The Middle Miocene climatic transition in the Southern Ocean: Evidence of paleoclimatic and hydrographic changes at Kerguelen plateau from planktonic foraminifers and stable isotopes

Middle Miocene (14.8–11.9 Ma) deep-sea sediments from ODP Hole 747A (Kerguelen Plateau, southern Indian Ocean) contain abundant, well-preserved and diverse planktonic foraminiferal assemblages. A detailed study of the climatic and hydrographic changes that occurred in this region during the Middle Miocene Climatic Transition led to the identification of an intense cooling phase (the Middle Miocene Shift). Abundance fluctuations of planktonic foraminiferal species with different paleoclimatic affinities, and oxygen and carbon stable isotopes have been integrated in a multi-proxy approach. Reconstruction of changes in foraminiferal faunal composition and diversity through time were the basis for identification of three foraminiferal biofacies. The most prominent faunal change took place at 13.8 Ma, when a fauna with warm-water affinity (marked by high abundance of Globorotalia miozea group and Globoturborotalita woodi plexus) was replaced by an oligotypic, opportunistic fauna with typical polar characters and dominated by neogloboquadrinids. This faunal change is interpreted as the result of foraminiferal migration from adjacent bioprovinces, caused by modifications in climate and hydrography. A positive 2.0‰ shift in δ¹⁸O (interpreted as the Mi3 event) and a related positive 1.0‰ shift in δ¹³C (corresponding to the CM6 event) accompanied this faunal turnover. These are interpreted to reflect substantial reorganization of Southern Ocean waters, the northward migration of the Polar Front and a strong increase in primary productivity. The second faunal change took place at 12.9 Ma and was characterized by the gradual decrease in abundance of the neogloboquadrinids and the recovery of Globorotalia praescitula/scitula group and Globigerinita glutinata. A positive 1.5‰ shift in δ¹⁸O (interpreted as the Mi4 event) and a concurrent gradual negative shift in δ¹³C accompanied this faunal change, witnessing further modifications of the climate/ocean system. Variations in sea surface temperature, considered as the main factor causing changes of surface hydrography at the Kerguelen Plateau, seem to have been driven by obliquity and long-term eccentricity, thus suggesting a key role played by the astronomical forcing on the evolution of Southern Ocean dynamics during the Middle Miocene. Also an evident 1.2 Myr modulation of the δ¹³C record suggests a main control of the long-term obliquity cycles on the carbon cycle dynamics. Particularly, the Mi3/CM6 events exactly fit with a node of the 1.2 Myr modulation cycles. This confirms the key role played by orbital parameters on high-latitude temperatures and Antarctic ice volume, and indirectly on global carbon burial and/or productivity. This climatic transition was marked also by changes in surface hydrography. From 14.8 to 13.8 Ma an intermediate-strength thermocline controlled by seasonality developed just below the photic zone. Weaker seasonality characterized the interval from 13.8 to 12.9 Ma, when the thermocline became shallower and sharper and favored intermediate-water foraminifers. From 12.9 Ma, seasonality increased again and an intermediate-strength thermocline re-developed.     

Crystal structure of a novel type of odorant-binding protein from Anopheles gambiae, belonging to the C-plus class

Agam (Anopheles gambiae) relies on its olfactory system to target human prey, leading eventually to the injection of Plasmodium falciparum, the malaria vector. OBPs (odorant-binding proteins) are the first line of proteins involved in odorant recognition. They interact with olfactory receptors and thus constitute an interesting target for insect control. In the present study, we undertook a large-scale analysis of proteins belonging to the olfactory system of Agam with the aim of preventing insect bites by designing strong olfactory repellents. We determined the three-dimensional structures of several Agam OBPs, either alone or in complex with model compounds. In the present paper, we report the first three-dimensional structure of a member of the C-plus class of OBPs, AgamOBP47, which has a longer sequence than classical OBPs and contains six disulfide bridges. AgamOBP47 possesses a core of six α-helices and three disulfide bridges, similar to the classical OBP fold. Two extra loops and the N- and C-terminal extra segments contain two additional α-helices and are held in conformation by three disulfide bridges. They are located either side of the classical OBP core domain. The binding site of OBP47 is located between the core and the additional domains. Two crevices are observed on opposite sides of OBP47, which are joined together by a shallow channel of sufficient size to accommodate a model of the best-tested ligand. The binding sites of C-plus class OBPs therefore exhibit different characteristics, as compared with classical OBPs, which should lead to markedly diverse functional implications.     

A Thermolabile Aldolase A Mutant Causes Fever-Induced Recurrent Rhabdomyolysis without Hemolytic Anemia

Aldolase A deficiency has been reported as a rare cause of hemolytic anemia occasionally associated with myopathy. We identified a deleterious homozygous mutation in the ALDOA gene in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses. We show that the underlying mechanism involves an exacerbation of aldolase A deficiency at high temperatures that affected myoblasts but not erythrocytes. The aldolase A deficiency was rescued by arginine supplementation in vitro but not by glycerol, betaine or benzylhydantoin, three other known chaperones, suggesting that arginine-mediated rescue operated by a mechanism other than protein chaperoning. Lipid droplets accumulated in patient myoblasts relative to control and this was increased by cytokines, and reduced by dexamethasone. Our results expand the clinical spectrum of aldolase A deficiency to isolated temperature-dependent rhabdomyolysis, and suggest that thermolability may be tissue specific. We also propose a treatment for this severe disease.

