Processing Pathways in Mental Arithmetic—Evidence from Probabilistic Fiber Tracking

Numerical cognition is a case of multi-modular and distributed cerebral processing. So far neither the anatomo-functional connections between the cortex areas involved nor their integration into established frameworks such as the differentiation between dorsal and ventral processing streams have been specified. The current study addressed this issue combining a re-analysis of previously published fMRI data with probabilistic fiber tracking data from an independent sample. We aimed at differentiating neural correlates and connectivity for relatively easy and more difficult addition problems in healthy adults and their association with either rather verbally mediated fact retrieval or magnitude manipulations, respectively. The present data suggest that magnitude- and fact retrieval-related processing seem to be subserved by two largely separate networks, both of them comprising dorsal and ventral connections. Importantly, these networks not only differ in localization of activation but also in the connections between the cortical areas involved. However, it has to be noted that even though seemingly distinct anatomically, these networks operate as a functionally integrated circuit for mental calculation as revealed by a parametric analysis of brain activation.     

Extremely Sensitive Photonic Crystal Fiber–Based Cancer Cell Detector in the Terahertz Regime

A new photonic crystal fiber (PCF)–based, hollow-core, optical waveguide is proposed and numerically investigated to quickly identify numerous species of cancerous cells in the human body. Typical and cancerous cells have different refractive indices (RIs), and via this characteristic, the other important optical parameters are evaluated. The guiding properties of this proposed cancer cell sensor are analyzed in the COMSOL Multiphysics environment which used the finite element method as mathematical tool to solve differential equations. Furthermore, to ensure the highest simulation accuracy, extremely fine mesh elements are introduced. The simulation studies confirm that the proposed sensor, at 2.5 THz, achieves an extremely high relative sensitivity of almost 98% with negligible loss (< 0.025 dB/cm). Furthermore, a high numerical aperture (NA) and spot size, with low modal area, enhance the propagation characteristics of the sensor to a new height. The sensor’s physical structure is very simple so that it can be easily fabricated with modern fabrication technology. Thus, it seems that this sensor will open a new door in the field of detecting and diagnosing different cancer cells.

     

Human Serum Albumin Can Regulate Amyloid-β Peptide Fiber Growth in the Brain Interstitium: IMPLICATIONS FOR ALZHEIMER DISEASE

Alzheimer disease is a neurodegenerative disorder characterized by extracellular accumulation of amyloid-β peptide (Aβ) in the brain interstitium. Human serum albumin (HSA) binds 95% of Aβ in blood plasma and is thought to inhibit plaque formation in peripheral tissue. However, the role of albumin in binding Aβ in the cerebrospinal fluid has been largely overlooked. Here we investigate the effect of HSA on both Aβ(1-40) and Aβ(1-42) fibril growth. We show that at micromolar cerebrospinal fluid levels, HSA inhibits the kinetics of Aβ fibrillization, significantly increasing the lag time and decreasing the total amount of fibrils produced. Furthermore, we show that the amount of amyloid fibers generated directly correlates to the proportion of Aβ not competitively bound to albumin. Our observations suggest a significant role for HSA regulating Aβ fibril growth in the brain interstitium.     

Co-distribution of Tropomyosin and α-Actinin With Actin in Psammobatis extenta Electrocytes Brings Out Their Similarity with Muscle Fiber Cytoplasm

Electric organs of Psammobatis extenta (Rajiformes) electric fish derive from myoblasts of the caudal region [16]. Here we study the presence of muscle proteins, actin and the actin-binding proteins, α-actinin and tropomyosin, in the electrocytes by means of biochemical approaches, scanning electron microscopy and immunocytochemical methods. NBD-phallacidin is employed to detect the filamentous form of actin (F-actin). Immunoblots of actin and α-actinin from P. extenta skeletal and smooth muscle show that the electric organ forms of actin and α-actinin correspond to muscle types. Scanning electron microscopy shows that P. extenta electrocytes are highly polarized cells, semicircular in shape, with an anterior, concave innervated face and a posterior, convex, non-innervated face. The immunofluorescence patterns of α-actinin and tropomyosin distribution are similar to those of actin, in that these epitopes appear to occur throughout the entire electrocyte cytoplasm. F-actin, as revealed by NBD-phallacidin fluorescence, was also found throughout the cytoplasm. This is the first time that evidence is presented to demonstrate the existence of muscle actin in this weak electric fish species electrocyte. The close evolutionary connection to that of muscle cells is discussed.     

