514 research outputs found
Stealing Home in Hollywood: Why the Takeover of the Los Angeles Dodgers Illustrates the Unjust Nature of Major League Baseball\u27s Antitrust Exemption
The article discusses Major League Baseball\u27s (MLB) takeover of the Los Angeles Dodgers baseball team from owner Frank McCourt following his divorce from his wife Jamie, as well as MLB\u27s alleged unjust antitrust exemption as of September 2012. The author argues that McCourt could have challenged the anti-competitive takeover practices of MLB and its commissioner Bud Selig since McCourt\u27s attempt to broker a television deal with Fox Sports did not break any of MLB\u27s rules
Stealing Home in Hollywood: Why the Takeover of the Los Angeles Dodgers Illustrates the Unjust Nature of Major League Baseball\u27s Antitrust Exemption
The article discusses Major League Baseball\u27s (MLB) takeover of the Los Angeles Dodgers baseball team from owner Frank McCourt following his divorce from his wife Jamie, as well as MLB\u27s alleged unjust antitrust exemption as of September 2012. The author argues that McCourt could have challenged the anti-competitive takeover practices of MLB and its commissioner Bud Selig since McCourt\u27s attempt to broker a television deal with Fox Sports did not break any of MLB\u27s rules
Identification and Characterization of a Broadly Cross-Reactive HIV-1 Human Monoclonal Antibody That Binds to Both gp120 and gp41
Identification of broadly cross-reactive HIV-1-neutralizing antibodies (bnAbs) may assist vaccine immunogen design. Here we report a novel human monoclonal antibody (mAb), designated m43, which co-targets the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein (Env). M43 bound to recombinant gp140 s from various primary isolates, to membrane-associated Envs on transfected cells and HIV-1 infected cells, as well as to recombinant gp120 s and gp41 fusion intermediate structures containing N-trimer structure, but did not bind to denatured recombinant gp140 s and the CD4 binding site (CD4bs) mutant, gp120 D368R, suggesting that the m43 epitope is conformational and overlaps the CD4bs on gp120 and the N-trimer structure on gp41. M43 neutralized 34% of the HIV-1 primary isolates from different clades and all the SHIVs tested in assays based on infection of peripheral blood mononuclear cells (PBMCs) by replication-competent virus, but was less potent in cell line-based pseudovirus assays. In contrast to CD4, m43 did not induce Env conformational changes upon binding leading to exposure of the coreceptor binding site, enhanced binding of mAbs 2F5 and 4E10 specific for the membrane proximal external region (MPER) of gp41 Envs, or increased gp120 shedding. The overall modest neutralization activity of m43 is likely due to the limited binding of m43 to functional Envs which could be increased by antibody engineering if needed. M43 may represent a new class of bnAbs targeting conformational epitopes overlapping structures on both gp120 and gp41. Its novel epitope and possibly new mechanism(s) of neutralization could helpdesign improved vaccine immunogens and candidate therapeutics
Incidence of skeletal deformities in induced triploid rainbow trout Oncorhynchus mykiss (Walbaum, 1792)
Due to the cytogenetic incompatibility, triploid fish are usually infertile and are not affected by a decline in growth, survival and meat quality, which accompanies the process of sexual maturation in diploid specimens. Thus, artificial triploidization has been proposed for fish production in the case of species with early sexual maturation, such as rainbow trout. However, the use of this technique is limited by increased ratios of skeletal deformities observed in triploid specimens. The main objective of this research was to compare the proportion and variety of body abnormalities in diploid and triploid 14-month-old rainbow trout from commercial stocks, using external body shape examination, radiography and whole-mount skeletal staining. Individuals with externally observed body deformities (scoliosis, humpback, shortened tail and jaw deformities) accounted for 0.45% of the diploid stock and 3.83% of the triploid stock. X-rays and whole-mount skeletal staining of deformed individuals showed spine deformities, including compressions and fusions of vertebrae. Abnormalities observed in diploid and triploid rainbow trout examined during this study were non-lethal, however, they may negatively affect the condition of fish. Fish with skeletal deformities are not aesthetically pleasing, thus an increased ratio of such deformations in fish produced for commercial purposes may result in real economic losses
Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism
This is a non-final version of an article published in final form in AIDS. 28 November 2012 - Volume 26 - Issue 18 - p 2275–2284Objectives: To characterize the nature and dynamics of the neutralizing antibody
(NAb) response and escape in chronically HIV-2 infected patients.Methods: Twenty-eight chronically infected adults were studied over a period of 1-4
years. The neutralizing activity of plasma IgG antibodies against autologous and
heterologous primary isolates was analyzed using a standard assay in TZM-bl cells. Coreceptor
usage was determined in GHOST cells. The sequence and predicted 3Dstructure
of the C2V3C3 Env region were determined for all isolates.Results: Only 50% of the patients consistently produced IgG NAbs to autologous and
contemporaneous virus isolates. In contrast, 96% of the patients produced IgG
antibodies that neutralized at least two isolates of a panel of six heterologous R5
isolates. Breadth and potency of the neutralizing antibodies were positively associated
with the number of CD4+ T cells and with the titer and avidity of C2V3C3-specific
binding IgG antibodies. X4 isolates were obtained only from late stage disease patients
and were fully resistant to neutralization. The V3 loop of X4 viruses was longer, had a
higher net charge and differed markedly in secondary structure compared to R5 viruses.Conclusions: Most HIV-2 patients infected with R5 isolates produce C2V3C3-specific
neutralizing antibodies whose potency and breadth decreases as the disease progresses.
