Presentation of ICAM-1 protein at the cell surface of oral keratinocytes in the presence of adrenomedullin and corticotrophin.

Increasing evidence suggests that adrenomedullin (AM) and corticotrophin (ACTH) are immunomodulatory. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the recruitment of leukocytes not only from peripheral blood into inflamed tissues but also into epithelia. We have investigated the effects of AM and ACTH on the expression of ICAM-1 by human oral keratinocytes. The human oral keratinocyte cell line H357 was incubated with either AM or ACTH for up to 8 hrs and ICAM-1 expression was measured by cell surface ELISA. ICAM-1 was up regulated by both peptides and this was attenuated by the adenylyl cyclase inhibitor SQ22,536 and the NF-kappaB inhibitor SN-50. H357 cells constitutively express ICAM-1 mRNA and expression of this gene was significantly modulated by AM and ACTH. Furthermore AM caused translocation of NF-kappaB from the cytoplasm to the nucleus. This is the first report describing up regulation of ICAM-1 in oral keratinocytes by AM and ACTH and the results suggest both cAMP and NF-kappaB may play a role. These results further suggest both peptides may have an immunostimulatory role in oral muocsa and skin.     

DNA end resection: Many nucleases make light work

Double-strand breaks (DSBs) are deleterious DNA lesions and if left unrepaired result in severe genomic instability. Cells use two main pathways to repair DSBs: homologous recombination (HR) or non-homologous end joining (NHEJ) depending on the phase of the cell cycle and the nature of the DSB ends. A key step where pathway choice is exerted is in the ‘licensing’ of 5′–3′ resection of the ends to produce recombinogenic 3′ single-stranded tails. These tails are substrate for binding by Rad51 to initiate pairing and strand invasion with homologous duplex DNA. Moreover, the single-stranded DNA generated after end processing is important to activate the DNA damage response. The mechanism of end processing is the focus of this review and we will describe recent findings that shed light on this important initiating step for HR. The conserved MRX/MRN complex appears to be a major regulator of DNA end processing. Sae2/CtIP functions with the MRX complex, either to activate the Mre11 nuclease or via the intrinsic endonuclease, in an initial step to trim the DSB ends. In a second step, redundant systems remove long tracts of DNA to reveal extensive 3′ single-stranded tails. One system is dependent on the helicase Sgs1 and the nuclease Dna2, and the other on the 5′–3′ exonuclease Exo1.     

A Paradoxical Kind of Sleep in Drosophila melanogaster

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Muscle co-activation around the knee in drop jumping using the co-contraction index.

The purpose of this study was to examine the co-activation of the rectus femoris (RF) and biceps femoris (BF) during drop jumping exercises using the co-contraction index (CI). Ten trained male long jumpers performed drop jumps from 20 cm (DJ20), 40 cm (DJ40) and 60 cm (DJ60) on a force platform. Surface electromyographic (EMG) activity of the RF and BF, vertical ground reaction force data and knee joint angular displacement and angular velocities were recorded and normalized as percentage of maximum isometric values. The CI was calculated for the pre-contact, braking and propulsive phases of the jump using four methods: (1) by dividing the double integrated antagonistic activity by the sum of the RF and BF EMG; (2) by finding the amount of overlap between the linear envelopes of the agonist and antagonist muscles and dividing by the number of data points; (3) by calculating the co-contraction at any instant point of time; and (4) by dividing the BF integrated activity by the total registered muscle activity around the knee. The CI ranged from 13.03+/-9.33 to 70.80+/-25.81%, depending on the estimation method used. A two-way analysis of variance (ANOVA) indicated that the CI was not affected by drop jumping height (p>0.05) while it was significantly higher (p<0.05) in the pre-contact phase compared to the braking and propulsion phases. The CI can be useful when examining muscle co-activation using EMG measurements in drop jumps. However, the conclusions on muscle co-activation depend on the equation used to estimate CI and therefore a commonly accepted method is necessary.     

