BeTe (Lupus Milenia #2) BeTe. (Lupus #25). by To ask other readers questions about BeTe, please sign up. Recent Questions. ada yg punya pdf nya ?. H I L M A N LUPUS Milenia (2) BETE Thi s One 5XYG5-G3DL SS. Penerbit Sekolah () Lupus Milenia 2 BeTe () Lupus Milenia 3 PDKT().. Novel. Lupus Read On Wikipedia Edit History Talk Page Print Download PDF. +. Lupus Milenia: Bete - Ebook written by. Read this book using Google Play Books app on Lupus Milenia: Bete. Gramedia Pustaka Utama. 2. Add to Wishlist.
|Language:||English, German, Arabic|
|Genre:||Science & Research|
|ePub File Size:||22.62 MB|
|PDF File Size:||13.76 MB|
|Distribution:||Free* [*Sign up for free]|
Lupus adalah tokoh fiksi dalam serial novel berjudul sama karangan Hilman Hariwijaya. Novel Lupus . Lupus Milenia 2 - BeTe(); Lupus Milenia 3. automotive ebook pdf novel indonesia terbaru - update terbaru di part 2 yaa click here. boy sitter pdf di bawah ini berasal dari. download lupus milenia 2 bete. Download now any manual for DAEWOO DWD F DAEWOO FR Di blog ini, disediakan link download beberapa seri novel Lupus dan Olga. Lupus Milenia 2 - BeTe () Lupus Milenia 3 - PDKT ()
For traits found in just one or a few breeds, linkage and GWAS have also been highly successful despite the increased difficulty of fine mapping across large linkage blocks see [ 34 ] for a recent review. Furthermore, haplotype-based and FST-based methods to detect recent selection can improve the power of traditional GWAS and find genomic regions underlying selected phenotypes even if they are only present in a single breed. For example, excessive skin wrinkling found almost exclusively in the Shar Peis breed was mapped to hyaluronan synthase 2 HAS2 using an FST-based approach [ 44 ].
The recent introduction of higher-density genotyping arrays such as the K Illumina HD array should further improve the power of these methods from what was possible with older 20 to 60 K SNP arrays. The dog as a model of human genetic disease An important application of trait mapping in dogs is the discovery of variants underlying genetic disease.
Traditional GWAS using well phenotyped cases and controls have proved highly successful in finding regions containing causal variants underlying more than 70 Mendelian diseases in dogs see Additional data file 1.
In addition, dogs occupy a valuable intermediate position between the human and mouse genetic systems, increasing their utility as a model system [ 48 ]. Despite mice and humans last sharing a common ancestor more recently than dogs and humans approximately 75 million years ago versus approximately 87 million years ago , the faster rate of evolution in the rodent lineage means that there is less sequence divergence between human and dogs than between humans and mice, and therefore approximately Mb more human sequence can be syntenically aligned to the dog genome than to that of the mouse [ 1 ].
Furthermore, dogs are more similar to humans than are mice in terms of body size, longevity and behavior, which also leads to similarity in various genetic pathologies. Finally, dogs have co-habited with humans longer than any other domestic animal, sharing our nutritional and pathogenic environment during our species' unprecedented shift from a hunter-gatherer lifestyle to agriculture.
Some human adaptations to this dramatic environmental shift that contribute through antagonistic pleiotropy to disease such as highly reactive immune systems that protect from infectious disease but predispose individuals to autoimmune disorders [ 49 , 50 ] might have evolved in parallel in dogs. Strong artificial selection has contributed to the diversity of disorders exhibited in dogs.
Independent, severe founder effects for each breed cause diseases that are at extremely low prevalence in natural dog populations to, by chance, reach appreciable frequency in one or a few breeds, either from the founder bottleneck itself or through the subsequent propagation of popular sires harboring the variant [ 51 ]. In particular, some recessive disorders caused by loss-of-function mutations and some cancers can be rare in humans but common in certain dog breeds for example, osteosarcoma [ 52 ] and amyotropic lateral sclerosis ALS -like canine degenerative myelopathy [ 53 ].
