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Background: A number of studies have examined time intervals between care steps in breast cancer diagnosis and treatment. The objective of this study was to document the elapsed time from first clinical or mammographic detection of breast abnormality to initiation of first adjuvant therapy in women with invasive breast cancer in Nova Scotia and to examine the effect of age, disease stage and place of residence on these intervals.Methods: All dates were abstracted from patient charts and the Oncology Patient Information System. Eligible women were those with invasive breast cancer detected by Sept. 1, 1999, who were referred to 1 of 2 provincial cancer treatment centres by Sept. 1, 2000. All time intervals were calculated in days, and only patients experiencing both care events defining an interval were included in the analysis of time to event for that interval. We used proportional hazards regression analysis to evaluate the influence of patient age, disease stage and place of residence on times between care events.Results: A total of 776 new diagnoses of breast cancer were reported to the Nova Scotia Cancer Registry over the study period. Of the 776, 467 met the inclusion criteria, and 364 patients were eligible for analysis. The overall median time from clinical or mammographic detection of breast cancer to initiation of first adjuvant therapy was 91 days (interquartile range 72-123 days). Disease stage was the strongest predictor of elapsed time: the median interval from disease detection to initiation of first adjuvant therapy for patients with stage I disease was 118 days, as compared with 85 days for those with stage II disease and 75 days for those with stage III disease (adjusted hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.6-2.8). Patients aged 70 years or more at diagnosis experienced longer elapsed times (median interval 98 days) than did younger patients (93 days for those aged 50-69 years and 82 days for those aged 49 years or less) (adjusted HR 1.6, 95% CI 1.1-2.4).Interpretation: Women aged 70 or more and those with stage I breast cancer experienced longer elapsed times from disease detection to initiation of first adjuvant therapy than did younger women and those with more advanced disease. These findings may have implications for the design of interventions to minimize intervals between steps in breast cancer care and should be validated within the Canadian context. Future investigation exploring the full spectrum of breast cancer care may lead to a more complete understanding of processes and gaps in the current system. [ABSTRACT FROM AUTHOR]

Calmodulin (CaM)-like proteins (CMLs) are the largest family of calcium-binding proteins in plants, yet the functions of most CMLs are unknown. Arabidopsis CML13 and CML14 are closely related paralogs that interact with the isoleucine-glutamine (IQ) domains of myosins, IQ-domain proteins and CaM-binding transcription activators (CAMTAs). Here, we explored the physiological roles of CML13 and CML14 during development by using dexamethasone (Dex)-inducible RNA silencing to suppress either CML13 or CML14 transcript levels. In the absence of inducible suppression, CML13- and CML14-RNA-interference lines were indistinguishable from wild-type (WT) plants throughout development. In contrast, induction of silencing treatment led to rapid increases in RNA-hairpin production that correlated with a targeted reduction in CML13 or CML14 transcript levels and a range of developmental and morphological effects. RNA-suppression treatment did not impair the germination of CML13- or 14-RNA-interference lines, but these seedlings were chlorotic, displayed high mortality and failed to achieve seedling establishment. Under Dex treatment, seeds of CML13- and CML14-RNA-interference lines exhibited differential sensitivity to exogenous ABA compared to WT seeds. Induced RNA suppression of mature plants led to reduced silique length, shorter roots and rapid leaf senescence in CML13- and 14-RNA-interference plants, which correlated with increased gene expression of the senescence marker Senescence-Associated Gene13 (SAG13). Plants induced for RNA suppression at 2 weeks post-germination exhibited a much stronger phenotype than treatment of 3-, 4- or 5-week-old plants. Collectively, our data indicate that both CML13 and CML14 are essential for normal development and function across a broad range of tissues and developmental stages., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Root systems of most land plants are colonised by arbuscular mycorrhiza fungi. The symbiosis supports nutrient acquisition strategies predominantly associated with plant access to inorganic phosphate. The nutrient acquisition is enhanced through an extensive network of external fungal hyphae that extends out into the soil, together with the development of fungal structures forming specialised interfaces with root cortical cells. Orthologs of the bHLHm1;1 transcription factor, previously described in soybean nodules (GmbHLHm1) and linked to the ammonium facilitator protein GmAMF1;3, have been identified in Medicago ( Medicago truncatula) roots colonised by AM fungi. Expression studies indicate that transcripts of both genes are also present in arbuscular containing root cortical cells and that the MtbHLHm1;1 shows affinity to the promoter of MtAMF1;3 . Both genes are induced by AM colonisation. Loss of Mtbhlhm1;1 expression disrupts AM arbuscule abundance and the expression of the ammonium transporter MtAMF1;3 . Disruption of Mtamf1;3 expression reduces both AM colonisation and arbuscule development. The respective activities of MtbHLHm1;1 and MtAMF1;3 highlight the conservation of putative ammonium regulators supporting both the rhizobial and AM fungal symbiosis in legumes.

