"That imperfect instrument": Galton's whistle, Bierce's damned thing, and the phenomenon of superior nonhuman sensory range.

When the Galton whistle was introduced in the 1870s, it was the first demonstration many had encountered of the phenomenon that nonhumans sometimes exceed humans in sensory range, for example perceiving ultraviolet light and ultrasonic signals. While some empirical research had explored this possibility beforehand, this area of perceptual research progressed slowly. A horror short story by Ambrose Bierce in 1893, "The Damned Thing," used the concept of superior nonhuman sensory range as a twist ending, seemingly anticipating scientific discoveries to come or at least understanding the implications of the early findings well in advance of the field.

HIV-1-Specific Chimeric Antigen Receptor T Cells Fail To Recognize and Eliminate the Follicular Dendritic Cell HIV Reservoir .

The major obstacle to a cure for HIV infection is the persistence of replication-competent viral reservoirs during antiretroviral therapy. HIV-specific chimeric antigen receptor (CAR) T cells have been developed to target latently infected CD4 T cells that express virus either spontaneously or after intentional latency reversal. Whether HIV-specific CAR-T cells can recognize and eliminate the follicular dendritic cell (FDC) reservoir of HIV-bound immune complexes (ICs) is unknown.

Multivariate profiling of African green monkey and rhesus macaque T lymphocytes.

The complexity of immune responses limits the usefulness of univariate methods in answering complex immunology questions. To demonstrate the utility of a multivariate approach, we employ such approach to compare T cells of African green monkeys (AGMs) and rhesus macaques (RMs). Among the most prominent distinguishing features we found were lower CD3 and higher CD28 surface expression in AGMs compared to RMs.

Alpha-1-antitrypsin interacts with gp41 to block HIV-1 entry into CD4+ T lymphocytes.

Background: Study of a clinic case reveals that alpha-1-antitrypsin (AAT) deficiency is related to CD4+ T cell count decline and AIDS progression, suggesting that AAT might be an endogenous inhibitor of HIV/AIDS. Previous study shows that AAT inhibits HIV-1 replication in infected host cells and the C-terminus fragment of AAT, VIRIP, interferes with HIV-1 infection. However, it is still unclear whether and how intact AAT inhibits HIV-1 infection.

Low-density lipoprotein receptor-related protein 1 mediates α1-antitrypsin internalization in CD4+ T lymphocytes.

In α1-antitrypsin-deficient HIV patients, an accelerated decline of CD4(+) T cell numbers is observed, suggesting that α1-antitrypsin is a potential endogenous HIV inhibitor. In infected T lymphocytes, α1-antitrypsin potently blocks NF-κB activation and HIV-1 replication by directly interacting with IκBα in the cytosol, thereby altering its ubiquitination pattern. However, the mechanism of α1-antitrypsin entry into the cytosol, where IκBα locates, remains unclear.

Use of prednisolone as monotherapy in the treatment of feline pemphigus foliaceus: a retrospective study of 37 cats.

Background: Prednisone doses of up to 8 mg/kg/day have been used to treat feline pemphigus foliaceus (PF). Oral prednisolone has more favourable pharmacokinetics in cats than prednisone; therefore, lower doses of prednisolone may be effective in treating feline PF.

Hypothesis/objectives: To assess the dose of prednisolone required to induce and maintain remission of PF in cats.

Canine pyoderma gangrenosum: a case series of two dogs.

Background: Pyoderma gangrenosum (PG) is a rare disease, which, to the best of the authors' knowledge, has been the subject of only one case report in the peer-reviewed veterinary literature.

Hypothesis/objectives: To describe the history, clinical signs, diagnostic findings and treatment outcome in two cases of canine PG.

Animals: Two client-owned dogs presented to a private veterinary referral practice between 2008 and 2010 who received a diagnosis of PG by specialist veterinary dermatologists.

The evolution of HIV: inferences using phylogenetics.

Molecular phylogenetics has revolutionized the study of not only evolution but also disparate fields such as genomics, bioinformatics, epidemiology, ecology, microbiology, molecular biology and biochemistry. Particularly significant are its achievements in population genetics as a result of the development of coalescent theory, which have contributed to more accurate model-based parameter estimation and explicit hypothesis testing. The study of the evolution of many microorganisms, and HIV in particular, have benefited from these new methodologies.

Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-1 and SIV infections.

