The extreme yet transient nature of glacial erosion.

Ice can sculpt extraordinary landscapes, yet the efficacy of, and controls governing, glacial erosion on geological timescales remain poorly understood and contended, particularly across Polar continental shields. Here, we assimilate geophysical data with modelling of the Eurasian Ice Sheet - the third largest Quaternary ice mass that spanned 49°N to 82°N - to decipher its erosional footprint during the entire last ~100 ka glacial cycle. Our results demonstrate extreme spatial and temporal heterogeneity in subglacial erosion, with rates ranging from 0 to 5 mm a-1 and a net volume equating to ~130,000 km3 of bedrock excavated to depths of ~190 m. A hierarchy of environmental controls ostensibly underpins this complex signature: lithology, topography and climate, though it is basal thermodynamics that ultimately regulates erosion, which can be variously protective, pervasive, or, highly selective. Our analysis highlights the remarkable yet fickle nature of glacial erosion - critically modulated by transient ice-sheet dynamics - with its capacity to impart a profound but piecemeal geological legacy across mid- and high latitudes.

Surviving salt fluctuations: stress and recovery in Halobacterium salinarum, an extreme halophilic Archaeon.

Halophilic proteins subjected to below about 15% salt in vitro denature through misfolding, aggregation and/or precipitation. Halobacteria, however, have been detected in environments of fluctuating salinity such as coastal salterns and even around fresh water springs in the depths of the Dead Sea. In order to identify the underlying mechanisms of low salt survival, we explored the reactivation capacity of Halobacterium (Hbt) salinarum sub-populations after incubation in low salt media and recovery in physiological salt. Respiratory oxygen consumption was assessed in stressed cells and cell viability was estimated by Live/Dead staining and flow cytometry. In vivo neutron scattering experiments showed that the recovery of Hbt salinarum sub-populations exposed to severe low salt conditions is related to a rapid retrieval of functional molecular dynamics in the proteome. In the hypothesis that the observations on Hbt salinarum have wider relevance, they could be of key ecological significance for the dispersion of extremophiles when environmental fluctuations become severe.

Autocatalytic association of proteins by covalent bond formation: a Bio Molecular Welding toolbox derived from a bacterial adhesin.

Unusual intramolecular cross-links present in adhesins from Gram-positive bacteria have been used to develop a generic process amenable to biotechnology applications. Based on the crystal structure of RrgA, the Streptococcus pneumoniae pilus adhesin, we provide evidence that two engineered protein fragments retain their ability to associate covalently with high specificity, in vivo and in vitro, once isolated from the parent protein. We determined the optimal conditions for the assembly of the complex and we solved its crystal structure at 2 Å. Furthermore, we demonstrate biotechnological applications related to antibody production, nanoassembly and cell-surface labeling based on this process we named Bio Molecular Welding.

Inner gorges cut by subglacial meltwater during Fennoscandian ice sheet decay.

The century-long debate over the origins of inner gorges that were repeatedly covered by Quaternary glaciers hinges upon whether the gorges are fluvial forms eroded by subaerial rivers, or subglacial forms cut beneath ice. Here we apply cosmogenic nuclide exposure dating to seven inner gorges along ~500 km of the former Fennoscandian ice sheet margin in combination with a new deglaciation map. We show that the timing of exposure matches the advent of ice-free conditions, strongly suggesting that gorges were cut by channelized subglacial meltwater while simultaneously being shielded from cosmic rays by overlying ice. Given the exceptional hydraulic efficiency required for meltwater channels to erode bedrock and evacuate debris, we deduce that inner gorges are the product of ice sheets undergoing intense surface melting. The lack of postglacial river erosion in our seven gorges implicates subglacial meltwater as a key driver of valley deepening on the Baltic Shield over multiple glacial cycles.

Crystal structure of human survivin reveals a bow tie-shaped dimer with two unusual alpha-helical extensions.

