The cost of being “real”: black authenticity,colourism, and Billboard Rap Chart rankings

Research on black authenticity identifies “oppressive othering” and “white standards of beauty”, particularly lighter skin tone, as key components. Few studies disentangle which of these two theoretical components matter the most for a particular outcome. Rap music, whose lyrics are often categorized as authentic expressions of blackness, offers an intriguing case to compare the effects of “oppressive othering” (as alcohol and drug lyrics) and “white standards of beauty” (as the rap artist’s skin tone) on national music charts. Analysing artists’ skin tone and lyrical content of songs ranked on Billboard Rap Year-End Charts from 2007 to 2011, results show that lighter skin tone is significantly and positively related to higher chart rankings. Alcohol and drug lyrics, however, had a non-significant effect. Implications are discussed in relation to the effects of the commodified imagery of “authentic” blackness in the new digital era of music.     

Pumpless,unidirectional microphysiological system for testing metabolism-dependent chemotherapeutic toxicity

Drug development is often hindered by the failure of preclinical models to accurately assess and predict the efficacy and safety of drug candidates. Body-on-a-chip (BOC) microfluidic devices, a subset of microphysiological systems (MPS), are being created to better predict human responses to drugs. Each BOC is designed with separate organ chambers interconnected with microfluidic channels mimicking blood recirculation. Here, we describe the design of the first pumpless, unidirectional, multiorgan system and apply this design concept for testing anticancer drug treatments. HCT-116 colon cancer spheroids, HepG2/C3A hepatocytes, and HL-60 promyeloblasts were embedded in collagen hydrogels and cultured within compartments representing “colon tumor”, “liver,” and “bone marrow” tissue, respectively. Operating on a pumpless platform, the microfluidic channel design provides unidirectional perfusion at physiologically realistic ratios to multiple channels simultaneously. The metabolism-dependent toxic effect of Tegafur, an oral prodrug of 5-fluorouracil, combined with uracil was examined in each cell type. Tegafur-uracil treatment induced substantial cell death in HCT-116 cells and this cytotoxic response was reduced for multicellular spheroids compared to single cells, likely due to diffusion-limited drug penetration. Additionally, off-target toxicity was detected by HL-60 cells, which demonstrate that such systems can provide useful information on dose-limiting side effects. Collectively, this microscale cell culture analog is a valuable physiologically-based pharmacokinetic drug screening platform that may be used to support cancer drug development.     

Comparisons of mescal bean alkaloids with mescaline, delta 9-THC and other psychotogens

Prior to the discovery of peyote, many American Indian tribes of the Southwest apparently used seeds of the Texas Mountain Laurel. The seeds are commonly referred to as “mescal beans,” “red beans,” and “dry whiskey,” and were utilized by the Indians to induce visions and serve as a divinatory medium for various ceremonial purposes. Indications that this material is a part of the modern drug scene prompted studies in which the three major alkaloids from this plant (cytisine, sparteine, and methylcytisine) were compared with a variety of known psychoactive compounds [N, N-dimethyltryptamine (DMT), mescaline, psilocybin, amphetamine, Δ⁹ - tetrahydrocannabinol (THC), and pentobarbital] to determine whether similarities in behavioral effects exist. Rats were tested for gross locomotor activity, locomotor activity pattersn (“pauses” and “bursts”), locomotor skill (rotorod testing), and conditioned avoidance response. A Duncan's Multiple Range Comparison of all of the drugs at several dose levels of each revealed that the alkaloids produced responses similar to the responses produced by the known hallucinogenic drugs (mescaline, DMT, psilocybin) and clearly dissimilar to normal saline, amphetamine, pentobarbital, and THC.     

