bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue hypoxia correlates with intensity of interictal spikes
Authors: Geneslaw Andrew S , Zhao Mingrui , Ma Hongtao , Schwartz Theodore H
Published: February 2011

Interictal spikes (IISs) represent burst firing of a small focal population of hypersynchronous, hyperexcitable cells. Whether cerebral blood flow (CBF) is adequate to meet the metabolic demands of this dramatic increase in membrane excitability is unknown. Positron emission tomography, single photon emission computed tomography, and functional magnetic resonance imaging studies have shown increases in CBF and hypometabolism, thus indicating the likelihood of adequate perfusion. We measured tissue oxygenation and CBF in a rat model of IIS using oxygen electrodes and laser-Doppler flowmetry. A ∼3-second dip in tissue oxygenation was shown, followed by more prolonged tissue hyperoxygenation, in spite of a 25% increase in CBF. Increases in the number of spikes, as well as in their amplitude and spike width further amplified these responses, and a decrease in interspike interval decreased the CBF response. Altering the anesthetic did not influence our results. Taken together, these findings indicate that frequent, high-amplitude IISs may produce significant tissue hypoxia, which has implications for patients with epilepsy and noninvasive techniques of seizure localization.
Free Flap Reconstruction of Self-Inflicted Submental Gunshot Wounds
Authors: Dean Nichole R. , McKinney Shane M. , Wax Mark K. , Louis Patrick J. , Rosenthal Eben L.
Published: February 2011

In this study, we review outcomes for 15 patients with self-inflicted submental gunshot wounds requiring free flap reconstruction. Patients presented to two tertiary care centers over a 7-year period. Mean age was 46 years (range, 16 to 76 years), 67% ( n = 10) had a psychiatric history, and four were known to abuse illicit substances. Patients with oromandibular involvement required on average a total of 2.8 procedures, and those with midface (3.7) or combined defects (6) required more total procedures ( p = 0.21). Donor sites included osteocutaneous radial forearm ( n = 8), fibula ( n = 4), fasciocutaneous radial forearm ( n = 5), and anterior lateral thigh ( n = 1). Median length of hospitalization was 8 days. Overall complication rate was 33% ( n = 5), and included hematoma ( n = 1), fistula ( n = 1), and mandibular malunion ( n = 2). Most patients were able to tolerate a regular or soft diet (92%), maintain oral competency (58%), and demonstrate intelligible speech (92%) at a median time to follow-up of 12 months. Despite the devastating nature of this injury, free flap reconstruction of self-inflicted submental gunshot wounds results in acceptable functional results for the majority of patients.
Bilateral Mandibular Condylysis from Systemic Sclerosis: Case Report of Surgical Correction with Bilateral Total Temporomandibular Joint Replacement
Authors: Doucet Jean-Charles , Morrison Archie D.
Published: February 2011

Systemic sclerosis (SSc) is a multisystem connective tissue disease of unknown etiology. The hallmark of SSc is scleroderma, referring to the presence of thickened, hardened skin. Oral and maxillofacial manifestations of the disease are numerous including masklike appearance, trismus, muscular atrophy, thin atrophied lips, secondary microstomia, xerostomia, rigidity of tongue and lips, widening of the periodontal ligament space, trigeminal neuralgia, and resorption of the mandible. A 35-year-old woman with limited cutaneous SSc presented with bilateral mandibular condylysis, severe class II mandibular deficiency, and large anterior open bite and limited range of mandibular opening at 27 mm. Surgical correction consisted of bilateral total temporomandibular joint reconstruction with stock prostheses combined with Le Fort I maxillary impaction and functional advancement genioplasty. This resulted in a functional occlusion with elimination of her open bite and a more esthetic profile. Her occlusion has remained stable at 7 months. The incidence of mandibular resorption in SSc has been found to be 20% to 33%. The mandibular angles are most commonly involved (37.6%), followed by the condyle (20.8%), coronoid process (20.0%), and the posterior border of the ascending ramus (14.4%). Bilateral condylysis is present in 13.7% of the cases. Very few cases of surgical correction of malocclusion induced by SSc-related condylysis have been reported in the literature. To the best of our knowledge, this is the first case report of bilateral condylysis from SSc where surgical replacement of the resorbed condyles was attempted. Bilateral total temporomandibular joint replacement can give these patients a functional occlusion, improved facial balance, and improved quality of life.
Periplasmic vestibule plays an important role for solute recruitment, selectivity, and gating in the Rh/Amt/MEP superfamily
Authors: Akgun Ugur , Khademi Shahram
Published: February 2011

AmtB, a member of the Rh/Amt/MEP superfamily, is responsible for ammonia transport in
Escherichia coli
. The ammonia pathway in AmtB consists of a narrow hydrophobic lumen in between hydrophilic periplasmic and cytoplasmic vestibules. A series of molecular dynamics simulations (greater than 0.4 μs in total) were performed to determine the mechanism of solute recruitments and selectivity by the periplasmic vestibule. The results show that the periplasmic vestibule plays a crucial role in solute selectivity, and its solute preferences follow the order of

