Functional correlates of positional and gender-specific renal asymmetry in drosophila

Accordingly, the physical asymmetry of the tubules in the body cavity is directly adaptive. Now that the detailed machinery underlying internal asymmetry is starting to be delineated, our work invites the investigation, not just of tissues in isolation, but in the context of their unique physical locations and milieux

Распространенность остеопороза в сельских районах Южной Индии и его связь с общими вторичными факторами риска

Background. Osteoporosis is a common metabolic disorder characterised by decreased bone mass and weakened micro-architecture of bone tissue. After 50 years of age, one in three women and one in five men experience osteoporotic fractures. This is projected to cause a yearly loss of 5.8 million healthy life years to disability. The number of patients who attend the outpatient clinic and emergency department of Sanjay Gandhi Institute of Trauma and Orthopaedics with fragility fractures has been increasing, hence to know the prevalence of osteoporosis in the general population who were asymptomatic, we decided to conduct a study in the rural areas of south India. Aims: 1) to estimate the prevalence of osteoporosis among the population above 50 years in rural areas of south India; 2) to determine the correlation between common secondary risk factors for osteoporosis like tobacco consumption, alcohol, diabetes, and hypertension. Results. The prevalence of osteoporosis in the rural population was more in females at 42.2%, whereas the males had a prevalence of 32.5%. Among the population with habits of tobacco consumption and alcohol consumption, the prevalence was 78% and 30.6% respectively. 20.2% of non-smokers and 39.7% of non-alcoholics were osteoporotic. Among the population with comorbidities, 53.6% of diabetes and 55.4% of hypertensives were osteoporotic. 33.7% of non-diabetics were osteoporotic, and 29.5% of hypertensives were osteoporotic. The correlation between osteoporosis and the individual risk factors ranged between weak negative to moderately positive (r = -0.2 to 0.5). The correlation between the combination of all the four risk factors and osteoporosis is weakly positive (r = 0.339), which is highly significant (p0.001). Conclusion. Overall, the findings of this study suggest that addictive habits such as tobacco and alcohol consumption may have a significant impact on bone health, with a higher prevalence of osteopenia and osteoporosis observed in individuals with these habits. Comorbidities such as diabetes and hypertension were also found to be associated with a higher prevalence of osteoporosis. These findings emphasize the importance of early detection and prevention of addictive habits and comorbidities to reduce the risk of osteopenia and osteoporosis. Furthermore, the study highlights the need for further research to fully understand the complex relationships between sociodemographic factors, addictive habits, comorbidities, and bone health.Актуальность. Остеопороз распространенное метаболическое расстройство, характеризующееся уменьшением массы костной ткани и ослаблением микроархитектуры костей. После 50 лет каждая третья женщина и каждый пятый мужчина сталкиваются с остеопоротическими переломами. Это приводит к ежегодной потере 5,8 млн лет здоровой жизни (HLY) из-за инвалидности. Количество пациентов, обращающихся в поликлинику и отделение неотложной помощи Института травматологии и ортопедии им. Санджая Ганди с патологическими переломами, из года в год увеличивается. Чтобы определить распространенность остеопороза среди населения, не имеющего симптомов данного заболевания, мы решили провести исследование в сельских районах Южной Индии. Цели исследования: 1) оценить распространенность остеопороза среди населения старше 50 лет в сельских районах Южной Индии; 2) определить связь между общими вторичными факторами риска остеопороза, такими как употребление табака и алкоголя, диабет, гипертония. Результаты. Распространенность остеопороза в сельских районах была выше у женщин и составила 42,2%, в то время как у мужчин распространенность составила 32,5%. Среди лиц, употребляющих табак и алкоголь, распространенность составила 78,0% и 30,6% соответственно. Остеопороз был выявлен у 20,2% некурящих и у 39,7% не употребляющих алкоголь. Среди лиц с сопутствующими заболеваниями остеопороз выявлен у 53,6% диабетиков и 55,4% гипертоников. Связь между остеопорозом и отдельными факторами риска колебалась от слабо отрицательной до умеренно положительной (r = -0,2 до 0,5). Связь между комбинацией всех четырех факторов риска и остеопорозом была слабо положительной (r = 0,339) и имела высокую значимость (p0,001). Заключение. Результаты данного исследования свидетельствуют о значительном влиянии вредных привычек, таких как употребление табака и алкоголя, на здоровье костей, с более высокой распространенностью остеопении и остеопороза у лиц с этими привычками. Сопутствующие заболевания, такие как диабет и гипертония, также связаны с более высокой распространенностью остеопороза. Эти свидетельствует о важности раннего выявления сопутствующих заболеваний и отказа от вредных привычек для снижения риска развития остеопении и остеопороза. Необходимы дальнейшие исследования для полного понимания сложных взаимосвязей между социодемографическими факторами, привычками, сопутствующими заболеваниями и здоровьем костей

