bluuebunny/crossref_metadata_2025 huggingface dataset:
Subjective Experiences of Space and Time: Self, Sensation, and Phenomenal Time
Authors: Vimal Ram Lakhan Pandey
Published: July 2019

The investigation of subjective experiences (SEs) of space and time is at the core of consciousness research. The term ‘space’ includes the subject and objects. The SE of subject, I-ness, is defined as ‘Self’. The SEs of objects, subject’s external body, and subject’s internal states such as feelings, thoughts, and so on can be investigated using the proto-experience (PE)-SE framework. The SE of time is defined as ‘phenomenal time’ (which includes past, present and future) and the SE of space as ‘phenomenal space’. The three non-experiential materialistic models are as follows: (I) The quantum-dissipation model [25] can connect the discrete neural signals to classical electromagnetic field to ‘quantum field theory and chaos theory’ for explaining memory. (II) The soliton-catalytic model [8] hypothesizes that all living processes including micro- and macro-processes can be explained by catalysis process. (III) The ‘sensation from evolution of action’ model [13] proposes that SEs are internalized during evolution. All these models can address to some extent the function of structures, such as perception. They cannot address explanatory gap. The complementary experiential PE-SE framework [37] addresses this psycho-physical gap and elucidates the SEs of space and time.
26Al/10Be Age of Peking Man
Authors: Shen Guanjun , Gao Xing , Gao Bin , Granger Darryl
Published: July 2019

The chronological position of Peking Man, or Homo erectus pekinensis, has long been pursued, but has remained problematic due to lack of a suitable dating method^1-7^. Here we report cosmogenic ^26^Al/ ^10^Be burial dating of quartz sediments and artifacts from the lower strata of Zhoukoudian Locality 1 where the remains of early members of the Peking Man family were discovered. This study marks the first radioisotopic dating of any early hominin site in China beyond the range of mass spectrometric U-series dating. The weighted mean of six meaningful measurements, 0.75 +/-; 0.09 (0.11) Ma (million years), provides the best age estimate for lower cultural Layers ^7-10^. Together with previously reported U-series^3^ and paleomagnetic^4^ data, as well as sedimentological considerations^8, 9^ these layers may be further correlated to S6-S7 in Chinese loess stratigraphy or marine isotope stages 17-18, in the range of ~0.68-0.75 Ma. These ages are substantially older than previously supposed and may imply hominin presence in northern China throughout early Middle Pleistocene climate cycles.
A Secret of Hypnosis: A Dynamic Rubber Hand Illusion
Authors: Asai Tomohisa , Sugimori Eriko , Tanno Yoshihiko
Published: July 2019

Presenting a suggestion of heaviness to a person in a hypnotic trance (e.g., "your arm is getting heavier and heavier") tends to result in a corresponding change in the person's body position (e.g., the arm lowers). This phenomenon may be a result of activation of the mirror neuron system, which leads the subject to anticipate actual weight on the arm. The mirror system underlies people's ability to sense, in the absence of actual sensory input, experiences of other people. Perhaps this system allows the same anticipatory experience regarding non-human objects. In this study, we showed participants a picture of a rubber hand holding what appeared to be a lightweight rubber ball. In reality, the ball was weighted with sand. We instructed participants to move their arms to a horizontal position and hold them immobile. Those participants who knew the actual weight of the ball tended to raise their arms above the horizontal, perhaps in response to their expectation of the need to resist the weight of the ball. This illusional phenomenon might be similar to that induced by the hypnotic suggestion of heaviness. That is, the body's response may reflect activity in the mirror system, which anticipates greater weight.
Off-target response to decoy oligodeoxynucleotide treatment
Authors: Robson Ewan , Jeffs Aaron , Eccles Michael
Published: July 2019

*Background:*

The transcription factor PAX2 regulates key developmental processes, including mediation of resistance to apoptosis. Inappropriate PAX2 expression has been implicated in facilitating tumour survival, and we have previously shown that siRNA-mediated blockade of PAX2 signalling at the transcript level in EJ bladder carcinoma cells promotes cell death. In this study, we attempted to disrupt PAX2 transcriptional activity in EJ cells by using a decoy oligodeoxynucleotide (ODN).

*Results:*

We could not show an interaction between PAX2 and our PAX2 decoy ODN, and in both PAX2-positive EJ and PAX2-negative HEK293 control cells, decoy and control ODN transfection resulted in a marked retardation of cell growth, irrespective of sequence, but not in COS7 and NZM4 melanoma cells.

