Development Function Research Articles

Multi-Subject Analysis for Brain Developmental Patterns Discovery via Tensor Decomposition of MEG Data.

Identification of informative signatures from electrophysiological signals is important for understanding brain developmental patterns, where techniques such as magnetoencephalography (MEG) are particularly useful. However, less attention has been given to fully utilizing the multidimensional nature of MEG data for extracting components that describe these patterns. Tensor factorizations of MEG yield components that encapsulate the data's multidimensional nature, providing parsimonious models identifying latent brain patterns for meaningful summarization of neural processes. To address the need for meaningful MEG signatures for studies of pediatric cohorts, we propose a tensor-based approach for extracting developmental signatures of multi-subject MEG data. We employ the canonical polyadic (CP) decomposition for estimating latent spatiotemporal components of the data, and use these components for group level statistical inference. Using CP decomposition along with hierarchical clustering, we were able to extract typical early and late latency event-related field (ERF) components that were discriminative of high and low performance groups ([Formula: see text]) and significantly correlated with major cognitive domains such as attention, episodic memory, executive function, and language comprehension. We demonstrate that tensor-based group level statistical inference of MEG can produce signatures descriptive of the multidimensional MEG data. Furthermore, these features can be used to study group differences in brain patterns and cognitive function of healthy children. We provide an effective tool that may be useful for assessing child developmental status and brain function directly from electrophysiological measurements and facilitate the prospective assessment of cognitive processes.

Interactive Effects of Temperature and Plant Host on the Development Parameters of Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae).

Simple SummaryThe beet armyworm Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae) is an economic pest that causes significant damage to various vegetables and field crops in Korea. Timely forecasting of pest emergence and occurrence plays a vital role in pest management. To predict the spring emergence and population dynamics of S. exigua, constant temperature-mediated developmental parameters of S. exigua were studied with linear and nonlinear models on different plant hosts. The temperature and plant host significantly influenced the development of S. exigua. The total developmental time decreased with the increase in temperature, although there was no development at extreme temperatures. We developed a forecasting model, and our findings predicted the spring emergence of S. exigua in June. Thus, continuous monitoring of S. exigua in crop fields is needed to be ready to take advanced management measures against S. exigua.This study investigated the effects of different temperatures (15, 20, 25, 27, 30, 35, and 40 °C) on the development rate of Spodoptera exigua (Hübner) eggs, larvae, pupae, and total immatures on plant hosts (soybean, maize, potato, and green pea). The eggs of S. exigua developed successfully at all the tested temperatures, except at 40 °C. The total developmental time (egg-adult) decreased with an increasing temperature from 15 to 35 °C on plant hosts. Stage-specific parameters such as the lower threshold temperature (TH) were determined using linear and nonlinear models (Sharpe-Schoolfield-Ikemoto [SSI]). The lower developmental threshold (LDT) and thermal constant (K) were determined using a linear model. The LDT and K for the total immature stage had respective values of 11.9 °C and 397.27° -day (DD) on soybean, 11.6 °C and 458.34° -day (DD) on maize, 11.2 °C and 446.23° -day (DD) on potato, 10.7 °C and 439.75° -day (DD) on green pea, and 12.2 °C and 355.82° -day (DD) on the artificial diet. The emergence frequency of adult S. exigua over the full range of constant temperatures was simulated using nonlinear developmental rate functions and the Weibull function. This study predicted the spring emergence date in the first to second weeks of June, with approximately five generations for plant hosts. The interaction of temperature and plant host also influenced the development and longevity of the adults. Overall, the findings of this study may be useful for predicting the number of generations, occurrence, population dynamics in crop fields, and management of S. exigua.

Expression of Key Factors of the Hippo Signaling Pathway in Yak (Bos grunniens) Mammary Gland.

