Diagnostic histochemistry and clinical-pathological testings as molecular pathways to pathogenesis and treatment of the ageing neuromuscular system: a personal view

AbstractAgeing of the neuromuscular system in elderhood ingravescently contributes to slowness, weakness, falling and death, often accompanied by numbness and pain. This article is to put in perspective examples from a half-century of personal and team neuromuscular histochemical–pathological and clinical–pathological research, including a number of lucky and instructive accomplishments identifying new treatments and new diseases. A major focus currently is on some important, still enigmatic, aspects of the ageing neuromuscular system. It is also includes some of the newest references of others on various closely-related aspects of this ageing system. The article may help guide others in their molecular-based endeavors to identify paths leading to discovering new treatments and new pathogenic aspects. These are certainly needed – our ageing and unsteady constituents are steadily increasing. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis

The multiple ADP/ATP translocase genes are differentially expressed during human muscle development

The expression of the genes encoding the three isoforms of the human ADP/ATP translocase (T1, T2, and T3) has been analyzed at different stages of myogenic differentiation in an in vitro muscle cell system and compared with that in mature muscle. The results indicate that the three stages of muscle differentiation corresponding to myoblast proliferation, myotube formation, and mature muscle fibers are characterized by a different pattern of expression of the ADP/ATP translocase genes. In particular, the two T2-specific mRNAs are present at high, similar levels in myoblasts and myotubes and markedly decrease in amount in mature adult muscle. By contrast, the T3-specific mRNA is present in high amount in growing myoblasts, decreases markedly in myotubes, and is barely detectable in adult muscle. Finally, the T1-specific mRNA is present at a high level in adult muscle and is not detectable in either myoblasts or myotubes. Therefore, T1 gene expression appears to be a marker of a late stage in myogenesis. A parallel investigation of expression of the myosin heavy chain mRNA revealed absence of hybridization with the specific probe in RNA from proliferating myoblasts, a significant hybridization in myotube RNA, and a strong signal in adult muscle RNA

Order flows, fundamentals and exchange rates

We examine the links between end-user order flows as seen by a major European commercial bank and macroeconomic fundamentals. We show that both exchange rate changes and flows are only weakly related to macroeconomic news announcements and hypothesize that 'the cat is already out of the bag' by the time the news is announced. Instead, order flows of financial and corporate customers reflect in real time the evolution of macroeconomies. The actions of the banks receiving the order flows in turn reveal the information to the market as a whole, which prices the exchange rate accordingly. By the time the news is announced, the exchange rate already contains the majority of the information

Asymptomatic rheumatic heart disease in South African schoolchildren: Implications for addressing chronic health conditions through a school health service

When new evidence comes to light, it compels us to contemplate the implications of such evidence for health policy and practice. This article examines recent research evidence on the prevalence of asymptomatic rheumatic heart disease (RHD) in  South Africa and considers the implications for the Integrated School Health  Programme (ISHP). RHD is still a major burden of disease in developing countries, and elimination of this preventable condition ranks high among World Heart  Federation goals. If left untreated, it becomes a chronic health condition that  individuals have to cope with into their adult lives. The ISHP regards the health  needs of children with chronic health conditions, which include conditions such as RHD, as a key service component. However, the chronic health component of the ISHP is still poorly developed and can benefit from good evidence to guide implementation. A recent study to ascertain the prevalence of RHD in asymptomatic schoolchildren through mass screening affords an opportunity to reflect on whether, and how, asymptomatic chronic health conditions in schoolchildren could be addressed, and what the implications would be if this were done through a school-based programme such as the ISHP

Topological kink plasmons on magnetic-domain boundaries.

Two-dimensional topological materials bearing time reversal-breaking magnetic fields support protected one-way edge modes. Normally, these edge modes adhere to physical edges where material properties change abruptly. However, even in homogeneous materials, topology still permits a unique form of edge modes - kink modes - residing at the domain boundaries of magnetic fields within the materials. This scenario, despite being predicted in theory, has rarely been demonstrated experimentally. Here, we report our observation of topologically-protected high-frequency kink modes - kink magnetoplasmons (KMPs) - in a GaAs/AlGaAs two-dimensional electron gas (2DEG) system. These KMPs arise at a domain boundary projected from an externally-patterned magnetic field onto a uniform 2DEG. They propagate unidirectionally along the boundary, protected by a difference of gap Chern numbers ([Formula: see text]) in the two domains. They exhibit large tunability under an applied magnetic field or gate voltage, and clear signatures of nonreciprocity even under weak-coupling to evanescent photons