Diseases can also be associated with variants selected for a pleiotropic effect - for example, dermoid sinus, a neural tube defect in dogs, is caused by the same variant that produces the ridgeback coat phenotype [ 42 ]. Finally, the large selective sweeps containing artificially selected variants can also harbor linked disease variants that hitchhiked to high frequency during the sweep.
It is perhaps not coincidental that the gene underlying lens dislocation in terriers [ 54 ] is adjacent to a gene implicated in controlling body size among small breed dogs B Hoopes, personal communication.
The genetic architecture of canine phenotypic variation Mapping causal variants for quantitative traits is generally more difficult than mapping monogenic traits, if only because accurate phenotyping and controlling for genetic background can be problematic.
Nevertheless, GWAS have elucidated dozens of regions underlying quantitative variation in dogs, although most of the causal variants in these regions remain undiscovered. As next-generation sequencing costs decline and more and more canine genomes are sequenced, candidate loci in these regions and others should begin to emerge, improving our understanding of the genetic basis of phenotypic variation in this system. In particular, advances in targeted sequence capture seq-cap and DNA barcoding currently enable efficient sequencing and analysis of multiple individuals across candidate qualitative trait loci QTL regions [ 55 , 56 ].
Several studies have performed multi-breed GWAS for body weight and morphological measurements [ 8 , 44 , 57 , 58 ]. Despite great differences in the breeds and marker sets used by each, the results are highly consistent for several traits. GWAS across 80 breeds for 50 body and skeletal dimensions has revealed strong evidence that each trait is primarily explained by a few loci of major effect [ 8 ].
Figure 4 QTL mapping of body-size variants in the domestic dog. The blue dots indicate the -log10 P-values of association for a trait at each marker after controlling for genetic relatedness among breeds. Figure reproduced from [ 8 ].
Does this simplified genetic architecture characterize other complex canine phenotypes, including those associated with behavior, longevity and common multifactorial diseases? Analyses of highly differentiated genomic regions among breeds which might represent the 'low-hanging fruit' for across-breed mapping studies show that, overwhelmingly, the highest differentiated regions correspond to known morphological traits involving body size, proportion, coat characteristics and ear type [ 8 ].
Although these regions can also be associated with other traits - IGF1, for example, has also been implicated by GWAS as significantly affecting boldness, age of death and prevalence of several diseases [ 57 , 58 ] - the most parsimonious explanation is that selection towards breed standards has led to stronger differentiation at loci affecting morphology than those affecting other traits.
Perhaps this result is not surprising, as behavior can be difficult to quantify and disease prevalence and longevity, while highly breed-dependent, are not breed-defining characters undergoing direct diversifying selection. Even for morphological variation, the influence of QTLs of major effect may be overstated. Portuguese water dogs were chosen to study body-size variation because they exhibit high intra-breed variation for size; other breeds also have intermediate IGF1 frequencies and it is not clear if they exhibit more intra-breed variation in body size than other breeds or if they possess loci that 'canalize' IGF1 and other high-effect QTLs to reduce their effects.
In addition to the uncertainties regarding the simplified architecture underlying additive genetic variance in dogs, the degree to which non-additivity dominance and recessiveness and epistasis interactions between loci have an impact on complex traits in dogs is also uncertain.
Although Lark [ 60 ] found a non-additive epistatic interaction between IGF1 and a locus on the X chromosome controlling body size, most studies of complex traits in dogs have assumed additivity and ignored the X chromosome Boyko et al. In addition, even the estimates for the proportion of variation explained by QTLs of large effect such as IGF1 might be overstated. If diversifying selection is strong and several loci contribute to the trait but only the ones of largest effect are detected, then these large-effect loci will be associated with both the morphological effect they engender and also with the effects of the rare or small-effect loci that were also swept to some degree but not detected.
Nevertheless, dogs have clearly exhibited a shift in the genetic architecture of complex traits towards variants of large effect for several important phenotypes. This shift facilitates complex-trait mapping, making the dog an extremely important model system.
The extent to which this shift has affected non-morphological variation and whether this simplification extends to other aspects of genetic architecture is still unclear. Important insights into evolutionary biology, including the nature of standing genetic variation and the genomic consequences of adaptation to new environmental pressures, could be gained by determining the degree to which domestication, selective breeding and the genetic structure of the canine genome have each altered the genomic architecture of complex traits in this species.
