Resistance to macrolide, lincosamide, streptogramin, ketolide, and oxazolidinone antibiotics

Macrolides have enjoyed a resurgence as new derivatives and related compounds have come to market. These newer compounds have become important in the treatment of community-acquired pneumoniae and nontuberculosis-Mycobacterium diseases. In this review, the bacterial mechanisms of resistance to the macrolide, lincosamide, streptogramin, ketolide, and oxazolidinone antibiotics, the distribution of the various acquired genes that confer resistance, as well as mutations that have been identified in clinical and laboratory strains are examined.     

Conjugates of abscisic acid, brassinosteroids, ethylene, gibberellins, and jasmonates

Phytohormones, including auxins, abscisic acid, brassinosteroids, cytokinins, ethylene, gibberellins, and jasmonates, are involved in all aspects of plant growth, and developmental processes as well as environmental responses. However, our understanding of hormonal homeostasis is far from complete. Phytohormone conjugation is considered as a part of the mechanism to control cellular levels of these compounds. Active phytohormones are changed into multiple forms by acylation, esterification or glycosylation, for example. It seems that conjugated compounds could serve as pool of inactive phytohormones that can be converted to active forms by de-conjugation reactions. Some conjugates are thought to be temporary storage forms, from which free active hormones can be released after hydrolysis. It is also believed that conjugation serves functions, such as irreversible inactivation, transport, compartmentalization, and protection against degradation. The nature of abscisic acid, brassinosteroid, ethylene, gibberellin, and jasmonate conjugates is discussed.     

The Effect of Age and Gender on Al, B, Ba, Ca, Cu, Fe, K, Li, Mg, Mn, Na, P, S, Sr, V, and Zn Contents in Rib Bone of Healthy Humans

The effect of age and gender on major, minor, and trace element contents in the intact rib bone of 80 relatively healthy 15–55-year-old women and men was investigated. Contents or upper limit of contents of 16 chemical elements in the rib bone were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Mean values (M?±?SΕΜ) for the mass fraction of Ba, Ca, Cu, Fe, K, Li, Mg, Na, P, S, Sr, and Zn (milligram per kilogram of dry bone) were as follows: 2.54?±?0.16, 171,400?±?4,050, 1.35?±?0.22, 140?±?11, 1,874?±?71, 0.049?±?0.011, 2,139?±?38, 5,378?±?88, 75,140?±?1,660, 1,881?±?51, 291?±?20, and 92.8?±?1.5, respectively. The upper limits of contents of Al, B, Mn, and V were <7.20, <0.65, <0.36, and <0.03, respectively. Statistically significant tendency for the Ca, Mg, and P content to decrease with age was found in the human rib bone, regardless of gender. The mass fraction of Fe in the male rib bone increases with age. It was shown that higher Ca, Mg, Na, P, and Sr mass fractions as well as lower Fe content were typical of female ribs as compared to those in male ribs.     

Earth, sky, wind, and weather

This paper seeks to understand what it means to live 'in the open'. It begins with an account of experiments that test whether children have acquired a scientifically correct understanding of the shape of the earth, according to which people live all around on the outside of a solid sphere. This understanding cannot accommodate the phenomenon of the sky, in relation to which the earth can appear only as the ground of human habitation. James Gibson's ecological approach to perception offers a possible alternative, depicting earth and sky as complementary hemispheres. Yet for Gibson, this earth-sky can be inhabited only insofar as it is furnished with objects. To that extent, it ceases to be open. Drawing on elements of Merleau-Ponty's phenomenology, it is argued that in the open world persons and things relate not as closed forms but by virtue of their common immersion in the generative fluxes of the medium – in wind and weather. Fundamental to life is the process of respiration, by which organisms continually disrupt any boundary between earth and sky, binding substance and medium together in forging their own growth and movement. Thus to inhabit the open is not to be stranded on the outer surface of the earth but to be caught up in the transformations of the weather-world.     

Reference values for the concentrations of As,Cd, Co,Cr, Cu,Fe, I,Hg, Mn,Mo, Ni,Pb, Se,and Zn in selected human tissues and body fluids

This report attempts to formulate reference ranges of elemental concentrations for 15 trace elements in selected human tissues and body fluids. A set of samples consisting of whole blood, blood serum, urine, milk, liver, and hair were chosen and considered for 15 elements of biological significance: As, Cd, Co, Cr, Cu, F, Fe, I, Hg, Mn, Mo, Ni, Pb, Se, and Zn. The results represent wholly or partially data received from 40 countries of the global regions of Africa, Asia, Europe, North, South, and Central America, Australia, and New Zealand. This survey, even if qualitative, has been useful in demonstrating certain trends of trace-element scenarios around the world. It is of course recognized that both diet and environment exert a strong influence on the distribution pattern of several elements, such as As, Cd, Mn, Pb, Se, and Zn. A limited comparison of the available information on soil status of different countries reflected some interesting associations for elements, such as Mn and Zn. Importantly, this study revealed that only a few countries were in a position to identify a reasonable amount of data on samples requested for this project. Regretably, for a number of countries, any dependable data for even such essential elements as Cu, Fe, and Zn were not available. In view of the nutritional importance of many elements, the time is ripe for concerted efforts by intergovernmental agencies to initiate investigations or commission task forces/projects to generate reliable reference data for selected global regions, which sadly lack data of any kind at present.     

