Retro-orbital injections in mice

Intravenous vascular access is technically challenging in the adult mouse and even more challenging in neonatal mice. The authors describe the technique of retro-orbital injection of the venous sinus in the adult and neonatal mouse. This technique is a useful alternative to tail vein injection for the administration of non-tumorigenic compounds. The authors report that they have routinely used this technique in the adult mouse to administer volumes up to 150?μl without incident. Administration of retro-orbital injections is more challenging in neonatal mice but can reliably deliver volumes up to 10?μl.     

Incidence and Risk Factors of Homicide–Suicide in Swiss Households: National Cohort Study

Background

Homicide–suicides are rare but catastrophic events. This study examined the epidemiology of homicide-suicide in Switzerland.

Methods

The study identified homicide–suicide events 1991–2008 in persons from the same household in the Swiss National Cohort, which links census and mortality records. The analysis examined the association of the risk of dying in a homicide–suicide event with socio-demographic variables, measured at the individual-level, household composition variables and area-level variables. Proportional hazards regression models were calculated for male perpetrators and female victims. Results are presented as age-adjusted hazard ratios (HR) with 95% confidence intervals (95%CI).

Results

The study identified 158 deaths from homicide–suicide events, including 85 murder victims (62 women, 4 men, 19 children and adolescents) and 68 male and 5 female perpetrators. The incidence was 3 events per million households and year. Firearms were the most prominent method for both homicides and suicides. The risk of perpetrating homicide-suicide was higher in divorced than in married men (HR 3.64; 95%CI 1.56–8.49), in foreigners without permanent residency compared to Swiss citizens (HR 3.95; 1.52–10.2), higher in men without religious affiliations than in Catholics (HR 2.23; 1.14–4.36) and higher in crowded households (HR 4.85; 1.72–13.6 comparing ≥2 with <1 persons/room). There was no association with education, occupation or nationality, the number of children, the language region or degree of urbanicity. Associations were similar for female victims.

Conclusions

This national longitudinal study shows that living conditions associated with psychological stress and lower levels of social support are associated with homicide-suicide events in Switzerland.     

Glutamate utilization promotes meningococcal survival in vivo through avoidance of the neutrophil oxidative burst

Polymorphonuclear neutrophil leucocytes (PMNs) are a critical part of innate immune defence against bacterial pathogens, and only a limited subset of microbes can escape killing by these phagocytic cells. Here we show that Neisseria meningitidis, a leading cause of septicaemia and meningitis, can avoid killing by PMNs and this is dependent on the ability of the bacterium to acquire L-glutamate through its GltT uptake system. We demonstrate that the uptake of available L-glutamate promotes N. meningitidis evasion of PMN reactive oxygen species produced by the oxidative burst. In the meningococcus, L-glutamate is converted to glutathione, a key molecule for maintaining intracellular redox potential, which protects the bacterium from reactive oxygen species such as hydrogen peroxide. We show that this mechanism contributes to the ability of N. meningitidis to cause bacteraemia, a critical step in the disease process during infections caused by this important human pathogen.     

Flowering phenological pattern in crowns of four temperate deciduous tree species and its reproductive implications

Temperate deciduous forest trees flower in spring, a period that starts when the trees lack leaves and when weather is unpredictable, including frost events, and ends when the forest becomes green and vertical microclimatic gradients are established. This paper asks whether there are spatio-temporal patterns in the development of flowering in trees, and how they relate to reproductive processes. Using a crane, flowering phenology was studied in the crowns of ca. 200 trees of four species, from early spring (ash) through the period of leaf-unfolding (maples) to early summer (lime). Flowering levels in different crown regions were documented quantitatively and repeatedly during the flowering season and compared among individuals and among species. Early-flowering trees displayed a clear and consistent acropetalous and centrifugal flowering pattern, while this pattern disappeared in species that flowered after leaves unfolded. This pattern was superposed on the basic flowering rhythm of each species, and was influenced by effects of direct sunlight, acting at a small scale in early spring and at a large scale in early summer. As this acropetalous centrifugal pattern contrasts the microclimatic gradients that develop only after leaves unfold, it might indicate physiological processes in the 'awakening' of trees, as well as evolutionary processes that took place in temperate trees during adaptation to a temperate climate.     

