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Lysinuric protein intolerance (LPI) is a rare autosomal disease caused by defective cationic amino acid (CAA) transport due to mutations in SLC7A7 , which encodes for the y + LAT1 transporter. LPI patients suffer from a wide variety of symptoms, which range from failure to thrive, hyperammonemia, and nephropathy to pulmonar alveolar proteinosis (PAP), a potentially life-threatening complication. Hyperammonemia is currently prevented by citrulline supplementation. However, the full impact of this treatment is not completely understood. In contrast, there is no defined therapy for the multiple reported complications of LPI, including PAP, for which bronchoalveolar lavages do not prevent progression of the disease. The lack of a viable LPI model prompted us to generate a tamoxifen-inducible Slc7a7 knockout mouse ( Slc7a7 -/- ). The Slc7a7 -/- model resembles the human LPI phenotype, including malabsorption and impaired reabsorption of CAA, hypoargininemia and hyperammonemia. Interestingly, the Slc7a7 -/- mice also develops PAP and neurological impairment. We observed that citrulline treatment improves the metabolic derangement and survival. On the basis of our findings, the Slc7a7 -/- model emerges as a promising tool to further study the complexity of LPI, including its immune-like complications, and to design evidence-based therapies to halt its progression., Competing Interests: The authors declare no conflict of interests.

Macrophages exert potent effector functions against invading microorganisms but constitute, paradoxically, a preferential niche for many bacterial strains to replicate. Using a model of infection by Salmonella Typhimurium, we have identified a molecular mechanism regulated by the nuclear receptor LXR that limits infection of host macrophages through transcriptional activation of the multifunctional enzyme CD38. LXR agonists reduced the intracellular levels of NAD + in a CD38-dependent manner, counteracting pathogen-induced changes in macrophage morphology and the distribution of the F-actin cytoskeleton and reducing the capability of non-opsonized Salmonella to infect macrophages. Remarkably, pharmacological treatment with an LXR agonist ameliorated clinical signs associated with Salmonella infection in vivo, and these effects were dependent on CD38 expression in bone-marrow-derived cells. Altogether, this work reveals an unappreciated role for CD38 in bacterial-host cell interaction that can be pharmacologically exploited by activation of the LXR pathway., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

While Cystic Fibrosis is characterized by a high phenotypic variability, a correlation is reported between the pancreatic status and the CFTR genotype. Here we report an unusual case of a child with Cystic Fibrosis (F508del-duplication of exons 1–3 genotype) diagnosed at 8 years old for pancreatic insufficiency and non-pathological sweat test, in absence of respiratory symptoms and acute episodes of pancreatitis. Nasal potential differences and intestinal current measurements were normal, while the short-circuit current measured on patient-derived colonoids grown on Transwell® indicated the presence of a reduced CFTR-dependent current relative to non-CF colonoids with, a modest improvement of CFTR activity record following treatment with elexacaftor/tezacaftor/ivacaftor. This case opens the discussion on the importance of performing CFTR sequencing and the search for large gene rearrangements in cases of pancreatic insufficiency of unclear etiology, also in the presence of non-pathological sweat test. Children with CF and non-pathological sweat chloride are likely to develop higher concentrations if they truly have CF. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs)‐based intercellular communication (through exosomes, microvesicles, and apoptotic bodies) is conserved across all kingdoms of life. In recent years, exosomes have gained much attention for targeted pharmaceutical administration due to their unique features, nanoscale size, and capacity to significantly contribute to cellular communication. As drug delivery vehicles, exosomes have several advantages over alternative nanoparticulate drug delivery technologies. A key advantage lies in their comparable makeup to the body's cells, which makes them non‐immunogenic. However, exosomes vesicles face several challenges, including a lack of an effective and standard production technique, decreased drug loading capacity, limited characterization techniques, and underdeveloped isolation and purification procedures. Exosomes are well known for their long‐term safety and natural ability to transport intercellular nucleic acids and medicinal compounds across the blood‐brain‐barrier (BBB). Therefore, in addition to revealing new insights into exosomes' distinctiveness, the growing availability of new analytical tools may drive the development of next‐generation synthetic systems. Herein, light is shed on exosomes as drug delivery vehicles in anti‐infective therapy by reviewing the literature on primary articles published between 2002 and 2023. Additionally, the benefits and limitations of employing exosomes as vehicles for therapeutic drug delivery are also discussed. [ABSTRACT FROM AUTHOR]