Symbiotic interactions between rhizobia and legumes result in the formation of root nodules, which fix nitrogen that can be used for plant growth. Rhizobia usually invade legume roots through a plant-made tunnel-like structure called an infection thread (IT). RPG (Rhizobium-directed polar growth) encodes a coiled-coil protein that has been identified in Medicago truncatula as required for root nodule infection, but the function of RPG remains poorly understood. In this study, we identified and characterized RPG in Lotus japonicus and determined that it is required for IT formation. RPG was induced by Mesorhizobium loti or purified Nodulation factor and displayed an infection-specific expression pattern. Nodule inception (NIN) bound to the RPG promoter and induced its expression. We showed that RPG displayed punctate subcellular localization in L. japonicus root protoplasts and in root hairs infected by M. loti. The N-terminal predicted C2 lipid-binding domain of RPG was not required for this subcellular localization or for function. CERBERUS, a U-box E3 ligase which is also required for rhizobial infection, was found to be localized similarly in puncta. RPG co-localized and directly interacted with CERBERUS in the early endosome (TGN/EE) compartment and near the nuclei in root hairs after rhizobial inoculation. Our study sheds light on an RPG-CERBERUS protein complex that is involved in an exocytotic pathway mediating IT elongation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Neonatal circumcision (NNC) is the most frequently performed surgical procedure worldwide and is generally considered safe in Western societies. Deaths attributed to NNC are seldom reported and are mostly explained by lack of adherence to medical standards. We reviewed our emergency department database for circumcision-related emergency admissions. During 2000-2013, 19 previously healthy neonates were admitted for acute complications after circumcision. Four were admitted for bleeding, with hemophilia identified in two cases and von Willebrand disease in one. Eight boys required emergency surgery, three for severe bleeding. Four boys with amputation of the glans underwent immediate surgical reconstruction. One infant was taken to the operating room to remove an obstructing Plastibell ring. Seven boys were admitted to the intensive care unit with severe bleeding or sepsis, three of whom ultimately progressed to hemorrhagic or septic shock. Two of these children died of their complications. We estimate that the annual incidence of severe complications requiring hospitalization after NNC in the Greater Toronto Area was approximately 0.01%, and the incidence of fatalities over the 14-yr review period was approximately 0.0012%. Our results indicate that the risk of serious complications and death as a result of NNC is greater than generally assumed., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Gait modifications are effective in reducing the first peak knee abduction moment (PKAM), a surrogate for knee loading. Reliance on 3D motion capture currently restricts these modifications to the laboratory. Therefore, our purpose was to test the feasibility of a novel wearable biofeedback system to train (1) toe-in and trunk lean modifications and (2) combined toe-in and trunk lean modifications to reduce PKAM during overground walking outside of the laboratory. Twelve healthy participants practiced modifications in a university hallway directly after performing five normal walking trials. The wearable feedback system provided real-time haptic biofeedback during training trials to inform participants if they were within the prescribed modification range (7-12 deg greater than baseline). Participants were instructed to move to the next modification only once they felt comfortable and could perform it with minimal errors. Following training, five trials of each modification were immediately performed in the gait laboratory without feedback. All participants successfully modified their foot progression and trunk angle using the wearable system. At post-test, PKAM decreased from baseline by 62%, 55%, and 28% during combined, trunk leanand toe-in gait, respectively. The wearable feedback system was effective to modify participants' foot and trunk angle by the prescribed amount, resulting in reduced PKAM during all modifications at post-test. Participants were also able to perform a combined modification, although it took longer to report feeling comfortable doing so. This study demonstrates that a wearable feedback system is feasible to modify kinematic parameters and train gait modifications outside the laboratory., (Copyright © 2021 by ASME.)

