Journal articles on the topic 'Synthesis of carbocyclic cleft molecules'

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1

Kimber, Marc C., Andrew C. Try, Leoni Painter, Margaret M. Harding, and Peter Turner. "Synthesis of Functionalized Chiral Carbocyclic Cleft Molecules Complementary to Tröger's Base Derivatives." Journal of Organic Chemistry 65, no. 10 (May 2000): 3042–46. http://dx.doi.org/10.1021/jo991741p.

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2

Lee, Connie K. Y., Jennifer L. Groneman, Peter Turner, Louis M. Rendina, and Margaret M. Harding. "Synthesis and X-ray crystallographic analysis of chiral pyridyl substituted carbocyclic molecular clefts." Tetrahedron 62, no. 20 (May 2006): 4870–78. http://dx.doi.org/10.1016/j.tet.2006.03.014.

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3

Halder, Joydev, Debabrata Das, and Samik Nanda. "A distinctive transformation based diversity oriented synthesis of small ring carbocycles and heterocycles from biocatalytically derived enantiopure α-substituted-β-hydroxyesters." Organic & Biomolecular Chemistry 16, no. 14 (2018): 2549–75. http://dx.doi.org/10.1039/c8ob00233a.

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4

Jilka, Priti, Claire Millington, Mark R. J. Elsegood, Josef W. A. Frese, Simon Teat, and Marc C. Kimber. "The selective mono and difunctionalization of carbocyclic cleft molecules with pyridyl groups and X-ray crystallographic analysis." Tetrahedron 66, no. 48 (November 2010): 9327–31. http://dx.doi.org/10.1016/j.tet.2010.10.027.

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5

Koga, Masakazu, Koichi Tamai, Mitsunori Ueda, Toshinori Uchida, Toshiyuki Yamamuro, Masahiro Shigeta, Masaharu Yamamoto, Takaaki Suzuki, and Toshiaki Saeki. "Synthesis and Properties of Carbocyclic 5′- Nor Oligodeoxynucleotides as Potential Antisense Molecules." Phosphorus, Sulfur, and Silicon and the Related Elements 177, no. 8-9 (August 2002): 2099–100. http://dx.doi.org/10.1080/10426500213320.

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6

Llona-Minguez, Sabin, and Simon P. Mackay. "Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ0)." Beilstein Journal of Organic Chemistry 10 (June 11, 2014): 1333–38. http://dx.doi.org/10.3762/bjoc.10.135.

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A convergent and stereoselective synthesis of chiral cyclopentyl- and cyclohexylamine derivatives of nucleoside Q precursor (PreQ0) has been accomplished. This synthetic route allows for an efficient preparation of 4-substituted analogues with interesting three-dimensional character, including chiral cyclopentane-1,2-diol and -1,2,3-triol derivatives. This unusual substitution pattern provides a useful starting point for the discovery of novel bioactive molecules.
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7

Al-Saad, Dalya, Misal Giuseppe Memeo, and Paolo Quadrelli. "#Nitrosocarbonyls 1: Antiviral Activity ofN-(4-Hydroxycyclohex-2-en-1-yl)quinoline-2-carboxamide against the Influenza A Virus H1N1." Scientific World Journal 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/472373.

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Influenza virus flu A H1N1 still remains a target for its inhibition with small molecules. Fleeting nitrosocarbonyl intermediates are at work in a short-cut synthesis of carbocyclic nucleoside analogues. The strategy of the synthetic approaches is presented along with thein vitroantiviral tests. The nucleoside derivatives were tested for their inhibitory activity against a variety of viruses. Promising antiviral activities were found for specific compounds in the case of flu A H1N1.
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8

Grillo, Alessandro, and Bruno Mattia Bizzarri. "Catalytic Enantioselective Diels Alder Reaction: Application in the Synthesis of Antiviral Agents." Catalysts 12, no. 2 (January 25, 2022): 150. http://dx.doi.org/10.3390/catal12020150.

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The Diels–Alder reaction (DAR) is one of the most effective and reliable strategies for the construction of six-membered carbocyclic and heterocyclic rings, and it is widely used in the synthesis of organic molecules and drugs. Due to the high regio- and stereo-selectivity and its versatility, DARs have represented a powerful tool for organic chemistry for many years. In addition, the asymmetric DAR has become a fundamental synthetic approach in the preparation of optically active six-membered rings and natural compounds. The COVID-19-related pandemic requires continuous research; DAR represents an useful method to obtain optically active intermediates for the synthesis of antiviral agents under different catalytic conditions. We would like to highlight an intriguing synthetic procedure applied to the development of novel synthetic protocols that are potentially useful against a large panel of viruses and other unmet diseases.
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9

Roberts, S. M., and N. M. Williamson. "The Use of Enzymes for the Preparation of Biologically Active Natural Products and Analogues in Optically Active Form." Current Organic Chemistry 1, no. 1 (May 1997): 1–20. http://dx.doi.org/10.2174/1385272801666220121181731.

