A LRRK2-Dependent EndophilinA Phosphoswitch Is Critical for Macroautophagy at Presynaptic Terminals.

Synapses are often far from the soma and independently cope with proteopathic stress induced by intense neuronal activity. However, how presynaptic compartments turn over proteins is poorly understood. We show that the synapse-enriched protein EndophilinA, thus far studied for its role in endocytosis, induces macroautophagy at presynaptic terminals. We find that EndophilinA executes this unexpected function at least partly independent of its role in synaptic vesicle endocytosis. EndophilinA-induced macroautophagy is activated when the kinase LRRK2 phosphorylates the EndophilinA-BAR domain and is blocked in animals where EndophilinA cannot be phosphorylated. EndophilinA-phosphorylation promotes the formation of highly curved membranes, and reconstitution experiments show these curved membranes serve as docking stations for autophagic factors, including Atg3. Functionally, deregulation of the EndophilinA phosphorylation state accelerates activity-induced neurodegeneration. Given that EndophilinA is connected to at least three Parkinson's disease genes (LRRK2, Parkin and Synaptojanin), dysfunction of EndophilinA-dependent synaptic macroautophagy may be common in this disorder

Effect of microstructural evolution on magnetic properties of Ni thin films

Copyright © Indian Academy of Sciences.The magnetic properties of Ni thin films, in the range 20–500 nm, at the crystalline-nanocrystalline interface are reported. The effect of thickness, substrate and substrate temperature has been studied. For the films deposited at ambient temperatures on borosilicate glass substrates, the crystallite size, coercive field and magnetization energy density first increase and achieve a maximum at a critical value of thickness and decrease thereafter. At a thickness of 50 nm, the films deposited at ambient temperature onto borosilicate glass, MgO and silicon do not exhibit long-range order but are magnetic as is evident from the non-zero coercive field and magnetization energy. Phase contrast microscopy revealed that the grain sizes increase from a value of 30–50 nm at ambient temperature to 120–150 nm at 503 K and remain approximately constant in this range up to 593 K. The existence of grain boundary walls of width 30–50 nm is demonstrated using phase contrast images. The grain boundary area also stagnates at higher substrate temperature. There is pronounced shape anisotropy as evidenced by the increased aspect ratio of the grains as a function of substrate temperature. Nickel thin films of 50 nm show the absence of long-range crystalline order at ambient temperature growth conditions and a preferred [111] orientation at higher substrate temperatures. Thin films are found to be thermally relaxed at elevated deposition temperature and having large compressive strain at ambient temperature. This transition from nanocrystalline to crystalline order causes a peak in the coercive field in the region of transition as a function of thickness and substrate temperature. The saturation magnetization on the other hand increases with increase in substrate temperature.University Grants Commission for Centre of Advanced Studies in Physic

Consensus criteria for sensitive detection of minimal neuroblastoma cells in bone marrow, blood and stem cell preparations by immunocytology and QRT-PCR: recommendations by the International Neuroblastoma Risk Group Task Force

Disseminating disease is a predictive and prognostic indicator of poor outcome in children with neuroblastoma. Its accurate and sensitive assessment can facilitate optimal treatment decisions. The International Neuroblastoma Risk Group (INRG) Task Force has defined standardised methods for the determination of minimal disease (MD) by immunocytology (IC) and quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) using disialoganglioside GD2 and tyrosine hydroxylase mRNA respectively. The INRG standard operating procedures (SOPs) define methods for collecting, processing and evaluating bone marrow (BM), peripheral blood (PB) and peripheral blood stem cell harvest by IC and QRT-PCR. Sampling PB and BM is recommended at diagnosis, before and after myeloablative therapy and at the end of treatment. Peripheral blood stem cell products should be analysed at the time of harvest. Performing MD detection according to INRG SOPs will enable laboratories throughout the world to compare their results and thus facilitate quality-controlled multi-centre prospective trials to assess the clinical significance of MD and minimal residual disease in heterogeneous patient groups