Background: Elastin insufficiency causes recurrent vascular stenoses. Hemizygous deletion of the elastin gene ( ELN ) causes Williams-Beuren syndrome (WBS), while single nucleotide variants in ELN cause nonsyndromic supravalvar aortic stenosis (SVAS). Our objective was to compare cardiovascular disease outcomes in patients with WBS and nonsyndromic SVAS., Methods: Patients (81 WBS, 42 nonsyndromic SVAS) with cardiovascular disease were included in this retrospective single center study. Freedom from surgical and catheter interventions and reinterventions was compared. Vascular tissue from 8 patients and 6 controls was analyzed for arterial wall architecture., Results: Patients with nonsyndromic SVAS presented at a younger age (median 0.3 [0.4-0.7] years) compared with patients with WBS (1.3 [0.2-3.0] years) and had lower freedom from surgical/catheter interventions compared with patients with WBS, with median event-free survival 1.1 (0.3-5.9) versus 4.7 (2.4-13.3) years, respectively (hazard ratio, 1.62 [95% CI, 1.02-2.56]; P =0.04). Patients with nonsyndromic SVAS also had a lower freedom from reinterventions ( P =0.054 by log-rank test). This was related in part to a higher frequency of primary and reinterventions for concomitant valvar aortic stenosis. Histology revealed abnormal intimal and medial thickening, disorganized and fragmented elastic fibers, reduced smooth muscle calponin expression, and increased macrophage marker, CD68, expression in the arterial walls in patients with WBS and nonsyndromic SVAS compared with controls., Conclusions: Patients with nonsyndromic SVAS require early and more frequent vascular and valvular interventions and reinterventions, in particular for concomitant valvar aortic stenosis compared with patients with WBS. This provides important prognostic information to guide counseling of affected families with cardiovascular disease and may guide primary intervention strategies based on predicted risk of restenosis.

Background: The optimal blood flow and pressure to perfuse pediatric hearts from donation after circulatory death (DCD) on the ex vivo perfusion system has not been elucidated. This study sought to investigate the optimal perfusion strategy for pediatric DCD hearts by using a juvenile porcine model comparing pressure- vs flow-targeted strategy., Methods: The hearts of the juvenile DCD pigs were explanted, and the coronary arteries were perfused for 2 hours by the ex vivo heart perfusion system with 2 different perfusion strategies; pressure-targeted perfusion (target coronary perfusion pressure: 40 mm Hg, group A) and flow-targeted perfusion (target coronary perfusion flow: 10 ml/kg/min, group B). The working model heart perfusion was used to assess systolic and diastolic myocardial performance., Results: The body weight, warm and cold ischemic time, and ex vivo perfusion time were comparable between the groups. In the working model, group B showed significantly preserved cardiac output (A: 70.5 ± 15.3 ml/kg/min vs B: 113.8 ± 15.0 ml/kg/min, p < 0.01), stroke volume (A: 0.4 ± 0.1 ml/kg vs B: 0.7 ± 0.1 ml/kg, p < 0.01), and ejection fraction (A: 18.8% ± 5.9% vs B: 35.0% ± 10.6%, p < 0.01). E/e' and Tei index were also significantly preserved in group B. The percentage gain of heart weight after ex vivo (net increase of the heart weight divided by heart weight at baseline) was significantly smaller in group B (A: 20.0% ± 5.3% vs B: 11.6% ± 5.0%, p < 0.05). Troponin-I, myocardial hemorrhage, oxidative stress markers; myeloperoxidase and 8-hydroxy-2'-deoxyguanosine were also significantly lower after ex vivo perfusion in group B (p < 0.05)., Conclusions: The tightly controlled flow-targeted myocardial perfusion strategy for DCD donor hearts achieved better myocardial performance by causing less myocardial edema and limiting myocardial reperfusion injury., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The phytohormone abscisic acid (ABA) regulates plant responses to abiotic stress, such as drought and high osmotic conditions. The multitude of functionally redundant components involved in ABA signaling poses a major challenge for elucidating individual contributions to the response selectivity and sensitivity of the pathway. Here, we reconstructed single ABA signaling pathways in yeast for combinatorial analysis of ABA receptors and coreceptors, downstream-acting SnRK2 protein kinases, and transcription factors. The analysis shows that some ABA receptors stimulate the pathway even in the absence of ABA and that SnRK2s are major determinants of ABA responsiveness by differing in the ligand-dependent control. Five SnRK2s, including SnRK2.4 known to be active under osmotic stress in plants, activated ABA-responsive transcription factors and were regulated by ABA receptor complexes in yeast. In the plant tissue, SnRK2.4 and ABA receptors competed for coreceptor interaction in an ABA-dependent manner consistent with a tight integration of SnRK2.4 into the ABA signaling pathway. The study establishes the suitability of the yeast system for the dissection of core signaling cascades and opens up future avenues of research on ligand-receptor regulation., (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)

