Selective vulnerability to atrophy in sporadic Creutzfeldt-Jakob disease.

OBJECTIVE: Identification of brain regions susceptible to quantifiable atrophy in sporadic Creutzfeldt-Jakob disease (sCJD) should allow for improved understanding of disease pathophysiology and development of structural biomarkers that might be useful in future treatment trials. Although brain atrophy is not usually present by visual assessment of MRIs in sCJD, we assessed whether using voxel-based morphometry (VBM) can detect group-wise brain atrophy in sCJD. METHODS: 3T brain MRI data were analyzed with VBM in 22 sCJD participants and 26 age-matched controls. Analyses included relationships of regional brain volumes with major clinical variables and dichotomization of the cohort according to expected disease duration based on prion molecular classification (i.e., short-duration/Fast-progressors (MM1, MV1, and VV2) vs. long-duration/Slow-progressors (MV2, VV1, and MM2)). Structural equation modeling (SEM) was used to assess network-level interactions of atrophy between specific brain regions. RESULTS: sCJD showed selective atrophy in cortical and subcortical regions overlapping with all but one region of the default mode network (DMN) and the insulae, thalami, and right occipital lobe. SEM showed that the effective connectivity model fit in sCJD but not controls. The presence of visual hallucinations correlated with right fusiform, bilateral thalami, and medial orbitofrontal atrophy. Interestingly, brain atrophy was present in both Fast- and Slow-progressors. Worse cognition was associated with bilateral mesial frontal, insular, temporal pole, thalamus, and cerebellum atrophy. INTERPRETATION: Brain atrophy in sCJD preferentially affects specific cortical and subcortical regions, with an effective connectivity model showing strength and directionality between regions. Brain atrophy is present in Fast- and Slow-progressors, correlates with clinical findings, and is a potential biomarker in sCJD.

The attractant, but not the trap design, affects the capture of Drosophila suzukii in berry crops.

Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) is recognized as an invasive pest in Europe and North America. In Mexico, it is one of the main insect pests of soft-skinned fruits such as blueberries, strawberries, raspberries, blackberries, plums, and guava. Previous studies have shown that D. suzukii uses visual and chemical cues during host plant searching. This knowledge has been used to develop traps and attractants for monitoring D. suzukii. In this study, five trap designs were evaluated to monitor D. suzukii under field conditions. Traps were baited with SuzukiiTrap®, Z-Kinol, an attractant based on acetoin and methionol, or apple cider vinegar (ACV) enriched with 10% ethanol (EtOH) with the synergistic action of carbon dioxide (CO2). Our results suggested that the attractant was the determining factor in capturing D. suzukii, while trap design seemed to play a modest role. We found that traps baited with Z-Kinol captured the highest number of D. suzukii compared to that caught by traps baited with SuzukiiTrap®, or ACV + EtOH + CO2. The highest catch numbers occurred in blackberry, followed by strawberry, raspberry, and blueberry. Traps captured more females than males. The results obtained may be useful for monitoring D. suzukii populations in Mexico and elsewhere, particularly in states where soft fruit crops are a component of agricultural activities.

Herbivore-Induced Volatiles from Maize Plants Attract Chelonus insularis, an Egg-Larval Parasitoid of the Fall Armyworm.

Chelonus insularis (Hymenoptera: Braconidae) is an egg-larval endoparasitoid that attacks several lepidopteran species, including the fall armyworm (FAW), Spodoptera frugiperda, as one of its main hosts. In this study, we identified the volatiles emitted by maize plants undamaged and damaged by S. frugiperda larvae that were attractive to virgin C. insularis females. In a Y-glass tube olfactometer, parasitoid females were more attracted to activated charcoal extracts than Porapak Q maize extracts. Chemical analysis of activated charcoal extracts from maize plants damaged by S. frugiperda larvae by gas chromatography coupled with electroantennography (GC-EAD) showed that the antennae of virgin female wasps consistently responded to three compounds, identified by gas chromatography-mass spectrometry (GC-MS) as α-pinene, α-longipinene and α-copaene. These compounds are constitutively released by maize plants but induction via herbivory affects their emissions. α-Longipinene and α-copaene were more abundant in damaged maize plants than in healthy ones, whereas α-pinene was produced in higher amounts in healthy maize plants than in damaged ones. Female parasitoids were not attracted to EAD-active compounds when evaluated singly; however, they were attracted to the binary blend α-pinene + α-copaene, which was the most attractive blend, even more attractive than the tertiary blend (α-pinene + α-longipinene + α-copaene) and the damaged maize plant extracts. We conclude that C. insularis is attracted to a blend of herbivore-induced volatiles emitted by maize plants.

