Serial Pathways Research Articles

Household Income and Offspring Education Explain Blacks' Diminished Returns of Parental Education.

High parental education promotes various aspects of offspring well-being including reducing their risk of depression/anxiety, criminal justice involvement, and welfare reliance. However, according to minorities' diminished returns, these benefits are not equal across racial groups, with Black families experiencing diminished returns of parental education compared to White families. This study explores the role of household income and offspring educational attainment as potential serial pathways that operate as mechanisms underlying diminished returns of parental education on offspring outcomes in Black families. Gender differences in these effects were also explored. Utilizing data from the Future of Families and Child Wellbeing Study (FFCWS) over a 22-year follow-up period (seven waves), we examined the serial mediation by household income and offspring educational attainment in explaining the relationship between parental education and offspring outcomes namely depression, anxiety, criminal justice involvement, and welfare reliance [Temporary Assistance for Needy Families (TANF) and Supplemental Nutrition Assistance Program (SNAP)]. We used structural equation modeling (SEM) with household income as the first mediator and young adult education as the second mediator. Multi-group models were used to explore gender differences in these paths. The study confirmed the role of our proposed serial mediators for Blacks' weaker effects of parental education on offspring outcomes. We observed weaker effects of first affects household income, with this effect being for Black families compared to White families, which then impacted educational attainment of the offspring. The findings indicate that household income plays a crucial mediating role, but its effect is weaker in Black families. Additionally, the educational attainment of offspring from highly educated Black parents is less effective in improving outcomes compared to their White peers, further contributing to diminished returns. Some gender differences were observed for the effects of educational attainment on economic and health outcomes of young adults. The study underscores the need to reconsider traditional assumptions about the comparability of family conditions and outcomes across racial groups with similar levels of parental education. The findings highlight the importance of targeted policies and interventions aimed at enhancing the economic stability and educational outcomes of Black families to address these disparities. Policies should focus on promoting the economic well-being of highly educated Black parents and improving the educational outcomes of their children.

Optogenetic manipulation of a value-coding pathway from the primate caudate tail facilitates saccadic gaze shift

In the primate basal ganglia, the caudate tail (CDt) encodes the historical values (good or bad) of visual objects (i.e., stable values), and electrical stimulation of CDt evokes saccadic eye movements. However, it is still unknown how output from CDt conveys stable value signals to govern behavior. Here, we apply a pathway-selective optogenetic manipulation to elucidate how such value information modulates saccades. We express channelrhodopsin-2 in CDt delivered by viral vector injections. Selective optical activation of CDt-derived terminals in the substantia nigra pars reticulata (SNr) inhibits SNr neurons. Notably, these SNr neurons show inhibitory responses to good objects. Furthermore, the optical stimulation causes prolonged excitation of visual-saccadic neurons in the superior colliculus (SC), and induces contralateral saccades. These SC neurons respond more strongly to good than to bad objects in the contralateral hemifield. The present results demonstrate that CDt facilitates saccades toward good objects by serial inhibitory pathways through SNr.

Predicting the growth patterns in early mathematics achievement from cognitive and environmental factors among Chinese kindergarten children

One hundred and seventy-three Chinese kindergarten children (85 girls, Mage = 67.25 months) were assessed on measures of domain-general cognitive skills (nonverbal IQ, inhibition, and working memory), approximate number system acuity (nonsymbolic estimation and symbolic estimation), and early mathematics achievement at the beginning of the academic year. Their parents completed a questionnaire on family's factors (family's socioeconomic status, parents' numeracy expectations, and the home numeracy environment). In addition, children were reassessed on early mathematics achievement at the halfway and end of the academic year. Analysis with latent growth modelling showed that nonverbal IQ, working memory, nonsymbolic estimation, symbolic estimation, family's socioeconomic status, and parents' numeracy expectations uniquely predicted the intercept in early mathematics achievement, while the home numeracy environment uniquely predicted the growth rate. In addition, path analysis showed that the home numeracy environment also indirectly predicted the intercept in early mathematics achievement through nonsymbolic estimation and symbolic estimation, while parents' numeracy expectations indirectly predicted the slope of early mathematics achievement through the home numeracy environment and indirectly predicted the intercept of early mathematics achievement through serial pathways.

