Default Destination Research Articles

Inclusive assimilation: middle-class Asian parenting in suburban America

ABSTRACT Previous studies find that Asian American parents enforce a strict academics-centered success frame upon their children. However, there is limited research on the actual standards of successful childrearing from the perspective of parents. Drawing on in-depth interviews with middle-class parents of Chinese and Indian descent in New Jersey (N = 44) conducted between December 2020 and January 2022, I contest the conception of a unidirectional parental assimilation process that presumes White middle-class families to be the default destination for assimilation. I argue that middle-class Asian American parenting can be better understood as an ‘inclusive assimilation’ process. Parents not only aim for a well-rounded education for their children as touted by White parents but, similarly to Black and Hispanic families, also embrace racial socialization efforts in their parenting, partly in response to the rise in anti-Asian violence observed during the COVID-19 pandemic.

Is the United States Keeping Pace in the Global Competition for Skilled Talent?

Historically the default destination for high-skilled temporary migrants, the United States now finds itself competing globally for high-skilled workers. With the means to apply for visas to work in several developed nations, these talented workers now have a choice of destinations. In order to assess the proposition that the United States should pattern immigration reform on practices in countries that place great value in skilled talent, this policy brief will examine the differences in temporary skilled immigrant visas among the developed English-speaking nations: the United States, Australia, the United Kingdom, and Canada. We review the differences in application processing times, filing fees, denial rates, and numbers of admitted skilled workers, relative to population, between these countries. The skilled temporary visa system in the United States is lagging in all significant measures, with longer processing times, significantly higher filing costs, and escalating rates of denial. Consequently, global talent is choosing to take its skills to countries such as Canada in increasing numbers.

Using collaborative community care to deal with the emergency department frailty epidemic.

Mr R.B. smiled at me, eyes dull in his shrunken face. ‘I just want to go home’ , he said. Exasperation radiated from his daughter. ‘But Dad, you’ll fall again. The carers are only there twice a day. Who’s going to help the rest of the time? Take the community hospital bed, Dad.’ A long pause. ‘I just want to go home’ , he said. One day after discharge, Mr R.B. had returned to A&E. Deconditioned after a long surgical admission he had waited hours for transport home, declining sandwiches — he didn’t like egg or cheese. Once home, too tired to eat, he nevertheless took his insulin. Worried about his new catheter bag overflowing, he slept poorly. The following morning, tired and weak with low sugar levels, he suffered an almost inevitable fall struggling to juggle sticks, catheter bag, and hearing aids. His pendant alarm signalled his return to hospital. Mr R.B, (although fictitious) captures perfectly the conundrum of the frail patient. Multiple comorbidities and reduced physiological reserve conspire against their independence. Until recently, hospital admission has been their default destination. However, with ever tighter budget constrictions, an ageing population, and the over-representation in resource utilisation among frail older patients, innovative relationships are needed to promote individual autonomy and minimise the toll on public services. The ‘frailty phenotype’ is a relatively recent concept. Despite the operational definition as an ‘age-related state of decreased physiological reserves characterized by a weakened response to stressors and an increased risk of poor …

Using Xenopus laevis Oocytes to Functionally Characterize Plant Transporters.

Functionally characterizing plant membrane transport proteins is challenging. Typically, heterologous systems are used to study them. Immature eggs (oocytes) of the South African clawed frog Xenopus laevis are considered an ideal expression system for such studies. These large oocytes have a low number of endogenous transport systems in their plasma membranes and highly express foreign mRNA; the oocyte plasma membrane is the default destination of integral membrane proteins that lack recognized organellar sorting signals. These features facilitate almost background-free characterization of putative plant membrane transporters. Here we describe how to isolate Xenopus laevis oocytes, prepare capped sense RNA (cRNA) of the maize boron importer TASSEL-LESS1 (TLS1) as an example, microinject the cRNA into the isolated oocytes, and functionally assess the boron import capabilities of TLS1 in an oocyte swelling assay. These protocols can be easily adapted to study other plant and non-plant transporters with putative import function. © 2019 by John Wiley & Sons, Inc.

Cytoplasmic long noncoding RNAs are frequently bound to and degraded at ribosomes in human cells.

Recent footprinting studies have made the surprising observation that long noncoding RNAs (lncRNAs) physically interact with ribosomes. However, these findings remain controversial, and the overall proportion of cytoplasmic lncRNAs involved is unknown. Here we make a global, absolute estimate of the cytoplasmic and ribosome-associated population of stringently filtered lncRNAs in a human cell line using polysome profiling coupled to spike-in normalized microarray analysis. Fifty-four percent of expressed lncRNAs are detected in the cytoplasm. The majority of these (70%) have >50% of their cytoplasmic copies associated with polysomal fractions. These interactions are lost upon disruption of ribosomes by puromycin. Polysomal lncRNAs are distinguished by a number of 5′ mRNA-like features, including capping and 5′UTR length. On the other hand, nonpolysomal “free cytoplasmic” lncRNAs have more conserved promoters and a wider range of expression across cell types. Exons of polysomal lncRNAs are depleted of endogenous retroviral insertions, suggesting a role for repetitive elements in lncRNA localization. Finally, we show that blocking of ribosomal elongation results in stabilization of many associated lncRNAs. Together these findings suggest that the ribosome is the default destination for the majority of cytoplasmic long noncoding RNAs and may play a role in their degradation.