Simple SummaryThe Hippo signaling pathway plays a significant role in regulating the organ development processes of mammals. Our research aimed to investigate the expression and distribution of key members of the Hippo signaling pathway in yak mammary glands during different stages. Using immunohistochemistry, Western blot, and relative quantitative real-time polymerase chain reaction techniques, we found that the protein and mRNA expression levels of MST1, LATS1, YAP1 and TEAD1 in the yak’s mammary gland varies with the growth, lactation, and dry periods. The differential expression in the yak’s mammary gland at different stages strongly suggests that the Hippo signaling pathway plays an important role in regulating the mammary gland development processes under different physiological conditions.Due to its rich nutritional value, yak milk is an important food source in the alpine pastoral areas. However, yaks have a low milk yield. The Hippo pathway participates in cell proliferation and organ development. We aimed to determine the regulatory mechanism of this pathway in yak mammary cells. A greater understanding of how the expression of its essential genes influence the reproductive cycle could lead to improvements in lactation performance. The expression levels of the key genes MST1, LATS1, YAP1, and TEAD1 were detected by quantitative real-time PCR, Western blotting, and immunohistochemistry during the growth, lactation, and dry periods (GP, LP and DP, respectively). The MST1 and LATS1 mRNA and protein expression level was highest during GP and lowest during LP. The YAP1 and TEAD1 mRNA and protein expression level decreased from GP to LP and DP. MST1 and LATS1 were expressed in the cytoplasm whereas YAP1 and TEAD1 were expressed in the nucleus and cytoplasm, respectively. The differential expression of MST1, LATS1, YAP1, and TEAD1 expression in the yak mammary gland during different developmental stages strongly suggests that they play an important role in the regulation of developmental functions under different physiological conditions.

Childhood-Onset Neurodegeneration with Cerebellar Atrophy Syndrome: Severe Neuronal Degeneration and Cardiomyopathy with Loss of Tubulin Deglutamylase Cytosolic Carboxypeptidase 1

The cytoskeleton is a dynamic filamentous network with various cellular and developmental functions. The loss of cytosolic carboxypeptidase 1 (CCP1) causes neuronal death. Childhood-onset neurodegeneration with cerebellar atrophy (CONDCA, OMIM no.: 618276) is an extremely rare disease caused by ATP/GTP binding protein 1 (AGTPBP1) gene-related CCP1 dysfunction of microtubules affecting the cerebellum, spinal motor neurons, and peripheral nerves. Also, possible problems are expected in tissues where the cytoskeleton plays a dynamic role, such as cardiomyocytes. In the present study, we report a novel homozygous missense (NM_015239: c.2447A > C, p. Gln816Pro) variant in the AGTPBP1 gene that c.2447A > C variant has never been reported in a homozygous state in the Genome Aggregation (gnomAD; v2.1.1) database, identified by whole-exome sequencing in a patient with a seizure, dystonia, dilated cardiomyopathy (DCM), and accompanying atrophy of caudate nuclei, putamen, and cerebellum. Unlike other cases in the literature, we expand the phenotype associated with AGTPBP1 variants to include dysmorphic features, idiopathic DCM which could be reversed with supportive treatments, seizure patterns, and radiological findings. These findings expanded the spectrum of the AGTPBP1 gene mutations and associated possible manifestations. Our study may help establish appropriate genetic counseling and prenatal diagnosis for undiagnosed neurodegenerative patients.

Understanding complex genetic architecture of rice grain weight through QTL-meta analysis and candidate gene identification

Quantitative trait loci (QTL) for rice grain weight identified using bi-parental populations in various environments were found inconsistent and have a modest role in marker assisted breeding and map-based cloning programs. Thus, the identification of a consistent consensus QTL region across populations is critical to deploy in marker aided breeding programs. Using the QTL meta-analysis technique, we collated rice grain weight QTL information from numerous studies done across populations and in diverse environments to find constitutive QTL for grain weight. Using information from 114 original QTL in meta-analysis, we discovered three significant Meta-QTL (MQTL) for grain weight on chromosome 3. According to gene ontology, these three MQTL have 179 genes, 25 of which have roles in developmental functions. Amino acid sequence BLAST of these genes indicated their orthologue conservation among core cereals with similar functions. MQTL3.1 includes the OsAPX1, PDIL, SAUR, and OsASN1 genes, which are involved in grain development and have been discovered to play a key role in asparagine biosynthesis and metabolism, which is crucial for source-sink regulation. Five potential candidate genes were identified and their expression analysis indicated a significant role in early grain development. The gene sequence information retrieved from the 3 K rice genome project revealed the deletion of six bases coding for serine and alanine in the last exon of OsASN1 led to an interruption in the synthesis of α-helix of the protein, which negatively affected the asparagine biosynthesis pathway in the low grain weight genotypes. Further, the MQTL3.1 was validated using linked marker RM7197 on a set of genotypes with extreme phenotypes. MQTL that have been identified and validated in our study have significant scope in MAS breeding and map-based cloning programs for improving rice grain weight.