We describe five cases of posttraumatic anterior acute myocardial infarction in young patients, without previous heart disease. One case was treated with intracoronary thrombolysis and angioplasty, 3 cases received systemic thrombolysis, and the last one did not have any re-permeabilization therapy, having arrived to the hospital 72 hours after the episode. The coronary angiograms showed at the left anterior descending artery: thrombosis in 3 cases, coronary dissection in one case, and slow flow with no morphological lesions in the other. The case which not received thrombolytic therapy developed a severe left ventricular dysfunction. In conclusion we emphasize an early angiographic study, in order to decide the re-permeabilization therapy.

Copyright of Industrial Minerals & Processing / Huagong Kuangwu yu Jiagong is the property of Industrial Minerals & Processing Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: Automatic detection of births allows timely assistance, protecting offspring and mothers, without requiring continuous human surveillance. A mechanism based on Machine Learning was developed using wearable inertial sensors, enabled with real-time communication. This mechanism runs on a minicomputer housed in livestock facilities and uses inertial data classification to detect and notify the human operator of goat kidding events. Preliminary results demonstrate behavior changes four hours before kidding and allow for the identification of the kidding hour with an accuracy of 61%. The autonomous identification of animal births has a significant added value, since it enables for a prompt timely human intervention in the process, protecting the young and the mothers' health, without requiring continuous human surveillance. Wearable inertial sensors have been employed for a variety of animal monitoring applications, thanks to their low cost and the fact that they allow less invasive monitoring process. Alarms triggered by the occurrence of events must be generated close to the events to avoid delays caused by communication latency, which is why this type of mechanism is typically implemented at the network's edge and integrated with existing auxiliary mechanisms on the Internet. Although the detection of births in cattle has been carried out commercially for some years, there is no solution for small ruminants, especially goats, where the literature does not even report any attempts. The current work consisted of a first attempt at developing an automatic birth monitor using inertial sensing, as well as detection techniques based on Machine Learning, implemented in a network edge device to assure real-time alarm triggering. Thus, two concept drift detection techniques and seven kidding detection mechanisms were developed using data classification models. The work also includes the testing and comparison of learning results, both in terms of accuracy and of computational costs of the detection module, for algorithms implemented. The results revealed that, despite their simplicity, concept drift algorithms do not allow kidding detection, whereas classification-algorithm-based static learning models do, despite the unbalanced character of the dataset and its reduced size. The learning findings are quite promising in terms of computational cost and its suitability for deployment on edge devices. The algorithm demonstrates behavior changes four hours before kidding and allows for the identification of the kidding hour with an accuracy of 61%, as well as the capacity to improve the overall learning process with a larger dataset. [ABSTRACT FROM AUTHOR]

This study aimed to assess the main clinical and anamnestic characteristics of adult Cystic Fibrosis (CF) patients and to evaluate the association of frailty with the CF genotyping classification. In an observational cross-sectional study, all ambulatory CF patients over 18 years old who received a diagnosis at the Regional Cystic Fibrosis Center for adults were enrolled and assessed by spirometry for respiratory function, by ADL and IADL for functional status, and by the Study of Osteoporotic Fractures (SOF) Index for frailty. The study population consisted of 139 CF patients (mean age 32.89 ± 10.94 years old, 46% women). Most of the subjects were robust (60.4%). The pre-frail/frail group was more frequently females (p = 0.020), had a lower BMI (p = 0.001), worse respiratory function, a higher number of pulmonary exacerbations/years, cycles of antibiotic therapy, and hospitalization (all p < 0.001) with respect to robust patients. The pre-frail/frail subjects used more drugs and were affected by more CF-related diseases (all p < 0.001). In relation to logistic regression, the best predictor of the pre-frail/frail status was a low FEV1 level. The CF patients show similarities to older pre-frail/frail subjects, suggesting that CF might be considered an early expression of this geriatric syndrome. This finding could help to better define the possible progression of CF, but overall, it could also suggest the usefulness employing of some tools used in the management and therapy of frailty subjects to identify the more severe CF subjects. [ABSTRACT FROM AUTHOR]

