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UNLABELLED: During pilus assembly within the Gram-positive bacterial envelope, membrane-bound sortase enzymes sequentially crosslink specific pilus protein monomers through their cell wall sorting signals (CWSS), starting with a designated tip pilin, followed by the shaft made of another pilin, ultimately anchoring the fiber base pilin to the cell wall. To date, the molecular determinants that govern pilus tip assembly and the underlying mechanism remain unknown. Here, we addressed this in the model organism Actinomyces oris. This oral microbe assembles a pathogenically important pilus (known as type 2 fimbria) whose shafts, made of FimA pilins, display one of two alternate tip pilins-FimB or the coaggregation factor CafA-that share a markedly similar CWSS. We demonstrate that swapping the CWSS of CafA with that of FimB produces a functional hybrid, which localizes at the pilus tip and mediates polymicrobial coaggregation, whereas alanine-substitution of the conserved FLIAG motif within the CWSS hampers these processes. Remarkably, swapping the CWSS of the normal cell wall-anchored glycoprotein GspA with that of CafA promotes the assembly of hybrid GspA at the FimA pilus tip. Finally, exchanging the CWSS of the Corynebacterium diphtheriae shaft pilin SpaA with that of CafA leads to the FLIAG motif-dependent localization of the heterologous pilus protein SpaA at the FimA pilus tip in A. oris. Evidently, the CWSS and the FLIAG motif of CafA are both necessary and sufficient for its destination to the cognate pilus tip specifically assembled by a designated sortase in the organism. IMPORTANCE: Gram-positive pili, whose precursors harbor a cell wall sorting signal (CWSS) needed for sortase-mediated pilus assembly, typically comprise a pilus shaft and a tip adhesin. How a pilin becomes a pilus tip, nevertheless, remains undetermined. We demonstrate here in Actinomyces oris that the CWSS of the tip pilin CafA is necessary and sufficient to promote pilus tip assembly, and this functional assembly involves a conserved FLIAG motif within the CWSS. This is evidenced by the fact that an A. oris cell-wall anchored glycoprotein, GspA, or a heterologous shaft pilin from Corynebacterium diphtheriae, SpaA, engineered to have the CWSS of CafA in place of their CWSS, localizes at the pilus tip in a process that requires the FLIAG motif. Our findings provide the molecular basis for sortase-catalyzed pilus tip assembly that is very likely employed by other Gram-positive bacteria and potential bioengineering applications to display antigens at controlled surface distance.

The biphasic assembly of Gram-positive pili begins with the covalent polymerization of distinct pilins catalyzed by a pilus-specific sortase, followed by the cell wall anchoring of the resulting polymers mediated by the housekeeping sortase. In Actinomyces oris, the pilus-specific sortase SrtC2 not only polymerizes FimA pilins to assemble type 2 fimbriae with CafA at the tip, but it can also act as the anchoring sortase, linking both FimA polymers and SrtC1-catalyzed FimP polymers (type 1 fimbriae) to peptidoglycan when the housekeeping sortase SrtA is inactive. To date, the structure-function determinants governing the unique substrate specificity and dual enzymatic activity of SrtC2 have not been illuminated. Here, we present the crystal structure of SrtC2 solved to 2.10-Å resolution. SrtC2 harbors a canonical sortase fold and a lid typical for class C sortases and additional features specific to SrtC2. Structural, biochemical, and mutational analyses of SrtC2 reveal that the extended lid of SrtC2 modulates its dual activity. Specifically, we demonstrate that the polymerizing activity of SrtC2 is still maintained by alanine-substitution, partial deletion, and replacement of the SrtC2 lid with the SrtC1 lid. Strikingly, pilus incorporation of CafA is significantly reduced by these mutations, leading to compromised polymicrobial interactions mediated by CafA. In a srtA mutant, the partial deletion of the SrtC2 lid reduces surface anchoring of FimP polymers, and the lid-swapping mutation enhances this process, while both mutations diminish surface anchoring of FimA pili. Evidently, the extended lid of SrtC2 enables the enzyme the cell wall-anchoring activity in a substrate-selective fashion.

Angiogenesis plays a pivotal role in ischemic cardiovascular disease, accompanied by epigenetic regulation during this process. Sirtuin 6 (SIRT6) has been implicated in the regulation of DNA repair, transcription and aging, with its deacetylase activity fully studied. However, the role of SIRT6 demyristoylase activity remains less clear, with even less attention given to its myristoylated substrates. In this study, we report that endothelial specific SIRT6 knockout attenuated angiogenesis in mice, while SIRT6 was observed to promote migration and tube formation in endothelial cell. Notably, we further determined that SIRT6 affects the intracellular VEGFA and global myristoylation level under hypoxia. Moreover, ALK14 (myristic acids analogue) treatment and SIRT6 knockdown results in a significant decrease in VEGFA secretion under hypoxia, implying the involvement of SIRT6 demyristoylase activity in angiogenesis. Mechanistically, CLICK IT assay verified that VEGFA is a myristoylated substrate of SIRT6. Further, overexpression of SIRT6 mutants (R65A, G60A and H133Y) results in profound differences in VEGFA secretion, indicating that SIRT6 promotes VEGFA secretion through demyristoylation but not deacetylation. Finally, overexpression of SIRT6 rescued the diminishment of endothelial migration, tube formation and sprouting caused by ALK14 treatment. Overall, our study demonstrates that SIRT6 regulates angiogenesis by demyristoylating VEGFA and increasing VEGFA secretion. Therefore, modulation of SIRT6 demyristoylase activity may represent a therapeutic strategy for ischemic cardiovascular disease. In brief Feng et al. describe a function of the SIRT6 demytistoylase activity in regulation of VEGFA secretion in endothelial cells. Endothelial specific Sirt6 Knockout resulted in reduced blood flow recovery and serum VEGFA level after hind-limb ischemia surgery. The results of the endothelial phenotype experiment indicate that SIRT6 promotes angiogenesis. Finally, we identified that SIRT6 demyristoylates VEGFA to increase its secretion, which is a novel pathway of SIRT6 to regulate angiogenesis. [Display omitted] • Demyristoylation is a novel pathway for SIRT6 to promote angiogenesis in addition to deacetylation. • We report a new post-translational modification regulatory mechanism of VEGFA. • Mechanistically, CLICK IT assay verified that VEGFA is a myristoylated substrate of SIRT6. • We find that SIRT6 demyristoylates VEGFA to increase its secretion. [ABSTRACT FROM AUTHOR]

