Studies have shown that in the mammalian neuromuscular system stretch reflexes are localized within individual muscles. Neuromuscular compartmentalization, the partitioning of sensory output from muscles, and the partitioning of segmental pathways to motor nuclei have also been demonstrated. This evidence indicates that individual motor nuclei and the muscles they innervate are not homogeneous functional units. An analysis of the functional significance of reflex localization and partitioning suggests that segmental control mechanisms are based on subdivisions of motor nuclei–muscle complexes. (...) A partitioned organization of segmental control mechanisms could utilize (1) the potential functional diversity of muscle fiber types, (2) the variety of mechanical actions of individual muscles arising from their distributed origins and insertions, and (3) diverse architectural features such as intramuscular variations in pinnation and complex in-series and in-parallel arrangements of muscle fibers. The differentiated activity observed in some muscles during natural movements also calls for localized segmental control mechanisms. Partitioning may also play a role in mechanical interactions between contracting motor units and in increasing the stability of neuromuscular systems. The functional advantages of reflex localization and partitioning suggest they are probably common features of segmental systems, whose organization reflects the structure and function of their associated neuromuscular systems. (shrink)

The developing neuromuscular junction has provided an important paradigm for studying synapse formation. An outstanding feature of neuromuscular differentiation is the aggregation of acetylcholine receptors (AChRs) at high density in the postsynaptic membrane. While AChR aggregation is generally believed to be induced by the nerve, the mechanisms underlying aggregation remain to be clarified. A 43‐kD protein (43k) normally associated with the cytoplasmic aspect of AChR clusters has long been suspected of immobilizing AChRs by linking them to the cytoskeleton. (...) In recent studies, the AChR clustering activity of 43k has, at last, been demonstrated by expressing recombinant AChR and 43k in non‐muscle cells. Mutagenesis of 43k has revealed distinct domains within the primary structure which may be responsible for plasma membrane targeting and AChR binding. Other lines of study have provided clues as to how nerve‐derived (extracellular) AChR‐cluster inducing factors such as agrin might activate 43k‐driven postsynaptic membrane specialization. (shrink)

As we die, our respiratory pattern is altered and we seem to gasp and struggle for each breath. Such gasping is commonly seen as a clear sign of dyspnoea and suffering by families and loved ones, however, it is unclear whether it is perceived at all by the dying person. Narcotics and sedatives do not seem to affect these gasping respirations. In this issue of the Journal of Medical Ethics, we are asked to consider whether the last gasp of a (...) dying patient could be or, perhaps, even should be avoided by administering neuromuscular blockers to palliate dying patients. For many reasons, such as our current failure to alleviate pain and distress, stories of inadequate analgesia and sedation in critically ill paralysed patients and the inability to know the intent—whether to palliate or to euthanise—it would seem that administering neuromuscular blockers should not be ethically permissible. (shrink)

The appendages of Drosophila develop from the imaginal discs. During the extensive growth of these discs cell lineages are for the most part unfixed, suggesting a strong role for cell‐cell interactions in controlling the final pattern of differentiation. However, during early and middle stages of development, discs are subdivided by strict lineage restrictions into a small number of spatially distinct compartments. These compartments appear to be maintained by stably inheriting states of gene expression; the compartmentspecific expression of two (...) such ‘selector’ ‐ like genes, engrailed and apterous, are critical for anterior‐posterior and dorso‐ventral compartmentalization, respectively. Recent work suggests that one purpose of compartmentalization is to establish regions of specialized cells near compartment boundaries via intercompartmental induction, using molecules like the hedgehog protein. Thus, compartments can act as organizing centers for patterning within compartments. Evidence for non‐compartmental patterning mechanisms will also be discussed. (shrink)

