Primary Dysfunction Research Articles

Ciliary signaling proteins are mislocalized in the brains of Bardet-Biedl syndrome 1-null mice.

In the brain, primary cilia are found on most, if not all, central neurons. The importance of neuronal cilia is underscored by the fact that human diseases caused by primary cilia dysfunction, which are known as ciliopathies, are associated with neuropathologies, including neuropsychiatric disorders and learning and memory deficits. Neuronal cilia are enriched for certain G protein-coupled receptors and their downstream effectors, suggesting they sense and respond to neuromodulators in the extracellular milieu. GPCR ciliary localization is disrupted in neurons from mouse models of the ciliopathy Bardet-Biedl syndrome, with GPCRs failing to localize to cilia, indicating the Bardet-Biedl syndrome proteins are required for trafficking of G protein-coupled receptors into neuronal cilia. Yet, dopamine receptor 1 accumulates in cilia in the absence of Bardet-Biedl syndrome proteins, suggesting Bardet-Biedl syndrome proteins are required for normal ciliary import and export. To further explore the roles of the Bardet-Biedl syndrome proteins in neuronal cilia, we examined localization of ciliary signaling proteins in a new constitutive Bbs1 knockout mouse model. Interestingly, we find that two additional ciliary G protein-coupled receptors (Gpr161 and Gpr19) abnormally accumulate in cilia on Bardet-Biedl syndrome neurons. In addition, we find that the GPCR signaling protein β-arrestin accumulates in a subset of cilia in the brain, suggesting the presence of additional unidentified ciliary G protein-coupled receptors. These results confirm the importance of the Bardet-Biedl syndrome proteins in establishing ciliary GPCR pathways and indicate that loss of Bbs1 leads to complex changes in the localization of signaling proteins in the brain.

Red Blood Cells: A Newly Described Partner in Central Retinal Vein Occlusion Pathophysiology?

Central retinal vein occlusion (CRVO) is a frequent retinal disorder inducing blindness due to the occlusion of the central vein of the retina. The primary cause of the occlusion remains to be identified leading to the lack of treatment. To date, current treatments mainly target the complications of the disease and do not target the primary dysfunctions. CRVO pathophysiology seems to be a multifactorial disorder; several studies did attempt to decipher the cellular and molecular mechanisms underlying the vessel obstruction, but no consensual mechanism has been found. The aim of the current review is to give an overview of CRVO pathophysiology and more precisely the role of the erythroid lineage. The review presents emerging data on red blood cell (RBC) functions besides their role as an oxygen transporter and how disturbance of RBC function could impact the whole vascular system. We also aim to gather new evidence of RBC involvement in CRVO occurrence.

IL-4Rα signalling in B cells and T cells play differential roles in acute and chronic atopic dermatitis

Atopic dermatitis (AD) is a common pruritic inflammatory skin disease with complex environmental and genetic predisposing factors. Primary skin barrier dysfunction and aberrant T helper 2 (TH2) responses to common allergens, together with increased serum IgE antibodies, characterise the disease. B and T cells are essential in the disease manifestation, however, the exact mechanism of how these cells is involved is unclear. Targeting interleukin 4 receptor alpha (IL-4Rα), an IL-4/IL-13 signalling axis, with dupilumab shows efficacy in AD. We investigated the importance of IL-4Rα signalling specifically on B and T cells during acute and chronic models of AD. We used House dust mite (HDM) and Ovalbumin (OVA) in chronic models and a low-calcemic analog of vitamin D (MC903) for acute models of AD. We used mb1creIL-4Rα−/lox, iLCKcreIL-4Rα−/lox, LCKcreIL-4Rα−/lox, CD4creIL-4Rα−/lox, Foxp3creIL-4Rα−/lox and IL-4Rα−/lox littermate controls. IL-4Rα-responsive B cells were essential in serum IgE levels, but not in epidermal thickening in both chronic and acute models. IL-4Rα-responsive T cells were essential in epidermal thickening in the pan-T cell, but not CD4 or CD8 T cells suggesting the importance of γδT cells during acute AD. Our results suggest that IL-4Rα responsiveness on innate T cells regulates acute atopic dermatitis, while on B cells it regulates IgE.

Functions of the primary cilium in the kidney and its connection with renal diseases.

