Issues Relevant to C-H Activation at Platinum(II): Comparative Studies between Cationic, Zwitterionic, and Neutral Platinum(II) Compounds in Benzene Solution

Cationic late metal systems are being highly scrutinized due to their propensity to mediate so-called electrophilic C-H activation reactions. This contribution compares the reactivity of highly reactive cationic platinum(II) systems with structurally related but neutral species. Our experimental design exploits isostructural neutral and cationic complexes supported by bis(phosphine) ligands amenable to mechanistic examination in benzene solution. The data presented herein collectively suggests that neutral platinum complexes can be equally if not more reactive towards benzene than their cationic counter-parts. Moreover, a number of unexpected mechanistic distinctions between the two systems arise that help to explain their respective reactivity

Mining Microbial Communities: Exploring Symbiotic Bacteria as a Source of New Natural Products

As ubiquitous inhabitants of Earth, bacteria represent a diverse resource in the search for new natural products. In order for the field of natural products to progress, new and exciting sources of biodiversity must be continually accessed. Microbiomes, the community of commensal and pathogenic microorganisms that live in and on other organisms, present a unique opportunity to access new biological diversity. These symbiotic bacteria have proven to be prolific producers of natural products and represent relatively untapped resource of new secondary metabolites. Photorhabdus asymbiotica, a bacterial symbiont of an entomopathogenic nematode is an emerging health concern for humans. It engages in a bi-phasic lifestyle that switches between symbiotic and pathogenic phases. Its genome had been previously sequenced and our analysis of the secondary metabolite pathways indicated it had the genetic machinery necessary to produce multiple natural products. Extensive media screening studies were employed to induce the production of the encoded for natural products. Two known and one new proteasome inhibitors were isolated from the optimized culture conditions. The theory that P. asymbiotica’s lifestyle switch is governed in part by environmental cues was explored by injecting the bacterium into live crickets. Recovery of the bioactive natural products from the cricket corpus supported the belief that the nutrient composition of the insect gut plays a role in the life cycle switch of P. asymbiotica. The microbiomes of mammals are a rich and diverse source of bacteria. While these microbiomes are well studied in terms of populations, little is known about their ability to produce natural products. The biosynthetic potential of the microbiome of a feral hog was examined. One isolated organism, identified as a new strain of Brevibacillus latersporus, was chosen for further genomic and metabolomic characterization. Thirty two biosynthetic gene clusters were identified in the organism’s genome. Three known bioactive compounds were isolated along with two new natural products. A portion of the known and new natural products were matched up with their biosynthetic gene clusters. This work showed that symbiotic bacteria from small mammals are worthy of further investigation by natural product investigators. Finally, a method was developed to sample, isolate, and screen members of microbiome communities for biosynthetically talented and culturable organisms. By employing the use of liquid handling robots and specialized instrumentation, an efficient method for quickly evaluating organisms for secondary metabolites was created. By combining an efficient screening method and metabolomic investigations, a snap shot of the chemical products generated by microbiome members has been achieved

Non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk: differences by molecular subtype.

Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk of breast cancer, though findings have been inconsistent. This inconsistency may result from differences in etiology for breast tumors of different subtypes. We examined the association between NSAID use and breast cancer characterized by molecular subtypes in a population-based case-control study in Western New York. Cases (n = 1,170) were women with incident, primary, histologically confirmed breast cancer. Controls (n = 2,115) were randomly selected from NY Department of Motor Vehicles records (<65 years) or Medicare rolls (≥ 65 years). Participants answered questions regarding their use of aspirin and ibuprofen in the year prior to interview and their use of aspirin throughout their adult life. Logistic regression models estimated odds ratios (OR) and 95% confidence intervals (95% CI). Recent and lifetime aspirin use was associated with reduced risk, with no differences by subtype. Recent use of ibuprofen was significantly associated with increased risk of ER+/PR+(OR 1.33, 95% CI: 1.09-1.62), HER2- (OR 1.27, 95% CI: 1.05-1.53), and p53- breast cancers (OR 1.28, 95% CI: 1.04-1.57), as well as luminal A or B breast cancers. These findings support the hypothesis of heterogeneous etiologies of breast cancer subtypes and that aspirin and ibuprofen vary in their effects

Contacts between domestic livestock and wildlife at the Kruger National Park interface of the Republic of South Africa

One of the most important transboundary animal diseases (TADs) in the southern African region is foot-and-mouth disease (FMD). In this region, a pathway for spread of FMD virus is contacts between cattle and certain species of wildlife. The objective of this study was to evaluate contacts between cattle and wildlife in the Kruger National Park (KNP) and the adjacent Limpopo province for the time periods October 2006 to March 2007 and April to September 2007. In this study, 87 livestock owners and 57 KNP field rangers were interviewed. Fifteen (17%) livestock owners reported contacts between wildlife and cattle. More livestock owners reported observing contacts between cattle and all wildlife species during October–March than April–September (p = 0.012). However, no difference was found between these periods for contacts between cattle and individual wildlife species. A total of 18 (32%) field rangers reported contacts between cattle and wildlife. The most common species-specific contacts were between cattle and buffalo (63/year), cattle and impala (17/year) and cattle and lion (10/year). There were no significant differences in rangers reporting observed contacts between cattle and wildlife during October–March versus April–September or between rangers reporting observed contacts outside versus within the KNP. Overall, there was no evidence of higher contact rates between cattle and wildlife in the study area during October–March compared to April–September. Contact data collected in this study can be used to better understand the transmission of FMD virus in this region.Partially funded by Texas A&M University Foreign Animal Disease Defense Center through Dr. Gale Wagner.http://www.elsevier.com/locate/prevetmedab201