Automatic recognition of schwa variants in spontaneous Hungarian speech

This paper analyzes the nature of the process involved in optional vowel reduction in Hungarian, and the acoustic structure of schwa variants in spontaneous speech. The study focuses on the acoustic patterns of both the basic realizations of Hungarian vowels and their realizations as neutral vowels (schwas), as well as on the design, implementation, and evaluation of a set of algorithms for the recognition of both types of realizations from the speech waveform. The authors address the question whether schwas form a unified group of vowels or they show some dependence on the originally intended articulation of the vowel they stand for. The acoustic study uses a database consisting of over 4,000 utterances extracted from continuous speech, and recorded from 19 speakers. The authors propose methods for the recognition of neutral vowels depending on the various vowels they replace in spontaneous speech. Mel-Frequency Cepstral Coefficients are calculated and used for the training of Hidden Markov Models. The recognition system was trained on 2,500 utterances and then tested on 1,500 utterances. The results show that a neutral vowel can be detected in 72% of all occurrences. Stressed and unstressed syllables can be distinguished in 92% of all cases. Neutralized vowels do not form a unified group of phoneme realizations. The pronunciation of schwa heavily depends on the original articulation configuration of the intended vowel

Detection of GD2-positive cells in bone marrow samples and survival of patients with localised neuroblastoma

The impact of bone marrow (BM) GD2-positive cells on survival has been evaluated in 145 Italian children with localised neuroblastoma (NB) evaluated at diagnosis by anti-GD2 immunocytochemistry. Nineteen of these (13.1%) were found to be BM GD2-positive, with the number of positive cells ranging between 1 and 155 out of 1 × 106 total cells analysed. Seven/19 (38.8%) GD2-positive vs 12/126 (9.5%) GD2-negative patients relapsed. The 5-year event-free survival (EFS) and overall survival of the GD2-positive patients was significantly worse than that of the GD2-negative ones (62.2 vs 89.9%, P<0.001; and 74.9 vs 95.9%, P=0.005, respectively). GD2 positivity was not associated to other known risk factors, and in particular to Myc-N amplification and 1p deletion. Among Myc-N-negative patients, the EFS of those negative for both GD2 and 1p deletion was significantly better than in children positive for either one of these two markers (EFS=96.9 vs 66.0%, P<0.001). In conclusion, GD2 positivity may represent a prognostic marker for patients with non-metastatic NB without Myc-N amplification, and its combination with genetic alterations might help identifying patients that require a more careful follow-up

EUSEDcollab: a network of data from European catchments to monitor net soil erosion by water

As a network of researchers we release an open-access database (EUSEDcollab) of water discharge and suspended sediment yield time series records collected in small to medium sized catchments in Europe. EUSEDcollab is compiled to overcome the scarcity of open-access data at relevant spatial scales for studies on runoff, soil loss by water erosion and sediment delivery. Multi-source measurement data from numerous researchers and institutions were harmonised into a common time series and metadata structure. Data reuse is facilitated through accompanying metadata descriptors providing background technical information for each monitoring station setup. Across ten European countries, EUSEDcollab covers over 1600 catchment years of data from 245 catchments at event (11 catchments), daily (22 catchments) and monthly (212 catchments) temporal resolution, and is unique in its focus on small to medium catchment drainage areas (median = 43 km(2), min = 0.04 km(2), max = 817 km(2)) with applicability for soil erosion research. We release this database with the aim of uniting people, knowledge and data through the European Union Soil Observatory (EUSO)

Spintronic Majority Gates

In this paper we present an overview of two types of majority gate devices based on spintronic phenomena. We compare the spin torque majority gate and the spin wave majority gate and describe work on these devices. We discuss operating conditions for the two device concepts, circuit implication and how these reflect on materials choices for device implementation

Seeing Emotion with Your Ears: Emotional Prosody Implicitly Guides Visual Attention to Faces

Interpersonal communication involves the processing of multimodal emotional cues, particularly facial expressions (visual modality) and emotional speech prosody (auditory modality) which can interact during information processing. Here, we investigated whether the implicit processing of emotional prosody systematically influences gaze behavior to facial expressions of emotion. We analyzed the eye movements of 31 participants as they scanned a visual array of four emotional faces portraying fear, anger, happiness, and neutrality, while listening to an emotionally-inflected pseudo-utterance (Someone migged the pazing) uttered in a congruent or incongruent tone. Participants heard the emotional utterance during the first 1250 milliseconds of a five-second visual array and then performed an immediate recall decision about the face they had just seen. The frequency and duration of first saccades and of total looks in three temporal windows ([0–1250 ms], [1250–2500 ms], [2500–5000 ms]) were analyzed according to the emotional content of faces and voices. Results showed that participants looked longer and more frequently at faces that matched the prosody in all three time windows (emotion congruency effect), although this effect was often emotion-specific (with greatest effects for fear). Effects of prosody on visual attention to faces persisted over time and could be detected long after the auditory information was no longer present. These data imply that emotional prosody is processed automatically during communication and that these cues play a critical role in how humans respond to related visual cues in the environment, such as facial expressions