bluuebunny/crossref_metadata_2025 huggingface dataset:
Trypsin-like serine peptidase profiles in the egg, larval, and pupal stages of Aedes albopictus
Authors: Saboia-Vahia Leonardo , Borges-Veloso André , Mesquita-Rodrigues Camila , Cuervo Patricia , Dias-Lopes Geovane , Britto Constança , de Barros Silva Ana Paula , De Jesus Jose B
Published: February 2013

Background

Aedes albopictus, a ubiquitous mosquito, is one of the main vectors of dengue and yellow fever, representing an important threat to public health worldwide. Peptidases play key roles in processes such as digestion, oogenesis, and metamorphosis of insects. However, most of the information on the proteolytic enzymes of mosquitoes is derived from insects in the adult stages and is often directed towards the understanding of blood digestion. The aim of this study was to investigate the expression of active peptidases from the preimaginal stages of Ae. albopictus.

Methods

Ae. albopictus eggs, larvae, and pupae were analyzed using zymography with susbtrate-SDS-PAGE. The pH, temperature and peptidase inhibitor sensitivity was evaluated. In addition, the proteolytic activities of larval instars were assayed using the fluorogenic substrate Z-Phe-Arg-AMC.

Results

The proteolytic profile of the larval stage was composed of 8 bands ranging from 17 to 130 kDa. These enzymes displayed activity in a broad range of pH values, from 5.5 to 10.0. The enzymatic profile of the eggs was similar to that of the larvae, although the proteolytic bands of the eggs showed lower intensities. The pupal stage showed a complex proteolytic pattern, with at least 6 bands with apparent molecular masses ranging from 30 to 150 kDa and optimal activity at pH 7.5. Peptidases from larval instars were active from 10°C to 60°C, with optimal activity at temperatures between 37°C and 50°C. The proteolytic profile of both the larval and pupal stages was inhibited by phenyl-methyl sulfonyl-fluoride (PMSF) and Nα-Tosyl L-lysine chloromethyl ketone hydrochloride (TLCK), indicating that the main peptidases expressed during these developmental stages are trypsin-like serine peptidases.

Conclusion

The preimaginal stages of Ae. albopictus exhibited a complex profile of trypsin-like serine peptidase activities. A comparative analysis of the active peptidase profiles revealed differential expression of trypsin-like isoforms among the preimaginal stages, suggesting that some of these enzymes are stage specific. Additionally, a comparison of the peptidase expression between larvae from eggs collected in the natural environment and larvae obtained from the eggs of female mosquitoes maintained in colonies for a long period of time demonstrated that the proteolytic profile is invariable under such conditions.
Biochemical and physiological bases for utilization of dietary amino acids by young Pigs
Authors: Rezaei Reza , Wang Weiwei , Wu Zhenlong , Dai Zhaolai , Wang Junjun , Wu Guoyao
Published: February 2013

Protein is quantitatively the most expensive nutrient in swine diets. Hence it is imperative to understand the physiological roles played by amino acids in growth, development, lactation, reproduction, and health of pigs to improve their protein nutrition and reduce the costs of pork production. Due to incomplete knowledge of amino acid biochemistry and nutrition, it was traditionally assumed that neonatal, post-weaning, growing-finishing, and gestating pigs could synthesize sufficient amounts of all "nutritionally nonessential amino acids" (NEAA) to support maximum production performance. Therefore, over the past 50 years, much emphasis has been placed on dietary requirements of nutritionally essential amino acids as building blocks for tissue proteins. However, a large body of literature shows that NEAA, particularly glutamine, glutamate, arginine and proline regulate physiological functions via cell signaling pathways, such as mammalian target of rapamycin, AMP-activated protein kinase, extracellular signal-related kinase, Jun kinase, mitogen-activated protein kinase, and NEAA-derived gaseous molecules (e.g., nitric oxide, carbon monoxide, and hydrogen sulfide). Available evidence shows that under current feeding programs, only 70% and 55% of dietary amino acids are deposited as tissue proteins in 14-day-old sow-reared piglets and in 30-day-old pigs weaned at 21 days of age, respectively. Therefore, there is an urgent need to understand the roles and dietary requirements of NEAA in swine nutrition. This review highlights the basic biochemistry and physiology of absorption and utilization of amino acids in young pigs to enhance the efficacy of utilization of dietary protein and to minimize excretion of nitrogenous wastes from the body.
Analysis of ventilatory ratio as a novel method to monitor ventilatory adequacy at the bedside
Authors: Sinha Pratik , Fauvel Nicholas J , Singh Pradeep , Soni Neil
Published: February 2013

Introduction

Due to complexities in its measurement, adequacy of ventilation is seldom used to categorize disease severity and guide ventilatory strategies. Ventilatory ratio (VR) is a novel index to monitor ventilatory adequacy at the bedside.

VR

=

(

V

˙

E
m
e
a
s
u
r
e
d

×
P

a

C

O

2

m
e
a
s
u
r
e
d

)

/

(

V

˙

E
p
r
e
d
i
c
t
e
d

×
P

a

C

O

2

i
d
e
a
l

)

.

V

˙

E
p
r
e
d
i
c
t
e
d

is 100 mL.Kg-1.min-1 and
P

a

C

O

2

i
d
e
a
l

is 5 kPa. Physiological analysis shows that VR is influenced by dead space (VD/VT) and CO2 production

(

V

˙

C

O

2

)

. Two studies were conducted to explore the physiological properties of VR and assess its use in clinical practice.