*Conclusions:*

Our data indicate that decoy ODN transfection had off-target effects that inhibited cell growth in a cell line-dependent manner, and we suggest caution is required to determine the specificity of decoy ODN sequences before considering their application as a potential therapeutic agent.
Long-Lasting Context Dependence Constrains Neural Encoding Models in Rodent Auditory Cortex
Authors: Asari Hiroki , Zador Anthony
Published: July 2019

Acoustic processing requires integration over time. However classical linear encoding models, which typically integrate over a few hundred milliseconds, have failed to account fully for neural responses in the auditory cortex. We have used in vivo intracellular recording to measure neuronal integration times in anesthetized rats. Probing with natural sounds and other stimuli, we found that context-dependent effects in the primary auditory cortex could last for surprisingly long, up to four seconds or longer in some neurons. Thalamic neurons showed only a much faster form of adaptation, indicating that the long-lasting form originated in the cortex. Restricting knowledge of the stimulus history to only a few hundred milliseconds reduced the predictable component of the response to about half of that of the optimal infinite-history model. Our results demonstrate the importance of long-range temporal effects in auditory cortex, and suggest a potential neural substrate for stream segregation and other forms of auditory processing that require integration over time scales of seconds or longer.
MEMOFinder: combining de novo motif prediction methods with a database of known motifs
Authors: Wilczynski Bartek , Darzynkiewicz Milosz , Tiuryn Jerzy
Published: July 2019

*Background:*

Methods for finding overrepresented sequence motifs are useful in several key areas of computational biology. They aim at detecting very weak signals responsible for biological processes requiring robust sequence identification like transcription-factor binding to DNA or docking sites in proteins. Currently, general performance of the model-based motif-finding methods is unsatisfactory; however, different methods are successful in different cases. This leads to the practical problem of combining results of different motif-finding tools, taking into account current knowledge collected in motif databases.

*Results:*

We propose a new complete service allowing researchers to submit their sequences for analysis by four different motif-finding methods for clustering and comparison with a reference motif database. It is tailored for regulatory motif detection, however it allows for substantial amount of configuration regarding sequence background, motif database and parameters for motif-finding methods.*Availability:* The method is available online as a webserver at: http://bioputer.mimuw.edu.pl/software/mmf/. In addition, the source code is released on a GNU General Public License.
Suitability of dysphonia measurements for telemonitoring of Parkinson’s disease
Authors: Little Max , McSharry Patrick , Hunter Eric , Spielman Jennifer , Ramig Lorraine
Published: July 2019

We present an assessment of the practical value of existing traditional and non-standard measures for discriminating healthy people from people with Parkinson?s disease (PD) by detecting dysphonia. We introduce a new measure of dysphonia, Pitch Period Entropy (PPE), which is robust to many uncontrollable confounding effects including noisy acoustic environments and normal, healthy variations in voice frequency. We collected sustained phonations from 31 people, 23 with PD. We then selected 10 highly uncorrelated measures, and an exhaustive search of all possible combinations of these measures finds four that in combination lead to overall correct classification performance of 91.4%, using a kernel support vector machine. In conclusion, we find that non-standard methods in combination with traditional harmonics-to-noise ratios are best able to separate healthy from PD subjects. The selected non-standard methods are robust to many uncontrollable variations in acoustic environment and individual subjects, and are thus well-suited to telemonitoring applications.
The Predominance of Electric Transport in Synaptic Transmission
Authors: Noori Hamid Reza
Published: July 2019

The quantitative description of the motion of neurotransmitters in the synaptic cleft appears to be one of the most difficult problems in the modeling of synapses. Here we show in contradiction to the common view, that this process is merely governed by electric transport than diffusion forces.
Spindle oscillations are generated in the dorsal thalamus and modulated by the thalamic reticular nucleus
Authors: Liu Chun-Hua , Guo Yi Ping , Meng Xian-Kai , Yu Yan-Qin , Xiong Ying , Gao Li-Xia , Chan Ying-Shing , He Jufang
Published: July 2019

Spindle waves occur during the early stage of slow wave sleep and are thought to arise in the thalamic reticular nucleus (TRN), causing inhibitory postsynaptic potential spindle-like oscillations in the dorsal thalamus that are propagated to the cortex. We have found that thalamocortical neurons exhibit membrane oscillations that have spindle frequencies, consist of excitatory postsynaptic potentials, and co-occur with electroencephalographic spindles. TRN lesioning prolonged oscillations in the medial geniculate body (MGB) and auditory cortex (AC). Injection of GABA~A~ antagonist into the MGB decreased oscillation frequency, while injection of GABA~B~ antagonist increased spindle oscillations in the MGB and cortex. Thus, spindles originate in the dorsal thalamus and TRN inhibitory inputs modulate this process, with fast inhibition facilitating the internal frequency and slow inhibition limiting spindle occurrence.
Chronic cocaine enhances release of neuroprotective amino acid taurine: a microdialysis study
Authors: Yablonski-Alter Elena , Agovic Mervan , Gashi Eleonora , Lidsky Theodore , Freedman Eitan , Banerjee Shailesh
Published: July 2019

