Nephrotoxic Lesions from 5-Aminosalicylic Acid

5-Aminosalicylic acid given to rats as a single intravenous injection led to necrosis of the proximal convoluted tubules and of the renal papilla. These two lesions developed at the same time and the cortical lesions did not appear to be a consequence of the renal papillary necrosis. Since the compound possesses the molecular structure both of a phenacetin derivative and of a salicylate these observations may be relevant to the problem of renal damage incident to abuse of analgesic compounds and suggest the possibility that in this syndrome cortical lesions may develop independently of renal papillary necrosis.     

Pollen morphology of Trichosanthes (Cucurbitaceae)

The pollen morphology of 37 species of Trichosanthes was examined, using light microscopy, and scanning and transmission electron microscopy. On the basis of the diverse exine ornamentation it is possible to distinguish five pollen types. With aperture characters, two of them can be subdivided into subtypes. Two types can be characterised with ultrastructural features as well. It appeared that several of the types (alt. subtypes) correspond very well to existing macromorphological groupings. The most deviating type, including only the monotypic section Trichosanthes (T. cucumerina), shows verrucate ornamentation, a thick granular infratectum and a thin, indistinctly delimited nexine. It is similar to that of the Madagascan genus Tricyclandra.     

Notes on the genus Amorphophallus (Araceae) – 13. Evolution of pollen ornamentation and ultrastructure in Amorphophallus and Pseudodracontium

A strict consensus tree based on chloroplast and nuclear sequences (rbcL, matK, trnL, FLint2) from 46 Amorphophallus species, two Pseudodracontium species and six outgroups is used to develop a hypothesis for the evolution of ornamentation and ectexine ultrastructure in the pollen of Amorphophallus. There are four main clades: an exclusively African, largely psilate clade (‘African clade’), an Asian, largely psilate clade (‘Asian psilate clade’) and an Asian, largely striate clade consisting of a mainly continental SE Asian clade (‘continental SE Asian striate clade’) and one centred in Malesia (‘Malesian striate clade’). Ultrastructure provides a valuable contribution towards understanding pollen ornamentation in Amorphophallus. Pollen with a thin psilate ectexine without dark granules might be plesiomorphic in Amorphophallus. Then the diverse striate type would be derived. Within both striate clades, reversals to the psilate type occur. Striate pollen with psilate caps, which is nested in the continental SE Asian striate clade, is a synapomorphy of Pseudodracontium. The fossulate type is also diverse, and its distribution in the tree indicates a polyphyletic origin. Areolate, echinate and verrucate ornamentation, occur in single species in the tree, but are found also in species not included in the molecular analysis. All three are heterogeneous and probably polyphyletic too. Reticulate, scabrate and striate/scabrate ornamentation are autapomorphies, of which the reticulate type and the striate/scabrate type may derive from psilate and striate ornamentation, respectively. Of the four main clades, the Asian psilate and African clade seem to be basal, while both striate clades might have evolved from the Asian psilate clade via a species like A. rhizomatosus. Dark granules evolved more than once, which might explain their diverse size, shape and distribution.     

“Thinking a Lot” Among the Khwe of South Africa: A Key Idiom of Personal and Interpersonal Distress

“Thinking too much”, and variations such as “thinking a lot”, are common idioms of distress across the world. The contextual meaning of this idiom of distress in particular localities remains largely unknown. This paper reports on a systematic study of the content and cause, consequences, and social response and coping related to the local terms |x’an n|a te and |eu-ca n|a te, both translated as “thinking a lot”, and was part of a larger ethnographic study among the Khwe of South Africa. Semi-structured exploratory interviews with community members revealed that “thinking a lot” refers to a common experience of reflecting on personal and interpersonal problems. Consequences were described in emotional, psychological, social, behavioral, and physical effects. Coping strategies included social support, distraction, and religious practices. Our contextualized approach revealed meanings and experiences of “thinking a lot” that go beyond a psychological state or psychopathology. The common experience of “thinking a lot” is situated in socio-political, economic, and social context that reflect the marginalized and displaced position of the Khwe. We argue that “thinking a lot” and associated local meanings may vary across settings, may not necessarily indicate psychopathology, and should be understood in individual, interpersonal, community, and socio-political dimensions.     