Context Mild autonomous cortisol secretion (MACS) is diagnosed based on postdexamethasone cortisol >1.8 µg/dL. Scarce evidence exists on steroid circadian secretion and steroid metabolome in MACS. Objective To characterize 24-hour (h) urine steroid metabolome in patients with MACS and determine circadian differences in urine steroid profiling and cortisol concentrations in patients with MACS vs referent subjects. Methods Cross-sectional study, 2018-2023, at a referral center. Patients with MACS and age-, sex-, body mass index–, and menopausal status–matched referent subjects were included. Urine was collected over a 24 hour period as separate daytime and nighttime collections. High-resolution mass spectrometry assay was used to measure 25 steroids. A subgroup of patients and referent subjects was admitted for serum measurements of free and total cortisol every 2 hours. Outcomes were steroids, steroid sums, and ratios. Results Patients with MACS (n = 72) had lower µg/24 hour median androgens (2084 vs 3283, P <.001), higher glucocorticoids (15 754 vs 12936, P <.001), and higher glucocorticoid/androgen ratio (8.7 vs 3.9, P <.001) than referent subjects. Patients also had lower steroid day/night ratios than referent subjects, reflecting a higher relative nocturnal steroid production in MACS. In a subgroup of 12 patients with MACS and 10 referent subjects, the 24-hour areas under the curve for total and free serum cortisol were similar. However, evening mean total (5.3 vs 4.0 µg/dL, P =.056) and free (0.2 vs 0.1 µg/dL, P =.035) cortisol was higher in patients vs referent subjects. Conclusion Patients with MACS demonstrate an abnormal urine steroid metabolome, with a high glucocorticoid to androgen ratio, and a higher nocturnal steroid production. [ABSTRACT FROM AUTHOR]

Royal jelly (RJ), a substance secreted by the hypopharyngeal and mandibular glands of nurse worker bees, is widely used in medical products, dietary supplements, health foods, and cosmetics, owing to its potential health benefits. An understanding of secretory glands, such as the hypopharyngeal glands (HGs), and their interactions are necessary for RJ secretion. The RJ production cycle should be expanded for more effective production, which requires additional experience and training. However, the association between RJ secretion and HGs levels remains unclear. To close this gap, we conducted this review to investigate the most recent advancements in HGs and RJ secretion in Apis mellifera. These include techniques for enhancing RJ production, the morphology of HGs, RJ biological and effectiveness in the treatment of diseases, a comparison of the secretion of RJ signaling pathways in honey bees, associated genes, the proteins of HGs, and elements that could affect the secretion of HGs and the mechanism of RJ secretion. In order to help bee products strategy, our review may be valuable for a better understanding of the association between HGs and RJ secretion. The heads of bees have secretory glands, especially hypopharyngeal glands (HGs), and mandibular glands located in front of the worker bees head, which secretes through the mouthparts with three main functions: Saliva to mix with food, larval feeding secretion, chemicals to communicate with other bees, and anesthetic chemicals. HGs: Contain royal jelly (RJ) protein in nurse bees; however, invertase in foragers. Often changes function with age, in the young bee's lipids for RJ; old bees alarm pheromone 2-haptanone, and Isopentylic acetate. [ABSTRACT FROM AUTHOR]

Islet transplantation and more recently stem cell-derived islets were shown to successfully re-establish glycemic control in people with type 1 diabetes under immunosuppression. These results were achieved through intraportal infusion which leads to early graft losses and limits the capacity to contain and retrieve implanted cells in case of adverse events. Extra-hepatic sites and encapsulation devices have been developed to address these challenges and potentially create an immunoprotective or immune-privileged environment. Many strategies have achieved reversal of hyperglycemia in diabetic rodents. So far, the results have been less promising when transitioning to humans and larger animal models due to challenges in oxygenation and insulin delivery. We propose a versatile in vitro perfusion system to culture and experimentally study the function of centimeter-scale tissues and devices for insulin-secreting cell delivery. The system accommodates various tissue geometries, experimental readouts, and oxygenation tensions reflective of potential transplantation sites. We highlight the system's applications by using case studies to explore three prominent bioartificial endocrine pancreas (BAP) configurations: (I) with internal flow, (II) with internal flow and microvascularized, and (III) without internal flow. Oxygen concentration profiles modeled computationally were analogous to viability gradients observed experimentally through live/dead endpoint measurements and in case I, time-lapse fluorescence imaging was used to monitor the viability of GFP-expressing cells in real time. Intervascular BAPs were cultured under flow for up to 3 days and BAPs without internal flow for up to 7 days, showing glucose-responsive insulin secretion quantified through at-line non-disruptive sampling. This system can complement other preclinical platforms to de-risk and optimize BAPs and other artificial tissue designs prior to clinical studies. [ABSTRACT FROM AUTHOR]

The specific role that prolactin plays in lactational infertility, as distinct from other suckling or metabolic cues, remains unresolved. Here, deletion of the prolactin receptor (Prlr) from forebrain neurons or arcuate kisspeptin neurons resulted in failure to maintain normal lactation-induced suppression of estrous cycles. Kisspeptin immunoreactivity and pulsatile LH secretion were increased in these mice, even in the presence of ongoing suckling stimulation and lactation. GCaMP fibre photometry of arcuate kisspeptin neurons revealed that the normal episodic activity of these neurons is rapidly suppressed in pregnancy and this was maintained throughout early lactation. Deletion of Prlr from arcuate kisspeptin neurons resulted in early reactivation of episodic activity of kisspeptin neurons prior to a premature return of reproductive cycles in early lactation. These observations show dynamic variation in arcuate kisspeptin neuronal activity associated with the hormonal changes of pregnancy and lactation, and provide direct evidence that prolactin action on arcuate kisspeptin neurons is necessary for suppressing fertility during lactation in mice. [ABSTRACT FROM AUTHOR]

C-peptide is an equimolar by-product of insulin biosynthesis. It is used clinically to assess insulin secretion and differentiate types of diabetes. However, the lack of standardization across assays limits its broader application. This study aimed to examine discrepancies between the leading C-peptide measurement methods used in clinical laboratories and propose a solution to reduce them based on a complete traceability chain.Two sets of serum samples were distributed to 10 manufacturers of C-peptide assays. The first set (A, n=20) was analyzed independently by each manufacturer, who then returned their results to us. Subsequently, we sent out the second set (B, n=20) along with the reference values for set A. For set B, each manufacturer provided both non-calibrated and recalibrated values for each sample. The recalibration was performed according to each manufacturer’s internal standard protocols. We assessed how recalibration affected agreement between methods and alignment with the reference method. Non-parametric statistical approaches, including Passing-Bablok regression, level of agreement, and standard deviation analysis, were applied to compare data from multiple perspectives.Despite most manufacturers using the same WHO C-peptide calibrator material, significant disagreement was observed between methods prior to recalibration. Recalibration with matrix-appropriate serum samples reduced the discordance among assays, bringing them closer to the reference method. Overall, recalibration reduced both systematic bias and individual assay disagreement.These findings underscore the importance of appropriate calibration schemes to improve agreement across C-peptide assays, enhancing the accuracy of C-peptide testing for clinical practice. [ABSTRACT FROM AUTHOR]

