The PGRMC1 Antagonist AG-205 Inhibits Synthesis of Galactosylceramide and Sulfatide

Sulfatide synthesis in the human renal cancer cell line SMKT-R3 was strongly inhibited in the presence of low µM concentrations of AG-205, a progesterone receptor membrane component 1 (PGRMC1) antagonist. This was also the case in Chinese hamster ovary (CHO) cells stably transfected with UDP-galactose: ceramide galactosyltransferase and cerebroside sulfotransferase, the two enzymes required for sulfatide synthesis. In CHO cells synthesizing galactosylceramide but not sulfatide, galactosylceramide was also strongly reduced, suggesting an effect at the level of galactolipid synthesis. Notably, AG-205 inhibited galactosylceramide synthesis to a similar extent in wild type CHO cells and cells that lack PGRMC1 and/or PGRMC2. In vitro enzyme activity assays showed that AG-205 is an inhibitor of UDP-galactose: ceramide galactosyltransferase, but not cerebroside sulfotransferase. This study shows that PGRMC1 is only one of several targets of AG-205 and should be used with caution, especially in studies using cells synthesizing galactosylceramide and sulfatide.

Ingestion of an ample amount of meat substitute based upon a lysine-enriched, plant-based protein blend stimulates postprandial muscle protein synthesis to a similar extent as an isonitrogenous amount of chicken in healthy, young men

Plant-based proteins are considered to be less effective in their capacity to stimulate muscle protein synthesis when compared with animal-based protein sources, likely due to differences in amino acid contents. We compared the postprandial muscle protein synthetic response following the ingestion of a lysine-enriched plant-based protein product with an isonitrogenous amount of chicken. Twenty-four men (age: 24±5 y; BMI: 22.9±2.6 kg·m−2) participated in this parallel, double-blind, randomised controlled trial and consumed 40 g protein as a lysine-enriched wheat and chickpea protein product (Plant, n=12) or chicken breast fillet (Chicken, n=12). Primed, continuous intravenous L-[ring-13C6]-phenylalanine infusions were applied while repeated blood and muscle samples were collected over a 5h postprandial period to assess plasma amino acid responses, muscle protein synthesis rates, and muscle anabolic signalling responses. Postprandial plasma leucine and essential amino acid concentrations were higher following Chicken (P<0.001), while plasma lysine concentrations were higher throughout in Plant (P<0.001). Total plasma amino acid concentrations did not differ between interventions (P=0.181). Ingestion of both Plant and Chicken increased muscle protein synthesis rates from post-absorptive: 0.031±0.011 and 0.031±0.013 to postprandial: 0.046±0.010 and 0.055±0.015%∙h−1, respectively (P-time<0.001), with no differences between Plant and Chicken (P-interaction=0.068). Ingestion of 40 g protein in the form of a lysine-enriched plant-based protein product increases muscle protein synthesis rates to a similar extent as an isonitrogenous amount of chicken in healthy, young men. Plant-based protein products sold as meat replacers may be as effective as animal-based protein sources to stimulate postprandial muscle protein synthesis rates in healthy, young individuals.

Change to a healthy diet in people over 70 years old: the PREDIMED experience

Purpose It is difficult to change dietary habits and maintain them in the long run, particularly in elderly people. We aimed to assess whether adherence to the Mediterranean diet (MedDiet) and cardiovascular risk factor were similar in the middle-aged and oldest participants in the PREDIMED study. Methods We analyzed participants belonging to the first and fourth quartiles of age (Q1 and Q4, respectively) to compare between-group differences in adherence to the nutritional intervention and cardiovascular risk factor (CRF) control during a 3-year follow-up. All participants underwent yearly clinical, nutritional, and laboratory assessments during the following. Results A total of 2278 patients were included (1091 and 1187 in Q1 and Q4, respectively). At baseline, mean ages were 59.6 ± 2.1 years in Q1 and 74.2 ± 2.6 years in Q4. In Q4, there were more women, greater prevalence of hypertension and diabetes, and lower obesity and smoking rates than the younger cohort (P ≤ 0.001, all). Adherence to the MedDiet was similar in Q1 and Q4 at baseline (mean 8.7 of 14 points for both) and improved significantly (P < 0.01) and to a similar extent (mean 10.2 and 10.0 points, respectively) during follow-up. Systolic blood pressure, low density–lipoprotein cholesterol, and body weight were similarly reduced at 3 years in Q1 and Q4 participants. Conclusion The youngest and oldest participants showed improved dietary habits and CRFs to a similar extent after 3 years’ intervention. Therefore, it is never too late to improve dietary habits and ameliorate CRF in high-risk individuals, even those of advanced age. Registration The trial is registered in the London-based Current Controlled Trials Registry (ISRCTN number 35739639).