The Rattlesnake W Chromosome: A GC-Rich Retroelement Refugium with Retained Gene Function Across Ancient Evolutionary Strata.

Sex chromosomes diverge after the establishment of recombination suppression, resulting in differential sex-linkage of genes involved in genetic sex determination and dimorphic traits. This process produces systems of male or female heterogamety wherein the Y and W chromosomes are only present in one sex and are often highly degenerated. Sex-limited Y and W chromosomes contain valuable information about the evolutionary transition from autosomes to sex chromosomes, yet detailed characterizations of the structure, composition, and gene content of sex-limited chromosomes are lacking for many species. In this study, we characterize the female-specific W chromosome of the prairie rattlesnake (Crotalus viridis) and evaluate how recombination suppression and other processes have shaped sex chromosome evolution in ZW snakes. Our analyses indicate that the rattlesnake W chromosome is over 80% repetitive and that an abundance of GC-rich mdg4 elements has driven an overall high degree of GC-richness despite a lack of recombination. The W chromosome is also highly enriched for repeat sequences derived from endogenous retroviruses and likely acts as a “refugium” for these and other retroelements. We annotated 219 putatively functional W-linked genes across at least two evolutionary strata identified based on estimates of sequence divergence between Z and W gametologs. The youngest of these strata is relatively gene-rich, however gene expression across strata suggests retained gene function amidst a greater degree of degeneration following ancient recombination suppression. Functional annotation of W-linked genes indicates a specialization of the W chromosome for reproductive and developmental function since recombination suppression from the Z chromosome.

Ocimum sanctum, OscWRKY1, regulates phenylpropanoid pathway genes and promotes resistance to pathogen infection in Arabidopsis.

OscWRKY1 from Ocimum sanctum positively regulates phenylpropanoid pathway genes and rosmarinic acid content. OscWRKY1 overexpression promotes resistance against bacterial pathogen in Arabidopsis. WRKY transcription factor (TF) family regulates various developmental and physiological functions in plants. PAL genes encode enzymes which are involved in plant defense responses, but the direct regulation of PAL genes and phenylpropanoid pathway through WRKY TF's is not well characterized. In the present study, we have characterized an OscWRKY1 gene from Ocimum sanctum which shows induced expression by methyl jasmonate (MeJA), salicylic acid (SA), and wounding. The recombinant OscWRKY1 protein binds to the DIG-labeled (Digoxigenin) W-box cis-element TTGAC[C/T] and activates the LacZ reporter gene in yeast. Overexpression of OscWRKY1 enhances Arabidopsis resistance towards Pseudomonas syringae pv. tomato Pst DC3000. Upstream activator sequences of PAL and C4H have been identified to contain the conserved W-box cis-element (TTGACC) in both O. sanctum and Arabidopsis. OscWRKY1 was found to interact with W-box cis-element present in the PAL and C4H promoters. Silencing of OscWRKY1 using VIGS resulted in reduced expression of PAL, C4H, COMT, F5H and 4CL transcripts. OscWRKY1 silenced plants exhibit reduced PAL activity, whereas, the overexpression lines of OscWRKY1 in Arabidopsis exhibit increased PAL activity. Furthermore, the metabolite analysis of OscWRKY1 silenced plants showed reduced rosmarinic acid content. These results revealed that OscWRKY1 positively regulates the phenylpropanoid pathway genes leading to the alteration of rosmarinic acid content and enhances the resistance against bacterial pathogen in Arabidopsis.

Distinct developmental and degenerative functions of SARM1 require NAD+ hydrolase activity.

