Data issues in the life sciences

We review technical and sociological issues facing the Life Sciences as they transform into more data-centric disciplines - the "Big New Biology". Three major challenges are: 1) lack of comprehensive standards; 2) lack of incentives for individual scientists to share data; 3) lack of appropriate infrastructure and support. Technological advances with standards, bandwidth, distributed computing, exemplar successes, and a strong presence in the emerging world of Linked Open Data are sufficient to conclude that technical issues will be overcome in the foreseeable future. While motivated to have a shared open infrastructure and data pool, and pressured by funding agencies in move in this direction, the sociological issues determine progress. Major sociological issues include our lack of understanding of the heterogeneous data cultures within Life Sciences, and the impediments to progress include a lack of incentives to build appropriate infrastructures into projects and institutions or to encourage scientists to make data openly available.     

The fine structure of the melanocytes of the adult mouse hair follicle during their amelanotic phase (telogen and early anagen)

Melanocyte-precursor cells have been described previously in telogen and early anagen hair germs by observation of Epon sections using light microscopy. The existence of these precursor cells has not been generally accepted due to lack of ultrastructural evidence. It is our purpose to describe these cells using transmission electron microscopy. We studied hair germs of the dorsal skin of adult mice in the appropriate stages of the hair cycle prior to melanogenesis. Telogen melanocytes are distinguishable from adjacent keratocytes by their lack of desmosomes, lack of coarse clumps of microfilaments, sparsity of ribosomes, unusually few nuclear pores and presence of dendrites. Melanocytes in early anagen show extensive growth with abundant polysomes, elaborate RER and Golgi zones. They still differ from keratocytes in their lack of desmosomes and clumps of microfilament, and also in the occasional presence of premelanosomes.     

Hypothalamic paraventricular nucleus, but not vasopressin, participates in chronic hyperactivity of the HPA axis in diabetic rats

Diabetes mellitus (DM), as chronic stress activates the hypothalamo-pituitary-adrenocortical axis. We examined whether arginine vasopressin (AVP) and the hypothalamic paraventricular nucleus (PVN) participate in DM-induced chronic stress symptoms. AVP-deficient Brattleboro or PVN-lesioned Wistar rats were used with heterozygous or sham-operated controls. The rats were studied 2 wk after a single injection of streptozotocin. The appearance of DM (enhanced water consumption and blood glucose elevation) and the chronic stress-like somatic changes (body weight decrease, thymus involution, adrenal gland hypertrophy) were not influenced by the lack of AVP. By contrast, PVN lesion significantly attenuated DM-induced thymus involution and adrenal gland hypertrophy as well as the increase in water consumption. The corticotropin-releasing hormone mRNA in PVN was diminished by DM and elevated by the lack of AVP without interaction. DM elevated the proopiomelanocortin (POMC) mRNA in the anterior lobe of the pituitary. The lack of AVP had no effect, whereas lesioning the PVN significantly diminished the elevation. The elevated basal corticosterone plasma levels detectable in DM were influenced neither by the lack of AVP nor by lesioning the PVN. Thus the lack of AVP had no influence on DM-induced chronic stress symptoms, but lesioning the PVN attenuated part of them. However, the lack of elevation in POMC mRNA after PVN lesion, together with the maintained corticosterone elevation, suggests that direct adrenal gland activation occurs in untreated DM.     

Double antisense plants lacking ascorbate peroxidase and catalase are less sensitive to oxidative stress than single antisense plants lacking ascorbate peroxidase or catalase

The plant genome is a highly redundant and dynamic genome. Here, we show that double antisense plants lacking the two major hydrogen peroxide-detoxifying enzymes, ascorbate peroxidase (APX) and catalase (CAT), activate an alternative/redundant defense mechanism that compensates for the lack of APX and CAT. A similar mechanism was not activated in single antisense plants that lacked APX or CAT, paradoxically rendering these plants more sensitive to oxidative stress compared to double antisense plants. The reduced susceptibility of double antisense plants to oxidative stress correlated with suppressed photosynthetic activity, the induction of metabolic genes belonging to the pentose phosphate pathway, the induction of monodehydroascorbate reductase, and the induction of IMMUTANS, a chloroplastic homologue of mitochondrial alternative oxidase. Our results suggest that a co-ordinated induction of metabolic and defense genes, coupled with the suppression of photosynthetic activity, can compensate for the lack of APX and CAT. In addition, our findings demonstrate that the plant genome has a high degree of plasticity and will respond differently to different stressful conditions, namely, lack of APX, lack of CAT, or lack of both APX and CAT.     

