Effective extraction of polyribosomes from astrocytes enables future discoveries on translation regulation

Translation regulation is an important layer of gene expression:Generation of genome-wide expression datasets at multi-omics levels in spatial,temporal,and cell-type resolution is essential for deciphering brain complexity.Regulation of gene expression is a highly dynamic process aiming at the production of precise levels of gene products to guarantee optimal cellular function,in response to physiological cues.Speedy advances in next-generation sequencing enabled the understanding of epigenomic and transcriptomic dynamic landscapes of different brain regions along development,aging,and disease progression.However,the correlation of the“transcriptome”with protein levels is poor because numerous mRNAs are subjected to manipulation of their translation efficiency,to warrant a favorable result under certain conditions.Hence,it is widely accepted that regulation at the translation level is a vital layer of gene expression.Quantification of actively translated mRNA populations(i.e.,“translatome”)is a more reliable predictor of the“proteome”(Wang et al.,2020).

5-Fluorouracil dose escalation generated desensitized colorectal cancer cells with reduced expression of protein methyltransferases and no epithelial-to-mesenchymal transition potential

Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers.This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.Materials and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU.The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays.This was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized cells.Western blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation profiles.Results:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU.The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells.This was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell lines.Additionally,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.Conclusion:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be less aggressive than parental cells.

Comparison of carotenoid,chlorophyll concentrations and their biosynthetic transcript levels in different coloured cauliflower

Carotenoids and chlorophylls are among the most widely distributed pigments in nature that play essential roles in the photosynthetic apparatus and confer diverse colours in plants.Among all vegetables,cauliflower(Brassica oleracea L.ssp.var.botrytis)is rich in phytochemicals and is an important crop grown all over the world.This study investigates carotenoid and chlorophyll concentrations in differently pigmented cultivars and elucidates the role of transcriptional regulation of carotenoid accumulation including lutein andβ-carotene.Here,we characterised changes in pigments by UHPLC-DAD-ToF-MS and changes in transcript levels of carotenoid metabolic genes by qRT-PCR in florets and leaves of orange(‘Jaffa'and‘Sunset'),purple(‘Di Sicilia Violetto'and‘Graffiti'),green(‘Trevi')and white(‘Clapton')cultivars.Transcript levels of all carotenoid metabolic genes showed different transcript level patterns in the leaves and florets.Compared to the other cultivars,the orange cultivars had the highest levels ofβ-carotene in the florets and lutein in the leaves resulting in changes lutein/β-carotene ratios.In the green cultivar,higher transcript levels were also found,especially for phytoene synthase and phytoene desaturase genes of the core biosynthesis pathway.However,no increased carotenoid concentrations were observed,possibly due to a higher carotenoid turnover induced by the carotenoid cleavage dioxygenase 4 in the green cultivar.In the white(‘Clapton')and purple(‘Di Sicilia Violetto'and‘Graffiti')cultivars the phytoene desaturase transcript levels as well as carotenoid concentrations were low.Chlorophyll concentrations changed in trend comparable to the carotenoid concentrations and were only significantly lower in the leaves of the orange cultivar‘Jaffa'.Also,the chlorophyll a/b ratio changed in‘Jaffa'.In florets the highest chlorophylls concentrations were observed for the green cultivar(‘Trevi')and the purple cultivar(‘Di Sicilia Violetto').Taken together,the study demonstrates the complex source-sink relationship of carotenoid accumulation in different coloured cauliflower.

Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway

AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL EGF.Erlotinib and EGFR siRNA were used to intervene EGF treatment.Cellular viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,respectively.EGFR/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot assay.EGFR was also determined by immunofluorescence staining.RESULTS:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR expression.Erlotinib suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein expressions.Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin proteins.Similarly,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin proteins.CONCLUSION:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE cells.EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).

