A possible mechanism for exonuclease 1-independent eukaryotic mismatch repair

Mismatch repair contributes to genetic stability, and inactivation of the mammalian pathway leads to tumor development. Mismatch correction occurs by an excision-repair mechanism and has been shown to depend on the 5′ to 3′ hydrolytic activity exonuclease 1 (Exo1) in eukaryotic cells. However, genetic and biochemical studies have indicated that one or more Exo1-independent modes of mismatch repair also exist. We have analyzed repair of nicked circular heteroduplex DNA in extracts of Exo1-deficient mouse embryo fibroblast cells. Exo1-independent repair under these conditions is MutLα-dependent and requires functional integrity of the MutLα endonuclease metal-binding motif. In contrast to the Exo1-dependent reaction, we have been unable to detect a gapped excision intermediate in Exo1-deficient extracts when repair DNA synthesis is blocked. A possible explanation for this finding has been provided by analysis of a purified system comprised of MutSα, MutLα, replication factor C, proliferating cell nuclear antigen, replication protein A, and DNA polymerase δ that supports Exo1-independent repair in vitro. Repair in this system depends on MutLα incision of the nicked heteroduplex strand and dNTP-dependent synthesis-driven displacement of a DNA segment spanning the mismatch. Such a mechanism may account, at least in part, for the Exo1-independent repair that occurs in eukaryotic cells, and hence the modest cancer predisposition of Exo1-deficient mammalian cells.     

Gastropulmonary fistula after bariatric surgery

The Roux-en-Y gastric bypass is one of the most common operations for morbid obesity. Although rare, gastropulmonary fistulas are an important complication of this procedure. There is only one recently reported case of this complication. The present report describes the serious nature of this complication in a patient after an uneventful laparoscopic gastric bypass surgery.     

Brain dopaminergic modulation associated with executive function in Parkinson's disease

The progressive development of deficits in executive functions, including action planning, is a well‐known complication of Parkinson's disease. A dysfunction of the prefrontal lobe, which is known to be involved in the control of inhibitory processes, could explain the difficulties in initiating behavior or inhibiting ongoing actions in patients with PD. The strong dopaminergic innervation of the prefrontal cortex raises questions about the putative effects of dopa therapy on this cognitive impairment. In the present study, we used fMRI to examine the functional influence of dopa therapy on neural activity during a go/no‐go task in nine patients with and without levodopa treatment and in matched controls. Whereas the patient and control subjects exhibited the same performance during the go/no‐go task, different patterns of brain activation were observed depending on the dopaminergic status. The drug‐off state was characterized by more widely distributed brain activity, mainly in the bilateral caudate. Levodopa did not fully restore normal brain activation and induced changes in the pattern of cingulate cortex activity, which was more pronounced in the rostral part in the drug‐off state and in the caudal part after levodopa intake. These results support the idea of a critical role for dopamine in the control of executive functions in patients with PD. © 2009 Movement Disorder Society     

Vascular Risk Factors as Predictors of Sexual Function Following Coronary Artery Bypass Graft

IntroductionA strong association between cardiovascular risk factors and erectile dysfunction (ED) was suggested. Coronary artery bypass grafting (CABG) is the gold standard for surgical myocardial revascularization.AimWe herein evaluate the impact of vascular risk factors on postoperative sexual functions in patients undergo CABG.Main Outcome MeasuresED severity by the International Index of Erectile Function (IIEF-5) and penile duplex study.MethodsThe present study included 100 patients who underwent CABG. The patients were evaluated by an abridged form of the IIEF-5 questionnaire, followed by CABG. Six months after surgery the erectile function of all patients was revaluated utilizing the IIEF-5.ResultsNumber of risk factors was significantly associated with postoperative change in IIEF-5 score (P = 0.02). A post hoc analysis of the association revealed that patients with one risk factor were significantly more likely to have increased IIEF-5 scores (N = 18), whereas those with two or more risk factors were significantly more likely to have decreased IIEF-5 scores (N = 21, P < 0.05). Furthermore, those with no risk factors were significantly more likely to be stable (N = 8) compared with those with more than two risk factors, who were more likely to have decreased scores (P < 0.05). The hierarchical logistic regression results showed that when examining all risk factors simultaneously, because of multicollinearity, only hyperlipidemia was significantly associated with postoperative ED (odds ratio [OR] = 11.33, confirdence interval [CI] = 1.25, 102.82). Frequency of intercourse was also significantly associated with postoperative ED after controlling for risk factors (OR = 0.71, CI = 0.52, 0.97).ConclusionsThis data clearly shows that the number of cardiovascular risk factors is an essential predictive factor for sexual function following surgery. Only hyperlipidemia may play a predictive role for the future sexual function of patients undergo CABG. Mohamed OA, Hamed HA, Roaiah MF, Helmy T, Mahran A, and Bennett CJ. Vascular risk factors as predictors of sexual function following coronary artery bypass graft. J Sex Med 2009;6:2017–2023.     

