Vimentin: the conundrum of the intermediate filament gene family

Intermediate filaments are a major component of the “cytoskeleton” of “higher” eukaryotes. These filaments are composed of a number of different, although structurally related, proteins. Different intermediate filament protein genes are expressed in different tissues. Spontaneous and experimentally produced mutations in the intermediate filament genes indicate that these filaments function to enhance the mechanical stability of epidermal and muscle cells. As a result, the use of transgenic mice with “knockout” or dominant negative mutations in IF genes has become an important approach for investigating the significance of IFs in other cell types. However, a knockout mutation of vimentin (^-/-), the intermediate filament protein characteristically expressed in cells of mesenchymal origin, results in very subtle phenotypes that are not obviously related to cell fragility. Although experiments with cultured cells have described a variety of discrete changes in cell properties that are associated with vimentin expression or organization, there is no evidence yet that any of these properties are affected in the vimentin^-/- mouse. BioEssays 20:79–86, 1998. © 1998 John Wiley & Sons, Inc.     

Lessons from a tarantula: new insights into muscle thick filament and myosin interacting-heads motif structure and function

The tarantula skeletal muscle X-ray diffraction pattern suggested that the myosin heads were helically arranged on the thick filaments. Electron microscopy (EM) of negatively stained relaxed tarantula thick filaments revealed four helices of heads allowing a helical 3D reconstruction. Due to its low resolution (5.0 nm), the unambiguous interpretation of densities of both heads was not possible. A resolution increase up to 2.5 nm, achieved by cryo-EM of frozen-hydrated relaxed thick filaments and an iterative helical real space reconstruction, allowed the resolving of both heads. The two heads, “free” and “blocked”, formed an asymmetric structure named the “interacting-heads motif” (IHM) which explained relaxation by self-inhibition of both heads ATPases. This finding made tarantula an exemplar system for thick filament structure and function studies. Heads were shown to be released and disordered by Ca²⁺-activation through myosin regulatory light chain phosphorylation, leading to EM, small angle X-ray diffraction and scattering, and spectroscopic and biochemical studies of the IHM structure and function. The results from these studies have consequent implications for understanding and explaining myosin super-relaxed state and thick filament activation and regulation. A cooperative phosphorylation mechanism for activation in tarantula skeletal muscle, involving swaying constitutively Ser35 mono-phosphorylated free heads, explains super-relaxation, force potentiation and post-tetanic potentiation through Ser45 mono-phosphorylated blocked heads. Based on this mechanism, we propose a swaying-swinging, tilting crossbridge-sliding filament for tarantula muscle contraction.     

Direct measurement of critical concentrations and assembly rate constants at the two ends of an actin filament

Actin filament bundles isolated from Limulus sperm were used for quantitative electron microscope studies of F-actin assembly. The assembly rate constants were calculated. In addition, the critical concentrations (C_os) for both filament ends were directly determined. In 75 mM KCI and 1–5 mM Mg⁺⁺, the C_os were 0.1 μM and 0.5 μM for the barbed and pointed ends, respectively. Substitution of Ca⁺⁺ (20–200 μM) for Mg⁺⁺ resulted in C_os of 0.4 μM for both filament ends. Consistent with these findings, filament growth occurred only from the barbed ends of Limulus bundles “seeded” into F-actin solutions in KCI and Mg⁺⁺. Finally, filaments originally grown from the pointed filament ends of Limulus bundles were gradually lost as the actin solution reached steady state. These results demonstrate that actin filaments can “treadmill” under physiological conditions, albeit at very slow rates.     

Relevance of attributional and consequential information for environmental product labelling

Purpose

Considering the general agreement in the literature that environmental labelling should be based on consequential modelling, while all actually implemented environmental labelling schemes are based on attributional modelling, we investigate the arguments for this situation as provided in the literature, and whether a dual label, representing on the same label the attributional and consequential results for the same product, can be a relevant solution or at least contribute to a more informed discussion.

Methods

We developed a dual label for three hypothetical, comparable products and presented this for a small test audience, asking three questions, namely “Which product would you choose?”, “Was the attributional information useful?” and “Would you accept to have only the attributional information?”

Results and discussion

From this small pilot exercise, it appears that informed consumers may have a strong preference for consequential information and that the main problem in communicating consequential results is that they are perceived as less trustworthy and more uncertain due to the fact that the consequences are located in the future. It thus appears important to build into a consequential label some increased level of guarantee of future good behaviour.

Conclusions

We propose to apply the above questions to a more statistically representative audience to confirm or refute the findings of this little test exercise.

