From "one big clumsy mess" to "a fundamental part of my character." Autistic adults' experiences of motor coordination.

Altered motor coordination is common in autistic individuals affecting a range of movements such as manual dexterity, eye-hand coordination, balance and gait. However, motor coordination is not routinely assessed leading to undiagnosed and untreated motor coordination difficulties, particularly in adults. Few studies have investigated motor coordination difficulties and their impact from the viewpoint of autistic people.

Next-Generation Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Source for Mass Spectrometry Imaging and High-Throughput Screening.

Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is a hybrid, ambient ionization source that combines the advantages of electrospray ionization and matrix-assisted laser desorption/ionization, making it a versatile tool for both high-throughput screening (HTS) and mass spectrometry imaging (MSI) studies. To expand the capabilities of the IR-MALDESI source, an entirely new architecture was designed to overcome the key limitations of the previous source. This next-generation (NextGen) IR-MALDESI source features a vertically mounted IR-laser, a planar translation stage with computerized sample height control, an aluminum enclosure, and a novel mass spectrometer interface plate.

Preservatives from food-For food: Pea protein hydrolysate as a novel bio-preservative against O157:H7 on a lettuce leaf.

Fresh-cut fruits and vegetables are becoming particularly popular as healthy fast-food options; however, they present challenges such as accelerated rates of decay and increased risk for contamination when compared to whole produce. Given that food safety must remain paramount for producers and manufacturers, research into novel, natural food preservation solutions which can help to ensure food safety and protect against spoilage is on the rise. In this work, we investigated the potential of using a novel protein hydrolysate, produced by the enzymatic hydrolysis of (PSH), as a novel bio-preservative and its abilities to reduce populations of O157:H7 after inoculation on a lettuce leaf.

Corrigendum: Efficient Capsid Antigen Presentation From Adeno-Associated Virus Empty Virions .

[This corrects the article DOI: 10.3389/fimmu.2018.

Adeno-Associated Virus Serotype-Specific Inverted Terminal Repeat Sequence Role in Vector Transgene Expression.

Adeno-associated viral vectors have been successfully used in laboratory and clinical settings for efficient gene delivery. In these vectors, 96% of the adeno-associated virus (AAV) genome is replaced with a gene cassette of interest, leaving only the 145 bp inverted terminal repeat (ITR) sequences. These cis-elements, primarily from AAV serotype 2, are required for genome rescue, replication, packaging, and vector persistence.

The Influence of Murine Genetic Background in Adeno-Associated Virus Transduction of the Mouse Brain.

Adeno-associated virus (AAV) vectors have become an important tool for delivering therapeutic genes for a wide range of neurological diseases. AAV serotypes possess differential cellular tropism in the central nervous system. Although several AAV serotypes or mutants have been reported to transduce the brain efficiently, conflicting data occur across studies with the use of various rodent strains from different genetic backgrounds.

Double-stranded RNA innate immune response activation from long-term adeno-associated virus vector transduction.

Data from clinical trials for hemophilia B using adeno-associated virus (AAV) vectors have demonstrated decreased transgenic coagulation factor IX (hFIX) expression 6-10 weeks after administration of a high vector dose. While it is likely that capsid-specific cytotoxic T lymphocytes eliminate vector-transduced hepatocytes, thereby resulting in decreased hFIX, this observation is not intuitively consistent with restored hFIX levels following prednisone application. Although the innate immune response is immediately activated following AAV vector infection via TLR pathways, no studies exist regarding the role of the innate immune response at later time points after AAV vector transduction.

Efficient Capsid Antigen Presentation From Adeno-Associated Virus Empty Virions .

Adeno-associated virus (AAV) vectors have been successfully applied in clinical trials for hemophilic patients. Although promising, the clinical results suggest that the capsid-specific CD8+T cell response has a negative effect on therapeutic success. In an analysis using an engineered AAV virus carrying immune-dominant SIINFEKL peptide in the capsid backbone, we have previously demonstrated that capsid antigen presentation from full (genome containing) AAV capsids requires endosome escape and is proteasome dependent and that no capsid antigen presentation is induced from empty virions.

NEIL1 protects against aflatoxin-induced hepatocellular carcinoma in mice.

