Monosomy 9pter and trisomy 9q34.11qter in two sisters due to a maternal pericentric inversion

Pericentric inversions of chromosome 9 leading to unbalanced live-born offspring are relatively rare and so far only four cases have been reported. Here we present two sisters with an unbalanced recombinant chromosome 9 which resulted from a large maternal pericentric inversion inv(9)(p24.3q34.1). Further molecular characterisation of the aberrant chromosome 9 by 250k SNP array analysis showed a terminal 460 kb loss of 9p24.3 and a terminal 8.9 Mb gain of 9q34.11. We compared the clinical features of these two patients with the previous reported four cases as well as with patients with similar sized 9pter deletions or 9qter duplications. Based upon this study, we suggest that the recombinant chromosome 9 phenotype is mainly the result of duplication of a 3.4 Mb region of chromosome 9q34.11q34.13.     

Ferulic acid ethyl ester as a potential therapy in neurodegenerative disorders

Oxidative stress is involved in the onset, progression and pathogenesis of a number of diseases including neurodegenerative diseases. It is critical to develop a pharmacological approach to combat oxidative stress which may reduce the risk of diseases and help in promoting healthy life. In an attempt to reduce the side effects associated with allopathic medicines a number of studies are now focusing on developing treatment regimens from naturally occurring plant products. In this review, the protective role of ferulic acid (4-hydroxy-3-methoxycinnamic acid) (FA), a naturally occurring antioxidant compound found in fruit, some vegetables, and grains, and its ethyl ester derivative are discussed with respect to neurodegeneration. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.     

Translation initiation factor 4B homodimerization, RNA binding, and interaction with Poly(A)-binding protein are enhanced by zinc

The eukaryotic translation initiation factor (eIF) 4B promotes the RNA-dependent ATP hydrolysis activity and ATP-dependent RNA helicase activity of eIF4A and eIF4F during translation initiation. eIF4B also helps to organize the assembly of the translational machinery through its interactions with eIF4A, eIF4G, eIF3, the poly(A)-binding protein (PABP), and RNA. Although the function of eIF4B is conserved among plants, animals, and yeast, eIF4B is one of the least conserved of initiation factors at the sequence level. Mammalian eIF4B is a constitutive dimer; however, conflicting reports have suggested that plant eIF4B may exist as a monomer or a dimer. In this study, we show that eIF4B from wheat can form a dimer and we identify the region responsible for its dimerization. Zinc stimulated homodimerization of eIF4B and bound eIF4B with a Kd of 19.7 nM. Zinc increased the activity of the eIF4B C-terminal RNA-binding domain specifically. Zinc promoted the interaction between eIF4B and PABP but not the interaction between eIF4B and eIF4A or eIFiso4G, demonstrating that the effect of zinc was highly specific. The interaction between PABP and eIFiso4G was also stimulated by zinc but required significantly higher levels of zinc. Interestingly zinc abolished the ability of eIFiso4G to compete with eIF4B in binding to their overlapping binding sites in PABP by preferentially promoting the interaction between eIF4B and PABP. Our observations suggest that wheat eIF4B can dimerize but requires zinc. Moreover zinc controls the partner protein selection of PABP such that the interaction with eIF4B is preferred over eIFiso4G.     

New findings of Neurospora in Europe and comparisons of diversity in temperate climates on continental scales

The life cycles of the conidiating species of Neurospora are adapted to respond to fire, which is reflected in their natural history. Neurospora is found commonly on burned vegetation from the tropic and subtropical regions around the world and through the temperate regions of western North America. In temperate Europe it was unknown whether Neurospora would be as common as it is in North America because it has been reported only occasionally. In 2003 and 2004 a multinational effort surveyed wildfire sites in southern Europe. Neurospora was found commonly from southern Portugal and Spain (37 degrees N) to Switzerland (46 degrees N). Species collected included N. crassa, N. discreta, N. sitophila and N. tetrasperma. The species distribution and spatial dynamics of Neurospora populations showed both similarities and differences when compared between temperate Europe and western North America, both regions of similar latitude, climate and vegetation. For example the predominant species in western North America, N. discreta phylogenetic species 4B, is common but not predominant in Europe, whereas species rare in western North America, N. crassa NcB and N. sitophila, are much more common in Europe. The meiotic drive element Spore killer was also common in European populations of N. sitophila and at a higher proportion than anywhere else in the world. The methods by which organisms spread and adapt to new environments are fundamental ecosystem properties, yet they are little understood. The differences in regional diversity, reported here, can form the basis of testable hypotheses. Questions of phylogeography and adaptations can be addressed specifically by studying Neurospora in nature.     

