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Long noncoding RNAs (lncRNAs) are implicated in the autophagic-lysosomal pathway (ALP) and are closely linked to Parkinson's disease (PD) pathology. β-Glucocerebrosidase (GCase) has also been reported to be correlated with α-synuclein (α-syn) proteostasis. However, lncRNAs and α-syn in neural-derived L1CAM exosomes and GCase activity in the plasma of PD patients have not been studied. This study used an ultrasensitive methodology, fluorescence nanoparticle tracking analysis (NTA), to measure plasma L1CAM exosomes and Quanterix Simoa to measure α-syn concentrations in L1CAM exosomes. Eighty-five healthy controls and 93 PD patients were enrolled, and several scales were used to rate the severity of PD. Receiver operating characteristic (ROC) curves were applied to map the diagnostic accuracy of categorizing PD patients and healthy subjects. We found increased Linc-POU3F3 and α-syn concentrations in L1CAM exosomes and decreased GCase activity in PD patients compared with controls. The three biomarkers displayed obvious differences among PD patients based on gender, H-Y stage, and UPDRS-III distribution. Interestingly, Linc-POU3F3 was significantly positively correlated with α-syn in L1CAM exosomes and inversely correlated with GCase activity in PD patients. Significant correlations were observed among L1CAM exosomal Linc-POU3F3 levels, GCase activity, and PD severity, including motor/cognitive dysfunction. Additionally, the combination of Linc-POU3F3 and α-syn in L1CAM exosomes and GCase activity could discriminate PD patients from controls. These results suggest that L1CAM exosomal Linc-POU3F3, L1CAM exosomal α-syn, and GCase activity may shed light on the mechanism underlying the autophagic-lysosomal system in the pathogenesis of PD and could be used to assess the severity of PD.

An essay is presented on the social condition of deaf people in the U.S. The author mentions that deaf people were somehow able to connect and integrate to the greater American society through the emergence of American Sign Language and Deaf culture and enactment of laws which recognize the rights of deaf people including the American with Disabilities Act (ADA). However, it has been noted that effective communication access to law enforcement has been the main concern for the Deaf community.

A unique vertical bar among horizontal bars is salient and pops out perceptually. Physiological data have suggested that mechanisms in the primary visual cortex (V1) contribute to the high saliency of such a unique basic feature, but indicated little regarding whether V1 plays an essential or peripheral role in input-driven or bottom-up saliency. Meanwhile, a biologically based V1 model has suggested that V1 mechanisms can also explain bottom-up saliencies beyond the pop-out of basic features, such as the low saliency of a unique conjunction feature such as a red vertical bar among red horizontal and green vertical bars, under the hypothesis that the bottom-up saliency at any location is signaled by the activity of the most active cell responding to it regardless of the cell's preferred features such as color and orientation. The model can account for phenomena such as the difficulties in conjunction feature search, asymmetries in visual search, and how background irregularities affect ease of search. In this paper, we report nontrivial predictions from the V1 saliency hypothesis, and their psychophysical tests and confirmations. The prediction that most clearly distinguishes the V1 saliency hypothesis from other models is that task-irrelevant features could interfere in visual search or segmentation tasks which rely significantly on bottom-up saliency. For instance, irrelevant colors can interfere in an orientation-based task, and the presence of horizontal and vertical bars can impair performance in a task based on oblique bars. Furthermore, properties of the intracortical interactions and neural selectivities in V1 predict specific emergent phenomena associated with visual grouping. Our findings support the idea that a bottom-up saliency map can be at a lower visual area than traditionally expected, with implications for top-down selection mechanisms. [ABSTRACT FROM AUTHOR]

