GSK3s promote the phyB-ELF3-HMR complex formation to regulate plant thermomorphogenesis.

Although elevated ambient temperature causes many effects on plant growth and development, the mechanisms of plant high-ambient temperature sensing remain unknown. In this study, we show that GLYCOGEN SYNTHASE KINASE 3s (GSK3s) negatively regulate high-ambient temperature response and oligomerize upon high-temperature treatment. We demonstrate that GSK3 kinase BIN2 specifically interacts with the high-temperature sensor phytochrome B (phyB) but not the high-temperature sensor EARLY FLOWER 3 (ELF3) to phosphorylate and promote phyB photobody formation. Furthermore, we show that phosphorylation of phyB by GSK3s promotes its interaction with ELF3. Subsequently, we find that ELF3 recruits the phyB photobody facilitator HEMERA (HMR) to promote its association with phyB. Taken together, our data reveal a mechanism that GSK3s promote the phyB-ELF3-HMR complex formation in regulating plant thermomorphogenesis.

Anger recall mental stress decreases 123I-metaiodobenzylguanidine (123I-MIBG) uptake and increases heterogeneity of cardiac sympathetic activity in the myocardium in patients with ischemic cardiomyopathy.

BACKGROUND: Acute psychological stressors such as anger can precipitate ventricular arrhythmias, but the mechanism is incompletely understood. Quantification of regional myocardial sympathetic activity with 123I-metaiodobenzylguanidine (123I-mIBG) SPECT imaging in conjunction with perfusion imaging during mental stress may identify a mismatch between perfusion and sympathetic activity that may exacerbate a mismatch between perfusion and sympathetic activity that could create a milieu of increased vulnerability to ventricular arrhythmia. METHODS: Five men with ischemic cardiomyopathy (ICM), and five age-matched healthy male controls underwent serial 123I-mIBG and 99mTc-Tetrofosmin SPECT/CT imaging during an anger recall mental stress task and dual isotope imaging was repeated approximately 1 week later during rest. Images were reconstructed using an iterative reconstruction algorithm with CT-based attenuation correction. The mismatch of left ventricular myocardial 123I-mIBG and 99mTc-Tetrofosmin was assessed along with radiotracer heterogeneity and the 123I-mIBG heart-to-mediastinal ratios (HMR) were calculated using custom software developed at Yale. RESULTS: The hemodynamic response to mental stress was similar in both groups. The resting-HMR was greater in healthy control subjects (3.67 ± 0.95) than those with ICM (3.18 ± 0.68, P = .04). Anger recall significantly decreased the HMR in ICM patients (2.62 ± 0.3, P = .04), but not in normal subjects. The heterogeneity of 123I-mIBG uptake in the myocardium was significantly increased in ICM patients during mental stress (26% ± 8.23% vs. rest: 19.62% ± 9.56%; P = .01), whereas the 99mTc-Tetrofosmin uptake pattern was unchanged. CONCLUSION: Mental stress decreased the 123I-mIBG HMR, increased mismatch between sympathetic activity and myocardial perfusion, and increased the heterogeneity of 123I-mIBG uptake in ICM patients, while there was no significant change in myocardial defect size or the heterogeneity of 99mTc-Tetrofosmin perfusion. The changes observed in this proof-of-concept study may provide valuable information about the trigger-substrate interaction and the potential vulnerability for ventricular arrhythmias.

Cardiac 123I-MIBG normal uptake values are population-specific: Results from a cohort of controls over 60 years of age.

PURPOSE: Cardiac 123I-MIBG image interpretation is affected by population differences and technical factors. We recruited older adults without cognitive decline and compared their cardiac MIBG uptake with results from the literature. METHODS: Phantom calibration confirmed that cardiac uptake results from Japan could be applied to our center. We recruited 31 controls, 17 individuals with dementia with Lewy bodies (DLB) and 15 with Alzheimer's disease (AD). Images were acquired 20 minutes and four hours after injection using Siemens cameras with medium-energy low-penetration (MELP) collimators. Local normal heart-to-mediastinum (HMR) ratios were compared to Japanese results. RESULTS: Siemens gamma cameras with MELP collimators should give HMRs very close to the calibrated values used in Japan. However, our cut-offs with controls were lower at 2.07 for early and 1.86 for delayed images. Applying our lower cut-off to the dementia patients may increase the specificity of cardiac MIBG imaging for DLB diagnosis in a UK population without reducing sensitivity. CONCLUSIONS: Our local HMR cut-off values are lower than in Japan, higher than in a large US study but similar to those found in another UK center. UK centers using other cameras and collimators may need to use different cut-offs to apply our results.

