Abnormal MEG Oscillatory Activity during Visual Processing in the Prefrontal Cortices and Frontal Eye-Fields of the Aging HIV Brain

Objective

Shortly after infection, HIV enters the brain and causes widespread inflammation and neuronal damage, which ultimately leads to neuropsychological impairments. Despite a large body of neuroscience and imaging studies, the pathophysiology of these HIV-associated neurocognitive disorders (HAND) remains unresolved. Previous neuroimaging studies have shown greater activation in HIV-infected patients during strenuous tasks in frontal and parietal cortices, and less activation in the primary sensory cortices during rest and sensory stimulation.

Methods

High-density magnetoencephalography (MEG) was utilized to evaluate the basic neurophysiology underlying attentive, visual processing in older HIV-infected adults and a matched non-infected control group. Unlike other neuroimaging methods, MEG is a direct measure of neural activity that is not tied to brain metabolism or hemodynamic responses. During MEG, participants fixated on a centrally-presented crosshair while intermittent visual stimulation appeared in their top-right visual-field quadrant. All MEG data was imaged in the time-frequency domain using beamforming.

Results

Uninfected controls had increased neuronal synchronization in the 6–12 Hz range within the right dorsolateral prefrontal cortex, right frontal eye-fields, and the posterior cingulate. Conversely, HIV-infected patients exhibited decreased synchrony in these same neural regions, and the magnitude of these decreases was correlated with neuropsychological performance in several cortical association regions.

Conclusions

MEG-based imaging holds potential as a noninvasive biomarker for HIV-related neuronal dysfunction, and may help identify patients who have or may develop HAND. Reduced synchronization of neural populations in the association cortices was strongly linked to cognitive dysfunction, and likely reflects the impact of HIV on neuronal and neuropsychological health.     

Retinal Pigment Epithelium and Photoreceptor Preconditioning Protection Requires Docosanoid Signaling

Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are necessary for functional cell integrity. Preconditioning (PC), as we define it, is an acquired protection or resilience by a cell, tissue, or organ to a lethal stimulus enabled by a previous sublethal stressor or stimulus. In this study, we provide evidence that the omega-3 fatty acid docosahexaenoic acid (DHA) and its derivatives, the docosanoids 17-hydroxy docosahexaenoic acid (17-HDHA) and neuroprotectin D1 (NPD1), facilitate cell survival in both in vitro and in vivo models of retinal PC. We also demonstrate that PC requires the enzyme 15-lipoxygenase-1 (15-LOX-1), which synthesizes 17-HDHA and NPD1, and that this is specific to docosanoid signaling despite the concomitant release of the omega-6 arachidonic acid and eicosanoid synthesis. These findings advocate that DHA and docosanoids are protective enablers of PC in photoreceptor and retinal pigment epithelial cells.     

Structural and functional characterization of a novel T cell receptor co-regulatory protein complex, CD97-CD55

CD97, the archetypal member of the EGF-TM7 protein family, is constitutively expressed on granulocytes and monocytes and rapidly up-regulated on T and B cells following activation. The key isoform of CD97 expressed on leukocytes binds the complement regulatory protein CD55 (also termed decay-accelerating factor). CD97 has been shown recently to mediate co-stimulation of T cells via CD55. Here, we demonstrate that blocking the interaction between CD55 on monocytes and CD97 on T cells leads to inhibition of proliferation and interferon-gamma secretion. This implies that bidirectional interactions between CD97 and CD55 are involved in T cell regulation. Structural studies presented here reveal the molecular basis for this activity. We have solved the structure of EMR2, a very close homolog of CD97, using x-ray crystallography. NMR-based chemical shift mapping of the EMR2-CD55 interaction has allowed us to generate a model for the CD97-CD55 complex. The structure of the complex reveals that the T cell and complement regulatory activities of CD55 occur on opposite faces of the molecule. This suggests that CD55 might simultaneously regulate both the innate and adaptive immune responses, and we have shown that CD55 can still regulate complement when bound to CD97.     

