bluuebunny/crossref_metadata_2025 huggingface dataset:
The spatial and temporal patterns of odors sampled by lobsters and crabs in a turbulent plume
Authors: Reidenbach Matthew A. , Koehl M. A. R.
Published: August 2011

Odors are dispersed across aquatic habitats by turbulent water flow as filamentous, intermittent plumes. Many crustaceans sniff (take discrete samples of ambient water and the odors it carries) by flicking their olfactory antennules. We used planar laser-induced fluorescence to investigate how flicking antennules of different morphologies (long antennules of spiny lobsters, Panulirus argus; short antennules of blue crabs, Callinectes sapidus) sample fluctuating odor signals at different positions in a turbulent odor plume in a flume to determine whether the patterns of concentrations captured can provide information about an animal's position relative to the odor source. Lobster antennules intercept odors during a greater percentage of flicks and encounter higher peak concentrations than do crab antennules, but because crabs flick at higher frequency, the duration of odor-free gaps between encountered odor pulses is similar. For flicking antennules there were longer time gaps between odor encounters as the downstream distance to the odor source decreases, but shorter gaps along the plume centerline than near the edge. In contrast to the case for antennule flicking, almost all odor-free gaps were <500 ms at all positions in the plume if concentration was measured continuously at the same height as the antennules. Variance in concentration is lower and mean concentration is greater near the substratum, where leg chemosensors continuously sample the plume, than in the water where antennules sniff. Concentrations sampled by legs increase as an animal nears an odor source, but decrease for antennules. Both legs and antennules encounter higher concentrations near the centerline than at the edge of the plume.
Developmental expression of calcium transport proteins in extraembryonic membranes of oviparous and viviparous Zootoca vivipara (Lacertilia, Lacertidae)
Authors: Stewart James R. , Ecay Tom W. , Heulin Benoit , Fregoso Santiago P. , Linville Brent J.
Published: August 2011

The eggshell of oviparous lizards is a significant source of calcium for embryos, whereas the eggshell of viviparous lizards, when present, contains little calcium. In view of the potential cost to embryonic nutrition occasioned by the loss of eggshell calcium, the large number of independent origins of viviparity among lizards is surprising. Concomitant evolution of viviparity and calcium placentotrophy would ameliorate the loss of eggshell calcium, but a mechanism linking these events has yet to be discovered. Zootoca vivipara, a lizard with geographic variation in its mode of parity, is an excellent model for studying mechanisms of calcium transport to oviparous and viviparous embryos because each is highly dependent on calcium secreted by the uterus (eggshell or placenta) and ontogenetic patterns of embryonic calcium mobilization are similar. We compared developmental expression of the calcium transport protein calbindin-D28K in yolk splanchnopleure and chorioallantoic membranes of oviparous and viviparous embryos to test the hypothesis that the mechanism of calcium transport does not differ between modes of parity. We found that the ontogenetic pattern of protein expression is similar between reproductive modes and is correlated with calcium uptake from yolk and either eggshell or placenta. Calbindin-D28K is localized in the chorionic epithelium of embryos of both reproductive modes. These findings suggest that the embryonic calcium transport machinery is conserved in the transition between reproductive modes and that an adaptation of oviparous embryos for calcium uptake from eggshells functions similarly to transport calcium directly from uterine secretions.
Evolution of limb bone loading and body size in varanid lizards
Authors: Clemente Christofer J. , Withers Philip C. , Thompson Graham , Lloyd David
Published: August 2011

Geometric scaling predicts that stresses on limb bones and muscles should increase with body size. Mammals counter this size-related increase in stress partially through changes in bone geometry, but largely through changes in posture, with larger species having a more erect stance. However, the ability to counter size-related stresses in this fashion may be limited to those taxa that have a parasagittal gait (such as mammals), where legs are swung underneath the body. We examined locomotor kinematics for 11 species of varanid lizards (from 0.04 to 8 kg body mass) that have a sprawling gait, to determine how they moderate size-related stresses. Posture, as indicated by femur adduction and hip heights, did not change significantly with body size, beyond that expected from geometrical scaling. Instead, lizards mitigated size-related increases in stress by increasing duty factor and possibly reducing femur rotation. Incorporating these factors in biomechanical models predicted that both bending (∝M0.016, where M is mass) and torsional (∝M–0.049) stresses should be nearly independent of body size over the size range examined. However, increasing duty factor and reducing femur rotation probably have deleterious effects on speed, and this difference in kinematics with size may explain why speed scales lower for sprawling lizards than for parasagittal mammals (∝M0.17 and ∝M0.24, respectively). Further, paralleling conclusions for the synapsid lineage, these findings suggest that evolution from sprawling to upright posture did not occur in archosaurs as a response to larger size; rather, these archosaurs likely became upright first and larger later.
Hypoxia-induced mobilization of stored triglycerides in the euryoxic goby Gillichthys mirabilis
Authors: Gracey Andrew Y. , Lee Tsung-Han , Higashi Richard M. , Fan Teresa
Published: August 2011

