Time-dependent Nonlinear Optical Susceptibility of an Out-of-Equilibrium Soft Material

We investigate the time-dependent nonlinear optical absorption of a clay dispersion (Laponite) in organic dye (Rhodamine B) water solution displaying liquid-arrested state transition. Specifically, we determine the characteristic time $\tau_D$ of the nonlinear susceptibility build-up due as to the Soret effect. By comparing $\tau_D$ with the relaxation time provided by standard dynamic light scattering measurements we report on the decoupling of the two collective diffusion times at the two very different length scales during the aging of the out-of-equilibrium system. With this demonstration experiment we also show the potentiality of nonlinear optics measurements in the study of the late stage of arrest in soft materials

Laser beam filamentation in fractal aggregates

We investigate filamentation of a cw laser beam in soft matter such as colloidal suspensions and fractal gels. The process, driven by electrostriction, is strongly affected by material properties, which are taken into account via the static structure factor, and have impact on the statistics of the light filaments.Comment: 4 pages, 5 figures. Revised version with corrected figure 5. To be published in Phys. Rev. Let

Intra-arterial Onyx Embolization of Vertebral Body Lesions

While Onyx embolization of cerebrospinal arteriovenous shunts is well-established, clinical researchers continue to broaden applications to other vascular lesions of the neuraxis. This report illustrates the application of Onyx (eV3, Plymouth, MN) embolization to vertebral body lesions, specifically, a vertebral hemangioma and renal cell carcinoma vertebral body metastatic lesion

Idiopatski i sekundarni stečeni megakolon kod pasa udruženi su sa smanjenom vip-inervacijom u oštećenom kolonu

It is well established that megacolon in carnivores, including both cats and dogs, is a common finding. Megacolon occurs more often in the cat that the dog. Based on current data idiopathic megacolon is a common cause of constipation in cats (62% of constipated cats are affected by diopathic megacolon). There is no evidence of idiopathic megacolon in dogs and publications about this disease in this species is very scarce. We investigated the enteric nervous system in the dilated portion (DP) of the colon in dogs with idiopathic aquired (n=7) or secondary aquired megacolon (n=21) and compared the results with a normal colon in control dogs (n=3). Colonic sections of surgical specimens were investigated by conventional and immunohistochemical methods, including pan-neuronal markers (NSE, synaptophisin, and neurofilament) and VIP, as well as S-100 protein for detection of ganglionic glial cells. Compared to controls, the two megacolon groups showed no changes of density of enteric neurons in both submucosal and myenteric nervous plexuses in DP of the colon and of enteric glial cells. However, compared to controls and dogs with secondary megacolon, there was a significant decrease in the density of NFP-ir nerve fibers in the longitudinal muscle layer in dogs with idiopathic acquired megacolon. In addition, dogs with idiopathic megacolon display decreased VIP-ir in the myenteric plexus and lamina propria mucosae, and absence of VIP-ir neurons in the submucosal plexus of DP of the colon. Similar alterations, although of lesser severity, may be found in dogs with secondary aquired megacolon. We consider that both idiopathic and secondary aquired megacolon might occur on the basis of a dysplastic changes of VIP-ir enteric neurons.Poznato je da se magakolon javlja kod mesojeda, uključujući mačke i pse, pri čemu je ovo oboljenje daleko učestalije kod mačaka. Na osnovu dosadašnjih saznanja, idiopatski megakolon je čest uzročnik konstipacije kod mačaka i 62% mačaka sa konstipacijom ima idiopatski megakolon. Istovremeno, podaci o psima sa idiopatskim megakolonom veoma su oskudni. U ovom radu je proučavan enterični nervni sistem u dilatiranom delu kolona kod 7 pasa sa idiopatskim megakolonom i 21 psa sa sekundarnim stečenim megakolonom, a rezultati su upoređeni sa normalnim kolonom kod 3 kontrolne zdrave životinje. Tkivni preseci kolona bojeni su klasičnim histološkim i imunohistohemijskim metodama, pri čemu su primenjeni pan-neuronski markeri (NSE, sinaptofizin i neurofilament) i VIP, kao i S-100 protein za detekciju glijalnih ćelija u enteričnim ganglijama. Nisu otkrivene razlike u gustini enteričnih neurona u submukoznom i mijenteričnom pleksusu kod životinja sa megakolonom, kao ni razlike u gustini glijalnih ćelija enteričnih ganglija, u odnosu na kontrolnu grupu životinja. Međutim, u odnosu na kontrolnu grupu, kod životinja sa idiopatskim megakolonom dokazana je smanjena VIP-imunoreaktivnost (ir) u mienteričnom pleksusu i krznu mukoze, kao i kompletno odsustvo VIP-ir neurona u submukoznom pleksusu dilatiranog dela kolona. Slične promene, ali u manjem stepenu, postojale su kod pasa sa sekundarnim stečenim megakolonom. Može da se zaključi da u patogenezi idiopatskog i sekundarnog stečenog megakolona značajnu ulogu imaju displastične promene u VIP-ergičkim neuronima enteričkog nervnog sistema

Effect of sodium valproate on the conformational stability of the visual G Protein-coupled receptor rhodopsin