The gonadotropin-releasing hormone (GnRH) neurons represent the key output cells of the neural network controlling mammalian fertility. We used GCaMP fiber photometry to record the population activity of the GnRH neuron distal projections in the ventral arcuate nucleus where they merge before entering the median eminence to release GnRH into the portal vasculature. Recordings in freely behaving intact male and female mice revealed abrupt ~8 min duration increases in activity that correlated perfectly with the appearance of a subsequent pulse of luteinizing hormone (LH). The GnRH neuron dendrons also exhibited a low level of unchanging clustered, rapidly fluctuating baseline activity in males and throughout the estrous cycle in females. In female mice, a gradual increase in basal activity that exhibited ~80 min oscillations began in the afternoon of proestrus and lasted for 12 hr. This was associated with the onset of the LH surge that ended several hours before the fall in the GCaMP signal. Abrupt 8 min duration episodes of GCaMP activity continued to occur on top of the rising surge baseline before ceasing in estrus. These observations provide the first description of GnRH neuron activity in freely behaving animals. They demonstrate that three distinct patterns of oscillatory activity occur in GnRH neurons. These are comprised of low-level rapid baseline activity, abrupt 8 min duration oscillations that drive pulsatile gonadotropin secretion, and, in females, a gradual and very prolonged oscillating increase in activity responsible for the preovulatory LH surge. [ABSTRACT FROM AUTHOR]

Ca2+ tunneling requires both store-operated Ca2+ entry (SOCE) and Ca2+ release from the endoplasmic reticulum (ER). Tunneling expands the SOCE microdomain through Ca2+ uptake by SERCA into the ER lumen where it diffuses and is released via IP3 receptors. In this study, using high-resolution imaging, we outline the spatial remodeling of the tunneling machinery (IP3R1; SERCA; PMCA; and Ano1 as an effector) relative to STIM1 in response to store depletion. We show that these modulators redistribute to distinct subdomains laterally at the plasma membrane (PM) and axially within the cortical ER. To functionally define the role of Ca2+ tunneling, we engineered a Ca2+ tunneling attenuator (CaTAr) that blocks tunneling without affecting Ca2+ release or SOCE. CaTAr inhibits Cl- secretion in sweat gland cells and reduces sweating in vivo in mice, showing that Ca2+ tunneling is important physiologically. Collectively our findings argue that Ca2+ tunneling is a fundamental Ca2+ signaling modality. [ABSTRACT FROM AUTHOR]

Exocrine glands release a secretion to the body surface or into a lumen and are likely to be found in all insect taxa. Their secretions are diverse, serving many physiological, behavioral, and defensive functions. Much research has characterized gland structure and secretion identity and function, but little research has attempted to understand how these glands work to release secretion amounts in a timescale appropriate to function: How are some (e.g., physiological) secretions released in small amounts over long times, while others (e.g., defense) are released in large amounts infrequently? We describe a qualitative model, comprising intracellular, extracellular, and external compartments for secretion storage; rates of movement of secretion from one compartment to the next; physicochemical properties of secretions; and controlling behaviors, which may explain the release dynamics of secretions from these glands. It provides a template for quantitative dynamic studies investigating the operation, control, release, and biomimetics of exocrine glands. [ABSTRACT FROM AUTHOR]

A knowledge gap may exist when attempting to identify the pathogenetic mechanisms resulting in the syndrome of inappropriate antidiuretic hormone (SIADH) or hypotonic hyponatremia. Ectopic secretion of antidiuretic hormone [ADH] is the classic cause of SIADH. But another form of inappropriate secretion of ADH occurs when interleukin 6 is activated. Hypotonic hyponatremia can also occur in patients with cerebral salt wasting, but the secretion of ADH is appropriate, responding to volume depletion induced by excessive natriuresis. Reset osmostat (RO) is another cause of hypotonic hyponatremia caused by an unknown anomaly in the hypothalamus. This review discusses the pathophysiology of and the identical laboratory findings found in classic ectopic ADH secretion, interleukin 6-mediated ADH secretion, cerebral salt wasting-induced ADH secretion, and RO. This review also discusses potential methods to discern which hypotonic hyponatremic syndrome is present and current recommendations for treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: This study analyzes melatonin levels in dromedary camel seminal plasma and characterizes the presence of melatonin receptors (MT1 and MT2) on sperm membranes. Melatonin levels were found to be highest during the shorter days of the breeding season, though no direct link with testosterone levels was observed. Additionally, two melatonin receptors, MT1 and MT2, were identified on camel sperm, primarily located in the tail and post-acrosome regions. These findings are interesting and pave the way for future studies on the role of melatonin receptors in the physiology of dromedary camel semen. Camels (Camelus dromedarius) are seasonal short-day breeders, regulated by photoperiod and melatonin secretion. However, no studies have explored melatonin levels in camel seminal plasma or their relationship with testosterone, age, or climatic factors, nor is it known whether melatonin receptors exist in camel spermatozoa to respond to seminal melatonin. This study aimed to analyze melatonin levels in camel seminal plasma and its specific receptors in spermatozoa. Semen samples were obtained from November to March (breeding season). Testosterone and melatonin levels were measured in seminal plasma by ELISA. Melatonin receptors were localized in spermatozoa using immunofluorescence, and their presence was confirmed by Western Blot. Melatonin levels were higher from November to January and decreased in February and March. No correlation between testosterone and melatonin levels was found, but both hormones were negatively correlated with daylength (p = 0.0089 and p = 0.0688, respectively). Testosterone, but not melatonin, levels were affected by age. Two melatonin receptors (MT1, MT2) were detected on camel spermatozoa, with several immunotypes labeled mainly in the tail and post-acrosome region, but also in the acrosome and neck. Western Blot analysis confirmed the presence of these receptors, showing a 39 kDa band for MT1 and a 36 kDa band for MT2. Understanding melatonin's effects on sperm could help ejaculates' processing procedures, semen handling, and infertility issues in camels. [ABSTRACT FROM AUTHOR]

The non-image forming effects of light are moderated by various aspects such as dose, spectrum or temporal and spatial patterns. One of them, the spatial distribution of light within the field of view, has been scarcely researched. Although few studies suggest effects on melatonin secretion during night-time, the daytime effects remain unknown. In this project, we investigated the effect of three light directions – from above, below and the side – each illuminating different retinal regions. The luminance and the size of the light source were kept constant, thus realising the same vertical illuminance and melanopic irradiance at the eye for all scenes. Forty participants underwent a two hour protocol of cognitive tasks and subjective assessments of alertness and performance. Our results suggest stronger non-image forming-effects stimulation with lighting from above, whereas the effect of lighting from below and side differed slightly. [ABSTRACT FROM AUTHOR]

Cancer cells-derived extracellular vesicles can trigger the transformation of adipose-derived mesenchymal stem cells (ADMSC) into a pro-inflammatory, cancer-associated adipocyte (CAA) phenotype. Such secretome-mediated crosstalk between the adipose tissue and the tumor microenvironment (TME) therefore impacts tumor progression and metastatic processes. In addition, emerging roles of diet-derived phytochemicals, especially epigallocatechin-3-gallate (EGCG) among other polyphenols, in modulating exosome-mediated metabolic and inflammatory signaling pathways have been highlighted. Here, we discuss how selected diet-derived phytochemicals could alter the secretome signature as well as the crosstalk dynamics between the adipose tissue and the TME, with a focus on breast cancer. Their broader implication in the chemoprevention of obesity-related cancers is also discussed. [ABSTRACT FROM AUTHOR]

