Aberrant Morphological Features Research Articles

Neuroanatomical Correlates of Cognitive Dysfunction in 22q11.2 Deletion Syndrome.

22q11.2 Deletion Syndrome (22q11.2DS), the most common chromosomal microdeletion, presents as a heterogeneous phenotype characterized by an array of anatomical, behavioral, and cognitive abnormalities. Individuals with 22q11.2DS exhibit extensive cognitive deficits, both in overall intellectual capacity and focal challenges in executive functioning, attentional control, perceptual abilities, motor skills, verbal processing, as well as socioemotional operations. Heterogeneity is an intrinsic factor of the deletion's clinical manifestation in these cognitive domains. Structural imaging has identified significant changes in volume, thickness, and surface area. These alterations are closely linked and display region-specific variations with an overall increase in abnormalities following a rostral-caudal gradient. Despite the extensive literature developing around the neurocognitive and neuroanatomical profiles associated with 22q11.2DS, comparatively little research has addressed specific structure-function relationships between aberrant morphological features and deficient cognitive processes. The current review attempts to categorize these limited findings alongside comparisons to populations with phenotypic and structural similarities in order to answer to what degree structural findings can explain the characteristic neurocognitive deficits seen in individuals with 22q11.2DS. In integrating findings from structural neuroimaging and cognitive assessments, this review seeks to characterize structural changes associated with the broad neurocognitive challenges faced by individuals with 22q11.2DS.

Paraphyly of the subgenus Micronecta (Micronecta) Kirkaldy, 1897 (Hemiptera: Heteroptera: Micronectidae) based on mitochondrial genomes and nuclear rDNAs

The genus Micronecta Kirkaldy, 1897 is the most species-rich genus in the family Micronectidae, containing more than 160 species. Micronecta is currently divided into 11 subgenera, five of which are monotypic. Moreover, the subgenus Micronecta is an empirical mixture group. The definitions of some subgenera were based on only a few aberrant morphological features, which are specializations with few phylogenetic significances. The relationship between these subgenera remains unclear. In this study, we newly sequenced mitochondrial genomes (mitogenomes) and nuclear rDNAs (nrDNAs) for 13 Micronecta species, representing seven subgenera, and those for ten other water bugs. Our phylogenetic analyses showed that the subgenus Lundbladella represents the sister group to all other studied subgenera of Micronecta. The subgenus Unguinecta was the sister group to the clade that contains Dichaetonecta and Sigmonecta. More importantly, the subgenus Micronecta represents a paraphyletic group, which further forms a monophyletic group together with the subgenera Basileonecta and Ctenonecta. This is for the first time that the phylogeny of the genus Micronecta was investigated based on molecular data and the paraphyly of the subgenus Micronecta was revealed. Such evidence suggested the necessity of the revision of the taxonomic system of the genus in the future, and may also serve as a reference for the delimitation of subgeneric characters.

Aberrant Cytomorphological Features of Primary Plasma Cell Leukaemia: A Case Series

Primary Plasma Cell Leukaemia (pPCL) is a rare but distinctive sub-type of Plasma Cell Myeloma (PCM) comprising approximately 2-4% of cases of PCM and characterised by short remissions and survivals. Apart from these clinical distinctions, this entity also demonstrates unique cytomorphological features. The authors here attempted to highlight this unusual spectrum of leukaemic plasma cells, posing diagnostic challenges in the blood and bone marrow examinations. The cases presented in this series (48 years old male, 72 years old male,68 years old male and 63 years old female) patients, showed presence of atypical cells in the peripheral smear with few cells portraying the characteristic “hairy cell” morphology, the fourth case in addition, showed small sized plasma cells resembling lymphocytes. Bone marrow biopsy in three cases showed haematopoetic cells replaced by sheets of atypical plasma cells. In addition, the fourth case showed atypical cells having convoluted and notched nuclei giving a differential diagnosis of lymphoplasmacytic lymphoma and small B-cell lymphoma with plasmacytic differentiation. As plasma cell neoplasm was not suspected clinically in all four cases, flow cytometry was sought for confirmation which showed atypical cells expressing CD38 (+), CD138 (+), CD56 (–) with Cykappa (+) in first case, Cylambda (+) in the second case and Cykappa (+) in the fourth case with aberrant expression of cyclin D1 thus confirming a diagnosis of PCL in first two cases and PCM-lymphocytic type with PCL in the fourth case. Immunophenotyping was not performed in the third case due to financial constraints. This case series showcases this mélange of cytomorphological variations of plasma cells ranging from cells masquerading as hairy cells to small sized plasma cells resembling lymphocytes, each posing a unique diagnostic dilemma. This has been rarely discussed in prior published case series. Aberrant morphological features rarely seen in PCL, could lead the pathologist astray from the diagnosis, therefore appropriate use of ancillary tests are essential to arrive at a correct diagnosis.

