bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of PTZ-induced epileptic seizures on hippocampal expression of PSA-NCAM in offspring born to kindled rats
Authors: Rajabzadeh Aliakbar , Bideskan Alireza Ebrahimzadeh , Fazel Alireza , Sankian Mojtaba , Rafatpanah Houshang , Haghir Hossein
Published: July 2012

Background

Maternal epileptic seizures during pregnancy can affect the hippocampal neurons in the offspring. The polysialylated neural cell adhesion molecule (PSA-NCAM), which is expressed in the developing central nervous system, may play important roles in neuronal migration, synaptogenesis, and axonal outgrowth. This study was designed to assess the effects of kindling either with or without maternal seizures on hippocampal PSA-NCAM expression in rat offspring.

Methods

Forty timed-pregnant Wistar rats were divided into four groups: A) Kind+/Seiz+, pregnant kindled (induced two weeks prior to pregnancy) rats that received repeated intraperitoneal (i.p.) pentylenetetrazol, PTZ injections on gestational days (GD) 14-19; B) Kind-/Seiz+, pregnant non-kindled rats that received PTZ injections on GD14-GD19; C) Kind+/Seiz-, pregnant kindled rats that did not receive any PTZ injections; and D) Kind-/Seiz-, the sham controls. Following birth, the pups were sacrificed on PD1 and PD14, and PSA-NCAM expression and localization in neonates’ hippocampi were analyzed by Western blots and immunohistochemistry.

Results

Our data show a significant down regulation of hippocampal PSA-NCAM expression in the offspring of Kind+/Seiz+ (p = 0.001) and Kind-/Seiz+ (p = 0.001) groups compared to the sham control group. The PSA-NCAM immunoreactivity was markedly decreased in all parts of the hippocampus, especially in the CA3 region, in Kind+/Seiz+ (p = 0.007) and Kind-/Seiz+ (p = 0.007) group’s newborns on both PD1 and 14.

Conclusion

Our findings demonstrate that maternal seizures but not kindling influence the expression of PSA-NCAM in the offspring’s hippocampi, which may be considered as a factor for learning/memory and cognitive impairments reported in children born to epileptic mothers.
Finding minimum gene subsets with heuristic breadth-first search algorithm for robust tumor classification
Authors: Wang Shu-Lin , Li Xue-Ling , Fang Jianwen
Published: July 2012

Background

Previous studies on tumor classification based on gene expression profiles suggest that gene selection plays a key role in improving the classification performance. Moreover, finding important tumor-related genes with the highest accuracy is a very important task because these genes might serve as tumor biomarkers, which is of great benefit to not only tumor molecular diagnosis but also drug development.

Results

This paper proposes a novel gene selection method with rich biomedical meaning based on Heuristic Breadth-first Search Algorithm (HBSA) to find as many optimal gene subsets as possible. Due to the curse of dimensionality, this type of method could suffer from over-fitting and selection bias problems. To address these potential problems, a HBSA-based ensemble classifier is constructed using majority voting strategy from individual classifiers constructed by the selected gene subsets, and a novel HBSA-based gene ranking method is designed to find important tumor-related genes by measuring the significance of genes using their occurrence frequencies in the selected gene subsets. The experimental results on nine tumor datasets including three pairs of cross-platform datasets indicate that the proposed method can not only obtain better generalization performance but also find many important tumor-related genes.

Conclusions

It is found that the frequencies of the selected genes follow a power-law distribution, indicating that only a few top-ranked genes can be used as potential diagnosis biomarkers. Moreover, the top-ranked genes leading to very high prediction accuracy are closely related to specific tumor subtype and even hub genes. Compared with other related methods, the proposed method can achieve higher prediction accuracy with fewer genes. Moreover, they are further justified by analyzing the top-ranked genes in the context of individual gene function, biological pathway, and protein-protein interaction network.
Experiences of care planning in England: interviews with patients with long term conditions
Authors: Newbould Jenny , Burt Jenni , Bower Peter , Blakeman Tom , Kennedy Anne , Rogers Anne , Roland Martin
Published: July 2012

Background

The prevalence and impact of long term conditions continues to rise. Care planning for people with long term conditions has been a policy priority in England for chronic disease management. However, it is not clear how care planning is currently understood, translated and implemented in primary care. This study explores experience of care planning in patients with long term conditions in three areas in England.

Methods

We conducted semi-structured interviews with 23 predominantly elderly patients with multiple long term conditions. The interviews were designed to explore variations in and emergent experiences of care planning. Qualitative analysis of interview transcripts involved reflexively coding and re-coding data into categories and themes.

Results

No participants reported experiencing explicit care planning discussions or receiving written documentation setting out a negotiated care plan and they were unfamiliar with the term ‘care planning’. However, most described some components of care planning which occurred over a number of contacts with health care professionals which we term”reactive” care planning. Here, key elements of care planning including goal setting and action planning were rare. Additionally, poor continuity and coordination of care, lack of time in consultations, and patient concerns about what was legitimate to discuss with the doctor were described.

