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Genetically engineered mouse models have the potential to unravel fundamental biological processes and provide mechanistic insights into the pathogenesis of human diseases. We have previously observed that germline genetic variation at the TULP4 locus influences clinical characteristics in patients with myeloproliferative neoplasms. To elucidate the role of TULP4 in pathological and physiological processes in vivo, we generated a Tulp4 knockout mouse model. Systemic Tulp4 deficiency exerted a strong impact on embryonic development in both Tulp4 homozygous null (Tulp4−/−) and heterozygous (Tulp4+/−) knockout mice, the former exhibiting perinatal lethality. High‐resolution episcopic microscopy (HREM) of day 14.5 embryos allowed for the identification of multiple developmental defects in Tulp4−/− mice, including severe heart defects. Moreover, in Tulp4+/− embryos HREM revealed abnormalities of several organ systems, which per se do not affect prenatal or postnatal survival. In adult Tulp4+/− mice, extensive examinations of hematopoietic and cardiovascular features, involving histopathological surveys of multiple tissues as well as blood counts and immunophenotyping, did not provide evidence for anomalies as observed in corresponding embryos. Finally, evaluating a potential obesity‐related phenotype as reported for other TULP family members revealed a trend for increased body weight of Tulp4+/− mice. Research Highlights: To study the role of the TULP4 gene in vivo, we generated a Tulp4 knockout mouse model.Correlative analyses involving HREM revealed a strong impact of Tulp4 deficiency on murine embryonic development. [ABSTRACT FROM AUTHOR]

Background: Haemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) has a potentially high mortality rate. Anakinra, an interleukin‐1 receptor antagonist, is now recommended early in HLH/MAS, with intravenous (IV) use proposed in critically unwell patients. This systematic review establishes the literature relating to IV anakinra in secondary HLH/MAS (sHLH/MAS). Methods: We screened Embase, PubMed, and Medline, including all reports of IV anakinra for HLH or MAS. We extracted age, HLH/MAS trigger, continuous infusion or bolus dosing, and survival. Results: Twenty‐nine case reports/series identified 87 patients (median age 22 years, range 22 months to 84 years), all with sHLH. Amongst identifiable triggers, 43% were systemic infection, 33% rheumatological, 9% oncological. Children had predominantly a rheumatological trigger (48%), whilst adults were more commonly infection‐driven (50%). Overall, rheumatologically triggered disease showed greater survival (83.3%), particularly compared with oncological triggers (42.9%). Children had a greater survival, particularly under 10 years (83%, vs. adults, 63%). Conclusions: Despite IV anakinra recipients likely to be critically unwell, this cohort had similar disease triggers and survival compared to large historical cohorts, and enhances awareness of age and trigger‐specific survival patterns. IV anakinra had a wide therapeutic dosing range and tolerability, regardless of trigger, demonstrating substantial utility in severe sHLH/MAS. [ABSTRACT FROM AUTHOR]

"Chiral pool" compounds possessing well defined stereocenters and suitable functionality serve as excellent building blocks for the synthesis of natural products and therapeutically important compounds. Tartaric acid is a C2‐symmetric molecule available in both enantiomeric forms. It was extensively utilized in the synthesis of privileged chiral ligands/catalysts such as TADDOLs, and as a start point in the synthesis of plethora of compounds. The advent of several new C−C bond forming reactions offers opportunity for the development of novel synthetic strategies based on chiral pool compounds. We found that the desymmetrization of the bis‐dimethyl amide/Weinreb amide derived from tartaric acid can be accomplished by controlled addition of Grignard /organolithium reagents leading to the mono keto amides, the reduction of which affords the γ‐hydroxy amides. This account describes our research efforts of more than a decade on the synthesis and application of diverse γ‐hydroxy amides derived from tartaric acid in the total synthesis of structurally simple to complex bio‐active natural products. [ABSTRACT FROM AUTHOR]

