Aortic Valve Calcium in Relation to Subclinical Cardiac Dysfunction and Risk of Heart Failure.

BACKGROUND: The link between (mild) aortic valve calcium (AVC) with subclinical cardiac dysfunction and with risk of heart failure (HF) remains unclear. This research aims to determine the association of computed tomography-assessed AVC with echocardiographic measurements of cardiac dysfunction, and with HF in the general population. METHODS: We included 2348 participants of the Rotterdam Study cohort (mean age 68.5 years, 52% women), who had AVC measurement between 2003 and 2006, and without history of HF at baseline. Linear regression models were used to explore relationship between AVC and echocardiographic measures at baseline. Participants were followed until December 2016. Fine and Gray subdistribution hazard models were used to assess the association of AVC with incident HF, accounting for death as a competing risk. RESULTS: The presence of AVC or greater AVC were associated with larger mean left ventricular mass and larger mean left atrial size. In particular, AVC ≥800 showed a strong association (body surface area indexed left ventricular mass, ß coefficient: 22.01; left atrium diameter, ß coefficient: 0.17). During a median of 9.8 years follow-up, 182 incident HF cases were identified. After accounting for death events and adjusting for cardiovascular risk factors, one-unit larger log (AVC+1) was associated with a 10% increase in the subdistribution hazard of HF (subdistribution hazard ratio, 1.10 [95% CI, 1.03-1.18]), but the presence of AVC was not significantly associated with HF risk in fully adjusted models. Compared with the AVC=0, AVC between 300 and 799 (subdistribution hazard ratio, 2.36 [95% CI, 1.32-4.19]) and AVC ≥800 (subdistribution hazard ratio, 2.54 [95% CI, 1.31-4.90]) were associated with a high risk of HF. CONCLUSIONS: Presence and high levels of AVC were associated with markers of left ventricular structure, independent of traditional cardiovascular risk factors. Larger computed tomography-assessed AVC is an indicative of increased risk for the development of HF.

Presentation and management of hypoparathyroidism in a paediatric patient - a case report.

Hypoparathyroidism occurs due to insufficient parathyroid gland activity leading to abnormal calcium and phosphate levels. The presentation of hypoparathyroidism is rare in adults and mostly encountered in the paediatric population. We present a case of a 3.5-month-old male infant with the presenting complaint of an episode of afebrile generalized tonic-clonic seizure. Haematological, urinary, cerebro-spinal fluid and radiological investigations were unremarkable but a biochemical profile revealed hypocalcaemia, hyperphosphataemia and lowered vitamin D3 levels. Parathyroid hormone profile showed a decreased level, confirming diagnosis of hypoparathyroidism. Intravenous administration of calcium and magnesium in combination with oral activated vitamin D3 and phosphate binders managed to resolve symptoms and maintain normal levels. The rationale of this case is to confirm the necessity of early diagnosis to prevent irreversible sequelae of hypocalcaemia and regular monitoring of treatment to avoid side-effects of medication.

Characterization of two pathological gating-charge substitutions in Cav1.4 L-type calcium channels.

Cav1.4 L-type calcium channels are predominantly expressed at the photoreceptor terminals and in bipolar cells, mediating neurotransmitter release. Mutations in its gene, CACNA1F, can cause congenital stationary night-blindness type 2 (CSNB2). Due to phenotypic variability in CSNB2, characterization of pathological variants is necessary to better determine pathological mechanism at the site of action. A set of known mutations affects conserved gating charges in the S4 voltage sensor, two of which have been found in male CSNB2 patients. Here, we describe two disease-causing Cav1.4 mutations with gating charge neutralization, exchanging an arginine 964 with glycine (RG) or arginine 1288 with leucine (RL). In both, charge neutralization was associated with a reduction channel expression also reflected in smaller ON gating currents. In RL channels, the strong decrease in whole-cell current densities might additionally be explained by a reduction of single-channel currents. We further identified alterations in their biophysical properties, such as a hyperpolarizing shift of the activation threshold and an increase in slope factor of activation and inactivation. Molecular dynamic simulations in RL substituted channels indicated water wires in both, resting and active, channel states, suggesting the development of omega (ω)currents as a new pathological mechanism in CSNB2. This sum of the respective channel property alterations might add to the differential symptoms in patients beside other factors, such as genomic and environmental deviations.

