Evidence for gene duplication forming similar binding folds for NAD(P)H and FAD in pyridine nucleotide-dependent flavoenzymes

AbstractFor pyridine nucleotide-dependent flavoezymes, binding both FAD and NAD(P)H on a single amino-acids chain, we have found a high degree of internal sequence similarity for certain regions of FAD and NAD (P)H binding portions of the chain for any given protein. This was the case for a range of enzymes classes, including disulphide oxidoreductases (such as glutathione reductase, trypanothione reductase, lipoamide dehydrogenase, mercuric reductase), mono- and dioxygenases, nitrite reductaSE, alkyl hydroperoxidase and NADH dehydrogenase from E. coli. This provides strong support for gene duplication as the origin of at least part of the FAD and NAD(P)H recognising domains of such enzymes

The effect of deletions and reduplications on the expression of human α and ζ globin genes

A number of deletions have been documented among the non-α globin genes of man that are associated with repression of residual 3' genes. Opportunities to pursue similar structure function correlations among the α and ζ globin genes have been less frequent. The most common deletion observed has been that of one of the two a globin genes in cis on chromosome 16 due to the -3.7 type of α-Thal-2. It is found in 33% of 345 Black children in the Pediatric Sickle Cell Clinics of our center. The same α-Thal as semi a-2 condition has been documented by gene mapping or family studies or both among 48 newborn and adult Hb G Philadelphia (Hb G) heterozygotes from the Black population of the Southeastern USA and Caucasians from Northern Italy. Hb G is rather unique among hemoglobin variants because it has been observed in association with a diversity of a globin genotypes having 3, 2, 1 or O additional αA globin genes in cis or in trans to the αG gene. Quantification of the αG globin produced from each α6 globin qene in probands with the ααG/αα, -αG/αα, -αG/-α, -αG/-αG and -αG/-- genotypes show that there is considerable derepression of the αG globin gene in cis to the -3.7 α-Thal-2 deletion and of the αA genes in trans.peer-reviewe

Case Report Postobstructive Pulmonary Edema following Tonsillectomy/Adenoidectomy in a 2-Year-Old with Poland-Moebius Syndrome

A 2-year-old male with Poland-Moebius syndrome was transferred from a local hospital to the Pediatric ICU at Children's Hospital of Georgia for suspected postobstructive pulmonary edema (POPE) after tonsillectomy/adenoidectomy (T&A). The patient's respiratory status ultimately declined and he developed respiratory failure. Imaging suggested pulmonary edema as well as a leftsided pneumonia. Echocardiogram showed pulmonary hypertension and airway exam via direct fiberoptic bronchoscopy revealed tracheomalacia and bronchomalacia. He developed acute respiratory distress syndrome (ARDS) and remained intubated for ten days. This case highlights the association between congenital upper body abnormalities with cranial nerve dysfunction and the development of POPE with delayed resolution of symptoms. Patients with upper body abnormalities as above are at great risk of postoperative complications and should therefore be managed in a tertiary-care facility

Changes in the neural correlates of self-blame following mindfulness-based cognitive therapy in remitted depressed participants

Mindfulness-Based-Cognitive-Therapy (MBCT) reduces vulnerability for relapse into depression by helping individuals to counter tendencies to engage in maladaptive repetitive patterns of thinking and respond more compassionately to negative self-judgment. However, little is known about the neural correlates underlying these effects. To elucidate these correlates, we investigated fMRI brain activation during a task eliciting feelings of blaming oneself or others. Sixteen participants in remission from major depressive disorder (MDD) completed fMRI assessments before and after MBCT, alongside self-reported levels of self-compassion, mindfulness, and depression symptoms. Analyses of self-blame versus other-blame contrasts showed a reduction in activation in the bilateral dorsal anterior cingulate/medial superior frontal gyrus after MBCT compared to baseline. Further, exploratory analyses showed that increases in self-kindness after MBCT correlated with reduced activation in the posterior cingulate cortex (PCC)/precuneus in self-blame versus rest contrasts. These findings suggest that MBCT is associated with a reduction in activations in cortical midline regions to self-blame which may be mediated by increasing self-kindness. However, this is a small, uncontrolled study with 16 participants and therefore our results will need confirmation in a controlled study

The occurrence of α chain gene deletions and triplications among pediatric Hb S homozygotes

Approximately 40% of more than 100 young Hb S homozygotes attending the Pediatric Clinic of the Comprehensive Sickle Cell Center of the Medical College of Georgia in Augusta have an associated α-thalassemia-2 (α-thal-2) heteroztgosity, i.e. the -α/-α; βs/βs condition, or homozygosity, i.e. the -α/-α; βs/βs condition. These conditions are documented by pulse incubations of peripheral blood reticulocytes and by gene mapping using recombinant DNA probes. All α-thal-2 deletions are associated with a 16 Kb Bgl II α chain DNA fragment which arises from a deletion of the 3' end of the α2 gene, the 5' end of the α1 gene and includes the intergenic DNA. Fusion of the residual 3' and 5' ends of the α2 and α1 genes results in a single active a chain gene, i.e. the -3.7 Kb or Rightward type of deletion. Its 3' sequences belong to the α1 gene. The homozygosity for the condition and Hb S is characterized by higher Hb levels without an accompanying increase of Hb F percentages; a distinct microcytosis and hypochromia; splenomegaly and decreased α/non-α values.peer-reviewe