Monsoon-driven Saharan dust variability over the past 240,000 years.

Reconstructions of past Saharan dust deposition in marine sediments provide foundational records of North African climate over time scales of 103 to 106 years. Previous dust records show primarily glacial-interglacial variability in the Pleistocene, in contrast to other monsoon records showing strong precessional variability. Here, we present the first Saharan dust record spanning multiple glacial cycles obtained using 230Th normalization, an improved method of calculating fluxes. Contrary to previous data, our record from the West African margin demonstrates high correlation with summer insolation and limited glacial-interglacial changes, indicating coherent variability in the African monsoon belt throughout the late Pleistocene. Our results demonstrate that low-latitude Saharan dust emissions do not vary synchronously with high- and mid-latitude dust emissions, and they call into question the use of existing Plio-Pleistocene dust records to investigate links between climate and hominid evolution.

Onset and Evolution of Southern Annular Mode-Like Changes at Centennial Timescale.

The Southern Westerly Winds (SWW) are the surface expression of geostrophic winds that encircle the southern mid-latitudes. In conjunction with the Southern Ocean, they establish a coupled system that not only controls climate in the southern third of the world, but is also closely connected to the position of the Intertropical Convergence Zone and CO2 degassing from the deep ocean. Paradoxically, little is known about their behavior since the last ice age and relationships with mid-latitude glacier history and tropical climate variability. Here we present a lake sediment record from Chilean Patagonia (51°S) that reveals fluctuations of the low-level SWW at mid-latitudes, including strong westerlies during the Antarctic Cold Reversal, anomalously low intensity during the early Holocene, which was unfavorable for glacier growth, and strong SWW since ~7.5 ka. We detect nine positive Southern Annular Mode-like events at centennial timescale since ~5.8 ka that alternate with cold/wet intervals favorable for glacier expansions (Neoglaciations) in southern Patagonia. The correspondence of key features of mid-latitude atmospheric circulation with shifts in tropical climate since ~10 ka suggests that coherent climatic shifts in these regions have driven climate change in vast sectors of the Southern Hemisphere at centennial and millennial timescales.

Cross-calibration of S-NPP VIIRS moderate resolution reflective solar bands against MODIS Aqua over dark water scenes.

The Visible Infrared Imaging Radiometer Suite (VIIRS) is being used to continue the record of Earth Science observations and data products produced routinely from National Aeronautics and Space Administration (NASA) Moderate Resolution Imaging Spectroradiometer (MODIS) measurements. However, the absolute calibration of VIIRS's reflected solar bands is thought to be biased, leading to offsets in derived data products such as aerosol optical depth (AOD) as compared to when similar algorithms are applied to different sensors. This study presents a cross-calibration of these VIIRS bands against MODIS Aqua over dark water scenes, finding corrections to the NASA VIIRS Level 1 (version 2) reflectances between approximately +1 % and -7 % (dependent on band) are needed to bring the two into alignment (after accounting for expected differences resulting from different band spectral response functions), and indications of relative trending of up to ^0.35 % per year in some bands. The derived calibration gain corrections are also applied to the VIIRS reflectance and then used in an AOD retrieval, and are shown to decrease the bias and total error in AOD across the midvisible spectral region compared to the standard VIIRS NASA reflectance calibration. The resulting AOD bias characteristics are similar to those of NASA MODIS AOD data products, which is encouraging in terms of multisensor data continuity.

Radiocarbon constraints on the extent and evolution of the South Pacific glacial carbon pool.

During the last deglaciation, the opposing patterns of atmospheric CO2 and radiocarbon activities (Δ(14)C) suggest the release of (14)C-depleted CO2 from old carbon reservoirs. Although evidences point to the deep Pacific as a major reservoir of this (14)C-depleted carbon, its extent and evolution still need to be constrained. Here we use sediment cores retrieved along a South Pacific transect to reconstruct the spatio-temporal evolution of Δ(14)C over the last 30,000 years. In ∼2,500-3,600 m water depth, we find (14)C-depleted deep waters with a maximum glacial offset to atmospheric (14)C (ΔΔ(14)C=-1,000‰). Using a box model, we test the hypothesis that these low values might have been caused by an interaction of aging and hydrothermal CO2 influx. We observe a rejuvenation of circumpolar deep waters synchronous and potentially contributing to the initial deglacial rise in atmospheric CO2. These findings constrain parts of the glacial carbon pool to the deep South Pacific.

