Spontaneous spatiotemporal waves of gene expression from biological clocks in the leaf

The circadian clocks that drive daily rhythms in animals are tightly coupled among the cells of some tissues. The coupling profoundly affects cellular rhythmicity and is central to contemporary understanding of circadian physiology and behavior. In contrast, studies of the clock in plant cells have largely ignored intercellular coupling, which is reported to be very weak or absent. We used luciferase reporter gene imaging to monitor circadian rhythms in leaves of Arabidopsis thaliana plants, achieving resolution close to the cellular level. Leaves grown without environmental cycles for up to 3 wk reproducibly showed spatiotemporal waves of gene expression consistent with intercellular coupling, using several reporter genes. Within individual leaves, different regions differed in phase by up to 17 h. A broad range of patterns was observed among leaves, rather than a common spatial distribution of circadian properties. Leaves exposed to light-dark cycles always had fully synchronized rhythms, which could desynchronize rapidly. After 4 d in constant light, some leaves were as desynchronized as leaves grown without any rhythmic input. Applying light-dark cycles to such a leaf resulted in full synchronization within 2-4 d. Thus, the rhythms of all cells were coupled to external light-dark cycles far more strongly than the cellular clocks were coupled to each other. Spontaneous desynchronization under constant conditions was limited, consistent with weak intercellular coupling among heterogeneous clocks. Both the weakness of coupling and the heterogeneity among cells are relevant to interpret molecular studies and to understand the physiological functions of the plant circadian clock.     

Craniofacial and orbital dermoids in children

Dermoid cysts are congenital lesions that commonly arise from nondisjunction of surface ectoderm from deeper neuroectodermal structures. They tend to be found along planes of embryonic closure. Classification by site is helpful for diagnostic planning and surgical treatment. A distinction can be made between frontotemporal, orbital, frontoethmoidal, and calvarial lesions. The risk of extension into deeper tissues must be determined before surgical intervention. Simple lesions are amenable to direct excision. Deeper lesions often require a coordinated surgical approach between a neurosurgeon and craniofacial surgeon after thorough radiographic imaging. Follow-up through the developmental years is recommended for complex dermoid lesions.     

Loss of heterozygosity in 7q myeloid disorders: clinical associations and genomic pathogenesis

Loss of heterozygosity affecting chromosome 7q is common in acute myeloid leukemia and myelodysplastic syndromes, pointing toward the essential role of this region in disease phenotype and clonal evolution. The higher resolution offered by recently developed genomic platforms may be used to establish more precise clinical correlations and identify specific target genes. We analyzed a series of patients with myeloid disorders using recent genomic technologies (1458 by single-nucleotide polymorphism arrays [SNP-A], 226 by next-generation sequencing, and 183 by expression microarrays). Using SNP-A, we identified chromosome 7q loss of heterozygosity segments in 161 of 1458 patients (11%); 26% of chronic myelomonocytic leukemia patients harbored 7q uniparental disomy, of which 41% had a homozygous EZH2 mutation. In addition, we describe an SNP-A-isolated deletion 7 hypocellular myelodysplastic syndrome subset, with a high rate of progression. Using direct and parallel sequencing, we found no recurrent mutations in typically large deletion 7q and monosomy 7 patients. In contrast, we detected a markedly decreased expression of genes included in our SNP-A defined minimally deleted regions. Although a 2-hit model is present in most patients with 7q uniparental disomy and a myeloproliferative phenotype, haplodeficient expression of defined regions of 7q may underlie pathogenesis in patients with deletions and predominant dysplastic features.     

Role of novel DSP_p.Q986X genetic variation in arrhythmogenic right ventricular cardiomyopathy

Introduction

Arrhythmogenic right ventricular cardiomyopathy is an inherited disease characterized by a progressive myocardium fibrofatty replacement. This abnormality disrupts electrical transmission causing ventricular arrhythmias and sudden cardiac death. This genetic disease is transmitted mainly with an autosomal dominant pattern. Our aim was to identify the genetic defect responsible for the pathology in a Spanish family, and to perform its phenotype connotations.

Material and methods

A total of 15 individuals in a three-generation Spanish family were screened after the sudden cardiac death of one family member. All they underwent a complete physical examination, 12-lead electrocardiogram, 2-dimensional echocardiography, magnetic resonance imaging, exercise stress test, 24-h Holter and genetic testing.

