A bowhead whale in the eastern North Pacific

Bowhead whales occur in the Arctic year‐round. Their movements are largely correlated with seasonal expansions and reductions of sea ice, but a few recent extralimital sightings have occurred in the eastern and western North Atlantic and one was also documented in the western North Pacific over 50 years ago. Here we present details of a juvenile bowhead whale that was photographed and filmed from above and below the water while it was skim‐feeding in Caamaño Sound, BC, Canada on May 31, 2016. This sighting occurred over 2000 km southeast from the nearest known range for this species in the Bering Sea at a time that most bowhead whales in that region would have been migrating northeast. This sighting represents the first and only documentation of a bowhead whale in the eastern North Pacific to date.     

An investigation of residue-specific contributions to peptide desorption in MALDI-TOF mass spectrometry*

*Work supported by DGICYT (Grant PB94-0845) and by Generalitat de Catalunya (Centre de Referència de Biotecnologia.The MALDI-TOF mass spectra of a set of 240 analogs of the pentadecapeptide YTASARGDLAHLTTT, displaying single point replacements with all amino acids except Met, Cys and Trp, have been used to study the contribution of individual residues to peptide desorption. Replacements with non-polar aliphatic (except Ala) or aromatic residues at most positions tend to reinforce ion signals relative to the cognate sequence. Among polar residues, Arg shows also a clear tendency to enhance signal intensity at most positions. The responses recorded for replacements with a given amino acid can be averaged and normalized to give a mean response index, _m, which qualitatively expresses the relative contribution of that residue to the desorption of a generic peptide. HPLC analysis of the replacement set does not support a significant role of residue hydrophobicity in peptide desorption. The unique role of Arg in promoting peptide desorption may be related to a better stabilization of peptide-matrix adducts through guanidinium-carboxylate interaction.     

Reports on the free-living platyhelminthes from Australia: typhloplanoida, with the description of three new taxa

Five typhloplanoids from the Australian East Coast are reported, three of them new to science. Two taxa are members of Promesostomidae: Vauclusia conica n.g. n.sp., characterised by a cone-shaped stylet, the presence of a female bursa and a very long, partially-swollen female duct; Brinkmanniella australiensis n.sp. has a funnel-shaped stylet with a smooth distal tip. Pilamonila bimascula n.g. n.sp. is a representative of the Solenopharyngidae, characterised by a stylet within a cirrus. The known species found are Ceratopera axi and Ptychopera scutulifer.     

Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: a short review

Diabetes mellitus is one of the most common chronic diseases affecting millions of people worldwide. Cardiovascular complication including myocardial infarction is one of the major causes of death in diabetic patients. Diabetes mellitus induces abnormal pathological findings including cell hypertrophy, neuropathy, interstitial fibrosis, myocytolysis and apoptosis and lipid deposits in the heart. In addition, the cytoplasmic organelles of cardiomyocytes including the plasma membrane, mitochondrion and sarcoplasmic reticulum are also impaired in both type I and type II diabetes. Hyperglycaemia is a major aetiological factor in the development of diabetic cardiomyopathy in patients suffering from diabetes. Hyperglycaemia promotes the production of reactive oxygen (ROS) and nitrogen species (RNS). The release of ROS and RNS induces oxidative stress leading to abnormal gene expression, faulty signal transduction and apoptosis of cardiomyocytes. Hyperglycaemia also induces apoptosis by p53 and the activation of the cytochrome c-activated caspase-3 pathway. Stimulation of connective tissue growth factor and the formation of advanced glycation end products in extracellular matrix proteins induces collagen cross-linking and contribute to the fibrosis observed in the interstitium of the heart of diabetic subjects. In terms of signal transduction, defects in intracellular Ca2+ signalling due to alteration of expression and function of proteins that regulate intracellular Ca2+ also occur in diabetes. All of these abnormalities result in gross dysfunction of the heart. Beta-adrenoreceptor antagonists, ACE inhibitors, endothelin-receptor antagonist (Bonestan), adrenomedullin, hormones (insulin, IGF-1) and antioxidants (magniferin, metallothionein, vitamins C and E) reduce interstitial fibrosis and improve cardiac function in diabetic cardiomyopathy.     

Autocatalytic activation of acetyl-CoA synthase

Acetyl-CoA synthase (ACS ACS/CODH CODH/ACS) from Moorella thermoacetica catalyzes the synthesis of acetyl-CoA from CO, CoA, and a methyl group of a corrinoid-iron-sulfur protein (CoFeSP). A time lag prior to the onset of acetyl-CoA production, varying from 4 to 20 min, was observed in assay solutions lacking the low-potential electron-transfer agent methyl viologen (MV). No lag was observed when MV was included in the assay. The length of the lag depended on the concentrations of CO and ACS, with shorter lags found for higher [ACS] and sub-saturating [CO]. Lag length also depended on CoFeSP. Rate profiles of acetyl-CoA synthesis, including the lag phase, were numerically simulated assuming an autocatalytic mechanism. A similar reaction profile was monitored by UV-vis spectrophotometry, allowing the redox status of the CoFeSP to be evaluated during this process. At early stages in the lag phase, Co²⁺FeSP reduced to Co⁺FeSP, and this was rapidly methylated to afford CH₃-Co³⁺FeSP. During steady-state synthesis of acetyl-CoA, CoFeSP was predominately in the CH₃-Co³⁺FeSP state. As the synthesis rate declined and eventually ceased, the Co⁺FeSP state predominated. Three activation reductive reactions may be involved, including reduction of the A- and C-clusters within ACS and the reduction of the cobamide of CoFeSP. The B-, C-, and D-clusters in the subunit appear to be electronically isolated from the A-cluster in the connected subunit, consistent with the ~70 Å distance separating these clusters, suggesting the need for an in vivo reductant that activates ACS and/or CoFeSP.Abbreviations ACS acetyl-CoA synthase, also known as CODH (carbon monoxide dehydrogenase) or CODH/ACS or ACS/CODH - CH₃-Co³⁺FeSP, Co²⁺FeSP, and Co⁺FeSP corrinoid-iron-sulfur protein with the cobalamin in the methylated 3+, unmethylated 2+, and unmethylated 1+ states - CoA coenzyme A - DTT dithiothreitol - H-THF or THF tetrahydrofolic acid or tetrahydrofolate - MT methyl transferase - MV methyl viologen     