SARM1 is the founding member of the TIR-domain family of NAD+ hydrolases and the central executioner of pathological axon degeneration. SARM1-dependent degeneration requires NAD+ hydrolysis. Prior to the discovery that SARM1 is an enzyme, SARM1 was studied as a TIR-domain adaptor protein with non-degenerative signaling roles in innate immunity and invertebrate neurodevelopment, including at the Drosophila neuromuscular junction (NMJ). Here we explore whether the NADase activity of SARM1 also contributes to developmental signaling. We developed transgenic Drosophila lines that express SARM1 variants with normal, deficient, and enhanced NADase activity and tested their function in NMJ development. We find that NMJ overgrowth scales with the amount of NADase activity, suggesting an instructive role for NAD+ hydrolysis in this developmental signaling pathway. While degenerative and developmental SARM1 signaling share a requirement for NAD+ hydrolysis, we demonstrate that these signals use distinct upstream and downstream mechanisms. These results identify SARM1-dependent NAD+ hydrolysis as a heretofore unappreciated component of developmental signaling. SARM1 now joins sirtuins and Parps as enzymes that regulate signal transduction pathways via mechanisms that involve NAD+ cleavage, greatly expanding the potential scope of SARM1 TIR NADase functions.

Systematic Identification and Expression Analysis of the Auxin Response Factor (ARF) Gene Family in Ginkgo biloba L.

Auxin participates in various physiological and molecular response-related developmental processes and is a pivotal hormone that regulates phenotypic formation in plants. Auxin response factors (ARFs) are vital transcription factors that mediate downstream auxin signaling by explicitly binding to auxin-responsive genes’ promoters. Here, to investigate the possible developmental regulatory functions of ARFs in Ginkgo biloba, through employing comprehensive bioinformatics, we recognized 15 putative GbARF members. Conserved domains and motifs, gene and protein structure, gene duplication, GO enrichment, transcriptome expression profiles, and qRT-PCR all showed that Group I and III members were highly conserved. Among them, GbARF10b and GbARF10a were revealed as transcriptional activators in the auxin response for the development of Ginkgo male flowers through sequences alignment, cis-elements analysis and GO annotation; the results were corroborated for the treatment of exogenous SA. Moreover, the GbARFs expansion occurred predominantly by segmental duplication, and most GbARFs have undergone purifying selection. The Ka/Ks ratio test identified the functional consistence of GbARF2a and GbARF2c, GbARF10b, and GbARF10a in tissue expression profiles and male flower development. In summary, our study established a new research basis for exploring Ginkgo GbARF members’ roles in floral organ development and hormone response.

Abstract 2440: Investigating the role of Eya3 in the regulation of NF-kB signaling and tumor progression in TNBC

Abstract Triple Negative Breast Cancer (TNBC), characterized by low/absent expression of the estrogen receptor and the HER2 growth factor receptor, has high rates of metastasis and an overall poor prognosis largely due to a lack of targeted therapeutic options. The Eyes absent (Eya) family of proteins are transcriptional cofactors with both intrinsic tyrosine phosphatase and associated serine/threonine phosphatase activities. In addition to developmental functions, Eyas have been shown to play a role in promoting many hallmarks of cancer. Published work from our laboratory demonstrated that Eya3 is capable of upregulating expression of PD-L1 in TNBC tumors thereby suppressing anti-tumor CD8+ T-cell responses, and preliminary data suggests that Eya3 may also regulate the expression of various cytokines in this context. In tumor cells, innate immune signaling pathways, such as NF-kB, have been shown to promote tumor progression, immune evasion, and metastasis in many distinct tumor types. We hypothesize that, in addition to regulating CD8+ T-cell responses, Eya3 regulates innate immune signaling in TNBC cells to facilitate enhanced primary tumor growth and metastasis. Preliminary findings suggest that Eya3 is a key mediator of tumor progression and metastasis in TNBC and a strong regulator of NF-kB signaling in this context. Further exploration is warranted to determine the mechanism through which Eya3 regulates these phenotypes, whether Eya3-mediated NF-kB activation is a major contributor to the pro-metastatic phenotype of Eya3, and whether Eya3 could serve as a therapeutic target for preventing or treating disseminated TNBC. Citation Format: Connor J. Hughes, Rebecca Mallo, Kaiah Fields, Hengbo Zhou, Annika Gustafson, Deguang Kong, Jill Slansky, Rui Zhao, Heide L. Ford. Investigating the role of Eya3 in the regulation of NF-kB signaling and tumor progression in TNBC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2440.