The hallmark of HIV-1 and SIV infections is CD4(+) T cell depletion. Both direct cell killing and indirect mechanisms related to immune activation have been suggested to cause the depletion of T cells. We have now identified a mechanism by which immune activation-induced fibrosis of lymphoid tissues leads to depletion of naive T cells in HIV-1 infected patients and SIV-infected rhesus macaques.

HIV replication in CD4+ T lymphocytes in the presence and absence of follicular dendritic cells: inhibition of replication mediated by α-1-antitrypsin through altered IκBα ubiquitination.

Follicular dendritic cells (FDCs) increase HIV replication and virus production in lymphocytes by increasing the activation of NF-κB in infected cells. Because α-1-antitrypsin (AAT) decreases HIV replication in PBMCs and monocytic cells and decreases NF-κB activity, we postulated that AAT might also block FDC-mediated HIV replication. Primary CD4(+) T cells were infected with HIV and cultured with FDCs or their supernatant with or without AAT, and ensuing viral RNA and p24 production were monitored.

Follicular dendritic cells and human immunodeficiency virus type 1 transcription in CD4+ T cells.

HIV replication occurs throughout the natural course of infection in secondary lymphoid tissues and in particular within the germinal centers (GCs), where follicular dendritic cells (FDCs) are adjacent to CD4(+) T cells. Because FDCs provide signaling that increases lymphocyte activation, we postulated that FDCs could increase human immunodeficiency virus (HIV) replication. We cultured HIV-infected CD4(+) T cells alone or with FDCs and measured subsequent virus expression using HIV-p24 production and reverse transcription-PCR analyses.

Characterization of the follicular dendritic cell reservoir of human immunodeficiency virus type 1.

Throughout the natural course of human immunodeficiency virus (HIV) infection, follicular dendritic cells (FDCs) trap and retain large quantities of particle-associated HIV RNA in the follicles of secondary lymphoid tissue. We have previously found that murine FDCs in vivo could maintain trapped virus particles in an infectious state for at least 9 months. Here we sought to determine whether human FDCs serve as an HIV reservoir, based on the criteria that virus therein must be replication competent, genetically diverse, and archival in nature.

Proteomic and phototoxic characterization of melanolipofuscin: correlation to disease and model for its origin.

Purpose: Melanolipofuscin (MLF) is a complex granule, exhibiting properties of both melanosomes and lipofuscin (LF) granules, which accumulates in retinal pigment epithelial (RPE) cells and may contribute to the etiology of age-related macular degeneration (AMD). MLF accumulation has been reported by Feeney-Burns to more closely reflect the onset of AMD than the accumulation of lipofuscin. In an effort to assess the possible contribution MLF may have to the onset of AMD, we analyzed the phototoxicity and protein composition of MLF and compared those results to that of LF.

Comparative expression profiling in primary and immortalized endothelial cells: changes in gene expression in response to hydroxy methylglutaryl-coenzyme A reductase inhibition.

Immortalized cell lines offer significant logistical advantages over primary cells when used for in-vitro studies. Immortalized cells may, however, exhibit important differences relative to their primary cell counterparts. In this study, microarrays were used to make a genome-wide comparison between primary human umbilical vein endothelial cells (HUVECs) and EA.

Examining the proteins of functional retinal lipofuscin using proteomic analysis as a guide for understanding its origin.

Purpose: To elucidate the origins of biologically active retinal lipofuscin (RLF) by examining its protein composition.

Methods: Total protein and total lipid were extracted and quantified. Proteins in this lipoprotein granule were identified by limited-scale proteomic analysis using both two-dimensional (2D) gel electrophoresis and SDS-PAGE coupled with MALDI-QqToF MSMS and automated LCMSMS, respectively.

Follicular dendritic cell regulation of CXCR4-mediated germinal center CD4 T cell migration.

Follicular dendritic cells (FDCs) up-regulate the chemokine receptor CXCR4 on CD4 T cells, and a major subpopulation of germinal center (GC) T cells (CD4(+)CD57(+)), which are adjacent to FDCs in vivo, expresses high levels of CXCR4. We therefore reasoned that GC T cells would actively migrate to stromal cell-derived factor-1 (CXCL12), the CXCR4 ligand, and tested this using Transwell migration assays with GC T cells and other CD4 T cells (CD57(-)) that expressed much lower levels of CXCR4. Unexpectedly, GC T cells were virtually nonresponsive to CXCL12, whereas CD57(-)CD4 T cells migrated efficiently despite reduced CXCR4 expression.

