An important 2���-OH group for an RNA–protein interaction

We have investigated the role of 2���-OH groups in the specific interaction between the acceptor stem of Escherichia coli tRNACys and cysteine-tRNA synthetase. This interaction provides for the high aminoacylation specificity observed for cysteine-tRNA synthetase. A synthetic RNA microhelix that recapitulates the sequence of the acceptor stem was used as a substrate and variants containing systematic replacement of the 2���-OH by 2���-deoxy or 2���-O-methyl groups were tested. Except for position U73, all substitutions had little effect on aminoacylation. Interestingly, the deoxy substitution at position U73 had no effect on aminoacylation, but the 2���-O-methyl substitution decreased aminoacylation by 10-fold and addition of the even bulkier 2���-O-propyl group decreased aminoacylation by another 2-fold. The lack of an effect by the deoxy substitution suggests that the hydrogen bonding potential of the 2���-OH at position U73 is unimportant for aminoacylation. The decrease in activity upon alkyl substitution suggests that the 2���-OH group instead provides a monitor of the steric environment during the RNA–synthetase interaction. The steric role was confirmed in the context of a reconstituted tRNA and is consistent with the observation that the U73 base is the single most important determinant for aminoacylation and therefore is a site that is likely to be in close contact with cysteine-tRNA synthetase. A steric role is supported by an NMR-based structural model of the acceptor stem, together with biochemical studies of a closely related microhelix. This role suggests that the U73 binding site for cysteine-tRNA synthetase is sterically optimized to accommodate a 2���-OH group in the backbone, but that the hydroxyl group itself is not involved in specific hydrogen bonding interactions.

Retro and retroenantio analogs of cecropin-melittin hybrids.

Hybrid analogs of cecropin A (CA) and melittin (M), which are potent antibacterial peptides, have been synthesized. To understand the structural requirements for this antibacterial activity, we have also synthesized the enantio, retro, and retroenantio isomers of two of the hybrids and their N-terminally acetylated derivatives. All analogs of CA(1-13)M(1-13)-NH2 were as active as the parent peptide against five test bacterial strains, but one bacterial strain was resistant to the retro and retroenantio derivatives. Similarly, all analogs of CA(1-7)M(2-9)-NH2 were active against four strains, while two strains were resistant to the retro and retroenantio analogs containing free NH3+ end groups, but acetylation restored activity against one of them. From these data it was concluded that chirality of the peptide was not a critical feature, and full activity could be achieved with peptides containing either all L- or all D-amino acids in their respective right-handed or left-handed helical conformations. For most of the bacterial strains, the sequence of these peptides or the direction of the peptide bonds could be critical but not both at the same time. For some strains, both needed to be conserved.

Avaliação dos biomarcadores urinários no controle do tratamento de estenose de junção ureteropélvica em adultos