Introduction This study aimed to examine the correlation between the growth response in prepubertal children with idiopathic growth hormone (GH) deficiency after 1 year of treatment with GH to the initial clinical and biochemical parameters. Additionally, the secretion dynamics of GH was also studied by analyzing the GH stimulation test profiles in relation to the GH treatment response. Methods This retrospective study included 84 prepubertal children (47 males and 37 females) with a definitive diagnosis of GH deficiency. The GH secretory indexes GH max , GH secretion rate, and GH secretion volume were analyzed in relation to the response to recombinant human growth hormone (rhGH) treatment as defined by the index of responsiveness (IoR). Correlation and regression models were used to identify the best clinical and biochemical predictors to rhGH treatment. ResultsIoR was negatively correlated with the age (r=–0.607, p<0.01) and positively with the distance of child's height from its midparental height (MPH) r=0.466 (p<0.01) and pretreatment growth velocity (r=0.247, p<0.05). GH secretory indexes were correlated, and the highest association was observed between GH max and GH secretion volume (r=0.883, p<0.01). Among the GH secretory indexes, GH max was the best predictor of IoR (β coef. = –0.514, p<0.001) followed by the GH secretion volume (β coef. = –0.47, p<0.001) and GH secretion rate (β coef. = –0.367 p<0.001). Conclusions The age and the distance of child's height from its MPH are major predictors of GH treatment response in children with idiopathic GH deficiency. The calculation of the other GH secretory indexes GHSR and GHSV are not better predictors of response to GH than GH max. The combination of clinical and biochemical indexes may improve the pretreatment assessment of response to rhGH treatment. [ABSTRACT FROM AUTHOR]

Insulin treatment should be introduced in patients with slowly progressive type 1 diabetes (SPIDDM; definite), according to the revised diagnostic criteria of SPIDDM (2023). In contrast, SPIDDM (probable) patients are in a non‐insulin‐dependent state; therefore, a more flexible treatment can be considered, although sulfonylurea agents should be avoided. Insulin treatment has been shown to maintain endogenous insulin secretion capacity in SPIDDM (probable); however, this does not mean that all SPIDDM (probable) patients should use insulin from the early phase. Dipeptidyl peptidase‐4 inhibitors and biguanides might be the treatment of choice for SPIDDM (probable), but no evidence exists for other hypoglycemic agents. In any case, careful monitoring of the endogenous insulin secretion capacity should be carried out, and if a decrease in insulin secretion capacity is suspected, a change in treatment should be considered to prevent progression to an insulin‐dependent state. [ABSTRACT FROM AUTHOR]

Type VI secretion systems (T6SSs) are widespread bacterial protein secretion machines that inject toxic effector proteins into nearby cells, thus facilitating both bacterial competition and virulence. Pseudomonas aeruginosa encodes three evolutionarily distinct T6SSs that each export a unique repertoire of effectors. Owing to its genetic tractability, P. aeruginosa has served as a model organism for molecular studies of the T6SS. However, P. aeruginosa is also an opportunistic pathogen and ubiquitous environmental organism that thrives in a wide range of habitats. Consequently, studies of its T6SSs have provided insight into the role these systems play in the diverse lifestyles of this species. In this review, we discuss recent advances in understanding the regulation and toxin repertoire of each of the three P. aeruginosa T6SSs. We argue that these T6SSs serve distinct physiological functions; whereas one system is a dedicated defensive weapon for interbacterial antagonism, the other two T6SSs appear to function primarily during infection. We find support for this model in examining the signalling pathways that control the expression of each T6SS and co-ordinate the activity of these systems with other P. aeruginosa behaviours. Furthermore, we discuss the effector repertoires of each T6SS and connect the mechanisms by which these effectors kill target cells to the ecological conditions under which their respective systems are activated. Understanding the T6SSs of P. aeruginosa in the context of this organism's diverse lifestyles will provide insight into the physiological roles these secretion systems play in this remarkably adaptable bacterium. [ABSTRACT FROM AUTHOR]

Liver cancer is one of the most prevalent cancers worldwide. The first-line therapeutic drug sorafenib offers only a moderate improvement in patients' conditions. Therefore, an approach to enhancing its therapeutic efficacy is urgently needed. It has been revealed that hepatocellular carcinoma (HCC) cells with heightened intracellular quiescin sulfhydryl oxidase 1 (QSOX1) exhibit increased sensitivity to sorafenib. QSOX1 is a secreted disulfide catalyst, and it is widely recognized that extracellular QSOX1 promotes the growth, invasion, and metastasis of cancer cells through its participation in the establishment of extracellular matrix. Inhibiting QSOX1 secretion can increase intracellular QSOX1 and decrease extracellular QSOX1. Such an approach would sensitize HCC cells to sorafenib but remains to be established. Since (−)-epigallocatechin-3-gallate (EGCG) has been demonstrated to be an effective inhibitor of α-fetal protein secretion from HCC cells, we screened QSOX1 secretion inhibition using polyphenolic compounds. We examined eight dietary polyphenols (EGCG, quercetin, fisetin, myricetin, caffeic acid, chlorogenic acid, resveratrol, and theaflavin) and found that EGCG and quercetin effectively inhibited QSOX1 secretion from human HCC cells (HepG2 or Huh7), resulting in high intracellular QSOX1 and low extracellular QSOX1. The combination of EGCG or quercetin, both of which change the cellular distribution of QSOX1, with sorafenib, which has no influence on the cellular distribution of QSOX1, exhibited multiple synergistic effects against the HCC cells, including the induction of apoptosis and inhibition of invasion and metastasis. In conclusion, our current results suggest that dietary EGCG and quercetin have the potential to be developed as adjuvants to sorafenib in the treatment of HCC by modulating the cellular distribution of QSOX1. [ABSTRACT FROM AUTHOR]

Context Hypertension, a prevalent cardiovascular risk, often involves dysregulated aldosterone and its interaction with the mineralocorticoid receptor (MR). Experimental designs in animal models and human cohorts have demonstrated a sex and age dependency of aldosterone secretion that expands our pathophysiologic understanding. Objective This study explores the genetic variation of NR3C2, which encodes MR, in relation to aldosterone, considering age, sex, and race. Methods Incorporating 720 Caucasians and 145 Africans from the HyperPATH cohort, we investigated the impact of rs4835490, a single nucleotide risk allele variant, on aldosterone levels and vasculature. Results Notably, a significant association between rs4835490 and plasma aldosterone under liberal salt conditions emerged in individuals of European ancestry (P =.0002). Homozygous carriers of the risk A allele exhibited elevated plasma aldosterone levels (AA = 8.1 ±.9 vs GG = 4.9 ±.5 ng/dL). Additionally, aldosterone activation through posture (P =.025) and urinary excretion (P =.0122) showed notable associations. Moreover, genetic interactions with race, sex, and age were observed. Caucasian females under 50 years displayed higher plasma aldosterone, urine aldosterone, and posture aldosterone with the AA genotype compared to females over 50 years, suggesting a potential connection with menopausal or estrogen influences. Interestingly, such age-dependent interactions were absent in the African cohort. Conclusion Our study highlights the significance of the NR3C2 genetic variation and its interplay with age, sex, and race in aldosterone activation. The findings point toward an estrogen-modulating effect on MR activation, particularly in women, underlining the role of aldosterone dysregulation in hypertension development. This insight advances our comprehension of hypertension's complexities and opens avenues for personalized interventions. Clinical Trial Registration Number: NCT03029806 (registered January 24, 2017). [ABSTRACT FROM AUTHOR]

