Elemental distribution in cephalopod statoliths: NanoSIMS provides new insights into nano-scale structure

We have applied the novel analytical method NanoSIMS to cephalopod statoliths for the first time in order to analyse their chemical microstructure, using a spatial resolution of 400 nm. This technique makes it possible to analyse in situ nano-scale chemical variations between increment layers. In statoliths of the boreoatlantic armhook squid Gonatus fabricii, we found distinct concentration patterns indicating a periodicity in strontium and sodium distributions. Sr and Na show a negative relation, both elements showing alternating patterns where the increments vary in width between approximately 1 and 5 μm. Results suggest, that aragonite deposited during the night is rich in Na and poor in Sr, while aragonite deposited during the day is rich in Sr and poor in Na. This study demonstrates the excellent suitability of NanoSIMS for nano-scale microchemical analyses of aragonite, providing new information on calcification processes and individual life histories. Possible future fields of application include not only cephalopod statoliths, but also virtually all biomineralized tissues in aquatic organisms like fish otoliths, gastropod statoliths, bivalve shells, foraminifers and corals.     

Macromolecular composition of Palaeozoic scolecodonts: insights into the molecular taphonomy of zoomorphs

Dutta, S., Hartkopf‐Fröder, C., Mann, U., Wilkes, H., Brocke, R. & Bertram, N. 2010: Macromolecular composition of Palaeozoic scolecodonts: insights into the molecular taphonomy of zoomorphs. Lethaia, Vol. 43, pp. 334–343. Biogeochemistry and molecular taphonomy of biopolymers of marine zoomorphs are poorly known. In order to obtain insights into this issue we report on the biogeomacromolecular composition of hand‐picked, well‐preserved scolecodonts of Ordovician, Silurian and Devonian age using micro‐Fourier transform infrared (micro‐FTIR) spectroscopy, Curie point pyrolysis‐gas chromatography‐mass spectrometry (Cupy‐GC‐MS) and tetramethylammonium hydroxide (TMAH)‐assisted thermochemolysis‐GC‐MS. The present study reveals that scolecodonts are composed of both aliphatic and aromatic moieties. The micro‐FTIR spectra of scolecodonts are characterized by aliphatic CH_x (3000–2800 and 1460–1450/cm) and CH₃ (1375/cm) absorptions and aromatic C=C (1560–1610/cm) and CH (3050/cm and 700–900/cm) absorptions. The major pyrolysis products from the scolecodonts include aromatic hydrocarbons such as alkylbenzenes, alkylnaphthalenes and alkylphenols. Aliphatic hydrocarbons are represented by a homologous series of n‐alkenes and n‐alkanes. The compounds released upon thermochemolysis with TMAH are saturated and unsaturated fatty acids (as their methyl esters), n‐alkenes/alkanes and aromatic acids (as their methyl esters). No protein/amino acid‐derived compounds have been recognized in the pyrolysates or in the thermochemolysates, and it is concluded that protein/amino acid‐related compounds, which are commonly found in the jaws of extant polychaetes, were destroyed due to diagenetic processes. Obviously, excellent morphological preservation and low thermal alteration are not paralleled by a similar degree of chemical preservation. □Biogeomacromolecules, micro‐FTIR, pyrolysis‐GC‐MS, scolecodonts, thermochemolysis‐GC‐MS.     

GnRH deficiency: new insights from genetics

The acquisition of a sexually dimorphic phenotype is a critical event in mammalian development. Hypogonadotropic hypogonadism (HH) results from impaired secretion of GnRH. The patients display with delayed puberty, micropenis and cryptorchidism in the male reflecting gonadotropin insufficiency, and amenorrhea in the female. Kallmann's syndrome (KS) is defined by the association of HH and anosmia or hyposmia (absent smelling sense). Segregation analysis in familial cases has demonstrated diverse inheritance patterns, suggesting the existence of several genes regulating GnRH secretion. The X-linked form of the disease was associated with a genetic defect in the KALI gene located on the Xp22.3 region. KAL1 gene encodes an extracellular matrix glycoprotein anosmin-1, which facilitates neuronal growth and migration. Abnormalities in the migratory processes of the GnRH neurons with the olfactory neurons explain the association of HH with anosmia. Recently, mutations in the FGF recepteur 1 (FGFR1) gene were found in KS with autosomal dominant mode of inheritance. The role of FGFR1 in the function of reproduction requires further investigation. Besides HH with anosmia, there are isolated HH (IHH). No human GnRH mutations have been reported although hypogonadal mice due to a GnRH gene deletion exist. In patients with idiopathic HH and without anosmia an increasing number of GnRH receptor (GnRHR) mutations have been described which represent about 50% of familial cases. The clinical features are highly variable and there is a good relationship between genotype and phenotype. A complete loss of function is associated with the most severe phenotype with resistance to pulsatile GnRH treatment, absence of puberty and cryptorchidism in the male. In contrast, milder loss of function mutations causes incomplete failure of pubertal development. The preponderant role of GnRH in the secretion of LH by the gonadotrophs explains the difference of the phenotype between male and female with partial GnRH resistance. Affected females can have spontaneous telarche and normal breast development while affected males exhibit no pubertal development but normal testis volume, a feature described as "fertile-eunuch". High-dose pulsatile GnRH has been used to induce ovulation. Another gene, called GPR54, responsible for idiopathic HH has been recently described by segregation analysis in two different consanguineous families. The GPR54 gene is an orphan receptor, and its putative ligand is the product of the KISS-1 gene, called metastine. Their roles in the function of reproduction are still unknown.     

