bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amyloid β Oligomers Disrupt Blood–CSF Barrier Integrity by Activating Matrix Metalloproteinases
Authors: Brkic Marjana , Balusu Sriram , Van Wonterghem Elien , Gorlé Nina , Benilova Iryna , Kremer Anna , Van Hove Inge , Moons Lieve , De Strooper Bart , Kanazir Selma , Libert Claude , Vandenbroucke Roosmarijn E. 
Published: September 2015

The blood–CSF barrier (BCSFB) consists of a monolayer of choroid plexus epithelial (CPE) cells that maintain CNS homeostasis by producing CSF and restricting the passage of undesirable molecules and pathogens into the brain. Alzheimer's disease is the most common progressive neurodegenerative disorder and is characterized by the presence of amyloid β (Aβ) plaques and neurofibrillary tangles in the brain. Recent research shows that Alzheimer's disease is associated with morphological changes in CPE cells and compromised production of CSF. Here, we studied the direct effects of Aβ on the functionality of the BCSFB. Intracerebroventricular injection of Aβ1–42 oligomers into the cerebral ventricles of mice, a validated Alzheimer's disease model, caused induction of a cascade of detrimental events, including increased inflammatory gene expression in CPE cells and increased levels of proinflammatory cytokines and chemokines in the CSF. It also rapidly affected CPE cell morphology and tight junction protein levels. These changes were associated with loss of BCSFB integrity, as shown by an increase in BCSFB leakage. Aβ1–42 oligomers also increased matrix metalloproteinase (MMP) gene expression in the CPE and its activity in CSF. Interestingly, BCSFB disruption induced by Aβ1–42 oligomers did not occur in the presence of a broad-spectrum MMP inhibitor or in MMP3-deficient mice. These data provide evidence that MMPs are essential for the BCSFB leakage induced by Aβ1–42 oligomers. Our results reveal that Alzheimer's disease-associated soluble Aβ1–42 oligomers induce BCSFB dysfunction and suggest MMPs as a possible therapeutic target.SIGNIFICANCE STATEMENTNo treatments are yet available to cure Alzheimer's disease; however, soluble Aβ oligomers are believed to play a crucial role in the neuroinflammation that is observed in this disease. Here, we studied the effect of Aβ oligomers on the often neglected barrier between blood and brain, called the blood–CSF barrier (BCSFB). This BCSFB is formed by the choroid plexus epithelial cells and is important in maintaining brain homeostasis. We observed Aβ oligomer-induced changes in morphology and loss of BCSFB integrity that might play a role in Alzheimer's disease progression. Strikingly, both inhibition of matrix metalloproteinase (MMP) activity and MMP3 deficiency could protect against the detrimental effects of Aβ oligomer. Clearly, our results suggest that MMP inhibition might have therapeutic potential.
A Single Bolus of Docosahexaenoic Acid Promotes Neuroplastic Changes in the Innervation of Spinal Cord Interneurons and Motor Neurons and Improves Functional Recovery after Spinal Cord Injury
Authors: Liu Zhuo-Hao , Yip Ping K. , Adams Louise , Davies Meirion , Lee Jae Won , Michael Gregory J. , Priestley John V. , Michael-Titus Adina T. 
Published: September 2015