Cocaine inhibits high-affinity neurotransmitter uptake at the presynaptic nerve terminals to increase synaptic levels of dopamine, norepinephrine and serotonin^1^. This increase of synaptic dopamine may cause neurotoxicity^2,3^. At least two different mechanisms have been proposed for the development of dopamine-related neurotoxicity: 1) dopamine produces a free radical that may induce cell toxicity^2,3^ and 2) dopamine reduces glutamate transport at its presynaptic sites to increase synaptic levels of this amino acid^4^ and augments glutamate transmission by activating dopamine D1 receptors in different areas of the brain^5-7^. Increase in glutamatergic transmission mediated by the activation on N-methyl dextro-aspartate (NMDA) receptors has been shown to cause excitotoxicity and neuro-degeneration^8^. Others and we have reported protection against different psychotropic drug-induced neurotoxicity that may be achieved by prior or simultaneous administration of various pharmacological agents. For example, repeated treatment of rats with haloperidol induced neuronal damage that is ameliorated by prior administration of either GM1 ganglioside^9^ or the endogenous amino acid, taurine^10^. Similarly, chronic gestational cocaine exposure causes neurotoxicity that could be prevented by co-administration of clozapine^11^. To our knowledge, there is no information if chronic cocaine would enhance release of endogenous protective agents that may oppose the over activation of glutamatergic system. Here we show that repeated cocaine treatment increased synaptic levels of the neuroprotective amino acid taurine that opposes the excessive excitatory actions of the glutamatergic system in the rat brain. Thus, mammalian brain has an auto-protective mechanism to counter excitotoxicity and taurine or its synthetic derivative may be useful in the management and treatment of cocaine addiction and its neurotoxic effect.
First reports of computed tomographic colonography for the screening of colorectal polyps in acromegalic patients
Authors: Ramos Jr Odery , Boguszewski César Luiz , Teixeira Sandra , Boeving Anke , De Bem Ricardo , Parolim Benito , Pisani Júlio César , Prolla João Carlos
Published: July 2019

*Aim:* To analyze the CTC performance for the screening of colorectal polyps in acromegalic patients.

*Materials and Methods:*

A prospective study of 21 acromegalic patients, 12 male and 9 female, average age 49, who underwent CTC and CC. CTC was performed with a GE Helical Multislice Computed Tomography Apparatus. The colonoscopy was performed, in the same day, without previous knowledge of the CTC diagnostics. The study evaluated the capacity of CTC to detect patients with colorectal polyps and identify each colorectal lesion described by CC.

*Results:*

In two patients (2/21), CC was incomplete. However, in all patients CTC was complete. In Phase I (“Per Patient”), CTC diagnosed 8 of the 9 patients with colorectal polyps and showed 88% sensitivity, 75% specificity and 81% accuracy. In Phase II (“Per Polyp”), out of the 21 acromegalic patients included in this study, 12 presented normal findings at CC. A total of 19 polyps were identified in 9 patients. 10 of the 19 polyps were smaller than 10 mm, and 9 were equal to or larger than 10. CTC identified 7 of the 9 polyps ≥ 10 mm described by CC and only 6 of the 10 small polyps identified at CC were detected by CTC. The histological analysis of resected lesions revealed 12 tubular adenomas, 6 hyperplastic polyps and 1 colonic tubulo-villous adenoma with an adenocarcinoma focus. *Conclusion:* In this study, CTC was performed without complications and a complete and safe colorectal evaluation was possible in all acromegalic patients. Moreover, CTC showed good sensitivity to identify acromegalic patients with colorectal polyps.
Using Satellite Images in Determination of Malaria Outbreaks Potential Region
Authors: Ahmadian Marj Abolfazl , Mobasheri Mohammad Reza , Valadanzouje Mohammad Javad , Rezaie Yousef , Abaie Mohammad Reza
Published: July 2019

Malaria outbreaks are affecting nearly 40 percent of the earth's population most of whom are living in tropical and subtropical zones. Malaria is an infectious disease that is being transferred by the female mosquito of the species Anopheles. The life cycle of the malaria parasite develops in the anopheline and in the human body. These parasites require suitable environmental parameters in order to complete their development cycles within the mosquito. These parameters are temperature, humidity, vegetation and water. A temperature range of 25°C to 35°C and relative humidity range of 50 to 80 percent is suitable for developing malaria outbreaks. As the fly-range of the mosquito is limited to 2 to 4 kilometers and since water pools are necessary for breeding, then the vector abundance is significantly higher around water bodies. Vegetation cover has an indirect role on malaria vector abundance. The vegetated areas help moisture availability in the air and on the soil. To locate the high potential region for malaria outbreaks, one could extract the map of abovementioned parameters via remote sensing images. A 7ETM+ image of Landsat platform is used in this study and maps of parameters such as land surface temperature, air temperature, air humidity, water pools and patches and vegetated area were produced. A weighted combination of these layers showed acceptable agreement with the positive malaria cases collected in the stations. The methodology innovated in this study is fast and accurate enough to rely on.
New species from the deep Pacific suggest that carnivorous sponges date back to the Early Jurassic
Authors: Vacelet Jean , Kelly Michelle
Published: July 2019

Some deep-sea poecilosclerid sponges (Porifera) have developed a carnivorous feeding habit that is very surprising in sponges^1^. As shown by the typical morphology of their spicules, they most probably evolved from "normal sponges" under the difficult conditions of a deep-sea environment. Such evolution, which implies the loss of the diagnostic character of the phylum Porifera, i.e. a filter feeding habit through a complex aquiferous system, should be of great interest in the understanding of the origin of metazoans. Some scenarios, based on the hypothesis of the paraphyly of Porifera, allege that metazoans could derive from a sponge filter-feeding body plan. A difficulty, however, is to imagine the transition from a sponge grade of organization to other organization plans^2^. Carnivorous sponges demonstrate that a functional, non filter-feeding animal may derive from a conventional sponge body plan, albeit nothing is known of the age of this evolution. Here we report that newly discovered species of Chondrocladia from the deep Pacific display special spicules that were previously recorded only as isolated spicules from sediment dating back to the Early Jurassic and Miocene periods. This suggests that the evolution of carnivorous sponges from filter-feeding poecilosclerid demosponges could date back at least from the Early Mesozoic.
Carbon-driven Chemical Interactions between Alumina and Iron: A possible reaction pathway in Earth's interior
Authors: Khanna Rita , Ikram-ul Haq Mohammad , Sahajwalla Veena
Published: July 2019