Morphogen gradients: new insights from DPP.

The Drosophila TGFbeta family member Decapentaplegic (DPP) has been proposed to function as a morphogen to pattern cell fields in a number of developmental contexts. A series of recent reports add significantly to our knowledge of the mechanisms of DPP-gradient formation and interpretation. These reports identity additional genes and genetic circuitry necessary for this patterning system, and they highlight variations that might reflect developmental constraints within individual target cell fields.     

Mitochondrial complex I: new insights from inhibitor assays

Summary The NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial respiratory chain is by far the most complicated of the proton-translocating enzymes involved in the oxidative phosphorylation. Many clues regarding both electron transfer and proton translocation are still unknown. In this sense, inhibitor assays are relevant and useful pieces for elaborating a suitable model to explain the elusive bioenergetic mechanism of this enzyme. This short review presents the most recent advances in inhibitor studies and highlights the major controversies.Abbreviations ACG annonaceous acetogenin - MPP⁺ methylphenyl-pyridinium     

Hepatic lipase: new insights from genetic and metabolic studies.

Hepatic lipase catalyses the hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins. Genetic deficiency of this enzyme is associated with a unique plasma lipoprotein profile, characterized by hypertriglyceridemia and elevated concentrations of intermediate density lipoproteins and HDL. Recent studies have identified common polymorphisms in the hepatic lipase gene that are associated with low hepatic lipase activity and increased concentrations of large HDL. Association studies using these polymorphisms are elucidating the effects of variation in hepatic lipase activity on plasma lipoprotein concentrations and susceptibility to coronary atherosclerosis.     

Targeted therapies and autophagy: new insights from chronic myeloid leukemia

Patients who develop chronic myeloid leukemia (CML) are currently treated with tyrosine kinase inhibitors (TKIs), which inhibit the function of the oncogene BCR/Abl. Most CML cells undergo apoptosis when BCR/Abl tyrosine kinase activity is suppressed by TKIs. Cells surviving drug treatment are either stem cells (CML in early phase) or cells with BCR/Abl-dependent or -independent mechanisms of drug resistance (CML in advanced phase). Since survival of these cells is thought to be responsible for disease recurrence, it is critical to find ways to fully eradicate CML stem cells. We have recently shown that when CML cells, including stem cells, are exposed to TKI they activate an autophagic program, which relies on intracellular calcium and is not inhibited by Bcl-2. Pharmacological or RNAi-mediated inhibition of autophagy potentiates the effect of TKI in inducing death of CML cells, including the stem cells. These data strongly suggest that inhibition of autophagy may improve the therapeutic effects of TKIs in the treatment of CML. In addition, they give credence to the idea that in cancer cells autophagy is part of a stereotypic response to stress and specifically to abrogation of their main oncogenic signal(s).     

Mitochondrial uncoupling proteins: new insights from functional and proteomic studies

Mitochondria are the major sites of ATP synthesis through oxidative phosphorylation, a process that is weakened by proton leak. Uncoupling proteins are mitochondrial membrane proteins specialized in inducible proton conductance. They dissipate the proton electrochemical gradient established by the respiratory chain at the expense of reducing substrates. Several physiological roles have been suggested for uncoupling proteins, including roles in the control of the cellular energy balance and in preventive action against oxidative stress. This review focuses on new leads emerging from comparative proteomics about the involvement of uncoupling protein in the mitochondrial physiology. A brief overview on uncoupling proteins and on proteomics applied to mitochondria is also presented herein.     

The high fidelity of the cetacean stranding record: insights into measuring diversity by integrating taphonomy and macroecology

Stranded cetaceans have long intrigued naturalists because their causation has escaped singular explanations. Regardless of cause, strandings also represent a sample of the living community, although their fidelity has rarely been quantified. Using commensurate stranding and sighting records compiled from archived datasets representing nearly every major ocean basin, I demonstrated that the cetacean stranding record faithfully reflects patterns of richness and relative abundance in living communities, especially for coastlines greater than 2000 km and latitudinal gradients greater than 4°. Live-dead fidelity metrics from seven different countries indicated that strandings were almost always richer than live surveys; richness also increased with coastline length. Most death assemblages recorded the same ranked relative abundance as living communities, although this correlation decreased in strength and significance at coastline lengths greater than 15,000 km, highlighting the importance of sampling diversity at regional scales. Rarefaction analyses indicated that sampling greater than 10 years generally enhanced the completeness of death assemblages, although protracted temporal sampling did not substitute for sampling over longer coastlines or broader latitudes. Overall, this global live-dead comparison demonstrated that strandings almost always provided better diversity information about extant cetacean communities than live surveys; such archives are therefore relevant for macroecological and palaeobiological studies of cetacean community change through time.     