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Secretomes of cancer‐associated fibroblasts (CAFs) in colorectal cancer (CRC) contribute to malignancy. Detailed knowledge is available on the components and functions of CAF secretomes. Little is known about the regulation of CAF secretomes. Here, we searched for receptor‐like membrane‐bound molecules in CAFs, which may regulate the production and release of tumor‐activating secretomes. The adhesion molecule with Ig‐like domain 2 (AMIGO2) was significantly upregulated in cultivated CAFs compared to normal tissue‐associated fibroblasts (NAFs), and this was confirmed in patient‐derived tissues. AMIGO2 expression was low or absent in healthy colon, significantly increased in fibroblasts of primary CRC, and highest in the stromal tissues of CRC‐derived liver metastases. AMIGO2 expression in CAFs correlated with a higher T‐category, increased lymph node metastasis, progressed tumor stages and was associated with reduced survival in different cohorts of CRC patients. Interestingly, AMIGO2 expression was induced by transforming growth factor‐β and higher in female patients, who exhibit a more aggressive disease course. In functional studies, conditioned media of NAFs with experimentally induced AMIGO2 overexpression enhanced proliferation and migration of different CRC tumor cells, while siRNA‐mediated inhibition of AMIGO2 in CAFs attenuated these effects. Accordingly, therapeutic inhibition of the receptor‐like AMIGO2 protein in CRC CAFs could prevent tumorigenic secretomes in CRC. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

The microbiome of the uropygial gland and integuments where birds spread the uropygial secretion may play crucial roles for their hosts, but it has been poorly studied, especially in wild species. Exploring bacterial communities associated with the uropygial secretion of birds is particularly interesting in species under strong selection pressures due to pathogenic infection. Here, by high‐throughput 16S rRNA amplicon sequencing, we characterized and compared the bacterial communities of the uropygial gland surface of three African hornbill species (Family Bucerotidae), as well as the bill and feathers of females from two of these species and the nestlings of the other one. In accordance with previous knowledge of avian microbiomes, we expected to find differences associated with species identity, age and the sampled integument. Overall, we found that: 1) the microbiome was similar among species, 2) but there were slight differences associated with the sampled body regions. Moreover, 3) we observed no consistent variation in the microbiota with age, and 4) females and nestlings sharing a nest harboured more similar gland surface microbiota compared to females and nestlings that did not share a nest. These species often reuse nest cavities, sealing them with a plug made from diverse material. Once sealed, they remain enclosed in the nest for a long period. This behaviour opens the possibility that the nest environment is key shaping the microbiota of these species and might serve as a reservoir of the sampled bacterial communities. Moreover, behavioural mechanisms such as preening may contribute to the transmission of bacteria from the uropygial gland to other body regions, enhancing bacterial similarities. This study contributes to our understanding of the role of the nest environment in structuring bacterial communities in wild birds and provides the first thorough characterization of the microbiome inhabiting different body integuments of southern African hornbills. [ABSTRACT FROM AUTHOR]

The European hoopoe (Upupa epops) conforms a paradigmatic example of animals cultivating bacteria in their uropygial gland that protect them against pathogenic infections. We here explore the hypothesis that enterococci are the responsible bacteria of such beneficial effect. We did so by comparing the antimicrobial activity against three indicator bacteria of colonies isolated from cultures of enterococci and mesophilic bacteria from the uropygial skin or secretion of nestlings, brooding or non-brooding females, and males of the subspecies longirostris in Hainan (China). In accordance with the hypothesis, enterococci isolated from nesting birds are more active than those from non-nesting birds. Moreover, enterococci from the uropygial secretion were more active than those isolated from the skin or than mesophilic bacteria isolates. These results therefore support the hypothesis that, during the nesting phase, hoopoe females and nestlings cultivate enterococci in their uropygial gland with relatively high antimicrobial activity. [ABSTRACT FROM AUTHOR]

M2 macrophages promote adipose tissue thermogenesis which dissipates energy in the form of heat to combat obesity. However, the regulation of M2 macrophages by thermogenic adipocytes is unclear. Here, it is identified magnesium (Mg) as a thermogenic adipocyte‐secreted factor to promote M2 macrophage polarization. Mg transporter Cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4) induced by ADRB3‐PKA‐CREB signaling in thermogenic adipocytes during cold exposure mediates Mg efflux and Mg in turn binds to the DFG motif in mTOR to facilitate mTORC2 activation and M2 polarization in macrophages. In obesity, downregulation of CNNM4 expression inhibits Mg secretion from thermogenic adipocytes, which leads to decreased M2 macrophage polarization and thermogenesis. As a result, CNNM4 overexpression in adipocytes or Mg supplementation in adipose tissue ameliorates obesity by promoting thermogenesis. Importantly, an Mg wire implantation (AMI) approach is introduced to achieve adipose tissue‐specific long‐term Mg supplement. AMI promotes M2 macrophage polarization and thermogenesis and ameliorates obesity in mice. Taken together, a reciprocal regulation of thermogenic adipocytes and M2 macrophages important for thermogenesis is identified, and AMI is offered as a promising strategy against obesity. [ABSTRACT FROM AUTHOR]

Background: Bacillus subtilis is widely used for industrial enzyme production due to its capacity to efficiently secrete proteins. However, secretion efficiency of enzymes varies widely, and optimizing secretion is crucial to make production commercially viable. Previously, we have shown that overexpression of the xylanase XynA lowers expression of Clp protein chaperones, and that inactivation of CtsR, which regulates and represses clp transcription, increases the production of XynA. In the current study, we examined whether the same is the case for overexpression of the α-amylase AmyM from Geobacillus stearothermophilus by B. subtilis, and why XynA shows a different timing of secretion compared to AmyM. Results: Transcriptome analyses revealed that B. subtilis cells overexpressing AmyM exhibited a distinct profile compared to XynA overexpressing cells, however there were also similarities and in both cases expression of CtsR controlled genes was downregulated. In contrast to XynA, inactivation of CtsR did not improve AmyM production. Upregulation of other protein chaperones, including GroEL/ES and DnaJ/K, by inactivating their transcriptional repressor HrcA, had almost no effect on XynA yields and in fact considerably lowered that of AmyM. Despite using the same promoter, the production of XynA peaks well before AmyM reaches its optimal secretion rate. Transcriptome and ribosome profiling indicated that this is neither related to transcription nor to translation regulation. We show that the reduced secretion in the stationary phase is partially due to the activity of secreted proteases, but also due to the activity of the intracellular protease LonA. The absence of this protein resulted in a 140% and 20% increased production for XynA and AmyM, respectively. Conclusion: The combination of transcriptome and ribosome profiling offered important information to determine at which cellular level production bottlenecks occurred. This helped us to identify LonA protease as an important factor influencing enzyme production yields in B. subtilis. [ABSTRACT FROM AUTHOR]

