In vitro propagation of Dactylosphaera vitifolii SHIMER (Homoptera: Phylloxeridae) on shoot and root cultures of a Vitis hybrid

Using a Vitis hybrid, methods of long-term micropropagation of shoots and culture of hairy roots (transformed by Agrobacterium rhizogenes) were developed. The growth of these organ cultures was characterized. The cultures were used as feeding substrates for grapevine phylloxera. Starting with eggs, at 23.6°C the parthenogenetic life cycle of the aphid proceeded in vitro. Within 2 weeks after inoculation, more than 80 % of the shoot cultures responded with the formation of galls on young leaf blades and swellings on petioles, and, exceptionally, young shoots. At about the same time new eggs were deposited. Gall formation and propagation of phylloxera could be perpetuated for 2.5 years by aseptical transfer of eggs to freshly micropropagated shoots every 1-3 weeks. Within 1 week after inoculation, more than 90 % of the younger parts of root cultures harboured larvae and responded with curvatures and thickenings. After 2 weeks, phylloxera oviposited and during the following weeks the number of eggs and animals increased considerably. Thus, both forms of dual culture enable leaf and root gall formation and propagation of phylloxera excluding further organisms

Elucidating the influence of sensory neuropeptides on inherent metabolic behavior of murine macrophages under mechanical loading

Macrophages as precursor cells of osteoclasts are of importance during bone formation, whose physiologically well-balanced process is altered during osteoarthritis (OA). Mechanosensing within cells is necessary for growth and maturation of joints, whereas pathological stress can cause inflammation and disorders, such as articular cartilage degeneration or subchondral bone sclerosis in OA. The neuropeptides Substance P (SP) and α-calcitonin gene-related peptide (αCGRP), acting on the neurokinin-1 receptor (NK1R) and the calcitonin receptor-like receptor (CRLR)/ receptor activity-modifying protein (RAMP1), are involved in joint physiology and OA-associated degenerative processes and were shown to modulate osteoclastogenesis. Regarding these mechanisms, the topic of this work was to elucidate the combination of both mechanical loading and sensory neuropeptide stimulation on metabolic parameters of murine macrophages. RAW 264.7 macrophages were subjected to cyclic mechanical stretch. Neuropeptide receptor and neuropeptide gene and protein expression was assayed by PCR analysis and western blotting, respectively. Metabolic behavior of macrophages was analyzed by studying apoptosis, proliferation and adhesion, with and without neuropeptide stimulation after application of cyclic stretch. The expression of macrophage polarization markers and osteoclastogenesis-associated genes was examined after loading. Neuropeptide stimulation experiments were repeated on primary BMM after the surgical induction of OA. This study demonstrated the involvement of SP and αCGRP and their receptors in macrophage mechanotransduction and -regulation. Mechanoregulation via αCGRP-CRLR/RAMP1 interaction had never been previously addressed. Our results further indicate the regulation of RAMP1 in experimental conditions of mechanically induced stress. In agreement with results from other groups, we observed an autocrine negative feedback mechanism of NK1R/SP signaling. Furthermore, macrophages exposed to mechanical stress developed a sensitization for caspase 3/7-mediated apoptosis induction and an inhibited adhesion after αCGRP stimulation, pointing towards a preventive mechanism regarding detrimental inflammatory conditions by upregulation of macrophage apoptosis and a reduced macrophage migration. The M1 polarization after loading suggests a proinflammatory activity of mechanically stressed macrophages. If and how this would affect macrophage activity in vivo remains elusive. Furthermore, we observed that the gene expression of the RANK receptor was enhanced after mechanical loading leading to the assumption of a higher osteoclastogenic differentiation potential of macrophages. Additionally, the induction of experimental OA appears to alter the mechanotransduction of primary murine BMM, as we observed a higher proliferation rate and an increased sensitivity to apoptosis induction of BMM at 8 weeks post OA surgical induction in comparison to BMM from Sham-operated animals. From that, we conclude that altered cellular biomechanics, induced by OA, affect bone resident macrophage populations. The underlying molecular mechanisms remain unknown so far. Future studies could help to identify regulatory processes involved in the altered cellular reactivity and might contribute to the development of new treatment options that target pathological signaling pathways of macrophage mechanoregulation and neuropeptide sensitivity