Bone marrow-derived microglia confer neuroprotection to a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis(ALS) is a neurodegenerative disease that causes the progressive loss of both upper and lower motor neurons in the brain,brainstem,and spinal cord.The exact mechanisms of ALS are still unclear,but genetic and molecular studies have revealed some key factors that may contribute to motor neuron death.Besides motor neurons,other cell types in the nervous system,such as reactive astrocytes and activated microglia,also show pathological changes and secrete harmful substances and inflammatory cytokines(Appel et al.,2011).

Nucleotide Contribution to the Functioning of SERT, Na /K ATPase and GPCR Proteins

Purine nucleotides are crucial for the effective operation of cell membrane proteins maintaining the neurotransmitter responses of 5-HT. Major protein targets in the treatment of depression include SERT, N/K ATPase and GPCR. Each protein target is responsive to a specific complement of drugs: antidepressants (SERT), lithium and cardiogenic steroids (N/K ATPase), 5-HT receptor ligands (GPCR). Computational software is useful for comparing molecular similarity within ligand-ligand and ligand-nucleotide structures. Previous studies demonstrate that GPCR ligands of different pharmacologic classes display relative molecular similarity to nucleotide structures. The current study applies this methodology to compound structures modulating SERT and N/K ATPase receptors. Minimum energy conformers of SERT antagonists demonstrate relative molecular similarity to the structural template of GTP nucleotide. GTP template fits of 5-HT and psilocin are similar, whereas a SERT-like fit is one of several for the ketamine structure. Endogenous and pharmaceutical modulators of Na/K ATPase relate to adenine nucleotide. The fits of cardiogenic steroids to a cGMP template demonstrate similarities and differences between compounds. Relative molecular similarity within the structures of hormones, drugs and nucleotides has implications for neurotransmitter transport and cell signal transduction processes.

Micro-Arthropods in the Surroundings of Nests of Messor arenarius Ants in the Negev Desert in Israel

The present research investigated a segment of the micro-arthropod populations residing within nests of Messor arenarius ants in the Negev Desert of Israel. The total frequencies of micro-arthropods in the chaff of those ants’ nests were found to be higher than in the surrounding soil of the same nests. Acari (mites) were observed to be more abundant during the spring season, whereas their presence decreased during the summer months. Springtails (Collembola) were found to follow the Acari pattern, commonly found within the nests of those ants during spring but were absent during summer. Psocoptera order inhabiting soil habitats were infrequently encountered during spring, but their prevalence increased significantly during summer, particularly within the chaff of the ants’ nests, suggesting that chaff is their primary food source in the Negev Desert. Our research suggests that shifts in seasonality have important consequences on the distribution of soil invertebrate communities with implications on nutrient cycling.

Do medical students studying in the United Kingdom have an adequate factual knowledge of basic life support?

BACKGROUND: Healthcare professionals have a duty to maintain basic life support(BLS) skills. This study aims to evaluate medical students' factual knowledge of BLS and the training they receive.METHODS: A cross-sectional, closed-response questionnaire was distributed to the fi rst-and fourth-year students studying at institutions in the United Kingdom. The paper questionnaire sought to quantify respondent's previous BLS training, factual knowledge of the BLS algorithm using five multiple choice questions(MCQs), and valuate their desire for further BLS training. Students received 1 point for each correctly identifi ed answer to the 5 MCQ's.RESULTS: A total of 3,732 complete responses were received from 21 medical schools. Eighty percent(n=2,999) of students completed a BLS course as part of their undergraduate medical studies. There was a signifi cant difference(P<0.001) in the percentage of the fourth-year students selecting the correct answer in all the MCQ's compared to the fi rst-year students except in identifyingthe correct depth of compressions required during CPR(P=0.095). Overall 10.3%(95% CI 9.9% to 10.7%) of respondents correctly identified the answer to 5 MCQ's on BLS: 9% of the first-year students(n=194) and 12% of the fourth-year students(n=190). On an institutional level the proportion of students answering all MCQ's correctly ranged from 2% to 54% at different universities. Eighty-one percent of students(n=3,031) wished for more BLS training in their curriculum.CONCLUSION: Factual knowledge of BLS is poor among medical students in the UK. There is a disparity in standards of knowledge across institutions and respondents indicating that they would like more training.

