Phytate, the most abundant organic phosphorus compound in soil, dominates the biotic phosphorus input from terrestrial runoffs into aquatic systems. Microbial mineralization of phytate by phytases is a key process for recycling phosphorus in the biosphere. Bioinformatic studies were carried out on microbial genomes and environmental metagenomes in the NCBI and the CAMERA databases to determine the distribution of the four known classes of phytase in the microbial world. The b-propeller phytase is the only phytase family that can be found in aquatic environments and it is also distributed in soil and plant bacteria. The b-propeller phytase-like genes can be classified into several subgroups based on their domain structure and the positions of their conserved cysteine residues. Analysis of the genetic contexts of these subgroups showed that b-propeller phytase genes exist either as an independent gene or are closely associated with a TonB-dependent receptor-like gene in operons, suggesting that these two genes are functionally linked and thus may play an important role in the cycles of phosphorus and iron. Our work suggests that b-propeller phytases play a major role in phytate-phosphorus cycling in both soil and aquatic microbial communities.

Phytate, which is one of the dominant organic phosphorus compounds in nature, is very stable in soils. Although a substantial amount of phytate is carried from terrestrial to aquatic systems, it is a minor component of organic phosphorus in coastal sediments. The ephemeral nature of phytate implies the rapid hydrolysis of phytate under aquatic conditions. Among the four classes of known phytases that have been identified in terrestrial organisms, only beta-propeller phytase-like sequences have been identified in the aquatic environment. A novel beta-propeller phytase gene (phyS), cloned from Shewanella oneidensis MR-1, was found to encode a protein with two beta-propeller phytase domains. The characterization of recombinant full-length PhyS and its domains demonstrated that Domain II was the catalytic domain responsible for phytate hydrolysis. The full-length PhyS displayed a K(m) of 83 microM with a kcat of 175.9 min(-1) and the Domain II displayed a K(m) of 474 microM with a kcat of 10.6 min(-1). These results confirm that the phyS gene encodes a functional beta-propeller phytase, which is expressed in S. oneidensis under phosphorus deficient condition. The presence of multiple sequences with a high similarity to phyS in aquatic environmental samples and the widespread occurrence of the Shewanella species in nature suggest that the beta-propeller phytase family is the major class of phytases in the aquatic environment, and that it may play an important role in the recycling of phosphorus.

SummaryCKS proteins are evolutionarily conserved cyclin-dependent kinase (CDK) subunits whose functions are incompletely understood. Mammals have two CKS proteins. CKS1 acts as a cofactor to the ubiquitin ligase complex SCFSKP2 to promote degradation of CDK inhibitors, such as p27. Little is known about the role of the closely related CKS2. Using a Cks2−/− knockout mouse model, we show that CKS2 counteracts CKS1 and stabilizes p27. Unopposed CKS1 activity in Cks2−/− cells leads to loss of p27. The resulting unrestricted cyclin A/CDK2 activity is accompanied by shortening of the cell cycle, increased replication fork velocity, and DNA damage. In vivo, Cks2−/− cortical progenitor cells are limited in their capacity to differentiate into mature neurons, a phenotype akin to animals lacking p27. We propose that the balance between CKS2 and CKS1 modulates p27 degradation, and with it cyclin A/CDK2 activity, to safeguard replicative fidelity and control neuronal differentiation.

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PIN1 is a peptidyl-prolyl cis/trans isomerase (PPIase) that regulates multiple signaling pathways to control cell fate and is found to be over-expressed in cancers, including hepatocellular carcinoma (HCC). However, the regulation of PIN1 in HCC remains poorly defined. Micro-RNAs (miRNAs) have been reported to play a pivotal role in oncogenesis by targeting the 3′-untranslated region (UTR) of mRNAs encoded by oncogenes and tumour suppressor genes, thereby suppressing the levels of both oncoproteins and tumour suppressors. In this report, we aimed to identify miRNAs that suppress PIN1 expression and to determine their role in HCC. By searching the TargetScan database, miR-874-3p was identified as a potential negative regulator of PIN1. miR-874-3p was demonstrated to bind the 3′UTR of PIN1 mRNA directly to suppress expression of PIN1. Functionally, over-expression of miR-874-3p in HCC cell line PLC/PRF/5 inhibited cell growth and colony formation in-vitro, and promoted cellular apoptosis. Furthermore, these tumour suppressive functions conferred by miR-874-3p were abrogated by over-expression of PIN1. Similarly, expression of miR-874-3p in PLC/PRF/5 with PIN1 knocked-down did not further suppress cellular proliferation, suggesting that PIN1 was a major target of miR-874-3p. More importantly, miR-874-3p was found to be down-regulated in HCC tissues and its expression was negatively correlated with that of PIN1. Down-regulation of miR-874-3p was also associated with poorly differentiated tumour cells, more advanced staging, and inferior patient outcomes. In addition, over-expression of miR-874-3p suppressed tumour growth in vivo. Taken together, our data suggested that miR-874-3p plays a tumour suppressive role in HCC through down-regulation of PIN1.

A continued study of structural modification of S-trityl-L-cysteine reveals that for antileukemic activity, steric requirements of the trityl position appear to be more important than consideration of electron localization, hydrocarbon activity, or free radical stability. Activity of certain S-trityl-L-cysteinyl amino acids is observed but is of lesser degree than that of the parent S-trityl-L-cysteine. N-Substituted dipeptides and derivatives of S-trityl-L-cysteine are devoid of activity. Monohydroxymethyl-substituted S-trityl-L-cysteine still retains the original activity whereas the corresponding bis(hydroxymethyl) analog is inactive.

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There are several advantages to the supine position for the patient and the urologist, with greater versatility of stone manipulation along the whole upper urinary tract. There are a few limitations of the supine position, but they can be overcome. Performing PCNL with the patient in the supine position is a sound alternative to the conventional prone position.