The flotation mechanism of galena with xanthate as the collector is generally explained based on the mixed potential of the pulp, in which an anodic electron transfer reaction from the collector to the mineral is combined with an O2 cathodic reduction. Sodium sulphide, often used as a mineral activator, strongly influences the pulp’s mixed potential, and depending on the dosage applied, it can become a galena depressor reagent. In this way, the current study assesses galena flotability in the absence of collector, as well as in the presence of the collector potassium amyl xanthate (PAX) and sodium sulphide. The effect of an extremely cathodic potential was also studied through the addition of hydrogen peroxide. In addition, the effect of different stages in the oxidation of the galena surface on the flotability was investigated. Moreover, the zeta potential was measured and contact angle (wettability) tests were carried out. The contact angle measurements were taken for a distilled water, PAX solution and for a mixture of PAX and sodium sulphide solution on the oxidized and non-oxidized surface of galena. All the results showed that galena could be floated in all the PAX concentrations tested. It was observed that a moderate oxidation in the galena surface may contribute to an improvement of its flotation with PAX. However, extremely anodic and cathodic potentials cause flotability close to zero. The zeta potential results showed that sodium sulphide affected the interaction between PAX and galena. The measurements of the contact angle corroborated the results obtained in the microflotation tests. [ABSTRACT FROM AUTHOR]

The geroscience hypothesis proposes that addressing the biology of aging could directly prevent the onset or mitigate the severity of multiple chronic diseases. Understanding the interplay between key aspects of the biological hallmarks of aging is essential in delivering the promises of the geroscience hypothesis. Notably, the nucleotide nicotinamide adenine dinucleotide (NAD) interfaces with several biological hallmarks of aging, including cellular senescence, and changes in NAD metabolism have been shown to be involved in the aging process. The relationship between NAD metabolism and cellular senescence appears to be complex. On the one hand, the accumulation of DNA damage and mitochondrial dysfunction induced by low NAD+ can promote the development of senescence. On the other hand, the low NAD+ state that occurs during aging may inhibit SASP development as this secretory phenotype and the development of cellular senescence are both highly metabolically demanding. However, to date, the impact of NAD+ metabolism on the progression of the cellular senescence phenotype has not been fully characterized. Therefore, to explore the implications of NAD metabolism and NAD replacement therapies, it is essential to consider their interactions with other hallmarks of aging, including cellular senescence. We propose that a comprehensive understanding of the interplay between NAD boosting strategies and senolytic agents is necessary to advance the field. [ABSTRACT FROM AUTHOR]

In sheep and goats, the onset of maternal behavior at parturition is characterized by a first phase called maternal responsiveness during which the mother is attracted to any newborn. In a second phase, called maternal selectivity, the mother establishes a selective bond with her young so that she only accepts it at suckling. After a description of the behavioral expression of both phases, this chapter reviews the physiological, sensory, and neural mechanisms involved. These two behavioral processes are synchronized with parturition by the vaginocervical stimulation induced by the expulsion of the newborn. Olfactory cues provided by the neonate are involved in maternal responsiveness and selectivity. Oxytocin supported by estrogens is the key factor for maternal responsiveness. The neural network involved in maternal responsiveness is mainly hypothalamic and is different from the circuitry involved in selectivity, which mainly concerns olfactory processing regions. Visual and auditory cues are necessary for offspring recognition at a distance. This multisensory recognition suggests that mothers form a mental image of their young. Maternal experience renders mothers more responsive to maternally relevant physiology and to young-related sensory inputs., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Flotation reagents are significant for modifying the interfacial characteristics of mineral grains to achieve the effective separation of minerals. Since the 1960s, when quantum chemistry was first introduced into the study of flotation reagents, many achievements have been made, although some controversial topics remain. The application of quantum chemistry in the research of flotation reagents for the separation of various minerals in the past decade is herein comprehensively and systematically reviewed. The main directions and gaps of current research are pointed out, the theoretical basis for the design and development of novel flotation reagents is summarized, and more importantly, the potential for the targeting design and development of efficient, selective, and environmentally friendly flotation reagent molecules by means of quantum chemistry is explored. [ABSTRACT FROM AUTHOR]