Logical-Semantic Analysis and the Development of L.S. Vygotsky's Ideas About “Units” and “Elements” of Psychological Systems

Based on an analysis of L.S. Vygotsky's concepts of “units” and “elements” of psychological systems, this article highlights five of their attributes. It shows that these attributes are logically symmetrical, since in their wording they can be converted into one another by negation or by replacing some words with their opposites. This suggests that the concepts of the “unit” and “element” of a system are different poles of one theoretical construct of the activity of human psychology. Thus methods for the study of psychological systems by breaking them down into elements or by separating them into units can be seen as complementary. The article describes differences among the concepts of “unit,” “minimal unit,” and “cell” of a psychological system. It reviews several problems that are solvable using the “method of units,” as well as some concepts of the theory of psychological systems that are understood as holistic, conceptual, and active processes and/or results of human interaction with the world. Among the examples of such systems are “systems of psychological functions” (according to Vygotsky), as well as separate activities (according to A.N. Leontiev), human actions and operations (interactions with the world on the level of objects and mental or physical means). The “component” of a psychological system is defined as any “something” that in some sense belongs to or is included in human interaction with the world. A component that belongs to the system is called an “element” of it, but a component that is included in the functioning and development of the system is called a “part” of it. The article presents the mathematical and psychological foundation of these definitions. It identifies and discusses the substantial (independently existing) components of psychological systems and their attributes (properties and conditions). It describes the relationships between them using the bipolar theoretical constructs “part-element” and “substantial-attributive” component of a system.     

Scientific motherhood,responsibility, and hope: umbilical cord blood banking in South Korea

This paper explores how concepts of hope, motherhood, responsibility, and science are mobilized and transformed in the marketing strategies of private cord blood banks in South Korea. Cord blood banking provides a useful case study of the “political economy of hope,” which emphasizes future expectations over current utility. In particular, appeals to hope are rendered natural as being applied in relation to various concepts of motherhood (e.g. “scientific motherhood” and “consumer motherhood”), thereby refiguring ideas of a mother's responsibility to her child. In South Korea, cord blood banks rely heavily on the discourse of “scientific motherhood,” which is based on certain gender norms and ideas about science, modernity, and “advanced society.” By exploring the discourse of scientific motherhood, this study reexamines the “political economy of hope” through the lenses of gender and transnationalism.     

Exploration of the conformational landscape in pregnane X receptor reveals a new binding pocket

Ligand‐regulated pregnane X receptor (PXR), a member of the nuclear receptor superfamily, plays a central role in xenobiotic metabolism. Despite its critical role in drug metabolism, PXR activation can lead to adverse drug‐drug interactions and early stage metabolism of drugs. Activated PXR can induce cancer drug resistance and enhance the onset of malignancy. Since promiscuity in ligand binding makes it difficult to develop competitive inhibitors targeting PXR ligand binding pocket (LBP), it is essential to identify allosteric sites for effective PXR antagonism. Here, molecular dynamics (MD) simulation studies unravelled the existence of two different conformational states, namely “expanded” and “contracted”, in apo PXR ligand binding domain (LBD). Ligand binding events shifted this conformational equilibrium and locked the LBD in a single “ligand‐adaptable” conformational state. Ensemble‐based computational solvent mapping identified a transiently open potential small molecule binding pocket between α5 and α8 helices, named “α8 pocket”, whose opening‐closing mechanism directly correlated with the conformational shift in LBD. A virtual hit identified through structure‐based virtual screening against α8 pocket locks the pocket in its open conformation. MD simulations further revealed that the presence of small molecule at allosteric site disrupts the LBD dynamics and locks the LBD in a “tightly‐contracted” conformation. The molecular details provided here could guide new structural studies to understand PXR activation and antagonism.     

