Biology subjects

Kim, J. H.

Publications and source records attributed to Kim, J. H..

At least 127 records · Page 7Linked to original sources

bioRxiv2020

Sex-dependent effects of chronic exercise on cognitive flexibility in aging mice

Cognitive impairments associated with advanced age are a growing concern in our aging society. Such impairments are associated with alterations in brain structure and function, especially in the hippocampus, which changes to experience throughout life. It is well-known that regular exercise can maintain hippocampus volume. The hippocampus is critical for cognitive flexibility involved with extinction and reinstatement of conditioned fear. Therefore, we asked whether voluntary chronic exercise in middle-aged mice can improve extinction and/or reinstatement of conditioned fear compared to standard housing. Eight-month-old male and female C57Bl/6J mice had access to a running wheel or remained in standard housing until 11 months of age. Alongside control standard-housed young adult (3-month-old) mice, they received tone-footshock pairings, which were subsequently extinguished with tone-alone presentations the next day. Half of the mice then received a reminder treatment in the form of a single footshock. Both male and female 11-month-old mice housed in standard conditions exhibited impaired reinstatement compared to young adult mice. However, for males that had access to a running wheel from 8 months of age, the reminder treatment rescued reinstatement ability. This was not observed in females. Additionally, exercise during middle age in both sexes increased expression of Bdnf mRNA in the hippocampus, specifically exon 4 mRNA. These results show that, at least for males, physical exercise is beneficial for reducing age-related decline in cognitive abilities. Despite not rescuing their impaired reinstatement, exercise also increased Bdnf gene expression in the female hippocampus, which could potentially benefit other forms of hippocampal-dependent cognition.

neuroscience↗

bioRxiv2020

Depth relationships and measures of tissue thickness in dorsal midbrain

Dorsal human midbrain contains two nuclei with clear laminar organization, the superior and inferior colliculi. These nuclei extend in depth between the superficial dorsal surface of midbrain and a deep midbrain nucleus, the periaqueductal gray matter (PAG). The PAG, in turn, surrounds the cerebral aqueduct (CA). This study examined the use of two depth metrics to characterize depth and thickness relationships within dorsal midbrain using the superficial surface of midbrain and CA as references. The first utilized nearest-neighbor Euclidean distance from one reference surface, while the second used a level-set approach that combines signed distance from both reference surfaces. Both depth methods provided similar functional depth profiles generated by saccadic eye movements in a functional MRI task, confirming their efficacy for superficial functional activity. Next, the boundaries of the PAG were estimated using Euclidean distance together with elliptical fitting, indicating that the PAG can be readily characterized by a smooth surface surrounding PAG. Finally, we used the level-set approach to measure tissue depth between the superficial surface and the PAG, thus characterizing the variable thickness of the colliculi. Overall, this study demonstrates depth-mapping schemes for human midbrain that enables accurate segmentation of the PAG and consistent depth and thickness estimates of the superior and inferior colliculi.

neuroscience↗

bioRxiv2020

Preterm birth impedes structural and functional development of cerebellar Purkinje cells in the developing baboon cerebellum.

Human cerebellar development occurs late in gestation and is hindered by preterm birth. The fetal development of Purkinje cells, the primary output cells of the cerebellar cortex, is crucial for the structure and function of the cerebellum. However, morphological and electrophysiological features in Purkinje cells at different gestational ages, and the effects of neonatal intensive care unit (NICU) experience on cerebellar development are unexplored. Utilizing non-human primate baboon cerebellum, we investigated Purkinje cell development during the last trimester of pregnancy and the effect of NICU experience following premature birth on developmental features of Purkinje cells. Immunostaining and whole-cell patch clamp recordings of Purkinje cells in the baboon cerebellum at different gestational ages revealed that molecular layer width, driven by Purkinje dendrite extension, drastically increased and refinement of action potential waveform properties occurred throughout the last trimester of pregnancy. Preterm birth followed by NICU experience for 2 weeks impeded development of Purkinje cells, including action potential waveform properties, synaptic input, and dendrite extension compared with age-matched controls. In addition, these alterations impact Purkinje cell output, reducing the spontaneous firing frequency in deep cerebellar nucleus (DCN) neurons. Taken together, primate cerebellum undergoes developmental refinements during late gestation, and NICU experience following preterm birth alters morphological and physiological features in the cerebellum that can lead to functional deficits. Summary StatementBaboon cerebellum undergoes developmental refinements during late gestation, and NICU experience following preterm birth impacts cellular development in the cerebellum that can lead to functional deficits.

