Binding of Translationally Controlled Tumour Protein to the N-Terminal Domain of HDM2 Is Inhibited by Nutlin-3

Translationally Controlled Tumour Protein (TCTP), a highly conserved protein present in all eukaryotic organisms, has a number of intracellular and extracellular functions including an anti-apoptotic role. TCTP was recently shown to interact with both p53 and HDM2, inhibiting auto-ubiquitination of the latter and thereby promoting p53 degradation. In this study, we further investigated the interaction between TCTP and HDM2, mapping the reciprocal binding sites of TCTP and HDM2. TCTP primarily interacts with the N-terminal, p53-binding region of HDM2 through its highly basic domain 2. Furthermore, we discovered that Nutlin-3, a small molecule known to promote apoptosis and cell cycle arrest by blocking binding between HDM2 and p53, has a similar inhibitory effect on the interaction of HDM2 and TCTP. This result may provide an additional explanation of how Nutlin-derived compounds currently in clinical trials function to promote apoptosis in cancer cells.     

Cross-cultural variation in men's preference for sexual dimorphism in women's faces

Both attractiveness judgements and mate preferences vary considerably cross-culturally. We investigated whether men''s preference for femininity in women''s faces varies between 28 countries with diverse health conditions by analysing responses of 1972 heterosexual participants. Although men in all countries preferred feminized over masculinized female faces, we found substantial differences between countries in the magnitude of men''s preferences. Using an average femininity preference for each country, we found men''s facial femininity preferences correlated positively with the health of the nation, which explained 50.4% of the variation among countries. The weakest preferences for femininity were found in Nepal and strongest in Japan. As high femininity in women is associated with lower success in competition for resources and lower dominance, it is possible that in harsher environments, men prefer cues to resource holding potential over high fecundity.     

Polycyclic aromatic hydrocarbons (PAHs) in urban soils of Ahvaz metropolis; contamination,composition, distribution,potential sources,and cancer risk

Sixteen polycyclic aromatic hydrocarbons (PAHs) were investigated in urban soils of Ahvaz metropolis to assess the contamination, distribution, potential sources, and related health risks for local residents. For this purpose, a total of 39 topsoil samples from different parts of the city were collected and analyzed for PAHs using gas chromatography–mass spectrometry. PAHs analysis revealed that 4 -rings PAHs are the dominant compounds. Distribution maps revealed that outlet roads of the city and an area in city center, particularly an industrial area at Southwest of the city, West Saheli street, Pasdaran Blvd, Ahvaz-Ramhormoz Police Station, Khorramshahr bus terminal, and Daneshgah Square, are the contamination hotspots. PAHs diagnostic ratios and principal component analysis (PCA) showed both petrogenic and pyrogenic sources for these compounds, although, the results indicated the dominance of pyrogenic (combustion) origin, particularly traffic emission, incomplete combustion of fossil fuels and gasoline emissions. Furthermore, calculation of toxic equivalents and cancer risk showed a high carcinogenic risk especially through dermal contact and ingestion pathways; however, compared with adults, children faced more cancer risk in their daily life through their unconscious ingestion and dermal contact pathway.     

ATP-bound conformation of topoisomerase IV: a possible target for quinolones in Streptococcus pneumoniae

Topoisomerase IV, a C(2)E(2) tetramer, is involved in the topological changes of DNA during replication. This enzyme is the target of antibacterial compounds, such as the coumarins, which target the ATP binding site in the ParE subunit, and the quinolones, which bind, outside the active site, to the quinolone resistance-determining region (QRDR). After site-directed and random mutagenesis, we found some mutations in the ATP binding site of ParE near the dimeric interface and outside the QRDR that conferred quinolone resistance to Streptococcus pneumoniae, a bacterial pathogen. Modeling of the N-terminal, 43-kDa ParE domain of S. pneumoniae revealed that the most frequent mutations affected conserved residues, among them His43 and His103, which are involved in the hydrogen bond network supporting ATP hydrolysis, and Met31, at the dimeric interface. All mutants showed a particular phenotype of resistance to fluoroquinolones and an increase in susceptibility to novobiocin. All mutations in ParE resulted in resistance only when associated with a mutation in the QRDR of the GyrA subunit. Our models of the closed and open conformations of the active site indicate that quinolones preferentially target topoisomerase IV of S. pneumoniae in its ATP-bound closed conformation.     

The endangered forests of Bangladesh: why the process of implementation of the Convention on Biological Diversity is not working

Bangladesh has been a signatory to the Convention on Biological Diversity (CBD) although implementation of the convention has been poor. We independently assessed the extent to which the program of work (POW) of the CBD has been implemented in Bangladesh by carrying out workshops involving local communities, conservation organizations, universities, and government departments involved in forest conservation. Our analyses indicate that there is little or no understanding of the ecosystem approach that is central to the CBD; forestry practices remain primitive and largely ineffective; forest destruction continues at high rates; restoration of degraded forests are minimal; protected areas are small and ineffective; indigenous peoples’ rights are nominal and are outside any legislation; threats to species have been identified, but little is being done to reduce threats; there is no work on pollution and its mitigation; some work has been done to adapt to climate change; the institutional environment does not enable effective implementation of the ecosystem approach; laws and policies are ineffective; institutional capacity is poor; government will is limited or totally lacking; and knowledge base remains poor, although reporting has improved and various strategic plans have been formulated but never implemented. Thus, the implementation of CBD in Bangladesh requires systemic changes in policy at the institutional levels as well as complementary changes in attitudes and avenues of alternate income generation.     

Sleep and psychological factors are associated with meeting discharge criteria to return to sport following ACL reconstruction in athletes

This study aimed to determine if sleep quality and psychological factors were associated with time to meet the discharge criteria to return to sport (RTS) following anterior cruciate ligament reconstruction (ACL-R) among athletes. A cohort-study design included 89 athletes following ACL-R. Each participant completed a battery of questionnaires at 6 different time points: within 3 days of injury occurrence and at post-surgery (1.5 m, 3 m, 4.5 m, 6 m and when discharge criteria were met). Assessment included sleep quality and quantity, symptoms of depression, anxiety, stress, psychological readiness to RTS and fear of re-injury. The primary outcome was the time needed to meet all discharge criteria to RTS. Sleep parameters and psychological factors were not associated with time to meet the discharge criteria to RTS. However, athletes that had lower scores of anxiety (OR 1.2 (95% CI 1.0, 1.3) and insomnia (OR 1.2 (95% CI 1.0, 1.3) at baseline were more likely to meet the RTS discharge criteria. Athletes with better sleep quality at 3m, 4.5m and 6m were more likely to meet the RTS discharge criteria OR 1.3 (95% CI 1.1, 1.7), 2.0 (95% CI 1.1–3.4) and 1.4 (95% CI 1.0, 1.9) respectively. Sleep quality and psychological factors were not associated with time to meet the discharge criteria to RTS but impacted whether athletes adhered and completed their rehabilitation program or not. Monitoring sleep quality and psychological factors of athletes before and following ACL-R surgery is important to identify athletes who could have difficulties in adhering to and completing their rehabilitation program to RTS.