Retrograde Step Research Articles

Anna Mathews v Supreme Court of India: A retrograde step?

Anna Mathews v Supreme Court of India: A retrograde step?

Golgi-associated retrograde protein (GARP) complex-dependent endosomes to trans Golgi network retrograde trafficking is controlled by Rab4b

BackgroundThe trafficking of cargoes from endosomes to the trans-Golgi network requires numerous sequential and coordinated steps. Cargoes are sorted into endosomal-derived carriers that are transported, tethered, and fused to the trans-Golgi network. The tethering step requires several complexes, including the Golgi-associated retrograde protein complex, whose localization at the trans-Golgi network is determined by the activity of small GTPases of the Arl and Rab family. However, how the Golgi-associated retrograde protein complex recognizes the endosome-derived carriers that will fuse with the trans-Golgi network is still unknown.MethodsWe studied the retrograde trafficking to the trans-Golgi network by using fluorescent cargoes in cells overexpressing Rab4b or after Rab4b knocked-down by small interfering RNA in combination with the downregulation of subunits of the Golgi-associated retrograde protein complex. We used immunofluorescence and image processing (Super Resolution Radial Fluctuation and 3D reconstruction) as well as biochemical approaches to characterize the consequences of these interventions on cargo carriers trafficking.ResultsWe reported that the VPS52 subunit of the Golgi-associated retrograde protein complex is an effector of Rab4b. We found that overexpression of wild type or active Rab4b increased early endosomal to trans-Golgi network retrograde trafficking of the cation-independent mannose-6-phosphate receptor in a Golgi-associated retrograde protein complex-dependent manner. Conversely, overexpression of an inactive Rab4b or Rab4b knockdown attenuated this trafficking. In the absence of Rab4b, the internalized cation-independent mannose 6 phosphate receptor did not have access to VPS52-labeled structures that look like endosomal subdomains and/or endosome-derived carriers, and whose subcellular distribution is Rab4b-independent. Consequently, the cation-independent mannose-6-phosphate receptor was blocked in early endosomes and no longer had access to the trans-Golgi network.ConclusionOur results support that Rab4b, by controlling the sorting of the cation-independent mannose-6-phosphate receptor towards VPS52 microdomains, confers a directional specificity for cargo carriers en route to the trans-Golgi network. Given the importance of the endocytic recycling in cell homeostasis, disruption of the Rab4b/Golgi-associated retrograde protein complex-dependent step could have serious consequences in pathologies.

The Views of Practitioners on Care Act Easements during the Covid-19 Pandemic

The easements of the Care Act 2014, permitted by the Coronavirus Act 2020, were in place in very few English local authorities and then only for a short time, but they still rippled across the wider social care workforce. This paper reports findings from interviews with social workers in ten non-easement authorities and with other professionals in easement and non-easement authorities to explore their understandings of easements and their reflections on their use and impact on practice. The interview data are set in the context of a wider study that explored decision-making about the adoption of easements in local authorities. Frontline practitioners (N = 30) confirmed confusion about easements and suspicion that they were a retrograde step in people’s entitlements to care and support. These views were also set in a context of lack of pandemic preparedness in social care and reflections that the care system was already fragile after a sustained period of reductions to local authority budgets and rising need. Both a robust care infrastructure was needed, as well as better crisis or disaster preparedness and planning.

Measuring moral development in the pharmacy profession from undergraduate to established practitioner: a decadal longitudinal study.

The aim of this study is to measure and evaluate the moral reasoning of undergraduate pharmacy students as they progress through a British university, and onward through the early years of their professional practice. This study utilizes version 2 of Rest's Defining Issues Test in a longitudinal design, evaluating a single cohort of future pharmacists, which started a 4-year Master of Pharmacy degree program in 2008-09, completed their preregistration training, and progressed through their early careers. The final dataset was collected in 2019. Both descriptive and inferential statistical analysis was subsequently carried out. The cohort experienced significant moral growth during the 4 years of their undergraduate degree, where they were exposed to an ethical education designed to engage students at the "plus one" level of moral reasoning. There is also evidence for work-based augmentation of moral development between graduation from university and qualification as pharmacists. The subjects underwent a marked increase in moral development as they progressed through their undergraduate studies, followed by another sizeable, though not statistically significant developmental progression during the preregistration year. The retrograde step in moral development observed between newly qualified level and established practitioner level requires further investigation: structured interviews with participants, which focus on changes to their experiences in practice and how these affected their moral agency are already underway.