A Simple Methodological Approach for Counting and Identifying Culturable Viruses Adsorbed to Cellulose Nitrate Membrane Filters

We identified conditions under which Buffalo green monkey cells grew on the surfaces of cellulose nitrate membrane filters in such a way that they covered the entire surface of each filter and penetrated through the pores. When such conditions were used, poliovirus that had previously been adsorbed on the membranes infected the cells and replicated. A plaque assay method and a quantal method (most probable number of cytopathic units) were used to detect and count the viruses adsorbed on the membrane filters. Polioviruses in aqueous suspensions were then concentrated by adsorption to cellulose membrane filters and were subsequently counted without elution, a step which is necessary when the commonly used methods are employed. The pore size of the membrane filter, the sample contents, and the sample volume were optimized for tap water, seawater, and a 0.25 M glycine buffer solution. The numbers of viruses recovered under the optimized conditions were more than 50% greater than the numbers counted by the standard plaque assay. When ceftazidime was added to the assay medium in addition to the antibiotics which are typically used, the method could be used to study natural samples with low and intermediate levels of microbial pollution without decontamination of the samples. This methodological approach also allowed plaque hybridization either directly on cellulose nitrate membranes or on Hybond N+ membranes after the preparations were transferred.     

Phytoplankton Community Structure in the Drainage Network of a Mediterranean River System (Aliakmon,Greece)

Phytoplankton structure was studied in Aliakmon river basin in April (highflow) and September (lowflow) 1995 in 29 sampling sites. Abundance and biomass were generally low and ranged considerably between sites. Benthic diatoms contributed greatly to the suspended algal assemblages whereas trends of potamoplankton development were observed downstream. Limnoplankton and especially chlorophytes developed in the areas where lentic conditions prevailed. The nature of changes in phytoplankton seemed to be both longitudinal and temporal. Multivariate techniques revealed that areas with distinctive morphology, hydrology and anthropogenic inputs tended to have similar phytoplankton composition although no simple relation with physico-chemical factors can be shown. Human impact was more obvious on phytoplankton at the lowflow period. Generally, discharge played a significant role to the structure of phytoplankton communities.     

HDAC inhibition ameliorates cone survival in retinitis pigmentosa mice

Cone photoreceptor cell death in inherited retinal diseases, such as Retinitis Pigmentosa (RP), leads to the loss of high acuity and color vision and, ultimately to blindness. In RP, a vast number of mutations perturb the structure and function of rod photoreceptors, while cones remain initially unaffected. Extensive rod loss in advanced stages of the disease triggers cone death by a mechanism that is still largely unknown. Here, we show that secondary cone cell death in animal models for RP is associated with increased activity of histone deacetylates (HDACs). A single intravitreal injection of an HDAC inhibitor at late stages of the disease, when the majority of rods have already degenerated, was sufficient to delay cone death and support long-term cone survival in two mouse models for RP, affected by mutations in the phosphodiesterase 6b gene. Moreover, the surviving cones remained light-sensitive, leading to an improvement in visual function. RNA-seq analysis of protected cones demonstrated that HDAC inhibition initiated multi-level protection via regulation of different pro-survival pathways, including MAPK, PI3K-Akt, and autophagy. This study suggests a unique opportunity for targeted pharmacological protection of secondary dying cones by HDAC inhibition and creates hope to maintain vision in RP patients even in advanced disease stages.Subject terms: Neuroscience, Neurological disorders     

A critical analysis of the HIV-T4-cell-AIDS hypothesis

The data generally accepted as proving the HIV theory of AIDS, HIV cytopathy, destruction of T4 lymphocytes, and the relationship between T4 cells, HIV and the acquired immune deficiency clinical syndrome are critically evaluated. It is concluded these data do not prove that HIV preferentially destroys T4 cells or has any cytopathic effects, nor do they demonstrate that T4 cells are preferentially destroyed in AIDS patients, or that T4 cell destruction and HIV are either necessary or sufficient prerequisites for the development of the clinical syndrome.Knowledge is one. Its division into subjects is a concession to human weakness.