Repurposing FDA Approved Drugs as JNK3 Inhibitor for Prevention of Neuroinflammation Induced by MCAO in Rats.

BackgroundStress-associated kinases are considered major pathological mediators in several incurable neurological disorders. Importantly, among these stress kinases, the c-Jun NH2-terminal kinase (JNK) has been linked to numerous neuropathological conditions, including oxidative stress, neuroinflammation, and brain degeneration associated with brain injuries such as ischemia/reperfusion injury. In this study, we adopted a drug repurposing/reprofiling approach to explore novel JNK3 inhibitors from FDA-approved medications to supplement existing therapeutic strategies.Materials and MethodsWe performed in silico docking analysis and molecular dynamics simulation to screen potential candidates from the FDA approved drug library using the standard JNK inhibitor SP600125 as a reference. After the virtual screening, dabigatran, estazolam, leucovorin, and pitavastatin were further examined in ischemic stroke using an animal rodent model of focal cerebral ischemia using transient middle cerebral artery occlusion (t-MCAO). The selected drugs were probed for neuroprotective effectiveness by measuring the infarct area (%) and neurological deficits using a 28-point composite score. Biochemical assays including ELISA and immunohistochemical experiments were performed.ResultsWe obtained structural insights for dabigatran, estazolam, and pitavastatin binding to JNK3, revealing a significant contribution of the hydrophobic regions and significant residues of active site regions. To validate the docking results, the pharmacological effects of dabigatran, estazolam, leucovorin, and pitavastatin on MCAO were tested in parallel with the JNK inhibitor SP600125. After MCAO surgery, severe neurological deficits were detected in the MCAO group compared with the sham controls, which were significantly reversed by dabigatran, estazolam, and pitavastatin treatment. Aberrant morphological features and brain damage were observed in the ipsilateral cortex and striatum of the MCAO groups. The drugs restored the anti-oxidant enzyme activity and reduced the levels of oxidative stress-induced p-JNK and neuroinflammatory mediators such as NF-kB and TNF-ɑ in rats subjected to MCAO.ConclusionOur results demonstrated that the novel FDA-approved medications attenuate ischemic stroke-induced neuronal degeneration, possibly by inhibiting JNK3. Being FDA-approved safe medications, the use of these drugs can be clinically translated for ischemic stroke-associated brain degeneration and other neurodegenerative diseases associated with oxidative stress and neuroinflammation.

Morphological covariance in anatomical MRI scans can identify discrete neural pathways in the brain and their disturbances in persons with neuropsychiatric disorders