Conclusions

Amongst this population, elements of care planning were present in their accounts, but a structured, comprehensive process and consequent written record (as outlined in English Department of Health policy) was not evident. Further research needs to explore the advantages and disadvantages of different approaches to care planning for different patient groups.
Analysis of the Status of Chinese clinical practice guidelines development
Authors: Zheng Zhi-hong , Cui Shu-qi , Lu Xiao-qin , Zakus David , Liang Wan-nian , Huang Fang , Cao Xiao-na , Zhao Ya-li , Peng Xiao-xia , Rao Ke-qin , Wu Jing
Published: July 2012

Background

The work of developing clinical practice guidelines began just a little more than ten years ago in China. Up to now, there have been few studies about them.

Objectives

To review and analyze the status of Chinese clinical practice guidelines in 1997–2007.

Methods

All Chinese guidelines from 1997–2007 were collected, and made a regression analysis, and a citation analysis for evaluating the impact of guidelines. To analyze the developing quality, the most influential guidelines were evaluated with AGREE instrument, and each guideline was evaluated to check for any updating. In order to analyze the objective and target population, all guidelines were classified and counted separately according to disease/symptom center, and whether towards specialists or general practitioners.

Results

143 guidelines were collected. An exponential function equation was established for the trend in the number of guidelines. The immediacy index in every year was very low while the average citation rate was not. Both the percentages of highly cited and never cited were high. For the evaluation with AGREE, only the average score of clarity and presentation was high (89.9%); the remaining were much lower. Editorial independence scored 0. Only 27 (18.9%) of 143 guidelines, were found to be evidence-based. Only a few had ever been updated, with an average updating interval of 5.2 years. Only 2.1% were symptom-centered, and only 4.2% were aimed at general practitioners.

Conclusion

Much progress has been obtained for Chinese guidelines development. However, there were still defects, and greater efforts should be made in the future.
Microalgal biofactories: a promising approach towards sustainable omega-3 fatty acid production
Authors: Adarme-Vega T Catalina , Lim David K Y , Timmins Matthew , Vernen Felicitas , Li Yan , Schenk Peer M
Published: July 2012

Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) provide significant health benefits and this has led to an increased consumption as dietary supplements. Omega-3 fatty acids EPA and DHA are found in animals, transgenic plants, fungi and many microorganisms but are typically extracted from fatty fish, putting additional pressures on global fish stocks. As primary producers, many marine microalgae are rich in EPA (C20:5) and DHA (C22:6) and present a promising source of omega-3 fatty acids. Several heterotrophic microalgae have been used as biofactories for omega-3 fatty acids commercially, but a strong interest in autotrophic microalgae has emerged in recent years as microalgae are being developed as biofuel crops. This paper provides an overview of microalgal biotechnology and production platforms for the development of omega-3 fatty acids EPA and DHA. It refers to implications in current biotechnological uses of microalgae as aquaculture feed and future biofuel crops and explores potential applications of metabolic engineering and selective breeding to accumulate large amounts of omega-3 fatty acids in autotrophic microalgae.
Tumor penetration and epidermal growth factor receptor saturation by panitumumab correlate with antitumor activity in a preclinical model of human cancer
Authors: Freeman Daniel J , McDorman Kevin , Ogbagabriel Selam , Kozlosky Carl , Yang Bing-Bing , Doshi Sameer , Perez-Ruxio Juan Jose , Fanslow William , Starnes Charlie , Radinsky Robert
Published: July 2012

Background

Successful treatment of solid tumors relies on the ability of drugs to penetrate into the tumor tissue.

Methods

We examined the correlation of panitumumab (an anti-epidermal growth factor [EGFR] antibody) tumor penetration and EGFR saturation, a potential obstacle in large molecule drug delivery, using pharmacokinetics, pharmacodynamics, and tumor growth rate in an A431 epidermoid carcinoma xenograft model of human cancer. To determine receptor saturation, receptor occupancy, and levels of proliferation markers, immunohistochemical and flow cytometric methods were used. Pharmacokinetic data and modeling were used to calculate growth characteristics of panitumumab-treated tumors.

Results

Treatment with panitumumab in vivo inhibited pEGFR, Ki67 and pMAPK levels vs control. Tumor penetration and receptor saturation were dose- and time-dependent, reaching 100% and 78%, respectively. Significant tumor inhibition and eradication (p < 0.05) were observed; plasma concentration associated with tumor eradication was estimated to be 0.2 μg/ml. The tumor inhibition model was able to describe the mean tumor growth and death rates.

Conclusions

These data demonstrate that the antitumor activity of panitumumab correlates with its ability to penetrate into tumor tissue, occupy and inhibit activation of EGFR, and inhibit markers of proliferation and MAPK signaling.
Kalman interpolation filter for channel estimation of LTE downlink in high-mobility environments
Authors: Dai Xuewu , Zhang Wuxiong , Xu Jing , Mitchell John E , Yang Yang
Published: July 2012

The estimation of fast-fading LTE downlink channels in high-speed applications of LTE advanced is investigated in this article. In order to adequately track the fast time-varying channel response, an adaptive channel estimation and interpolation algorithm is essential. In this article, the multi-path fast-fading channel is modelled as a tapped-delay, discrete, finite impulse response filter, and the time-correlation of the channel taps is modelled as an autoregressive (AR) process. Using this AR time-correlation, we develop an extended Kalman filter to jointly estimate the complex-valued channel frequency response and the AR parameters from the transmission of known pilot symbols. Furthermore, the channel estimates at the known pilot symbols are interpolated to the unknown data symbols by using the estimated time-correlation. This article integrates both channel estimation at pilot symbols and interpolation at data symbol into the proposed Kalman interpolation filter. The bit error rate performance of our new channel estimation scheme is demonstrated via simulation examples for LTE and fast-fading channels in high-speed applications.
Coincidence and fixed points for contractions and cyclical contractions in partial metric spaces
Authors: Aydi Hassen , Vetro Calogero , Sintunavarat Wutiphol , Kumam Poom
Published: July 2012

We prove some coincidence and common fixed point results for three mappings satisfying a generalized weak contractive condition in ordered partial metric spaces. As application of the presented results, we give a unique fixed point result for a mapping satisfying a weak cyclical contractive condition. We also provide some illustrative examples.