Temporal masking curves were obtained from 12 normal-hearing and 16 hearing-impaired listeners using 200-ms, 1000-Hz pure-tone maskers and 20-ms, 1000-Hz fixed-level probe tones. For the delay times used here (>40 ms), temporal masking curves obtained from both groups can be well described by an exponential function with a single level-independent time constant for each listener. Normal-hearing listeners demonstrated time constants that ranged between 37 and 67 ms, with a mean of 50 ms. Most hearing-impaired listeners, with significant hearing loss at the probe frequency, demonstrated longer time constants (range 58-114 ms) than those obtained from normal-hearing listeners. Time constants were found to grow exponentially with hearing loss according to the function τ=52e0.011(HL), when the slope of the growth of masking is unity. The longest individual time constant was larger than normal by a factor of 2.3 for a hearing loss of 52 dB. The steep slopes of the growth of masking functions typically observed at long delay times in hearing-impaired listeners' data appear to be a direct result of longer time constants. When iterative fitting procedures included a slope parameter, the slopes of the growth of masking from normal-hearing listeners varied around unity, while those from hearing-impaired listeners tended to be less (flatter) than normal. Predictions from the results of these fixed-probe-level experiments are consistent with the results of previous fixed-masker-level experiments, and they indicate that deficiencies in the ability to detect sequential stimuli should be considerable in hearing-impaired listeners, partially because of extended time constants, but mostly because forward masking involves a recovery process that depends upon the sensory response evoked by the masking stimulus. Large sensitivity losses reduce the sensory response to high SPL maskers so that the recovery process is slower, much like the recovery process for low-level stimuli in normal-hearing listeners. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) represents an urgent public health mandate. AD is no longer considered a neural-centric disease; rather, a plethora of recent studies strongly implicate a critical role played by neuroinflammation in the pathogeneses of AD and other neurodegenerative conditions. A close functional connection between the immune system and central nervous system is increasingly recognized. In late-onset AD, aging represents the most significant risk factor. Here, from an immunological perspective, we summarize the prominent molecular and cellular changes in the periphery of aging individuals and AD patients. Moreover, we review the knowledge gained in the past several years that implicate specific arms of the peripheral immune system and other types of immune responses in modulating AD progression. Taken together, these findings collectively emphasize a dynamic role of a concert of brain-extrinsic, peripheral signals in the aging and degenerative processes in the CNS. We believe that a systematic view synthesizing the vast amounts of existing results will help guide the development of next-generation therapeutics and inform future directions of AD investigation. [ABSTRACT FROM AUTHOR]

We compared the performance of four rapid diagnostic tests (RDTs) for imported malaria, and particularly Plasmodium falciparum infection, using thick and thin blood smears as the gold standard. All the tests are designed to detect at least one protein specific to P. falciparum (Plasmodium histidine-rich protein 2 (PfHRP2) or Plasmodium LDH (PfLDH)) and one pan-Plasmodium protein (aldolase or Plasmodium LDH (pLDH)). 1,311 consecutive patients presenting to 9 French hospitals with suspected malaria were included in this prospective study between April 2006 and September 2008. Blood smears revealed malaria parasites in 374 cases (29%). For the diagnosis of P. falciparum infection, the three tests detecting PfHRP2 showed high and similar sensitivity (96%), positive predictive value (PPV) (90%) and negative predictive value (NPV) (98%). The PfLDH test showed lower sensitivity (83%) and NPV (80%), despite good PPV (98%). For the diagnosis of non-falciparum species, the PPV and NPV of tests targeting pLDH or aldolase were 94–99% and 52–64%, respectively. PfHRP2-based RDTs are thus an acceptable alternative to routine microscopy for diagnosing P. falciparum malaria. However, as malaria may be misdiagnosed with RDTs, all negative results must be confirmed by the reference diagnostic method when clinical, biological or other factors are highly suggestive of malaria. [ABSTRACT FROM AUTHOR]

Identifying the mechanisms through which genetic risk causes dementia is an imperative for new therapeutic development. Here, we apply a multistage, systems biology approach to elucidate the disease mechanisms in frontotemporal dementia. We identify two gene coexpression modules that are preserved in mice harboring mutations in MAPT, GRN and other dementia mutations on diverse genetic backgrounds. We bridge the species divide via integration with proteomic and transcriptomic data from the human brain to identify evolutionarily conserved, disease-relevant networks. We find that overexpression of miR-203, a hub of a putative regulatory microRNA (miRNA) module, recapitulates mRNA coexpression patterns associated with disease state and induces neuronal cell death, establishing this miRNA as a regulator of neurodegeneration. Using a database of drug-mediated gene expression changes, we identify small molecules that can normalize the disease-associated modules and validate this experimentally. Our results highlight the utility of an integrative, cross-species network approach to drug discovery. Evolutionarily conserved gene modules mediate neurodegenerative dementia in a variety of mouse models and in postmortem brain tissue from patients., Author(s): Vivek Swarup [sup.1] , Flora I. Hinz [sup.1] , Jessica E. Rexach [sup.1] , Ken-ichi Noguchi [sup.2] , Hiroyoshi Toyoshiba [sup.2] , Akira Oda [sup.2] , Keisuke Hirai [sup.2] [...]