Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationships Between Expression of Apolipoprotein E and &bgr;-Amyloid Precursor Protein Are Altered in Proximity to Alzheimer &bgr;-Amyloid Plaques: Potential Explanations From Cell Culture Studies

Theories regarding the initiation and progression of Alzheimer disease (AD) often consider potential roles played by elevations of &bgr;-amyloid precursor protein (&bgr;APP). Because it is the source of amyloid &bgr;-peptide, &bgr;APP may simply contribute more pathogenic stimulus when elevated; some analyses have, however, reported a decline in &bgr;APP in AD. We found a progressive increase in neuronal &bgr;APP expression with increasing age in the brains of nondemented individuals, whereas in AD patient samples, &bgr;APP antigenicity decreased in neuronal somata in a manner that correlated with accumulation of mature amyloid &bgr;-peptide plaques. In contrast, apolipoprotein E (ApoE) expression correlated with accumulation of plaques, and even greater amounts of ApoE were detected in plaques. Induction of &bgr;APP by glutamate in neuronal cell cultures was found to depend upon ApoE levels or activity. Thus, elevations in expression of ApoE and &bgr;APP by cellular stresses are likely normally linked in vivo, and uncoupling of this link, or other pathologic events in AD initiation, may leave neurons with diminished &bgr;APP expression, which might in turn reduce their resistance to stressors.
Apoptosis of estrogen‐receptor negative breast cancer and colon cancer cell lines by PTPα and src RNAi

We show that siRNA‐mediated suppression of protein tyrosine phosphatase α (PTPα) reduces Src activity 2 to 4‐fold in breast, colon and other human cancer cell lines. Src and PTPα RNAi induced apoptosis in estrogen receptor (ER)‐negative breast cancer and colon cancer cells, but not in immortalized noncancerous breast cells, ER‐positive breast cancer cells or other cancer cell types tested. RNAi of other Src family members (Fyn and Yes) or of PTP1B, a phosphatase previously suggested to be an activator of Src in breast cancer, had no effect. Although further tests with primary tumor tissues are required, the unexpected correlation between ER status and Src/PTPα dependence in breast cancer cell lines may be important for planning therapeutic strategies, and the insensitivity of normal breast cells to the RNAi highlights the potential of PTPα, which may be easier to target than Src, as a therapeutic target in ER‐negative breast cancer. © 2008 Wiley‐Liss, Inc.
The Escherichia coli ATP‐binding cassette (ABC) proteins

The recent completion of the Escherichia coli genome sequence (Blattner et al., 1997) has permitted an analysis of the complement of genomically encoded ATP‐binding cassette (ABC) proteins. A total of 79 ABC proteins makes this the largest paralogous family of proteins in E. coli. These 79 proteins include 97 ABC domains (as some proteins include more than one ABC domain) and are components of 69 independent functional systems (as many systems involve more than one ABC domain). The ABC domains are often, but not exclusively, the energy‐generating domains of multicomponent membrane‐bound transporters. Thus, 57 of the 69 systems are ABC transporters, of which 44 are periplasmic‐binding protein‐dependent uptake systems and 13 are presumed exporters. The genes encoding these ABC transporters occupy almost 5% of the genome. Of the 12 systems that are not obviously transport related, the function of only one, the excision repair protein UvrA, is known. A phylogenetic analysis suggests that the majority of ABC proteins can be assigned to 10 subfamilies. Together with statistical and, importantly, biological evidence, this analysis provides insight into the evolution and function of the ABC proteins.
Assessment of ecological regression in the study of colon, breast, ovary, non-Hodgkin's lymphoma, or prostate cancer and residential UV

Recent ecological studies have suggested a possible association between exposure to ultraviolet-B (UVB) radiation and reduction in the risk of various cancers; however, ecological studies are known to be subject to bias. The objective of this study was to demonstrate difficulties with the ecological approach. We conducted a multicountry ecological study using cancer incidence rates, residential UV levels, dietary intake, and different sociodemographic variables for 38 locations spanning 33 countries worldwide. The effect of residential UV exposure on cancer incidence was assessed using multiple linear regression models. The results of our multivariate analyses show no indication of an inverse association between residential UV levels and the risk of colon, non-Hodgkin's lymphoma (NHL), ovarian, prostate, or breast cancer in women. For colon cancer and NHL, a significant positive association was calculated. The rates of melanoma, which were used to examine the methods of this study, showed a strong and significant (P<0.01) association with solar radiation. Our results provide no evidence to support previous ecological results that UV exposure may reduce the risk of NHL, colon, breast, ovary, or prostate cancer. The study demonstrates the high sensitivity of ecological studies to adjustments for various confounders, and casts doubts on results of ecological analyses in this field.
The Impact of Real and Illusory Perturbations on the Early Trajectory Adjustments of Goal-Directed Movements