     

Germination of the Spores and Development of Primary and Secondary Protonema of Funaria hygrometrica

Abstract

1. The primary protonema of Funaria hygrometrica, cultivated on Knop's or Marchal's agar in the light, proved to consist of filaments with much chlorophyll, a hyaline membrane, perpendicular cross-walls and branches equal to the main filament (chloronema). These filaments grow on the surface of the agar, the branches may also grow vertically. Sometimes filaments with less chlorophyll occur immediately after the germination. The caulonema described by Sironval has not been observed. Thus the rhizoid-like forms mentioned in the literature should more likely be considered as a result of external conditions (see Schoene, Bauer, Heitz and Fitting). Therefore it remains doubtful if a distinction between rhizoids and chloronema on the primary protonema is of any importance as it is impossible to give a good definition of either form.

At the base of moss plants main filaments with brown membranes, oblique septa and without chlorophyll may develop (rhizoids). They grow on the surface or within the agar. In F. hygrometrica especially, the stem seems to influence the occurrence of these rhizoids. The main filaments form buds on the basal cell of the branches and thus serve for vegetative reproduction. The branches show the characteristics of the chloronema. This is contrary to the conclusion of Westerdijk that rhizoids would pass into chloronema only when they are damaged or when the growth of the end bud of the plant is inhibited. At the base of the plant, moreover, little ramified, short branches with oblique septa appear which do not produce buds.

2. Branches may develop in the first growth stages of the primary protonema at any point of the cells. One single cell of a main filament can produce none, one, or more than one branch. Later the branches appear immediately behind the acroscopic cross-wall except in a few cases. Each cell then produces one branch.

3. Buds always develop at the basal cell of a primary branch of a green main filament or of a rhizoid derived from a moss plant.

4. In two ways the protonema may fall into pieces, which can develop into new main filaments:

(a) By forming brood cells; rounded cells which get detached by splitting of the septum. This phenomenon is very frequent. Contrary to Servettaz's opinion it seems to occur particularly under unfavourable conditions.

(b) By forming special cells, tmemata, whose walls are rent. These occur on the primary protonema contrary to the observations of Correns and Bauer, but they are much less frequent than the brood cells. No observations have been made on the circumstances of their occurrence.     

Optimization of image quality and accuracy of low iodine concentration quantification as function of kVp pairs for abdominal imaging using dual-source CT: A phantom study

PurposeTo determine the suitable kVp pair for optimal image quality of the virtual monochromatic images (VMIs) and iodine quantification accuracy at low concentration, using a third generation dual-source CT (DSCT).Materials and methodsMulti-energy CT phantoms with and without body rings were scanned with a DSCT using four kVp pairs (tube “A”/“B” voltage): 100/Sn150, 90/Sn150, 80/Sn150 and 70/Sn150 kVp. The reference mAs was adjusted to obtain a CTDI_vol close to 11 mGy. HU values accuracy (RMSD_HU), noise (SD) and contrast-to-noise ratio (CNR) of iodine inserts of 0.5, 1, 2 and 5 mg/mL concentrations were assessed on VMIs at 40/50/60/70 keV. Iodine quantification accuracy was assessed using the RMSD_iodine and iodine bias (IB_iodine).ResultsThe RMSD_HU decreased when the tube “A” voltage increased. The mean noise value increased significantly with tube “A” voltage (p < 0.001) but decreased between 80/Sn150 and 90/Sn150 kVp for the small phantom (1.1 ± 0.1%; p = 0.047). The CNR significantly decreased with tube “A” voltage (p < 0.001), except between 80/Sn150 and 90/Sn150 kVp for all inserts and between 90/Sn150 kVp and 100/Sn150 kVp for the 1.0 and 0.5 mg/mL inserts in the large phantom. In the small phantom, no significant difference was found between 80/Sn150 kVp and 90/Sn150 kVp for all inserts and between 80/Sn150, 90/Sn150 and 100/Sn150 kVp for the 1 and 0.5 mg/mL inserts. The RMSD_iodine and IB_iodine decreased as the tube “A” voltage of the kVp pair increased.ConclusionThe kVp pair of 70/Sn150 led to better image quality in VMIs and sufficient iodine accuracy.     