Amino acids derived from protein digestion are important nutrients for the growth and maintenance of organisms. Approximately half of the 20 proteinogenic amino acids can be synthesized by mammalian organisms, while the other half are essential and must be acquired from the nutrition. Absorption of amino acids is mediated by a set of amino acid transporters together with transport of di- and tripeptides. They provide amino acids for systemic needs and for enterocyte metabolism. Absorption is largely complete at the end of the small intestine. The large intestine mediates the uptake of amino acids derived from bacterial metabolism and endogenous sources. Lack of amino acid transporters and peptide transporter delays the absorption of amino acids and changes sensing and usage of amino acids by the intestine. This can affect metabolic health through amino acid restriction, sensing of amino acids, and production of antimicrobial peptides. [ABSTRACT FROM AUTHOR]

Niobium (Nb) and Tantalum (Ta) are used to increase materials' mechanical resistance and produce lighter alloys. Worldwide Nb production reached 78 000 t in 2020. The reduced ore offer justifies the recycling of these metals from tin slag, contributing to the circular economy. Nb2O5 and Ta2O5 extraction either from the primary source or the tin slag is an industrial challenge. Nb and Ta dissolution processes already implemented are fluoride leaching, sulphuric leaching, alkaline leaching, and alkaline roasting. The fluoride process raises environmental concerns about waste control. The sulphuric method can be managed to have higher Nb and Ta extraction in a less aggressive process, if some changes are implemented, such as increasing the number of extraction steps, decreasing the pulp density, or increasing the temperature; however, the efficiency of this methodology must be tested for tin slag. The alkaline method seems to be more selective to Nb and Ta by reactants and temperature control. Despite those well‐established Nb and Ta treatments, they must be adapted to recover Nb and Ta from slag. The slag has low Nb and Ta content, while high Si and Ca concentrations exist in the matrix. This paper brings the main methods used to extract the Nb and Ta from the primary resources and an overview of Nb and Ta recovery from the slag. This investigation comes as a tool to guide the development of new methods to recover Nb and Ta from low‐grade sources such as tin slag. [ABSTRACT FROM AUTHOR]

Cerussite is a lead oxide mineral resource that is typically enriched through sulfidization flotation. The surface sulfidation degree and the high solubility of cerussite strongly affect the flotation ability of cerussite. In the current work, lead ions were used to pretreat cerussite to intensify its sulfidization flotation. The sulfidization mechanism regulating the lead ions pretreatment on cerussite was investigated by the micro-flotation test, ToF-SIMS, zeta potential measurement, adsorption test, and XPS. The results from the micro-flotation test demonstrated that the floatability of cerussite could be improved by adding an appropriate amount of lead ions. Compared with the treatment involving only Na2S, the maximum recovery increased by 17.57%. Adsorption experiments showed that lead modification improved the stability of xanthate products on the surface of cerussite. According to the measurement of zeta potential and the results of ToF-SIMS, the addition of lead ion Pb pretreatment increased the number of active Pb sites adsorbed by xanthate, thereby improving the formation of hydrophobic Pb-dilute precipitate. Therefore, the interaction between lead ions and the surface of cerussite enhances the strength and stability of the hydrophobic layer, resulting in enhanced hydrophobicity of cerussite. [ABSTRACT FROM AUTHOR]

A coagulation treatment is a separation technology widely used in industries as a pre-treatment step to remove the dissolved organic matter in wastewater. However, the type of coagulant, the optimized dose, and the treatment cost associated with various commercially employed coagulants must be investigated for the treatment of oil and gas produced water. In this study, five widely employed coagulants—ferric chloride, aluminum potassium sulphate, chitosan, sodium sulfide, and magnesium oxide—were tested for the treatment of actual complex oilfield-generated produced water. Water quality parameters such as the total suspended solids (TSS), total dissolved solids (TDS), turbidity, salinity, and pH were assessed for a better understanding of different coagulant activities against the produced water treatment. All the coagulants were efficient for the treatment of produced water. The findings of this study showed that ferric chloride led to the best removal of total solids (74.25%) of all water quality parameters, with treatment costs of USD 4 per m−3 of produced water. The results from this study contribute to the environmentally friendly, broader, and cost-effective application of a coagulation treatment to produced water. [ABSTRACT FROM AUTHOR]

