Ganglionic eminence: volumetric assessment of transient brain structure utilizing fetal magnetic resonance imaging.

OBJECTIVE: To provide quantitative magnetic resonance imaging (MRI) super-resolution-based three-dimensional volumetric reference data on the growth dynamics of the ganglionic eminence (GE) relative to cortical and total fetal brain volumes (TBV). METHODS: This was a retrospective study of fetuses without structural central nervous system anomalies or other confounding comorbidities that were referred for fetal MRI. Super-resolution reconstructions of 1.5- and 3-Tesla T2-weighted images were generated. Semiautomatic segmentation of TBV and cortical volume and manual segmentation of the GE were performed. Cortical volume, TBV and GE volume were quantified and three-dimensional reconstructions were generated to visualize the developmental dynamics of the GE. RESULTS: Overall, 120 fetuses that underwent 127 MRI scans at a mean gestational age of 27.23 ± 4.81 weeks (range, 20-37 weeks) were included. In the investigated gestational-age range, GE volume ranged from 74.88 to 808.75 mm3 and was at its maximum at 21 gestational weeks, followed by a linear decrease (R2 = 0.559) throughout the late second and third trimesters. A pronounced reduction in GE volume relative to cortical volume and TBV occurred in the late second trimester, with a decline in this reduction observed in the third trimester (R2 = 0.936 and 0.924, respectively). Three-dimensional rendering allowed visualization of a continuous change in the shape and size of the GE throughout the second and third trimesters. CONCLUSIONS: Even small compartments of the fetal brain, which are not easily accessible by standardized two-dimensional modalities, can be assessed precisely by super-resolution processed fetal MRI. The inverse growth dynamics of GE volume compared with TBV and cortical volume reflects the transitory nature and physiological involution of this (patho-)physiologically important brain structure. The normal development and involution of the GE is mandatory for normal cortical development. Pathological changes of this transient organ precede impairment of cortical structures, and their detection may allow an earlier diagnosis of such anomalies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Neuroimaging Features of Ectopic Cerebellar Tissue: A Case Series Study of a Rare Entity.

Ectopic cerebellar tissue is a rare entity likely secondary to multiple, interacting, developmental errors during embryogenesis. Multiple sites of ectopic cerebellar tissue have been reported, including extracranial locations; however, an intracranial location is most common. We report on the MR imaging findings of a multi-institutional series of 7 ectopic cerebellar tissue cases (2 males, 4 females, 1 fetal) ranging from 22 weeks 5 days' gestational age to 18 years of age. All cases of ectopic cerebellar tissue were diagnosed incidentally, while imaging was performed for other causes. Ectopic cerebellar tissue was infratentorial in 6/7 patients and supratentorial in 1/7 patients. All infratentorial ectopic cerebellar tissue was connected with the brain stem or cerebellum. MR imaging signal intensity was identical to the cerebellar gray and white matter signal intensity on all MR imaging sequences in all cases. Ectopic cerebellar tissue should be considered in the differential diagnoses of extra-axial masses with signal characteristics similar to those of the cerebellum. Surgical biopsy or resection is rarely necessary, and in most cases, MR imaging is diagnostic.

Magnetic resonance methods in fetal neurology.

Fetal magnetic resonance imaging (MRI) has become an established clinical adjunct for the in-vivo evaluation of human brain development. Normal fetal brain maturation can be studied with MRI from the 18th week of gestation to term and relies primarily on T2-weighted sequences. Recently diffusion-weighted sequences have gained importance in the structural assessment of the fetal brain. Diffusion-weighted imaging provides quantitative information about water motion and tissue microstructure and has applications for both developmental and destructive brain processes. Advanced magnetic resonance techniques, such as spectroscopy, might be used to demonstrate metabolites that are involved in brain maturation, though their development is still in the early stages. Using fetal MRI in addition to prenatal ultrasound, morphological, metabolic, and functional assessment of the fetus can be achieved. The latter is not only based on observation of fetal movements as an indirect sign of activity of the fetal brain but also on direct visualization of fetal brain activity, adding a new component to fetal neurology. This article provides an overview of the MRI methods used for fetal neurologic evaluation, focusing on normal and abnormal early brain development.