Rescue of astrocyte activity by the calcium sensor STIM1 restores long-term synaptic plasticity in female mice modelling Alzheimer's disease.

Calcium dynamics in astrocytes represent a fundamental signal that through gliotransmitter release regulates synaptic plasticity and behaviour. Here we present a longitudinal study in the PS2APP mouse model of Alzheimer's disease (AD) linking astrocyte Ca2+ hypoactivity to memory loss. At the onset of plaque deposition, somatosensory cortical astrocytes of AD female mice exhibit a drastic reduction of Ca2+ signaling, closely associated with decreased endoplasmic reticulum Ca2+ concentration and reduced expression of the Ca2+ sensor STIM1. In parallel, astrocyte-dependent long-term synaptic plasticity declines in the somatosensory circuitry, anticipating specific tactile memory loss. Notably, we show that both astrocyte Ca2+ signaling and long-term synaptic plasticity are fully recovered by selective STIM1 overexpression in astrocytes. Our data unveil astrocyte Ca2+ hypoactivity in neocortical astrocytes as a functional hallmark of early AD stages and indicate astrocytic STIM1 as a target to rescue memory deficits.

A cooperative knock-on mechanism underpins Ca2+-selective cation permeation in TRPV channels.

The selective exchange of ions across cellular membranes is a vital biological process. Ca2+-mediated signaling is implicated in a broad array of physiological processes in cells, while elevated intracellular concentrations of Ca2+ are cytotoxic. Due to the significance of this cation, strict Ca2+ concentration gradients are maintained across the plasma and organelle membranes. Therefore, Ca2+ signaling relies on permeation through selective ion channels that control the flux of Ca2+ ions. A key family of Ca2+-permeable membrane channels is the polymodal signal-detecting transient receptor potential (TRP) ion channels. TRP channels are activated by a wide variety of cues including temperature, small molecules, transmembrane voltage, and mechanical stimuli. While most members of this family permeate a broad range of cations non-selectively, TRPV5 and TRPV6 are unique due to their strong Ca2+ selectivity. Here, we address the question of how some members of the TRPV subfamily show a high degree of Ca2+ selectivity while others conduct a wider spectrum of cations. We present results from all-atom molecular dynamics simulations of ion permeation through two Ca2+-selective and two non-selective TRPV channels. Using a new method to quantify permeation cooperativity based on mutual information, we show that Ca2+-selective TRPV channel permeation occurs by a three-binding site knock-on mechanism, whereas a two-binding site knock-on mechanism is observed in non-selective TRPV channels. Each of the ion binding sites involved displayed greater affinity for Ca2+ over Na+. As such, our results suggest that coupling to an extra binding site in the Ca2+-selective TRPV channels underpins their increased selectivity for Ca2+ over Na+ ions. Furthermore, analysis of all available TRPV channel structures shows that the selectivity filter entrance region is wider for the non-selective TRPV channels, slightly destabilizing ion binding at this site, which is likely to underlie mechanistic decoupling.

Calcium Live Imaging at Multi-Scales from Cellular to Organ Level in Arabidopsis thaliana.

Plants must adapt to environmental constraints. For this, they are able to perceive several types of stress in isolation or in combination manner. At the cellular level, after the perception of stress, cell signaling is set up to allow the establishment of the specific response. The calcium ion is known to be one of the ubiquitous second messengers which is involved in most of the stresses perceived by the plant. Changes of free cytosolic calcium but also in other cellular compartments are able to activate or inactivate several mechanisms involved in the cell to cope with the changes of environmental conditions. Several calcium reporters have been intensively used to visualize calcium signals in different conditions. In this chapter, we will present only genetically encoded fluorescent reporters for calcium imaging in living plant tissues to measure variations in calcium at several scales. The FRET (fluorescence resonance energy transfer) YC3.60 and the intensiometric GCamP3 sensors will be used in this method chapter. The image analyses will be also detailed for fluorescence quantification of calcium variation.

A simple assessment of the effect of strontium on the urinary excretion of calcium in Sprague Dawley rats.