developmental biology↗

bioRxiv2020

Adolescent rats show estrous cycle-mediated sex differences in extinction of conditioned fear

Anxiety disorders are more prevalent in females than males, and frequently emerge during adolescence. Despite this, preclinical research commonly focuses on adult males. Here we use Pavlovian fear conditioning and extinction in adolescent male and female rats to understand sex- and age-dependent processes relevant to anxiety disorders. In experiment 1, 35-day-old male and female rats were exposed to 6 pairings of a conditioned stimulus (CS, a tone) with an aversive unconditioned stimulus (US, a footshock). The next day they were extinguished in a contextually distinct chamber, via 60 presentations of the CS without the US. Extinction recall was tested 24 hours later in the extinction context. Estrous phase was monitored by cytology on vaginal smears taken 1 hour after each behavioral session. In experiment 2, male and female rats were given sham surgery or gonadectomy at 21 days of age. They were then trained and tested as for experiment 1. We observed that females in proestrus or met/diestrus during extinction showed delayed extinction and impaired extinction recall the next day compared to males. Ovariectomy enhanced extinction for female rats, but orchidectomy delayed extinction for males. Plasma analyses showed that met/di/proestrus phases were associated with high estradiol levels. These findings suggest that high plasma estradiol levels impair extinction for adolescent females. While these results contradict what is observed in adult animals, they are consistent with the prevalence of anxiety disorders observed in females. Our findings have important implications for understanding and treating anxiety in adolescents, particularly where treatment involves extinction-based therapies.

animal behavior and cognition↗

bioRxiv2020

Purging of deleterious mutations during domestication in the predominant selfing crop soybean

As a predominant plant protein and oil source for both food and feed, soybean is unique in that both domesticated and wild types are predominantly selfing. Here we present a genome-wide variation map of 781 soybean accessions that include 418 domesticated (Glycine max) and 345 wild (Glycine soja) accessions and 18 of their natural hybrids. We identified 10.5 million single nucleotide polymorphisms and 5.7 million small indels that contribute to within- and between-population variations. We describe improved detection of domestication-selective sweeps and drastic reduction of overall deleterious alleles in domesticated soybean relative to wild soybean in contrast to the cost of domestication hypothesis. This resource enables the marker density of existing data sets to be increased to improve the resolution of association studies.

genomics↗

bioRxiv2020

Successful Correction of ALD Patient-derived iPSCs Using CRISPR/Cas9

X-linked adrenoleukodystrophy (ALD) caused by the ABCD1 mutation, is the most common inherited peroxisomal disease. It is characterized by three phenotypes: inflammatory cerebral demyelination, progressive myelopathy, and adrenal insufficiency, but there is no genotype-phenotype correlation. Hematopoietic stem cell transplantation can only be used in a few patients in the early phase of cerebral inflammation; therefore, most affected patients have no curative option. Previously, we reported the generation of an ALD patient-derived iPSC model and its differentiation to oligodendrocytes. In this study, we have performed the first genome editing of ALD patient-derived iPSCs using homology-directed repair (HDR). The mutation site, c.1534G>A [GenBank: NM_000033.4], was corrected by introducing ssODN and the CRISPR/Cas9 system. The cell line exhibited normal ALD protein expression following genome editing. We differentiated the intermediate oligodendrocytes from mutation-corrected iPSCs and the metabolic derangement of ALD tended to correct but was not statistically significant. Mutation-corrected iPSCs from ALD patient can be used in research into the pathophysiology of and therapeutics for ALD.

neuroscience↗

bioRxiv2020

An original structural fold underlies the multitask P1, a silencing suppressor encoded by the Rice yellow mottle virus