Environmental hypoxia is a common challenge that many aquatic organisms experience in their habitat. Responding to hypoxia requires metabolic reprogramming so that energy-demanding processes are regulated to match available energy reserves. In this study we explored the transcriptional control of metabolic reorganization in the liver of a hypoxia-tolerant burrow-dwelling goby, Gillichthys mirabilis. Gene expression data revealed that pathways associated with triglyceride hydrolysis were upregulated by hypoxia whereas pathways associated with triglyceride synthesis were downregulated. This finding was supported by tissue histology, which showed that the size of hepatic lipid droplets declined visibly during exposure to hypoxia. Proton nuclear magnetic resonance analysis confirmed the mobilization of hepatic triglycerides, which declined 2.7-fold after 5 days of hypoxia. The enzyme, adipose triglyceride lipase, was implicated in the mobilization of triglycerides because its expression increased at the level of both transcript and protein. This observation raises questions regarding the regulation of fat metabolism during hypoxia and the role played by the hypoxia-responsive gene leptin.
Ibuprofen-related renal tubular acidosis in pregnancy
Authors: Mallett Andrew , Lynch Matthew , John George T , Healy Helen , Lust Karin
Published: August 2011

Ibuprofen-related renal tubular acidosis (RTA) has not been previously described in pregnancy but its occurrence outside of pregnancy is being increasingly described. In this case, a 34-year-old woman presented in the third trimester of pregnancy with Type 1 or distal RTA related to ibuprofen and codeine abuse. It was complicated by acute on chronic renal dysfunction and hypokalemia. Delivery at 37 weeks gestation due to concerns of evolving preeclampsia resulted in the birth of a healthy neonate. RTA and hypokalemia were remediated and ibuprofen and codeine abuse ceased. Some renal dysfunction however continued. Thorough and repeated history taking as well as vigilance for this condition is suggested.
Implication of Ccr4-Not complex function in mRNA quality control in Saccharomyces cerevisiae
Authors: Assenholt Jannie , Mouaikel John , Saguez Cyril , Rougemaille Mathieu , Libri Domenico , Jensen Torben Heick
Published: August 2011

Production of messenger ribonucleoprotein particles (mRNPs) is subjected to quality control (QC). In Saccharomyces cerevisiae, the RNA exosome and its cofactors are part of the nuclear QC machinery that removes, or stalls, aberrant molecules, thereby ensuring that only correctly formed mRNPs are exported to the cytoplasm. The Ccr4-Not complex, which constitutes the major S. cerevisiae cytoplasmic deadenylase, has recently been implied in nuclear exosome–related processes. Consistent with a possible nuclear function of the complex, the deletion or mutation of Ccr4-Not factors also elicits transcription phenotypes. Here we use genetic depletion of the Mft1p protein of the THO transcription/mRNP packaging complex as a model system to link the Ccr4-Not complex to nuclear mRNP QC. We reveal strong genetic interactions between alleles of the Ccr4-Not complex with both the exosomal RRP6 and MFT1 genes. Moreover, Rrp6p-dependent in vivo QC phenotypes of Δmft1 cells can be rescued by codeletion of several Ccr4-Not components. We discuss how the Ccr4-Not complex may connect with the mRNP QC pathway.
Bivalirudin for Anticoagulation During Hypothermic Cardiopulmonary Bypass and Recombinant Factor VIIa for Iatrogenic Coagulopathy
Authors: Nagle Erin L , Tsu Laura V , Dager William E
Published: August 2011

Objective:

To describe management of anticoagulation with a decreased dose requirement of bivalirudin during cardiopulmonary bypass using deep hypothermic circulatory arrest (DHCA) and the reversal of the ensuing coagulopathy with recombinant factor VIIa (rFVIIa).

Case Summary:

A 46-year-old male developed chest pain, hypertension, and an aortic aneurysm requiring urgent surgical repair. At the time of surgery, the patient reported an allergy to heparin, so bivalirudin was used for anticoagulation (1 mg/kg loading dose, followed by intermittent infusions of 1.25-2.5 mg/kgm over the 5 hours of cardiopulmonary bypass). When the cooling process was initiated, bivalirudin was stopped in anticipation of loss of the clotting cascade function and potential slowing of drug elimination. Bivalirudin was restarted for 45 minutes during the rewarming period because of concern for potential clot formation in the bypass circuit with recovery of hemostasis; it was again stopped due to the patient's activated clotting time (ACT) of 504 seconds. Despite this measure, diffuse and severe coagulopathy was observed upon rewarming, with ACTs longer than 999 seconds. Although multiple blood products were administered, visualization of a clot in the surgical field was not notable. A total dose of rFVIIa 20 μg/kg was administered, resulting in visual clot formation within 4 minutes. On postsurgical day 6, bilateral asymptomatic distal deep vein thromboses were noted on imaging; on postsurgical day 8, fondaparinux 2.5 mg subcutaneously was administered daily to prevent clot extension. The patient was discharged on postoperative day 23 with no acute issues and no further anticoagulants.

Discussion:

Alternative anticoagulation agents such as bivalirudin are used in patients who have an allergy or contraindication to heparin. We propose that prolonged coagulopathy after the induction of hypothermia is due to decreased clotting cascade function as well as stowing of protease activity resulting in decreased bivalirudin elimination. We observed a positive response to low-dose rFVIIa, which could be due to activation of the extrinsic pathway and/or a thrombin burst, resulting in hemostasis. Currently, there is limited evidence supporting reversal of direct thrombin inhibitors with rFVIIa.