Results

Autopsy revealed the presence of biventricular arrhythmogenic dysplasia in deceased member. Six family members showed clinical symptoms but only three of them fulfilled definite diagnostic criteria of the disease. Genetic analysis showed a novel nonsense genetic variation in nine family members. All family members with clinical symptoms carried the genetic variation.

Conclusions

Genetic testing in families affected by arrhythmogenic right ventricular cardiomyopathy helps to identify the genetic cause responsible for the disease. The incomplete penetrance and variable phenotypic expression highlights the need of comprehensive genetic analysis and further phenotype implications of genetics to clarify the pathophysiology of the disease.     

Comparison of Buccal Infiltration of 4% Articaine With 1?:?100,000 and 1?:?200,000 Epinephrine for Extraction of Maxillary Third Molars With Pericoronitis: A Pilot Study

We compared the buccal infiltration of 4% articaine with 1 : 100,000 or 1 : 200,000 epinephrine without a palatal injection for the extraction of impacted maxillary third molars with chronic pericoronitis. This prospective, double-blind, controlled clinical trial involved 30 patients between the ages of 15 and 46 years who desired extraction of a partially impacted upper third molar with pericoronitis. Group 1 (15 patients) received 4% articaine with 1 : 100,000 epinephrine and group 2 (15 patients) received 4% articaine with 1 : 200,000 epinephrine by buccal infiltration. None of the patients in group 1 reported pain, but 3 patients in group 2 reported pain, which indicated a need for a supplementary palatal injection. The palatal injections were all successful in eliminating the pain. Two additional patients in group 2 experienced pain when the suture needle penetrated their palatal mucosa. Based on these results, 4% articaine with 1 : 100,000 epinephrine was found to be more effective for the removal of upper third molars in the presence of pericoronitis than 4% articaine hydrochloride with 1 : 200,000 epinephrine when only a buccal infiltration was used.Key Words: Articaine, Epinephrine, Molar extractionMaxillary third molar extraction is generally straightforward, due to the plasticity of the maxillary bone and to the low resistance to extraction movements. Nevertheless, the anesthetic technique needed for such extraction may be extremely uncomfortable because it requires palatal mucosal anesthesia.^1,2Studies have suggested that articaine has good diffusion through the hard and soft tissues, eliminating the need for the palatal injection in maxillary third molar extractions.^3–6 However, the anesthetic effect may be decreased or neutralized because the inflammation and low tissue pH affects tissue diffusion of the anesthetic, making the drug less effective.^7–9Pericoronitis is the most frequent inflammatory pathology associated with third molars and is caused by a combination of factors including trauma and food impaction with subsequent bacterial colonization and infection.^1,10–13 Clinically, it is characterized by the presence of erythema, swelling, and even ulceration in some cases.^1,14 The management of pericoronitis varies. Many authors have recommended using antibiotic therapy when there are signs of acute infection with systemic involvement such as fever. In cases of chronic or nonacute clinical manifestations, treatment should be limited to antiseptic mouthwashes, irrigation, and anti-inflammatory and/or anesthetic medication. Surgically, the usual treatment is the extraction of the impacted tooth.^1,11–15The aim of the present study was to evaluate the differences between articaine hydrochloride with 1 : 100,000 and 1 : 200,000 epinephrine (adrenaline) administered by buccal infiltration alone (without palatal infiltration) for the removal of impacted upper third molar teeth with pericoronitis.     

Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats

AIM: To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.METHODS: Rats with CCl₄-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups: Cirrhosis; Cirrhosis + IGF-1; Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin. An oral glutamine-challenge test was performed, and plasma and cerebral ammonia, glucose, bilirubin, transaminases, endotoxemia, brain water content and ileocecal cultures were measured and liver histology was assessed.RESULTS: Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups, and improved some liver function parameters (bilirubin, alanine aminotransferase and aspartate aminotransferase). These effects were associated with a significant reduction in cerebral water content. Blood and cerebral ammonia levels, and area-under-the-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals. By contrast, IGF-1 administration failed to improve most alterations observed in cirrhosis.CONCLUSION: By reducing gut bacterial overgrowth, only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema, alterations associated with hepatic encephalopathy.