Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical,Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats

Several studies have established an association between diabetes and alterations in bone metabolism; however, the underlying mechanism is not well established. Although zinc is recognized as a potential preventive agent against diabetes-induced bone loss, there is no evidence demonstrating its effect in chronic diabetic conditions. This study evaluated the effects of zinc supplementation in a chronic (90 days) type 1 diabetes-induced bone-loss model. Male Wistar rats were distributed in three groups: control, type 1 diabetes mellitus (T1DM), and T1DM plus zinc supplementation (T1DMS). Serum biochemical analysis; tibia histomorphometric, biomechanical, and collagen-content analyses; and femur mRNA expression were evaluated. Relative to T1DM, the zinc-supplemented group showed increased histomorphometric parameters such as TbWi and BAr and decreased TbSp, increased biomechanical parameters (maximum load, stiffness, ultimate strain, and Young’s modulus), and increased type I collagen content. Interestingly, similar values for these parameters were observed between the T1DMS and control groups. These results demonstrate the protective effect of zinc on the maintenance of bone strength and flexibility. In addition, downregulation of OPG, COL1A, and MMP-9 genes was observed in T1DMS, and the anabolic effects of zinc were evidenced by increased OC expression and serum ALP activity, both related to osteoblastogenesis, demonstrating a positive effect on bone formation. In contrast, T1DM showed excessive bone loss, observed through reduced histomorphometric and biomechanical parameters, characterizing diabetes-associated bone loss. The bone loss was also observed through upregulation of OPG, COL1A, and MMP-9 genes. In conclusion, zinc showed a positive effect on the maintenance of bone architecture and biomechanical parameters. Indeed, OC upregulation and control of expression of OPG, COL1A, and MMP-9 mRNAs, even in chronic hyperglycemia, support an anabolic and protective effect of zinc under chronic diabetic conditions. Furthermore, these results indicate that zinc supplementation could act as a complementary therapy in chronic T1DM.     

Histology Verification Demonstrates That Biospectroscopy Analysis of Cervical Cytology Identifies Underlying Disease More Accurately than Conventional Screening: Removing the Confounder of Discordance

Background

Subjective visual assessment of cervical cytology is flawed, and this can manifest itself by inter- and intra-observer variability resulting ultimately in the degree of discordance in the grading categorisation of samples in screening vs. representative histology. Biospectroscopy methods have been suggested as sensor-based tools that can deliver objective assessments of cytology. However, studies to date have been apparently flawed by a corresponding lack of diagnostic efficiency when samples have previously been classed using cytology screening. This raises the question as to whether categorisation of cervical cytology based on imperfect conventional screening reduces the diagnostic accuracy of biospectroscopy approaches; are these latter methods more accurate and diagnose underlying disease? The purpose of this study was to compare the objective accuracy of infrared (IR) spectroscopy of cervical cytology samples using conventional cytology vs. histology-based categorisation.

Methods

Within a typical clinical setting, a total of n = 322 liquid-based cytology samples were collected immediately before biopsy. Of these, it was possible to acquire subsequent histology for n = 154. Cytology samples were categorised according to conventional screening methods and subsequently interrogated employing attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. IR spectra were pre-processed and analysed using linear discriminant analysis. Dunn’s test was applied to identify the differences in spectra. Within the diagnostic categories, histology allowed us to determine the comparative efficiency of conventional screening vs. biospectroscopy to correctly identify either true atypia or underlying disease.

Results

Conventional cytology-based screening results in poor sensitivity and specificity. IR spectra derived from cervical cytology do not appear to discriminate in a diagnostic fashion when categories were based on conventional screening. Scores plots of IR spectra exhibit marked crossover of spectral points between different cytological categories. Although, significant differences between spectral bands in different categories are noted, crossover samples point to the potential for poor specificity and hampers the development of biospectroscopy as a diagnostic tool. However, when histology-based categories are used to conduct analyses, the scores plot of IR spectra exhibit markedly better segregation.

Conclusions

Histology demonstrates that ATR-FTIR spectroscopy of liquid-based cytology identifies the presence of underlying atypia or disease missed in conventional cytology screening. This study points to an urgent need for a future biospectroscopy study where categories are based on such histology. It will allow for the validation of this approach as a screening tool.     

Physiology,endocrinology and chemical communication in aggressive behaviour of fishes

Fishes show remarkably diverse aggressive behaviour. Aggression is expressed to secure resources; adjusting aggression levels according to context is key to avoid negative consequences for fitness and survival. Nonetheless, despite its importance, the physiological basis of aggression in fishes is still poorly understood. Several reports suggest hormonal modulation of aggression, particularly by androgens, but contradictory studies have been published. Studies exploring the role of chemical communication in aggressive behaviour are also scant, and the pheromones involved remain to be unequivocally characterized. This is surprising as chemical communication is the most ancient form of information exchange and plays a variety of other roles in fishes. Furthermore, the study of chemical communication and aggression is relevant at the evolutionary, ecological and economic levels. A few pioneering studies support the hypothesis that aggressive behaviour, at least in some teleosts, is modulated by “dominance pheromones” that reflect the social status of the sender, but there is little information on the identity of the compounds involved. This review aims to provide a global view of aggressive behaviour in fishes and its underlying physiological mechanisms including the involvement of chemical communication, and discusses the potential use of dominance pheromones to improve fish welfare. Methodological considerations and future research directions are also outlined.     