The nonmotile primary cilium is a sensory structure found on most mammalian cell types that integrates multiple signaling pathways involved in tissue development and postnatal function. As such, mutations disrupting cilia activities cause a group of disorders referred to as ciliopathies. These disorders exhibit a wide spectrum of phenotypes impacting nearly every tissue. In the kidney, primary cilia dysfunction caused by mutations in polycystin 1 (Pkd1), polycystin 2 (Pkd2), or polycystic kidney and hepatic disease 1 (Pkhd1), result in polycystic kidney disease (PKD), a progressive disorder causing renal functional decline and end-stage renal disease. PKD affects nearly 1 in 1000 individuals and as there is no cure for PKD, patients frequently require dialysis or renal transplantation. Pkd1, Pkd2, and Pkhd1 encode membrane proteins that all localize in the cilium. Pkd1 and Pkd2 function as a nonselective cation channel complex while Pkhd1 protein function remains uncertain. Data indicate that the cilium may act as a mechanosensor to detect fluid movement through renal tubules. Other functions proposed for the cilium and PKD proteins in cyst development involve regulation of cell cycle and oriented division, regulation of renal inflammation and repair processes, maintenance of epithelial cell differentiation, and regulation of mitochondrial structure and metabolism. However, how loss of cilia or cilia function leads to cyst development remains elusive. Studies directed at understanding the roles of Pkd1, Pkd2, and Pkhd1 in the cilium and other locations within the cell will be important for developing therapeutic strategies to slow cyst progression.

Study of aged central auditory function using the auditory middle latency response

ObjectiveInvestigate the auditory function of the elderly using the middle latency potentials. MethodologyGroup 1 (G1): 20 healthy individuals of both genders, older than 60 years, without hearing loss. Group 2 (G2): 20 healthy individuals of both sexes, older than 60 years, with hearing loss in frequencies from 4 to 8 kHz. Potential recording was performed with unilateral and bilateral stimulation and the Binaural Interaction Component was calculated. ResultsNa latency in C3A1 was greater in the stimulation of the right ear in G2 and the amplitude of Na-Pa was greater in the stimulation of the right ear and recording in C3A1 in G1. The latency of the Pa component was higher in the stimulation of the right ear recorded in C4A2. The Pb component in G2 by bilateral stimulation and recorded in C4A2 had higher latency. The first and second negative and positive peaks presented greater amplitude in G1. In C3A1, the 1st negative peak was more negative in G1 and the 2nd positive peak showed greater amplitude in C4A2 in both groups. ConclusionThe transmission of auditory information to the primary auditory cortex is impaired with aging, especially in unilateral stimulation, reinforced by losses in elderly people with peripheral hearing loss, such as in the binaural interaction at the cortical and subcortical levels. Thus, the AMLR has shown to be a sensitive examination to investigate neuroauditory disorders in the elderly, especially related to high-frequency hearing loss and primary auditory cortex dysfunctions caused by the aging process.

A human initial lymphatic chip reveals distinct mechanisms of primary lymphatic valve dysfunction in acute and chronic inflammation.

Interstitial fluid uptake and retention by lymphatic vessels (LVs) play a role in maintaining interstitial fluid homeostasis. While it is well-established that intraluminal lymphatic valves in the collecting LVs prevent fluid backflow (secondary lymphatic valves), a separate valve system in the initial LVs that only permits interstitial fluid influx into the LVs, preventing fluid leakage back to the interstitium (primary lymphatic valves), remains incompletely understood. Although lymphatic dysfunction is commonly observed in inflammation and autoimmune diseases, how the primary lymphatic valves are affected by acute and chronic inflammation has scarcely been explored and even less so using in vitro lymphatic models. Here, we developed a human initial lymphatic vessel chip where interstitial fluid pressure and luminal fluid pressure are controlled to examine primary lymph valve function. In normal conditions, lymphatic drainage (fluid uptake) and permeability (fluid leakage) in engineered LVs were maintained high and low, respectively, which was consistent with our understanding of healthy primary lymph valves. Next, we examined the effects of acute and chronic inflammation. Under the acute inflammation condition with a TNF-α treatment (2 hours), degradation of fibrillin and impeded lymphatic drainage were observed, which were reversed by treatment with anti-inflammatory dexamethasone. Surprisingly, the chronic inflammation condition (repeated TNF-α treatments during 48 hours) deposited fibrillin to compensate for the fibrillin loss, showing no change in lymphatic drainage. Instead, the chronic inflammation condition led to cell death and disruption of lymphatic endothelial cell-cell junctions, increasing lymphatic permeability and fluid leakage. Our human lymphatic model shows two distinct mechanisms by which primary lymphatic valve dysfunction occurs in acute and chronic inflammation.