ABSTRACTThe Rice Yellow Mottle sobemovirus (RYMV) belongs to the most damaging pathogens devastating rice fields in Africa. P1, a key protein for RYMV, was reported as a potent RNAi suppressor counteracting RNA silencing in plant reporter systems. Here we describe the complete 3D structure and dynamics of P1. Its N-terminal region contains ZnF1, a structural CCCC-type zinc finger strongly affine to zinc and a prominent short helix, rendering this region poorly amenable to structural changes. P1 C-terminal region contains ZnF2, an atypical HCHC-type ZnF that does not belong to any existing class of Zn finger proteins. ZnF2 appeared much less affine to zinc and more sensitive to oxidizing environments than ZnF1, and may serve as a sensor of plant redox status. The structure helped us to identify key residues essential for RYMV infectivity and spread in rice tissues through their participation in P1 oligomerization and folding. Altogether, our results provide the first complete structure of an antiviral silencing suppressor encoded by a virus infecting rice and highlight P1 structural and dynamical properties that may serve RYMV functions to infect and invade its host plant.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pathology↗

bioRxiv2019

Genome resequencing, improvement of variant calling, and population genomic analyses provide insights into the seedlessness in the genus Vitis

The seedlessness of grape derived from stenospermocarpy is one of the most prized traits of table or raisin grapes. It is controlled by a complex genetic system containing one major dominant gene and multiple minor recessive genes. Here, we collected dense variation data from high-depth resequencing data of seeded, seedless, and wild relative grape genomes sequenced to > 37x mean depth. Variant calls were made using a modified variant calling pipeline that was suitable for highly diverse interspecific grape accessions. The modified pipeline enabled us to call several million more variants than the commonly recommended pipeline. The quality was validated by Sanger sequencing data and subsequently supported by the genetic population structure and the phylogenetic tree constructed using the obtained variation data, results of which were generally consistent with known pedigree and taxonomic classifications. Variation data enabled us to confirm a major dominant gene and identify minor recessive loci for seedlessness. Incidentally, we found that grape cultivar Rizamat contains an ancestral chromosomal region of the major gene in Sultanina, a predominant seedlessness donor cultivar. Furthermore, we predicted new candidate causal genes including Vitvi01g00455, Vitvi08g01528, and Vitvi18g01237 associated with the minor seedless-regulating loci, which showed high homology with genes that regulate seed development in Arabidopsis. This study provides fundamental insights relevant to variant calling from genome resequencing data of diverse interspecific hybrid germplasms such as grape and will accelerate future efforts aimed at crop improvement.

genetics↗

bioRxiv2019

MyD88-Syk axis is a critical determinant for inflammatory response in macrophages

Inhibition of Syk or MyD88 decreased generation of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and consequent ROS/RNS-induced phagocytic activity in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Syk inhibition downregulated expression of ROS/RNS-generating enzymes by inhibiting the nuclear factor-kappa B (NF-kappa?B) signaling pathway and phagocytic activity by suppressing suppressor of cytokine signaling 1 (SOCS1) via its nitration in the LPS-stimulated RAW264.7 cells. Inhibition of ROS/RNS generation suppressed SOCS1 nitration, leading to a decrease in the phagocytic activity. Syk was activated by the interaction with MyD88, and the tyrosine 58 residue (Y58) in the hemi-immunoreceptor tyrosine-based activation motif (ITAM) of MyD88 was critical for interaction and consequent activation of Syk in macrophages. Src activated MyD88 by phosphorylation at Y58 via the Src kinase domain. Moreover, LPS-induced formation of filamentous actin (F-actin) and Ras-related C3 botulinum toxin substrate 1 (Rac1) activation induced Src activation. Conclusivley, these results suggest that the MyD88-Syk axis plays a pivotal role in macrophage-mediated inflammatory responses by inducing ROS/RNS generation and phagocytic activity via activation of Src and its upstream stimulators, F-actin and Rac1.

immunology↗

bioRxiv2019

Herpes Simplex Virus Infection, Acyclovir and IVIG Treatment All Independently Cause Gut Dysbiosis.

