The Human Parahippocampal Region: I. Temporal Pole Cytoarchitectonic and MRI Correlation

The temporal pole (TP) is the rostralmost portion of the human temporal lobe. Characteristically, it is only present in human and nonhuman primates. TP has been implicated in different cognitive functions such as emotion, attention, behavior, and memory, based on functional studies performed in healthy controls and patients with neurodegenerative diseases through its anatomical connections (amygdala, pulvinar, orbitofrontal cortex). TP was originally described as a single uniform area by Brodmann area 38, and von Economo (area TG of von Economo and Koskinas), and little information on its cytoarchitectonics is known in humans. We hypothesize that 1) TP is not a homogenous area and we aim first at fixating the precise extent and limits of temporopolar cortex (TPC) with adjacent fields and 2) its structure can be correlated with structural magnetic resonance images. We describe here the macroscopic characteristics and cytoarchitecture as two subfields, a medial and a lateral area, that constitute TPC also noticeable in 2D and 3D reconstructions. Our findings suggest that the human TP is a heterogeneous region formed exclusively by TPC for about 7 mm of the temporal tip, and that becomes progressively restricted to the medial and ventral sides of the TP. This cortical area presents topographical and structural features in common with nonhuman primates, which suggests an evolutionary development in human species

High-quality intake of carbohydrates is associated with lower prevalence of subclinical atherosclerosis in femoral arteries: The AWHS study

Background and aims: High-quality of the carbohydrates consumed, apart from their total amount, appear to protect from cardiovascular disease (CVD). However, the relationship between the quality of carbohydrates and the early appearance of atherosclerosis has not yet been described. Our objective was to estimate the association between the quality of dietary carbohydrates and subclinical atherosclerosis in femoral and carotid arteries. Methods: Cross-sectional study of femoral and carotid atherosclerosis assessed using ultrasounds of 2074 middle-aged males, 50.9 (SD 3.9) years old, with no previous CVD, and pertaining to the Aragon Workers’ Health Study (AWHS) cohort. Food frequency questionnaires were used to calculate a carbohydrate quality index (CQI) defined as: consumption of dietary fiber, a lower glycemic index, the ratio of whole grains/total grains, and the ratio of solid carbohydrates/total carbohydrates. The presence of plaques across four CQI intervals was studied using adjusted logistic regression models. Results: The CQI showed a direct inverse association with subclinical atherosclerosis in femoral territories. Participants with a higher consumption of high-quality carbohydrates (13–15 points) were less likely to have femoral plaques when compared with participants in the lowest index interval (4–6 points) (OR = 0.59; 95% CI = 0.39, 0.89; p = 0.005). No association was found between the CQI and the presence of subclinical atherosclerosis in carotid territories. A lower consumption of high-quality carbohydrates tended to be associated with a greater atherosclerosis extension, considered as the odds for having more affected territories (p = 0.011). Conclusions: Among middle-aged males, a high-quality intake of carbohydrates is associated with a lower prevalence of femoral artery subclinical atherosclerosis when compared with a lower consumption. Thus, indicating an early relationship between the quality of carbohydrates and the development of CVD. © 2021 The Author(s

Ultra-processed food consumption is associated with renal function decline in older adults: A prospective cohort study

Ultra-processed food (UPF) consumption has been associated with increased risk of cardiovascular risk factors and mortality. However, little is known on the UPF effect on renal function. The aim of this study is to assess prospectively the association between consumption of UPF and renal function decline. This is a prospective cohort study of 1312 community-dwelling individuals aged 60 and older recruited during 2008–2010 and followed up to December 2015. At baseline, a validated dietary history was obtained. UPF was identified according to NOVA classification. At baseline and at follow-up, serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) levels were ascertained and changes were calculated. A combined end-point of renal decline was considered: SCr increase or eGFR decreased beyond that expected for age. Logistic regression with adjustment for potential confounders was performed. During follow-up, 183 cases of renal function decline occurred. The fully adjusted odds ratios (95% CI) of renal function decline across terciles of percentage of total energy intake from UPF were 1.56 (1.02–2.38) for the second tercile, and 1.74 (1.14–2.66) for the highest tercile; p-trend was 0.026. High UPF consumption is independently associated with an increase higher than 50% in the risk of renal function decline in Spanish older adults