Methods

Both studies were conducted in adult mechanically ventilated ICU patients. In Study 1, volumetric capnography was used to estimate daily VD/VT and measure

V

˙

C

O

2

in 48 patients. Simultaneously, ventilatory ratio was calculated using arterial blood gas measurements alongside respiratory and ventilatory variables. This data was used to explore the physiological properties of VR. In Study 2, 224 ventilated patients had daily VR and other respiratory variables, baseline characteristics, and outcome recorded. The database was used to examine the prognostic value of VR.

Results

Study 1 showed that there was significant positive correlation between VR and VD/VT (modified r = 0.71) and

V

˙

C

O

2

(r = 0.14). The correlation between VR and VD/VT was stronger in mandatory ventilation compared to spontaneous ventilation. Linear regression analysis showed that VD/VT had a greater influence on VR than

V

˙

C

O

2

(standardized regression coefficient 1/1-VD/VT: 0.78,

V

˙

C

O

2

: 0.44). Study 2 showed that VR was significantly higher in non-survivors compared to survivors (1.55 vs. 1.32; P < 0.01). Univariate logistic regression showed that higher VR was associated with mortality (OR 2.3, P < 0.01), this remained the case after adjusting for confounding variables (OR 2.34, P = 0.04).

Conclusions

VR is an easy to calculate bedside index of ventilatory adequacy and appears to yield clinically useful information.
Haplotype-assisted accurate non-invasive fetal whole genome recovery through maternal plasma sequencing
Authors: Chen Shengpei , Ge Huijuan , Wang Xuebin , Pan Xiaoyu , Yao Xiaotian , Li Xuchao , Zhang Chunlei , Chen Fang , Jiang Fuman , Li Peipei , Jiang Hui , Zheng Hancheng , Zhang Lei , Zhao Lijian , Wang Wei , Li Songgang , Wang Jun , Wang Jian , Yang Huanming , Li Yingrui , Zhang Xiuqing
Published: February 2013

Background

The applications of massively parallel sequencing technology to fetal cell-free DNA (cff-DNA) have brought new insight to non-invasive prenatal diagnosis. However, most previous research based on maternal plasma sequencing has been restricted to fetal aneuploidies. To detect specific parentally inherited mutations, invasive approaches to obtain fetal DNA are the current standard in the clinic because of the experimental complexity and resource consumption of previously reported non-invasive approaches.

Methods

Here, we present a simple and effective non-invasive method for accurate fetal genome recovery-assisted with parental haplotypes. The parental haplotype were firstly inferred using a combination strategy of trio and unrelated individuals. Assisted with the parental haplotype, we then employed a hidden Markov model to non-invasively recover the fetal genome through maternal plasma sequencing.

Results

Using a sequence depth of approximately 44X against a an approximate 5.69% cff-DNA concentration, we non-invasively inferred fetal genotype and haplotype under different situations of parental heterozygosity. Our data show that 98.57%, 95.37%, and 98.45% of paternal autosome alleles, maternal autosome alleles, and maternal chromosome X in the fetal haplotypes, respectively, were recovered accurately. Additionally, we obtained efficient coverage or strong linkage of 96.65% of reported Mendelian-disorder genes and 98.90% of complex disease-associated markers.

Conclusions

Our method provides a useful strategy for non-invasive whole fetal genome recovery.
Moveout-based wave-equation migration velocity analysis
Authors: Zhang Yang , Biondi Biondo
Published: February 2013

Current wave-equation migration velocity analysis schemes suffer from problems such as severe nonlinearity (which causes the issue of cycle skipping) and imprecise objective functions (which can accrue velocity errors by honoring residuals caused by model complexity and incomplete acquisition). To provide an improvement, we developed an alternative method to perform wave-equation migration velocity analysis by maximizing the flatness of the angle-domain common image gathers. We replaced the ray-based tomographic operator with the wave-equation-based one, although keeping the conventional moveout-based tomography work flow. Instead of maximizing the image-stack-power objective function directly with respect to the slowness, we linked the objective function to the slowness indirectly through an intermediate moveout parameter. By focusing on the common image gather kinematics, this approach greatly reduced the risk of cycle skipping in the absence of low-frequency data, and it produced high-quality gradients. In addition, the proposed method did not require explicit picking of the moveout parameters. Our numerical examples demonstrated the great potential of this method: in the first example, in which there is a Gaussian-shaped slowness anomaly, our method produced a well-behaved gradient; in the second example, in which there is a horizontally gradual increase of slowness, the result verified that our method is robust against cycle skipping; in the third example, the result showed that our method works well with reflectors of variable dips. Finally, our test on the Marmousi models concluded that the proposed method converges to a high-quality model that uniformly flattens the angle-domain common-image gathers.
A role for Rab14 in the endocytic trafficking of GLUT4 in 3T3-L1 adipocytes
Authors: Reed Sam E. , Hodgson Lorna R. , Song Shuang , May Margaret T. , Mastick Cynthia C. , Verkade Paul , Tavaré Jeremy M.
Published: February 2013