ABSTRACT Examinations of goal-directed movements reveal a process of control that operates to make adjustments on the basis of the expected visual afference associated with the limb's movement. This experiment examined the impact of perturbations to the perceived and actual velocity of aiming movements when each was presented alone or in tandem with the other. Perturbations to perceived velocity were achieved by translating the background over which aiming movements were performed. An aiming stylus that discharged air either in the direction of the movement or in the direction opposite the movement generated the actual velocity perturbations. Kinematic analyses of the aiming movements revealed that only the actual perturbation influenced the control of early movement trajectories. The results are discussed with respect to the influence that visual information has on the control exerted against physical perturbations. Speculations are raised regarding how potential for perturbations influences the strategies adopted for minimizing their impact.
Emerging drugs for the treatment of dry eye disease

Introduction: Dry eye disease (DED) is a common, age-related ocular condition that in its mildest forms causes bothersome symptoms of ocular discomfort, fatigue, and visual disturbance that interfere with quality of life and in its more severe forms causes chronic pain and fluctuating vision. Though it is highly prevalent and costs billions of dollars to manage, current treatments have largely been inadequate, making it a frustrating condition, both for physicians and patients alike. Areas covered: This article will cover the recently discovered pathophysiology of DED that has prompted investigators to explore new molecules that target the core mechanisms that drive DED. These include anti-inflammatory/immune-modulatory drugs, secretagogues, lubricant, hormones, and autologous serum. Their potential mechanism of action and data from recent trials on efficacy/safety will be reviewed. Expert opinion: The emerging drugs have a vast range of putative mechanisms of action that may not only provide symptomatic relief but may potentially break the vicious cycle of DED and provide long-lasting cure. Current and future research may change our perspective on DED and redefine its treatment algorithms.
Confined placental mosaicism in term placentae: Analysis of 125 cases

In order to determine the incidence of confined placental mosaicism (CPM) in term placentae and to show the presence of specific sites and the effect on fetal development, 125 placentae from uneventful pregnancies were analysed by cytogenetic methods. The incidence was at least 4.8 per cent and there were no specific sites on the placenta. Although the number of cases is still too small, we found CPM to be associated with intrauterine growth retardation in six cases.
The Role of Vascular and Interstitial Compliance and Vascular Volume in the Regulation of Blood Volume in Two Species of Anuran

The objectives of this study were (1) to measure plasma (Vp), blood (Vb), extracellular (Ve), and interstitial fluid (Vist) volumes using the same techniques; (2) to measure the rate of plasma turnover; and (3) to characterize the three important variables required to interpret transvascular flux at an organismal level (vascular compliance [Cvas], interstitial compliance [Cist], and the whole‐body transvascular filtration coefficient [Fc]) in two species of anurans that differ in their capacity to regulate blood volume during dehydrational and hemorrhagic stress. The disappearance curve of Evans blue–labeled native plasma protein fitted a two‐component exponential decay model for both species, indicating that plasma proteins exchanged quickly between two kinetically distinct compartments, Vp and Ve. Vp calculated using serial sampling times <10 min were 61.0 mL kg−1 for Chaunus marinus and 40.5 mL kg−1 for Lithobates catesbeiana. Plasma turnover rate was 3% of Vp min−1 (1.8 mL min−1 kg−1) for C. marinus and 5.5% of Vp min−1 (2.2 mL min−1 kg−1) for L. catesbeiana. Chaunus marinus also had significantly greater Vb (84 to 53 mL kg−1), Vist (171 to 154 mL kg−1), and Ve (232 to 195 mL kg−1) than L. catesbeiana. Cvas was significantly greater in C. marinus (47.3 mL kPa−1 kg−1) compared with L. catesbeiana (27.7 mL kPa−1 kg−1). This difference reflects the interspecific differences in Vb because vascular distensibilities are similar (0.5% kPa−1). There were no interspecific differences in the Cist (500 mL kPa−1 kg−1) or Fc (2.5 mL kg−1 kPa−1 min−1 filtration calculation; 0.2–0.5 mL kPa−1 kg−1 min−1 fit to volume change data). Functionally, these circulatory/interstitial exchange variables of both anuran species exemplify a circulatory system with high rates of filtration (lymph formation) and with no capacity for transcapillary fluid uptake, hence requiring substantial lymphatic return to maintain vascular volume. The large Cist of both species provides a capacity to store extravascular volume with little perturbation of vascular pressure, but the resulting low interstitial pressures would create difficulties for extravascular fluid return to the dorsally located lymph hearts. The principal interspecific differences of greater Vb, Vp, Vist, and Cvas for the more terrestrial species, C. marinus, would stabilize cardiac function during hypovolemia (e.g., hemorrhage) and increase resistance to dehydration. This is consistent with this species' enhanced capacity to manage dehydrational and hemorrhagic challenges to blood volume regulation compared to L. catesbeiana.
The Spectrum of Human Kallikrein 6 (Zyme/Protease M/Neurosin) Expression in Human Tissues as Assessed by Immunohistochemistry

