A spatial memory signal shows that the parietal cortex has access to a craniotopic representation of space

Humans effortlessly establish a gist-like memory of their environment whenever they enter a new place, a memory that can guide action even in the absence of vision. Neurons in the lateral intraparietal area (LIP) of the monkey exhibit a form of this environmental memory. These neurons respond when a monkey makes a saccade that brings the spatial location of a stimulus that appeared on a number of prior trials, but not on the present trial, into their receptive fields (RFs). The stimulus need never have appeared in the neuron’s RF. This memory response is usually weaker, with a longer latency than the neuron’s visual response. We suggest that these results demonstrate that LIP has access to a supraretinal memory of space, which is activated when the spatial location of the vanished stimulus can be described by a retinotopic vector from the center of gaze to the remembered spatial location

Paroxysmal eye–head movements in Glut1 deficiency syndrome

Objective:To describe a characteristic paroxysmal eye–head movement disorder that occurs in infants with Glut1 deficiency syndrome (Glut1 DS).Methods:We retrospectively reviewed the medical charts of 101 patients with Glut1 DS to obtain clinical data about episodic abnormal eye movements and analyzed video recordings of 18 eye movement episodes from 10 patients.Results:A documented history of paroxysmal abnormal eye movements was found in 32/101 patients (32%), and a detailed description was available in 18 patients, presented here. Episodes started before age 6 months in 15/18 patients (83%), and preceded the onset of seizures in 10/16 patients (63%) who experienced both types of episodes. Eye movement episodes resolved, with or without treatment, by 6 years of age in 7/8 patients with documented long-term course. Episodes were brief (usually &lt;5 minutes). Video analysis revealed that the eye movements were rapid, multidirectional, and often accompanied by a head movement in the same direction. Eye movements were separated by clear intervals of fixation, usually ranging from 200 to 800 ms. The movements were consistent with eye–head gaze saccades. These movements can be distinguished from opsoclonus by the presence of a clear intermovement fixation interval and the association of a same-direction head movement.Conclusions:Paroxysmal eye–head movements, for which we suggest the term aberrant gaze saccades, are an early symptom of Glut1 DS in infancy. Recognition of the episodes will facilitate prompt diagnosis of this treatable neurodevelopmental disorder.</jats:sec

Prefrontal Neurons Coding Suppression of Specific Saccades

AbstractThe prefrontal cortex has been implicated in the suppression of unwanted behavior, based upon observations of humans and monkeys with prefrontal lesions. Despite this, there has been little direct neurophysiological evidence for a mechanism that suppresses specific behavior. In this study, we used an oculomotor delayed match/nonmatch-to-sample task in which monkeys had to remember a stimulus location either as a marker of where to look or as a marker of where not to look. We found a group of neurons in both the frontal eye field and the caudal prefrontal cortex that carried signals selective for the forbidden stimulus. The activity of these “don't look” neurons correlated with the monkeys' success or failure on the task. These results demonstrate a frontal signal that is related to the active suppression of one action while the subject performs another

Trafficking of plasmepsin II to the food vacuole of the malaria parasite Plasmodium falciparum

fA amily of aspartic proteases, the plasmepsins (PMs), plays a key role in the degradation of hemoglobin in the Plasmodium falciparum food vacuole. To study the trafficking of proPM II, we have modified the chromosomal PM II gene in P. falciparum to encode a proPM II–GFP chimera. By taking advantage of green fluorescent protein fluorescence in live parasites, the ultrastructural resolution of immunoelectron microscopy, and inhibitors of trafficking and PM maturation, we have investigated the biosynthetic path leading to mature PM II in the food vacuole. Our data support a model whereby proPM II is transported through the secretory system to cytostomal vacuoles and then is carried along with its substrate hemoglobin to the food vacuole where it is proteolytically processed to mature PM II

Response and Resistance to Paradox-Breaking BRAF Inhibitor in Melanomas

FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K-mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox-breaking RAF inhibitor (PLX8394) has been designed. Here, we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib. Furthermore, PLX8394 was efficacious against vemurafenibresistant BRAF splice variant-expressing tumors and reduced splice variant homodimerization. Importantly, PLX8394 did not induce paradoxical activation of ERK1/2 in wild-type BRAF cell lines or PDeX. Continued in vivo dosing of xenografts with PLX8394 led to the development of acquired resistance via ERK1/2 reactivation through heterogeneous mechanisms; however, resistant cells were found to have differential sensitivity to ERK1/2 inhibitor. These findings highlight the efficacy of a paradox-breaking selective BRAF inhibitor and the use of PDeX system to test the efficacy of therapeutic agents. © 2017 American Association for Cancer Research

Mechanistic explanations of community structure: Introduction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75364/1/j.1654-1103.1999.tb00597.x.pd

Application Of The Domestic Production Activities Tax Deduction (Relating To A Wide Range Of Industries)

Internal Revenue Code Section 199 is the domestic production activities deduction, which was enacted under the American Jobs Creation Act of 2004. This new deduction was to help compensate the repeal of the exterritorial income exclusion. Section 199 was intended to lower the tax burden on domestic manufacturers as well as to attract new investments in domestic manufacturing facilities.&nbsp; The deduction would yield tax breaks for certain types of businesses ranging large to small that predominately manufacture, produce, grow, or extract tangible personal property entirely or partially within the United States. &nbsp;The types of businesses, specifically, that will have an impact from Section 199 would be those in the film and sound recordings industries, companies in the construction business, and those in the field of architectural and engineering.&nbsp; In addition, those that qualified as doing business in any of the specific industries falling under Section 199 must be located and providing services in the United States. The Section 199 tax break will also benefit those in the business of producing electricity, natural gas, and water in the United States. The deduction is allowed to be taken for taxable years beginning after 2004, which creates many challenges. First, Section 199 establishes detailed tax concepts conditions, de minimis rules, exceptions, and safe harbors. Second, the deduction forces many businesses to implement new accounting systems to classify between qualifying and non-qualifying activities. &nbsp;All in all, this report explains how Section 199 works as well as benefits specific industries. However, important production eligibility issues remain in determining the production deduction for tangible property, which are the central items focused throughout this article. Furthermore, the research contain within, covers the guidance in Notice 2005-14, along with the proposed and final regulations to the rules under Section 199.&nbsp;&nbsp; An understanding of these rules will provide additional opportunities to qualify property and take advantage of tax breaks, yielding a better financial result to the taxpayer