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The enantioselective hydrolysis of chiral esters using esterases and lipases gives access to key optically active intermediates en route to prostaglandins, coriolic acid, the anti-HIV agent carbovir and mevinic acid type hypocholestemic agents. The hydrolysis of meso-esters using hydrolases is a very efficient strategy in organic synthesis and has been used to prepare the carbocyclic nucleosides neplanocin and risteromycin. Acylases have been used to prepare (-)-carbovir and both enantiomers of a GABA-mimetic from 2-azabicyclo[2.2.1)hept-5-en-3-one. The employment of nitrilases and nitrile hydratases is gaining in popularity; for example, prochiral 2-benzoyloxypropane-1,3-dinitrile is hydrolysed to (S)-3-benzoyloxy-4-cyanobutanoic acid with exquisite selectivity. Lipases in organic solvents can effect esterification, transesterification and interesterification reactions and this popular methodology has been used to prepare key norcarbocyclic nucleotides and carbocyclic oxetanocin A in single enantiomer form. Yeast­ catalysed reductions of ketones afford optically active secondary alcohols, typically employed for the synthesis of pheromones, fragrances and chemotactic agents such as leukotriene-84. Instead of a whole-cell system such as yeast, partially purified dehydrogenases can be employed to synthesise (S)-secondary alcohols, for examplan intermediate to the antifungal agent brefeldin-A. Biohydroxylations are important reactions and are being applied to a wide range of substrates. The oxidation of benzene and derivatives to the corresponding cyclohexadiene diols are classic examples and have provided a route to analogues of cyclophellitol. Similarly, mono-oxygenase catalysed Baeyer-Villiger reactions are now well-documented and have furnished intermediates to carbocyclic-AZT, lipoic acid and azadirachtin. Sulfoxides of high optical purity have been prepared by yeast-catalysed oxidation, while enzymes in the transferase and lyase classes have been used to make carbohydrates and amino acids. In conclusion, the science of biotransformations opens up numerous synthetic routes to a wide variety of target molecules that are not easily accessible by other methods of synthetic organic chemistry.
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10

Maycock, Christopher D., M. Teresa Barros, António G. Santos, and Lício S. Godinho. "An application of quinic acid to the synthesis of cyclic homochiral molecules: A common route to some interesting carbocyclic nucleoside precursors." Tetrahedron Letters 34, no. 49 (December 1993): 7985–88. http://dx.doi.org/10.1016/s0040-4039(00)61531-9.

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11

MAYCOCK, C. D., M. T. BARROS, A. G. SANTOS, and L. S. GODINHO. "ChemInform Abstract: An Application of Quinic Acid to the Synthesis of Cyclic Homochiral Molecules: A Common Route to Some Interesting Carbocyclic Nucleoside Precursors." ChemInform 25, no. 14 (August 19, 2010): no. http://dx.doi.org/10.1002/chin.199414279.

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12

Schaiff, W. T., K. A. Hruska, D. W. McCourt, M. Green, and B. D. Schwartz. "HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells." Journal of Experimental Medicine 176, no. 3 (September 1, 1992): 657–66. http://dx.doi.org/10.1084/jem.176.3.657.

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The major histocompatibility complex class II molecules are composed of two polymorphic chains which, in cells normally expressing them, transiently associate with a third, nonpolymorphic molecule, the invariant chain (Ii). To determine differences in the biology of class II molecules synthesized in the presence or absence of Ii, a comparative study was performed of BALB/c 3T3 cells that had been transfected with human class II HLA-DR molecules with or without cotransfection with human Ii. It was observed that in the absence of Ii, at least three high molecular weight proteins coimmunoprecipitate with HLA-DR molecules. These proteins did not coimmunoprecipitate with HLA-DR from cells cotransfected with Ii, nor did they coimmunoprecipitate with class I molecules from any of the transfectants. NH2-terminal sequence and/or Western blot analysis revealed the identity of two of the proteins as the endoplasmic reticulum (ER) resident stress proteins GRP94 and ERp72. Neither of these proteins was found to have an increased level of synthesis in the Ii- versus the Ii+ transfectants, indicating that their synthesis was not induced over constitutive levels. Fluorescence microscopy revealed that in the Ii- transfectants, the majority of the HLA-DR molecules were present in the ER, whereas in the Ii+ transfectants, the HLA-DR molecules were found in vesicular structures. We hypothesize that in the absence of Ii, ER resident stress proteins bind to class II molecules and retain them in the ER. This process, in turn, could prevent class II molecules from exiting the ER with endogenous peptides bound in their peptide binding cleft, and therefore could minimize autoimmune responses to endogenously processed self-peptides.
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13

Ferguson, Mark W. J. "Palate development." Development 103, Supplement (September 1, 1988): 41–60. http://dx.doi.org/10.1242/dev.103.supplement.41.

