bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of alkaline or liquid-ammonia treatment on crystalline cellulose: changes in crystalline structure and effects on enzymatic digestibility
Authors: Mittal Ashutosh , Katahira Rui , Himmel Michael E , Johnson David K
Published: November 2011

Background

In converting biomass to bioethanol, pretreatment is a key step intended to render cellulose more amenable and accessible to cellulase enzymes and thus increase glucose yields. In this study, four cellulose samples with different degrees of polymerization and crystallinity indexes were subjected to aqueous sodium hydroxide and anhydrous liquid ammonia treatments. The effects of the treatments on cellulose crystalline structure were studied, in addition to the effects on the digestibility of the celluloses by a cellulase complex.

Results

From X-ray diffractograms and nuclear magnetic resonance spectra, it was revealed that treatment with liquid ammonia produced the cellulose IIII allomorph; however, crystallinity depended on treatment conditions. Treatment at a low temperature (25°C) resulted in a less crystalline product, whereas treatment at elevated temperatures (130°C or 140°C) gave a more crystalline product. Treatment of cellulose I with aqueous sodium hydroxide (16.5 percent by weight) resulted in formation of cellulose II, but also produced a much less crystalline cellulose. The relative digestibilities of the different cellulose allomorphs were tested by exposing the treated and untreated cellulose samples to a commercial enzyme mixture (Genencor-Danisco; GC 220). The digestibility results showed that the starting cellulose I samples were the least digestible (except for corn stover cellulose, which had a high amorphous content). Treatment with sodium hydroxide produced the most digestible cellulose, followed by treatment with liquid ammonia at a low temperature. Factor analysis indicated that initial rates of digestion (up to 24 hours) were most strongly correlated with amorphous content. Correlation of allomorph type with digestibility was weak, but was strongest with cellulose conversion at later times. The cellulose IIII samples produced at higher temperatures had comparable crystallinities to the initial cellulose I samples, but achieved higher levels of cellulose conversion, at longer digestion times.

Conclusions

Earlier studies have focused on determining which cellulose allomorph is the most digestible. In this study we have found that the chemical treatments to produce different allomorphs also changed the crystallinity of the cellulose, and this had a significant effect on the digestibility of the substrate. When determining the relative digestibilities of different cellulose allomorphs it is essential to also consider the relative crystallinities of the celluloses being tested.
Brucellosis Ontology (IDOBRU) as an extension of the Infectious Disease Ontology
Authors: Lin Yu , Xiang Zuoshuang , He Yongqun
Published: November 2011

Background

Caused by intracellular Gram-negative bacteria Brucella spp., brucellosis is the most common bacterial zoonotic disease. Extensive studies in brucellosis have yielded a large number of publications and data covering various topics ranging from basic Brucella genetic study to vaccine clinical trials. To support data interoperability and reasoning, a community-based brucellosis-specific biomedical ontology is needed.

Results

The Brucellosis Ontology (IDOBRU: http://sourceforge.net/projects/idobru), a biomedical ontology in the brucellosis domain, is an extension ontology of the core Infectious Disease Ontology (IDO-core) and follows OBO Foundry principles. Currently IDOBRU contains 1503 ontology terms, which includes 739 Brucella-specific terms, 414 IDO-core terms, and 350 terms imported from 10 existing ontologies. IDOBRU has been used to model different aspects of brucellosis, including host infection, zoonotic disease transmission, symptoms, virulence factors and pathogenesis, diagnosis, intentional release, vaccine prevention, and treatment. Case studies are typically used in our IDOBRU modeling. For example, diurnal temperature variation in Brucella patients, a Brucella-specific PCR method, and a WHO-recommended brucellosis treatment were selected as use cases to model brucellosis symptom, diagnosis, and treatment, respectively. Developed using OWL, IDOBRU supports OWL-based ontological reasoning. For example, by performing a Description Logic (DL) query in the OWL editor Protégé 4 or a SPARQL query in an IDOBRU SPARQL server, a check of Brucella virulence factors showed that eight of them are known protective antigens based on the biological knowledge captured within the ontology.

Conclusions

IDOBRU is the first reported bacterial infectious disease ontology developed to represent different disease aspects in a formal logical format. It serves as a brucellosis knowledgebase and supports brucellosis data integration and automated reasoning.
Improving multiple removal using least-squares dip filters and independent component analysis
Authors: Donno Daniela
Published: November 2011

The suppression of multiple events is a crucial task in seismic data processing, and the adaptive subtraction of the predicted multiples is recognized as one of the main challenges for the success of the surface-related multiple elimination technique. The traditional least-squares matching approach can affect the primary events because the estimated multiples tend to adapt to the primaries under the minimum energy condition. We investigate two filtering techniques for improving the multiple removal results. In the first proposed method, we combine the advantages of the least-squares and pattern dip-based subtraction methods. Doing so, we exploit the separation of primaries and multiples in the dip domain, and then we apply the least-squares adaptive subtraction in each dip band before recomposing the data to obtain the final subtraction result. As a result of the dip decomposition, the primary-multiple interferences are reduced, allowing for a more reliable least-squares filtering. In the second method, we propose to replace the multiple subtraction step by a separation step using independent component analysis (ICA) methods. We employ the ICA method after least-squares adaptive filtering. Because of the non-Gaussian distributions of the involved signals, primaries and multiples can be separated by computing the optimal rotation between these two signals. We apply the ICA method in local 2D time-space windows to better compensate the space and time variant character of the data. Two-dimensional synthetic and field data examples demonstrate that the multiple subtraction results of both methods are indeed improved with respect to the classical least-squares method.
Incorporation of geology with rock physics enables subsalt poststack inversion: A case study in the Gulf of Mexico
Authors: Bui Huyen , Graham Jennifer , Kumar Singh Shantanu , Snyder Fred , Smith Martiris
Published: November 2011