Conclusions:

In the setting of DHCA, bivalirudin should be used cautiously, with frequent monitoring of the ACTs and potential cessation of the infusion in anticipation of prolonged drug effect with subsequent potential coagulopathy. If coagulopathy ensues, use of low-dose rFVIIa may be an option to initiate hemostasis. When using rFVIIa, it is important to consider the risk of thrombosis and monitor patients accordingly.
Inpatient and Outpatient Occurrence of Deep Vein Thrombosis and Pulmonary Embolism and Thromboprophylaxis Following Selected At-Risk Surgeries
Authors: Amin Alpesh N , Lin Jay , Thompson Stephen , Wiederkehr Daniel
Published: August 2011

Background

Despite evidence-based guidelines on prevention, many surgical patients remain at risk of deep vein thrombosis (DVT) and pulmonary embolism (PE).

Objective:

To quantify the provision of thromboprophylaxis and proportion of US surgical patients who develop DVT/PE, both in the hospital and postdischarge.

Methods:

This study was an observational, retrospective database analysis of national managed care data. Data were extracted from the Premier Perspective-i3 Pharma Informatics linked database on patients hospitalized between January 2005 and November 2007 for orthopedic surgery or major abdominal surgery. Patients were included if they were aged 18 years or older at the time of hospitalization and had at least 6 months of continuous plan enrollment prior to index hospitalization. Patients discharged to an acute care facility or with atrial fibrillation were excluded. Prophylaxis status was evaluated during index hospitalization and for 14 days postdischarge. The proportion of patients who developed DVT/PE was calculated during index hospitalization and for 30 days postdischarge.

Results:

The analysis included 19,581 patients following major abdominal surgery and 5315 patients following orthopedic surgery. Inpatient pharmacologic or mechanical thromboprophylaxis was received by 58.7% of abdominal surgery patients and 85.0% of orthopedic surgery patients; outpatient pharmacologic prophylaxis was received by 1.6% and 58.4% of patients, respectively. Total mean (SD) prophylaxis duration was 1.7 (3.7) days following abdominal surgery and 13.0 (11.6) days following orthopedic surgery. The proportion of abdominal surgery patients who developed symptomatic DVT/PE was 1.6%: 3.1% of orthopedic surgery patients developed symptomatic DVT/PE, with almost 40% of the events occurring postdischarge.

Conclusions:

Continued efforts are needed to prevent DVT/PE after abdominal and orthopedic surgery. Initiatives that encourage outpatient prophylaxis must ensure that appropriate prophylaxis of adequate duration is prescribed to all at-risk surgical patients to further reduce DVT/PE across the continuum of care. Pharmacists can play an important role in optimizing continuity of patient care in the prevention of DVT, in providing anticoagulation services that can help reduce the incidence of DVT/PE and bleeding complications, and in helping hospitals achieve performance measures.
Montelukast for Symptom Control of Interstitial Cystitis
Authors: Traut Jamie L , MacDonald Erin S , Spangler Mikayla L , Saxena Shailendra
Published: August 2011

Objective:

To describe the effects of montelukast, a leukotriene receptor antagonist commonly used in the treatment of allergic rhinitis and asthma, on the symptoms of interstitial cystitis (IC).

Case Summary:

A 64-year-old male had a history of IC with previous trials of solifenacin, dutasteride, and tamsulosin and little improvement in IC symptom reduction. When montelukast 10 mg was initiated for allergic rhinitis symptoms, a substantial improvement in urinary urgency and pain during therapy was noted. This improvement subsequently disappeared when montelukast was stopped.

Discussion:

IC, a rare occurrence in the male population, is related to an inflammatory process and has also been associated with inappropriate leukotriene release, which is the target of montelukast therapy. In general, treatment for IC Includes systemic medical therapy, local bladder treatment, surgical and neurosurgical procedures, and intravesical drug installation. Currently, montelukast is Food and Drug Administration approved for use in the treatment and prevention of mild-to-moderate asthma and exercise-induced asthma, as well as treatment of seasonal and perennial allergic rhinitis. While montelukast treatment did not cure the patient's IC, it improved his quality of life through substantial symptomatic relief, including less pain and urgency.

Conclusions:

Montelukast may be an effective treatment option in the management of interstitial cystitis. Further research is needed to substantiate this novel use.
Single-Agent, Broad-Spectrum Fluoroquinolones for the Outpatient Treatment of Low-Risk Febrile Neutropenia
Authors: Cooper Maryann R , Durand Cheryl R , Beaulac Matthew T , Steinberg Michael
Published: August 2011

Objective:

To evaluate the use of oral, single-agent, broad-spectrum fluoroquinolones in the treatment of low-risk febrile neutropenia (FN).

Data Sources:

MEDLINE via Ovid (1948 to May, week 3, 2011) and EMBASE (1980 to 2011, week 21) were searched using the terms febrile neutropenia, fluoroquinolone, quinolone derivative, levofloxacin, moxifloxacin, and neoplasm. References of selected articles, review articles, and treatment guidelines were reviewed.

Study Selection Ano Data Extraction:

Trials evaluating the efficacy of oral, single-agent, broad-spectrum fluoroquinolones in the treatment of chemotherapy-induced FN were included if the majority of patients in the study had low-risk FN. Trials involving pediatric patients, non-Food and Drug Administration-approved fluoroquinolones, or monotherapy with ciprofloxacin or ofloxacin were excluded. Data extracted included study design, patient demographics, antiinfective regimens, and treatment outcomes.