Intra- and inter-hemispheric effective connectivity in the human somatosensory cortex during pressure stimulation

BackgroundSlow-adapting type I (SA-I) afferents deliver sensory signals to the somatosensory cortex during low-frequency (or static) mechanical stimulation. It has been reported that the somatosensory projection from SA-I afferents is effective and reliable for object grasping and manipulation. Despite a large number of neuroimaging studies on cortical activation responding to tactile stimuli mediated by SA-I afferents, how sensory information of such tactile stimuli flows over the somatosensory cortex remains poorly understood. In this study, we investigated tactile information processing of pressure stimuli between the primary (SI) and secondary (SII) somatosensory cortices by measuring effective connectivity using dynamic causal modeling (DCM). We applied pressure stimuli for 3 s to the right index fingertip of healthy participants and acquired functional magnetic resonance imaging (fMRI) data using a 3T MRI system.ResultsDCM analysis revealed intra-hemispheric effective connectivity between the contralateral SI (cSI) and SII (cSII) characterized by both parallel (signal inputs to both cSI and cSII) and serial (signal transmission from cSI to cSII) pathways during pressure stimulation. DCM analysis also revealed inter-hemispheric effective connectivity among cSI, cSII, and the ipsilateral SII (iSII) characterized by serial (from cSI to cSII) and SII-level (from cSII to iSII) pathways during pressure stimulation.ConclusionsOur results support a hierarchical somatosensory network that underlies processing of low-frequency tactile information. The network consists of parallel inputs to both cSI and cSII (intra-hemispheric), followed by serial pathways from cSI to cSII (intra-hemispheric) and from cSII to iSII (inter-hemispheric). Importantly, our results suggest that both serial and parallel processing take place in tactile information processing of static mechanical stimuli as well as highlighting the contribution of callosal transfer to bilateral neuronal interactions in SII.

Electric impedance of human embryonic stem cell-derived retinal pigment epithelium

The barrier properties of epithelium are conventionally defined by transepithelial resistance (TER). TER provides information about the tightness of the epithelium. Electrical impedance spectroscopy (EIS) provides additional information regarding cell membrane properties, such as changes in electric capacitance and possible parallel or serial pathways that may correlate with the morphology of the cell layer. This study presents EIS of retinal pigment epithelial (RPE) cell model of the putative RPE differentiated from human embryonic stem cells (hESC-RPE). The generally utilized RPE cell model, ARPE-19, was used as immature control. The measured EIS was analyzed by fitting an equivalent electrical circuit model describing the resistive and capacitive properties of the RPE. Our results indicated that TER of hESC-RPE cells was close to the values of human RPE presented in the literature. This provides evidence that the stem cell-derived RPE in vitro can reach high-barrier function. Furthermore, hESC-RPE cells produced impedance spectra that can be modeled by the equivalent circuit of one time constant. ARPE-19 cells produced low-barrier properties, that is, an impedance spectra that suggested poor maturation of ARPE-19 cells. To conclude, EIS could give us means for non-invasively estimating the functionality and maturation of differentiated-RPE cells.

Integrating Serial Pathways in Radiotherapy Treatment Planning-impact on the Decision Making in Delivering Stereotactic Radiosurgery (SRS) vs. Fractionated Stereotactic Radiotherapy (FSRT)

Materials/Methods: 30 patients with 35 lesions in lung or liver were enrolled. They suffered from lung cancer, hepatocellular cancer, Klatskin tumor or lung metastases. Target delineation based on contrast enhanced PET/CT. Additional MRI information was taken into account in case of liver lesions. Planning target volume (PTV) included gross tumor volume (GTV), 2 mm set-up margin and safety margins based on list-mode detected motion. Normally, the patients underwent SBRT with 3 x 12.5 Gy to the 65% enclosing isodose. If stomach or small bowel had been touched by PTV the prescribed dose was 5 x 7.0 Gy. Clinical history, laboratory findings, early and late toxicity scores, PET/CT, and MRI in cases of liver lesions were gathered at the 6-week follow-up visit and then every 3 months. Results: All lesions were visible in PET/CT and movement was detected in all cases by list-mode based reconstruction. No early or late toxicity $ 2 (CTCAE v.3.0) was reported. With a median follow-up of 9.3 months, the local tumor control rate is 100%. Conclusions: List-mode capable PET/CT can easily solve problems in valid acquisition of tumor movements. The results show excellent tumor control and low toxicity, therefore it is very useful for high-precisions techniques with free breathing.