Survivin is a mitotic spindle-associated protein involved in linking mitotic spindle function to activation of apoptosis in mammalian cells. The structure of the full-length human survivin has been determined by X-ray crystallography to 2.7 A. Strikingly, the structure forms a very unusual bow tie-shaped dimer. It does not dimerize through a C-terminal coiled-coil, contrary to sequence analysis prediction. The C-terminal helices contain hydrophobic clusters with the potential for protein-protein interactions. The unusual shape and dimensions of survivin suggest it serves an adaptor function through its alpha-helical extensions.

Transglutaminase-catalyzed cross-linking of fibrils of collagen V/XI in A204 rhabdomyosarcoma cells.

Collagens V and XI are thought to form a core around which the major interstitial collagens, I and II, respectively, are organized during fibrillogenesis. We previously reported the presence of a heterotypic form of collagens V and XI, [alpha 1(XI)]2 alpha 2(V), in cultures of A204 rhabdomyosarcoma cells [Kleman, J.-P., Hartmann, D. J., Ramirez, F., & van der Rest, M. (1992) Eur. J. Biochem. 210, 329-335]. This collagen forms a matrix which remains highly insoluble, even when cells were cultured in the presence of beta-aminopropionitrile, an inhibitor of lysyl oxidase and thereby of "classical" collagen cross-linking. When the cells were cultured in the presence of putrescine, a competitive inhibitor of transglutaminase-catalyzed protein cross-linking, a drastic increase in collagen solubility was observed. This result indicates that a transglutaminase contributes to the covalent stabilization of the collagen matrix of these cells. A204 rhabdomyosarcoma cells express tissue transglutaminase as revealed by specific antibodies, and enzyme activity was detected in the cell layer during culture and in cell extracts. Both collagens V and XI are specific glutaminyl substrates for tissue transglutaminase in vitro, as shown by incorporation of [3H]putrescine. The highly homologous alpha 1 chains of collagens V and XI were the major targets for the cross-linking. Trypsin cleaved the [3H] label from the alpha 1 chain of collagen V, demonstrating that the cross-linking occurs in the non triple helical propeptide domains.

Another look at collagen V and XI molecules.

The fibrillar collagens are the most abundant proteins of extracellular matrices. Among them, collagens V and XI are quantitatively minor components which participate in the formation of the fibrillar collagen network. Since these collagens were discovered, studies have demonstrated that they may play a fundamental role in the control of fibrillogenesis, probably by forming a core within the fibrils. Another characteristic of these collagens is the partial retention of their N-propeptide extensions in tissue forms, an unusual observation in comparison to the other known fibrillar collagens. The tissue locations of collagens V and XI are different, but their structural and biological properties seem to be closely related. It has been shown that their primary structures are highly conserved at both the gene and protein levels, and that these conserved features are the bases of their similar biological properties. In particular, they are both resistant to mammalian collagenases, and surprisingly sensitive to trypsin treatment. Collagens V and XI are usually buried within the major collagen fibrils, although they have both cell adhesion and heparin binding sites which could be of crucial importance in physiological processes such as development and wound healing. It has became evident that several molecules are in fact heterotypic associations of chains from both collagens V and XI, demonstrating that these two collagens are not distinct types but a single type which can be called collagen V/XI.

Low incidence of lead related complications associated with nonthoracotomy implantable cardioverter defibrillator systems.

UNLABELLED: Implantable cardioverter defibrillators (ICDs) are increasingly being implanted without the need for thoracotomy. Long-term lead performance and stability were evaluated in 150 consecutive patients in whom 1 of 3 nonthoracotomy ICD lead systems was implanted over a 3-year period from September 1990. RESULTS: Twelve (8%) patients (7 males, 5 females) experienced 13 lead complications during a follow-up period of 12 +/- 10 months. Complications were related to intracardiac leads in 7 (4 dislodgments, 2 fractures, 1 right ventricular perforation) and patch leads in 6 (2 folding, 1 fracture, 1 erosion, and 2 hematomas) cases. Freedom from lead related complications at 1 year was 92% (95% confidence interval, 86%-95%). A significant difference in freedom from lead complications between the two most frequently implanted lead systems was observed (P = 0.02). Complication rates were similar in the initial 75 and the more recent 75 implants (P = 0.5). The median time between lead implant and detection of complications was 37 days (range 3-1,147). Complications were diagnosed before hospital discharge in only two cases. In five patients, complications were asymptomatic and in three of these, reoperation was required due to inadequate defibrillation thresholds. Reoperation was necessary in 9 of 12 patients. CONCLUSIONS: Nonthoracotomy ICD lead systems are associated with a low complication rate. Complications may or may not cause symptoms, usually occur after hospital discharge, and require reoperation. Complications are not related to a "learning curve." There is a significant difference in performance between different lead systems.