Association of cooking patterns with inflammatory and cardio-metabolic risk biomarkers

Diet has been clearly associated with cardiovascular disease, but few studies focus on the influence of cooking and food preservation methods on health. The aim of this study was to describe cooking and food preservation patterns, as well as to examine their association with inflammatory and cardio-metabolic biomarkers in the Spanish adult population. A cross-sectional study of 10, 010 individuals, representative of the Spanish population, aged 18 years or over was performed using data from the ENRICA study. Food consumption data were collected through a face-to-face dietary history. Cooking and food preservation patterns were identified by factor analysis with varimax rotation. Linear regression models adjusted for main confounders were built. Four cooking and food preservation patterns were identified. The Spanish traditional pattern (positively correlated with boiling and sautéing, brining, and light frying) tends to be cardio-metabolically beneficial (with a reduction in C-reactive protein (-7.69%)), except for high density lipoprotein cholesterol (HDL-c), insulin levels, and anthropometrics. The health-conscious pattern (negatively correlated with battering, frying, and stewing) tends to improve renal function (with a reduction in urine albumin (-9.60%) and the urine albumin/creatinine ratio (-4.82%)). The youth-style pattern (positively correlated with soft drinks and distilled alcoholic drinks and negatively with raw food consumption) tends to be associated with good cardio-metabolic health except, for lower HDL-c (-6.12%), higher insulin (+6.35%), and higher urine albumin (+27.8%) levels. The social business pattern (positively correlated with the consumption of fermented alcoholic drinks, food cured with salt or smoke, and cured cheese) tends to be detrimental for the lipid profile (except HDL-c), renal function (urine albumin +8.04%), diastolic blood pressure (+2.48%), and anthropometrics. Cooking and food preservation patterns showed a relationship with inflammatory and cardio-metabolic health biomarkers. The Spanish traditional pattern and the health-conscious pattern were associated with beneficial effects on health and should be promoted. The youth-style pattern calls attention to some concerns, and the social business pattern was the most detrimental one. These findings support the influence of cooking and preservation patterns on health

Influence of ageing and cooking method on sensory evaluation and aromatic compounds profile of meat from Retinta breed crossbreeding

Se estudió el efecto del tiempo de maduración y tipo de cocinado sobre la valoración sensorial y el perfil de los compuestos aromáticos de la carne de animales de los cruces de toros de las razas Retinta, Limousine, Pirenaica y Asturiana de los Valles con vacas Retintas. Se utilizaron dos paneles, uno para el efecto de la maduración y otro para el tipo de cocinado. El entrenamiento de los catadores y la temperatura de cocinado fueron idénticos en ambos casos, aunque los perfiles difieren entre sí. En la valoración sensorial no se encontraron interacciones entre efectos. El cruce sólo afectó a la terneza, siendo la carne de Pirenaica x Retinta y Retinta x Retinta algo más dura. La terneza, el flavor a hígado y el flavor ácido aumentaron con la maduración, al contrario que la jugosidad. El tipo de cocinado afectó a la terneza y a la facilidad al tragar, estando ambas variables inversamente correlacionadas. Se identificaron 50 compuestos aromáticos. El cruce tuvo menos influencia que el tipo de cocinado y se encontró una interacción significativa entre efectos para 15 de los compuestos, especialmente hidrocarburos. El cruce afectó al porcentaje de alcoholes, compuestos azufrados y cetonas pero no al resto y el tipo de cocinado, a todos los compuestos. Los hidrocarburos y las cetonas presentaron mayores concentraciones que el resto. Para todos los grupos de compuestos excepto para los azufrados, las cantidades detectadas fueron mayores cuando el método de cocinado fue la cocción.We studied the effect of ageing period and cooking method on sensory evaluation and aromatic compounds profile of meat from crosses of Retinta, Limousine, Pirenaica and Asturiana de los Valles bulls and Retinta dams. Two panels were used, one to study the ageing effect and another to compare the effect of cooking method. The training and temperature of cooking were identical in both cases, although the descriptive profiles are different among themselves. No interaction between effects was found in sensory evaluation. Crossbreeding only affected tenderness, being meat from Pirenaica x Retinta and Retinta x Retinta crosses slightly tougher. Tenderness, liver flavour and acid flavour increased with ageing, contrary to juiciness. The cooking method affected tenderness and ease swallowing, and both variables were inversely correlated. 50 aromatics compounds were identified and we found a significant interaction effects for 15 compounds, especially hydrocarbons. Crossbreeding affected the percentage of alcohols, ketones and sulphur compounds whereas cooking method affected to all compounds. Hydrocarbons and ketones showed higher concentrations than the rest of the compounds. All compounds except the ketone groups were affected by cooking method. For all groups of compounds except for the sulphur, the amounts detected were higher when the cooking method was water-boiling