High‐Resolution Analysis of Barrier Function

High-resolution analysis of epithelial barrier function adds substantial information to that provided by conventional transepithelial electrical resistance (TER) measurements. This chapter describes three high-resolution techniques. First, two variants of impedance spectroscopy are delineated. One-path impedance spectroscopy discriminates vertically between serial pathways, namely resistances of the epithelial cell layer and of subepithelial tissues. As a typical application, measurements on human sigmoid colon biopsies from patients suffering from Crohn's disease are reported. Two-path impedance spectroscopy allows to discriminate between trans- and paracellular resistance, and the general principle of this technique is outlined. Second, the conductance scanning technique is presented, which discriminates horizontally between optically distinct parallel pathways over a wide range of spatial resolutions. Using this technique, it was shown that occludin--in contrast to the then prevailing opinion--is not irreplaceable to barrier function. Third, three-dimensional confocal fluorescence imaging for depicting transepithelial transport processes is introduced. Using this method the transepithelial translocation of bacteria which generate focal leaks was discovered.

Many Drugs and Phytochemicals Can Be Activated to Biological Reactive Intermediates

The metabolism of drugs and other xenobiotics is exemplified by cytochrome P450-mediated oxidation to more hydrophilic compounds. Enzymatic oxidation of some functional groups, however, can result in transient reactive intermediates--a transformation that is common in nature. Some drugs and many phytochemicals that contain, for example, a thiophene ring are oxidized by cytochrome P450 to reactive intermediates, such as sulfoxides, that can covalently bond to thiol nucleophiles in macromolecules, such as proteins. Many other functional groups can be oxidized to reactive intermediates--for instance, olefins, alkynes, alkylamines, furans, and p-aminophenols. Because any consequence of a biological reactive intermediate (BRI) is dependent on many factors a number of BRIs are benign. Toxicity is determined by complex and specific arrays of parallel and/or serial pathways and cellular states, not by entities or individual reactions. Because the formation of reactive intermediates can correlate with unacceptable toxicity, it is important to understand if or how a compound may undergo this type of transformation. Not all substances that form reactive intermediates are toxic; many are not. Therefore, it is critical to understand the mechanism of metabolism in considering any toxicity relevance and in evaluating animal models. Indeed, the complex nature of these many interactions and entities underscores the fact that the presence of a BRI is not an accurate indicator of human toxicity. A BRI is neither good nor a priori bad. It is a potential detoxication product and an incidental fate of the xenobiotic.

Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression

Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression

Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression

BackgroundExperiencing emotions engages high-order orbitofrontal and medial prefrontal areas, and expressing emotions involves low-level autonomic structures and peripheral organs. How is information from the cortex transmitted to the periphery? We used two parallel approaches to map simultaneously multiple pathways to determine if hypothalamic autonomic centres are a key link for orbitofrontal areas and medial prefrontal areas, which have been associated with emotional processes, as well as low-level spinal and brainstem autonomic structures. The latter innervate peripheral autonomic organs, whose activity is markedly increased during emotional arousal.ResultsWe first determined if pathways linking the orbitofrontal cortex with the hypothalamus overlapped with projection neurons directed to the intermediolateral column of the spinal cord, with the aid of neural tracers injected in these disparate structures. We found that axons from orbitofrontal and medial prefrontal cortices converged in the hypothalamus with neurons projecting to brainstem and spinal autonomic centers, linking the highest with the lowest levels of the neuraxis. Using a parallel approach, we injected bidirectional tracers in the lateral hypothalamic area, an autonomic center, to label simultaneously cortical pathways leading to the hypothalamus, as well as hypothalamic axons projecting to low-level brainstem and spinal autonomic centers. We found densely distributed projection neurons in medial prefrontal and orbitofrontal cortices leading to the hypothalamus, as well as hypothalamic axonal terminations in several brainstem structures and the intermediolateral column of the spinal cord, which innervate peripheral autonomic organs. We then provided direct evidence that axons from medial prefrontal cortex synapse with hypothalamic neurons, terminating as large boutons, comparable in size to the highly efficient thalamocortical system. The interlinked orbitofrontal, medial prefrontal areas and hypothalamic autonomic centers were also connected with the amygdala.ConclusionsDescending pathways from orbitofrontal and medial prefrontal cortices, which are also linked with the amygdala, provide the means for speedy influence of the prefrontal cortex on the autonomic system, in processes underlying appreciation and expression of emotions.

