Functions of nuclear factor Y in nervous system development,function and health

Nuclear factor Y is a ubiquitous heterotrimeric transcription factor complex conserved across eukaryotes that binds to CCAAT boxes,one of the most common motifs found in gene promoters and enhancers.Over the last 30 years,research has revealed that the nuclear factor Y complex controls many aspects of brain development,including differentiation,axon guidance,homeostasis,disease,and most recently regeneration.However,a complete understanding of transcriptional regulatory networks,including how the nuclear factor Y complex binds to specific CCAAT boxes to perform its function remains elusive.In this review,we explore the nuclear factor Y complex’s role and mode of action during brain development,as well as how genomic technologies may expand understanding of this key regulator of gene expression.

Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier function.However, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could provide valuable insights into potential therapeutic strategies for Alzheimer's disease and related conditions.

MicroRNAs as potential biomarkers for diagnosis of post-traumatic stress disorder

Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress disorder.In addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate treatment.Evidence suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress disorder.We performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December 2023.These included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum exosomes.One of these studies had also used whole plasma.Two studies were excluded as they did not involve microRNA biomarkers.Most of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult subjects.In measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString panels.Only six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to controls.The miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/exosomes;and miR-18a-3p and-7-1-5p in blood plasma.Several important limitations identified in the studies need to be taken into account in future studies.Further studies are warranted with war veterans and recently traumatized children,adolescents,and adults having PTSD and use of animal models subjected to various stressors and the effects of suppressing or overexpressing specific microRNAs.

Gallbladder carcinoma in the era of artificial intelligence: Early diagnosis for better treatment

Gallbladder carcinoma(GBC)is the most common malignant tumor of biliary tract,with poor prognosis due to its aggressive nature and limited therapeutic options.Early detection of GBC is a major challenge,with most GBCs being detected accidentally during cholecystectomy procedures for gallbladder stones.This letter comments on the recent article by Deqing et al in the World Journal of Gastrointestinal Oncology,which summarized the various current methods used in early diagnosis of GBC,including endoscopic ultrasound(EUS)examination of the gallbladder for high-risk GBC patients,and the use of EUS-guided elasto-graphy,contrast-enhanced EUS,trans-papillary biopsy,natural orifice translu-minal endoscopic surgery,magnifying endoscopy,choledochoscopy,and confocal laser endomicroscopy when necessary for early diagnosis of GBC.However,there is a need for novel methods for early GBC diagnosis,such as the use of artificial intelligence and non-coding RNA biomarkers for improved screening protocols.Additionally,the use of in vitro and animal models may provide critical insights for advancing early detection and treatment strategies of this aggressive tumor.

Nucleoside modified mRNA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord

Spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular factors.Although the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(Khyeam et al.,2021).

Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.

Getting physical with medical education:Exercise based virtual anatomy review classes for medical students

The benefits of regular physical activity are well known.Yet,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary setting.To investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(MSK)anatomy course material.These synchronous sessions were co-taught by a group fitness instructor and an anatomy instructor.The fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously covered.After the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving MSK anatomy knowledge,PA levels,and mental wellbeing.Thirty participants completed surveys;a majority agreed that the classes increased understanding of MSK concepts(90.0%)and activity levels(97.7%).Many(70.0%)felt that the classes helped reduce stress.The majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social connectedness.Overall,medical students saw benefit in PA based interventions to supplement MSK course concepts.Along with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.

