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Brn-3.2: a Brn-3-related transcription factor with distinctive central nervous system expression and regulation by retinoic acid.

The identification and molecular characterization of Brn-3.2 has revealed a family of Brn-3-related mammalian POU proteins that share homology with the C. elegans developmental regulator Unc-86 and extended similarity with the Drosophila neurodevelopmental gene I-POU, which defines a novel POU-IV box. Brn-3.2 exhibits DNA binding properties similar to those of Brn-3.0, but its expression is uniquely regulated by retinoic acid in teratocarcinoma and neuroblastoma cells. In the developing PNS and retina, the expression pattern of Brn-3.2 is similar to that of Brn-3.0. In the caudal CNS (spinal cord, hindbrain, and midbrain) Brn-3.2 and Brn-3.0 are initially coexpressed, but diverge later in development. Rostral to the midbrain, Brn-3.2 and Brn-3.0 exhibit nonoverlapping patterns of expression, suggesting divergence of gene function in more recently evolved structures. Our analysis suggests that in the CNS Brn-3.2 is selectively expressed in postmitotic neurons, implying a role in specifying terminally differentiated neuronal phenotypes.

Amino Acid Sequence↗

Protein translocation across the endoplasmic reticulum.

In the past year, dramatic progress has been made in our understanding of protein biogenesis at the initial steps of the eukaryotic secretory pathway. New insights have refined our view of protein targeting to the endoplasmic reticulum membrane and provided the best glimpse so far of the subsequent translocation step. The interactions of three GTP-binding proteins have been found to result in a novel cycle of GTP binding and hydrolysis to regulate protein targeting. Experiments with fluorescent probes have revealed that the nascent chain enters an aqueous environment within the membrane sealed off from the cytosol. In vitro reconstitution experiments have shown surprising simplicity in the number of polypeptides required to facilitate translocation across a synthetic membrane and to promote the integration of membrane proteins. Furthermore, new genetic and functional similarities between divergent organisms have been discovered, providing convincing evidence of the evolutionary conservation of strategies used in the targeting and translocation of polypeptides.

Animals↗

Trout CC chemokines: comparison of their sequences and expression patterns.

Several thousand EST sequences were recently made available in the EMBL sequence database from the rainbow trout Oncorhynchus mykiss. BLAST based searches were utilised to identify sequences resembling mammalian CC chemokines within these ESTs. Fifteen new and unique CC chemokine-like sequences were identified for trout, bringing the total of known CC chemokine sequences in trout to 18 when including those already published. Some of these trout chemokines appeared highly related (in pairs) suggesting recent duplication events or tight evolutionary constraints. Phylogenetically, the trout chemokine sequences grouped with both inducible and constitutive mammalian CC chemokine subtypes, suggesting early divergence of these functional groups. Expression analyses on gill and head kidney show constitutive expression of many of these trout CC chemokines in these lymphoid-rich tissues. However, induction of some of the chemokines structurally related to 'inducible' CC chemokines was observed in a trout macrophage-like cell line (RTS-11) in response to stimulation with recombinant TNFalpha.

Amino Acid Sequence↗

Neural correlates of symbolic and non-symbolic arithmetic.

Recent evidence suggests that areas in and around the intraparietal sulcus (IPS) represent magnitude in a stimulus-independent format. However, it has not been established whether the same is true for mental arithmetic or whether activation for higher level numerical processing diverges as a function of stimulus format. We addressed this question in a functional imaging study by presenting participants with simple addition problems using both symbolic (Arabic numerals) and non-symbolic (arrays of dots) stimuli. Conjunction analysis revealed common neural substrates for symbolic and non-symbolic addition in the anterior IPS bilaterally, left posterior IPS, medial frontal gyrus and left precentral gyrus. Right parietal and frontal cortex showed greater activation for non-symbolic addition. Our results demonstrate that mental arithmetic, studied using addition problems, is processed within the IPS independent of stimulus form. Additionally we examined whether exact and approximate addition conditions activated different neural substrates as a function of stimulus format. We did not find any differences between exact and approximate addition using symbolic and non-symbolic stimuli. This could be due to the inability of the participants to suppress exact calculation for single-digit addition problems. In contrast to recent findings, we found no significant activation for exact addition condition in left, language-related areas.

