Discovery of novel avermectins with unprecedented insecticidal activity

Summary A new class of insecticidal and antiparasitic agents, 4-amino-4-deoxy avermectins, has been developed by chemical modification of avermectin B₁. The most effective of these compounds are 1500-fold more potent than avermectin B₁ (abamectin) against the beet armywormSpodoptera exigua and show similar potency against other lepidopteran larvae.     

Ant fauna (Hymenoptera: Formicidae) of the Socotra Archipelago (Yemen): zoogeography,distribution and description of a new species

The animal fauna of the Socotra Archipelago is influenced by three biogeographical regions, the Afrotropical, the Oriental and the Palaearctic. Consequently, the Archipelago shares faunal elements of these three regions in addition to unique endemic taxa. The ant fauna of Socotra Island was studied and is reviewed based on literature and newly collected material. In total, 28 species, belonging to 10 genera and four subfamilies, were collected from the main island. Eighteen of these (64%) are successful invasive species, seven are native (25%), and three are considered endemic (11%), Cardiocondyla longiceps Seifert, Monomorium elghazalyi sp. nov. and Monomorium nimihil Collingwood et al. Two genera are recorded for the first time from the island, Hypoponera Santschi, and Syllophopsis Santschi. Ten species are recorded for the first time, Cardiocondyla mauritanica Forel, Cardiocondyla minutior Forel, Monomorium atomum Forel, Monomorium dichroum Forel, Monomorium exiguum Forel, Pheidole pallidula (Nylander), Syllophopsis cryptobia (Santschi), Tetramorium pauper Forel, Tetramorium transformans Santschi and Hypoponera punctatissima (Roger). Ten invasive species are recorded from Socotra, reflecting human impacts on the Archipelago. These species are Tapinoma melanocephalum (Fabricius), Cardiocondyla emeryi Forel, Monomorium exiguum Forel, Pheidole indica Mayr, Syllophopsis cryptobia (Santschi), Tetramorium lanuginosum Mayr, Tetramorium simillimum (Smith), Tetramorium caldarium (Roger), Trichomyrmex destructor (Jerdon) and Trichomyrmex mayri (Forel). Our survey indicated a mixture of Afrotropical faunal elements (10 species, 36%), followed by cosmopolitan (nine species, 32%), Palaearctic (five species, 18%) and Oriental (four species, 14%) taxa. Two new synonyms of Monomorium exiguum Forel are proposed: Monomorium exiguum Forel = Monomorium baushare Collingwood & Agosti syn. nov. = Monomorium qarahe Collingwood & Agosti syn. nov. Tetramorium transformans Santschi is removed from synonymy with Tetramorium caldarium (Roger) and elevated to species rank. Ecological and biological notes for each species are given. Distribution maps for all species known from the Socotra Archipelago are provided.

http://zoobank/urn:lsid:zoobank.org:pub:89612083-9CE6-48E8-8975-1CE5334E098B     

Oncogenically active MYD88 mutations in human lymphoma

The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) remains the least curable form of this malignancy despite recent advances in therapy. Constitutive nuclear factor (NF)-κB and JAK kinase signalling promotes malignant cell survival in these lymphomas, but the genetic basis for this signalling is incompletely understood. Here we describe the dependence of ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1 receptor signalling, and the discovery of highly recurrent oncogenic mutations affecting MYD88 in ABC DLBCL tumours. RNA interference screening revealed that MYD88 and the associated kinases IRAK1 and IRAK4 are essential for ABC DLBCL survival. High-throughput RNA resequencing uncovered MYD88 mutations in ABC DLBCL lines. Notably, 29% of ABC DLBCL tumours harboured the same amino acid substitution, L265P, in the MYD88 Toll/IL-1 receptor (TIR) domain at an evolutionarily invariant residue in its hydrophobic core. This mutation was rare or absent in other DLBCL subtypes and Burkitt's lymphoma, but was observed in 9% of mucosa-associated lymphoid tissue lymphomas. At a lower frequency, additional mutations were observed in the MYD88 TIR domain, occurring in both the ABC and germinal centre B-cell-like (GCB) DLBCL subtypes. Survival of ABC DLBCL cells bearing the L265P mutation was sustained by the mutant but not the wild-type MYD88 isoform, demonstrating that L265P is a gain-of-function driver mutation. The L265P mutant promoted cell survival by spontaneously assembling a protein complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1 phosphorylation, NF-κB signalling, JAK kinase activation of STAT3, and secretion of IL-6, IL-10 and interferon-β. Hence, the MYD88 signalling pathway is integral to the pathogenesis of ABC DLBCL, supporting the development of inhibitors of IRAK4 kinase and other components of this pathway for the treatment of tumours bearing oncogenic MYD88 mutations.     

Signaling pathways and the cerebral cavernous malformations proteins: lessons from structural biology

Cerebral cavernous malformations (CCM) are neurovascular dysplasias that result in mulberry-shaped lesions predominantly located in brain and spinal tissues. Mutations in three genes are associated with CCM. These genes encode for the proteins KRIT1/CCM1 (krev interaction trapped 1/cerebral cavernous malformations 1), cerebral cavernous malformations 2, osmosensing scaffold for MEKK3 (CCM2/malcavernin/OSM), and cerebral cavernous malformations 3/programmed cell death 10 (CCM3/PDCD10). There have been many significant recent advances in our understanding of the structure and function of these proteins, as well as in their roles in cellular signaling. Here, we provide an update on the current knowledge of the structure of the CCM proteins and their functions within cellular signaling, particularly in cellular adhesion complexes and signaling cascades. We go on to discuss subcellular localization of the CCM proteins, the formation and regulation of the CCM complex signaling platform, and current progress towards targeted therapy for CCM disease. Recent structural studies have begun to shed new light on CCM protein function, and we focus here on how these studies have helped inform the current understanding of these roles and how they may aid future studies into both CCM-related biology and disease mechanisms.     

Revertant mosaicism in genodermatoses

Inherited monogenic skin disorders include blistering disorders, inflammatory disorders, and disorders of differentiation or development. In most cases, the skin is broadly involved throughout the affected individual’s lifetime, but rarely, appearance of normal skin clones has been described. In these cases of revertant mosaicism, cells undergo spontaneous correction to ameliorate the effects of genetic mutation. While targeted reversion of genetic mutation would have tremendous therapeutic value, the mechanisms of reversion in the skin are poorly understood. In this review, we provide an overview of genodermatoses that demonstrate widespread reversion and their corrective mechanisms, as well as the current research aimed to understand this “natural gene therapy”.     

Increased rate of melanization in hemolymph of American cockroaches (Periplaneta americana) and house crickets (Acheta domesticus) intoxicated by insecticides

Treatment of house crickets and American cockroaches with any one of a variety of insecticides increased the rate of melanization in hemolymph incubated with diphenol substrates.