Lipoxygenase inhibition by novel fatty acid ester from Annona squamosa seeds

Studies on the seeds of Annona squamosa yielded a novel lipoxygenase inhibitor fatty acid ester, (+) - annonlipoxy (1). Compound 1 was screened for its enzyme inhibitory activity against lipoxygenase (E.C.1.14.18.1), exhibiting activity with IC(50) 69.05 +/- 5.06 microm. Baicalein (IC(50) 22.6 +/- 0.5 microm) was used as a positive control. Crude extracts of Annona squamosa fruit pulp and seeds were screened for its enzyme inhibitory activity against lipoxygenase and acetylcholinesterase. The crude ethanolic extract of fruit pulp and seeds of Annona squamosa also exhibited lipoxygenase activity with 22.2 and 26.7% inhibition, while the pet.ether extract of seeds of A. squamosa exhibited 52.7% inhibition at a concentration of 40 microg/200 ml. The crude ethanolic extract of seeds of Annona squamosa was also bioassayed for acetylcholinesterase inhibition and it was found inactive.     

Individual‐specific variation in the respiratory activities of HMECs and their bioenergetic response to IGF1 and TNFα

Metabolic reprograming is a hallmark of cancer cells. However, the roles of pre‐existing differences in normal cells metabolism toward cancer risk is not known. In order to assess pre‐existing variations in normal cell metabolism, we have quantified the inter‐individual variation in oxidative metabolism of normal primary human mammary epithelial cells (HMECs). We then assessed their response to selected cytokines such as insulin growth factor 1 (IGF1) and tumor necrosis factor alpha (TNFα), which are associated with breast cancer risk. Specifically, we compared the oxidative metabolism of HMECs obtained from women with breast cancer and without cancer. Our data show considerable inter‐individual variation in respiratory activities of HMECs from different women. A bioenergetic parameter called pyruvate‐stimulated respiration (PySR) was identified as a key distinguishing feature of HMECs from women with breast cancer and without cancer. Samples showing PySR over 20% of basal respiration rate were considered PySR^+ve and the rest as PySR^?ve. By this criterion, HMECs from tumor‐affected breasts (AB) and non‐tumor affected breasts (NAB) of cancer patients were mostly PySR^?ve (88% and 89%, respectively), while HMECs from non‐cancer patients were mostly PySR^+ve (57%). This suggests that PySR^?ve/+ve phenotypes are individual‐specific and are not caused by field effects due to the presence of tumor. The effects of IGF1 and TNFα treatments on HMECs revealed that both suppressed respiration and extracellular acidification. In addition, IGF1 altered PySR^?ve/+ve phenotypes. These results reveal individual‐specific differences in pyruvate metabolism of normal breast epithelial cells and its association with breast cancer risk.

     

Isolation and characterization of BADH2 gene from in vitro propagated <Emphasis Type="Italic">Pandanus amaryllifolius</Emphasis> Roxb

The 2-acetyl-1-pyrroline (2AP) induced ‘basmati rice’ aroma is plausibly the highest among the plant kingdom in Pandanus amaryllifolius Roxb. The defective/truncated allelic forms of betaine aldehyde dehydrogenase (BADH2) gene is the major contributing factor behind the accumulation of this fragrance. The present study reports the isolation and characterization of the full-length BADH2 gene from P. amaryllifolius Roxb. The in silico analysis involving homology modelling and docking studies revealed the deficiency in catalytic efficiency of Pandanus BADH2 towards its substrate γ-aminobutyraldehyde (GAB-ald) as compared to the functional BADH2 gene of rice. We have also studied the tissue-specific expression of the BADH2 gene in different plant parts of in vivo donor and in vitro propagated P. amaryllifolius Roxb. In addition to the leaves, we are reporting histochemical localization of 2AP for the first time in the roots of P. amaryllifolius.     

Factors associated with in-hospital mortality of adult tetanus patients–a multicenter study from Bangladesh

BackgroundTetanus, a vaccine-preventable disease, is still occurring in the elderly population of low- and middle-income countries with a high case-fatality rate. The objective of the study was to elucidate the factors associated with in-hospital mortality of tetanus in Bangladesh.MethodsThis prospective observational study, conducted in two specialized infectious disease hospitals, conveniently selected adult tetanus patients (≥18 years) for inclusion. Data were collected through a preformed structured questionnaire. Kaplan Meier survival analysis and univariate and multivariable Cox regression analysis were carried out to assess factors associated with in-hospital mortality among patients. All analysis was done using Stata (version 16) and SPSS (version 26).ResultsA total of 61 tetanus cases were included, and the overall in-hospital mortality rate was 34.4% (n = 21). Patients had an average age of 46.49 ±15.65 years (SD), and the majority were male (96.7%), farmers (57.4%), and came from rural areas (93.4%). Survival analysis revealed that the probability of death was significantly higher among patients having an age of ≥ 40 years, incubation time of ≤12 days, onset time of ≤ 4 days, and having complication(s). However, on multivariable Cox regression analysis, age (adjusted hazard ratio [aHR] 4.03, 95% Confidence Interval [CI] 1.07–15.17, p = 0.039) and onset time (≤4 days) (aHR 3.33; 95% CI 1.05–10.57, p = 0.041) came as significant predictors of in-hospital mortality after adjusting for incubation period and complications.ConclusionOlder age and short onset time are the two most important determinants of in-hospital mortality of tetanus patients. Hence, these patients require enhanced emphasis and care.