Granule secretion is an essential platelet function that contributes not only to haemostasis but also to wound healing, inflammation, and atherosclerosis. Granule secretion from platelets is facilitated, at least in part, by Soluble N-ethylmaleimide-Sensitive Factor (NSF) Attachment Protein Receptor (SNARE) complex-mediated granule fusion. Although α-synuclein is a protein known to modulate the assembly of the SNARE complex in other cells, its role in platelet function remains poorly understood. In this study, we provide evidence that α-synuclein is critical for haemostasis using α-synuclein-deficient (−/−) mice. The genetic deletion of α-synuclein resulted in impaired platelet aggregation, secretion, and adhesion in vitro. In vivo haemostasis models showed that α-synuclein−/− mice had prolonged bleeding times and activated partial thromboplastin times (aPTTs). Mechanistically, platelet activation induced α-synuclein serine (ser) 129 phosphorylation and re-localisation to the platelet membrane, accompanied by an increased association with VAMP 8, syntaxin 4, and syntaxin 11. This phosphorylation was calcium (Ca2+)- and RhoA/ROCK-dependent and was inhibited by prostacyclin (PGI2). Our data suggest that α-synuclein regulates platelet secretion by facilitating SNARE complex formation. [ABSTRACT FROM AUTHOR]

Marcks and Marcksl1 are abundant proteins that shuttle between the cytoplasm and membrane to modulate multiple cellular processes, including cytoskeletal dynamics, proliferation, and secretion. Here, we performed loss- and gain-of-function experiments in Xenopus laevis to reveal the novel roles of these proteins in spinal cord development and regeneration. We show that Marcks and Marcksl1 have partly redundant functions and are required for normal neurite formation and proliferation of neuro-glial progenitors during embryonic spinal cord development and for its regeneration during tadpole stages. Rescue experiments in Marcks and Marcksl1 loss-of-function animals further suggested that some of the functions of Marcks and Marcksl1 in the spinal cord are mediated by phospholipid signaling. Taken together, these findings identify Marcks and Marcksl1 as critical new players in spinal cord development and regeneration and suggest new pathways to be targeted for therapeutic stimulation of spinal cord regeneration in human patients. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the effect of oestrogen and progesterone at the beginning of the menstrual cycle in delaying entry into the fertile window? SUMMARY ANSWER Both oestrogen and progesterone contribute to a delay in the onset of the fertile window. WHAT IS KNOWN ALREADY Oestrogen enhances cervical mucus secretion while progesterone inhibits it. STUDY DESIGN, SIZE, DURATION Observational study. Daily observation of 220 menstrual cycles contributed by 88 women with no known menstrual cycle disorder. PARTICIPANTS/MATERIALS, SETTING, METHODS Women recorded cervical mucus daily and collected first-morning urine samples for analysis of oestrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FHS, and LH. They underwent serial ovarian ultrasound examinations. The main outcome measure was the timing within the cycle of the onset of the fertile window, as identified by the appearance of mucus felt or seen at the vulva. MAIN RESULTS AND THE ROLE OF CHANCE Low oestrogen secretion and persistent progesterone secretion during the first week of the menstrual cycle both negatively affect mucus secretion. Doubling oestrogen approximately doubled the odds of entering the fertile window (OR: 1.82 95% CI=1.23; 2.69). Increasing PDG from below 1.5 to 4 µg/mg creatinine was associated with a 2-fold decrease in the odds of entering the fertile window (OR: 0.51 95% CI=0.31; 0.82). Prolonged progesterone secretion during the first week of the menstrual cycle was also statistically significantly associated with higher LH secretion. Finally, the later onset of the fertile window was associated with statistically significant persistently elevated LH secretion during the luteal phase of the previous menstrual cycle. LIMITATIONS, REASONS FOR CAUTION This post hoc study was conducted to assess the potential impact of residual progesterone secretion at the beginning of the menstrual cycle. It was conducted on an existing data set because of the scarcity of data available to answer the question. Analysis with other datasets with similar hormone results would be useful to confirm these findings. WIDER IMPLICATIONS OF THE FINDINGS This study provides evidence for residual progesterone secretion in the early latency phase of some menstrual cycles, which may delay the onset of the fertile window. This progesterone secretion may be supported by subtly increased LH secretion during the few days before and after the onset of menses, which may relate to follicular waves in the luteal phase. Persistent progesterone secretion should be considered in predicting the onset of the fertile window and in assessing ovulatory dysfunction. STUDY FUNDING/COMPETING INTEREST(S) The authors declare no conflicts of interest. No funding was provided for this secondary data analysis. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Chinese herbs contain substances that regulate female hormones. Our study confirmed that Zingiberis rhizoma carbonisata contains Zingiberis rhizoma-based carbon dots (ZR-CDs), which exert regulatory effects on serum oestradiol and FSH in mice and show impacts on endometrial growth and follicular development that potentially affect the ability of female fertility. ZR-CDs were characterized to clarify the microstructure, optical features, and functional group characteristics. It shows that ZR-CDs are spherical carbon nanostructures ranging from 0.97 to 2.3 nm in diameter, with fluorescent properties and a surface rich in functional groups. We further investigated the impact of ZR-CDs on oestradiol and FSH in serum, growth, and the development of ovarian and uterine using normal female mice and exogenous oestradiol intervention model. It was observed that ZR-CDs accelerated oestrogen metabolism and attenuated oestradiol-induced endometrial hyperplasia. Simultaneously, ZR-CDs triggered an increase in FSH, even in the presence of high-serum oestradiol that inhibits FSH secretion. Our findings suggest that ZR-CDs could be a potential therapeutic treatment for anovulatory menstruation. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are related intestinal L-cell derived secretory products. GLP-1 has been extensively studied in terms of its influence on metabolism, but less attention has been devoted to GLP-2 in this regard. The current study compares the effects of these proglucagon-derived peptides on pancreatic beta-cell function, as well as on glucose tolerance and appetite. The insulin secretory effects of GLP-1 and GLP-2 (10−12–10−6 M) were investigated in BRIN-BD11 beta-cells as well as isolated mouse islets, with the impact of test peptides (10 nM) on real-time cytosolic cAMP levels further evaluated in mouse islets. The impact of both peptides (10−8–10−6 M) on beta-cell growth and survival was also studied in BRIN BD11 cells. Acute in vivo (peptides administered at 25 nmol/kg) glucose homeostatic and appetite suppressive actions were then examined in healthy mice. GLP-1, but not GLP-2, concentration dependently augmented insulin secretion from BRIN-BD11 cells, with similar observations made in isolated murine islets. In addition, GLP-1 substantially increased [cAMP]cyt in islet cells and was significantly more prominent than GLP-2 in this regard. Both GLP-1 and GLP-2 promoted beta-cell proliferation and protected against cytokine-induced apoptosis. In overnight fasted healthy mice, as well as mice trained to eat for 3 h per day, the administration of GLP-1 or GLP-2 suppressed appetite. When injected conjointly with glucose, both peptides improved glucose disposal, which was associated with enhanced glucose-stimulated insulin secretion by GLP-1, but not GLP-2. To conclude, the impact of GLP-1 and GLP-2 on insulin secretion is divergent, but the effects of beta-cell signaling and overall health are similar. Moreover, the peripheral administration of either hormone in rodents results in comparable positive effects on blood glucose levels and appetite. [ABSTRACT FROM AUTHOR]