Copyright of Abanico Veterinario is the property of Sistema Superior Editorial and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study aims to investigate the effects of pH and chemical reagents to model and optimize the flotation process of a complex lead ore containing 2.44 wt% Pb. For this purpose, the effects of pulp pH, collectors (PAX and R404), depressant (FeSo4), and activator (Na2S) concentrations were studied using response surface methodology. Furthermore, the influence of these parameters was studied on flotation kinetics parameters. The optimization studies indicated that the desired Pb recovery (84.1%) and grade (26.6%) was obtained from the test, which was performed with the optimum flotation conditions: 75 g/t PAX, 80 g/t FeSo4, 735 g/t Na2S, 20 g/t R404 and pH 9.5. The results of statistical analyses showed that the pulp pH, PAX concentration, and interactions between pH-R404 concentration and PAX concentration-R404 concentration were the most influential parameters on concentrate grade and recovery. From the kinetic studies, it was observed that the flotation rate coefficient and ultimate recovery were strongly dependent on the pulp pH. The flotation rate coefficient increased with enhancing the pH from 8 to 9.5 and after that reduced with increasing the pH to 11. [ABSTRACT FROM AUTHOR]

Animal activity during the night period is of enormous importance, since it represents approximately half of animals' lives, and monitoring it during this period makes it possible to detect problems related to well-being and safety, and allows us to infer energy expenditure on the basis of their activity level. The present study analyzes a sheep activity dataset created during the night period to validate non-invasive techniques of monitoring that can be used to infer energy expenditure at night and to detect abnormal nocturnal activity. The study allowed us to detect cyclic changes in activity during the night period, which is composed of inactive and active periods, and to identify sheep lying positions. The analysis of the joint activity of the flock allowed us to perceive a time lag in the rest cycles, which consisted of periods of activity of ewes undone between elements of the flock. Although it does not allow us to identify the components of the period of inactivity, since the method used does not monitor brain activity, the results allow us to confirm the cyclical character of the nocturnal activity of sheep that has been reported in the literature, as well as their typical posture when lying down. Although this is an exploratory application with a very small number of animals, the similarity between the results obtained and the results documented in the existing literature, which have mostly been obtained using invasive methods, is encouraging, and suggests it is possible to rely on activity monitoring processes based on inertial sensors. [ABSTRACT FROM AUTHOR]

Ca2+ and Mg2+ are the most dominating unavoidable ions in the smithsonite flotation. In this paper, the effect of Ca2+ (Mg2+) on the surface of smithsonite sulfidization in a system where water molecules are present was investigated using density functional based tight binding (DFTB+) simulations for the first time. The results indicated that the adsorption of hydrated Ca2+ complexes is stronger than that of hydrated Mg2+ complexes on the hydrated smithsonite (101) surface. In addition, at low concentrations of sodium sulfide, there is no adsorption of HS- on the surface pre-adsorbed with hydrated Ca2+ complexes, but only on the surface pre-adsorbed with hydrated Mg2+ complexes. At high concentrations of Na2S, S2- weakens the adsorption of hydrated Ca2+ complexes due to competitive adsorption, but the presence of S2- could desorb hydrated Mg2+ complexes from the surface. The results compared the differences in effects of Ca2+ and Mg2+ on smithsonite sulfidization, which could provide an atomic scale basis for researching the surface sulfidization of oxide minerals. [ABSTRACT FROM AUTHOR]