Docosahexaenoic acid (DHA) is an ω-3 polyunsaturated fatty acid that is essential in brain development and has structural and signaling roles. Acute DHA administration is neuroprotective and promotes functional recovery in animal models of adult spinal cord injury (SCI). However, the mechanisms underlying this recovery have not been fully characterized. Here we investigated the effects of an acute intravenous bolus of DHA delivered after SCI and characterized DHA-induced neuroplasticity within the adult injured spinal cord. We found robust sprouting of uninjured corticospinal and serotonergic fibers in a rat cervical hemisection SCI model. A mouse pyramidotomy model was used to confirm that this robust sprouting was not species or injury model specific. Furthermore, we demonstrated that corticospinal fibers sprouting to the denervated side of the cord following pyramidotomy contact V2a interneurons. We also demonstrated increased serotonin fibers and synaptophysin in direct contact with motor neurons. DHA also increased synaptophysin in rat cortical cell cultures. A reduction in phosphatase and tensin homolog (PTEN) has been shown to be involved in axonal regeneration and synaptic plasticity. We showed that DHA significantly upregulates miR-21 and downregulates PTEN in corticospinal neurons. Downregulation of PTEN and upregulation of phosphorylated AKT by DHA were also seen in primary cortical neuron cultures and were accompanied by increased neurite outgrowth. In summary, acute DHA induces anatomical and synaptic plasticity in adult injured spinal cord. This study shows that DHA has therapeutic potential in cervical SCI and provides evidence that DHA could exert its beneficial effects in SCI via enhancement of neuroplasticity.SIGNIFICANCE STATEMENTIn this study, we show that an acute intravenous injection of docosahexaenoic acid (DHA) 30 min after spinal cord injury induces neuroplasticity. We found robust sprouting of uninjured corticospinal and serotonergic fibers in a rat hemisection spinal cord injury model. A mouse pyramidotomy model was used to confirm that the robust sprouting involved V2a interneurons. We show that DHA significantly upregulates miR-21 and phosphorylated AKT, and downregulates phosphatase and tensin homolog (PTEN), which is involved in suppressing anatomical plasticity, in corticospinal neurons and in primary cortical neuron cultures. We conclude that acute DHA can induce anatomical and synaptic plasticity. This provides direct evidence that DHA could exert its beneficial effects in spinal cord injury via neuroplasticity enhancement.
Prox1Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence-Derived GABAergic Cortical Interneurons
Authors: Miyoshi Goichi , Young Allison , Petros Timothy , Karayannis Theofanis , McKenzie Chang Melissa , Lavado Alfonso , Iwano Tomohiko , Nakajima Miho , Taniguchi Hiroki , Huang Z. Josh , Heintz Nathaniel , Oliver Guillermo , Matsuzaki Fumio , Machold Robert P. , Fishell Gord 
Published: September 2015

Neurogliaform (RELN+) and bipolar (VIP+) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been elucidated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss ofProx1impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP). Interestingly, Prox1 promotes the maturation of CGE-derived interneuron subtypes through intrinsic differentiation programs that operate in tandem with extrinsically driven neuronal activity-dependent pathways. ThusProx1represents the first identified transcription factor specifically required for the embryonic and postnatal acquisition of CGE-derived cortical interneuron properties.SIGNIFICANCE STATEMENTDespite the recognition that 30% of GABAergic cortical interneurons originate from the caudal ganglionic eminence (CGE), to date, a specific transcriptional program that selectively regulates the development of these populations has not yet been identified. Moreover, while CGE-derived interneurons display unique patterns of tangential and radial migration and preferentially populate the superficial layers of the cortex, identification of a molecular program that controls these events is lacking.Here, we demonstrate that the homeodomain transcription factorProx1is expressed in postmitotic CGE-derived cortical interneuron precursors and is maintained into adulthood. We found thatProx1function is differentially required during both embryonic and postnatal stages of development to direct the migration, differentiation, circuit integration, and maintenance programs within distinct subtypes of CGE-derived interneurons.
Modulating Hippocampal Plasticity withIn VivoBrain Stimulation
Authors: Rohan Joyce G. , Carhuatanta Kim A. , McInturf Shawn M. , Miklasevich Molly K. , Jankord Ryan 
Published: September 2015