Increased visual after-effects in migraine following pattern adaptation extend to simultaneous tilt illusion

Much previous research into visual processing in migraine supports a model of abnormal cortical processing, in between the headache attacks, that is characterised by hyperexcitability, heightened responsiveness, a lack of habituation and/or a lack of intra-cortical inhibition. Shepherd (2001) reported two adaptation studies that challenged this view, one using the tilt after-effect, the second using the motion after-effect. Models of cortical function in migraine based on hyperexcitability and a lack of inhibition lead to specific predictions in an adaptation study: there should have been smaller after-effects in people with migraine than in people without. Both experiments, however, revealed larger after-effects in the migraine group than in the control group. Here, these results are extended to the simultaneous tilt illusion and an identical pattern of results was obtained: there were consistently larger effects in the migraine group than in the control group. The results from the three experiments are not consistent with a lack of inhibition in migraine. The results are discussed in terms of alternative models of cortical function, including a lack of excitation and reduced central energy reserves.     

Poverty and Health Ethics in Developing Countries

Developing countries face difficulties of exploitation, dehumanisation and lack of ethical professionalism, to an extent that developed countries do not encounter. Poverty-related difficulties include lack of infrastructure, unreasonable dominance of defence-related expenses in the budget, lack of a sufficient number of health care providers, absence of accountability for serious medical malpractice, as well as exploitation of patients in pharmaceutical trials. This country report presents the case of Bangladesh, one of the poorest countries in the world and therefore a good example for the deplorable condition of the health sector in developing countries.     

Pulmonary aspergilloma. Case reports from Malaysia

Pulmonary aspergilloma is by no means uncommon in Malaysia. The lack of documentation of its occurrence in Malaysia, is mainly due to the lack of clinical awareness, and the absence of facilities for the proper diagnosis of the infection.     

Synthesis and antitumor activity of a series of 1,2-diaminocyclohexanepalladium(II) dicarboxylate complexes

A series of complexes of the type [Pd(O O(DACH)] (O O = dicarboxylate ligand, DACH = 1,2-diaminocyclohexane) has been prepared. These complexes have been characterized by elemental analysis and infrared spectroscopy. The complexes have been screened in vivo for antitumor activity against the L1210 leukemia cell line. These palladium complexes lack antitumor activity, which may be due to (1) lack of solubility and/or (2) lack of stability of the complexes in solution.     

Phosphatidylcholine and choline homeostasis

Phosphatidylcholine (PC) is made in mammalian cells from choline via the CDP-choline pathway. Animals obtain choline primarily from the diet or from the conversion of phosphatidylethanolamine (PE) to PC followed by catabolism to choline. The main fate of choline is the synthesis of PC. In addition, choline is oxidized to betaine in kidney and liver and converted to acetylcholine in the nervous system. Mice that lack choline kinase (CK) alpha die during embryogenesis, whereas mice that lack CKbeta unexpectedly develop muscular dystrophy. Mice that lack CTP:phosphocholine cytidylyltransferase (CT) alpha also die during early embryogenesis, whereas mice that lack CTbeta exhibit gonadal dysfunction. The cytidylyltransferase beta isoform also plays a role in the branching of axons of neurons. An alternative PC biosynthetic pathway in the liver uses phosphatidylethanolamine N-methyltransferase to catalyze the formation of PC from PE. Mice that lack the methyltransferase survive but die from steatohepatitis and liver failure when placed on a choline-deficient diet. Hence, choline is an essential nutrient. PC biosynthesis is required for normal very low density lipoprotein secretion from hepatocytes. Recent studies indicate that choline is recycled in the liver and redistributed from kidney, lung, and intestine to liver and brain when choline supply is attenuated.     

Critical phases of the brain development

Various effects were shown to act alter the proceeding of histogenetic processes in the embryonic neural tissue. Studies in mice revealed that, depending on the embryogenesis stage when a lack of serotonin occurred, the lack of this monoamine entails either death of the embryo or a teratogenic effect, or underdevelopment of brain structures. In the rat model of a shorten hypoxia, a disorder of neural tissue histogenesis in early stages of development, was found, as well as a reduction of its sensitivity to lack of oxygen by the end of embryogenesis.     