One of the main goals of seismic inversion is to obtain high-resolution relative and absolute impedance for reservoir properties prediction. We aim to study whether the results from seismic inversion of subsalt data are sufficiently robust for reliable reservoir characterization. Approximately [Formula: see text] of poststack, wide-azimuth, anisotropic (vertical transverse isotropic) wave-equation migration seismic data from 50 Outer Continental Shelf blocks in the Green Canyon area of the Gulf of Mexico were inverted in this study. A total of four subsalt wells and four subsalt seismic interpreted horizons were used in the inversion process, and one of the wells was used for a blind test. Our poststack inversion method used an iterative discrete spike inversion method, based on the combination of space-adaptive wavelet processing to invert for relative acoustic impedance. Next, the dips were estimated from seismic data and converted to a horizon-like layer sequence field that was used as one of the inputs into the low-frequency model. The background model was generated by incorporating the well velocities, seismic velocity, seismic interpreted horizons, and the previously derived layer sequence field in the low-frequency model. Then, the relative acoustic impedance volume was scaled by adding the low-frequency model to match the calculated acoustic impedance logs from the wells for absolute acoustic impedance. Finally, the geological information and rock physics data were incorporated into the reservoir properties assessment for sand/shale prediction in two main target reservoirs in the Miocene and Wilcox formations. Overall, the poststack inversion results and the sand/shale prediction showed good ties at the well locations. This was clearly demonstrated in the blind test well. Hence, incorporating rock physics and geology enables poststack inversion in subsalt areas.
Menin Missense Mutants Encoded by the MEN1 Gene that Are Targeted to the Proteasome: Restoration of Expression and Activity by CHIP siRNA
Authors: Canaff Lucie , Vanbellinghen Jean-François , Kanazawa Ippei , Kwak Hayeon , Garfield Natasha , Vautour Line , Hendy Geoffrey N.
Published: November 2011

Context:

In multiple endocrine neoplasia type 1 (MEN1) characterized by tumors of parathyroid, enteropancreas, and anterior pituitary, missense mutations in the MEN1 gene product, menin, occur in a subset of cases. The mutant proteins are degraded by the proteasome. However, whether their expression and activity can be restored is not known.

Objective:

Our objective was to functionally characterize a panel of 16 menin missense mutants, including W423R and S443Y identified in new MEN1 families, with respect to protein stability, targeting to the proteasome and restoration of expression by proteasome inhibitors and expression and function by small interfering RNA technology.

Methods:

Flag-tagged wild-type (WT) and missense menin mutant expression vectors were transiently transfected in human embryonic kidney (HEK293) and/or rat insulinoma (Rin-5F) cells.

Results:

The majority of mutants were short-lived, whereas WT menin was stable. Proteasome inhibitors MG132 and PS-341 and inhibition of the chaperone, heat-shock protein 70 (Hsp70), or the ubiquitin ligase, COOH terminus of Hsp70-interacting protein (CHIP), by specific small interfering RNA, restored the levels of the mutants, whereas that of WT menin was largely unaffected. Inhibition of CHIP restored the ability of mutants to mediate normal functions of menin: TGF-β up-regulation of the promoters of its target genes, the cyclin-dependent kinase inhibitors p15 and p21 as well as TGF-β inhibition of cell numbers.

Conclusion:

When the levels of missense menin mutants that are targeted to the proteasome are normalized they may function similarly to WT menin. Potentially, targeting specific components of the proteasome chaperone pathway could be beneficial in treating a subset of MEN1 cases.
“Why Is Any of This Important to Me Anyway?”: Some Thoughts from a Doctor-Poet
Authors: Colquhoun Glenn
Published: November 2011

The practice of medicine and the practice of writing poetry are often considered to require competing skills. The New Zealand doctor-poet Glenn Colquhoun looks at the similarities between the two activities and argues that narrative and metaphor play important roles in the creative moment at the core of both disciplines. He argues that, along with objectivity, subjectivity is a valuable way of “knowing” in medicine. He illustrates his points with a selection of poems drawn from his practice and an essay exploring the importance of the subjective in decoding the consultation between doctor and patient.
Survival of the Depressed: The Discourse of Darwinian Psychiatry
Authors: Montgomery Scott L.
Published: November 2011