Convenient Preparation and Spectroscopic Characterization of 7R-Hydroxymatairesinol.

The preparation of 7R-HMR (allo-hydroxymatairesinol) is reported by: (a) NaBH4 kinetic reduction of 7R/7S diastereomeric mixture; and (b) epimerization of the C7 hydroxyl group by Mitsunobu reaction and subsequent ester hydrolysis. The availability of highly pure target compound (7R-HMR) made it possible to confirm the structure of the target compound and to complete the full spectroscopic characterization.

Beer and beer-based beverage contain lignans.

Lignans are members of a broad group of plant phenols that can positively affect human health. They occur in negligible quantities in processed foodstuffs such as lager beer. The aim of this work was to utilize the high levels of lignans in the knots of spruce trees (Picea abies) to increase the lignans content in beer, without negatively impacting the natural taste and aroma. By means of lignans addition in the forms of spruce knot chips or different extracts made from spruce knots during the wort boiling were produced beer and beer-based beverages with lignans content ranging from 34 to 174 mg/L.

Glibenclamide and HMR1098 normalize Cantú syndrome-associated gain-of-function currents.

Cantú syndrome (CS) is caused by dominant gain-of-function mutation in ATP-dependent potassium channels. Cellular ATP concentrations regulate potassium current thereby coupling energy status with membrane excitability. No specific pharmacotherapeutic options are available to treat CS but IKATP channels are pharmaceutical targets in type II diabetes or cardiac arrhythmia treatment. We have been suggested that IKATP inhibitors, glibenclamide and HMR1098, normalize CS channels. IKATP in response to Mg-ATP, glibenclamide and HMR1098 were measured by inside-out patch-clamp electrophysiology. Results were interpreted in view of cryo-EM IKATP channel structures. Mg-ATP IC50 values of outward current were increased for D207E (0.71 ± 0.14 mmol/L), S1020P (1.83 ± 0.10), S1054Y (0.95 ± 0.06) and R1154Q (0.75 ± 0.13) channels compared to H60Y (0.14 ± 0.01) and wild-type (0.15 ± 0.01). HMR1098 dose-dependently inhibited S1020P and S1054Y channels in the presence of 0.15 mmol/L Mg-ATP, reaching, at 30 µmol/L, current levels displayed by wild-type and H60Y channels in the presence of 0.15 mmol/L Mg-ATP. Glibenclamide (10 µmol/L) induced similar normalization. S1054Y sensitivity to glibenclamide increases strongly at 0.5 mmol/L Mg-ATP compared to 0.15 mmol/L, in contrast to D207E and S1020P channels. Experimental findings agree with structural considerations. We conclude that CS channel activity can be normalized by existing drugs; however, complete normalization can be achieved at supraclinical concentrations only.

Tumor genetic alterations and features of the immune microenvironment drive myelodysplastic syndrome escape and progression.

The transformation and progression of myelodysplastic syndromes (MDS) to secondary acute myeloid leukemia (sAML) involve genetic, epigenetic, and microenvironmental factors. Driver mutations have emerged as valuable markers for defining risk groups and as candidates for targeted treatment approaches in MDS. It is also evident that the risk of transformation to sAML is increased by evasion of adaptive immune surveillance. This study was designed to explore the immune microenvironment, immunogenic tumor-intrinsic mechanisms (HLA and PD-L1 expression), and tumor genetic features (somatic mutations and altered karyotypes) in MDS patients and to determine their influence on the progression of the disease. We detected major alterations of the immune microenvironment in MDS patients, with a reduced count of CD4+ T cells, a more frequent presence of markers related to T cell exhaustion, a more frequent presence of myeloid-derived suppressor cells (MDSCs), and changes in the functional phenotype of NK cells. HLA Class I (HLA-I) expression was normally expressed in CD34+ blasts and during myeloid differentiation. Only two out of thirty-six patients with homozygosity for HLA-C groups acquired complete copy-neutral loss of heterozygosity in the HLA region. PD-L1 expression on the leukemic clone was also increased in MDS patients. Finally, no interplay was observed between the anti-tumor immune microenvironment and mutational genomic features. In summary, extrinsic and intrinsic immunological factors might severely impair immune surveillance and contribute to clonal immune escape. Genomic alterations appear to make an independent contribution to the clonal evolution and progression of MDS.