Cirrus cloud optical and microphysical property retrievals from eMAS during SEAC4RS using bi-spectral reflectance measurements within the 1.88 µm water vapor absorption band.

Previous bi-spectral imager retrievals of cloud optical thickness (COT) and effective particle radius (CER) based on the Nakajima and King (1990) approach, such as those of the operational MODIS cloud optical property retrieval product (MOD06), have typically paired a non-absorbing visible or near-infrared wavelength, sensitive to COT, with an absorbing shortwave or midwave infrared wavelength sensitive to CER. However, in practice it is only necessary to select two spectral channels that exhibit a strong contrast in cloud particle absorption. Here it is shown, using eMAS observations obtained during NASA's SEAC4RS field campaign, that selecting two absorbing wavelength channels within the broader 1.88 µm water vapor absorption band, namely the 1.83 and 1.93 µm channels that have sufficient differences in ice crystal single scattering albedo, can yield COT and CER retrievals for thin to moderately thick single-layer cirrus that are reasonably consistent with other solar and IR imager-based and lidar-based retrievals. A distinct advantage of this channel selection for cirrus cloud retrievals is that the below-cloud water vapor absorption minimizes the surface contribution to measured cloudy TOA reflectance, in particular compared to the solar window channels used in heritage retrievals such as MOD06. This reduces retrieval uncertainty resulting from errors in the surface reflectance assumption, as well as reduces the frequency of retrieval failures for thin cirrus clouds.

Southern Annular Mode-like changes in southwestern Patagonia at centennial timescales over the last three millennia.

Late twentieth-century instrumental records reveal a persistent southward shift of the Southern Westerly Winds during austral summer and autumn associated with a positive trend of the Southern Annular Mode (SAM) and contemporaneous with glacial recession, steady increases in atmospheric temperatures and CO2 concentrations at a global scale. However, despite the clear importance of the SAM in the modern/future climate, very little is known regarding its behaviour during pre-Industrial times. Here we present a stratigraphic record from Lago Cipreses (51°S), southwestern Patagonia, that reveals recurrent ~200-year long dry/warm phases over the last three millennia, which we interpret as positive SAM-like states. These correspond in timing with the Industrial revolution, the Mediaeval Climate Anomaly, the Roman and Late Bronze Age Warm Periods and alternate with cold/wet multi-centennial phases in European palaeoclimate records. We conclude that SAM-like changes at centennial timescales in southwestern Patagonia represent in-phase interhemispheric coupling of palaeoclimate over the last 3,000 years through atmospheric teleconnections.

[Causes of failed osteosynthesis of ankle fractures]. / Ursachen der fehlgeschlagenen Osteosynthese am Sprunggelenk.

Ankle fractures are the most common osseous injuries of the lower extremity. In most cases, open reduction and internal fixation is indicated due to fracture dislocation. Operations of the ankle are generally considered classic, standardized, training procedures. An exact reconstruction with correct length and rotation of the joint as well as stabilization of the tibiofibular ligamentous complex is essential. Beside age and gender of the patient, outcome depends on fracture morphology and comorbidities, e. g., osteoporosis, vascular status, neuropathic disorders, and diabetes mellitus. Additional chondral lesions, extensive closed or open soft tissue injuries, and compartment syndrome due to trauma impact can lead to further problems in the postoperative period. Furthermore, iatrogenic complications like fixed malpositions, instabilities, and implant-associated failure of osteosynthesis may also occur. This article illustrates the causes of preventable mistakes and points out options to increase clinical outcome.

Inhibitors of N(alpha)-acetyl-L-ornithine deacetylase: synthesis, characterization and analysis of their inhibitory potency.