Seismological and geochemical observations have revealed a complex structure for the earth's core-mantle boundary (CMB) region, with lateral and chemical heterogeneities. The presence of higher than expected concentrations of siderophile elements (Ni, Co, Pt etc) in the earth's mantle, iron enrichment of the lower mantle relative to the upper mantle, and a possible carbon flux from the core suggest the possibility of continual long-term exchange of materials between the core and the mantle. The chemical interactions of molten iron with complex mantle oxides and diffusion have been postulated as key mechanisms. A number of studies have been carried out on the reduction reactions taking into account the extreme conditions of high-temperature and high-pressure in earth's interior. These studies have, however, neglected to consider the influence of carbon on these reactions. The earth's metallic core is rich in carbon (~ 5 wt% C), and there is a growing evidence for the presence of carbon in the earth's mantle as well. Carbon can affect redox conditions through chemical interactions with oxygen, and is a critical element in determining the oxidation state of siderophile elements. Here we present a study of the interactions between liquid iron and alumina-carbon substrates at 1,823K in argon atmosphere, and report on the formation of a Fe-Al~0.25-0.5~ alloy at ambient pressure. Iron induced reduction of alumina in the absence of carbon, has been previously reported to occur only at pressures above 60 GPa and temperatures of 2,200K. Our results demonstrate that carbon enriched iron is capable of reducing alumina in regions of much lower pressures. These chemical reactions could provide an important mechanism for the reduction reactions occurring in earth's interior, and be responsible for far higher levels of heterogeneities than currently believed.
Real-time imaging of the medullary circuitry involved in the generation of spontaneous muscle sympathetic nerve activity in awake human subjects
Authors: Macefield Vaughan , Henderson Luke
Published: July 2019

In order to understand the central neural processes involved in blood pressure regulation we recorded muscle sympathetic nerve activity (MSNA) via a tungsten microelectrode in the common peroneal nerve while performing functional Magnetic Resonance Imaging (fMRI) of the brainstem at 3T. Blood Oxygen Level Dependent (BOLD) changes in signal intensity were measured over 4 s every 8 s (200) volumes. Using the MSNA as the input model, we found that increases in sympathetic outflow were associated with robust increases in signal intensity in the region of the rostal ventrolateral medulla (RVLM). Reciprocal decreases in signal intensity occurred in the regions of the nucleus tractus solitarius (NTS) and caudal ventrolateral medulla (CVLM). We show for the first time that this combined approach of recording sympathetic neural activity and fMRI can provide "real-time" imaging of the neural processes responsible for the generation of sympathetic nerve activity in awake human subjects.
The Oxidative Reaction of Potassium Permanganate with Mycolic Acids Leads to a Unique Diagnostic Pattern for Mycobacterium Tuberculosis
Authors: khatami Mohsen
Published: July 2019

In an oxidative reaction, potassium permanganate reacts with the mycolic acid component of M.tuberculosis and gives rise to a unique saponified pattern specific for M.tuberculosis. This brown orange pattern makes it possible to identify M.tuberculosis in a typical laboratory sample. The method avoids the complexity of other methods with special regard to save time and costs.
Where did Words Come from? A Linking Theory of Sound Symbolism and Natural Language Evolution
Authors: Reilly Jamie , Biun David , Cowles Wind , Peelle Jonathan
Published: July 2019

Where did words come from? The traditional view is that the relation between the sound of a word and its meaning is arbitrary. An alternative hypothesis, known as sound symbolism, holds that form-meaning correspondence is systematic. Numerous examples of sound symbolism exist across natural language phyla. Moreover, cross-linguistic similarities suggest that sound symbolism represents a language universal. For example, many unrelated languages affix an "ee" sound to words in order to emphasize size distinctions or express affection (e.g., look at the teeny weeny baby); other such phonetic universals are evident for object mass, color, brightness, and aggression. We hypothesize that sound symbolism reflects sensitivity to an ecological law (i.e., Hooke's Law) governing an inverse relation between object mass and acoustic resonance. In two experiments healthy adults showed high agreement in matching pure tones to color swatches and nonwords to novel objects as linear functions of frequency and luminance. These results support a degree of non-arbitrariness in integrating visual and auditory information. We discuss implications for sound symbolism as a factor underlying language evolution.
ARHI (DIRAS 3), an Imprinted Tumor Suppressor Gene, Binds to Importins, and Blocks Nuclear Translocation of Stat3
Authors: Huang Shaoyi , Chang In Soon , Lin Wenbo , Luo Robert , Lu Zhen , Lu Yiling , Zhang Ke , Liao Warren , Tao Tao , Bast Robert , Chen Xiaomin , Yu Yinhua
Published: July 2019