. Based on our results,

recruitment is initiated by its interaction with either E70 or E225, highly conserved residues located at the entrance of the vestibule. Subsequently, the backbone carbonyl groups at the periplasmic vestibule direct

to the conserved aromatic cage at the bottom of the vestibule (known as the Am1 site). The umbrella sampling simulations suggest that the conserved residue D160 is not directly involved in the ammonia conduction; rather its main function is to keep the structure of periplasmic vestibule intact. The MD simulations also revealed that two partially stacked phenyl rings of F107 and F215, separating the periplasmic vestibule from the hydrophobic lumen, flip open and closed simultaneously with a frequency of approximately 10
8
flipping events per second. These results show how the periplasmic vestibule selectively recruits

to the Am1 site, and also that the synchronized flipping of two phenyl rings potentially facilitates the solute transition from the periplasmic vestibule to the hydrophobic lumen in the Rh/Amt/MEP superfamily.
Two developmental modules establish 3D beak-shape variation in Darwin's finches
Authors: Mallarino Ricardo , Grant Peter R. , Grant B. Rosemary , Herrel Anthony , Kuo Winston P. , Abzhanov Arhat
Published: February 2011

Bird beaks display tremendous variation in shape and size, which is closely associated with the exploitation of multiple ecological niches and likely played a key role in the diversification of thousands of avian species. Previous studies have demonstrated some of the molecular mechanisms that regulate morphogenesis of the prenasal cartilage, which forms the initial beak skeleton. However, much of the beak diversity in birds depends on variation in the premaxillary bone. It forms later in development and becomes the most prominent functional and structural component of the adult upper beak/jaw, yet its regulation is unknown. Here, we studied a group of Darwin's finch species with different beak shapes. We found that
TGFβIIr
,
β-catenin
, and
Dickkopf-3
, the top candidate genes from a cDNA microarray screen, are differentially expressed in the developing premaxillary bone of embryos of species with different beak shapes. Furthermore, our functional experiments demonstrate that these molecules form a regulatory network governing the morphology of the premaxillary bone, which differs from the network controlling the prenasal cartilage, but has the same species-specific domains of expression. These results offer potential mechanisms that may explain how the tightly coupled depth and width dimensions can evolve independently. The two-module program of development involving independent regulating molecules offers unique insights into how different developmental pathways may be modified and combined to induce multidimensional shifts in beak morphology. Similar modularity in development may characterize complex traits in other organisms to a greater extent than is currently appreciated.
Two rotary motors in F-ATP synthase are elastically coupled by a flexible rotor and a stiff stator stalk
Authors: Wächter André , Bi Yumin , Dunn Stanley D. , Cain Brian D. , Sielaff Hendrik , Wintermann Frank , Engelbrecht Siegfried , Junge Wolfgang
Published: February 2011

ATP is synthesized by ATP synthase (F
O
F
1
-ATPase). Its rotary electromotor (F
O
) translocates protons (in some organisms sodium cations) and generates torque to drive the rotary chemical generator (F
1
). Elastic power transmission between F
O
and F
1
is essential for smoothing the cooperation of these stepping motors, thereby increasing their kinetic efficiency. A particularly compliant elastic domain is located on the central rotor (
c
10–15
/
ϵ
/
γ
), right between the two sites of torque generation and consumption. The hinge on the active lever on subunit β adds further compliance. It is under contention whether or not the peripheral stalk (and the “stator” as a whole) also serves as elastic buffer. In the enzyme from
Escherichia coli
, the most extended component of the stalk is the homodimer
b

2

, a right-handed α-helical coiled coil. By fluctuation analysis we determined the spring constant of the stator in response to twisting and bending, and compared wild-type with
b
-mutant enzymes. In both deformation modes, the stator was very stiff in the wild type. It was more compliant if
b
was elongated by 11 amino acid residues. Substitution of three consecutive residues in
b
by glycine, expected to destabilize its α-helical structure, further reduced the stiffness against bending deformation. In any case, the stator was at least 10-fold stiffer than the rotor, and the enzyme retained its proton-coupled activity.
Grazer cues induce stealth behavior in marine dinoflagellates
Authors: Selander Erik , Jakobsen Hans H. , Lombard Fabien , Kiørboe Thomas
Published: February 2011

Chain formation is common among phytoplankton organisms but the underlying reasons and consequences are poorly understood. Here we show that chain formation is strongly impaired by waterborne cues from copepod grazers in the dinoflagellate
Alexandrium tamarense
. Chains of
Alexandrium
cells exposed to copepod cues responded by splitting into single cells or shorter chains. Motion analysis revealed significantly lower swimming velocities for single cells compared with chains, with two- to fivefold higher simulated predator encounter rates for two- and four-cell chains, respectively. In addition, the few remaining two-cell chains in grazed treatments were swimming at approximately half the speed of two-cell chains in treatments without grazers, which reduced encounter rates with grazers to values similar to that of single cells. Chain length plasticity and swimming behavior constitute unique mechanisms to reduce encounters with grazers. We argue that dinoflagellates can regulate the balance between motility and predator avoidance by adjusting chain length. The high predator encounter rate for motile chains may have contributed to the low prevalence of chain formation in motile phytoplankton compared with in nonmotile phytoplankton where chain formation is more common.
Computational functions of neurons and circuits signaling injury: Relationship to pain behavior
Authors: Mendell Lorne M.
Published: February 2011