The KLK6 gene is a new member of the human kallikrein gene family and encodes for a secreted protease, human kallikrein 6 (hK6; also known as zyme/protease M/neurosin). No study has as yet reported detailed immunohistochemical localization of hK6 in human tissues. Our purpose was to examine the expression of hK6 in human tissues by immunohistochemistry. We have analyzed 199 paraffin blocks from archival, current, and autopsy material prepared from almost every normal human tissue. We employed an hK6-specific polyclonal rabbit antibody and avidin-biotin to localize hK6 by IHC. The staining pattern, the distribution of the immunostaining, and its intensity were studied in detail. The IHC expression of zyme was generally cytoplasmic. Various normal human tissues expressed the protein abundantly. Glandular epithelia constituted the main immunoexpression sites, with representative organs being the breast, prostate, kidney, endometrium, colon, appendix, salivary glands, bile ducts, and gallbladder. The small intestine, stomach, endocervix, Fallopian tube, epididymis, bronchus, and upper respiratory tract showed a focal expression as well. Choroid plexus epithelium, peripheral nerves, and some neuroendocrine cells (including the islets of Langerhans, cells in the anterior pituitary gland, and adrenal medulla) expressed the protein strongly and diffusely. A characteristic immunostaining was observed in the Hassall's corpuscles of the thymus, the oxyphilic cells of the thyroid and parathyroid glands, the primordial follicles of the ovary, dendritic cells mainly in the spleen, and in various cells of the placenta.
Antifungal efficacy of lasers against dermatophytes and yeasts in vitro

Abstract Purpose: Approximately 2–13% of the world population suffers from onychomycosis. Recently, lasers have been introduced for treatment. However, no effect was found with in vitro laser irradiation of pathogens on agar plates. This study aimed to investigate the efficacy of laser irradiation against fungi using an alternative in vitro approach. Materials and methods: Lasers of 808, 980 and 1064 nm were used to heat cell culture media and a nail clipping. Trichophyton rubrum. T. interdigitale. Microsporum gypseum. Candida albicans. C. parapsilosis, and C. guilliermondii species were subcultured and subjected to laser treatments (808/980 nm: 9–27 J/cm2, 6 ms, 12 × 12 or 12 × 50 mm and 1064 nm: 50–240 J/cm2, 90 ms, 5–10 mm). After irradiation, the fungal elements were transferred onto agar plates using conventional and Drigalski spatulas and were incubated for 6 days. Results: The highest increase in temperature was found using a 980-nm laser with a pulse duration of 6 ms and a fluence of 27 J/cm2. The histology work-up revealed a dissection of the nail plate from the nail bed tissue after laser irradiation. Growth inhibition was only found for C. guilliermondii and T. interdigitale. All other pathogens presented only reduced growth, and C. albicans growth was unaffected. Conclusions: This study demonstrates a clear thermal effect for linear scanning 980-nm and long-pulsed 1064-nm laser systems on either nail clippings or cell culture media. Complete pathogen growth impairment was achieved if temperatures were measured above 50 °C. The results for the 1064-nm system were almost comparable to 980 nm results.
The site of an immune-selected point mutation in the transmembrane protein of human immunodeficiency virus type 1 does not constitute the neutralization epitope