Reflective consciousness and the emergence of memes: serial evolutionary pathways?

Among the most important questions that confront the scientific and philosophical understanding of the human mind, the exact role that consciousness plays in the way we perceive our external and internal worlds is one. We do not yet understand the biological mechanisms that underlie our conscious thoughts, our ability to reflect on our lives and on ourselves. What has also not been adequately understood are some closely related problems. These questions pertain to how consciousness evolved in the first place in the biological world, attained its present state of complexity and the directions in which it continues to evolve today, particularly in humans ­ the only species that everyone agrees is `conscious'. This essay discusses aspects of consciousness in non-human species, considers why reflective consciousness needed to evolve at all, and speculates about a likely evolutionary pathway that this form of consciousness may have generated in relatively recent times. I suggest that memes may have evolved to the fullest extent in humans, a species that is reflectively conscious, and that memetic fitness may be increasingly regulating the further evolution of the human race. I conclude with the example of altruism and point out that its evolution in humans is best explained by a memetic model.

Parallel cortical networks for volitional control of swallowing in humans.

A number of studies have demonstrated the involvement of parallel networks in the control of voluntary sequential motor procedures. We sought to determine whether a parallel network organization may be found for complex, sequentially based motor systems that are the product of both voluntary and automatic control processes. Specifically, we sought to determine whether the cortical organizational scheme for voluntary repetitive swallowing in adult humans is characterized by a hierarchical dual-projection model or by modules organized into parallel systems. We utilized functional magnetic resonance imaging (fMRI) to investigate cortical function during normal swallowing tasks in eight healthy human adults. Subjects performed both dry (saliva) and bolus (3 ml/bolus of water) swallows. Activation during swallowing tasks localized to sensorimotor areas (M1, S1, and SMA), S2, premotor cortex, posterior parietal cortex, cingulate gyrus, inferior frontal gyrus, the cerebellum, the insular cortex, auditory cortex, corpus callosum, and the basal ganglia and thalamus. Principal components analysis (PCA) of these regions revealed five functional clusters or modules: (1) sensorimotor areas and cingulate gyrus; (2) inferior frontal gyrus, S2, corpus callosum, basal ganglia and thalamus; (3) premotor cortex and posterior parietal cortex; (4) cerebellum; and (5) insula. Analysis of the functional relationship between these areas demonstrated two parallel loops defined by connections to either the cerebellum or insula and connected through the sensorimotor-cingulate module. Path analysis was performed to test the hypothesis of modules organized into parallel loops versus a hierarchical dual-projection model consisting of two separate, singular hierarchical serial pathways from the sensorimotor cortex or insula to the thalamus. These results support the model of modules organized into parallel loops (P=0.8), but not the hierarchical dual-projection model (P<0.0001). Organization of the control of voluntary repetitive swallowing into two parallel systems may confer the ability to effectively coordinate and integrate this highly complex sequentially based motor behavior.

Visual response properties of cells in the ventral and dorsal parts of the macaque inferotemporal cortex.

We recorded from cells in the anterio-ventral (TEav) and anterio- dorsal (TEad) parts of area TE of the inferotemporal cortex and examined their responses to a set of 100 visual stimuli in awake, fixating monkeys. In both TEav and TEad we found that, depending on the stimulus, the time course of responses varied considerably within individual cells and that there were three main factors in the variation. One factor is variance in the balance between the initial transient part of responses around 130 ms after stimulus onset and the later part after 240 ms from stimulus onset. The later parts of responses were more stimulus selective. The second factor is variance in the latency of response onset and peak and the third is variance in the speed of decay from the peak within the initial part of the responses. Stronger responses had shorter onset and peak latencies and longer decay times. The results suggest that stimulus images can be discriminated very rapidly in TEav and TEad by detecting differences in response onset. TEav cells differed from TEad cells in that they were more difficult to activate than TEad cells: the proportion of responsive TEav cells was smaller, the maximal responses of individual cells were smaller than in TEad and the number of stimuli that evoked significant responses in individual responsive cells was also smaller than in TEad. Moreover, TEav cells, overall, responded more strongly to more colorful object images than less colorful ones, while TEad cells did not show such a tendency. However, the minimum onset latency of individual cells and the sharpness of stimulus selectivity did not differ significantly between TEav and TEad. Responses of TEav cells are as selective as those of TEad cells, although there remains a possibility that the domain of selectivity differs between the two areas. These results support an earlier anatomical finding that TEav and TEad are located at the same hierarchical level of separate serial pathways rather than at successive stages of a single pathway.