Nuclear genes resolve mesozoic-aged divergences in the insect order Lepidoptera.

Compared to the number of genes available for study of both younger and older divergences, few genes have yet been identified that can strongly resolve phylogenetic splits of Mesozoic age ( approximately 65-250 mya). Thus, reconstruction of Mesozoic-age phylogenies, exemplified by basal divergences within the major orders of holometabolous insects, is likely to be especially dependent on combining multiple lines of evidence. This study tests the potential of the 18S ribosomal RNA gene for reconstructing Mesozoic-aged divergences within the insect order Lepidoptera and its ability when combined with a second, previously analyzed nuclear gene (phosphoenolpyruvate carboxykinase, PEPCK) to strongly resolve these relationships. 18S sequences were obtained for 21 taxa, representing major clades of Lepidoptera plus outgroups from the other "panorpoid orders. A well-corroborated morphology-based "test phylogeny was used to evaluate the effects of partitioning the 18S gene according to variable versus conserved domains, paired versus unpaired sites in the secondary structure, and transition versus transversion substitutions. Likelihood and unweighted parsimony analyses of the 18S data recover the "test phylogeny" almost completely, with no improvement of agreement or support provided by any form of weighting or partitioning. No conflict in signal between 18S and PEPCK was detected by the partition homogeneity test. Combined parsimony analysis yielded strong bootstrap support for nearly all relationships, much higher than for either gene alone, thereby also providing strong evidence on several hypotheses about the early evolution of lepidopteran-plant interactions. These genes in combination may be widely useful for resolving insect divergences of comparable age.

Phylogenetic utility of the nuclear gene dopa decarboxylase in noctuoid moths (Insecta: Lepidoptera: noctuoidea).

Phylogenetic utility for the nuclear gene encoding dopa decarboxylase (DDC), little used in systematics, was recently demonstrated within the noctuid moth subfamily Heliothinae. Here we extend the test of the utility of a 709-bp DDC fragment to deeper levels, analyzing 49 species representing major groups across the superfamily Noctuoidea. Parsimony, distance, and maximum-likelihood analyses recover all or nearly all of a set of "test clades" supported by clear morphological synapomorphies, spanning a wide range of taxonomic levels. DDC also upholds a recent proposal that the Noctuidae are paraphyletic. Nt3 contributes a majority of the signal and recovers the basal split between Notodontidae and all other noctuoids, despite a plateau of nt3 divergence at this level. However, nonsynonymous changes also support groups at all levels, and in contrast to nt3, amino acid divergence shows no plateau. The utility of DDC promises to extend back to the early Tertiary and Cretaceous, a time span for which few suitable genes have been identified.

More taxa or more characters revisited: combining data from nuclear protein-encoding genes for phylogenetic analyses of Noctuoidea (Insecta: Lepidoptera).

A central question concerning data collection strategy for molecular phylogenies has been, is it better to increase the number of characters or the number of taxa sampled to improve the robustness of a phylogeny estimate? A recent simulation study concluded that increasing the number of taxa sampled is preferable to increasing the number of nucleotide characters, if taxa are chosen specifically to break up long branches. We explore this hypothesis by using empirical data from noctuoid moths, one of the largest superfamilies of insects. Separate studies of two nuclear genes, elongation factor-1 alpha (EF-1 alpha) and dopa decarboxylase (DDC), have yielded similar gene trees and high concordance with morphological groupings for 49 exemplar species. However, support levels were quite low for nodes deeper than the subfamily level. We tested the effects on phylogenetic signal of (1) increasing the taxon sampling by nearly 60%, to 77 species, and (2) combining data from the two genes in a single analysis. Surprisingly, the increased taxon sampling, although designed to break up long branches, generated greater disagreement between the two gene data sets and decreased support levels for deeper nodes. We appear to have inadvertently introduced new long branches, and breaking these up may require a yet larger taxon sample. Sampling additional characters (combining data) greatly increased the phylogenetic signal. To contrast the potential effect of combining data from independent genes with collection of the same total number of characters from a single gene, we simulated the latter by bootstrap augmentation of the single-gene data sets. Support levels for combined data were at least as high as those for the bootstrap-augmented data set for DDC and were much higher than those for the augmented EF-1 alpha data set. This supports the view that in obtaining additional sequence data to solve a refractory systematic problem, it is prudent to take them from an independent gene.

