Evidence of a distinct lipid fraction in historical parchments: a potential role in degradation?

Parchment, a biologically based material obtained from the processed hides of animals such as cattle and sheep, has been used for millennia as a writing medium. Although numerous studies have concentrated on the structure and degradation of collagen within parchment, little attention has been paid to noncollagenous components, such as lipids. In this study, we present the results of biochemical and structural analyses of historical and newly manufactured parchment to examine the potential role that lipid plays in parchment stability. The lipid fraction extracted from the parchments displayed different fatty acid compositions between historical and reference materials. Gas chromatography, small-angle X-ray scattering, and solid-state NMR were used to identify and investigate the lipid fraction from parchment samples and to study its contribution to collagen structure and degradation. We hypothesize that the origin of this lipid fraction is either intrinsic, attributable to incomplete fat removal in the manufacturing process, or extrinsic, attributable to microbiological attack on the proteinaceous component of parchments. Furthermore, we consider that the possible formation of protein-lipid complexes in parchment over the course of oxidative degradation may be mediated by reactive oxygen species formed by lipid peroxidation.     

Recombinant antibodies: towards a new generation of antivenoms?

Poisoning by scorpion venoms is a major health hazard in tropical and subtropical regions and serum therapy, which was discovered in 1894, remains the only specific treatment. No real progress has been made since this time and the therapeutic use of antivenoms which still consists in polyclonal antibody fragments from the sera of immunized animals may be associated with major drawbacks. Protein engineering now allows to design novel recombinant antibody fragments which are superior to polyclonal antivenoms in homogeneity, specific activity and possibly safety. Several single-chain antibody fragments (scFvs) which neutralize scorpion toxins have been produced and characterized over the last few years. These scFvs can also be used as building blocks to engineer more complex structures including multivalent monospecific antibody fragments (diabodies, triabodies) and bispecific molecules (tandem-scFv). Some of these molecules neutralize scorpion neurotoxins and protect mice from experimental envenoming. Thus, research projects currently underway suggest that new strategies might soon be available to treat poisonings in the absence of socio-economic considerations.     

A new look at computation of the complexity index in mangroves: do disturbed forests have clues to analyze canopy height patchiness?

This paper proposes some guidelines to compute complexity index in those mangroves where either seasonal or strong disturbances have occurred. We surveyed 31 mangrove localities in Buenaventura Bay, Central Pacific Coast of Colombia, where structural parameters were measured within a 0.1 ha plot. Also, most likely disturbances were noted for each plot. Complexity index was calculated in its classical form using the arithmetic mean of the three tallest trees(maximal mean) and alternatively using: a) the total mean: the height average of all trees recorded in each plot; and b) the mode: the most frequent tree height class (10 cm intervals) within each plot. Afterwards, we compared the three computations and discussed there liability of each one according to the current state by plot. In addition, all structural parameters were sorted in two diameter at breast height (dbh) cohorts (2.5–10 cm and ≥ 10 cm) to figure out which contributes more to the forest structure. We conclude the following: (a) The mean of the three tallest trees is not a good estimator of forest development when seasonal or strong disturbances occur since complexity index based in it always overestimates forest structure. (b) Seasonal disturbances and recruitment produce mosaic forests. The best estimator of this condition is the mean height which encompasses both central tendency and variability. (c) The modal height is also helpful to establish the dominant cohort when forests show two or more storied-canopies, or intermediate cohorts are missing. It also applies when a new stock of recruits is entering in a mature forest (the modal or maximal heights can be used interchangeably in this case). (d) Maximal height is the best estimator for uniformly developed forests with closed canopies and/or a single dominant tall-cohort. (e) If one is not confident about which height type to include to compute the complexity index, we recommend to sort out structure data by dbh-cohorts and calculate indices for both of them. This will show which cohort is contributing most to forest complexity. Finally, we suggest to exclude non-mangrove species from the complexity index computation since they mostly do not contribute significantly to forest basal area. This revised version was published online in July 2006 with corrections to the Cover Date.     

GPCRs heterodimerization: a new way towards the discovery of function for the orphan receptors?

G protein-coupled receptors (GPCRs), also called seven transmembrane domain (7TM) proteins, represent the largest family of cell surface receptors. GPCRs control a variety of physiological processes, are involved in multiple diseases and are major drug targets. Despite a vast effort of academic and industrial research, more than one hundred receptors remain orphans. These orphan GPCRs offer a great potential for drug discovery, as almost 60% of currently prescribed drugs target GPCRs. Deorphenization strategies have concentrated mainly on the identification of the natural ligands of these proteins. Recent advances have shown that orphan GPCRs, similar to orphan nuclear receptors, can regulate the function of non-orphan receptors by heterodimerization. These findings not only help to better understand the extraordinary diversity of GPCRs, but also open new perspectives for the identification of the function of these orphan receptors that hold great therapeutic potential.     

