Endocytosis of the ASGP receptor H1 is reduced by mutation of tyrosine-5 but still occurs via coated pits

The clustering of plasma membrane receptors in clathrin-coated pits depends on determinants within their cytoplasmic domains. In several cases, individual tyrosine residues were shown to be necessary for rapid internalization. We have mutated the single tyrosine at position 5 in the cytoplasmic domain of the major subunit H1 of the asialoglycoprotein receptor to alanine. Expressed in fibroblasts cells, the mutant protein was accumulated in the plasma membrane, and its rate of internalization was reduced by a factor of four. The residual rate of endocytosis, however, was still significantly higher than that of resident plasma membrane proteins. Upon acidification of the cytoplasm, which specifically inhibits the formation of clathrin-coated vesicles but not uptake of the fluid phase marker Lucifer yellow, residual endocytosis was blocked. By immunoelectron microscopy mutant H1 could be directly demonstrated in coated pits. The fraction of wild-type and mutant H1 present in coated pits as determined by immunogold localization correlated well with the respective rates of internalization. Thus, mutation of tyrosine-5 only partially inactivates recognition of H1 for incorporation into coated pits

Silence and Denial: Walt Whitman and the Brooklyn Bridge

Exposes as pure conjecture statements from journalists to the effect that Whitman celebrated the building of the Brooklyn Bridge, and demonstrates that Whitman\u27s response was, surprisingly, silence, arguing that the reason for Whitman\u27s lack of enthusiasm was his awareness that the bridge "endangered a world in which he had made deep personal investments," not the least of which was the enduring experience of crossing Brooklyn ferry in his poem, "Crossing Brooklyn Ferry.

Common upper respiratory tract problems in the elderly - A guide to clinical diagnosis and prudent prescription

Upper respiratory tract infections (URTIs) in the elderly (those aged 65 years and older) are not more common than in younger people, but complications are more common. In uenza and respiratory syncitial virus are the two most common pathogens affecting morbidity and mortality. Hospitalisation, bronchitis, pneumonia and death are all significantly increased in the elderly. In uenza vaccine is recommended for all persons aged 65 and older. Antibiotics have no benefit in the treatment or prevention of complications from in uenza. Otitis media and tonsillitis are uncommon. Sinusitis should be treated with antibiotics. Amoxycillin remains the drug of choice for patients who are not allergic to penicillin. Pneumococcal vaccine is recommended as prophylaxis against pneumococcal pneumonia, which is often seen as a complication of in uenza. Chronic idiopathic cough, anosmia, gastroesophageal re ux disease, asthma and chronic post-nasal drip may all present as upper respiratory tract-like illness. There is no benefit from using common cough mixtures or many other OTC preparations for the management of URTIs, as their side effects are significantly greater in older persons

When to start antiretroviral therapy in adults: the results of HPTN 052 move us closer to a ‘test-and-treat’ policy

When is the best time to initiate antiretroviral therapy (ART) in adults? This is a vital question in HIV treatment and prevention services. More specifically, is the 350 cells/μl CD4 count threshold recommended by current World Health Organization (WHO) guidelines sufficient, or should we move to a ‘test-and-treat’ approach in which anyone who tests HIV-positive is offered ART, irrespective of their CD4 count? The recently announced results of the HPTN 052 trial take us closer, but not all the way, to a test-and-treat approach

World Health Organization guidelines should not change the CD4 count threshold for antiretroviral therapy initiation

The World Health Organization (WHO) currently recommends that HIV-positive adults start antiretroviral therapy (ART) at CD4 counts <350 cells/μl. Several countries have changed their guidelines to recommend ART irrespective of CD4 count or at a threshold of 500 CD4 cells/μl. Consequently, WHO is currently revising its treatment guidelines and considering recommending ART initiation at CD4 counts <500 cells/μl. Such decisions are critically important, as WHO guidelines inform healthcare policies in developing countries and are used by activists in their advocacy work. Changing the CD4 initiation point from 350 to 500 cells/μl would, however, be premature and have profound cost implications on Global Fund, President’s Emergency Plan for AIDS Relief (PEPFAR) and developing country health budgets. We should be willing to campaign for such a change in guidelines despite cost implications, if supported by evidence. However, the evidence remains outstanding.S Afr J HIV Med 2013;14(1):6-7. DOI:10.7196/SAJHIVMED.90

Combining CubeSat Modularity and Integration A Unified CubeSat-PocketQube Board Standard

The evolution of CubeSat construction and architecture took a turn in 2012, when a new paradigm for CubeSat design was presented by Tyvak. Previously, most CubeSats had consisted of vertically stacked modular boards, each designed for a specific subsystem. The presentation called to light: Smartphone electronics are compact and tightly integrated, as opposed to large interchangeable desktop parts CubeSats could do the same to integrate components into a single board. Modularity was wasteful of space

Echoes of Lysenko: state-sponsored pseudo-science in South Africa

A major factor hampering the rollout of highly active antiretroviral treatment (HAART) for HIV/AIDS in the public health sector is state support of pseudo-science. This paper examines state-sponsored pseudo-science in South Africa with a particular focus on the case of Matthias Rath and his claim that HAART is an ineffective and harmful form of treatment and that multivitamins should instead be used as a substitute to treat and cure AIDS.? The paper examines similarities and differences between state support in South Africa for AIDS-denialists such as Rath and state support in the former Soviet Union for Lysenko, a pseudo-scientist who lacked scientific training. In both cases, state support for pseudo-science has had policy implications, and resulted in many deaths