Identifying the therapeutic zone in globus pallidus deep brain stimulation for Parkinson's disease.

OBJECTIVE: The globus pallidus internus (GPI) has been demonstrated to be an effective surgical target for deep brain stimulation (DBS) treatment in patients with medication-refractory Parkinson's disease (PD). The ability of neurosurgeons to define the area of greatest therapeutic benefit within the globus pallidus (GP) may improve clinical outcomes in these patients. The objective of this study was to determine the best DBS therapeutic implantation site within the GP for effective treatment in PD patients. METHODS: The authors performed a retrospective review of 56 patients who underwent bilateral GP DBS implantation at their institution during the period from January 2015 to January 2020. Each implanted contact was anatomically localized. Patients were followed for stimulation programming for at least 6 months. The authors reviewed preoperative and 6-month postsurgery clinical outcomes based on data from the Unified Parkinson's Disease Rating Scale Part III (UPDRS III), dyskinesia scores, and levodopa equivalent daily dose (LEDD). RESULTS: Of the 112 leads implanted, the therapeutic cathode was most frequently located in the lamina between the GPI external segment (GPIe) and the GP externus (GPE) (n = 40). Other common locations included the GPE (n = 24), the GPIe (n = 15), and the lamina between the GPI internal segment (GPIi) and the GPIe (n = 14). In the majority of patients (73%) a monopolar programming configuration was used. At 6 months postsurgery, UPDRS III off medications (OFF) and on stimulation (ON) scores significantly improved (z = -4.02, p < 0.001), as did postsurgery dyskinesia ON scores (z = -4.08, p < 0.001) and postsurgery LEDD (z = -4.7, p < 0.001). CONCLUSIONS: Though the ventral GP (pallidotomy target) has been a commonly used target for GP DBS, a more dorsolateral target may be more effective for neuromodulation strategies. The assessment of therapeutic contact locations performed in this study showed that the lamina between GPI and GPE used in most patients is the optimal central stimulation target. This information should improve preoperative GP targeting.

Understanding costs and benefits of thermal plasticity for pest management: insights from the integration of laboratory, semi-field and field assessments of Ceratitis capitata (Diptera: Tephritidae).

The relative costs and benefits of thermal acclimation for manipulating field performance of pest insects depend upon a number of factors including which traits are affected and how persistent any trait changes are in different environments. By assessing plastic trait responses of Ceratitis capitata (Mediterranean fruit fly) across three distinct operational environments (laboratory, semi-field, and field), we examined the influence of different thermal acclimation regimes (cool, intermediate [or handling control], and warm) on thermal tolerance traits (chill-coma recovery, heat-knockdown time, critical thermal minimum and critical thermal maximum) and flight performance (mark-release-recapture). Under laboratory conditions, thermal acclimation altered thermal limits in a relatively predictable manner and there was a generally positive effect across all traits assessed, although some traits responded more strongly. By contrast, dispersal-related performance yielded strongly contrasting results depending on the specific operational environment assessed. In semi-field conditions, warm- or cold-acclimated flies were recaptured more often than the control group at cooler ambient conditions suggesting an overall stimulatory influence of thermal variability on low-temperature dispersal. Under field conditions, a different pattern was identified: colder flies were recaptured more in warmer field conditions relative to other treatment groups. This study highlights the trait- and context-specific nature of how thermal acclimation influences traits of thermal performance and tolerance. Consequently, laboratory and semi-field assessments of dispersal may not provide results that extend into the field setting despite the apparent continuum of environmental complexity among them (laboratory < semi-field < field).

Cool storage of Queensland fruit fly pupae for improved management of mass production schedules.

BACKGROUND: Cool storage is a valuable means of manipulating insect development time. The Queensland fruit fly (Q-fly) is Australia's most economically significant pest of fruit crops. The present study investigates cool storage of Q-fly pupae for increasing production flexibility for sterile insect technique programs. Development time, survival and fly quality were assessed following continuous storage of 1-day-old pupae at temperatures ranging from 13 to 25 °C. RESULTS: Survival was reduced almost to zero by pupal storage at 13 and 15 °C, was greatly reduced by storage at 17 °C, and was modestly reduced by storage at 19 °C. Pupal development time was extended by 16 days at 17 °C and by 9 days at 19 °C. Cool storage negatively affected flight ability and depleted lipid reserves. Cool storage at 19 °C enhanced the ability of 3-day-old adults to recover from chill-coma compared to control flies, indicating cold acclimation. CONCLUSION: There is potential for use of cool storage in Q-fly mass rearing, especially to improve alignment between production and field releases. For the purpose of delaying the development time of Q-fly pupae with minimal quality reduction, storage at 23 °C is recommended for 1-day-old pupae. © 2019 Society of Chemical Industry.