Neurological and psychological applications of transcranial lasers and LEDs.

Transcranial brain stimulation with low-level light/laser therapy (LLLT) is the use of directional low-power and high-fluency monochromatic or quasimonochromatic light from lasers or LEDs in the red-to-near-infrared wavelengths to modulate a neurobiological function or induce a neurotherapeutic effect in a nondestructive and non-thermal manner. The mechanism of action of LLLT is based on photon energy absorption by cytochrome oxidase, the terminal enzyme in the mitochondrial respiratory chain. Cytochrome oxidase has a key role in neuronal physiology, as it serves as an interface between oxidative energy metabolism and cell survival signaling pathways. Cytochrome oxidase is an ideal target for cognitive enhancement, as its expression reflects the changes in metabolic capacity underlying higher-order brain functions. This review provides an update on new findings on the neurotherapeutic applications of LLLT. The photochemical mechanisms supporting its cognitive-enhancing and brain-stimulatory effects in animal models and humans are discussed. LLLT is a potential non-invasive treatment for cognitive impairment and other deficits associated with chronic neurological conditions, such as large vessel and lacunar hypoperfusion or neurodegeneration. Brain photobiomodulation with LLLT is paralleled by pharmacological effects of low-dose USP methylene blue, a non-photic electron donor with the ability to stimulate cytochrome oxidase activity, redox and free radical processes. Both interventions provide neuroprotection and cognitive enhancement by facilitating mitochondrial respiration, with hormetic dose-response effects and brain region activational specificity. This evidence supports enhancement of mitochondrial respiratory function as a generalizable therapeutic principle relevant to highly adaptable systems that are exquisitely sensitive to energy availability such as the nervous system.

Low-level light therapy improves cortical metabolic capacity and memory retention.

Cerebral hypometabolism characterizes mild cognitive impairment and Alzheimer's disease. Low-level light therapy (LLLT) enhances the metabolic capacity of neurons in culture through photostimulation of cytochrome oxidase, the mitochondrial enzyme that catalyzes oxygen consumption in cellular respiration. Growing evidence supports that neuronal metabolic enhancement by LLLT positively impacts neuronal function in vitro and in vivo. Based on its effects on energy metabolism, it is proposed that LLLT will also affect the cerebral cortex in vivo and modulate higher-order cognitive functions such as memory. In vivo effects of LLLT on brain and behavior are poorly characterized. We tested the hypothesis that in vivo LLLT facilitates cortical oxygenation and metabolic energy capacity and thereby improves memory retention. Specifically, we tested this hypothesis in rats using fear extinction memory, a form of memory modulated by prefrontal cortex activation. Effects of LLLT on brain metabolism were determined through measurement of prefrontal cortex oxygen concentration with fluorescent quenching oximetry and by quantitative cytochrome oxidase histochemistry. Experiment 1 verified that LLLT increased the rate of oxygen consumption in the prefrontal cortex in vivo. Experiment 2 showed that LLLT-treated rats had an enhanced extinction memory as compared to controls. Experiment 3 showed that LLLT reduced fear renewal and prevented the reemergence of extinguished conditioned fear responses. Experiment 4 showed that LLLT induced hormetic dose-response effects on the metabolic capacity of the prefrontal cortex. These data suggest that LLLT can enhance cortical metabolic capacity and retention of extinction memories, and implicate LLLT as a novel intervention to improve memory.

Low-level light therapy of the eye and brain.

