Reduced Fronto-Temporal and Limbic Connectivity in the 22q11.2 Deletion Syndrome: Vulnerability Markers for Developing Schizophrenia?

The 22q11.2 deletion syndrome (22q11DS) is a widely recognized genetic model allowing the study of neuroanatomical biomarkers that underlie the risk for developing schizophrenia. Recent advances in magnetic resonance image analyses enable the examination of structural connectivity integrity, scarcely used in the 22q11DS field. This framework potentially provides evidence for the disconnectivity hypothesis of schizophrenia in this high-risk population. In the present study, we quantify the whole brain white matter connections in 22q11DS using deterministic tractography. Diffusion Tensor Imaging was acquired in 30 affected patients and 30 age- and gender-matched healthy participants. The Human Connectome technique was applied to register white matter streamlines with cortical anatomy. The number of fibers (streamlines) was used as a measure of connectivity for comparison between groups at the global, lobar and regional level. All statistics were corrected for age and gender. Results showed a 10% reduction of the total number of fibers in patients compared to controls. After correcting for this global reduction, preserved connectivity was found within the right frontal and right parietal lobes. The relative increase in the number of fibers was located mainly in the right hemisphere. Conversely, an excessive reduction of connectivity was observed within and between limbic structures. Finally, a disproportionate reduction was shown at the level of fibers connecting the left fronto-temporal regions. We could therefore speculate that the observed disruption to fronto-temporal connectivity in individuals at risk of schizophrenia implies that fronto-temporal disconnectivity, frequently implicated in the pathogenesis of schizophrenia, could precede the onset of symptoms and, as such, constitutes a biomarker of the vulnerability to develop psychosis. On the contrary, connectivity alterations in the limbic lobe play a role in a wide range of psychiatric disorders and therefore seem to be less specific in defining schizophrenia.     

Djebelemur,a Tiny Pre-Tooth-Combed Primate from the Eocene of Tunisia: A Glimpse into the Origin of Crown Strepsirhines

Background

Molecular clock estimates of crown strepsirhine origins generally advocate an ancient antiquity for Malagasy lemuriforms and Afro-Asian lorisiforms, near the onset of the Tertiary but most often extending back to the Late Cretaceous. Despite their inferred early origin, the subsequent evolutionary histories of both groups (except for the Malagasy aye-aye lineage) exhibit a vacuum of lineage diversification during most part of the Eocene, followed by a relative acceleration in diversification from the late Middle Eocene. This early evolutionary stasis was tentatively explained by the possibility of unrecorded lineage extinctions during the early Tertiary. However, this prevailing molecular view regarding the ancient origin and early diversification of crown strepsirhines must be viewed with skepticism due to the new but still scarce paleontological evidence gathered in recent years.

Methodological/Principal Findings

Here, we describe new fossils attributable to Djebelemur martinezi, a≈50 Ma primate from Tunisia (Djebel Chambi). This taxon was originally interpreted as a cercamoniine adapiform based on limited information from its lower dentition. The new fossils provide anatomical evidence demonstrating that Djebelemur was not an adapiform but clearly a distant relative of lemurs, lorises and galagos. Cranial, dental and postcranial remains indicate that this diminutive primate was likely nocturnal, predatory (primarily insectivorous), and engaged in a form of generalized arboreal quadrupedalism with frequent horizontal leaping. Djebelemur did not have an anterior lower dentition as specialized as that characterizing most crown strepsirhines (i.e., tooth-comb), but it clearly exhibited a transformed antemolar pattern representing an early stage of a crown strepsirhine-like adaptation (“pre-tooth-comb”).

Conclusions/Significance

These new fossil data suggest that the differentiation of the tooth-comb must postdate the djebelemurid divergence, a view which hence constrains the timing of crown strepsirhine origins to the Middle Eocene, and then precludes the existence of unrecorded lineage extinctions of tooth-combed primates during the earliest Tertiary.     