ARHI (DIRAS3) is an imprinted tumor suppressor gene whose expression is lost in the majority of breast and ovarian cancers. Unlike its homologs Ras and Rap, ARHI functions as a tumor suppressor. Our previous study showed that ARHI can interact with transcription activator Stat3 and inhibit its nuclear translocation in human breast and ovarian cancer cells. To identify proteins that interact with ARHI in nuclear translocation, we have performed proteomic analysis and identified several importins that can associate with ARHI. To further explore this novel finding, we have purified 10 GST-importin fusion proteins (importin 7, 8, 13, b1, a1, a3, a5, a6, a7 as well as mutant a1). Using a GST-pull down assay, we found that ARHI can bind strongly to most importins; however, its binding is significantly reduced with an importin a1 mutant which contains an altered nuclear localization signal (NLS) domain. In addition, an ARHI N-terminal deletion mutant (NTD) exhibits much less binding to all importins than does wild type ARHI ARHI and NTD proteins were purified and tested for their ability to inhibit nuclear importation of proteins in HeLa cells. ARHI protein inhibits interaction of Ran-importin complexes with GFP fusion proteins that contain an NLS domain and a beta-like import receptor binding domain, blocking their nuclear localization. Addition of ARHI also blocked nuclear localization of phosphorylated Stat3&x03B2;. By GST-pull down assays, we found that ARHI could compete for Ran-importins binding. Thus, ARHI-induced disruption of importin binding to cargo proteins including Stat3 could serve as an important regulatory mechanism that contributes to the tumor suppressor function of ARHI.
pFAR plasmids: New Eukaryotic Expression Vectors for Gene Therapy, devoid of Antibiotic Resistance Markers
Authors: Marie Corinne , Richard Magali , Vandermeulen Gaelle , Quiviger Mickael , Preat Veronique , Scherman Daniel
Published: July 2019

Efficient production of eukaryotic expression vectors requires the selection of plasmid-containing bacteria. To avoid the risk of dissemination of antibiotic resistance markers, we developed a new system to produce a family of plasmids Free of Antibiotic Resistance genes, called pFARs. The strategy is based on the suppression of a chromosomal nonsense mutation by a plasmid-borne function. The amber mutation was introduced into the Escherichia coli thyA gene that encodes a thymidylate synthase required for dTMP synthesis, resulting in thymidine auxotrophy. In parallel, a small plasmid vector that carries an amber suppressor t-RNA gene was entirely synthesised. The introduction of pFAR plasmids into an optimised thyA mutant restored normal growth to the auxotrophic strain, and led to an efficient production of monomeric supercoiled plasmids, as required for clinical trials. Luciferase activities measured after intramuscular injection and electrotransfer of LUC-encoding pFAR vector were similar to those obtained with a commercial vector containing the same expression cassette. Interestingly, whereas luciferase activities decreased within three weeks after intradermal electrotransfer of conventional expression vectors, sustained levels were observed with the pFAR derivative. Thus, pFAR plasmids represent a novel family of biosafe eukaryotic expression vectors, suitable for gene therapy.
Early Life Relict Feature in Peptide Mass Distribution
Authors: Zubarev Roman , Artemenko Konstantin , Zubarev Alexander , Mayrhofer Corina , Fung Eva
Published: July 2019

Molecular mass of a biomolecule is characterized in mass spectroscopy by the monoisitopic mass M~mono~ and the average isotopic mass M~av~. We found that peptide masses mapped on a plane made by two parameters derived from M~mono~ and M~av~ form a peculiar global feature in form of a band-gap 5-7 ppm wide stretching across the whole peptide galaxy, with a narrow (FWHM 0.2 ppm) line in the centre. The a priori probability of such a feature to emerge by chance is less than 1:100. Peptides contributing to the central line have elemental compositions following the rules S=0; Z = (2C - N - H)/2 =0, which nine out of 20 amino acid residues satisfy. The relative abundances of amino acids in the peptides contributing to the central line correlate with the consensus order of emergence of these amino acids, with ancient amino acids being overrepresented in on-line peptides. Thus the central line is a relic of ancient life, and likely a signature of its emergence in abiotic synthesis. The linear correlation between M~av~ and M~mono~ reduces the complexity of polypeptide molecules, which may have increased the rate of their abiotic production. This, in turn may have influenced the selection of these amino acid residues for terrestrial life. Assuming the line feature is not spurious, life has emerged from elements with isotopic abundances very close to terrestrial levels, which rules out most of the Galaxy.
Vestibular effects on cerebral blood flow
Authors: Serrador Jorge , Black F. Owen , Schlegel Todd , Wood Scott
Published: July 2019

Humans demonstrate a number of unique adaptations that allow the maintenance of blood pressure and brain blood flow after transition to the upright position. While these adaptations maintain heart-level mean arterial pressure similar to supine values, the brain remains ~30 cm above the heart, resulting in a ~25% decrease in perfusion pressure. To maintain brain blood flow, the cerebral vessels must dilate in response to this change in position. While several physiological systems are involved in adaptation to the upright posture, including cerebral autoregulation, the unique role that the vestibular system plays in helping to maintain brain blood flow is just beginning to be elucidated. Since the vestibular system not only assists in balance control and locomotion but provides direct information about the body's position relative to gravity, it can, within milliseconds, detect a change in posture. Thus it is possible that a vestibular signal indicating upright could assist in this necessary cerebral vasodilation. In this work we demonstrate a direct effect of vestibular activation on cerebral blood flow regulation. By stimulating the otoliths, the organs that sense gravity, using sinusoidal translation or tilt in the dark at five frequencies, we found that cerebral blood flow was modulated according to the frequency of stimulation. In addition, changes in cerebral blood flow were in opposition to blood pressure changes, likely indicating a direct effect of otolith activation on cerebral blood flow regulation. We anticipate these findings may lead to new treatment modalities for cerebral hypoperfusion under a variety of circumstances. For example, with aging there is well documented vestibular loss that might contribute to a general age-associated reduction in global cerebral blood flow. Similarly, patients with orthostatic intolerance could have vestibular impairment that exacerbates cerebral hypoperfusion when upright.
Positive and Negative Congruency Effects in Masked Priming: A Neuro-computational Model Based on Representation Strength and Attention
Authors: Sohrabi Ahmad , West Robert
Published: July 2019