Focal accumulation of aromaticity at the CDRH3 loop mitigates 4E10 polyreactivity without altering its HIV neutralization profile

Broadly neutralizing antibodies (bnAbs) against HIV-1 are frequently associated with the presence of autoreactivity/polyreactivity, a property that can limit their use as therapeutic agents. The bnAb 4E10, targeting the conserved Membrane proximal external region (MPER) of HIV-1, displays almost pan-neutralizing activity across globally circulating HIV-1 strains but exhibits nonspecific off-target interactions with lipid membranes. The hydrophobic apex of the third complementarity-determining region of the heavy chain (CDRH3) loop, which is essential for viral neutralization, critically contributes to this detrimental effect. Here, we have replaced the aromatic/hydrophobic residues from the apex of the CDRH3 of 4E10 with a single aromatic molecule through chemical modification to generate a variant that preserves the neutralization potency and breadth of 4E10 but with reduced autoreactivity. Collectively, our study suggests that the localized accumulation of aromaticity by chemical modification provides a pathway to ameliorate the adverse effects triggered by the CDRH3 of anti-HIV-1 MPER bnAbs.This study was supported by the following Grants: European Commission (790012 SI H2020-MSCA-IF-2017) (E.R.); US NIAID, NIH grant R01 AI143563 (M.B. Z.); James B. Pendleton Charitable Trust (M.B.Z.); JSPS grant 20H03228 (J. M.M.C.); Spanish MCIU (RTI2018-095624-B-C21; MCIU/AEI/FEDER, UE) (J.L.N.), Basque Government (IT1196-19) (J.L.N.). C.E. acknowledges funding from Medical Research Council (grant number MC_UU_12010/unit programs G0902418 and MC_UU_12025), Wolfson Foundation, Deutsche Forschungsgemeinschaft (Excellence Cluster Balance of the Microverse, Collaborative Research Center 1278 Polytarget), Leibniz Association (Leibniz Campus Infectooptics), Wellcome Institutional Strategic Support Fund, Oxford internal funds (EPA Cephalosporin Fund and John Fell Fund), and support from the Micron Oxford Advanced Bioimaging Unit (Wellcome Trust funding 107457/Z/15/Z). This work was also supported by the Platform Project for Supporting Drug Discovery and Life Science Research [Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)] from AMED (JP21am0101091). S.I. received a predoctoral fellowship from the BasqueGovernment. P.C. would like to acknowledge the University of the Basque Country (DOCREC18/01), the Basque Government (POS_2018_1_0066) and the European Commission (H2020-MSCA-IF-2019-ST project 892232 FILM-HIV) for funding his position. This research was also supported by the CIFAR Azrieli Global Scholar program (J-P.J.), the Ontario Early Researcher Awards program (J-P.J.), and the Canada Research Chairs program (J-P.J.). Part of the biophysical data presented in this manuscript were collected at the Hospital for Sick Children Structural & Biophysical Core facility supported by the Canada Foundation for Innovation and Ontario Research Fund

Atrophy in the parahippocampal gyrus as an early biomarker of Alzheimer’s disease

