Parkin uses the UPS to ship off dysfunctional mitochondria

Parkin is a ubiquitin E3 ligase that is implicated in familial Parkinson disease (PD). Previous studies have established its role in mitophagy, a pathway whereby dysfunctional mitochondria are targeted for autophagic degradation. We recently reported that a major function of Parkin in dysfunctional mitochondria is to activate the ubiquitin-proteasome system (UPS) for proteolysis of multiple outer membrane proteins, and that such activation of the UPS is a critical step in Parkin-mediated mitophagy. Here, we discuss the possible roles of the UPS in mitophagy and the pathogenesis of PD

Towards a human resources management approach in supply chain management

Supply chain management (SCM) has grown as a discipline since the field attracted attention in the 1980s. However, it is observed that effective implementation of SCM is limited because the current focus is too task-based and information-centric. The concept is often conflated, in practice, with subcontractor management, where numerical flexibility is pertinent. At the same time, consideration of human resources management (HRM) in SCM has been limited. Strategic fit within supply chains tends to emphasise taskbased numerical flexibility, rather than genuine consideration and development of human resources. On the other hand, HRM has, until recently, rarely taken into account interorganisational characteristics that typify the construction industry. Therefore, this research intends to plug the gap by examining the use of human resources in construction supply chains, with a view of developing good practice for HRM in construction SCM. To achieve this, a two-phase research methodology comprising a scoping phase and case study phase will be ensued

Transitions from AFDC to SSI Prior to Welfare Reform – Policy Brief

The Supplemental Security Income (SSI) and Temporary Assistance for Needy Families (TANF) programs serve overlapping target groups. SSI serves adults and children with disabilities from low-income families, while TANF serves low-income families with children. Consequently, policy changes in one program can affect the other. The target group for Aid to Families with Dependent Children (AFDC), TANF’s predecessor, also overlapped with SSI’s target group. Many have anticipated that the replacement of AFDC with TANF in August 1996 would eventually increase SSI participation as TANF recipients with disabilities sought SSI benefits to avoid TANF work requirements and time limits

Emerging functions of mammalian mitochondrial fusion and fission

Mitochondria provide a myriad of services to the cell, including energy production, calcium buffering and regulation of apoptosis. How these diverse functions are coordinated among the hundreds of mitochondria in a given cell is largely unknown, but is probably dependent on the dynamic nature of mitochondria. In this review, we explore the latest developments in mitochondrial dynamics in mammals. These studies indicate that mitofusins and OPA1 are essential for mitochondrial fusion, whereas Fis1 and Drp1 are essential for mitochondrial fission. The overall morphology of the mitochondrial population depends on the relative activities of these two sets of proteins. In addition to the regulation of mitochondrial shape, these molecules also play important roles in cell and tissue physiology. Perturbation of mitochondrial fusion results in defects in mitochondrial membrane potential and respiration, poor cell growth and increased susceptibility to cell death. These cellular observations may explain why mitochondrial fusion is essential for embryonic development. Two inherited neuropathies, Charcot–Marie–Tooth type 2A and autosomal dominant optic atrophy, are caused by mutations in mitofusin 2 and OPA1, suggesting that proper regulation of mitochondrial dynamics is particularly vital to neurons. Mitochondrial fission accompanies several types of apoptotic cell death and appears important for progression of the apoptotic pathway. These studies provide insight into how mitochondria communicate with one another to coordinate mitochondrial function and morphology

Communications for Next Generation single chip computers

It is the thesis of this report that much of what is presently thought to require specialized VLSI functions might instead be achieved by combinations of fast general purpose single chip computers with upgraded communication facilities. To this end, the characteristics of applications of this nature are first surveyed briefly and some working principles established. In the light of these, three different chip philosophies are explored in some detail. This study shows that some upgrading of typical single chip I/O will definitely be necessary, but that this upgrading does not have to be complex and that true multiprocessor-multibus operation could be achieved without excessive cost

The Prefusogenic Intermediate of HIV-1 gp41 Contains Exposed C-peptide Regions

The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein is composed of a complex between the surface subunit gp120, which binds to cellular receptors, and the transmembrane subunit gp41. Upon activation of the envelope glycoprotein by cellular receptors, gp41 undergoes conformational changes that mediate fusion of the viral and cellular membranes. Prior to formation of a fusogenic "trimer-of-hairpins" structure, gp41 transiently adopts a prefusogenic conformation whose structural features are poorly understood. An important approach toward understanding structural conformations of gp41 during HIV-1 entry has been to analyze the structural targets of gp41 inhibitors. We have constructed epitope-tagged versions of 5-Helix, a designed protein that binds to the C-peptide region of gp41 and inhibits HIV-1 membrane fusion. Using these 5-Helix variants, we examined which conformation of gp41 is the target of 5-Helix. We find that although 5-Helix binds poorly to native gp41, it binds strongly to gp41 activated by interaction of the envelope protein with either soluble CD4 or membrane-bound cellular receptors. This preferential interaction with activated gp41 results in the accumulation of 5-Helix on the surface of activated cells. These results strongly suggest that the gp41 prefusogenic intermediate is the target of 5-Helix and that this intermediate has a remarkably "open" structure, with exposed C-peptide regions. These results provide important structural information about this intermediate that should facilitate the development of HIV-1 entry inhibitors and may lead to new vaccine strategies

Impacts of Expanding Health Care Coverage on the Employment and Earnings of Participants in the SSI Work Incentive Program - Policy Brief

While people with disabilities often say that a loss of public health insurance is a deterrent to work, it is rare to find situations in which they might actually exhibit such a behavioral response to a change in access. Expansions in the income threshold for SSI work incentives program (Sections 1619(a) and (b)) provide an opportunity to observe such a response. Section 1619(b) allows SSI recipients to maintain Medicaid eligibility even if their income is above the level that makes them ineligible for SSI payments. If earnings increase beyond the 1619(b) threshold, however, the person loses their SSI and Medicaid eligibility. Section 1619(b) income thresholds vary significantly across states and over time. Stapleton and Tucker (2000) use the variation in Section 1619(b) income thresholds to examine the employment, earnings and program participation patterns of SSI recipients who have incomes near the threshold level for their state. They find strong evidence that many SSI recipients restrain their earnings to stay below the 1619(b) threshold. It is important to note, however, that the findings only provide evidence on the behavior of a small portion of the population with disabilities (i.e., SSI recipients who work). Nonetheless, this evidence seems to provide strong empirical support for the hypothesis that lack of access to health insurance is an important work disincentive for people with disabilities. They also find that 1619(b) participation varies significantly from month to month. Consequently, cross-sectional estimates on the share of SSI recipients participating in 1619(b) significantly understate the share of SSI recipients who ever participate. These findings are consistent with previous findings that cross-sectional estimates of employment tend to understate multi-period employment patterns for the broader population with disabilities

NMR studies of membrane structure and dynamics

Over the past decade, there has been considerable interest in the motional state of the phospholipid bilayer membrane. The motivation underlying these efforts has been the contention that the phospholipid bilayer is the basic matrix in which membrane proteins are embedded to form the biological membrane, and that the permeability and mechanical properties of the membrane, as well as the enzymatic activity of membrane proteins, are dependent upon the fluidity of the bilayer, especially the motional state of the hydrocarbon chains