Intracellular hyaluronan: a new frontier for inflammation?

A variety of obstacles have hindered the ultrastructural localization of hyaluronan (HA). These include a lack of adequate fixation techniques to prevent the loss of HA, the lack of highly sensitive and specific probes, and a lack of accessibility due to the masking of HA by HA-binding macromolecules such as proteoglycans and glycoproteins. Despite these problems, a number of studies, both biochemical and histochemical, have been published indicating that HA is not restricted to the extracellular milieu, but is also present intracellularly. This review focuses on the possible functions of intracellular HA, its potential relationships to extracellular HA structures, and implications for inflammatory processes.     

Atypical mannolipids characterize Thy-1-negative lymphoma mutants.

Essentially all eukaryotic cells, including murine lymphomas, express surface proteins, such as Thy-1, which are anchored by a phosphoinositol mannolipid. Putative mannolipid anchor precursors can be detected in these cells. Six distinct Thy-1-negative lymphoma mutants lack complete mannolipids, and three mutants synthesize atypical mannolipids. The absence of complete mannolipids can account for the lack of expression of multiple mannolipid-anchored proteins and may also account for the lack of lipid anchoring in the human disease paroxysmal nocturnal hemoglobinuria. Structural information on the mannolipids of wild-type and mutant cells indicates that anchor biosynthesis in these cells may involve both transmembrane flip-flop of intermediates and a deacylation step.     

Immunochemical studies on lactate dehydrogenase A subunit deficiencies.

In lactate dehydrogenase (LDH) A subunit deficiency, is there not only a lack of activity but also a lack of subunit production? We demonstrated three remarkable points to answer this question: There are no proteins that immunologically react with anti-A subunits. There are no heterotetramers that react with anti-B subunits. B subunits seem to be genetically produced at normal level, and all of them form only one isoenzyme, LDH-B4. From these points, we concluded that there is a complete lack of A subunit production or production of incomplete A subunits that can neither react with anti-A subunits nor form heterotetramers.     

Cell-mediated immunity to Eimeria in the fowl: the absence of cross-species protection is not due to the lack of cross-reactive T cells.

Immunity to Eimeria species in the fowl has been shown to be species specific and it has been proposed that the lack of cross-protection between the species of Eimeria is due to the absence of T cells which recognize antigens from a heterologous species. When this hypothesis was tested the results showed that antigens from E. tenella elicited a strong specific response by cells from birds immune to E. tenella. In contrast cells from birds which were immune to E. acervulina responded to a similar magnitude to both E. tenella and E. acervulina antigens. This indicates that the lack of cross-protection is not due to the lack of cross-reactive T cells.     

Patternhunter II: highly sensitive and fast homology search

Extending the single optimized spaced seed of PatternHunter(20) to multiple ones, PatternHunter II simultaneously remedies the lack of sensitivity of Blastn and the lack of speed of Smith-Waterman, for homology search. At Blastn speed, PatternHunter II approaches Smith-Waterman sensitivity, bringing homology search methodology research back to a full circle.     

Methylation-independent and methylation-dependent chemotaxis in Rhodobacter sphaeroides and Rhodospirillum rubrum.

In vivo and in vitro methylation, methanol production assays, and the use of specific antibodies raised against the sensory transducing protein Tar in Escherichia coli all failed to demonstrate the presence of methyl-accepting chemotaxis proteins (MCPs) in the photosynthetic bacterium Rhodobacter sphaeroides, although such proteins did exist in another photosynthetic bacterium, Rhodospirillum rubrum. The range of chemicals to which Rhodobacter sphaeroides responds, the lack of an all-or-none response, and the lack of true repellents indicate an alternative chemosensory pathway. The existence of MCPs in Rhodospirillum rubrum means that the lack of MCPs is not the result of a phototrophic metabolism, but may be connected to the unidirectional flagellar motor of Rhodobacter sphaeroides.     

Goats for the poor: Some keys to successful promotion of goat production among the poor

This article describes Heifer International's experience promoting goats for the poor. Heifer International provides livestock to the poor in 55 countries using a value-based participatory approach. Drawing from recent case studies conducted in China, Peru, Romania and Tanzania, the benefits to the poor and major constraints are outlined. Constraints to livestock raising include the lack of good breeding stock, lack of veterinary and extension services, lack of credit and access to markets. Focusing more assistance on women farmers would improve impact on the poor. Value-based holistic community development with self-help groups creates a foundation for increasing farmer incomes by providing a forum for education, mutual support and developing markets.     