General Utility of the Chicken βB1-Crystallin Promoter to Drive Protein Expression in Lens Fiber Cells of Transgenic Mice

Transgenic mouse technology has been very valuable for the study of lens fiber cells since they can not be propagated in cell culture. The targeting of transgenes to the lens has traditionally been done with the A-crystallin promoter. However, while lens-specific, transgenic lines made with the A-crystallin promoter express the transgene at levels 100–300-fold lower than endogenous A-crystallin. Here we propose an alternative, the chicken B1-crystallin promoter (–432/+30). Transgenic mice made with this promoter have successfully expressed CAT, d/n m-calpain, Wee1, and B2-crystallin mRNA at levels comparable to the endogenous B1-crystallin gene and no eye abnormalities such as cataracts, have resulted. All of the transgenic lines made with the chicken B1-crystallin promoter have expressed the transgene in the lens fiber cells, and the best lines express at levels close to endogenous B1-crystallin. While RNA expression is very high, only moderate protein expression has been achieved, implying that the high protein expression of the crystallins is partially controlled at the level of translation. Thus, the chicken B1-crystallin promoter directs high level RNA expression to lens fiber cells, which may be especially useful for the expression of ribozyme and anti-sense RNAs in addition to ectopic proteins.     

Do Energy Density and Dietary Fiber Influence Subsequent 5‐Year Weight Changes in Adult Men and Women?

Objective: We examined whether associations between dietary components and, in particular, energy density (ED) predicted subsequent 5‐year weight changes. Research Methods and Procedures: The present longitudinal population study was part of the Danish World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) and the 1936 cohort dietary studies. Effects of components were studied in relation to subsequent 5‐year weight changes in 862 men and 900 women, 30 to 60 years old. Linear multiple regression analyses were conducted. Results: Mean 5‐year changes in body weight (BW) were 1.2 ± 3.9 and 1.3 ± 4.6 kg for men and women, respectively. In general, neither ED nor any of the dietary components was associated with subsequent change in BW. In women, ED was positively associated with weight gain among the obese (BMI > 30 kg/m²) and inversely associated with weight gain in normal‐weight women (BMI < 25 kg/m²) (p = 0.01). However, in men there was a non‐ significant inverse trend between ED and weight gain in the obese and no significant interaction. Discussion: To our knowledge, this is the first prospective study to examine the associations between ED and subsequent changes in BW, and despite a general belief that ED is a major determinant of obesity, the present study did not generally lend support for an association. However, among certain subgroups, an energy‐dense diet may be a risk factor for weight development.     

Glucose Level Measurement Using Photonic Crystal Fiber–based Plasmonic Sensor

In this study, we demonstrate the design of a photonic crystal fiber (PCF)-based plasmonic sensor to measure the glucose level of urine. The sensor is designed by placing a small segment of PCF between a lead-in and a lead-out single-mode fiber. We utilize the finite element method to simulate the proposed plasmonic sensor for the measurement of glucose level in urine. To offer external sensing, the cladding layer of the PCF was coated by a thin layer of gold where the gold-coated PCF was immersed in the urine sample. As a result, the urine can easily interact with the plasmonic layer of the sensor. In the outermost laser of the PCF, we considered a perfectly matched layer as a boundary condition. The simulation results confirm excellent wavelength and amplitude sensitivities where the maximum wavelength sensitivity was 2500 nm/RIU and amplitude sensitivity was 152 RIU^?1 with a sensing resolution of 4?×?10^?6. For optimization of the plasmonic sensor, we varied the physical parameters of the cladding air holes and the thickness of the gold layer during the simulation. We strongly believe that the proposed plasmonic sensor will play a significant role to pave the way for achieving a simple but effective PCF-based glucose sensor.