The terminology and classification of steles: Historical perspective and the outlines of a system

Discussion focuses on the history of classification of the steles of vascular plants, from Jeffrey (1898) to the present. Recent stelar classifications are largely based (1) on Jeffrey’s system (protostele vs. siphonostele, the latter with ectophloic vs. amphiphloic types), (2) on the system developed by the early British morphologists, notably Brebner (1902), Gwynne-Vaughan (1901), Tansley (1907-08), and Tansley and Lulham (1902) (protostele vs. medullated protostele vs. solenostele vs. dictyostele vs. eustele, with various subtypes), or (3) on a combination of the preceding two systems, the British usually superimposed upon the Jeffreyian, although generally erratically so. An extended classification of three main stelar types and 25 stelar subtypes derived from Brebner (1902), Gwynne-Vaughan (1901), Jeffrey (1898), Tansley (1907-08), and others is presented in outline form with accompanying etymology, synonymy, examples, and with detailed notes on controversial taxa, classificatory rationale, and historical aspects. Recognized are (1) “protostele” (divided into “ectophloic,” “endophloic,” and “amphiphloic,” with 7, 1, and 1 subtypes respectively), (2) “siphonostele” (divided into “ectophloic” with 2 subtypes and “amphiphloic,” the latter divided into “solenostele” and “dictyostele” with 3 subtypes each, plus “siphonostele incertae sedis”), and (3) “eustele” (divided into “eustele sensu stricto” with 4 subtypes, “pseudosiphonostele,” “reduced eustele,” and “polycyclic eustele”).     

Plant reproductive phenology over four years including an episode of general flowering in a lowland dipterocarp forest,Sarawak, Malaysia

The first systematic observation of a general flowering, a phenomenon unique to lowland mixed-dipterocarp forests in Southeast Asia, is presented. During general flowering, which occurs at irregular intervals of 3–10 yr, nearly all dipterocarp species together with species of other families come heavily into flower. We monitored reproductive phenology of 576 individual plants representing 305 species in 56 families in Sarawak, Malaysia. Observations continued for 53 mo from August 1992 and covered one episode of a general flowering cycle. Among 527 effective reproductive events during 43 mo, 57% were concentrated in the general flowering period (GFP) of 10 mo in 1996. We classified 257 species into flowering types based on timing and frequency of flowering. The most abundant type was “general flowering” (35%), which flowered only during GFP. The others were “supra-annual” (19%), “annual” (13%), and “sub-annual” (5%) types. General flowering type and temporal aggregation in reproductive events were commonly found among species in various categories of taxonomic groups, life forms, pollination systems, and fruit types. Possible causes for general flowering, such as promotion of pollination brought about by interspecific synchronization and paucity of climatic cues suitable for flowering trigger, are proposed, in addition to the predator satiation hypothesis of Janzen (1974) .     

Schistosoma mansoni: development of the vitelline cell, its role in drug sequestration, and changes induced by Astiban.

The ultrastructure of four stages in the development of the vitelline cell of Schistosoma mansoni has been described, and the effect of different regimes of Astiban on the morphology of these cells was investigated. The drug had a highly selective action, rapidly destroying those cells at a stage of granular endoplasmic reticulum development, had a less immediate effect on the “mature” cells, and had no apparent effect on the first stages in development. These cells persisted and were able to continue development when the drug was withdrawn. Acid phosphatase tests at an ultrastructural level showed a considerable increase in activity in the cytosegresomes of affected “mature” cells. The ribosomal complexes present in the “mature” cells represent the early stages of cytosegresome formation, and these cytosegresomes increased in number in affected “mature” cells. X-ray analysis of both araldite and cryosections in the transmission electron microscope revealed a concentration of the element antimony in the cytosegresomes and vitelline droplets. On this basis, it is suggested that cytosegresomes play a role in drug sequestration by the vitelline cells.     

Myths of meritocracy: caste,karma and the new racism,a comparative study

The discourse of karma (behaviour), confounded with inherent psychic and material substance of the person/group (guna), was at the heart of India’s caste ideology. This systematic and intuitive, albeit convoluted and phantasmic doctrine was critical to bridge the discrepancy between a pantheistic religious imaginary and the reality of exclusion and abjection. Although “karma” evokes an exotic orient, this ideology is near identical with the ideas of “idleness” and “instant gratification” used to make sense of racial inequities in the contemporary United States. In both cases, the idea of behavioural and moral deficiency is used to justify evident abjection and discrimination, within the frame of an encompassing ideology of social equality. Thus, this use of the notions of “work” and “discipline”, extrapolated to the moral quality of the group or individual, is no passing argument of the “new racism”. It is a proven ploy of assigning blame on the victim.     

