface area of the globular domain increases monotonically with polyQ length. This stimulates sharp increases in gain-of-function interactions in cells for expanded polyQ, and one of these interactions is with the stress-granule protein Fus. Our results highlight plausible connections between Httex1 structure and routes to neurotoxicity.     

基于信息熵的我国日降水量随机性和时空差异性

我国日降水过程呈现明显的随机性与时空差异性,如何准确认识其时空变化规律对洪涝灾害防治等实际工作的影响具有重要意义.本文基于1961—2013年全国520个气象站点的日降水数据,选用信息熵指标研究我国日降水量的随机性.结果表明:研究期间,我国东南地区日降水量的随机性大于西北地区,且不同等级日降水量随机性的空间分布存在差异,小雨(降雨量0.1~10 mm,P_0)等级日降水量随机性较大,差异不明显,中雨(10~25 mm,P₁₀)、大雨(25~50 mm,P₂₅)等级日降水量随机性最大,差异明显,暴雨及以上(≥50 mm,P₅₀)等级日降水量随机性最小,差异最明显.整体上,日降水的信息熵值呈上升趋势,表明全球气候变化下我国大部分地区日降水量的随机性增大,尤其表现为极端暴雨发生的频次明显增大.日降水信息熵的空间分布及其变化趋势可以很好地综合反映我国日降水量随机性的空间分布格局,可为洪涝灾害防治、农业规划布局、生态环境规划等提供科学依据.