Generation of a tree shrew breast cancer model using lentivirus expressing PIK3CA-H1047R

DEAR EDITOR,Breast cancer is the most common malignant tumor in women,posing a serious threat to health. Tree shrews(Tupaia belangeri chinensis) are evolutionarily closer to humans than rodents and are emerging as an attractive experimental animal model for breast cancer. The PIK3CA gene is frequently mutated in both human and tree shrew breast tumors. Herein, we effectively overexpressed PIK3CA-H1047R in the mammary epithelial cells of tree shrews using a lentivirus to induce breast tumors.

Fusarium wilt of banana:Current update and sustainable disease control using classical and essential oils approaches

Fusarium species were reported to produce biofilms.Biofilms are superficial societies of microbes bounded and endangered by being situated or taking place outside a cell or cells.The most destructive fungal diseases caused by phytopathogens are as a result of biofilms formation.Fusarium wilt of banana(Panama disease)is caused by a soil-borne pathogen called Fusarium oxysporum f.sp.cubense.Fusarium oxysporum occurs in a form of a species complex(FOSC)which encompasses a crowd of strains.Horizontal genetic factor transfer may donate to the observed assortment in pathogenic strains,while sexual reproduction is unknown in the FOSC.Fusarium wilt is a notorious disease on several crops worldwide.Yield loss caused by this pathogen is huge,and significant to destroy crop yields annually,thereby affecting the producer countries in various continents of the world.The disease is also resistant to various synthetic chemical fungicides.However,excessive use of synthetic fungicides during disease control could be lethal to humans,animals,and plants.This calls for alternative eco-friendly management of this disease by targeting the biofilms formation and finally suppressing this devastating phytopathogen.In this review,we,therefore,described the damage caused by Fusarium wilt disease,the concept of filamentous fungal biofilms,classical control strategies,sustainable disease control strategies using essential oils,and prevention and control of vegetables Fusarium wilt diseases.

Use of endolumenal functional lumen imaging probe in investigating paediatric gastrointestinal motility disorders

Investigating gastrointestinal(GI)motility disorders relies on diagnostic tools to assess muscular contractions,peristalsis propagation and the integrity and coordination of various sphincters.Manometries are the gold standard to study the GI motor function but it is increasingly acknowledged that manometries do not provide a complete picture in relation to sphincters competencies and muscle fibrosis.Endolumenal functional lumen imaging probe(EndoFLIP)an emerging technology,uses impedance planimetry to measure hollow organs cross sectional area,distensibility and compliance.It has been successfully used as a complementary tool in the assessment of the upper and lower oesophageal sphincters,oesophageal body,the pylorus and the anal canal.In this article,we aim to review the uses of EndoFLIP as a tool to investigate GI motility disorders with a special focus on paediatric practice.The majority of EndoFLIP studies were conducted in adult patients but the uptake of the technology in paediatrics is increasing.EndoFLIP can provide a useful complementary data to the existing GI motility investigation in both children and adults.

Self-reported ischemic heart disease: Prevalence, sociodemographics, health behavior, health-care utilization, and quality of life