Vocal size exaggeration may have contributed to the origins of vocalic complexity

Vocal tract elongation, which uniformly lowers vocal tract resonances (formant frequencies) in animal vocalizations, has evolved independently in several vertebrate groups as a means for vocalizers to exaggerate their apparent body size. Here, we propose that smaller speech-like articulatory movements that alter only individual formants can serve a similar yet less energetically costly size-exaggerating function. To test this, we examine whether uneven formant spacing alters the perceived body size of vocalizers in synthesized human vowels and animal calls. Among six synthetic vowel patterns, those characterized by the lowest first and second formant (the vowel /u/ as in ‘boot’) are consistently perceived as produced by the largest vocalizer. Crucially, lowering only one or two formants in animal-like calls also conveys the impression of a larger body size, and lowering the second and third formants simultaneously exaggerates perceived size to a similar extent as rescaling all formants. As the articulatory movements required for individual formant shifts are minor compared to full vocal tract extension, they represent a rapid and energetically efficient mechanism for acoustic size exaggeration. We suggest that, by favouring the evolution of uneven formant patterns in vocal communication, this deceptive strategy may have contributed to the origins of the phonemic diversification required for articulated speech. This article is part of the theme issue ‘Voice modulation: from origin and mechanism to social impact (Part II)’.

Home-Based HIIT and Traditional MICT Prescriptions Improve Cardiorespiratory Fitness to a Similar Extent Within an Exercise Referral Scheme for At-Risk Individuals

Exercise referral schemes (ERS) are used to promote physical activity within primary care. Traditionally, ERS are conducted in a gym or leisure-center setting, with exercise prescriptions based on moderate-intensity continuous training (MICT). Home-based high-intensity interval training (Home-HIIT) has the potential to reduce perceived barriers to exercise, including lack of time and access to facilities, compared to traditional MICT prescription used with ERS and improve health related outcomes. We hypothesized that Home-HIIT would mediate greater improvement in cardiorespiratory fitness (CRF) by virtue of greater adherence and compliance to the exercise prescription, compared to MICT.Methods: Patients enrolled on an ERS (Liverpool, United Kingdom) were recruited for a pragmatic trial. Participants self-selected either 12 weeks of MICT (45–135 min/week at 50–70% HRmax) or Home-HIIT (4–9 min × 1 min intervals at ≥80% of HRmax, interspersed with 1 min rest). The primary outcome was the change in CRF (VO2peak) at post-intervention (12 weeks) and follow-up (3-month post intervention), using intention-to-treat analysis.Results: 154 participants (age 48 ± 10y; BMI 30.5 ± 6.1 kg/m2) were recruited between October 2017 and March 2019, 87 (56%) participants chose Home-HIIT and 67 (44%) MICT. VO2peak increased post-intervention in both groups (MICT 3.9 ± 6.0 ml.kg–1.min–1, Home-HIIT 2.8 ± 4.5 ml.kg–1.min–1, P &lt; 0.001), and was maintained at follow-up (P &lt; 0.001). Fat mass was only reduced post MICT (MICT −1.5 ± 6.3 kg, P &lt; 0.05, Home-HIIT −0.2 ± 2.0 kg, P = 1.00), but the reduction was not maintained at follow-up (MICT −0.6 ± 5.1 kg, Home-HIIT 0.0 ± 2.2 kg, P &gt; 0.05). Adherence to the prescribed programs was similar (MICT 48 ± 35%, Home-HIIT 39 ± 36%, P = 0.77).Conclusion: This is the first study to evaluate the use of Home-HIIT for individuals in a primary care setting. Contrary to our hypothesis, adherence to both exercise prescriptions was poor, and CRF improved to a similar extent in both groups with improvements maintained at 3-month follow-up. We provide evidence that, although not superior, Home-HIIT could be an effective and popular additional exercise choice for patients within primary care based ERS.Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04553614].

