Limited transmission of SARS-CoV-2 in schools in Ireland during the 2020-2021 school year.

BackgroundThe role of schools in SARS-CoV-2 transmission has been a debated topic since the beginning of the COVID-19 pandemic.AimTo examine SARS-CoV-2 transmission in all schools in Ireland during the 2020-21 school year.MethodsIn a national descriptive cross-sectional study, we investigated PCR-confirmed cases of COVID-19 among students (aged < 20 years) and staff (aged ≥ 20 years) who attended school during their infectious period to identify school close contacts.

Three segment ligation of a 104 kDa multi-domain protein by SrtA and OaAEP1.

NMR spectroscopy is an excellent tool for studying protein structure and dynamics which provides a deeper understanding of biological function. As the size of the biomolecule of interest increases, it can become advantageous to dilute the number of observed signals in the NMR spectrum to decrease spectral overlap and increase resolution. One way to limit the number of resonances in the NMR data is by selectively labeling a smaller domain within the larger macromolecule, a process called segmental isotopic labeling.

Humidity gradients in the air spaces of leaves.

Stomata are orifices that connect the drier atmosphere with the interconnected network of more humid air spaces that surround the cells within a leaf. Accurate values of the humidities inside the substomatal cavity, w, and in the air, w, are needed to estimate stomatal conductance and the CO concentration in the internal air spaces of leaves. Both are vital factors in the understanding of plant physiology and climate, ecological and crop systems.

LRET-derived HADDOCK structural models describe the conformational heterogeneity required for DNA cleavage by the Mre11-Rad50 DNA damage repair complex.

The Mre11-Rad50-Nbs1 protein complex is one of the first responders to DNA double-strand breaks. Studies have shown that the catalytic activities of the evolutionarily conserved Mre11-Rad50 (MR) core complex depend on an ATP-dependent global conformational change that takes the macromolecule from an open, extended structure in the absence of ATP to a closed, globular structure when ATP is bound. We have previously identified an additional 'partially open' conformation using luminescence resonance energy transfer (LRET) experiments.

A Survey of Reported Disease-Related Mutations in the MRE11-RAD50-NBS1 Complex.

The MRE11-RAD50-NBS1 (MRN) protein complex is one of the primary vehicles for repairing DNA double strand breaks and maintaining the genomic stability within the cell. The role of the MRN complex to recognize and process DNA double-strand breaks as well as signal other damage response factors is critical for maintaining proper cellular function. Mutations in any one of the components of the MRN complex that effect function or expression of the repair machinery could be detrimental to the cell and may initiate and/or propagate disease.

Mutation of Conserved Mre11 Residues Alter Protein Dynamics to Separate Nuclease Functions.

Naked and protein-blocked DNA ends occur naturally during immune cell development, meiosis, and at telomeres as well as from aborted topoisomerase reactions, collapsed replication forks, and other stressors. Damaged DNA ends are dangerous in cells and if left unrepaired can lead to genomic rearrangement, loss of genetic information, and eventually cancer. Mre11 is part of the Mre11-Rad50-Nbs1 complex that recognizes DNA double-strand breaks and has exonuclease and endonuclease activities that help to initiate the repair processes to resolve these broken DNA ends.

An Innovative and Accessible Biofeedback Intervention for Improving Self-Regulatory Skills in Pediatric Chronic Pain: A Pilot Study.

Although biofeedback has been considered an effective treatment component for pediatric chronic pain, little research has examined the generalizability to activities outside of the treatment setting. The current study aimed to examine the effects of a biofeedback intervention involving individual and group sessions to facilitate increased self-regulatory skills for chronic pain management and to translate these skills to meaningful activities promoting functional restoration. Participants included 104 adolescents (ages 12-18) attending an intensive interdisciplinary pain rehabilitation program for chronic pain/symptoms and completed biofeedback training as part of the program.

Adjacent mutations in the archaeal Rad50 ABC ATPase D-loop disrupt allosteric regulation of ATP hydrolysis through different mechanisms.