The aim of this study was to present the prevalence of self-reported Ischemic Heart Disease (IHD) based on a national population-based survey and to characterize people with self-reported IHD with respect to health behavior, risk factors, health-care services utilization and health-related HRQoL;further to compare people with self-reported IHD to those with other chronic illness and people without chronic illness. Based on the Danish Health Interview Survey 2005 (SUSY), a sample of 10,983 persons aged 35 years or older was examined. Data was collected through personal interviews (response rate = 66.7%) and self-administered questionnaires (51.5%). The sample was divided into three mutual exclusive groups: IHD;other chronic illnesses;and no chronic illness. The prevalence of IHD was 5.6% (5.2 - 6.0). The disease was more common in men than women, and the average age was 67.5 years. People with self-reported IHD were characterized as having poorer health behaviors;more risk factors: 40% smokers, 21% sedentary lifestyle, 26% obese;higher utilization of the health-care services;and poorer HRQoL. When compared to people with other chronic diseases, people with IHD continued to show the same characteristics. The IHD group had more problems affecting their daily lives than the other two groups. The issues that affected the people with IHD have also been shown to increase the load on the health-care system. Therefore, it is important to the patients, health-care, and society that the prevalence of IHD is reduced and the burden of disease is made a priority.

Peptide self‐assembly as a strategy for facile immobilization of redox enzymes on carbon electrodes

Redox-enzyme‐mediated electrochemical processes such as hydrogen production,nitrogen fixation,and CO_(2) reduction are at the forefront of the green chemistry revolution.To scale up,the inefficient two‐dimensional(2D)immobilization of redox enzymes on working electrodes must be replaced by an efficient dense 3D system.Fabrication of 3D electrodes was demonstrated by embedding enzymes in polymer matrices.However,several requirements,such as simple immobilization,prolonged stability,and resistance to enzyme leakage,still need to be addressed.The study presented here aims to overcome these gaps by immobilizing enzymes in a supramolecular hydrogel formed by the self‐assembly of the peptide hydrogelator fluorenylmethyloxycarbonyldiphenylalanine.Harnessing the self‐assembly process avoids the need for tedious and potentially harmful chemistry,allowing the rapid loading of enzymes on a 3D electrode under mild conditions.Using the[FeFe]hydrogenase enzyme,high enzyme loads,prolonged resistance against electrophoresis,and highly efficient hydrogen production are demonstrated.Further,this enzyme retention is shown to arise from its interaction with the peptide nanofibrils.Finally,this method is successfully used to retain other redox enzymes,paving the way for a variety of enzyme‐mediated electrochemical applications.

DNA methylation biomarkers for early detection of gastric and colorectal cancers

Cancer is one of the leading causes of death worldwide.The early diagnosis of cancer remains one of the greatest cancer research challenges.Epigenetic alterations,such as altered DNA methylation,that occur during the early stages of carcinogenesis have been proposed as candidate cancer biomarkers.In recent years detection of small amounts of methylated DNA in samples,including blood and stool,has demonstrated the feasibility of DNA methylation as a molecular cancer biomarker.The translational promise of aberrant DNA methylation includes screening and detecting cancer,evaluating prognosis,assessing treatment efficacy,and detecting minimal residual disease(Figure 1).

Cytotoxicity of Cholesterol Oxides and the Consequences of Relative Molecular Similarity to cGMP Nucleotide

Cholesterol and cholesterol oxides impact on the functional properties of cells, in respect of the intracellular and extracellular distribution of compounds across cell membranes, carcinogenesis and drug resistance. Abnormal levels of cholesterol oxides and steroids in cancerous tissues promote interest in steroid receptor cross-talk during cell-signalling and the steroid metabolome of cancer patients. The research literature links the cytotoxic properties of oxysterols to interference with the NO/cGMP pathway. cGMP participates in cell-signalling and has a molecular structure that relates to cancer-inducing and cancer-preventing agents. This study uses a molecular modelling approach to compare the structures of cholesterol oxides to cGMP. Cholesterol and cholesterol oxide structures fit to a cGMP structural template in several ways, some of which are replicated by corticosteroids and gonadal steroid hormones. The results of this study support the concept that cholesterol oxides modulate cell apoptosis and autophagy via the NO/cGMP pathway and in conjunction with steroid hormones participate in modulating regulation of cell function by cGMP.

