Effect of simulated microgravity on human lymphocytes

During space flight the function of the immune system changes significantly. Several papers reported that postflight the number and the proportion of circulating leukocytes in astronauts are modified (Leach, 1992), the in vitro mitogen induced T cell activation is depressed (Cogoli et al., 1985; Konstantinova et al. 1993) and there are detectable differences in cytokine production of leukocytes as well (Talas et al. 1983; Batkai et al. 1988; Chapes et al. 1992). One of the possible modifying forces is the microgravity condition itself. Our aim was to analyse mechanisms responsible for changing leukocyte functions in low gravity environment. For terrestrial simulation of microgravity we used a Rotary Cell Culture System (RCCS) developed by NASA. We investigated the effect of simulated microgravity on separated human peripheral blood mononuclear cells (PBMCs). We detected the populations of different cells by antibodies conjugated to fluorofors using a Flow Cytometer. Since space flight reduces the number of peripheral blood lymphocytes (Stowe et al., 1999) we supposed that apoptotic (programmed cell death) processes might be involved. This hypothesis was supported by the result of our earlier experiment demonstrating that simulated microgravity increased the level of secreted Tumor Necrosis Factor-alpha (TNFalpha, a known apoptotic signal molecule) significantly (Batkai et al. 1999).     

Regional Ileitis in Pigs Isolation of Campylobacter from Affected Ileal Mucosa

In the last few years special interest has been focused on enteric diseases localized to the lower alimentary tract, especially the ileum of weaned pigs. An increasing frequency of disorders of unknown aetiology described as regional ileitis (Emsbo 1951), necrotic enteritis (Jubb & Kennedy 1970), and intestinal adenomatosis (Rowland et al. 1973) has been reported. The changes include thickening of the ileal mucosa with hypertrophy of the muscular wall. The normal structure of villi is replaced by a proliferation of crypt cells. Necrosis of the mucosa and granulation-tissue proliferation in the submucosa occur in later stages. Regional ileitis in man (Crohn et al. 1932) which is described as a chronic enteric disease with granulomatous inflammatory changes localized to segments of the ileum is also attracting increasing attention in medical research (Liljefors 1972). The lesions are also found in the colon, and the presence of a transmissible agent involved in the aetiology of Crohn's disease has been discussed on the basis of animal experiments (Cave et al. 1973). The disease in pigs is accompanied by haematological changes, including decreased concentration of total serum protein, albumin, alkaline phosphatase, and zinc (Martinsson et al. 1974, 1976).     

WIDESPREAD OCCURRENCE OF THE OCEANIC ULTRAPLANKTER, PRASINOCOCCUS CAPSULATUS (PRASINOPHYCEAE), THE DIAGNOSTIC "GOLGI-DECAPORE COMPLEX" AND THE NEWLY DESCRIBED POLYSACCHARIDE "CAPSULAN"

A nonmotile green nanoalga was isolated from the waters over the Cayman Trench in March 1979 and has been maintained in culture as clone URI 266G (CCMP 1202). It was observed to form a copious polysaccharide capsule that presumably originated in the Golgi body and was secreted through a crown of 10 pores in the cell wall, the “decapore.” This multilaminate apical area, lying adjacent to the Golgi, underwent structural changes during morphogenesis. The polysaccharide precursors that coalesced to form the capsule apparently became stainable and visible as they exited the decapore when they cross-linked with divalent ions in seawater. Cell wall precursors, or a cell wall lamina, surrounded the daughter cells both during synchronous binary fission and after cell separation, with the maternal capsule perhaps acting as a template. Similar prasinophyte isolates have been obtained from widespread areas of the North Atlantic and were divided into two subgroups on the basis of their pigment complement (Hooks et al. 1988). One subgroup, typified by clone Ω 48-23 (CCMP 1203), was described by Guillard et al. (1991) as Pycnococcus provasolii Guillard within a new family, the Pycnococcaceae. The other subgroup, typified by clone URI 266G (CCMP 1202), contained two unique carotenoids, one of which was uriolide (Foss et al. 1986). Subsequently, Miyashita et al. (1993) described an alga from the western Pacific Ocean that is indistinguishable from URI 266G in both pigment composition and ultrastructure that they named Prasinococcus capsulatus Miyashita et Chihara and placed tentatively in the Pycnococcaceae. They described a curious asexual budding fission. Here we suggest an alternative form of cell division analogous to that observed in the other described Pycnococcaceae. We used theultrastructure of cells in exponential and stationary phases of growth to illustrate synchronous asexual binary fission, the “Golgi-decapore complex,” and its apparent role in capsule formation. A unique sulfated and carboxylated polyanionic polysaccharide named capsulan is released from this complex.     

