Atypical processing of auditory temporal complexity in autistics

Autistics exhibit a contrasting combination of auditory behavior, with enhanced pitch processing abilities often coexisting with reduced orienting towards complex speech sounds. Based on an analogous dissociation observed in vision, we expected that autistics’ auditory behavior with respect to complex sound processing may result from atypical activity in non-primary auditory cortex. We employed fMRI to explore the neural basis of complex non-social sound processing in 15 autistic and 13 non-autistics, using a factorial design in which auditory stimuli varied in spectral and temporal complexity. Spectral complexity was modulated by varying the harmonic content, whereas temporal complexity was modulated by varying frequency modulation depth. The detection task was performed similarly by autistics and non-autistics. In both groups, increasing spectral or temporal complexity was associated with activity increases in primary (Heschl's gyrus) and non-primary (anterolateral and posterior superior temporal gyrus) auditory cortex Activity was right-lateralized for spectral and left-lateralized for temporal complexity. Increasing temporal complexity was associated with greater activity in anterolateral superior temporal gyrus in non-autistics and greater effects in Heschl's gyrus in autistics. While we observed similar hierarchical functional organization for auditory processing in both groups, autistics exhibited diminished activity in non-primary auditory cortex and increased activity in primary auditory cortex in response to the presentation of temporally, but not of spectrally complex sounds. Greater temporal complexity effects in regions sensitive to acoustic features and reduced temporal complexity effects in regions sensitive to more abstract sound features could represent a greater focus towards perceptual aspects of speech sounds in autism.     

Acute cranial decompression in Meckel-Gruber syndrome and slit-ventricle syndrome with craniocephalic disproportion

Slit-ventricle syndrome (SVS) is characterized by headaches associated with subnormal ventricular size in patients with shunt-treated hydrocephalus. It commonly occurs in children who have had shunts placed at an early age and is diagnosed when computed tomography scans are carried out to investigate suspected shunt obstruction with an accompanying rise in intracranial pressure (ICP). Overdrainage of cerebrospinal fluid may additionally result in craniocephalic disproportion, potentially by dampening the normal expansile pulsations of the dura against the skull, which leads to craniostenosis. Management is controversial because many strategies have only short-term benefit, and surgical intervention is understandably often seen as a last resort.We present a case of a child with SVS and craniocephalic disproportion who was treated with urgent cranial expansion due to rising ICP. Intraoperative ICP monitoring demonstrates a rapid and sustained drop in ICP, and the patient made an uneventful return to his premorbid condition. We conclude that cranial vault expansion should be considered as an effective treatment for postshunt craniocephalic disproportion in patients with SVS.     

Polymorphic variants of DNMT3A and the risk of endometriosis

Objective

Overexpression of DNA methyltransferase 3A (DNMT3A) and aberrant methylation of various genes in eutopic endometrium have been demonstrated in women with endometriosis. We aimed to study whether DNMT3A polymorphisms could be a genetic risk factor for endometriosis and endometriosis-related infertility.

Study design

We studied 5 SNPs (rs2289195, rs7590760, rs13401241, rs749131 and rs1550117) located in the DNMT3A gene in 357 women with endometriosis and 640 controls.

Results

We did not observe significant differences between genotype and allele frequencies of rs2289195, rs7590760, rs13401241, rs749131 and rs1550117 SNPs in women with endometriosis, endometriosis-related infertility, and controls. The lowest p values of the trend test were observed for DNMT3A rs1550117 in endometriosis and endometriosis-related infertility (p_trend = 0.049 and p_trend = 0.055, respectively).

Conclusions

Our results did not supply evidence for the contribution of SNPs located in DNMT3A to either endometriosis or endometriosis-related infertility.     

Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in diamond-blackfan anemia

Diamond-Blackfan anemia (DBA) is an inherited form of pure red cell aplasia that usually presents in infancy or early childhood and is associated with congenital malformations in ～30-50% of patients. DBA has been associated with mutations in nine ribosomal protein (RP) genes in about 53% of patients. We completed a large-scale screen of 79 RP genes by sequencing 16 RP genes (RPL3, RPL7, RPL8, RPL10, RPL14, RPL17, RPL19, RPL23A, RPL26, RPL27, RPL35, RPL36A, RPL39, RPS4X, RPS4Y1, and RPS21) in 96 DBA probands. We identified a de novo two-nucleotide deletion in RPL26 in one proband associated with multiple severe physical abnormalities. This mutation gives rise to a remarkable ribosome biogenesis defect that affects maturation of both the small and the large subunits. We also found a deletion in RPL19 and missense mutations in RPL3 and RPL23A, which may be variants of unknown significance. Together with RPL5, RPL11, and RPS7, RPL26 is the fourth RP regulating p53 activity that is linked to DBA.     

Sex differences in memory of emotional images: a behavioral and electrophysiological investigation

Current research suggests that emotional responses differ between men and women. Sex differences regarding emotional effects on memory have been recently studied through brain imaging techniques. However, the majority of investigations have often neglected to balance the variable of emotional intensity (arousal) across pleasant and unpleasant pictures. Additionally, men and women were often mixed or studied separately. The current study aims at comparing men and women's electrophysiological responses related to emotional memory of photographic material. These responses were measured using Event Related brain Potentials (ERP) in response to a task of episodic memory of emotional images. The frontal N200, the parietal P300 and the central LPC were compared in 17 men and 17 women matched for age, social economic status, education and intelligence. Behavioral results showed that, in men, reaction times were modulated by valence, whereas for women, reaction times were mainly modulated by arousal. Accuracy was affected by both emotional valence and arousal, but only in women. ERP analyses revealed that emotional valence influenced earlier time components (frontal N200 and parietal P300), whereas arousal influenced memory in the later time component (central LPC). Moreover, sex differences, mediated by valence and arousal, were found in ERP responses at different times in the processing stream.     

Exploring the neural correlates of social stereotyping

Judging people on the basis of cultural stereotypes is a ubiquitous facet of daily life, yet little is known about how this fundamental inferential strategy is implemented in the brain. Using fMRI, we measured neural activity while participants made judgments about the likely actor (i.e., person-focus) and location (i.e., place-focus) of a series of activities, some of which were associated with prevailing gender stereotypes. Results revealed that stereotyping was underpinned by activity in areas associated with evaluative processing (e.g., ventral medial prefrontal cortex, amygdala) and the representation of action knowledge (e.g., supramarginal gyrus, middle temporal gyrus). In addition, activity accompanying stereotypic judgments was correlated with the strength of participants' explicit and implicit gender stereotypes. These findings elucidate how stereotyping fits within the neuroscience of person understanding.     

Evaluation of the In Vitro Cytotoxic Activity of Ursolic Acid PLGA Nanoparticles against Pancreatic Ductal Adenocarcinoma Cell Lines

Among all the types of cancer, Pancreatic Ductal Adenocarcinoma remains one of the deadliest and hardest to fight and there is a critical unmet need for new drugs and therapies for its treatment. Naturally derived compounds, such as pentacyclic triterpenoids, have gathered attention because of their high cytotoxic potential towards pancreatic cancer cells, with a wide biological activity spectrum, with ursolic acid (UA) being one of the most interesting. However, due to its minimal water solubility, it is necessary to prepare a nanocarrier vehicle to aid in the delivery of this compound. Poly(lactic-co-glycolic acid) or PLGA polymeric nanocarriers are an essential tool for ursolic acid delivery and can overcome the lack in its biological activity observed after incorporating within liposomes. We prepared UA-PLGA nanoparticles with a PEG modification, to achieve a long circulation time, by using a nanoprecipitation method and subsequently performed an MTT cytotoxicity assay towards AsPC-1 and BxPC-3 cells, with TEM visualization of the nanoparticles and their cellular uptake. We established repeatable preparation procedures of the nanoparticles and achieved biologically active nanocarriers with an IC50 below 30 µM, with an appropriate size for intravenous dosage (around 140 nm), high sample homogeneity (below 0.2) and reasonable encapsulation efficiency (up to 50%). These results represent the first steps in the development of potentially effective PDAC therapies based on novel biologically active and promising triterpenoids.