The outer segment serves as a default destination for the trafficking of membrane proteins in photoreceptors

Baker et al. 2008. J. Cell Biol. doi:10.1083/jcb.200806009 [OpenUrl][1][Abstract/FREE Full Text][2] [1]: {openurl}?query=rft_id%253Dinfo%253Adoi%252F10.1083%252Fjcb.200806009%26rft_id%253Dinfo%253Apmid%252F18981232%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%

The outer segment serves as a default destination for the trafficking of membrane proteins in photoreceptors

Photoreceptors are compartmentalized neurons in which all proteins responsible for evoking visual signals are confined to the outer segment. Yet, the mechanisms responsible for establishing and maintaining photoreceptor compartmentalization are poorly understood. Here we investigated the targeting of two related membrane proteins, R9AP and syntaxin 3, one residing within and the other excluded from the outer segment. Surprisingly, we have found that only syntaxin 3 has targeting information encoded in its sequence and its removal redirects this protein to the outer segment. Furthermore, proteins residing in the endoplasmic reticulum and mitochondria were similarly redirected to the outer segment after removing their targeting signals. This reveals a pattern where membrane proteins lacking specific targeting information are delivered to the outer segment, which is likely to reflect the enormous appetite of this organelle for new material necessitated by its constant renewal. This also implies that every protein residing outside the outer segment must have a means to avoid this “default” trafficking flow.

Pulse-step models of control strategies for dynamic ocular accommodation and disaccommodation

Dynamic properties and control strategies of step responses by accommodation and disaccommodation differ from one another. Peak velocity of accommodation increases with response magnitude, while peak velocity and peak acceleration of disaccommodation increase with starting position. These dynamic properties can be modeled as control strategies that use independent acceleration-pulse and velocity-step components that are integrated respectively into phasic-velocity signals that control movement and tonic-position signals that control magnitude. Accommodation is initiated toward its final destination by an acceleration-pulse whose width increases with response magnitude to increase peak velocity. Disaccommodation is initiated toward a default destination (the far point) by an acceleration-pulse whose height increases with dioptric distance of the starting position to increase peak velocity and peak acceleration. Both responses are completed and maintained by tonic-position signals whose amplitudes are proportional to the final destination. Mismatched amplitudes of phasic-velocity and tonic-position signals in disaccommodation produce unstable step responses.

The Signal Sequence of Exported Protein-1 Directs the Green Fluorescent Protein to the Parasitophorous Vacuole of Transfected Malaria Parasites

The malaria parasite, Plasmodium falciparum, spends part of its life cycle inside the erythrocytes of its human host. In the mature stages of intraerythrocytic growth, the parasite undertakes extensive remodeling of its adopted cellular home by exporting proteins beyond the confines of its own plasma membrane. To examine the signals involved in export of parasite proteins, we have prepared transfected parasites expressing a chimeric protein comprising the N-terminal region of the Plasmodium falciparum exported protein-1 appended to green fluorescent protein. The majority of the population of the chimeric protein appears to be correctly processed and trafficked to the parasitophorous vacuole, indicating that this is the default destination for protein secretion. Some of the protein is redirected to the parasite food vacuole and further degraded. Photobleaching studies reveal that the parasitophorous vacuole contains subcompartments that are only partially interconnected. Dual labeling with the lipid probe, BODIPY-TR-ceramide, reveals the presence of membrane-bound extensions that can bleb from the parasitophorous vacuole to produce double membrane-bound compartments. We also observed regions and extensions of the parasitophorous vacuole, where there is segregation of the lumenal chimera from the lipid components. These regions may represent sites for the sorting of proteins destined for the trafficking to sites beyond the parasitophorous vacuole membrane.

The destination for single-pass membrane proteins is influenced markedly by the length of the hydrophobic domain.