Insulin enhances the uptake of glucose into adipocytes and muscle cells by promoting the redistribution of the glucose transporter isoform 4 (GLUT4) from intracellular compartments to the cell surface. Rab GTPases regulate the trafficking itinerary of GLUT4 and several have been found on immunopurified GLUT4 vesicles. Specifically, Rab14 has previously been implicated in GLUT4 trafficking in muscle although its role, if any, in adipocytes is poorly understood. Analysis of 3T3-L1 adipocytes using confocal microscopy demonstrated that endogenous GLUT4 and endogenous Rab14 exhibited a partial colocalisation. However, when wild-type Rab14 or a constitutively-active Rab14Q70L mutant were over-expressed in these cells, the colocalisation with both GLUT4 and IRAP became extensive. Interestingly, this colocalisation was restricted to enlarged ‘ring-like’ vesicular structures (mean diameter 1.3 µm), which were observed in the presence of over-expressed wild-type Rab14 and Rab14Q70L, but not an inactive Rab14S25N mutant. These enlarged vesicles contained markers of early endosomes, and were rapidly filled by GLUT4 and transferrin undergoing endocytosis from the plasma membrane. The Rab14Q70L mutant reduced basal and insulin-stimulated cell surface GLUT4 levels, probably by retaining GLUT4 in an insulin-insensitive early endosomal compartment. Furthermore, shRNA-mediated depletion of Rab14 inhibited the transit of GLUT4 through early endosomal compartments towards vesicles/tubules in the perinuclear region. Given the previously reported role of Rab14 in trafficking between endosomes and the Golgi complex, we propose that the primary role of Rab14 in GLUT4 trafficking is to control the transit of internalised GLUT4 from early endosomes into the Golgi complex, rather than direct GLUT4 translocation to the plasma membrane.
SQL-1, homologue of the Golgi protein GMAP210, modulates Intraflagellar Transport in C. elegans
Authors: Broekhuis Joost R. , Rademakers Suzanne , Burghoorn Jan , Jansen Gert
Published: February 2013

Primary cilia are microtubule-based organelles, which have important sensory functions. For their function cilia rely on the delivery of specific proteins, both by intracellular trafficking and intraflagellar transport (IFT). In C. elegans' cilia, anterograde IFT is mediated by kinesin-II and OSM-3. Previously, we have shown that expression of a dominant active G protein α subunit (GPA-3QL) in amphid channel neurons affects the coordination of kinesin-II and OSM-3 and cilia length, suggesting that environmental signals can modulate these processes. Here, we show that loss-of-function of sql-1 (suppressor of gpa-3QL NO. 1), which encodes the homologue of the mammalian Golgi protein GMAP210, suppresses the gpa-3QL cilia length phenotype. SQL-1 localizes to the Golgi apparatus, where it contributes to maintaining Golgi organization. Loss of sql-1 by itself does not affect cilia length, while overexpression of sql-1 results in longer cilia. Using live imaging of fluorescently tagged IFT proteins, we show that in sql-1 mutants OSM-3 moves faster, kinesin-II moves slower, and that some complex A and B proteins move at an intermediate velocity, while others move at the same velocity as OSM-3. This indicates that mutation of sql-1 destabilizes the IFT complex. Finally, we show that simultaneous inactivation of sql-1 and activation of gpa-3QL affects the velocity of OSM-3. In summary, we show that in C. elegans the Golgin protein SQL-1 plays an important role in maintaining the stability of the IFT complex.
Stromal Cell-Derived Factor 2 Like-1 (SDF2L1) Associates with the Endoplasmic Reticulum-Associated Degradation (ERAD) Machinery and Retards the Degradation of Mutant Proinsulin in Pancreatic β-Cells
Authors: Tiwari Akansha , Schuiki Irmgard , Zhang Liling , Allister Emma M. , Wheeler Michael B. , Volchuk Allen
Published: February 2013

Stromal Cell Derived Factor 2 Like-1 (SDF2L1) is an endoplasmic reticulum (ER) localized protein whose function is undefined. Here we show that SDF2L1 protein levels are increased in response to ER stress-inducing compounds, but not other cell stressors we tested in insulinoma cell lines. SDF2L1 protein levels were also induced by expression of misfolded proinsulin in insulinoma cells and in islets from diabetic mice. By immunoprecipitation and binding assays we found that SDF2L1 interacts with the ER chaperone GRP78/BiP, the ERAD machinery and with misfolded proinsulin. Unexpectedly, knock-down of SDF2L1 in INS-1 (Insulin 2 C96Y-GFP) cells increased the degradation kinetics of mutant proinsulin, suggesting that SDF2L1 may regulate substrate availability for the ERAD system. We suggest that SDF2L1 may increase the time misfolded proteins have to achieve a correctly folded conformation and thus SDF2L1 may act as a buffer for substrate availability for ERAD in pancreatic β-cells.
Myotubularin and PtdIns3P remodel the sarcoplasmic reticulum in muscle in vivo
Authors: Amoasii Leonela , Hnia Karim , Chicanne Gaëtan , Brech Andreas , Cowling Belinda S. , Müller Martin Michael , Schwab Yannick , Koebel Pascale , Ferry Arnaud , Payrastre Bernard , Laporte Jocelyn
Published: February 2013