Simultaneous bimanual movements are not merely the sum of two unimanual movements. Here, we considered the unimanual/bimanual motor system as comprising three components: unimanual-specific, bimanual-specific, and overlapping. If the force-generating system controlling the same limb differs between unimanual and bimanual movements, unimanual exercise would be expected to fatigue the unimanual-specific and overlapping parts in the force-generating system but not the bimanual-specific part. Therefore, we predicted that the decrease in bimanual force generation induced by unimanual neuromuscular fatigue would be smaller (...) than the decrease in unimanual force generation. Sixteen healthy right-handed adults performed unimanual and bimanual maximal handgrip measurements before and after a submaximal fatiguing handgrip task. In the fatigue task, participants were instructed to maintain unimanual handgrip force at 50% of their maximal handgrip force until the time to task failure. Each participant performed this task in a left-hand fatigue condition and a right-hand fatigue condition, in a random order. Although the degree of neuromuscular fatigue was comparable in both conditions, as expected, the decrease in bimanual right handgrip force was significantly smaller than those during unimanual right performance in the RF condition, but not in the LF condition. These results indicate that for the right-hand, neuromuscular fatigue in unimanual handgrip does not completely affect simultaneous bimanual handgrip. Regarding the underlying mechanisms, we propose that although neuromuscular fatigue caused by unimanual handgrip reduces the motor output of unimanual-specific and overlapping parts in the force-generating system, when simultaneous bimanual handgrip is performed, the overlapping part and the bimanual-specific part generate motor output, thus decreasing the force reduction. (shrink)

Biological objects are often constructive dynamic systems whose structures evolve as a consequence of their internal dynamics, which in turn is affected by the overall structure. As very few tools are presently adapted to tackle constructive dynamic systems, they constitute fascinating challenges for modeling/simulation. In cell biology, the secretory process in eukaryotic cells corresponds to this type of system, as it appears to autonomously generate new structures as a result of its molecular dynamics. Here I briefly review the only documented (...) case of a membrane-bounded intracellular compartment whose very existence strictly depends on its continued functioning. Indeed, the Golgi apparatus of the yeast Saccharomyces cerevisiae appears at steady-state as a continuously renewed set of transitory membrane-bounded structures that self-mature, rather than as a permanent entity. On the basis of this case and of recent advances in related molecular studies, a detailed model is proposed, that encompasses the birth of a yeast Golgi element and bridges its molecular and morphogenetic aspects. This model is extended to briefly outline three evolutionary inventions, from S. cerevisiae to another yeast, Pichia pastoris, on to plant, and on to animal cells: stacking, stabilizing and aggregating the primary Golgi elements. (shrink)

This paper is a summary and extension of almost four decades of research directed toward an explication of the human mind. To achieve a precise, testable proposition that defines mind, I follow a historically rich tradition of materialism. First, an empirical basis is established wherein electropsychologically measured events from the brain, eyes, somatic and speech musculature occur almost simultaneously during a variety of cognitions. The inference is that these covert reactions form components of neuromuscular circuits governed by cybernetic principles. (...) Conversely, when the striated musculature is totally inactive, cognitions are absent. The conclusion is that muscular components of the circuits are necessary for cognitions. An explication of the human mind emerges as the selective interaction of bodily systems to generate contents of mind and to program covert and overt behavior. Clinical and educational applications follow. (shrink)

Recent developments in novel therapies for neuromuscular diseases offer parents new perspectives on their affected children's future. This article examines how the emergence of new therapies impacts the lives of parents of children with Duchenne muscular dystrophy or spinal muscular atrophy type 2, two genetic neuromuscular disorders characterized by progressive muscle degeneration. Aiming for a first‐person perspective, fieldwork was conducted utilizing participant observation, semistructured interviews, and several internet sources. Six families with a total of 12 persons, all living (...) in Denmark, were included in the interviews. Two types of parents were identified who were at opposite ends in dealing with the new therapies—the cure optimists and the cure pragmatists. Different hopes resulted in different narratives for their children's futures. The article raises questions about how and when children with chronic diseases should be involved in their parent's hopes for a cure and highlights the dilemmas facing health professionals working in the field of children with chronic diseases for which the prospects of a cure are improving. We conclude that health professionals must find a way to carefully balance guidance and information about experimental medicines, including the fact that experimental medicine sometimes fails, does not work as well as hoped for, or does not become available, with sustaining parental hopes for their children's future. (shrink)