Large-scale automated synthesis of human functional neuroimaging data

The rapid growth of the literature on neuroimaging in humans has led to major advances in our understanding of human brain function but has also made it increasingly difficult to aggregate and synthesize neuroimaging findings. Here we describe and validate an automated brain-mapping framework that uses text-mining, meta-analysis and machine-learning techniques to generate a large database of mappings between neural and cognitive states. We show that our approach can be used to automatically conduct large-scale, high-quality neuroimaging meta-analyses, address long-standing inferential problems in the neuroimaging literature and support accurate 'decoding' of broad cognitive states from brain activity in both entire studies and individual human subjects. Collectively, our results have validated a powerful and generative framework for synthesizing human neuroimaging data on an unprecedented scale.     

Butyrylcholinesterase interactions with amylin may protect pancreatic cells in metabolic syndrome

The metabolic syndrome (MetS) is a risk factor for type 2 diabetes mellitus (T2DM). However, the mechanisms underlying the transition from MetS to T2DM are unknown. Our goal was to study the potential contribution of butyrylcholinesterase (BChE) to this process. We first determined the hydrolytic activity of BChE in serum from MetS, T2DM and healthy individuals. The ‘Kalow’ variant of BChE (BChE‐K), which has been proposed to be a risk factor for T2DM, was genotyped in the last two groups. Our results show that in MetS patients serum BChE activity is elevated compared to T2DM patients and healthy controls (P < 0.001). The BChE‐K genotype showed similar prevalence in T2DM and healthy individuals, excluding this genotype as a risk factor for T2DM. However, the activity differences remained unexplained. Previous results from our laboratory have shown BChE to attenuate the formation of β‐amyloid fibrils, and protect cultured neurons from their cytotoxicity. Therefore, we next studied the in vitro interactions between recombinant human butyrylcholinesterase and amylin by surface plasmon resonance, Thioflavine T fluorescence assay and cross‐linking, and used cultured pancreatic β cells to test protection by BChE from amylin cytotoxicity. We demonstrate that BChE interacts with amylin through its core domain and efficiently attenuates both amylin fibril and oligomer formation. Furthermore, application of BChE to cultured β cells protects them from amylin cytotoxicity. Taken together, our results suggest that MetS‐associated BChE increases could protect pancreatic β‐cells in vivo by decreasing the formation of toxic amylin oligomers.     

Embolization with Onyx in iatrogenic bleeding of the gluteal region

We report a unique method using transcatheter Onyx embolization in a bleeding due to morphine injection in the gluteal region. A 47-year-old man with a rare blood type presented a painful gluteal hematoma due to iatrogenic injury. A computed tomographic angiography verified bleeding from a suspected branch of the deep femoral artery. Because of the unbearable pain, the hematoma was evacuated by means of computed tomography (CT)-guided puncture and the insertion of a pigtail catheter combined with the injection of a human plasminogen activation agent (t-PA). The initial result was positive. To stop the bleeding, angiographic embolization with Onyx was successfully used. Onyx can be used in small vessel bleedings and might offer the advantage of selective embolization in cases where the access to the bleeding vessel is challenging or time-consuming.     

Nitroxides inhibit peroxyl radical-mediated DNA scission and enzyme inactivation

Nitroxides are cell-permeable stable radicals that protect biomolecules from oxidative damage in several ways. The mechanisms of protection studied to date include removal of superoxide radicals as SOD-mimics, oxidation of transition metal ions to preempt the Fenton reaction, and scavenging carbon-centered radicals. However, there is no agreement regarding the reaction of piperidine nitroxides with peroxyl radicals. The question of whether they can protect by scavenging peroxyl radicals is important because these radicals are formed in the presence of oxygen abundant in biological tissues. To further our understanding of the antioxidative behavior of piperidine nitroxides, we studied their effect on biochemical systems exposed to the water soluble radical initiator 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH). AAPH thermally decomposes to yield tert-amidinopropane radicals (t-AP(*)) that readily react with oxygen to form peroxyl radicals (t-APOO(*)). It has recently been reported that piperidine nitroxides protect plasmid DNA from t-AP(*) though not from t-APOO(*). The present study was directed at the question of whether these nitroxides can protect biological systems from damage inflicted by peroxyl radicals. The reaction of nitroxides with AAPH-derived radicals was followed by cyclic voltammetry and electron paramagnetic resonance spectroscopy, whereas the accumulation of peroxide was iodometrically assayed. Assaying DNA damage in vitro, we demonstrate that piperidine nitroxides protect from both t-AP(*) and t-APOO(*). Similarly, nitroxides inhibit AAPH-induced enzyme inactivation. The results indicate that piperidine nitroxides protect the target molecule by reacting with and detoxifying peroxyl radicals.