The sarcoplasmic reticulum (SR) is a specialized form of endoplasmic reticulum (ER) in skeletal muscle and is essential for calcium homeostasis. The mechanisms involved in SR remodeling and maintenance of SR subdomains are elusive. In this study, we identified myotubularin (MTM1), a phosphoinositide phosphatase mutated in X-linked centronuclear myopathy (XLCNM, or myotubular myopathy), as a key regulator of phosphatidylinositol 3-monophosphate (PtdIns3P) levels at the SR. MTM1 is predominantly located at the SR cisternae of the muscle triads and Mtm1 deficient mouse muscles and myoblasts from XLCNM patients exhibit abnormal SR/ER networks. In vivo modulation of MTM1 enzymatic activity in skeletal muscle using ectopic expression of wild-type or a dead-phosphatase MTM1 protein leads to differential SR remodeling. Active MTM1 is associated to flat membrane stacks, while dead-phosphatase MTM1 mutant promotes highly curved cubic membranes originating from the SR and enriched in PtdIns3P. Over-expression of a tandem FYVE domain with high affinity for PtdIns3P alters the shape of the SR cisternae at the triad. Our findings, supported by the parallel analysis of the Mtm1-null mouse and in vivo study, reveal a direct function of MTM1 enzymatic activity in SR remodeling and a key role for PtdIns3P in promoting SR membrane curvature in skeletal muscle. We propose that alteration in SR remodeling is a primary cause of X-linked centronuclear myopathy. The tight regulation of PtdIns3P on specific membrane subdomains may be a general mechanism to control membrane curvature.
14-3-3 proteins sequester a pool of soluble TRIM32 ubiquitin ligase to repress autoubiquitination and cytoplasmic body formation
Authors: Ichimura Tohru , Taoka Masato , Shoji Ikuo , Kato Hiroki , Sato Tomonobu , Hatakeyama Shigetsugu , Isobe Toshiaki , Hachiya Naomi
Published: February 2013

Deregulated expression of tripartite-motif protein 32 (TRIM32, an E3 ubiquitin-protein ligase) contributes to various diseases. Here we report, using quantitative proteomics and biochemistry, that 14-3-3 proteins bind to phosphorylated TRIM32 and prevent TRIM32 autoubiquitination and the formation of TRIM32-containing cytoplasmic bodies, potential autoregulatory mechanisms that can reduce the concentration of soluble free TRIM32. The 14-3-3–TRIM32 interaction was dependent on protein kinase A–catalyzed phosphorylation of TRIM32 at Ser651. We found that the inhibitory effect of 14-3-3 is, in part, a consequence of disrupting TRIM32's propensity to undergo higher order self-association without affecting its dimerization. Consequently, dimerized TRIM32 bound to 14-3-3 was sequestered in a distinct cytoplasmic pool away from the microtubule network, whereas a TRIM32 mutant that cannot bind 14-3-3 underwent multimerization and was unavailable to facilitate cell growth. Our results reveal a novel connection between ubiquitination and phosphorylation pathways, which could modulate a variety of cell events by stimulating the formation of the 14-3-3/TRIM32 signaling complex.
Ectopic eyes outside the head inXenopustadpoles provide sensory data for light-mediated learning
Authors: Blackiston Douglas J. , Levin Michael
Published: February 2013

A major roadblock in the biomedical treatment of human sensory disorders, including blindness, has been an incomplete understanding of the nervous system and its ability to adapt to changes in sensory modality. Likewise, fundamental insight into the evolvability of complex functional anatomies requires understanding brain plasticity and the interaction between the nervous system and body architecture. While advances have been made in the generation of artificial and biological replacement components, the brain's ability to interpret sensory information arising from ectopic locations is not well understood. We report the use of eye primordia grafts to create ectopic eyes along the body axis of Xenopus tadpoles. These eyes are morphologically identical to native eyes and can be induced at caudal locations. Cell labeling studies reveal that eyes created in the tail send projections to the stomach and trunk. To assess function we performed light-mediated learning assays using an automated machine vision and environmental control system. The results demonstrate that ectopic eyes in the tail of Xenopus tadpoles could confer vision to the host. Thus ectopic visual organs were functional even when present at posterior locations. These data and protocols demonstrate the ability of vertebrate brains to interpret sensory input from ectopic structures and incorporate them into adaptive behavioral programs. This tractable new model for understanding the robust plasticity of the central nervous system has significant implications for regenerative medicine and sensory augmentation technology.
Neglected losses and key costs: tracking the energetics of walking and running
Authors: Bertram John E. A. , Hasaneini S. Javad
Published: February 2013

As one of the most energetically demanding daily activities, locomotion has attracted substantial investigative attention. Although legged locomotion has been well described, it is currently not well understood. Looking at energy accounting might be a good pathway with which to solve this problem. One relatively simple way of analyzing energy management is to look directly at the flow of mechanical energy into and out of the system, in terms of costs and losses (with some attention to the mechanisms responsible for this flow). In this commentary we argue that a key source of energetic loss has largely been neglected: the redirection of body motion from downward to upward at each step. We discuss the role of this loss and the compensating energetic costs, identifying some of the general features of the trade-offs that determine gait optimization strategies. We find that even at a conceptual level, a focus on the main mechanism of loss and the strategies available to the organism to effectively compensate for losses can yield substantial insight into observations as diverse as the functional limits of a playground swing through to the strikingly different effect of reduced gravity on human walking and running. Such insight changes the interpretation of fundamental features of leg function, such as push-off timing and the role of elastic deflection during stance.
Second addendum to the synoptic review of red algal genera
Authors: Schneider Craig W. , Wynne Michael J.
Published: February 2013

A second addendum to Schneider and Wynne’s (Schneider, C.W. and M.J. Wynne. 2007. A synoptic review of the classification of red algal genera a half a century after Kylin’s “Die Gattungen der Rhodophyceen”. Bot. Mar. 50: 197–249.) “Synoptic review” of red algal genera and their classification is presented, with an updating of names of new taxa at the generic level and higher. In the past few years, the hierarchy of some genera has changed due to new subfamilies, which are cited and referenced below. There have also been the descriptions of some higher taxa in the past few years.
Condensed conifer tannins as antifungal agents in liquid culture
Authors: Anttila Anna-Kaisa , Pirttilä Anna Maria , Häggman Hely , Harju Anni , Venäläinen Martti , Haapala Antti , Holmbom Bjarne , Julkunen-Tiitto Riitta
Published: February 2013