Background: The proprioceptive neuromuscular facilitation reciprocal contraction pattern has the potential to increase the maximum rate of torque development. However, it is a more complex resistive exercise task and may interfere with improvements in the maximum rate of torque development due to motor skill learning, as observed for unidirectional contractions. The purpose of this study was to examine the cost-benefit of using the PNF exercise technique to increase the maximum rate of torque development.Methods: Twenty-six participants completed isometric maximal extension-to-flexion (...) or flexion-only contractions at the wrist. Ten of the assigned contractions were performed on each of three sessions separated by 48-h for skill acquisition. Retention was assessed with 5 contractions performed 2-weeks after acquisition. Torque and surface electromyographic activity were analyzed for evidence of facilitated contractions between groups, as well as alterations in muscle coordination assessed across test sessions. The criterion measures were: mean maximal isometric wrist flexion toque; the maximal rate of torque development ; root-mean-square error variability of the rate of torque versus torque phase-plane; the rate of wrist flexion muscle activation ; a coactivation ratio for wrist flexor and extensor sEMG activity; and wrist flexor electromechanical delay.Results: There were no significant differences between groups with respect to maximal wrist flexion torque, dτ/dtmax or RMSE variability of torque trajectories. Both groups exhibited a progressive increase in maximal strength and in dτ/dtmax from the start of acquisition to retention. RMSE was lowest after a 2-week rest interval. There were no significant differences between groups in the rate of muscle activation or the coactivation ratio. There was a reduction in coactivation that was retained after a 2-week rest interval. Alternatively, EMD was significantly greater in the experimental group across all sessions. However, both groups had a similar pattern of improvement to the third consecutive day of testing, but returned close to baseline value after the 2-week rest interval.Discussion: The wrist extension-to-flexion contraction pattern did not result in a greater maximal rate of torque development than simple contractions of the wrist flexors. There was no difference between groups with respect to motor skill learning. The main adaptation in neuromotor control was a decrease in coactivation, not the maximal rate of muscle activation. (shrink)

Many individuals with disabling conditions have difficulty with gait and balance control that may result in a fall. Exoskeletons are becoming an increasingly popular technology to aid in walking. Despite being a significant aid in increasing mobility, little attention has been paid to exoskeleton features to mitigate falls. To develop improved exoskeleton stability, quantitative information regarding how a user reacts to postural challenges while wearing the exoskeleton is needed. Assessing the unique responses of individuals to postural perturbations while wearing an (...) exoskeleton provides critical information necessary to effectively accommodate a variety of individual response patterns. This report provides kinematic and neuromuscular data obtained from seven healthy, college-aged individuals during posterior support surface translations with and without wearing a lower limb exoskeleton. A 2-min, static baseline standing trial was also obtained. Outcome measures included a variety of 0 dimensional measures such as center of pressure RMS, peak amplitude, velocities, pathlength, and electromyographic RMS, and peak amplitudes. These measures were obtained during epochs associated with the response to the perturbations: baseline, response, and recovery. T-tests were used to explore potential statistical differences between the exoskeleton and no exoskeleton conditions. Time series waveforms of the COP and EMG data were also analyzed. Statistical parametric mapping was used to evaluate the 1D COP and EMG waveforms obtained during the epochs with and without wearing the exoskeleton. The results indicated that during quiet stance, COP velocity was increased while wearing the exoskeleton, but the magnitude of sway was unchanged. The OD COP measures revealed that wearing the exoskeleton significantly reduced the sway magnitude and velocity in response to the perturbations. There were no systematic effects of wearing the exoskeleton on EMG. SPM analysis revealed that there was a range of individual responses; both behaviorally and among neuromuscular activation patterns. Using both the OD and 1D measures provided a more comprehensive representation of how wearing the exoskeleton impacts the responses to posterior perturbations. This study supports a growing body of evidence that exoskeletons must be personalized to meet the specific capabilities and needs of each individual end-user. (shrink)