A new histone at the centromere?

The centromere is a classic system to study epigenetic specification, and most research has focused on a specialized histone variant, CENP-A, that is required for kinetochore assembly. Now Nishino et?al. reveal a new level of complexity for centromeric chromatin, by showing that the kinetochore complex CENP-T-W-S-X shares structural and functional properties with canonical histones.     

The “discovery” of lipid droplets: A brief history of organelles hidden in plain sight

Mammalian lipid droplets (LDs), first described as early as the 1880s, were virtually ignored for more than 100 years. Between 1991 and the early 2000s, however, a series of discoveries and conceptual breakthroughs led to a resurgent interest in obesity as a disease, in the metabolism of intracellular triacylglycerol (TAG), and in the physical locations of LDs as cellular structures with their associated proteins. Insights included the recognition that obesity underlies major chronic diseases, that appetite is hormonally controlled, that hepatic steatosis is not a benign finding, and that diabetes might fundamentally be a disorder of lipid metabolism. In this brief review, I describe the metamorphosis of LDs from overlooked globs of stored fat to dynamic organelles that control insulin resistance, mitochondrial oxidation, and viral replication.     

A prospective look at substance use and criminal behavior in urban ADHD youth: what is the role of maltreatment history on outcome?

Children with attention-deficit/hyperactivity disorder (ADHD) are at heightened risk of antisocial behavior during adolescence/early adulthood. Here, we characterize the antisocial outcomes of a sample of urban, lower-socioeconomic-status, ethnically diverse ADHD youth and investigate the impact of maltreatment history on criminal and substance use disorder (SUD) outcomes. Ninety-eight participants diagnosed with ADHD in childhood were re-assessed 10 years later and compared with controls. Regression analyses investigated the effect of maltreatment on antisocial outcomes among four groups based on ADHD and maltreatment status. ADHD subjects and controls did not differ in rates of arrest, conviction, incarceration, or recidivism. ADHD youth were younger at their first arrest with higher rates of SUDs when compared to controls. Controls and ADHD subjects with maltreatment had significantly higher rates of SUDs compared to the no-ADHD/no-maltreatment group. Only ADHD youth with maltreatment had significantly higher rates of arrest than the reference group. In contrast to prior studies, ADHD youth did not differ from controls on most measures of antisocial behavior. Maltreatment increased the rate of arrest only among ADHD youth, though increased the rate of SUD for ADHD youth and controls. This suggests that ADHD youth, in the absence of maltreatment, are at no greater risk of SUDs or arrest than controls without maltreatment.     

Radwaste at sea: A new era of polarization or a new basis for consensus?

Abstract

A coalition of third world nations, led by the Pacific island countries and those European nations who have developed land‐based disposal programs for their radioactive wastes, seek to amend the London Convention on Dumping (the international treaty controlling ocean disposal of radioactive and other wastes) in order to ban ocean disposal of low‐level radioactive wastes. Pro‐dumping nations maintain that the treaty may only be amended based on science and that current scientific research indicates that low‐level waste represents neither a threat to the integrity of the marine environment nor human health. Anti‐dumping nations, on the other hand, argue that the same science, particularly the models used to predict the fate and the effects of these wastes, exhibits sufficient uncertainty to preclude judgments about the absence of harm from future disposal activities. These differing conclusions mirror differing assessments of risk. These assessments build on the differing social, political, and economic values placed on use of the ocean and on conflicting conceptions of the fundamental rights and obligations of nations whose use of the ocean may impinge on the resources of others. Each side's continued intransigence may result in unilateral ocean disposal activities with serious consequences for the London Convention on Dumping (LDC) and its control over other wastes transported to sea for disposal. Initiatives of anti‐dumping nations to expand the LDC's decision‐making framework to examine the social, economic, and political issues underlying each side's interpretation of scientific evidence offer hope to address the underlying non‐scientific issues and perhaps to strengthen decision‐making within the LDC.     

Does nitric oxide play a role in maternal tolerance towards the foetus?

In pregnancy there occurs maternal tolerance to the foetus. Several mechanisms have been proposed to explain this phenomenon. The main immune population in the decidua are macrophages and natural killer cells, but with some "special" suppressor characteristics. There is also a predominant TH2 response. The non classical MCH type I HLA-G is expressed by trophoblasts and can suppress lymphomononuclear cytotoxicity. Other system to avoid the immune system is the expression of indoleamine-2,3-dioxygenase, that suppresses T cell activation by degrading tryptophan. Even though in the placenta there is a high production of nitric oxide, a well-known immune modulator, low attention has been paid to its role in maternal tolerance. There are many data showing that NO affects the IDO, CD95/CD95-L and the balance between TH1/TH2. Maybe NO could interact with several mechanisms at the same time, which could modify the tolerogenic activity depending on the concentration and the presence of other factors in the medium.     