In the last decades, many wood preservatives have been prohibited for their ecotoxicity. The present article is focusing on the conifer-derived condensed tannins as environment-friendly options for the substitution of artificial wood preservatives. Eight different tannin fractions were extracted from spruce cones, spruce barks, and pine cones. The parameters of tannin extraction, such as the methods of purification and concentration of active components in the extracts, have been investigated. The cone and bark extracts were tested for the growth inhibition of eight brown-rot fungi, three white-rot fungi, and four soft-rot fungi in liquid cultures. The cone tannins provided a more efficient fungal growth inhibition than bark tannins. Purification increased the antifungal properties of the extracts. The growth of brown-rot fungi was inhibited by the tannins already at low concentrations. However, the extracts were not effective against the white-rot or soft-rot fungi. More investigation is needed concerning the tannin source and the purification procedure of the extracts before tannins can be considered as an ecologically benign wood preservative.
Bats at the end of the world: new distributional data and fossil records from Patagonia, Argentina
Authors: Sauthier Daniel E. Udrizar , Teta Pablo , Formoso Anahí E. , Bernardis Adela , Wallace Patricio , Pardiñas Ulyses F.J.
Published: February 2013

We report new recent and fossil records in Patagonia for six and three bat species, respectively. These findings significantly increase the previously known number of localities for these mammals in this entire region, filling gaps between previous references for some species (e.g., Histiotus macrotus) and/or extending by 140–350 km the range of others (e.g., Myotis chiloensis, M. levis, Lasiurus varius). In addition, we report for the second time the vespertilionid bat Lasiurus blossevillii in Patagonia. Fossils are mostly restricted to the Late Holocene epoch, and the recorded assemblages are similar to the recent ones. A preliminary analysis of richness indicates that bat diversity south of the Colorado River (around 39°S) decreases from five to six species in the northwestern to one species in the southeastern, changing abruptly around 43°S–46°S. Compared with similar latitudes of the Northern Hemisphere, bat diversity in the Neotropics follows a similar pattern, with <20 taxa occurring south of 35°S.
Predicted distributions and conservation status of two threatened Southeast Asian small carnivores: the banded civet and Hose’s civet
Authors: Jennings Andrew P. , Mathai John , Brodie Jedediah , Giordano Anthony J. , Veron Geraldine
Published: February 2013

Knowledge of the distribution and habitat preferences of a species is of paramount importance when assessing its conservation status. We used accurately recorded occurrence records and ecological niche modelling to predict the distribution of two threatened and poorly known small carnivore species that occur in Southeast Asia, the banded civet (Hemigalus derbyanus) and Hose’s civet (Diplogale hosei), and analysed their spatial niche differentiation for habitat and elevation. We then identified possible anthropogenic threats, and used our modelling predictions to recommend surveying priorities. The predicted distribution of the banded civet was principally in lowland evergreen forest in southern Myanmar/Thailand, Peninsular Malaysia, Sumatra, Borneo and three Mentawai Islands (Siberut, Sipora and South Pagai), and for Hose’s civet in evergreen forest across the higher elevation regions of Borneo. Our niche analyses suggested that there is a tendency for these two species to separate spatially along an elevation gradient: the banded civet is mainly found in lowland areas, whereas Hose’s civet primarily occurs at higher elevations. Our study strongly indicated that these two viverrids are forest-dependent species that may be threatened by forest loss, degradation and fragmentation. Field surveys should be prioritised in areas where each species is predicted to occur and no records currently exist.
Wnt Signal Specifies the Intrathalamic Limit and Its Organizer Properties by Regulating Shh Induction in the Alar Plate
Authors: Martinez-Ferre Almudena , Navarro-Garberi Maria , Bueno Carlos , Martinez Salvador
Published: February 2013

The structural complexity of the brain depends on precise molecular and cellular regulatory mechanisms orchestrated by regional morphogenetic organizers. The thalamic organizer is the zona limitans intrathalamica (ZLI), a transverse linear neuroepithelial domain in the alar plate of the diencephalon. Because of its production of Sonic hedgehog, ZLI acts as a morphogenetic signaling center.Shhis expressed early on in the prosencephalic basal plate and is then gradually activated dorsally within the ZLI. The anteroposterior positioning and the mechanism inducingShhexpression in ZLI cells are still partly unknown, being a subject of controversial interpretations. For instance, separate experimental results have suggested that juxtaposition of prechordal (rostral) and epichordal (caudal) neuroepithelium, anteroposterior encroachment of alar lunatic fringe (L-fng) expression, and/or basal Shh signaling is required for ZLI specification. Here we investigated a key role of Wnt signaling in the molecular regulation of ZLI positioning andShhexpression, using experimental embryologyin ovoin the chick. EarlyWntexpression in the ZLI regulatesGli3andL-fngto generate a permissive territory in whichShhis progressively induced by planar signals of the basal plate.
The Perirhinal Cortex and Recognition Memory Interference
Authors: Watson Hilary C. , Lee Andy C. H.
Published: February 2013