The parasitism of <Emphasis Type="Italic">Flamingolepis liguloides</Emphasis> (Gervais, 1847) (Cestoda,Hymenolepididae) in <Emphasis Type="Italic">Artemia salina</Emphasis> (Crustacea,Branchiopoda) in two saline lakes in Algeria

Studies revealed the role of Artemia salina as intermediate host in the life-cycle of a cestode species parasitizing flamingos, i.e. Flamingolepis liguloides. Cysticercoids of this parasite were found for the first time in the Algerian populations of Artemia salina in winter of 2000 and 2001 in Chott Marouane and spring of 2003 in Sebkha Ez-Zemoul. The prevalence ranged between 10 and 33% for the two examined Artemia populations. The intensity of infection was 1–3 cysticercoids per individual. The abdomen was the most targeted site of infection (95% of the population of Sebkha Ez-Zemoul) followed by the thorax and the ovisac. Infected females were less fertile than uninfected ones (24.83 vs 43.70 cysts/brood) in Sebkha Ez-Zemoul or castrated in Chott Marouane.     

Pathophysiological response to experimental diffuse brain trauma differs as a function of developmental age

The purpose of experimental models of traumatic brain injury (TBI) is to reproduce selected aspects of human head injury such as brain edema, contusion or concussion, and functional deficits, among others. As the immature brain may be particularly vulnerable to injury during critical periods of development, and pediatric TBI may cause neurobehavioral deficits, our aim was to develop and characterize as a function of developmental age a model of diffuse TBI (DTBI) with quantifiable functional deficits. We modified a DTBI rat model initially developed by us in adult animals to study the graded response to injury as a function of developmental age - 7-, 14- and 21-day-old rats compared to young adult (3-month-old) animals. Our model caused motor deficits that persisted even after the pups reached adulthood, as well as reduced cognitive performance 2 weeks after injury. Moreover, our model induced prominent edema often seen in pediatric TBI, particularly evident in 7- and 14-day-old animals, as measured by both the wet weight/dry weight method and diffusion-weighted MRI. Blood-brain barrier permeability, as measured by the Evans blue dye technique, peaked at 20 min after trauma in all age groups, with a second peak found only in adult animals at 24 h after injury. Phosphorus MR spectroscopy showed no significant changes in the brain energy metabolism of immature rats with moderate DTBI, in contrast to significant decreases previously identified in adult animals.     

Retrograde and anterograde transport of HIV protein gp120 in the nervous system

Neurodegeneration and gliosis are prominent pathological features of subjects with human immunodeficiency virus (HIV) dementia complex (HAD). In these patients, neurodegeneration occurs in uninfected neurons. In addition, these patients develop sensory neuropathy despite the antiretroviral therapy. The HIV protein gp120, which mimics some of the pathological alterations seen in HAD, is retrogradely transported in rodent neurons. However, it is still unclear whether gp120 can also be transported anterogradely and whether axonal transport can occur in the peripheral nervous system (PNS). To determine whether gp120 is transported retrogradely and/or anterogradely, we injected gp120IIIB together with the retrograde tracer fluoro-ruby (FR) or the anterograde tracer 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyamine perchlorate (DiI) into the rat superior colliculi. We discovered that gp120 is retrogradely transported with FR along a direct pathway from the superior colliculus to the retina and anterogradely transported with DiI to several areas of the occipital cortex. To determine whether gp120 is also axonally transported in the peripheral nerves, gp120 and FR were injected into the sciatic nerve. No gp120 immunoreactivity was found in the sciatic nerve or dorsal root ganglia, suggesting that gp120 axonal transport does not occur in the PNS. Gp120 axonal transport may play a role in neuronal injury. Therefore, we examined apoptosis at various time points after gp120 injection. Activated caspase-3 was evident within neurons transporting gp120. These results indicate that axonal transport of gp120 might exacerbate the pathogenesis of HIV-1.     

Stress alters personal moral decision making

While early studies of moral decision making highlighted the role of rational, conscious executive processes involving frontal lobe activation more recent work has suggested that emotions and gut reactions have a key part to play in moral reasoning. Given that stress can activate many of the same brain regions that are important for and connected to brain centres involved in emotional processing we sought to evaluate if stress could influence moral decision making. Sixty-five undergraduate volunteers were randomly assigned to control (n=33) and experimental groups (n=32). The latter underwent the Trier Social Stress Test (TSST) and induction of stress was assessed by measurement of salivary cortisol levels. Subjects were then required to provide a response to thirty moral dilemmas via a computer interface that recorded both their decision and reaction time. Three types of dilemmas were used: non-moral, impersonal moral and personal moral. Using a binary logistic model there were no significant predicators of utilitarian response in non-moral and impersonal moral dilemmas. However the stressed group and females were found to predict utilitarian responses to personal moral dilemmas. When comparing percentage utilitarian responses there were no significant differences noted for the non-moral and impersonal moral dilemmas but the stressed group showed significantly less utilitarian responses compared to control subjects. The stress response was significantly negatively correlated with utilitarian responses. Females also showed significantly less utilitarian responses than males. We conclude that activation of the stress response predisposed participants to less utilitarian responses when faced with high conflict personal moral dilemmas and suggest that this offers further support for dual process theory of moral judgment. We also conclude that females tend to make less utilitarian personal moral decisions compared to males, providing further evidence that there are gender differences in moral reasoning.