Low-level light therapy (LLLT) using red to near-infrared light energy has gained attention in recent years as a new scientific approach with therapeutic applications in ophthalmology, neurology, and psychiatry. The ongoing therapeutic revolution spearheaded by LLLT is largely propelled by progress in the basic science fields of photobiology and bioenergetics. This paper describes the mechanisms of action of LLLT at the molecular, cellular, and nervous tissue levels. Photoneuromodulation of cytochrome oxidase activity is the most important primary mechanism of action of LLLT. Cytochrome oxidase is the primary photoacceptor of light in the red to near-infrared region of the electromagnetic spectrum. It is also a key mitochondrial enzyme for cellular bioenergetics, especially for nerve cells in the retina and the brain. Evidence shows that LLLT can secondarily enhance neural metabolism by regulating mitochondrial function, intraneuronal signaling systems, and redox states. Current knowledge about LLLT dosimetry relevant for its hormetic effects on nervous tissue, including noninvasive in vivo retinal and transcranial effects, is also presented. Recent research is reviewed that supports LLLT potential benefits in retinal disease, stroke, neurotrauma, neurodegeneration, and memory and mood disorders. Since mitochondrial dysfunction plays a key role in neurodegeneration, LLLT has potential significant applications against retinal and brain damage by counteracting the consequences of mitochondrial failure. Upon transcranial delivery in vivo, LLLT induces brain metabolic and antioxidant beneficial effects, as measured by increases in cytochrome oxidase and superoxide dismutase activities. Increases in cerebral blood flow and cognitive functions induced by LLLT have also been observed in humans. Importantly, LLLT given at energy densities that exert beneficial effects does not induce adverse effects. This highlights the value of LLLT as a novel paradigm to treat visual, neurological, and psychological conditions, and supports that neuronal energy metabolism could constitute a major target for neurotherapeutics of the eye and brain.

In vivo low-level light therapy increases cytochrome oxidase in skeletal muscle.

Low-level light therapy (LLLT) increases survival of cultured cells, improves behavioral recovery from neurodegeneration and speeds wound healing. These beneficial effects are thought to be mediated by upregulation of mitochondrial proteins, especially the respiratory enzyme cytochrome oxidase. However, the effects of in vivo LLLT on cytochrome oxidase in intact skeletal muscle have not been previously investigated. We used a sensitive method for enzyme histochemistry of cytochrome oxidase to examine the rat temporalis muscle 24 h after in vivo LLLT. The findings showed for the first time that in vivo LLLT induced a dose- and fiber type-dependent increase in cytochrome oxidase in muscle fibers. LLLT was particularly effective at enhancing the aerobic capacity of intermediate and red fibers. The findings suggest that LLLT may enhance the oxidative energy metabolic capacity of different types of muscle fibers, and that LLLT may be used to enhance the aerobic potential of skeletal muscle.

Mitochondrial optic neuropathy: In vivo model of neurodegeneration and neuroprotective strategies.

This review summarizes the characteristics of a rodent toxicologic model of optic neuropathy induced by the mitochondrial complex I inhibitor rotenone. This model has been developed to fulfill the demand for a drug-screening tool providing a sound mechanistic context to address the role of mitochondrial dysfunction in the pathogenesis of neurodegenerative disorders. It features biochemical, structural, and functional retinal deficits that resemble those of patients with Leber's hereditary optic neuropathy, a mitochondrial disease characterized by selective degeneration of retinal ganglion cells, and for which an environmental component is believed to play a major triggering role. The available data support the efficiency, sensitivity, and versatility of the model for providing insights into the mechanisms of neurodegeneration, including mitochondrial dysfunction, oxidative stress and excitotoxicity. Screening work with this model has provided proof-of-principle that interventions targeting the electron transport chain, such as USP methylene blue and near-infrared light therapy, are effective at preventing neurodegeneration induced by mitochondrial dysfunction in vivo. Prospective developments of this model include the use of neuronal reporter genes for in vivo non-invasive assessment of retinal degeneration at different time points, and its combination with genetic approaches to elucidate the synergism of environmental and genetic factors in neurodegeneration.

Olfactory response of the Mexican fruit fly (Diptera: Tephritidae) to Citrus aurantium volatiles.

We investigated the behavioral and electrophysiological responses of male and female Mexican fruit fly, Anastrepha ludens (Loew) (Diptera: Tephritidae), to volatiles of bitter orange fruit, Citrus aurantium L. In field cage tests, the number of A. ludens caught in Multilure traps baited with mature green bitter orange fruit was significantly higher than the number captured in traps baited with ripe yellow bitter orange fruit and control (unbaited traps). Both sexes were more attracted to mature green bitter orange fruit extracts than to controls in both flight tunnel and field cage assays. Gas chromatography-mass spectrometry analysis of the mature green bitter orange fruit volatiles identified 10 different compounds. Limonene was the most abundant volatile compound, followed by an unknown compound, tentatively identified as trans-ocimene. Linalool, beta-pinene, and methyl salicylate were found in lower proportions. Both sexes of A. ludens evoked higher antennal response to linalool, methyl salicylate, and to a blend of these four components in comparison with limonene, and beta-pinene. In flight tunnel, both sexes were more attracted and landed more often on spheres baited with the four-component blend compared with control spheres. In field cage tests, Multilure traps baited with the four-component blend captured significantly more A. ludens flies than traps baited with hydrolyzed protein or control traps.