A series of N (alpha)-acyl (alkyl)- and N (alpha)-alkoxycarbonyl-derivatives of L- and D-ornithine were prepared, characterized, and analyzed for their potency toward the bacterial enzyme N (alpha)-acetyl-L-ornithine deacetylase (ArgE). ArgE catalyzes the conversion of N (alpha)-acetyl-L-ornithine to L-ornithine in the fifth step of the biosynthetic pathway for arginine, a necessary step for bacterial growth. Most of the compounds tested provided IC(50) values in the muM range toward ArgE, indicating that they are moderately strong inhibitors. N (alpha)-chloroacetyl-L-ornithine (1g) was the best inhibitor tested toward ArgE providing an IC(50) value of 85 microM while N (alpha)-trifluoroacetyl-L-ornithine (1f), N (alpha)-ethoxycarbonyl-L-ornithine (2b), and N (alpha)-acetyl-D-ornithine (1a) weakly inhibited ArgE activity providing IC(50) values between 200 and 410 microM. Weak inhibitory potency toward Bacillus subtilis-168 for N (alpha)-acetyl-D-ornithine (1a) and N (alpha)-fluoro- (1f), N (alpha)-chloro- (1g), N (alpha)-dichloro- (1h), and N (alpha)-trichloroacetyl-ornithine (1i) was also observed. These data correlate well with the IC(50) values determined for ArgE, suggesting that these compounds might be capable of getting across the cell membrane and that ArgE is likely the bacterial enzymatic target.

Synthesis of N-succinyl-L,L-diaminopimelic acid mimetics via selective protection.

The search for potential inhibitors that target so far unexplored bacterial enzyme mono-N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) has stimulated a development of methodology for quick and efficient preparation of mono-N-acylated 2,6-diaminopimelic acid (DAP) derivatives bearing the different carboxyl groups or lipophilic moieties on their amino group.

A sheep model for fracture treatment in osteoporosis: benefits of the model versus animal welfare.

Animal models are necessary to evaluate new options for the treatment of fractures in osteoporotic bone. They permit both the biological response of a living system and the influence of the pathological processes to be taken into account. A sheep model for osteoporosis was established by combining oestrogen deficiency, calcium and vitamin D-deficient diet with steroid medication. Bone mineral density (BMD) was reduced by >30% after 12 weeks of combined treatment. Osteoporosis similar to the human situation with corresponding changes in the micro-architecture and mechanical properties of bone was observed. This publication focuses on the impressive results obtained with the model and contrasts them with considerations of animal welfare. Considerable side-effects associated with steroid medication became manifest. Animals in the treatment groups showed signs of infection of various degrees due to the immunosuppressive effect of the medication. The infections were mostly caused by Corynebacterium pseudotuberculosis. Antibody testing revealed a 100% prevalence of infection in this breed of sheep. A modification of the steroid treatment, i.e. less-frequent injections, reduced the incidence of side-effects. This sheep model shows a significant and reproducible reduction in cancellous BMD of >30%, including relevant changes in biomechanical properties and increased fracture risk. However, the severity of the side-effects cannot be overlooked. The model must be improved if it is to be used in the future. Options to reduce the side-effects are discussed.

Secretory granule behaviour adjacent to the plasma membrane before and during exocytosis: total internal reflection fluorescence microscopy studies.

Our current notions of different granule pools, granule interaction with the plasma membrane, and ultimately granule and plasma membrane soluble N-ethylmaleimide-sensitive-factor attachment protein (SNARE) interactions, result largely from inferences based upon biochemical alterations of secretion kinetics. Another view of events comes from studies using total internal reflection fluorescence microscopy (TIRFM) to investigate granule behaviour immediately adjacent to the plasma membrane. The motions of secretory (chromaffin) granules in bovine chromaffin cells visualized by TIRFM are highly restricted, as if granules are caged or tethered. These small motions are regulated by ATP and Ca2+, two factors that increase priming of the secretory response. There is no evidence that granules decrease their motion immediately before secretion. To the contrary, there is a tendency for granules to increase their motions and travel within a few hundred milliseconds of fusion. Hence, the notion of a long-lived docked state as a prelude to fusion does not encompass the physical reality of molecular scale motions, multiple tethering states and significant travel immediately preceding the exocytotic event. Increased travel may increase the probability of granules interacting productively with the plasma membrane constituents, thereby, increasing the probability of fusion.