Assembling composite DNA modules from custom DNA parts has become routine due to recent technological breakthroughs such as Golden Gate modular cloning. Using Golden Gate, one can efficiently assemble custom transcription units and piece units together to generate higher-order assemblies. Although Golden Gate cloning systems have been developed to assemble DNA plasmids required for experimental work in model species, they are not typically applicable to organisms from other kingdoms. Consequently, a typical molecular biology laboratory working across kingdoms must use multiple cloning strategies to assemble DNA constructs for experimental assays. To simplify the DNA assembly process, we developed a multi-kingdom (MK) Golden Gate assembly platform for experimental work in species from the kingdoms Fungi, Eubacteria, Protista, Plantae, and Animalia. Plasmid backbone and part overhangs are consistent across the platform, saving both time and resources in the laboratory. We demonstrate the functionality of the system by performing a variety of experiments across kingdoms including genome editing, fluorescence microscopy, and protein interaction assays. The versatile MK system therefore streamlines the assembly of modular DNA constructs for biological assays across a range of model organisms.

Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) is a rare, autosomal dominant disorder of interstitial lung development, leading to pulmonary hypertension, and death in infancy. Associated features include malformations of the heart, gastrointestinal tract, and genitourinary system. ACDMPV is caused by heterozygous variants in the FOXF1 gene or microdeletions involving FOXF1. We present a male infant with ACDMPV, hypoplastic left heart sequence (HLHS), duodenal atresia, and imperforate anus due to a de novo, in frame deletion in FOXF1: c.209&#95;214del (p.Thr70&#95;Leu71del). Previous reports have suggested that microdeletions involving FOXF1 are associated with ACDMPV with congenital heart defects, including HLHS, gastrointestinal atresias, and other anomalies; whereas likely pathogenic variants within FOXF1 have not been reported with ACDMPV and HLHS. This is the first patient reported with ACDMPV, HLHS, imperforate anus, and duodenal atresia associated with a likely pathogenic variant in the FOXF1 gene., (© 2019 Wiley Periodicals, Inc.)

Basketball players sometimes claim to know when their shot is good, even before it goes in. This is likely because shooter proprioception can help determine shot outcome, even before their eyes confirm it. This phenomenon, however, has not been systematically explored for collegiate and recreational shooters. This study compared how well collegiate shooters and recreational shooters could predict outcomes of their own free throws without seeing the shot result. Forty collegiate and recreational shooters shot standard free throws while wearing liquid-crystal occlusion glasses that activated to occlude vision immediately following ball release during each shot. After each shot, shooters verbally predicted shot outcome as "in" or "out", and predicted results were compared with actual outcomes. As anticipated, for made shots, collegiate shooters more accurately predicted their own shots than recreational shooters. However, unexpectedly, for missed shots, collegiate shooters were worse than recreational shooters and were even significantly worse than chance. Further analysis found that collegiate shooters exhibited a significantly higher bias toward predicting their shots as "in". Understanding how shooters of different skill levels perceive their own shot could inform future training strategies for improving shooter accuracy., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To discuss the role of investigations after death in children as part of a supplement on "Death and Dying in the PICU.", Data Sources: Literature review, personal experience, and expert opinion., Data Selection: Not applicable., Data Extraction: Moderated by three experts on investigations after death in children., Data Synthesis: Not relevant., Conclusions: A multidisciplinary cliniciopathologic conference is important after the death of a child in order to help bring closure to the family and to attempt to address any concerns they may have about the care. It is also an important part of the quality of care process for a tertiary care institution and provides an unique opportunity for ongoing medical education. The model of a multidisciplinary cliniciopathologic conference used by the Ontario Coroner's Office to investigate sudden and unexpected deaths in children under 5 years old, which has been functioning for over 30 years, is described. Reports from this Pediatric Death Review Committee have been influential in improving the care of children in the province of Ontario.