Nonthoracotomy- versus thoracotomy-implantable defibrillators. Intention-to-treat comparison of clinical outcomes.

BACKGROUND: Nonthoracotomy-implantable cardioverter/defibrillator (ICD) systems may represent a significant advance in the treatment of patients with life-threatening ventricular arrhythmias, but their merits relative to those of the well-established thoracotomy systems remain largely unknown. The objective of this study was to compare the short- and long-term clinical outcomes after attempted ICD implantation via a nonthoracotomy versus thoracotomy approach in similar groups of patients. METHODS AND RESULTS: Between September 1990 and December 1992, 212 consecutive patients underwent attempted ICD system implantation without concomitant cardiac surgery at a single institution. Approach selection was not randomized but rather was based primarily on hardware availability. Primary comparisons of short- and long-term outcome were performed according to the "intention-to-treat" principle. Implantation was attempted via a nonthoracotomy approach in 120 patients (57%) and via a thoracotomy approach in 92 patients (43%). Prior cardiac surgery was more prevalent in the nonthoracotomy patients; otherwise, groups did not differ significantly in terms of prognostically relevant clinical characteristics. Nonthoracotomy implantation was successful in 101 patients (84%). After crossover to thoracotomy implantation (14 patients), the eventual success rate for ICD system implantation was 96% in the nonthoracotomy group. Thoracotomy implantation was successful in 89 patients (97%). Operative mortality was 3.3% in the nonthoracotomy and 4.3% in the thoracotomy groups (P = .73). Nonthoracotomy group patients were less likely to experience postoperative congestive heart failure (6% versus 16%; P = .02) or supraventricular arrhythmia (6% versus 18%; P = .004) and had significantly shorter postoperative intensive care and total hospitalization. Total hospital costs were significantly lower in the nonthoracotomy group ($32,205 versus $37,265; P = .001). After a follow-up of 16 +/- 9 months, there were 17 deaths in the nonthoracotomy group (none sudden) and 12 deaths in the thoracotomy group (1 sudden). One- and 2-year Kaplan-Meier survival probabilities were .87 (95% CI, .78 to .91) and .80 (95% CI, .68 to .88) in the nonthoracotomy group and .90 (95% CI, .82 to .95) and .87 (95% CI, .77 to .93) in the thoracotomy group (P = .56; log-rank test). CONCLUSIONS: Nonthoracotomy ICD implantation is associated with reduced surgical morbidity, postoperative hospital care requirement, and hospital costs and has similar efficacy in preventing sudden death relative to the thoracotomy approach. From these nonrandomized data, it appears that a nonthoracotomy approach should be considered preferable in most patients requiring ICD therapy.

A technique for rapid transfemoral catheterization of the coronary sinus with multielectrode catheters.

To minimize procedural and fluoroscopic times and avoid the risks of vascular injury and pneumothorax, some investigators have advocated elimination of routine placement of a coronary sinus (CS) catheter during electrophysiological procedures. We hypothesized that expedient and reproducible CS catheterization could be performed with minimal patient risk by utilizing a femoral vein approach. Fifty consecutive patients referred for radiofrequency ablative procedures underwent attempted CS catheterization using a 6-French steerable, quadripolar catheter via a femoral vein. Procedures were performed utilizing single-plane fluoroscopy without contrast angiographic aid by operators experienced in the technique. Successful catheterization was defined by the attainment, in < 15 minutes, of a stable catheter position with the distal electrode at or beyond the lateral margin of the heart. Successful catheterization of the CS was achieved in 47 (94%) patients. Selective pacing of the left atrium without patient discomfort was possible in all, eliminating the need for a right atrial pacing catheter. The median time to successful catheterization was 1.4 minutes (range 0.3-14.7). Only six patients required > 5 minutes. The median fluoroscopic time required was 1.2 minutes (range 0.3-12.7). No clinical variable was predictive of catheterization failure or time to successful catheterization. No complications were observed as a result of this technique. This prospective evaluation demonstrates that catheterization of the CS via a femoral vein approach is highly successful, expedient, and safe. The ability to selectively pace the left atrium may eliminate the requirement for a right atrial catheter.