Pain, paradox, and value

The author argues that "as soon as one begins to study the understanding and management of pain in science, human medicine, and veterinary medicine, one begins to encounter a variety of apparent paradoxes." He contends that these paradoxes, ten of which he identifies and discusses in this essay, are based on flawed philosophical and valuational assumptions underlying science and medicine. Rollins concludes that, as social morality increasingly has an impact on science, a new ideology will evolve that is more receptive to the moral universe and more capable of a "coherent vision of pain, one which acknowledges that the medical notion of adequacy of anaesthesia is as much a moral as a scientific one."     

Ammonium Sulfate Fractionation of Sera: Mouse, Hamster, Guinea Pig, Monkey, Chimpanzee, Swine, Chicken, and Cattle

Optimal (NH(4))(2)SO(4) concentrations were sought for serum fractionation in order to obtain the gamma globulin as free as possible from other serum components while maintaining a reasonable recovery. Various ammonium sulfate concentrations were used to fractionate sera from mice, hamsters, guinea pigs, monkeys, chimpanzees, swine, chicken, and cattle. All precipitates and supernatants were analyzed by electrophoresis to study the effects of various treatments on the composition of these materials. Approximately 75% of all the gamma globulins were recovered when each serum was fractionated with its optimal sulfate concentration. These optimals were determined to be as follows: three precipitations in 35% saturated ammonium sulfate (SAS) for hamster, chimpanzee, swine, and chicken serum; one precipitation in 35% SAS followed by two in 40% SAS for mouse and guinea pig serum; one precipitation in 30% SAS and then two in 40% SAS for monkey serum; and one precipitation in 30% SAS followed by two in 35% SAS for cattle serum.     

Membranes,viruses, detergents,and endosomes

The fluid mosaic model for biological membranes was formulated 40 years ago. Ten years later endosomes were discovered as important prelysosomal organelles. At the outset of my research career, I was fortunate to witness both these turning points in biochemistry and cell biology from close up, and to participate in some of the studies. In this short essay, I will describe how this came about, and also try to provide some background as to the general starting situation in those not so distant pioneering years of membrane biology.     

Uniqueness, advantages, challenges, solutions, and perspectives in therapeutics applying RNA nanotechnology

The field of RNA nanotechnology is rapidly emerging. RNA can be manipulated with the simplicity characteristic of DNA to produce nanoparticles with a diversity of quaternary structures by self-assembly. Additionally RNA is tremendously versatile in its function and some RNA molecules display catalytic activities much like proteins. Thus, RNA has the advantage of both worlds. However, the instability of RNA has made many scientists flinch away from RNA nanotechnology. Other concerns that have deterred the progress of RNA therapeutics include the induction of interferons, stimulation of cytokines, and activation of other immune systems, as well as short pharmacokinetic profiles in vivo. This review will provide some solutions and perspectives on the chemical and thermodynamic stability, in vivo half-life and biodistribution, yield and production cost, in vivo toxicity and side effect, specific delivery and targeting, as well as endosomal trapping and escape.     

Electromagnetic fields: mechanism,cell signaling,other bioprocesses,toxicity, radicals,antioxidants and beneficial effects

Electromagnetic fields (EMFs) played a role in the initiation of living systems, as well as subsequent evolution. The more recent literature on electrochemistry is documented, as well as magnetism. The large numbers of reports on interaction with living systems and the consequences are presented. An important aspect is involvement with cell signaling and resultant effects in which numerous signaling pathways participate. Much research has been devoted to the influence of man-made EMFs, e.g., from cell phones and electrical lines, on human health. The degree of seriousness is unresolved at present. The relationship of EMFs to reactive oxygen species (ROS) and oxidative stress (OS) is discussed. There is evidence that indicates a relationship involving EMFs, ROS, and OS with toxic effects. Various articles deal with the beneficial aspects of antioxidants (AOs) in countering the harmful influence from ROS-OS associated with EMFs. EMFs are useful in medicine, as indicated by healing bone fractures. Beneficial effects are recorded from electrical treatment of patients with Parkinson’s disease, depression, and cancer.     