Adult↗

Transcription factor families in Arabidopsis: major progress and outstanding issues for future research.

Transcription factors (TFs) are a group of proteins that control cellular processes by regulating the expression of downstream target genes. Recent progress has been made in the cloning and characterization of Arabidopsis TFs on the genome scale, especially on the cloning of open reading frames (ORFs), sequence analysis and the expression profiling of different TF families. Huge difference in numbers of subfamily members were found for Arabidopsis MYB, C2H2 (Zn), C3H-type 1 (Zn), C3H-type 2 (Zn) TFs by independent research groups, mainly because of differences in bioinformatic search stringency. However, the Arabidopsis and rice genomes contain very different numbers of TFs in the WRKY, NAC, bZIP, MADS, ALFIN-like, GRAS and C2C2 (Zn)-dof families, indicating a possible divergence of biological functions from dicots to monocots. TFs have also been found to play key roles in the biosynthesis and signaling of plant hormones, in cell growth and differentiation, and in photomorphogenesis.

Abscisic Acid↗

Molecular mechanisms underlying the modulation of exocytotic noradrenaline release via presynaptic receptors.

The release of noradrenaline from nerve terminals is modulated by a variety of presynaptic receptors. These receptors belong to one of the following three receptor superfamilies: transmitter-gated ion channels, G protein-coupled receptors (GPCR), and membrane receptors with intracellular enzymatic activities. For representatives of each of these three superfamilies, receptor activation has been reported to cause either an enhancement or a reduction of noradrenaline release. As these receptor classes display greatly diverging structures and functions, a multitude of different molecular mechanisms are involved in the regulation of noradrenaline release via presynaptic receptors. This review gives a short overview of the presynaptic receptors on noradrenergic nerve terminals and summarizes the events involved in vesicle exocytosis in order to finally delineate the most important signaling cascades that mediate the modulation via presynaptic receptors. In addition, the interactions between the various presynaptic receptors are described and the underlying molecular mechanisms are elucidated. Together, these presynaptic signaling mechanisms form a sophisticated network that precisely adapts the amount of noradrenaline being released to a given situation.

Animals↗

Two distinctive apomorphine-induced phenotypes in the Roman high- and low-avoidance rats.

Strain differences in spontaneous locomotor activity and the behavioral patterns induced by dopaminergic agonists in rodents can disclose differential genetic susceptibilities to dopaminergic dysfunction (i.e. vulnerability to psychosis). Psychogenetic selection of hypoemotional Roman High-Avoidance (RHA) and hyperemotional Low-Avoidance (RLA) rats leads to divergence in dopaminergic function as well. The present study was designed to characterize their spontaneous activity and their responses to apomorphine (0.067-3 mg/kg, s.c.) as compared to those of the standard Sprague-Dawley (SD) strain. The Roman strains displayed higher spontaneous activity than SD rats and RHA exhibited the higher response to novelty which agrees with a higher sensitivity to apomorphine in this strain. The biphasic effect induced by apomorphine (locomotor inhibition and yawning at low doses but stimulation of locomotion and stereotyped behavior at higher ones) was reproduced in the standard SD strain. Low doses were less effective inducing locomotor inhibition in RHA whereas these animals were much more sensitive to high dose-induced stereotyped behavior. In contrast, RLA was characterized as a high-yawning strain and low doses of apomorphine also induced a striking motor inhibition suggesting functional enhancement of dopamine receptors mediating these behaviors. The detailed and distinctive behavioral profiles described in this work suggest between strain differences both at the presynaptic and postsynaptic dopaminergic function and may serve as paths to better specify functional mechanisms in future studies of risk of developing dopaminergic dysfunctions.

Animals↗

Nested deletion analysis of Wheat streak mosaic virus HC-Pro: Mapping of domains affecting polyprotein processing and eriophyid mite transmission.

