An epigenetic change in a moth is generated by temperature and transmitted to many subsequent generations mediated by RNA.

Epigenetic changes in sexually reproducing animals may be transmitted usually only through a few generations. Here we discovered a case where epigenetic change lasts 40 generations. This epigenetic phenomenon occurs in the short antennae (sa) mutation of the flour moth (Ephestia kuehniella). We demonstrate that is probably determined by a small RNA (e.g., piRNA, miRNA, tsRNA) and transmitted in this way to subsequent generations through the male and female gametes. The observed epigenetic change cancels sa mutation and creates a wild phenotype (a moth that appears to have no mutation). It persists for many generations (40 recorded). This epigenetic transgenerational effect (suppression homozygous mutation for short antennae) in the flour moth is induced by changes during ontogenetic development, such as increased temperature on pupae development, food, different salts in food, or injection of RNA from the sperm of already affected individuals into the eggs. The epigenetic effect may occasionally disappear in some individuals and/or progeny of a pair in the generation chain in which the effect transfers. We consider that the survival of RNA over many generations has adaptive consequences. It is mainly a response to environmental change that is transmitted to offspring via RNA. In this study, we test an interesting epigenetic effect with an unexpected length after 40 generations and test what is its cause. Such transfer of RNA to subsequent generations may have a greater evolutionary significance than previously thought. Based on some analogies, we also discuss of the connection with the SIR2 gene.

Nailing of three- and four-part fractures of the humeral head -- long-term results.

BACKGROUND AND PURPOSE: Long term outcome of the treatment of displaced complex fractures of humeral head is rare in the literature especially in greater cohorts. Main purpose of our study was the assessment of long term results of intramedullary nailing of 3-4 part fractures. PATIENTS AND METHODS: 137 patients with 137 three or four-part fractures of the humeral head treated by intramedullary nailing were reassessed after an average follow-up time of 57 (27-93) months. The whole cohort consisted of 85 three-part fractures, 38 four-part fractures and 14 fracture-dislocations. Radiographic and clinical outcome - absolute Constant score (CS(abs)) and relative Constant score (compared to the contralateral side - CS(rel)) were evaluated. The rate of complications was recorded. Analysis of the influence of quality of achieved reduction on final functional result and on the development of complications was performed. RESULTS: 125 fractures healed uneventfully. Mean long term CS(rel) was 81% of the unaffected side. Mean CS(rel) was 85% in 3-part fractures, 73% in four-part fractures, 80% in three-part fracture-dislocations and 70% in four-part fracture-dislocations. 96 (70%) patients achieved excellent or good results (CS(rel) higher than 80%), 17 (12.4%) satisfactory results and 24 (17.5%) poor results (CS(rel) less than 60%). No significant difference was observed in functional results between different age groups. No incidence of non-union was observed, 4 losses of reduction were encountered. We observed 17 cases of complete humeral head necrosis, 14 of them in the group of 4-part fractures. Reduction quality strongly influenced functional result and development of head necrosis. In the group of excellent reduction mean CS(rel) was 88% and the rate of necrosis was 2%. Moderate reduction quality deteriorated CS(rel) to 70% and head necrosis rate rose up to 28%. If reduction was poor, mean CS(rel) was 52% and the rate of complete necrosis rose to 60%. CONCLUSION: Long term results confirmed nailing as appropriate treatment strategy for all types of humeral head fractures with limitation of excellent reduction in every age group. Moderate or even poor reduction significantly deteriorates functional results and increases rate of complete necrosis of the humeral head. If good reduction cannot be achieved, treatment strategy should be changed.

Alternative NADH dehydrogenase (NDH2): intermembrane-space-facing counterpart of mitochondrial complex I in the procyclic Trypanosoma brucei.

The respiratory chain of the procyclic stage of Trypanosoma brucei contains the standard complexes I through IV, as well as several alternative enzymes contributing to electron flow. In this work, we studied the function of an alternative NADH : ubiquinone oxidoreductase (NDH2). Depletion of target mRNA was achieved using RNA interference (RNAi). In the non-induced and RNAi-induced cell growth, membrane potential change, alteration in production of reactive oxygen species, overall respiration, enzymatic activities of complexes I, III and/or IV and distribution of NADH : ubiquinone oxidoreductase activities in glycerol gradient fractions were measured. Finally, respiration using different substrates was tested on digitonin-permeabilized cells. The induced RNAi cell line exhibited slower growth, decreased mitochondrial membrane potential and lower sensitivity of respiration to inhibitors. Mitochondrial glycerol-3-phosphate dehydrogenase was the only enzymatic activity that has significantly changed in the interfered cells. This elevation as well as a decrease of respiration using NADH was confirmed on digitonin-permeabilized cells. The data presented here together with previously published findings on complex I led us to propose that NDH2 is the major NADH : ubiquinone oxidoreductase responsible for cytosolic and not for mitochondrial NAD+ regeneration in the mitochondrion of procyclic T. brucei.

Cognitive outcome after EC-IC bypass surgery in hemodynamic cerebral ischemia.

OBJECTIVE: The purpose of this study was to evaluate cognitive functions in patients undergoing extracranial-intracranial (EC-IC) bypass surgery for cerebral ischemia. POPULATION AND METHODS: From August 2003 to January 2009, 276 patients with occluded internal carotid arteries (ICA) were screened. Forty of these met the criteria for a low-flow EC-IC bypass. These patients were identified based on evidence of exhausted vasomotor reactivity (VMR) using the Doppler CO(2) test and CT perfusion. These patients were invited to have a complete battery of neuropsychological tests preoperatively and 12 months after surgery. Complete neurocognitive testing was finished in 20 patients. RESULTS: This group of 20 patients showed preoperative cognitive impairment ranging from mild to medium-severe. There were no cases of stroke ipsilateral to the operated side during the follow-up period. VMR improvement was seen in all patients within 6 months of surgery. A comparison using a paired t-test demonstrated significant improvement 12 months after surgery in the following neuropsychological tests: WAIS-R (p = 0.01), Number Collection Test (p = 0.02), Trail Making Test (p = 0.03), and Benton Visual Retention Test (p = 0.05). Repeat analysis of variance (ANOVA) suggested the following predictors associated with cognitive improvement:the presence of ophthalmic collateral flow (p = 0.04), preoperative amaurosis fugax (p = 0.02), and external watershed infarction detected by MRI (p = 0.04). CONCLUSION: Patients with occlusion of the ICA and exhausted VMR have cognitive impairment prior to EC-IC bypass surgery. Twelve months after surgery, there is significant improvement in various areas of cognition.