Aggression and Anxiety: Social Context and Neurobiological Links

Psychopathologies such as anxiety- and depression-related disorders are often characterized by impaired social behaviours including excessive aggression and violence. Excessive aggression and violence likely develop as a consequence of generally disturbed emotional regulation, such as abnormally high or low levels of anxiety. This suggests an overlap between brain circuitries and neurochemical systems regulating aggression and anxiety. In this review, we will discuss different forms of male aggression, rodent models of excessive aggression, and neurobiological mechanisms underlying male aggression in the context of anxiety. We will summarize our attempts to establish an animal model of high and abnormal aggression using rats selected for high (HAB) vs. low (LAB) anxiety-related behaviour. Briefly, male LAB rats and, to a lesser extent, male HAB rats show high and abnormal forms of aggression compared with non-selected (NAB) rats, making them a suitable animal model for studying excessive aggression in the context of extremes in innate anxiety. In addition, we will discuss differences in the activity of the hypothalamic–pituitary–adrenal axis, brain arginine vasopressin, and the serotonin systems, among others, which contribute to the distinct behavioural phenotypes related to aggression and anxiety. Further investigation of the neurobiological systems in animals with distinct anxiety phenotypes might provide valuable information about the link between excessive aggression and disturbed emotional regulation, which is essential for understanding the social and emotional deficits that are characteristic of many human psychiatric disorders

Comparison of data characterizing the clinical effectiveness of the fluocinolone intravitreal implant (ILUVIEN) in patients with diabetic macular edema from the real world, non-interventional ICE-UK study and the FAME randomized controlled trials

Objective: To compare the effectiveness and safety of the fluocinolone acetonide (FAc) intravitreal implant between the observational Iluvien Clinical Evidence study in the United Kingdom (ICE-UK) and the Fluocinolone Acetonide in Diabetic Macular Edema (FAME) randomized controlled trials (RCTs) in people with diabetic macular edema (DME). Clinical Trials Registration: NCT00344968. Methods: This study selected patients randomized to receive 0.2 µg/day FAc insert (FAc treated eyes) or sham injection (control eyes) from the FAME RCTs, and patients’ first FAc treated eye and non-FAc treated fellow (control) eye from the ICE-UK study. Outcomes included change in visual acuity (VA), central foveal thickness (CFT), and intraocular pressure (IOP). Results: After 12 months follow-up, mean change in VA was 5.0 letters improvement (p < .001) and 1.6 letters improvement (p = .003) in FAME FAc treated and control eyes, and 3.8 letters (p = .012) and –2.1 letters (p = .056) in ICE-UK FAc treated and control eyes, respectively. Mean change in CFT was –144 µm (p < .001) vs –72 µm (p < .001) in FAME FAc treated and control eyes and –113 µm (p < .001) vs –13 µm (p < .001) in ICE-UK FAc treated and control eyes. For eyes with a follow-up of 12 months, 77 (22.3%) and 15 (8.6%) FAME FAc treated and control eyes and 25 (18.7%) and six (4.3%) ICE-UK FAc treated and control eyes required emergent IOP-lowering therapy. Conclusions: Statistically significant improvements in VA 12 months after FAc implantation were observed in both the real-world study and in the RCTs. The improvement in VA and CFT in the RCTs was marginally greater than in the real-world study; however, recruits in the real-world study had more severe visual morbidity at baseline. Whilst there were many changes in the care of people with DME over this time, these data all support the value of treatment with FAc intravitreal implant

Brain oxytocin correlates with maternal aggression: Link to anxiety

The oxytocinergic system is critically involved in the regulation of maternal behavior, which includes maternal aggression. Because aggression has been linked to anxiety, we investigated the maternal aggression and the role of brain oxytocin in lactating Wistar rats selectively bred for high anxiety-related behavior (HAB) or low anxiety-related behavior (LAB) during the 10 min maternal defense test. HAB dams displayed more maternal aggression against a virgin intruder compared with LAB dams, resulting in more defensive behavior and higher anxiety of HAB-defeated virgins. The different levels of aggression were accompanied by opposite oxytocin release patterns within the paraventricular nucleus (PVN; HAB, increase; LAB, decrease). Furthermore, oxytocin release was higher within the central nucleus of the amygdala (CeA) of HAB dams compared with LABs. A direct correlation between the offensive behavior displayed during the maternal defense test and local oxytocin release was found in both the PVN and CeA. Using retrodialysis, blockade of endogenous oxytocin action by infusion of an oxytocin receptor antagonist (des-Gly-NH2,d(CH2)5[Tyr(Me)2,Thr4]OVT) into the PVN or CeA reduced maternal aggression of HAB dams, whereas infusion of synthetic oxytocin into the PVN tended to increase aggression toward the intruder in LAB dams. There were no significant differences in oxytocin receptor mRNA expression or oxytocin receptor binding between lactating HAB and LAB dams. Therefore, differences in intracerebral release patterns of oxytocin, rather than differences at the level of oxytocin receptors, are critical for the regulation of maternal aggressive behavior