GC3 heterogeneity and body temperature in vertebrates

A recent paper by Belle et al. (J. Mol. Evol. 55 (2002) 356) reported an analysis of mean GC(3) (the GC level of third codon positions) and standard deviations of GC(3) of vertebrate genomes as related to body temperature, and concluded that "the thermal stability hypothesis does not appear to explain the general patterns of composition", apparently contradicting a previous working hypothesis from our laboratory. We have analyzed the data of Belle et al. and find that their data not only do not contradict the thermal stability hypothesis, but if anything support it.     

MHC-dependent mate choice in humans: why genomic patterns from the HapMap European American dataset support the hypothesis

The role of the major histocompatibility complex (MHC) in mate choice in humans is controversial. Nowadays, the availability of genetic variation data at genomic scales allows for a careful assessment of this question. In 2008, Chaix et al. reported evidence for MHC-dependent mate choice among European American spouses from the HapMap 2 dataset. Recently, Derti et al. suggested that this observation was not robust. Furthermore, when Derti et al. applied similar analyses to the HapMap 3 European American samples, they did not see a significant effect. Although some of the points raised by Derti et al. are relevant, we disagree with the reported absence of evidence for MHC-dependent mate choice within the HapMap samples. More precisely, we show here that the MHC dissimilarity among HapMap 3 European American spouses is still extreme in comparison to the rest of the genome, even after multiple testing correction. This finding supports the hypothesis of MHC-dependent mate choice in some human populations.     

A case of acute myelomonocytic leukaemia associated with therapy: Feulgen-DNA microdensitometric determinations.

A cytochemical study of a case of acute myelomonocytic leukaemia, which arose after radiation therapy and polychemotherapy for Hodgkin's disease, is presented. The distribution of the DNA content of the circulating blood cells appears to be different from the unimodal diploid distribution reported in the literature for acute myelomonocytic leukamias not associated with therapy. This finding seems to strengthen the hypothesis, already put forward by Marinone et al. (1979), that a particular pattern of DNA content distribution could be characteristic of leukaemias linked to chemotherapy and radiotherapy.     

Comment on "Unbiased statistical analysis for multi-stage proteomic search strategies"

Everett et al. recently reported on a statistical bias that arises in the target-decoy approach to false discovery rate estimation in two-pass proteomics search strategies as exemplified by X!Tandem. This bias can cause serious underestimation of the false discovery rate. We argue here that the "unbiased" solution proposed by Everett et al., however, is also biased and under certain circumstances can also result in a serious underestimate of the FDR, especially at the protein level.     

Nucleotide sequence of the gene for the delta 5-3-ketosteroid isomerase of Pseudomonas testosteroni

The structural gene for the delta 5-3-ketosteroid isomerase of Pseudomonas testosteroni has been sequenced by the dideoxy method. The sequence obtained confirms the amino acid (aa) sequence of Benson et al. [J. Biol. Chem. 246 (1971) 7514-7525] at all but 5 aa residues of the 125-aa polypeptide. Amino acid residues 22, 24, 33, and 38, reported to be asparagines by Benson et al., are found to be encoded by aspartic acid codons. Amino acid residue 77, reported to be a glutamine by Benson et al., is encoded by a glutamic acid codon. The identification of aa 38 as aspartic acid, coupled with its presence in the active site, as indicated by previous affinity and photoaffinity-labeling studies and confirmed independently by x-ray crystallographic studies, strengthens the hypothesis that Asp-38 is the aa responsible for the 4 beta to 6 beta proton transfer which is part of the enzymatic reaction.     