Primary Objective: To examine the effect of concussion on indices of attention using magnetoencephalography., Methods and Procedures: Thirteen patients were recruited from the emergency department and scanned within 3-6 days of injury. Five returned for follow-up scans one and three months post-injury. Thirteen healthy controls also completed testing. During MEG acquisition, participants performed the Attention Network Test (ANT). Cognitive evoked responses to this task include a cue-evoked P300m, a contingent magnetic variation (CMV) and a target-evoked P300m. The Rivermead Postconcussion Symptom Questionnaire and Sport Concussion Assessment Tool (SCAT3) were administered in all sessions., Results: Patients suffering from concussion had slower response times and benefitted more from spatial cues than did controls. Global activation for all three evoked responses was lower for patients than controls. In a small sample of patients who returned for follow-up, the CMV and target P300m improved with recovery., Conclusions: MEG-evoked responses to the ANT reveal neurophysiological evidence of attentional dysfunction within days of injury. A pattern of improvement was also observed over the course of three months for the P300m, while behavioural performance did not change significantly. Further development of this method may yield a useful adjunct to neurological examination for concussion diagnosis and monitoring.

Plants sense microbial signatures via activation of pattern recognition receptors (PPRs), which trigger a range of cellular defences. One response is the closure of plasmodesmata, which reduces symplastic connectivity and the capacity for direct molecular exchange between host cells. Plasmodesmal flux is regulated by a variety of environmental cues but the downstream signalling pathways are poorly defined, especially the way in which calcium regulates plasmodesmal closure. Here, we identify that closure of plasmodesmata in response to bacterial flagellin, but not fungal chitin, is mediated by a plasmodesmal-localized Ca 2+ -binding protein Calmodulin-like 41 (CML41). CML41 is transcriptionally upregulated by flg22 and facilitates rapid callose deposition at plasmodesmata following flg22 treatment. CML41 acts independently of other defence responses triggered by flg22 perception and reduces bacterial infection. We propose that CML41 enables Ca 2+ -signalling specificity during bacterial pathogen attack and is required for a complete defence response against Pseudomonas syringae., (© 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.)

Background: Communication between health care providers (HCPs) and patients and/or their caregivers in the chaotic emergency department (ED) context can be challenging and potentially impact health outcomes and patient satisfaction. Studies examining strategies to improve communication of patient and caregivers expectations of care in an ED are widely dispersed., Methods: We conducted a scoping review of the published and grey literature to examine the extent, range and nature of existing research evidence regarding strategies to enhance communication of patient and caregiver expectations of care in an ED., Results: Of the 599 articles retrieved, 24 met the inclusion criteria. Most of the studies identified included patients (n=9) or caregivers (n=8) as the population of interest, while the remainder examined the expectations of a mix of patients, parents/caregivers, and/or HCPs (n=7). The majority (n=21) of the studies did not communicate patient/caregiver expectations to HCPs., Conclusion: This scoping review highlights the paucity of available research literature evaluating strategies to communicate patient and caregiver ED expectations. Our findings identify the need for experimental designs in future studies to evaluate implementation strategies for ED expectation tools with a particular emphasis on measuring the impact of sharing patient expectations with HCPs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In root nodules rhizobia enter host cells via infection threads. The release of bacteria to a host cell is possible from cell wall-free regions of the infection thread. We hypothesized that the VAMP721d and VAMP721e exocytotic pathway, identified before in Medicago truncatula, has a role in the local modification of cell wall during the release of rhizobia. To clarify the role of VAMP721d and VAMP721e we used Glycine max, a plant with a determinate type of nodule. The localization of the main polysaccharide compounds of primary cell walls was analysed in control vs nodules with partially silenced GmVAMP721d. The silencing of GmVAMP721d blocked the release of rhizobia. Instead of rhizobia-containing membrane compartments - symbiosomes - the infected cells contained big clusters of bacteria embedded in a matrix of methyl-esterified and de-methyl-esterified pectin. These clusters were surrounded by a membrane. We found that GmVAMP721d-positive vesicles were not transporting methyl-esterified pectin. We hypothesized that they may deliver the enzymes involved in pectin turnover. Subsequently, we found that GmVAMP721d is partly co-localized with pectate lyase. Therefore, the biological role of VAMP721d may be explained by its action in delivering pectin-modifying enzymes to the site of release., (© 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.)