Effect of chronic fluoxetine treatment on audiogenic epilepsy,symptoms of anxiety and depression in rats of four lines

Anxiety (Anx) and depression (Dp) levels were evaluated in rats of 4 lines: 2 of them (KM and “4”) exhibited audiogenic seizures (AS), and 2 (Wistar and “0”) had no AS. In KM rats (with AS), Anx and Dp levels were higher than in Wistars (without AS), while in “4” and “0” rats with the related genetic background but contrasting in AS severity, Anx and Dp indices were not different. Fluoxetine treatment exerted antidepressant effect in all rat lines irrespective of its effect on AS. Thus, phenotypic expression of AS is not directly associated with the mechanisms of Anx and Dp development.     

Chronotype,gender and general health

Background: Light–dark alternation has always been the strongest external circadian “zeitgeber” for humans. Due to its growing technological preference, our society is quickly transforming toward a progressive “eveningness” (E), with consequences on personal circadian preference (chronotype), depending on gender as well. The aim of this study was to review the available evidence of possible relationships between chronotype and gender, with relevance on disturbances that could negatively impact general health, including daily life aspects. Methods: Electronic searches of the published literature were performed in the databases MEDLINE and Web of Science, by using the Medical Subject Heading (MeSH), when available, or other specific keywords. Results: Results were grouped into four general areas, i.e. (a) “General and Cardiovascular Issues”, (b) “Psychological and Psychopathological Issues”, (c) “Sleep and Sleep-Related Issues” and (d) “School and School-Related Issues”. (a) E is associated with unhealthy and dietary habits, smoking and alcohol drinking (in younger subjects) and, in adults, with diabetes and metabolic syndrome; (b) E is associated with impulsivity and anger, depression, anxiety disorders and nightmares (especially in women), risk taking behavior, use of alcohol, coffee and stimulants, psychopathology and personality traits; (c) E has been associated, especially in young subjects, with later bedtime and wake-up time, irregular sleep–wake schedule, subjective poor sleep, school performance and motivation, health-related quality of life; (d) E was associated with lowest mood and lower overall grade point average (especially for women). Conclusions: Eveningness may impact general health, either physical or mental, sleep, school results and achievements, especially in younger age and in women. The role of family support is crucial, and parents should be deeply informed that abuse of technological devices during night hours may lead to the immature adjustment function of children’s endogenous circadian pacemakers.     

Embryonic development of Eucorydia yasumatsui Asahina,with special reference to external morphology (Insecta: Blattodea,Corydiidae)

As the first step in the comparative embryological study of Blattodea, with the aim of reconstructing the groundplan and phylogeny of Dictyoptera and Polyneoptera, the embryonic development of a corydiid was examined and described in detail using Eucorydia yasumatsui . Ten to fifteen micropyles are localized on the ventral side of the egg, and aggregated symbiont bacterial “mycetomes” are found in the egg. The embryo is formed by the fusion of paired blastodermal regions, with higher cellular density on the ventral side of the egg. This type of embryo formation, regarded as one of the embryological autapomorphies of Polyneoptera, was first demonstrated for “Blattaria” in the present study. The embryo undergoes embryogenesis of the short germ band type, and elongates to its full length on the ventral side of the egg. The embryo undergoes katatrepsis and dorsal closure, and then finally, it acquires its definitive form, keeping its original position on the ventral side of the egg, with its anteroposterior axis never reversed throughout development. The information obtained was compared with that of previous studies on other insects. “Micropyles grouped on the ventral side of the egg” is thought to be a part of the groundplan of Dictyoptera, and “possession of bacteria in the form of mycetomes” to be an apomorphic groundplan of Blattodea. Corydiid embryos were revealed to perform blastokinesis of the “non‐reversion type (N)”, as reported in blaberoid cockroaches other than Corydiidae (“Ectobiidae,” Blaberidae, etc.) and in Mantodea; the embryos of blattoid cockroaches (Blattidae and Cryptocercidae) and Isoptera undergo blastokinesis of the “reversion type (R),” in which the anteroposterior axis of the embryo is reversed during blastokinesis. Dictyopteran blastokinesis types can be summarized as “Mantodea (N) + Blattodea [= Blaberoidea (N) + Blattoidea (R) + Isoptera (R)]”.     