Human Trafficking: Iconic Victims, Folk Devils and the Nationality and Borders Act 2022

On 28 April 2022, the Westminster Parliament passed the controversial Nationality and Borders Act. The Act is the single biggest overhaul of the UK's immigration system in decades. The Act aims to deter illegal entry into the UK; remove more easily those with no right to be in the UK; and increase the overall fairness of the system. Notwithstanding these seemingly laudable objectives, however, this article argues that the Act represents a retrograde step in the protection of victims of human trafficking. Relying upon Nils Christie's ‘ideal/iconic victims’ and Stanley Cohen's ‘folk devils’ critique, the article contends that, in an age of heightened securitisation and moral panics, the Act will create ‘folk devils’ of victims of trafficking who do not self‐identify, and unduly penalise victims of trafficking who have committed offences in the course, or as a consequence, of being trafficked.

Human growth hormone and insulin, from tissue extracts to recombinant DNA technology, their biosimilars and analogues in treatment of Endocrine Disorders

Forty years ago, recombinant DNA technology caused a revolution in the way growth disorders and diabetes could be treated. Bacteria or human cells were modified so as to be able to produce human hormones instead of relying on cadaveric material in the case of growth disorders and porcine insulin in the case of diabetics. The new technology also removed the risk of contracted hepatitis or fatal Creutzfeldt Jacob disease. A signal peptide was used to transport the new protein into the periplasmic space giving rise to an exact, correctly folded version of monomeric human growth hormone. More eligible patients could be treated, resulting not only in a large number of clinical trials. Daily tiny subcutaneous injections were found to be much more effective than twice or thrice weekly in the treatment of children and adults, The progress for recombinant human insulin turned out to be somewhat different. Insulin is a more complicated protein, with an Alpha and Beta chain joined by two disulphide bridges, but is produced in the human pancreas as a single chain, proinsulin, the C peptide is removed to make the active molecule. Recombinant insulin development was in a way the opposite to growth hormone since human insulin acts faster than porcine. Short fast and long-acting analogues have been developed all to improve the treatment regimens for both type 1 and type 2 diabetics, A similar development is now taking place in the growth hormone field. Depot preparations for weekly administration are under development to achieve better compliance. One recently approved depot uses an analogue, modified in one amino acid of the peptide chain to permit acylation and albumin binding. In a way this is a retrograde step and it remains to be seen if the patient’s growth and metabolic responses are comparable to the daily administration of tiny amount of recombinant natural sequence hormone over several years of treatment.

Contemporary Campus Life

It is with a certain hesitation that one opens a new book about the work experience written by a former colleague. Flicking nervously to the index I am relieved to see my name is not mentioned, only moments later to be mortified on flicking through his 244-page apologia to see my name up in lights. So, we shall start with a shoddy index. That and the 1970s drab brown cover do not speak well for a good read. Then the acknowledgements contain this ominous paragraph: ‘These chapters are constituted and rewritten from columns published in UKZNdabaOnline, with others from UKZNtouch, SUBtext, Wits Review, the Sunday Times and some other published and original materials. The first of these he wrote as the Griot, the oral storyteller of African communities. The chapters have been edited, updated and the original ideas elaborated on and offered here in essay form, rather than as columns.’ So, the 1970s are pushed back to the 1950s when in South Africa the common if quaintly outdated practice of selected published columns actually sold books. A quarter of a century ago I recall advising a celebrated journalist and broadcaster not to even think of such a retrograde step. And yet, like some remarkable madcap Grand Design, Tomaselli has succeeded where others have failed. The book is a success.

Reflections on proposed modifications to the regulation of genetically modified food labeling in Brazil.

Given the uncertainty surrounding the safety of genetically modified organisms (GMOs), the precautionary principle and constitution provide that consumers should have the right to access adequate information on the presence of transgenics through food labelling. This article discusses the implications of proposed modifications to GM food labelling in Brazil. Current labelling legislation and the government agencies involved in labelling do not guarantee that food products not bearing GMO labels are free of transgenics. The approval of Chamber of Deputies Bill No. 34/2015 goes against the Consumer Protection Code by undermining consumer autonomy and choice. In addition, it is likely to weaken the country's biosurveillance capabilities to identify and seize products that have a harmful effect on the health of humans, animals and the environment. The proposed changes constitute a retrograde step in the regulation of food labelling in Brazil and violate the individual and collective rights enshrined in the Federal Constitution, Consumer Protection Code, and international agreements signed by Brazil.