     

Are Metals Accumulated in Human Hair Affected by Naturally Occurring Asbestos Fiber Contamination? A Case Study from a Rural Area of China

Little is known about the link between metals accumulated in human and asbestos fiber contamination in the environment. Therefore, hair samples of 368 subjects (128 males and 240 females) from a rural area contaminated by crocidolite asbestos fibers were collected to investigate the distributions of 17 metals accumulated in human. The results showed that the mean concentrations of As, Al, Ba, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Na, Ni, Pb, Sr, and Zn in hair of the total subjects were 0.23, 23.36, 4.33, 0.11, 0.05, 0.70, 10.53, 29.74, 0.37, 241.57, 3.52, 0.08, 153.21, 0.72, 4.26, 10.96, and 113.35 mg/kg, respectively. Moreover, approximately 86.14, 52.17, 73.91, 85.05, 80.98, 74.46, and 53.80 % of the hair samples of the total subjects contained much higher concentrations of Al, Ba, Fe, Mg, Mn, Na, and Sr compared with the highest reference values, respectively. The mean concentrations of the determined metals (except for As, Co, Cr, Hg, and Mo) significantly varied among different age groups for both male and females. The results of correlation analysis and cluster analysis revealed that strong correlations were found between Al, Fe, Zn, Mg, and Na accumulated in human from the study area. These might suggest that Al, Ba, Fe, Mg, Mn, Na, and Sr were significantly derived from contamination of crocidolite asbestos fibers. Zn, Mg, and Na might also originate from diet. However, Cd, Mo, Co, As, Cr, Hg, Ni, Mn, Pb, and Ba accumulated in human seemed to be mainly derived from soil. It can be concluded that metals accumulated in human hair have a link with asbestos fiber contamination in the environment.     

Is the Cross-Bridge Stiffness Proportional to Tension during Muscle Fiber Activation?

The cross-bridge stiffness can be used to estimate the number of S1 that are bound to actin during contraction, which is a critical parameter for elucidating the fundamental mechanism of the myosin motor. At present, the development of active tension and the increase in muscle stiffness due to S1 binding to actin are thought to be linearly related to the number of cross-bridges formed upon activation. The nonlinearity of total stiffness with respect to active force is thought to arise from the contribution of actin and myosin filament stiffness to total sarcomere elasticity. In this work, we reexamined the relation of total stiffness to tension during activation and during exposure to N-benzyl-p-toluene sulphonamide, an inhibitor of cross-bridge formation. In addition to filament and cross-bridge elasticity, our findings are best accounted for by the inclusion of an extra elasticity in parallel with the cross-bridges, which is formed upon activation but is insensitive to the subsequent level of cross-bridge formation. By analyzing the rupture tension of the muscle (an independent measure of cross-bridge formation) at different levels of activation, we found that this additional elasticity could be explained as the stiffness of a population of no-force-generating cross-bridges. These findings call into question the assumption that active force development can be taken as directly proportional to the cross-bridge number.     

Dietary Fiber and Saturated Fat Intake Associations with Cardiovascular Disease Differ by Sex in the Malm? Diet and Cancer Cohort: A Prospective Study

Background

The aim of the study was to examine associations between intake of macronutrients and dietary fiber and incident ischemic cardiovascular disease (iCVD) in men and women.

Methods

We used data from 8,139 male and 12,535 female participants (aged 44–73 y) of the Swedish population-based Malmö Diet and Cancer cohort. The participants were without history of CVD and diabetes mellitus, and had reported stable dietary habits in the study questionnaire. Diet was assessed by a validated modified diet history method, combining a 7-d registration of cooked meals and cold beverages, a 168-item food questionnaire (covering other foods and meal patterns), and a 1-hour diet interview. Sociodemographic and lifestyle data were collected by questionnaire. iCVD cases, which included coronary events (myocardial infarctions or deaths from chronic ischemic heart disease) and ischemic strokes, were ascertained via national and local registries. Nutrient-disease associations were examined by multivariate Cox regressions.