(M,R)-systems, (P,M,C)-nets, hierarchical decay, and biological aging: reminiscences of Robert Rosen

I have the pleasure to present a number of personal experiences that I had with Robert Rosen, both as his student and as a research colleague, and I will describe how this affected my academic career over the past decades. As a matter of fact, Rosen's work with (M,R)-systems as well as his continuing mentorship guided me into my own research in gerontology and geriatrics. Amazingly, this still continues to affect my work in complexity theory after 30 years.     

Principles of nuclear medicine imaging: planar, SPECT, PET, multi-modality, and autoradiography systems

The underlying principles of nuclear medicine imaging involve the use of unsealed sources of radioactivity in the form of radiopharmaceuticals. The ionizing radiations that accompany the decay of the administered radioactivity can be quantitatively detected, measured, and imaged in vivo with instruments such as gamma cameras. This paper reviews the design and operating principles, as well as the capabilities and limitations, of instruments used clinically and preclinically for in vivo radionuclide imaging. These include gamma cameras, single-photon emission computed tomography (SPECT) scanners, and positron emission tomography (PET) scanners. The technical basis of autoradiography is reviewed as well.     

Treatment-resistant depression: definition,prevalence, detection,management, and investigational interventions

Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population.     

Photons, clocks, and consciousness

Light profoundly impacts human consciousness through the stimulation of the visual system and powerfully regulates the human circadian system, which, in turn, has a broad regulatory impact on virtually all tissues in the body. For more than 25 years, the techniques of action spectroscopy have yielded insights into the wavelength sensitivity of circadian input in humans and other mammalian species. The seminal discovery of melanopsin, the photopigment in intrinsically photosensitive retinal ganglion cells, has provided a significant turning point for understanding human circadian phototransduction. Action spectra in humans show that the peak wavelength sensitivity for this newly discovered sensory system is within the blue portion of the spectrum. This is fundamentally different from the three-cone photopic visual system, as well as the individual rod and cone photoreceptor peaks. Studies on rodents, nonhuman primates, and humans indicate that despite having a different wavelength fingerprint, these classic visual photoreceptors still provide an element of input to the circadian system. These findings open the door to innovations in light therapy for circadian and affective disorders, as well as possible architectural light applications.     

Ethnobotany of Ghalegay, District Swat, Pakistan

Ethnobotanical study of plants revealed that the local community of Ghalegy, District Swat, invariably uses 126 species of 59 families for various purposes. Based on their traditional local uses, fifty-seven species （45.2%） were classifted as medicinal, forty-seven as fire wood （37.3 % ）, forty-five as forage （35.7 % ）, twenty-eight as honey bee species （22.2%）, twenty-seven as vegetable species （21.4%）, 25 as edible fruits （14 wild and llcultivated）, thirteen as timberwood （10.3%）, twelve as ornamental （9.5%）, eleven as furniture wood, ten as shelter and thatch makers （7.9%）, ten as fencing （7.9%）, five as poisonous （4%）, four as religious/superstitious species, three species used in making hand sticks and wooden tools （2.4%）, three as utensil cleaner species （2.4%）, three as evil repellent and one as fish poisoning species. The area is in plant resources and traditional knowledge but it needs ecological management for its sustainability.     

Calmodulin, activated cyclic nucleotide phosphodiesterase, microtubules, and vinca alkaloids

Calmodulin 1.8 and 10.6 microM, inhibited the polymerization of bovine brain microtubules by 30 and 50%, respectively. Two 55,000- to 68,000-dalton calmodulin-binding protein as well as calmodulin-dependent and -independent phosphodiesterases (PDE) were found associated with microtubule proteins. Among the antimicrotubule drugs, such as colchicine, podophyllotoxin, griseofulvin, and vinca alkaloids (vinblastine, desacetylvinblastine amide, and vincristine), the vinca alkaloids were selective inhibitors of calmodulin-activated PDE activity. This action of vinca alkaloids resides in the catharanthine moiety of vinblastine molecule. An alpha 2 inhibitor, yohimbine, affects the microtubules, and a series of alpha-adrenoceptor blocking agents were examined for their effects on calmodulin-dependent PDE. The relative order of the potency is phenoxybenzamine = dibenamine greater than phentolamine greater than yohimbine greater than prazosin greater than tolazoline, and the first four drugs in this series were selective inhibitors of calmodulin action. Inasmuch as phenoxybenzamine and dibenamine are alkylating agents, the effects of antineoplastic alkylating agents on the calmodulin action were also examined. Busulphan, melphalan, 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea, and streptozotocin (up to 4 mM) were not selective inhibitors of calmodulin action. Maytansine, a vinca alkaloid-type antimicrotubule agents as well as an alkylating agent, selectively inhibited the calmodulin with a potency similar to vincristine. In addition, phenoxybenzamine affected Ca2+-dependent fluorescence induced by the interaction between calmodulin and hydrophobic fluorescent probes, whereas vinblastine was ineffective. However, the binding of vinblastine to calmodulin is calcium dependent. Studies such as these suggest the importance of physical and structural considerations in drugs binding to calmodulin as well as at least two different binding sites for drugs on calmodulin.     