This study was aimed at investigating the impact of varying concentrations of strontium (Sr) on calcium (Ca) excretion via the urine and determine its impact on kidney stone formation. Twenty adult male Sprague Dawley rats weighing between 200 and 300 g were selected. The rats were randomly divided into four groups of five. One group was used as a control group while the other three groups were experimental. The diet of the rats was modulated over a 12 week period to investigate the impact of Sr on the urinary excretion of Ca. Urinary samples were collected every 2 weeks from the rats. The rats were fed water ad libitum. After the study the rats were euthanised and their kidneys harvested. Urine and kidney samples from the rats were analysed using Total Reflection X-Ray Fluorescence (TXRF). In the urine excretion of Ca increased with increased intake of Sr in the diet. Sr excretion via the urine also increased with increased dietary intake. There was a correlation of 0.835 at the significance level of 0.01 between Ca and Sr in the urine. However, for the kidneys, the varying concentration of Sr did not impact the retention of Ca in the kidneys. There was increased retention of Sr in the kidneys with increased dietary intake. In this study an increase of Sr in the diet resulted in an increase in urinary excretion of Ca.

Prohexadione-calcium alleviates the leaf and root damage caused by salt stress in rice (Oryza sativa L.) at the tillering stage.

Salt stress, as a principal abiotic stress, harms the growth and metabolism of rice, thus affecting its yield and quality. The tillering stage is the key growth period that controls rice yield. Prohexadione-calcium (Pro-Ca) can increase the lodging resistance of plants by reducing plant height, but its effects on rice leaves and roots at the tillering stage under salt stress are still unclear. This study aimed to evaluate the ability of foliar spraying of Pro-Ca to regulate growth quality at the rice tillering stage under salt stress. The results showed that salt stress reduced the tillering ability of the rice and the antioxidant enzyme activity in the roots. Salt stress also reduced the net photosynthetic rate (Pn), stomatal conductance (Gs) and intercellular CO2 concentration (Ci) of the rice leaves and increased the contents of osmotic regulatory substances in the leaves and roots. The application of exogenous Pro-Ca onto the leaves increased the tiller number of the rice under salt stress and significantly increased the photosynthetic capacity of the leaves. Additionally, it increased the activities of antioxidant enzymes and the AsA content. The contents of an osmotic regulation substance, malondialdehyde (MDA), and H2O2 in the leaves and roots also decreased. These results suggested that Pro-Ca can increase the tillering ability, photosynthetic capacity, osmotic adjustment substance content levels and antioxidant enzyme activity levels in rice and reduce membrane lipid peroxidation, thus improving the salt tolerance of rice at the tillering stage.

Structural insights into latency of the metallopeptidase ulilysin (lysargiNase) and its unexpected inhibition by a sulfonyl-fluoride inhibitor of serine peptidases.

Peptidases are regulated by latency and inhibitors, as well as compatibilization and cofactors. Ulilysin from Methanosarcina acetivorans, also called lysargiNase, is an archaeal metallopeptidase (MP) that is biosynthesized as a zymogen with a 60-residue N-terminal prosegment (PS). In the presence of calcium, it self-activates to yield the mature enzyme, which specifically cleaves before basic residues and thus complements trypsin in proteomics workflows. Here, we obtained a low-resolution crystal structure of proulilysin, in which 28 protomers arranged as 14 dimers form a continuous double helix of 544 Å pitch that parallels cell axis b of the crystal. The PS includes two α-helices and obstructs the active-site cleft of the catalytic domain (CD) by traversing it in the opposite orientation of a substrate, and a cysteine blocks the catalytic zinc according to a "cysteine-switch mechanism". Moreover, the PS interacts through its first helix with an "S-loop" of the CD, which acts as an "activation segment" that lacks one of two essential calcium cations. Upon PS removal during maturation, the S-loop adopts its competent conformation and binds the second calcium ion. Next, we found that in addition to general MP inhibitors, ulilysin was competitively and reversibly inhibited by 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF; Ki = 4 µM). This is a compound that normally forms an irreversible covalent complex with serine peptidases but does not inhibit MPs. A high-resolution crystal structure of the complex revealed that the inhibitor penetrates the specificity pocket of ulilysin. A primary amine of the inhibitor salt-bridges an aspartate at the pocket bottom, thus mimicking the basic side chain of substrates. In contrast, the sulfonyl fluoride warhead is not involved and the catalytic zinc ion is freely accessible. Thus, the usage of inhibitor cocktails of peptidases, which typically contain AEBSF at ∼25-fold higher concentrations than the determined Ki, should be avoided when working with ulilysin. Finally, the structure of the complex, which occurred as a crystallographic dimer recurring in previous mature ulilysin structures, unveiled an N-terminal product fragment that delineated the non-primed side of the cleft. These results complement prior structures of ulilysin with primed-side product fragments and inhibitors.