OBSERVATIONS ON THE LIFE HISTORY OF PAPENFUSSIELLA CALLITRICHA (PHAEOPHYCEAE,CHORDARIALES) IN CULTURE1

Papenfussiella callitricha (Rosenv.) Kylin from eastern Canada was studied in culture. Zoids from unilocular sporangia develop into microscopic, filamentous, dioecious gametophytes which produce isogametes in filament cells and few-chambered plurilocular gametangia. Unfused gametes germinate to reproduce the gametophytes. Fusion takes place between a settled (“female”) and a motile (“male”) gamete. The zygote gives rise to a filamentous plethysmothallus that reproduces asexually by zoids formed in thallus cells and in few-chambered plurilocular zoidangia. Erect macrothalli are produced on the plethysmothallus, beginning with the formation of upright filaments. Later on, these filaments become the terminal assimilators of the macrothalli. Further assimilatory filaments, rhizoids, and unilocular sporangia are produced in a branching region at the base of the terminal assimilator. Zoids from unilocular sporangia formed in culture germinate to reestablish the gametophyte phase. Chromosome counts yielded n = 19 ± 3 for the gametophytes, and 32 ± 6 for the sporophyte, both plethysmothallus and macrothallus.     

Serum tumor markers in bile duct cancer – a review

Abstract

Context: Bile duct cancer (BDC) is a disease with a very grave prognosis, often diagnosed too late.

Objective: The aim of this review is to evaluate available literature on tumor markers in serum from patients with BDC.

Methods: Using the search words “serum markers”, “bile duct cancer”, “cholangiocarcinoma”, “biomarker” and “tumor marker”, a search was carried out.

Results: Seventy-five studies were included in the review.

Conclusion: CA19-9 is by far the most studied and most promising diagnostic and/or prognostic marker in BDC. But also the different mucins are interesting as new markers of BDC in serum.     

A Strong to Fragile Transition in a Model of Liquid Silica

Abstract

The transport properties of an ionic model for liquid silica [1] at high temperatures and pressure are investigated using molecular dynamics simulations. With increasing pressure, a clear change from “strong” to “fragile” behaviour (according to Angell's classification of glass-forming liquids) is observed, albeit only on the small viscosity range that can be explored in MD simulations. This change is related to structural changes, from an almost perfect four-fold coordination to an imperfect five or six-fold coordination.     

An historical perspective of the discovery of titin filaments –Part 2

In 2017, a Special Issue of Biophysical Reviews was devoted to “Titin and Its Binding Partners. The issue contained a review: “An historical perspective of the discovery of titin filaments” by dos Remedios and Gilmour that was intended to be a history of the discovery of the giant protein titin, previously named connectin. The review took readers back to the earliest discovery of the so-called third filament component of skeletal and cardiac muscle sarcomeres and ended in 1969. Recently, my colleague Shin’ichi Ishiwata gently reminded me of two papers published in 1990 and 1993 that were unwittingly omitted from the original historical perspective. In the first paper (J Cell Biol 110:53–62, 1990), Funatsu et al. examined the elastic filaments in skeletal muscle using a combination of light and electron microscopy, but they also measured resting as well as passive stiffness mechanical measurements to establish that connectin (titin) is responsible for both stiffness and fiber tension. In the second paper (J Cell Biol 120:711–724, 1993), Funatsu et al. used permeabilised cardiac muscle myocytes (from rabbit papillary muscles) and focussed on filament ultrastructure using either freeze-substitution or deep-etched replica methods to visualise connectin/titin filaments in fibers with and without actin and myosin filaments.     

Social evaluation of municipal solid waste management systems from a life cycle perspective: a systematic literature review

Purpose

The social aspects of municipal solid waste management (MSWM) systems are underpinning their sustainability and effectiveness. The assessment of these systems from a life cycle perspective is widespread throughout environmental life cycle assessment (LCA), but few studies have used social life cycle assessment (S-LCA). The present study is an innovative review with the objective to analyse and describe the current level of development of S-LCA applications in MSWM, and to identify the main methodological challenges and best practices, aiming at recommending approaches to harmonise future S-LCA applications in MSWM.

Materials and methods

A systematic review of the literature found 36 relevant scientific articles. These were submitted to bibliometric and content analysis, which includes an analysis of how methodological aspects of the four phases of S-LCA were applied in comparison with best practice and existing guidelines.

Results and discussion

There was a predominance of case studies in developing countries (59%) and evaluation of the stages of collection/transportation, pre-processing (sorting) and landfilling (55%). There were more studies focusing on stakeholders, “workers” and “local communities” and in the impact subcategories “employment”, “working hours”, “health and safety/working conditions”, “community involvement/participation” and “health and safety/living conditions of community”. There was great variability in the application of the method (47% of the studies included methodological developments). However, the 39% based on UNEP guidelines were closer to a methodological consensus.

