Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Prospective Cohort Study

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.

For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.

Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

/pdf/guidelines-for-the-use-and-interpretation-of-assays-for-ijf2t30pbq.pdf

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース)

Thank you for downloading an introduction to the event related potential technique. Maybe you have knowledge that, people have look hundreds times for their favorite readings like this an introduction to the event related potential technique, but end up in malicious downloads. Rather than reading a good book with a cup of tea in the afternoon, instead they are facing with some malicious bugs inside their laptop.

An Introduction To The Event Related Potential Technique

Introduction Transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (dlPFC) improves dual task walking in older adults, when tested just after stimulation. The acute effects of tDCS on the cortical physiology of walking, however, remains unknown. Methods In a previous study, older adults with slow gait and executive dysfunction completed a dual task walking assessment before and after 20 min of tDCS targeting the left dlPFC or sham stimulation. In a subset of seven participants per group, functional near-infrared spectroscopy (fNIRS) was used to quantify left and right prefrontal recruitment defined as the oxygenated hemoglobin response to usual and dual task walking (ΔHbO2), as well as the absolute change in this metric from usual to dual task conditions (i.e., ΔHbO2cost). Paired t-tests examined pre- to post-stimulation differences in each fNIRS metric within each group. Results The tDCS group exhibited pre- to post-stimulation reduction in left prefrontal ΔHbO2cost (p = 0.03). This mitigation of dual task “cost” to prefrontal recruitment was induced primarily by a reduction in left prefrontal ΔHbO2 specifically within the dual task condition (p = 0.001), an effect that was observed in all seven participants within this group. Sham stimulation did not influence ΔHbO2cost or ΔHbO2 in either walking condition (p > 0.35), and neither tDCS nor sham substantially influenced right prefrontal recruitment (p > 0.16). Discussion This preliminary fNIRS data suggests that tDCS over the left dlPFC may modulate prefrontal recruitment, as reflected by a relative reduction in the oxygen consumption of this brain region in response to dual task walking.

Transcranial Direct Current Stimulation May Reduce Prefrontal Recruitment During Dual Task Walking in Functionally Limited Older Adults – A Pilot Study

Mutations in the l eucine-rich repeat kinase 2 ( LRRK2 ) gene are an important monogenic cause of Parkinson’s disease (PD). Reported non-motor features of LRRK2 PD include depression, anxiety and bipolar disorder,1 but suicide has not been systematically investigated. As part of our LRRK2 Ashkenazi Jewish Consortium study we assessed the history of death by suicide in probands and first-degree relatives with and without LRRK2 G2019S mutations.

The sample comprised participants from the Ashkenazi Jewish LRRK2 Consortium study sites in Tel Aviv (Tel Aviv Medical Center) and New York (Columbia University Irving Medical Center and Mount Sinai Beth Israel).2 PD probands were screened for the LRRK2 G2019S mutation.3 Genetic status of the first-degree relatives was not known. Questionnaire and pedigree information was systematically collected on LRRK2 PD and non- LRRK2 mutation, idiopathic PD (IPD) probands, and evaluated for suicide as cause of death among first-degree relatives. The odds of suicide among first-degree relatives was compared using a logistic generalised estimating equation, accounting for family membership, site and sex using Stata V.14 (StataCorp, 2015, Stata Statistical Software: Release 14. College Station, TX).

No LRRK2 PD or IPD was known to commit suicide during the course of the study. (Study follow-up ranged from 0 to 5 years, and the mean duration among those with at least one follow-up visit was 3.4 years). LRRK2 PD probands were more likely to report a death in a first-degree …

/pdf/evidence-for-increased-completed-suicide-in-first-degree-ps7akvs3zo.pdf

Evidence for increased completed suicide in first-degree relatives of LRRK2 G2019S mutation Parkinson's disease.

Intensive treadmill training improves gait in moderately impaired multiple sclerosis individuals

Virtual reality-treadmill training to improve gait in people with multiple sclerosis

Stress tests, e.g., the cardiac stress test, are standard clinical screening tools aimed to unmask clinical pathology. As such stress tests indirectly measure physiological reserves. The term reserve has been developed to account for the dis-junction, often observed, between pathology and clinical manifestation. It describes a physiological capacity that is utilized in demanding situations. However, developing a new and reliable stress test based screening tool is complex, prolonged, and relies extensively on domain knowledge. We propose a novel model-free machine–learning framework, the Stress Test Performance Scoring (STEPS) framework, to model expected performance in a stress test. A performance scoring function is trained with measures taken during the performance in a given task while exploiting information regarding the stress test set-up and subjects’ medical state. Multiple ways of aggregating performance scores at different stress levels are suggested and are examined with an extensive simulation study. When applied to a real-world data example, an AUC of 84.35[95%CI : 70.68 −95.13] was obtained for the STEPS framework to distinguish subjects with neurodegeneration from controls. In summary, STEPS improved screening by exploiting existing domain knowledge and state-of-the-art clinical measures. The STEPS framework can ease and speed up the production of new stress tests.

/pdf/a-novel-performance-scoring-quantification-framework-for-1v5uwckd.pdf

Anat Mirelman

Papers

Transcranial Direct Current Stimulation May Reduce Prefrontal Recruitment During Dual Task Walking in Functionally Limited Older Adults – A Pilot Study

Evidence for increased completed suicide in first-degree relatives of LRRK2 G2019S mutation Parkinson's disease.

Intensive treadmill training improves gait in moderately impaired multiple sclerosis individuals

Virtual reality-treadmill training to improve gait in people with multiple sclerosis

A novel performance scoring quantification framework for stress test set-ups