Resource pulses,species interactions,and diversity maintenance in arid and semi-arid environments

Arid environments are characterized by limited and variable rainfall that supplies resources in pulses. Resource pulsing is a special form of environmental variation, and the general theory of coexistence in variable environments suggests specific mechanisms by which rainfall variability might contribute to the maintenance of high species diversity in arid ecosystems. In this review, we discuss physiological, morphological, and life-history traits that facilitate plant survival and growth in strongly water-limited variable environments, outlining how species differences in these traits may promote diversity. Our analysis emphasizes that the variability of pulsed environments does not reduce the importance of species interactions in structuring communities, but instead provides axes of ecological differentiation between species that facilitate their coexistence. Pulses of rainfall also influence higher trophic levels and entire food webs. Better understanding of how rainfall affects the diversity, species composition, and dynamics of arid environments can contribute to solving environmental problems stemming from land use and global climate change.     

Structural basis of HP1/PXVXL motif peptide interactions and HP1 localisation to heterochromatin

HP1 family proteins are adaptor molecules, containing two related chromo domains that are required for chromatin packaging and gene silencing. Here we present the structure of the chromo shadow domain from mouse HP1beta bound to a peptide containing a consensus PXVXL motif found in many HP1 binding partners. The shadow domain exhibits a novel mode of peptide recognition, where the peptide binds across the dimer interface, sandwiched in a beta-sheet between strands from each monomer. The structure allows us to predict which other shadow domains bind similar PXVXL motif-containing peptides and provides a framework for predicting the sequence specificity of the others. We show that targeting of HP1beta to heterochromatin requires shadow domain interactions with PXVXL-containing proteins in addition to chromo domain recognition of Lys-9-methylated histone H3. Interestingly, it also appears to require the simultaneous recognition of two Lys-9-methylated histone H3 molecules. This finding implies a further complexity to the histone code for regulation of chromatin structure and suggests how binding of HP1 family proteins may lead to its condensation.     

The development of potent non-peptidic PTP-1B inhibitors

The SAR from our peptide libraries was exploited to design a series of potent deoxybenzoin PTP-1B inhibitors. The introduction of an ortho bromo substituent next to the difluoromethylphosphonate warhead gave up to 20-fold increase in potency compared to the desbromo analogues. In addition, these compounds were orally bioavailable and active in the animal models of non-insulin dependent diabetes mellitus (NIDDM).     

Evolution of pigment cell regression in the cavefish Astyanax: a late step in melanogenesis

Pigmentation and eyes are often lost in cave-adapted animals. Although the mechanisms of eye degeneration are beginning to be understood, little is known about the evolutionary and developmental processes involved in pigment cell regression. In teleost embryos, a population of neural crest cells migrates into the body wall and differentiates into melanophores, xanthophores, and iridophores. All three pigment cell types are present in the eyed surface-dwelling form (surface fish) of the teleost Astyanax mexicanus. However, melanophores are absent or substantially reduced in number in various derived populations of the conspecific blind cave-dwelling form (cavefish). We show here that tyrosinase-positive melanoblasts are present in cavefish. DiI labeling revealed a population of trunk neural crest cells in cavefish embryos that migrate to locations normally occupied by differentiated melanophores. We also discovered a cell population in cavefish embryos and adults resembling melanoblasts in several features, including the ability to synthesize melanin when supplied with the tyrosinase substrate l-dopa. DiI-tyrosinase double-labeling and neural keel explant experiments showed that the tyrosinase-positive cells are derived from the neural crest. The number of melanoblasts varies in different adult cavefish populations relative to the extent of melanophore reduction. Although cavefish melanoblasts can synthesize melanin from exogenous l-dopa, they are unable to convert exogenous l-tyrosine to l-dopa and melanin. We conclude that pigment cell regression in cavefish is mediated by an evolutionary change late in melanogenesis that may involve an impediment in the ability to convert l-tyrosine to l-dopa and melanin.     

Qualification of analytical instruments for use in the pharmaceutical industry: A scientific approach

The purpose of the use of analytical instruments is to generate reliable data. Instrument qualification helps fulfill this purpose. No authoritative guide exists that considers the risk of instrument failure and combines that risk with users' scientific knowledge and ability to use the instrument to deliver reliable and consistent data. In the absence of such a guide, the qualification of analytical instruments has become a subjective and often fruitless document-generating exercise. Taking its cue from the new FDA initiative, “Pharmaceutical GMP's for the 21st Century,” an efficient, science- and risk-based process for AIQ was discussed at a workshop on analytical instrument qualification. This report represents the distillate of deliberations on the complicated issues associated with the various stages of analytical instrument qualification. It emphasizes AIQ's place in the overall process of obtaining quality reliable data from analytical instruments and offers an efficient process for its performance, one that focuses on scientific value rather than on producing documents. Implementing such a process should remove ambiguous interpretations by various groups.