The basic circuitry of the “pain pathway” mediating transmission of information from the periphery to the brain is well known, consisting of specialized sensory fibers known as nociceptors projecting to specific spinal cord neurons, which in turn project on to the thalamus and cerebral cortex. Here we survey some of the unique properties of these circuits, such as peripheral and central sensitization, and the segmental and descending modulatory control of synaptic transmission. We also review evidence indicating dissociation between nociceptor activity and behavioral indications of pain. Together, these considerations point to the need for a more quantitative approach to the nociceptive system, specifically the interactions at peripheral, spinal, and supraspinal levels as well as between them, to more fully understand how the activity in nociceptive neurons individually and collectively is related to the pain response.
Microbial alignment in flow changes ocean light climate
Authors: Marcos  , Seymour Justin R. , Luhar Mitul , Durham William M. , Mitchell James G. , Macke Andreas , Stocker Roman
Published: February 2011

The growth of microbial cultures in the laboratory often is assessed informally with a quick flick of the wrist: dense suspensions of microorganisms produce translucent “swirls” when agitated. Here, we rationalize the mechanism behind this phenomenon and show that the same process may affect the propagation of light through the upper ocean. Analogous to the shaken test tubes, the ocean can be characterized by intense fluid motion and abundant microorganisms. We demonstrate that the swirl patterns arise when elongated microorganisms align preferentially in the direction of fluid flow and alter light scattering. Using a combination of experiments and mathematical modeling, we find that this phenomenon can be recurrent under typical marine conditions. Moderate shear rates (0.1 s
−1
) can increase optical backscattering of natural microbial assemblages by more than 20%, and even small shear rates (0.001 s
−1
) can increase backscattering from blooms of large phytoplankton by more than 30%. These results imply that fluid flow, currently neglected in models of marine optics, may exert an important control on light propagation, influencing rates of global carbon fixation and how we estimate these rates via remote sensing.
Anthropogenic and environmental drivers of modern range loss in large mammals
Authors: Yackulic Charles B. , Sanderson Eric W. , Uriarte María
Published: February 2011

The extinction of a species is inevitably preceded by the extirpation of a series of local populations. Ecological theory predicts that vulnerability to extirpation varies between populations and is ultimately linked to environmental heterogeneity. If populations of a species are present in multiple regions separated by abrupt changes in environmental conditions (e.g., biomes), spatial variation in vulnerability to extirpation may be closely linked to the distribution of these regions. In the absence of abrupt shifts in environmental conditions, populations at the edge of a species’ range should have low growth rates and be more vulnerable to extirpation, whereas populations located in the core of the species’ range should be exposed to more favorable environmental conditions, have higher growth rates, and be less vulnerable. Here, we ask whether the distribution of biomes or range position better reflects spatial variation in vulnerability for 43 mammal species distributed through four continents. We control for the distribution of human threats and quantify the importance of protected areas in population persistence. We conclude that the distribution of biomes is a better predictor of vulnerability than position in the geographic range. We also find that core populations are less vulnerable than edge populations (after controlling for threats levels and protected areas). Protected areas are important for the persistence of most species we studied. By providing a measure of vulnerability linked directly to the distribution of threats, our results offer insights for scaling up from species vulnerability to extinction risk.
Vertical nanopillars for highly localized fluorescence imaging
Authors: Xie Chong , Hanson Lindsey , Cui Yi , Cui Bianxiao
Published: February 2011

Observing individual molecules in a complex environment by fluorescence microscopy is becoming increasingly important in biological and medical research, for which critical reduction of observation volume is required. Here, we demonstrate the use of vertically aligned silicon dioxide nanopillars to achieve below-the-diffraction-limit observation volume in vitro and inside live cells. With a diameter much smaller than the wavelength of visible light, a transparent silicon dioxide nanopillar embedded in a nontransparent substrate restricts the propagation of light and affords evanescence wave excitation along its vertical surface. This effect creates highly confined illumination volume that selectively excites fluorescence molecules in the vicinity of the nanopillar. We show that this nanopillar illumination can be used for in vitro single-molecule detection at high fluorophore concentrations. In addition, we demonstrate that vertical nanopillars interface tightly with live cells and function as highly localized light sources inside the cell. Furthermore, specific chemical modification of the nanopillar surface makes it possible to locally recruit proteins of interest and simultaneously observe their behavior within the complex, crowded environment of the cell.
Attention-driven auditory cortex short-term plasticity helps segregate relevant sounds from noise
Authors: Ahveninen Jyrki , Hämäläinen Matti , Jääskeläinen Iiro P. , Ahlfors Seppo P. , Huang Samantha , Lin Fa-Hsuan , Raij Tommi , Sams Mikko , Vasios Christos E. , Belliveau John W.
Published: February 2011