Nutritional, Textural, Sensory Properties and Storage Stability Evaluation of Newly Formulated Strawberry Bar

An analytical study was conducted to develop a strawberry bar and analysis of the nutritional quality and storage stability of a newly formulated strawberry bar. In proximate analysis moisture, ash, pH, acidity, vitamin C, total phenolic content, and antioxidant of strawberry pulp were found 82%, 0.5%, 2.57, 1.38%, 49 mg/100g, 0.33%, 75.17% whereas, in the strawberry bar, it was found 18%, 0.71%, 2.10, 1.10%, 22 mg/100g, 0.14%, 56.13% respectively. For textural properties analysis, the textural profile of the strawberry bar such as hardness, factorability, viscosity, cohesiveness, adhesiveness, springiness, gumminess, chewiness, probe diameter, threshold, filtering range of strawberry bar was found 5.538 × 104 N/m, 0.000 N/m2, 1.687 × 104 N/m2, 0.6636, 2.908 × 103 J/m3, 0.8664, 3.675 × 104 N/m2, 3.184 × 104 N/m2, 20.000 mm, 5 N, 0.4 N respectively whereas the maximum level was 17.4 N at 29.628 seconds and the minimum level was -5.3 N at 30.166 seconds. The sensory evaluation of the strawberry bar was conducted based on nine-point hedonic scales. The sensory evaluation results indicated that the appearance of the strawberry bar was liked very much and the taste, texture, color, aroma, and overall acceptability of the strawberry bar were liked moderately by panelists. In microbiological analysis, the Total Viable Count (TVC) and Total Coliform Count (TCC) of the strawberry bar were found safe levels for up to third days. But on the sixth day, the TCC of the strawberry bar was not found and the TVC of the strawberry bar was found 17 × 104 cfu/g respectively which is higher than the permitted value (Gulf Standard: 105 cfu/g). From the microbial point of view, the newly formulated strawberry bar was safe to consume for up to 3 days but not for 6 days.

Assessment of the Water Quality of the Benin River, Southern Nigeria, Prior to the Seaport Development Project

Water resources in the form of rivers, oceans and seas are prime natural resources that man has either explored or exploited. The need for clean water is on the increase and water degradation due to industrialization and development has further exacerbated the state of water bodies’ degradation. The need to assess the quality status of the Benin River prior to the seaport development was inherent to document the baseline of the physicochemical parameters of the study stretch. Four stations were studied from Ajoki to opposite Young Town between January 2019 and December 2020. Physicochemical parameters and heavy metals for water were collected and analyzed adhering to quality assurance/control measures and standard procedures. Significant spatial variations (P < 0.001) were observed in water physicochemical parameters, except pH across the four stations. Principal Component Analysis (PCA), Pollution Load Index and Water Quality Index (WQI) were used to establish a relationship among water quality parameters and determine the water quality status. The first six components of PCA accounted for 87.77% of observed variations. WQI for sampling Station 2 was very poor for drinking (90.46) and Stations 1, 3 and 4 were unsuitable (113.13 - 188.21) for human consumption. PLI showed turbidity as the major pollutant across stations. The concentrations of heavy metals in the Benin River stretch are within background concentration level, except Fe and Cd. The mean dissolved oxygen was below the recommended level of 7 mg/l for aquatic life. The continuous monitoring of this stretch of the River during the seaport development activities and during operational stage is very paramount to prevent further degradation of the environment.