Structural evidence that the methionyl aminopeptidase from Escherichia coli is a mononuclear metalloprotease.

The Co and Fe K-edge extended X-ray absorption fine structure (EXAFS) spectra of the methionyl aminopeptidase from Escherichia coli (EcMetAP) have been recorded in the presence of 1 and 2 equiv of either Co(II) or Fe(II) (i.e., [Co(II)_(EcMetAP)], [Co(II)Co(II)(EcMetAP)], [Fe(II)_(EcMetAP)], and [Fe(II)Fe(II)(EcMetAP)]). The Fourier transformed data of both [Co(II)_(EcMetAP)] and [Co(II)Co(II)(EcMetAP)] are dominated by a peak at ca. 2.05 A, which can be fit assuming 5 light atom (N,O) scatterers at 2.04 A. Attempts to include a Co-Co interaction (in the 2.4-4.0 A range) in the curve-fitting parameters were unsuccessful. Inclusion of multiple-scattering contributions from the outer-shell atoms of a histidine-imidazole ring resulted in reasonable Debye-Waller factors for these contributions and a slight reduction in the goodness-of-fit value (f '). These data suggest that a dinuclear Co(II) center does not exist in EcMetAP and that the first Co atom is located in the histidine-ligated side of the active site. The EXAFS data obtained for [Fe(II)_(EcMetAP)] and [Fe(II)Fe(II)(EcMetAP)] indicate that Fe(II) binds to EcMetAP in a similar site to Co(II). Since no X-ray crystallographic data are available for any Fe(II)-substituted EcMetAP enzyme, these data provide the first glimpse at the Fe(II) active site of MetAP enzymes. In addition, the EXAFS data for [Co(II)Co(II)(EcMetAP)] incubated with the antiangiogenesis drug fumagillin are also presented.

Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal activity.

Phosphatidylinositol 4,5-biphosphate (PIP2) has been implicated in a variety of cellular processes, including synaptic vesicle recycling. However, little is known about the spatial distribution of this phospholipid in neurons and its dynamics. In this study, we have focused on these questions by transiently expressing the phospholipase C (PLC)-delta1 pleckstrin homology (PH) domain fused to green fluorescent protein (GFP) in cultured hippocampal neurons. This PH domain binds specifically and with high affinity to PIP2. Live confocal imaging revealed that in resting cells, PH-GFP is localized predominantly on the plasma membrane. Interestingly, no association of PH-GFP with synaptic vesicles in quiescent neurons was observed, indicating the absence of detectable PIP2 on mature synaptic vesicles. Electrical stimulation of hippocampal neurons resulted in a decrease of the PH-GFP signal at the plasma membrane, most probably due to a PLC-mediated hydrolysis of PIP2. This was accompanied in the majority of presynaptic terminals by a marked increase in the cytoplasmic PH-GFP signal, localized most probably on freshly endocytosed membranes. Further investigation revealed that the increase in PH-GFP signal was dependent on the activation of N-methyl-D-aspartate receptors and the consequent production of nitric oxide (NO). Thus, PIP2 in the presynaptic terminal appears to be regulated by postsynaptic activity via a retrograde action of NO.

Inhibition of the aminopeptidase from Aeromonas proteolytica by L-leucinephosphonic acid. Spectroscopic and crystallographic characterization of the transition state of peptide hydrolysis.