Microalgae-based technology is widely utilized in wastewater treatment and resource recovery. However, the practical implementation of microalgae-based technology is hampered by the difficulty in separating microalgae from treated water due to the low density of microalgae. This review is designed to find the current status of the development and utilization of microalgae biogranulation technology for better and more cost-effective wastewater treatment. This review reveals that the current trend of research is geared toward developing microalgae-bacterial granules. Most previous works were focused on studying the effect of operating conditions to improve the efficiency of wastewater treatment using microalgae-bacterial granules. Limited studies have been directed toward optimizing operating conditions to induce the secretion of extracellular polymeric substances (EPSs), which promotes the development of denser microalgae granules with enhanced settling ability. Likewise, studies on the understanding of the EPS role and the interaction between microalgae cells in forming granules are scarce. Furthermore, the majority of current research has been on the cultivation of microalgae-bacteria granules, which limits their application only in wastewater treatment. Cultivation of microalgae granules without bacteria has greater potential because it does not require additional purification and can be used for border applications. Highlights: The most recent development in microalgae biogranulation research is highlighted. Factors affecting microalgae granule development are discussed for the first time. Duration to develop granules is a crucial aspect that needs further research. Cultivation of single-species microalgae for rapid harvesting needs more attention. [ABSTRACT FROM AUTHOR]

Introduction: Intercostal nerve transfer is a surgical technique used to restore function in patients with total brachial plexus injury. Stem cell and secretome therapy has been explored as a potential treatment for brachial plexus injuries. This study aimed to compare the functional and histologic outcome of intercostal nerve transfer to median nerve with local stem cells or secretome injection in total type brachial plexus injuries. Materials and methods: This was a double-blinded, randomized controlled study (RCT). We included patients with neglected total type brachial plexus injury (BPI) who underwent nerve transfer and local injection of either umbilical cord-derived mesenchymal stem cells (UC-MSC) or secretome into median nerve–flexor digitorum superficialis (FDS) neuromuscular junction (NMJ). We measured preoperative and 8-month postoperative FDS muscle strength, SF-36, DASH score, and histologic assessment. We then analyzed the difference outcome between those two groups. Result: A total of 15 patients were included in this study. Our study found that after nerve transfer and implantation with either UC-MSC or secretome, significant postoperative improvements were observed in physical functioning, role limitations, energy/fatigue, emotional well-being, social functioning, pain, general health, and DASH scores, particularly in the overall cohort and the secretome group. When we compared the mean difference of clinical outcome from preoperative to postoperative between UC-MSC and secretome groups, the UC-MSC group showed better improvement of health change in SF-36 subgroup compared to secretome group. From the analysis, there was no significant difference in the histologic outcomes (inflammation, regeneration, and fibrosis) in overall cohort between preoperative and postoperative cohort. There was also no significant difference in mean change of the histologic outcomes (inflammation, regeneration, and fibrosis) preoperative and postoperatively between UC-MSC and secretome groups. Discussion and conclusion: Implantation of either UC-MSC or secretome along with nerve transfer may provide clinical improvement, while to achieve histologic improvement, further conditioning should be performed. [ABSTRACT FROM AUTHOR]

Mild autonomous cortisol secretion (MACS) has thus far been associated with several comorbidities, among which osteoporosis and fractures appear to be highly prevalent. Recent guidelines for adrenal incidentalomas have updated the definition of MACS, currently formulated on serum cortisol after a 1-mg dexamethasone test above 1.8 µg/dL or 50 nmol/L. Previous studies on bone health in adrenal incidentalomas had adopted different definitions of MACS, producing heterogeneous results in terms of fracture prevalence. This review aims to summarize the clinical impact of MACS in relation to fractures, bone quantity and quality, by providing a thorough update on MACS-related osteoporosis (MACS-ROP). This area has a large room for research, and management of this comorbidity still needs to be elucidated. [ABSTRACT FROM AUTHOR]

Plant economics, the way plants allocate and utilize resources, affect multiple soil processes through interactions with root and associated microbial communities. However, the interplay between plant economics and microbial ecological strategies remains poorly understood, which is crucial for integrated manipulation of plant‐ and microbe‐mediated functions in mitigating climate change and sustaining soil health.We used a field experiment with 11 cover crop species grown monocultures in the same base soil to test whether microbial ecological strategies are associated with plant economic strategies and if their interactions are linked to soil functions. A principal component analysis (PCA) was performed on root and leaf traits to identify the loadings of cover crop species on the plant trait space. Metagenomic analysis of rhizosphere microbial communities was conducted to infer their ecological strategies based on genetically encoded community‐aggregated traits.We found a synchronous relationship between the conservation gradient of plant economic strategies and the trade‐offs in microbial ecological strategies. Conservative plant strategists, such as Lolium multiflorum, Triticum turgidum and Brassica juncea, fostered microbial communities characterized by high growth yield potentials (Y‐strategies). This included increased microbial carbon fixation pathways, citrate cycle, ribosome and valine, leucine and isoleucine biosynthesis. As a result, microbial metabolic efficiency improved, shown by higher microbial biomass carbon content and a lower metabolic quotient (qCO2), led to enhanced soil organic carbon accumulation. In comparison, acquisitive plants like Astragalus sinicus, Vicia villosa, Trifolium incarnatum and Medicago sativa stimulated microbial resource‐acquisition strategies (A‐strategies). This included enhanced bacterial chemotaxis, secretion systems, biotin metabolism and cell motility pathways, which in turn increased soil exoenzyme activity and accelerated soil nitrogen mineralization. Consequently, these species enhanced soil nitrogen availability and had substantial feedbacks on subsequent main crop productivity.Synthesis. This study demonstrates how plant economic strategies influence the balance between different microbial ecological strategies, specifically the trade‐offs in Y‐ and A‐strategies. These interactions exert control over carbon and nitrogen dynamics in the soil ecosystem. The findings provide insights for implementing nature‐based solutions to improve agroecosystem management practices. [ABSTRACT FROM AUTHOR]

Blood vessels play a crucial role in maintaining the stem cell niche in both tumours and developing organs. Cell competition is critical for tumour progression. We hypothesise that blood vessels may act as a regulator of this process. As a pioneer, the secretions of blood vessels regulate the intensity of cell competition, which is essential for tumour invasion and developmental organ extension. Brd4 expresses highly in endothelial cells within various tumours and is positively correlated with numerous invasive genes, making it an ideal focal point for further research on the relationship between blood vessels and cell competition. Our results indicated that the absence of endothelial Brd4 led to a reduction in neural stem cell mortality and compromised cell competition. Endothelial Brd4 regulated cell competition was dependent on Testican2. Testican2 was capable of depositing Sparc and acted as a suppressor of Sparc. Compromised cell competition resulted in the depletion of neural stem cells and accelerated brain ageing. Testican2 could rescue the run‐off of neural stem cells and accelerate the turnover rate of neurons. AD patients show compromised cell competition. Through the cloning of a point mutant of Brd4 identified in a subset of AD patients, it was demonstrated that the mutant lacked the ability to promote cell competition. This study suggests a novel approach for treating age‐related diseases by enhancing the intensity of cell competition. [ABSTRACT FROM AUTHOR]