Antennae-whipping behavior in the American lobster, Homarus Americanus (Milne-Edwards)

Electrophysiological techniques were employed to demonstrate that an acrylic coating blocks the mechanosensory activity of the cuticular hair organs on the chelipeds of Homarus americanus (Milne-Edwards) without eliciting spurious activity in their innervation.Agonistic encounters between animals with acrylic on the dorsal surface of the claws (experimental), on the ventral surface of the claws (“plastic” control), and absent (“bare” control) were observed. Experimental animals responded to <3% of all antennae-whips, while “plastic” control animals responded to 73%, and “bare” control animals to 64%, of all antennae-whips. We conclude that antennae-whipping is a form of tactile communication, in which information probably is received through mechanosensory activity in the cuticular hair organs on the dorsal surface of the chelipeds.     

The taxonomy,chronostratigraphy and paleobiogeography of glyptosaurine lizards (Glyptosaurinae,Anguidae)

Glyptosaurine lizards (Glyptosaurinae, Anguidae) are an extinct group of heavily armored lizards known from North America, Europe and Asia. Glyptosaurine lizards, taxa that possess fully developed tuberculated dermal armor, appear to have been established in North America by late early Puercan time (To3). “Proxestops,” a taxon distinguished by a combination of vermiculate and tuberculated osteoderm sculpturing, is considered to be a non-glyptosaurine, a sister taxon of the Glyptosaurinae. Known from only fragmentary remains, its wide chronostratigraphic distribution suggests that “Proxestops” is a form genus that, in all probability, represents more than one taxon, that ranges from the middle Paleocene to the early Eocene of North America. Moreover, the taxa Odaxosaurus piger, Parodaxosaurus sanjuanensis and “Proxestops” are best considered “proto-glyptosaurines”. “Melanosaurins” and glyptosaurins were well-established by the early Eocene, especially in North America, and are here documented by their type species and chronostratigraphic levels. Both tribes are present in Europe (MP7), too, but the record is not as estensive as that of North America. The North American taxon Gaultia silvaticus (Wa0) is transitional between a “melanosaurin” and glyptosaurin. Because it lacks the well-defined hexagonal osteoderms that characterize the Glyptosaurini, it is removed from that group and considered to be a “melanosaurin”. The “melanosaurin” taxon “Xestops” savagei (Wa4–Wa6) cannot be referred to Xestops (Br2) based on non-corresponding elements and because superficial similarity does not justify assignment to this taxon. Arpadosaurus sepulchralis (Wa6?), whose holotype is a fragmentary right frontal, is considered a subjective junior synonym of A. gazinorum, based on minor differences in the epidermal scale pattern that probably represent individual variation. “Glyptosaurus” agmodon (Wa6?), based on a partial right maxilla, cannot be referred to Glyptosaurus (sensu stricto), and the material upon which this taxon is based bears strong resemblance to material identified as cf. “?Paraglyptosaurus” yatkolai (Wa5–Wa6). “Glyptosaurus” rhodinos (Wa5) is based on an incomplete parietal, and its reference to Glyptosaurus is considered problematic. Eoglyptosaurus donohoei (Wa7) is probably valid and is re-established here. Glyptosaurus (sensu stricto) is known solely from the middle Eocene (Br2) by G. sylvestris. Dimetoposaurus wyomingensis (Br3) is removed from Xestops vagans because its synonymy was based on superficial similarities. Helodermoides tuberculatus, the largest and last glyptosaurin (Ch3), is restricted to the Chadronian of North America. Only the “melanosaurin” Peltosaurus granulosus (Or2–Or3), which includes the species P. abbotti, seems to have crossed the Eocene-Oligocene boundary, and appears to be largely restricted to the Orellan, but extended into the Arikareean. European glyptosaurines are also represented by both glyptosaurins and “melanosaurins” early in the Eocene (MP7). Placosauriops-like “melanosaurins” are known from Dormaal (MP7), and the glyptosaurin taxon?Placosaurus ragei occurs at the same level. “Placosauriops abderhaldeni” has been identified from the Grube Messel (MP11), but this assignment remains dubious because the species has not been adequately diagnosed, and the holotype species is from the Geiseltal (MP13), which is some 4.5 million years younger. Placosauriops weigelti (MP13) is the only valid species of this genus. Paraxestops stehlini (MP14) is not referable to the North American taxon Xestops, and its relationship to Placosauriops has not been studied. The late Eocene glyptosaurins Placosaurus estesi (MP17) and P. rugosus (MP18) are the last glyptosaurines known from Europe and appear to have gone extinct at the Eocene-Oligocene boundary, casulties perhaps of the “Grande Coupure”. Asian glyptosaurines are known solely from one species, Stenoplacosaurus mongoliensis, from the middle Eocene (Sharamurunian) of China. Glyptosaurines most likely originated in North America, diversified by late Paleocene time, and rapidly spread across the North Atlantic into Europe by the early Eocene. Both “melanosaurins” and glyptosaurins took a foothold in Europe by the early Neustrian, but the glyptosaurins, aside from one occurrence (Dormaal, MP7), were conspicuously absent for most of Neustrian through early Robiacian time. In North America, glyptosaurins diversified during the early and middle Eocene, while in Europe small “melanosaurins” were a prominent part of the paleoherpetofauna, and glyptosaurins are unknown for most of the Neustrian through the Geiseltalian, in both the fossilferous Lagerstätten of Messel and Geiseltal. Stenoplacosaurus is the only known glyptosaurin glyptosaurine from Asia, and its abrupt appearance during the late Eocene suggests the possiblity of a Beringian dispersal from North America into Asia.     

