Neural representations of absolute and relative magnitudes in symbolic and nonsymbolic formats.

Humans differ from other animal species in their unique ability to use symbols to represent numerical information. This ability is thought to emerge from the "neural recycling" of mechanisms supporting nonsymbolic magnitudes in the intraparietal sulcus (IPS), a hypothesis that has been applied to both absolute magnitudes (e.g., whole numbers) and relative magnitudes (e.g., fractions). Yet, evidence for the neuronal recycling hypothesis is inconsistent for absolute magnitudes and scarce for relative magnitudes. Here, we investigated to what extent the neural representations of absolute and relative magnitudes in symbolic and nonsymbolic formats overlap in the IPS. In a functional magnetic resonance imaging (fMRI) adaptation design, 48 adult participants were sequentially presented with lines, whole numbers, line ratios, and fractions that varied (vs. not varied) in magnitudes. Univariate analyses showed that the extent to which IPS mechanisms associated with whole numbers relied on mechanisms associated with lines depended upon participants' arithmetic fluency. Multivariate analyses revealed that the right IPS encoded differences in format (nonsymbolic vs. symbolic) across both absolute and relative magnitudes. Therefore, IPS activity associated with magnitude processing may depend on the presentation format (nonsymbolic vs. symbolic) more than it depends on the type of magnitude (absolute vs. relative), at least for most adult participants.

The ratio processing system and its role in fraction understanding: Evidence from a match-to-sample task in children and adults with and without dyscalculia.

It has been hypothesised that the human neurocognitive architecture may include a perceptual ratio processing system (RPS) that supports symbolic fraction understanding. In the present study, we aimed to provide further evidence for the existence of the RPS by exploring whether individuals with a range of math skills are indeed perceptually sensitive to non-symbolic ratio magnitudes. We also aimed to test to what extent the RPS may underlie symbolic fraction processing in those individuals. In a match-to-sample task, typical adults, elementary school children, and adults with dyscalculia were asked to match a non-symbolic ratio (i.e., target) to one of two non-symbolic ratios (i.e., the match and distractor). We found that all groups of participants were sensitive to the ratio between the match and the distractor, suggesting a common reliance on the RPS. This ratio sensitivity was also observed in another group of typical adults who had to choose which of two symbolic fractions match a non-symbolic ratio, indicating that the RPS may also contribute to symbolic fraction understanding. However, no ratio dependence was observed when participants had to choose which of two symbolic fractions match another symbolic fraction, suggesting that reliance on the RPS in symbolic fraction processing is limited and may not support exact fraction processing.

Azadirachtin inhibits amyloid formation, disaggregates pre-formed fibrils and protects pancreatic ß-cells from human islet amyloid polypeptide/amylin-induced cytotoxicity.

The human islet amyloid polypeptide (hIAPP) or amylin is the major constituent of amyloidogenic aggregates found in pancreatic islets of type 2 diabetic patients that have been associated with ß-cell dysfunction and/or death associated with type 2 diabetes mellitus (T2DM). Therefore, developing and/or identifying inhibitors of hIAPP aggregation pathway and/or compound that can mediate disaggregation of preformed aggregates holds promise as a medical intervention for T2DM management. In the current study, the anti-amyloidogenic potential of Azadirachtin (AZD)-a secondary metabolite isolated from traditional medicinal plant Neem (Azadirachta indica)-was investigated by using a combination of biophysical and cellular assays. Our results indicate that AZD supplementation not only inhibits hIAPP aggregation but also disaggregates pre-existing hIAPP fibrils by forming amorphous aggregates that are non-toxic to pancreatic ß-cells. Furthermore, AZD supplementation in pancreatic ß-cells (INS-1E) resulted in inhibition of oxidative stress; along with restoration of the DNA damage, lipid peroxidation and the associated membrane damage, endoplasmic reticulum stress and mitochondrial membrane potential. AZD treatment also restored glucose-stimulated insulin secretion from pancreatic islets exposed to hIAPP. All-atom molecular dynamics simulation studies on full-length hIAPP pentamer with AZD suggested that AZD interacted with four possible binding sites in the amyloidogenic region of hIAPP. In summary, our results suggest AZD to be a promising candidate for combating T2DM and related amyloidogenic disorders.

miRNAs: early prognostic biomarkers for Type 2 diabetes mellitus?

Type 2 diabetes mellitus (T2DM) has reached epidemic proportions and is associated with peripheral insulin resistance. The currently used therapies aim to delay progression of T2DM. Their efficacy could drastically be improved if implemented at earlier stages. Classical diagnostic markers (blood glucose and HbA1C) are generally detected once metabolic imbalance has already set in. Therefore, development of biomarkers for early diagnosis would help identify individuals at risk for developing T2DM. Along with genetic predisposition, epigenetics also plays a major role in T2DM development. In this review, we discuss the potential role of early diagnostic markers such as circulating miRNAs, studies done so far and challenges to be considered while taking into account the novel role of miRNAs as prognostic biomarkers.