Data Synthesis:

Four clinical trials were included. One trial compared levofloxacin with piperacillin/tazobactam with a success rate (afebrile at 72 hours) of 76.5% in the levofloxacin group compared with 88.3% in the piperacillin/tazobactam group. This trial was not limited to low-risk patients. The remaining 3 trials investigated moxifloxacin monotherapy in low-risk patients. Two of these were noncontrolled trials with success rates (afebrile at 5 days) of 91 % and 95%. The final trial randomized patients to moxifloxacin or ceftriaxone and had success rates (hospital discharge at 48 hours) of 79.2% and 73.9%, respectively. In all 4 trials, treatment of FN with levofloxacin or moxifloxacin was deemed to be safe and effective. Although all studies had positive results, they were limited by small sample sizes and the absence of universal use of control comparisons.

Conclusions:

Use of oral, single-agent, broad-spectrum fluoroquinolones for outpatient treatment of FN in low-risk patients has shown promising results. At this time, this type of therapy should be limited to low-risk patients. Future clinical trials should include larger sample sizes and a comparison with existing first-line oral therapy–oral ciprofloxacin plus amoxicillin/clavulanate.
Porous carbon layers for counter electrodes in dye-sensitized solar cells: Recent advances and a new screen-printing method
Authors: Ito Seigo , Mikami Yuuki
Published: August 2011

We review the recent literature on carbon catalyst layers for dye-sensitized solar cells (DSCs), and then report an improved fabrication method for screen-printed carbon counter electrodes. The carbon-printing ink was prepared by mixing carbon black, TiO2 nanoparticles, α-terpineol, and ethyl cellulose using a mortar, an ultrasonic homogenizer, and a rotary evaporator. Scanning electron microscopy (SEM) showed that the resulting screen-printed carbon layers were flatter and smoother at nano- and micro-scales than a carbon layer prepared using water-based ink. The photovoltaic performance of the screen-printed catalyst layers was similar to the photoenergy conversion of platinum counter electrodes. The highest cell efficiency with a carbon counter electrode was 7.11 % at a light intensity of 100 mW cm-2.
Ligand-independent activation of the arylhydrocarbon receptor by ETK (Bmx) tyrosine kinase helps MCF10AT1 breast cancer cells to survive in an apoptosis-inducing environment
Authors: Fujisawa Yasuko , Li Wen , Wu Dalei , Wong Patrick , Vogel Christoph , Dong Bin , Kung Hsing-Jien , Matsumura Fumio
Published: August 2011

It has been reported that the arylhydrocarbon receptor (AHR) is overexpressed in certain types of breast tumors. However, so far no concrete evidence has been provided yet as to why and how the overexpressed AHR in those cancer cells is functionally activated without exogenous ligands. Here we show that the AHR was functionally activated when estrogen receptor-negative, AHR overexpressing MCF10AT1 human breast cancer cells (designated P20E) were subjected to serum starvation. Transfection of cells with ETK-KQ, a plasmid for kinase-dead epithelial and endothelial tyrosine kinase (ETK), attenuated this AHR activation. Artificial over-expression of ETK in P20E cells through transfection with wild-type ETK plasmid (ETK-wt) caused up-regulation of cytochrome P4501a1 (CYP1A1; a marker of functional activation of AHR). Furthermore, ablation of ETK expression by a specific antisense oligonucleotide or AG879, a specific inhibitor of ETK kinase suppressed activation of AHR induced by omeprazole, a strong ligand-independent activator of AHR. Activation of ETK in those cells conferred them resistance to UVB- as well as doxorubicin-induced apoptosis, both of which were reversed by ETK-KQ. Together, these findings support our conclusion that ETK is the tyrosine kinase responsible for the functional activation of the AHR in these mammary epithelial cells.
Functional and evolutional implications of natural channel-enzyme fusion proteins
Authors: Song Jie , Wu Binghua , Beitz Eric
Published: August 2011

Channeling of ions or substrates across membranes and enzymatic activity are two highly distinct biochemical concepts. They are usually studied by different research groups, which focus on either subject. Nature has provided a challenge for specialized scientists by fusing genes coding for a transmembrane channel domain with an enzyme domain. There are examples of fusion proteins consisting of an N-terminal ion channel or sensor and a C-terminal, cytosolic kinase domain (or other enzymes involved in signaling) of which either domain may influence the functionality of the other. The physiological role of such fusions may reside in coupling ion flux or membrane potential sensing to cellular responses or vice-versa. Other examples can be found in metabolism. We have identified and characterized an ar-senite-conducting aquaglyceroporin carrying a C-terminal ar-senate reductase domain. Here, a function in the detoxification of arsenic is obvious, with the enzyme domain generating the substrate for the channel domain, which immediately shuttles the toxic metabolite out of the cell. We see two advantages in this latter concept: lowering of the cellular toxicity due to rapid release of the substrate and energetic coupling of the reaction enthalpy to extrusion due to high local substrate gradients. In this overview, we summarize and discuss the current view on functional and physiological aspects of channel/enzyme fusion proteins.
Evaluation of the Testing and Analysis Methods in ASTM E2760-10 Creep-Fatigue Crack Growth Testing Standard for a Range of Steels
Authors: Mehmanparast A. , Davies C. M. , Nikbin K. M.
Published: August 2011

