Botulinum neurotoxins (BoNTs) are among the most potent toxins known and are also used to treat an increasing number of medical disorders. There are seven well-established serotypes (BoNT/A-G), which all act as zinc-dependent endopeptidases targeting specific members of the SNARE proteins required for synaptic vesicle exocytosis in neurons. A new toxin serotype, BoNT/X, was recently identified. It

Human NUDT22 belongs to the diverse NUDIX family of proteins, but has, until now, remained uncharacterized. Here we show that human NUDT22 is a Mg2+-dependent UDP-glucose and UDP-galactose hydrolase, producing UMP and glucose 1-phosphate or galactose 1-phosphate. We present the structure of human NUDT22 alone and in a complex with the substrate UDP-glucose. These structures reveal a partially cons

Botulinum neurotoxins (BoNTs), produced by various Clostridium strains, are a family of potent bacterial toxins and potential bioterrorism agents. Here we report that an Enterococcus faecium strain isolated from cow feces carries a BoNT-like toxin, designated BoNT/En. It cleaves both VAMP2 and SNAP-25, proteins that mediate synaptic vesicle exocytosis in neurons, at sites distinct from known BoNT

This paper presents a time-interleaved pipelined-SAR converter targeting a multi-band mobile communication receiver. The input buffer is based on a super-source follower and linearized by selecting a specific bias current and drain bias resistor. Time interleaved sampling time mismatch is resolved by using a common sample and hold circuit, and gain mismatch is corrected by fine tuning respective s

With a diverse network of substrates, NUDIX hydrolases have emerged as a key family of nucleotide-metabolizing enzymes. NUDT5 (also called NUDIX5) has been implicated in ADP-ribose and 8-oxo-guanine metabolism and was recently identified as a rheostat of hormone-dependent gene regulation and proliferation in breast cancer cells. Here, we further elucidate the physiological relevance of known NUDT5

MTH1 hydrolyzes oxidized nucleoside triphosphates, thereby sanitizing the nucleotide pool from oxidative damage. This prevents incorporation of damaged nucleotides into DNA, which otherwise would lead to mutations and cell death. The high level of reactive oxygen species in cancer cells leads to a higher level of oxidized nucleotides in cancer cells compared to that in nonmalignant cells, making c

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

The fragmentation of high-energy gluons at small opening angles is largely unconstrained by present measurements. Gluon splitting to b-quark pairs is a unique probe into the properties of gluon fragmentation because identified b-tagged jets provide a proxy for the quark daughters of the initial gluon. In this study, key differential distributions related to the g→bb process are measured using 33 f

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative,

A search for four-top-quark production, tttt, is presented. It is based on proton-proton collision data with a center-of-mass energy s=13 TeV collected by the ATLAS detector at the Large Hadron Collider during the years 2015 and 2016, corresponding to an integrated luminosity of 36.1 fb-1. Data are analyzed in both the single-lepton and opposite-sign dilepton channels, characterized by the presenc

Extracting the latent knowledge from Twitter by applying spatial clustering on geotagged tweets provides the ability to discover events and their locations. DBSCAN (density-based spatial clustering of applications with noise), which has been widely used to retrieve events from geotagged tweets, cannot efficiently detect clusters when there is significant spatial heterogeneity in the dataset, as it

Since the 1970s, the degrowth idea has been proposed by scholars, public intellectuals and activists as a powerful call to reject the obsession of neoliberal capitalism with economic growth, an obsession which continues apace despite the global ecological crisis and rising inequalities. In the past decade, degrowth has gained momentum and become an umbrella term for various social movements which

This paper investigates the relationships between product architectures and global operations networks and their impact on operational performance, based on survey data from 82 Swedish manufacturers. We find that modular and integral product architectures are associated with different characteristics of the global operations network, and that global operations network designs are characterised by

Manufacturing firms with multiple product groups do not need to involve all factories in the production of all product groups. Some factories may specialize on a small set of products, while others participate in the manufacturing of a broader set of products. However, current theories on international manufacturing networks do not explain in detail how organizations design international manufactu

Heart failure (HF) is a morbid and heritable disorder for which the biological mechanisms are incompletely understood. We therefore examined genetic associations with HF in a large national biobank, and assessed whether refined phenotypic classification would facilitate genetic discovery. Methods: We defined all-cause HF among 488 010 participants from the UK Biobank and performed a genome-wide a