There has recently been an increase in interest in the effects of visual interference on memory processing, with the aim of elucidating the role of the perirhinal cortex (PRC) in recognition memory. One view argues that the PRC processes highly complex conjunctions of object features, and recent evidence from rodents suggests that these representations may be vital for buffering against the effects of pre-retrieval interference on object recognition memory. To investigate whether PRC-dependent object representations play a similar role in humans, we used functional magnetic resonance imaging to scan neurologically healthy participants while they performed a novel interference-match-to-sample task. This paradigm was specifically designed to concurrently assess the impact of object versus spatial interference, on recognition memory for objects or scenes, while keeping constant the amount of object and scene information presented across all trials. Activity at retrieval was examined, within an anatomically defined PRC region of interest, according to the demand for object or scene memory, following a period of object compared with spatial interference. Critically, we found greater PRC activity for object memory following object interference, compared with object memory following scene interference, and no difference between object and scene interference for scene recognition. These data demonstrate a role for the human PRC during object recognition memory, following a period of object, but not scene interference, and emphasize the importance of representational content to mnemonic processing.
Noise-Induced Hearing Loss (NIHL) as a Target of Oxidative Stress-Mediated Damage: Cochlear and Cortical Responses after an Increase in Antioxidant Defense
Authors: Fetoni Anna Rita , De Bartolo Paola , Eramo Sara Letizia Maria , Rolesi Rolando , Paciello Fabiola , Bergamini Christian , Fato Romana , Paludetti Gaetano , Petrosini Laura , Troiani Diana
Published: February 2013

This study addresses the relationship between cochlear oxidative damage and auditory cortical injury in a rat model of repeated noise exposure. To test the effect of increased antioxidant defenses, a water-soluble coenzyme Q10analog (Qter) was used. We analyzed auditory function, cochlear oxidative stress, morphological alterations in auditory cortices and cochlear structures, and levels of coenzymes Q9and Q10(CoQ9and CoQ10, respectively) as indicators of endogenous antioxidant capability. We report three main results. First, hearing loss and damage in hair cells and spiral ganglion was determined by noise-induced oxidative stress. Second, the acoustic trauma altered dendritic morphology and decreased spine number of II–III and V–VI layer pyramidal neurons of auditory cortices. Third, the systemic administration of the water-soluble CoQ10analog reduced oxidative-induced cochlear damage, hearing loss, and cortical dendritic injury. Furthermore, cochlear levels of CoQ9and CoQ10content increased. These findings indicate that antioxidant treatment restores auditory cortical neuronal morphology and hearing function by reducing the noise-induced redox imbalance in the cochlea and the deafferentation effects upstream the acoustic pathway.
The Cooperation of Sustained and Phasic Inhibitions Increases the Contrast of ITD-Tuning in Low-Frequency Neurons of the Chick Nucleus Laminaris
Authors: Yamada Rei , Okuda Hiroko , Kuba Hiroshi , Nishino Eri , Ishii Takahiro M. , Ohmori Harunori
Published: February 2013

Neurons in the nucleus laminaris (NL) of birds detect the coincidence of binaural excitatory inputs from the nucleus magnocellularis (NM) on both sides and process the interaural time differences (ITDs) for sound localization. Sustained inhibition from the superior olivary nucleus is known to control the gain of coincidence detection, which allows the sensitivity of NL neurons to ITD tolerate strong-intensity sound. Here, we found a phasic inhibition in chicken brain slices that follows the ipsilateral NM inputs after a short time delay, sharpens coincidence detection, and may enhance ITD sensitivity in low-frequency NL neurons. GABA-positive small neurons are distributed in and near the NL. These neurons generate IPSCs in NL neurons when photoactivated by a caged glutamate compound, suggesting that these GABAergic neurons are interneurons that mediate phasic inhibition. These IPSCs have fast decay kinetics that is attributable to the α1-subunit of the GABAAreceptor, the expression of which dominates in the low-frequency region of the NL. Model simulations demonstrate that phasic IPSCs narrow the time window of coincidence detection and increase the contrast of ITD-tuning during low-level, low-frequency excitatory input. Furthermore, cooperation of the phasic and sustained inhibitions effectively increases the contrast of ITD-tuning over a wide range of excitatory input levels. We propose that the complementary interaction between phasic and sustained inhibitions is the neural mechanism that regulates ITD sensitivity for low-frequency sound in the NL.
Active Avoidance Learning Requires Prefrontal Suppression of Amygdala-Mediated Defensive Reactions
Authors: Moscarello Justin M. , LeDoux Joseph E.
Published: February 2013

Signaled active avoidance (AA) paradigms train subjects to prevent an aversive outcome by performing a learned behavior during the presentation of a conditioned cue. This complex form of conditioning involves pavlovian and instrumental components, which produce competing behavioral responses that must be reconciled for the subject to successfully avoid an aversive stimulus. In signaled AA paradigm for rat, we tested the hypothesis that the instrumental component of AA training recruits infralimbic prefrontal cortex (ilPFC) to inhibit central amygdala (CeA)-mediated Pavlovian reactions. Pretraining lesions of ilPFC increased conditioned freezing while causing a corresponding decrease in avoidance; lesions of CeA produced opposite effects, reducing freezing and facilitating avoidance behavior. Pharmacological inactivation experiments demonstrated that ilPFC is relevant to both acquisition and expression phases of AA learning. Inactivation experiments also revealed that AA produces an ilPFC-mediated diminution of pavlovian reactions that extends beyond the training context, even when the conditioned stimulus is presented in an environment that does not allow the avoidance response. Finally, injection of a protein synthesis inhibitor into either ilPFC or CeA impaired or facilitated AA, respectively, showing that avoidance training produces two opposing memory traces in these regions. These data support a model in which AA learning recruits ilPFC to inhibit CeA-mediated defense behaviors, leading to a robust suppression of freezing that generalizes across environments. Thus, ilPFC functions as an inhibitory interface, allowing instrumental control over an aversive outcome to attenuate the expression of freezing and other reactions to conditioned threat.
Pathological Activity in Mediodorsal Thalamus of Rats with Spinal Cord Injury Pain
Authors: Whitt Jessica L. , Masri Radi , Pulimood Nisha S. , Keller Asaf
Published: February 2013