The development of the ASTM E2760-10, “Creep/Fatigue Crack Growth Testing” standard has initiated a phase of testing, analysis, and round robin initiatives associated with high temperature cyclic loading crack growth tests. Creep and fatigue are two complex independent mechanisms which may assist each other to drive the crack. A simplification of the macro creep/fatigue crack growth response of structures is therefore required. Using a linear cumulative damage method, as proposed in ASTM E2760, and other codes of practice, data for a range of steels are analysed. Limited crack growth data, using test methods similar to ASTM E2760, from previous collaborative projects for a range of steels are presented and analysed to identify the difficulties in the process. Creep-fatigue crack growth tests at frequencies ranging from 10 to 0.001 Hz are examined to consider the testing methodologies and in order to assess the effect of data scatter, dwell times, and the interaction region between creep crack growth (CCG) and fatigue crack growth mechanisms. Given the limited data available and the level of scatter, it can still be shown that the linear cumulative summation of static and high frequency data may be sufficient to predict creep/fatigue interaction both in terms of C* and ΔK, and the level of creep ductility will dictate appropriateness of the correlating parameter employed. Finally, in order to show that the level of data scatter can be dealt with in a predictive manner, the crack initiation and growth rates are also analysed using the NSW CCG model.
MMP2-9 Cleavage of Dystroglycan Alters the Size and Molecular Composition of Schwann Cell Domains
Authors: Court Felipe A. , Zambroni Desirée , Pavoni Ernesto , Colombelli Cristina , Baragli Chiara , Figlia Gianluca , Sorokin Lydia , Ching William , Salzer James L. , Wrabetz Lawrence , Feltri M. Laura
Published: August 2011

Myelinating glial cells exhibit a spectacular cytoarchitecture, because they polarize on multiple axes and domains. How this occurs is essentially unknown. The dystroglycan–dystrophin complex is required for the function of myelin-forming Schwann cells. Similar to other tissues, the dystroglycan complex in Schwann cells localizes with different dystrophin family members in specific domains, thus promoting polarization. We show here that cleavage of dystroglycan by matrix metalloproteinases 2 and 9, an event that is considered pathological in most tissues, is finely and dynamically regulated in normal nerves and modulates dystroglycan complex composition and the size of Schwann cell compartments. In contrast, in nerves of Dy2j/2jmice, a model of laminin 211 deficiency, metalloproteinases 2 and 9 are increased, causing excessive dystroglycan cleavage and abnormal compartments. Pharmacological inhibition of cleavage rescues the cytoplasmic defects of Dy2j/2jSchwann cells. Thus, regulated cleavage may be a general mechanism to regulate protein complex composition in physiological conditions, whereas unregulated processing is pathogenic and a target for treatment in disease.
p38α and p38β Mitogen-Activated Protein Kinases Determine Cholinergic Transdifferentiation of Sympathetic Neurons
Authors: Loy Bernhard , Apostolova Galina , Dorn Roland , McGuire Victoria A. , Arthur J. Simon C. , Dechant Georg
Published: August 2011

Although the p38 mitogen-activated protein kinases are active in many neuronal populations in the peripheral and central nervous systems, little is known about the physiological functions of p38 in postmitotic neurons. We report that p38 activity determinesin vitroandin vivothe switch from noradrenergic to cholinergic neurotransmission that occurs in sympathetic neurons on exposure to the neuropoietic cytokines CNTF and LIF. This transdifferentiation serves as a model for the plastic mechanisms that enable mature neurons to change some of their central functions without passing through the cell cycle. We demonstrate that in postmitotic neurons, p38 and STAT pathways are concurrently activated by neuropoietic cytokine treatment for at least 12 h overlapping with changes in neurotransmitter marker gene expression. Inhibition of p38 blocks the upregulation of the nuclear matrix protein Satb2 and of cholinergic markers by CNTF without affecting STAT3 phosphorylation. Conversely, overexpression of p38α or β in the absence of cytokines stimulates cholinergic marker expression. The neurotransmitter switchin vitrois impaired in neurons isolated from p38β−/−mice. Consistent with thesein vitroresults, a substantial loss of cells expressing cholinergic properties is observedin vivoin the stellate ganglion of mature mice deficient in the p38β isoform.
Fast and Slow Gamma Rhythms Are Intrinsically and Independently Generated in the Subiculum
Authors: Jackson Jesse , Goutagny Romain , Williams Sylvain
Published: August 2011

Gamma rhythms are essential for memory encoding and retrieval. Despite extensive study of these rhythms in the entorhinal cortex, dentate gyrus, CA3, and CA1, almost nothing is known regarding their generation and organization in the structure delivering the most prominent hippocampal output: the subiculum. Here we show using a complete rat hippocampal preparationin vitrothat the subiculum intrinsically and independently generates spontaneous slow (25–50 Hz) and fast (100–150 Hz) gamma rhythms during the rising phase and peak of persistent subicular theta rhythms. These two gamma frequencies are phase modulated by theta rhythms without any form of afferent input from the entorhinal cortex or CA1. Subicular principal cells and interneurons phase lock to both fast and slow gamma, and single cells are independently phase modulated by each form of gamma rhythm, enabling selective participation in neural synchrony at both gamma frequencies at different times. Fast GABAergic inhibition is required for the generation of fast gamma, whereas slow gamma is generated by excitatory and inhibitory mechanisms. In addition, the transverse subicular axis exhibits gamma rhythm topography with faster gamma coupling arising in the distal subiculum region. The subiculum therefore possesses a unique intrinsic circuit organization that can autonomously regulate the timing and topography of hippocampal output synchronization. These results suggest the subiculum is a third spontaneous gamma generator in the hippocampal formation (in addition to CA3 and the entorhinal cortex), and these gamma rhythms likely play an active role in mediating the flow of information between the hippocampus and multiple cortical and subcortical brain regions.
Sex Differences in the Use of Anticipatory Brain Activity to Encode Emotional Events
Authors: Galli Giulia , Wolpe Noham , Otten Leun J.
Published: August 2011

