Organoids and the genetically encoded self‐assembly of embryonic stem cells

Understanding the mechanisms of early embryonic patterning and the timely allocation of specific cells to embryonic regions and fates as well as their development into tissues and organs, is a fundamental problem in Developmental Biology. The classical explanation for this process had been built around the notion of positional information. Accordingly the programmed appearance of sources of Morphogens at localized positions within a field of cells directs their differentiation. Recently, the development of organs and tissues from unpatterned and initially identical stem cells (adult and embryonic) has challenged the need for positional information and even the integrity of the embryo, for pattern formation. Here we review the emerging area of organoid biology from the perspective of Developmental Biology. We argue that the events underlying the development of these systems are not purely linked to “self‐organization,” as often suggested, but rather to a process of genetically encoded self‐assembly where genetic programs encode and control the emergence of biological structures.     

E‐cadherin expression is associated with somatostatin analogue response in acromegaly

Acromegaly is a rare disease resulting from hypersecretion of growth hormone (GH) and insulin‐like growth factor 1 (IGF1) typically caused by pituitary adenomas, which is associated with increased mortality and morbidity. Somatostatin analogues (SSAs) represent the primary medical therapy for acromegaly and are currently used as first‐line treatment or as second‐line therapy after unsuccessful pituitary surgery. However, a considerable proportion of patients do not adequately respond to SSAs treatment, and therefore, there is an urgent need to identify biomarkers predictors of response to SSAs. The aim of this study was to examine E‐cadherin expression by immunohistochemistry in fifty‐five GH‐producing pituitary tumours and determine the potential association with response to SSAs as well as other clinical and histopathological features. Acromegaly patients with tumours expressing low E‐cadherin levels exhibit a worse response to SSAs. E‐cadherin levels are associated with GH‐producing tumour histological subtypes. Our results indicate that the immunohistochemical detection of E‐cadherin might be useful in categorizing acromegaly patients based on the response to SSAs.     

Substrate specificity of the phenolic acid decarboxylase from Lactobacillus plantarum and related bacteria analyzed by molecular dynamics and docking

Journal of Plant Biochemistry and Biotechnology - The phenolic acid decarboxylase (PAD) is a 44 kDa homodimeric, thermolabile and acid-resistant enzyme that some bacteria have developed as...     

A biogeographical analysis of Muhlenbergia (Poaceae: Chloridoideae: Cynodonteae: Muhlenbergiinae)

A phylogeny based on the analysis of six DNA sequence markers (ITS, ndhA intron, rpl32-trnL, rps3, rps16 intron, and rps16-trnK) is used to infer ancestral areas and divergence times, and reconstruct the biogeographical history and evolution of 150 of the 183 (82%) species of Muhlenbergia. Our results suggest that the genus originated 9.3 mya in the Sierra Madre (Occidental and Oriental) in Mexico, splitting into six lineages: M. ramulosa diverging 8.2 mya, M. subg. Muhlenbergia at 5.9 mya, M. subg. Pseudosporobolus at 5.9 mya, M. subg. Clomena at 5.4 mya, M. subg. Bealia at 4.3 mya, and M. subg. Trichochloa at 1 mya, each of these with a high probability of Sierra Madrean origin. Our results further suggest that founder-event speciation from Sierra Madre to South America occurred independently multiple times in all five subgenera during the Pleistocene and late Pliocene. One long-distance dispersal event most likely originating from Central or Eastern North America to East and Central Asia occurred 1.6–1 mya in M. subg. Muhlenbergia. In our cladogram, members of M. subg. Trichochloa show little genetic resolution, suggesting very low levels of divergence among the species, and this may be a consequence of rapid radiation.     

The behaviour of deoxyhexose trihaloacetimidates in selected glycosylations

Armed deoxyhexose glycosyl donors are very reactive and sometimes too uncontrollably activated in glycosylation reactions; yields can be thereby reduced, especially when unreactive glycosyl acceptors are involved. In this paper, the behaviour of a range of deoxyhexose trihaloacetimidate (trichloro- and N-phenyl trifluoro-) donors is compared in some selected glycosylations towards biologically relevant targets. The selected N-phenyl trifluoroacetimidates often afforded best results in terms of both donor synthesis and glycosylation yield.     

A proteomics analysis of cell signaling alterations in colorectal cancer

To gain further insight into alterations in cellular pathways, tumor profiling, and marker discovery in colorectal cancer (CRC) we used a new antibody microarray specific for cell signaling. Soluble protein extracts were prepared from paired tumor/normal biopsies of 11 patients diagnosed with colorectal carcinoma at different stages; four liver carcinomas were used as a reference. Antibody microarray analysis identified 46 proteins that were differentially expressed between normal colorectal epithelium and adenocarcinoma. These proteins gave a specific signature for CRC, different from other tumors, as well as a panel of novel markers and potential targets for CRC. Twenty-four proteins were validated by using a specific colorectal cancer tissue microarray and immunoblotting analysis. Together with some previously well known deregulated proteins in CRC (beta-catenin, c-MYC, or p63), we found new potential markers preferentially expressed in CRC tumors: cytokeratin 13, calcineurin, CHK1, clathrin light chain, MAPK3, phospho-PTK2/focal adhesion kinase (Ser-910), and MDM2. CHK1 antibodies were particularly effective in discriminating between tumoral and normal mucosa in CRC. Moreover a global picture of alterations in signaling pathways in CRC was observed, including a significant up-regulation of different components of the epidermal growth factor receptor and Wnt/beta-catenin pathways and the down-regulation of p14(ARF). The experimental approach described here should be applicable to other pathologies and neoplastic processes.     

Structural characterization of the L0 cytoplasmic loop of human multidrug resistance protein 6 (MRP6)

ABCC6 is a member of the C subfamily of ATP-binding cassette transporters whose mutations are correlated to Pseudoxanthoma elasticum, an autosomal recessive, progressive disorder characterized by ectopic mineralization and fragmentation of elastic fibers. Structural studies of the entire protein have been hindered by its large size, membrane association, and domain complexity. Studies previously performed have contributed to shed light on the structure and function of the nucleotide binding domains and of the N-terminal region. Here we report the expression in E. coli of the polypeptide E₂₀₅-G₂₇₉ contained in the cytoplasmic L0 loop. For the first time structural studies in solution were performed. Far-UV CD spectra showed that L0 is structured, assuming predominantly α-helix in TFE solution and turns in phosphate buffer. Fluorescence spectra indicated some flexibility of the regions containing aromatic residues. ¹H NMR spectroscopy identified three helical regions separated by more flexible regions.