Concluding remarks and future perspectives Over the past decade, genetic analysis of dogs has not only enriched our understanding of their origins, but also led to the discovery of causal variants underlying myriad diverse phenotypes and diseases. Conversely, and despite the importance in the central Andes of domestic camelids as producers of meat, wool, and dung, there is virtually no record of dogs having been kept to help with herding llamas Lama glama or alpacas Vicugna pacos , at least prior to the Spanish conquest Schwartz , p.
Jesse ; but note that neither Bonavia nor Dransart mentions this in their respective syntheses. Nor, in sharp contrast with the situation in Mesoamerica where they were widely used as a source of animal protein, is there much evidence that dogs were eaten. Other uses were even more marginal: a single reported example, among the Chono of southern Chile, of weaving dog hair to make clothes Cooper b , p. From a practical standpoint, then, and while they certainly also featured in ritual and cosmology, where people kept dogs it was primarily as hunting aids and pets, rather than for the more varied uses attested elsewhere in North America or the Old World.
To summarise the argument thus far, relative to their earlier presence in North America dogs appear to have been latecomers to southern Mesoamerica and Central America, first becoming evident archaeologically not long before their appearance in Ecuador c. Once in South America, what may have been quite a small founding population Witt et al.
There is currently no evidence to push back their presence in the far north of the continent before the first millennium BC; published finds are restricted to the lower Magdalena River and the area immediately south of the La Guajira Peninsula. Further south, dogs were apparently absent from siteia in pre-Columbian times, though Stahl presents evidence for the taming of native South American canids, a process also attested for a much wider range of mammals and birds. This is unlikely to be due to sampling error given the number of archaeological sites investigated Acosta et al.
Download novel lupus milenia 2 bete
In any event, dogs do not seem to have reached southern and central Patagonia at all; both there and in Tierra del Fuego the first dogs were probably European introductions pace Cardich et al. The picture is sketchy and clearly at risk of being skewed by preservation and research biases, but the late entrance of dogs into the Neotropics compared to North America, the slowness with which they expanded beyond the Andean world and its Pacific coasts, and their absence from vast swathes of the continent as late as the sixteenth century stand out.
Indeed, the large scale of this patterning, covering highly diverse taphonomic modes and research histories, makes it unlikely that it is biased by sampling limitations. Given that where they do and did occur dogs are—and were—typically highly valued as companions and hunting aids, can disease help account for this patterning and, if so, what diseases might have been involved?
However, several of these are relatively recent introductions, having arrived only in the aftermath of European invasion in the sixteenth century. In some cases this reflects the arrival of a new pathogen able to take advantage of a range of hosts, including dogs, while in others it reflects the additional arrival of new vectors capable of transmitting the infection to dogs and other animals. An incomplete list of such diseases would include rabies, surra a trypanosomal disease related to canine [and human] trypanosomiasis , canine babesiosis, and visceral leishmaniasis caused by infection with Leishmania infantum chagasi.
DOWNLOAD EBOOK LUPUS HILMAN HARIWIJAYA
Genetic data sometimes confirm an exotic origin e. Eiras et al. Likewise, although canine monocytic ehrlichiosis is now one of the most important diseases to infect dogs in parts of Brazil Labruna et al. Instead of examining the effects of these recent introductions, however, I turn now to diseases of likely pre-Columbian antiquity.
As I have already observed, the native dogs of the Americas share a recent common ancestry with grey wolves van Asch et al. Coyotes extended a few hundred kilometres further south: archaeological evidence definitely places them in Belize before Columbus, and historical records indicate that they were either already present, or expanded very quickly, as far south as Nicaragua and Costa Rica by the end of the sixteenth century, with further spread occurring during the twentieth century Hidalgo-Mihart et al.
Like wolves, however, coyotes did not occur in South America. It follows from this that when domestic dogs entered South and most of Central America they may have found themselves confronted with wholly novel diseases of which they had no prior experience, even though such diseases may have been hosted by wild canids endemic to those regions Figs. Richardson et al. More generally, we can use the veterinary literature to identify diseases of likely pre-Columbian antiquity capable of infecting domestic dogs in South America.