A biodiversity hotspot in turmoil: Doing away with circular 5/2001 could have catastrophic consequences for Sri Lanka's forests

AbstractIn 2017, Sri Lanka set a goal to increase its forest cover to 32% by 2030 (Sri Lanka UN‐REDD, 2017). However, on November 4th 2020, the government published circular MWFC/1/2020 revoking the circular 5/2001 of August 10th 2001, one of the country's most crucial forest protection directives. The revocation of the 5/2001 circular could severely hamper this target, posing a threat of deforestation to a variety of ecosystems which are not part of any formally designated protected areas (PA) in Sri Lanka, also known as Other State Forests. This includes forested areas adjoining PAs which are crucial for habitat connectivity and standalone state forest lands. Such a retrograde step could have potentially catastrophic ramifications on Sri Lanka's declining forest cover. It would also severely weaken the country's commitments to inter alia, the UNREDD Programme, Kyoto protocol and CBD. We therefore call on the Government of Sri Lanka to urgently reconsider and reverse this decision.

Abandoning print is a retrograde step

The announcement of a new and improved website for The Pharmaceutical Journal must be welcomed (Pharm J 2020;305[7944]:394), but the total abandonment of a print version is a highly damaging and retrograde step for the Royal Pharmaceutical Society and the profession. Before I am accused of a Luddite attitude and of failing to keep up […]

Tenecteplase (and common sense) in short supply during the COVID ‐19 pandemic

Tenecteplase (and common sense) in short supply during the <scp>COVID</scp> ‐19 pandemic

Who Reads Food Labels? Selected Predictors of Consumer Interest in Front-of-Package and Back-of-Package Labels during and after the Purchase.

The paper aims to identify selected predictors of food label use to extend our knowledge about consumer behavior related to food purchases. Two types of information were examined: front-of-package (FOP) and back-of-package (BOP), and two contexts of reading labels were distinguished: during shopping and at home. Various types of potential predictors were tested, including demographic (e.g., age, gender, household size, place of living), socioeconomic (e.g., education, professional activity, income), behavioral (e.g., purchasing certain types of products), and psychographic (e.g., importance attached to various types of information) criteria. The survey was conducted with the use of the CAWI (Computer-Assisted Web Interviews) methodology in a sample of 1051 Polish consumers. Quota sampling was applied based on sex, age, education, place of living (urban vs. rural), and region. Descriptive statistics, t-tests, ANOVAs, Pearson correlation coefficients, and multiple and retrograde step regressions were applied. In retrograde step regression models, only one predictor (self-rated knowledge about nutrition healthiness) turned out to be significant for all four measures of label reading. The remaining predictors were specific to selected measures of reading labels. The importance of the information about the content of fat and that about the health effects of consuming a food product were significant predictors of three types of food label use. This study confirms the necessity to investigate reading labels in fine-grained models, adapted to different types of labels and different contexts of reading. Our results show that demographic or socioeconomic variables are not significant predictors of reading food labels for a large group of Polish consumers.

Polanyi’s embeddedness and shareholder stewardship: a contextual analysis of current Anglo-American perspectives on corporate governance

Polanyi saw the economy as properly embedded in society and argued that the capitalist free market, in commodifying social relations of production, seeks to disembed the economy from society. The resulting lack of continuity between society and economy, he maintained, created conflict which necessarily required state intervention. The market economy, therefore, in contrast to neoclassical/neoliberal economics’ vision of an autonomous, self-regulating market, required more, not less, state intervention to sustain it than alternative, more embedded economies. This article explores this conflict in the context of a specific neoliberal claim: that institutional shareholders are capable of being good 'stewards' of the companies in which they invest. Utilising Polanyi’s embeddedness, this article assesses the 'stewardship' approach as it is manifested in the US and in the UK. This approach is posited on a vision of a disembedded, self-regulating market. Putting it into practice is thus a retrograde step which will only exacerbate the problems created by the market-based corporate governance strategies which have prevailed since the late 1970s onwards.