INTRODUÇÃO E OBJETIVO: A estenose de junção ureteropélvica (EJUP) é importante causa de obstrução do trato urinário e pode levar a deterioração progressiva da função renal. Há espaço para o aprimoramento de novos métodos diagnósticos capazes de discriminar hidronefrose e uropatia obstrutiva. Acredita-se que os biomarcadores urinários podem fornecer indícios de lesão renal precoce na obstrução urinária. Neste contexto, KIM-1 pode elevar-se na urina por lesão tubular proximal, NGAL por lesão no túbulo proximal, distal ou alça de Henle, CA19-9 por produção excessiva no túbulo obstruído e ?2-microglobulina (beta2M) por injúria ao glomérulo ou ao túbulo proximal. O objetivo do presente estudo foi avaliar as propriedades diagnósticas dos biomarcadores urinários citados em adultos com EJUP, sendo o primeiro estudo na literatura a avaliar tais moléculas nesta população. MÉTODOS: Foram estudados de modo prospectivo pacientes consecutivos acima de 18 anos com diagnóstico de EJUP submetidos a pieloplastia videolaparoscópica de dezembro de 2013 a fevereiro de 2015. Foram excluídos do estudo pacientes com EJUP bilateral, rim contralateral patológico, EJUP em rim único, antecedentes de tratamento cirúrgico para estenose de JUP ou taxa de filtração glomerular inferior a 60 ml/min/1,73m2. Cada paciente forneceu quatro amostras de urina para medição de biomarcadores, uma no pré-operatório e outras com 1, 3 e 6 meses de seguimento pós-operatório. O grupo controle foi constituído por voluntários saudáveis sem hidronefrose à ultrassonografia. RESULTADOS: Foram incluídos 47 pacientes com idade média de 38,6 ± 12,7 anos (intervalo 19 a 64 anos), sendo 17 (36,2%) do sexo masculino e 30 (62,8%) do sexo feminino. O grupo controle foi composto por 40 indivíduos semelhantes ao grupo com EJUP no que concerne idade (p = 0,95) e sexo (p = 0,82). KIM-1 foi o marcador com melhores propriedades diagnósticas, apresentando área sob a curva (AUC) de 0,79 (95% CI 0,70 a 0,89). O NGAL, por sua vez, teve AUC de 0,71 (95% CI 0,61 a 0,83), CA19- 9 teve AUC de 0,70 (95% CI 0,60 a 0,81) e (beta2M) apresentou AUC de 0,61 (95% CI 0,50 a 0,73), sendo o único biomarcador com propriedades inadequadas neste cenário. O KIM-1 foi o marcador mais sensível com o ponto de corte 170,4 pg/mg de creatinina (sensibilidade 91,4%, especificidade 59,1%) e o CA 19-9 o mais específico para o ponto de corte de 51,3 U/mg de creatinina (sensibilidade 48,9%, especificidade 88,0%), enquanto o NGAL foi o que apresentou maior queda após desobstrução, com 90,0% dos pacientes apresentando clareamento superior a 50%. CONCLUSÕES: A avaliação dos biomarcadores urinários é útil no diagnóstico de obstrução em adultos com EJUP submetidos a pieloplastia videolaparoscópica. O KIM-1 foi o marcador mais sensível e o CA 19-9 o mais específico, enquanto o NGAL foi o que apresentou maior que com a desobstrução. Houve queda das concentrações dos marcadores após pieloplastia no período estudado. O papel exato dos biomarcadores urinários no cenário de obstrução em adultos deve ser mais amplamente investigado

Organocatalytic Asymmetric α-Chlorination of 1,3-Dicarbonyl Compounds Catalyzed by 2-Aminobenzimidazole Derivatives

Bifunctional chiral 2-aminobenzimidazole derivatives 1 and 2 catalyze the enantioselective stereodivergent α-chlorination of β-ketoesters and 1,3-diketone derivatives with up to 50% ee using N-chlorosuccinimide (NCS) or 2,3,4,4,5,6-hexachloro-2,5-cyclohexadien-1-one as electrophilic chlorine sources.

Letter from S. Brown to William Tudor,

One letter thanking Tudor for sending Brown a memoir of the late William Tudor.

(Table 1) Granulometry, soil pH, carbonate content and color description of soil profiles obtained in Xinghai, Tibet

Large parts of the eastern half of the Tibetan Plateau are covered between (3,500) 4,000 and nearly 6,000 m a.s.l. by alpine sedge mats (key species Kobresia pygmea), which attain an extension of ca. 450,000 km**2. It is considered to be the world's largest alpine ecosystem. Moreover, there exist isolated (relic) forests in the same area up to an altitude of 4,700 m a.s.l. mainly consisting of juniper (Juniperus) and spruce (Picea). Large parts of the Kobresia ecosystem are expected to be a grazing-resistant replacement formation, replacing forests and grass-dominated plant communities due to human and/or climatic impact. Recently, a research project was launched to increase knowledge about the properties and genesis of these forests and sedge mats (Present-day dynamics and Holocene landscape history of fragmented forest biocoenoses in Tibet; headed by G. Miehe, Marburg).

