Paranode Abnormalities and Oxidative Stress in Optic Nerve Vulnerable to Secondary Degeneration: Modulation by 670 nm Light Treatment

Secondary degeneration of nerve tissue adjacent to a traumatic injury results in further loss of neurons, glia and function, via mechanisms that may involve oxidative stress. However, changes in indicators of oxidative stress have not yet been demonstrated in oligodendrocytes vulnerable to secondary degeneration in vivo. We show increases in the oxidative stress indicator carboxymethyl lysine at days 1 and 3 after injury in oligodendrocytes vulnerable to secondary degeneration. Dihydroethidium staining for superoxide is reduced, indicating endogenous control of this particular reactive species after injury. Concurrently, node of Ranvier/paranode complexes are altered, with significant lengthening of the paranodal gap and paranode as well as paranode disorganisation. Therapeutic administration of 670 nm light is thought to improve oxidative metabolism via mechanisms that may include increased activity of cytochrome c oxidase. Here, we show that light at 670 nm, delivered for 30 minutes per day, results in in vivo increases in cytochrome c oxidase activity co-localised with oligodendrocytes. Short term (1 day) 670 nm light treatment is associated with reductions in reactive species at the injury site. In optic nerve vulnerable to secondary degeneration superoxide in oligodendrocytes is reduced relative to handling controls, and is associated with reduced paranode abnormalities. Long term (3 month) administration of 670 nm light preserves retinal ganglion cells vulnerable to secondary degeneration and maintains visual function, as assessed by the optokinetic nystagmus visual reflex. Light at a wavelength of 670 nm may serve as a therapeutic intervention for treatment of secondary degeneration following neurotrauma.     

Drought and small-bodied herbivores modify nutrient cycling in the semi-arid shortgrass steppe

Plant Ecology - Climate change will increase the frequency of droughts over the next century, with severe consequences for ecosystem function in semi-arid grasslands. The shortgrass steppe (SGS)...     

Rapid Depletion of Target Proteins Allows Identification of Coincident Physiological Responses

Targeted protein degradation is a powerful tool that can be used to create unique physiologies depleted of important factors. Current strategies involve modifying a gene of interest such that a degradation peptide is added to an expressed target protein and then conditionally activating proteolysis, either by expressing adapters, unmasking cryptic recognition determinants, or regulating protease affinities using small molecules. For each target, substantial optimization may be required to achieve a practical depletion, in that the target remains present at a normal level prior to induction and is then rapidly depleted to levels low enough to manifest a physiological response. Here, we describe a simplified targeted degradation system that rapidly depletes targets and that can be applied to a wide variety of proteins without optimizing target protease affinities. The depletion of the target is rapid enough that a primary physiological response manifests that is related to the function of the target. Using ribosomal protein S1 as an example, we show that the rapid depletion of this essential translation factor invokes concomitant changes to the levels of several mRNAs, even before appreciable cell division has occurred.     

Specialized visual learning of facial signals of quality in the paper wasp,Polistes dominula

Some primates and one species of paper wasp recognize faces using specific processing strategies to extract individual identity information from conspecific faces. Explanations for the evolution of face specialization typically focus on the complexity associated with individual recognition because all currently identified species with face specialization use faces for individual recognition. In the present study, we show an independent evolution of face specialization in a paper wasp species with facial patterns that signal quality rather than individual identity. Quality signals are simpler to process than individual identity signals because quality signals do not require simultaneous integration across multiple stimuli or learning and memory. Therefore, the results of the present study suggest that the complexity of processing may not be the key factor favouring the evolution of specialization. Instead, the predictable location of socially important signals relative to other anatomical features may allow easy categorization of features, thereby favouring specialized visual processing. Given that visual quality signals are found in many taxa, specific‐processing mechanisms for social signals may be widespread. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 113 , 992–997.     

Embryotoxicity of phenytoin in adrenalectomized CD-1 mice.

It has been proposed that the anticonvulsant drug phenytoin (PHT) and glucocorticoids induce orofacial clefting by the same mechanism. Previous work had demonstrated that PHT treatment significantly increased endogenous maternal corticosterone concentrations for approximately 48 hr after dosing in A/J mice. The purpose of the present investigation was to determine whether PHT is embryotoxic in the absence of endogenous maternal glucocorticoids. Maternal adrenal glands were removed on Day 7 of gestation, and the incidence of clefting after PHT treatment was determined. There was a high level of maternal toxicity following adrenalectomy (ADX) and PHT treatment at either 60 or 75 mg/kg. This increased toxicity did not appear to be due to altered maternal drug levels in ADX mice. There was a significant increase in the clefting incidence among offspring of ADX dams treated with PHT at 60 mg/kg. This dose of PHT did not elevate maternal corticosterone levels in ADX dams. These data suggest that PHT is capable of producing clefts in the absence of endogenous maternal corticosterone.     

Obesity Reduction Black Intervention Trial (ORBIT): 18‐Month Results

Obesity is a chronic condition that is prevalent in black women. The Obesity Reduction Black Intervention Trial (ORBIT) was a randomized controlled weight loss and weight‐loss maintenance (WLM) trial. Participants (N = 213) were randomized to the intervention or control groups in August 2005 and September 2006. Follow‐up data were collected 6 and 18 months after randomization. The main outcome was change in weight and BMI from baseline to 18 months. The mean weight at baseline was 104.9 kg, and the mean weight loss in the intervention group at 6 months was 3.0 kg and a gain of 0.2 kg in the control group (mean difference between groups in weight change at 6 months, adjusting for baseline weight and cohort, ?3.27 kg; 95% confidence interval (CI), ?4.50 to ?2.05 kg; P < 0.001). Both groups gained weight between 6 and 18 months (mean 1.0 kg in the intervention group and 0.1 kg in the control group). However, intervention participants lost significantly more weight than control participants during the 18‐month intervention (adjusted mean difference between groups at 18 months, ?2.83 kg; 95% CI, ?4.71 to ?0.95; P = 0.003). At 18 months, intervention participants were more likely than control participants to have lost at least 5% of baseline weight (24% vs. 12%, P < 0.04). Our results indicate that the ORBIT program did promote weight loss and weight‐loss maintenance. However, the results also clearly illustrate there is more to learn about what will contribute to meaningful weight loss and maintenance in this population.     

Nickel(II) complexes stabilized by bis[N-(6-pivalamido-2-pyridylmethyl)]benzylamine: Synthesis and characterization of complexes stabilized by a hydrogen bonding network

Intramolecular hydrogen bonds in metalloproteins are key in directing reactivity yet these effects have been difficult to achieved in synthetic systems. We have been developing a synthetic system that uses hydrogen-bonding interactions to modulate the secondary coordination around a transition metal ion. This was accomplished with the ligand bis[N-(6-pivalamido-2-pyridylmethyl)]benzylamine (H₂pmb), which contains two carboxyamido units appended from pyridine rings. Several nickel complexes were prepared and structurally characterized. In particular, we found that the appended carboxyamido groups either provide intramolecular H-bond donors or can be converted to bind directly to a metal center. We established that the complex Ni^IIH₂pmb(Cl)₂ can be sequentially deprotonated with potassium tert-butoxide, causing coordination of the carboxyamido oxygen atoms and concomitant loss of the chloro ligands. The chloro ligands were also removed with silver(I) salts in the presence of acetate ions and the complex Ni^IIH₂pmb(κ²-OAc)(κ¹-OAc) was isolated, in which an intramolecular H-bonding network occurs between the H₂pmb ligand and the coordinate acetato ligands.