Results

During a mean follow-up of 13.5 years, we identified 1,089 male and 687 female iCVD cases. High fiber intakes were associated with lower incidence rates of iCVD in women and of ischemic stroke in men. In post-hoc analysis, we discovered statistically significant interactions between intake of fiber and saturated fat; these interactions also differed between men and women (p<0.001).

Conclusions

In this well-defined population, a high fiber intake was associated with lower risk of iCVD, but there were no robust associations between other macronutrients and iCVD risk. Judging from this study, gender-specific nutrient analysis may be preferable in epidemiology.     

A Rosemary Extract Rich in Carnosic Acid Selectively Modulates Caecum Microbiota and Inhibits β-Glucosidase Activity,Altering Fiber and Short Chain Fatty Acids Fecal Excretion in Lean and Obese Female Rats

Background

Carnosic acid (CA) and rosemary extracts (RE) show body-weight, energy metabolism and inflammation regulatory properties in animal models but the mechanisms are not yet understood. Gut microbiota plays an important role in the host metabolism and inflammatory status and is modulated by the diet. The aim of this research was to investigate whether a RE enriched in CA affected caecum microbiota composition and activity in a rat model of genetic obesity.

Methods and Principal Findings

A RE (40% CA) was administered with the diet (0.5% w/w) to lean (fa/+) and obese (fa/fa) female Zucker rats for 64 days. Changes in the microbiota composition and β-glucosidase activity in the caecum and in the levels of macronutrients and short chain fatty acids (SCFA) in feces were examined. The RE increased the Blautia coccoides and Bacteroides/Prevotella groups and reduced the Lactobacillus/Leuconostoc/Pediococccus group in both types of animals. Clostridium leptum was significantly decreased and Bifidobacterium increased only in the lean rats. β-Glucosidase activity was significantly reduced and fecal fiber excretion increased in the two genotypes. The RE also increased the main SCFA excreted in the feces of the obese rats but decreased them in the lean rats reflecting important differences in the uptake and metabolism of these molecules between the two genotypes.

Conclusions

Our results indicate that the consumption of a RE enriched in CA modifies microbiota composition and decreases β-glucosidase activity in the caecum of female Zucker rats while it increases fiber fecal elimination. These results may contribute to explain the body weight gain reducing effects of the RE. The mutated leptin receptor of the obese animals significantly affects the microbiota composition, the SCFA fecal excretion and the host response to the RE intake.     

Polarized Micro Raman Spectroscopic Studies of Nucleic Acid: Local Raman Tensors in Inosine-5′-monophosphoric Acid and the Orientation of Ekypoxanthine Residue in Poly(rI). Poly(rC) Fiber

Abstract

The polarized Raman spectra of a single crystal of the barium salt of inosine monophosphoric acid hexahydratc (Ba-IMP.6H₂O) have been observed with 488.0 nm excitation. For each Raman band, the relative intensities of aa, bb, cc, ab and bc tensor components have been determined. The tensor quotients from the crystal were augmented with measured depolarization ratios in solution. From these experimental data, the shape and orientation of the localized Raman scattering tensor were deduced for each of the normal modes of the hypoxanthine residue, phosphate moiety and ribose portion. The hypoxanthine residue gives a strong Raman band around 1553 cm^?1, which shows rather large depolarization ratio, p = 0.32, in aqueous solution, and shows a great scattering anisotropy in the single crystal of IMP. The shape and orientation of the Raman tensor associated to this 1553 cm^?1 vibration have been determined: one of its principal axes (y-axis) is directed along the long axis (N1-N7) of the hypoxanthine residue and the relative magnitudes of its components are given as r ₁ = α_xx/α_zz = ?1, r ₂ = α_yy/α_zz = 12. Next, a general relation has been shown between the orientation angles (θ and χ) of such a local Raman tensor in a uniaxial biological fiber and the anisotropy of Raman scattering intensities from the fiber. By the use of this relation, a discussion has been made of the orientation of the hypoxanthine residue in a poly(r1). poly(rC) duplex fiber.