Fissuroderes, a new genus of Kinorhyncha (Cyclorhagida) from the deep sea and continental shelf of New Zealand and from the continental shelf of Costa Rica

Specimens of Kinorhyncha collected by RV Sonne from the continental shelf off the coast of Costa Rica and from the deep sea East of New Zealand as well as by RV Kaharoa in the Firth of Thames are identified as five new species of a new genus Fissuroderes gen. nov. which is distinguished from all other kinorhynch genera by a ring-like cuticle in the first trunk segment and a cuticle with midventral and lateral articulations resulting in two sternal plates and one tergal plate in segments 2-10. Fissuroderes higginsi sp. nov. can be distinguished from all other species of Fissuroderes by a laterodorsal spine in segment 2 and the lack of a lateroventral spine in segment 8. Fissuroderes rangi sp. nov. is recognized from all other species by the lack of a ventrolateral spine in segment 2, the lack of a lateroventral spine in segment 5, an extremely elongate spinose tergal extension of segment 11 and a prominent midventral spinose process of the sternal plates in segment 11. Fissuroderes papai sp. nov. is identified by the short spinose process of the sternal plate of segment 11. Only Fissuroderes thermoi sp. nov. possesses bilobed sternal plates in segment 11 and a short conical tergal extension. Fissuroderes novaezealandia sp. nov. differs from F. higginsi sp. nov. in the lack of a laterodorsal spine in segment 2, the lack of an accessory spine in a lateral position in segment 8, the lack of a sublateral spine in segment 10, the existence of a lateroventral spine in segment 8 and in the lack of a subdorsal type 2-gland cell outlet in segment 2. The former species differs from F. papai sp. nov. in the lack of a lateroventral spine in segment 8, the lack of longitudinal indentations in the posterior part of the trunk cuticle of each segment and in the existence of an elongate spinose tergal extension of segment 11 and of many fine hairs on the surface of the cuticle. Fissuroderes is included into the Echinoderidae which is suggested to enclose also the genera Echinoderes and Cephalorhyncha. Echinoderes nybakkeni Higgins, 1988 is now combined as Cephalorhyncha nybakkeni (Higgins, 1988) comb. nov.     

Role of the Nfo (YqfS) and ExoA apurinic/apyrimidinic endonucleases in protecting Bacillus subtilis spores from DNA damage

The Bacillus subtilis enzymes ExoA and Nfo (originally termed YqfS) are endonucleases that can repair apurinic/apyrimidinic (AP) sites and strand breaks in DNA. We have analyzed how the lack of ExoA and Nfo affects the resistance of growing cells and dormant spores of B. subtilis to a variety of treatments, some of which generate AP sites and DNA strand breaks. The lack of ExoA and Nfo sensitized spores (termed alpha-beta-) lacking the majority of their DNA-protective alpha/beta-type small, acid-soluble spore proteins (SASP) to wet heat. However, the lack of these enzymes had no effect on the wet-heat resistance of spores that retained alpha/beta-type SASP. The lack of either ExoA or Nfo sensitized wild-type spores to dry heat, but loss of both proteins was necessary to sensitize alpha-beta- spores to dry heat. The lack of ExoA and Nfo also sensitized alpha-beta-, but not wild-type, spores to desiccation. In contrast, loss of ExoA and Nfo did not sensitize growing cells or wild-type or alpha-beta- spores to hydrogen peroxide or t-butylhydroperoxide. Loss of ExoA and Nfo also did not increase the spontaneous mutation frequency of growing cells. exoA expression took place not only in growing cells, but also in the forespore compartment of the sporulating cell. These results, together with those from previous work, suggest that ExoA and Nfo are additional factors that protect B. subtilis spores from DNA damage accumulated during spore dormancy.     

Life without centrioles: cilia in the spotlight

Centrioles are critical cellular components that form the architectural core of both centrosomes and basal bodies, the nucleating structures of cilia. New work, including a study in this issue (), highlights the unexpected finding that lack of centrioles does not impede development in the fruit fly. Rather, flies reach maturity but then die because their sensory neurons lack cilia.