Surgical anatomy of innervation of the gallbladder in humans and Suncus murinus with special reference to morphological understanding of gallstone formation after gastrectomy

AIM： To clarify the innervation of human gallbladder,with special reference to morphological understanding of gallstone formation after gastrectomy.METHODS： The liver, gallbladder and surrounding structures were immersed in a 10 mg/L solution of alizarin red S in ethanol to stain the peripheral nerves in cadavers （n = 10）. Innervation in the areas was completely dissected under a binocular microscope. Similarly,innervation in the same areas of 10 Suncus murinus （S. murinus） was examined employing whole mount immunohistochemistry.RESULTS： Innervation of the gallbladder occurred predominantly through two routes. One was from the anterior hepatic plexus, the innervation occurred along the cystic arteries and duct. Invariably this route passed through the hepatoduodenal ligament. The other route was from the posterior hepatic plexus, the innervation occurred along the cystic duct ventrally. This route also passed through the hepatoduodenal ligament dorsally.Similar results were obtained in S. murinus.CONCLUSION： The route from the anterior hepatic plexus via the cystic artery and/or duct is crucial for preserving gallbladder innervation. Lymph node dissection specifically in the hepatoduodenal ligament may affect the incidence of gallstones after gastrectomy.Furthermore, the route from the posterior hepatic plexus via the common bile duct and the cystic duct to the gallbladder should not be disregarded. Preservation of the plexus may attenuate the incidence of gallstone formation after gastrectomy.

Practice and exploration of educational innovation in the teaching process of anatomy

In the advent of knowledge economy and information society,the society urgently needs talents with high-quality,creativity and comprehensive development.School education plays an extremely important role in educating creative innovation.

Clinical anatomy of hepatic vessels by computed tomography angiography:A minireview

The liver has a complex vascular anatomy with a unique dual blood supply.Clinical conditions of the liver vary widely and include disorders originating in the vascular and biliary systems as well as the parenchyma.In most vascular disorders,the effects on the liver are generally subclinical because of its abundant blood supply.However,early diagnosis of such vascular diseases can significantly reduce patient morbidity and mortality.Because imaging findings of vascular disease are not always readily apparent,diagnosis can be difficult.Computed tomography angiography is an excellent imaging modality for visualizing the vascular anatomy of patients for treatment planning.In this review article,we focus on the vascular anatomy of the liver and the imaging findings in some acute hepatic vascular diseases.

Surgical anatomy of the innervation of pylorus in human and Suncus murinus, in relation to surgical technique for pylorus-preserving pancreaticoduodenectomy

AIM： To clarify the innervation of the antro-pyloric region in humans from a clinico-anatomical perspective. METHODS： The stomach, duodenum and surrounding structures were dissected in 10 cadavers, and immersed in a 10mg/L solution of alizarin red S in ethanol to stain the peripheral nerves. The distribution details were studied to confirm innervations in the above areas using a binocular microscope. Similarly, innervations in 10 Suncus murinus were examined using the method of whole-mount imm unohistochemistry. RESULTS： The innervation of the pyloric region in humans involved three routes： One arose from the anterior hepatic plexus via the route of the suprapyloric/supraduodenal branch of the right gastric artery; the second arose from the anterior and posterior gastric divisions, and the third originated from the posterior-lower region of the pyloric region, which passed via the infrapyloric artery or retroduodenal branches and was related to the gastroduodenal artery and right gastroepiploic artery. For Suncus murinus, results similar to those in humans were observed. CONCLUSION： There are three routes of innervation of the pyloric region in humans, wherein the route of the right gastric artery is most important for preserving pyloric region innervation. Function will be preserved by more than 80% by preserving the artery in pylorus-preserving pancreaticoduodenectomy （PPPD）. However, the route of the infrapyloric artery should not be disregarded. This route is related to several arteries （the right gastroepiploic and gastroduodenal arteries）, and the preserving of these arteries is advantageous for preserving pyloric innervation in PPPD. Concurrently, the nerves of Latarjet also play an important role in maintaining innervation of the antro-pyloric region in PPPD. This is why pyloric function is not damaged in some patients when the right gastric artery is dissected or damaged in PPPD.