Evolution and phylogenetic utility of the period gene in Lepidoptera.

Evolution and phylogenetic utility of the period gene are explored through sequence analysis of a relatively conserved 909-bp fragment in 26 lepidopteran species. Taxa range from tribes to superfamilies, primarily within the putative clade Macrolepidotera plus near outgroups, and include both strongly established and problematic groupings. Their divergence dates probably range from the late Cretaceous through much of the Tertiary. Comparisons within the same set of closely related species show that amino acid substitutions in period occur 4.9 and 44 times as frequently as they do in two other nuclear genes--dopa decarboxylase and elongation factor-1 alpha, respectively. In contrast, rates of observed synonymous substitution are within 60% of each other for these three genes. Synonymous changes in period approach saturation by the family level, whereas nonsynonymous and amino acid divergences across the Macrolepidoptera are less than half the maximal values reported for this gene. Phylogenetic analyses of period strongly supported groupings at the family level and below. In contrast to previous analyses at this level with other nuclear genes, much of the information lies in nonsynonymous change. Relationships up to the superfamily level were recovered with decreasing effectiveness, and little, if any, signal was apparent regarding relationships among superfamilies. This could reflect rapid radiation of the superfamilies, however, rather than saturation in the period locus; thus, period, in combination with other genes, remains a plausible candidate for approaching the difficult problems of lepidopteran family and superfamily relationships.

Two nuclear genes yield concordant relationships within Attacini (Lepidoptera: Saturniidae).

To extend initial characterizations of their phylogenetic utility, sequences from the nuclear genes for elongation factor-1 alpha (EF-1 alpha) and dopa decarboxylase (DDC) are tested for phylogenetic concordance with each other and with previous morphological evidence within the giant silk moth tribe Attacini (Lepidoptera: Saturniidae). The sampling of DDC is expanded from the 690 basepairs of previous studies to 1051 basepairs in the current study. All nine attacine genera are sampled. EF-1 alpha and DDC agree in the placement of seven of nine genera, with placement of the other two not in strong conflict. Combination of the gene sequences results in a nearly fully resolved tree that is consistent with EF-1 alpha alone and agrees with morphology in five of eight groups. Conflict between molecules and morphology is confined to deeper-level relationships within Attacini, where node support for the molecular hypotheses, but not the morphological hypotheses, is generally very strong. A strong signal is contributed by synonymous substitutions in both genes, and by nonsynonymous change particularly in DDC. The molecular phylogeny supports a revision of attacine biogeography in that neither East Asian nor New World genera form monophyletic groups.

A new nuclear gene for insect phylogenetics: dopa decarboxylase is informative of relationships within Heliothinae (Lepidoptera: Noctuidae).

The lack of a readily accessible roster of nuclear genes informative at various taxonomic levels is a bottleneck for molecular systematics. In this report, we describe the first phylogenetic application of the sequence that encodes the enzyme dopa decarboxylase (DDC). For 14 test species within the noctuid moth subfamily Heliothinae that represent the previously best-supported groupings, a 690-bp fragment of DDC resolved relationships that are largely concordant with prior evidence from elongation factor-1 alpha (EF-1 alpha), morphology, and allozymes. Although both synonymous and nonsynonymous changes occur in DDC substantially more rapidly than they do in EF-1 alpha, DDC divergences within Heliothinae are below saturation at all codon positions. Analysis of DDC and EF-1 alpha in combination resulted in increased bootstrap support for several groupings. As a first estimate of previously unresolved relationships, DDC sequences were analyzed from 16 additional heliothines, for a total of 30 heliothine species plus outgroups. Previous relationships based on DDC were generally stable with increased taxon sampling, although a two- to eightfold downweighting of codon position 3 was required for complete concordance with the 14-species result. The weighted strict consensus trees were largely resolved and were congruent with most although not all previous hypotheses based on either morphology or EF-1 alpha. The proposed phylogeny suggests that the major agricultural pest heliothines belong to a single clade, characterized by polyphagy and associated life history traits, within this largely host-specific moth subfamily. DDC holds much promise for phylogenetic analysis of Tertiary-age animal groups.