Opsin 3 mediates UVA-induced keratinocyte supranuclear melanin cap formation.

Solar ultraviolet (UV) radiation-induced DNA damage is a major risk factor for skin cancer development. UV-induced redistribution of melanin near keratinocyte nuclei leads to the formation of a supranuclear cap, which acts as a natural sunscreen and protects DNA by absorbing and scattering UV radiation. However, the mechanism underlying the intracellular movement of melanin in nuclear capping is poorly understood. In this study, we found that OPN3 is an important photoreceptor in human epidermal keratinocytes and is critical for UVA-mediated supranuclear cap formation. OPN3 mediates supranuclear cap formation via the calcium-dependent G protein-coupled receptor signaling pathway and ultimately upregulates Dync1i1 and DCTN1 expression in human epidermal keratinocytes via activating calcium/CaMKII, CREB, and Akt signal transduction. Together, these results clarify the role of OPN3 in regulating melanin cap formation in human epidermal keratinocytes, greatly expanding our understanding of the phototransduction mechanisms involved in physiological function in skin keratinocytes.

Predicting Significant Coronary Obstruction in a Population with Suspected Coronary Disease and Absence of Coronary Calcium: CORE-64 / CORE320 Studies. / Predição de Obstrução Coronariana Significativa em População com Suspeita de Doença Coronariana e Ausência de Cálcio Coronariano: CORE-64 e CORE320.

BACKGROUND: Coronary artery calcium (CAC) scanning can be performed using non-contrast computed tomography to predict cardiovascular events, but has less value for risk stratification in symptomatic patients. OBJECTIVE: To identify and validate predictors of significant coronary obstruction (SCO) in symptomatic patients without coronary artery calcification. METHODS: A total of 4,258 participants were screened from the CORE64 and CORE320 studies that enrolled patients referred for invasive angiography, and from the Quanta Registry that included patients referred for coronary computed tomography angiography (CTA). Logistic regression models evaluated associations between cardiovascular risk factors, CAC, and SCO. An algorithm to assess the risk of SCO was proposed for patients without CAC. Significance level of 5% was used in the analyses. RESULTS: Of the 509 participants of the CORE study, 117 (23%) had zero coronary calcium score; 13 (11%) patients without CAC had SCO. Zero calcium score was related to younger age, female gender, lower body mass index, no diabetes, and no dyslipidemia. Being a current smoker increased ~3.5 fold the probability of SCO and other CV risk factors were not significantly associated. Considering the clinical findings, an algorithm to further stratify zero calcium score patients was proposed and had a limited performance in the validation cohort (AUC 58; 95%CI 43, 72). CONCLUSION: A lower cardiovascular risk profile is associated with zero calcium score in a setting of high-risk patients. Smoking is the strongest predictor of SCO in patients without CAC.

FUNDAMENTO: A avaliação do Escore de Cálcio Coronariano (ECC) pode ser realizada por tomografia computadorizada sem contraste para prever eventos cardiovasculares, mas tem menor valor na estratificação de risco em pacientes sintomáticos. OBJETIVO: Identificar e validar preditores de obstrução coronariana significativa (OCS) em pacientes sintomáticos sem calcificação da artéria coronária. MÉTODOS: Um total de 4258 participantes foram rastreados dos estudos CORE64 e CORE 320, nos quais foram avaliados pacientes encaminhados para angiografia invasiva, e do Quanta Registry que incluiu pacientes encaminhados para angiotomografia. Modelos de regressão logística avaliaram associações entre fatores de risco cardiovascular, ECC e OCS. Um nível de significância de 5% foi usado nas análises. RESULTADOS: Dos 509 participantes do estudo CORE, 117 (23%) apresentaram um ECC igual a zero; 13 (11%) pacientes sem cálcio coronariano apresentaram OCS. A ausência de cálcio coronariano correlacionou-se com idade mais jovem, sexo feminino, índice de massa corporal mais baixo, ausência de diabetes, e ausência de dislipidemia. O fato de ser fumante atual aumentou em 3,5 vezes a probabilidade de OCS e outros fatores de risco cardiovasculares não apresentaram associação significativa. Considerando os achados clínicos, um algoritmo para estratificar os pacientes com ECC igual a zero foi proposto, e tiveram desempenho limitado na coorte de validação (AUC 58; IC95% 43, 72). CONCLUSÃO: Um perfil de risco cardiovascular mais baixo está associado a um ECC igual a zero em pacientes de alto risco. Tabagismo é o preditor mais forte de OCS em pacientes com ausência de cálcio coronariano.