Chemical,biochemical, preclinical and clinical studies of Ganoderma lucidum polysaccharide as an approved drug for treating myopathy and other diseases in China

Ganoderma lucidum is an edible medicinal mushroom known as “Lingzhi” in China and “Reishi or Manetake” in Japan. It is a highly prized vitality‐enhancing herb for more than 2000 years. G. lucidum polysaccharide (GLPS) has been identified as one of the major bioactive components and developed into a drug named “Ji 731 Injection” in China since 1973. The large‐scale production of the drug began in 1985 and approved by the Chinese FDA as “Polysaccharidum of G. lucidum Karst Injection” (Ling Bao Duo Tang Zhu She Ye) in 2000, which is applied intramuscularly. After more than forty years of clinical use, its efficacy, safety and long‐term tolerability have been recognized by neurologists. It is one of a few non‐hormonal drugs used for treating refractory myopathy. It is also used for combination therapy, which reduces the amount of glucocorticoid required for myopathy patient who is in remission. In addition, it reduces adverse reactions and improves the quality of life for cancer patients during chemotherapy. We found 81 qualified chemical, biochemical, preclinical and clinical studies of GLPS both in English and in Chinese spanning from 1973 to 2017 by searching CNKI (China National Knowledge Infrastructure), Wanfang database and PubMed. The molecular mechanisms underlying GLPS's antioxidant, anti‐tumour, immune‐modulatory, hypoglycaemic, hypolipidaemic and other activities are discussed. Both preclinical and clinical studies are either deliberated or indexed in the current article. We aimed at providing a molecular picture as well as a clinical basis to comprehend GLPS as one of few polysaccharide‐based modern medicines with complicated chemical and pharmacological properties that prevent it from entering the world's market.     