Spinal cord injury (SCI) results not only in motor deficits, but produces, in many patients, excruciating chronic pain (SCI pain). We have previously shown, in a rodent model, that SCI causes suppression of activity in the GABAergic nucleus, the zona incerta (ZI), and concomitant increased activity in one of its main targets, the posterior nucleus of the thalamus (PO); the increased PO activity is correlated with the maintenance and expression of hyperalgesia after SCI. Here, we test the hypothesis that SCI causes a similar pathological increase in other thalamic nuclei regulated by the ZI, specifically the mediodorsal thalamus (MD), which is involved in the emotional-affective aspects of pain. We recorded single and multiunit activity from MD of either anesthetized or awake rats, and compared data from rats with SCI with data from sham-operated controls (anesthetized experiments) or with data from the same animals prelesion (awake experiments). Consistent with our hypothesis, MD neurons from rats with SCI show significant increases in spontaneous firing rates and in the magnitude and duration of responses to noxious stimuli. In a subset of anesthetized animals, similar changes in activity of MD neurons were produced by pharmacologically inactivating ZI in naive rats, suggesting that the changes in the MD after SCI are related to suppressed inhibition from the ZI. These data support our hypothesis that SCI pain results, at least in part, from a loss of inhibition to thalamic nuclei associated with both the sensory-discriminative and emotional-affective components of pain.
Suppression of Spontaneous Activity before Visual Response in the Primate V1 Neurons during a Visually Guided Saccade Task
Authors: Lee Jungah , Kim Kayeon , Chung Sooyoung , Lee Choongkil
Published: February 2013

Visually guided saccadic eye movements are thought to involve multiple stages of processing in diverse brain structures including the primary visual cortex (V1). The variability of neural activity in each of these structures may present ambiguities for downstream stages in identifying sensory and motor signals among spontaneous discharges. The response time of saccadic eye movements made toward a visual target is correlated with the time of the first spikes in V1 that are evoked by the target (Lee et al., 2010). This suggests that downstream neurons receiving the output of V1 are faced with a challenging task of discriminating first spikes of visual response against spontaneous discharge. Here we report a novel response property of the macaque V1 neurons. Immediately before neurons discharge a burst of activity to a visual saccade target, spontaneous discharges were transiently suppressed. This suppression was maximal ∼18 ms after target onset. Based on simulations of artificial spike trains, we propose that the transient suppression enhances temporal contrast for identifying the onset of visual response by increasing the reliability of detection of response onset by downstream neurons, thereby facilitating visually guided behavioral responses.
Cortical Metabolic Activity Matches the Pattern of Visual Suppression in Strabismus
Authors: Adams Daniel L. , Economides John R. , Sincich Lawrence C. , Horton Jonathan C.
Published: February 2013

When an eye becomes deviated in early childhood, a person does not experience double vision, although the globes are aimed at different targets. The extra image is prevented from reaching perception in subjects with alternating exotropia by suppression of each eye's peripheral temporal retina. To test the impact of visual suppression on neuronal activity in primary (striate) visual cortex, the pattern of cytochrome oxidase (CO) staining was examined in four macaques raised with exotropia by disinserting the medial rectus muscles shortly following birth. No ocular dominance columns were visible in opercular cortex, where the central visual field is represented, indicating that signals coming from the central retina in each eye were perceived. However, the border strips at the edges of ocular dominance columns appeared pale, reflecting a loss of activity in binocular cells from disruption of fusion. In calcarine cortex, where the peripheral visual field is represented, there were alternating pale and dark bands resembling ocular dominance columns. To interpret the CO staining pattern, [3H]proline was injected into the right eye in two monkeys. In the right calcarine cortex, the pale CO columns matched the labeled proline columns of the right eye. In the left calcarine cortex, the pale CO columns overlapped the unlabeled columns of the left eye in the autoradiograph. Therefore, metabolic activity was reduced in the ipsilateral eye's ocular dominance columns which serve peripheral temporal retina, in a fashion consistent with the topographic organization of suppression scotomas in humans with exotropia.
A Small Group of Neurosecretory Cells Expressing the Transcriptional Regulatoraponticand the NeuropeptidecorazoninMediate Ethanol Sedation in Drosophila
Authors: McClure Kimberly D. , Heberlein Ulrike
Published: February 2013

In the fruit flyDrosophila melanogaster, as in mammals, acute exposure to a high dose of ethanol leads to stereotypical behavioral changes beginning with increased activity, followed by incoordination, loss of postural control, and eventually, sedation. The mechanism(s) by which ethanol impacts the CNS leading to ethanol-induced sedation and the genes required for normal sedation sensitivity remain largely unknown. Here we identify the geneapontic(apt), an Myb/SANT-containing transcription factor that is required in the nervous system for normal sensitivity to ethanol sedation. Using genetic and behavioral analyses, we show thataptmediates sensitivity to ethanol sedation by acting in a small set of neurons that express Corazonin (Crz), a neuropeptide likely involved in the physiological response to stress. The activity of Crz neurons regulates the behavioral response to ethanol, as silencing and activating these neurons affects sedation sensitivity in opposite ways. Furthermore, this effect is mediated by Crz, as flies with reducedcrzexpression show reduced sensitivity to ethanol sedation. Finally, we find that bothaptandcrzare rapidly upregulated by acute ethanol exposure. Thus, we have identified two genes and a small set of peptidergic neurons that regulate sensitivity to ethanol-induced sedation. We propose that Apt regulates the activity of Crz neurons and/or release of the neuropeptide during ethanol exposure.
Linear Processing of Interaural Level Difference Underlies Spatial Tuning in the Nucleus of the Brachium of the Inferior Colliculus
Authors: Slee Sean J. , Young Eric D.
Published: February 2013