Herpes simplex virus 1 (HSV) is a ubiquitous human virus resident in a majority of the global population as a latent infection. Acyclovir (ACV), is the standard of care drug used to treat primary and recurrent infections, supplemented in some patients with intravenous immunoglobulin (IVIG) treatment to suppress deleterious inflammatory responses. We found that HSV, ACV and IVIG can all independently disrupt the gut bacterial community in a sex biased manner when given to uninfected mice. Treatment of HSV infected mice with ACV or IVIG alone or together revealed complex interactions between these drugs and infection that caused pronounced sex biased dysbiosis. ACV reduced Bacteroidetes levels in male but not female mice, while levels of the Anti-inflammatory Clostridia (AIC) were reduced in female but not male mice, which is significant as these taxa are associated with protection against the development of GVHD in hematopoietic stem cell transplant (HSCT) patients. Gut barrier dysfunction is associated with GVHD in HSCT patients and ACV also decreased Akkermansia muciniphila, which is important for maintaining gut barrier functionality. Cumulatively, our data suggest that long-term prophylactic ACV treatment of HSCT patients may contribute to GVHD and potentially impact immune reconstitution. These data have important implications for other clinical settings, including HSV eye disease and genital infections, where ACV is given long-term. Author SummaryPrimary and reactivated HSV and VZV infections are treated with Acyclovir (ACV), an antiviral drug that blocks viral DNA synthesis. In some patients IVIG is used as adjunctive therapy to block deleterious inflammation. Long term preventative treatment of patients who receive stem transplants for various blood cancers has been successful in preventing life threatening reactivated HSV and VZV infections, but GVHD remains a major factor limiting transplant success. Studies reported here reveal that HSV infection, ACV and IVIG given alone can all disrupt the gut microbiota and that complex interactions between these drugs and infection results in even more pronounced sex biased changes in the gut bacteria community structure. Importantly, ACV treatment decreased the levels of specific bacterial taxa, including the anti-inflammatory Clostriodia and Bacteroidetes that have been shown to protect against development of GVHD in stem cell transplant patients. These data suggest that long term preventative treatment of patients with ACV may contribute to GVHD in transplant patients and have negative consequences in other HSV induced diseases treated long term with ACV. The health effects of long term ACV and IVIG treatments warrant further clinical studies.

microbiology↗

bioRxiv2019

Metastatic function of METTL18 in breast cancer via actin methylation and Src

Recently, a SET domain containing 3 (SETD3) was identified as an actin histidine methyltransferase, functioning to control replication and pathogenesis in multiple mouse models for enterovirus infection as well as the regulation of smooth muscle contractility linked to primary dystocia. Here, in this study, we report another type of actin histidine methyltransferase, METTL18, that regulates the metastatic potential of breast cancer in human. Among methyltransferases, METTL18 was highly amplified in human breast cancer. In particular, poor prognosis was associated with high expression of METTL18 in HER2-negative breast cancer patients. This gene product was also found to be a critical component of metastatic responses. Loss of METTL18 expression significantly reduced metastatic responses of breast tumor cells both in vitro and in vivo. Mechanistically, it was observed that METTL18 increased actin polymerization, upregulated complex formation with HSP90AA1 and Src, enhanced the activity of an intermediate form of Src with tyrosine phosphorylation at both Y416 and Y527, and induced cellular metastatic responses, including morphological change, migration, and invasion of MDA-MB-231 cells in vitro and in mice. Methylated actin at His73 served as a critical site for interaction with HSP90AA1 and Src to activate p85/PI3K and STAT3. Our findings suggest that METTL18 plays critical roles in metastatic responses of HER2-negative breast cancer cells via actin polymerization and the generation of an intermediate form of Src.

cancer biology↗

bioRxiv2019

Foreign body responses in central nervous system mimic natural wound responses and alter biomaterial functions

Biomaterials hold promise for diverse therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign body responses (FBRs) in vivo, or about how such responses influence biomaterial function. Here, we probed these factors using a platform of injectable hydrogels readily modified to present interfaces with different representative physiochemical properties to host cells. We show that biomaterial FBRs mimic specialized multicellular CNS wound responses not present in peripheral tissues, which serve to isolate damaged neural tissue and restore barrier functions. Moreover, we found that the nature and intensity of CNS FBRs are determined by definable properties. For example, cationic, anionic or nonionic interfaces with CNS cells elicit quantifiably different levels of stromal cell infiltration, inflammation, neural damage and amyloid production. The nature and intensity of FBRs significantly influenced hydrogel resorption and molecular delivery functions. These results characterize specific molecular mechanisms that drive FBRs in the CNS and have important implications for developing effective biomaterials for CNS applications.