This article focuses on the role of the interchromatin compartment (IC) in shaping nuclear landscapes. The IC is connected with nuclear pore complexes (NPCs) and harbors splicing speckles and nuclear bodies. It is postulated that the IC provides routes for imported transcription factors to target sites, for export routes of mRNA as ribonucleoproteins toward NPCs, as well as for the intranuclear passage of regulatory RNAs from sites of transcription to remote functional sites (IC hypothesis). IC channels are lined by less‐compacted (...) euchromatin, called the perichromatin region (PR). The PR and IC together form the active nuclear compartment (ANC). The ANC is co‐aligned with the inactive nuclear compartment (INC), comprising more compacted heterochromatin. It is postulated that the INC is accessible for individual transcription factors, but inaccessible for larger macromolecular aggregates (limited accessibility hypothesis). This functional nuclear organization depends on still unexplored movements of genes and regulatory sequences between the two compartments. (shrink)

Study in the period of coronavirus disease 2019 lockdown and the effect of different exercise training programs on the quality of life dimension are limited. This randomized control study as a part of which the impact of an 8-week neuromuscular training program on the 90 healthy young individuals’ QoL after COVID-19 lockdown was assessed using a short form of the WHOQOL-BREF questionnaire comprising of four domains. The intervention group took part in a neuromuscular training program consisting of dynamic (...) neuromuscular stabilization and whole-body vibration training. In contrast, the control group did not participate in any programmed physical activity. From pre- to post-intervention test, the NT group significantly and substantially improved [mean change ] all the QoL domains, physical for 12.78 scores, psychological for 13.12 scores, social relationships for 20.57 scores, and environmental for 24.40 scores. These results suggest that the NT program could enhance QoL in young and healthy participants following COVID-19 lockdown. (shrink)

The development of bacterial resistance to antibiotics is one of the best documented examples of contemporary biological evolution. Variability in the mechanisms of resistance depends on the diversity of genotypes in the huge bacterial populations, and also on the diversity of selective pressures that are produced along the antibiotic concentration gradients formed in the highly compartmentalized human body during therapy. These antibiotic gradients can be conceived as comprising selective compartments, each one of them defined as the concentration able to (...) select a particular genetic variant. In vitro experimental models confirm that some antibiotic resistant variants are selected only at certain selective concentrations of antibiotics. The correspondence between selective compartments and selectable variants could offer a way of describing more accurately the antibiotic selective landscapes and for taking measures to prevent the development of a major threat to the future of modern medicine. (shrink)

The development of bacterial resistance to antibiotics is one of the best documented examples of contemporary biological evolution. Variability in the mechanisms of resistance depends on the diversity of genotypes in the huge bacterial populations, and also on the diversity of selective pressures that are produced along the antibiotic concentration gradients formed in the highly compartmentalized human body during therapy. These antibiotic gradients can be conceived as comprising selective compartments, each one of them defined as the concentration able to (...) select a particular genetic variant. In vitro experimental models confirm that some antibiotic resistant variants are selected only at certain selective concentrations of antibiotics. The correspondence between selective compartments and selectable variants could offer a way of describing more accurately the antibiotic selective landscapes and for taking measures to prevent the development of a major threat to the future of modern medicine. (shrink)

This article discusses the notion of emergent concerned groups and explores how these groups contribute to shaping the relations between technoscience, politics, and economic markets. The first part presents the case of the French Association of patients suffering from muscular dystrophies. This history suggests that under certain conditions, emergent concerned groups are able to impose a new form of articulation between scientific research and political identities by directly linking the issues of research content and results to that of their place (...) in the collective. The second part argues that the evolution of economic markets, combined with that of science and technology, leads to a multiplication of those emergent concerned groups. The study of the conditions under which these emergent groups become legitimate stakeholders as well as the analysis of their impact on market organization and technoscientific institutions are key research topics for the near future. (shrink)

Background In the Netherlands, using drugs to deliberately end the life of a severely defective newborn baby who is in extreme suffering can be permissible under very precise circumstances. This does not mean that all Dutch neonatologists are willing to engage in such behaviour. This paper discusses the use of neuromuscular blockers (NMBs) in connection with abstention decisions in neonatology and the boundaries between ‘deliberate ending of life’ and other end-of-life decisions. These boundaries are of paramount importance because, of (...) all end-of-life decisions, only ‘deliberate ending of life’ must be reported by the responsible doctor and exposes him to the risk of being prosecuted. Methods 14 Dutch neonatologists were presented with a hypothetical case of a severely asphyxiated baby who faces a long dying process after withdrawal of ‘medically futile’ (zinloos) life-sustaining ventilation. Doctors were asked whether it is acceptable to administer NMBs in this situation and whether such behaviour should be reported. Results and conclusions Doctors' responses were heterogeneous, showing that the acceptability of using NMBs in certain situations and the boundaries between end-of-life decisions are currently a subject of discussion among Dutch neonatologists. Many respondents reported feeling threatened by the potential involvement of the criminal law authorities in the system of control over ‘deliberate ending of life’. (shrink)