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In all vertebrates, the secondary palate arises as bilateral outgrowths from the maxillary processes. In birds and most reptiles, these palatal shelves grow initially horizontally, but do not fuse with each other resulting in physiological cleft palate. In crocodilians, shelf fusion occurs resulting in an intact secondary palate. Mammalian palatal shelves initially grow vertically down the side of the tongue, but elevate at a precise time to a horizontal position above the dorsum of the tongue and fuse with each other to form an intact palate. Palatal shelf-elevation is the result of an intrinsic shelf elevating force, chiefly generated by the progressive accumulation and hydration of hyaluronic acid. In all vertebrates the nasal epithelium differentiates into pseudostratified ciliated columnar cells and the oral epithelia differentiates into stratified squamous cells, but the medial edge epithelial (MEE) phenotype differs in different groups. In mammals, the MEE of opposing shelves adhere to each other to form an epithelial seam which then disrupts by cell death and cell migration into the mesenchyme accompanied by an epitheliomesenchymal transformation. In birds, the MEE keratinize resulting in cleft palate whereas, in alligators, the MEE migrate onto the nasal aspect of the palate. In all vertebrates, this regional, temporal and species-specific epithelial differentiation is specified by the underlying mesenchyme. Signalling of this interaction is complex but involves both extracellular matrix and soluble factors e.g. minor collagen types, tenascin, EGF, TGFα, TGFβ, PDGF, FGF. These soluble growth factors have a biphasic effect: directly on the epithelia and on the mesenchyme where they stimulate or inhibit cell division and synthesis of specific extracellular matrix molecules. The extracellular matrix molecules (and bound growth factors) synthesized by the mesenchymal cells may then directly affect the epithelium. These signals cause differential gene expression via second messenger systems e.g. cAMP, cGMP, Ca2+, pH, pI etc. Molecular markers for nasal, medial and oral epithelial cell differentiation include the types of cytokeratin intermediate filaments and specific cell surface molecules recognized by monoclonal antibodies: the genes for such molecules are probably expressed in response to mesenchymal signals. Using such an approach, it is possible to go from a morphological description of palate development to a cellular analysis of the mechanisms involved and then to identification of candidate genes that may be important for screening and diagnosis of cleft palate.
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14

Naeem, Fawad, Humaira Nadeem, Aun Muhammad, Muhammad Ammar Zahid, and Adil Saeed. "Synthesis, α-Amylase Inhibitory Activity and Molecular Docking Studies of 2,4-Thiazolidinedione Derivatives." Open Chemistry Journal 5, no. 1 (November 30, 2018): 134–44. http://dx.doi.org/10.2174/1874842201805010134.

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Introduction:2,4-Thiazolidinedione and its derivatives exhibit a variety of pharmacological activities including antidiabetic, antiviral, antifungal, anti-inflammatory, anti-cancer and aldose reductase inhibitory activities. Keeping in mind the pharmacological potential of 2,4-Thiazolidinedione derivatives as antidiabetic agents, seven arylidene derivatives of 2,4-thiazolidinedione1(a-g)and four corresponding acetic acid derivatives 2(a-d)have been synthesized by a three-step procedure.Methods:All the synthesized compounds were characterized by elemental analysis, FTIR,1HNMR, and13CNMR and further screened for their α-amylase inhibitory potential.Results:All the compounds1(a-g)and2(a-d)showed varying degree of α-amylase inhibition, especially compound1c(IC50= 6.59μg/ml),1d(IC50=2.03μg/ml) and1g(IC50= 3.14μg/ml) displayed significantly potent α-amylase inhibition as compared to the standard acarbose (IC50= 8.26μg/ml). None of the acetic acid derivatives of 5-arylidene-2,4-thiazolidinedione showed prominent inhibitory activity. Docking results indicated that the best binding conformation was found inside the active site cleft of enzyme responsible for hydrolysis of carbohydrates.Conclusion:Therefore, it can be concluded that 2,4-thiazolidinedione derivatives can be used as effective lead molecules for the development of α-amylase inhibitors for the management of diabetes.
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15

Itoh, Yuzuru, Markus J. Bröcker, Shun-ichi Sekine, Gifty Hammond, Shiro Suetsugu, Dieter Söll, and Shigeyuki Yokoyama. "Decameric SelA•tRNASec Ring Structure Reveals Mechanism of Bacterial Selenocysteine Formation." Science 340, no. 6128 (April 4, 2013): 75–78. http://dx.doi.org/10.1126/science.1229521.