The nature of the interaction of the transition-state analogue inhibitor L-leucinephosphonic acid (LPA) with the leucine aminopeptidase from Aeromonas proteolytica (AAP) was investigated. LPA was shown to be a competitive inhibitor at pH 8.0 with a K(i) of 6.6 microM. Electronic absorption spectra, recorded at pH 7.5 of [CoCo(AAP)], [CoZn(AAP)], and [ZnCo(AAP)] upon addition of LPA suggest that LPA interacts with both metal ions in the dinuclear active site. EPR studies on the Co(II)-substituted forms of AAP revealed that the environments of the Co(II) ions in both [CoZn(AAP)] and [ZnCo(AAP)] become highly asymmetric and constrained upon the addition of LPA and clearly indicate that LPA interacts with both metal ions. The X-ray crystal structure of AAP complexed with LPA was determined at 2.1 A resolution. The X-ray crystallographic data indicate that LPA interacts with both metal centers in the dinuclear active site of AAP and a single oxygen atom bridge is absent. Thus, LPA binds to the dinuclear active site of AAP as an eta-1,2-mu-phosphonate with one ligand to the second metal ion provided by the N-terminal amine. A structural comparison of the binding of phosphonate-containing transition-state analogues to the mono- and bimetallic peptidases provides insight into the requirement for the second metal ion in bridged bimetallic peptidases. On the basis of the results obtained from the spectroscopic and X-ray crystallographic data presented herein along with previously reported mechanistic data for AAP, a new catalytic mechanism for the hydrolysis reaction catalyzed by AAP is proposed.

Restriction of secretory granule motion near the plasma membrane of chromaffin cells.

We used total internal reflection fluorescence microscopy to study quantitatively the motion and distribution of secretory granules near the plasma membrane (PM) of living bovine chromaffin cells. Within the approximately 300-nm region measurably illuminated by the evanescent field resulting from total internal reflection, granules are preferentially concentrated close to the PM. Granule motion normal to the substrate (the z direction) is much slower than would be expected from free Brownian motion, is strongly restricted over tens of nanometer distances, and tends to reverse directions within 0.5 s. The z-direction diffusion coefficients of granules decrease continuously by two orders of magnitude within less than a granule diameter of the PM as granules approach the PM. These analyses suggest that a system of tethers or a heterogeneous matrix severely limits granule motion in the immediate vicinity of the PM. Transient expression of the light chains of tetanus toxin and botulinum toxin A did not disrupt the restricted motion of granules near the PM, indicating that SNARE proteins SNAP-25 and VAMP are not necessary for the decreased mobility. However, the lack of functional SNAREs on the plasma or granule membranes in such cells reduces the time that some granules spend immediately adjacent to the PM.

Rab3a binding and secretion-enhancing domains in Rim1 are separate and unique. Studies in adrenal chromaffin cells.

Rim1 was identified in brain by its ability to bind Rab3a-GTP and has been postulated to be a Rab3a effector protein. Like Rabphilin3, it modulates secretion and contains a zinc finger and two C2 domains. We have investigated the structural basis for the ability of Rim1 to bind Rab3a-GTP and to stimulate exocytosis in chromaffin cells. Both full-length and N-terminal Rim1 enhance secretion 40-50% in both intact and permeabilized cells. The abilities of Rim1 to enhance secretion and to bind Rab3a-GTP reside on distinct and relatively small domains that act independently. A approximately 30-amino acid sequence immediately N-terminal of the zinc finger constitutes the minimal Rab3a-GTP binding domain. This short sequence is not found in Rabphilin3 and is entirely different from the zinc finger and flanking regions of Rabphilin3 that bind Rab3a-GTP. The zinc finger domain in Rim1 is unnecessary for Rab3a-GTP binding but, alone, enhances secretion. An analysis of the characteristics of the enhancement of secretion in permeabilized chromaffin cells indicates that N-terminal Rim1 does not alter the sensitivity of secretion to Ca(2+) but, instead, increases the rate of ATP-dependent priming of secretion.

An Algorithm for Optimizing Rotational Control of Globodera rostochiensis on Potato Crops in Bolivia.