Chromosomal localization of the human apoprotein CI gene and of a polymorphic apoprotein AII gene

Human apoprotein(apo) CI and apo AII cDNA probes have been used to analyze the segregation of the human genes in panels of human-mouse hybrids. The apo CI (APOCI) gene segregates with chromosome 19 and the apo AII (APOA2) gene with chromosome 1. Somatic cell hybrids containing chromosome translocations were used to map the apo AII gene to the 1p21-1qter region. Human APOA2 is polymorphic for the restriction endonuclease Msp I. Comparison of human and mouse chromosome 1 reveals a conserved group including apo AII, renin and peptidase genes and suggests that APOA2 will be found distal to this group on human chromosome 1. The mouse apo AII gene is closely linked with genes that regulate HDL structure. Similar HDL regulatory genes will probably be found near human APOA2.     

Connective tissue reinforcing structures of the digital tendon sheaths of the human hand

At a greater number of humid preparated human hands, all the ligamentous supports of the digital tendon sheath were exposed and their dimensions were determined. The osteofibrous channels, which contain the long flexor tendons of the digits, were bounded on the one hand by transversely concave shaft areas of the phalanges and the palmar ligaments and on the other side by the fibrous parts of the tendon sheath. From the second to the 5th finger, it has a regular extension of length, which begins proximal at the heads of the metacarpal bones and runs distal to the base of the nail phalanx. In some cases, there is a continuous communication between the digital tendon sheath of the little finger and the carpal synovial sheath. The tendon sheath of the flexor pollicis longus muscle in comparison with it is always in an open communication with the radial synovial sac of the wrist. At the fibrous supports of the digital tendon sheath, one can find constant and inconstant ligamentous structures. Regular shaped ligaments consist of annular fibers (A1 to A5). The proximal complex of fiber supports is a formation of the A1 and A2 ligaments. The band A1 can be divided into 2 ligaments both of roughly equal length, which lay between the head of the metacarpal bone and the base of the proximal phalanx. The strongest fibrous support of the whole digital tendon sheath represents the band A2. It is attached to the midth of the proximal phalanx and increases in strength from proximal to distal. The middle length varies between 6.7 mm at the thumb and 18.7 mm at the middle finger. The distal margin is strengthened by fibrocartilage tissue to be in accordance with the important function as a pulley. The annular band A4 forms the distal supporting complex height above the shaft of the middle phalanx. At the 2nd to the 5th finger it is, with a middle length of 6 to 7 mm, very much shorter than A2 and restrains first of all the tendon of the flexor digitorum profundus muscle. In the area of the interphalangeal joints, we can find the annular bands A3 and A5, which fiber texture is formed variable. Both ligaments are attached on either both sides with the joint capsule and the palmar plate. The other inconstant supports of the digital sheaths are systematically recorded indeed (C1 to C3), but only in exceptional cases they exist of cruciform fibers (Lig. cruciatum).(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of chorionic villus sampling and early pregnancy counselling on uptake of prenatal diagnosis.

An early pregnancy counselling clinic was introduced to improve the uptake of prenatal diagnosis and to offer chorionic villus sampling to women aged 38 and over by their expected date of delivery. Ninety eight (62%) unselected older mothers were seen before 11 weeks'' gestation, and 23 (32%) of those with viable pregnancies elected to undergo chorionic villus sampling compared with 38 (52%) electing amniocentesis. A quarter of the patients booking before 11 weeks had a miscarriage. Because of the future potential demand for chorionic villus sampling counselling during pregnancy and referral of eligible patients should occur as early as possible.     

Regional chromosomal localisation of APOA2 to 1q21–1q23

Summary Using in situ hybridisation, we have mapped APOA2 to the 1q21–1q23 region of chromosome 1. DNA hybridisation to somatic cell hybrids made from cells carrying a balanced translocation between X and 1 confirms the localisation as proximal to 1q23. This was further confirmed by the presence of two polymorphic alleles in a cell line carrying a deletion of 1q25–1q32.