Conclusion

In general, studies need more detail and clarity in describing the methodological decisions used. Improvements are needed for issues that limit the S-LCA method, including the difficulties of covering the entire life cycle, relating impacts to the functional unit, standardizing impact assessment methods, addressing allocation and data quality issues and interpretation of results and their limitations. Improvements can be achieved by using participatory methods in the selection of categories, subcategories and impact indicators, as well as by clarifying the definition of a product system and detailing “cut-off criteria” of processes/organizations and the impact of these decisions on results.

     

ROLE OF GROWTH SUBSTANCES IN THE FILAMENT GROWTH OF FUCHSIA HYBRIDA CV “BRILLIANT”

Filaments of Fuchsia hybrida cv “Brilliant” double in length within 24 hr after bud opening. Filament growth characterized by fresh wt increase and cell elongation was significantly inhibited in vitro by l-aminocyclopropane-l-carboxylic acid (ACC) but was not promoted by any growth regulator tested. Ions of Co²⁺ blocked the inhibitive effects of ACC in vitro suggesting that ethylene produced from ACC is the growth inhibiting substance. Ethylene levels surrounding the filaments within the closed bud decreased during development, and premature opening of the sepals which released the ethylene into the atmosphere resulted in rapid filament growth. The ACC levels were found to be much higher in the anthers than the filaments. This suggests that ethylene produced from floral organs other than filaments regulates filament elongation in Fuchsia. This is the first report of filament growth which cannot be promoted by application of growth regulators but which is inhibited by ethylene.     

Synthesis of “Reversed” and “Double Headed” Nucleosides

Abstract

The synthesis of several partially and fully deprotected “reversed” nucleosides are described starting from “reversed” 5-iodouracil-1-yl nucleoside 1. The preparation of a novel purine-purine and mixed purine-pyrimidine “double headed” nucleosides via “reversed” purine nucleoside 12 is also described.     

Quantification Methodology of “Health Human Resources” Related to “Health Technologies” Based on Indicators “RhSan”, “TechSan” and “RhTech”: Application to Senegal

ObjectivesAfter a century of spectacular advances, healthcare systems are facing unprecedented crisis, linked to shortage of health human resources and health technologies. In fact, availability of care depends on both technological and human resources of health. The objective of this study is to develop indicators that can measure qualitatively human resources and technologies of health in healthcare facilities, in order to assess availability of care in sub-Saharan African countries.Materials and MethodsRegarding “health technology” related to “medical devices”, an indicator called “TechSan” for “Technologies de Santé” was previously developed and published (Ndione FB et al. (2019) [6]). To address the deficiencies in usual indicators related to health human resources, a second indicator called “RhSan” for “Ressources humaines de santé” in French is proposed. This indicator assigns a weight to each health worker taking into account his specific “level of medical knowledge” and “experience”. In order to correlate “RhSan” with “TechSan”, a third indicator called “RhTech” is also developed to assess matches between “health technologies” and “health human resources” and establish realistic availability of care. These indicators have the advantage to be consolidated by specialty such as laboratory, imaging, surgery, and “mother and child care”.ResultsThe application of TechSan, RhSan and RhTech to data collected in Senegal in 2016, enabled to assess the distribution of “health technology” and “health human resources” in this country. They also permit the mapping of care availability per specialty in Senegal. The results show a strong oversupply of Dakar in terms of both human resources and technologies of health compared to other Senegalese regions. Oppositely, Sedhiou, Kaffrine, Matam and Kédougou are poorly endowed showing limits of the Senegalese health pyramid system.ConclusionTechSan, RhSan and RhTech can provide reliable decision-making tools in order to elaborate health policies in sub-Saharan African countries on more rigorous basis.     

An Inexpensive Microscope Lamp for Critical Illumination

A microscope lamp with light of adjustable intensity, which will afford critical illumination of a quality satisfactory for the most exacting cytological work, can be constructed for about $7.50. The essential parts needed are: auto headlight bulb, radio power transformer, radio “potentiometer”, and simple plano-convex lens. A ground glass is not used with 4 and 2 mm. objectives, a solid source of light being obtained by placing the bulb so that one filament coil is directly behind the other. This light source is brought to a focus by the condensing lens at a field diaphragm and this image is projected by the microscope condenser into the plane of focus of the microscope.     

