Influence of Sulfur-Containing Diamino Acid Structure on Covalently Crosslinked Copolypeptide Hydrogels.

Biologically occurring non-canonical di-α-amino acids were converted into new di-N-carboxyanhydride (di-NCA) monomers in reasonable yields with high purity. Five different di-NCAs were separately copolymerized with tert-butyl-l-glutamate NCA to obtain covalently crosslinked copolypeptides capable of forming hydrogels with varying crosslinker density. Comparison of hydrogel properties with residue structure revealed that different di-α-amino acids were not equivalent in crosslink formation. Notably, l-cystine was found to produce significantly weaker hydrogels compared to l-homocystine, l-cystathionine, and l-lanthionine, suggesting that l-cystine may be a sub-optimal choice of di-α-amino acid for preparation of copolypeptide networks. The di-α-amino acid crosslinkers also provided different chemical stability, where disulfide crosslinks were readily degraded by reduction, and thioether crosslinks were stable against reduction. This difference in response may provide a means to fine tune the reduction sensitivity of polypeptide biomaterial networks

Testing theories of post-error slowing

People tend to slow down after they make an error. This phenomenon, generally referred to as post-error slowing, has been hypothesized to reflect perceptual distraction, time wasted on irrelevant processes, an a priori bias against the response made in error, increased variability in a priori bias, or an increase in response caution. Although the response caution interpretation has dominated the empirical literature, little research has attempted to test this interpretation in the context of a formal process model. Here, we used the drift diffusion model to isolate and identify the psychological processes responsible for post-error slowing. In a very large lexical decision data set, we found that post-error slowing was associated with an increase in response caution and—to a lesser extent—a change in response bias. In the present data set, we found no evidence that post-error slowing is caused by perceptual distraction or time wasted on irrelevant processes. These results support a response-monitoring account of post-error slowing

An Ultra-short Period Rocky Super-Earth with a Secondary Eclipse and a Neptune-like Companion around K2-141

Ultra-short period (USP) planets are a class of low mass planets with periods shorter than one day. Their origin is still unknown, with photo-evaporation of mini-Neptunes and in-situ formation being the most credited hypotheses. Formation scenarios differ radically in the predicted composition of USP planets, it is therefore extremely important to increase the still limited sample of USP planets with precise and accurate mass and density measurements. We report here the characterization of an USP planet with a period of 0.28 days around K2-141 (EPIC 246393474), and the validation of an outer planet with a period of 7.7 days in a grazing transit configuration. We derived the radii of the planets from the K2 light curve and used high-precision radial velocities gathered with the HARPS-N spectrograph for mass measurements. For K2-141b we thus inferred a radius of $1.51\pm0.05~R_\oplus$ and a mass of $5.08\pm0.41~M_\oplus$, consistent with a rocky composition and lack of a thick atmosphere. K2-141c is likely a Neptune-like planet, although due to the grazing transits and the non-detection in the RV dataset, we were not able to put a strong constraint on its density. We also report the detection of secondary eclipses and phase curve variations for K2-141b. The phase variation can be modeled either by a planet with a geometric albedo of $0.30 \pm 0.06$ in the Kepler bandpass, or by thermal emission from the surface of the planet at $\sim$3000K. Only follow-up observations at longer wavelengths will allow us to distinguish between these two scenarios.Comment: 16 pages, 10 figures., accepted for publication in A

Dynamic Assignment and Maintenance of Positional Identity in the Ventral Neural Tube by the Morphogen Sonic Hedgehog

During development of the vertebrate neural tube, cells acquire their positional identity from not only the spatial level of the Sonic Hedgehog signaling gradient, but also the temporal duration

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Influence of Sulfur-Containing Diamino Acid Structure on Covalently Crosslinked Copolypeptide Hydrogels.

Biologically occurring non-canonical di-α-amino acids were converted into new di-N-carboxyanhydride (di-NCA) monomers in reasonable yields with high purity. Five different di-NCAs were separately copolymerized with tert-butyl-l-glutamate NCA to obtain covalently crosslinked copolypeptides capable of forming hydrogels with varying crosslinker density. Comparison of hydrogel properties with residue structure revealed that different di-α-amino acids were not equivalent in crosslink formation. Notably, l-cystine was found to produce significantly weaker hydrogels compared to l-homocystine, l-cystathionine, and l-lanthionine, suggesting that l-cystine may be a sub-optimal choice of di-α-amino acid for preparation of copolypeptide networks. The di-α-amino acid crosslinkers also provided different chemical stability, where disulfide crosslinks were readily degraded by reduction, and thioether crosslinks were stable against reduction. This difference in response may provide a means to fine tune the reduction sensitivity of polypeptide biomaterial networks