Evolution by natural selection has provided one of the grand narratives of the modern era and a way to build stories about the origin and features of organic life. Biologizing aspects of human behavior and society has been a recurrent theme and, although recognized as having led to abuses like eugenics, it has never disappeared. It exists today in the field of evolutionary psychology and its offshoot, Darwinian psychiatry. This fledgling discipline posits the mind as developing during the long period of hunter-gatherer existence, with some emotional states and behaviors now maladapted to modern society. The texts that employ this mismatch theory to explain phobias and depression contain an unstable mixture of narrative techniques and metaphoric uses of computers, electronic technology, the discourse of economics, of architecture, among others. A frequent technique is to make literal jumps between defense mechanisms of lower-order animals and fearful emotional states in humans. The origins of depression thus become a subject discussed with rhetorical naïveté that interweaves figurative language with sometimes contradictory images. Darwin would not be pleased.
Narratives, Metaphors, and the Clinical Relationship
Authors: Fuks Abraham , Kreiswirth Martin , Boudreau Donald , Sparks Tabitha
Published: November 2011

The stories that develop between physician and patient are an important aspect of what has been described as narrative medicine. These stories are unique forms of narrative in that they are jointly constructed and enable the development of the clinical bond or relationship necessary for the physician to help the patient deal with his or her illness. Such a conduit for healing permits the repair or reconstitution of the broken story of illness, clarifying the meaning of illness for that particular patient. These clinical narratives are enriched by color, nuance, and detail from metaphorical tropes. However, the comprehension of such metaphors by the clinician requires an ability to listen, a penchant to decipher idiosyncratic understanding, and a capacity to honor the patient's particularity.
Natural Durability of the Heartwood of Coast Redwood [Sequoia Sempervirens (D.Don) Endl.] and its Prediction Using near Infrared Spectroscopy
Authors: Jones Trevor , Meder Roger , Low Charlie , O'Callahan Diahanna , Chittenden Colleen , Ebdon Nicholas , Thumm Armin , Riddell Mark
Published: November 2011

The heartwood of plantation-grown coast redwood trees from three forests in the North Island, New Zealand, was evaluated using in vitro decay tests with fungal cultures to determine variation in natural durability and its prediction using near infrared (NIR) spectroscopy. The NIR spectra were acquired from the solid wood surface, prior to decay testing, using a fibre-optic probe attached to a Bruker MPA FT-NIR spectrometer and an imaging spectrograph coupled to a NIR line camera. The partial least squares (PLS) regression models of mass loss with fungal decay testing, based on spectra collected with the FT-NIR spectrometer, had better predictive performance than the NIR line camera, as evidenced by fewer latent variables and slightly better R2. The ratios of prediction to deviation ( RPD) were 1.3 to 1.4 for both the spectrometer and camera system, which suggests the PLS regression models could be used to segregate the heartwood of coast redwood for high- and low values of natural durability.
Towards the in-forest Assessment of Kraft Pulp Yield: Comparing the Performance of Laboratory and Hand-Held Instruments and Their Value in Screening Breeding Trials
Authors: Meder Roger , Brawner Jeremy T. , Downes Geoffrey M. , Ebdon Nicholas
Published: November 2011

The non-destructive prediction of Kraft pulp yield in standing trees using near infrared (NIR) spectroscopy has been typically performed by removing 5 mm or 12 mm increment cores from candidate trees in the forest and returning the samples to the laboratory for analysis. It would be desirable to perform in-field prediction using a portable NIR device; for example, to rapidly screen individual trees in a breeding trial prior to selecting trees for further sampling. This paper compares the performance of a laboratory-based full-range Fourier transform NIR system with two portable NIR devices operating at two different spectral ranges (950–1800 nm and 1600–2400 nm). Calibrations, explaining commercially useful amounts of variance in Kraft pulp yield ( R2 = 0.85–0.94) and cellulose content ( R2 = 0.92–0.96), were developed for the laboratory NIR and both hand-held portable NIR instruments using woodmeal. This demonstrates that the wavelength range and resolution of the portable instruments are suitable for the prediction of Kraft pulp yield and cellulose content. In an initial in-forest trial, calibration of Kraft pulp yield ranged between R2 = 0.4–0.6 across two sites and two sampling periods. While there are still a number of in-forest sampling issues to be resolved around seasonal sampling, the implication is that low-cost, hand-held NIR systems are a feasible alternative to laboratory-based NIR systems for routine assessment of Kraft pulp yield.
Insuring Long-Term Care in the United States
Authors: Brown Jeffrey R , Finkelstein Amy
Published: November 2011

Long-term care expenditures constitute one of the largest uninsured financial risks facing the elderly in the United States and thus play a central role in determining the retirement security of elderly Americans. In this essay, we begin by providing some background on the nature and extent of long-term care expenditures and insurance against those expenditures, emphasizing in particular the large and variable nature of the expenditures and the extreme paucity of private insurance coverage. We then provide some detail on the nature of the private long-term care insurance market and the available evidence on the reasons for its small size, including private market imperfections and factors that limit the demand for such insurance. We highlight how the availability of public long-term care insurance through Medicaid is an important factor suppressing the market for private long-term care insurance. In the final section, we describe and discuss recent long-term care insurance public policy initiatives at both the state and federal level.
It's about Space, It's about Time, Neuroeconomics and the Brain Sublime
Authors: van Rooij Marieke , Van Orden Guy
Published: November 2011