The meiotic LINC complex component KASH5 is an activating adaptor for cytoplasmic dynein.

Cytoplasmic dynein-driven movement of chromosomes during prophase I of mammalian meiosis is essential for synapsis and genetic exchange. Dynein connects to chromosome telomeres via KASH5 and SUN1 or SUN2, which together span the nuclear envelope. Here, we show that KASH5 promotes dynein motility in vitro, and cytosolic KASH5 inhibits dynein's interphase functions. KASH5 interacts with a dynein light intermediate chain (DYNC1LI1 or DYNC1LI2) via a conserved helix in the LIC C-terminal, and this region is also needed for dynein's recruitment to other cellular membranes. KASH5's N-terminal EF-hands are essential as the interaction with dynein is disrupted by mutation of key calcium-binding residues, although it is not regulated by cellular calcium levels. Dynein can be recruited to KASH5 at the nuclear envelope independently of dynactin, while LIS1 is essential for dynactin incorporation into the KASH5-dynein complex. Altogether, we show that the transmembrane protein KASH5 is an activating adaptor for dynein and shed light on the hierarchy of assembly of KASH5-dynein-dynactin complexes.

Sniffing out Ca2+ signaling in olfactory cilia.

JGP study (Takeuchi and Kurahashi. 2023. J. Gen. Physiol.https://doi.org/10.1085/jgp.202213165) reveals that segregation of signals within sensory cilia allows Ca2+ to play opposing roles in olfactory signal transduction.

Solving the insoluble: calciprotein particles mediate bulk mineral transport.

Protein mineral complexes, or calciprotein particles, are formed by calcium, phosphate, and the plasma protein fetuin-A. Crystalline calciprotein particles cause soft tissue calcification, oxidative stress, and inflammation, all well-known complications in chronic kidney disease. The T50 calcification propensity test measures how long it takes for amorphous calciprotein particles to crystallize. A study in this volume demonstrates remarkably low calcification propensity in cord blood, despite high mineral concentration. This hints to previously unidentified calcification inhibitors.

Acetylcholine regulation of GnRH neuronal activity: A circuit in the medial septum.

In vertebrates, gonadotropin-releasing hormone (GnRH)-secreting neurons control fertility by regulating gonadotrophs in the anterior pituitary. While it is known that acetylcholine (ACh) influences GnRH secretion, whether the effect is direct or indirect, and the specific ACh receptor (AChR) subtype(s) involved remain unclear. Here, we determined 1) whether ACh can modulate GnRH cellular activity and 2) a source of ACh afferents contacting GnRH neurons. Calcium imaging was used to assay GnRH neuronal activity. With GABAergic and glutamatergic transmission blocked, subtype-specific AChR agonists and antagonists were applied to identify direct regulation of GnRH neurons. ACh and nicotine caused a rise in calcium that declined gradually back to baseline after 5-6 min. This response was mimicked by an alpha3-specific agonist. In contrast, muscarine inhibited GnRH calcium oscillations, and blocking M2 and M4 together prevented this inhibition. Labeling for choline acetyltransferase (ChAT) and GnRH revealed ChAT fibers contacting GnRH neurons, primarily in the medial septum (MS), and in greater number in females than males. ChAT positive cells in the MS are known to express p75NGFRs. Labeling for p75NGFR, ChAT and GnRH indicated that ChAT fibers contacting GnRH cells originate from cholinergic cells within these same rostral areas. Together, these results indicate that cholinergic cells in septal areas can directly regulate GnRH neurons.

Effect of magnesium on vascular calcification in chronic kidney disease patients: a systematic review and meta-analysis.