BACKGROUND: The extensive consumption of eggs and their utilization as an ingredient in food products globally offer excellent potential for increasing dietary omega‐3 polyunsaturated fatty acid (PUFA) intake. Thus far, research involving dietary focused on changes in their physical properties after boiling, protein denaturation, storage stability, and other characteristics. However, minimal reports are available regarding the evaluation of nutritional changes. Therefore, this study comprehensively investigated the impact of cooking on the nutritional quality and volatile compound profile of ordinary and omega‐3 eggs. RESULTS: Compared with ordinary eggs, those enriched with omega‐3 fatty acids contained higher proportions of total omega‐3 PUFAs and α‐tocopherol. However, no significant difference was evident between the amino acid compositions of the two types of eggs. Omega‐3 eggs boiled for 20 min at 75 °C showed higher levels of omega‐3 PUFAs, total tocopherol, and essential amino acids while increasing the heating time and temperature reduced these nutrients. Heat treatment significantly decreased the ketones and alcohol content while increasing the hydrocarbons level. The overall variations in the metabolic response due to cooking temperature were evidenced by the multiple metabolic associations and clustering on the principal component analysis (PCA) plane and heat map. CONCLUSION: The findings provided useful information for ensuring quality retention in eggs, especially those enriched with omega‐3. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Our previous findings have shown that the chlorophyllides composites have anticancer activities to breast cancer cell lines (MCF-7 and MDA-MB-231). In the present study, microarray gene expression profiling was utilized to investigate the chlorophyllides anticancer mechanism on the breast cancer cells lines. Results showed that chlorophyllides composites induced upregulation of 43 and 56 differentially expressed genes (DEG) in MCF-7 and MDA-MB-231 cells, respectively. In both cell lines, chlorophyllides composites modulated the expression of annexin A4 (ANXA4), chemokine C-C motif receptor 1 (CCR1), stromal interaction molecule 2 (STIM2), ethanolamine kinase 1 (ETNK1) and member of RAS oncogene family (RAP2B). Further, the KEGG annotation revealed that chlorophyllides composites modulated DEGs that are associated with the endocrine system in MCF-7 cells and with the nervous system in MDA-MB-231 cells, respectively. The expression levels of 9 genes were validated by quantitative reverse transcription PCR (RT-qPCR). The expression of CCR1, STIM2, ETNK1, MAGl1 and TOP2A were upregulated in both chlorophyllides composites treated-MCF-7 and MDA-MB-231 cells. The different expression of NLRC5, SLC7A7 and PKN1 provided valuable information for future investigation and development of novel cancer therapy. [ABSTRACT FROM AUTHOR]

A variety of morphologies of ZnO elongated nano‐ and microstructures doped with Li and Tb are obtained by a vapor–solid method. The amount of Tb incorporated depends on the morphology which is controlled by the amount of Li in the initial mixture and the growth conditions. X‐ray diffraction and Raman experiments show the good crystalline quality of the samples. A small quantity of Tb3+ ions seems to be present in the structures, as both cathodoluminescence and photoluminescence suggest. The intensity of the ZnO and Tb3+ intrashell emission bands is strongly influenced by the amount of Li due to the different positions that it can occupy in the ZnO lattice. This fact leads to variations in the defect structure that change the concentration of native defects and the rare earth surroundings. The elongated structures also show waveguiding behavior and Fabry–Perot optical resonant modes with good quality factor. [ABSTRACT FROM AUTHOR]

