A dopaminergic switch for fear to safety transitions

Overcoming aversive emotional memories requires neural systems that detect when fear responses are no longer appropriate so that they can be extinguished. The midbrain ventral tegmental area (VTA) dopamine system has been implicated in reward and more broadly in signaling when a better-than-expected outcome has occurred. This suggests that it may be important in guiding fear to safety transitions. We report that when an expected aversive outcome does not occur, activity in midbrain dopamine neurons is necessary to extinguish behavioral fear responses and engage molecular signaling events in extinction learning circuits. Furthermore, a specific dopamine projection to the nucleus accumbens medial shell is partially responsible for this effect. In contrast, a separate dopamine projection to the medial prefrontal cortex opposes extinction learning. This demonstrates a novel function for the canonical VTA-dopamine reward system and reveals opposing behavioral roles for different dopamine neuron projections in fear extinction learning

The conserved Fanconi anemia nuclease Fan1 and the SUMO E3 ligase Pli1 act in two novel Pso2-independent pathways of DNA interstrand crosslink repair in yeast

DNA interstrand cross-links (ICLs) represent a physical barrier to the progression of cellular machinery involved in DNA metabolism. Thus, this type of adduct represents a serious threat to genomic stability and as such, several DNA repair pathways have evolved in both higher and lower eukaryotes to identify this type of damage and restore the integrity of the genetic material. Human cells possess a specialized ICL-repair system, the Fanconi anemia (FA) pathway. Conversely yeasts rely on the concerted action of several DNA repair systems. Recent work in higher eukaryotes identified and characterized a novel conserved FA component, FAN1 (Fanconi anemia-associated nuclease 1, or FANCD2/FANCI-associated nuclease 1). In this study, we characterize Fan1 in the yeast Schizosaccharomyces pombe. Using standard genetics, we demonstrate that Fan1 is a key component of a previously unidentified ICL-resolution pathway. Using high-throughput synthetic genetic arrays, we also demonstrate the existence of a third pathway of ICL repair, dependent on the SUMO E3 ligase Pli1. Finally, using sequence-threaded homology models, we predict and validate key residues essential for Fan1 activity in ICL repair

Diabetic gastroparesis: Therapeutic options

Gastroparesis is a condition characterized by delayed gastric emptying and the most common known underlying cause is diabetes mellitus. Symptoms include nausea, vomiting, abdominal fullness, and early satiety, which impact to varying degrees on the patient’s quality of life. Symptoms and deficits do not necessarily relate to each other, hence despite significant abnormalities in gastric emptying, some individuals have only minimal symptoms and, conversely, severe symptoms do not always relate to measures of gastric emptying. Prokinetic agents such as metoclopramide, domperidone, and erythromycin enhance gastric motility and have remained the mainstay of treatment for several decades, despite unwanted side effects and numerous drug interactions. Mechanical therapies such as endoscopic pyloric botulinum toxin injection, gastric electrical stimulation, and gastrostomy or jejunostomy are used in intractable diabetic gastroparesis (DG), refractory to prokinetic therapies. Mitemcinal and TZP-101 are novel investigational motilin receptor and ghrelin agonists, respectively, and show promise in the treatment of DG. The aim of this review is to provide an update on prokinetic and mechanical therapies in the treatment of DG

Underestimation of Staphylococcus aureus (MRSA and MSSA) carriage associated with standard culturing techniques:One third of carriers missed

ObjectivesNasal carriers of Staphylococcus (S.) aureus (MRSA and MSSA) have an increased risk for healthcare-associated infections. There are currently limited national screening policies for the detection of S. aureus despite the World Health Organization’s recommendations. This study aimed to evaluate the diagnostic performance of molecular and culture techniques in S. aureus screening, determine the cause of any discrepancy between the diagnostic techniques, and model the potential effect of different diagnostic techniques on S. aureus detection in orthopaedic patients.MethodsPaired nasal swabs for polymerase chain reaction (PCR) assay and culture of S. aureus were collected from a study population of 273 orthopaedic outpatients due to undergo joint arthroplasty surgery.ResultsThe prevalence of MSSA nasal colonization was found to be between 22.4% to 35.6%. The current standard direct culturing methods for detecting S. aureus significantly underestimated the prevalence (p = 0.005), failing to identify its presence in approximately one-third of patients undergoing joint arthroplasty surgery.ConclusionModelling these results to national surveillance data, it was estimated that approximately 5000 to 8000 S. aureus surgical site infections could be prevented, and approximately $140 million to$950 million (approximately £110 million to £760 million) saved in treatment costs annually in the United States and United Kingdom combined, by using alternative diagnostic methods to direct culture in preoperative S. aureus screening and eradication programmes.</p

Internal quality of eggs coated with whey protein concentrate Qualidade interna de ovos de galinha cobertos com concentrado protéico de soro de leite bovino

The functional properties of foods can be preserved when they are coated with edible films, since both the loss of moisture and the transport of O2 and CO2 are reduced. The objectives of this work were: to compare weight loss, Haugh units, and albumen pH between fresh eggs and eggs coated with whey protein concentrate (WPC), under six storage periods (3, 7, 10, 14, 21 and 28 days), at 25°C. During the entire storage period, regardless of whether the eggs were coated or not, the Haugh unit values and the weight loss decreased, and differences between values from the first to the last period were lower for coated eggs. Albumen pH increased. The Haugh unit values for coated eggs were similar to those found in literature references when the same storage period was considered.<br>As vantagens de utilizar filmes e coberturas comestíveis podem ser justificadas pela manutenção das propriedades funcionais dos alimentos, através da diminuição da perda de umidade e da diminuição da troca de gases (O2 e CO2). Aplicação de cobertura em ovos com casca reduz a perda de peso e mantém a qualidade interna do produto. Os objetivos deste trabalho foram comparar a perda de peso, os valores de unidades Haugh e o pH do albume de ovos com e sem cobertura à base de concentrado protéico de soro de leite, armazenados a 25°C, por 3, 7, 10, 14, 21 e 28 dias. Durante todo o período de armazenamento houve decréscimo dos valores de unidades Haugh e perda de peso, tanto para os ovos com cobertura como para os ovos sem cobertura. O pH do albume aumentou para os ovos com e sem cobertura, a variação dos valores nos ovos com cobertura foi menor do que para os ovos sem cobertura. A cobertura de concentrado protéico de soro de leite reduz o transporte de vapor de água e gás (CO2) através dos poros da casca do ovo. Essa cobertura mantém o pH da clara de ovo na faixa de 8, durante quatro semanas de armazenamento e, desse modo, consegue manter as características necessárias para boa conservação do produto