DNA damage is the driving force for mutation and genomic instability, which can both lead to cell death or carcinogenesis. DNA double strand breaks are detected and processed in part by the Mre11-Rad50-Nbs1 protein complex. Although the Mre11-Rad50-Nbs1 complex is essential, several spontaneous mutations have been noted in various cancers.

A dynamic allosteric pathway underlies Rad50 ABC ATPase function in DNA repair.

The Mre11-Rad50 protein complex is an initial responder to sites of DNA double strand breaks. Many studies have shown that ATP binding to Rad50 causes global changes to the Mre11-Rad50 structure, which are important for DNA repair functions. Here we used methyl-based NMR spectroscopy on a series of mutants to describe a dynamic allosteric pathway within Rad50.

Inhibition of 53BP1 favors homology-dependent DNA repair and increases CRISPR-Cas9 genome-editing efficiency.

Programmable nucleases, such as Cas9, are used for precise genome editing by homology-dependent repair (HDR). However, HDR efficiency is constrained by competition from other double-strand break (DSB) repair pathways, including non-homologous end-joining (NHEJ). We report the discovery of a genetically encoded inhibitor of 53BP1 that increases the efficiency of HDR-dependent genome editing in human and mouse cells.

The RNF168 paralog RNF169 defines a new class of ubiquitylated histone reader involved in the response to DNA damage.

Site-specific histone ubiquitylation plays a central role in orchestrating the response to DNA double-strand breaks (DSBs). DSBs elicit a cascade of events controlled by the ubiquitin ligase RNF168, which promotes the accumulation of repair factors such as 53BP1 and BRCA1 on the chromatin flanking the break site. RNF168 also promotes its own accumulation, and that of its paralog RNF169, but how they recognize ubiquitylated chromatin is unknown.

The amino acid distribution in rachis xylem sap and phloem exudate of Vitis vinifera 'Cabernet Sauvignon' bunches.

Amino acids are essential to grape berry and seed development and they are transferred to the reproductive structures through the phloem and xylem from various locations within the plant. The diurnal and seasonal dynamics of xylem and phloem amino acid composition in the leaf petiole and bunch rachis of field-grown Cabernet Sauvignon are described to better understand the critical periods for amino acid import into the berry. Xylem sap was extracted by the centrifugation of excised leaf petioles and rachises, while phloem exudate was collected by immersing these structures in an ethylenediaminetetraacetic acid (EDTA) buffer.

Outbreak of hepatitis A infection associated with the consumption of frozen berries, Ireland, 2013--linked to an international outbreak.

In May 2013, a European alert was issued regarding a hepatitis A virus (HAV) outbreak in Italy. In June 2013, HAV subgenotype IA with an identical sequence was identified in Ireland in three cases who had not travelled to Italy. The investigation consisted of descriptive epidemiology, a case-control study, microbiological testing of human and food specimens, molecular typing of positive specimens and food traceback.

Structure and mechanism of action of the hydroxy-aryl-aldehyde class of IRE1 endoribonuclease inhibitors.

Endoplasmic reticulum (ER) stress activates the unfolded protein response and its dysfunction is linked to multiple diseases. The stress transducer IRE1α is a transmembrane kinase endoribonuclease (RNase) that cleaves mRNA substrates to re-establish ER homeostasis. Aromatic ring systems containing hydroxy-aldehyde moieties, termed hydroxy-aryl-aldehydes (HAA), selectively inhibit IRE1α RNase and thus represent a novel chemical series for therapeutic development.

Some properties of the walls of metaxylem vessels of maize roots, including tests of the wettability of their lumenal wall surfaces.

Background And Aims: Since the proposal of the cohesion theory there has been a paradox that the lumenal surface of vessels is rich in hydrophobic lignin, while tension in the rising sap requires adhesion to a hydrophilic surface. This study sought to characterize the strength of that adhesion in maize (Zea mays), the wettability of the vessel surface, and to reconcile this with its histochemical and physical nature.

Methods: Wettability was assessed by emptying the maize root vessels of sap, perfusing them with either water or oil, and examining the adhesion (as revealed by contact angles) of the two liquids to vessel walls by cryo-scanning electron microscopy.