Novel Therapeutic strategies in the Management of Cardiomyopathies.

Cardiomyopathies are a heterogeneous group of disorders that consist of primary dysfunction in cardiac contractility, myocardial relaxation, restrictive ventricular filling, and cardiac rhythm anomalies. This review discusses a limited number of cardiomyopathic disorders and the treatment modalities used to manage them. Studies in elucidating pathophysiological mechanisms that underlie the development of these cardiomyopathies are leading to the development of novel therapeutic strategies. While some modalities have found expression in current practice recommendation guidelines, others are on the horizon. While treatment strategies of cardiomyopathies are too large to discuss comprehensively in a single review, we present the current therapeutic landscape for cardiomyopathies. We also provide an update on the preclinical treatment options.

Transcriptomic analyses reveal neuronal specificity of Leigh syndrome associated genes.

Leigh syndrome is a rare, inherited, complex neurometabolic disorder with genetic and clinical heterogeneity. Features present in affected patients range from classical stepwise developmental regression to ataxia, seizures, tremor, and occasionally psychiatric manifestations. Currently, more than 100 monogenic causes of Leigh syndrome have been identified, yet the pathophysiology remains unknown. Here, we sought to determine the cellular specificity within the brain of all genes currently associated with Leigh syndrome. Further, we aimed to investigate potential genetic commonalities between Leigh syndrome and other disorders with overlapping clinical features. Enrichment of our target genes within the brain was evaluated with co-expression (CoExp) network analyses constructed using existing UK Brain Expression Consortium data. To determine the cellular specificity of the Leigh associated genes, we employed expression weighted cell type enrichment (EWCE) analysis of single-cell RNA-Seq data. Finally, CoExp network modules demonstrating enrichment of Leigh syndrome associated genes were then utilised for synaptic gene ontology analysis and heritability analysis. CoExp network analyses revealed that Leigh syndrome associated genes exhibit the highest levels of expression in brain regions most affected on MRI in affected patients. EWCE revealed significant enrichment of target genes in hippocampal and somatosensory pyramidal neurons and interneurons of the brain. Analysis of CoExp modules enriched with our target genes revealed preferential association with pre-synaptic structures. Heritability studies suggested some common enrichment between Leigh syndrome and Parkinson disease and epilepsy. Our findings suggest a primary mitochondrial dysfunction as the underlying basis of Leigh syndrome, with associated genes primarily expressed in neuronal cells.

Post-traumatic Trigeminal Neuropathy Associated With Endodontic Therapy: A Systematic Review.

A painful or non-painful trigeminal nerve lesion brought on by trauma that exhibits symptoms and/or clinical evidence of trigeminal nerve dysfunction is known as painful post-traumatic trigeminal neuropathy (PTTN). In relation to this, the term post-traumatic persistent dentoalveolar pain (PDAP) is an idiopathic condition of chronic neuropathic origin that manifests as a diagnostic challenge for dental practitioners. Neuropathic pain is defined by the International Association for the Study of Pain (IASP) as "pain initiated or caused by a primary lesion or dysfunction in the nervous system." PDAP is located primarily in the teeth and jaws. This study systematically reviews how likely it is to get painful PTTNif the patient receivedendodontic therapy and the duration between doing root canal therapy (RCT) and getting PTTN. A systematic review was carried out using key search terms from PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) with English as the only permitted language. There were strict inclusion requirements. The 10 articles that were included showed a prevalence of an endodontic procedure anywhere from three to 48 months following post-endodontic treatment, and it mainly affects females in their mid-40s with no variation regarding the areas, whether it is in the maxilla or mandible. The lack of information about the association between RCT and PTTN led practitioners to make wrong diagnoses, which made the patient unwilling to seek further help. So, in this review, we identified some visible characteristics that can help in that process.

Primary Cilia Dysfunction in Neurodevelopmental Disorders beyond Ciliopathies.

Primary cilia are specialized, microtubule-based structures projecting from the surface of most mammalian cells. These organelles are thought to primarily act as signaling hubs and sensors, receiving and integrating extracellular cues. Several important signaling pathways are regulated through the primary cilium including Sonic Hedgehog (Shh) and Wnt signaling. Therefore, it is no surprise that mutated genes encoding defective proteins that affect primary cilia function or structure are responsible for a group of disorders collectively termed ciliopathies. The severe neurologic abnormalities observed in several ciliopathies have prompted examination of primary cilia structure and function in other brain disorders. Recently, neuronal primary cilia defects were observed in monogenic neurodevelopmental disorders that were not traditionally considered ciliopathies. The molecular mechanisms of how these genetic mutations cause primary cilia defects and how these defects contribute to the neurologic manifestations of these disorders remain poorly understood. In this review we will discuss monogenic neurodevelopmental disorders that exhibit cilia deficits and summarize findings from studies exploring the role of primary cilia in the brain to shed light into how these deficits could contribute to neurologic abnormalities.