Investigation of anterior cingulate cortex gamma-aminobutyric acid and glutamate-glutamine levels in obsessive-compulsive disorder using magnetic resonance spectroscopy.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a relatively common and disabling psychiatric disorder whose pathophysiology is incompletely understood. In this study, we utilized magnetic resonance spectroscopy (MRS) in an effort to provide a better understanding of the role of brain gamma-aminobutyric acid (GABA) and glutamate in the pathophysiology of OCD. We hypothesized that beyond the separate effects of these neurotransmitter systems, a disruption in the balance between GABA and glutamate could be particularly relevant to OCD. METHODS: We obtained MRS measures of GABA and glutamate concentrations in the anterior cingulate cortex from 23 adult patients with OCD and 20 sex- and age-matched healthy community volunteers. Established clinical rating scales were used to assess the severities of OCD, anxiety, and depression symptoms. Statistical analysis involved the assessment of patient-control group differences in the individual measures of GABA and glutamate, as well as in the ratio of the GABA to glutamate measures. Additionally, we explored whether differences in the MRS measures existed between two subgroups of patients formed according to the severity of their OCD symptoms. Finally, we assessed the relations of demographic and clinical variables to the MRS measures. RESULTS: Patients with OCD displayed a higher estimated GABA level and a higher GABA to glutamate ratio than healthy participants, but no significant group differences were observed in the measure of glutamate. The MRS measures did not vary by subgroup and showed no correlations with demographic and clinical variables. CONCLUSIONS: These results indicate that GABA abnormalities within the anterior cingulate cortex contribute to the pathophysiology of OCD. The results fail to provide evidence that glutamate abnormalities alone are involved in adult OCD. Yet, it seems that a disruption in the balance between glutamate and GABA neurotransmission may have a particularly important role to play in OCD pathophysiology.

Comparison of sensory perception and verbal expression of Korean Kimchi stews between Chinese consumers and Korean trained panelists.

BACKGROUND: Sensory drivers of liking in foreign food markets are difficult to identify because the expression of perceived characteristics varies depending on cultural differences. We aimed to identify differences in the perception and expression of a Korean home meal replacement product (Kimchi stew) between 10 Korean trained panelists versus 50 eastern Chinese consumers (EC) and 54 northern Chinese consumers (NC) using descriptive analysis and rate-all-that-apply (RATA) tests. Regional differences between the EC and NC groups were also investigated. RESULTS: Sensory representations of the six Kimchi stew samples were similar between the Korean trained and Chinese consumer panels. Use of simple sensory RATA terms was similar among the groups. However, EC, who have a daily diet with mild flavors, associated consumer terms with negative connotations, such as odd flavor and sharp, with burning sensation and seasoning, implying the influence of regional food cultures. CONCLUSION: RATA could elicit foreign consumers' sensory representations of an unfamiliar ethnic food that was comparable to that from descriptive analysis, assisting researchers in understanding target consumers' sensory perceptions in a more cost- and time-effective manner. The inclusion of consumer terms in a RATA list and its correlation with descriptive analysis by a native descriptive panel can help with the understanding of foreign consumers' verbal expressions. © 2018 Society of Chemical Industry.

7-Hydroxymatairesinol improves body weight, fat and sugar metabolism in C57BJ/6 mice on a high-fat diet.

7-Hydroxymatairesinol (7-HMR) is a plant lignan abundant in various concentrations in plant foods. The objective of this study was to test HMRLignan™, a purified form of 7-HMR, and the corresponding Picea abies extract (total extract P. abies; TEP) as dietary supplements on a background of a high-fat diet (HFD)-induced metabolic syndrome in mice and in the 3T3-L1 adipogenesis model. Mice, 3 weeks old, were fed a HFD for 60 d. Subgroups were treated with 3 mg/kg body weight 7-HMR (HMRLignan™) or 10 mg/kg body weight TEP by oral administration. 7-HMR and TEP limited the increase in body weight (-11 and -13 %) and fat mass (-11 and -18 %) in the HFD-fed mice. Epididymal adipocytes were 19 and -12 % smaller and the liver was less steatotic (-62 and -65 %). Serum lipids decreased in TEP-treated mice (-11 % cholesterol, -23 % LDL and -15 % TAG) and sugar metabolism was ameliorated by both lignan preparations, as shown by a more than 70 % decrease in insulin secretion and insulin resistance. The expression of several metabolic genes was modulated by the HFD with an effect that was reversed by lignan. In 3T3-L1 cells, the 7-HMR metabolites enterolactone (ENL) and enterodiol (END) showed a 40 % inhibition of cell differentiation accompanied by the inhibited expression of the adipogenic genes PPARγ, C/EBPα and aP2. Furthermore, END and ENL caused a 10 % reduction in TAG uptake in HEPA 1-6 hepatoma cells. In conclusion, 7-HMR and TEP reduce metabolic imbalances typical of the metabolic syndrome and obesity in male mice, whereas their metabolites inhibit adipogenesis and lipid uptake in vitro.

