Characterization of the first adult de novo case of 46,X,der(Y)t(X;Y)(p22.3;q11.2)

Herein, we describe a case of an infertile man detected in postnatal diagnosis with FISH characterization and array-CGH used for genome-wide screening which allowed the identification of a complex rearrangement involving sex chromosomes, apparently without severe phenotypic consequences. The deletion detected in our patient has been compared with previously reported cases leading us to propose a hypothetical diagnostic algorithm that would be useful in similar clinical situations, with imperative multi disciplinary approach integrated with genetic counseling. Our patient, uniquely of reproductive age, is one of six reported cases of duplication of Xp22.3 (~ 8.4 Mb) segment and contemporary deletion of Yq (~ 42.9 Mb) with final karyotype as follows:

46,X,der(Y),t(X;Y)(Ypter → Yq11.221::Xp22.33 → Xpter).ish der(Y) (Yptel+,Ycen+,RP11-529I21+,RP11-506M9-Yqtel −,Xptel +). arrXp22.33p22.31(702–8,395,963, 8,408,289x1), Yq11.221q12 (14,569,317x1, 14,587,321–57,440,839x0)     

Polyphasic Detection of Cyanobacteria in Terrestrial Biofilms

Cyanobacterial populations detected on buildings by traditional methods are mainly filamentous, whereas direct microscopy shows that they are principally coccoid morphotypes that often cannot be isolated in culture, but may grow on artificial media when the spatial biofilm relationships are maintained. The polyphasic strategy described here was to select morphologically distinct colonies from rehydrated biofilms for direct DNA amplification, allowing uncultured organisms to be sequenced and their morphology to be characterized by microscopy. DNA data banks currently contain many entries for cyanobacteria of unrecorded morphology, which does not facilitate identification, although genetic variability in a population may be assessed. The sequence homologies of the present biofilm organisms (EMBL accession numbers AJ619681 to 619690) with those in DNA databanks were low, indicating differences between xerophytic cyanobacteria on walls and aquatic species comprising the majority in the databases. Further development of databases for the populations found in this environment, subject to temperature extremes, repeated desiccation and high UV and salt levels, is required.     

The multiple forms of bovine seminal ribonuclease: Structure and stability of a C-terminal swapped dimer

Bovine seminal ribonuclease (BS-RNase) acquires an interesting anti-tumor activity associated with the swapping on the N-terminal. The first direct experimental evidence on the formation of a C-terminal swapped dimer (C-dimer) obtained from the monomeric derivative of BS-RNase, although under non-native conditions, is here reported. The X-ray model of this dimer reveals a quaternary structure different from that of the C-dimer of RNase A, due to the presence of three mutations in the hinge peptide 111–116. The mutations increase the hinge peptide flexibility and decrease the stability of the C-dimer against dissociation. The biological implications of the structural data are also discussed.     

An Ancestral Recombination Graph for Diploid Populations with Skewed Offspring Distribution

A large offspring-number diploid biparental multilocus population model of Moran type is our object of study. At each time step, a pair of diploid individuals drawn uniformly at random contributes offspring to the population. The number of offspring can be large relative to the total population size. Similar “heavily skewed” reproduction mechanisms have been recently considered by various authors (cf. e.g., Eldon and Wakeley 2006, 2008) and reviewed by Hedgecock and Pudovkin (2011). Each diploid parental individual contributes exactly one chromosome to each diploid offspring, and hence ancestral lineages can coalesce only when in distinct individuals. A separation-of-timescales phenomenon is thus observed. A result of Möhle (1998) is extended to obtain convergence of the ancestral process to an ancestral recombination graph necessarily admitting simultaneous multiple mergers of ancestral lineages. The usual ancestral recombination graph is obtained as a special case of our model when the parents contribute only one offspring to the population each time. Due to diploidy and large offspring numbers, novel effects appear. For example, the marginal genealogy at each locus admits simultaneous multiple mergers in up to four groups, and different loci remain substantially correlated even as the recombination rate grows large. Thus, genealogies for loci far apart on the same chromosome remain correlated. Correlation in coalescence times for two loci is derived and shown to be a function of the coalescence parameters of our model. Extending the observations by Eldon and Wakeley (2008), predictions of linkage disequilibrium are shown to be functions of the reproduction parameters of our model, in addition to the recombination rate. Correlations in ratios of coalescence times between loci can be high, even when the recombination rate is high and sample size is large, in large offspring-number populations, as suggested by simulations, hinting at how to distinguish between different population models.     