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The 21st amino acid, selenocysteine (Sec), is synthesized on its cognate transfer RNA (tRNASec). In bacteria, SelA synthesizes Sec from Ser-tRNASec, whereas in archaea and eukaryotes SepSecS forms Sec from phosphoserine (Sep) acylated to tRNASec. We determined the crystal structures of Aquifex aeolicus SelA complexes, which revealed a ring-shaped homodecamer that binds 10 tRNASec molecules, each interacting with four SelA subunits. The SelA N-terminal domain binds the tRNASec-specific D-arm structure, thereby discriminating Ser-tRNASec from Ser-tRNASer. A large cleft is created between two subunits and accommodates the 3′-terminal region of Ser-tRNASec. The SelA structures together with in vivo and in vitro enzyme assays show decamerization to be essential for SelA function. SelA catalyzes pyridoxal 5′-phosphate–dependent Sec formation involving Arg residues nonhomologous to those in SepSecS. Different protein architecture and substrate coordination of the bacterial enzyme provide structural evidence for independent evolution of the two Sec synthesis systems present in nature.
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16

Masuyer, Geoffrey. "Crystal Structure of Exotoxin A from Aeromonas Pathogenic Species." Toxins 12, no. 6 (June 15, 2020): 397. http://dx.doi.org/10.3390/toxins12060397.

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Aeromonas exotoxin A (AE) is a bacterial virulence factor recently discovered in a clinical case of necrotising fasciitis caused by the flesh-eating Aeromonas hydrophila. Here, database mining shows that AE is present in the genome of several emerging Aeromonas pathogenic species. The X-ray crystal structure of AE was solved at 2.3 Å and presents all the hallmarks common to diphthamide-specific mono-ADP-ribosylating toxins, suggesting AE is a fourth member of this family alongside the diphtheria toxin, Pseudomonas exotoxin A and cholix. Structural homology indicates AE may use a similar mechanism of cytotoxicity that targets eukaryotic elongation factor 2 and thus inhibition of protein synthesis. The structure of AE also highlights unique features including a metal binding site, and a negatively charged cleft that could play a role in interdomain interactions and may affect toxicity. This study raises new opportunities to engineer alternative toxin-based molecules with pharmaceutical potential.
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17

WARRENER, R. N., D. N. BUTLER, and R. A. RUSSELL. "ChemInform Abstract: Building BLOCKs in Synthesis. Part 2. Fundamental Principles of BLOCK Design and Assembly in the Production of Large, Rigid Molecules with Functional Units (Effectors) Precisely Located on a Carbocyclic Framework." ChemInform 29, no. 33 (June 20, 2010): no. http://dx.doi.org/10.1002/chin.199833346.

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18

Sathiyamoorthy, Karthik, J. Vijayalakshmi, Bhramara Tirupati, Lixin Fan, and Mark A. Saper. "Structural analyses of the Haemophilus influenzae peptidoglycan synthase activator LpoA suggest multiple conformations in solution." Journal of Biological Chemistry 292, no. 43 (September 8, 2017): 17626–42. http://dx.doi.org/10.1074/jbc.m117.804997.

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In many Gram-negative bacteria, the peptidoglycan synthase PBP1A requires the outer membrane lipoprotein LpoA for constructing a functional peptidoglycan required for bacterial viability. Previously, we have shown that the C-terminal domain of Haemophilus influenzae LpoA (HiLpoA) has a highly conserved, putative substrate-binding cleft between two α/β lobes. Here, we report a 2.0 Å resolution crystal structure of the HiLpoA N-terminal domain. Two subdomains contain tetratricopeptide-like motifs that form a concave groove, but their relative orientation differs by ∼45° from that observed in an NMR structure of the Escherichia coli LpoA N domain. We also determined three 2.0–2.8 Å resolution crystal structures containing four independent full-length HiLpoA molecules. In contrast to an elongated model previously suggested for E. coli LpoA, each HiLpoA formed a U-shaped structure with a different C-domain orientation. This resulted from both N-domain twisting and rotation of the C domain (up to 30°) at the end of the relatively immobile interdomain linker. Moreover, a previously predicted hinge between the lobes of the LpoA C domain exhibited variations of up to 12°. Small-angle X-ray scattering data revealed excellent agreement with a model calculated by normal mode analysis from one of the full-length HiLpoA molecules but even better agreement with an ensemble of this molecule and two of the partially extended normal mode analysis-predicted models. The different LpoA structures helped explain how an outer membrane-anchored LpoA can either withdraw from or extend toward the inner membrane-bound PBP1A through peptidoglycan gaps and hence regulate the synthesis of peptidoglycan necessary for bacterial viability.
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19

Spohr, Ulrike, Eugenia Paszkiewicz-Hnatiw, Naohiko Morishima, and Raymond U. Lemieux. "Molecular recognition XI. The synthesis of extensively deoxygenated derivatives of the H-type 2 human blood group determinant and their binding by an anti-H-type 2 monoclonal antibody and the lectin 1 of Ulexeuropaeus." Canadian Journal of Chemistry 70, no. 1 (January 1, 1992): 254–71. http://dx.doi.org/10.1139/v92-036.