     

Acute Changes In Knee‐Extensors Torque,Fiber Pennation,and Tendon Characteristics

The aim of the current study was to examine the relationships between quadriceps torque, vastus lateralis pennation angle (θ), and patella tendon stiffness (K) at 07:45 and 17:45 h. Using short‐duration static contractions, simultaneous recordings were made of vastus lateralis (VL) electromyograph (EMG), θ and patella tendon K. Peak isometric extension torque (Peak torque Ext_corr) increased by 29.4±6.5% at a knee angle of 70° (p=0.03) in the evening compared to the morning. In the contracted muscle, a 35.0±11.0% (p=0.02) time‐of‐day (TOD)‐related change in θ (to a greater evening compared to morning θ) was observed. Morning and evening measures of θ were also made, both at rest and at a standardized force level (250 N), to separate architecture change effects from increased torque capacity effects. Significant increments in θ in both the resting muscle (13.0±5.1%, p=0.046) and during the standardized exertions (8.0±3.1%, p=0.04) were observed in the evening versus the morning. Increases in θ with TOD were significantly correlated with the 40% (p=0.018) decrease in K both during the standardized contractions (r=0.788, p<0.001) and at rest (r=0.77, p=0.026). These data show that TOD affects K and θ and that these two important factors involved in in‐vivo muscle torque generation capacity are associated. The data also show that despite the potentially deleterious effects of the direction of the changes in both K and θ with TOD, peak torque Ext_corr still shows a significant upward shift in the evening relative to the morning.     

The Role in Cell Binding of a β1-bend within the Triple Helical Region in Collagen αl(I) Chain: Structural and Biological Evidence for Conformational Tautomerism on Fiber Surface

Summary

In its physiological solid state, type I collagen serves as a host for many types of cells. Only the molecules on fiber surface are available for interaction. In this interfacial environment, the conformation of a cell binding domain can be expected to fluctuate between the collagen fold and a distinctive non-collagen molecular marker for recognition and allosteric binding. If the cell binding domain can be localized in contiguous residues within the exposed half of a turn of the triple helix (approximately 15 residues), the need for extensive structural modification and unraveling of the triple helix is avoided.

We examined the conformational preferences and biological activity of a synthetic 15- residue peptide (P-15), analogous to the sequence ⁷⁶⁶GTPGPQGIAGQRGVV⁷⁸⁰ in the al (I) chain. Theoretical studies showed a high potential for a stable β-bend for the central GIAG sequence. The flanking sequences showed facile transition to extended conformations. Circular dichroism of the synthetic peptide in anisotropic solvents confirmed the presence of β-strand and β-bend structures.

P-15 inhibited fibroblast binding to collagen in a concentration dependent manner, with near maximal inhibition occurring at a concentration of 7.2×10^?6 M. The temporal pattern of cell attachment was altered markedly in the presence of P-15. No inhibition was seen with a peptide P-15 (AI), an analogue of P-15 with the central IA residues reversed to AI or with collagen-related peptides (Pro-Pro-Gly)₁₀, (Pro-Pro-Gly)₁₀, and polyproline, and with several unrelated peptides.

Our studies suggest a molecular mechanism for cell binding to collagen fibers based on a conformational transition in collagen molecules on the fiber surface. Since the energy barrier between the collagen fold and β-strand conformation is low, a local conformational change may be possible in molecules on the fiber surface because of their location in an anisotropic environment. Our observations also suggest that the sequence incorporated in P-15 may be a specific ligand for cells. Unlike other reported cell binding peptides, the residues involved in this interaction are non-polar.