Concise stereocontrolled routes to fumagillol,fumagillin, and TNP-470

A concise, diastereoselective synthesis of (+/-)-fumagillol (3) and formal, enantioselective syntheses of the potent angiogenesis inhibitors fumagillin (1) and TNP-470 (2) are reported. The origin of asymmetry is a highly diastereoselective Diels-Alder reaction using a diene with a chiral oxazolidinone auxiliary. The stereochemical course of a key conjugate addition reaction is controlled by the cup-shaped architecture of a cis-fused bicyclic enal. Other key steps include a facile hetero-Claisen rearrangement and a site-selective Sharpless epoxidation.     

Two new species of Tovlinius Zaitzev, from China, with a key to the genera of Bombyliinae from China and a second key to the world species (Diptera, Bombyliidae, Bombyliinae, Bombyliini)

The genus Tovlinius Zaitzev is a Palaearctic genus with just one previously described species, Tovlinius albissimus Zaitzev. Tovlinius is here recorded from China for the first time, and two new species Tovlinius pyramidatussp. n. and Tovlinius turriformissp. n. are described and illustrated. A key to the genera of Bombyliinae from China and a second key to the World species of Tovlinius are also presented herein.     

Pancreatic cancer,stroma, and exosomes

Journal of Physiology and Biochemistry - In the pathogenesis of pancreatic adenocarcinoma, tumor stroma plays a key role in both aggressiveness, immune evasion, resistance to chemotherapy, and the...     

Presence of a drifting algal bed in the Mar Piccolo basin,Taranto (Ionian Sea,Southern Italy)

A survey is reported of the drifting algal community in Mar Piccolo, a polluted basin subject to sewage outlets. The key role was played by a few key species, mainly floridean red algae.     

The Structure,Regulation, and Function of Human Matrix Metalloproteinase-13

Matrix metalloproteinase-13 (MMP-13) is a proteolytic enzyme that belongs to a large family of extracellular matrix-degrading endopeptidases that are characterized by a zinc-binding motif at their catalytic sites. MMP-13 has a key role in the MMP activation cascade and appears to be critical in bone metabolism and homeostasis. It also has an important role in tumor invasion and metastasis. This commentary provides a detailed overview of the regulatory mechanisms, structure, and function of human MMP-13 and highlights the key factors involved in the biology of this important molecule.     

The structure,regulation, and function of human matrix metalloproteinase-13

Matrix metalloproteinase-13 (MMP-13) is a proteolytic enzyme that belongs to a large family of extracellular matrix-degrading endopeptidases that are characterized by a zinc-binding motif at their catalytic sites. MMP-13 has a key role in the MMP activation cascade and appears to be critical in bone metabolism and homeostasis. It also has an important role in tumor invasion and metastasis. This commentary provides a detailed overview of the regulatory mechanisms, structure, and function of human MMP-13 and highlights the key factors involved in the biology of this important molecule.     

Discovery and gram-scale synthesis of BMS-593214, a potent,selective FVIIa inhibitor

A 6-amidinotetrahydroquinoline screening hit was driven to a structurally novel, potent, and selective FVIIa inhibitor through a combination of library synthesis and rational design. An efficient gram-scale synthesis of the active enantiomer BMS-593214 was developed, which required significant optimization of the key Povarov annulation. Importantly, BMS-593214 showed antithrombotic efficacy in a rabbit arterial thrombosis model. A crystal structure of BMS-593214 bound to FVIIa highlights key contacts with Asp 189, Lys 192, and the S2 pocket.     

Increasing carbohydrate diversity via amine oxidation: aminosugar, hydroxyaminosugar, nitrososugar, and nitrosugar biosynthesis in bacteria

Bacterial secondary metabolites often contain carbohydrate attachments that play a significant role in conferring biological activity. A small proportion of these bioactive sugars are derived from aminosugar oxidation to ultimately provide hydroxyaminosugars, nitrososugars, and nitrosugars. Recent advances in the elucidation of hydroxyaminosugar-, nitrososugar-, and nitrosugar-containing natural product gene clusters have enabled the proposal of biosynthetic pathways, the in vitro characterization of aminosugar oxidases, and the structure determination of key enzymes. This article focuses upon the key enzymatic transformations in aminosugar, hydroxyaminosugar, nitrososugar, and nitrosugar biosynthesis, as well as the unique chemical reactivity of alkoxyaminosugars, with a particular focus upon developments within the past two years.     