Neuroeconomics has investigated which regions of the brain are associated with the factors contributing to economic decision making, emphasizing the position in space of brain areas associated with the factors of decision making—cognitive or emotive, rational or irrational. An alternative view of the brain has given priority to time over space, investigating the temporal patterns of brain dynamics to determine the nature of the brain's intrinsic dynamics, how its various activities change over time. These two ways of approaching the brain are contrasted in this essay to gauge the contemporary status of neuroeconomics.
Molecular Genetics and Economics
Authors: Beauchamp Jonathan P , Cesarini David , Johannesson Magnus , van der Loos Matthijs J. H. M , Koellinger Philipp D , Groenen Patrick J. F , Fowler James H , Rosenquist J. Niels , Thurik A. Roy , Christakis Nicholas A
Published: November 2011

The costs of comprehensively genotyping human subjects have fallen to the point where major funding bodies, even in the social sciences, are beginning to incorporate genetic and biological markers into major social surveys. How, if at all, should economists use and combine molecular genetic and economic data from these surveys? What challenges arise when analyzing genetically informative data? To illustrate, we present results from a “genome-wide association study” of educational attainment. We use a sample of 7,500 individuals from the Framingham Heart Study; our dataset contains over 360,000 genetic markers per person. We get some initially promising results linking genetic markers to educational attainment, but these fail to replicate in a second large sample of 9,500 people from the Rotterdam Study. Unfortunately such failure is typical in molecular genetic studies of this type, so the example is also cautionary. We discuss a number of methodological challenges that face researchers who use molecular genetics to reliably identify genetic associates of economic traits. Our overall assessment is cautiously optimistic: this new data source has potential in economics. But researchers and consumers of the genoeconomic literature should be wary of the pitfalls, most notably the difficulty of doing reliable inference when faced with multiple hypothesis problems on a scale never before encountered in social science.
Oral sex practices, oral human papillomavirus and correlations between oral and cervical human papillomavirus prevalence among female sex workers in Lima, Peru
Authors: Brown B , Blas M M , Cabral A , Carcamo C , Gravitt P E , Halsey N
Published: November 2011

Few data exist on oral human papillomavirus (HPV) prevalence in female sex workers (FSWs). Information regarding oral sex practices of 185 Peruvian FSWs, 18-26 years of age, was obtained via survey and compared with HPV testing results of oral rinse samples. Oral HPV prevalence was 14/185 (7.6%); four (28.9%) HPV genotypes were carcinogenic. One hundred and eighty-two participants reported having had oral sex; 95% reported condom use during oral sex with clients and 9.5% with partners. Women who had oral sex more than three times with their partners in the past month were more likely to have oral HPV than women who had oral sex three times or less (P = 0.06). Ten (71.4%) women with oral HPV were HPV-positive at the cervix; conversely 8.3% of women with cervical HPV were HPV-positive in the oral cavity. The prevalence of oral HPV was relatively low, considering the high rates of oral sex practiced by these women.
Sledging is still a seasonal source of serious injury in Scottish children
Authors: Regan L A , Cooper J G
Published: November 2011

In 2002 it was highlighted that sledging results in serious injuries in the paediatric population and safety recommendations were made. The aim of this study was to re-examine the number, severity and aetiology of sledging-related trauma. This was a retrospective study performed in the Paediatric Emergency Department (PED) of the Royal Aberdeen Children's Hospital (RACH) during two periods totalling 12 days, when there was continuous snow ground cover. Records of all attendances were scrutinized to identify patients with sledging injuries. The nature, mechanism and severity of injury, and subsequent management were then analysed. Of 403 PED attendances, 45 (11%) were sledging related with 16 (36%) fractures and 13 (29%) head injuries. Eight patients (18%) were admitted to hospital and three (7%) required an operation. Collision with a stationary object was the most common reason for injury (51%), followed by the adoption of a dangerous sledging position or use of a stationary jump. No patients were wearing a helmet. In conclusion, there has been little change in the epidemiology and aetiology of paediatric sledging injuries since 2002. Work is needed to inform parents of the previously recommended safety measures that could reduce the morbidity of this activity without detracting from the enjoyment.
MicroRNA-mediated gene silencing: are we close to a unifying model?
Authors: James Victoria , Wong Sybil C.K. , Sharp Tyson V.
Published: November 2011

MicroRNAs (miRNAs) comprise a group of small non-coding RNA –21 nucleotides in length. They act as post-transcriptional regulators of gene expression by forming base pairing interactions with target messenger RNA (mRNA). At least 1000 miRNAs are predicted to be expressed in humans and are encoded for in the genome of almost all organisms. Functional studies indicate that every cellular process studied thus far is regulated at some level by miRNAs. Given this expansive role, it is not surprising that disruption of this crucial pathway underlies the initiation of, or in the least, contributes to the development and progression of numerous human diseases and physiological disorders. This review will focus on the latest developments in uncovering the mechanism(s) of miRNA-mediated silencing with specific reference to the function of terminal effector proteins, how translation of target mRNA is inhibited and whether we are moving towards understanding this fundamental gene silencing paradigm.
Checklist of marine benthic green algae (Chlorophyta) on Hainan, a subtropical island off the coast of China: comparisons between the 1930s and 1990–2009 reveal environmental changes
Authors: Titlyanov Eduard A. , Titlyanova Tamara V. , Xia Bangmei , Bartsch Inka
Published: November 2011