(En)countering counterfeits in Bangkok: the urban spatial interlegalities of intellectual property law, enforcement and tolerance

In a Bangkok mall a fibreglass policeman warning against intellectual property (IP) piracy stands just metres away from vendors selling fake DVDs; a scene indicative of incomplete and unsuccessful attempts by foreign governments (the US and EU in particular) and corporate actors at enrolment towards ever-higher IP standards – the ‘IP ratchet’ that Drahos (2004 Intellectual property and pharmaceutical markets: a nodal governance approach Temple Law Review 77 401–24) describes. But the scene also reflects cultural resistance at the local level. Both readings exemplify the range of historical, cultural, and politico-legal factors at play that can only be understood through engagement with vendors and consumers in the markets and malls of Bangkok. IP laws may achieve partial ‘closure’ but are regularly changing, contested, variably enforced, and subject to existing social norms such as the ‘cult of imitation’, cultures of legal informality, and a lack of social contract. We found that this lack of legal closure was most pronounced in the day-to-day operation of the Pratunam Market. Whilst other sites host regular crack-downs by police, the IP-specific DSI force, and the Thai courts, markets like Pratunam are mostly immune despite being a transnational trade node for the production and export of counterfeit garments with other developing countries, and a non-conforming node in the IP enforcement context. In the face of persistent efforts to transpose Euro-American IP laws in countries like Thailand, alternative and resistant nodes representing ‘spaces of interlegalities’ are likely to persevere because of the historical context, and the socio-cultural norms of these places

About direct Dark Matter detection in Next-to-Minimal Supersymmetric Standard Model

Direct dark matter detection is considered in the Next-to-Minimal Supersymmetric Standard Model (NMSSM). The effective neutralino-quark Lagrangian is obtained and event rates are calculated for the Ge-73 isotope. Accelerator and cosmological constraints on the NMSSM parameter space are included. By means of scanning the parameter space at the Fermi scale we show that the lightest neutralino could be detected in dark matter experiments with sizable event rate.Comment: latex, 12 pages, 2 ps-figures; extra LEP constraint is included, extra figure is added, recorrected version, resubmitted to Phys.Rev.

The 21Na(p,gamma)22Mg Reaction and Oxygen-Neon Novae

The 21Na(p,gamma)22Mg reaction is expected to play an important role in the nucleosynthesis of 22Na in Oxygen-Neon novae. The decay of 22Na leads to the emission of a characteristic 1.275 MeV gamma-ray line. This report provides the first direct measurement of the rate of this reaction using a radioactive 21Na beam, and discusses its astrophysical implications. The energy of the important state was measured to be E$_{c.m.}$= 205.7 $\pm$ 0.5 keV with a resonance strength $\omega\gamma = 1.03\pm0.16_{stat}\pm0.14_{sys}$ meV.Comment: Accepted for publication in Physical Review Letter

Magnetically-defined topological edge plasmons in edgeless electron gas

Topological materials bear gapped excitations in bulk yet protected gapless excitations at boundaries. Magnetoplasmons (MPs), as high-frequency density excitations of two-dimensional electron gas (2DEG) in a perpendicular magnetic field, embody a prototype of band topology for bosons. The time-reversal-breaking magnetic field opens a topological gap for bulk MPs up to the cyclotron frequency; topologically-protected edge magnetoplasmons (EMPs) bridge the bulk gap and propagate unidirectionally along system's boundaries. However, all the EMPs known to date adhere to physical edges where the electron density terminates abruptly. This restriction has made device application extremely difficult. Here we demonstrate a new class of topological edge plasmons -- domain-boundary magnetoplasmons (DBMPs), within a uniform edgeless 2DEG. Such DBMPs arise at the domain boundaries of an engineered sign-changing magnetic field and are protected by the difference of gap Chern numbers (+/-1) across the magnetic domains. They propagate unidirectionally along the domain boundaries and are immune to domain defects. Moreover, they exhibit wide tunability in the microwave frequency range under an applied magnetic field or gate voltage. Our study opens a new direction to realize high-speed reconfigurable topological devices.Comment: 7 pages, 6 figure

The evolution of metazoan extracellular matrix

The modular domain structure of extracellular matrix (ECM) proteins and their genes has allowed extensive exon/domain shuffling during evolution to generate hundreds of ECM proteins. Many of these arose early during metazoan evolution and have been highly conserved ever since. Others have undergone duplication and divergence during evolution, and novel combinations of domains have evolved to generate new ECM proteins, particularly in the vertebrate lineage. The recent sequencing of several genomes has revealed many details of this conservation and evolution of ECM proteins to serve diverse functions in metazoa.Howard Hughes Medical Institut