Abstract Summary

Using recent technical advances involving exome analysis, we identified a new missense mutation in the ALDOA gene, encoding a key enzyme in the glycolytic pathway. The patients presented with severe recurrent rhabdomyolysis without hemolytic anemia. The decrease of aldolase A activity in myoblasts was enhanced at high temperature and could explain the fever-induced rhabdomyolysis. By contrast, enzyme thermolability was not found in erythrocytes, possibly accounting for the unusual clinical phenotype of the patients. Enzyme thermolability was rescued by arginine supplementation in vitro but not by other chaperone compounds.     

In‐depth protein profiling of the postsynaptic density from mouse hippocampus using data‐independent acquisition proteomics

Located at neuronal terminals, the postsynaptic density (PSD) is a highly complex network of cytoskeletal scaffolding and signaling proteins responsible for the transduction and modulation of glutamatergic signaling between neurons. Using ion‐mobility enhanced data‐independent label‐free LC‐MS/MS, we established a reference proteome of crude synaptosomes, synaptic junctions, and PSD derived from mouse hippocampus including TOP3‐based absolute quantification values for identified proteins. The final dataset across all fractions comprised 49 491 peptides corresponding to 4558 protein groups. Of these, 2102 protein groups were identified in highly purified PSD in at least two biological replicates. Identified proteins play pivotal roles in neurological and synaptic processes providing a rich resource for studies on hippocampal PSD function as well as on the pathogenesis of neuropsychiatric disorders. All MS data have been deposited in the ProteomeXchange with identifier PXD000590 ( http://proteomecentral.proteomexchange.org/dataset/PXD000590 ).     

Purification and characterisation of an odorant-binding protein from cow nasal tissue

Cow nasal tissue contains a protein which shows specific binding activity for 'green' smelling compounds such as 2-isobutyl-3-methoxypyrazine. This protein has now been purified using anion-exchange fast protein liquid chromatography. The protein has a relative molecular mass of 40 0000-44 000, s = 3.1 +/- 0.3 S, pI = 4.7 +/- 0.1 with an absorbance maximum at 278 nm, and consists of two subunits with an identical relative molecular mass of 19 000. It is localised in the soluble fraction of cells from the olfactory mucosa and respiratory mucosa from the middle part of the maxillary and nasal turbinates, and is absent from all other tissues tested.     

Porcine VEG Proteins and Tear Prealbumins

Small soluble proteins, belonging to the lipocalin family aresecreted in large amounts by tongue von Ebner's glands and lachrymalglands. In humans, the lingual protein, called VEG, and thelachrymal protein, called tear prealbumin, have shown identicalcDNA sequences. In the pig, we have purified homodimeric proteinswith subunits of 17 kDa, both from von Ebner's glands and fromlachrymal glands. In both cases, the proteins can be resolvedinto two isoforms on a chromatofocusing column. Partial aminoacidsequences and full cDNA sequences have been obtained for themore abundant forms purified from both tissues. The two proteinsappear to be identical, as in humans. The reason why the sameprotein is expressed in different tissues, as well as its physiologicalfunction, still remain to be clarified.     

Respiratory system mechanics in sedated, paralyzed, morbidly obese patients

Pelosi, P., M. Croci, I. Ravagnan, M. Cerisara, P. Vicardi,A. Lissoni, and L. Gattinoni. Respiratory system mechanics insedated, paralyzed, morbidly obese patients J. Appl.Physiol. 82(3): 811-818, 1997.The effects ofinspiratory flow and inflation volume on the mechanical properties ofthe respiratory system in eight sedated and paralyzed postoperativemorbidly obese patients (aged 37.6 ± 11.8 yr who had never smokedand had normal preoperative seated spirometry) were investigated byusing the technique of rapid airway occlusion during constant-flowinflation. With the patients in the supine position, we measured theinterrupter resistance (Rint,rs), which in humans probably reflectsairway resistance, the "additional" resistance (Rrs) due toviscoelastic pressure dissipation and time-constant inequalities, andstatic respiratory elastance (Est,rs). Intra-abdominalpressure (IAP) was measured by using a bladder catheter, and functionalresidual capacity was measured by the helium-dilution technique. Theresults were compared with a previous study on 16 normal anesthetizedparalyzed humans. Compared with normal persons, we found that in obesesubjects: 1) functional residualcapacity was markedly lower (0.645 ± 0.208 liter) and IAP washigher (24 ± 2.2 cmH₂O);2) alveolar-arterial oxygenationgradient was increased (178 ± 59 mmHg);3) the volume-pressure curve of therespiratory system was curvilinear with an "inflection" point;4) Est,rs, Rint,rs, and Rrs werehigher than normal (29.3 ± 5.04 cmH₂O/l, 5.9 ± 2.4 cmH₂O ^· l^{1 ·} s,and 6.4 ± 1.6 cmH₂O ^· l^{1 ·} s,respectively); 5) Rint,rs increasedwith increasing inspiratory flow, Est,rs did not change, and Rrsdecreased progressively; and 6) withincreasing inflation volume, Rint,rs and Est,rs decreased, whereasRrs rose progressively. Overall, our data suggest that obesesubjects during sedation and paralysis are characterized by hypoxemiaand marked alterations of the mechanical properties of the respiratorysystem, largely explained by a reduction in lung volume due to theexcessive unopposed IAP.