Women and men differ in the way they experience emotional events. Previous work has indicated that the impact of an emotional event depends on how it is anticipated. Separately, it has been shown that anticipation affects memory formation. Here, we assessed whether anticipatory brain activity influences the encoding of emotional events into long-term memory and, in addition, how biological sex affects the use of such activity. Electrical brain activity was recorded from the scalps of healthy men and women while they performed an incidental encoding task (indoor/outdoor judgments) on pleasant, unpleasant, and neutral pictures. Pictures were preceded by a cue that indicated the valence of the upcoming item. Memory was tested after a 20 min delay with a recognition task incorporating the remember/know procedure. Brain activity before picture onset predicted later memory of an event. Crucially, the role of anticipatory activity depended entirely on the valence of a picture and the sex of an individual. Right-lateralized anticipatory activity selectively influenced the encoding of unpleasant pictures in women, but not in men. These findings indicate that anticipatory processes influence the way in which women encode negative events into memory. The selective use of such activity may indicate that anticipatory activity is one mechanism by which individuals regulate their emotions.
Memory-Guided Learning: CA1 and CA3 Neuronal Ensembles Differentially Encode the Commonalities and Differences between Situations
Authors: Bahar Amir S. , Shirvalkar Prasad R. , Shapiro Matthew L.
Published: August 2011

Memory influences learning, but how neural signals support such transfer are unknown. To investigate these mechanisms, we trained rats to perform a standard spatial memory task in a plus maze and tested how training affected learning and neural coding in two new task variants. A switch task exchanged the start and goal locations in the same environment, whereas, an altered environment task contained unfamiliar local and distal cues. Learning was facilitated in both variants compared with the acquisition of the standard task. In the switch task, performance was largely maintained, and was accompanied by immediate and stable place-field remapping. Place-field maps in CA1 were anticorrelated in the standard and switch sessions, and the anticorrelation covaried with switch performance. Simultaneously, CA3 maps were uncorrelated overall in the standard and switch, though many CA3 cells had fields in shifted locations in the same maze arms. In the altered environment, performance was initially impaired, and place fields changed dynamically. CA1 fields were initially unstable, and their stabilization correlated with improving performance. Most CA3 cells, however, stopped firing on the maze in the altered environment, even as the same cells maintained prominent fields in standard sessions recorded before and after. CA1 and CA3 place fields thus revealed different coding dynamics that correlated with both learning and memory performance. Together, CA1 and CA3 ensembles represented the similarities and differences between new and familiar situations through concurrent rate and place remapping.
Anatomical Evidence for the Involvement of the Macaque Ventrolateral Prefrontal Area 12r in Controlling Goal-Directed Actions
Authors: Borra Elena , Gerbella Marzio , Rozzi Stefano , Luppino Giuseppe
Published: August 2011

The macaque ventrolateral prefrontal (VLPF) area 12r is thought to be involved in higher-order nonspatial information processing. We found that this area is connectionally heterogeneous, and the intermediate part is fully integrated in a cortical network involved in selecting and controlling object-oriented hand and mouth actions. Specifically, intermediate area 12r displayed dense connections with the caudal half of area 46v and orbitofrontal areas and relatively strong extraprefrontal connections involving the following: (1) the hand- and mouth-related ventral premotor area F5 and the anterior intraparietal (AIP) area, jointly involved in visuomotor transformations for grasping; (2) the SII sector that is connected to AIP and F5; (3) a sector of the inferotemporal area TEa/m, primarily corresponding to the sector densely connected to AIP; and (4) the insular and opercular frontal sectors, which are connected to AIP and F5. This connectivity pattern differed markedly from those of the caudal and rostral parts of area 12r. Caudal area 12r displayed dense connections with the caudal part of the VLPF, including oculomotor areas 8/FEF and 45B, relatively weak orbitofrontal connections and extraprefrontal connections limited to the inferotemporal cortex. Rostral area 12r displayed connections mostly with rostral prefrontal and orbitofrontal areas and relatively weaker connections with the fundus and the upper bank of the superior temporal sulcus. The present data suggest that the intermediate part of area 12r is involved in nonspatial information processing related to object properties and identity, for selecting and controlling goal-directed hand and mouth actions.
Ultrafast Population Encoding by Cortical Neurons
Authors: Tchumatchenko Tatjana , Malyshev Aleksey , Wolf Fred , Volgushev Maxim
Published: August 2011