Magnetic resonance spectroscopy of current hand amputees reveals evidence for neuronal-level changes in former sensorimotor cortex.

Deafferentation is accompanied by large-scale functional reorganization of maps in the primary sensory and motor areas of the hemisphere contralateral to injury. Animal models of deafferentation suggest a variety of cellular-level changes including depression of neuronal metabolism and even neuronal death. Whether similar neuronal changes contribute to patterns of reorganization within the contralateral sensorimotor cortex of chronic human amputees is uncertain. We used functional MRI-guided proton magnetic resonance spectroscopy to test the hypothesis that unilateral deafferentation is associated with lower levels of N-acetylaspartate (NAA, a putative marker of neuronal integrity) in the sensorimotor hand territory located contralateral to the missing hand in chronic amputees (n = 19) compared with the analogous hand territory of age- and sex-matched healthy controls (n = 28). We also tested whether former amputees [i.e., recipients of replanted (n = 3) or transplanted (n = 2) hands] exhibit NAA levels that are indistinguishable from controls, possible evidence for reversal of the effects of deafferentation. As predicted, relative to controls, current amputees exhibited lower levels of NAA that were negatively and significantly correlated with the time after amputation. Contrary to our prediction, NAA levels in both replanted and transplanted patients fell within the range of the current amputees. We suggest that lower levels of NAA in current amputees reflects altered neuronal integrity consequent to chronic deafferentation. Thus local changes in NAA levels may provide a means of assessing neuroplastic changes in deafferented cortex. Results from former amputees suggest that these changes may not be readily reversible through reafferentation.NEW & NOTEWORTHY This study is the first to use functional magnetic resonance-guided magnetic resonance spectroscopy to examine neurochemical mechanisms underlying functional reorganization in the primary somatosensory and motor cortices consequent to upper extremity amputation and its potential reversal through hand replantation or transplantation. We provide evidence for selective alteration of cortical neuronal integrity associated with amputation-related deafferentation that may not be reversible.

Effects of ATP-sensitive potassium channel blockers on vascular hyporeactivity, mesenteric blood flow, and survival in lipopolysaccharide-induced septic shock model.

In this study, the possible therapeutic effects of various ATP-sensitive potassium channel (KATP) blockers (glibenclamide, repaglinide, 5-HD, HMR-1098) have been tested in experimental septic shock model. Rats were given lipopolysaccharide (1 mg·kg(-1)) to create experimental shock model and 4 h later, under 400 mg·kg(-1) chloral hydrate anesthesia, parameters such as blood pressure, mesenteric blood flow, the response of mesenteric circulation to phenylephrine (vasoconstrictor stimulation), and organ and oxidative damage were analyzed. Also 75 mg·kg(-1) lethal dose of lipopolysaccharide was given to mice and effects of KATP blockers on survival have been tested. Non-selective blocker glibenclamide with sulphonylurea structure and sarcolemmal KATP channel blocker HMR-1098, which have the similar chemical structure, have improved the pathological parameters such as decrease in mesenteric blood flow, vascular hyporeactivity, but could not prevent the decrease in blood pressure, and oxidative and organ damage that were observed in the shock model. Also, both blockers have decreased the mortality rate from 80% to 40%-50%. Similar (preventive) therapeutic effects were not observed with non-selective blocker repaglinide and mitochondrial KATP channel blocker 5-HD, which were non-sulphonylurea structure. As a result, only KATP channel blockers that have sulphonylurea structure can be a new therapeutic approach in septic shock.