A complete checklist of intertidal to shallow subtidal marine green seaweeds (Chlorophyta) growing on the subtropical island of Hainan (China) is presented here for the first time. It covers data from extensive recent (1990–2009) and historical (1933–1935) collections, and additional published records from various time periods. Data were analyzed by time period. We postulate that environmental changes on Hainan Island documented since the 1980s (e.g., degradation of coral reefs, development of tourism and mariculture farms) are reflected in the green algal species complement and in the dominance or absence of specific algal groups during different time periods. In total, 105 green algal taxa were recorded, including 37 new to Hainan Island, and 18 new records for China. There was a clearly evident change in floristic composition between early and recent collections. In the 1930s, there was a dominance of Caulerpaceae, Codiaceae and Cladophoraceae. By 1990/1992, the numbers of Ulvaceae had increased 1.6-fold and numbers of Cladophoraceae 1.7-fold. Both families contain many opportunistic species that prefer nutrient-enriched or degraded environments. At the same time, species richness of Codiaceae, Caulerpaceae and Udotaceae, families with complex thallus structures, decreased considerably. The floristic differences between the 1990/1992 and 2008/2009 collections were minor.
Vibration method for grading of large cross-section coniferous timber species
Authors: Arriaga Francisco , Íñiguez-González Guillermo , Esteban Miguel , Divos Ferenc
Published: November 2011

The non-destructive testing (NDT) of timber using the longitudinal vibration method is based on the natural frequency of wood which is in relation to its quality. In the present paper, the suitability of this tool is investigated and the results of grading 395 pieces are presented. Structural timber of Radiata pine (Pinus radiata D. Don.), Scots pine (Pinus sylvestris L.), and Laricio pine [Pinus nigra ssp. salzmannii (Dunal) Franco] from Spanish sources were investigated. The specimens were tested for bending according to the European standard EN 408 (2003) and the values of strength and stiffness were compared with the results estimated by means of NDT. The vibration equipment applied permits the measurement of the longitudinal natural frequency and mass of the specimen, and then the density and the dynamic modulus of elasticity can be calculated. There is a strong relationship between the static modulus of elasticity obtained from the bending test and the dynamic modulus of elasticity obtained by the NDT technique. There is an acceptable relationship between modulus of rupture and dynamic modulus of elasticity if the visual defects (knot sizes) are taken into account. Acoustic measurements have become widely acceptable, and they have great potential for stress grading of coniferous timber.
Hydrophobisation of mechanical pulp fibres with sodium dodecyl sulphate functionalised layered double hydroxide particles
Authors: Lange Carl , Lundin Tom , Fardim Pedro
Published: November 2011

Hydrogen peroxide bleached spruce (Picea abies L.) made of thermo mechanical pulp (BTMP) fibres were modified with layered double hydroxides (LDH). The LDH particles were precipitated onto the BTMP fibre surfaces from aqueous solutions of urea and NaOH. The modified BTMP was further functionalised with sodium dodecyl sulphate (SDS) surfactant to produce pulp with hydrophobic character. The contact angle measurement with water on paper showed that the functionalisation with SDS was successful. The apparent contact angles varied in between the initial θ= 75° of the reference pulp up to θ= 135° of the SDS functionalised pulp. A hydrophobic surface was obtained already with 2.0% weight to weight ratio of SDS in pulp suspension. A high affinity between the LDH particles and the BTMP fibres was found as well. The investigated fibre modification route offers a new feasible tool in fibre surface treatment.
5-HT3AReceptor-Bearing White Matter Interstitial GABAergic Interneurons Are Functionally Integrated into Cortical and Subcortical Networks
Authors: von Engelhardt Jakob , Khrulev Sergey , Eliava Marina , Wahlster Sarah , Monyer Hannah
Published: November 2011

In addition to axons and surrounding glial cells, the corpus callosum also contains interstitial neurons that constitute a heterogeneous cell population. There is growing anatomical evidence that white matter interstitial cells (WMICs) comprise GABAergic interneurons, but so far there is little functional evidence regarding their connectivity. The scarcity of these cells has hampered electrophysiological studies. We overcame this hindrance by taking recourse to transgenic mice in which distinct WMICs expressed enhanced green fluorescence protein (EGFP). The neuronal phenotype of the EGFP-labeled WMICs was confirmed by their NeuN positivity. The GABAergic phenotype could be established based on vasoactive intestinal peptide and calretinin expression and was further supported by a firing pattern typical for interneurons. Axons and dendrites of many EGFP-labeled WMICs extended to the cortex, hippocampus, and striatum. Patch-clamp recordings in acute slices showed that they receive excitatory and inhibitory input from cortical and subcortical structures. Moreover, paired recordings revealed that EGFP-labeled WMICs inhibit principal cells of the adjacent cortex, thus providing unequivocal functional evidence for their GABAergic phenotype and demonstrating that they are functionally integrated into neuronal networks.
Stress-Activated Protein Kinase MKK7 Regulates Axon Elongation in the Developing Cerebral Cortex
Authors: Yamasaki Tokiwa , Kawasaki Hiroshi , Arakawa Satoko , Shimizu Kimiko , Shimizu Shigeomi , Reiner Orly , Okano Hideyuki , Nishina Sachiko , Azuma Noriyuki , Penninger Josef M. , Katada Toshiaki , Nishina Hiroshi
Published: November 2011