Evolving concepts in radiofrequency catheter ablation of atrioventricular nodal reentry tachycardia.

Our results and those of others (Table I) suggest that both anatomic and electrogram (potential) approaches are highly successful in eliminating AVNRT. The use of slow-pathway potentials appears to minimize lesion delivery and to be associated with a very small likelihood of complete AV block. Approaches aimed directly at the midseptum also appear to reduce lesion delivery. It is important, however, to understand that the fast and slow AV-nodal pathways are not always confined to anterosuperior (fast) and posteroinferior (slow) locations (at least as they are determined fluoroscopically). On occasion, the slow pathway may be ablated anteriorly and the fast pathway posteriorly. Our three inadvertent successful fast-pathway ablations support these findings. We prefer to conceptualize the AV node as having three ablation zones. Ablation in the anterosuperior zone most often affects fast-pathway conduction; ablation in the posteroinferior zone most often affects slow pathway conduction; and ablation in the midseptal region predominantly affects slow-pathway conduction. Lesions applied to the midseptum do, however, appear more likely to affect inadvertently the fast (or both) pathway(s), probably because of the anatomic convergence of the posteroinferior and anterosuperior AV-nodal approaches in this region. A preliminary report by Wu et al. supports this three-zone concept. The subsequent larger series reported by this group has raised concern that midseptal approaches may be associated with too great a risk of complete AV block. On the other hand, approaches guided exclusively by potentials may be associated with much longer procedure times. Controversy exists over the acceptable end point for ablation procedures. We have not found it necessary routinely to eliminate dual-nodal conduction to maintain a low (3.2%) overall recurrence rate. Aggressive attempts to eliminate all evidence of slow-pathway conduction must be balanced against the risk of inadvertent complete AV block. In conclusion, cumulative data and our clinical experience with ablation of AVNRT suggest that it is possible to be both pragmatic and highly successful. The key components of our approach are (1) an anatomically based, systematic, time-limited search for potentials; (2) elimination of unnecessary lesions that are too atrial or too ventricular to involve the reentrant circuit; (3) a caudocephalad approach that avoids excessively anterior initial lesions, which may result in inadvertent complete AV block; and (4) avoidance of unnecessary lesions in the most inferoposterior sector, which results in patient discomfort and low clinical efficacy. This approach is safe (with minimal risk of AV block), reproducible, and efficacious.

Diversity in the processing events at the N-terminus of type-V collagen.