The processing speed of the brain depends on the ability of neurons to rapidly relay input changes. Previous theoretical and experimental studies of the timescale of population firing rate responses arrived at controversial conclusions, some advocating an ultrafast response scale but others arguing for an inherent disadvantage of mean encoded signals for rapid detection of the stimulus onset. Here we assessed the timescale of population firing rate responses of neocortical neurons in experiments performed in the time domain and the frequency domainin vitroandin vivo. We show that populations of neocortical neurons can alter their firing rate within 1 ms in response to somatically delivered weak current signals presented on a fluctuating background. Signals with amplitudes of miniature postsynaptic currents can be robustly and rapidly detected in the population firing. We further show that population firing rate of neurons of rat visual cortexin vitroand cat visual cortexin vivocan reliably encode weak signals varying at frequencies up to ∼200–300 Hz, or ∼50 times faster than the firing rate of individual neurons. These results provide coherent evidence for the ultrafast, millisecond timescale of cortical population responses. Notably, fast responses to weak stimuli are limited to the mean encoding. Rapid detection of current variance changes requires extraordinarily large signal amplitudes. Our study presents conclusive evidence showing that cortical neurons are capable of rapidly relaying subtle mean current signals. This provides a vital mechanism for the propagation of rate-coded information within and across brain areas.
Functional Heterogeneity of Macaque Lateral Intraparietal Neurons
Authors: Premereur Elsie , Vanduffel Wim , Janssen Peter
Published: August 2011

The macaque lateral intraparietal area (LIP) has been implicated in many cognitive processes, ranging from saccade planning and spatial attention to timing and categorization. Importantly, different research groups have used different criteria for including LIP neurons in their studies. While some research groups have selected LIP neurons based on the presence of memory-delay activity, other research groups have used other criteria such as visual, presaccadic, and/or memory activity. We recorded from LIP neurons that were selected based on spatially selective saccadic activity but regardless of memory-delay activity in macaque monkeys. To test anticipatory climbing activity, we used a delayed visually guided saccade task with a unimodal schedule of go-times, for which the conditional probability that the go-signal will occur rises monotonically as a function of time. A subpopulation of LIP neurons showed anticipatory activity that mimicked the subjective hazard rate of the go-signal when the animal was planning a saccade toward the receptive field. A large subgroup of LIP neurons, however, did not modulate their firing rates according to the subjective hazard function. These non-anticipatory neurons were strongly influenced by salient visual stimuli appearing in their receptive field, but less so by the direction of the impending saccade. Thus, LIP contains a heterogeneous population of neurons related to saccade planning or visual salience, and these neurons are spatially intermixed. Our results suggest that between-study differences in neuronal selection may have contributed significantly to the findings of different research groups with respect to the functional role of area LIP.
Synaptic Autoregulation by Metalloproteases and γ-Secretase
Authors: Restituito Sophie , Khatri Latika , Ninan Ipe , Mathews Paul M. , Liu Xin , Weinberg Richard J. , Ziff Edward B.
Published: August 2011

The proteolytic machinery comprising metalloproteases and γ-secretase, an intramembrane aspartyl protease involved in Alzheimer's disease, cleaves several substrates in addition to the extensively studied amyloid precursor protein. Some of these substrates, such as N-cadherin, are synaptic proteins involved in synapse remodeling and maintenance. Here we show, in rats and mice, that metalloproteases and γ-secretase are physiologic regulators of synapses. Both proteases are synaptic, with γ-secretase tethered at the synapse by δ-catenin, a synaptic scaffolding protein that also binds to N-cadherin and, through scaffolds, to AMPA receptor and a metalloprotease. Activity-dependent proteolysis by metalloproteases and γ-secretase takes place at both sides of the synapse, with the metalloprotease cleavage being NMDA receptor-dependent. This proteolysis decreases levels of synaptic proteins and diminishes synaptic transmission. Our results suggest that activity-dependent substrate cleavage by synaptic metalloproteases and γ-secretase modifies synaptic transmission, providing a novel form of synaptic autoregulation.
Effects of Training of Processing Speed on Neural Systems
Authors: Takeuchi Hikaru , Taki Yasuyuki , Hashizume Hiroshi , Sassa Yuko , Nagase Tomomi , Nouchi Rui , Kawashima Ryuta
Published: August 2011

Processing speed (PS) training improves performance on untrained PS tasks in the elderly. However, PS training's effects on the PS of young adults and on neural mechanisms are still unknown. In humans, we investigated this issue using psychological measures, voxel-based morphometry, then-back task [a typical task for functional magnetic resonance imaging (fMRI) studies with conditions of 0-back (simple cognitive processes) and 2-back tasks (working memory; WM)], resting-state fMRI for the analysis of functional connectivity between brain regions during rest (resting-FC), and intensive adaptive training of PS. PS training was associated with (1) significant or substantial improvement in the performance of PS measures, (2) changes in the gray matter structures of the left superior temporal gyrus and the bilateral regions around the occipitotemporal junction, (3) changes in functional activity that are related to simple cognitive processes (but not those of WM) in the left perisylvian region, and (4) increased resting-FC between the left perisylvian area and the area that extends to the lingual gyrus and calcarine cortex. These results confirm the PS-training-induced plasticity in PS and the training-induced plasticity of functions and structures that are associated with speeded cognitive processes. The observed neural changes caused by PS training may give us new insights into how PS training, and possibly other cognitive training, can improve PS.
Age-dependent Homeostatic Plasticity of GABAergic Signaling in Developing Retinal Networks
Authors: Hennig Matthias H. , Grady John , van Coppenhagen James , Sernagor Evelyne
Published: August 2011