The c-Jun NH2-terminal protein kinase (JNK), which belongs to the mitogen-activated protein kinase family, plays important roles in a broad range of physiological processes. JNK is controlled by two upstream regulators, mitogen-activated protein kinase kinase (MKK) 7 and MKK4. To elucidate the physiological functions of MKK7, we usedNestin-Creto generate a novel mouse model in which themkk7gene was specifically deleted in the nervous system (Mkk7flox/floxNestin-Cremice). These mice were indistinguishable from their control littermates in gross appearance during embryogenesis but died immediately after birth without breathing. Histological examination showed that the mutants had severe defects in brain development, including enlarged ventricles, reduced striatum, and minimal axon tracts. Electron microscopy revealed abnormal accumulations of filamentous structures and autophagic vacuoles inMkk7flox/floxNestin-Crebrain. Further analysis showed that MKK7 deletion decreased numbers of TAG-1-expressing axons and delayed neuronal migration in the cerebrum. Neuronal differentiation was not altered.In uteroelectroporation studies showed that contralateral projection of axons by layer 2/3 neurons was impaired in the absence of MKK7. Moreover, MKK7 regulated axon elongation in a cell-autonomous mannerin vivo, a finding confirmedin vitro. Finally, phosphorylation levels of JNK substrates, including c-Jun, neurofilament heavy chain, microtubule-associated protein 1B, and doublecortin, were reduced inMkk7flox/floxNestin-Crebrain. Our findings demonstrate that the phenotype ofMkk7flox/floxNestin-Cremice differs substantially from that ofMkk4flox/floxNestin-Cremice, and establish that MKK7-mediated regulation of JNK is uniquely critical for both axon elongation and radial migration in the developing brain.
A Distinct Contribution of Short-Wavelength-Sensitive Cones to Light-Evoked Activity in the Mouse Pretectal Olivary Nucleus
Authors: Allen Annette E. , Brown Timothy M. , Lucas Robert J.
Published: November 2011

Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) combine inputs from outer-retinal rod/cone photoreceptors with their intrinsic phototransduction machinery to drive a wide range of so-called non-image-forming (NIF) responses to light. Defining the contribution of each photoreceptor class to evoked responses is vital for determining the degree to which our sensory capabilities depend on melanopsin and for optimizing NIF responses to benefit human health. We addressed this problem by recording electrophysiological responses in the mouse pretectal olivary nucleus (PON) (a target of ipRGCs and origin of the pupil light reflex) to a range of gradual and abrupt changes in light intensity. Dim stimuli drove minimal changes in PON activity, suggesting that rods contribute little under these conditions. To separate cone from melanopsin influences, we compared responses to short (460 nm) and longer (600/655 nm) wavelengths in mice carrying a red shifted cone population (Opn1mwR) or lacking melanopsin (Opn4−/−). Our data reveal a surprising difference in the quality of information available from medium- and short-wavelength-sensitive cones. The majority cone population (responsive to 600/655 nm) supported only transient changes in firing and responses to relatively sudden changes in light intensity. In contrast, cones uniquely sensitive to the shorter wavelength (S-cones) were better able to drive responses to gradual changes in illuminance, contributed a distinct off inhibition, and at least partially recapitulated the ability of melanopsin to sustain responses under continuous illumination. These data reveal a new role for S-cones unrelated to color vision and suggest renewed consideration of cone contributions to NIF vision at shorter wavelengths.
Serum Response Factor Is Required for Cortical Axon Growth But Is Dispensable for Neurogenesis and Neocortical Lamination
Authors: Lu Paul P. Y. , Ramanan Narendrakumar
Published: November 2011

Previous studies have shown that neuron-specific deletion of serum response factor (SRF) results in deficits in tangential cell migration, guidance-dependent circuit assembly, activity-dependent gene expression, and synaptic plasticity in the hippocampus. Furthermore, SRF deletion in mouse embryonic stem cells causes cell deathin vitro. However, the requirement of SRF for early neuronal development including neural stem cell homeostasis, neurogenesis, and axonal innervations remains unknown. Here, we report that SRF is critical for development of major axonal tracts in the forebrain. Conditional mutant mice lacking SRF in neural progenitor cells (Srf-Nestin-cKO) exhibit striking deficits in cortical axonal projections including corticostriatal, corticospinal, and corticothalamic tracts, and they show a variable loss of the corpus callosum. Neurogenesis and interneuron specification occur normally in the absence of SRF and the deficits in axonal projections were not due to a decrease or loss in cell numbers. Radial migration of neurons and neocortical lamination were also not affected. No aberrant cell death was observed during development, whereas there was an increase in the number of proliferative cells in the ventricular zone from embryonic day 14 to day 18. Similar axonal tract deficits were also observed in mutant mice lacking SRF in the developing excitatory neurons of neocortex and hippocampus (Srf-NEX-cKO). Together, these findings suggest distinct roles for SRF during neuronal development; SRF is specifically required in a cell-autonomous manner for axonal tract development but is dispensable for cell survival, neurogenesis, neocortical lamination, and neuronal differentiation.
Fast-Activating Voltage- and Calcium-Dependent Potassium (BK) Conductance Promotes Bursting in Pituitary Cells: A Dynamic Clamp Study
Authors: Tabak Joël , Tomaiuolo Maurizio , Gonzalez-Iglesias Arturo E. , Milescu Lorin S. , Bertram Richard
Published: November 2011

