Serial stereotactic biopsy of brainstem lesions in adults improves diagnostic accuracy compared with MRI only.

Objective: The aim of the current prospective study was to analyse the validity of MRI based diagnosis of brainstem gliomas which was verified by stereotactic biopsy and follow-up evaluation as well as to assess prognostic factors and risk profile. Methods: Between 1998 and 2007, all consecutive adult patients with radiologically suspected brainstem glioma were included. The MRI based diagnosis of the lesions was made independently by an experienced neuroradiologist. Histopathological evaluation was performed in all patients from paraffin embedded specimens obtained by multimodal image guided stereotactic serial biopsy technique. Histopathological results were compared with prior radiological assessment. Length of survival was estimated with the Kaplan–Meier method and prognostic factors were calculated using the Cox model. Results: 46 adult patients were included. Histological evaluation revealed pilocytic astrocytoma (n=2), WHO grade II glioma (n=14), malignant glioma (n=12), metastasis (n=7), lymphoma (n=5), cavernoma (n=1), inflammatory disease (n=2) or no tumour/ gliosis (n=3). Perioperative morbidity was 2.5% (n=1). There was no permanent morbidity and no mortality. All patients with ‘‘no tumour’’ or ‘‘inflammatory disease’’ survived. Patients with low grade glioma and malignant glioma showed a 1 year survival rate of 75% and 25%, respectively; the 1 year survival rate for patients with lymphoma or metastasis was 30%. In the subgroup with a verified brainstem glioma, negative predictors for length of survival were higher tumour grade (p=0.002) and Karnofsky performance score (70 (p=0.004). Conclusion: Intra-axial brainstem lesions with a radiological pattern of glioma represent a very heterogeneous tumour group with completely different outcomes. Radiological features alone are not reliable for diagnostic classification. Stereotactic biopsy is a safe method to obtain a valid tissue diagnosis, which is indispensible for treatment decision

Laboratory Rearing of \u3ci\u3eLycaeides Melissa Samuelis\u3c/i\u3e (Lepidoptera: Lycaenidae), An Endangered Butterfly in Michigan

The Karner blue butterfly (Lycaeides melissa samuelis) is listed as a federally endangered species in the United States. It occurs in oak savanna and pine barren habitats from eastern Minnesota to New Hampshire. In 1994, we successfully reared Karner blue larvae under controlled laboratory conditions for experimental purposes, and report on those rearing methods here. We collected 20 female Karner blue adults of the spring generation from two areas in Michigan, and housed them in cages in an environmental chamber at 240 -26°C for 5 days. The female butterflies produced 154 eggs, of which 72 hatched in an average of 4.5 days, and 68 first instars survived. Eggs, larvae and pupae were kept in a growth chamber at 24°C. Developmental time from egg to adult averaged 26 days; the average duration of each instar ranged from 3 to 4 days, and the average pupal duration was 8 days. Thirty three lab- oratory-reared Karner blue larvae successfully completed the 4 instars, and were released as adults into maternal collection sites. Laboratory rearing may be a viable means of providing Karner blue individuals for reintroduction into areas where the species is extirpated, for supplementation of small populations, or for research. Ultimately, such methods may become an integral part in the recovery of this and other rare invertebrate species

Light thermal relics enabled by a second Higgs

Sub-GeV thermal relic dark matter typically requires the existence of a lightmediator particle. We introduce the light two-Higgs-doublet portal, illustratedby a minimal UV-complete model for sub-GeV dark matter with kinematicallyforbidden annihilations into leptons. All new physics states in this scenariolie at or below the electroweak scale, affecting Higgs physics, the muonanomalous magnetic moment and potentially neutrino masses. Observation ofradiative dark matter annihilation by future MeV gamma-ray telescopes would bekey to unambiguously identify the scenario.<br

Light thermal relics enabled by a second Higgs

Sub-GeV thermal relic dark matter typically requires the existence of a lightmediator particle. We introduce the light two-Higgs-doublet portal, illustratedby a minimal UV-complete model for sub-GeV dark matter with kinematicallyforbidden annihilations into leptons. All new physics states in this scenariolie at or below the electroweak scale, affecting Higgs physics, the muonanomalous magnetic moment and potentially neutrino masses. Observation ofradiative dark matter annihilation by future MeV gamma-ray telescopes would bekey to unambiguously identify the scenario.<br

