Cage effects control the mechanism of methane hydroxylation in zeolites

Catalytic conversion of methane to methanol remains an economically tantalizing but fundamentally challenging goal. Current technologies based on zeolites deactivate too rapidly for practical application. We found that similar active sites hosted in different zeolite lattices can exhibit markedly different reactivity with methane, depending on the size of the zeolite pore apertures. Whereas zeolite with large pore apertures deactivates completely after a single turnover, 40% of active sites in zeolite with small pore apertures are regenerated, enabling a catalytic cycle. Detailed spectroscopic characterization of reaction intermediates and density functional theory calculations show that hindered diffusion through small pore apertures disfavors premature release of CH3 radicals from the active site after C-H activation, thereby promoting radical recombination to form methanol rather than deactivated Fe-OCH3 centers elsewhere in the lattice.

Cage and maternal effects on the bacterial communities of the murine gut

Findings from gut microbiome studies are strongly influenced by both experimental and analytical factors that can unintentionally bias their interpretation. Environment is also critical. Both co-housing and maternal effects are expected to affect microbiomes and have the potential to confound other manipulated factors, such as genetics. We therefore analysed microbiome data from a mouse experiment using littermate controls and tested differences among genotypes (wildtype versus colitis prone-mdr1a−/−), gut niches (stool versus mucus), host ages (6 versus 18 weeks), social groups (co-housed siblings of different genotypes) and maternal influence. We constructed a 16S phylogenetic tree from bacterial communities, fitting random forest models using all 428,234 clades identified. Models discriminated all criteria except host genotype, where no community differences were found. Host social groups differed in abundant, low-level, taxa whereas intermediate phylogenetic and abundance scales distinguished ages and niches. Thus, a carefully controlled experiment treating evolutionary clades of microbes equivalently without reference to taxonomy, clearly identifies whether and how gut microbial communities are distinct across ecologically important factors (niche and host age) and other experimental factors, notably cage effects and maternal influence. These findings highlight the importance of considering such environmental factors in future microbiome studies.

Suspected Lonely Mouse Syndrome as a Cage Effect in a Drug Safety Study

Studies have demonstrated that buprenorphine, a front line drug for veterinary analgesia, may alleviate symptoms of chronic pain. A cage side observation protocol was used to record behavioral signs in a mouse clinical trial of extended release buprenorphine. A retrospective review of the observations for signs of pain and stress revealed that mice given a fivefold overdose of buprenorphine (16.25 mg/kg) showed lethargy and facial signs associated with stress. However, similar signs were observed in the drug-free control mice as early as Day 3 of single-cage housing. This appears to be the first report of cage effects in a clinical trial for a veterinary drug.