Investigating the Effect of COVID-19 Infection on Professional Athletes’ Post-Infection with a Focus on Fatigue and Chronic Fatigue Syndrome

Introduction and Objectives: COVID-19 has been reported to cause long-term sequela including persistent fatigue and Chronic Fatigue Syndrome (CFS) in the general population. However, it remains to be seen if similar effects are observed in an athlete population. The aetiology and pathophysiology are poorly understood but is thought to be multi-factorial. Patient reported outcome measures are commonly used to improve patient-centred outcomes (PROMs). They are essential to assess patient quality of life post-COVID infection. This paper aims to assess the effect of COVID-19 on athletes’ long-term fatigue and CFS and identify the PROMs used to characterise this. Methodology: Articles were selected for extraction based on the eligibility criteria and PRISMA guidelines. The inclusion criteria required papers to assess competitive athletes over eighteen years of age who were clinically diagnosed with COVID-19. Articles were extracted to assess different variables including type of sport, type of athlete and ethnicity. Key terms were obtained using MeSH trees and utilised with Web of Science and NCBI Pubmed. Papers were graded by quality using the Hawker quality assessment tool. Results and Discussion: Forty articles (N = 40) were identified for full-text screening (N = 8). Eight were selected for extraction based on the eligibility criteria. Data was obtained on athlete characteristics, sport characteristics, properties of PROM measurement techniques and fatigue presentation. Male athletes were found to be 10% - 50% more likely than female athletes to suffer from persistent fatigue symptoms (N = 2). Persistent fatigue was present in 9% - 10% Athletes from mixed backgrounds and genders (N = 2). Initial fatigue was documented to be between 47% - 56% (N = 2). A heterogenous range of PROMs were utilised to assess symptoms including fatigue and excluded emotional or mental fatigue. Conclusion: COVID-19 is associated with signs of persisting fatigue and potentially CFS in athlete populations. More work needs to be done to develop standardised and validated PROMs specific to CFS.

Analysis of Regional Differences in Bone Mineral Density Acquisition Factors in Young Women

Purpose: Obtaining high peak bone mass (PBM) and maintaining bone mass is important for the prevention of osteoporosis. This study aimed to examine the regional differences in bone mineral density and factors associated with its acquisition from exercise. Design: The study population included 75 women of 18 - 22 years of age in East Japan and 104 women of 18 - 27 years of age in West Japan. The speed of sound (SOS) of the calcaneus was measured, and the young adult mean (%YAM) was calculated from the SOS. The subjects’ medical history, family history of osteoporosis, and exercise habits were examined using a self-administered questionnaire. Results: There were a significantly greater number of subjects with low %YAM in West Japan. The exercise history and exercise time were significantly higher in West Japan, and the exercise intensity score tended to be higher in East Japan during junior high and high school. A multiple regression analysis by region revealed that the following factors had a significant positive association with the SOS: exercise intensity at elementary school and outdoor sports at junior high school in East Japan;and exercise time at elementary school, muscle mass, and outdoor sports at junior high school in West Japan. On the other hand, exercise time in junior high school in West Japan showed a negative association with the SOS. Conclusions: Regional differences in bone mineral density existed, suggesting a trend toward lower bone mineral density in West Japan. Exercise history and time tended to be higher in West Japan, and exercise intensity scores tended to be higher in East Japan, suggesting that exercise intensity may be more important than exercise time for obtaining bone mineral density.

Adult neurogenesis:a real hope or a delusion?

Adult neurogenesis,the process of creating new neurons,involves the coordinated division,migration,and differentiation of neural stem cells.This process is restricted to neurogenic niches located in two distinct areas of the brain:the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle,where new neurons are generated and then migrate to the olfactory bulb.Neurogenesis has been thought to occur only during the embryonic and early postnatal stages and to decline with age due to a continuous depletion of neural stem cells.Interestingly,recent years have seen tremendous progress in our understanding of adult brain neurogenesis,bridging the knowledge gap between embryonic and adult neurogenesis.Here,we discuss the current status of adult brain neurogenesis in light of what we know about neural stem cells.In this notion,we talk about the importance of intra cellular signaling molecules in mobilizing endogenous neural stem cell prolife ration.Based on the current understanding,we can declare that these molecules play a role in targeting neurogenesis in the mature brain.However,to achieve this goal,we need to avoid the undesired proliferation of neural stem cells by controlling the necessary checkpoints,which can lead to tumorigenesis and prove to be a curse instead of a blessing or hope.