A series of in-frame and nested deletion mutations which progressively removed 5'-proximal sequences of the Wheat streak mosaic virus (WSMV) HC-Pro coding region (1152 nucleotides) was constructed and evaluated for pathogenicity to wheat. WSMV HC-Pro mutants with 5'-proximal deletions of 12 to 720 nucleotides systemically infected wheat. Boundary sequences flanking the deletions were stable and unaltered by passage through plants for all deletion mutants except HCD12 (lacking HC-Pro codons 3-6) that exhibited strong bias for G to A substitution at nucleotide 1190 in HC-Pro codon 2 (aspartic acid to asparagine). HC-Pro mutants with 5'-proximal deletions of up to 720 nucleotides retained autoproteolytic activity in vitro. In contrast, 5'-proximal deletion of 852 nucleotides of the HC-Pro coding region (HCD852) abolished both infectivity and in vitro proteolytic activity, confirming that the proteolytic domain of WSMV HC-Pro resides within the carboxy-terminal third of the protein and includes the cysteine proteinase motif (GYCY) conserved among four genera of the family Potyviridae. Inoculation of wheat with HC-Pro deletion mutants also bearing the GUS reporter gene revealed that HCD852 was unable to establish primary infection foci in inoculated leaves, indicating that processing of the P3 amino-terminus was essential. Deletion of as few as 24 nucleotides of HC-Pro (codons 3-10) eliminated transmission by the eriophyid mite vector Aceria tosichella Keifer. Collectively, these results demonstrated similar organization of proteinase and vector transmission functional domains among divergent HC-Pro homologues encoded by potyviruses and tritimoviruses.

Amino Acid Sequence↗

AI-enabled viral genomics: from virus discovery to host prediction and emerging variant forecasting.

The rapid expansion of metagenomic sequencing has generated vast repositories of viral sequence data that far outpace our capacity to interpret them using conventional approaches. Highly divergent sequences, sparse functional annotation, and taxonomically uneven sampling present fundamental challenges for reference-dependent methods, which lose sensitivity precisely for novel and understudied viruses with high public health relevance. Artificial intelligence (AI) provides a new avenue to address these challenges by enabling predictive inference from viral genomes and proteins while reducing dependence on sequence similarity. In this Review, we discuss representative advances in AI for virus discovery, taxonomic classification and functional annotation, prediction of host range and zoonotic potential, and efforts toward forecasting emerging variants. These advances are transforming viral genomics from a largely descriptive discipline into one with increasing predictive capability. We also critically assess the major challenges that constrain current approaches, including the availability of high-quality and representative datasets, rigorous model evaluation, biological interpretability and responsible governance for increasingly capable AI models.

Artificial Intelligence↗

Structural components of the synaptonemal complex, SYCP1 and SYCP3, in the medaka fish Oryzias latipes.

The synaptonemal complex (SC) is a meiosis-specific structure essential for synapsis of homologous chromosomes. For the first time in any non-mammalian vertebrates, we have isolated cDNA clones encoding two structural components of the SC, SYCP1 and SYCP3, in the medaka, and investigated their protein expression during gametogenesis. As in the case of mammals, medaka SYCP1 and SYCP3 are expressed solely in meiotically dividing cells. In the diplotene stage, SYCP1 is diminished at desynaptic regions of chromosomes and completely lost on the chromosomes at later stages. SYCP3 is localized along the arm and centromeric regions of chromosomes at metaphase I, and its existence on the whole chromosomes persists up to anaphase I, a situation different from that reported in the mouse, in which SYCP3 is confined to the centromeric regions but lost on the arm regions at metaphase I. Thus, the expression patterns of SC components are different in mammals and fish despite the resemblance in morphological structure of the SC, suggesting divergence in the function of the SC in regulation of meiosis-specific chromosomal behavior. Since the antibody against medaka SYCP3 is cross-reactive to other fishes, it should be generally useful for a meiosis-specific marker in fish germ cells.

Animals↗

Structures for the proopiomelanocortin family genes proopiocortin and proopiomelanotropin in the sea lamprey Petromyzon marinus.