Microalgae as source of biofuel,food, fodder,and medicines

Current status and future prospects of such problem as the production of microalgae and their application for biofuel generation (biodiesel, biohydrogen, bioethanol), as well as other products, is discussed in the review. The use of microalgae in human food, fodder, cosmetics, dyes, polysaccharides, antioxidants, medicines, and other products is quite promising. Presently, microalgae are noncompetitive with plant materials, due to economic reasons, in serving as a source of biofuel. Thereby, it is urgently necessary in modern biotechnology to improve the methods for the production of microalgae and search for new ways of their processing.     

Loosdrecht Lakes,origin, eutrophication,restoration and research programme

The Loosdrecht Lakes area is briefly described, light has been shed on its morphology, history, the process of eutrophication with its concomitant phenomena, as well as the planned restoration and research programme.     

Silverleaf nightshade,Solarium elaeagnifolium,origin, distribution,and relation to man

Silverleaf nightshade (Solanum elaeagnifolium) is a perennial weed that has become increasingly troublesome over the past several decades. Extensive use of soil-applied herbicides, accompanied by a reduction in annual weed competition and reduced tillage, have contributed to its spread and establishment as a serious pest. Crop plants are affected directly via competition and allelopathy or indirectly as the nightshade plants serve as hosts for destructive phytophagous insects or fungal pathogens. Probably native to the southwestern United States and northern Mexico,S. elaeagnifolium is now found in many semiarid regions of the world. Plants were used by the Pima, Kiowa and Navajo Indians in the preparation of food and in the tanning of leather. Containing the toxic glycoalkaloids solanine and solasonine, plants can cause livestock poisonings. The fruits, however, are a source of solasodine, which is used in the commercial manufacture of steroidal hormones.     

Cadmium transport, resistance, and toxicity in bacteria, algae, and fungi

Cadmium is an important environmental pollutant and a potent toxicant to bacteria, algae, and fungi. Mechanisms of Cd toxicity and resistance are variable, depending on the organism. It is very clear that the form of the metal and the environment it is studied in, play an important role in how Cd exerts its effect and how the organism(s) responds. A wide range of Cd concentrations have been used to designate resistance in organisms. To date, no concentration has been specified that is applicable to all species studied under standardized conditions. Cadmium exerts its toxic effect(s) over a wide range of concentrations. In most cases, algae and cyanobacteria are the most sensitive organisms, whereas bacteria and fungi appear to be more resistant. In some bacteria, plasmid-encoded resistance can lead to reduced Cd2+ uptake. However, some Gram-negative bacteria without plasmids are just as resistant to Cd as are bacteria containing plasmids encoding for Cd resistance. According to Silver and Misra (1984), there is no evidence for enzymatic or chemical transformations associated with Cd resistance. Insufficient information is available on the genetics of Cd uptake and resistance in cyanobacteria and algae. Mechanisms remain largely unknown at this point in time. Cadmium is toxic to these organisms, causing severe inhibition of such physiological processes as growth, photosynthesis, and nitrogen fixation at concentrations less than 2 ppm, and often in the ppb range (Tables 2 and 3). Cadmium also causes pronounced morphological aberrations in these organisms, which are probably related to deleterious effects on cell division. This may be direct or indirect, as a result of Cd effects on protein synthesis and cellular organelles such as mitochondria and chloroplasts. Cadmium is accumulated internally in algae (Table 4) as a result of a two-phase uptake process. The first phase involves a rapid physicochemical adsorption of Cd onto cell wall binding sites, which are probably proteins and (or) polysaccharides. This is followed by a lag period and then a slow, steady intracellular uptake. This latter phase is energy dependent and may involve transport systems used to accumulate other divalent cations, such as Mn2+ and Ca2+. Some data indicate that Cd resistance, and possibly uptake, in algae and cyanobacteria is controlled by a plasmid-encoded gene(s). Although considerable information is available on Cd toxicity to, and uptake in fungi, further work is clearly needed in several areas. There is little information about Cd uptake by filamentous fungi, and even in yeasts, information on the specificity, kinetics, and mechanisms of Cd uptake is limited.(ABSTRACT TRUNCATED AT 400 WORDS)