The processing of human collagen type-V chains was studied using anti-peptide polyclonal antibodies raised against peptide sequences at the N-terminal non-triple-helical region of pro-alpha 1(V) and pro-alpha 2(V) chains. The anti-peptide polyclonal antibody raised against positions 48-57 of the N-terminal alpha 2(V) sequence recognized the mature form of the human alpha 2(V) chain extracted without any proteolytic treatment from several tissues in the presence of a mixture of protease inhibitors. It also recognized the pro-alpha 2(V) and pN-alpha 2(V) collagen chains secreted in the cell-culture media of the rhabdomyosarcoma A204 cell line. The pN-alpha 2(V) collagen chain from this cell line migrated during electrophoresis with the alpha 2(V) chain obtained from tissues. This demonstrates that the alpha 2(V) chain in tissues is incompletely processed and is present as the pN-alpha 2(V) collagen chain which lacks the C-propeptide. In comparison, an anti-peptide polyclonal antibody raised against residues at positions 284-299 of the N-terminal alpha 1(V) human sequence failed to recognize the mature form of the alpha 1(V) chain while it reacted with the pN-alpha 1(V) collagen chain form. These results suggest that the alpha 1(V) chain undergoes a processing event in the N-terminal region that involves the removal of at least the first 284 residues. Amino acid sequence analysis was performed on cyanogen-bromide-generated or trypsin-generated peptides of the two electrophoretic bands obtained for the tissue form of collagen V. The slower-migrating band corresponding to the intact alpha 1(V) chain gave, as expected, only sequences corresponding to the alpha 1(V) chain. However, the band previously considered to be the intact alpha 2(V) chain also gave sequences for the alpha 1(V) chain in addition to the alpha 2(V) chain. This result indicates the presence in tissue extracts of a further processed form of alpha 1(V) chain which migrates with the intact alpha 2(V) chain. On further analysis, we observed that the two bands of the tissue form of collagen V occurred in a 1:1 ratio whereas, after the pepsin digestion to remove non-collagenous regions, two bands were observed with an alpha 1(V)/alpha 2(V) chain ratio of 3:1. These results indicate that the alpha 1(V) chain exists in an additional stoichiometry, different from [alpha 1(V)]2 alpha 2(V).(ABSTRACT TRUNCATED AT 400 WORDS)

The human rhabdomyosarcoma cell line A204 lays down a highly insoluble matrix composed mainly of alpha 1 type-XI and alpha 2 type-V collagen chains.

The biosynthesis of collagen by the A204 cell line was examined using polyclonal antibodies raised against collagen type V and type XI. The study of the pepsin-digested collagen showed that it is composed mainly of alpha 1(XI) and alpha 2(V) collagen chains in an apparent 2:1 ratio, suggesting the formation of heterotypic molecules [alpha 1(XI)]2 alpha 2(V). The existence of this chain stoichiometry was further demonstrated by immunoprecipitation of the molecule with an antibody recognizing alpha 2(V) but not alpha 1(XI) collagen chains. Electron microscopy analyses of 24-h cultures showed that this matrix is composed of thin fibrils, that can be decorated with immunogold-labelled anti-(type-V collagen) IgG, but not with anti-(type-XI collagen) IgG. The collagen matrix laid down by A204 cells is highly insoluble. In the presence of beta-aminopropionitrile, an inhibitor of lysyl oxidase, only a small proportion of intact collagen could be extracted without proteolytic treatment. Immunoblotting of intact medium collagen from cultures performed in the presence of beta-aminopropionitrile showed four distinct bands with each antibody. The migration of the bands, stained with anti-(type-V collagen) IgG, had apparent molecular masses of 127, 149, 161 and 198 kDa (compared to globular standards) while the bands stained with anti-(type-XI collagen) IgG had apparent masses of 145, 182, 207 and 225 kDa. These data indicate that type-V and type-XI collagen chains can assemble in heterotypic isoforms. In this system, the synthesized isoforms are able to aggregate into a highly cohesive matrix and they undergo a proteolytic processing closely similar to that of other fibrillar collagens.

Assessment of a cold air breathing aid.

During nasal breathing, heat and humidity are exchanged over a 160 cm(2) area of mucous membrane. This capacity is not sufficient for airway comfort during cold air breathing. Similarly, airway discomfort and constriction may be experienced during exercise-induced mouth breathing in marginally cold temperatures. In asthmatics and sensitive persons such airway discomfort rapidly transforms to broncho-constriction and related breathing problems. The Lungplus mouth-held breathing aid contains a coil of corrugated aluminium foil that provides a heat and moisture exchange area of 1200 cm(2) (Model 1) with a minimal breathing resistance. The present experiment was designed to quantify improved airway comfort using the device. Ninety-one subjects were exposed to each of three rooms with average air temperatures of +20, +3 and -15 degrees C, with a corresponding relative humidity of 50, 70 and 90%. For each condition, subjects gave subjective numerical assessments of the airway sensation during nose, mouth and Lungplus breathing, respectively. At each room temperature, mouth breathing resulted in a less comfortable airway rating than did breathing through the nose, which in turn resulted in a less comfortable rating than the Lungplus breathing condition.