Organic building blocks at inorganic nanomaterial interfaces

This tutorial review presents our perspective on designing organic molecules for the functionalization of inorganic nanomaterial surfaces, through the model of an “anchor-functionality” paradigm. This “anchor-functionality” paradigm is a streamlined design strategy developed from a comprehensive range of materials (e.g., lead halide perovskites, II–VI semiconductors, III–V semiconductors, metal oxides, diamonds, carbon dots, silicon, etc.) and applications (e.g., light-emitting diodes, photovoltaics, lasers, photonic cavities, photocatalysis, fluorescence imaging, photo dynamic therapy, drug delivery, etc.). The structure of this organic interface modifier comprises two key components: anchor groups binding to inorganic surfaces and functional groups that optimize their performance in specific applications. To help readers better understand and utilize this approach, the roles of different anchor groups and different functional groups are discussed and explained through their interactions with inorganic materials and external environments

Smoking, Variation In N-acetyltransferase 1 (nat1) And 2 (nat2), And Risk Of Non-hodgkin Lymphoma: A Pooled Analysis Within The Interlymph Consortium

Studies of smoking and risk of non-Hodgkin lymphoma (NHL) have yielded inconsistent results, possibly due to subtype heterogeneity and/or genetic variation impacting the metabolism of tobacco-derived carcinogens, including substrates of the N-acetyltransferase enzymes NAT1 and NAT2. We conducted a pooled analysis of 5,026 NHL cases and 4,630 controls from seven case-control studies in the international lymphoma epidemiology consortium to examine associations between smoking, variation in the N-acetyltransferase genes NAT1 and NAT2, and risk of NHL subtypes. Smoking data were harmonized across studies, and genetic variants in NAT1 and NAT2 were used to infer acetylation phenotype of the NAT1 and NAT2 enzymes, respectively. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for risk of NHL and subtypes were calculated using joint fixed effects unconditional logistic regression models. Current smoking was associated with a significant 30 % increased risk of follicular lymphoma (n = 1,176) but not NHL overall or other NHL subtypes. The association was similar among NAT2 slow (OR 1.36; 95 % CI 1.07-1.75) and intermediate/rapid (OR 1.27; 95 % CI 0.95-1.69) acetylators (p (interaction) = 0.82) and also did not differ by NAT1*10 allelotype. Neither NAT2 phenotype nor NAT1*10 allelotype was associated with risk of NHL overall or NHL subtypes. The current findings provide further evidence for a modest association between current smoking and follicular lymphoma risk and suggest that this association may not be influenced by variation in the N-acetyltransferase enzymes

'MRI-negative PET-positive' temporal lobe epilepsy (TLE) and mesial TLE differ with quantitative MRI and PET: a case control study

Background: \u27MRI negative PET positive temporal lobe epilepsy\u27 represents a substantial minority of temporal lobe epilepsy (TLE). Clinicopathological and qualitative imaging differences from mesial temporal lobe epilepsy are reported. We aimed to compare TLE with hippocampal sclerosis (HS+ve) and non lesional TLE without HS (HS-ve) on MRI, with respect to quantitative FDG-PET and MRI measures.Methods: 30 consecutive HS-ve patients with well-lateralised EEG were compared with 30 age- and sex-matched HS+ve patients with well-lateralised EEG. Cerebral, cortical lobar and hippocampal volumetric and co-registered FDG-PET metabolic analyses were performed.Results: There was no difference in whole brain, cerebral or cerebral cortical volumes. Both groups showed marginally smaller cerebral volumes ipsilateral to epileptogenic side (HS-ve 0.99, p = 0.02, HS+ve 0.98, p &lt; 0.001). In HS+ve, the ratio of epileptogenic cerebrum to whole brain volume was less (p = 0.02); the ratio of epileptogenic cerebral cortex to whole brain in the HS+ve group approached significance (p = 0.06). Relative volume deficits were seen in HS+ve in insular and temporal lobes. Both groups showed marked ipsilateral hypometabolism (p &lt; 0.001), most marked in temporal cortex. Mean hypointensity was more marked in epileptogenic-to-contralateral hippocampus in HS+ve (ratio: 0.86 vs 0.95, p &lt; 0.001). The mean FDG-PET ratio of ipsilateral to contralateral cerebral cortex however was low in both groups (ratio: HS-ve 0.97, p &lt; 0.0001; HS+ve 0.98, p = 0.003), and more marked in HS-ve across all lobes except insula.Conclusion: Overall, HS+ve patients showed more hippocampal, but also marginally more ipsilateral cerebral and cerebrocortical atrophy, greater ipsilateral hippocampal hypometabolism but similar ipsilateral cerebral cortical hypometabolism, confirming structural and functional differences between these groups.<br /