Default-mode network functional connectivity is closely related to metabolic activity.

Over the last decade, the brain's default-mode network (DMN) and its function has attracted a lot of attention in the field of neuroscience. However, the exact underlying mechanisms of DMN functional connectivity, or more specifically, the blood-oxygen level-dependent (BOLD) signal, are still incompletely understood. In the present study, we combined 2-deoxy-2-[(18) F]fluoroglucose positron emission tomography (FDG-PET), proton magnetic resonance spectroscopy ((1) H-MRS), and resting-state functional magnetic resonance imaging (rs-fMRI) to investigate more directly the association between local glucose consumption, local glutamatergic neurotransmission and DMN functional connectivity during rest. The results of the correlation analyzes using the dorsal posterior cingulate cortex (dPCC) as seed region showed spatial similarities between fluctuations in FDG-uptake and fluctuations in BOLD signal. More specifically, in both modalities the same DMN areas in the inferior parietal lobe, angular gyrus, precuneus, middle, and medial frontal gyrus were positively correlated with the dPCC. Furthermore, we could demonstrate that local glucose consumption in the medial frontal gyrus, PCC and left angular gyrus was associated with functional connectivity within the DMN. We did not, however, find a relationship between glutamatergic neurotransmission and functional connectivity. In line with very recent findings, our results lend further support for a close association between local metabolic activity and functional connectivity and provide further insights towards a better understanding of the underlying mechanism of the BOLD signal.

The impact of the microvascular resistance on the measures of stenosis severity.

The relationship between measures of stenosis and microvascular resistance is of importance due to medical decisions being based on these values. This research investigates the impact of varying microvascular resistance on fractional flow reserve (FFR) and hyperaemic stenosis resistance (hSR). Microvascular resistance is classified using hyperaemic microvascular resistance (hMR). Additionally, hMR using the upstream pressure value (hMRPa) has also been calculated and is compared to hMR measured conventionally. Tests were conducted at three different degrees of stenosis (quantified by percent area) in a coronary flow circuit with varying downstream resistance to simulate the microvasculature. Pressure and flow values are recorded across the stenosed section, allowing for calculation of the diagnostic indexes. Results indicate that for a constant degree of stenosis, FFR would increase with increasing microvascular resistance while hSR would remain almost constant. hMRPa was found to approach hMR as the stenosis severity decreased, and the pressure gradient decreased. In the results shown here, with sufficiently high downstream resistance, an 84 % stenosis could produce an FFR value over 0.8. This result suggests that there is the potential for misdiagnosis of the severity of stenosis when combined with elevated microvascular resistance. Consequently, decisions on the clinical significance of a stenosis, classified by FFR, need to consider the effect of the microvascular resistance.

Efficacy of convenience meal-type foods designed for diabetes in the management of metabolic syndrome based on a 3-week trial.

OBJECTIVES: This study aimed to assess the effect of meal-type food for diabetes on improving metabolic syndrome risk factors in adults. METHODS: The participants were adult men and women aged 40-55 y with 1 or more risk factors for metabolic syndrome. They were provided with a diabetic diet (a meal-type food) and general diet in the form of home meal replacement for 3 wk. The current research used a crossover design. All participants had iso-caloric meal replacement per day, and there was a 2-wk washout period between each diet. The nutritional standards of a diabetic diet were based on the guidelines of the Ministry of Food and Drug Safety, which are: <50% carbohydrates, <10% sugars, <7% saturated fat, and >10 g dietary fiber. The average caloric content was 489.1 ± 45.0 kcal. The composition of the general diet was similar to that of the diabetic diet; however, there were differences in sugar content. In total, 15 participants were included in the research, and there was no significant difference between the 2 groups in terms of nutrient intake during the intervention period. RESULTS: Body weight (P = 0.001), body mass index (P = 0.004), waist circumference (P = 0.030), triacylglycerol (P = 0.002), total cholesterol (P = 0.001), and low-density lipoprotein cholesterol (P = 0.008) levels were significantly lower in the diabetic diet intervention period than before and after 3 wk of the intervention. In addition, reduction in body weight (P = 0.001), body mass index (P = 0.006), waist circumference (P = 0.032), and triacylglycerol (P = 0.036) and total cholesterol (P = 0.007) levels in the diabetic diet intervention period significantly differed compared with those in the general diet intervention period. CONCLUSIONS: Replacing 1 meal per day with meal-type food for diabetes improved body composition and blood lipid levels in adults with metabolic syndrome risk factors.