In BioEssays, vol. I. no. 5, p. 227, P. A. Lawrence discussed the selector gene hypothesis and its implications for development. In the following article, D. Gubb presents an alternative view of the genetic control of development.

Because rate of force development is an emerging outcome measure for the assessment of neuromuscular function in unfatigued conditions, and it represents a valid alternative/complement to the classical evaluation of pure maximal strength, this scoping review aimed to map the available evidence regarding RFD as an indicator of neuromuscular fatigue. Thus, following a general overview of the main studies published on this topic, we arbitrarily compared the amount of neuromuscular fatigue between the “gold standard” measure and peak, (...) early and late RFD. Seventy full-text articles were included in the review. The most-common fatiguing exercises were resistance exercises, endurance exercises/locomotor activities, isokinetic contractions, and simulated/real sport situations. The most widely tested tasks were knee extension and plantar flexion. The reason for evaluating RFD was lacking in 36% of the studies. On average, the amount of fatigue for MVF was comparable to late RFD but lower compared to both peak RFD and early RFD. Even if the rationale for evaluating RFD in the fatigued state was often lacking and the specificity between test task and fatiguing exercise characteristics was not always respected in the included studies, RFD seems to be a valid indicator of neuromuscular fatigue. Based on our arbitrary analyses, peak RFD and early phase RFD appear even to be more sensitive to quantify neuromuscular fatigue than MVF and late phase RFD. (shrink)

Although the precise function of utrophin at the postsynaptic membrane of the neuromuscular junction still remains unclear, despite recent genetic ‘knockout’ experiments(1,2), a separate study in a transgenic mouse model system for Duchenne muscular dystrophy (DMD) has nonetheless shown that overexpression of utrophin into extrasynaptic regions of muscle fibers can functionally compensate for the lack of dystrophin and alleviate the muscle pathology(3). In this context, the next step is to identify the mechanisms presiding over expression of utrophin at the (...) neuromuscular synapse in attempts to induce its expression throughout DMD muscle fibers. In fact, additional studies have shown that an important DNA element contained with the utrophin promoter may confer synapse‐specific expression to the utrophin gene(4,5). Identification of the events culminating in the transaction of the utrophin gene within synaptic myonuclei should provide important cues for the development of an effective therapeutic strategy for DMD. (shrink)

Selective protein degradation maintains cellular homeostasis, but this process is disrupted in many diseases. Targeted protein degradation (TPD) approaches, built upon existing cellular mechanisms, are promising methods for therapeutically regulating protein levels. Here, we review the diverse palette of tools that are now available for doing so throughout the gene expression pathway and in specific cellular compartments. These include methods for directly removing targeted proteins via the ubiquitin proteasome system with proteolysis targeting chimeras (PROTACs) or dephosphorylation targeting chimeras (DEPTACs). (...) Similar effects can also be achieved through the lysosomal system with autophagy‐targeting chimeras (AUTACs), autophagosome tethering compounds (ATTECs), and lysosome targeting chimeras (LYTACs). Other methods act upstream to degrade RNAs (ribonuclease targeting chimeras; RIBOTACs) or transcription factors (transcription factor targeting chimeras; TRAFTACs), offering control throughout the gene expression process. We highlight the evolution and function of these methods and discuss their clinical implications in diverse disease contexts. (shrink)