Resistance to antibody neutralization occurs in late stage disease and is usually
associated with X4 viral tropism and major changes in V3 sequence and conformation.
Our studies support a model of HIV-2 pathogenesis in which the neutralizing antibodies
play a central role and have clear implications for the vaccine field.Fundação para a Ciência e Tecnologia, Portuga
Horse Racing Regulatory Reform through Constructive Engagement by Industry Stakeholders with State Regulators
P04-19. Analysis of the binding of multiple clades of HIV-1 by a modified virus capture assay
Epilepsy and hypertension: The possible link for sudden unexpected death in epilepsy?
Epilepsy affects about 50 million people worldwide. Sudden unexpected death in epilepsy (SUDEP) is the main cause of death in epilepsy accounting for up to 17% of all deaths in epileptic patients, and therefore remains a major public health problem. SUDEP likely arises from a combination and interaction of multiple risk factors (such as being male, drug resistance, frequent generalized tonic-clonic seizures) making risk prediction and mitigation challenging. While there is a general understanding of the physiopathology of SUDEP, mechanistic hypotheses linking risk factors with a risk of SUDEP are still lacking. Identifying cross-talk between biological systems implicated in SUDEP may facilitate the development of improved models for SUDEP risk assessment, treatment and clinical management. In this review, the aim was to explore an overlap between the pathophysiology of hypertension, cardiovascular disease and epilepsy, and discuss its implication for SUDEP. Presented herein, evidence in literature in support of a cross-talk between the renin–angiotensin system (RAS) and sympathetic nervous system, both known to be involved in the development of hypertension and cardiovascular disease, and as one of the underlying mechanisms of SUDEP. This article also provides a brief description of local RAS in brain neuroinflammation and the role of centrally acting RAS inhibitors in epileptic seizure alleviation
Influence of genetic factors on early hypertensive complications
Choroby układu krążenia są główną przyczyną zachorowalności,
zgonów i inwalidztwa w rozwiniętych
krajach świata. Najważniejszym czynnikiem ryzyka
prowadzącym do rozwoju powikłań narządowych
jest nadciśnienie tętnicze. Niniejszy artykuł jest
poświęcony głównie powikłaniom naczyniowym
(zaburzenia funkcji śródbłonka i przebudowa ściany
tętnic) oraz mikroalbuminurii. W pracy opisano aktualny
stan wiedzy o wpływie wybranych czynników
genetycznych na predyspozycję do rozwoju powikłań
nadciśnienia tętniczego. Czynniki te obejmują warianty
polimorficzne genów kandydatów, zaangażowanych
między innymi w regulację ciśnienia krwi,
hemostazę, stres oksydacyjny i proces zapalny.
Stwierdzenie predyspozycji genetycznej do rozwoju
wczesnych powikłań sercowo-naczyniowych jest niezwykle
istotnym czynnikiem ryzyka wystąpienia poważniejszych powikłań — zawału serca czy udaru
mózgu — i może zrewolucjonizować metody diagnostyki
chorób, oceny ryzyka i prognozowania oraz
wyboru terapii.
Nadciśnienie Tętnicze 2011, tom 15, nr 2, strony 125–142.Hypertension is the most prevalent risk factor for cardiovascular
disease (CVD), the leading cause of death
worldwide, especially in developed countries. Genetic
and environmental determinants play important roles
in hypertension and its complications. This publication
gives a short introduction to the pathogenesis of CVD
and summarizes the current findings of the genetic factors
involved. This review focuses on a better understanding
of the role of candidate genes polymorphisms
that play a crucial role in blood pressure regulation,
hemostatic processes, oxidative stress and inflammatory
responses leading to endothelial damage, and as a result,
to vascular remodeling and microalbuminuria.
Those gene variants could contribute to inter-individual
differences in susceptibility to and outcome of essential
hypertension. Therefore, the major challenge in cardiovascular
medicine is to find a way of predicting the risk
of hypertension complications by genetic markers that,
used with imaging techniques, could lead to the development
of new and better diagnostic and therapeutic
methods.
Arterial Hypertension 2011, vol. 15, no 2, pages 125–142
Inter-clutch egg differences and androgenesis in rainbow trout (Oncorhynchus mykiss, Walbaum 1792)
Ionizing radiation (IR) is applied to inactivate the nuclear genome in rainbow trout eggs during induced androgenetic development. However, IR-generated reactive oxygen species (ROS) may affect developmental potential of eggs and reduce the effectiveness of androgenesis. To verify this assumption, androgenetic development of rainbow trout was induced in eggs irradiated with 350 Gy of X-rays. Survival rates, pH of the ovarian fluid and activity of antioxidant enzymes, including SOD, CAT and GPx, were examined in non-irradiated and irradiated eggs originating from four females. Survival rates of androgenetic embryos developing in eggs produced by different females varied from 1% to 57% and these inter-clutch differences were significant. Eggs from female F4, which showed the highest developmental competence for androgenesis, also showed increased activities of SOD, CAT and GPx enzymes. The pH value of the ovarian fluid of each female was over 8 before and after irradiation, therefore it seems that radiation did not affect the ovarian fluid pH. Considering the above-mentioned inter-clutch differences, a strong maternal effect on the effectiveness of androgenesis can be assumed. Eggs with increased activity of antioxidant enzymes before irradiation should be expected to show increased developmental competence for androgenesis
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