Acknowledging the uniformitarian assumptions involved, this may suggest where, how, and under what conditions such infections can take place, as well as their consequences.
That canid populations are susceptible to novel diseases, some transmitted via domestic dogs, is well attested, and today such infections pose a major threat to the survival of several wild South American canids Fiorello et al.
This led to the hypothesis that DMT is an endogenous hallucinogen 96, 97 , and later it was proposed to be a neurotransmitter or neuromodulator The vast majority of the initial research into the reasons for the presence of psychoactive tryptamines in the human body has sought their involvement in mental illness. Until now, very little has been known about the function of DMT in cellular and general physiological processes, and the emphasis of research mostly aimed the understanding of its psychedelic properties Recently, we and others demonstrated that DMT has the capability to modulate immune responses in in vitro human primary cell cultures 88, In these studies, DMT was shown to act as a non-competitive inhibitor of indoleamine 2,3-dioxygenase IDO and as a strong inducer of anti-tumor cytotoxic activity in the co-cultures of human PBMCs and a glioma cell line MoDCs are key cell types of the mammalian immune system connecting and orchestrating innate and adaptive immune responses as professional antigen-presenting cells APCs These are in line with previous findings showing the immunomodulatory potential of ayahuasca in humans mostly affecting the number and ratio of lymphocyte subpopulations.
Notably, the number of circulating NK cells, a cell type involved in anti-viral and anti-cancer immune responses, increased significantly , The anti-cancer activity of ayahuasca has already been reviewed in a paper by Schenberg However, it is important to keep in mind that ayahuasca is a complex decoction that, besides DMT, contains several other components according to the admixture plants used in the making process.
Furthermore, ayahuasca can be administered in various Tryptamines: Endogenous Regulators of Inflammation and Tumor Immunity? Tryptamines are members of a large family of monoamine alkaloids that are widespread in nature and abundant in all the three Kingdoms of life plants, fungi, and animals. Their main feature is a common indole ring, a backbone that is structurally related to the amino acid tryptophan. This tryptamine backbone designates many biologically active compounds, such as psychedelics Frontiers in Immunology www.
Nevertheless, ayahuasca consumption in a highly controlled clinical setting emerges as a very promising model for investigating the possible immunomodulatory effects of DMT in humans Importantly, it is possible that the observed anti-inflammatory and immunosuppressive effects may counteract with the anticancer activity, therefore further investigations are needed to elucidate the complex in vivo consequences of DMT administration.
The mentioned studies demonstrate and propose new biological roles for DMT, which may act as a systemic endogenous regulator of inflammation and immune homeostasis. This is of particular importance, since Th1 and Th17 cells and the cytokines they secrete are key players in the etiology and symptomatology of many chronic inflammatory and autoimmune diseases of the CNS and other tissues , Moreover, the mobilization of innate immune mechanisms is also well established in many psychiatric and neurological disorders 6.
Thus, as a target for future pharmacological investigations, DMT emerges as a potent and promising candidate in novel therapies of peripheral and CNS autoimmune diseases such as multiple sclerosis or amyotrophic lateral sclerosis and cancer. The results obtained so far suggest that LSD may interfere with the elements of the immune system by altering mainly the activity of lymphocytes in mammals.
Lupus (tokoh fiksi)
High doses of this substance may alleviate or inhibit adaptive autoimmune responses, while lower doses may positively influence the antiviral or anti-cancer immunity through the modulation of NK cell activation.
However, detailed analyses on the complex in vivo effects of LSD on immune functions are yet to be performed. Phenethylamines: Regulating Inflammation and Cytotoxicity Phenethylamines or substituted phenethylamines are members of a large and diverse group of organic compounds, which derive from phenethylamine itself.
Some of them are neurotransmitters, such as dopamine and epinephrine, other members of the family are psychoactive substances e. This large family also includes a variety of drug classes, such as dopamine agents e. Considering the vast number and diversity of substituted phenethylamines, a comprehensive review about the complex immunological effects of these compounds would exceed the limits of this paper.