Gnathostomes express a common proopiomelanocortin (POMC) gene in the pars distalis (PD) and the pars intermedia (PI) of the pituitary gland. In contrast, the sea lamprey Petromyzon marinus expresses one distinct gene in each lobe; proopiocortin (POC) encoding adrenocorticotropic hormone (ACTH) and beta-endorphin (END) is expressed in the PD and proopiomelanotropin (POM) encoding melanophore-stimulating hormone (MSH), and a different beta-END is expressed in the PI. We characterized the genomic structure of the sea lamprey POC and POM genes including their 5'-flanking regions. Both genes have two introns at positions similar to those of gnathostomes. Each exon encodes genetic information seen in the gnathostome POMC gene: exon 1 encodes an untranslated nucleotide sequence, exon 2 encodes a signal peptide and the N-terminal short part of POC or POM, and exon 3 encodes all other parts including ACTH, MSHs or beta-END. Intron-A of POM (2289 bp) is six times longer than that of POC (379 bp). The POM intron-A has three transposon-like sequences (TnL-1, -2, -3), the total length of which is 1781 bp, suggesting that it has expanded via the insertion of TnLs. The 5'-flanking region of the POC gene contains two TATA boxes, a CCAAT box, eight E boxes, STAT, RAIE, and one binding site each for Ptx1, Pit-1, and Tpit. The POM gene contains four TATA boxes, eight E boxes, three STATs, two RAIEs, two CRE-like elements, and one binding site for Pit1. However, there is virtually no similarity between the two genes in the distribution of the elements. The transcriptional regulation of POC and POM may have diverged with the functional differentiation of the two genes.

Adrenocorticotropic Hormone↗

The internal transcribed spacer of nuclear ribosomal DNA in the gymnosperm Gnetum.

We analyze the structure of the internal transcribed spacers ITS1 and ITS2 of the nuclear ribosomal DNA in the gymnosperm Gnetum, using a phylogenetic framework derived mainly from an intron in the nuclear low-copy LEAFY gene. Gnetum comprises 25-35 species in South America, Africa, and Asia, of which we sampled 16, each with two to six clones. Criteria used to assess ITS functionality were highly divergent nucleotide substitution, GC content, secondary structure, and incongruent phylogenetic placement of presumed paralogs. The length of ITS1 ranged from 225 to 986 bp and that of ITS2 from 259 to 305 bp, the largest ranges so far reported from seed plants. Gnetum ITS1 contains two informative sequence motifs, but different from other gymnosperms, there are only few and short (7-13 bp) tandem repeats. Gnetum ITS2 contains two structural motifs, modified in different clades by shortening of stems and loops. Conspecific sequences grouped together except for two recombinant pseudogenes that had ITS1 of one clade and ITS2 of another. Most of the pseudogenic ITS copies, paralogs, and putative chimeras occurred in a clade that according to a fossil-calibrated chloroplast-DNA clock has an age of a few million years. Based on morphology and chromosome numbers, the most plausible causes of the observed high levels of ITS polymorphism are hybridization, allopolyploidy, and introgression.

Base Composition↗

Ancient gene duplication and domain shuffling in the animal cyclic nucleotide phosphodiesterase family.

The animal cyclic nucleotide phosphodiesterases (PDEs) comprise at least seven subtypes, PDE1-7, which differ from each other in domain organization and primary function, and they diverged from an ancestral gene by gene duplication and domain shuffling during animal evolution. To obtain rough estimates for the divergence times of these subtypes, cloning of PDE cDNAs from Ephydatia fluviatilis (freshwater sponge) by RT-PCR was carried out. We obtained four cDNAs, EFPDE1, EFPDE2, EFPDE3, and EFPDE4, which are possibly homologs of the vertebrate PDE1, PDE2, PDE3, and PDE4, respectively, judging from the sequence similarity, domain organization, and branching pattern in the phylogenetic tree. The phylogenetic tree of the PDE family revealed that most gene duplications and domain shufflings that gave rise to different subtypes had been completed in the early evolution of animals before the separation of sponges and eumetazoans.

3',5'-Cyclic-AMP Phosphodiesterases↗

The amino acid sequence of a lamprey (Entosphenus japonicus) liver fatty acid-binding protein identified its close relationship to cardiac fatty acid-binding proteins of Mammalia.