MSC:47H10, 54H25.
Recurrent/moderate hypoglycemia induces hippocampal dendritic injury, microglial activation, and cognitive impairment in diabetic rats
Authors: Won Seok Joon , Yoo Byung Hoon , Kauppinen Tiina M , Choi Bo Young , Kim Jin Hee , Jang Bong Geom , Lee Min Woo , Sohn Min , Liu Jialing , Swanson Raymond A , Suh Sang Won
Published: July 2012

Background

Recurrent/moderate (R/M) hypoglycemia is common in type 1 diabetes. Although mild or moderate hypoglycemia is not life-threatening, if recurrent, it may cause cognitive impairment. In the present study, we sought to determine whether R/M hypoglycemia leads to neuronal death, dendritic injury, or cognitive impairment.

Methods

The experiments were conducted in normal and in diabetic rats. Rats were subjected to moderate hypoglycemia by insulin without anesthesia. Oxidative stress was evaluated by 4-Hydroxy-2-nonenal immunostaining and neuronal death was determined by Fluoro-Jade B staining 7 days after R/M hypoglycemia. To test whether oxidative injury caused by NADPH oxidase activation, an NADPH oxidase inhibitor, apocynin, was used. Cognitive function was assessed by Barnes maze and open field tests at 6 weeks after R/M hypoglycemia.

Results

The present study found that oxidative injury was detected in the dendritic area of the hippocampus after R/M hypoglycemia. Sparse neuronal death was found in the cortex, but no neuronal death was detected in the hippocampus. Significant cognitive impairment and thinning of the CA1 dendritic region was detected 6 weeks after hypoglycemia. Oxidative injury, cognitive impairment, and hippocampal thinning after R/M hypoglycemia were more severe in diabetic rats than in non-diabetic rats. Oxidative damage in the hippocampal CA1 dendritic area and microglial activation were reduced by the NADPH oxidase inhibitor, apocynin.

Conclusion

The present study suggests that oxidative injury of the hippocampal CA1 dendritic region by R/M hypoglycemia is associated with chronic cognitive impairment in diabetic patients. The present study further suggests that NADPH oxidase inhibition may prevent R/M hypoglycemia-induced hippocampal dendritic injury.
Effects of anti-inflammatory vagus nerve stimulation on the cerebral microcirculation in endotoxinemic rats
Authors: Mihaylova Stanka , Killian Anke , Mayer Konstantin , Pullamsetti Soni Savai , Schermuly Ralph , Rosengarten Bernhard
Published: July 2012

Background

In sepsis syndromes the severity of the inflammation triggers microvascular dysfunction and early organ failure. We studied the effects of anti-inflammatory vagus nerve stimulation on the cerebral microcirculatory integrity in an endotoxinemic rat model.

Methods

In both control and endotoxinemic (5 mg/kg lipopolysaccharide i.v.) rats, the effect of cervical bilateral vagotomy with or without left-sided distal vagus nerve stimulation were compared to non-vagotomized, nonstimulated group (sham). Neurovascular coupling was analyzed by electrical forepaw stimulation, EEG, and cortical laser-Doppler flow recording. Resting cerebral blood flow, evoked potentials and hemodynamic responses, were obtained over a period of 4.5 hours. Regulation of the nitric oxide system (iNOS expression and nitrite/nitrate measurements), cytokines (IFN-γ, TNF-α, IL-6, IL-10), hypoxic and apoptosis signaling molecules (HIF-2α, Bax) were measured at the end of experiments.

Results

In endotoxinemic rats, vagus nerve stimulation tended to increase anti-inflammatory cytokine levels and resulted in a stabile hemodynamic response (28 ± 13%; versus baseline). Vagotomized animals incurred a pro-inflammatory response (7 ± 4%;P < 0.0001 versus baseline) and produced more HIF-2α than vagotomized vagus nerve stimulated (VNS) animals. Evoked potential amplitudes were stabilized in VNS (15 ± 7 μV; n.s. versus baseline) as compared to vagotomised rats (8 ± 5 μV;P < 0.001 versus baseline). However, no effects were observed on apoptosis markers or nitric oxide levels.