Acute intoxication cases admitted to the emergency department of a university hospital

BACKGROUND: This study aimed to describe the clinical and socio-demographic aspects of acute poisoning in 2010 in Duzce City, Northwest Anatolian Region of Turkey.METHODS: Acute poisoning was due to the intentional ingestion of drugs in young and adult people(≥16), who were treated at the Emergency Service of Duzce University Medical Hospital, Turkey from January 1, 2010 to December 31, 2010. In this retrospective and descriptive study, 95 patients were diagnosed with intoxications and 30 of them intentionally ingested drugs to commit suicide. Records of the patients diagnosed with intoxication were obtained from the Clinical Archive of the hospital. Their diagnoses were established according to the International Statistical Classification of Diseases and Related Health Problems. Codes X60-X84 of this classification were used to classify self-infringed drug injuries and drug poisoning.RESULTS: In this series, 35(36.8%) patients were male and 60 patients(63.2%) female. The male/female ratio was 1.0/1.7. The mean age of the patients was 33.1±14.2 years; 17(17.9%) patients were below 20 years old and 9(9.5%) were older than 50 years. Of these patients, 29(30.5%) were single, 7(7.4%) divorced or separated, and 59(62.1%) married. Their mean time for admission to the emergency service after the incident was 208±180(15–660) minutes. The mean time for admission to the emergency service for patients with food intoxication after the incident was 142±160 minutes, for those with drug intoxication 173±161 minutes, for those with carbon monoxide(CO) intoxication 315±209 minutes, and for those with undefined intoxication 289±166 minutes(P=0.005). Most of the intoxication cases occurred in winter(41.1%, 39 of 95 patients). Admissions to the emergency service were most common in December and April(21 and 16 of 95 patients, respectively). Sixty-five(68.4%) cases were involved in non-deliberate poisoning, whereas 30(31.6%) were involved in deliberate poisoning. Twenty-six of the 95 patients with acute poisonings had mortality risk at admission, however only one died from CO intoxication in the emergency service(1.1%). Suicide attempts were more common in females than in males(21 of 30 patients, 70%, P<0.05). CONCLUSION: In Duzce City of Turkey, most intoxication cases occurred in winter, especially in December. They had non-deliberate poisoning, but deliberate poisoning in suicide attempts was more common in females than in males.

The Anatomy of Dorsal Ramus Nerves and Its Implications in Lower Back Pain

This article reviews the relationship between the spinal dorsal ramus system and low back pain, including the anatomy, clinical findings, pathogenesis and treatment of low back pain mediated by spinal dorsal ramus and zygapophysial (facet) joint syndrome. Each spinal dorsal ramus arises from the spinal nerve and then divides into a medial and lateral branch. The medial branch supplies the tissues from the midline to the zygapophysial joint line and innervates two to three adjacent zygapophysial joints and their related soft tissues. The lateral branch innervates the tissues lateral to the zygapophysial joint line. The clinical pain presentations follow these anatomic distributions, which can be used for localizing the involved dorsal ramus. The diagnosis can be confirmed by performing a single dorsal ramus block that results in relief of pain and muscle spasm. Etiologically, any factor that stimulates the spinal dorsal ramus can cause low back pain, which is distinct from zygapophysial joint syndrome. Clinically, L1 and L2 are the most common sites of dorsal rami involvement. Treatment includes spinal dorsal ramus injection therapy and percutaneous neurotomy. Summarily, irritation of the spinal dorsal ramus system is a potential source of low back pain. Based on the anatomy and clinical presentation, the involved spinal dorsal ramus can be localized and treated.

The combined application of stem cells and three-dimensional bioprinting scaffolds for the repair of spinal cord injury

Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.