Technology mediator: a new role for the reference librarian?

The Arizona Health Sciences Library has collaborated with clinical faculty to develop a federated search engine that is useful for meeting real-time clinical information needs. This article proposes a technology mediation role for the reference librarian that was inspired by the project, and describes the collaborative model used for developing technology-mediated services for targeted users.     

Plant lipid bodies and cell-cell signaling: A new role for an old organelle?

Plant lipid droplets are found in seeds and in post-embryonic tissues. Lipid droplets in seeds have been intensively studied, but those in post-embryonic tissues are less well characterised. Although known by a variety of names, here we will refer to all of them as lipid bodies (LBs). LBs are unique spherical organelles which bud off from the endoplasmic reticulum, and are composed of a single phospholipid (PL) layer enclosing a core of triacylglycerides. The PL monolayer is coated with oleosin, a structural protein that stabilizes the LB, restricts its size, and prevents fusion with adjacent LBs. Oleosin is uniquely present at LBs and is regarded as a LB marker. Although initially viewed as simple stores for energy and carbon, the emerging view is that LBs also function in cytoplasmic signalling, with the minor LB proteins caleosin and steroleosin in a prominent role. Apart from seeds, a variety of vegetative and floral structures contain LBs. Recently, it was found that numerous LBs emerge in the shoot apex of perennial plants during seasonal growth arrest and bud formation. They appear to function in dormancy release by reconstituting cell-cell signalling paths in the apex. As apices and orthodox seeds proceed through comparable cycles of dormancy and dehydration, the question arises to what degree LBs in apices share functions with those in seeds. We here review what is known about LBs, particularly in seeds, and speculate about possible unique functions of LBs in post-embryonic tissues in general and in apices in particular.     

Glycosylation at the fetomaternal interface: does the glycocode play a critical role in implantation?

During pregnancy, the heavily glycosylated surfaces of the implanting blastocyst and maternal uterine epithelium interact in a highly controlled and specific manner. Examination of this interface in species that show interdigitation of embryonic and maternal surfaces (epitheliochorial placentation) shows that each has its own particular pattern of glycosylation or glycotype, and that closely related and/or interbreeding species e.g. horse and donkey or llama and guanaco, have very similar glycotypes. Implantation of interspecies hybrids is facilitated, when the blastocyst has an outer cell layer bearing glycans that are compatible with the maternal host. We refer to this mutual compatibility as a glycocode. The probability that hybrid embryo glycotypes differ from those normally associated with the host species may account for the high pregnancy failure rates seen in interspecies breeding. We suggest the maternal host selects between genotypically distinct embryos, and this selection depends partly on cell surface glycosylation. We infer that the glycocode plays a critical role in implantation, for if the survival of modified genotypes results in fitter offspring with altered placental glycosylation, selection pressure downstream may in turn act to drive adaptations in the maternal surface glycotype to produce a complementary glycocode, thus leading eventually to the creation of new species. We speculate that glycan microheterogeneity plays a specific role in this process.     

Therapeutic imprinting of the immune system: towards a remission of AIDS in primates?

This correspondence was written in response to the comments by Young et al. Following careful evaluation of the relevant dataset, each of the points brought up by Young et al. has been addressed in this response. We anticipate this will clarify our findings regarding ERV_mch8, an ecotropic endogenous retrovirus that was shown to have cerebellum-specific and age-dependent expression patterns in C57BL/6J mice.     

Role of autophagy in the clearance of mutant huntingtin: a step towards therapy?

Macroautophagy (henceforth referred to simply as autophagy) is a bulk degradation process involved in the clearance of long-lived proteins, protein complexes and organelles. A portion of the cytosol, with its contents to be degraded, is enclosed by double-membrane structures called autophagosomes/autophagic vacuoles, which ultimately fuse with lysosomes where their contents are degraded. In this review, we will describe how induction of autophagy is protective against toxic intracytosolic aggregate-prone proteins that cause a range of neurodegenerative diseases. Autophagy is a key clearance pathway involved in the removal of such proteins, including mutant huntingtin (that causes Huntington’s disease), mutant ataxin-3 (that causes spinocerebellar ataxia type 3), forms of tau that cause tauopathies, and forms of alpha-synuclein that cause familial Parkinson’s disease. Induction of autophagy enhances the clearance of both soluble and aggregated forms of such proteins, and protects against toxicity of a range of these mutations in cell and animal models. Interestingly, the aggregates formed by mutant huntingtin sequester and inactivate the mammalian target of rapamycin (mTOR), a key negative regulator of autophagy. This results in induction of autophagy in cells with these aggregates.