Measuring the developmental function of peer review: a multi-dimensional, cross-disciplinary analysis of peer review reports from 740 academic journals.

Reviewers do not only help editors to screen manuscripts for publication in academic journals; they also serve to increase the rigor and value of manuscripts by constructive feedback. However, measuring this developmental function of peer review is difficult as it requires fine-grained data on reports and journals without any optimal benchmark. To fill this gap, we adapted a recently proposed quality assessment tool and tested it on a sample of 1.3 million reports submitted to 740 Elsevier journals in 2018–2020. Results showed that the developmental standards of peer review are shared across areas of research, yet with remarkable differences. Reports submitted to social science and economics journals show the highest developmental standards. Reports from junior reviewers, women and reviewers from Western Europe are generally more developmental than those from senior, men and reviewers working in academic institutions outside Western regions. Our findings suggest that increasing the standards of peer review at journals requires effort to assess interventions and measure practices with context-specific and multi-dimensional frameworks.

Claudin-5a is essential for the functional formation of both zebrafish blood-brain barrier and blood-cerebrospinal fluid barrier

BackgroundMammalian Claudin-5 is the main endothelial tight junction component maintaining blood-brain barrier (BBB) permeability, while Claudin-1 and -3 seal the paracellular space of choroid plexus (CP) epithelial cells contributing to the blood-cerebrospinal fluid barrier (BCSFB). In zebrafish, two paralogs of claudin-5a and -5b are expressed while their roles in the formation of BBB and BCSFB are unclear.MethodsThe expression patterns of Claudin-5a and -5b in zebrafish brains were systematically analyzed by immunofluorescence (IF) assay. The developmental functions of Claudin-5a and -5b were characterized by generating of claudin-5a and -5b mutants respectively. Meanwhile, the cerebral inflammation and cell apoptosis in claudin-5a-/- were assessed by live imaging of transgenic zebrafish, RT-qPCR, IF, and TUNEL assay. The integrity of BBB and BCSFB was evaluated by in vivo angiographic and dye permeation assay. Finally, RT-qPCR, whole-mount RNA in situ hybridization (WISH), and transmission electron microscopy (TEM) analyses were performed to investigate the development of cerebral vessels and choroid plexus.ResultsWe showed that Claudin-5a and -5b are both expressed in zebrafish cerebrovascular endothelial cells (ECs). In addition, Claudin-5a was strongly expressed in CP epithelial cells. Loss of Claudin-5b showed no effect on zebrafish vasculogenesis or BBB function. In contrast, the knockout of claudin-5a caused a lethal phenotype of severe whole-brain oedema, ventricular dilatation, and cerebral hernia in zebrafish larvae, although the cerebral vasculogenesis and the development of CP were not altered. In claudin-5a-/- , although ultrastructural analysis of CP and cerebral capillary showed intact integrity of epithelial and endothelial tight junctions, permeability assay indicated a disruption of both BBB and BCSFB functions. On the molecular level, it was found that ZO-1 was upregulated in the CP epithelium of claudin-5a-/-, while the notch and shh pathway responsible for CP development was not affected due to loss of Claudin-5a.ConclusionsOur findings verified a non-functional role of zebrafish Claudin-5b in the BBB and identified Claudin-5a as the ortholog of mammalian Claudin-5, contributing to the development and the functional maintenance of both BBB and BCSFB.

