Immune Abnormalities in Autism Spectrum Disorder—Could They Hold Promise for Causative Treatment?

Autism spectrum disorders (ASD) are characterized by impairments in language and communication development, social behavior, and the occurrence of stereotypic patterns of behavior and interests. Despite substantial speculation about causes of ASD, its exact etiology remains unknown. Recent studies highlight a link between immune dysfunction and behavioral traits. Various immune anomalies, including humoral and cellular immunity along with abnormalities at the molecular level, have been reported. There is evidence of altered immune function both in cerebrospinal fluid and peripheral blood. Several studies hypothesize a role for neuroinflammation in ASD and are supported by brain tissue and cerebrospinal fluid analysis, as well as evidence of microglial activation. It has been shown that immune abnormalities occur in a substantial number of individuals with ASD. Identifying subgroups with immune system dysregulation and linking specific cellular immunophenotypes to different symptoms would be key to defining a group of patients with immune abnormalities as a major etiology underlying behavioral symptoms. These determinations would provide the opportunity to investigate causative treatments for a defined patient group that may specifically benefit from such an approach. This review summarizes recent insights into immune system dysfunction in individuals with ASD and discusses the potential implications for future therapies.     

Dispersal of four fritillary butterflies within identical landscape

Both species-specific traits and landscape configuration, such as area and connectivity of habitat patches plus the character of uninhabitable matrix, affect animal movements in fragmented landscapes. Difficulties with disentangling species-specific and landscape effects have obscured comparisons among species, hindering the understanding of dispersal in metapopulations. To circumvent this complication, we performed a mark–recapture study of four related nymphalid butterflies within identical landscape and in single season. The studied species were three Melitaeinae checkerspots (Euphydryas aurinia, Melitaea athalia, Melitaea diamina) and one Argynnini fritillary (Brenthis ino). Applying the Virtual Migration model revealed that (1) except for mortality within habitat, model parameters differed from those found for the studied species elsewhere; (2) the three Melitaeinae species were more akin in movement parameters than the Argynnini representative (i.e., B. ino); (3) within Melitaeinae, differences between sexes were more prominent than differences among species; (4) Melitaeinae males left natal patches more readily than females, while the opposite applied to B. ino; (5) males of M. diamina and both sexes of B. ino exhibited highest values of dispersal mortality; (6) except for females of M. diamina and both sexes of B. ino, immigration and emigration scaled with area in females but not in males. Finding (1) demonstrates that geometry of habitat network affects mobility considerably and that transferring dispersal parameters across systems is unwarranted. Still, (2–6) demonstrate that within identical networks, related species follow similar dispersal patterns, suggesting that conservation scenarios suitable for a well-studied model species would suite related species as well.     

Human Cytomegalovirus UL50 and UL53 Recruit Viral Protein Kinase UL97, Not Protein Kinase C,for Disruption of Nuclear Lamina and Nuclear Egress in Infected Cells

Herpesvirus nucleocapsids traverse the nuclear envelope into the cytoplasm in a process called nuclear egress that includes disruption of the nuclear lamina. In several herpesviruses, a key player in nuclear egress is a complex of two proteins, whose homologs in human cytomegalovirus (HCMV) are UL50 and UL53. However, their roles in nuclear egress during HCMV infection have not been shown. Based largely on transfection studies, UL50 and UL53 have been proposed to facilitate disruption of the nuclear lamina by recruiting cellular protein kinase C (PKC), as occurs with certain other herpesviruses, and/or the viral protein kinase UL97 to phosphorylate lamins. To investigate these issues during HCMV infection, we generated viral mutants null for UL50 or UL53. Correlative light electron microscopic analysis of null mutant-infected cells showed the presence of intranuclear nucleocapsids and the absence of cytoplasmic nucleocapsids. Confocal immunofluorescence microscopy revealed that UL50 and UL53 are required for disruption of the nuclear lamina. A subpopulation of UL97 colocalized with the nuclear rim, and this was dependent on UL50 and, to a lesser extent, UL53. However, PKC was not recruited to the nuclear rim, and its localization was not affected by the absence of UL50 or UL53. Immunoprecipitation from cells infected with HCMV expressing tagged UL53 detected UL97 but not PKC. In summary, HCMV UL50 and UL53 are required for nuclear egress and disruption of nuclear lamina during HCMV infection, and they recruit UL97, not PKC, for these processes. Thus, despite the strong conservation of herpesvirus nuclear egress complexes, a key function can differ among them.     