neuroscience↗

bioRxiv2019

Frameshift mutations of YPEL3 alter the sensory circuit function in Drosophila

A frameshift mutation in Yippee-like (YPEL) 3 was recently found from a rare human disorder with peripheral neurological conditions including hypotonia and areflexia. The YPEL gene family is highly conserved from yeast to human, but their functions are poorly defined. Moreover, the pathogenicity of the human YPEL3 variant is completely unknown. To tackle these issues, we generated a Drosophila model of human YPEL3 variant by CRISPR-mediated In-del mutagenesis. Gene-trap analysis suggests that Drosophila YPEL3 (dYPEL3) is predominantly expressed in subsets of neurons, including nociceptors. Analysis on chemical nociception induced by allyl-isothiocyanate (AITC), a natural chemical stimulant, revealed a reduced nociceptive response in dYPEL3 mutants. Subsequent circuit analysis showed a reduction in the activation of second-order neurons (SONs) in the pathway without affecting nociceptor activation upon AITC treatment. Although the gross axonal and dendritic development of nociceptors was not affected, the synaptic contact between nociceptors and SONs were decreased by dYPEL3 mutations. Together, these suggest that the frameshift mutation in human YPEL3 causes neurological conditions by weakening synaptic connection through presynaptic mechanisms.

neuroscience↗

bioRxiv2019

Gametophytes and embryo ontogeny: understanding the reproductive calendar of Cypripedium japonicum Thunb. (Cypripedoideae, Orchidaceae)

Among the flowering plants, the gametophyte development and reproductive biology of orchids is particularly poorly understood. Cypripedium japonicum is a perennial herb, native to East Asia. Due to its limited distribution, the species is included in the Endangered category of the IUCN Red List. Light microscopy and SEM methods were used to study the development of the gametes and embryo. The complete reproductive cycle was developed based on our observations. Anther development begins under the soil and meiosis of pollen cells begins 3 weeks before anthesis, possibly during early April. The megaspore mother cells develop just after pollination in early May and mature in mid-late June. The pattern of embryo sac formation is bisporic and there are six nuclei. Triple fertilization results in the endosperm nucleus. A globular embryo is formed after multiple cell division and 9 weeks after pollination the entire embryo sac is occupied by embryo. Overall comparisons of the features of gametophyte and embryo development in C. japonicum suggest that previous reports on the embryology of Cypripedium are not sufficient to characterize the entire genus. Based on the available information a reproductive calendar showing the key reproductive events leading to embryo formation has been prepared.\n\nHighlightManual pollination, reproductive biology and seed development process in Cypripedium japonicum Thunb., a ladys slipper orchid endemic to East Asia

developmental biology↗

bioRxiv2019

Inhibition of IRF4 in dendritic cells by PRR-independent and -dependent signals inhibit Th2 and promote Th17 responses

Cyclic AMP (cAMP) is involved in multiple biological processes. However, little is known about its role in shaping immunity. Here we show that cAMP-PKA-CREB signaling (a pattern recognition receptor [PRR]-independent) regulates conventional type-2 Dendritic Cells (cDC2s), but not cDC1s and reprograms their Th17-inducing properties via repression of IRF4 and KLF4, transcription factors (TFs) for Th2 induction. Genetic loss of IRF4 phenocopies the effects of cAMP signaling on Th17-induction, indicating that the cAMP effect is secondary to repression of IRF4. Moreover, signaling in cDC2s by a PRR-dependent microbial product, curdlan, represses IRF4 and KLF4, resulting in a pro-Th17 phenotype. These results define a novel signaling pathway by which cDC2s display plasticity and provide a new molecular basis for the novel cDC2 and cDC17 classification. In addition, the data reveal that cAMP signaling can alter DCs function and fate by repressing IRF4 and KLF4, a pathway that can be harnessed for immuno-regulation.

immunology↗

bioRxiv2019

Electronic Health Records Based Prediction of Future Incidence of Alzheimers Disease Using Machine Learning