Biogenic Selenium Nanoparticles Synthesized by Lactobacillus casei ATCC 393 Alleviate Acute Hypobaric Hypoxia-Induced Intestinal Barrier Dysfunction in C57BL/6 Mice.

Exposure to hypobaric hypoxia at high altitude will cause different tissue and organ damage over a long period of time. Studies have shown that hypobaric hypoxia can cause severe primary intestinal barrier dysfunction, and then cause multiple organ dysfunction. Our previous research showed that selenium nanoparticles (SeNPs) synthesized by Lactobacillus casei ATCC 393 (L. casei ATCC 393) can effectively alleviate intestinal barrier dysfunction caused by oxidative stress and inflammationin mice. This study was conducted to investigate the protective effect of biological SeNPs synthesized by L. casei ATCC 393 on intestinal barrier function in acute hypobaric hypoxic stress mice. The results showed that compared with the hypobaric hypoxic, the SeNPs synthesized by L. casei ATCC 393 by oral administration could effectively alleviate the shortening of intestinal villi, which decreased the level of diamine oxidase (DAO) and myeloperoxidase (MPO), and the expression level of tight junction protein in ileum was increased. In addition, SeNPs significantly increased the activities of superoxide dismutase (SOD), cyclooxygenase (COX-1) and glutathione peroxidase (GPx), and decreased the level of malondialdehyde (MDA), and inhibit the increase of hypoxia related factor. SeNPs effectively regulate the intestinal microecology disorder caused by hypobaric hypoxia stress, and maintain the intestinal microecology balance. In addition, oral administration of SeNPs had better protective effect on intestinal barrier function of mice under hypobaric hypoxia stress. These results suggested that SeNPs synthesized by L. casei ATCC 393 can effectively alleviate the damage of intestinal barrier function under acute hypobaric hypoxic stress, which may be closely related to the antioxidant activity of SeNPs.

The role of bacterial vaginosis in the development of inflammatory diseases of the female genital organs and the formation of disorders of the placental complex in the early stages of pregnancy

ABSTRACT. This paper presents some features of microbiocenosis of the vulva and vagina in pregnant women against the background of inflammatory diseases of the female genital organs and the role of bacterial vaginosis in the development of primary placental dysfunction during the formation of the placental complex. Goal. To determine the species composition of the microflora of vaginal contents in pregnant women by means of bacterioscopic, bacteriological research methods, polymerase chain reaction, pH-metry of vaginal discharge. Materials and methods. We used bacterioscopic, bacteriological, ultrasound research methods, polymerase chain reaction, and pH-metry of vaginal secretions. Studies of uteroplacental blood circulation were carried out on the ultrasonic diagnostic device "SonoAce 8000 Life". According to the set goal, a study was conducted on 87 women at 6-7 and 12-14 weeks of gestation. The main group consisted of 47 women with signs of bacterial vaginosis, the control group consisted of 40 practically healthy women. The results. In the women of the main group, the growth of contamination of the mucous membrane of the vulva and vagina with vaginal gardnerella is characteristic - 53.9%. To diagnose the formation of primary placental dysfunction, a dopplerometric study of blood flow indicators in uterine arteries revealed a significant increase in vascular resistance indices in 34 (46.7%) (p>0.05) pregnant women of the main observation group. Conclusions. The revealed features of the microbiocenosis of the genital tract in pregnant women in the early stages of guttation of patients with inflammatory diseases of the female genital organs indicate that the leading role in the development of inflammatory diseases of the female genital organs is played by the violation of the ecosystem of the vagina. These diagnostic criteria will make it possible to detect the insufficiency of the placental bed, to diagnose primary placental dysfunction at the preclinical stage (at 8-12 weeks of pregnancy).

Primary Cilia: The New Face of Craniofacial Research.