How can we concentrate on relevant sounds in noisy environments? A “gain model” suggests that auditory attention simply amplifies relevant and suppresses irrelevant afferent inputs. However, it is unclear whether this suffices when attended and ignored features overlap to stimulate the same neuronal receptive fields. A “tuning model” suggests that, in addition to gain, attention modulates feature selectivity of auditory neurons. We recorded magnetoencephalography, EEG, and functional MRI (fMRI) while subjects attended to tones delivered to one ear and ignored opposite-ear inputs. The attended ear was switched every 30 s to quantify how quickly the effects evolve. To produce overlapping inputs, the tones were presented alone vs. during white-noise masking notch-filtered ±1/6 octaves around the tone center frequencies. Amplitude modulation (39 vs. 41 Hz in opposite ears) was applied for “frequency tagging” of attention effects on maskers. Noise masking reduced early (50–150 ms; N1) auditory responses to unattended tones. In support of the tuning model, selective attention canceled out this attenuating effect but did not modulate the gain of 50–150 ms activity to nonmasked tones or steady-state responses to the maskers themselves. These tuning effects originated at nonprimary auditory cortices, purportedly occupied by neurons that, without attention, have wider frequency tuning than ±1/6 octaves. The attentional tuning evolved rapidly, during the first few seconds after attention switching, and correlated with behavioral discrimination performance. In conclusion, a simple gain model alone cannot explain auditory selective attention. In nonprimary auditory cortices, attention-driven short-term plasticity retunes neurons to segregate relevant sounds from noise.
Extrasynaptic δ-containing GABA
A
receptors in the nucleus accumbens dorsomedial shell contribute to alcohol intake
Authors: Nie Hong , Rewal Mridula , Gill T. Michael , Ron Dorit , Janak Patricia H.
Published: February 2011

Recent findings suggest that extrasynaptic δ-subunit–containing GABA
A
receptors are sensitive to low-to-moderate concentrations of alcohol, raising the possibility that these receptors mediate the reinforcing effects of alcohol after consumption of one or a few drinks. We used the technique of viral-mediated RNAi to reduce expression of the GABA
A
receptor δ-subunit in adult rats in localized regions of the nucleus accumbens (NAc) to test the hypothesis that δ-subunit–containing GABA
A
receptors in the NAc are necessary for oral alcohol consumption. We found that knockdown of the δ-subunit in the medial shell region of the NAc, but not in the ventral or lateral shell or in the core, reduced alcohol intake. In contrast, δ-subunit knockdown in the medial shell did not affect intake of a 2% sucrose solution, suggesting that the effects of GABA
A
receptor δ-subunit reduction are specific to alcohol. These results provide strong evidence that extrasynaptic δ-subunit–containing GABA
A
receptors in the medial shell of the NAc are critical for the reinforcing effects of oral ethanol.
Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration
Authors: Shi Hui , He Xiaoxiao , Wang Kemin , Wu Xu , Ye Xiaosheng , Guo Qiuping , Tan Weihong , Qing Zhihe , Yang Xiaohai , Zhou Bing
Published: February 2011

Aptamers have emerged as promising molecular probes for in vivo cancer imaging, but the reported “always-on” aptamer probes remain problematic because of high background and limited contrast. To address this problem, we designed an activatable aptamer probe (AAP) targeting membrane proteins of living cancer cells and achieved contrast-enhanced cancer visualization inside mice. The AAP displayed a quenched fluorescence in its free state and underwent a conformational alteration upon binding to target cancer cells with an activated fluorescence. As proof of concept, in vitro analysis and in vivo imaging of CCRF-CEM cancer cells were performed by using the specific aptamer, sgc8, as a demonstration. It was confirmed that the AAP could be specifically activated by target cancer cells with a dramatic fluorescence enhancement and exhibit improved sensitivity for CCRF-CEM cell analysis with the cell number of 118 detected in 200 μl binding buffer. In vivo studies demonstrated that activated fluorescence signals were obviously achieved in the CCRF-CEM tumor sites in mice. Compared to always-on aptamer probes, the AAP could substantially minimize the background signal originating from nontarget tissues, thus resulting in significantly enhanced image contrast and shortened diagnosis time to 15 min. Furthermore, because of the specific affinity of sgc8 to target cancer cells, the AAP also showed desirable specificity in differentiating CCRF-CEM tumors from Ramos tumors and nontumor areas. The design concept can be widely adapted to other cancer cell-specific aptamer probes for in vivo molecular imaging of cancer.
Late Neandertals and the intentional removal of feathers as evidenced from bird bone taphonomy at Fumane Cave 44 ky B.P., Italy
Authors: Peresani Marco , Fiore Ivana , Gala Monica , Romandini Matteo , Tagliacozzo Antonio
Published: February 2011

A large and varied avifaunal bone assemblage from the final Mousterian levels of Grotta di Fumane, northern Italy, reveals unusual human modifications on species that are not clearly relatable to feeding or utilitarian uses (i.e., lammergeier, Eurasian black vulture, golden eagle, red-footed falcon, common wood pigeon, and Alpine chough). Cut, peeling, and scrape marks, as well as diagnostic fractures and a breakthrough, are observed exclusively on wings, indicating the intentional removal of large feathers by Neandertals. The species involved, the anatomical elements affected, and the unusual type and location of the human modifications indicate an activity linked to the symbolic sphere and the behavioral modernity of this European autochthonous population.
RNA methylation by Radical SAM enzymes RlmN and Cfr proceeds via methylene transfer and hydride shift
Authors: Yan Feng , Fujimori Danica Galonić
Published: February 2011