Background: Surgical and catheter-based interventions on pulmonary veins are associated with pulmonary vein stenosis (PVS), which can progress diffusely through the "upstream" pulmonary veins. The mechanism has been rarely studied. We used a porcine model of PVS to assess disease progression with emphasis on the potential role of endothelial-mesenchymal transition (EndMT)., Methods: Neonatal piglets underwent bilateral pulmonary vein banding (banded, n = 6) or sham operations (sham, n = 6). Additional piglets underwent identical banding and stent implantation in a single-banded pulmonary vein 3 weeks postbanding (stented, n = 6). At 7 weeks postbanding, hemodynamics and upstream PV pathology were assessed., Results: Banded piglets developed pulmonary hypertension. The upstream pulmonary veins exhibited intimal thickening associated with features of EndMT, including increased transforming growth factor (TGF)-β1 and Smad expression, loss of endothelial and gain of mesenchymal marker expression, and coexpression of endothelial and mesenchymal markers in banded pulmonary vein intimal cells. These immunopathologic changes and a prominent myofibroblast phenotype in the remodeled pulmonary veins were consistently identified in specimens from patients with PVS, in vitro TGF-β1-stimulated cells isolated from piglet and human pulmonary veins, and human umbilical vein endothelial cells. After stent implantation, decompression of a pulmonary vein was associated with reappearance of endothelial marker expression, suggesting the potential for plasticity in the observed pathologic changes, followed by rapid in-stent restenosis., Conclusions: Neonatal pulmonary vein banding in piglets recapitulates critical aspects of clinical PVS and highlights a pathologic profile consistent with EndMT, supporting the rationale for evaluating therapeutic strategies designed to exploit reversibility of upstream pulmonary vein pathology., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Many signalling pathways in plants are regulated by the second messenger calcium (Ca(2+)). In the standard model, Ca(2+)-sensor proteins, such as CaM (calmodulin), detect Ca(2+) signals and subsequently regulate downstream targets to advance the signal transduction cascade. In addition to CaM, plants possess many CMLs (CaM-like proteins) that are predicted to function as Ca(2+) sensors, but which remain largely uncharacterized. In the present study, we examined the biochemical properties, subcellular localization and tissue-specific distribution of Arabidopsis CML43. Our data indicate that CML43 displays characteristics typical of Ca(2+) sensors, including high-affinity Ca(2+) binding, conformational changes upon Ca(2+) binding that expose hydrophobic regions and stabilization of structure in the presence of Mg(2+) or Ca(2+). In vivo localization analysis demonstrates that CML43 resides in cytosolic and nuclear compartments. Transgenic plants expressing a CML43:GUS (β-glucoronidase) promoter reporter gene revealed that CML43 promoter activity is restricted almost exclusively to root tips under normal growth conditions. GUS reporter activity in these transgenic plants was strongly increased when exposed to the defence compound SA (salicylic acid). Furthermore, immunoblot analysis revealed that the CML43 protein accumulates following treatment with SA. Collectively, our findings suggest that CML43 functions as a Ca(2+) sensor in root tips during both normal growth and plant immune response.