ТЕСТ ЯК ЕФЕКТИВНИЙ ЗАСІБ ОЦІНЮВАННЯ ЯКОСТІ ЗНАНЬ СТУДЕНТІВ

Testing is one of the effective methods to evaluate the level of students’ skills and knowledge. The main purpose of testing is to develop the integrated technology, procedure and instrument for objective and reliable assessment of students’ academic achievements. As an evaluating tool, tests perform diagnostic, educational, developmental, administrative and prognostic functions. They could be applied at different stages of education process in order to obtain prompt and efficient data on the quality of students’ knowledge. Effective tests to meet certain requirements: compliance with the purpose, content and criterion of testing; determination of the difficulty level; detailed students’ instruction and previous partial approbation. Most teachers develop and use tests consisting of four levels of difficulty to assess students’ academic achievements. Among the advantages of test assessments, we define: standardized answers; time saving capacity; large amount of students’ skills and knowledge evaluated at a time; a number of students assessed; application of the computer technologies for students’ assessment etc. However, some drawbacks of tests are: high probability of the correct answer chosen by chance; assessment of students’ final results, not the process; certain categoricity of the answers. The attitude of students for higher education to the assessment of knowledge by means of testing is presented. The efficiency of students’ test assessment depends on the implementation of a number of methodological and organizational features. Along with other control tools, test tasks with computer support are very effective instruments, which stimulate better preparedness for classes and increase motivation to study the subjects. Interrogations can be substituted by computer tests during exams, knowledge checks, etc. The development and implementation of new approaches to the evaluation of a program achievements of the subjects of the educational the process increases the requirements for the quality of control, measurement and evaluation by means of testing in the conditions of distance learning.

Unravelling the sex-specific diversity and functions of adrenal gland macrophages.

SummaryDespite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We define the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and use genetic models to explore the developmental mechanisms yielding macrophage diversity. We define populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identify a female-specific subset with low major histocompatibility complex (MHC) class II expression. In adulthood, monocyte recruitment dominates adrenal gland macrophage maintenance in female mice. Adrenal gland macrophage sub-tissular distribution follows a sex-dimorphic pattern, with MHC class IIlow macrophages located at the cortico-medullary junction. Macrophage sex dimorphism depends on the presence of the cortical X-zone. Adrenal gland macrophage depletion results in altered tissue homeostasis, modulated lipid metabolism, and decreased local aldosterone production during stress exposure. Overall, these data reveal the heterogeneity of adrenal gland macrophages and point toward sex-restricted distribution and functions of these cells.

Problematyka zabawy w rozwoju dzieci przedszkolnych w świetle literatury przedmiotu

The aim of the author’s discussion is to present an overview of the issue of play and its importance for development of preschool children. The first part of the article focused on the reference to the definition and function of play. In the next part, various theories and classifications of play were presented. In the last part, play of younger and older preschool children was characterized. The conclusions emphasized the importance of the developmental function of play, as well as described it as the basic form of activity for preschool children.

Classifying Minority Stress Disclosure on Social Media with Bidirectional Long Short-Term Memory

Because of their stigmatized social status, sexual and gender minority (SGM; e.g., gay, transgender) people experience minority stress (i.e., identity-based stress arising from adverse social conditions). Given that minority stress is the leading framework for understanding health inequity among SGM people, researchers and clinicians need accurate methods to detect minority stress. Since social media fulfills important developmental, affiliative, and coping functions for SGM people, social media may be an ecologically valid channel for detecting minority stress. In this paper, we propose a bidirectional long short-term memory (BI-LSTM) network for classifying minority stress dis-closed on Reddit. Our experiments on a dataset of 12,645 Reddit posts resulted in an average accuracy of 65%.

Adolescent sleep shapes social novelty preference in mice.

Sleep disturbances frequently occur in neurodevelopmental disorders such as autism, but the developmental role of sleep is largely unexplored, and a causal relationship between developmental sleep defects and behavioral consequences in adulthood remains elusive. Here, we show that in mice, sleep disruption (SD) in adolescence, but not in adulthood, causes long-lasting impairment in social novelty preference. Furthermore, adolescent SD alters the activation and release patterns of dopaminergic neurons in the ventral tegmental area (VTA) in response to social novelty. This developmental sleep function is mediated by balanced VTA activity during adolescence; chemogenetic excitation mimics, whereas silencing rescues, the social deficits of adolescent SD. Finally, we show that in Shank3-mutant mice, improving sleep or rectifying VTA activity during adolescence ameliorates adult social deficits. Together, our results identify a critical role of sleep and dopaminergic activity in the development of social interaction behavior.

Helix-Loop-Helix Proteins in Adaptive Immune Development.

