Restrictions to the adaptation of influenza A virus H5 hemagglutinin to the human host

The binding specificities of a panel of avian influenza virus subtype H5 hemagglutinin (RA) proteins bearing mutations at key residues in the receptor binding site were investigated. The results demonstrate that two simultaneous mutations in the receptor binding site resulted in H5 RA binding in a pattern similar to that shown by human viruses. Coexpression of the ion channel protein, M2, from most avian and human strains tested protected H5 RA conformation during trafficking, indicating that no genetic barrier to the reassortment of the H5 surface antigen gene with internal genes of human viruses existed at this level.

Diaspora return of transnational migrants to Trinidad and Tobago: the additional contributions of social remittances

Current enthusiasm among development stakeholders for the enticement and recruitment ‘back home’ of skilled Diaspora migrants has predominantly revolved around how human capital gains and transfers of capital, knowledge, technical skills and workplace entrepreneurialism and innovation can be facilitated. In this article, we widen the conceptual basis of this dimension of the migration–development nexus, by bringing the additional contributions of the social remittances that return migrants offer, and practice, into the mix. As evidence, the article examines how and why a sample of ‘middling’1 Trinidadian transnational professionals engage in social development activities and why experiences vary widely on their return. Their views are appraised through the verbal optic of their narratives, which they shared with us during in-depth interviews. Several among these Diaspora returnees appear to be agents for the diffusion and infusion of social capital and non-monetary, social remittances in the homeland to which they have returned in mid-life and mid-career. Others are disappointed, or frustrated, and have their hopes dashed, leading to thoughts of re-migration, or re-return. Despite such difficulties, we find that family belonging and national pride strengthens many of these return migrants’ development potential through their deeply felt commitments to local ‘capacity-building’.

Legal outlier, again? U.S. felon suffrage: comparative and international human rights perspectives

The judiciousness of American felon suffrage policies has long been the subject of scholarly debate, not least due to the large number of affected Americans: an estimated 5.3 million citizens are ineligible to vote as a result of a criminal conviction. This article offers comparative law and international human rights perspectives and aims to make two main contributions to the American and global discourse. After an introduction in Part I, Part II offers comparative law perspectives on challenges to disenfranchisement legislation, juxtaposing U.S. case law against recent judgments rendered by courts in Canada, South Africa, Australia, and by the European Court of Human Rights. The article submits that owing to its unique constitutional stipulations, as well as to a general reluctance to engage foreign legal sources, U.S. jurisprudence lags behind an emerging global jurisprudential trend that increasingly views convicts’ disenfranchisement as a suspect practice and subjects it to judicial review. This transnational judicial discourse follows a democratic paradigm and adopts a “residual liberty” approach to criminal justice that considers convicts to be rights-holders. The discourse rejects regulatory justifications for convicts’ disenfranchisement, and instead sees disenfranchisement as a penal measure. In order to determine its suitability as a punishment, the adverse effects of disenfranchisement are weighed against its purported social benefits, using balancing or proportionality review. Part III analyzes the international human rights treaty regime. It assesses, in particular, Article 25 of the International Covenant on Civil and Political Rights (“ICCPR”), which proclaims that “every citizen” has a right to vote without “unreasonable restrictions.” The analysis concludes that the phrase “unreasonable restrictions” is generally interpreted in a manner which tolerates certain forms of disenfranchisement, whereas other forms (such as life disenfranchisement) may be incompatible with treaty obligations. This article submits that disenfranchisement is a normatively flawed punishment. It fails to treat convicts as politically-equal community members, degrades them, and causes them grave harms both as individuals and as members of social groups. These adverse effects outweigh the purported social benefits of disenfranchisement. Furthermore, as a core component of the right to vote, voter eligibility should cease to be subjected to balancing or proportionality review. The presumed facilitative nature of the right to vote makes suffrage less susceptible to deference-based objections regarding the judicial review of legislation, as well as to cultural relativity objections to further the international standardization of human rights obligations. In view of this, this article proposes the adoption of a new optional protocol to the ICCPR proscribing convicts’ disenfranchisement. The article draws analogies between the proposed protocol and the ICCPR’s “Optional Protocol Aiming at the Abolition of the Death Penalty.” If adopted, the proposed protocol would strengthen the current trajectory towards expanding convicts’ suffrage that emanates from the invigorated transnational judicial discourse.

Intracellular trafficking, localization, and mobilization of platelet-borne thiol isomerases

OBJECTIVE: Thiol isomerases facilitate protein folding in the endoplasmic reticulum, and several of these enzymes, including protein disulfide isomerase and ERp57, are mobilized to the surface of activated platelets, where they influence platelet aggregation, blood coagulation, and thrombus formation. In this study, we examined the synthesis and trafficking of thiol isomerases in megakaryocytes, determined their subcellular localization in platelets, and identified the cellular events responsible for their movement to the platelet surface on activation. APPROACH AND RESULTS: Immunofluorescence microscopy imaging was used to localize protein disulfide isomerase and ERp57 in murine and human megakaryocytes at various developmental stages. Immunofluorescence microscopy and subcellular fractionation analysis were used to localize these proteins in platelets to a compartment distinct from known secretory vesicles that overlaps with an inner cell-surface membrane region defined by the endoplasmic/sarcoplasmic reticulum proteins calnexin and sarco/endoplasmic reticulum calcium ATPase 3. Immunofluorescence microscopy and flow cytometry were used to monitor thiol isomerase mobilization in activated platelets in the presence and absence of actin polymerization (inhibited by latrunculin) and in the presence or absence of membrane fusion mediated by Munc13-4 (absent in platelets from Unc13dJinx mice). CONCLUSIONS: Platelet-borne thiol isomerases are trafficked independently of secretory granule contents in megakaryocytes and become concentrated in a subcellular compartment near the inner surface of the platelet outer membrane corresponding to the sarco/endoplasmic reticulum of these cells. Thiol isomerases are mobilized to the surface of activated platelets via a process that requires actin polymerization but not soluble N-ethylmaleimide-sensitive fusion protein attachment receptor/Munc13-4-dependent vesicular-plasma membrane fusion.