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The relative potencies of a wide variety of deoxygenated derivatives of the methyl glycoside of α-L-Fuc-(1 → 2)-β-D-Gal-(1 → 4)- β-D-GlcNAc (the H-type 2 human blood group related trisaccharide) for the inhibition of the binding of an artificial H-type 2 antigen by the lectin I of Ulexeuropaeus confirmed the previous evidence that the key and productive interaction involves only the three hydroxyl groups of the α-L-fucose unit, the hydroxyl at the 3-position of the β-D-galactose residue, and the nonpolar groups in their immediate environment. Except for the acetamido group and the hydroxymethyl of the β-D-Gal unit, which stay in the aqueous phase, on complex formation the remaining three hydroxyl groups appear to come to reside at or near the periphery of the combining site since their replacement by hydrogen causes relatively small changes (< ± 1 kcal/mol) in the stability of the complex (ΔG0). Relatively much larger but compensating changes occur for the enthalpy and entropy terms, and these may arise primarily from the differences in the water structure about the periphery of the combining site and the oligosaccharide both prior to and after complexation. It is proposed that steric constraints lead to an ordered state of the water molecules hydrogen-bonded to the polar groups within the cleft formed by the key region of the amphiphilic combining site. Their release to form less ordered clusters of more strongly hydrogen-bonded water molecules in bulk solution would contribute importantly to the driving force for complexation. It is demonstrated that the surface used for the binding of H-type 2-OMe by a monoclonal anti-H antibody is virtually identical to that used by the Ulex lectin. Keywords: molecular recognition, H-type 2 blood group determinant and deoxygenated derivatives, lectin I of Ulexeuropaeus, anti-H-type 2 monoclonal antibody, enthalpy–entropy compensation.
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20

Gregory, Louise Cheryl, and Mehul Tulsidas Dattani. "The Molecular Basis of Congenital Hypopituitarism and Related Disorders." Journal of Clinical Endocrinology & Metabolism 105, no. 6 (November 8, 2019): e2103-e2120. http://dx.doi.org/10.1210/clinem/dgz184.

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Abstract Context Congenital hypopituitarism (CH) is characterized by the presence of deficiencies in one or more of the 6 anterior pituitary (AP) hormones secreted from the 5 different specialized cell types of the AP. During human embryogenesis, hypothalamo–pituitary (HP) development is controlled by a complex spatio-temporal genetic cascade of transcription factors and signaling molecules within the hypothalamus and Rathke’s pouch, the primordium of the AP. Evidence Acquisition This mini-review discusses the genes and pathways involved in HP development and how mutations of these give rise to CH. This may present in the neonatal period or later on in childhood and may be associated with craniofacial midline structural abnormalities such as cleft lip/palate, visual impairment due to eye abnormalities such as optic nerve hypoplasia (ONH) and microphthalmia or anophthalmia, or midline forebrain neuroradiological defects including agenesis of the septum pellucidum or corpus callosum or the more severe holoprosencephaly. Evidence Synthesis Mutations give rise to an array of highly variable disorders ranging in severity. There are many known causative genes in HP developmental pathways that are routinely screened in CH patients; however, over the last 5 years this list has rapidly increased due to the identification of variants in new genes and pathways of interest by next-generation sequencing. Conclusion The majority of patients with these disorders do not have an identified molecular basis, often making management challenging. This mini-review aims to guide clinicians in making a genetic diagnosis based on patient phenotype, which in turn may impact on clinical management.
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21

Kaur, Jasweer, and Rachna Hora. "‘2TM proteins’: an antigenically diverse superfamily with variable functions and export pathways." PeerJ 6 (May 11, 2018): e4757. http://dx.doi.org/10.7717/peerj.4757.