The outline area of new cysts of Globodera rostochiensis was measured by image analysis. A linear regression of this value against egg content provided a basis for adjusting the egg number for cyst size. This adjusted egg content provides an estimate of the relative fullness of a cyst with eggs. This value showed an exponential decline in eggs over 3.5 years since the last potato crop. It corresponds to an average loss in the dormant egg population of 32.8 +/- 5.6%/year for 26 fields at Toralapa, Bolivia. This value compared well with a mean decline of 40 +/- 4%/year for 42 fields after measuring viable eggs/100 g soil on two occasions one year apart. The new approach allows declines to be estimated at one time point. The decline in lipid content of the dormant, unhatched second-stage juveniles (J2) was 17 +/- 6% per annum as measured by image analysis after Oil red O staining. This may be sufficient to compromise infectivity after 3 to 4 years of dormancy. A standard model was modified to consider the effect of both lipid depletion during dormancy and choice of susceptible potato on the population dynamics of G. rostochiensis under rotational control. It is concluded that a few cultivars may impose lower populations on G. rostochiensis in 3 to 4-year rotations than the majority used in Bolivia.

Latrotoxin stimulates secretion in permeabilized cells by regulating an intracellular Ca2+ - and ATP-dependent event: a role for protein kinase C.

alpha-Latrotoxin, a component of black widow spider venom, stimulates transmitter release from nerve terminals and intact chromaffin cells and enhances secretion from permeabilized chromaffin cells already maximally stimulated by Ca(2+). In this study we demonstrate that chromaffin cells contain a protein antigenically similar to the cloned Ca(2+)-independent receptor for alpha-latrotoxin. Although this receptor has homology to the secretin family of G-protein-linked receptors, pertussis toxin has no effect on the ability of alpha-latrotoxin to enhance secretion, suggesting that neither G(i) nor G(o) is involved in the response. Furthermore, in the absence of Ca(2+), alpha-latrotoxin does not stimulate polyphosphoinositide-specific phospholipase C. alpha-Latrotoxin specifically enhances ATP-dependent secretion in permeabilized cells. An in situ assay for protein kinase C reveals that alpha-latrotoxin augments the activation of protein kinase C by Ca(2+), and use of protein kinase inhibitors demonstrates that this activation is important for the toxin's enhancing effect. This enhancement of secretion requires Ca(2+) concentrations above 3 microm and is not supported by Ba(2+) or nonhydrolyzable guanine nucleotides, which do not stimulate protein kinase C. We conclude that alpha-latrotoxin stimulates secretion in permeabilized cells by regulating a Ca(2+)- and ATP-dependent event involving protein kinase C.

A pleckstrin homology domain specific for phosphatidylinositol 4, 5-bisphosphate (PtdIns-4,5-P2) and fused to green fluorescent protein identifies plasma membrane PtdIns-4,5-P2 as being important in exocytosis.

Kinetically distinct steps can be distinguished in the secretory response from neuroendocrine cells with slow ATP-dependent priming steps preceding the triggering of exocytosis by Ca(2+). One of these priming steps involves the maintenance of phosphatidylinositol 4, 5-bisphosphate (PtdIns-4,5-P(2)) through lipid kinases and is responsible for at least 70% of the ATP-dependent secretion observed in digitonin-permeabilized chromaffin cells. PtdIns-4,5-P(2) is usually thought to reside on the plasma membrane. However, because phosphatidylinositol 4-kinase is an integral chromaffin granule membrane protein, PtdIns-4,5-P(2) important in exocytosis may reside on the chromaffin granule membrane. In the present study we have investigated the localization of PtdIns-4,5-P(2) that is involved in exocytosis by transiently expressing in chromaffin cells a pleckstrin homology (PH) domain that specifically binds PtdIns-4, 5-P(2) and is fused to green fluorescent protein (GFP). The PH-GFP protein predominantly associated with the plasma membrane in chromaffin cells without any detectable association with chromaffin granules. Rhodamine-neomycin, which also binds to PtdIns-4,5-P(2), showed a similar subcellular localization. The transiently expressed PH-GFP inhibited exocytosis as measured by both biochemical and electrophysiological techniques. The results indicate that the inhibition was at a step after Ca(2+) entry and suggest that plasma membrane PtdIns-4,5-P(2) is important for exocytosis. Expression of PH-GFP also reduced calcium currents, raising the possibility that PtdIns-4,5-P(2) in some manner alters calcium channel function in chromaffin cells.