Conclusions

Vagus nerve stimulation in endotoxinemic rats had a positive effect on neurovascular coupling and stabilized evoked potentials.
On the kinetics of anaerobic power
Authors: Moxnes John F , Hausken Kjell , Sandbakk Øyvind
Published: July 2012

Background

This study investigated two different mathematical models for the kinetics of anaerobic power. Model 1 assumes that the work power is linear with the work rate, while Model 2 assumes a linear relationship between the alactic anaerobic power and the rate of change of the aerobic power. In order to test these models, a cross country skier ran with poles on a treadmill at different exercise intensities. The aerobic power, based on the measured oxygen uptake, was used as input to the models, whereas the simulated blood lactate concentration was compared with experimental results. Thereafter, the metabolic rate from phosphocreatine break down was calculated theoretically. Finally, the models were used to compare phosphocreatine break down during continuous and interval exercises.

Results

Good similarity was found between experimental and simulated blood lactate concentration during steady state exercise intensities. The measured blood lactate concentrations were lower than simulated for intensities above the lactate threshold, but higher than simulated during recovery after high intensity exercise when the simulated lactate concentration was averaged over the whole lactate space. This fit was improved when the simulated lactate concentration was separated into two compartments; muscles + internal organs and blood. Model 2 gave a better behavior of alactic energy than Model 1 when compared against invasive measurements presented in the literature. During continuous exercise, Model 2 showed that the alactic energy storage decreased with time, whereas Model 1 showed a minimum value when steady state aerobic conditions were achieved. During interval exercise the two models showed similar patterns of alactic energy.

Conclusions

The current study provides useful insight on the kinetics of anaerobic power. Overall, our data indicate that blood lactate levels can be accurately modeled during steady state, and suggests a linear relationship between the alactic anaerobic power and the rate of change of the aerobic power.
Glutamine supplementation in a child with inherited GS deficiency improves the clinical status and partially corrects the peripheral and central amino acid imbalance
Authors: Häberle Johannes , Shahbeck Noora , Ibrahim Khalid , Schmitt Bernhard , Scheer Ianina , O’Gorman Ruth , Chaudhry Farrukh A , Ben-Omran Tawfeg
Published: July 2012

Glutamine synthetase (GS) is ubiquitously expressed in mammalian organisms and is a key enzyme in nitrogen metabolism. It is the only known enzyme capable of synthesising glutamine, an amino acid with many critical roles in the human organism. A defect inGLUL, encoding for GS, leads to congenital systemic glutamine deficiency and has been described in three patients with epileptic encephalopathy. There is no established treatment for this condition.

Here, we describe a therapeutic trial consisting of enteral and parenteral glutamine supplementation in a four year old patient with GS deficiency. The patient received increasing doses of glutamine up to 1020 mg/kg/day. The effect of this glutamine supplementation was monitored clinically, biochemically, and by studies of the electroencephalogram (EEG) as well as by brain magnetic resonance imaging and spectroscopy.

Treatment was well tolerated and clinical monitoring showed improved alertness. Concentrations of plasma glutamine normalized while levels in cerebrospinal fluid increased but remained below the lower reference range. The EEG showed clear improvement and spectroscopy revealed increasing concentrations of glutamine and glutamate in brain tissue. Concomitantly, there was no worsening of pre-existing chronic hyperammonemia.

In conclusion, supplementation of glutamine is a safe therapeutic option for inherited GS deficiency since it corrects the peripheral biochemical phenotype and partially also improves the central biochemical phenotype. There was some clinical improvement but the patient had a long standing severe encephalopathy. Earlier supplementation with glutamine might have prevented some of the neuronal damage.
Measurement of multiple biomarkers in advanced stage heart failure patients treated with pulmonary artery catheter guided therapy
Authors: Zilinski Jodi L , Shah Ravi V , Gaggin Hanna K , Gantzer Mary Lou , Wang Thomas J , Januzzi James L
Published: July 2012

Introduction

This study was carried out to investigate the prognostic utility of biomarkers in advanced stage heart failure (HF) patients requiring ICU admission for pulmonary artery catheter (PAC) guided therapy.

Methods

Thirty patients admitted to an ICU for PAC guided HF therapy were enrolled; concentrations of soluble ST2 (sST2), highly sensitive troponin I, an experimental ultrasensitive troponin I, amino-terminal pro-B type natriuretic peptide, cystatin C, and myeloperoxidase were measured over the first 48 hours. Outcomes included response of filling pressures and hemodynamics to tailored therapy and 90-day event-free survival (death, left ventricular assist device implantation, transplant).

Results

Of the biomarkers evaluated, only sST2 concentrations were higher in those who failed to achieve goals for central venous pressure ((CVP), 225.3 versus 104.6 ng/mL; P = 0.003) and pulmonary capillary wedge pressure ((PCWP), 181.7 versus 88.2 ng/mL; P = 0.05). Only sST2 concentrations were associated with adverse events (186.7 versus 92.2 ng/mL; P = 0.01). In age-adjusted Cox proportional hazards analysis, an elevated sST2 during the first 48 hours following ICU admission independently predicted 90-day outcomes (Hazard Ratio = 5.53; P = 0.03) superior to the Simplified Acute Physiology Score for this application; in Kaplan-Meier analysis the risk associated with elevated sST2 concentrations was present early and sustained through the duration of follow-up (log rank P = 0.01).

Conclusions

In patients undergoing HF therapy guided by invasive monitoring, sST2 concentrations were associated with impending failure to reduce filling pressures and predicted impending events. Elevated sST2 values early in the ICU course theoretically could assist therapeutic decision-making in advanced stage HF patients.