Assessing the effect of dynamics on the closed-loop protein-folding hypothesis

The closed-loop (loop-n-lock) hypothesis of protein folding suggests that loops of about 25 residues, closed through interactions between the loop ends (locks), play an important role in protein structure. Coarse-grain elastic network simulations, and examination of loop lengths in a diverse set of proteins, each supports a bias towards loops of close to 25 residues in length between residues of high stability. Previous studies have established a correlation between total contact distance (TCD), a metric of sequence distances between contacting residues (cf. contact order), and the log-folding rate of a protein. In a set of 43 proteins, we identify an improved correlation ( r 2 = 0.76), when the metric is restricted to residues contacting the locks, compared to the equivalent result when all residues are considered ( r 2 = 0.65). This provides qualified support for the hypothesis, albeit with an increased emphasis upon the importance of a much larger set of residues surrounding the locks. Evidence of a similar-sized protein core/extended nucleus (with significant overlap) was obtained from TCD calculations in which residues were successively eliminated according to their hydrophobicity and connectivity, and from molecular dynamics simulations. Our results suggest that while folding is determined by a subset of residues that can be predicted by application of the closed-loop hypothesis, the original hypothesis is too simplistic; efficient protein folding is dependent on a considerably larger subset of residues than those involved in lock formation. </jats:p

Mapping an atlas of tissue-specific drosophila melanogaster metabolomes by high resolution mass spectrometry

Metabolomics can provide exciting insights into organismal function, but most work on simple models has focussed on the whole organism metabolome, so missing the contributions of individual tissues. Comprehensive metabolite profiles for ten tissues from adult Drosophila melanogaster were obtained here by two chromatographic methods, a hydrophilic interaction (HILIC) method for polar metabolites and a lipid profiling method also based on HILIC, in combination with an Orbitrap Exactive instrument. Two hundred and forty two polar metabolites were putatively identified in the various tissues, and 251 lipids were observed in positive ion mode and 61 in negative ion mode. Although many metabolites were detected in all tissues, every tissue showed characteristically abundant metabolites which could be rationalised against specific tissue functions. For example, the cuticle contained high levels of glutathione, reflecting a role in oxidative defence; the alimentary canal (like vertebrate gut) had high levels of acylcarnitines for fatty acid metabolism, and the head contained high levels of ether lipids. The male accessory gland uniquely contained decarboxylated S-adenosylmethionine. These data thus both provide valuable insights into tissue function, and a reference baseline, compatible with the FlyAtlas.org transcriptomic resource, for further metabolomic analysis of this important model organism, for example in the modelling of human inborn errors of metabolism, aging or metabolic imbalances such as diabetes

Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor.

Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a 'wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model

First Steps towards Underdominant Genetic Transformation of Insect Populations

The idea of introducing genetic modifications into wild populations of insects to stop them from spreading diseases is more than 40 years old. Synthetic disease refractory genes have been successfully generated for mosquito vectors of dengue fever and human malaria. Equally important is the development of population transformation systems to drive and maintain disease refractory genes at high frequency in populations. We demonstrate an underdominant population transformation system in Drosophila melanogaster that has the property of being both spatially self-limiting and reversible to the original genetic state. Both population transformation and its reversal can be largely achieved within as few as 5 generations. The described genetic construct {Ud} is composed of two genes; (1) a UAS-RpL14.dsRNA targeting RNAi to a haploinsufficient gene RpL14 and (2) an RNAi insensitive RpL14 rescue. In this proof-of-principle system the UAS-RpL14.dsRNA knock-down gene is placed under the control of an Actin5c-GAL4 driver located on a different chromosome to the {Ud} insert. This configuration would not be effective in wild populations without incorporating the Actin5c-GAL4 driver as part of the {Ud} construct (or replacing the UAS promoter with an appropriate direct promoter). It is however anticipated that the approach that underlies this underdominant system could potentially be applied to a number of species. Figure