MicroRNAs as potential biomarkers for diagnosis of schizophrenia and influence of antipsychotic treatment

Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizophrenia is a chro nic,severe,and disabling mental disorder with late adolescence or early adulthood onset,Antipsychotics are the most commonly used drugs to treat schizophrenia,but those currently in use do not fully reverse all three types of symptoms characte rizing this condition.Schizophrenia is frequently misdiagnosed,resulting in a delay of or inappropriate treatment.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of schizophrenia.The recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate rials.From the studies that had validated the preliminary findings,potential candidate biomarkers for schizophrenia in adults could be miR-22-3p,-30e-5p,-92a-3p,-148b-5p,-181a-3p,-181a-5p,-181b-5p,-199 b-5p,-137 in whole blood,and miR-130b,-193a-3p in blood plasma.Antipsychotic treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood plasma.Further studies are warranted with adolescents and young adults having schizophrenia and consideration should be given to using animal models of the disorder to investigate the effect of suppressing or overexpressing specific microRNAs.

Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

Multiple pretreatments can effectively improve the functionality of mesenchymal stem cells

In this editorial,we offer our perspective on the groundbreaking study entitled“Hypoxia and inflammatory factor preconditioning enhances the immunosup-pressive properties of human umbilical cord mesenchymal stem cells”,recently published in World Journal of Stem Cells.Despite over three decades of research on the clinical application of mesenchymal stem cells(MSCs),only a few therapeutic products have made it to clinical use,due to multiple preclinical and clinical challenges yet to be addressed.The study proved the hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics,which revealed the combination of inflammatory factors and hypoxic preconditioning offers a promising approach to enhance the function of MSCs.As we delve deeper into the intricacies of pretreat-ment methodologies,we anticipate a transformative shift in the landscape of MSC-based therapies,ultimately contributing to improved patient outcomes and advancing the field as a whole.

Macro-Micro-Anatomy of the Lingual Artery

The macro-micro-anatomy of the lingual artery of 25 adult cadavers wasstudied.The origin of the artery is rather concentrated and the greater cornu of thehyoid bone can be used as the indicator.The entrance of the artery into the hyoglossusmuscle is almost constantly along the posterior border of the muscle,where the artery issuperficially located and easily to be exposed,and has a constant relationship with thevein and hypoglossal nerve.Thus the lingual artery can be used as the artery of a recipientarea in case of tongue reconstruction.The deep lingual artery has two types ofbranches;the short ones mainly supply the muscles of tongue while the long ones mainlysupply the mucosa by forming a submucosal network.In the muscles of tongue,minutearterioles run tortuously along the muscular fibers with abundant anastomoses betweeneach other,but no anastomosis is found to cross over the rnidline of the tongue.Be-neath the mucosa,there is an arterial network spreading all over the whole tongue notlimited to one side.The relationship of the arterial architecture to the structure and thefunctions of the tongue and its clinical significance were discussed.

Mitochondrial targeting sequence of magnetoreceptor MagR:More than just targeting

Iron-sulfur clusters(ISC)are essential cofactors for proteins involved in various biological processes,such as electron transport,biosynthetic reactions,DNA repair,and gene expression regulation.ISC assembly protein IscA1(or MagR)is found within the mitochondria of most eukaryotes.Magnetoreceptor(MagR)is a highly conserved A-type iron and iron-sulfur cluster-binding protein,characterized by two distinct types of iron-sulfur clusters,[2Fe-2S]and[3Fe-4S],each conferring unique magnetic properties.MagR forms a rod-like polymer structure in complex with photoreceptive cryptochrome(Cry)and serves as a putative magnetoreceptor for retrieving geomagnetic information in animal navigation.Although the N-terminal sequences of MagR vary among species,their specific function remains unknown.In the present study,we found that the N-terminal sequences of pigeon MagR,previously thought to serve as a mitochondrial targeting signal(MTS),were not cleaved following mitochondrial entry but instead modulated the efficiency with which iron-sulfur clusters and irons are bound.Moreover,the N-terminal region of MagR was required for the formation of a stable MagR/Cry complex.Thus,the N-terminal sequences in pigeon MagR fulfil more important functional roles than just mitochondrial targeting.These results further extend our understanding of the function of MagR and provide new insights into the origin of magnetoreception from an evolutionary perspective.