Bayesian DNA copy number analysis

Background  

Some diseases, like tumors, can be related to chromosomal aberrations, leading to changes of DNA copy number. The copy number of an aberrant genome can be represented as a piecewise constant function, since it can exhibit regions of deletions or gains. Instead, in a healthy cell the copy number is two because we inherit one copy of each chromosome from each our parents.     

Subdivision and developmental fate of the head mesoderm in Drosophila melanogaster

In this paper, we define temporal and spatial subdivisions of the embryonic head mesoderm and describe the fate of the main lineages derived from this tissue. During gastrulation, only a fraction of the head mesoderm (primary head mesoderm; PHM) invaginates as the anterior part of the ventral furrow. The PHM can be subdivided into four linearly arranged domains, based on the expression of different combinations of genetic markers (tinman, heartless, snail, serpent, mef-2, zfh-1). The anterior domain (PHMA) produces a variety of cell types, among them the neuroendocrine gland (corpus cardiacum). PHMB, forming much of the “T-bar” of the ventral furrow, migrates anteriorly and dorsally and gives rise to the dorsal pharyngeal musculature. PHMC is located behind the T-bar and forms part of the anterior endoderm, besides contributing to hemocytes. The most posterior domain, PHMD, belongs to the anterior gnathal segments and gives rise to a few somatic muscles, but also to hemocytes. The procephalic region flanking the ventral furrow also contributes to head mesoderm (secondary head mesoderm, SHM) that segregates from the surface after the ventral furrow has invaginated, indicating that gastrulation in the procephalon is much more protracted than in the trunk. We distinguish between an early SHM (eSHM) that is located on either side of the anterior endoderm and is the major source of hemocytes, including crystal cells. The eSHM is followed by the late SHM (lSHM), which consists of an anterior and posterior component (lSHMa, lSHMp). The lSHMa, flanking the stomodeum anteriorly and laterally, produces the visceral musculature of the esophagus, as well as a population of tinman-positive cells that we interpret as a rudimentary cephalic aorta (“cephalic vascular rudiment”). The lSHM contributes hemocytes, as well as the nephrocytes forming the subesophageal body, also called garland cells.     

Ternary complex formation of human immunodeficiency virus type 1 Env, CD4, and chemokine receptor captured as an intermediate of membrane fusion

Human immunodeficiency virus (HIV) Env-induced fusion is highly temperature dependent. When effector and target cells were coincubated at 37 degrees C, there was a kinetic delay before fusion commenced. When effector and target cells were coincubated for varied times at 23 degrees C, a temperature that does not permit fusion, a temperature-arrested stage was created. Raising temperature to 37 degrees C from the 23 degrees C intermediate eliminated the kinetic delay. Inhibitors (T22, AMD3100, and Sch-C) that block fusion by binding chemokine receptors were added after creating the intermediate so as to assess the extent of engagement between gp120 and chemokine receptors at that stage. For both CXCR4 and CCR5 as coreceptors, increasingly long times of coincubation at 23 degrees C reduced the efficacy of the coreceptor-binding inhibitors in blocking fusion. This implies that an increasing number of ternary Env/CD4/coreceptor complexes form over time at 23 degrees C. It also shows that ternary complex formation has a lower temperature threshold than the downstream steps that include Env folding into a six-helix bundle; this provides an experimental means to separate coreceptor binding by gp120 from the subsequent refolding of gp41 into a six-helix bundle structure. As the time of cell coincubation at 23 degrees C was prolonged, more cells quickly fused upon the raising of the temperature to 37 degrees C, and the increase quantitatively correlated with the greater percentage of fusion that was resistant to drugs. Therefore the pronounced kinetic delay in HIV Env-induced fusion is caused predominantly by the time needed for ternary complexes to form.     

Ubiquitin Ser65 phosphorylation affects ubiquitin structure,chain assembly and hydrolysis

The protein kinase PINK1 was recently shown to phosphorylate ubiquitin (Ub) on Ser65, and phosphoUb activates the E3 ligase Parkin allosterically. Here, we show that PINK1 can phosphorylate every Ub in Ub chains. Moreover, Ser65 phosphorylation alters Ub structure, generating two conformations in solution. A crystal structure of the major conformation resembles Ub but has altered surface properties. NMR reveals a second phosphoUb conformation in which β5-strand slippage retracts the C-terminal tail by two residues into the Ub core. We further show that phosphoUb has no effect on E1-mediated E2 charging but can affect discharging of E2 enzymes to form polyUb chains. Notably, UBE2R1- (CDC34), UBE2N/UBE2V1- (UBC13/UEV1A), TRAF6- and HOIP-mediated chain assembly is inhibited by phosphoUb. While Lys63-linked poly-phosphoUb is recognized by the TAB2 NZF Ub binding domain (UBD), 10 out of 12 deubiquitinases (DUBs), including USP8, USP15 and USP30, are impaired in hydrolyzing phosphoUb chains. Hence, Ub phosphorylation has repercussions for ubiquitination and deubiquitination cascades beyond Parkin activation and may provide an independent layer of regulation in the Ub system.     

