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Proteolysis plays an important role in mitochondrial biogenesis, from the processing of newly imported precursor proteins to the degradation of mitochondrial targeting peptides. Disruption of peptide degradation activity in yeast, plant and mammalian mitochondria is known to have deleterious consequences for organism physiology, highlighting the important role of mitochondrial peptidases. In the p
Botulinum neurotoxins (BoNTs), the most potent toxins known, are potential bioterrorism agents. It is well established that all seven serotypes of BoNTs (BoNT/A-G) require complex gangliosides as co-receptors. Here, we report that BoNT/DC, a presumed mosaic toxin between BoNT/D and BoNT/C1, binds and enters efficiently into neurons lacking complex gangliosides and shows no reduction in toxicity in
The NUDIX enzymes are involved in cellular metabolism and homeostasis, as well as mRNA processing. Although highly conserved throughout all organisms, their biological roles and biochemical redundancies remain largely unclear. To address this, we globally resolve their individual properties and inter-relationships. We purify 18 of the human NUDIX proteins and screen 52 substrates, providing a subs
In this presentation we review the evolution of radio access networks and introduce 5G, based on the current plans and expectations, as reported in the recent series of the Ericsson Mobility Reports. Standardization is an on-going effort, and much industry research is devoted to finding a good match of requirements - balancing system performance, flexibility and implementation imphcations. We pres
Botulinum neurotoxins are highly toxic substances and are all encoded together with one of two alternative gene clusters, the HA or the OrfX gene cluster. Very little is known about the function and structure of the proteins encoded in the OrfX gene cluster, which in addition to the toxin contains five proteins (OrfX1, OrfX2, OrfX3, P47, and NTNH). We here present the structures of OrfX2 and P47,
Fragment-based lead discovery has emerged as a leading drug development strategy for novel therapeutic targets. Although fragment-based drug discovery benefits immensely from access to atomic-resolution information, structure-based virtual screening has rarely been used to drive fragment discovery and optimization. Here, molecular docking of 0.3 million fragments to a crystal structure of cancer t
Here we present a two-step diastereoselective methodology building on a multicomponent aza-Diels-Alder reaction. Using previously unexplored cyclic ketones, heterocyclic amines and cyclopentadiene derivatives, we obtained novel spiro-heterocyclic frameworks at the interphase between "drug-like" molecules and natural products.
Botulinum neurotoxins are known to have seven serotypes (BoNT/A-G). Here we report a new BoNT serotype, tentatively named BoNT/X, which has the lowest sequence identity with other BoNTs and is not recognized by antisera against known BoNTs. Similar to BoNT/B/D/F/G, BoNT/X cleaves vesicle-associated membrane proteins (VAMP) 1, 2 and 3, but at a novel site (Arg66-Ala67 in VAMP2). Remarkably, BoNT/X
Botulinum neurotoxin B is a Food and Drug Administration-approved therapeutic toxin. However, it has lower binding affinity toward the human version of its major receptor, synaptotagmin II (h-Syt II), compared to mouse Syt II, because of a residue difference. Increasing the binding affinity to h-Syt II may improve botulinum neurotoxin B's therapeutic efficacy and reduce adverse effects. Here we ut
The tetanus neurotoxin (TeNT) is a highly potent toxin produced by Clostridium tetani that inhibits neurotransmission of inhibitory interneurons, causing spastic paralysis in the tetanus disease. TeNT differs from the other clostridial neurotoxins by its unique ability to target the central nervous system by retrograde axonal transport. The crystal structure of the tetanus toxin reveals a "closed"
In this article, we review the evolution of radio access networks and introduce fifth generation (5G), based on the current plans and expectations, as reported in the 2017 Ericsson Mobility Reports. Standardization is an ongoing effort, and much industry research is devoted to finding a good match of requirements, including balancing system performance, flexibility, and implementation implications
The use of a wake-up receiver (WUR) is an attractive means to reduce power consumption. However, when the wake-up signal (WUS) is sent in-band, the use of a WUR may potentially reduce the spectrum efficiency of the system. In this paper, we propose to multiplex the WUS, based on ON-OFF keying, with the user data using FDMA or OFDMA to allow for spectrum efficient use of WURs. The proposed WUR arch
Arbetet omfattar uppföljningav ställda kriterier förlåg klimatpåverkan från betong vid upphandling av betongstommeför brf. Viva i Göteborg. Kriterierna följdes upp dels genom att LCA studien som genomförtsunder programskedet uppdaterades med data för den färdigupphandlade byggnadenoch dels genom att interljuva ett urval av aktörer för att få en inblick över hur branschen ser på de ställda kraven. This work includes monitoring of set criteria for low climate impact from concrete in procurement of concrete structures for brf. Viva in Gothenburg. The criteria were followed up by updating the LCA study performed during the program phase with new data for the completed building, plus a selection of the project stakeholders were also interviewed to gain an insight into how the industry received
IEEE 1687 enables flexible access to on-chip instruments via dynamically reconfigurable networks. Reconfiguration allows reducing instrument access time by keeping only those instruments on the scan-path which are required for each access. To perform reconfiguration and execute commands described in instrument access procedures, scan vectors are generated in a process called retargeting. These vec
Purpose – This paper will examine the unsafe work practices that are plaguing the construction industry. Statistics show that four out of five of all workplace accidents are attributed to unsafe behaviour. Research studies have sought to understand worker self-protection. For example, it is difficult to make predictions of conditions that influenced worker’s behaviour to act unsafely or safely in
