2,5-anhydro-d-hexitols: syntheses of 2,5-anhydro-d-altritol and 2,5-anhydro-d-iditol

2,5-Anhydro-d-altritol (2a) and the previously-unknown 2,5-anhydro-d-iditol (3a) have been prepared from 2,5-anhydro-d-mannitol (1a). The preparation of 3a from the intermediate epoxide 7b is particularly sensitive to pH, and a mechanism is proposed to explain this. Attention is drawn to the limitations of the trifluoroperacetic acid-disodium hydrogenphosphate procedure for the epoxidation of alkenes of diminished reactivity.     

Analysis of Gene Expression in 3D Spheroids Highlights a Survival Role for ASS1 in Mesothelioma

To investigate the underlying causes of chemoresistance in malignant pleural mesothelioma, we have studied mesothelioma cell lines as 3D spheroids, which acquire increased chemoresistance compared to 2D monolayers. We asked whether the gene expression of 3D spheroids would reveal mechanisms of resistance. To address this, we measured gene expression of three mesothelioma cell lines, M28, REN and VAMT, grown as 2D monolayers and 3D spheroids. A total of 209 genes were differentially expressed in common by the three cell lines in 3D (138 upregulated and 71 downregulated), although a clear resistance pathway was not apparent. We then compared the list of 3D genes with two publicly available datasets of gene expression of 56 pleural mesotheliomas compared to normal tissues. Interestingly, only three genes were increased in both 3D spheroids and human tumors: argininosuccinate synthase 1 (ASS1), annexin A4 (ANXA4) and major vault protein (MVP); of these, ASS1 was the only consistently upregulated of the three genes by qRT-PCR. To measure ASS1 protein expression, we stained 2 sets of tissue microarrays (TMA): one with 88 pleural mesothelioma samples and the other with additional 88 pleural mesotheliomas paired with matched normal tissues. Of the 176 tumors represented on the two TMAs, ASS1 was expressed in 87 (50%; staining greater than 1 up to 3+). For the paired samples, ASS1 expression in mesothelioma was significantly greater than in the normal tissues. Reduction of ASS1 expression by siRNA significantly sensitized mesothelioma spheroids to the pro-apoptotic effects of bortezomib and of cisplatin plus pemetrexed. Although mesothelioma is considered by many to be an ASS1-deficient tumor, our results show that ASS1 is elevated at the mRNA and protein levels in mesothelioma 3D spheroids and in human pleural mesotheliomas. We also have uncovered a survival role for ASS1, which may be amenable to targeting to undermine mesothelioma multicellular resistance.     

Engineering recombinant antibodies for immunotherapy

Recombinant antibody fragments binding with high affinity to their target can be obtained either from hybridomas or directly from antibody libraries on filamentous phage. These fragments are devoid of any activity other than antigen binding, and have to be processed and functionalized in order to be suitable for clinical applications. This article presents the authors’ view on the procedures and the features that are important for effective transformation of recombinant antibodies into useful immunotherapeutic agents. The topics presented include phage display methodologies, engineering of high-affinity binding, purification, and functionalization strategies of recombinant antibodies.     

Chromosome Number of Cidaris cidaris (Cidaridae,Echinoidea)

The diploid number 44 has been determined, with reserve, for the echinoid Cidaris cidaris, thus further supporting the hypothesis that the phylum Echinodermata is characterized by an astonishing stability of chromosome numbers. The spermatogonial chromosomes of C. cidaris are very minute and heterocyclic elements are absent.     

A new FMS architecture based upon networked DSP servo technology

This paper presents a critical evaluation of existing FMS architectures and the academic and industrial design and development strategies used during their formulation. The paper seeks to address the need for, and value of, existing architectures within the industrial arena. More importantly however, this paper puts forward a new two-tier distributed control architecture for FMS based upon new (real-time) networkable DSP servo control methodologies developed by one of the authors for Softronics in Australia. The ramifications of these methodologies are substantial, not only in terms of FMS control, but in the overall simplification of such systems and the development of flexible fixturing devices over the coming decade. This paper also postulates on how new FMS architectures can be developed from such technologies and details why such architectures could be more appropriate to industry needs than those that are currently in existence.     

Two new species of Heptapterus (Siluriformes: Heptapteridae) from the Uruguay River basin,Brazil

As part of an ongoing taxonomic revision of the genus Heptapterus from the Laguna dos Patos and Uruguay River drainages and Atlantic coastal streams of southern Brazil and Uruguay, two new species closely related to Heptapterus mustelinus were identified. Both species are endemic to small tributaries of the Uruguay River. The two new species are distinguished from each other and from other species of Heptapterus by arrangement of cephalic and trunk laterosensory systems, number of vertebrae and number of dorsal, pectoral and anal-fin rays. Phylogenetic analyses of mitochondrial DNA (coI and cytb) sequence data further supports distinctiveness of the two new species.     

Zebrafish disease models in hematology: Highlights on biological and translational impact

Zebrafish (Danio rerio) has proven to be a versatile and reliable in vivo experimental model to study human hematopoiesis and hematological malignancies. As vertebrates, zebrafish has significant anatomical and biological similarities to humans, including the hematopoietic system. The powerful genome editing and genome-wide forward genetic screening tools have generated models that recapitulate human malignant hematopoietic pathologies in zebrafish and unravel cellular mechanisms involved in these diseases. Moreover, the use of zebrafish models in large-scale chemical screens has allowed the identification of new molecular targets and the design of alternative therapies. In this review we summarize the recent achievements in hematological research that highlight the power of the zebrafish model for discovery of new therapeutic molecules. We believe that the model is ready to give an immediate translational impact into the clinic.