Phylogenetic utility of elongation factor-1 alpha in noctuoidea (Insecta: Lepidoptera): the limits of synonymous substitution.

To test its phylogenetic utility, nucleotide sequence variation in a 1,240-bp fragment of the elongation factor-1 alpha (EF-1 alpha) gene was examined in 49 moth species representing the major groups of the superfamily Noctuoidea. Both parsimony and distance analyses supported the monophyly of nearly all groups for which there are clear morphological synapomorphies. Clades of subfamily rank and lower, probably mid-Tertiary and younger, were strongly supported. The third codon position contains 88% of variable sites, and approaches saturation at approximately 20% sequence divergence, possibly due to among-site rate heterogeneity and composition bias; higher divergences occur only in association with shifts in composition. Surprisingly, the few nonsynonymous changes appear no more phylogenetically reliable than synonymous changes. Signal strength for basal divergences is weak and fails to improve with character weighting; thus, dense taxon sampling is probably needed for strong inference from EF-1 alpha regarding deeper splits in Noctuoidea (probably early Tertiary). EF-1 alpha synonymous changes show promise for phylogeny reconstruction within Noctuidae and other groups of Tertiary age.

A nuclear gene for higher level phylogenetics: phosphoenolpyruvate carboxykinase tracks mesozoic-age divergences within Lepidoptera (Insecta).

The sequence of phosphoenolpyruvate carboxykinase (PEPCK) has been previously identified as a promising candidate for reconstructing Mesozoic-age divergences (Friedlander, Regier, and Mitter 1992, 1994). To test this hypothesis more rigorously, 597 nucleotides of aligned PEPCK coding sequence (approximately 30% of the coding region) were generated from 18 species representing Mesozoic-age lineages of moths (Insecta: Lepidoptera) and outgroup taxa. Relationships among basal Lepidoptera are well established by morphological analysis, providing a strong test for the utility of a gene which has not previously been used in systematics. Parsimony and other phylogenetic analyses were conducted on nucleotides by codon positions (nt1, nt2, nt3) separately and in combination, and on amino acids, for comparison to the test phylogeny. The highest concordance was achieved with nt1 + nt2, for which one of two most-parsimonious trees was identical to the test phylogeny, and with all nucleotides when nt3 was down-weighted sevenfold or higher, for which a single most-parsimonious tree identical to the test phylogeny resulted. Substitutions in nt3 approached saturation in many, but not all, pairwise comparisons and their exclusion or severe downweighting greatly increased the degree of concordance with the test phylogeny. Neighbor-joining analysis confirms this finding. The utility of PEPCK for phylogenetics is demonstrated over a time span for which few other suitable genes are currently available.

A highly conserved nuclear gene for low-level phylogenetics: elongation factor-1 alpha recovers morphology-based tree for heliothine moths.

Molecular systematists need increased access to nuclear genes. Highly conserved, low copy number protein-encoding nuclear genes have attractive features for phylogenetic inference but have heretofore been applied mostly to very ancient divergences. By virtue of their synonymous substitutions, such genes should contain a wealth of information about lower-level taxonomic relationships as well, with the advantage that amino acid conservatism makes both alignment and primer definition straightforward. We tested this postulate for the elongation factor-1 alpha (EF-1 alpha) gene in the noctuid moth subfamily Heliothinae, which has probably diversified since the middle Tertiary. We sequenced 1,240 bp in 18 taxa representing heliothine groupings strongly supported by previous morphological and allozyme studies. The single most parsimonious gene tree and the neighbor-joining tree for all nucleotides show almost complete concordance with the morphological tree. Homoplasy and pairwise divergence levels are low, transition/transversion ratios are high, and phylogenetic information is spread evenly across gene regions. The EF-1 alpha gene and presumably other highly conserved genes hold much promise for phylogenetics of Tertiary age eukaryote groups.