Investigations into the use of transcranial direct current stimulation (tDCS) in relieving symptoms of neurological disorders and enhancing cognitive or motor performance have exhibited promising results. However, the mechanisms by which tDCS effects brain function remain under scrutiny. We have demonstrated thatin vivotDCS in rats produced a lasting effect on hippocampal synaptic plasticity, as measured using extracellular recordings.Ex vivopreparations of hippocampal slices from rats that have been subjected to tDCS of 0.10 or 0.25 mA for 30 min followed by 30 min of recovery time displayed a robust twofold enhancement in long-term potentiation (LTP) induction accompanied by a 30% increase in paired-pulse facilitation (PPF). The magnitude of the LTP effect was greater with 0.25 mA compared with 0.10 mA stimulations, suggesting a dose-dependent relationship between tDCS intensity and its effect on synaptic plasticity. To test the persistence of these observed effects, animals were stimulatedin vivofor 30 min at 0.25 mA and then allowed to return to their home cage for 24 h. Observation of the enhanced LTP induction, but not the enhanced PPF, continued 24 h after completion of 0.25 mA of tDCS. Addition of the NMDA blocker AP-5 abolished LTP in both control and stimulated rats but maintained the PPF enhancement in stimulated rats. The observation of enhanced LTP and PPF after tDCS demonstrates that non-invasive electrical stimulation is capable of modifying synaptic plasticity.SIGNIFICANCE STATEMENTResearchers have used brain stimulation such as transcranial direct current stimulation on human subjects to alleviate symptoms of neurological disorders and enhance their performance. Here, using rats, we have investigated the potential mechanisms of howin vivobrain stimulation can produce such effect. We recorded directly on viable brain slices from rats after brain stimulation to detect lasting changes in pattern of neuronal activity. Our results showed that 30 min of brain stimulation in rats induced a robust enhancement in synaptic plasticity, a neuronal process critical for learning and memory. Understanding such molecular effects will lead to a better understanding of the mechanisms by which brain stimulation produces its effects on cognition and performance.
3D Shape Perception in Posterior Cortical Atrophy: A Visual Neuroscience Perspective
Authors: Gillebert Céline R. , Schaeverbeke Jolien , Bastin Christine , Neyens Veerle , Bruffaerts Rose , De Weer An-Sofie , Seghers Alexandra , Sunaert Stefan , Van Laere Koen , Versijpt Jan , Vandenbulcke Mathieu , Salmon Eric , Todd James T. , Orban Guy A. , Vandenberghe Rik 
Published: September 2015

Posterior cortical atrophy (PCA) is a rare focal neurodegenerative syndrome characterized by progressive visuoperceptual and visuospatial deficits, most often due to atypical Alzheimer's disease (AD). We applied insights from basic visual neuroscience to analyze 3D shape perception in humans affected by PCA. Thirteen PCA patients and 30 matched healthy controls participated, together with two patient control groups with diffuse Lewy body dementia (DLBD) and an amnestic-dominant phenotype of AD, respectively. The hierarchical study design consisted of 3D shape processing for 4 cues (shading, motion, texture, and binocular disparity) with corresponding 2D and elementary feature extraction control conditions. PCA and DLBD exhibited severe 3D shape-processing deficits and AD to a lesser degree. In PCA, deficient 3D shape-from-shading was associated with volume loss in the right posterior inferior temporal cortex. This region coincided with a region of functional activation during 3D shape-from-shading in healthy controls. In PCA patients who performed the same fMRI paradigm, response amplitude during 3D shape-from-shading was reduced in this region. Gray matter volume in this region also correlated with 3D shape-from-shading in AD. 3D shape-from-disparity in PCA was associated with volume loss slightly more anteriorly in posterior inferior temporal cortex as well as in ventral premotor cortex. The findings in right posterior inferior temporal cortex and right premotor cortex are consistent with neurophysiologically based models of the functional anatomy of 3D shape processing. However, in DLBD, 3D shape deficits rely on mechanisms distinct from inferior temporal structural integrity.SIGNIFICANCE STATEMENTPosterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive visuoperceptual dysfunction and most often an atypical presentation of Alzheimer's disease (AD) affecting the ventral and dorsal visual streams rather than the medial temporal system. We applied insights from fundamental visual neuroscience to analyze 3D shape perception in PCA. 3D shape-processing deficits were affected beyond what could be accounted for by lower-order processing deficits. For shading and disparity, this was related to volume loss in regions previously implicated in 3D shape processing in the intact human and nonhuman primate brain. Typical amnestic-dominant AD patients also exhibited 3D shape deficits. Advanced visual neuroscience provides insight into the pathogenesis of PCA that also bears relevance for vision in typical AD.
Characterization of Cortical Networks and Corticocortical Functional Connectivity Mediating Arbitrary Visuomotor Mapping
Authors: Brovelli Andrea , Chicharro Daniel , Badier Jean-Michel , Wang Huifang , Jirsa Viktor 
Published: September 2015

