Tunable supramolecular gel properties by varying thermal history

YesThe possibility of using differential pre‐heating prior to supramolecular gelation to control the balance between hydrogen‐bonding and aromatic stacking interactions in supramolecular gels and obtain consequent systematic regulation of structure and properties is demonstrated. Using a model aromatic peptide amphiphile, Fmoc‐tyrosyl‐leucine (Fmoc‐YL) and a combination of fluorescence, infrared, circular dichroism and NMR spectroscopy, it is shown that the balance of these interactions can be adjusted by temporary exposure to elevated temperatures in the range 313–365 K, followed by supramolecular locking in the gel state by cooling to room temperature. Distinct regimes can be identified regarding the balance between H‐bonding and aromatic stacking interactions, with a transition point at 333 K. Consequently, gels can be obtained with customizable properties, including supramolecular chirality and gel stiffness. The differential supramolecular structures also result in changes in proteolytic stability, highlighting the possibility of obtaining a range of supramolecular architectures from a single molecular structure by simply controlling the pre‐assembly temperature.FP7 Ideas: European Research Council. Grant Number: 25877

Unravelling the temporal association between lameness and body condition score in dairy cattle using a multistate modelling approach

Recent studies have reported associations between lameness and body condition score (BCS) in dairy cattle, however the impact of change in the dynamics of BCS on both lameness occurrence and recovery is currently unknown. The aim of this study was to investigate in a longitudinal study the effect of change in BCS on the transitions from the non-lame to lame, and lame to non-lame states. A total of 731 cows with 6889 observations from 4 UK herds were included in the study. Mobility score (MS) and body condition score (BCS) were recorded every 13-15 days from July 2010 until December 2011. A multilevel multistate discrete time event history model was built to investigate the transition of lameness over time. There were 1042 non-lame episodes and 593 lame episodes of which approximately 50% (519/1042) of the non-lame episodes transitioned to the lame state and 81% (483/593) of the lame episodes ended with a transition to the non-lame state. Cows with a lower BCS at calving (BCS Group 1 (1.00-1.75) and Group 2 (2.00-2.25)) had a higher probability of transition from non-lame to lame and a lower probability of transition from lame to non-lame compared to cows with BCS 2.50-2.75 i.e. they were more likely to become lame and if lame, they were less likely to recover. Similarly, cows who suffered a greater decrease in BCS (compared to their BCS at calving) had a higher probability of becoming lame and a lower probability of recovering in the next 15 days. An increase in BCS from calving was associated with the converse effect i.e. a lower probability of cows moving from the non-lame to the lame state and higher probability of transition from lame to non-lame. Days of lactation, months of calving and parity was associated with both lame and non-lame transitions and there was evidence of heterogeneity among cows in lameness occurrence and recovery. This study suggests loss of BCS and increase of BCS could influence the risk of becoming lame and the chance of recovery from lameness. Regular monitoring and maintenance of BCS on farms could be a key tool for reducing lameness. Further work is urgently needed in this area to allow a better understanding of the underlying mechanisms behind these relationships

Balancing end-to-end budgets of the Georges Bank ecosystem

Author Posting. © Elsevier, 2007. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Progress In Oceanography 74 (2007): 423-448, doi:10.1016/j.pocean.2007.05.003.Oceanographic regimes on the continental shelf display a great range in the time scales of physical exchange, biochemical processes and trophic transfers. The close surface-to-seabed physical coupling at intermediate scales of weeks to months means that the open ocean simplification to a purely pelagic food web is inadequate. Top-down trophic depictions, starting from the fish populations, are insufficient to constrain a system involving extensive nutrient recycling at lower trophic levels and subject to physical forcing as well as fishing. These pelagic-benthic interactions are found on all continental shelves but are particularly important on the relatively shallow Georges Bank in the northwest Atlantic. We have generated budgets for the lower food web for three physical regimes (well mixed, transitional and stratified) and for three seasons (spring, summer and fall/winter). The calculations show that vertical mixing and lateral exchange between the three regimes are important for zooplankton production as well as for nutrient input. Benthic suspension feeders are an additional critical pathway for transfers to higher trophic levels. Estimates of production by mesozooplankton, benthic suspension feeders and deposit feeders, derived primarily from data collected during the GLOBEC years of 1995-1999, provide input to an upper food web. Diets of commercial fish populations are used to calculate food requirements in three fish categories, planktivores, benthivores and piscivores, for four decades, 1963-2002, between which there were major changes in the fish communities. Comparisons of inputs from the lower web with fish energetic requirements for plankton and benthos indicate that we obtained reasonable agreement for the last three decades, 1973 to 2002. However, for the first decade, the fish food requirements were significantly less than the inputs. This decade, 1963-1972, corresponds to a period characterized by a strong Labrador Current and lower nitrate levels at the shelf edge, demonstrating how strong bottom-up physical forcing may determine overall fish yields.The research was done under the aegis of the U.S.-GLOBEC Northwest Atlantic Georges Bank Study, a program sponsored jointly by the U.S. National Science Foundation and the U.S. National Oceanic and Atmospheric Administration. We acknowledge NOAA-CICOR award NA17RJ1233 (J.H. Steele), NSF awards OCE0217399 (D.J. Gifford), OCE0217122 (J.J. Bisagni) and OCE0217257 (M.E. Sieracki). W.T. Stockhausen was supported by the NOAA Sponsored Coastal Ocean Research Program