Minimal realization of light thermal Dark Matter

We propose a minimal UV-complete model for kinematically forbidden Dark Matter (DM) leading to a sub-GeV thermal relic. Our crucial realization is that the two-Higgs-doublet model can provide a light mediator through which the DM can annihilate into SM leptons, avoiding indirect detection constraints. The DM mass is predicted to be very close to the mass of the leptons, which can potentially be identified from DM annihilation into gamma-rays. Due to sizable couplings to muons in reproducing the DM relic abundance, this framework naturally favors a resolution to the $(g-2)_\mu$ anomaly. Furthermore, by embedding this setup to the Zee model, we show that the phenomenon of neutrino oscillations is inherently connected to the observed relic abundance of DM. All new physics involved in our framework lies at or below the electroweak scale, making it testable at upcoming colliders, beam-dump experiments, and future sub-GeV gamma-ray telescopes

Susceptibility of the Endangered Karner Blue Butterfly (Lepidoptera: Lycaenidae) to \u3ci\u3eBacillus Thuringiensis\u3c/i\u3e Var. \u3ci\u3eKurstaki\u3c/i\u3e Used for Gypsy Moth Suppression in Michigan

We investigated the phenological and physiological susceptibility of the endangered Karner blue butterfly (Lycaeides melissa samuelis) to Bacillus thuringiensis var. kurstaki (Bt), a product widely used for gypsy moth (Lymantria dispar) suppression in Michigan and other infested states. We monitored phenology of the bivoltine Karner blue in two regions of Michigan from 1993 to 1995 to determine if larval stages overlapped temporally with the period of Bt application for gypsy moth suppression. Karner blue larvae of the spring generation were found during the period that Bt was applied in nearby areas in 1993 only. However, spring-generation adults or newly laid eggs were observed up to 11 days before applications in 1994 and 1995. Since Karner blue eggs develop within one week, summer-generation larvae were most likely present during or shortly after 1994 and 1995 Bt application periods. These larvae would have been at risk, assuming Bt persistence of 4 to 6 days. Physiological susceptibility of Karner blue larvae to Bt was determined in a laboratory bioassay. Larvae were reared on wild lupine (Lupinus perennis) foliage that was untreated, or sprayed with Bt formulations at rates of 30-37 or 90 BIU/ha. A similar bioassay with second instar gypsy moth larvae on similarly treated white oak (Quercus alba) foliage was conducted concurrently. Karner blue survival was 100%, 27% and 14% on control, low and high Bt treatments, respectively. Early and late Karner blue instars were equally susceptible to Bt. Survival of gypsy moth was 80%, 33% and 5% on control, low and high Bt treatments, respectively, and did not differ significantly from Karner blue survival. We conclude that Karner blue is both phenologically and physiologically susceptible to Bt used for gypsy moth suppression, although the larval generation at risk and extent of phenological overlap may vary from year to year

Impact of alpha-synuclein spreading on the nigrostriatal dopaminergic pathway depends on the onset of the pathology

Misfolded alpha-synuclein spreads along anatomically connected areas through the brain, prompting progressive neurodegeneration of the nigrostriatal pathway in Parkinson's disease. To investigate the impact of early stage seeding and spreading of misfolded alpha-synuclein along with the nigrostriatal pathway, we studied the pathophysiologic effect induced by a single acute alpha-synuclein preformed fibrils (PFFs) inoculation into the midbrain. Further, to model the progressive vulnerability that characterizes the dopamine (DA) neuron life span, we used two cohorts of mice with different ages: 2-month-old (young) and 5-month-old (adult) mice. Two months after a-synuclein PFFs injection, we found that striatal DA release decreased exclusively in adult mice. Adult DA neurons showed an increased level of pathology spreading along with the nigrostriatal pathway accompanied with a lower volume of alpha-synuclein deposition in the midbrain, impaired neurotransmission, rigid DA terminal composition, and less microglial reactivity compared with young neurons. Notably, preserved DA release and increased microglial coverage in the PFFs-seeded hemisphere coexist with decreased large-sized terminal density in young DA neurons. This suggests the presence of a targeted pruning mechanism that limits the detrimental effect of alpha-synuclein early spreading. This study suggests that the impact of the pathophysiology caused by misfolded alpha-synuclein spreading along the nigrostriatal pathway depends on the age of the DA network, reducing striatal DA release specifically in adult mice