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Malaria is a disease that affects millions of people annually. An intracellular habitat and lack of protein synthesizing machinery in erythrocytes pose numerous difficulties for survival of the human pathogenPlasmodium falciparum. The parasite refurbishes the infected red blood cell (iRBC) by synthesis and export of several proteins in an attempt to suffice its metabolic needs and evade the host immune response. Immune evasion is largely mediated by surface display of highly polymorphic protein families known as variable surface antigens. These include the two trans-membrane (2TM) superfamily constituted by multicopy repetitive interspersed family (RIFINs), subtelomeric variable open reading frame (STEVORs) andPlasmodium falciparumMaurer’s cleft two trans-membrane proteins present only inP. falciparumand some simian infectingPlasmodiumspecies. Their hypervariable region flanked by 2TM domains exposed on the iRBC surface is believed to generate antigenic diversity. Though historically named “2TM superfamily,” several A-type RIFINs and some STEVORs assume one trans-membrane topology. RIFINs and STEVORs share varied functions in different parasite life cycle stages like rosetting, alteration of iRBC rigidity and immune evasion. Additionally, a member of the STEVOR family has been implicated in merozoite invasion. Differential expression of these families in laboratory strains and clinical isolates propose them to be important for host cell survival and defense. The role of RIFINs in modulation of host immune response and presence of protective antibodies against these surface exposed molecules in patient sera highlights them as attractive targets of antimalarial therapies and vaccines. 2TM proteins arePlasmodiumexport elements positive, and several of these are exported to the infected erythrocyte surface after exiting through the classical secretory pathway within parasites. Cleaved and modified proteins are trafficked after packaging in vesicles to reach Maurer’s clefts, while information regarding delivery to the iRBC surface is sparse. Expression and export timing of the RIFIN andPlasmodium falciparumerythrocyte membrane protein1 families correspond to each other. Here, we have compiled and comprehended detailed information regarding orthologues, domain architecture, surface topology, functions and trafficking of members of the “2TM superfamily.” Considering the large repertoire of proteins included in the 2TM superfamily and recent advances defining their function in malaria biology, a surge in research carried out on this important protein superfamily is likely.
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Apple, Jacki. "Some Speculation on the Future of the Body and Soul." M/C Journal 2, no. 9 (January 1, 2000). http://dx.doi.org/10.5204/mcj.1821.