RlmN and Cfr are Radical SAM enzymes that modify a single adenosine nucleotide—A2503—in 23S ribosomal RNA. This nucleotide is positioned within the peptidyl transferase center of the ribosome, which is a target of numerous antibiotics. An unusual feature of these enzymes is their ability to carry out methylation of amidine carbons of the adenosine substrate. To gain insight into the mechanism of methylation catalyzed by RlmN and Cfr, deuterium labeling experiments were carried out. These experiments demonstrate that the newly introduced methyl group is assembled from an
S
-adenosyl-L-methionine (SAM)-derived methylene fragment and a hydrogen atom that had migrated from the substrate amidine carbon. Rather than activating the adenosine nucleotide of the substrate by hydrogen atom abstraction from an amidine carbon, the 5′-deoxyadenosyl radical abstracts hydrogen from the second equivalent of SAM to form the SAM-derived radical cation. This species, or its corresponding sulfur ylide, subsequently adds into the substrate, initiating hydride shift and
S
-adenosylhomocysteine elimination to complete the formation of the methyl group. These findings indicate that rather than acting as methyltransferases, RlmN and Cfr are methyl synthases. Together with the previously described 5′-deoxyadenosyl and 3-amino-3-carboxypropyl radicals, these findings demonstrate that all three carbon atoms attached to the sulfonium center in SAM can serve as precursors to carbon-derived radicals in enzymatic reactions.
Molecular basis of substrate-induced permeation by an amino acid antiporter
Authors: Kowalczyk Lukasz , Ratera Mercè , Paladino Antonella , Bartoccioni Paola , Errasti-Murugarren Ekaitz , Valencia Eva , Portella Guillem , Bial Susanna , Zorzano Antonio , Fita Ignacio , Orozco Modesto , Carpena Xavier , Vázquez-Ibar José Luis , Palacín Manuel
Published: February 2011

Transporters of the amino acid, polyamine and organocation (APC) superfamily play essential roles in cell redox balance, cancer, and aminoacidurias. The bacterial L-arginine/agmatine antiporter, AdiC, is the main APC structural paradigm and shares the “5 + 5 inverted repeat” fold found in other families like the Na
+
-coupled neurotransmitter transporters. The available AdiC crystal structures capture two states of its transport cycle: the open-to-out apo and the outward-facing Arg
+
-bound occluded. However, the role of Arg
+
during the transition between these two states remains unknown. Here, we report the crystal structure at 3.0 Å resolution of an Arg
+
-bound AdiC mutant (N101A) in the open-to-out conformation, completing the picture of the major conformational states during the transport cycle of the 5 + 5 inverted repeat fold-transporters. The N101A structure is an intermediate state between the previous known AdiC conformations. The Arg
+
-guanidinium group in the current structure presents high mobility and delocalization, hampering substrate occlusion and resulting in a low translocation rate. Further analysis supports that proper coordination of this group with residues Asn101 and Trp293 is required to transit to the occluded state, providing the first clues on the molecular mechanism of substrate-induced fit in a 5 + 5 inverted repeat fold-transporter. The pseudosymmetry found between repeats in AdiC, and in all fold-related transporters, restraints the conformational changes, in particular the transmembrane helices rearrangements, which occur during the transport cycle. In AdiC these movements take place away from the dimer interface, explaining the independent functioning of each subunit.
Redesigning allosteric activation in an enzyme
Authors: Rana Sadhna , Pozzi Nicola , Pelc Leslie A. , Di Cera Enrico
Published: February 2011

Enzyme activation by monovalent cations is widely documented in plants and the animal world. In type II enzymes, activation entails two steps: binding of the monovalent cation to its allosteric site and transduction of this event into enhanced catalytic activity. The effect has exquisite specificity for either Na
+
or K
+
, the most abundant cations present in physiological environments. Enzymes requiring K
+
such as kinases and molecular chaperones are not activated as well or at all by the larger cation Cs
+
or the smaller cations Na
+
and Li
+
. Enzymes requiring Na
+
such as β-galactosidase and clotting proteases are not activated as well by Li
+
, or the larger cations K
+
, Rb
+
, and Cs
+
. Efforts to switch specificity between Na
+
and K
+
in this large class of enzymes and completely redesign the mechanism of allosteric transduction leading to enhanced catalytic activity have so far been unsuccessful. Here we show how mutagenesis of two loops defining the Na
+
binding site of thrombin, a Na
+
-activated clotting protease, generates a construct that is most active in the presence of K
+
toward synthetic and physiological substrates. The effect is the result of a higher binding affinity and more efficient allosteric transduction of binding into enhanced catalytic activity for K
+
compared to Na
+
, which represents a complete reversal of the properties of wild type. In addition, the construct features altered specificity toward physiological substrates resulting in a significant anticoagulant profile. The findings are relevant to all Na
+
-activated proteases involved in blood coagulation and the complement system.
Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain
Authors: Auger Catherine J. , Coss Dylan , Auger Anthony P. , Forbes-Lorman Robin M.
Published: February 2011