Motherese in Interaction: At the Cross-Road of Emotion and Cognition? (A Systematic Review)

Various aspects of motherese also known as infant-directed speech (IDS) have been studied for many years. As it is a widespread phenomenon, it is suspected to play some important roles in infant development. Therefore, our purpose was to provide an update of the evidence accumulated by reviewing all of the empirical or experimental studies that have been published since 1966 on IDS driving factors and impacts. Two databases were screened and 144 relevant studies were retained. General linguistic and prosodic characteristics of IDS were found in a variety of languages, and IDS was not restricted to mothers. IDS varied with factors associated with the caregiver (e.g., cultural, psychological and physiological) and the infant (e.g., reactivity and interactive feedback). IDS promoted infants’ affect, attention and language learning. Cognitive aspects of IDS have been widely studied whereas affective ones still need to be developed. However, during interactions, the following two observations were notable: (1) IDS prosody reflects emotional charges and meets infants’ preferences, and (2) mother-infant contingency and synchrony are crucial for IDS production and prolongation. Thus, IDS is part of an interactive loop that may play an important role in infants’ cognitive and social development.     

The impact of encroachment of mangroves into saltmarshes on saltwater mosquito habitats

Will mangrove encroachment into saltmarshes affect saltwater mosquito habitats? To address this, we synthesized information from two perspectives: 1) at a detailed level, the immature mosquito habitat within mangroves; 2) at a more general or regional level, changes due to mangrove expansion into saltmarshes. This is a synthesis of two research projects. One showed that mosquito larval habitats in mangroves are complex, related to the detailed interactions between topography and tidal patterns and that not all parts of a mangrove forest are suitable habitat. The other, based on remote sensing and analysis of rainfall data, showed that mangrove encroachment in eastern Australia is related to both climate and human land use over several decades (1972–2004). An important question emerged: when mangroves encroach into saltmarshes will they displace saltmarsh immature mosquito habitats or will they replace them with mangrove ones? There is no simple answer: it will vary with climate change and sea level scenario and how these affect the system. We conclude that mosquito management, which is locally implemented, needs to be integrated with land use planning systems, which often operate at a more general level.     

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo.     

Osmotin from Calotropis procera latex: new insights into structure and antifungal properties

This study aimed at investigating the structural properties and mechanisms of the antifungal action of CpOsm, a purified osmotin from Calotropis procera latex. Fluorescence and CD assays revealed that the CpOsm structure is highly stable, regardless of pH levels. Accordingly, CpOsm inhibited the spore germination of Fusarium solani in all pH ranges tested. The content of the secondary structure of CpOsm was estimated as follows: α-helix (20%), β-sheet (33%), turned (19%) and unordered (28%), RMSD 1%. CpOsm was stable at up to 75°C, and thermal denaturation (T(m)) was calculated to be 77.8°C. This osmotin interacted with the negatively charged large unilamellar vesicles (LUVs) of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-1-glycerol (POPG), inducing vesicle permeabilization by the leakage of calcein. CpOsm induced the membrane permeabilization of spores and hyphae from Fusarium solani, allowing for propidium iodide uptake. These results show that CpOsm is a stable protein, and its antifungal activity involves membrane permeabilization, as property reported earlier for other osmotins and thaumatin-like proteins.     

胃癌细胞中SMAD-4与TGF-β通过抑制RAS/ERK途径促进PTEN表达

SMAD-4在肿瘤抑制方面有重要作用,但它在肿瘤发生中的作用及其与细胞周期进程中的一种关键调控因子——PTEN(phosphatase and tensin homolog deleted on chromosome 10)的关系仍存在争议.分别在人胚肾细胞(293T)及人胃癌细胞(MGC-803)中研究SMAD-4及TGF-β信号通路对PTEN基因表达的影响.结果发现,在293T细胞中,SMAD-4与TGF-β促进PTEN表达,而MGC-803细胞中,SMAD-4与TGF-β抑制PTEN转录.进一步研究发现,胃癌细胞中,SMAD-4与转化生长因子β(TGF-β)对PTEN的抑制可被PD98059(MEK抑制剂)解除.此外,SMAD-4的核转移也明显促进PTEN表达,并且PD98059存在下,SMAD-4与TGF-β协同刺激可促进胃癌细胞凋亡.综上,实验发现,SMAD-4作为一种co-Smad蛋白,通过TGF-β信号途径影响PTEN表达.