Detection of mobile genetic elements conferring resistance to heavy metals in Salmonella 4,[5],12:i:- and Salmonella Typhimurium serovars and their association with antibiotic resistance.

Salmonella enterica subsp. enterica serovar Typhimurium variant 4,[5],12:i:- (referred to as S. 4,[5],12:i:-) has emerged rapidly as the predominant Salmonella serovar in pigs, often associated with the acquisition of antibiotic resistance (ABR) and heavy metal resistance (HMR) genes. Our study analysed 78 strains of S. 4,[5],12:i:- (n = 57) and S. Typhimurium (n = 21), collected from 1999 to 2021, to investigate the evolution of mobile genetic elements (MGEs) containing HMR and ABR genes. Five MGEs harbouring HMR genes were identified: pUO-STVR2, pSTM45, pUO-STmRV1, SGI-4 and MREL. Among the strains, 91.23 % (52/57) of S. 4,[5],12:i:- carried at least one of these elements, compared to only 14.29 % (3/21) of S. Typhimurium. Since 2008, S. 4,[5],12:i:- have shifted from predominantly carrying pUO-STmRV1 to the emergence of SGI-4 and MREL, reducing ABR genes, reflecting the European Union ban on the use of antibiotics as feed additives. Increased resistance to copper and silver in S. 4,[5],12:i:-, conferred by SGI-4 and MREL, reflected that their acquisition was linked to the ongoing use of heavy metals in food-animal production. However, strains carrying SGI-4 and MREL still exhibit multidrug resistance, emphasising the need for targeted interventions to mitigate multidrug-resistant Salmonella spread in veterinary and public health settings.

Particularities of coronary physiology in patients with atrial fibrillation: insights from combined pressure and flow indices measurements.

Background: Symptoms suggestive of myocardial ischemia are frequently encountered in patients with atrial fibrillation (AF) even in the absence of obstructive coronary artery disease. Nevertheless, an in-depth characterisation of coronary physiology in patients with AF is currently lacking. Objectives: We aim to provide an insight into the characteristics of coronary physiology in AF, by performing simultaneous invasive measurements of coronary flow- and pressure- indices in a real-life population of patients with AF and indication of coronary angiography. Methods: This is a prospective open label study including patients with permanent or persistent AF and indication of coronary angiography showing intermediate coronary stenosis requiring routine physiological assessment (n = 18 vessels from 14 patients). We measured FFR (fractional flow reserve), and Doppler-derived coronary flow indices, including CFR (coronary flow reserve) and HMR (hyperaemic microvascular resistance). Results: From the analysed vessels, 18/18 vessels (100%) presented a pathological CFR (<2.5), indicative of coronary microvascular dysfunction (CMD), and 3/18 (17%) demonstrated obstructive epicardial coronary disease (FFR ≤ 0.8). A large proportion of vessels (15/18; 83%) showed discordant FFR/CFR with preserved FFR and low CFR. 47% of the coronary arteries in patients with AF and non-obstructive epicardial coronary disease presented structural CMD (HMR ≥ 2.5 mmHg/cm/s), and were associated with high BMR and an impaired response to adenosine. Conversely, vessels from patients with AF and non-obstructive epicardial coronary disease with functional CMD (HMR < 2.5 mmHg/cm/s) showed higher bAPV. The permanent AF subpopulation presented increased values of HMR and BMR compared to persistent AF, while structural CMD was more often associated with persistent symptoms at 3 months, taking into account the limited sample size of our study. Conclusion: Our findings highlight a systematically impaired CFR in patients with AF even in the absence of obstructive epicardial coronary disease, indicative of CMD. In addition, patients with AF presented more prevalent structural CMD (HMR ≥ 2.5 mmHg/cm/s), characterized by reduced hyperaemic responses to adenosine, possibly interfering with the FFR assessment.

Persistent cell contacts enable E-cadherin/HMR-1- and PAR-3-based symmetry breaking within a developing C. elegans epithelium.

