A Formal Treatment of Generalized Preferential Attachment and its Empirical Validation

Generalized preferential attachment is defined as the tendency of a vertex to acquire new links in the future with respect to a particular vertex property. Understanding which properties influence link acquisition tendency (LAT) gives us a predictive power to estimate the future growth of network and insight about the actual dynamics governing the complex networks. In this study, we explore the effect of age and degree on LAT by analyzing data collected from a new complex-network growth dataset. We found that LAT and degree of a vertex are linearly correlated in accordance with previous studies. Interestingly, the relation between LAT and age of a vertex is found to be in conflict with the known models of network growth. We identified three different periods in the network's lifetime where the relation between age and LAT is strongly positive, almost stationary and negative correspondingly

Determination of ochratoxin a in baby foods by ELISA and HPLC

Ochratoxin A, is a well-known nephrotoxic, hepatotoxic and carcinogenic mycotoxin, produced by some species of mould genera such as Aspergillus spp. and Penicillium spp. under various environmental conditions, such as moisture and temperature. The main sources of Ochratoxin A intake for humans are cereals and cereal derived products, when they are consumed in large quantities, as in the case of breakfast cereals and cereal based baby foods principally consumed by babies. In this study, a total of 150 samples (50 infant formulas, 50 follow-on formulas, and 50 cereal based supplementary foods for infants and children) were obtained randomly from various supermarkets and pharmacies in Istanbul, and 52 out of 150 (34.7%) analysed samples were contaminated with Ochratoxin A. None of the examined baby food samples were above the Turkish Food Codex maximum limit of Ochratoxin A in baby, infant, and young children foods (0.5 μg kg−1). These results reinforce the idea of strict and routine quality controls and good hygiene practices have to be performed in every step of production to minimize the potential risk of Ochratoxin A contamination

Synthesis of 4,5-disubstituted-2-thioxo-1,2,3,4-tetrahydropyrimidines and investigation of their acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase I/II inhibitory and antioxidant activities.

A series of tetrahydropyrimidinethiones were synthesized from thiourea, β-diketones and aromatic aldehydes, such as p-tolualdehyde, p-anisaldehyde, o-tolualdehyde, salicylaldehyde and benzaldehyde. These cyclic thioureas showed good inhibitory action against acetylcholine esterase (AChE), butyrylcholine esterase (BChE), and human (h) carbonic anhydrase (CA) isoforms I and II. AChE and BChE inhibitions were in the range of 6.11-16.13 and 6.76-15.68 nM, respectively. hCA I and II were effectively inhibited by these compounds, with Ki values in the range of 47.40-76.06 nM for hCA I, and of 30.63-76.06 nM for hCA II, respectively. The antioxidant activity of the cyclic thioureas was investigated by using different in vitro antioxidant assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH·) radical scavenging, Cu2+ and Fe3+ reducing, and Fe2+ chelating activities

Activity Dependent Protein Degradation Is Critical for the Formation and Stability of Fear Memory in the Amygdala

Protein degradation through the ubiquitin-proteasome system [UPS] plays a critical role in some forms of synaptic plasticity. However, its role in memory formation in the amygdala, a site critical for the formation of fear memories, currently remains unknown. Here we provide the first evidence that protein degradation through the UPS is critically engaged at amygdala synapses during memory formation and retrieval. Fear conditioning results in NMDA-dependent increases in degradation-specific polyubiquitination in the amygdala, targeting proteins involved in translational control and synaptic structure and blocking the degradation of these proteins significantly impairs long-term memory. Furthermore, retrieval of fear memory results in a second wave of NMDA-dependent polyubiquitination that targets proteins involved in translational silencing and synaptic structure and is critical for memory updating following recall. These results indicate that UPS-mediated protein degradation is a major regulator of synaptic plasticity necessary for the formation and stability of long-term memories at amygdala synapses

Human Neurobrucellosis with Intracerebral Granuloma Caused by a Marine Mammal Brucella spp.

We present the first report of community-acquired human infections with marine mammal–associated Brucella spp. and describe the identification of these strains in two patients with neurobrucellosis and intracerebral granulomas. The identification of these isolates as marine mammal strains was based on omp2a sequence and amplification of the region flanking bp26

Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy

Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ΔΨm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control

The pharmacological regulation of cellular mitophagy

Small molecules are pharmacological tools of considerable value for dissecting complex biological processes and identifying potential therapeutic interventions. Recently, the cellular quality-control process of mitophagy has attracted considerable research interest; however, the limited availability of suitable chemical probes has restricted our understanding of the molecular mechanisms involved. Current approaches to initiate mitophagy include acute dissipation of the mitochondrial membrane potential (ΔΨm) by mitochondrial uncouplers (for example, FCCP/CCCP) and the use of antimycin A and oligomycin to impair respiration. Both approaches impair mitochondrial homeostasis and therefore limit the scope for dissection of subtle, bioenergy-related regulatory phenomena. Recently, novel mitophagy activators acting independently of the respiration collapse have been reported, offering new opportunities to understand the process and potential for therapeutic exploitation. We have summarized the current status of mitophagy modulators and analyzed the available chemical tools, commenting on their advantages, limitations and current applications