Field evaluation of potential fruit-derived lures for Anastrepha obliqua (Diptera: Tephritidae).

Previous studies have shown that a nine-component blend (ethyl butyrate, isopropyl butyrate, hexan-1-ol, propyl butyrate, isobutyl butyrate, ethyl hexanoate, isopentyl butyrate, ethyl benzoate, and ethyl octanoate) isolated from Spondias mombin L. (Anacardiaceae) fruit are attractive to both sexes of West Indian fruit fly, Anastrepha obliqua (Macquart) (Diptera: Tephritidae), in laboratory and field cage tests. In this study, we evaluated the effectiveness of traps baited with the nine-component blend in capturing wild A. obliqua in a mango, Mangifera indica L. variety Ataulfo) orchard. In addition, we tested other S. mombin-derived lures to determine whether any of these effectively mimic the nine-component blend in attracting A. obliqua. In all trials, we compared the attractiveness of the S. mombin-derived lures against hydrolyzed protein, the standard bait for monitoring A. obliqua. We found that, in some trials, there was no difference in the number of females caught by traps baited with the nine-component blend or with hydrolyzed protein. In other trials, traps baited with hydrolyzed protein captured more females than traps baited with the nine-component blend. For males, in general there were no differences in the number of flies caught by traps baited either with the nine-component blend or with hydrolyzed protein. Traps baited with other S. mombin-derived lures captured fewer A. obliqua than traps baited with hydrolyzed protein. Traps baited with S. mombin-derived lures caught fewer species of nontarget tephritid flies and nontarget insects than traps baited with hydrolyzed protein.

A new potential attractant for Anastrepha obliqua from Spondias mombin fruits.

Nonirradiated males and females of Anastrepha obliqua (Macquart) were attracted to and landed more frequently on ripe fruits of Spondias mombin L. than on artificial fruit in wind tunnel bioassays. Porapak Q volatile extracts of S. mombin were also attractive and elicited landing on artificial fruit for both sexes. Combined gas chromatographic-electroantennographic detection (GC-EAD) analysis of volatile extracts showed that nine volatile compounds elicited repeatable antennal responses from females and males. The EAD-active compounds were identified by GC-mass spectrometry (MS) as follows: ethyl butyrate, isopropyl butyrate, hexan-1-ol, propyl butyrate, isobutyl butyrate, ethyl hexanoate, isopentyl butyrate, ethyl benzoate, and ethyl octanoate. In wind tunnel bioassays, males and females were attracted and landed more frequently on lures containing the nine-component blend of synthetic compounds than on unscented controls. Field cage bioassays showed that multilure traps baited with the nine-synthetic blend captured significantly more A. obliqua than traps baited with hydrolyzed protein or water.

Induction of apoptosis and effect on CD20+ using rituximab on autologous peripheral blood stem cell harvests from patients with B cell lymphomas.

Purging of neoplastic cells for autologous stem cell transplantation is usually done in vivo by administering chemotherapy and/or other agents before harvesting. It is also possible to decrease malignant cells counts directly in the cell harvest. In this study, we ascertained the effect of anti-CD20 monoclonal antibody and rituximab administration on peripheral blood hematopoietic stem cells. Five samples of stem cell harvests from different patients with B cell lymphoma were obtained. Each sample was divided in two tubes with calcium gluconate (20 mEq/50 microl). Rituximab (1 mg/600,000 mononuclear cells) was added to one of the tubes. Using flow cytometry, CD19, CD20 (B cell markers), and CD95 (apoptosis marker), expression was measured at baseline and 24 h after the addition of rituximab. A one-sided t-test with equal variances was used to analyze the results. Immediately after rituximab addition, CD20 expression became null. No significant difference in variation of CD19 expression was detected after the addition of rituximab (-3.64% control vs. 0.63% rituximab, p = 0.69). Mean variations of percentage of CD95 expression were 2.9% (controls) and 10.52% (rituximab tubes) (p = 0.06). We conclude that rituximab is capable of initiating apoptosis in vitro. We found no decrease in the CD19+ cell count, used as a surrogate marker for CD20+ cells, meaning that, at least in 24 h, apoptosis activation is not capable of decreasing CD20+ cell numbers. In vitro purging of peripheral blood stem cells harvests with rituximab could be part of a broader therapeutic strategy to be offered to lymphoproliferative disorder patients.