Rhodopsin is the G protein-coupled receptor of rod photoreceptor cells that mediates vertebrate vision at low light intensities. Mutations in rhodopsin cause inherited retinal degenerative diseases such as retinitis pigmentosa. Several therapeutic strategies have attempted to address and counteract the deleterious effect of rhodopsin mutations on the conformation and function of this photoreceptor protein, but none has been successful in efficiently preventing retinal degeneration in humans. These approaches include, among others, the use of small molecules, known as pharmacological chaperones, that bind to the receptor stabilizing its proper folded conformation. Valproic acid, in its sodium valproate form, has been used as an anticonvulsant in epileptic patients and in the treatment of several psychiatric disorders. More recently, this compound has been tested as a potential therapeutic agent for the treatment of retinal degeneration associated with retinitis pigmentosa caused by rhodopsin mutations. We now report on the effect of sodium valproate on the conformational stability of heterologously expressed wild-type rhodopsin and a rhodopsin mutant, I307N, which has been shown to be an appropriate model for studying retinal degeneration in mice. We found no sign of enhanced stability for the dark inactive conformation of the I307N mutant. Furthermore, the photoactivated conformation of the mutant appears to be destabilized by sodium valproate as indicated by a faster decay of its active conformation. Therefore, our results support a destabilizing effect of sodium valproate on rhodopsin I307N mutant associated with retinal degeneration. These findings, at the molecular level, agree with recent clinical studies reporting negative effects of sodium valproate on the visual function of retinitis pigmentosa patients.This research was supported by grant PID2019-104817GB-I00 from Ministerio de Ciencia e Innovación (MICINN).Peer ReviewedPostprint (published version

Individual and collective stock dynamics: intra-day seasonalities

We establish several new stylised facts concerning the intra-day seasonalities of stock dynamics. Beyond the well known U-shaped pattern of the volatility, we find that the average correlation between stocks increases throughout the day, leading to a smaller relative dispersion between stocks. Somewhat paradoxically, the kurtosis (a measure of volatility surprises) reaches a minimum at the open of the market, when the volatility is at its peak. We confirm that the dispersion kurtosis is a markedly decreasing function of the index return. This means that during large market swings, the idiosyncratic component of the stock dynamics becomes sub-dominant. In a nutshell, early hours of trading are dominated by idiosyncratic or sector specific effects with little surprises, whereas the influence of the market factor increases throughout the day, and surprises become more frequent.Comment: 9 pages, 7 figure

ΔNp73, A Dominant-Negative Inhibitor of Wild-type p53 and TAp73, Is Up-regulated in Human Tumors

p73 has significant homology to p53. However, tumor-associated up-regulation of p73 and genetic data from human tumors and p73-deficient mice exclude a classical Knudson-type tumor suppressor role. We report that the human TP73 gene generates an NH2 terminally truncated isoform. ΔNp73 derives from an alternative promoter in intron 3 and lacks the transactivation domain of full-length TAp73. ΔNp73 is frequently overexpressed in a variety of human cancers, but not in normal tissues. ΔNp73 acts as a potent transdominant inhibitor of wild-type p53 and transactivation-competent TAp73. ΔNp73 efficiently counteracts transactivation function, apoptosis, and growth suppression mediated by wild-type p53 and TAp73, and confers drug resistance to wild-type p53 harboring tumor cells. Conversely, down-regulation of endogenous ΔNp73 levels by antisense methods alleviates its suppressive action and enhances p53- and TAp73-mediated apoptosis. ΔNp73 is complexed with wild-type p53, as demonstrated by coimmunoprecipitation from cultured cells and primary tumors. Thus, ΔNp73 mediates a novel inactivation mechanism of p53 and TAp73 via a dominant-negative family network. Deregulated expression of ΔNp73 can bestow oncogenic activity upon the TP73 gene by functionally inactivating the suppressor action of p53 and TAp73. This trait might be selected for in human cancers

Paraneoplastic cerebellar degeneration as a presentation of breast cancer – a case report and review of the literature

Paraneoplastic cerebellar degeneration is part of a rare spectrum of neurological syndromes whereby gynaecological, lung or breast cancers present primarily with neurological manifestations. The presence of onconeural antibodies and PET scanning help in the challenging diagnosis of these conditions but despite the treatment of the primary cancer, the prognosis for the neurological symptoms is poor

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of big data (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA\u27s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Common Alzheimer's disease risk variant within the CLU gene affects white matter microstructure in young adults

There is a strong genetic risk for late-onset Alzheimer's disease (AD), but so far few gene variants have been identified that reliably contribute to that risk. A newly confirmed genetic risk allele C of the clusterin (CLU) gene variant rs11136000 is carried by similar to 88% of Caucasians. The C allele confers a 1.16 greater odds of developing late-onset AD than the T allele. AD patients have reductions in regional white matter integrity. We evaluated whether the CLU risk variant was similarly associated with lower white matter integrity in healthy young humans. Evidence of early brain differences would offer a target for intervention decades before symptom onset. We scanned 398 healthy young adults (mean age, 23.6 +/- 2.2 years) with diffusion tensor imaging, a variation of magnetic resonance imaging sensitive to white matter integrity in the living brain. We assessed genetic associations using mixed-model regression at each point in the brain to map the profile of these associations with white matter integrity. Each Callele copy of the CLU variant was associated with lower fractional anisotropy-a widely accepted measure of white matter integrity-in multiple brain regions, including several known to degenerate in AD. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. Young healthy carriers of the CLU gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing AD later in life