In vivo imaging reveals reduced activity of neuronal circuits in a mouse tauopathy model

Pathological alterations of tau protein play a significant role in the emergence and progression of neurodegenerative disorders. Tauopathies are characterized by detachment of the tau protein from neuronal microtubules, and its subsequent aberrant hyperphosphorylation, aggregation and cellular distribution. The exact nature of tau protein species causing neuronal malfunction and degeneration is still unknown. In the present study, we used mice transgenic for human tau with the frontotemporal dementia with parkinsonism-associated P301S mutation. These mice are prone to develop fibrillar tau inclusions, especially in the spinal cord and brainstem. At the same time, cortical neurons are not as strongly affected by fibrillar tau forms, but rather by soluble tau forms. We took advantage of the possibility to induce formation of neurofibrillary tangles in a subset of these cortical neurons by local injection of preformed synthetic tau fibrils. By using chronic in vivo two-photon calcium imaging in awake mice, we were able for the first time to follow the activity of individual tangle-bearing neurons and compare it to the activity of tangle-free neurons over the disease course. Our results revealed strong reduction of calcium transient frequency in layer 2/3 cortical neurons of P301S mice, independent of neurofibrillary tangle presence. These results clearly point to the impairing role of soluble, mutated tau protein species present in the majority of the neurons investigated in this study

Long-term dynamics of aberrant neuronal activity in awake Alzheimer's disease transgenic mice

Alzheimer's disease (AD) is associated with aberrant neuronal activity, which is believed to critically determine disease symptoms. How these activity alterations emerge, how stable they are over time, and whether cellular activity dynamics are affected by the amyloid plaque pathology remains incompletely understood. We here repeatedly recorded the activity from identified neurons in cortex of awake APPPS1 transgenic mice over four weeks during the early phase of plaque deposition using in vivo two-photon calcium imaging. We found that aberrant activity during this stage largely persisted over the observation time. Novel highly active neurons slowly emerged from former intermediately active neurons. Furthermore, activity fluctuations were independent of plaque proximity, but aberrant activity was more likely to persist close to plaques. These results support the notion that neuronal network pathology observed in models of cerebral amyloidosis is the consequence of persistent single cell aberrant neuronal activity, a finding of potential diagnostic and therapeutic relevance for AD

Relationship Between Jump Capacity and Performance in BMX Cycling

The objective of this study is to assess the relationship between the results obtained on different vertical jump tests and the top score recorded during a BMX (Bicycle Moto-Cross) test and the rider''s performance. To do so, 10 BMX pilots participated in this study; 5 regarded as the elite group (EG) (age: 18.8 +/- 3.7, weight: 68.4 +/- 8.5 kg, height: 174 +/- 9 cm and previous BMX experience: 8 +/- 3.8 years) and 5 regarded as the recreational group (RG) (age: 19.8 +/- 4.8, weight: 69.2 +/- 11.7 kg, height: 170 +/- 9 cm, previous BMX experience: 4.2 +/- 1.3 years). Vertical jump capacity was obtained using the Bosco protocol, i.e. vertical squat jump (SJ), vertical countermovement jump (CMJ), drop jump (DJ) and repetitive jump (RJ), and time in race in a BMX circuit was determined. The results indicate a direct relationship between the time used to complete the circuit and the height of the jump reached in SJ (r: -.801; p:.017), CMJ (r : -.798; p :.018) and DJ (r : -.782; p:.022). This all suggests that assessing jump capacity using the Bosco test may be a useful tool for assessing BMX performance