Holoprosencephaly: new models, new insights

Holoprosencephaly (HPE) is a common congenital malformation that is characterised by a failure to divide the forebrain into left and right hemispheres and is usually accompanied by defects in patterning of the midline of the face. HPE exists in inherited, autosomal dominant (familial) forms and mutation-associated sporadic forms, but environmental factors are also implicated. There are several features of HPE that are not well understood, including the extremely variable clinical presentation, even among obligate carriers of familial mutations, and the restriction of structural anomalies to the ventral anterior midline, despite association with defects in signal transduction pathways that regulate development of many additional body structures. The new animal models described in this review may help unravel these puzzles. Furthermore, these model systems suggest that human HPE arises from a complex interaction between the timing and strength of developmental signalling pathways, genetic variation and exposure to environmental agents.     

Virus-host interactions: new insights from the small RNA world

RNA silencing has a known role in the antiviral responses of plants and insects. Recent evidence, including the finding that the Tat protein of human immunodeficiency virus (HIV) can suppress the host's RNA-silencing pathway and may thus counteract host antiviral RNAs, suggests that RNA-silencing pathways could also have key roles in mammalian virus-host interactions.     

Mitochondrial tyrosine phosphoproteome: new insights from an up-to-date analysis

Tyrosine phosphorylation is a newcomer in the mitochondrial signaling and is currently emerging as an important mechanism for regulating mitochondrial processes. But to what extent? By analyzing an updated draft of the mitochondrial tyrosine phosphoproteome, the following observations can be drawn: more than a hundred mitochondrial proteins undergo tyrosine phosphorylation, phosphotyrosine proteins are distributed in each of the submitochondrial compartments, and mitochondrial tyrosine phosphorylated proteins are involved in a variety of functions as metabolism (electron transport chain, Krebs cycle, fatty acid and amino acid metabolism), solute and protein transport, mitochondrial translation machinery, quality protein assessment, oxidative stress, apoptosis, fission, and other. This large and varied collection suggests that tyrosine phosphorylation could be a widespread mechanism in modulating mitochondrial functions. Moreover the in silico model is here used to explore potential effects of tyrosine phosphorylation on selected mitochondrial proteins pointing out some future perspectives in this field.     

Succinate: quinone oxidoreductases: new insights from X-ray crystal structures

Membrane-bound succinate dehydrogenases (succinate:quinone reductases, SQR) and fumarate reductases (quinol:fumarate reductases, QFR) couple the oxidation of succinate to fumarate to the reduction of quinone to quinol and also catalyse the reverse reaction. SQR (respiratory complex II) is involved in aerobic metabolism as part of the citric acid cycle and of the aerobic respiratory chain. QFR is involved in anaerobic respiration with fumarate as the terminal electron acceptor, and is part of an electron transport chain catalysing the oxidation of various donor substrates by fumarate. QFR and SQR complexes are collectively referred to as succinate:quinone oxidoreductases (EC 1.3.5.1), have very similar compositions and are predicted to share similar structures. The complexes consist of two hydrophilic and one or two hydrophobic, membrane-integrated subunits. The larger hydrophilic subunit A carries covalently bound flavin adenine dinucleotide and subunit B contains three iron-sulphur centres. QFR of Wolinella succinogenes and SQR of Bacillus subtilis contain only one hydrophobic subunit (C) with two haem b groups. In contrast, SQR and QFR of Escherichia coli contain two hydrophobic subunits (C and D) which bind either one (SQR) or no haem b group (QFR). The structure of W. succinogenes QFR has been determined at 2.2 A resolution by X-ray crystallography (C.R.D. Lancaster, A. Kr?ger, M. Auer, H. Michel, Nature 402 (1999) 377-385). Based on this structure of the three protein subunits and the arrangement of the six prosthetic groups, a pathway of electron transfer from the quinol-oxidising dihaem cytochrome b to the site of fumarate reduction and a mechanism of fumarate reduction was proposed. The W. succinogenes QFR structure is different from that of the haem-less QFR of E. coli, described at 3.3 A resolution (T.M. Iverson, C. Luna-Chavez, G. Cecchini, D.C. Rees, Science 284 (1999) 1961-1966), mainly with respect to the structure of the membrane-embedded subunits and the relative orientations of soluble and membrane-embedded subunits. Also, similarities and differences between QFR transmembrane helix IV and transmembrane helix F of bacteriorhodopsin and their implications are discussed.