Trial registration

ClinicalTrials.gov Identifier: NCT00595738
Staphylococcus epidermidis pan-genome sequence analysis reveals diversity of skin commensal and hospital infection-associated isolates
Authors: Conlan Sean , Mijares Lilia A ,   NISC Comparative Sequencing Program, Becker Jesse , Blakesley Robert W , Bouffard Gerard G , Brooks Shelise , Coleman Holly , Gupta Jyoti , Gurson Natalie , Park Morgan , Schmidt Brian , Thomas Pamela J , Otto Michael , Kong Heidi H , Murray Patrick R , Segre Julia A
Published: July 2012

Background

While Staphylococcus epidermidis is commonly isolated from healthy human skin, it is also the most frequent cause of nosocomial infections on indwelling medical devices. Despite its importance, few genome sequences existed and the most frequent hospital-associated lineage, ST2, had not been fully sequenced.

Results

We cultivated 71 commensal S. epidermidis isolates from 15 skin sites and compared them with 28 nosocomial isolates from venous catheters and blood cultures. We produced 21 commensal and 9 nosocomial draft genomes, and annotated and compared their gene content, phylogenetic relatedness and biochemical functions. The commensal strains had an open pan-genome with 80% core genes and 20% variable genes. The variable genome was characterized by an overabundance of transposable elements, transcription factors and transporters. Biochemical diversity, as assayed by antibiotic resistance and in vitro biofilm formation, demonstrated the varied phenotypic consequences of this genomic diversity. The nosocomial isolates exhibited both large-scale rearrangements and single-nucleotide variation. We showed that S. epidermidis genomes separate into two phylogenetic groups, one consisting only of commensals. The formate dehydrogenase gene, present only in commensals, is a discriminatory marker between the two groups.

Conclusions

Commensal skin S. epidermidis have an open pan-genome and show considerable diversity between isolates, even when derived from a single individual or body site. For ST2, the most common nosocomial lineage, we detect variation between three independent isolates sequenced. Finally, phylogenetic analyses revealed a previously unrecognized group of S. epidermidis strains characterized by reduced virulence and formate dehydrogenase, which we propose as a clinical molecular marker.
Developmental features of DNA methylation during activation of the embryonic zebrafish genome
Authors: Andersen Ingrid S , Reiner Andrew H , Aanes Håvard , Aleström Peter , Collas Philippe
Published: July 2012

Background

Zygotic genome activation (ZGA) occurs at the mid-blastula transition (MBT) in zebrafish and is a period of extensive chromatin remodeling. Genome-scale gametic demethylation and remethylation occurs after fertilization, during blastula stages, but how ZGA relates to promoter DNA methylation states is unknown. Using methylated DNA immunoprecipitation coupled to high-density microarray hybridization, we characterize genome-wide promoter DNA methylation dynamics before, during and after ZGA onset, in relation to changes in post-translational histone modifications and gene expression.

Results

We show methylation of thousands of promoters before ZGA and additional methylation after ZGA, finding more dynamic methylation -1 to 0 kb upstream of the transcription start site than downstream. The MBT is marked by differential methylation of high and low CpG promoters, and we identify hypomethylated promoters that are mostly CG-rich and remain hypomethylated through the MBT. Hypomethylated regions constitute a platform for H3K4me3, whereas H3K9me3 preferentially associates with methylated regions. H3K27me3 associates with either methylation state depending on its coincidence with H3K4me3 or H3K9me3. Cohorts of genes differentially expressed through the MBT period display distinct promoter methylation patterns related to CG content rather than transcriptional fate. Lastly, although a significant proportion of genes methylated in sperm are unmethylated in embryos, over 90% of genes methylated in embryos are also methylated in sperm.

Conclusions

Our results suggest a pre-patterning of developmental gene expression potential by a combination of DNA hypomethylation and H3K4 trimethylation on CG-rich promoters, and are consistent with a transmission of DNA methylation states from gametes to early embryos.
The Impossibility of Skepticism
Authors: Greco Daniel
Published: July 2012

Epistemologists and philosophers of mind both ask questions about belief. Epistemologists ask normative questions about belief—which beliefs ought we to have? Philosophers of mind ask metaphysical questions about belief—what are beliefs, and what does it take to have them? While these issues might seem independent of one another, there is potential for an interesting sort of conflict: the epistemologist might think we ought to have beliefs that, according to the philosopher of mind, it is impossible to have. This essay argues that this conflict does arise and that it creates problems for traditional skeptical views in epistemology. In particular, it argues that on certain popular views about the nature of belief, it is impossible to adopt the near-global agnosticism recommended by the skeptical epistemologist. On other plausible views, it is possible only in special circumstances, and this limitation undermines skeptical epistemological claims. The only views about the nature of belief on which there are no metaphysical hurdles to adopting the agnosticism recommended by the skeptic are views that face powerful objections—objections that are completely independent of antiskeptical epistemological considerations.
Subjectivism without Desire
Authors: Dorsey Dale
Published: July 2012

