Metabolite concentrations, fluxes and free energies imply efficient enzyme usage.

In metabolism, available free energy is limited and must be divided across pathway steps to maintain a negative ΔG throughout. For each reaction, ΔG is log proportional both to a concentration ratio (reaction quotient to equilibrium constant) and to a flux ratio (backward to forward flux). Here we use isotope labeling to measure absolute metabolite concentrations and fluxes in Escherichia coli, yeast and a mammalian cell line. We then integrate this information to obtain a unified set of concentrations and ΔG for each organism. In glycolysis, we find that free energy is partitioned so as to mitigate unproductive backward fluxes associated with ΔG near zero. Across metabolism, we observe that absolute metabolite concentrations and ΔG are substantially conserved and that most substrate (but not inhibitor) concentrations exceed the associated enzyme binding site dissociation constant (Km or Ki). The observed conservation of metabolite concentrations is consistent with an evolutionary drive to utilize enzymes efficiently given thermodynamic and osmotic constraints

Candida albicans Infection Decreases The Expression Of The Na+-K+-2Cl– Cotransporter 1 In T84 and Madin Darby Canine Kidney Cells

The commensal human fungal pathogen, Candida albicans, prior to infect the human body, must penetrate the intestinal mucosal barrier. To do so, it needs to bypass the different protective mechanisms such as fluid secretion. The basolateral Na+-K+-2Cl– cotransporter 1 (NKCC1) is a key protein regulating fluid secretion in the intestine. We hypothesize that C. albicans decreases fluid secretion prior to invasion by inducing NKCC1 internalization. In our experiments, we used Madin Darby canine kidney (MDCK) cells expressing a GFP-NKCC1 fluorescent tag and T84 cells, a human colonic cell line. Cells were infected with 100,000 C. albicans for varying lengths of time, fixed, stained and mounted for fluorescence microscopy. The number of internalized vesicles was evaluated using FIJI. Our results show that in MDCK cells, C. albicans only increased NKCC1 internalization at the 30-minute time point (P\u3c0.05), all subsequent time points were not significant. Similarly, infecting T84 cells with C. albicans significantly induced NKCC1 internalization at the 30-minute (P\u3c0.05), 1 hour (P\u3c0.05), and 90-minute (P\u3c0.05) time points. Past 90 minutes, we observed a sharp decline in the number of internalized vesicles that continued to decrease through 6 hours of exposure to C. albicans. Finally, in C. albicans-T84 infected cells, using an immunoblot approach, we found that total NKCC1 protein expression was decreased by ~20% (P\u3c0.05) compared to uninfected cells. Our results suggest that C. albicans induces internalization of NKCC1, and subsequent degradation of NKCC1, which would decrease fluid secretion and allow adhesion, and invasion of the epithelium

Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy

Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy

Reading Guide to Explore Gastronomic Arts and Sciences Research and Education : Reviews of Food Studies and Japanese Food Textbooks and Essays

Food studies is an interdisciplinary research that addresses phenomena related to food. It is necessary to give an overview of this new research area and develop teaching programs to learn food studies. This article introduces textbooks and anthologies on food studies and Japanese food. This paper takes four food studies textbooks Food: The Key Concepts, Food Studies: An Introduction to Research Methods, Food: A Very Short Introduction, Food Studies: A Hands-On Guide, three food studies anthologies (Food and Culture: A Reader, Routledge Handbook of Food Studies, The Handbook of Food Research), and three academic books on Japanese food culture and history (Devouring Japan: Global Perspectives on Japanese Culinary Identity, Japan's Cuisines: Food, place and identity, Branding Japanese Food: from Meitbutsu to Washoku), which are used in higher education in Europe and the United States. This paper reviews the outline, the authors and editors, and how to utilize each books and essays.Non peer reviewe

Influence of Topology on the Ultrafast Carrier Dynamics in MoTe2

Transport properties of Weyl semimetals are intimately connected to the underlying band structure. The signature of Weyl semimetals are linear dispersing bands that touch, forming Weyl points that result in high charge carrier mobilities. The layered transition metal dichalcogenide MoTe2, undergoes a temperature dependent phase transition that directly converts the trivial 1Tprime phase to the nontrivial Td phase, providing an opportunity to understand how the formation of a Weyl point manifests in the ultrafast carrier dynamics. In this study, we use resonant X-ray photoemission to monitor the element specific evolution of excited carriers 1Tprime-MoTe2 and in the vicinity of the Weyl point in Td-MoTe2. We find that the delocalization time of 1Tprime-MoTe2 is a factor 1.5 times faster than in Td-MoTe2. We argue that this is a result of the change in the density of states and screening length, to a higher carrier scattering rate in Td-MoTe2. Our study tracks the fate of carriers in MoTe2 on sub-fs time-scales and with atomic site specificity

Correction: A Feasible and Efficacious Mobile-Phone Based Lifestyle Intervention for Filipino Americans with Type 2 Diabetes: Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/diabetes.8156.]