Protocol of single cells preparation for time of flight secondary ion mass spectrometry

There are several techniques like time of flight secondary ion mass spectrometry (ToF SIMS) that require a special protocol for preparation of biological samples, in particular, those containing single cells due to high vacuum conditions that must be kept during the experiment. Frequently, preparation methodology involves liquid nitrogen freezing what is not always convenient. In our studies, we propose and validate a protocol for preparation of single cells. It consists of four steps: (i) paraformaldehyde fixation, (ii) salt removal, (iii) dehydrating, and (iv) sample drying under ambient conditions. The protocol was applied to samples with single melanoma cells i.e. WM115 and WM266-4 characterized by similar morphology. The surface and internal structures of cells were monitored using atomic force, scanning electron and fluorescent microscopes, used to follow any potential protocol-induced alterations. To validate the proposed methodology for sample preparation, ToF SIMS experiments were carried out using C₆₀⁺ cluster ion beam. The applied principal component analysis (PCA) revealed that chemical changes on cell surface of melanoma cells were large enough to differentiate between primary and secondary tumor sites.     

Functional role of the MrpA- and MrpD-homologous protein subunits in enzyme complexes evolutionary related to respiratory chain complex I

NADH:quinone oxidoreductase or complex I is a large membrane bound enzyme complex that has evolved from the combination of smaller functional building blocks. Intermediate size enzyme complexes exist in nature that comprise some, but not all of the protein subunits in full size 14-subunit complex I. The membrane spanning complex I subunits NuoL, NuoM and NuoN are homologous to each other and to two proteins from one particular class of Na⁺/H⁺ antiporters, denoted MrpA and MrpD. In complex I, these ion transporter protein subunits are prime candidates for harboring important parts of the proton pumping machinery. Using a model system, consisting of Bacillus subtilis MrpA and MrpD deletion strains and a low copy expression plasmid, it was recently demonstrated that NuoN can rescue the strain deleted for MrpD but not that deleted for MrpA, whereas the opposite tendency was seen for NuoL. This demonstrated that the MrpA-type and MrpD-type proteins have unique functional specializations. In this work, the corresponding antiporter-like protein subunits from the smaller enzymes evolutionarily related to complex I were tested in the same model system. The subunits from 11-subunit complex I from Bacillus cereus behaved essentially as those from full size complex I, corroborating that this enzyme should be regarded as a bona fide complex I. The hydrogenase-3 and hydrogenase-4 antiporter-like proteins on the other hand, could substitute equally well for MrpA or MrpD at pH 7.4, suggesting that these enzymes have intermediate forms of the antiporter-like proteins, which seemingly lack the functional specificity.     

A comparative study on two closely relative Tulipa L. taxa from NE Anatolia

This study presents observations on the anatomical, palynological and ecological features of Tulipa gumusanica Terzio?lu and its morphologically similar relative, T. armena Boiss. var. armena, in order to clarify their similarities and differences. We found that these taxa have some important differences with regard to anatomical, palynological and ecological features, as well as morphological traits. General anatomical traits of both examined taxa are similar, both having isolateral leaves with distinct hypodermis and a stem with distinct monolayer collenchyma close to the epidermis. However, some anatomical characters such as mesophyll width, average number of stomata on lower epidermis, and epidermal cells on upper epidermis are found to be important in delimiting these taxa. In addition, considerable differences have been observed in pollen shape and size. The species differ ecologically in that T. gumusanica prefers slightly acidic soil with low organic content in the woodland, whereas T. armena var. armena prefers slightly alkali soil with high organic content in steppe vegetation.