Global distribution of hepatocellular carcinomas (HCCs) is dominated by its incidence in developing countries, accounting for >700,000 estimated deaths per year, with dietary exposures to aflatoxin (AFB) and subsequent DNA adduct formation being a significant driver. Genetic variants that increase individual susceptibility to AFB-induced HCCs are poorly understood. Herein, it is shown that the DNA base excision repair (BER) enzyme, DNA glycosylase NEIL1, efficiently recognizes and excises the highly mutagenic imidazole ring-opened AFB-deoxyguanosine adduct (AFB-Fapy-dG).

Adeno-associated Virus (AAV) Assembly-Activating Protein Is Not an Essential Requirement for Capsid Assembly of AAV Serotypes 4, 5, and 11.

Unlabelled: Adeno-associated virus (AAV) vectors have made great progress in their use for gene therapy; however, fundamental aspects of AAV's capsid assembly remain poorly characterized. In this regard, the discovery of assembly-activating protein (AAP) sheds new light on this crucial part of AAV biology and vector production. Previous studies have shown that AAP is essential for assembly; however, how its mechanistic roles in assembly might differ among AAV serotypes remains uncharacterized.

Identification and characterization of nuclear and nucleolar localization signals in the adeno-associated virus serotype 2 assembly-activating protein.

Unlabelled: Assembly-activating protein (AAP) of adeno-associated virus serotype 2 (AAV2) is a nucleolar-localizing protein that plays a critical role in transporting the viral capsid VP3 protein to the nucleolus for assembly. Here, we identify and characterize AAV2 AAP (AAP2) nuclear (NLS) and nucleolar (NoLS) localization signals near the carboxy-terminal region of AAP2 (amino acid positions 144 to 184) (AAP2(144-184)). This region contains five basic-amino-acid-rich (BR) clusters, KSKRSRR (AAP2BR1), RRR (AAP2BR2), RFR (AAP2BR3), RSTSSR (AAP2BR4), and RRIK (AAP2BR5), from the amino terminus to the carboxy terminus.

Pyrosequencing: applicability for studying DNA damage-induced mutagenesis.

Site-specifically modified DNAs are routinely used in the study of DNA damage-induced mutagenesis. These analyses involve the creation of DNA vectors containing a lesion at a pre-determined position, DNA replication, and detection of mutations at the target site. The final step has previously required the isolation of individual DNA clones, hybridization with radioactively labeled probes, and verification of mutations by Sanger sequencing.

Novel parallelized quadrupole/linear ion trap/Orbitrap tribrid mass spectrometer improving proteome coverage and peptide identification rates.

Proteome coverage and peptide identification rates have historically advanced in line with improvements to the detection limits and acquisition rate of the mass spectrometer. For a linear ion trap/Orbitrap hybrid, the acquisition rate has been limited primarily by the duration of the ion accumulation and analysis steps. It is shown here that the spectral acquisition rate can be significantly improved through extensive parallelization of the acquisition process using a novel mass spectrometer incorporating quadrupole, Orbitrap, and linear trap analyzers.

Front-end electron transfer dissociation: a new ionization source.

Electron transfer dissociation (ETD), a technique that provides efficient fragmentation while depositing little energy into vibrational modes, has been widely integrated into proteomics workflows. Current implementations of this technique, as well as other ion-ion reactions like proton transfer, involve sophisticated hardware, lack robustness, and place severe design limitations on the instruments to which they are attached. Described herein is a novel, electrical discharge-based reagent ion source that is located in the first differentially pumped region of the mass spectrometer.

Mutagenic spectra arising from replication bypass of the 2,6-diamino-4-hydroxy-N(5)-methyl formamidopyrimidine adduct in primate cells.

DNA exposures to electrophilic methylating agents that are commonly used during chemotherapeutic treatments cause diverse chemical modifications of nucleobases, with reaction at N7-dG being the most abundant. Although this base modification frequently results in destabilization of the glycosyl bond and spontaneous depurination, the adduct can react with hydroxide ion to yield a stable, ring-opened MeFapy-dG, and this lesion has been reported to persist in animal tissues. Results from prior in vitro replication bypass investigations of the MeFapy-dG adduct had revealed complex spectra of replication errors that differed depending on the identity of DNA polymerase and the local sequence context.

Variable penetrance of metabolic phenotypes and development of high-fat diet-induced adiposity in NEIL1-deficient mice.