Positive priming effects have been found with a short time between the prime and the target, while negative priming effects (i.e., a congruent prime causes longer RTs) have been found with a long time between the prime and the target. In the current study, positive and negative priming effects were found using stimuli that have strong and weak representations, respectively, without changing the time between prime and target. A model was developed that fits our results. The model also fits a wide range of previous results in this area. In contrast to other approaches our model depends on attentional neuro-modulation not motor self-inhibition.
Predictive Models of Insulin Resistance Derived from Simple Morphometric and Metabolic Measurements Related to Obesity in Baboons.
Authors: Chavez Alberto , Gastaldelli Amalia , Lopez-Alvarenga Juan Carlos , Guardado-Mendoza Rodolfo , Leland Michelle , Tejero M. Elizabeth , Sorice GianPio , Davalli Alberto , Bastarrachea Raul , Comuzzie Anthony , DeFronzo Ralph , Folli Franco
Published: July 2019

Non-human primates are valuable models for the study of insulin resistance and human obesity. In baboons, insulin sensitivity levels can be evaluated directly with the euglycemic clamp and is highly predicted by adiposity, metabolic markers of obesity and impaired glucose metabolism (i.e. percent body fat by DXA and hemoglobin A1C). However, a simple method to screen and identify obese insulin resistant baboons for inclusion in interventional studies is not available. We characterized a population of obese nondiabetic, insulin resistant baboons using the euglycemic clamp technique and used a multivariate linear regression analysis (after adjustment for gender) to test three different predictive models for insulin sensitivity. In the first model, abdominal circumference explained 63% of insulin mediated glucose uptake. The second model, which included fasting plasma insulin (log transformed) and abdominal circumference, explained 69% of insulin-stimulated glucose uptake. The third model, which contained abdominal circumference and 1/log (FPI+FPG), explained 70% of insulin sensitivity. In baboons, simple morphometric measurements of adiposity/obesity, i.e. abdominal circumference, plus baseline markers of glucose metabolism, i.e. fasting plasma glucose and insulin, provide a feasible method to screen and identify overweight/obese insulin resistant baboons for inclusion interventional studies aimed to study human obesity and type 2 diabetes.
Hexose-6-phosphate dehydrogenase modulates the effect of inhibitors and alternative substrates of 11[beta]-hydroxysteroid dehydrogenase 1
Authors: Balázs Zoltán , Nashev Lyubomir , Chandsawangbhuwana Charlie , Baker Michael , Odermatt Alex
Published: July 2019

Intracellular glucocorticoid reactivation is catalyzed by 11[beta]-hydroxysteroid dehydrogenase 1 (11[beta]-HSD1), which functions predominantly as a reductase in cells expressing hexose-6-phosphate dehydrogenase (H6PDH). We recently showed that the ratios of cortisone to cortisol and 7-keto- to 7-hydroxy-neurosteroids are regulated by 11[beta]-HSD1 and very much depend on co-expression with H6PDH, providing cosubstrate NADPH. Here, we investigated the impact of H6PDH on the modulation of 11[beta]-HSD1-dependent inter-conversion of cortisone and cortisol by inhibitors and alternative substrates. Using HEK-293 cells expressing 11[beta]-HSD1 or co-expressing 11[beta]-HSD1 and H6PDH, we observed significant differences of 11[beta]-HSD1 inhibition by natural and pharmaceutical compounds as well as endogenous hormone metabolites. Furthermore, we show potent and dose-dependent inhibition of 11[beta]-HSD1 by 7-keto-DHEA in differentiated human THP-1 macrophages and in HEK-293 cells over-expressing 11[beta]-HSD1 with or without H6PDH. In contrast, 7-ketocholesterol (7-KC) did not inhibit 11[beta]-HSD1 in HEK-293 cells, even in the presence of H6PDH, but inhibited 11[beta]-HSD1 reductase activity in differentiated THP-1 macrophages (IC~50~ = 8.1 +/- 0.9 [mu]M). 7-keto-DHEA but not 7-KC inhibited 11[beta]-HSD1 in HEK-293 cell lysates. In conclusion, cellular factors such as H6PDH can significantly modulate the effect of inhibitors and alternative 7-oxygenated substrates on intracellular glucocorticoid availability.
Memristive model of amoeba's learning
Authors: Pershin Yuriy , La Fontaine Steven , Di Ventra Massimiliano
Published: July 2019