Fatty acid-binding proteins (FABPs) constitute a large, tissue-specific multigene family in animals. While liver FABPs of Aves, Reptilia, and Amphibia are close homologs of mammalian liver FABPs, the shark liver protein belongs to the mammalian heart FABP subfamily. We purified an FABP from the liver of lamprey, Entosphenus japonicus, by gel filtration and anion-exchange chromatography. Amino acid sequences determined for lysyl endopeptidase peptides covered nearly the entire molecule except for N- and C-terminal short segments. Examination of the phylogenetic relationship from the sequence identified the lamprey liver protein as a member of mammalian heart-type FABPs. Since livers of bony fish contain both hepatic and cardiac FABPs, expression of the FABP gene in the vertebrate liver appears to change from the heart-type to liver-type within Pisciformes, with bony fish being in a transition stage. This may be related to the evolutionary and physiological divergence of liver function and lipid metabolism of these lower vertebrates.

Amino Acid Sequence↗

The uvsF gene region in Aspergillus nidulans codes for a protein with homology to DNA replication factor C.

The UV-sensitive mutant uvsF201 of Aspergillus nidulans shows increased spontaneous and UV-induced mutation and generally resembles mutants defective in nucleotide excision repair (NER). Fully-complementing uvsF clones were isolated from cosmid and cDNA libraries for sequencing. The uvsF gene is approximately 3.75 kb long and codes for a predicted polypeptide of 1092 amino acids (aa). Three small introns are clustered early in the coding region of the protein. A major part of the sequence shows homology to human, mouse and yeast RFC1 genes which code for the large subunit of the DNA replication factor C. The uvsF gene product may therefore function primarily in general DNA replication but in addition be required for the replication step of DNA repair. Extended sequencing of the uvsF gene region identified a second closely adjacent gene of unknown function which is divergently transcribed from a small (0.2 kb) intergenic promoter region.

Amino Acid Sequence↗

Invertebrate myogenesis: looking back to the future of muscle development.

Recent studies in invertebrates have provided important mechanistic insights into several general aspects of muscle development. Two new genes have been identified that are involved in muscle fusion in Drosophila and a novel maternal component was shown to be responsible for myogenic determination in an ascidian. In addition, genetic analyses of nematode and Drosophila homologues of factors known to be myogenic regulators in other species yielded surprising findings about both the evolutionary conservation and divergence of these functions. Drosophila myogenesis has become a highly informative model for understanding the interplay between the signaling and transcriptional networks that underlie cell-fate specification during embryonic development.

Animals↗

A statistical test for the difference in the amounts of DNA variation between two populations.

A statistical test for the difference in the amounts of DNA variation between two populations is developed. The test statistic involves the covariance of the amount of variation between two populations, which is given by a function of their divergence time, T0. Accordingly, the power (rejection probability) of the test depends on T0. In this article, T0 is treated as unknown because it is very difficult to estimate. The test is most conservative when T0 = infinity is assumed because the covariance is zero. If T0 = 0 is assumed, the largest value of the rejection probability is obtained. Thus, the test provides a range of rejection probability unless we have a reliable estimate of T0. The test is applied to the PgiC region in three mustard species: Leavenworthia stylosa, L. crassa and L. uniflora. The results of our test show that the level of variation in L. stylosa is significantly higher than those in the other species.

DNA, Plant↗

Development of categorical identification of native and non-native bilabial stops: infants, children and adults.

Using an infant speech identification (ISI) procedure, English language environment infants, two- and six-year-old children, and adults were tested for their identification of sounds on a native (voiced/voiceless bilabial stop) and a non-native (prevoiced/voiced bilabial stop) speech continuum. Categorical perception of the two contrasts diverged as a function of age, increasing for the native contrast and decreasing for the non-native between two and six years. In Experiment 2, subjects of the same four ages were tested for their identification of a continuum of harmonic tones varying in pitch. Comparison of the results of Experiment 1 with the essentially continuous perception of this pitch continuum supports the view that the perception of the native contrast becomes more categorical with age, while perception of the non-native contrast becomes less categorical, especially at six years. Experiment 3, in which adults were tested on the three continua with a multi-trial open set procedure, demonstrated that results with the ISI procedure in Experiments 1 and 2 are comparable to results with more traditional methods. The results of the three experiments are discussed in terms of the role of specific linguistic experience in the development of categorical speech perception.

Adult↗