The electrical activity pattern of endocrine pituitary cells regulates their basal secretion level. Rat somatotrophs and lactotrophs exhibit spontaneous bursting and have high basal levels of hormone secretion, while gonadotrophs exhibit spontaneous spiking and have low basal hormone secretion. It has been proposed that the difference in electrical activity between bursting somatotrophs and spiking gonadotrophs is due to the presence of large conductance potassium (BK) channels on somatotrophs but not on gonadotrophs. This is one example where the role of an ion channel type may be clearly established. We demonstrate here that BK channels indeed promote bursting activity in pituitary cells. Blocking BK channels in bursting lacto-somatotroph GH4C1 cells changes their firing activity to spiking, while further adding an artificial BK conductance via dynamic clamp restores bursting. Importantly, this burst-promoting effect requires a relatively fast BK activation/deactivation, as predicted by computational models. We also show that adding a fast-activating BK conductance to spiking gonadotrophs converts the activity of these cells to bursting. Together, our results suggest that differences in BK channel expression may underlie the differences in electrical activity and basal hormone secretion levels among pituitary cell types and that the rapid rate of BK channel activation is key to its role in burst promotion.
Diverse Precerebellar Neurons Share Similar Intrinsic Excitability
Authors: Kolkman Kristine E. , McElvain Lauren E. , Lac Sascha du
Published: November 2011

The cerebellum dedicates a majority of the brain's neurons to processing a wide range of sensory, motor, and cognitive signals. Stereotyped circuitry within the cerebellar cortex suggests that similar computations are performed throughout the cerebellum, but little is known about whether diverse precerebellar neurons are specialized for the nature of the information they convey.In vivorecordings indicate that firing responses to sensory or motor stimuli vary dramatically across different precerebellar nuclei, but whether this reflects diverse synaptic inputs or differentially tuned intrinsic excitability has not been determined. We targeted whole-cell patch-clamp recordings to neurons in eight precerebellar nuclei which were retrogradely labeled from different regions of the cerebellum in mice. Intrinsic physiology was compared across neurons in the medial vestibular, external cuneate, lateral reticular, prepositus hypoglossi, supragenual, Roller/intercalatus, reticularis tegmenti pontis, and pontine nuclei. Within the firing domain, precerebellar neurons were remarkably similar. Firing faithfully followed temporally modulated inputs, could be sustained at high rates, and was a linear function of input current over a wide range of inputs and firing rates. Pharmacological analyses revealed common expression of Kv3 currents, which were essential for a wide linear firing range, and of SK (small-conductance calcium-activated potassium) currents, which were essential for a wide linear input range. In contrast, membrane properties below spike threshold varied considerably within and across precerebellar nuclei, as evidenced by variability in postinhibitory rebound firing. Our findings indicate that diverse precerebellar neurons perform similar scaling computations on their inputs but may be differentially tuned to synaptic inhibition.
Multiple Reference Frames in Cortical Oscillatory Activity during Tactile Remapping for Saccades
Authors: Buchholz Verena N. , Jensen Ole , Medendorp W. Pieter
Published: November 2011

Single-unit recordings have shown that the brain uses multiple reference frames in spatial processing. The brain could use this neural architecture to implicitly create multiple modes of representation at the population level, with each reference frame weighted as a function of task demands. Using magnetoencephalography, we tested this hypothesis by studying the reference frames in rhythmic neuronal synchronization—a population measure—during tactile remapping for saccades. Human subjects fixated either to the left or right of the body midline, while a tactile stimulus was applied to an invisible fingertip, located either left or right of fixation. After a variable delay, they looked at the remembered stimulus location. Results show a transient body-centered, stimulus-induced gamma-band response (70–90 Hz) in somatosensory areas, contralateral to the stimulated hand. Concurrently, a gamma-band response occurred in posterior parietal cortex (PPC), contralateral to the gaze-centered location of the stimulus, even though the stimulus was not seen. The temporal overlap of these early representations suggests that there is a fast bottom-up sensory-induced remapping in PPC, taking into account the relative positions of eyes and hand. The gaze-centered representation in PPC was sustained in a high gamma range (85–115 Hz) and increased in power closer to the initiation of the saccade. Lower-frequency rhythms (alpha, beta) showed body-centered power modulations in somatosensory areas in anticipation of the stimulus and a mixture of reference frames in PPC after stimulus presentation. We conclude that oscillatory activity reflects the time-varying coding of information in body- and gaze-centered reference frames during tactile remapping for saccades.
The Sound of Consciousness: Neural Underpinnings of Auditory Perception
Authors: Brancucci Alfredo , Franciotti Raffaella , D'Anselmo Anita , della Penna Stefania , Tommasi Luca
Published: November 2011