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Two-component dendritic gel: Effect of spacer chain length on the supramolecular chiral assembly

Contains fulltext : 60356.pdf (publisher's version ) (Closed access)The present study investigates in detail the physical gelation of toluene induced by the addition of simple aliphatic diamines to a dendritic L-lysine-based peptide. The gel-phase material obtained was characterized using differential scanning calorimetry, scanning electron microscopy, small-angle X-ray scattering, circular dichroism, H-1 NMR, and X-ray diffraction. When the length of the aliphatic diamine is incrementally increased (C6-C12), the thermally reversible gel-sol transition temperature is dramatically increased (4-105 degreesC). This paper shows that the molecular information preset in the diamine is transcribed into the supramolecular assembly on the microscale and that this, in turn, controls the highly tunable macroscopic materials properties. The results also demonstrate the importance of chirality in the assembly process and highlight the role played by the aliphatic diamine in modulating the transcription of chirality from the molecular to the microscopic level.8 p

A direct comparison of one- and two-component dendritic self-assembled materials: elucidating molecular recognition pathways

This paper compares and contrasts, for the first time, one- and two-component gelation systems that are direct structural analogues and draws conclusions about the molecular recognition pathways that underpin fibrillar self-assembly. The new one-component systems comprise L-lysine-based dendritic headgroups covalently connected to an aliphatic diamine spacer chain via an amide bond, One-component gelators with different generations of headgroup (from first to third generation) and different length spacer chains are reported. The self-assembly of these dendrimers in toluene was elucidated using thermal measurements, circular dichroism (CD) and NMR spectroscopies, scanning electron microscopy (SEM), and small-angle X-ray scattering (SAXS). The observations are compared with previous results for the analogous two-component gelation system in which the dendritic headgroups are bound to the aliphatic spacer chain noncovalently via acid-amine interactions. The one-component system is inherently a more effective gelator, partly as a consequence of the additional covalent amide groups that provide a new hydrogen bonding molecular recognition pathway, whereas the two-component analogue relies solely on intermolecular hydrogen bond interactions between the chiral dendritic headgroups. Furthermore, because these amide groups are important in the assembly process for the one-component system, the chiral information preset in the dendritic headgroups is not always transcribed into the nanoscale assembly, whereas for the two-component system, fiber formation is always accompanied by chiral ordering because the molecular recognition pathway is completely dependent on hydrogen bond interactions between well-organized chiral dendritic headgroups

Introducing chemical functionality in fmoc-peptide gels for cell culture

Aromatic short peptide derivatives, i.e. peptides modified with aromatic groups such as 9-fluorenylmethoxycarbonyl (Fmoc), can self-assemble into self-supporting hydrogels. These hydrogels have some similarities to extracellular matrices due to their high hydration, relative stiffness and nanofibrous architecture. We previously demonstrated that Fmoc-diphenylalanine (Fmoc-F2) provides a suitable matrix for two-dimensional (2D) or three-dimensional (3D) culture of primary bovine chondrocytes. In this paper we investigate whether the introduction of chemical functionality, such as NH2, COOH or OH, enhances compatibility with different cell types. A series of hydrogel compositions consisting of combinations of Fmoc-F2 and n-protected Fmoc amino acids, lysine (K, with side chain R = (CH2)4NH2), glutamic acid (D, with side chain R = CH2COOH), and serine (S, with side chain R = CH2OH) were studied. All compositions produced fibrous scaffolds with fibre diameters in the range of 32-65 nm as assessed by cryo-scanning electron microscopy and atomic force microscopy. Fourier transform infrared spectroscopy analysis suggested that peptide segments adopt a predominantly antiparallel β-sheet conformation. Oscillatory rheology results show that all four hydrogels have mechanical profiles of soft viscoelastic materials with elastic moduli dependent on the chemical composition, ranging from 502 Pa (Fmoc-F2/D) to 21.2 KPa (Fmoc-F2). All gels supported the viability of bovine chondrocytes as assessed by a live-dead staining assay. Fmoc-F2/S and Fmoc-F2/D hydrogels in addition supported viability for human dermal fibroblasts (HDF) while Fmoc-F2/S hydrogel was the only gel type that supported viability for all three cell types tested. Fmoc-F2/S was therefore investigated further by studying cell proliferation, cytoskeletal organization and histological analysis in 2D culture. In addition, the Fmoc-F2/S gel was shown to support retention of cell morphology in 3D culture of bovine chondrocytes. These results demonstrate that introduction of chemical functionality into Fmoc-peptide scaffolds may provide gels with tunable chemical and mechanical properties for in vitro cell culture