Organoid-based modeling of intestinal development,regeneration, and repair

The intestinal epithelium harbors a remarkable adaptability to undergo injury-induced repair. A key part of the regenerative response is the transient reprogramming of epithelial cells into a fetal-like state, which drives uniform proliferation, tissue remodeling, and subsequent restoration of the homeostatic state. In this review, we discuss how Wnt and YAP signaling pathways control the intestinal repair response and the transitioning of cell states, in comparison with the process of intestinal development. Furthermore, we highlight how organoid-based applications have contributed to the characterization of the mechanistic principles and key players that guide these developmental and regenerative events. Subject terms: Development, Gastrointestinal diseases, Stem-cell research     

Thermal proteome profiling: Insights into protein modifications,associations, and functions

Tracking proteins’ biophysical characteristics on a proteome-wide scale can provide valuable information on their functions and interactions. Thermal proteome profiling (TPP) is a multiplexed quantitative proteomics approach that measures changes in protein thermal stability—a key biophysical property—across different cellular states. Developed in 2014, as a target-deconvolution assay for drugs and other small molecules, TPP has since evolved to a system-level biochemical omics technique providing insights into context-dependent changes in protein states. In this review, we summarise key advances in the experimental and data analysis pipeline that have aided this transformation and discuss the recent developments and applications of TPP.     

The role of glycoproteins in neural development, function, and disease

Glycoproteins play key roles in the development, structuring, and subsequent functioning of the nervous system. However, the complex glycosylation process is a critical component in the biosynthesis of CNS glycoproteins that may be susceptible to the actions of toxicological agents or may be altered by genetic defects. This review will provide an outline of the complexity of this glycosylation process and of some of the key neural glycoproteins that play particular roles in neural development and in synaptic plasticity, in the mature CNS. Finally, the potential of glycoproteins as targets for CNS disorders will be discussed.     

The identification of potent, selective, and bioavailable cathepsin S inhibitors

Highly potent, selective, and bioavailable inhibitors of human, mouse, or rat cathepsin S are described. The key structural features combine a sulfonyl moiety attached to a large group in P2 and a small substituent in P3.     

Evolution of virulence in opportunistic pathogens: generalism, plasticity, and control

Standard virulence evolution theory assumes that virulence factors are maintained because they aid parasitic exploitation, increasing growth within and/or transmission between hosts. An increasing number of studies now demonstrate that many opportunistic pathogens (OPs) do not conform to these assumptions, with virulence factors maintained instead because of advantages in non-parasitic contexts. Here we review virulence evolution theory in the context of OPs and highlight the importance of incorporating environments outside a focal virulence site. We illustrate that virulence selection is constrained by correlations between these external and focal settings and pinpoint drivers of key environmental correlations, with a focus on generalist strategies and phenotypic plasticity. We end with a summary of key theoretical and empirical challenges to be met for a fuller understanding of OPs.     

Cell walls,cell shape,and bacterial actin homologs

The synthesis of the peptidoglycan layer, one of the key determinants of cell shape in B. subtilis, has been shown by Daniel and Errington to occur in a helical pattern. This pattern is generated by the actin homolog Mbl.     

Rural-to-Urban Labor Migration,Household Livelihoods,and the Rural Environment in Chongqing Municipality,Southwest China

Rural migration and its relationship to the rural environment have attracted increasing research interest in recent decades. Rural migration constitutes a key component of human population movement, while rural areas contain most of the world’s natural resources such as land and forests. This study empirically evaluates a conceptual framework incorporating rural household livelihoods as an integrative mediating factor between rural migration and the rural environment in the context of rural-to-urban labor migration in Chongqing Municipality, Southwest China. The analysis draws on data collected through household surveys and key informant interviews from four villages. Results confirm the hypothesis that labor-migrant and non-labor-migrant households differ significantly in livelihood activities including agricultural production, agricultural technology use, income and consumption, and resource use and management. Implications for the subsequent environmental outcomes of rural labor out-migration and corresponding natural resource management and policy in rural origin areas are discussed.     

Wuhan, China and Pittsburgh, USA: Urban Environmental Health Past, Present, and Future

This article briefly reviews environmental history in the “Sister Cities” of Wuhan, China and Pittsburgh, USA. Specifically, it analyzes key changes in air, water, land, and sustainability in each of the two cities in terms of both “driving forces” and of the actions of key stakeholders (policymakers, educators, industry/business, nongovernmental organizations [NGOs], and the public). It concludes by discussing prospects for synergies between the two cities in continuing to improve environmental health, and the implications of these ideas for other cities in both the “developing” and the “developed” world.     

A new species of Halacarsantia Wolff, 1989 (Crustacea, Isopoda, Asellota, Santiidae) from Wistari Reef, southern Great Barrier Reef, Australia

Halacarsantia acutasp. n. is described from Wistari Reef, Capricorn Group, southern Great Barrier Reef, the first record of the genus from Australia. The new species differs from its congeners in having antenna flagellum composed of 8 articles; epipod apically acute, without setae, broad maxilliped endite and pereopod 1 basis with a short projection. A key to species of the genus is provided.