PURPOSE: To evaluate the effects of magnesium (Mg) supplementation on vascular calcification (VC) in patients with chronic kidney disease (CKD). METHODS: PubMed, Embase, Cochrane Library, Medline, Web of Science, CNKI, VIP, and WanFang databases were searched from build to July 2022. Randomized controlled trials (RCT) and non-RCT related to whether Mg supplementation inhibits VC in patients with CKD were included. The literature was screened according to inclusion and exclusion criteria, and quality evaluation and data collection were performed. Meta-analysis was performed using Review Manager 5.4 software. RESULTS: 8 RCTs and 1 non-RCT studies with a total of 496 patients were eventually included. Compared to control groups, Mg supplementation increased serum Mg levels (SMD = 1.26, 95% CI: -0.70 to 1.82, p < 0.001), but it was not statistically significant in alleviating the degree of VC, increasing T50, and reducing serum phosphorus (P) levels in patients with CKD (all p > 0.05). Oral Mg reduced left (WMD=-0.06, 95% CI. -0.11 to -0.01, p = 0.03) and right (WMD=-0.07, 95% CI: -0.13 to -0.01, p = 0.02) carotid intima-media thickness (cIMT). Additionally, calcium (Ca) (SMD=-0.43, 95% CI: -0.74 to -0.11, p = 0.008) and parathyroid hormone (PTH) (SMD=-0.43, 95% CI: -0.75 to -0.11, p = 0.008) levels were reduced by increasing dialysate Mg concentration. CONCLUSIONS: Mg supplementation increased serum Mg levels and reduced Ca, PTH, and cIMT, but it did not reduce VC scores in patients with CKD. This still requires further studies with larger samples to evaluate the effect of Mg supplementation on VC.

Denosumab-induced hypocalcemia post bariatric surgery-a severe and protracted course: a case report.

BACKGROUND: Denosumab is known to cause abnormalities in calcium homeostasis. Most of such cases have been described in patients with underlying chronic kidney disease or severe vitamin D deficiency. Previous bariatric surgery could also contribute to hypocalcemia and deterioration in bone health. CASE PRESENTATION: We present a case of a 61-year-old Malay female with worsening bilateral limb weakness, paresthesia, and severe carpopedal spasm a week after receiving subcutaneous denosumab for osteoporosis. She had a history of gastric bypass surgery 20 years ago. Post gastric bypass surgery, she was advised and initiated on lifelong calcium, vitamin D, and iron supplementations that she unfortunately stopped taking 5 years after surgery. Her last serum blood tests, prior to initiation on denosumab, were conducted in a different center, and she was told that she had a low calcium level; hence, she was advised to restart her vitamin and mineral supplements. Laboratory workup revealed severe hypocalcemia (adjusted serum calcium of 1.33 mmol/L) and mild hypophosphatemia (0.65 mmol/L), with normal magnesium and renal function. Electrocardiogram showed a prolonged QTc interval. She required four bolus courses of intravenous calcium gluconate, and three courses of continuous infusions due to retractable severe hypocalcemia (total of 29 vials of 10 mL of 10% calcium gluconate intravenously). In view of her low vitamin D level of 33 nmol/L, she was initiated on a loading dose of cholecalciferol of 50,000 IU per week for 8 weeks. However, despite a loading dose of cholecalciferol, multiple bolus courses, and infusions of calcium gluconate, her serum calcium hovered around only 1.8 mmol/L. After 8 days of continuous intravenous infusions of calcium gluconate, high doses of calcitriol 1.5 µg twice daily, and 1 g calcium carbonate three times daily, her serum calcium stabilized at approximately 2.0 mmol/L. She remained on these high doses for over 2 months, before they were gradually titrated down to ensure sustainability of a safe calcium level. CONCLUSION: This case report highlights the importance of screening for risk factors for iatrogenic hypocalcemia and ensuring normal levels before initiating denosumab. The patient history of bariatric surgery could have worsened the hypocalcemia, resulting in a more severe presentation and protracted response to oral calcium and vitamin D supplementation.

Brain fatty acid and transcriptome profiles of pig fed diets with different levels of soybean oil.