Subjectivism about well-being holds that ϕ is intrinsically good for x if and only if, and to the extent that, ϕ is valued, under the proper conditions, by x. Given this statement of the view, there is room for intramural dissent among subjectivists. One important source of dispute is the phrase “under the proper conditions”: Should the proper conditions of valuing be actual or idealized? What sort of idealization is appropriate? And so forth. Though these concerns are of the first importance, this essay focuses on a second source of dispute. As stated, subjectivists must account for what it means for an individual x to value ϕ under any conditions. Though there has been some disagreement, most subjectivists hold that x values ϕ if and only if x desires ϕ. This essay argues that subjectivists have erred in accepting a desiderative theory of valuing. Instead, it argues that subjectivists should hold that x values ϕ to the extent that x judges or believes that ϕ is good for x. The resulting “judgment subjectivism” is intuitively superior to, and maintains important structural advantages over, its desiderative rival.
Median fin function during the escape response of bluegill sunfish (Lepomis macrochirus). II: Fin-ray curvature
Authors: Chadwell Brad A. , Standen Emily M. , Lauder George V. , Ashley-Ross Miriam A.
Published: July 2012

Although kinematic analysis of individual fin rays provides valuable insight into the contribution of median fins to C-start performance, it paints an incomplete picture of the complex movements and deformation of the flexible fin surface. To expand our analysis of median fin function during the escape response of bluegill sunfish (Lepomis macrochirus), patterns of spanwise and chordwise curvature of the soft dorsal and anal fin surfaces were examined from the same video sequences previously used in analysis of fin-ray movement and orientation. We found that both the span and chord undergo undulation, starting in the anterior region of either fin. Initiated early in Stage 1 of the C-start, the undulation travels in a postero-distal direction, reaching the trailing edge of the fins during early Stage 2. Maximum spanwise curvature typically occurred among the more flexible posterior fin rays, though there was no consistent correlation between maximum curvature and fin-ray position. Undulatory patterns suggest different mechanisms of action for the fin regions. In the anterior fin region, where the fin rays are oriented dorsoventrally, undulation is directed primarily chordwise, initiating a transfer of momentum into the water to overcome the inertia of the flow and direct the water posteriorly. Within the posterior region, where the fin rays are oriented caudally, undulation is predominantly directed spanwise; thus, the posterior fin region acts to ultimately accelerate this water towards the tail to increase thrust forces. Treatment of median fins as appendages with uniform properties does not do justice to their complexity and effectiveness as control surfaces.
Taste preference for amino acids is dependent on internal nutritional state inDrosophila melanogaster
Authors: Toshima Naoko , Tanimura Teiichi
Published: July 2012

Like mammals, insects need to ingest proteins from foods because they cannot synthesise several amino acids. Amino acids are also essential nutrients for Drosophila melanogaster, especially for female egg production, but how flies detect amino acids and how the feeding response to amino acids is regulated are unknown. In this study, the two-choice preference test, the proboscis extension reflex test and a CAFE assay were performed to explore the ability of D. melanogaster to detect and discriminate amino acids. To determine whether D. melanogaster change their feeding preference to amino acids after being deprived of them, as previously reported in the locust, two groups of flies raised on the usual medium or on glucose medium were compared. Amino-acid-deprived flies demonstrated enhanced preference to an amino acid mixture and to several amino acids. These flies ingested amino acids even when they were replete with glucose. The proboscis extension reflex to particular amino acids was induced only in amino-acid-deprived flies. Our findings indicate that the sensitivity of labellar taste cells to amino acids may change when flies are deficient in amino acid supply, and also reveal that the detection pathways for individual amino acids may differ. We suggest the existence of an amino acid receptor and a monitoring system regulating the feeding responses to amino acids.
The dive response redefined: underwater behavior influences cardiac variability in freely diving dolphins
Authors: Noren Shawn R. , Kendall Traci , Cuccurullo Veronica , Williams Terrie M.
Published: July 2012

A hallmark of the dive response, bradycardia, promotes the conservation of onboard oxygen stores and enables marine mammals to submerge for prolonged periods. A paradox exists when marine mammals are foraging underwater because activity should promote an elevation in heart rate (fH) to support increased metabolic demands. To assess the effect of the interaction between the diving response and underwater activity on fH, we integrated interbeat fH with behavioral observations of adult bottlenose dolphins diving and swimming along the coast of the Bahamas. As expected for the dive response, fH while resting during submergence (40±6 beats min−1) was significantly lower than fH while resting at the water surface (105±8 beats min−1). The maximum recorded fH (fH,max) was 128±7 beats min−1, and occurred during post-dive surface intervals. During submergence, the level of bradycardia was modified by activity. Behaviors such as simple head bobbing at depth increased fH by 40% from submerged resting levels. Higher heart rates were observed for horizontal swimming at depth. Indeed, the dolphins operated at 37–58% of their fH,max while active at depth and approached 57–79% of their fH,max during anticipatory tachycardia as the animals glided to the surface. fH was significantly correlated with stroke frequency (range=0–2.5 strokes s−1, r=0.88, N=25 dives) and calculated swim speed (range=0–5.4 m s−1, r=0.88, N=25 dives). We find that rather than a static reflex, the dive response is modulated by behavior and exercise in a predictable manner.
Measuring airborne components of seismic body vibrations in a Middle-Asian sand-dwelling Insectivora species, the piebald shrew (Diplomesodon pulchellum)
Authors: Volodin Ilya A. , Zaytseva Alexandra S. , Ilchenko Olga G. , Volodina Elena V. , Chebotareva Anastasia L.
Published: July 2012