Effects of Aronia polyphenols on the physico-chemical properties of whey, soy, and pea protein isolate dispersions

Bioactive compounds including polyphenols (PP) have been observed to naturally form non-covalent complexation interactions with proteins under mild pH and temperature conditions, affecting protein structures and functionality. Previously, addition of Aronia berry PP to liquid dispersions containing whey protein isolate (WPI) and sucrose was found to alter characteristics including viscosity, surface tension, and particle sizes, with changes being attributed to protein-PP interactions. In this study we aimed to investigate whether Aronia PP would interact with soy and pea protein isolates (SPI and PPI, respectively) to a similar extent as with WPI in liquid protein-sucrose-PP mixtures. We hypothesized that formulations containing PPI (comprised of larger proteins) and hydrolyzed SPI (containing more carboxyl groups) may exhibit increased viscosities and decreased aggregate sizes due to enhanced protein-PP interactions. Concentrated liquid dispersions of varied ratios of protein to sucrose contents, containing different protein isolates (WPI, SPI, and PPI), and varied Aronia PP concentrations were formulated, and physical properties were evaluated to elucidate the effects of PP addition. PP addition altered physical characteristics differently depending on the protein isolate used, with changes attributed to protein-PP interactions. SPI and PPI appeared to have higher propensities for PP interactions and exhibited more extensive shifts in physical properties than WPI formulations. These findings may be useful for practical applications such as formulating products containing fruit and proteins to obtain desirable sensory attributes. Graphical abstract

Monochannel Preference in Autism Spectrum Conditions Revealed by a Non-Visual Variant of Rubber Hand Illusion

Individuals with autism spectrum conditions (ASC) are less susceptible to multisensory delusions, such as rubber hand illusion (RHI). Here, we investigate whether a monochannel variant of RHI is more effective in inducing an illusory feeling of ownership in ASC. To this aim, we exploit a non-visual variant of the RHI that, excluding vision, leverages only on the somatosensory channel. While the visual-tactile RHI does not alter the perceived hand position in ASC individuals, the tacto-tactile RHI effectively modulates proprioception to a similar extent as that found in typical development individuals. These findings suggest a more effective integration of multiple inputs originating from the same sensory channel in ASC, revealing a monochannel preference in this population.

A synthetic phytosiderophore analog, proline-2′-deoxymugineic acid, is efficiently utilized by dicots

Purpose Phytosiderophores (PS) from grasses solubilize sparingly soluble iron (Fe), and the resultant PS-Fe is an Fe source even for dicots. Recently, the synthetic PS proline-2′-deoxymugineic acid (PDMA) has been developed as a moderately biodegradable Fe fertilizer for grasses. We aimed to investigate whether PDMA-Fe is also a good Fe source for dicots. Methods The availability of PDMA-Fe to cucumber was evaluated in a calcareous substrate and hydroponic cultures at pH 7.0–9.0 by determining chlorophyll level, PSII activity, and Fe uptake. EDDHA-Fe, EDTA-Fe, and citrate-Fe were used as controls. The reducibility of Fe chelates by roots was measured to determine the mechanism underlying differences in availability. Expressions of Fe deficiency-inducible genes were analyzed to estimate the Fe status in plants. Results The application of PDMA-Fe and EDDHA-Fe to a calcareous substrate reduced Fe-deficient chlorosis to a similar extent; however, the shoot Fe concentration was higher in the PDMA-Fe treatment. In the hydroponic culture, the availability of PDMA-Fe was higher than that of the other chelates at all pH levels, and this was confirmed by higher PSII activity and lower expression of Fe deficiency-inducible genes. The reducibility assay revealed that the reduction level of PDMA-Fe was greater than that of EDTA-Fe and citrate-Fe under alkaline pH. Conclusions PDMA-Fe is utilized by cucumber roots more efficiently than traditional synthetic chelates in both calcareous substrate and hydroponic cultures. The higher availability of PDMA-Fe may be attributed to its higher reducibility. Our findings suggest that PDMA-Fe could be a good Fe fertilizer for dicots.

Differentiation and Grouping Practices as a Response to Heterogeneity – Teachers’ Implementation of Inclusive Teaching Approaches in Regular, Inclusive and Special Classrooms

Addressing students’ individual needs is a crucial component of inclusive teaching. However, empirical evidence comparing practices such as differentiation and grouping strategies within inclusive, regular and special classes is still lacking. The present study contrasts these settings using data from the German National Educational Panel Study (NEPS). Data from 1034 teachers (755 regular, 89 inclusive, 190 special teachers) teaching the subject German in secondary school (grade 5 to grade 8) were used. Results show the highest use of differentiation in special school classes. Teachers’ use the majority of grouping practices to a similar extent when comparing the three educational settings. Class size and the number of students with migration background were predictors for teachers’ use of differentiation, whereas patterns of grouping strategies were predicted by students’ gender and teachers’ experience.

Lying (non-)parents: Being a parent does not reduce dishonesty

Many studies point to how parenthood can affect behavior. Here, we provide a large-sample (N = 2,008) analysis of whether people with children are less likely to cheat in a private die-rolling task. Our findings suggest that both parents and non-parents lie and do so to a similar extent. However, when parents are reminded of their children prior to the task, they lie less compared to a treatment without a reminder.