从泛甲壳动物新假说评述节肢动物系统进化的研究进展

Giribet et al(2001)构建的节肢动物系统树中,将六足动物（昆虫）完全合并到甲壳动物之中,共同构成一个新的类群：泛甲壳动物（Pancrustacea）。这与近百年来经典的节肢动物系统发生概念有很大的不同。现拟重温上个世纪以来最主要的4个假说,简要评述节肢动物系统发生研究的近况,并给予展望。     

Pathological and molecular mechanisms of prostate carcinogenesis: implications for diagnosis, detection, prevention, and treatment

Prostate cancer is an increasing threat throughout the world. As a result of a demographic shift in population, the number of men at risk for developing prostate cancer is growing rapidly. For 2002, an estimated 189,000 prostate cancer cases were diagnosed in the U.S., accompanied by an estimated 30,200 prostate cancer deaths [Jemal et al., 2002]. Most prostate cancer is now diagnosed in men who were biopsied as a result of an elevated serum PSA (>4 ng/ml) level detected following routine screening. Autopsy studies [Breslow et al., 1977; Yatani et al., 1982; Sakr et al., 1993], and the recent results of the Prostate Cancer Prevention Trial (PCPT) [Thompson et al., 2003], a large scale clinical trial where all men entered the trial without an elevated PSA (<3 ng/ml) were subsequently biopsied, indicate the prevalence of histologic prostate cancer is much higher than anticipated by PSA screening. Environmental factors, such as diet and lifestyle, have long been recognized contributors to the development of prostate cancer. Recent studies of the molecular alterations in prostate cancer cells have begun to provide clues as to how prostate cancer may arise and progress. For example, while inflammation in the prostate has been suggested previously as a contributor to prostate cancer development [Gardner and Bennett, 1992; Platz, 1998; De Marzo et al., 1999; Nelson et al., 2003], research regarding the genetic and pathological aspects of prostate inflammation has only recently begun to receive attention. Here, we review the subject of inflammation and prostate cancer as part of a "chronic epithelial injury" hypothesis of prostate carcinogenesis, and the somatic genome and phenotypic changes characteristic of prostate cancer cells. We also present the implications of these changes for prostate cancer diagnosis, detection, prevention, and treatment.     

"Wunder" F-BAR domains: going from pits to vesicles

Clathrin-mediated endocytosis is a key mechanism by which cells take up extracellular cargo. In this issue, Shimada et al. (2007) reveal the mode of action of the F-BAR domain, which deepens the initial membrane pit that forms during clathrin-mediated endocytosis.     

Numb: "Adapting" notch for endocytosis

During sensory organ precursor divisions in Drosophila, the numb gene product segregates asymmetrically into one of the two daughter cells, to which it confers a specific fate by inhibiting Notch signaling. In this issue of Developmental Cell, Berdnik et al. show that Numb recruits alpha-Adaptin and that this physical interaction plays a role in downregulating Notch, presumably by stimulating endocytosis of Notch.     

Microstructural analysis of deformation-induced hypoxic damage in skeletal muscle

Deep pressure ulcers are caused by sustained mechanical loading and involve skeletal muscle tissue injury. The exact underlying mechanisms are unclear, and the prevalence is high. Our hypothesis is that the aetiology is dominated by cellular deformation (Bouten et al. in Ann Biomed Eng 29:153-163, 2001; Breuls et al. in Ann Biomed Eng 31:1357-1364, 2003; Stekelenburg et al. in J App Physiol 100(6):1946-1954, 2006) and deformation-induced ischaemia. The experimental observation that mechanical compression induced a pattern of interspersed healthy and dead cells in skeletal muscle (Stekelenburg et al. in J App Physiol 100(6):1946-1954, 2006) strongly suggests to take into account the muscle microstructure in studying damage development. The present paper describes a computational model for deformation-induced hypoxic damage in skeletal muscle tissue. Dead cells stop consuming oxygen and are assumed to decrease in stiffness due to loss of structure. The questions addressed are if these two consequences of cell death influence the development of cell injury in the remaining cells. The results show that weakening of dead cells indeed affects the damage accumulation in other cells. Further, the fact that cells stop consuming oxygen after they have died, delays cell death of other cells.     