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It's the beginning of 2000 and the 21st century is all mapped out. Since we've just had that time at the end of a decade (not to mention the end of the century, as well as the Christian calendar "millennium"), when all the pundits came out to review where we had been and forecast where we are going, we should have expected a profundity of future-casting. But neither the familiar prognostications of the coming apocalypse spewing forth from the Religious Right, nor the usual statistical projections made by "experts" on such things as population growth, world politics, economic cycles, new products and shifting job markets, etc. will provide any help in reading the map we have already drawn up, or translating the directional signs. The future is now. It occupies the same domain as the past. Both are inhabitants of the present moment. History, memory, desire, imagination, the creative instinct, and the impetus to act, unfold and are realised as the future becomes the present. We cannot help but tinker with the universe. The future is what we make it and there are an infinite number of possible timelines. Or maybe not. It's the beginning of 2000 and the 21st century is all mapped out. The Human Genome Project1 is about to decode our physiology. We are preparing for the next evolution of the species. The battle between the cyberneticists and the geneticists for a new and improved version of homo sapiens version 3.0 has just begun. The question of where it will lead is open-ended. Will the insatiable quest for self-improvement lead to enlightenment -- a world with less suffering, hunger, disease, violence, and greed? Or, will we be the makers of our own extinction, and end up as a version of Star Trek's Borg -- the ultimate consumers, assimilating automatons devouring everything they encounter, and utterly devoid of the qualities that make us human? As an example of a hypothetical biological and social future the Borg are an interesting model -- a synthesis of a utopian socialist dream and the capitalist imperative of acquisition in the information age. As organic/cybernetic humanoid machines with one unified mind, equal and undifferentiated, untroubled by ego or id, individual ambitions, desires or passions, loneliness, alienation, or imagination they are the ultimate homogeneous collective. At the same time they are both the perfect corporate entity -- masters of the merger, the hostile takeover ("resistance is futile"), and a mindless population programmed to consume and continually upgrade each and every new technology and product. But the Borg don't invent; they only appropriate. Postmodern androids to the core! And we are presently very busy making new discoveries, creating and inventing, and transforming theories into things which tell us not only what is possible, but probable. One of the determining factors in the course of our future is whether or not our belief in technology over other values turns us into the puppets instead of the puppeteers, slaves to masters of our own invention -- be it HAL, Dr. Frankenstein's monster, or the Terminator. Let us consider some possible future scenarios, based not on fiction, but on what already exists, or is about to do so. Facts No one now disputes that the transformation of stem cells into new body parts, cloning technology, genetic engineering, nanotechnology, and microchip replacements not only could, but will dramatically change medicine and extend life in the coming century. In strictly medical terms, the implementation of all these technologies will bring about extraordinary relief of both the physical and psychological pain and suffering caused by debilitating, disabling, or disfiguring disease or injuries, not to mention the lives saved, and the genetic diseases prevented. Current research has found that not only stem cells taken from human embryos or fetuses could be directed to grow replacements for ailing hearts, livers or other organs, but that some stem cells taken from adult tissue could be converted into other types of cells -- brain cells becoming blood cells, or bone marrow becoming liver. The application of this technology is dazzling -- transformative biology, and it is just over the horizon2. Recently, scientists announced the creation of the first artificial cornea made from human cells. It could help restore the sight of those with certain kinds of eye damage. At the same time cybernetics is playing an equally important part. In development is a mini-computer that essentially takes over damaged visual functions and projects them onto a screen. One model expected to be ready for market within three years is a version of Geordie's visor in Star Trek: Next Generation. Another is a microchip that is inserted behind the eye3. In his newest book Fuzzy Future: From Society and Science to Heaven in a Chip, University of Southern California electrical engineering professor Bart Kosco, author of Fuzzy Thinking (1993), projects his theories onto everything from smart machines, the politics of genomes (who owns you, your genetic material, that is) and the environment (who owns the sea, or for that matter the air) to the problem of human mortality. Kosco foresees the day when we may be able to download our brains onto a microchip, thus achieving digital immortality via a gradual (fuzzy) transformation in which the brain's "meat" is replaced piece by piece with nanochips that work ever faster, better, and more creatively than old-fashioned neurons and synapses. The use of microchips to repair or replace damaged cells or portions of the brain is one thing, but as a means to greatly increase mental capacity, and gain everlasting life by "leaving your gray matter pickled in a jar" in favour of a computer in your skull is another. Would you still be you? While researchers have currently found new molecules in the brain that play a role in creating memories and learning, it does not ensure wisdom in how we put our knowledge to work. That great benefits await us, in the prevention and treatment of disease and the disintegration due to aging, is not in dispute. Nor is the enhanced capacity of a healthier society in body and mind. What constitutes the latter is. We are still left with ethical questions about the uses of technology, and spiritual and philosophical questions about what it means to be human. What are the political and social ramifications of biotechnology? British television playwright Dennis Potter's last work Cold Lazarus represents the ethical dilemmas of a future world capable of robbing a man's soul against his will. Scientists, whose funding is controlled by one or another governing media megalomaniac, seek to experience the 20th century through the genuine memories of the late Daniel Feeld, whose frozen head they have obtained. Their biochemical experiments are no less despicable than the CEO who wants to broadcast Feeld's "consciousness" worldwide twenty-four hours a day. Political opposition exists only in the form of a clandestine "terrorist" organization known as R.O.N. (Reality Or Nothing). If we were to base our forecasts on the patterns of history, just such a techno-fascist corporate future awaits us. If we are to judge by the dominant values of the present, the economic priorities of the marketplace will overpower the dissenting voices, placing not only the natural environment at risk, but our social environment as well. What will such a society do about the underclasses when smart machines have taken over their work, and they haven't the means to buy our goods, only consume precious resources; that is, when they are no longer "necessary" to the economic system. Will they be technologically phased out or upgraded? Fast