Adaptive behaviors are built on the arbitrary linkage of sensory inputs to actions and goals. Although the sensorimotor and associative frontostriatal circuits are known to mediate arbitrary visuomotor mappings, the underlying corticocortico dynamics remain elusive. Here, we take a novel approach exploiting gamma-band neural activity to study the human cortical networks and corticocortical functional connectivity mediating arbitrary visuomotor mapping. Single-trial gamma-power time courses were estimated for all Brodmann areas by combing magnetoencephalographic and MRI data with spectral analysis and beam-forming techniques. Linear correlation and Granger causality analyses were performed to investigate functional connectivity between cortical regions. The performance of visuomotor associations was characterized by an increase in gamma-power and functional connectivity over the sensorimotor and frontoparietal network, in addition to medial prefrontal areas. The superior parietal area played a driving role in the network, exerting Granger causality on the dorsal premotor area. Premotor areas acted as relay from parietal to medial prefrontal cortices, which played a receiving role in the network. Link community analysis further revealed that visuomotor mappings reflect the coordination of multiple subnetworks with strong overlap over motor and frontoparietal areas. We put forward an associative account of the underlying cognitive processes and corticocortical functional connectivity. Overall, our approach and results provide novel perspectives toward a better understanding of how distributed brain activity coordinates adaptive behaviors.SIGNIFICANCE STATEMENTIn everyday life, most of our behaviors are based on the arbitrary linkage of sensory information to actions and goals, such as stopping at a red traffic light. Despite their automaticity, such behaviors rely on the activity of a large brain network and elusive interareal functional connectivity. We take a novel approach exploiting noninvasive recordings of human brain activity to reveal the cortical networks and corticocortical functional connectivity mediating visuomotor mappings. Parietal areas were found to play a driving role in the network, whereas premotor areas acted as relays from parietal to medial prefrontal cortices, which played a receiving role. Overall, our approach and results provide novel perspectives toward a better understanding of how distributed brain activity coordinates adaptive behaviors.
Idolatrous Reading
Authors: Carens Timothy L. 
Published: September 2015

Timothy L. Carens, “Idolatrous Reading: Subversive Fantasy and Domestic Ideology” (pp. 238–266)
In nineteenth-century Britain, patriarchal culture revealed its anxieties about female subjectivity and anxiety through an extensive debate about what young women should read. As critics have already shown, many writers in the period disparaged romantic novels by comparing them to unhealthy food, addictive drugs, or even illicit sexual encounters. The figure of idolatry played a significant role in this debate as well, suggesting that young female readers might betray the true god of the middle-class patriarchal order by worshiping more gratifying alternatives. If the language of idolatry generally connoted heretical transgression, emergent feminist writers such as Mary Elizabeth Braddon found that they could also use it to articulate a woman’s longing for the power to shape her own dreams. In Braddon’s The Doctor’s Wife (1864), a figure used to disparage women who neglect their role within the domestic order thus acquires a new and intensely ironic life as a way to imagine an escape from it.
α‐Synuclein oligomers pump it up!
Authors: Kahle Philipp J , Sugeno Naoto , Skodras Angelos 
Published: September 2015

Oligomeric forms of the Parkinson's disease‐causing protein α‐synuclein are suspected to mediate neurodegeneration, but the mechanisms are not understood. The present study of Shrivastava et al (2015) provides a fresh insight into this old mystery. α‐Synuclein oligomers are shown by a combination of top state‐of‐the‐art biochemical and super‐resolution microscopy methods to sequester the neuronal sodium–potassium pump. Such perturbation of ion currents would ultimately lead to Ca2+ excitotoxicity.
A Genomic Selection Index Applied to Simulated and Real Data
Authors: Ceron-Rojas J Jesus , Crossa José , Arief Vivi N , Basford Kaye , Rutkoski Jessica , Jarquín Diego , Alvarado Gregorio , Beyene Yoseph , Semagn Kassa , DeLacy Ian 
Published: September 2015