Therefore, this section focuses on two phenethylamines, DOI and MDMA, which have already been described as potential immunomodulators in higher vertebrate species. These psychedelics have several similarities in their pharmacological action as both of them exhibit a certain degree of agonistic activity at serotonin receptors.
Dimethoxyiodoamphetamine was originally designed and used as a radioligand for the mapping of 5-HT2 receptors , In this report, DOI was shown to inhibit the constitutively high protein-level expression of intracellular adhesion molecule 1 ICAM-1 , vascular adhesion molecule 1 VCAM-1 , the inflammatory cytokine IL-6, and the activity Lysergamides: Modulating Lymphocyte Functions Lysergic acid diethylamide also know as LSD or lysergide is a psychedelic substance of the ergoline family.
Its pharmacological effects are very complex as it affects several serotonin, as well as all dopamine and adrenoreceptor subtypes. Since most serotonergic psychedelics do not exhibit dopaminergic activity, LSD is quite unique in this regard An early study demonstrated that LSD was able to interfere with antibody production in rabbit In this report, LSD was shown to skew the antibody profile of activated B cells to produce low molecular weight proteins by influencing the process of translation.
Excess tryptophan abrogated the effect of LSD on protein synthesis suggesting that the phenomenon may occur at the point of tryptophan insertion during translation. However, the data provided did not adequately support a peptide termination mechanism rather reflected an amino acid analog effect being simulated by LSD This latter, low concentration can easily Frontiers in Immunology www. The most researched phenethylamine, MDMA, has also been described as an anti-inflammatory and immunosuppressive agent.
Early studies reported that MDMA could increase the activity of mouse NK and T helper cells in in vitro cultures at low concentrations 0.
Furthermore, several groups reported that MDMA negatively affected in vivo immune responses to various pathogens in animal models , — In agreement with these findings, both acute and chronic MDMA administrations were demonstrated to cause immunosuppression in humans characterized by a significant decrease in T lymphocyte and parallel increase in NK cell functions.
Long-term use of MDMA, however, was associated with a decrease in the total number of circulating lymphocyte populations. These results suggest that acute administration of MDMA favors anti-inflammatory immune responses and has a tendency to polarize adaptive immunity toward antibody production. Simultaneously, the activity of NK cells is increased pointing to a complex effect on immune homeostasis.
This may reflect to an anti-inflammatory potential of MDMA without significantly decreasing the effectiveness of antiviral or anti-tumor immunity; however, further in vivo studies are needed to unravel the details of this complex immunomodulatory action. A similar mechanism may lead to the preference of a given pathway through kinase or receptor—adaptor bias An interesting contemporary approach to the topic has been carried out by using systems biology, bioinformatics, and biophysics, as tools of better understanding.
This approach emphasizes that instead of single cell analyses, one should move toward a more holistic understanding of signaling systems. The meta-network of biological entities is considered to possess both microscopic and macroscopic dynamics as observed in physical sciences. The origin of averaging effects from stochastic responses of a single cell when collected to form a population should also be taken into account , It is very likely that the emergence of an average cell deterministic response e.
Consequently, the stochastic fluctuations in the inflammatory response of a single immune cell or a single signaling pathway are necessary to induce probabilistic differentiation from identical cells or interacting pathways of the same receptor family.
This might allow multicellular organisms or complex, interacting signaling networks to switch cell fates or states to yield diversity, fine-tuning, and reach the proper response that cannot be achieved by a purely deterministic system.
Recent studies of multi-component, non-linear modeling of different TLR pathways verified the success of this idea by identifying cross-talk mechanisms between the MyD and TRIF-dependent pathways and led to the concept of signaling flux redistribution SFR , This proposal is based on the law of conservation where the removal of MyD88 leads to increased activation of the entire alternative TRIF-pathway.
Thus, total signaling flux information from a receptor through final downstream gene activation in the network is conserved. An important limitation of this double-model hypothesis is that available experimental data supporting the proposed interactions is mostly scarce. Thus, further studies are needed to confirm its relevance in future immunopharmacotherapies, especially as far as translational aspects and human clinical trials are concerned.
While PRRs were shown to be crucial for innate and adaptive host defense, their inappropriate activation has been associated with autoimmunity and inflammatory diseases.