The neuromuscular junction has been used for several decades as an excellent model system to examine the cellular and molecular events involved in the formation and maintenance of a differentiated chemical synapse. In this context, several laboratories have focused their efforts over the last 15 years on the important contribution of transcriptional mechanisms to the regulation of the development and plasticity of the postsynaptic apparatus in muscle fibers. Converging lines of evidence now indicate that post‐transcriptional events, operating at the (...) level of mRNA stability and targeting, are likely to also play key roles at the neuromuscular junction. Here, we present the recent findings highlighting the role of these additional molecular events and extend our review to include data showing that post‐transcriptional events are also important in the control of the expression of genes encoding synaptic proteins in muscle cells placed under different conditions. Finally, we discuss the possibility that mis‐regulation of post‐transcriptional events can occur in certain neuromuscular diseases and cause abnormalities of the neuromuscular junction. BioEssays 25:25–31, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

The main aim of our study was to determinate whether a repeated bout (RB) (vs. first bout [FB]) of sprint interval cycling exercise (SIE) is sufficient to mitigate SIE-induced psychological and physiological biomarker kinetics within 48 h after the exercise. Ten physically active men (age, 22.6 ± 5.2 years; VO2max, 44.3 ± 5.7 ml/kg/min) performed the FB of sprint interval cycling exercise (12 repeats of 5 s each) on one day and the RB 2 weeks later. The following parameters were (...) measured: motor performance (voluntary, electrically induced and isokinetic skeletal muscle contraction torque, and central activation ratio [CAR]); stress markers (BDNF, cortisol, norepinephrine, and epinephrine); inflammatory markers (IL-6, IL-10, and TNF-); metabolic markers (glucose and lactate); muscle and rectal temperature; cycling power output; and psychological perceptions. The average cycling power output and neuromuscular fatigue after exercise did not differ between the FB and RB. There were significant decreases in cortisol and BDNF concentration at 12 h (P < 0.05) and 24 h (P < 0.001) after the FB, respectively. The decrease in cortisol concentration observed 12 h after exercise was significantly greater after the RB (P < 0.05) than after the FB. The immune-metabolic response to the RB (vs. FB) SIE was suppressed and accompanied by lower psychological exertion. Most of the changes in psychological and physiological biomarkers in the FB and RB were closely related to the response kinetics of changes in BDNF concentration. (shrink)

The present study examined the effects of transcranial direct current stimulation using Halo Sport on the time to exhaustion in relation with muscle activities and corticomuscular coupling of agonist and antagonist muscles during a sustained isometric fatiguing contraction performed with the elbow flexors. Twenty healthy male college students were randomly assigned to tDCS group and control group. The two group participants performed two experimental sessions which consisted of pre-fatigue isometric maximal voluntary contraction, sustained submaximal voluntary contractions performed to exhaustion, and (...) post-fatigue MVC with the right elbow flexor muscles. Sham stimulation and tDCS were applied for control and tDCS group participants 20 min prior to the second session test, respectively. MVC strength in pre- and post-fatigue test, TTE, electroencephalogram, and electromyography of biceps brachii and triceps brachii were recorded during the tests. It was found that tDCS using the Halo Sport device significantly increased TTE and thus improved muscular endurance performance. The improvement may be partly related to the improvement of neuromuscular efficiency as reflected by decrease of antagonistic muscle coactivation activities, which may be related to cortical originated central processing mechanism of neuromuscular activities. (shrink)

Rare neuromuscular diseases are a group of pathologies characterized by a progressive loss of muscular strength, atrophy, fatigue, and other muscle-related symptoms, which affect quality of life levels. The low prevalence, high geographical dispersion and disability of these individuals involve difficulties in accessing health and social care services. Teleassistance is presented as a useful tool to perform psychosocial interventions in these situations. The main aim of this research is to assess the effects of a teleassistance psychosocial program on the (...) QoL levels of people with RNMDs who have different levels of disability. A sample of 73 participants was divided into an experimental group, which participated in the intervention, and a control wait list group. QoL was evaluated through the SIP and the SF-36, and disability through the WHO-DAS II. The participants with a moderate to severe level of disability were those who most benefited from the intervention. The results also revealed that the psychosocial teleassistance program was suitable to improve physical and psychosocial aspects of people suffering from a rare neuromuscular disease with a moderate level of disability, but just psychosocial aspects in those with a severe level of disability. (shrink)

During late embryonic and early postnatal development, synaptic connections are extensively modified so that some functional connections are weakened and eliminated from a neural circuit while others are strengthened and maintained. The mechanisms that underlie synapse elimination are beginning to be understood from studies of the neuromuscular junction. A recent paper(1) provides some intriguing insights into the role proteases may play in the developmental disassembly of neuromuscular synapses.