We previously reported the in vitro generation of a neutralization-resistant variant of the molecularly cloned isolate of human immunodeficiency virus type 1 (HIV-1), HXB2D. The molecular basis for the resistance was shown to be a point mutation in the env gene, causing the substitution of threonine for alanine at position 582 of gp41. Here, we show the variant to be resistant to syncytium inhibition as well as to neutralization by the immune-selecting serum. Moreover, 30% of HIV-positive human sera able to neutralize the parental virus have significantly decreased ability to neutralize the variant. As the A-to-T substitution thus has general relevance to the interaction of HIV-1 with the host immune system, we investigated further the biologic and immunologic bases for the altered properties. Synthetic peptides corresponding to the 582 region failed to compete in infectivity, neutralization, or syncytium inhibition assays and did not elicit neutralizing antibodies. Furthermore, human antibodies, affinity purified on synthetic peptide resins, bound to gp41 and peptides from the 582 region but did not possess neutralizing antibody activity. Some viral constructs in which the AVERY sequence in the 582 region was altered by site-directed mutagenesis were not infectious, indicating that the primary structure in this region is crucial for viral infectivity. Constructs predicted to possess a local secondary structure similar to that of the variant nevertheless behaved like the parental virus and remained neutralization sensitive. These results suggest that the requirements for neutralization resistance in this region are very precise. Our results with synthetic peptides show that the 582 region does not by itself constitute a neutralization epitope. Moreover, the degree of flexibility in amino acid substitution which allows maintenance of neutralization sensitivity suggests that position 582 does not form part of a noncontiguous neutralization epitope. The basis for neutralization resistance of the immune-selected variant is more likely a conformational change altering a neutralization epitope at a distant site.
Euryhaline pufferfish NBCe 1 differs from nonmarine species NBCe 1 physiology

Min-Hwang Chang, Consuelo Plata, Yukihiro Kurita, Akira Kato, Shigehisa Hirose, and Michael F. Romero Departments of Physiology and Biomedical Engineering and Nephrology and Hypertension and O’Brien Urology Research Center, Mayo Clinic College of Medicine, Rochester, Minnesota; Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio; Department of Biological Sciences, Tokyo Institute of Technology, Yokohama, Japan; and Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
NIGELLA SATIVA PROTECTS AGAINST FORMALDEHYDE-INDUCED NEUROTOXICITY IN THE RAT FRONTAL CORTEX

Objectives: Nigella sativa (NS) is well known for its strong antioxidant properties. The aim of this study was to investigate the potential protective effect of NS, as a potent antioxidant and free radical scavenger, on the rat frontal cortex following formaldehyde (FA)-induced neuronal injury and oxidative stress. Methods: Forty albino rats were divided into four groups (n=10, each): control group received 1 ml distilled water, NS treated group crushed seeds of NS at a single daily dose of 180 mg/kg/bw orally for two weeks, FA-treated group 10 mg/kg/bw FA i.p. daily for two weeks, and FA and NS treated group received 10 mg/kg/bw FA i.p. followed by a single dose of NS (180 mg/kg/bw) orally for 2 weeks. The animals then were sacrificed and the frontal lobes were excised. Frontal cortex was stained with hematoxylen-eosin and caspase-3 immunohistochemistry to identify cell morphology and apoptosis. Lipid peroxide, nitric oxide, superoxide dismutase and glutathione levels were measured. Results: Histological examination revealed severe neurodegenerative changes in frontal cortex neurons in the FA-treated group as observed with hematoxylen-eosin and caspase-3 immunohistochemistry. However, these changes were partly prevented in the FA and NS-treated group. Apoptotic cell index in the frontal cortex decreased significantly in FA and NS treated rats compared to FA-treated rats. In the FA-treated group, lipid peroxide levels increased, while nitric oxide and glutathione levels decreased significantly compared with controls. In the FA + NS treated group, nitric oxide, glutathione and superoxide dismutase levels increased and lipid peroxide level decreased significantly when compared with the FA-treated group. Conclusion: NS administration protects frontal cortex neurons against oxidative damage induced by FA. Keywords: cerebral cortex; formaldehyde; neuronal injury; Nigella sativa; oxidative stress; rat
Protective Effects of Paeoniflorin Against Corticosterone‐induced Neurotoxicity in PC12 Cells