Psychedelics, by modulating the activity of 5-HT1 , 5-HT2 , and sigmar-1 receptors, are potent anti-inflammatory agents 70, , , — The molecular biological background of these effects has not been investigated so far. Two models are proposed here to cover the possible biochemical dynamics of these interactions. On the one hand, i regulation may occur through the alteration of the cytokine-pattern of activated cells. On the other hand, ii a complex Frontiers in Immunology www. I am also very grateful to the Reviewers for their appropriate and constructive suggestions.
Szabo A, Rajnavolgyi E. Am J Clin Exp Immunol 2 3 — Differences in agonist-independent activity of 5-Ht2A and 5-HT2c receptors revealed by heterologous expression.
Naunyn Schmiedebergs Arch Pharmacol 1 —7. Biochem J Pt 2 — Am J Physiol 6 Pt 2 :F— J Biol Chem 23 —9. Barnes NM, Sharp T. A review of central 5-HT receptors and their function.
Neuropharmacology 38 8 — Ras involvement in signal transduction by the serotonin 5-HT2B receptor. J Biol Chem 6 —7. The serotoninergic receptors of human dendritic cells: identification and coupling to cytokine release.
J Immunol 10 —9. The serotonin 5-HT2C receptor is a prominent serotonin receptor in basal ganglia: evidence from functional studies on serotoninmediated phosphoinositide hydrolysis.
J Neurochem 69 4 — Serotonin activates murine alveolar macrophages through 5-HT2C receptors. Brain Behav Immun 14 3 — J Virol 87 24 —8. Expression of 5HT1a receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-hydroxytryptamine. J Immunol 3 — Serotonin modulates immune function in T cells from HIV-seropositive subjects. Clin Immunol Immunopathol 84 2 — Miller AH.
Norman cousins lecture. Mechanisms of cytokine-induced behavioral changes: psychoneuroimmunology at the translational interface.
Brain Behav Immun 23 2 — Adrenergic and serotoninergic receptors mediate the immunological activation of corticosterone secretion in male rats.
Gynecol Endocrinol 10 3 — Serotonin and hallucinogens. Neuropsychopharmacology 21 2 Suppl S—23S. Greyer M, Nichols D. Serotonin-related psychedelic drugs. In: Squire L, editor.
Encyclopedia of Neuroscience. Oxford: Academic Press Classical hallucinogens as antidepressants?
A review of pharmacodynamics and putative clinical roles. Ther Adv Psychopharmacol 4 4 — Frecska E, Luna LE. The adverse effects of hallucinogens from intramural perspective. Neuropsychopharmacol Hung 8 4 — Quan N, Banks WA. Brain-immune communication pathways. Brain Behav Immun 21 6 — The brain-immune-gut triangle: innate immunity in psychiatric and neurological disorders.
Curr Immunol Rev —8. Luna LE. The healing practices of a Peruvian shaman. J Ethnopharmacol 11 2 — Winkelman M. A cross-cultural study of shamanistic healers. J Psychoactive Drugs 21 1 — An historical perspective. Psychiatr Clin North Am 7 3 — Alper KR. Ibogaine: a review.
Alkaloids Chem Biol — Prue R, Voss RW. Indigenous healing practice: ayahuasca. Opening a discussion. J Pastoral Care Counsel 68 1—2 Felten DL. Neurotransmitter signaling of cells of the immune system: important progress, major gaps. Brain Behav Immun 5 1 :2—8. Mossner R, Lesch KP. Role of serotonin in the immune system and in neuroimmune interactions.
Brain Behav Immun 12 4 — The immunoregulatory role of dopamine: an update. Brain Behav Immun 24 4 —8. Serotonin modulation of macrophage polarization: inflammation and beyond. Adv Exp Med Biol —Historia Al Arsy added it Jul 22, Br J Pharmacol 1 — Pharmacologic profile of MDMA 3,4-methylenedioxymethamphetamine at various brain recognition sites.
J Neuroimmunol 1—2 —9. Sarat dengan humor orisinal, terutama unik dalam gaya bahasa dan pilihan kata yang seenaknya. Expression of 5HT1a receptors on activated human T cells.