The main aim of the present study was to compare volume differences in the hippocampus and parahippocampal gyrus as biomarkers of Alzheimer’s disease (AD). Based on the previous findings, we hypothesized that there would be significant volume differences between cases of healthy aging, amnestic mild cognitive impairment (aMCI), and mild AD. Furthermore, we hypothesized that there would be larger volume differences in the parahippocampal gyrus than in the hippocampus. In addition, we investigated differences between the anterior, middle, and posterior parts of both structures. We studied three groups of participants: 18 healthy participants without memory decline, 18 patients with aMCI, and 18 patients with mild AD. 3 T T1-weighted MRI scans were acquired and gray matter volumes of the anterior, middle, and posterior parts of both the hippocampus and parahippocampal gyrus were measured using a manual tracing approach. Volumes of both the hippocampus and parahippocampal gyrus were significantly different between the groups in the following order: healthy > aMCI > AD. Volume differences between the groups were relatively larger in the parahippocampal gyrus than in the hippocampus, in particular, when we compared healthy with aMCI. No substantial differences were found between the anterior, middle, and posterior parts of both structures. Our results suggest that parahippocampal volume discriminates better than hippocampal volume between cases of healthy aging, aMCI, and mild AD, in particular, in the early phase of the disease. The present results stress the importance of parahippocampal atrophy as an early biomarker of AD

Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments

The contribution of membrane interfacial interactions to recognition of membrane-embedded antigens by antibodies is currently unclear. This report demonstrates the optimization of this type of antibodies via chemical modification of regions near the membrane but not directly involved in the recognition of the epitope. Using the HIV-1 antibody 10E8 as a model, linear and polycyclic synthetic aromatic compounds are introduced at selected sites. Molecular dynamics simulations predict the favorable interactions of these synthetic compounds with the viral lipid membrane, where the epitope of the HIV-1 glycoprotein Env is located. Chemical modification of 10E8 with aromatic acetamides facilitates the productive and specific recognition of the native antigen, partially buried in the crowded environment of the viral membrane, resulting in a dramatic increase of its capacity to block viral infection. These observations support the harnessing of interfacial affinity through site-selective chemical modification to optimize the function of antibodies that target membrane-proximal epitopes.We are grateful to Professor Ueda (Kyushu University) for valuable advice. C.D. acknowledges RES (Red Espanola de Supercomputacio ' n) for providing computational resources. S.I. received a pre-doctoral fellowship from the Basque Government. P.C. acknowledges a research associate contract from the University of the Basque Country (DOCREC18/01) and a postdoctoral fellowship from the Basque Government (POS_2018_1_0066).This study was supported by the following grants: European Commission (790012 SI H2020MSCA-IF-2017 to E.R., J.-P.J., and J.L.N.); US NIAID (NIH) (R01 AI143563 to M.B.Z.); James B. Pendleton Charitable Trust (to M.B.Z.); Grant-in-Aid for Scientific Research on Innovative Areas "Chemistry for Multimolecular Crowding Biosystems, JSPS KAKENHI (JP17H06349 to A.O.); JSPS KAKENHI (15K06962 and 20H03228 to J.M.M.C.); Spanish MINECO (BIO2015-64421R and MINECO/AEI/FEDER, UE to J.L.N.); Spanish MCIU (RTI2018-095624B-C21 and MCIU/AEI/FEDER, UE to J.L.N.); and the Basque Government (IT1196-19) (to J.L.N.). C.E. acknowledges funding from Medical Research Council (MC_UU_12010/unit programs G0902418 and MC_UU_12025), Wolfson Foundation, Deutsche Forschungsgemeinschaft (Research unit 1905, Excellence Cluster Balance of the Microverse, Collaborative Research Centre 1278 Polytarget), Wellcome Institutional Strategic Support Fund, Oxford internal funds (EPA Cephalosporin Fund and John Fell Fund), and support from the Micron Oxford Advanced Bioimaging Unit (Wellcome Trust funding 107457/Z/15/Z). This research was undertaken, in part, thanks to funding from the CIFAR Azrieli Global Scholar program (to J.-P.J.) and the Canada Research Chairs program (950-231604 to J.-P.J.). This work was also supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS] from AMED JP19am0101091)