BACKGROUND: The high similarity in anatomical and neurophysiological processes between pigs and humans make pigs an excellent model for metabolic diseases and neurological disorders. Lipids are essential for brain structure and function, and the polyunsaturated fatty acids (PUFA) have anti-inflammatory and positive effects against cognitive dysfunction in neurodegenerative diseases. Nutrigenomics studies involving pigs and fatty acids (FA) may help us in better understanding important biological processes. In this study, the main goal was to evaluate the effect of different levels of dietary soybean oil on the lipid profile and transcriptome in pigs' brain tissue. RESULTS: Thirty-six male Large White pigs were used in a 98-day study using two experimental diets corn-soybean meal diet containing 1.5% soybean oil (SOY1.5) and corn-soybean meal diet containing 3.0% soybean oil (SOY3.0). No differences were found for the brain total lipid content and FA profile between the different levels of soybean oil. For differential expression analysis, using the DESeq2 statistical package, a total of 34 differentially expressed genes (DEG, FDR-corrected p-value < 0.05) were identified. Of these 34 DEG, 25 are known-genes, of which 11 were up-regulated (log2 fold change ranging from + 0.25 to + 2.93) and 14 were down-regulated (log2 fold change ranging from - 3.43 to -0.36) for the SOY1.5 group compared to SOY3.0. For the functional enrichment analysis performed using MetaCore with the 34 DEG, four pathway maps were identified (p-value < 0.05), related to the ALOX15B (log2 fold change - 1.489), CALB1 (log2 fold change - 3.431) and CAST (log2 fold change + 0.421) genes. A "calcium transport" network (p-value = 2.303e-2), related to the CAST and CALB1 genes, was also identified. CONCLUSION: The results found in this study contribute to understanding the pathways and networks associated with processes involved in intracellular calcium, lipid metabolism, and oxidative processes in the brain tissue. Moreover, these results may help a better comprehension of the modulating effects of soybean oil and its FA composition on processes and diseases affecting the brain tissue.

Association of coronary artery calcium with heart rate variability in the Brazilian Longitudinal Study of Adult Health - ELSA-Brasil.

Current data shows that the autonomic and vascular systems can influence each other. However, only a few studies have addressed this association in the general population. We aimed to investigate whether heart rate variability (HRV) was associated with coronary artery calcium (CAC) in a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We examined baseline data from 3138 participants (aged 35 to 74 years) without previous cardiovascular disease who underwent CAC score assessment and had validated HRV recordings. Prevalent CAC was defined as a CAC score>0, and HRV analyses were performed over 5-min segments. We detected CAC score>0 in 765 (24.4%) participants. Subgroup analyses in older participants (≥49 years) adjusted for sociodemographic and clinical variables revealed that CAC score>0 was associated with lower values of standard deviation of NN intervals (SDNN) (odds ratio [OR]=1.32; 95%CI: 1.05,1.65), root mean square of successive differences between adjacent NN intervals (RMSSD) (OR=1.28; 95%CI: 1.02,1.61), and low frequency (LF) (OR=1.53, 95%CI: 1.21,1.92). Interaction analysis between HRV indices and sex in age-stratified groups revealed significant effect modification: women showed increased OR for prevalent CAC in the younger group, while for men, the associations were in the older group. In conclusion, participants aged ≥49 years with low SDNN, RMSSD, and LF values were more likely to present prevalent CAC, suggesting a complex interaction between these markers in the pathogenesis of atherosclerosis. Furthermore, our results suggested that the relationship between CAC and HRV might be sex- and age-related.

[Imaging of spatiotemporal pattern of synaptic inputs during memory replay].

Dendrites receive excitatory synaptic inputs from upstream cell ensembles to trigger action potentials at the cell body. The efficiency of excitatory synaptic inputs on neuronal output depends on the spatiotemporal pattern of synaptic inputs. However, technical limitations still make it unclear how synaptic inputs are organized along dendrites in both space and time. Spine calcium imaging, which records synaptic inputs as calcium transients at individual spines using calcium ion-sensitive fluorophores, is a unique method for studying the spatiotemporal patterns of synaptic input. We developed a functional multiple-spine calcium imaging (fMsCI) that combines whole-cell patch-clamp recording and spinning-disk confocal imaging to observe hundreds of synaptic inputs simultaneously. Using this method, we discovered sequential synaptic inputs that accompanied sharp wave ripple oscillations. In this review, I will discuss the function of sequential synaptic inputs and the potential uses of fMsCI to better understand neurological disorders.