Size-Dependent Dissociation of Carbon Monoxide on Cobalt Nanoparticles

[[abstract]]In situ soft X-ray absorption spectroscopy (XAS) was employed to study the adsorption and dissociation of carbon monoxide molecules on cobalt nanoparticles with sizes ranging from 4 to 15 nm. The majority of CO molecules adsorb molecularly on the surface of the nanoparticles, but some undergo dissociative adsorption, leading to oxide species on the surface of the nanoparticles. We found that the tendency of CO to undergo dissociation depends critically on the size of the Co nanoparticles. Indeed, CO molecules dissociate much more efficiently on the larger nanoparticles (15 nm) than on the smaller particles (4 nm). We further observed a strong increase in the dissociation rate of adsorbed CO upon exposure to hydrogen, clearly demonstrating that the CO dissociation on cobalt nanoparticles is assisted by hydrogen. Our results suggest that the ability of cobalt nanoparticles to dissociate hydrogen is the main parameter determining the reactivity of cobalt nanoparticles in Fischer–Tropsch synthesis.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]紙本[[booktype]]電子

Robust RT-qPCR Data Normalization: Validation and Selection of Internal Reference Genes during Post-Experimental Data Analysis

Reverse transcription and real-time PCR (RT-qPCR) has been widely used for rapid quantification of relative gene expression. To offset technical confounding variations, stably-expressed internal reference genes are measured simultaneously along with target genes for data normalization. Statistic methods have been developed for reference validation; however normalization of RT-qPCR data still remains arbitrary due to pre-experimental determination of particular reference genes. To establish a method for determination of the most stable normalizing factor (NF) across samples for robust data normalization, we measured the expression of 20 candidate reference genes and 7 target genes in 15 Drosophila head cDNA samples using RT-qPCR. The 20 reference genes exhibit sample-specific variation in their expression stability. Unexpectedly the NF variation across samples does not exhibit a continuous decrease with pairwise inclusion of more reference genes, suggesting that either too few or too many reference genes may detriment the robustness of data normalization. The optimal number of reference genes predicted by the minimal and most stable NF variation differs greatly from 1 to more than 10 based on particular sample sets. We also found that GstD1, InR and Hsp70 expression exhibits an age-dependent increase in fly heads; however their relative expression levels are significantly affected by NF using different numbers of reference genes. Due to highly dependent on actual data, RT-qPCR reference genes thus have to be validated and selected at post-experimental data analysis stage rather than by pre-experimental determination

Female Drosophila melanogaster Gene Expression and Mate Choice: The X Chromosome Harbours Candidate Genes Underlying Sexual Isolation

Background: The evolution of female choice mechanisms favouring males of their own kind is considered a crucial step during the early stages of speciation. However, although the genomics of mate choice may influence both the likelihood and speed of speciation, the identity and location of genes underlying assortative mating remain largely unknown. Methods and Findings: We used mate choice experiments and gene expression analysis of female Drosophila melanogaster to examine three key components influencing speciation. We show that the 1,498 genes in Zimbabwean female D. melanogaster whose expression levels differ when mating with more (Zimbabwean) versus less (Cosmopolitan strain) preferred males include many with high expression in the central nervous system and ovaries, are disproportionately X-linked and form a number of clusters with low recombination distance. Significant involvement of the brain and ovaries is consistent with the action of a combination of pre- and postcopulatory female choice mechanisms, while sex linkage and clustering of genes lead to high potential evolutionary rate and sheltering against the homogenizing effects of gene exchange between populations. Conclusion: Taken together our results imply favourable genomic conditions for the evolution of reproductive isolation through mate choice in Zimbabwean D. melanogaster and suggest that mate choice may, in general, act as an even more important engine of speciation than previously realized

Phenotypic Plasticity of the Drosophila Transcriptome

Phenotypic plasticity is the ability of a single genotype to produce different phenotypes in response to changing environments. We assessed variation in genome-wide gene expression and four fitness-related phenotypes of an outbred Drosophila melanogaster population under 20 different physiological, social, nutritional, chemical, and physical environments; and we compared the phenotypically plastic transcripts to genetically variable transcripts in a single environment. The environmentally sensitive transcriptome consists of two transcript categories, which comprise ∼15% of expressed transcripts. Class I transcripts are genetically variable and associated with detoxification, metabolism, proteolysis, heat shock proteins, and transcriptional regulation. Class II transcripts have low genetic variance and show sexually dimorphic expression enriched for reproductive functions. Clustering analysis of Class I transcripts reveals a fragmented modular organization and distinct environmentally responsive transcriptional signatures for the four fitness-related traits. Our analysis suggests that a restricted environmentally responsive segment of the transcriptome preserves the balance between phenotypic plasticity and environmental canalization