Self-produced seismic vibrations have been found for some subterranean rodents but have not been reported for any Insectivora species, although seismic sensitivity has been confirmed for blind sand-dwelling chrysochlorid golden moles. Studying the vocal behaviour of captive piebald shrews, Diplomesodon pulchellum, we documented vibrations, apparently generated by the whole-body wall muscles, from 11 (5 male, 6 female) of 19 animals, placed singly on a drum membrane. The airborne waves of the vibratory drumming were digitally recorded and then analysed spectrographically. The mean frequency of vibration was 160.5 Hz. This frequency matched the periodicity of the deep sinusoidal frequency modulation (159.4 Hz) found in loud screech calls of the same subjects. The body vibration was not related to thermoregulation, hunger-related depletion of energy resources or fear, as it was produced by well-fed, calm animals, at warm ambient temperatures. We hypothesize that in the solitary, nocturnal, digging desert piebald shrew, body vibrations may be used for seismic exploration of substrate density, to avoid energy-costly digging of packed sand for burrowing and foraging. At the same time, the piercing quality of screech calls due to the deep sinusoidal frequency modulation, matching the periodicity of body vibration, may be important for agonistic communication in this species.
Myo-inositol as a main metabolite in overwintering flies: seasonal metabolomic profiles and cold stress tolerance in a northern drosophilid fly
Authors: Vesala Laura , Salminen Tiina S. , Koštál Vladimir , Zahradníčková Helena , Hoikkala Anneli
Published: July 2012

Coping with seasonal changes in temperature is an important factor underlying the ability of insects to survive over the harsh winter conditions in the northern temperate zone, and only a few drosophilids have been able to colonize sub-polar habitats. Information on their winter physiology is needed as it may shed light on the adaptive mechanisms of overwintering when compared with abundant data on the thermal physiology of more southern species, such as Drosophila melanogaster. Here we report the first seasonal metabolite analysis in a Drosophila species. We traced changes in the cold tolerance and metabolomic profiles in adult Drosophila montana flies that were exposed to thermoperiods and photoperiods similar to changes in environmental conditions of their natural habitat in northern Finland. The cold tolerance of diapausing flies increased noticeably towards the onset of winter; their chill coma recovery times showed a seasonal minimum between late autumn and early spring, whereas their survival after cold exposure remained high until late spring. The flies had already moderately accumulated glucose, trehalose and proline in autumn, but the single largest change occurred in myo-inositol concentrations. This increased up to 400-fold during the winter and peaked at 147 nmol mg−1 fresh mass, which is among the largest reported accumulations of this compound in insects.
Evaporative water loss, relative water economy and evaporative partitioning of a heterothermic marsupial, the monito del monte (Dromiciops gliroides)
Authors: Withers Philip C. , Cooper Christine E. , Nespolo Roberto F.
Published: July 2012

We examine here evaporative water loss, economy and partitioning at ambient temperatures from 14 to 33°C for the monito del monte (Dromiciops gliroides), a microbiotheriid marsupial found only in temperate rainforests of Chile. The monito's standard evaporative water loss (2.58 mg g−1 h−1 at 30°C) was typical for a marsupial of its body mass and phylogenetic position. Evaporative water loss was independent of air temperature below thermoneutrality, but enhanced evaporative water loss and hyperthermia were the primary thermal responses above the thermoneutral zone. Non-invasive partitioning of total evaporative water loss indicated that respiratory loss accounted for 59–77% of the total, with no change in respiratory loss with ambient temperature, but a small change in cutaneous loss below thermoneutrality and an increase in cutaneous loss in and above thermoneutrality. Relative water economy (metabolic water production/evaporative water loss) increased at low ambient temperatures, with a point of relative water economy of 15.4°C. Thermolability had little effect on relative water economy, but conferred substantial energy savings at low ambient temperatures. Torpor reduced total evaporative water loss to as little as 21% of normothermic values, but relative water economy during torpor was poor even at low ambient temperatures because of the relatively greater reduction in metabolic water production than in evaporative water loss. The poor water economy of the monito during torpor suggests that negative water balance may explain why hibernators periodically arouse to normothermia, to obtain water by drinking or via an improved water economy.
Encephalic photoreception and phototactic response in the troglobiont Somalian blind cavefish Phreatichthys andruzzii
Authors: Tarttelin Emma E. , Frigato Elena , Bellingham James , Di Rosa Viviana , Berti Roberto , Foulkes Nicholas S. , Lucas Robert J. , Bertolucci Cristiano
Published: July 2012

Many physiological and behavioural responses to changes in environmental lighting conditions are mediated by extraocular photoreceptors. Here we investigate encephalic photoreception in Phreatichthys andruzzii, a typical cave-dwelling fish showing an extreme phenotype with complete anophthalmy and a reduction in size of associated brain structures. We firstly identified two P. andruzzii photopigments, orthologues of rod opsin and exo-rod opsin. In vitro, both opsins serve as light-absorbing photopigments with λmax around 500 nm when reconstituted with an A1 chromophore. When corrected for the summed absorption from the skin and skull, the spectral sensitivity profiles shifted to longer wavelengths (rod opsin: 521 nm; exo-rod opsin: 520 nm). We next explored the involvement of both opsins in the negative phototaxis reported for this species. A comparison of the spectral sensitivity of the photophobic response with the putative A2 absorbance spectra corrected for skin/skull absorbance indicates that the A2 versions of either or both of these pigments could explain the observed behavioural spectral sensitivity.
Trafficking of bdelloid rotifer late embryogenesis abundant proteins
Authors: Tripathi Rashmi , Boschetti Chiara , McGee Brian , Tunnacliffe Alan
Published: July 2012