The tonoplast was proposed as a default destination of membrane-bound proteins without specific targeting signals. To investigate the nature of this targeting, we created type I fusion proteins with green fluorescent protein followed by the transmembrane domain of the human lysosomal protein LAMP1. We varied the length of the transmembrane domain from 23 to either 20 or 17 amino acids by deletion within the hydrophobic domain. The resulting chimeras, called TM23, TM20, and TM17, were expressed either transiently or stably in tobacco. TM23 clearly accumulated in the plasmalemma, as confirmed by immunoelectron microscopy. In contrast, TM17 clearly was retained in the endoplasmic reticulum, and TM20 accumulated in small mobile structures. The nature of the TM20-labeled compartments was investigated by coexpression with a marker localized mainly in the Golgi apparatus, AtERD2, fused to a yellow fluorescent protein. The strict colocalization of both fluorescent proteins indicated that TM20 accumulated in the Golgi apparatus. To further test the default destination of type I membrane proteins, green fluorescent protein was fused to the 19-amino acid transmembrane domain of the plant vacuolar sorting receptor BP-80. The resulting chimera also accumulated in the Golgi instead of in post-Golgi compartments, where native BP-80 localized. Additionally, when the transmembrane domain of BP-80 was lengthened to 22 amino acids, the reporter escaped the Golgi and accumulated in the plasma membrane. Thus, the tonoplast apparently is not a favored default destination for type I membrane proteins in plants. Moreover, the target membrane where the chimera concentrates is not unique and depends at least in part on the length of the membrane-spanning domain.

Vps10p cycles between the late-Golgi and prevacuolar compartments in its function as the sorting receptor for multiple yeast vacuolar hydrolases.

VPS10 (Vacuolar Protein Sorting) encodes a large type I transmembrane protein (Vps10p), involved in the sorting of the soluble vacuolar hydrolase carboxypeptidase Y (CPY) to the Saccharomyces cerevisiae lysosome-like vacuole. Cells lacking Vps10p missorted greater than 90% CPY and 50% of another vacuolar hydrolase, PrA, to the cell surface. In vitro equilibrium binding studies established that the 1,380-amino acid lumenal domain of Vps10p binds CPY precursor in a 1:1 stoichiometry, further supporting the assignment of Vps10p as the CPY sorting receptor. Vps10p has been immunolocalized to the late-Golgi compartment where CPY is sorted away from the secretory pathway. Vps10p is synthesized at a rate 20-fold lower that that of its ligand CPY, which in light of the 1:1 binding stoichiometry, requires that Vps10p must recycle and perform multiple rounds of CPY sorting. The 164-amino acid Vps10p cytosolic domain is involved in receptor trafficking, as deletion of this domain resulted in delivery of the mutant Vps10p to the vacuole, the default destination for membrane proteins in yeast. A tyrosine-based signal (YSSL80) within the cytosolic domain enables Vps10p to cycle between the late-Golgi and prevacuolar/endosomal compartments. This tyrosine-based signal is homologous to the recycling signal of the mammalian mannose-6-phosphate receptor. A second yeast gene, VTH2, encodes a protein highly homologous to Vps10p which, when over-produced, is capable of suppressing the CPY and PrA missorting defects of a vps10 delta strain. These results indicate that a family of related receptors act to target soluble hydrolases to the vacuole.

Yeast Kex1p is a Golgi-associated membrane protein: deletions in a cytoplasmic targeting domain result in mislocalization to the vacuolar membrane.

We have investigated the localization of Kex1p, a type I transmembrane carboxypeptidase involved in precursor processing within the yeast secretory pathway. Indirect immunofluorescence demonstrated the presence of Kex1p in a punctate organelle resembling the yeast Golgi apparatus as identified by Kex2p and Sec7p (Franzusoff, A., K. Redding, J. Crosby, R. S. Fuller, and R. Schekman. 1991. J. Cell Biol. 112:27-37). Glycosylation studies of Kex1p were consistent with a Golgi location, as Kex1p was progressively N-glycosylated in an MNN1-dependent manner. To address the basis of Kex1p targeting to the Golgi apparatus, we examined the cellular location of a series of carboxy-terminal truncations of the protein. The results indicate that a cytoplasmically exposed carboxy-terminal domain is required for retention of this membrane protein within the Golgi apparatus. Deletions of the retention region or overproduction of wild-type Kex1p led to mislocalization of Kex1p to the vacuolar membrane. This unexpected finding is discussed in terms of models involving either the vacuole as a default destination for membrane proteins, or by endocytosis to the vacuole following their default localization to the plasma membrane.

The diffusion of new genetic tests for predicting disease.

This paper examines the pathways by which new genetic tests will become available to the public. In view of the scarcity of genetic specialists, the pathway is likely to involve primary care physicians. Other pathways entail state-mandated testing, community-based programs, or testing by laboratories without much involvement of primary care physicians. When testing does become available the "destination" will be either family-centered testing or population-oriented screening. The deterrent to screening will not be the inability to detect disease-causing mutations but the costs and attitudes of providers and the public. When tests are provided primarily to provide information about risks to future children, some people will oppose screening on religious or moral grounds. When there are no inexpensive treatments, some will fear that insurance companies and employers will use tests to deny them health care coverage. Some may not want to know their risks for disorders about which little can be done. For common, multifactorial disorders, genetic tests will have low predictive value. Because of these problems, the decision to be tested, regardless of the destination, requires that "testees" be fully informed and consent to testing. When acceptance rates are low, screening is less likely to be cost-effective; family-centered testing becomes the default destination.