Recently, behavioural intelligence of the plasmodia of the true slime mold has been demonstrated. It was shown that a large amoeba-like cell Physarum polycephalum subject to a pattern of periodic environmental changes learns and changes its behaviour in anticipation of the next stimulus to come. Currently, it is not known what specific mechanisms are responsible for such behaviour. Here, we show that such behaviour can be mapped into the response of a simple electronic circuit consisting of an LC contour and a memory-resistor (a memristor) to a train of voltage pulses that mimic environment changes. We identify a possible microscopic origin of the memristive behaviour in the Physarum polycephalum, which together with the naturally occurring biological oscillators, forms the basis of the amoeba's learning. These microscopic memristive features are likely to occur in other unicellular as well as multicellular organisms, albeit in different forms. Therefore, the above memristive circuit model, which has learning properties, is useful to better understand the origins of primitive intelligence.
Aging-associated Alteration in the Cardiac MIF-AMPK Cascade in Response to Ischemic Stress
Authors: Ma Heng , Wang Jingying , Lane Erin , Leng Lin , Wang Wenkui , Ren Jun , Bucala Richard , Li Ji
Published: July 2019

An important role for a macrophage migration inhibitory factor (MIF)-AMP-activated protein kinase (AMPK) signaling pathway in ameliorating myocardial damage following ischemia/reperfusion has been described. An aging-associated reduction in AMPK activity may be associated with a decline in the ability of cardiac cells to activate the MIF-AMPK cascade, thereby resulting in reduced tolerance to ischemic insults. To test this hypothesis, in vivo regional ischemia was induced by occlusion of the left anterior descending (LAD) coronary artery in young (4-6 months) and aged (24-26 months) mice. The ischemic AMPK activation response was impaired in aged hearts compared to young ones (p<0.01). Notably, cardiac MIF expression in aged hearts was lower than in young hearts (p<0.01). Dual staining data clearly demonstrated larger infarct size in aged hearts following ischemia and reperfusion compared to young hearts (p<0.05). Ischemia-induced AMPK activation in MIF knock out (MIF KO) hearts was blunted, leading to greater contractile dysfunction of MIF KO cardiomyocytes during hypoxia than that of wild type (WT) cardiomyocytes. Finally exogenous recombinant MIF significantly reversed the contractile dysfunction of aged cardiomyocytes in response to hypoxia. We conclude that an aging-associated reduction in ischemic AMPK activation contributes to ischemic intolerance in aged hearts.
Dynamic reorganization of the middle fusiform gyrus: long-term bird expertise predicts decreased face selectivity
Authors: Kung Chun-Chia , Ellis Colin , Tarr Michael
Published: July 2019

What is the functional relationship between face-selective and expertise-predicated object-selective regions in the human middle fusiform gyrus? In two separate fMRI experiments, superior behaviorally-measured bird expertise predicts both higher middle fusiform gyrus selectivity for birds and, concomitantly, lower selectivity for faces. This finding suggests a long-term dynamic reorganization of the neural mechanisms underlying the visual recognition of faces and non-face.
Aqueous Electrolyte Ionization over Extreme Ranges as Simple Fundamental Relation with Density and Believed Universal; Sodium Chloride Ionization from 0^o^ to 1000^o^C and to 1000 MPa (10000 Atm.)
Authors: Marshall William L.
Published: July 2019

The chemical nature of aqueous electrolyte ionization is illustrated by a simple relationship with water as a reactant believed to correlate ionization of aqueous sodium chloride approaching infinite dilution over the entire range of temperature and pressure [0 to 1000^o^C; 0.1 to 1000 MPa (10000 Atm)]. The derived equation accurately and smoothly describes the ionization constant of sodium chloride [K(NaCl)] in both water and water strongly diluted by inert solvent. Effects of water density on ionization are quantitatively and simply described that oppose conventional theory that ionization is a function only of dielectric constant, and theorists should apply this simplicity with density in understanding aqueous electrolyte ionization. There appears to be no substantive evidence for Pitzer's earlier proposal (1983) that K(NaCl) with decreasing very low densities (if known) would diverge sharply downward by several orders of magnitude. Classical ionization theories are limited in universal application, and it seems that theory must adjust to this observed simple fundamental relationship.
Biospheric context of Siberian development
Authors: Alexandrov Georgii , Inoue Gen , Matsunaga Tsuneo
Published: July 2019

Productivity of ecosystems surrounding a city is important for supporting its activities in a sustainable way. The total terrestrial net primary production (NPP) shows biosphere potential to supply primary food energy source for all non-autotrophic species including humans. Humans appropriate approximately 20% of NPP, in average. Even in the relatively well-populated regions of Siberia, NPP per capita exceeds the average level by several times suggesting the window of opportunity for achieving sustainable development. (3 pages, 1086 words, 2 maps)
Increasing Insect Reactions in Alaska: Is this Related to Changing Climate?
Authors: Demain Jeffrey , Gessner Bradford , McLaughlin Joseph , Sikes Derek , Foote Timothy
Published: July 2019