Although some DNA methylation patterns are altered by steroid hormone exposure in the developing brain, less is known about how changes in steroid hormone levels influence DNA methylation patterns in the adult brain. Steroid hormones act in the adult brain to regulate gene expression. Specifically, the expression of the socially relevant peptide vasopressin (AVP) within the bed nucleus of the stria terminalis (BST) of adult brain is dependent upon testosterone exposure. Castration dramatically reduces and testosterone replacement restores AVP expression within the BST. As decreases in mRNA expression are associated with increases in DNA promoter methylation, we explored the hypothesis that AVP expression in the adult brain is maintained through sustained epigenetic modifications of the AVP gene promoter. We find that castration of adult male rats resulted in decreased AVP mRNA expression and increased methylation of specific CpG sites within the AVP promoter in the BST. Similarly, castration significantly increased estrogen receptor α (ERα) mRNA expression and decreased ERα promoter methylation within the BST. These changes were prevented by testosterone replacement. This suggests that the DNA promoter methylation status of some steroid responsive genes in the adult brain is actively maintained by the presence of circulating steroid hormones. The maintenance of methylated or demethylated states of some genes in the adult brain by the presence of steroid hormones may play a role in the homeostatic regulation of behaviorally relevant systems.
Core promoter recognition complex changes accompany liver development
Authors: D’Alessio Joseph A. , Ng Raymond , Willenbring Holger , Tjian Robert
Published: February 2011

Recent studies of several key developmental transitions have brought into question the long held view of the basal transcriptional apparatus as ubiquitous and invariant. In an effort to better understand the role of core promoter recognition and coactivator complex switching in cellular differentiation, we have examined changes in transcription factor IID (TFIID) and cofactor required for Sp1 activation/Mediator during mouse liver development. Here we show that the differentiation of fetal liver progenitors to adult hepatocytes involves a wholesale depletion of canonical cofactor required for Sp1 activation/Mediator and TFIID complexes at both the RNA and protein level, and that this alteration likely involves silencing of transcription factor promoters as well as protein degradation. It will be intriguing for future studies to determine if a novel and as yet unknown core promoter recognition complex takes the place of TFIID in adult hepatocytes and to uncover the mechanisms that down-regulate TFIID during this critical developmental transition.
Three-dimensional axon morphologies of individual layer 5 neurons indicate cell type-specific intracortical pathways for whisker motion and touch
Authors: Oberlaender Marcel , Boudewijns Zimbo S. R. M. , Kleele Tatjana , Mansvelder Huibert D. , Sakmann Bert , de Kock Christiaan P. J.
Published: February 2011

The cortical output layer 5 contains two excitatory cell types, slender- and thick-tufted neurons. In rat vibrissal cortex, slender-tufted neurons carry motion and phase information during active whisking, but remain inactive after passive whisker touch. In contrast, thick-tufted neurons reliably increase spiking preferably after passive touch. By reconstructing the 3D patterns of intracortical axon projections from individual slender- and thick-tufted neurons, filled in vivo with biocytin, we were able to identify cell type-specific intracortical circuits that may encode whisker motion and touch. Individual slender-tufted neurons showed elaborate and dense innervation of supragranular layers of large portions of the vibrissal area (total length, 86.8 ± 5.5 mm). During active whisking, these long-range projections may modulate and phase-lock the membrane potential of dendrites in layers 2 and 3 to the whisking cycle. Thick-tufted neurons with soma locations intermingling with those of slender-tufted ones display less dense intracortical axon projections (total length, 31.6 ± 14.3 mm) that are primarily confined to infragranular layers. Based on anatomical reconstructions and previous measurements of spiking, we put forward the hypothesis that thick-tufted neurons in rat vibrissal cortex receive input of whisker motion from slender-tufted neurons onto their apical tuft dendrites and input of whisker touch from thalamic neurons onto their basal dendrites. During tactile-driven behavior, such as object location, near-coincident input from these two pathways may result in increased spiking activity of thick-tufted neurons and thus enhanced signaling to their subcortical targets.
Microtubule depolymerization in
Caenorhabditis elegans
touch receptor neurons reduces gene expression through a p38 MAPK pathway
Authors: Bounoutas Alexander , Kratz John , Emtage Lesley , Ma Charles , Nguyen Ken C. , Chalfie Martin
Published: February 2011

Microtubules are integral to neuronal development and function. They endow cells with polarity, shape, and structure, and their extensive surface area provides substrates for intracellular trafficking and scaffolds for signaling molecules. Consequently, microtubule polymerization dynamics affect not only structural features of the cell but also the subcellular localization of proteins that can trigger intracellular signaling events. In the nematode
Caenorhabditis elegans
, the processes of touch receptor neurons are filled with a bundle of specialized large-diameter microtubules. We find that conditions that disrupt these microtubules (loss of either the MEC-7 β-tubulin or MEC-12 α-tubulin or growth in 1 mM colchicine) cause a general reduction in touch receptor neuron (TRN) protein levels. This reduction requires a p38 MAPK pathway (DLK-1, MKK-4, and PMK-3) and the transcription factor CEBP-1. Cells may use this feedback pathway that couples microtubule state and MAPK activation to regulate cellular functions.
Differentiation of the maize subgenomes by genome dominance and both ancient and ongoing gene loss
Authors: Schnable James C. , Springer Nathan M. , Freeling Michael
Published: February 2011