Evidence of dramatic biodiversity loss in a wet biotope calls for urgent conservation strategies

Abstract

The small lake “Lago di Corree”, located in the middle Volturno plain (Campania Region, Italy), is a biotope belonging to the Roccamonfina–foce Garigliano Regional Park. It is a “habitat island” in a landscape matrix characterised by intensive agriculture. In the present investigation, plant biodiversity loss, assessed by means of historical and recent field floristic surveys, is related to the lake dynamics and landscape transformation inferred using remote sensing (photointerpretation). A dramatic reduction of plant diversity, and the regional-scale local extinction of several aquatic species are reported     

An electron microscopic study on the innervation of the gill filaments of a lamprey,Lampetra japonica

This paper reports observations on the innervation of gill filaments of the lamprey, Lampetra japonica. Nerve fibers run on each side of the afferent filament artery (AFA nerve) and in the connective tissue compartment along the efferent filament artery (EFA nerve). The AFA nerve supplies vasomotor fibers to the afferent filament artery and arteriovenous anastomoses and special visceral motor fibers to branchial muscle fibers (musculus compressor branchialis circularis). Nerve endings of the vasomotor fibers contain large, cored vesicles (60–180 nm in diameter) with a variable number of small, clear vesicles (30–70 μm in diameter), whereas those of the visceral motor fibers have many small, clear vesicles with few large, cored vesicles. The EFA nerve supplies vasomotor fibers to the efferent filament artery. Their endings, containing mixtures of predominantly large, cored vesicles and small, clear vesicles make close synaptic contacts with reticular cells. The latter in turn are connected with each other or with smooth muscle cells in the wall of the efferent filament artery by nexuses. No nerves are found in the axial plate between the afferent and efferent filament arteries nor in the secondary lamellae of individual gill filaments. No afferent nerve supply to the gill filament has been found.     

The Rise of Man's Best Friend: The Popularity of Dogs as Companion Animals in Late Eighteenth-Century London as Reflected by the Dog Tax of 1796

ABSTRACT

The history of the relationship between humans and their companion animals is long and more than a little complex. This is in large part due to the special status of these animals. Over the years these animals have evolved socially from that of an impersonal “object” to a “subject,” i.e. a sentient being with a recognized mental and emotional life. Histories of this change in relationship are rare. This is due mainly to a lack of source material; little is available and what there is is rarely reflective of a general population. Recently, records of a 1796 English dog tax have become available and they provide a fairly complete overview of the status of the dog as a companion animal in late eighteenth-century London.

The evidence indicates the dog was very popular as a companion animal in late eighteenth-century English urban society. While some of these creatures were former working-class canines others were what might be described as “professional companion animals” i.e. creatures who had no previous work history. The tax records further indicate that concern as to specific breed was still in the future. Dogs often received a generic title such as “yard dog” or “lapdog” or “housedog.” What is particularly interesting from these records is the number of mixed breed creatures—animals with the title of either “mongrel” or “curr.” (At least three Londoners kept foxes as pets.) There is also an almost total absence of kennels of hunting dogs in eighteenth-century London. Other historical records suggest this to be a recent phenomenon. Lastly, this outline appears to correlate strongly with the literary remarks, material accoutrements, and even religious practices of the late eighteenth-century urban dog population of England.     

Binding of Nucleic Acids to Intermediate Filaments of the Vimentin Type and Their Effects on Filament Formation and Stability

Abstract

Guanine-rich polynucleotides such as poly(dG), oligo(dG)_12–18 or poly(rG) were shown to exert a strong inhibitory effect on vimentin filament assembly and also to cause disintegration of preformed filaments in vitro. Gold-labeled oligo(dG)₂₅ was preferentially localized at the physical ends of the aggregation and disaggregation products and at sites along filaments with a basic periodicity of 22.7 nm. Similar effects were observed with heat-denatured eukaryotic nuclear DNA or total rRNA although these nucleic acids could affect filament formation and structure only at ionic strengths lower than physiological. However, whenever filaments were formed or stayed intact, they appeared associated with the nucleic acids. These electron microscopic observations were corroborated by sucrose gradient analysis of complexes obtained from preformed vimentin filaments and radioactively labeled heteroduplexes. Among the duplexes of the DNA type, particularly poly(dG)·poly(dC), and, of those of the RNA type, preferentially poly(rA)·poly(rU), were carried by the filaments with high efficiency into the pellet fraction. Single-stranded 18S and 28S rRNA interacted only weakly with vimentin filaments. Nevertheless, in a mechanically undisturbed environment, vimentin filaments could be densely decorated with intact 40S and 60S ribosomal subunits as revealed by electron microscopy. These results indicate that, in contrast to single-stranded nucleic acids with their compact random coil configuration, double-stranded nucleic acids with their elongated and flexible shape have the capability to stably interact with the helically arranged, surface-exposed amino-terminal polypeptide chains of vimentin filaments. Such interactions might be of physiological relevance in regard to the transport and positioning of nucleic acids and nucleoprotein particles in the various compartments of eukaryotic cells. Conversely, nucleic acids might be capable of affecting the cytoplasmic organization of vimentin filament networks through their filament-destabilizing potentials.