We hypothesize that coordinated functional activity within discrete neural circuits induces morphological organization and plasticity within those circuits. Identifying regions of morphological covariation that are independent of morphological covariation in other regions therefore may therefore allow us to identify discrete neural systems within the brain. Comparing the magnitude of these variations in individuals who have psychiatric disorders with the magnitude of variations in healthy controls may allow us to identify aberrant neural pathways in psychiatric illnesses.We measured surface morphological features by applying nonlinear, high-dimensional warping algorithms to manually defined brain regions. We transferred those measures onto the surface of a unit sphere via conformal mapping and then used spherical wavelets and their scaling coefficients to simplify the data structure representing these surface morphological features of each brain region. We used principal component analysis (PCA) to calculate covariation in these morphological measures, as represented by their scaling coefficients, across several brain regions. We then assessed whether brain subregions that covaried in morphology, as identified by large eigenvalues in the PCA, identified specific neural pathways of the brain. To do so, we spatially registered the subnuclei for each eigenvector into the coordinate space of a Diffusion Tensor Imaging dataset; we used these subnuclei as seed regions to track and compare fiber pathways with known fiber pathways identified in neuroanatomical atlases.We applied these procedures to anatomical MRI data in a cohort of 82 healthy participants (42 children, 18 males, age 10.5±2.43years; 40 adults, 22 males, age 32.42±10.7years) and 107 participants with Tourette's Syndrome (TS) (71 children, 59 males, age 11.19±2.2years; 36 adults, 21 males, age 37.34±10.9years). We evaluated the construct validity of the identified covariation in morphology using DTI data from a different set of 20 healthy adults (10 males, mean age 29.7±7.7years). The PCA identified portions of structures that covaried across the brain, the eigenvalues measuring the magnitude of the covariation in morphology along the respective eigenvectors. Our results showed that the eigenvectors, and the DTI fibers tracked from their associated brain regions, corresponded with known neural pathways in the brain. In addition, the eigenvectors that captured morphological covariation across regions, and the principal components along those eigenvectors, identified neural pathways with aberrant morphological features associated with TS. These findings suggest that covariations in brain morphology can identify aberrant neural pathways in specific neuropsychiatric disorders.

Prevalence of aberrant dental morphological details in 6-10 year old school children in an Indian population.

Background:Variations in the structure of teeth have always been a great curiosity to the dentist from the scientific and practical point of view.Aim:To evaluate the prevalence of a few aberrant morphological features namely, cusp of Carabelli in primary maxillary second molar and in permanent first molar, five cusp in primary maxillary second molar and permanent first molar, shoveling and double shoveling with respect to permanent maxillary central incisors, four cusped primary mandibular second molar and permanent first molar, six cusped primary mandibular second molar and permanent first molar and seven cusped primary mandibular second molar and permanent first molar in 6–10 year old children belonging to the East Bengaluru, a City in India.Design:A cross-sectional survey was conducted among 2111 children by two stage sampling method. Type III examination was performed. The findings were subjected to Chi-square test.Results:83.8% of the studied population had one or more of the variations checked for, as mentioned above. The variation most commonly seen was double shoveling (66.6%) followed by shoveling (65.7%). No significant results were observed in any trait with respect to gender.Conclusion:This study is the first of its kind, providing a baseline data of the prevalence of morphological details in the pediatric Indian population.

Morphometry of hilar ectopic granule cells in the rat

Granule cell (GC) neurogenesis in the dentate gyrus (DG) does not always proceed normally. After severe seizures (e.g., status epilepticus [SE]) and some other conditions, newborn GCs appear in the hilus. Hilar ectopic GCs (EGCs) can potentially provide insight into the effects of abnormal location and seizures on GC development. Additionally, hilar EGCs that develop after SE may contribute to epileptogenesis and cognitive impairments that follow SE. Thus, it is critical to understand how EGCs differ from normal GCs. Relatively little morphometric information is available on EGCs, especially those restricted to the hilus. This study quantitatively analyzed the structural morphology of hilar EGCs from adult male rats several months after pilocarpine-induced SE, when they are considered to have chronic epilepsy. Hilar EGCs were physiologically identified in slices, intracellularly labeled, processed for light microscopic reconstruction, and compared to GC layer GCs, from both the same post-SE tissue and the NeuroMorpho database (normal GCs). Consistently, hilar EGC and GC layer GCs had similar dendritic lengths and field sizes, and identifiable apical dendrites. However, hilar EGC dendrites were topologically more complex, with more branch points and tortuous dendritic paths. Three-dimensional analysis revealed that, remarkably, hilar EGC dendrites often extended along the longitudinal DG axis, suggesting increased capacity for septotemporal integration. Axonal reconstruction demonstrated that hilar EGCs contributed to mossy fiber sprouting. This combination of preserved and aberrant morphological features, potentially supporting convergent afferent input to EGCs and broad, divergent efferent output, could help explain why the hilar EGC population could impair DG function.