The E/ID protein axis is instrumental for defining the developmental progression and functions of hematopoietic cells. The E proteins are dimeric transcription factors that activate gene expression programs and coordinate changes in chromatin organization. Id proteins are antagonists of E protein activity. Relative levels of E/Id proteins are modulated throughout hematopoietic development to enable the progression of hematopoietic stem cells into multiple adaptive and innate immune lineages including natural killer cells, B cells and T cells. In early progenitors, the E proteins promote commitment to the T and B cell lineages by orchestrating lineage specific programs of gene expression and regulating VDJ recombination of antigen receptor loci. In mature B cells, the E/Id protein axis functions to promote class switch recombination and somatic hypermutation. E protein activity further regulates differentiation into distinct CD4+ and CD8+ T cells subsets and instructs mature T cell immune responses. In this review, we discuss how the E/Id proteins define the adaptive immune system lineages, focusing on their role in directing developmental gene programs.

Understanding astrocyte differentiation: Clinical relevance, technical challenges, and new opportunities in the omics era.

Astrocytes are a major type of glial cells that have essential functions in development and homeostasis of the central nervous system (CNS). Immature astrocytes in the developing CNS support neuronal maturation and possess neural‐stem‐cell‐like properties. Mature astrocytes partially lose these functions but gain new functions essential for adult CNS homeostasis. In pathological conditions, astrocytes become “reactive”, which disrupts their mature homeostatic functions and reactivates some immature astrocyte‐like properties, suggesting a partial reversal of astrocyte maturation. The loss of homeostatic astrocyte functions contributes to the pathogenesis of various neurological conditions, and therefore activating maturation‐promoting mechanisms may be a promising therapeutic strategy to restore homeostasis. Manipulating the mechanisms underlying astrocyte maturation might also allow to facilitate CNS regeneration by enhancing developmental functions of adult astrocytes. However, such therapeutic strategies are still some distance away because of our limited understanding of astrocyte differentiation and maturation, due to biological and technical challenges, including the high degree of similarity of astrocytes with neural stem cells and the shortcomings of astrocyte markers. Current advances in systems biology have a huge potential to overcome these challenges. Recent transcriptomic analyses have already revealed new astrocyte markers and new regulators of astrocyte differentiation. However, the epigenomic changes that presumably occur during astrocyte differentiation remain an important, largely unexplored area for future research. Emerging technologies such as CRISPR/Cas9‐based functional screens will further improve our understanding of the mechanisms underlying astrocyte differentiation. This may open up new clinical approaches to restore homeostasis in neurological disorders and/or promote CNS regeneration.This article is categorized under:Neurological Diseases > Genetics/Genomics/EpigeneticsNeurological Diseases > Stem Cells and DevelopmentNeurological Diseases > Molecular and Cellular Physiology

Proteins Involved in Synaptic Plasticity Are Downregulated in the Cerebrospinal Fluid of Infants With Clinical Sepsis Complicated by Neuroinflammation.

Newborn infants are prone to sepsis and related inflammation of different organs. Neuroinflammation has been associated with long-term adverse neuronal (neuropsychiatric/neurodegenerative) outcomes, including attention deficit hyperactivity disorder (ADHD) or even Alzheimer's disease. Despite a vast number of findings on sepsis-induced inflammatory responses in the central nervous system (CNS), how neuroinflammation affects brain development remains largely elusive. In this study, neonates with clinical sepsis and screened for meningitis were included and classified by the neuroinflammation status based on cerebrospinal fluid (CSF) parameters (INF vs. NOINF). CSF samples collected from clinical screening were subjected to proteomics analysis. Proteins with differential abundance were subjected to enrichment analysis to reveal affected biological pathways. INF and NOINF infants had similar demographic data and hematological and biochemical parameters in blood and CSF. The CSF proteomes were essentially different between the two groups. All 65 proteins with differential abundance showed lower abundance in the INF group and functionally covered pivotal developmental processes, including axonal and synaptic function and extracellular homeostasis. CSF proteins, PTPRZ1 and IGFBP4, were correlated with C-reactive protein (CRP) and ratios of immature/total neutrophils in blood. In general, a substantial change in the CSF protein profile was found under neuroinflammation, and these changes are related to systemic conditions. The results suggest that changes in CSF proteins may be involved in sepsis-affected neurodevelopment, such as disturbances in circuit formation, which has the potential to predispose neonates to long-term adverse outcomes.