The spatial location of sounds is an important aspect of auditory perception, but the ways in which space is represented are not fully understood. No space map has been found within the primary auditory pathway. However, a space map has been found in the nucleus of the brachium of the inferior colliculus (BIN), which provides a major auditory projection to the superior colliculus. We measured the spectral processing underlying auditory spatial tuning in the BIN of unanesthetized marmoset monkeys. Because neurons in the BIN respond poorly to tones and are broadly tuned, we used a broadband stimulus with random spectral shapes (RSSs) from which both spatial receptive fields and frequency sensitivity can be derived. Responses to virtual space (VS) stimuli, based on the animal's own ear acoustics, were compared with the predictions of a weight-function model of responses to the RSS stimuli. First-order (linear) weight functions had broad spectral tuning (approximately three octaves) and were excitatory in the contralateral ear, inhibitory in the ipsilateral ear, and biased toward high frequencies. Responses to interaural time differences and spectral cues were relatively weak. In cross-validation tests, the first-order RSS model accurately predicted the measured VS tuning curves in the majority of neurons, but was inaccurate in 25% of neurons. In some cases, second-order weighting functions led to significant improvements. Finally, we found a significant correlation between the degree of binaural weight asymmetry and the best azimuth. Overall, the results suggest that linear processing of interaural level difference underlies spatial tuning in the BIN.
Identification of Nonvisual Photomotor Response Cells in the Vertebrate Hindbrain
Authors: Kokel David , Dunn Timothy W. , Ahrens Misha B. , Alshut Rüdiger , Cheung Chung Yan J. , Saint-Amant Louis , Bruni Giancarlo , Mateus Rita , van Ham Tjakko J. , Shiraki Tomoya , Fukada Yoshitaka , Kojima Daisuke , Yeh Jing-Ruey J. , Mikut Ralf , von Lintig Johannes , Engert Florian , Peterson Randall T.
Published: February 2013

Nonvisual photosensation enables animals to sense light without sight. However, the cellular and molecular mechanisms of nonvisual photobehaviors are poorly understood, especially in vertebrate animals. Here, we describe the photomotor response (PMR), a robust and reproducible series of motor behaviors in zebrafish that is elicited by visual wavelengths of light but does not require the eyes, pineal gland, or other canonical deep-brain photoreceptive organs. Unlike the relatively slow effects of canonical nonvisual pathways, motor circuits are strongly and quickly (seconds) recruited during the PMR behavior. We find that the hindbrain is both necessary and sufficient to drive these behaviors. Usingin vivocalcium imaging, we identify a discrete set of neurons within the hindbrain whose responses to light mirror the PMR behavior. Pharmacological inhibition of the visual cycle blocks PMR behaviors, suggesting that opsin-based photoreceptors control this behavior. These data represent the first known light-sensing circuit in the vertebrate hindbrain.
Mechanistic and Structural Determinants of NMDA Receptor Voltage-Dependent Gating and Slow Mg2+Unblock
Authors: Clarke Richard J. , Glasgow Nathan G. , Johnson Jon W.
Published: February 2013

NMDA receptor (NMDAR)-mediated currents depend on membrane depolarization to relieve powerful voltage-dependent NMDAR channel block by external magnesium (Mgo2+). Mgo2+unblock from native NMDARs exhibits a fast component that is consistent with rapid Mgo2+-unbinding kinetics and also a slower, millisecond time scale component (slow Mgo2+unblock). In recombinant NMDARs, slow Mgo2+unblock is prominent in GluN1/2A (an NMDAR subtype composed of GluN1 and GluN2A subunits) and GluN1/2B receptors, with slower kinetics observed for GluN1/2B receptors, but absent from GluN1/2C and GluN1/2D receptors. Slow Mgo2+unblock from GluN1/2B receptors results from inherent voltage-dependent gating, which increases channel open probability with depolarization. Here we examine the mechanisms responsible for NMDAR subtype dependence of slow Mgo2+unblock. We demonstrate that slow Mgo2+unblock from GluN1/2A receptors, like GluN1/2B receptors, results from inherent voltage-dependent gating. Surprisingly, GluN1/2A and GluN1/2B receptors exhibited equal inherent voltage dependence; faster Mgo2+unblock from GluN1/2A receptors can be explained by voltage-independent differences in gating kinetics. To investigate the absence of slow Mgo2+unblock in GluN1/2C and GluN1/2D receptors, we examined the GluN2 S/L site, a site responsible for several NMDAR subtype-dependent channel properties. Mutating the GluN2 S/L site of GluN2A subunits from serine (found in GluN2A and GluN2B subunits) to leucine (found in GluN2C and GluN2D) greatly diminished both voltage-dependent gating and slow Mgo2+unblock. Therefore, the residue at the GluN2 S/L site governs the expression of both slow Mgo2+unblock and inherent voltage dependence.