Purpose: Congenital bilateral absence of the vas deferens (CBAVD) is a major cause of obstructive azoospermia and male factor infertility. CBAVD is mainly caused by mutations in the genes encoding CFTR (cystic fibrosis transmembrane conductance regulator) and ADGRG2 (adhesion G protein-coupled receptor G2). This study aimed to describe CFTR and ADGRG2 variations in 46 Chinese CBAVD patients and evaluated sperm retrieval and assisted reproductive technology outcomes. Methods: The CFTR and ADGRG2 genes were sequenced and analyzed by whole-exome sequencing (WES), and variations were identified by Sanger sequencing. Bioinformatic analysis was performed. We retrospectively reviewed the outcomes of patients undergoing sperm retrieval surgery and intracytoplasmic sperm injection (ICSI). Results: In total, 35 of 46 (76.09%) patients carried at least one variation in CFTR, but no copy number variants or ADGRG2 variations were found. In addition to the IVS9-5 T allele, there were 27 CFTR variations, of which 4 variations were novel and predicted to be damaging by bioinformatics. Spermatozoa were successfully retrachieved in 46 patients, and 39 of the patients had their own offspring through ICSI. Conclusion: There are no obvious hotspot CFTR mutations in Chinese CBAVD patients besides the IVS9-5 T allele. Therefore, WES might be the best detection method, and genetic counseling should be different from that provided to Caucasian populations. After proper counseling, all patients can undergo sperm retrieval from their epididymis or testis, and most of them can have their own children through ICSI. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide (NAD) acts as a cofactor in several oxidation-reduction (redox) reactions and is a substrate for a number of nonredox enzymes. NAD is fundamental to a variety of cellular processes including energy metabolism, cell signaling, and epigenetics. NAD homeostasis appears to be of paramount importance to health span and longevity, and its dysregulation is associated with multiple diseases. NAD metabolism is dynamic and maintained by synthesis and degradation. The enzyme CD38, one of the main NAD-consuming enzymes, is a key component of NAD homeostasis. The majority of CD38 is localized in the plasma membrane with its catalytic domain facing the extracellular environment, likely for the purpose of controlling systemic levels of NAD. Several cell types express CD38, but its expression predominates on endothelial cells and immune cells capable of infiltrating organs and tissues. Here we review potential roles of CD38 in health and disease and postulate ways in which CD38 dysregulation causes changes in NAD homeostasis and contributes to the pathophysiology of multiple conditions. Indeed, in animal models the development of infectious diseases, autoimmune disorders, fibrosis, metabolic diseases, and age-associated diseases including cancer, heart disease, and neurodegeneration are associated with altered CD38 enzymatic activity. Many of these conditions are modified in CD38-deficient mice or by blocking CD38 NADase activity. In diseases in which CD38 appears to play a role, CD38-dependent NAD decline is often a common denominator of pathophysiology. Thus, understanding dysregulation of NAD homeostasis by CD38 may open new avenues for the treatment of human diseases. [ABSTRACT FROM AUTHOR]

In humans, more than 50 transporters are responsible for the traffic and balance of amino acids within and between cells and tissues, and half of them have been associated with disease [1]. Covering all common amino acids, Heteromeric Amino acid Transporters (HATs) are one class of such transporters. This review first highlights structural and functional studies that solved the atomic structure of HATs and revealed molecular clues on substrate interaction. Moreover, this review focuses on HATs that have a role in the central nervous system (CNS) and that are related to neurological diseases, including: (i) LAT1/CD98hc and its role in the uptake of branched chain amino acids trough the blood brain barrier and autism. (ii) LAT2/CD98hc and its potential role in the transport of glutamine between plasma and cerebrospinal fluid. (iii) y+LAT2/CD98hc that is emerging as a key player in hepatic encephalopathy. xCT/CD98hc as a potential therapeutic target in glioblastoma, and (iv) Asc-1/CD98hc as a potential therapeutic target in pathologies with alterations in NMDA glutamate receptors. [ABSTRACT FROM AUTHOR]

In the CNS, amino acid (AA) neurotransmitters and neurotransmitter precursors are subject to tight homeostatic control mediated by blood-brain barrier (BBB) solute carrier amino acid transporters (AATs). Since the BBB is composed of multiple closely apposed cell types and opportunities for human in vivo studies are limited, we used in vitro and computational approaches to investigate human BBB AAT activity and regulation. Quantitative real-time PCR (qPCR) of the human BBB endothelial cell model hCMEC/D3 (D3) was used to determine expression of selected AAT, tight junction (TJ), and signal transduction (ST) genes under various culture conditions. L-leucine uptake data were interrogated with a computational model developed by our group for calculating AAT activity in complex cell cultures. This approach is potentially applicable to in vitro cell culture drug studies where multiple "receptors" may mediate observed responses. Of 7 Leu AAT genes expressed by D3 only the activity of SLC7A5-SLC3A2/LAT1-4F2HC (LAT1), SLC43A2/LAT4 (LAT4) and sodium-dependent AATs, SLC6A15/B0AT2 (B0AT2), and SLC7A7/y+LAT1 (y+LAT1) were calculated to be required for Leu uptake. Therefore, D3 Leu transport may be mediated by a potentially physiologically relevant functional cooperation between the known BBB AAT, LAT1 and obligatory exchange (y+LAT1), facilitative diffusion (LAT4), and sodium symporter (B0AT2) transporters. [ABSTRACT FROM AUTHOR]