A transcriptomics assessment of oxygen-temperature interactions reveals novel candidate genes underlying variation in thermal tolerance and survival.

While single stress responses are fairly well researched, multiple, interactive stress responses are not-despite the obvious importance thereof. Here, using D. melanogaster, we investigated the effects of simultaneous exposures to low O2 (hypoxia) and varying thermal conditions on mortality rates, estimates of thermal tolerance and the transcriptome. We used combinations of 21 (normoxia), 10 or 5kPa O2 with control (23°C), cold (4°C) or hot (31°C) temperature exposures before assaying chill coma recovery time (CCRT) and heat knock down time (HKDT) as measures of cold and heat tolerance respectively. We found that mortality was significantly affected by temperature, oxygen partial pressure (PO2) and the interaction between the two. Cold treatments resulted in low mortality (<5%), regardless of PO2 treatment; while hot treatments resulted in higher mortality (∼20%), especially at 5kPa O2 which was lethal for most flies (∼80%). Both CCRT and HKDT were significantly affected by temperature, but not PO2, of the treatments, and the interaction of temperature and PO2 was non-significant. Hot treatments led to significantly longer CCRT, and shorter HKDT in comparison to cold treatments. Global gene expression profiling provided the first transcriptome level response to the combined stress of PO2 and temperature, showing that stressful treatments resulted in higher mortality and induced transcripts that were associated with protein kinases, catabolic processes (proteases, hydrolases, peptidases) and membrane function. Several genes and pathways that may be responsible for the protective effects of combined PO2 and cold treatments were identified. We found that urate oxidase was upregulated in all three cold treatments, regardless of the PO2. Small heat shock proteins Hsp22 and Hsp23 were upregulated after both 10 and 21kPa O2-hot treatments. Collectively, the data from PO2-hot treatments suggests that hypoxia does exacerbate heat stress, through an as yet unidentified mechanism. Hsp70B and an unannotated transcript (CG6733) were significantly differentially expressed after 5kPa O2-cold and 10kPa O2-hot treatments relative to their controls. Downregulation of these transcripts was correlated with reduced thermal tolerance (longer CCRT and shorter HKDT), suggesting that these genes may be important candidates for future research.

Effects of nutrient and water restriction on thermal tolerance: A test of mechanisms and hypotheses.

Nutritional deprivation or desiccation can influence thermal tolerance by impacting the insects' ability to evaporatively cool, maintain cell membrane integrity and conduct protective or repair processes. Recovery from chilling is also linked to the re-establishment of iono- and osmo-regulatory homeostasis. Here, using Mediterranean fruit fly (Ceratitis capitata, Diptera: Tephritidae), we manipulated water and nutrient availability to test the mechanistic expectation that changes in whole organism lipid and water content can elicit variation in cold or heat tolerance (scored as chill coma recovery time and heat knockdown time). We measured body condition (body water and lipid content) as well as heat shock protein 70 gene (hsp70) and protein (HSP70) levels. A significant reduction in body water content with water restriction did not translate into differences in chill coma recovery. When nutrient restriction was coupled with water deprivation, this resulted in a significant reduction (-54%) of heat knockdown time in females but male flies were unaffected. There was no evidence for an hsp70 or HSP70 response under any of the stress treatments and therefore no correlation with heat or cold tolerance. Heat hardening decreased all hsp levels. Therefore, although body water and total body lipid content differed between the treatment groups, the contribution of these factors to thermal tolerance was inconsistent with mechanistic expectations in heat knockdown time and insignificant for chill coma recovery. These results therefore highlight that the effects of resource restriction on thermal limits in insects are mechanistically more complex than previous models of stress resistance have suggested.

Dispersal propensity, but not flight performance, explains variation in dispersal ability.

Enhanced dispersal ability may lead to accelerated range expansion and increased rates of population establishment, thereby affecting population genetic structure and evolutionary potential. Morphological, behavioural and physiological traits that characterize dispersive individuals from residents are poorly understood for many invertebrate systems, especially in non-polymorphic pterygote species. Here we examined phenotypic differences between dispersal-prone and philopatric individuals from repeated mark-release-recapture (MRR) experiments using an invasive agricultural pest, Ceratitis capitata Comprehensive morphometric assessment and subsequent minimal adequate modelling using an information theoretic approach identified thorax mass : body mass ratio as a key predictor of disperser flies under semi-natural conditions. Performance differences in flight ability were then examined under controlled laboratory conditions to assess whether greater thorax mass : body mass ratio was associated with enhanced flight ability. The larger thorax : body mass ratio was associated with measurable differences in mean flight duration, most predominantly in males, and also by their willingness to disperse, scored as the number and duration of voluntary flights. No other measures of whole-animal flight performance (e.g. mean and peak vertical force, total or maximum flight duration) differed. Variation in voluntary behaviour may result in significant alterations of movement behaviour and realized dispersal in nature. This phenomenon may help explain intraspecific variation in the dispersal ability of insects.