Tissue-wide patterning is essential to multicellular development, requiring cells to individually generate polarity axes and coordinate them in space and time with neighbors. Using the C. elegans intestinal epithelium, we identified a patterning mechanism that is informed by cell contact lifetime asymmetry and executed via the scaffolding protein PAR-3 and the transmembrane protein E-cadherin/HMR-1. Intestinal cells break symmetry as PAR-3 and HMR-1 recruit apical determinants into punctate "local polarity complexes" (LPCs) at homotypic contacts. LPCs undergo an HMR-1-based migration to a common midline, thereby establishing tissue-wide polarity. Thus, symmetry breaking results from PAR-3-dependent intracellular polarization coupled to HMR-1-based tissue-level communication, which occurs through a non-adhesive signaling role for HMR-1. Differential lifetimes between homotypic and heterotypic cell contacts are created by neighbor exchanges and oriented divisions, patterning where LPCs perdure and thereby breaking symmetry. These cues offer a logical and likely conserved framework for how epithelia without obvious molecular asymmetries can polarize.

Development and Quality Characteristics of Elderly-Friendly Pulpo a La Gallega Prepared Using Texture-Modified Octopus (Octopus vulgaris) Arms.

Considering the need for developing new senior-friendly processed seafood, this study aimed to develop octopus pulpo with high preference and excellent quality characteristics for elderly individuals by optimizing the vinegar immersion and sous vide softening treatment conditions for octopus (Octopus vulgaris) arms. The optimal sous vide heating temperature (70.0-100.0 °C), time (69.5-170.5 min), and vinegar concentration (0.2-0.8%) were established using response surface methodology (RSM). The pulpo prototype was produced using an octopus arm softened under optimal conditions and seasoned with a potato and olive oil sauce. The physicochemical and nutritional properties of the prototype were evaluated, followed by sensory evaluation and safety assessments. The hardness of softened octopuses obtained by 0.48% vinegar immersion and sous vide treatment (84.3 °C, 139.8 min), determined using RSM, was 394.5 × 1000 N/m2, showing a reduction of 83.0%; this was confirmed by electron microscopic observation. The texture of the pulpo prototype with softened octopus arms showed the highest preference (8.4 points) and high physicochemical and nutritional properties. Overall, the octopus pulpo a La Gallega prototype produced using texture-modified octopus arms was suitable for consumption by elderly people with chewing disorders and could help improve their quality of life.

SARS-CoV-2 Infection Dysregulates Host Iron (Fe)-Redox Homeostasis (Fe-R-H): Role of Fe-Redox Regulators, Ferroptosis Inhibitors, Anticoagulants, and Iron-Chelators in COVID-19 Control.

Severe imbalance in iron metabolism among SARS-CoV-2 infected patients is prominent in every symptomatic (mild, moderate to severe) clinical phase of COVID-19. Phase-I - Hypoxia correlates with reduced O2 transport by erythrocytes, overexpression of HIF-1α, altered mitochondrial bioenergetics with host metabolic reprogramming (HMR). Phase-II - Hyperferritinemia results from an increased iron overload, which triggers a fulminant proinflammatory response - the acute cytokine release syndrome (CRS). Elevated cytokine levels (i.e. IL6, TNFα and CRP) strongly correlates with altered ferritin/TF ratios in COVID-19 patients. Phase-III - Thromboembolism is consequential to erythrocyte dysfunction with heme release, increased prothrombin time and elevated D-dimers, cumulatively linked to severe coagulopathies with life-threatening outcomes such as ARDS, and multi-organ failure. Taken together, Fe-R-H dysregulation is implicated in every symptomatic phase of COVID-19. Fe-R-H regulators such as lactoferrin (LF), hemoxygenase-1 (HO-1), erythropoietin (EPO) and hepcidin modulators are innate bio-replenishments that sequester iron, neutralize iron-mediated free radicals, reduce oxidative stress, and improve host defense by optimizing iron metabolism. Due to its pivotal role in 'cytokine storm', ferroptosis is a potential intervention target. Ferroptosis inhibitors such as ferrostatin-1, liproxstatin-1, quercetin, and melatonin could prevent mitochondrial lipid peroxidation, up-regulate antioxidant/GSH levels and abrogate iron overload-induced apoptosis through activation of Nrf2 and HO-1 signaling pathways. Iron chelators such as heparin, deferoxamine, caffeic acid, curcumin, α-lipoic acid, and phytic acid could protect against ferroptosis and restore mitochondrial function, iron-redox potential, and rebalance Fe-R-H status. Therefore, Fe-R-H restoration is a host biomarker-driven potential combat strategy for an effective clinical and post-recovery management of COVID-19.