It has long been believed that membrane proteins present in degradative compartments such as endolysosomes or vacuoles would be destined for destruction. Now however, it appears that mechanisms and machinery exist in simple eukaryotes such as yeast and more complex organisms such as mammals that can rescue potentially “doomed” membrane proteins by retrieving them from these “late” compartments and recycling them back to the Golgi complex. In yeast, a sorting nexin dimer containing Snx4p can recognize and retrieve the (...) Atg27p membrane protein while in mammals, the AP5 complex (with SPG11 and SPG15) directs the recycling of Golgi‐localized proteins along with the cation‐independent mannose 6‐phosphate receptor (CIMPR). Although the respective machinery is different, there is much commonality between yeast and mammals regarding the mechanisms of retrieval and the physiological importance of these late recycling pathways. (shrink)

Means–ends decoupling, the institutionally induced implementation of ineffective practices, has become increasingly common. Extant theory suggests that means–ends decoupling has real consequences, which makes it unstable and difficult for organizations to sustain. Yet little is known of how, and with what outcomes, firms organize such means–ends decoupling. We examine organizing via multiple qualitative and longitudinal case studies of how Swedish fast fashion retailers implement and manage the collection of used garments. We find that firms combine two organizational arrangements: structural and (...) temporal core–compartment separations, which mitigate consequences of means–ends decoupling by obscuring and justifying efficiency gaps. Thereby we provide a theoretical explanation for how means–ends decoupling can persist over time. (shrink)

Electroencephalographic correlates of movement have been studied extensively over many years. In the present work, we focus on investigating neural correlates that originate from the spine and study their connectivity to corresponding signals from the sensorimotor cortex using multivariate autoregressive models. To study cortico-spinal interactions, we simultaneously measured spinal cord potentials and somatosensory evoked potentials of wrist movements elicited by neuromuscular electrical stimulation. We identified directional connections between spine and cortex during both the extension and flexion of the wrist (...) using only non-invasive recording techniques. Our connectivity estimation results are in alignment with various studies investigating correlates of movement, i.e., we found the contralateral side of the sensorimotor cortex to be the main sink of information as well as the spine to be the main source of it. Both types of movement could also be clearly identified in the time-domain signals. (shrink)

In this review essay, I review in detail Abram de Swann's fine new book, The Killing Compartments. The book is a theoretical analysis of the varieties and causes of genocides and other mass asymmetrical killing campaigns. I then suggest several criticisms of his analysis.

Abstractβ1,4‐galactosyltransferase is unusual among the glycosyltransferases in that it is found in two subcellular compartments where it performs two distinct functions. In the trans‐Golgi complex, galactosyltransferase participates in oligosaccharide biosynthesis, as do the other glycosyltransferases. On the cell surface, however, galactosyltransferase associates with the cytoskeleton and functions as a receptor for extracellular oligosaccharide ligands. Although we now know much regarding galactosyltransferase function in these two compartments, little is known about how it is targeted to these different sites. By (...) cloning the galactosyltransferase gene products, certain features of the protein have been identified that may be critical for its expression on the cell surface or retention within the Golgi complex. This article discusses recent studies which suggest that a cytoplasmic sequence unique to one galactosyltransferase isoform is required for targeting a portion of this protein to the plasma membrane, enabling it to function as a cell adhesion molecule. These findings allow one to manipulate surface galactosyltransferase expression, either positively or negatively, and perturb galactosyltransferase‐dependent cellular interactions during fertilization and development. (shrink)

Decisions about long-term ventilation in children can be clinically contentious and ethically challenging. In this article, the relevant legal, professional and moral principles inherent in such cases are explored. We commend the central importance of deliberation in the assessment of best interests, and propose a practical framework to assist the parent–clinical team to reach decisions in as transparent and equitable a manner as possible.