Dispersal propensity in Tetrahymena thermophila ciliates - a reaction norm perspective.

Dispersal and phenotypic plasticity are two main ways for species to deal with rapid changes of their environments. Understanding how genotypes (G), environments (E), and their interaction (genotype and environment; G × E) each affects dispersal propensity is therefore instrumental for predicting the ecological and evolutionary responses of species under global change. Here we used an actively dispersing ciliate to quantify the contributions of G, E, and G × E on dispersal propensity, exposing 44 different genotypes to three different environmental contexts (densities in isogenotype populations). Moreover, we assessed the condition dependence of dispersal, that is, whether dispersal is related to morphological, physiological, or behavioral traits. We found that genotypes showed marked differences in dispersal propensity and that dispersal is plastically adjusted to density, with the overall trend for genotypes to exhibit negative density-dependent dispersal. A small, but significant G × E interaction indicates genetic variability in plasticity and therefore some potential for dispersal plasticity to evolve. We also show evidence consistent with condition-dependent dispersal suggesting that genotypes also vary in how individual condition is linked to dispersal under different environmental contexts thereby generating complex dispersal behavior due to only three variables (genes, environment, and individual condition).

Ontogenetic variation in cold tolerance plasticity in Drosophila: is the Bogert effect bogus?

Ontogenetic variation in plasticity is important to understanding mechanisms and patterns of thermal tolerance variation. The Bogert effect postulates that, to compensate for their inability to behaviourally thermoregulate, less-mobile life stages of ectotherms are expected to show greater plasticity of thermal tolerance than more-mobile life stages. We test this general prediction by comparing plasticity of thermal tolerance (rapid cold-hardening, RCH) between mobile adults and less-mobile larvae of 16 Drosophila species. We find an RCH response in adults of 13 species but only in larvae of four species. Thus, the Bogert effect is not as widespread as expected.

Ecologically relevant measures of tolerance to potentially lethal temperatures.

The acute thermal tolerance of ectotherms has been measured in a variety of ways; these include assays where organisms are shifted abruptly to stressful temperatures and assays where organisms experience temperatures that are ramped more slowly to stressful levels. Ramping assays are thought to be more relevant to natural conditions where sudden abrupt shifts are unlikely to occur often, but it has been argued that thermal limits established under ramping conditions are underestimates of true thermal limits because stresses due to starvation and/or desiccation can arise under ramping. These confounding effects might also impact the variance and heritability of thermal tolerance. We argue here that ramping assays are useful in capturing aspects of ecological relevance even though there is potential for confounding effects of other stresses that can also influence thermal limits in nature. Moreover, we show that the levels of desiccation and starvation experienced by ectotherms in ramping assays will often be minor unless the assays involve small animals and last for many hours. Empirical data illustrate that the combined effects of food and humidity on thermal limits under ramping and sudden shifts to stressful conditions are unpredictable; in Drosophila melanogaster the presence of food decreased rather than increased thermal limits, whereas in Ceratitis capitata they had little impact. The literature provides examples where thermal limits are increased under ramping presumably because of the potential for physiological changes leading to acclimation. It is unclear whether heritabilities and population differentiation will necessarily be lower under ramping because of confounding effects. Although it is important to clearly define experimental methods, particularly when undertaking comparative assessments, and to understand potential confounding effects, thermotolerance assays based on ramping remain an important tool for understanding and predicting species responses to environmental change. An important area for further development is to identify the impact of rates of temperature change under field and laboratory conditions.

Thermal tolerance in widespread and tropical Drosophila species: does phenotypic plasticity increase with latitude?

The distribution of insects can often be related to variation in their response to thermal extremes, which in turn may reflect differences in plastic responses or innate variation in resistance. Species with widespread distributions are expected to have evolved higher levels of plasticity than those from restricted tropical areas. This study compares adult thermal limits across five widespread species and five restricted tropical species of Drosophila from eastern Australia and investigates how these limits are affected by developmental acclimation and hardening after controlling for environmental variation and phylogeny. Irrespective of acclimation, cold resistance was higher in the widespread species. Developmental cold acclimation simulating temperate conditions extended cold limits by 2°-4°C, whereas developmental heat acclimation under simulated tropical conditions increased upper thermal limits by <1°C. The response to adult heat-hardening was weak, whereas widespread species tended to have a larger cold-hardening response that increased cold tolerance by 2°-5°C. These patterns persisted after phylogenetic correction and when flies were reared under high and low constant temperatures. The results do not support the hypothesis that widely distributed species have larger phenotypic plasticity for thermal tolerance limits, and Drosophila species distributions are therefore more closely linked to differences in innate thermal tolerance limits.