Plasma levels of D-dimer: a crosslinked fibrin-degradation product in female breast cancer.

Plasma levels of D-dimer, a degradation product of crosslinked fibrin, were determined in 73 patients with breast cancer. In these patients, significantly elevated plasma levels of D-dimer were found, as compared to healthy controls (P less than 0.0001). In addition, we observed a moderate correlation between plasma levels of D-dimer and those of CA15-3 (r = 0.40; P less than 0.001) and between D-dimer and carcinoembryonic antigen (r = 0.39; P less than 0.01). Plasma levels of thrombin-antithrombin III complex (TAT), reflecting the activation of thrombin, were also significantly elevated in patients with breast cancer (P less than 0.0001), and a poor, but significant correlation between carcinoembryonic antigen and TAT (r = 0.25; P less than 0.05) was found. We concluded that the increase in plasma D-dimer and TAT levels might reflect an enhanced activation of the clotting system in patients with breast cancer.

Phylogenetic studies of insect-plant interactions: Insights into the genesis of diversity.

Phylogenetic analyses (and related historical evidence) can be used to test hypotheses about the oppurtinity for coevolution among plants and insect herbivores, the role of plant chemistry in mediating host shifts, the reality of coevolutionary 'arms races', and the role of novel defensive or counterdefensive characteristics in enhancing rates of diversification. Recent analyses provide evidence on each of these hypotheses. The strong phylogenetic component in many insect-plant associations suggests that host shifts by insects are often strongly constrained, that insect diets may not be 'optimal', and that the trophic structure and species diversity of local communities strongly reflect evolutionary history.

Evidence of pheromonal constancy among sexual and asexual females in a population of fall cankerworm,Alsophila pometaria (Lepidoptera: Geometridae).

The compounds (Z,Z,Z)-3,6,9-nonadecatriene (I), (Z,Z,Z,E)-(II), and (Z,Z,Z,Z)-3,6,9,11-nonadecatetraene (III) have been implicated as components of the female sex pheromone of the fall cankerworm. Chromatographie determination of the proportions of these compounds in individual females of sympatric asexual and sexual reproductive forms of the species, with concurrent analysis of the electrophoretic profiles of the same females, showed that the I: II: III proportion of compounds was constant across electrophoretically differing asexual genotypes and between these and the sexual form. Life-history characters, in contrast, typically show great variation among these genetic groups. The results indicate that pheromonal constancy is maintained in a reproductive system that is theoretically vulnerable to selective pressures that would lead to heterogeneity in the species' pheromonal communication channel.

Population genetic consequences of feeding habits in some forest lepidoptera.

BY SURVEYING VARIATION AT ALLOZYME LOCI IN SEVERAL PHYTOPHAGOUS LEPIDOPTERAN SPECIES (GEOMETRIDAE), WE HAVE TESTED TWO HYPOTHESES ABOUT THE RELATIONSHIP OF GENETIC VARIATION TO ENVIRONMENTAL HETEROGENEITY: (1) that allozyme polymorphisms may exist because of associations between genotypes and "niches" (different host plants, in this instance), and (2) that the overall genetic variation of a species is correlated with environmental heterogeneity (or breadth of the species' overall ecological niche).-Genetic differentiation among samples of oligophagous or polyphagous species taken from different host species was observed in one of three species, at only one of seven polymorphic loci. The data thus provide no evidence for pronounced genetic substructuring, or "host race" formation in these sexually reproducing species, although host plant-genotype associations in a parthenogenetic moth give evidence of the potential for diversifying selection.-In a comparison of allozyme variation in polyphagous ("generalized") and oligophagous ("specialized") species, heterozygosity appeared to be higher in specialized species, at all polymorphic loci but one. It is possible that this unexpected result arises from a functional relation between breadth of diet and genetic variation.