External characteristics of the eggs and the ultrastructure of wax-secreting pores and sensory pits of all five nymphal stages and the adults of the planthopper Euricania clara Kato, 1932 are described and illustrated using both light and scanning electron microscopy (SEM). A key to five nymphal instars of Euricania clara is provided. The structure of stomata-like wax pores on different parts of the adult body and the distribution of nymphal sensory pits and wax plates are described and compared with 6 other species of Ricaniidae. This study shows that ultrastructural features on the egg surface vary among species of Ricaniidae. The patterns of wax-pore plates and pits on abdominal segment 6 can be used to distinguish two allied genera, Pochazia and Ricania. Wax-secreting plates on the ventral surface of the anal tube of the female adult can be used to distinguish the genus Euricania from Pochazia and Ricania. [ABSTRACT FROM AUTHOR]

Biostimulation aims to optimize reproductive parameters as part of animal management practices by modulating animal sensory systems. Chemical signals, mostly known as pheromones, have a great potential in this regard. This study was conducted to determine the influence of short-term male rabbit exposure to different biological secretions, potentially pheromone-mediated, on reproductive parameters of males. Four groups of 18 males each were exposed to A) doe urine, B) 2-phenoxyethanol, C) doe vaginal swab, and D) distilled water (control), three times over a 2.5h exposure window, just before semen collection. Semen volume, sperm concentration and motility, as well as subpopulation analysis of the spermatozoa were assessed for each condition. Additionally, testosterone levels in blood samples were monitored at five time points over the 2.5 h exposure window. We found a higher percentage of motile, progressive, fast progressive and mid-progressive spermatozoa in any of the three experimental groups compared to the control group. In contrast, the semen volume and the percentage of immotile and non-progressive spermatozoa was generally higher in the control group. We then identified a higher proportion of a subpopulation of fast and progressive spermatozoa in groups A, B, and C compared to group D. Our data indicates that sperm motility increases when animals are exposed to specific biological fluids potentially containing pheromones, and that an increase in sperm volume does not correlate with an increase in spermatozoa concentration, progressiveness, and speed. Finally, no differences in testosterone levels were found among comparisons, although males of groups A and C (exposed to natural female biological fluids) showed a tendency towards higher testosterone levels. In conclusion, our results indicate that rabbit sperm quality increases upon exposure to the biological secretions proposed, thereby supporting further investigation into their molecular identity. This exploration could eventually pave the way for implementing the use of pheromones in rabbit husbandry to enhance reproductive and productive parameters in farmed rabbits. • Buck semen quality increases upon exposure to specific female biological fluids. • Doe urine, vaginal fluid, and 2-phenoxyethanol are potential biostimulators. • Concentration and progressiveness of spermatozoa were enhanced in exposed rabbits. • Exposure to doe urine and vaginal fluid tended to increase testosterone levels. • Pheromone biostimulation is a natural method to improve animal production. [ABSTRACT FROM AUTHOR]

Experimental studies have shown that V-type ATPase-driven H+ secretion is dependent on transepithelial voltage. On this basis, the "voltage hypothesis" of urinary acidification by the collecting duct was derived. Accordingly, it has been supposed that the lumen-negative potential created by the reabsorption of Na+ via the epithelial Na+ channel (ENaC) enhances electrogenic H+ secretion via V-type H+-ATPase. This concept continues to be widely used to explain acid/base disorders. Importantly, however, a solid proof of principle for the voltage hypothesis in physiologically relevant situations has not been reached. Rather, it has been challenged by recent in vivo functional studies. In this review, we outline the arguments and experimental observations explaining why voltage-coupled H+ secretion in the collecting duct often appears poorly applicable for rationalizing changes in H+ secretion as a function of more or less ENaC function in the collecting duct. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii, the causative agent of toxoplasmosis, infects cells and replicates inside via the secretion of factors stored in specialized organelles (rhoptries, micronemes, and dense granules) and the capture of host materials. The genesis of the secretory organelles and the processes of secretion and endocytosis depend on vesicular trafficking events whose molecular bases remain poorly known. Notably, there is no characterization of the BAR (Bin/Amphiphysin/Rvs) domaincontaining proteins expressed by T. gondii and other apicomplexans, although such proteins are known to play critical roles in vesicular trafficking in other eukaryotes. Here, by combining structural analyses with in vitro assays and cellular observations, we have characterized TgREMIND (regulators of membrane interacting domains), involved in the genesis of rhoptries and dense granules, and TgBAR2 found at the parasite cortex. We establish that TgREMIND comprises an F-BAR domain that can bind curved neutral membranes with no strict phosphoinositide requirement and exert a membrane remodeling activity. Next, we establish that TgREMIND contains a new structural domain called REMIND, which negatively regulates the membranebinding capacities of the F-BAR domain. In parallel, we report that TgBAR2 contains a BAR domain with an extremely basic membrane-binding interface able to deform anionic membranes into very narrow tubules. Our data show that T. gondii codes for two atypical BAR domain-containing proteins with very contrasting membrane-binding properties, allowing them to function in two distinct regions of the parasite trafficking system. [ABSTRACT FROM AUTHOR]

Background: Skin is the largest organ in the human body. Some skin parameters like moisturization and sebum secretion play a vital role in the skin's functioning. This study aims to assess the effects of topical chemical peels of different concentrations and pH, applied manually and with ultrasounds, on the level of hydration, erythema, pigmentation, and sebum secretion of the skin. Methods: The study involved 90 Caucasian females, aged 25 to 59, with dry, dehydrated skin, skin with erythema or pigmentation disorders. The patients were randomly divided into three equal groups. The subjects from Group A were applied 10% mandelic acid with 25% gluconolactone of pH 4.0 manually. In Group B, 40% mandelic acid of pH 1.5 was used. The subjects from Group C were applied 10% mandelic acid with 25% gluconolactone of pH 4.0 via sonophoresis. A series of six procedures in weekly intervals was performed. Skin functional parameters (skin hydration, erythema, and melanin indicators) were taken before the first procedure, after 14 days, 28 days, and 42 days. Results: In Group A, the level of moisturization of the skin increased statistically significantly (p = 0.0100) however, the sebum secretion and erythema did not change. In Group B, the level of moisturization improved statistically significantly, as well as erythema (p = 0.0001). Sebum secretion in the final measurement increased. The moisturization and erythema in Group C did not differ statistically significantly. On the other hand, the sebum secretion increased significantly. Conclusions: Very superficial chemical peels significantly alter selected skin parameters. AHAs and PHAs applied using the ultrasound method do not affect the level of hydration, erythema, or pigmentation of the skin. [ABSTRACT FROM AUTHOR]