Neuroprotection has been proposed as one of the acting mechanisms of antidepressants. Paeoniflorin, a monoterpene glycoside, has been reported to display antidepressant‐like effects in animal models of behavioural despair. The present study aimed to examine the protective effect of paeoniflorin treatment on corticosterone‐induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. Paeoniflorin was shown to elevate cell viability, decrease levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) in corticosterone‐treated PC12 cells. Paeoniflorin also reversed the reduced nerve growth factor (NGF) mRNA level caused by corticosterone in PC12 cells. The results suggest that paeoniflorin exerts a neuroprotective effect on corticosterone‐induced neurotoxicity in PC12 cells, at least in part, via the inhibition of oxidative stress and the up‐regulation of NGF expression. This neuroprotective effect may be one of the action pathways that accounts for the in vivo antidepressant activity of paeoniflorin. Copyright © 2011 John Wiley & Sons, Ltd.
Recombinant bacille Calmette–Guérin (BCG) expressing human interferon‐alpha 2B demonstrates enhanced immunogenicity

To increase its immunostimulatory properties, BCG was genetically engineered to secrete recombinant human interferon‐alpha 2B (rhIFN‐α) under control of the mycobacterial heat shock protein (hsp)60 promoter and the α antigen signal sequence. Expression of rhIFN‐α was readily detectable by ELISA and on Western blotting. When compared with control BCG, rhIFN‐α BCG was substantially more active in inducing the production of IFN‐γ and IFN‐inducible protein 10 (IP‐10) from human peripheral blood mononuclear cells, while IL‐10 production was correspondingly decreased. These effects were reversible upon antibody neutralization of rhIFN‐α. Among 10 patients tested, rhIFN‐α BCG enhanced IFN‐γ production in all patients ranging from 1·4‐ to 23·7‐fold with a general trend toward greatest enhancement among those with weakest baseline responses to control BCG. Correspondingly, rhIFN‐α BCG decreased IL‐10 production in all patients by 1·2–4·8‐fold. The onset of IFN‐γ production induced by rhIFN‐α BCG was also more rapid, occurring within 4 h after stimulation versus > 24 h with wild‐type BCG. The observation that the maximum IFN‐γ induction depends on the simultaneous presence of both IFN‐α and BCG highlights the advantages of rhIFN‐α BCG. Taken together, these immunostimulatory properties of rhIFN‐α BCG suggest that it may be a superior agent for immunotherapeutic protocols involving live BCG in humans.
Minimally Invasive Laminectomy for Lumbar Spinal Stenosis in Patients with and without Preoperative Spondylolisthesis: Clinical Outcome and Reoperation Rate

Introduction Surgical decompression is the intervention of choice for lumbar spinal stenosis (LSS) when nonoperative treatment has failed. Standard open laminectomy is an effective procedure. Minimally invasive laminectomy through tubular retractors is an alternative procedure. The aim of our cohort study was to evaluate the clinical and radiographic outcome of this procedure in LSS patients with or without preoperative spondylolisthesis. Materials and Methods Patients with LSS without spondylolisthesis and with stable spondylolisthesis who underwent MIS tubular laminectomy between 2004 and 2011 were included. Demographic, perioperative, and radiographic data were collected. Clinical outcome was evaluated by Oswestry disability index (ODI) and visual analog scale (VAS) scores, as well as by MacNab criteria. Results In a total of 110 patients, preoperative spondylolisthesis at the level of spinal stenosis was present in 52.5%. ODI and VAS pain scores at a mean follow-up of 28.8 months revealed a median improvement of 16% in ODI, 2.75 in VAS back, and 3 in VAS leg scores, compared with the preoperative baseline (p < 0.0001). The reoperation rate requiring fusion was 3.5%. Patients with and without preoperative spondylolisthesis had no significant differences in their clinical outcome or the reoperation rate. Conclusion MIS laminectomy is an effective procedure for treatment of LSS. Reoperation rates for instability are lower than reported after open laminectomy. Functional improvement is similar in patients with and without preoperative spondylolisthesis. This procedure can be a viable alternative to open laminectomy. Routine fusion may not be indicated in all patients with LSS and spondylolisthesis. Disclosure of Interest None declared