RETRACTED: Mitosis inhibits DNA double-strand break repair to guard against telomere fusions.

Mitotic cells inactivate DNA double-strand break (DSB) repair, but the rationale behind this suppression remains unknown. Here, we unravel how mitosis blocks DSB repair and determine the consequences of repair reactivation. Mitotic kinases phosphorylate the E3 ubiquitin ligase RNF8 and the nonhomologous end joining factor 53BP1 to inhibit their recruitment to DSB-flanking chromatin.

Nucleosome acidic patch promotes RNF168- and RING1B/BMI1-dependent H2AX and H2A ubiquitination and DNA damage signaling.

Histone ubiquitinations are critical for the activation of the DNA damage response (DDR). In particular, RNF168 and RING1B/BMI1 function in the DDR by ubiquitinating H2A/H2AX on Lys-13/15 and Lys-118/119, respectively. However, it remains to be defined how the ubiquitin pathway engages chromatin to provide regulation of ubiquitin targeting of specific histone residues.

53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark.

53BP1 (also called TP53BP1) is a chromatin-associated factor that promotes immunoglobulin class switching and DNA double-strand-break (DSB) repair by non-homologous end joining. To accomplish its function in DNA repair, 53BP1 accumulates at DSB sites downstream of the RNF168 ubiquitin ligase. How ubiquitin recruits 53BP1 to break sites remains unknown as its relocalization involves recognition of histone H4 Lys 20 (H4K20) methylation by its Tudor domain.

A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice.

DNA double-strand break (DSB) repair pathway choice is governed by the opposing activities of 53BP1 and BRCA1. 53BP1 stimulates nonhomologous end joining (NHEJ), whereas BRCA1 promotes end resection and homologous recombination (HR). Here we show that 53BP1 is an inhibitor of BRCA1 accumulation at DSB sites, specifically in the G1 phase of the cell cycle.

Quantitative cryo-analytical scanning electron microscopy (CEDX): an important technique useful for cell-specific localization of salt.

Advances in the techniques required for the X-ray microanalysis of cryo-fixed, naturally hydrated plant tissues in the cryo-scanning electron microscope have reached the stage that accurate, cell-specific localization and quantification of the nutrient and toxic elements can be achieved. Advances are described in the successive processes of cryo-fixation, cryo-planing to produce flat surfaces, monitored minimal etching to reveal cell outlines, coating with aluminum, spectrum collection, and quantification by comparison with comparable frozen standard solutions of the elements.

Water loss from leaf mesophyll stripped of the epidermis.

Water vapour flux (rate of water loss) from the mesophyll of isolated Agapanthus praecox Willd. leaf pieces without an epidermis was investigated by loss of mass into unstirred air at relative humidities (RHs) of 0.993-0.

Differential shrinkage of mesophyll cells in transpiring cotton leaves: implications for static and dynamic pools of water, and for water transport pathways.

Shrinkage of palisade cells during transpiration, previously measured for sclerophyllous leaves of Eucalyptus where cells shrank equally, was compared with shrinkage in thin mesophytic leaves of cotton (Gossypium hirsutum L.). Selected vapour pressure differences (Δe) from 0.

Development and persistence of sandsheaths of Lyginia barbata (Restionaceae): relation to root structural development and longevity.

Background And Aims: Strongly coherent sandsheaths that envelop perennial roots of many monocotyledonous species of arid environments have been described for over a century. This study, for the first time, details the roles played by the structural development of the subtending roots in the formation and persistence of the sheaths.

Methods: The structural development of root tissues associated with persistent sandsheaths was studied in Lyginia barbata, native to the Western Australian sand plains.

Adherence to hypoglycaemic medication among people with type 2 diabetes in primary care.

Aims: To assess levels and correlates of adherence to hypoglycaemic medication among patients offered organised general practice diabetes care.

Methods: 60 patients prescribed oral hypoglycaemic medication were recruited to a two-month prospective study. Prescribed doses taken and days on which the prescribed number of doses was taken were measured by MEMS (Medication Event Monitoring System).