SEK1-dependent JNK1 activation prolongs cell survival during G-Rh2-induced apoptosis

We provide here evidence that c-Jun N-terminal protein kinase 1 (JNK1) activity is differentially up-regulated during apoptosis of SK-HEP-1 cells after treatment with ginsenoside Rh2 (G-Rh2). The G-Rh2-mediated JNK1 activation that occurred for the first 10-30min was associated with SEK1 activity, but thereafter, the sustained activation was associated not with SEK1 activity, but with proteolytic cleavage of JNK1-associated p21(WAF1/CIP1). Supporting this is that the expression of the dominant negative SEK1 mutant effectively blocked the early JNK1 activation phase but did not alter the sustained activation phase or apoptosis. Furthermore, expression of p21D112N, an uncleavable mutant of p21(WAF1/CIP1), suppressed the later JNK1 activation. Moreover, the stable overexpression of ectopic JNK1 suppressed apoptosis while expression of the dominant negative JNK1 mutant promoted it. We propose that the early SEK1-associated JNK1 activation phase acts to prolong cell survival in response to apoptosis-inducing agents, thereby serving as an intervening checkpoint prior to the commitment to apoptosis.     

The mobility of curium-244 dioxide in the bronchially intubated rat.

The mobility of curium dioxide in the rat after pulmonary intubation has been investigated by administering suspensions containing different particle size ranges of the oxide. A major factor influencing the movement of curium from lungs to blood is the formation of hydroxide or hydrous oxide particles about 0.001 micrometer in diameter. This process is sufficiently rapid for the lung clearance kinetics of the dioxide to resemble those of a soluble compound more closely than those of an insoluble one. Filtration of 0.001 micrometer particles through the kidneys results in considerably enhanced excretion of curium relative to administered curium citrate. It is concluded that current metabolic models, which assume that solubility in the lung is a prerequisite for transport in body fluids, do not adequately describe the behaviour of curium fromthe standpoint of radiological protection.     

A stereo-controlled synthesis of 2,4-dimethyl-4-hydroxy-16-phenylhexadecanoic acid 1,4-lactone and its PPAR activities

A novel class of natural PPAR agonists, 2,4-dimethyl-4-hydroxy-16-phenylhexadecanoic acid 1,4-lactone (1), were discovered in marine natural product libraries. The synthesis of 1 was accomplished starting from vinylmethyl ketone. Ring formation of the α,γ dialkyl γ-lactone was achieved via the stereo-controlled reaction of a ketyl radical anion with a chiral methacrylate. In the PPAR agonistic assay, the most potent of the four stereoisomers had EC₅₀ values of 12 μM for mPPARα, 9 μM for mPPARδ and >100 μM for mPPARγ.     

Bayesian Markov Random Field Analysis for Protein Function Prediction Based on Network Data

Inference of protein functions is one of the most important aims of modernbiology. To fully exploit the large volumes of genomic data typically producedin modern-day genomic experiments, automated computational methods for proteinfunction prediction are urgently needed. Established methods use sequence orstructure similarity to infer functions but those types of data do not sufficeto determine the biological context in which proteins act. Currenthigh-throughput biological experiments produce large amounts of data on theinteractions between proteins. Such data can be used to infer interactionnetworks and to predict the biological process that the protein is involved in.Here, we develop a probabilistic approach for protein function prediction usingnetwork data, such as protein-protein interaction measurements. We take aBayesian approach to an existing Markov Random Field method by performingsimultaneous estimation of the model parameters and prediction of proteinfunctions. We use an adaptive Markov Chain Monte Carlo algorithm that leads tomore accurate parameter estimates and consequently to improved predictionperformance compared to the standard Markov Random Fields method. We tested ourmethod using a high quality S.cereviciae validation networkwith 1622 proteins against 90 Gene Ontology terms of different levels ofabstraction. Compared to three other protein function prediction methods, ourapproach shows very good prediction performance. Our method can be directlyapplied to protein-protein interaction or coexpression networks, but also can beextended to use multiple data sources. We apply our method to physical proteininteraction data from S. cerevisiae and provide novelpredictions, using 340 Gene Ontology terms, for 1170 unannotated proteins and weevaluate the predictions using the available literature.