Strings Inside Walls in N=1 Super Yang-Mills

We conjecture the existence of strings bounded inside walls in SU$(n)$ $\N=1$ Super Yang-Mills theory. These strings carry $\Z_{[k,n]}$ quantum number, where $[k,n]$ is the greatest common divisor between $k$, the charge of the wall, and $n$. We provide field-theoretical arguments and string-theoretical evidences, both from MQCD and from gauge-gravity correspondence. We interpret this result from the point of view of the low-energy effective action living on the $k$-wall.Comment: 25 pp. Major changes. In particular, following the recent work arXiv:0807.1908 we have been able to give a field theoretical proof of the statement. We have also corrected an important erroneous interpretation in the previous version regarding the 2+1 effective action; Typo

Determinant and Weyl anomaly of Dirac operator: a holographic derivation

We present a holographic formula relating functional determinants: the fermion determinant in the one-loop effective action of bulk spinors in an asymptotically locally AdS background, and the determinant of the two-point function of the dual operator at the conformal boundary. The formula originates from AdS/CFT heuristics that map a quantum contribution in the bulk partition function to a subleading large-N contribution in the boundary partition function. We use this holographic picture to address questions in spectral theory and conformal geometry. As an instance, we compute the type-A Weyl anomaly and the determinant of the iterated Dirac operator on round spheres, express the latter in terms of Barnes' multiple gamma function and gain insight into a conjecture by B\"ar and Schopka.Comment: 11 pages; new comments and references added, typos correcte

Embelin as Lead Compound for New Neuroserpin Polymerization Inhibitors

Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a severe and lethal neurodegenerative disease. Upon specific point mutations in the SERPINI1gene-coding for the human protein neuroserpin (NS) the resulting pathologic NS variants polymerize and accumulate within the endoplasmic reticulum of neurons in the central nervous system. To date, embelin (EMB) is the only known inhibitor of NS polymerization in vitro. This molecule is capable of preventing NS polymerization and dissolving preformed polymers. Here, we show that lowering EMB concentration results in increasing size of NS oligomers in vitro. Moreover, we observe that in cells expressing NS, the polymerization of G392E NS is reduced, but this effect is mediated by an increased proteasomal degradation rather than polymerization impairment. For these reasons we designed a systematic chemical evolution of the EMB scaffold aimed to improve its anti-polymerization properties. The effect of EMB analogs against NS polymerization was assessed in vitro. None of the EMB analogs displayed an anti-polymerization activity better than the one reported for EMB, indicating that the EMB\u2013NS interaction surface is very specific and highly optimized. Thus, our results indicate that EMB is, to date, still the best candidate for developing a treatment against NS polymerizatio

Embelin as lead compound for new neuroserpin polymerization inhibitors

Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a severe and lethal neurodegenerative disease. Upon specific point mutations in the SERPINI1gene-coding for the human protein neuroserpin (NS) the resulting pathologic NS variants polymerize and accumulate within the endoplasmic reticulum of neurons in the central nervous system. To date, embelin (EMB) is the only known inhibitor of NS polymerization in vitro. This molecule is capable of preventing NS polymerization and dissolving preformed polymers. Here, we show that lowering EMB concentration results in increasing size of NS oligomers in vitro. Moreover, we observe that in cells expressing NS, the polymerization of G392E NS is reduced, but this effect is mediated by an increased proteasomal degradation rather than polymerization impairment. For these reasons we designed a systematic chemical evolution of the EMB scaffold aimed to improve its anti-polymerization properties. The effect of EMB analogs against NS polymerization was assessed in vitro. None of the EMB analogs displayed an anti-polymerization activity better than the one reported for EMB, indicating that the EMB–NS interaction surface is very specific and highly optimized. Thus, our results indicate that EMB is, to date, still the best candidate for developing a treatment against NS polymerization