The neural correlates of consciousness (NCC), i.e., patterns of brain activity that specifically accompany a particular conscious experience, have been investigated mainly in the visual system using particularly suited paradigms, such as binocular rivalry and multistable percepts in combination with neural recordings or neuroimaging. Through the same principles, we look here for possible NCC in the auditory modality exploiting the properties of the Deutsch's illusion, a stimulation condition in which a sequence of two specular dichotic stimuli presented in alternation causes an illusory segregation of pitch and side (ear of origin), which can yield up to four different auditory percepts per dichotic stimulus. Using magnetoencephalography in humans, we observed cortical activity specifically accompanying conscious experience of pitch inside an early bilateral network, including the Heschl's gyrus, the middle temporal gyrus, the right inferior, and the superior frontal gyri. The conscious experience of perceived side was instead accompanied by later activity observed bilaterally in the inferior parietal lobe and in the superior frontal gyrus. These results suggest that the NCC are not independent of stimulus features and modality and that, even at the higher cortical levels, the different aspects of a single perceptual scene may not be simultaneously processed.
A Wide Diversity of Cortical GABAergic Interneurons Derives from the Embryonic Preoptic Area
Authors: Gelman Diego , Griveau Amélie , Dehorter Nathalie , Teissier Anne , Varela Carolina , Pla Ramón , Pierani Alessandra , Marín Oscar
Published: November 2011

GABA-containing (GABAergic) interneurons comprise a very heterogeneous group of cells that are crucial for cortical function. Different classes of interneurons specialize in targeting specific subcellular domains of excitatory pyramidal cells or other interneurons, which provides cortical circuits with an enormous capability for information processing. As in other regions of the CNS, cortical interneuron diversity is thought to emerge from the genetic specification of different groups of progenitor cells within the subpallium. Most cortical interneurons originate from two main regions, the medial and the caudal ganglionic eminences (MGE and CGE, respectively). In addition, it has been shown that progenitors in the embryonic preoptic area (POA) also produce a small population of cortical GABAergic interneurons. Here, we show that the contribution of the POA to the complement of cortical GABAergic interneurons is larger than previously believed. Using genetic fate mapping andin uterotransplantation experiments, we demonstrate thatDbx1-expressing progenitor cells in the POA give rise to a small but highly diverse cohort of cortical interneurons, with some neurochemical and electrophysiological characteristics that were previously attributed to MGE- or CGE-derived interneurons. There are, however, some features that seem to distinguish POA-derived interneurons from MGE- or CGE-derived cells, such as their preferential laminar location. These results indicate that the mechanisms controlling the specification of different classes of cortical interneurons might be more complex than previously expected. Together with earlier findings, our results also suggest that the POA generates nearly 10% of the GABAergic interneurons in the cerebral cortex of the mouse.
“Small Axonless Neurons”: Postnatally Generated Neocortical Interneurons with Delayed Functional Maturation
Authors: Le Magueresse Corentin , Alfonso Julieta , Khodosevich Konstantin , Arroyo Martín Ángel A. , Bark Christine , Monyer Hannah
Published: November 2011

GABAergic interneurons of the mouse cortex are generated embryonically in the ventral telencephalon. Recent evidence, however, indicated that a subset of cortical cells expressing interneuronal markers originate in the neonatal subventricular zone. This has raised interest in the functional development and incorporation of these postnatally generated cells into cortical circuits. Here we demonstrate that these cells integrate in the cortex, and that they constitute two distinct GABAergic interneuronal classes. Whereas one class reflects the tail end of embryonic interneuron genesis, the other class comprises interneurons that are exclusively generated perinatally and postnatally. The latter constitute a novel subclass of interneurons. They are preferentially located in the deeper layers of the olfactory and orbital cortices, exhibit a unique firing pattern and slow functional maturation. Based on their distinct morphology we termed them “small axonless neurons” and indeed, unlike other cortical neurons, they communicate with their neuronal partners via dendrodendritic synapses. Finally, we provide evidence that the number of small axonless neurons is enhanced by odor enrichment, a further indication that they integrate into neural circuits and participate to olfactory processing.
Adrift toward Empire
Authors: Senseney John R.
Published: November 2011

In seeking the origins of the celebrated portico-framed fora of Imperial Rome, John R. Senseney explores the earliest recognizable example of this architectural type, a lost porticus of the 160s BCE built by the victorious commander Gnaeus Octavius. Adrift toward Empire: The Lost Porticus Octavia in Rome and the Origins of the Imperial Fora adduces ancient testimony to aid our understanding of the purposes and formal appearance of this pivotal monument. While the author suggests that Octavius emulated a Hellenistic model, he does not posit that the patron necessarily sought to associate his triumph with those of his Greek forebears. Those meanings did, however, become attached to the building type by later viewers and the architects who created the Imperial fora. In order to appreciate this phenomenon, the author questions the usefulness of fixed categories like "Hellenistic" and "Roman" and argues for a history sensitive to the fluidic intentions and changing meanings of architecture.