The bdelloid rotifer Adineta ricciae is an asexual microinvertebrate that can survive desiccation by entering an ametabolic state known as anhydrobiosis. Two late embryogenesis abundant (LEA) proteins, ArLEA1A and ArLEA1B, have been hypothesized to contribute to desiccation tolerance in these organisms, since in vitro assays suggest that ArLEA1A and ArLEA1B stabilize desiccation-sensitive proteins and membranes, respectively. To examine their functions in vivo, it is important to analyse the cellular distribution of the bdelloid LEA proteins. Bioinformatics predicted their translocation into the endoplasmic reticulum (ER) via an N-terminal ER translocation signal and persistence in the same compartment via a variant C-terminal retention signal sequence ATEL. We assessed the localization of LEA proteins in bdelloids and in a mammalian cell model. The function of the N-terminal sequence of ArLEA1A and ArLEA1B in mediating ER translocation was verified, but our data showed that, unlike classical ER-retention signals, ATEL allows progression from the ER to the Golgi and limited secretion of the proteins into the extracellular medium. These results suggest that the N-terminal ER translocation signal and C-terminal ATEL sequence act together to regulate the distribution of rotifer LEA proteins within intracellular vesicular compartments, as well as the extracellular space. We speculate that this mechanism allows a small number of LEA proteins to offer protection to a large number of desiccation-sensitive molecules and structures both inside and outside cells in the bdelloid rotifer.
Electronic individual identification of zebrafish using radio frequency identification (RFID) microtags
Authors: Cousin Xavier , Daouk Tarek , Péan Samuel , Lyphout Laura , Schwartz Marie-Elise , Bégout Marie-Laure
Published: July 2012

Although individual electronic tagging using passive integrated acoustic (PIT) tags is established, it is mainly for fish >60 mm in length and is unsuitable for fish of <30 mm, like zebrafish. We used radio frequency identification (RFID) microtags (1 mm in diameter and 6 mm in length, with a mass of ~10 mg) to individually identify juvenile zebrafish (length 16–42 mm, mass 138–776 mg) for the first time, and studied the effects of intracoelomic implantation on fish survival and microtag loss, growth, spawning and exploratory behaviour. After 5.5 months, both high survival (82%) and low microtag loss (11%) were achieved. The smallest surviving fish weighed 178 mg, and success in microtag reading was 73% for the size class 350–450 mg (26 mm). Greater success was achieved when fish were larger at the time of tagging but no negative effects on growth were observed for any size class and some tagged fish spawned. No significant differences in behavioural responses could be detected between tagged fish and untagged controls after 2 months. Overall, the results suggest that the tagging method is highly suitable for fish as small as zebrafish juveniles. We think this method will provide significant advances for researchers of the ever-growing fish model community and more generally for all small-fish users. Tagging is essential when one needs to identify fish (e.g. particular genotypes with no external cue), to run longitudinal monitoring of individual biological traits (e.g. growth) or to repeat assays with the same individual at discrete points in time (e.g. behaviour studies). Such a method will find applications in physiology, genetics, behaviour and (eco)toxicology fields.
Intracellular Na+, K+ and Cl− activities in Acheta domesticus Malpighian tubules and the response to a diuretic kinin neuropeptide
Authors: Coast Geoffrey M.
Published: July 2012

The mechanism of primary urine production and the activity of a diuretic kinin, Achdo-KII, were investigated in Malpighian tubules of Acheta domesticus by measuring intracellular Na+, K+ and Cl− activities, basolateral membrane voltage (Vb), fluid secretion and transepithelial ion transport. Calculated electrochemical gradients for K+ and Cl− across the basolateral membrane show they are actively transported into principal cells, and basolateral Ba2+-sensitive K+ channels do not contribute to net transepithelial K+ transport and fluid secretion. A basolateral Cl− conductance was revealed after the blockade of K+ channels with Ba2+, and a current carried by the passive outward movement of Cl− accounts for the hyperpolarization of Vb in response to Ba2+. Ion uptake via Na+/K+/2Cl− cotransport, driven by the inwardly directed Na+ electrochemical gradient, is thermodynamically feasible, and is consistent with the actions of bumetanide, which reduces fluid secretion and both Na+ and K+ transport. The Na+ gradient is maintained by its extrusion across the apical membrane and by a basolateral ouabain-sensitive Na+/K+-ATPase. Achdo-KII has no significant effect on the intracellular ion activities or Vb. Electrochemical gradients across the apical membrane were estimated from previously published values for the levels of Na+, K+ and Cl− in the secreted fluid. The electrochemical gradient for Cl− favours passive movement into the lumen, but falls towards zero after stimulation by Achdo-KII. This coincides with a twofold increase in Cl− transport, which is attributed to the opening of an apical Cl− conductance, which depolarises the apical membrane voltage.