Momentum modes of M5-branes in a 2d space

We study M5 branes by considering the selfdual strings parallel to a plane. With the internal oscillation frozen, each selfdual string gives a 5d SYM field. All selfdual strings together give a 6d field with 5 scalars, 3 gauge degrees of freedom and 8 fermionic degrees of freedom in adjoint representation of U(N). Selfdual strings with the same orientation have the SYM-type interaction. For selfdual strings with the different orientations, which could also be taken as the unparallel momentum modes of the 6d field on that plane or the (p,q) (r,s) strings on D3 with (p,q)\neq (r,s), the [i,j]+[j,k]\rightarrow [i,k] relation is not valid, so the coupling cannot be written in terms of the standard N \times N matrix multiplication. 3-string junction, which is the bound state of the unparallel [i,j] [j,k] selfdual strings, may play a role here.Comment: 37 pages, 5 figures, to appear in JHEP; v2: reference adde

Glycosylation Tunes Neuroserpin Physiological and Pathological Properties

Neuroserpin (NS) is a member of the serine protease inhibitors superfamily. Specific point mutations are responsible for its accumulation in the endoplasmic reticulum of neurons that leads to a pathological condition named familial encephalopathy with neuroserpin inclusion bodies (FENIB). Wild-type NS presents two N-glycosylation chains and does not form polymers in vivo, while non-glycosylated NS causes aberrant polymer accumulation in cell models. To date, all in vitro studies have been conducted on bacterially expressed NS, de facto neglecting the role of glycosylation in the biochemical properties of NS. Here, we report the expression and purification of human glycosylated NS (gNS) using a novel eukaryotic expression system, LEXSY. Our results confirm the correct N-glycosylation of wild-type gNS. The fold and stability of gNS are not altered compared to bacterially expressed NS, as demonstrated by the circular dichroism and intrinsic tryptophan fluorescence assays. Intriguingly, gNS displays a remarkably reduced polymerisation propensity compared to non-glycosylated NS, in keeping with what was previously observed for wild-type NS in vivo and in cell models. Thus, our results support the relevance of gNS as a new in vitro tool to study the molecular bases of FENIB

Immune regulation of neurodevelopment at the mother–foetus interface: the case of autism

Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by deficits in social communication and stereotypical behaviours. ASD’s aetiology remains mostly unclear, because of a complex interaction between genetic and environmental factors. Recently, a strong consensus has developed around ASD’s immune-mediated pathophysiology, which is the subject of this review. For many years, neuroimmunological studies tried to understand ASD as a prototypical antibody- or cell-mediated disease. Other findings indicated the importance of autoimmune mechanisms such as familial and individual autoimmunity, adaptive immune abnormalities and the influence of infections during gestation. However, recent studies have challenged the idea that autism may be a classical autoimmune disease. Modern neurodevelopmental immunology shows the double-edged nature of many immune effectors, which can be either beneficial or detrimental depending on tissue homeostasis, stressors, neurodevelopmental stage, inherited and de novo gene mutations and other variables. Nowadays, mother–child interactions in the prenatal environment appear to be crucial for the occurrence of ASD. Studies of animal maternal–foetal immune interaction are being fruitfully carried out using different combinations of type and timing of infection, of maternal immune response and foetal vulnerability and of resilience factors to hostile events. The derailed neuroimmune crosstalk through the placenta initiates and maintains a chronic foetal neuroglial activation, eventually causing the alteration of neurogenesis, migration, synapse formation and pruning. The importance of pregnancy can also allow early immune interventions, which can significantly reduce the increasing risk of ASD and its heavy social burden

The ionization of Mg by electron impact at 1000 eV studied by (e, 2e) experiments

The ionization of Mg 3s and 2p and He 1s has been studied in (e, 2e) experiments at about 1000 eV incident energy and 20 eV ejected electron energy for a momentum transfer between 0.5 and 2.1 au. The comparison with the predictions of the distorted wave Born approximation model shows a generally good agreement between experiment and theory. The differences observed between the He and Mg angular distributions can be explained as an initial state effect and are attributed to the differences between the He 1s and Mg 3s wavefunctions in the momentum space