Ancient tetraploidies are found throughout the eukaryotes. After duplication, one copy of each duplicate gene pair tends to be lost (fractionate). For all studied tetraploidies, the loss of duplicated genes, known as homeologs, homoeologs, ohnologs, or syntenic paralogs, is uneven between duplicate regions. In maize, a species that experienced a tetraploidy 5–12 million years ago, we show that in addition to uneven ancient gene loss, the two complete genomes contained within maize are differentiated by ongoing fractionation among diverse inbreds as well as by a pattern of overexpression of genes from the genome that has experienced less gene loss. These expression differences are consistent over a range of experiments quantifying RNA abundance in different tissues. We propose that the universal bias in gene loss between the genomes of this ancient tetraploid, and perhaps all tetraploids, is the result of selection against loss of the gene responsible for the majority of total expression for a duplicate gene pair. Although the tetraploidy of maize is ancient, biased gene loss and expression continue today and explain, at least in part, the remarkable genetic diversity found among modern maize cultivars.
Structures of the atlastin GTPase provide insight into homotypic fusion of endoplasmic reticulum membranes
Authors: Bian Xin , Klemm Robin W. , Liu Tina Y. , Zhang Miao , Sun Sha , Sui Xuewu , Liu Xinqi , Rapoport Tom A. , Hu Junjie
Published: February 2011

The generation of the tubular network of the endoplasmic reticulum (ER) requires homotypic membrane fusion that is mediated by the dynamin-like, membrane-bound GTPase atlastin (ATL). Here, we have determined crystal structures of the cytosolic segment of human ATL1, which give insight into the mechanism of membrane fusion. The structures reveal a GTPase domain and athree-helix bundle, connected by a linker region. One structure corresponds to a prefusion state, in which ATL molecules in apposing membranes interact through their GTPase domains to form a dimer with the nucleotides bound at the interface. The other structure corresponds to a postfusion state generated after GTP hydrolysis and phosphate release. Compared with the prefusion structure, the three-helix bundles of the two ATL molecules undergo a major conformational change relative to the GTPase domains, which could pull the membranes together. The proposed fusion mechanism is supported by biochemical experiments and fusion assays with wild-type and mutant full-length
Drosophila
ATL. These experiments also show that membrane fusion is facilitated by the C-terminal cytosolic tails following the two transmembrane segments. Finally, our results show that mutations in ATL1 causing hereditary spastic paraplegia compromise homotypic ER fusion.
Parent–adolescent relationships and social adjustment: The case of a collectivistic culture
Authors: Scharf Miri , Wiseman Hadas , Farah Faten
Published: February 2011

This study examined how parent–adolescent relationships are related to adolescent loneliness, interpersonal difficulties and school adjustment among Israeli Arabs. Two hundred and thirty‐one 11th graders (103 boys and 128 girls) and their homeroom teachers participated. Four groups of adolescents were identified according to parenting practice profiles: Adolescents in the harsh parenting group reported the highest levels of loneliness, those in the distant and mixed groups reported midway levels of loneliness, and those in the warm group showed the lowest degree of loneliness and the lowest levels of interpersonal problems. Overall, boys reported higher levels of peer‐related loneliness and lower levels of affinity for aloneness than girls. Gender interacted significantly with parenting group, with girls in the harsh parenting group exhibiting greater parent‐related loneliness and affinity for loneliness, while boys exhibited more peer‐related loneliness. The important role that parents play in their children's social adjustment is discussed in relation to gender and culture.
Serial Recall of Rhythms and Verbal Sequences: Impacts of Concurrent Tasks and Irrelevant Sound
Authors: Hall Debbora , Gathercole Susan E.
Published: February 2011

Rhythmic grouping enhances verbal serial recall, yet very little is known about memory for rhythmic patterns. The aim of this study was to compare the cognitive processes supporting memory for rhythmic and verbal sequences using a range of concurrent tasks and irrelevant sounds. In Experiment 1, both concurrent articulation and paced finger tapping during presentation and during a retention interval impaired rhythm recall, while letter recall was only impaired by concurrent articulation. In Experiments 2 and 3, irrelevant sound consisted of irrelevant speech or tones, changing-state or steady-state sound, and syncopated or paced sound during presentation and during a retention interval. Irrelevant speech was more damaging to rhythm and letter recall than was irrelevant tone sound, but there was no effect of changing state on rhythm recall, while letter recall accuracy was disrupted by changing-state sound. Pacing of sound did not consistently affect either rhythm or letter recall. There are similarities in the way speech and rhythms are processed that appear to extend beyond reliance on temporal coding mechanisms involved in serial-order recall.
Picking winners: W. H. and W. L. Bragg at the Royal Institution
Authors: Thomas Sir John Meurig
Published: February 2011

Apart from their extraordinary skills in attracting and nurturing outstanding co-workers and technical staff, W. H. Bragg and W. L. Bragg were extremely successful, as were some of their predecessors (notably Faraday, Dewar and Rideal) in attracting Friday Evening Discourse and other speakers to the Royal Institution. An examination of the names and subjects of the talks given in the Bragg eras shows how well their programme of events reflected the intellectual life of the nation.
Calling under pressure: short-finned pilot whales make social calls during deep foraging dives
Authors: Jensen Frants H. , Perez Jacobo Marrero , Johnson Mark , Soto Natacha Aguilar , Madsen Peter T.
Published: February 2011