A formal total synthesis of the marine macrolide iriomoteolide 3a is described. Salient features of the synthesis include the elaboration of a β-keto phosphonate derived from D-(−)-tartaric acid and the extension of a chiral butyrolactone derived from L-glutamic acid. Ring-closing metathesis is employed to construct the macrolactone core of the natural product. [ABSTRACT FROM AUTHOR]

A novel ring contraction/rearrangement sequence leading to functionalized 2,8-oxymethano-bridged di- and triquinane compounds is observed in the reaction of various substituted 1-methyl-4-isopropenyl-6-oxabicylo[3.2.1]octan-8-ones with Lewis acids. The reaction is novel and is unprecedented for the synthesis of di- and triquinane frameworks. [ABSTRACT FROM AUTHOR]

Aim This study examines possible predictors of physical and social functioning in adolescents with rheumatological conditions. Condition-related variables and psychosocial variables were studied, and their relative contribution as predictors was examined. Methods The study population was one hundred and twelve adolescents (11-18 years) attending secondary and tertiary paediatric rheumatology outpatient clinics in south-west England. These adolescents completed validated self-report accounts of disease history, pain and functioning (condition-related variables) and the Bath Adolescent Pain Questionnaire (psychosocial variables). Correlation and regression analyses were used to establish influences on physical and social functioning, examining condition-related variables and psychosocial variables as separate blocks. Results Physical functioning was independently associated with age at onset, intensity of pain, presence of depression and pain-specific anxiety. Social functioning was only associated with general anxiety. The presence of an inflammatory diagnosis had no bearing on optimal functioning in this study. Conclusion Condition-related variables (age at onset, pain intensity) and psychosocial variables (depression, pain-specific anxiety) were equally important for physical functioning, whereas psychosocial variables (general anxiety) were more influential for social functioning. Understanding the impact of disease and associated variables in the adolescent rheumatology population should optimize targeted multidisciplinary rehabilitation for the young person and their family. [ABSTRACT FROM AUTHOR]

Total synthesis of the polyhydroxy caprolactam amide natural product, bengamide E, is accomplished starting from tartaric acid. Key reactions in the synthesis include desymmetrization of the bis(dimethylamide) unit of tartaric acid, Zn(BH4)2-mediated anti-selective reduction, and a Horner-Wadsworth-Emmons olefination. [ABSTRACT FROM AUTHOR]

A formal total synthesis of the 20-membered marine macrolide, palmerolide A from chiral pool tartaric acid is described. Elaboration of a γ-hydroxy amide, which is derived from the desymmetrization of tartaric acid amide, and Boord olefination are the pivotal reactions employed for the synthesis of the chiral building blocks, and Stille coupling and ring-closing metathesis (RCM) are used to assemble the macrolactone. [ABSTRACT FROM AUTHOR]

In addition to the (E)-selective title reaction, simple furyl propargyl carbinols are transformed via an unexpected dehydration/ketalisation sequence to separable E/Z isomers of conjugated enynes. [ABSTRACT FROM AUTHOR]

The seven step synthesis of the starting materials is described. [ABSTRACT FROM AUTHOR]

The isopropenyl substituted starting compounds (I) are prepared in a 3 step sequence starting from a known, geraniol-derived building block. [ABSTRACT FROM AUTHOR]

The article presents chemical equations related to the article "Total Synthesis of the Indole Alkaloids Henrycinol A (Ia) and B (Ib)" by M. Sridharan and others, published in the periodical "Tetrahedron" in 2014.

The article presents a chemical formula related to the article "Total Synthesis of (+)-Anamarine" by K. R. Prasad and others, published in the periodical "Tetrahedron" in 2014.

The article presents chemical equations related to the article "Total Synthesis of (+)-Seimatopolide A" by K. R. Prasad and O. Revu, published in the periodical "Journal of Organic Chemistry" in 2014.

The enantioselective alkylation of aldehydes with diethylzinc is achieved in the presence of a chiral sulfinamide as optimal catalyst. [ABSTRACT FROM AUTHOR]

The article presents the chemical steps involved in the synthesis of isochromanones and isoquinolones.