The primary cilium is a solitary, sensory organelle that extends from the surface of nearly every vertebrate cell, including craniofacial cells. This organelle converts chemical and physical external stimuli into intracellular signaling cascades and mediates several well-known signaling pathways simultaneously. Thus, the primary cilium is considered a cellular signaling nexus and amplifier. Primary cilia dysfunction directly results in a collection of diseases and syndromes that typically affect multiple organ systems, including the face and teeth. Despite this direct connection, primary cilia are largely unexplored in craniofacial research. In this review, I briefly summarize craniofacial abnormalities tied to the primary cilium and examine the existing information on primary cilia in craniofacial development and repair. I close with a discussion on preliminary studies that motivate future areas of exploration that are further supported by studies performed in long bone and kidney cells.

An update on maternal cardiac hemodynamics in fetal growth restriction and pre-eclampsia.

Pre-eclampsia and fetal growth restriction (FGR) have been long related to primary placental dysfunction, caused by abnormal trophoblast invasion. Nevertheless, emerging evidence has led to a new hypothesis for the origin of pre-eclampsia and FGR. Suboptimal maternal cardiovascular adaptation has been shown to result in uteroplacental hypoperfusion, ultimately leading to placental hypoxic damage with secondary dysfunction. In this review, we summarize current evidence on maternal cardiac hemodynamics in FGR and pre-eclampsia. We also discuss the different approaches for antihypertensive treatment according to the hemodynamic phenotype observed in pre-eclampsia and FGR.

Surgical approach to combined mitral and tricuspid valve disease: good neighbourhood rules.

Tricuspid regurgitation afflicts more than one-third of patients with mitral valve disease during their clinical history, and negatively affects their outcomes, increasing mortality and hospitalizations for heart failure and reducing the quality of life. A renewed interest in the 'neglected valve' has increased the frequency of the combined treatment of these two diseases. Undoubtedly necessary in patients with degenerative mitral valve disease in the presence of two severe valve defects, tricuspid annuloplasty has proven to be safe and effective even if performed prophylactically, when tricuspid annular dilation coexists with primary mitral dysfunction. In the absence of survival benefits, however, this additional surgical procedure increases the risk of high-grade atrio-ventricular blocks and the need for a definitive pacemaker. On the other hand, the role of surgery has been scaled down in patients with functional mitral and tricuspid regurgitation. In this context, a multidisciplinary approach is needed and transcatheter alternatives are increasingly the chosen treatment option. A new therapeutic algorithm is therefore looming on the horizon. In the future, the treatment of tricuspid and mitral valve disease may be considered two potentially distinct and successive phases of an integrated heart failure patients care process.

Outcomes of stent grafts for treatment of central venous disease in hemodialysis patients.

To evaluate the effectiveness of stent graft (SG) for the treatment of central venous disease (CVD) in hemodialysis patients. Between January 2014 and April 2022, 122 patients on hemodialysis with symptomatic CVD were treated with percutaneous transluminal angioplasty (PTA) and bare-metal stent (BMS) or SG placement. The mean follow-up was 14.5 months (IQR: 8.0, 24.2). Patency rates of the target sites were calculated using Kaplan-Meier and log-rank studies. Multivariate Cox proportional hazard models were used to evaluate the association between various characteristics and target site primary patency. Technical success rate was 100%. At 3, 6, 12, and 24 months, the target sites primary patency rates were 86.4%, 74.2%, 45.1%, and 30.4% for PTA; 94.7%, 78.6%, 60.8%, and 45.6% for BMS; and 94.0%, 92.0%, 82.4%, and 66.8% for SG, respectively, and the assisted primary patency rates were 86.5%, 80.4%, 63.8%, and 46.0% for PTA; 94.7%, 89.5%, 77.5%, and 71.1% for BMS; 100%, 100%, 97.8%, and 83.4% for SG, respectively. The Kaplan-Meier analysis indicated that SGs achieved better primary and assisted primary patency than PTA or BMS (p<0.05). SG use and concomitant stenosis were the independent predictors of target site primary patency dysfunction in the multivariate analysis. This study confirmed the better long-term patency of SG in comparison with PTA and BMS for the treatment of CVD in hemodialysis patients.

Current considerations for heart-kidney transplantation.

Cardiorenal syndrome is a complex syndrome characterized by dysfunction of the heart and kidneys in an interdependent fashion and is further divided into different subtypes based on primary organ dysfunction. Simultaneous Heart-Kidney transplantation is the treatment of choice for end-stage irreversible dysfunction of both organs, however it may be avoided with determination of cardiorenal subtype and management of primary organ dysfunction. This article discusses types of cardiorenal syndrome, indications and concerns regarding the use of simultaneous heart-kidney transplantation, and outlines algorithms for determination of need for dual vs. single organ transplantation.