HPLC同时测定大叶冬青叶中10种多酚成分的含量及抗氧化活性研究

建立HPLC同时测定大叶冬青叶中新绿原酸、绿原酸、隐绿原酸、咖啡酸、对羟基肉桂酸、芦丁、异槲皮苷、异绿原酸B、异绿原酸A和异绿原酸C 10种多酚类化合物的定量分析方法,研究不同产地及不同采收时期大叶冬青叶中10种多酚类化合物的含量差异及其抗氧化活性。采用HPLC测定大叶冬青叶50%甲醇提取液中10种多酚类成分的含量,并选用DPPH法对其抗氧化活性进行初步探索。结果表明,10种多酚类化合物分离效果较好,标准曲线在检测范围内具有良好的线性(r>0.999 5),平均加样回收率在96.58%～112.03%,RSD<4%(n=6)。大叶冬青叶50%甲醇提取液抗氧活性良好。本实验建立的方法快速、准确、重复性好,可用于同时测定大叶冬青叶中新绿原酸、绿原酸、隐绿原酸、咖啡酸、对羟基肉桂酸、芦丁、异槲皮苷、异绿原酸B、异绿原酸A、异绿原酸C 10种成分的含量;不同产地、不同采收时期大叶冬青叶中10种多酚类化合物含量存在一定差异;不同来源大叶冬青叶50%甲醇提取液抗氧化能力具有明显差异。     

Population persistence under high mutation rate: From evolutionary rescue to lethal mutagenesis

Populations may genetically adapt to severe stress that would otherwise cause their extirpation. Recent theoretical work, combining stochastic demography with Fisher's geometric model of adaptation, has shown how evolutionary rescue becomes unlikely beyond some critical intensity of stress. Increasing mutation rates may however allow adaptation to more intense stress, raising concerns about the effectiveness of treatments against pathogens. This previous work assumes that populations are rescued by the rise of a single resistance mutation. However, even in asexual organisms, rescue can also stem from the accumulation of multiple mutations in a single genome. Here, we extend previous work to study the rescue process in an asexual population where the mutation rate is sufficiently high so that such events may be common. We predict both the ultimate extinction probability of the population and the distribution of extinction times. We compare the accuracy of different approximations covering a large range of mutation rates. Moderate increase in mutation rates favors evolutionary rescue. However, larger increase leads to extinction by the accumulation of a large mutation load, a process called lethal mutagenesis. We discuss how these results could help design “evolution‐proof” antipathogen treatments that even highly mutable strains could not overcome.     

The effects of weak selection on neutral diversity at linked sites

The effects of selection on variability at linked sites have an important influence on levels and patterns of within-population variation across the genome. Most theoretical models of these effects have assumed that selection is sufficiently strong that allele frequency changes at the loci concerned are largely deterministic. These models have led to the conclusion that directional selection for selectively favorable mutations, or against recurrent deleterious mutations, reduces nucleotide site diversity at linked neutral sites. Recent work has shown, however, that fixations of weakly selected mutations, accompanied by significant stochastic changes in allele frequencies, can sometimes cause higher diversity at linked sites when compared with the effects of fixations of neutral mutations. This study extends this work by deriving approximate expressions for the mean conditional times to fixation and loss of mutations subject to selection, and analyzing the conditions under which selection increases rather than reduces these times. Simulations are used to examine the relations between diversity at a neutral site and the fixation and loss times of mutations at a linked site that is subject to selection. It is shown that the long-term level of neutral diversity can be increased over the purely neutral value by recurrent fixations and losses of linked, weakly selected dominant or partially dominant favorable mutations, or linked recessive or partially recessive deleterious mutations. The results are used to examine the conditions under which associative overdominance, as opposed to background selection, is likely to operate.     

Review Times in Statistical Journals: Tilting at Windmills?

Using limited data, I argue that the review times in statistics are far too long for the field to keep pace with the rapidly changing environment in science. I note that statisticians do not appear to believe in statistics because data on the review process are not widely available to members of the profession. I suggest a few changes that could be made to speed up the review process, although it would appear that a change in our culture is required before the problem will be solved.     

Gramicidin toxicity in NG108-15 cells: protective effects of acetamidine and guanidine

Studies were conducted using a novel in vitro approach to investigate the efficacy of acetamidine hydrochloride (ACE) and guanidine hydrochloride (GUAN), previously shown to block gramicidin D (GRAM) channels in artificial membranes, in preventing the toxic effects of GRAM in NG108-15 (neuroblastoma×glioma hybrid) cells. Specifically, intracellular microelectrode techniques were employed to examine changes in membrane resting potential (V _m) and input resistance (R _in). At 1 mol/L, ACE significantly reduced loss of V _m induced by 1 or 10 g/ml GRAM, although higher concentrations of ACE did not afford enhanced antagonism. GUAN, in contrast, produced a concentration-dependent antagonism of GRAM-induced V _m and R _in loss, with high concentrations (10 or 100 mol/L) completely preventing diminutions in both V _m and R _in. In control cells superfused without GRAM, ACE produced a direct, concentration-dependent reduction in V _m and R _in, whereas GUAN hyperpolarized NG108-15 cells but did not alter R _in. These data represent the initial demonstration of the reversal of GRAM toxicity in an intact cell system.