Serotonin DepletionIn VivoInhibits the Branching of Olfactory Projection Neurons in the Lobster Deutocerebrum

Serotonin depletion during embryogenesis has been shown previously to retard the growth of the olfactory and accessory lobes of the lobster deutocerebrum (Benton et al., 1997). The present study was undertaken to determine whether morphological changes in the interneurons innervating these lobes contribute to this growth retardation. We examined the effects of in vivo serotonin depletion using 5,7-dihydroxytryptamine (5,7-DHT) on the morphology of the olfactory projection neurons, one of two major classes of interneurons that innervate both lobes. Intracellular dye fills of olfactory projection neurons in normal embryos showed that each neuron extensively innervates either the olfactory or accessory lobe before projecting to neuropil regions in the protocerebrum. In embryos injected with 5,7-DHT, however, the deutocerebral arbors of 13.5% of the olfactory projection neurons examined were either markedly reduced compared with normal neurons or absent. Affected neurons also exhibited a number of additional aberrant morphological features suggesting that these neurons represent cells that were affected during their initial morphogenesis. Olfactory projection neurons with aberrant morphologies were also encountered, although less frequently (7.5% of the neurons examined), in control (sham-injected) embryos indicating that the sham injections can affect the development of the brain. This observation provides insights into the nature of effects seen in control embryos in previous experiments (Benton et al., 1997). The results of the present study indicate that in vivo serotonin depletion inhibits the branching of olfactory projection neurons and suggest, therefore, that one of the functions of serotonin during normal development is to promote the ingrowth of these neurons into the deutocerebral neuropils.

Abnormal cell divisions in leaf primordia caused by the expression of the rice homeobox gene OSH1 lead to altered morphology of leaves in transgenic tobacco.

Transgenic tobacco plants were generated carrying a rice homeobox gene, OSH1, controlled by the promoter of a gene encoding a tobacco pathogenesis-related protein (PR1a). These lines were morphologically abnormal, with wrinkled and/or lobed leaves. Histological analysis of shoot apex primordia indicates arrest of lateral leaf blade expansion, often resulting in asymmetric and anisotrophic growth of leaf blades. Other notable abnormalities included abnormal or arrested development of leaf lateral veins. Interestingly, OHS1 expression was undetectable in mature leaves with the aberrant morphological features. Thus, OSH1 expression in mature leaves is not necessary for abnormal leaf development. Northern blot and in situ hybridization analyses indicate that PR1a-OSH1 is expressed only in the shoot apical meristem and in very young leaf primordia. Therefore, the aberrant morphological features are an indirect consequence of ectopic OSH1 gene expression. The only abnormality observed in tissues expressing the transgene was periclinal (rather than anticlinal) division in mesophyll cells during leaf blade initiation. This generates thicker leaf blades and disrupts the mesophyll cell layers, from which vascular tissues differentiate. The OSH1 product appears to affect the mechanism controlling the orientation of the plane of cell division, resulting in abnormal periclinal division of mesophyll cell, which in turn results in the gross morphological abnormalities observed in the transgenic lines.

Morphological classification of the yeast vacuolar protein sorting mutants: evidence for a prevacuolar compartment in class E vps mutants.

The collection of vacuolar protein sorting mutants (vps mutants) in Saccharomyces cerevisiae comprises of 41 complementation groups. The vacuoles in these mutant strains were examined using immunofluorescence microscopy. Most of the vps mutants were found to possess vacuolar morphologies that differed significantly from wild-type vacuoles. Furthermore, mutants representing independent vps complementation groups were found to share aberrant morphological features. Six distinct classes of vacuolar morphology were observed. Mutants from eight vps complementation groups were defective both for vacuolar segregation from mother cells into developing buds and for acidification of the vacuole. Another group of mutants, represented by 13 complementation groups, accumulated a novel organelle distinct from the vacuole that contained a late-Golgi protein, active vacuolar H(+)-ATPase complex, and soluble vacuolar hydrolases. We suggest that this organelle may represent an exaggerated endosome-like compartment. None of the vps mutants appeared to mislocalize significant amounts of the vacuolar membrane protein alkaline phosphatase. Quantitative immunoprecipitations of the soluble vacuolar hydrolase carboxypeptidase Y (CPY) were performed to determine the extent of the sorting defect in each vps mutant. A good correlation between morphological phenotype and the extent of the CPY sorting defect was observed.