Vertical Dimensions of Mandible in Class II Subdivision Malocclusion with Skeletal Asymmetry

• Advancements in 3-dimensional imaging analysis, utilizing cone-beam computed tomography (CBCT), have allowed for further investigation of skeletal asymmetry. • While past 2-dimensional studies attributed dentoalveolar deviation to unilateral Class II malocclusion, recent 3D studies have found a primarily skeletal contribution.1 • There is much debate on the impact of condylar morphology on malocclusion in patients with Class II subdivision and significant skeletal asymmetry.2 • Some authors concluded that condylar characteristics are not correlated with skeletal asymmetry, while others reported a correlation between a greater condyle angulation and skeletal asymmetry.2-

Using Biofeedback to Reduce Spatiotemporal Asymmetry Impairs Dynamic Balance in People Post-Stroke

Background. People poststroke often walk with a spatiotemporally asymmetric gait, due in part to sensorimotor impairments in the paretic lower extremity. Although reducing asymmetry is a common objective of rehabilitation, the effects of improving symmetry on balance are yet to be determined. Objective. We established the concurrent validity of whole-body angular momentum as a measure of balance, and we determined if reducing step length asymmetry would improve balance by decreasing whole-body angular momentum. Methods. We performed clinical balance assessments and measured wholebody angular momentum during walking using a full-body marker set in a sample of 36 people with chronic stroke. We then used a biofeedback-based approach to modify step length asymmetry in a subset of 15 of these individuals who had marked asymmetry and we measured the resulting changes in whole-body angular momentum. Results. When participants walked without biofeedback, whole-body angular momentum in the sagittal and frontal plane was negatively correlated with scores on the Berg Balance Scale and Functional Gait Assessment supporting the validity of whole-body angular momentum as an objective measure of dynamic balance. We also observed that when participants walked more symmetrically, their wholebody angular momentum in the sagittal plane increased rather than decreased. Conclusions. Voluntary reductions of step length asymmetry in people poststroke resulted in reduced measures of dynamic balance. This is consistent with the idea that after stroke, individuals might have an implicit preference not to deviate from their natural asymmetry while walking because it could compromise their balance. Clinical Trials Number: NCT03916562

Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1

Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density

Política ambiental chilena y política indígena en la coyuntura de los tratados internacionales (1990-2010)

Se analizan las políticas medio ambientales e indígenas durante el período 1990- 2010 de gobiernos de la Concertación, los tratados internacionales sobre el medio ambiente que inciden en el uso de recursos naturales en territorios huilliche. Se concluye que la política pública medioambiental, por su naturaleza reactiva, en el contexto de los mercados globales, se ha visto sobrepasada por la hegemonía del poder de las transnacionales que invierten en los commodities forestal, minero, agropecuario, amparadas por una legislación ambiental débil y un discurso político obsecuente.Indigenous and environmental policy is analyzed during the period 1990-2010, during the governments of the Concertación, those international treaties relating to the environment which may have direct incidence on the natural resources in huilliche territory. The conclusion is that public environmental policy, due to its reactive nature, in the context of global markets, has been overcome by a hegemony of power amongs transnationals which invest in forestry, mining and agro commodities, all of which are sheltered by weak environmental legislation and an obsequious political discourse.Analisamos as políticas ambientais e indígenas durante o período de 1990 - 2010 de governos da Concertación, os tratados internacionais sobre o meio ambiente que afetam o uso de recursos naturais em territórios huilliche. Conclui-se que a política pública ambiental, por sua natureza reativa, no contexto dos mercados globais foi ultrapassada pela hegemonia do poder transnacional de investir em commodities silvicultura, mineração, agricultura, protegida pela legislação ambiental fraca eo discurso político obsequioso