Bilateral organization of parallel and serial pathways in the dentate gyrus demonstrated by current-source density analysis in the rat.

1. Membrane currents evoked in the dentate gyrus (DG) by stimulation of afferent pathways from the entorhinal cortex (EC) and contralateral DG were examined by current-source density (CSD) analysis in urethan-anesthetized rats. Stimulation of each afferent pathway evoked membrane currents with distinct spatial and temporal organization in the DG. CSD and anatomic analysis revealed that afferent input from the EC activated the DG bilaterally through parallel and serial pathways. The analysis provided a detailed description of the location, timing, and relative amplitude of evoked monosynaptic and multisynaptic currents in the DG. 2. Orthodromic stimulation of the perforant path (PP) evoked a large ipsilateral excitatory postsynaptic current (iEPSC) at a latency of 2.5-4 ms in the middle and outer stratum moleculare (STM) of the DG, and a population spike that was generated by an excitatory inward current at a latency of 5-9 ms in the stratum granulosum. 3. A variable, low-amplitude ipsilateral inward current followed the population spike at a latency of 13-16 ms in the inner STM, which is the site of synaptic terminals of the associational and commissural pathways arising from neurons in the hilus of the DG. Orthodromic stimulation of the commissural pathway from the hilus of the contralateral DG also evoked an inward current in the inner STM at a latency of 2-6 ms, which was 40-60% of the amplitude of the monosynaptic iEPSC. 4. Orthodromic stimulation of the EC evoked a low-amplitude contralateral excitatory postsynaptic current (cEPSC) at a latency of 3-6 ms in the outer and middle STM of the contralateral DG, which was generated by monosynaptic transmission in the sparse crossed pathway from the EC. In contrast to the variable, low-amplitude inward current in the inner STM that followed the iEPSC, the cEPSC was consistently followed by a large inward current at a latency of 8-14 ms in the inner STM of the contralateral DG. 5. The large inward current in the inner STM of the contralateral DG was abolished by transection of the PP ipsilateral and rostral to the stimulating electrode, but was unaffected by transection of the PP at a similar location in the hemisphere contralateral to the stimulating electrode. These observations suggested that this current was most likely generated by a multisynaptic pathway involving the ipsilateral PP and the commissural pathway arising from the hilus of the DG. 6. In conclusion, efferents from the EC activated the DG bilaterally by parallel and serial pathways. Parallel monosynaptic pathways from the EC activated homologous distal segments of granule cell dendrites bilaterally, by a massive input to the ipsilateral DG and a sparse input to the contralateral DG. Sequential propagation from the EC through a multisynaptic pathway that included the commissural pathway from the hilus of the DG bilaterally activated the proximal segments of granule cell dendrites at longer latencies. The amplitude of the multisynaptic currents generated by serial pathways in the proximal dendrites varied inversely with the amplitudes of the monosynaptic currents evoked by parallel pathways in the distal dendrites. These observations may have implications for synaptic integration, associative properties, and information processing in the DG.

Process for the selective hydrogenolysis of CCl 2F 2 (CFC-12) into CH 2F 2 (HFC-32)

The conversion of waste CCl 2F 2 (CFC-12) into high added value product CH 2F 2 (HFC-32) seems technically and economically feasible with a selected palladium on activated carbon catalyst. This catalyst shows a remarkable constant selectivity to HFC-32 in the range between 70% and 90% at all conversion levels with varying process conditions. Small amount of impurities, like Al, Fe or Cr, present in the activated carbon can have a significant effect on the catalyst performance. These impurities act as Friedel-Crafts catalyst thus catalyzing the unwanted chlorine-fluorine exchange. The chlorine-fluorine exchange can be sufficiently suppressed by removing the impurities from the activated carbon support prior to introduction of the palladium. The mechanism of the reaction follows mainly parallel rather than the expected serial pathways. A reaction scheme is proposed, which explains the high selectivity to HFC-32 by formation of a CF 2-carbene, which preferentially desorbs as HFC-32.