This case describes the clinical course and autopsy findings of a 5-year-old girl with PHACES syndrome. While the etiopathogenesis of this condition is not yet understood, the pathological changes documented support the concept that the primary defect in PHACES syndrome is an arteriopathy.

Objective: A recent increase in the number of infants presenting at autopsy with rib fractures associated with cardio-pulmonary resuscitation (CPR) precipitated a study to determine whether such a phenomenon was related to recent revision of paediatric resuscitation guidelines., Methods: We conducted a review of autopsy reports from 1997 to 2008 on 571 infants who had CPR performed prior to death., Results: Analysis of the study population revealed CPR-related rib fractures in 19 infants (3.3%), 14 of whom died in the 2006-2008 period. The difference in annual frequency of CPR-related fractures between the periods before and after revision of paediatric CPR guidelines was statistically highly significant., Conclusions: The findings indicate that CPR-associated rib fractures have become more frequent in infants since changes in CPR techniques were introduced in 2005. This has important implications for both clinicians and pathologists in their assessment of rib fractures in this patient population., (Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.)

Calmodulin(CaM)-regulated protein phosphorylation forms an important component of Ca(2+) signaling in animals but is less understood in plants. We have identified a CaM-binding receptor-like kinase from soybean nodules, GmCaMK1, a homolog of Arabidopsis CRLK1. We delineated the CaM-binding domain (CaMBD) of GmCaMK1 to a 24-residue region near the C-terminus, which overlaps with the kinase domain. We have demonstrated that GmCaMK1 binds CaM with high affinity in a Ca(2+)-dependent manner. We showed that GmCaMK1 is expressed broadly across tissues and is enriched in roots and developing nodules. Finally, we examined the CaMBDs of the five-member GmCaMK family in soybean, and orthologs present across taxa., (Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

We report here the identification of a patient with muscle-specific glycogen synthase deficiency. The 8-year-old patient showed no prior signs of distress before collapsing during a bout of exercise, resulting in death. Initial post-mortem analysis of tissues suggested death was due to metabolic complications of mitochondrial myopathy, but upon further examination it was found that the anomalies were indicative of mitochondrial proliferation and oxidative compensation. A homozygous two base pair deletion was identified in exon 2 of GYS1, and the parents and sibling were confirmed as heterozygous carriers of the deletion. This case highlights the importance of differentiating between mitochondrial compensatory phenomena and true mitochondrial disease, and suggests that GYS1 deficiency could be a common cause of sudden cardiac death in children. Children with abnormal cardiac responses to increased workloads as well as those with defined myocardial disease should therefore be tested for GYS1 deficiency.

Calcium (Ca(2+)) is a key second messenger in eukaryotes where it regulates a diverse array of cellular processes in response to external stimuli. An important Ca(2+) sensor in both animals and plants is calmodulin (CaM). In addition to evolutionarily conserved CaM, plants possess a unique family of CaM-like (CML) proteins. The majority of these CMLs have not yet been studied, and investigation into their physical properties and cellular functions will provide insight into Ca(2+) signal transduction in plants. Here we describe the characterization of CML42, a 191-amino acid Ca(2+)-binding protein from Arabidopsis. Ca(2+) binding to recombinant CML42 was assessed by fluorescence spectroscopy, NMR spectroscopy, microcalorimetry, and CD spectroscopy. CML42 displays significant alpha-helical secondary structure, binds three molecules of Ca(2+) with affinities ranging from 30 to 430 nm, and undergoes a Ca(2+)-induced conformational change that results in the exposure of one or more hydrophobic regions. Gene expression analysis revealed CML42 transcripts at various stages of development and in many cell types, including the support cells, which surround trichomes (leaf hairs) on the leaf surface. Using yeast two-hybrid screening we identified a putative CML42 interactor; kinesin-interacting Ca(2+)-binding protein (KIC). Because KIC is a protein known to function in trichome development, we examined transgenic CML42 knockout plants and found that they possess aberrant trichomes with increased branching. Collectively, our data support a role for CML42 as a Ca(2+) sensor that functions during cell branching in trichomes.