Liquid Ventilation Reconditions Isolated Rat Lungs Following Ischemia-Reperfusion Injury.

Lung transplantation remains the only curative treatment for end-stage pulmonary disease. Lung ischemia-reperfusion injury (IRI) is a major contributor to primary allograft dysfunction and donor organ nonutilization. The alveolar macrophage is a key inflammatory mediator in IRI. Ex vivo lung perfusion (EVLP) has been investigated to rehabilitate lungs before transplant but has failed to provide significant improvements after IRI. We hypothesized that liquid ventilation (LV) could be utilized for ex vivo lung reconditioning in a rat IRI model. We compared EVLP with LV in an isolated ex vivo rat lung with an aqueous ventilant using quantitative physiological and immunological parameters. We observed improved physiological parameters and mechanical clearance of alveolar macrophages and cytokines halting the propagation of the inflammatory response in IRI. While the wide applicability to large animal or human transplantation have yet to be explored, these findings represent a method for lung reconditioning in the setting of significant IRI that could widen the lung organ donation pool and limit morbidity and mortality associated with ischemia-induced primary graft dysfunction.

Addison’s disease triggered by infection with mycobacterium abscessus, but not by adrenal tuberculosis or MAC pulmonary disease, in a subject with type 2 diabetes mellitus: case report

BackgroundAddison’s disease is primary adrenal dysfunction and is characterized by decrease of cortisol level and increase of adrenocorticotropic hormone (ACTH) level. It is known that infection is one of main causes of Addison’s disease. Among various infections, tuberculous infection accounts for the majority of them. Recently the number of subjects with non-tuberculous mycobacterial infection has been increased, and the infection can also bring about Addison’s disease. Mycobacterium avium complex (MAC) pulmonary disease accounts for the majority of non-tuberculous mycobacterial infection.Case presentationAn 83-year-old female was suspected of having adrenal failure in our outpatient care and hospitalized in our institution. There was pigmentation in her face, hands and legs, especially in auricle and nail beds in her hands and legs. In rapid ACTH load test (0.25 mg of 1–24 ACTH), cortisol level was not increased at all. An abdominal computed tomography (CT) showed swelling of both adrenal glands accompanied by calcification. QuantiFERON test was negative and mycobacterium tuberculosis complex was negative in PCR test using bronchial lung lavage fluid. These data ruled out the possibility of adrenal tuberculosis. It is known that MAC pulmonary disease accounts for the majority of non-tuberculous mycobacterial infection. In this subject, however, anti-MAC antibody was negative and MAC-related bacteria were not detected in PCR test using bronchial lung lavage fluid. These data ruled out the possibility of MAC pulmonary disease. Mycobacterium abscessus (Mab) was positive in bronchial lung lavage fluid culture. Based on these data, we diagnosed this subject with Addison’s disease triggered by infection with mycobacterium abscessus, but not by adrenal tuberculous or MAC pulmonary disease. Decreased sodium level and increased eosinophil number were normalized and appetite loss was markedly mitigated after starting hydrocortisone therapy. A chest CT which was taken about 6 months later showed drastic reduction of consolidation in the upper lobe of the left lung although calcification in the adrenal gland was still observed.ConclusionsWe should bear in mind the possibility of Addison’s disease triggered by another type of infection rather than adrenal tuberculosis or MAC pulmonary disease.

Metabolic regulation of the neural stem cell fate: Unraveling new connections, establishing new concepts.

The neural stem cell niche is a key regulator participating in the maintenance, regeneration, and repair of the brain. Within the niche neural stem cells (NSC) generate new neurons throughout life, which is important for tissue homeostasis and brain function. NSCs are regulated by intrinsic and extrinsic factors with cellular metabolism being lately recognized as one of the most important ones, with evidence suggesting that it may serve as a common signal integrator to ensure mammalian brain homeostasis. The aim of this review is to summarize recent insights into how metabolism affects NSC fate decisions in adult neural stem cell niches, with occasional referencing of embryonic neural stem cells when it is deemed necessary. Specifically, we will highlight the implication of mitochondria as crucial regulators of NSC fate decisions and the relationship between metabolism and ependymal cells. The link between primary cilia dysfunction in the region of hypothalamus and metabolic diseases will be examined as well. Lastly, the involvement of metabolic pathways in ependymal cell ciliogenesis and physiology regulation will be discussed.