Developing retinal ganglion cells fire in correlated spontaneous bursts, resulting in propagating waves with robust spatiotemporal features preserved across development and species. Here we investigate the effects of homeostatic adaptation on the circuits controlling retinal waves. Mouse retinal waves were recordedin vitrofor up to 35 h with a multielectrode array in presence of the GABAAantagonist bicuculline, allowing us to obtain a precise, time-resolved characterization of homeostatic effects in this preparation. Experiments were performed at P4–P6, when GABAAsignaling is depolarizing in ganglion cells, and at P7–P10, when GABAAsignaling is hyperpolarizing. At all ages, bicuculline initially increased the wave sizes and other activity metrics. At P5–P6, wave sizes decreased toward control levels within a few hours while firing remained strong, but this ability to compensate disappeared entirely from P7 onwards. This demonstrates that homeostatic control of spontaneous retinal activity maintains specific network dynamic properties in an age-dependent manner, and suggests that the underlying mechanism is linked to GABAAsignaling.
Electrical Synaptic Input to Ganglion Cells Underlies Differences in the Output and Absolute Sensitivity of Parallel Retinal Circuits
Authors: Murphy Gabe J. , Rieke Fred
Published: August 2011

Parallel circuits throughout the CNS exhibit distinct sensitivities and responses to sensory stimuli. Ambiguities in the source and properties of signals elicited by physiological stimuli, however, frequently obscure the mechanisms underlying these distinctions. We found that differences in the degree to which activity in two classes of Off retinal ganglion cell (RGC) encode information about light stimuli near detection threshold were not due to obvious differences in the cells' intrinsic properties or the chemical synaptic input the cells received; indeed, differences in the cells' light responses were largely insensitive to block of fast ionotropic glutamate receptors. Instead, the distinct responses of the two types of RGCs likely reflect differences in light-evoked electrical synaptic input. These results highlight a surprising strategy by which the retina differentially processes and routes visual information and provide new insight into the circuits that underlie responses to stimuli near detection threshold.
Loss of PSD-95 Enrichment Is Not a Prerequisite for Spine Retraction
Authors: Woods Georgia F. , Oh Won Chan , Boudewyn Lauren C. , Mikula Sarah K. , Zito Karen
Published: August 2011

Changes in neuronal structure are thought to underlie long-term behavioral modifications associated with learning and memory. In particular, considerable evidence implicates the destabilization and retraction of dendritic spines along with the loss of spine synapses as an important cellular mechanism for refining brain circuits, yet the molecular mechanisms regulating spine elimination remain ill- defined. The postsynaptic density protein, PSD-95, is highly enriched in dendritic spines and has been associated with spine stability. Because spines with low levels of PSD-95 are more dynamic, and the recruitment of PSD-95 to nascent spines has been associated with spine stabilization, we hypothesized that loss of PSD-95 enrichment would be a prerequisite for spine retraction. To test this hypothesis, we used dual-color time-lapse two-photon microscopy to monitor rat hippocampal pyramidal neurons cotransfected with PSD-95-GFP and DsRed-Express, and we analyzed the relationship between PSD-95-GFP enrichment and spine morphological changes. Consistent with our hypothesis, we found that the majority of spines that retracted were relatively unenriched for PSD-95-GFP. However, in the subset of PSD-95-GFP-enriched spines that retracted, spine shrinkage and loss of PSD-95-GFP were tightly coupled, suggesting that loss of PSD-95-GFP enrichment did not precede spine retraction. Moreover, we found that, in some instances, spine retraction resulted in a significant enrichment of PSD-95-GFP on the dendritic shaft. Our data support a model of spine retraction in which loss of PSD-95 enrichment is not required prior to the destabilization of spines.
Patients with surgically cured primary hyperparathyroidism have a reduced quality of life compared with population-based healthy sex-, age-, and season-matched controls
Authors: Amstrup Anne Kristine , Rejnmark Lars , Mosekilde Leif
Published: August 2011

Objective

Primary hyperparathyroidism (PHPT) is associated with feelings of fatigue and depression, as well as limitation to physical and mental functioning. These quality of life (QoL) characteristics improve after parathyroidectomy. However, whether former patients fully regain QoL compared with healthy controls is largely unknown.

Design and patients

Cross-sectional study. Fifty-one former PHPT patients, successfully treated by surgery (mean time since parathyroidectomy 7.4 (range 5–15) years), and 51 sex- and age-matched healthy controls.

Methods

The 36-item Short-Form Health Survey version 2 and the WHO-Five Well-being Index. The surveys included questions on overall physical and mental health, functioning, and limitation in daily life activities.

Results

Former patients scored significantly lower compared with controls in physical functioning (P=0.01), role limitation caused by emotional problems (P=0.01), vitality (P<0.001), and general health (P=0.01). Compared with the controls, cases had a lower median (interquartile range) score of physical component summary (PCS; 54.9 (47.9–58.7) vs 49.6 (45.2–55.9),P=0.03) and mental component summary (MCS; 55.4 (49.7–58.1) vs 52.5 (44.7–55.5),P=0.04). There was no association between time since operation and PCS or MCS. Compared with controls, cases had higher body mass index (BMI; 26.0±4.7 vs 28.8±6.0 kg/m2,P<0.001) and a higher frequency of cardiovascular diseases (CVD; 41.2 vs 62.7%,P=0.03). After adjustment for differences in BMI and CVD, PCS did no longer differ between groups. However, adjustments did not change the finding of a lower MCS in cases compared with controls.

Conclusion

Even though QoL may improve substantially after surgery, former PHPT patients still have reduced QoL compared with healthy controls.