Microarray analysis of differentiation-specific gene expression during 3T3-L1 adipogenesis.

During cellular differentiation and development, it is recognized that many complex molecular mechanisms as well as precise patterns of differentially expressed genes occur in directing precursor cells toward a given lineage. Using microarray-based technology, we examined gene expression across the course of 3T3-L1 adipocyte differentiation. Total cellular RNA was isolated at times 0, 2, 8, 16, 24, 48, and 96 h following treatment with either standard hormonal inducers of differentiation; insulin, dexamethasone, isobutylmethylxanthine (IDX), or IDX plus trichostatin A (TsA), a histone deacetylase inhibitor and potent adipogenic inhibitor.

Cyclosporin: applications in small animal dermatology.

Cyclosporin has been increasingly used for the treatment of skin diseases in small animals. Reported uses include the treatment of atopy, cutaneous lupus erythematosus, feline acquired alopecia resembling pseudopelade of humans, pemphigus erythematosus, pemphigus foliaceus, perianal fistulae and sebaceous adenitis. In addition, cyclosporin has been used anecdotally for several other skin diseases.

Follicular dendritic cell-mediated up-regulation of CXCR4 expression on CD4 T cells and HIV pathogenesis.

Follicular dendritic cells (FDCs) represent a major reservoir of HIV, and active infection occurs surrounding these cells, suggesting that this microenvironment is highly conducive to virus transmission. Because CD4 T cells around FDCs in germinal centers express the HIV coreceptor, CXCR4, whereas CD4 lymphocytes in many other sites do not, it prompted the hypothesis that FDCs may increase CXCR4 expression on CD4 T cells, thereby facilitating infection. To test this, HIV receptor/coreceptor expression was determined on CD4 T cells cultured with or without FDCs, and its consequence to infection was assessed by measuring virus binding and entry.

Follicular dendritic cell contributions to HIV pathogenesis.

Early after infection, large quantities of HIV are trapped on follicular dendritic cells (FDCs) thus establishing a potent reservoir of infectious virus adjacent to highly susceptible CD4-bearing T lymphocytes. Throughout much of the disease course, active HIV infection is largely confined to sites surrounding FDCs suggesting that this microenvironment is highly conducive to infection. FDCs maintain HIV infectivity and trapped virus can cause infection even in the presence of neutralizing antibody.

Microarray analysis of gene expression during early adipocyte differentiation.

The molecular mechanisms that regulate cellular differentiation during development and throughout life are complex. It is now recognized that precise patterns of differentially expressed genes ultimately direct a particular cell toward a given lineage and many of these are regulated during the earliest stages of differentiation. Using a microarray-based expression analysis, we have examined gene expression profiles during the first 24 h of 3T3-L1 adipocyte differentiation.

Successor states in a four-state ambiguous figure.

The satiation theory of ambiguous figures holds that interpretation shifts are caused by fatigue of neural arrangements responsible for the prevailing interpretation. A four-state multistable figure is introduced, in which two depicted cubes can be seen as connected or unconnected and as facing up or facing down. Observers viewed the figure for 4 min.

Follicular dendritic cells and the persistence of HIV infectivity: the role of antibodies and Fcgamma receptors.

Large quantities of HIV are found trapped on the surface of follicular dendritic cells (FDCs), and virus persists on these cells until they ultimately die. We recently found that FDCs maintain HIV infectivity for long periods in vivo and in vitro. Because FDCs trap Ags (and virus) in the form of immune complexes and are rich in FcgammaRs, we reasoned that Ab and FcgammaRs may be required for FDC-mediated maintenance of HIV infectivity.

Proteasomal degradation of retinoblastoma-related p130 during adipocyte differentiation.

Within 24 h of hormonally stimulated 3T3-L1 adipocyte differentiation, there are dramatic changes in the protein levels of p130 and p107, two members of the retinoblastoma tumor suppressor gene family. Designated the "p103:p107" switch, this alteration is characterized by a rapid and transient drop in p130 protein levels accompanied by a transient increase in both p107 mRNA and protein levels. Using protease inhibitors, the specific proteolytic pathway involved in degradation of p130 was examined.