Forward Let's not jump too far ahead. Maybe just to 2050. You can grow your own body part replacements, not just internal organs, but muscle, nerve tissue, skin. You can rejuvenate. Living to 120 or longer will not be unusual. The manufacture of body parts will be a big biotech business. Invest now! But will this technology be available to anyone and everyone, or only those who can afford it? Will we have parts kept in cold storage ready and waiting? Organs grown from extractions of our own foetal tissue perhaps. If it is a right not a privilege, how will our society deal with the problems of overpopulation? Will only those over a certain age -- say 80 -- who are viewed as "contributing" or "productive" members of society be eligible for new organs? Or will your lifestyle and health habits be a factor? No new livers for recalcitrant unreformed alcoholics? Will there be a ranking system of qualifications? Who will decide what they will be? Never mind arms and drugs. Consider this black market in the making! Subterranean high-tech operating rooms, organ factories, contraband stem cells, DNA, "smart" nanochips. Fast Forward And what about those microchips for brain functions? Not just for disease but for self-improvement. You might be able to improve your personality the way you can have a face-lift or breast implants. Then again, microchips could replace both pharmacology and psychotherapy in the treatment of mental disease, or merely antisocial or criminally aberrant behaviour, a new form of rehabilitation. As for sheer brain power, there would be no end to your capacity to absorb information, memorize and catalogue it, or to calculate stock market transactions. And just think of the lawsuits bound to jam up the courts, should someone have the misfortune to get a faulty chip, or even one that doesn't live up to expectations. Advertising is bound to promise you the answer to your dreams. The insertion of these parts by choice is one thing, but suppose it is forced on you by a government or a corporation. Or even by a parent while you are too young to fight back, the ones who want their offspring to be a math genius, Olympic athlete, or musical prodigy. Then again, genetic engineering may take care of some of that. Babies to order. By the end of this century you might not even have to have one the old messy way. Or you might not even be allowed to. Your genetically selected child might be grown in a computer-controlled organic womb. No more unwanted pregnancies. No more crack babies, or Downs Syndrome, or spina bifida4. We've been messing around for quite some time with a lot of things we don't know or haven't considered the consequences of in terms of the long term ecological balance of life and all its interdependent systems: cross-species genetic implants in plants and animals; plants altered to kill insects that are food for another creature on the food chain. And so on up the ladder: tomatoes that only look like tomatoes, but aren't really tomatoes any more. A perfect example of surface over substance. While we are so sure of our technological mastery, the actual "apocalypse" may well be of our own making when the forces of nature wreak havoc and pay us back for our abuses and arrogance. Or perhaps it will be nature's way of resetting the balance of things by greatly reducing the human population. Or it just might turn out this way. The newly evolved, genetically and cybernetically enhanced humanoids 3.0 survive and adapt (to 3.5), while the great mass of old humans become an endangered species like the Siberian tiger. Present Tense If you think this is all just science fiction, consider this. Already a number of young men in Silicon Valley or at M.I.T. walk around all day every day with one eye and ear always focused on the little headset computer screen that keeps them perpetually "on-line", plugged in. Do they look a little like the Borg? Well yes. Or, think about this. About a year ago a bill came up in the California state legislature proposing that a microchip be inserted in all newborn infants, like the ones you can put in your dog so you can track her if she gets lost or stolen. Same principle with babies. The bill was defeated. But very soon we will all be locatable, "on-line". No chance of disappearing in the 21st century when the wilderness is about to become another "theme" park, and when, at this very moment, you can be traced every time you use a plastic card or make a phone call. What a scary thought for dissidents, revolutionaries, battered women, or anyone who just wants to "get away from it all". In the 21st century, Huxley's "savages" would have as hard a time surviving or avoiding capture as a wolf in Arizona. How will our civil rights, our human rights be affected at the present rate of invasion into our privacy. Is your body your own? And what about your mind? What exactly will the "right to your life" mean? Will "smart" machines have that right? How will we define a sentient being? And so here we are. The 21st century is all mapped out. Maps can be misread. Maps can be wrong. The place that has been charted can be changed. By a force of nature, or an act of will. Or better still, by an act of conscience or consciousness, for it is an energy force with transformative powers. We could become better in our hearts and souls. We could use our knowledge with grace. Now go out and draw a new map(s). Happy New Century! Footnotes Huge advances in genomics, the science of deciphering the basic genetic pattern of life, were made in 1999, including the complete gene sequence for three microbes, a third of the base pairs in human DNA, along with one complete chromosome, number 22, and a rough draft of the entire human genome is expected by March 2000. For more about the Human Genome Project check out the following Website: http://www.ornl.gov/hgmis/ and all its links. Also http://www.turbulence.org/ for Bionet :: Recombinant by Eugene Thacker, an artist's "attempt to assemble a body of discourse surrounding contemporary molecular genetics and biotechnology at the end of the millenium". Science journal editor Floyd E. Bloom optimistically predicts that "although much remains to be done to convert today's results into tomorrow's treatments and tools, the likelihood of success seems high". Researchers in this field are: May Griffith, Research Scientist, University of Ottowa Eye Institute, Professor, Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario Gislin Dagnelie, Researcher, Lions Vision Research and Rehabilitation Center, Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland Dr. Thomas Friberg, Professor, Ophthalmology, Chairman, Department of Ophthalmology, Director of Retina and Vitreous Service, The Eye and Ear Institute of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania Dr. Terry Ernest, Professor, Chairman, Ophthalmology and Visual Science, University of Chicago Medical Center, University of Chicago, Chicago, Illinois A congenital cleft of the vertebral column with hernial protrusion of the meninges (membranes that envelop the brain and spinal cord). Citation reference for this article MLA style: Jacki Apple. "Some Speculation on the Future of the Body and Soul." M/C: A Journal of Media and Culture 2.9 (2000). [your date of access] <http://www.uq.edu.au/mc/0001/body.php>. Chicago style: Jacki Apple, "Some Speculation on the Future of the Body and Soul," M/C: A Journal of Media and Culture 2, no. 9 (2000), <http://www.uq.edu.au/mc/0001/body.php> ([your date of access]). APA style: Jacki Apple. (2000) Some speculation on the future of the body and soul. M/C: A Journal of Media and Culture 2(9). <http://www.uq.edu.au/mc/0001/body.php> ([your date of access]).
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