Toothed whales rely on sound to echolocate prey and communicate with conspecifics, but little is known about how extreme pressure affects pneumatic sound production in deep-diving species with a limited air supply. The short-finned pilot whale (Globicephala macrorhynchus) is a highly social species among the deep-diving toothed whales, in which individuals socialize at the surface but leave their social group in pursuit of prey at depths of up to 1000 m. To investigate if these animals communicate acoustically at depth and test whether hydrostatic pressure affects communication signals, acoustic DTAGs logging sound, depth and orientation were attached to 12 pilot whales. Tagged whales produced tonal calls during deep foraging dives at depths of up to 800 m. Mean call output and duration decreased with depth despite the increased distance to conspecifics at the surface. This shows that the energy content of calls is lower at depths where lungs are collapsed and where the air volume available for sound generation is limited by ambient pressure. Frequency content was unaffected, providing a possible cue for group or species identification of diving whales. Social calls may be important to maintain social ties for foraging animals, but may be impacted adversely by vessel noise.
Disentangling the effect of genes, the environment and chance on sex ratio variation in a wild bird population
Authors: Postma Erik , Heinrich Franziska , Koller Ursina , Sardell Rebecca J. , Reid Jane M. , Arcese Peter , Keller Lukas F.
Published: February 2011

Sex ratio theory proposes that the equal sex ratio typically observed in birds and mammals is the result of natural selection. However, in species with chromosomal sex determination, the same 1 : 1 sex ratio is expected under random Mendelian segregation. Here, we present an analysis of 14 years of sex ratio data for a population of song sparrows (Melospiza melodia) on Mandarte Island, at the nestling stage and at independence from parental care. We test for the presence of variance in sex ratio over and above the binomial variance expected under Mendelian segregation, and thereby quantify the potential for selection to shape sex ratio. Furthermore, if sex ratio variation is to be shaped by selection, we expect some of this extra-binomial variation to have a genetic basis. Despite ample statistical power, we find no evidence for the existence of either genetic or environmentally induced variation in sex ratio, in the nest or at independence. Instead, the sex ratio variation observed matches that expected under random Mendelian segregation. Using one of the best datasets of its kind, we conclude that female song sparrows do not, and perhaps cannot, adjust the sex of their offspring. We discuss the implications of this finding and make suggestions for future research.
Inheritance, ecology and the evolution of the canoes of east Oceania
Authors: Beheim Bret A. , Bell Adrian V.
Published: February 2011

We consider patterns in the evolution of canoe technology in the eastern Pacific relative to three general processes: movement of canoe traits along the Polynesian settlement sequence, adaptations to local island environment, and post-settlement interaction between island groups. Using model selection methods on the distributions of canoe technology, we show that social and ecological covariates together consistently outperform each considered individually, though knowledge of island area and post-settlement trading spheres does not add explanatory power. In particular, decorative canoe traits are not effectively explained by either our ecological or transmission models. We also estimate negative effects from both settlement sequence and island geomorphology, consistent with the die-off of particular canoe designs on resource-rich high island groups such as Hawaii and New Zealand. This decline in measured traits may be owing to the lifting of ecological constraints on population size or building materials.
Assured fitness returns in a social wasp with no worker caste
Authors: Lucas Eric R. , Field Jeremy
Published: February 2011

The theory of assured fitness returns proposes that individuals nesting in groups gain fitness benefits from effort expended in brood-rearing, even if they die before the young that they have raised reach independence. These benefits, however, require that surviving nest-mates take up the task of rearing these young. It has been suggested that assured fitness returns could have favoured group nesting even at the origin of sociality (that is, in species without a dedicated worker caste). We show that experimentally orphaned brood of the apoid waspMicrostigmus nigrophthalmuscontinue to be provisioned by surviving adults for at least two weeks after the orphaning. This was the case for brood of both sexes. There was no evidence that naturally orphaned offspring received less food than those that still had mothers in the nest. Assured fitness returns can therefore represent a real benefit to nesting in groups, even in species without a dedicated worker caste.
Polymethylated Myricetin in Trichomes of the Wild Tomato Species Solanum habrochaites and Characterization of Trichome-Specific 3′/5′- and 7/4′-Myricetin O-Methyltransferases
Authors: Schmidt Adam , Li Chao , Shi Feng , Jones A. Daniel , Pichersky Eran
Published: February 2011

Flavonoids are a class of metabolites found in many plant species. They have been reported to serve several physiological roles, such as in defense against herbivores and pathogens and in protection against harmful ultraviolet radiation. They also serve as precursors of pigment compounds found in flowers, leaves, and seeds. Highly methylated, nonglycosylated derivatives of the flavonoid myricetin flavonoid, have been previously reported from a variety of plants, but O-methyltransferases responsible for their synthesis have not yet been identified. Here, we show that secreting glandular trichomes (designated types 1 and 4) and storage glandular trichomes (type 6) on the leaf surface of wild tomato (Solanum habrochaites accession LA1777) plants contain 3,7,3′-trimethyl myricetin, 3,7,3′,5′-tetramethyl myricetin, and 3,7,3′,4′,5′-pentamethyl myricetin, with gland types 1 and 4 containing severalfold more of these compounds than type 6 glands and with the tetramethylated compound predominating in all three gland types. We have also identified transcripts of two genes expressed in the glandular trichomes and showed that they encode enzymes capable of methylating myricetin at the 3′ and 5′ and the 7 and 4′ positions, respectively. Both genes are preferentially expressed in secreting glandular trichome types 1 and 4 and to a lesser degree in storage trichome type 6, and the levels of the proteins they encode are correspondingly higher in types 1 and 4 glands compared with type 6 glands.