AbstractA genomic selection index (GSI) is a linear combination of genomic estimated breeding values that uses genomic markers to predict the net genetic merit and select parents from a nonphenotyped testing population. Some authors have proposed a GSI; however, they have not used simulated or real data to validate the GSI theory and have not explained how to estimate the GSI selection response and the GSI expected genetic gain per selection cycle for the unobserved traits after the first selection cycle to obtain information about the genetic gains in each subsequent selection cycle. In this paper, we develop the theory of a GSI and apply it to two simulated and four real data sets with four traits. Also, we numerically compare its efficiency with that of the phenotypic selection index (PSI) by using the ratio of the GSI response over the PSI response, and the PSI and GSI expected genetic gain per selection cycle for observed and unobserved traits, respectively. In addition, we used the Technow inequality to compare GSI vs. PSI efficiency. Results from the simulated data were confirmed by the real data, indicating that GSI was more efficient than PSI per unit of time.
Transcriptomic Features of Bovine Blastocysts Derived by Somatic Cell Nuclear Transfer
Authors: Min Byungkuk , Cho Sunwha , Park Jung Sun , Lee Yun-Gyeong , Kim Namshin , Kang Yong-Kook 
Published: September 2015

Abstract
Reprogramming incompletely occurs in most somatic cell nuclear transfer (SCNT) embryos, which results in misregulation of developmentally important genes and subsequent embryonic malfunction and lethality. Here we examined transcriptome profiles in single bovine blastocysts derived by in vitro fertilization (IVF) and SCNT. Different types of donor cells, cumulus cell and ear-skin fibroblast, were used to derive cSCNT and fSCNT blastocysts, respectively. SCNT blastocysts expressed 13,606 genes on average, similar to IVF (13,542). Correlation analysis found that both cSCNT and fSCNT blastocyst groups had transcriptomic features distinctive from the IVF group, with the cSCNT transcriptomes closer to the IVF ones than the fSCNT. Gene expression analysis identified 56 underrepresented and 78 overrepresented differentially expressed genes in both SCNT groups. A 400-kb locus harboring zinc-finger protein family genes in chromosome 18 were found coordinately down-regulated in fSCNT blastocysts, showing a feature of reprogramming-resistant regions. Probing into different categories of genes important for blastocyst development revealed that genes involved in trophectoderm development frequently were underrepresented, and those encoding epigenetic modifiers tended to be overrepresented in SCNT blastocysts. Our effort to identify reprogramming-resistant, differentially expressed genes can help map reprogramming error-prone loci onto the genome and elucidate how to handle the stochastic events of reprogramming to improve cloning efficiency.
Post-transcriptional Mechanisms Contribute Little to Phenotypic Variation in Snake Venoms
Authors: Rokyta Darin R , Margres Mark J , Calvin Kate 
Published: September 2015

Abstract
Protein expression is a major link in the genotype–phenotype relationship, and processes affecting protein abundances, such as rates of transcription and translation, could contribute to phenotypic evolution if they generate heritable variation. Recent work has suggested that mRNA abundances do not accurately predict final protein abundances, which would imply that post-transcriptional regulatory processes contribute significantly to phenotypes. Post-transcriptional processes also appear to buffer changes in transcriptional patterns as species diverge, suggesting that the transcriptional changes have little or no effect on the phenotypes undergoing study. We tested for concordance between mRNA and protein expression levels in snake venoms by means of mRNA-seq and quantitative mass spectrometry for 11 snakes representing 10 species, six genera, and three families. In contrast to most previous work, we found high correlations between venom gland transcriptomes and venom proteomes for 10 of our 11 comparisons. We tested for protein-level buffering of transcriptional changes during species divergence by comparing the difference between transcript abundance and protein abundance for three pairs of species and one intraspecific pair. We found no evidence for buffering during divergence of our three species pairs but did find evidence for protein-level buffering for our single intraspecific comparison, suggesting that buffering, if present, was a transient phenomenon in venom divergence. Our results demonstrated that post-transcriptional mechanisms did not contribute significantly to phenotypic evolution in venoms and suggest a more prominent and direct role for cis-regulatory evolution in phenotypic variation, particularly for snake venoms.