Precisely timed inhibition facilitates action potential firing for spatial coding in the auditory brainstem

The integration of excitatory and inhibitory synaptic inputs is fundamental to neuronal processing. In the mammalian auditory brainstem, neurons compare excitatory and inhibitory inputs from the ipsilateral and contralateral ear, respectively, for sound localization. However, the temporal precision and functional roles of inhibition in this integration process are unclear. Here, we demonstrate by in vivo recordings from the lateral superior olive (LSO) that inhibition controls spiking with microsecond precision throughout high frequency click trains. Depending on the relative timing of excitation and inhibition, neuronal spike probability is either suppressed or-unexpectedly-facilitated. In vitro conductance-clamp LSO recordings establish that a reduction in the voltage threshold for spike initiation due to a prior hyperpolarization results in post-inhibitory facilitation of otherwise sub-threshold synaptic events. Thus, microsecond-precise differences in the arrival of inhibition relative to excitation can facilitate spiking in the LSO, thereby promoting spatial sensitivity during the processing of faint sounds

The incidence of interstitial lung disease 1995–2005: a Danish nationwide population-based study

<p>Abstract</p> <p>Background</p> <p>Current data on incidence of interstitial lung diseases (ILDs) are sparse and concerns about an increasing trend have been raised. We examined incidence rates (IRs) of ILDs and changes in IRs between 1995 and 2005.</p> <p>Methods</p> <p>All persons with a first-time hospital discharge or outpatient diagnosis of ILD were identified through the Danish National Registry of Patients, which covers all Danish hospitals. Crude and age-standardised IRs were computed for ILD overall, as well as stratified by ILD subcategories.</p> <p>Results</p> <p>A total of 21,765 patients with ILD were identified. Between 1995 and 1998 the overall standardised IR of ILD decreased from 27.14 (95% CI 25.82–28.46) per 100,000 person-years to 19.36 (95% CI 18.26–20.46) per 100,000 person-years. After 1998 the IR increased considerably, peaking at 34.34 (95% CI 32.84–35.85) per 100,000 person-years in 2002. Subsequently there was a slight decrease. The highest IR was observed in the non-specific category "Respiratory disorders in diseases classified elsewhere". By ILD subcategory, the greatest average increase during the study period was observed in "Respiratory disorders in diseases classified elsewhere".</p> <p>Conclusion</p> <p>The incidence rate of ILD in Denmark increased during the study period, most pronounced for ILDs associated with systemic diseases.</p

Nonapeptide influences on social behaviour: effects of vasotocin and isotocin on shoaling and interaction in zebrafish

Nonapeptides are important regulators of social behaviour across vertebrate taxa. While their role in simple grouping behaviour has been explored in estrildid finches, other taxa are understudied, prompting us to investigate nonapeptide influences on shoaling behaviour in zebrafish. Subjects received injections of isotocin, an isotocin antagonist, vasotocin, a vasotocin antagonist, or saline, followed by a test of grouping behaviour. Vasotocin decreased social interaction with the shoal. Unexpectedly, the vasotocin antagonist also reduced social interaction with the shoal, as well as general shoaling behaviour. Isotocin and its antagonist had minimal effects on grouping behaviours. These results suggest social interaction and shoaling are discrete aspects of sociality differentially influenced by vasotocin, although we cannot discount possible anxiogenic effects of vasotocin. Contrasting these results with studies in other systems demonstrates that each nonapeptide’s role in social behaviour varies across taxa, and cautions against a simplistic characterisation of nonapeptides as prosocial regulators of behaviour