Experimental Evidence Leading to an Alternative Explanation of Why <Emphasis Type="Italic">D</Emphasis>-tyrosine Sometimes Crystallizes Faster than Its <Emphasis Type="Italic">L</Emphasis>-Enantiomer

On the occasions when D-tyrosine is observed to crystallize faster than its L-enantiomer, it is the result of a diastereomeric interaction between an airborne, non-racemic, chiral influence--probably a fungal spore--and the tyrosine enantiomers, enhancing the degree of crystal nucleation of D-tyrosine over L-tyrosine. This explanation, supported by experimental evidence, is presented as a more plausible alternative to the Shinitzky-Deamer hypothesis (Shinitzky et al., Progress in biological chirality, Elsevier, Amsterdam, pp. 329-337, 2004; Deamer et al., Chirality, 19:751-763, 2007) which relies on the parity violation energy difference between enantiomers, a femtojoule to picojoule per mole theoretical energy range.     

Reprogramming is essential in nuclear transfer

Fertile offspring have been produced by nuclear transfer from adult somatic cells in several mammalian species (Wilmut et al., 1997; Kato et al., 1998; Wakayama et al., 1998; Polejaeva et al., 2000; Chesne et al., 2002; Shin et al., 2002; Zhou et al., 2003). Various possible causes have been suggested for the overall low efficiency (Perry and Wakayama, 2002). Notably, however, it has not yet been clearly demonstrated whether reprogramming after nuclear transfer is necessary for successful cloning. Here we show that reprogramming is essential in nuclear transfer, by comparing the developmental efficiency after the transfer of cumulus cell nuclei with that for zygote nuclei. Nuclear transfers from blastomeres of a series of pre-implantation stages showed further that, as development proceeds, the nuclei progressively lose their potency and become more difficult to reprogram upon their transfer into enucleated MII oocytes. We also found that naturally ovulated oocytes are much better recipients of a nucleus than are superovulated oocytes, which have been used in all the nuclear transfer experiments reported so far. This indicates that cloning efficiency can also be increased to some extent by technical improvements. All these results enable us to distinguish more clearly between the inherent problem of reprogramming and technical problems associated with materials, manipulation, and in vitro culture.     

Transposons reanimated in mice

Transposons have proved valuable in the genetic modification of many organisms but not mammals. New work reported by Ding et al. (2005) in this issue of Cell and by Collier et al. (2005) and Dupuy et al. (2005) in a recent issue of Nature now reveals that insertional mutagenesis in mammalian cells is possible thanks to modified derivatives of the piggyBac and Sleeping Beauty DNA transposons. However, the slow rate of proliferation of DNA transposons suggests that derivatives of the L1 retrotransposon might be more powerful for mutagenesis of germline cells. In either case, the future of transposon-driven genetic analyses of mice and other mammals looks promising.     

Mechanic stimulation of the soles support zones as a countermeasure of the contractile properties decline under microgravity conditions

Decrease in muscle contractility is an inevitable consequence of exposure in microgravity. A wealth of currently accumulated facts is indicative of profound modifications in structure and function of the skeletal muscles in the absence of gravity. Investigations with humans during space flights of varying duration (L.I. Kakurin et al., 1971; I.B. Kozlovskaya et al., 1984, 1987, 1991;.), ground-based simulation studies (A.M. Genin et al., 1969; L.S. Grigorieva et al., 1983), and numerous experiments with animals (E.I. IIyina-Kakueva et al., 1979; O.M. Edgerton et al 1991; B.S. Shenkman et al., 1994) made it evident that removal of gravitational loading is fraught with significant reductions in the contractile properties of muscular fibers, especially noticeable in muscles-extensors. Results of ground-based simulation studies led to the hypothesis that changes in muscle contractility developing already after few days in microgravity conditions are consequent to reduction in support afferentation that plays an important role in initiation and maintenance of the activity of tonic motor units (A.V. Kirenskaya et al., 1986). In view of the above, an idea has been proposed to prevent losses in tonic muscles contractility by application of artificial support. Testing of this hypothesis was the theme of the present investigation.