Optimization of mycophenolic acid production in solid state fermentation using response surface methodology

Mycophenolic acid (MPA) can be produced in solid state fermentation. An isolate of Penicillium brevi-compactum ATCC 16024 grown on moist wheat bran produced a titre of 425 mg per kg of wheat bran. Central composite rotatable design and response surface methodology were employed to derive a statistical model for media optimization towards production of mycophenolic acid. Five levels with a five factorial design were adopted. The correlation coefficient was 0.82, ensuring a satisfactory adjustment of the model to the experimental values. This statistical design was very effective in improving the titre of mycophenolic acid up to 3286 mg per kg of wheat bran. Received 24 July 1998/ Accepted in revised form 4 December 1998     

Emission analysis of RE3+ (RE = Sm,Dy):B2O3‐TeO2‐Li2O‐AlF3 glasses

This article reports on the optical properties of 0.5% mol of Sm³⁺, Dy³⁺ ion‐doped B₂O₃‐TeO₂‐Li₂O‐AlF₃ (LiAlFBT) glasses. The glass samples were characterized by optical absorption and emission spectra. Judd‐Ofelt theory was applied to analyze the optical absorption spectra and calculate the intensity parameters and radiative properties of the emission transitions. The emission spectra of Sm³⁺ and Dy³⁺:LiAlFBT glasses showed a bright reddish‐orange emission at 598 nm (⁴G_5/2 → ⁶H_7/2) and an intense yellow emission at 574 nm (⁴F_9/2 → ⁶H_13/2), respectively. Full width at half maximum (FWHM), stimulated emission cross section, gain bandwidth and optical gain values were also calculated to extend the applications of the Sm³⁺ and Dy³⁺:LiAlFBT glasses. Copyright © 2012 John Wiley & Sons, Ltd.     

New immortalized cell lines of patients with small supernumerary marker chromosome: towards the establishment of a cell bank.

Sixteen newly established cell lines with small supernumerary marker chromosomes (sSMC) derived from chromosomes 1, 2, 4, 6, 7, 8, 14, 15, 16, 18, 19, 21, and 22 are reported. Two sSMC are neocentric and derived from 15q24.1-qter and 2q35-q36, respectively. Two further cases each present with two sSMC of different chromosomal origin. sSMC were characterized by multicolor fluorescence in situ hybridization for their chromosomal origin and genetic content. Moreover, uniparental disomy of the sister chromosomes of the sSMC was excluded in all nine cases studied for that reason. The 16 cases provide information to establish a refined genotype-phenotype correlation of sSMC and are available for future studies.     

Responses of pyramidal tract and corticorubral neurons to stimulation of lateral hypothalamic structures in cats

Responses of pyramidal tract neurons and corticorubral and unidentified neurons in the pericruciate area of the cortex to electrical stimulation in the posterior, tuberal, and anterior zones of the lateral hypothalamus and also to electrodermal stimulation of all four limbs were studied in cats anesthetized with chloralose. The proportion of pyramidal tract, corticorubral, and unidentified neurons which responded to hypothalamic stimulation was 73.3, 55.7, and 79.1% respectively. Data on the possibility of monosynaptic activation of some pyramidal tract neurons and unidentified cells were obtained. The presence of less stable and longer-latency responses of corticorubral neurons indicated the absence of a monosynaptic pathway for realization of ascending hypothalamic influences on neurons of the cortical extrapyramidal system. Some cortical neurons responded to stimulation of more than one zone of the hypothalamus. Pyramidal tract neurons and corticorubral neurons with axon collaterals running into the region of the hypothalamus were discovered for the first time. It was shown that most neurons of the pericruciate area of the cortex to which the ascending influence of the hypothalamus is directed have a large bilateral receptive field and respond to electrodermal stimulation of several limbs.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 14, No. 3, pp. 298–306, May–June, 1982.     

On a New Strategy of Preventive Oncology

The etiology of cancer is much wider than separately taken causal agent and rests against the most complicated interrelation and mutuality of many external and internal influences. Our researches with use of fluorescing antibodies to AFP, CEA and Ca-19-9 have shown that they are intensively besieged on a surface of cultivated malignant cells. It is the basic mechanism of tolerance and immunological escape, which is similar to pregnancy when «the maximal immunological most favored status” to developing fetus (semiallogenic transplant) is provided. The earliest revealing of first cancer cells, before steady community of cells and tumor angiogenesis were formed, has particular importance in the fight against cancer. The necessity of the specific completion of the weakened antineoplastic resistibility of people from high oncological risk groups is substantiated. The activity in this direction brought forth the design of embryonic anti-tumor modulator (EATM). EATM is composed of a wide pool of fetal proteins and proteoglycans isolated exceptionally from normal embryonic substances.