Medical services policy in respect of detainees: evolution and outstanding issues

Alleged and confirmed abuse of civilians arrested or detained by the UK Armed Forces has been the subject of four formal enquiries, and all have used medical evidence and/or addressed...

The Impact of Brexit on Francophone Africa

Whereas the impact of Brexit on Anglophone Africa was a major issue in the controversial British discussions on the pros and cons of Brexit, possible repercussions on French-speaking Africa have been rarely mentioned up to now. Yet, the range of possible Brexit effect is impressive, including the revival of progressive social networks in Francophone Africa. The latter are already demanding more political and economic sovereignty, for example with respect to the increasingly anachronistic F CFA currency. Yet, in view of the lack of countervailing power of Britain within the EU in the case of Brexit, the murky network of Francafrique could be re-vitalized and consolidated as well. Finally, the Brexit and its spread-effects could also impact negatively on acquired human rights, both in Europe and in Africa. The withdrawal in general will have widely disregard implications for hitherto shared ethics. In fact, the Brexit constitutes a retrograde step in promoting a political and socio-cultural climate which could become similar to that of Apartheid South Africa. This includes the pursuit of ultranationalist goals and compromising on established human rights, for example with respect to growing inequality and the crusade against infidels and outsiders. More generally, the Brexit will also impact negatively on acquired ethics concerning popular articipation, both in Europe and in Africa.

Deontic power, authority, and governance in international politics

Barnett and Duvall have offered a highly useful constructivist taxonomy of power in response to the rationalist question of why constructivists formerly lacked a theory of power. However, in applying their taxonomy of power to the question of global governance, they draw upon a specific interpretation of their ‘structural’ form of power from the radical theory of Steven Lukes. This move generates a number of ontological and analytic issues that constructivists normally avoid. This article offers three amendments to Barnett and Duvall’s thesis. These involve the (1) recognition and use of the subsumption of the constitutive forms of power that they theorize within the concept of ‘deontic power’, introduced in the institutional philosophy of John Searle and (2) recognition that the posited distinction between subjective and objective interests returns us to a rationalist and materialist ontology that resolves the question of actor interests and motivations through exogenous imputation by the analyst – a retrograde step for constructivist theory that can and should be avoided. (3) In developing the deontic bases of the constitutive forms of power introduced by Barnett and Duvall, we will recover the social means by which power can be exercised as authority.

Apportionment of Damages for Contributory Negligence: The Causal Potency Criterion

The courts in several common law jurisdictions have adopted a causal potency criterion forthe purposes of apportioning damages for contributory negligence. It has recently beensuggested that Canadian courts should follow suit. This article explores the causal potencycriterion. It is argued that the criterion has been left unexplained with the result that it is anempty concept. Moreover, no compelling justification has been offered in support of takingcausal potency into account. Accordingly, adopting the causal potency criterion would bea retrograde step for Canadian tort law.

Will subspecialisation benefit the practice of Australasian emergency medicine? No.

Will subspecialisation benefit the practice of Australasian emergency medicine? No.

RDA: the Emperor’s New Code

Argues that the RDA was an unnecessary waste of time and money. The few improvements it makes in catalogue records could have been accomplished far more cheaply, promptly, and easily by modifying AACR2. Argues that RDA's abandonment of the ISBD is a retrograde and damaging step.

Addressing challenges for future strategic-level emergency management: reframing, networking, and capacity-building.

The mounting frequency and intensity of natural hazards, alongside growing interdependencies between social-technical and ecological systems, are placing increased pressure on emergency management. This is particularly true at the strategic level of emergency management, which involves planning for and managing non-routine, high-consequence events. Drawing on the literature, a survey, and interviews and workshops with Australia's senior emergency managers, this paper presents an analysis of five core challenges that these pressures are creating for strategic-level emergency management. It argues that emphasising 'emergency management' as a primary adaptation strategy is a retrograde step that ignores the importance of addressing socio-political drivers of vulnerabilities. Three key suggestions are presented that could assist the country's strategic-level emergency management in tackling these challenges: (i) reframe emergency management as a component of disaster risk reduction rather than them being one and the same; (ii) adopt a network governance approach; and (iii) further develop the capacities of strategic-level emergency managers.