(Table 1) Age determination of sediment cores of the Labrador Sea

A close look at the sedimentology of Heinrich event 4 from the northwest Labrador Sea indicates that an extended ice margin, perhaps greater than before Heinrich events 1 or 2 (H-1 and H-2), existed in the Hudson Strait region pre-Heinrich event 4 (H-4) and, that on the basis of characteristics of the sediment unit, Heinrich event-4 was different than Heinrich events 1 or 2 (i.e., larger ice sheet collapse(?), longer duration(?), "dirtier" icebergs(?)). Other data from across the southern and eastern margin of the Laurentide Ice Sheet, as well as Greenland and the North Atlantic, support this interpretation, possibly indicating a relative mid-Wisconsin glacial maximum pre-Heinrich event 4. Many of these data also indicate that Heinrich event 4 (35 ka) resulted in serious climatic and oceanographic reorganizations. We suggest that Heinrich event 4 gutted the Hudson Strait, leaving it devoid of ice for Heinrich event 3. We further hypothesize that Heinrich event 3 did not originate from axial ice transport along the Hudson Strait; thus Heinrich event 3 may be more analogous to the proposed northward advancing ice from Ungava Bay during Heinrich event 0 than to the more typical down-the-strait flow during H-1, H-2, and H-4. Consequently, the climatic and oceanographic impacts resulting from Heinrich events are highly susceptible to the type, origin, and magnitude of ice sheet collapse, something which varied per Heinrich event during the last glacial period.

[Calligraphic specimen, 1206, i.e. 1791 or 1792].

Exquisite album of calligraphy (muraqqaʻ / murakkaa) employing ḥadīth of the Prophet executed by the celebrated Ottoman calligrapher Mahmud Celâleddin Efendi (d.1829) in imitation of a model executed by the master calligrapher Hafız Osman Efendi (d.1698).

Ausführliche Abhandlung der römischen Alterthümer /

Includes indexes and errata.

Naẓm al-Jamīʻ al-ṣaghīr, [late 15th century?].

Fine copy of Abū Naṣr al-Farāḥī's (d.1242) versification of al-Jamīʻ al-ṣaghīr fī al-furūʻ, the well-known legal treatise by Muḥammad ibn al-Ḥasan al-Shaybānī (d.804). Excerpts from Kashf al-ẓunūn addressing these two works appear on leaf affixed to 'title page' (p.5).

A treatise on the eye, the manner and phaenomena of vision. In two volumes /

Mode of access: Internet.

Clavis Homerica, sive Lexicon vocabulorum omnium, quae in Homeri Iliade et potissima parte Odysseae continentur : cum indice locupletissimo necnon de dialectis et figuris appendice : quibus accessere varia elogia seu testimonia de Homero : etiam Michaelis Apostolii Proverbia Graeco-Latina.

Dunbar's "Rules, &c. of Homer's versification," in English: p. [v]-vii.

A General history of New England, from the discovery to MDCLXXX /

Mode of access: Internet.

Dramatic works of William Shakspeare, with a life of the poet and notes, original and selected.

v.2. Midsummer-night's dream. Love's labor's lost. Merchant of Venice. As y@u like it. All's well that ends well. Taming of the shrew.--v.3. Winter's tale. Comedy of errors. Macbeth. King John. King Richard the second. King Henry the fourth, pt. 1st.--v.4. King Henry the fourth, pt. 2d. King Henry the fifth. King Henry the sixth, pt. 1st - 3d.--v.5. King Richard the third. King Henry the eighth. Troilus and Cressida. Timon of Athens. Coriolanus.--v.7. King Lear. Romeo and Juliet. Hamlet, prince of Denmark. Othello, the Moor of Venice.

The Two Americas : Their complete history, from the earliest discoveries to the present day /

Earlier editions appeared under title: The People's history of America.