Study on morphology,pathogenicity and genetic diversity of Wilsonomyces carpophilus isolates,the causal agent of shot hole of stone fruit trees based on RAPD-PCR in Iran

Shot hole disease is one of the most important diseases of stone fruit trees in Iran. The disease is wide spread among orchards of Prunus spp. During spring and summer of 2007, 80 monoconidial isolates of the pathogen were recovered from infected leaves, fruits and twigs of different Prunus spp. in West Azerbaijan, Tehran, Ghazvin and Razavi Khorasan provinces of Iran and were studied taxonomically. Based on morphological and physiological characteristics and growth optimal temperature, all isolates were identified as Wilsonomyces carpophilus. Seedlings of stone fruits (apricot, almond, peach, nectarine, plum, sweet cherry and sour cherry) were used for pathogenicity tests. All seedlings were susceptible to the fungal isolates and showed disease symptoms on twigs, leaves, buds and petioles. Genetic diversity of 28 selected fungal isolates was investigated based on DNA fingerprinting by random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR), using four random primers. Based on cluster analysis of the PCR results from the four primers, 10 fingerprinting groups (clonal lineages) and 27 haplotypes were identified. Clonal lineages “C”, “D” and “E”, each with six haplotypes formed the biggest clonal lineages, but other clonal lineages (“B”, “F”, “G”, “H”, “I” and “J”) included only one isolate. No correlation was detected among clonal lineages with the location of selected isolates and their host species. A correlation was found between the substrate (fruit, twig or leaf) and clonal lineages, particularly in “C” clonal lineage. The results showed that the fungus population had high genetic diversity which is distributed among the different areas of Iran.     

Effects of electromagnetic field,cisplatin and morphine on cytotoxicity and expression levels of DNA repair genes

Morphine (Mor) is widely used as an analgesic drug in cancers and in combination with chemotherapy is known to have DNA damaging effects on non-targeted cell. This study surveyed the effect of Mor in combination with 50-Hz electromagnetic field (EMF) and co-treatment of cisplatin in combination with Mor and EMF on the expression of genes involved in DNA repair pathways. MCF-7 and SH-SY5Y cells were treated with 5.0 µM Mor and then exposed to 50-Hz 0.50 mT EMF in the intermittent pattern of 15 min field-on/15 min field-off. Gene expression, cisplatin and bleomycin cytotoxicity were measured using real-time PCR and MTT assay. Mor treated cells showed significant down-regulation of the examined genes, while in “Mor?+?EMF” treatments the genes were not significantly changed. IC₅₀ of cisplatin was significantly elevated in both cell lines when co-treated with “Mor?+?EMF” compared with Mor treated cells. Non-homologous end joining (NHEJ) related genes were significantly decreased in co-treatment of cisplatin and “Mor?+?EMF” which led to bleomycin higher cytotoxicity in SH-SY5Y not in MCF-7. Our data is promising for providing a cell line-specific sensitization by combination of cisplatin and “Mor?+?EMF” treatment with local administration of double strand breaking agents.     

Transition from physiological to pathophysiological indices as exemplified by amyloidosis in periodic disease,non-insulin-dependent diabetes mellitus,and Alzheimer’s disease

Theoretical studies on amyloidosis have been performed. The results promote understanding of primary causes and molecular mechanisms of the formation of pathological protein and permits tracing the transitions from physiological indices to pathological ones in periodic disease (PD), non-insulin-dependent diabetes mellitus (NIDDM), and Alzheimer’s disease (AD). Blockage of the biochemical target by a biologically active substance (drug) at the initial stage of disease makes it possible to avoid formation of pathology. The concept of a “situational physiological skip” is introduced. A new class of drugs (situational controllers of metabolism) that affect transitions from the normal state to pathology in initial periods of disease can be developed. The rational way of finding the prototype of a new drug with a new mechanism of action is computer-aided the developmenrt of a drug on the basis of the spatial structure the target protein. The development of inner structure of proteins related to pathology should be based on distinct grouping of patients according to their genotypes and phenotypes.