During the summer of 2006, Fairbanks Alaska experienced its first two known cases of fatal anaphylaxis as a result of Hymenoptera stings, presumably from yellowjackets. An increase in insect bites and stings has been observed throughout the state.Has there been an increased incidence of medical visits due to insect bites and stings in Alaska in recent years? We conducted a retrospective review of three independent patient databases in Alaska to identify trends of patients seeking medical care for adverse reactions following insect bites and stings. For each database, an insect bite or sting episode warranting medical care was defined as a claim for the Clinical Modification of the International Classification of Diseases, Ninth Revision (ICD-9-CM), codes E905.3 (venomous insect; Hymenoptera); E906.4 (bite; non-venomous arthropod), and 989.5 (toxic effect; venom). Increases in bite and sting events in each region were compared to temperature changes in the same region. Each database revealed a statistically significant trend in patients seeking care for reactions to insect bites and stings. Fairbanks Memorial Hospital Emergency Department reported a four-fold increase in patients in 2006 compared to previous years (1992-2005). The Allergy Asthma and Immunology Center of Alaska reported a three-fold increase in patients from 1999 - 2002 to 2003- 2007. A retrospective review of the Alaska Medicaid database between 1999 and 2006 showed increases in billings for insect bites and stings among all regions, with the largest percentage increases occurring in the most northern areas. Alaska has experienced an increase in insect bites and stings, most dramatically indicated by two anaphylaxis deaths due to Hymenoptera stings. Statistically significant increases in patients seeking medical care for insect bite and sting related events are observed throughout the state, with 5 of the 6 regions experiencing at least a 6 degree Fahrenheit increase in winter temperature since 1950.
Searching the World-Wide-Web using nucleotide and peptide sequences
Authors: Ganesan Natarajan , Bennett Nicholas , Kalyanasundaram Bala , Velauthapillai Mahe , Squier Richard
Published: July 2019

*Background:*

No approaches have yet been developed to allow instant searching of the World-Wide-Web by just entering a string of sequence data. Though general search engines can be tuned to accept ‘processed’ queries, the burden of preparing such ‘search strings’ simply defeats the purpose of quickly locating highly relevant information. Unlike ‘sequence similarity’ searches that employ dedicated algorithms (like BLAST) to compare an input sequence from defined databases, a direct ‘sequence based’ search simply locates quick and relevant information about a blunt piece of nucleotide or peptide sequence. This approach is particularly invaluable to all biomedical researchers who would often like to enter a sequence and quickly locate any pertinent information before proceeding to carry out detailed sequence alignment.

*Results:*

Here, we describe the theory and implementation of a web-based front-end for a search engine, like Google, which accepts sequence fragments and interactively retrieves a collection of highly relevant links and documents, in real-time. e.g. flat files like patent records, privately hosted sequence documents and regular databases.

*Conclusions:*

The importance of this simple yet highly relevant tool will be evident when with a little bit of tweaking, the tool can be engineered to carry out searches on all kinds of hosted documents in the World-Wide-Web.*Availability:* Instaseq is free web based service that can be accessed by visiting the following hyperlink on the WWWhttp://instaseq.georgetown.edu
Microbial ecosystem constructed in water for successful organic hydroponics
Authors: Shinohara Makoto , Ohmori Hiromi , Uehara Yoichi
Published: July 2019

Conventional hydroponics systems generally use only chemical fertilisers, not organic ones, since there are no microbial ecosystems present in such systems to mineralise organic compounds to inorganic nutrients. Addition of organic compounds to the hydroponic solution generally has phytotoxic effects and causes poor plant growth. We developed a novel hydroponic culture method using organic fertiliser. A microbial ecosystem was constructed in hydroponic solution by regulating the amounts of organic fertiliser and soil, with moderate aeration. The microbial ecosystem mineralised organic nitrogen to nitrate-nitrogen via ammonification and nitrification. A 97.6% efficiency of nitrate-nitrogen generation from the organic nitrogen in the organic fertiliser was achieved. The culture solution containing the microbial ecosystem was usable as a hydroponic solution. Vegetable plants grew well in our organic hydroponics system under continuous addition of organic fertiliser, and the yield and quality approximated those of vegetables grown by conventional hydroponics.
Temperature factor analysis of outer membrane β-stranded porin crystal structures suggests the pore is not uniformly rigid
Authors: Krishnaswamy S. , Kumar Abhishek
Published: July 2019

Outer membrane beta-stranded porins form a diverse and complex set of proteins which allow passage of molecules across the membrane interface have been analyzed here from a biophysical and structural perspective using atomic temperature factors or B-factors. Generally atomic temperature factors of molecules from crystal structures indicate the degree of mobility or disorder seen in the crystal structure. Structures of six porins (four 16 stranded beta barrel porins and two 8 stranded beta barrel porins) were taken from the PDB for the analysis based on resolution (better than 3.0 Å) and R-factor (< 0.23). The residue distribution and mobility distribution was found to be characteristic of each of the porins. The mobility and residue distribution amongst the secondary structural elements were found to follow the level of homology at the sequence and structural level. The loops (L2 and L3) that had defined functional roles in structural terms were found to have lower temperature factors than the other loops. The turn regions that are thought to face the periplasmic region in the cell, showed higher temperature factors. For both the 16 stranded and the 8 stranded barrels it was found one part of the barrel (the lower wall or 'inner' wall comprising the trimer interface in the case of the 16 stranded barrels) was more rigid and the other half of the barrel (the higher or 'outer' wall) showed more mobility as seen from the temperature factors. This seems to be an intrinsic structural component of the beta barrels.