Nationwide population-based cohort provides a new opportunity to build a completely automated risk prediction model based on individuals history of health and healthcare beyond existing risk prediction models. We tested the possibility of machine learning models to predict future incidence of Alzheimers disease (AD) using large-scale administrative health data. From the Korean National Health Insurance Service database between 2002 and 2010, we obtained de-identified health data in elders above 65 years (N=40,736) containing 4,894 unique clinical features including ICD-10 codes, medication codes, laboratory values, history of personal and family illness, and socio-demographics. To define incident AD two operational definitions were considered: "definite AD" with diagnostic codes and dementia medication (n=614) and "probable AD" with only diagnosis (n=2,026). We trained and validated a random forest, support vector machine, and logistic regression to predict incident AD in 1,2,3, and 4 subsequent years. For predicting future incidence of AD in balanced samples (bootstrapping), the machine learning models showed reasonable performance in 1-year prediction with AUC of 0.775 and 0.759, based on "definite AD" and "probable AD" outcomes, respectively; in 2-year, 0.730 and 0.693; in 3-year, 0.677 and 0.644; in 4-year, 0.725 and 0.683. The results were similar when the entire (unbalanced) samples were used. Important clinical features selected in logistic regression included hemoglobin level, age, and urine protein level. This study may shed a light on the utility of the data-driven machine learning model based on large-scale administrative health data in AD risk prediction, which may enable better selection of individuals at risk for AD in clinical trials or early detection in clinical settings.

bioinformatics↗

bioRxiv2019

Stxbp1/Munc18-1 haploinsufficiency in mice recapitulates key features of STXBP1 encephalopathy and impairs cortical inhibition

Mutations in genes encoding synaptic proteins cause many neurodevelopmental disorders, but the underlying pathogeneses are poorly understood. Syntaxin-binding protein 1 (STXBP1) is an essential component of the neurotransmitter release machinery. Its de novo heterozygous mutations are among the most frequent causes of neurodevelopmental disorders including intellectual disabilities and epilepsies. These disorders, collectively referred to as STXBP1 encephalopathy, affect a broad spectrum of neurological and neuropsychiatric features common among neurodevelopmental disorders. To gain insight into STXBP1 encephalopathy pathogenesis, we generated new Stxbp1 null alleles in mice and found that Stxbp1 haploinsufficiency impaired cognitive, psychiatric, and motor functions and caused cortical hyperexcitability and seizures. Surprisingly, Stxbp1 haploinsufficiency reduced neurotransmission from cortical parvalbumin- and somatostatin-expressing GABAergic interneurons by differentially decreasing the synaptic strength and connectivity, respectively. These results demonstrate that Stxbp1 haploinsufficient mice recapitulate key features of STXBP1 encephalopathy and indicate that inhibitory dysfunction is likely a key contributor to the disease pathogenesis.

neuroscience↗

bioRxiv2019

Elav-mediated exon skipping and alternative polyadenylation of the Dscam1 gene is required for axon outgrowth

Many metazoan genes express alternative long 3' UTR isoforms in the nervous system, but their functions remain largely unclear. In Drosophila melanogaster, the Dscam1 gene generates short and long (Dscam1-L) 3' UTR isoforms due to alternative polyadenylation (APA). Here, we found that the RNA-binding protein Embryonic Lethal Abnormal Visual System (Elav) impacts Dscam1 biogenesis at two levels, including regulation of long 3' UTR biogenesis and skipping of an upstream exon (exon 19). MinION long-read sequencing confirmed the connectivity of this alternative splicing event to the long 3' UTR. Knockdown or CRISPR deletion of Dscam1-L impaired axon growth in Drosophila. The Dscam1 long 3' UTR was found to be required for correct Elav-mediated skipping of exon 19. Elav thus co-regulates APA and alternative splicing to generate specific Dscam1 transcripts that are essential for neural development. This coupling of APA to alternative splicing might represent a new class of regulated RNA processing.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC=\"FIGDIR/small/613059_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (45K):\norg.highwire.dtl.DTLVardef@1a23558org.highwire.dtl.DTLVardef@5c3dddorg.highwire.dtl.DTLVardef@1e1808forg.highwire.dtl.DTLVardef@1bf3888_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIElav regulates Dscam1 long 3' UTR (Dscam1-L) biogenesis\nC_LIO_LILong-read sequencing reveals connectivity of long 3' UTR to skipping of upstream exon 19\nC_LIO_LILoss of Dscam1-L impairs axon outgrowth\nC_LIO_LIDscam1 long 3' UTR is required for correct splicing of exon 19\nC_LI

molecular biology↗