Exposure to chronic and acute oxidative stress is correlated with many human diseases, including, but not limited to, cancer, heart disease, diabetes, and obesity. In addition to cellular lipids and proteins, cellular oxidative stress can result in damage to DNA bases, especially in mitochondrial DNA. We previously described the development of spontaneous late-onset obesity, hepatic steatosis, hyperinsulinemia, and hyperleptinemia in mice that are deficient in the DNA glycosylase nei-like 1 (NEIL1), which initiates base excision repair of several oxidatively damaged bases.

First experimental demonstration of a photonic band gap channel-drop filter at 240 GHz.

We have designed, fabricated, and tested a novel photonic band gap (PBG) channel-drop filter (CDF) operating at around 240 GHz. A PBG CDF is a device that allows the channeling of selected frequencies from continuous spectra into separate waveguides through select defects in a PBG structure. It is compact and configurable, and thus, it can be employed for millimeter-wave spectrometry with applications in communications, radio astronomy, and radar receivers for remote sensing and nonproliferation.

Larger field sizes: an advantage of the dynamic wedge.

This case study describes a clinical situation in which dynamically wedged beams provide treatment options that are not available using conventional physical wedges. The process of planning and delivery are reviewed briefly.

Dose to the contralateral breast: a comparison of two techniques using the enhanced dynamic wedge versus a standard wedge.

The dose to the contralateral breast has been associated with an increased risk of developing a second breast malignancy. Varying techniques have been devised and described in the literature to minimize this dose. Metal beam modifiers such as standard wedges are used to improve the dose distribution in the treated breast, but unfortunately introduce an increased scatter dose outside the treatment field, in particular to the contralateral breast.

A method for total skin electron treatment for infants.

Diseases such as mycosis fungoides require the treatment of a patient's total skin surface with superficial radiation. In a unique clinical situation, a 14-month-old child presented with a need for total skin treatment. A typical total skin technique requires overlapping electron beams, using 6 body positions, each with the gantry rotated for 2 angulations, or '6 positions-12 fields'.

Developmental changes in the contextual control of recognition.

In three experiments, we explored potential developmental differences in the contextual control of target recognition using elementary perceptual features that differed only in their spatial relations. Three- and 6-month-old infants were trained in the presence of black horizontal and vertical line segments arranged as Ls, Ts, or +s on a pink background and were tested in the presence of the same line segments in a different spatial arrangement. At both ages, target recognition required a match between the primitive perceptual features in the test context and those present during training.

An in vivo study of the effects of ischaemia on uterine contraction, intracellular pH and metabolites in the rat.

There are no data concerning the functional or metabolic effects of hypoxia in vivo in smooth muscle. We have therefore used 31P-NMR spectroscopy and intra-uterine pressure measurements to examine simultaneously, in vivo, the effect of ischaemia on uterine metabolites, intracellular pH (pHi) and force. A 1-2 cm portion of uterus from day 1 postpartum anaesthetized rats was exteriorized and an NMR surface coil placed on it.

Effects of hypoxia on force produced by agonists and depolarization and arising spontaneously in the rat uterus.

The effects of cyanide and nitrogen on contractile activity in rat uteri was investigated. Hypoxia significantly reduced contractile activity produced either spontaneously, or by application of carbachol (50 mumol l-1) or oxytocin (20 nmol l-1) in preparations from pregnant and nonpregnant rats. Hypoxia had, however, significantly smaller effects on agonist-evoked than on spontaneous contractions.

Alternative pathways for training the general internist and the medical subspecialist.

Considerable attention is being directed from within the discipline of internal medicine to a perceived need for changes in the curriculum for postgraduate training of the internist. Much of this attention has been focused on the training required to properly prepare the general internist for the evolving system of health care. A proposal is presented to change the pattern of training of both the general internist and the medical subspecialist.

Documentation of ovoid cap size.

The need for precise documentation in radiation oncology is paramount; assurance of the quality of therapy delivered is the responsibility of everyone engaged in the treatment of cancer patients. Although all aspects of quality assurance require meticulous attention to detail, the documentation of brachytherapy procedures, both written dose prescription and film verification, is particularly important as no single method of dose reporting is universally accepted and used. The size of ovoid caps used in brachytherapy applications for gynecologic malignancies cannot be verified on treatment planning films, as the caps are not radio-opaque.