Assessment of oxidative status and genotoxicity in photocopier operators: a pilot study

Occupational exposure to photocopiers has been indicated as being responsible for a number of health complaints, particularly effects on the respiratory, immunological, and nervous systems. In this study, we investigated oxidative and genotoxic damage in photocopier operators by assessing catalase activity (CAT), reduced vs. oxidized glutathione ratio (GSH/GSSG), level of lipid peroxidation (TBARS), damage index by Comet assay (DICA), and buccal cells with micronuclei (BCMN). Our results reveal that the TBARS levels in operators were increased (27%; p<0.05) but that no significant alterations to GSH/GSSG or CAT activity were observed. The DICA and the number of BCMN were significantly increased (134% and 100%, respectively; p<0.05) in the exposed group. There was a significant association between the time in months spent at work and DNA damage in lymphocytes (r(s)?=?0.720; p<0.001) and buccal cell with MN (r(s)?=?0.538; p<0.001). Because laser printers and photocopiers have become increasingly used, it is important to control human exposure using reliable biomarkers.     

An actin-dependent mechanism for long-range vesicle transport

Intracellular transport is vital for the function, survival and architecture of every eukaryotic cell. Long-range transport in animal cells is thought to depend exclusively on microtubule tracks. This study reveals an unexpected actin-dependent but microtubule-independent mechanism for long-range transport of vesicles. Vesicles organize their own actin tracks by recruiting the actin nucleation factors Spire1, Spire2 and Formin-2, which assemble an extensive actin network from the vesicles' surfaces. The network connects the vesicles with one another and with the plasma membrane. Vesicles move directionally along these connections in a myosin-Vb-dependent manner to converge and to reach the cell surface. The overall outward-directed movement of the vesicle-actin network is driven by recruitment of vesicles to the plasma membrane in the periphery of the oocyte. Being organized in a dynamic vesicle-actin network allows vesicles to move in a local random manner and a global directed manner at the same time: they can reach any position in the cytoplasm, but also move directionally to the cell surface as a collective. Thus, collective movement within a network is a powerful and flexible mode of vesicle transport.     

The proteoglycan Trol controls the architecture of the extracellular matrix and balances proliferation and differentiation of blood progenitors in the Drosophila lymph gland

The heparin sulfate proteoglycan Terribly Reduced Optic Lobes (Trol) is the Drosophila melanogaster homolog of the vertebrate protein Perlecan. Trol is expressed as part of the extracellular matrix (ECM) found in the hematopoietic organ, called the lymph gland. In the normal lymph gland, the ECM forms thin basement membranes around individual or small groups of blood progenitors. The pattern of basement membranes, reported by Trol expression, is spatio-temporally correlated to hematopoiesis. The central, medullary zone which contain undifferentiated hematopoietic progenitors has many, closely spaced membranes. Fewer basement membranes are present in the outer, cortical zone, where differentiation of blood cells takes place. Loss of trol causes a dramatic change of the ECM into a three-dimensional, spongy mass that fills wide spaces scattered throughout the lymph gland. At the same time proliferation is reduced, leading to a significantly smaller lymph gland. Interestingly, differentiation of blood progenitors in trol mutants is precocious, resulting in the break-down of the usual zonation of the lymph gland. which normally consists of an immature center (medullary zone) where cells remain undifferentiated, and an outer cortical zone, where differentiation sets in. We present evidence that the effect of Trol on blood cell differentiation is mediated by Hedgehog (Hh) signaling, which is known to be required to maintain an immature medullary zone. Overexpression of hh in the background of a trol mutation is able to rescue the premature differentiation phenotype. Our data provide novel insight into the role of the ECM component Perlecan during Drosophila hematopoiesis.     

The convergence of Notch and MAPK signaling specifies the blood progenitor fate in the Drosophila mesoderm

Blood progenitors arise from a pool of pluripotential cells (“hemangioblasts”) within the Drosophila embryonic mesoderm. The fact that the cardiogenic mesoderm consists of only a small number of highly stereotypically patterned cells that can be queried individually regarding their gene expression in normal and mutant embryos is one of the significant advantages that Drosophila offers to dissect the mechanism specifying the fate of these cells. We show in this paper that the expression of the Notch ligand Delta (Dl) reveals segmentally reiterated mesodermal clusters (“cardiogenic clusters”) that constitute the cardiogenic mesoderm. These clusters give rise to cardioblasts, blood progenitors and nephrocytes. Cardioblasts emerging from the cardiogenic clusters accumulate high levels of Dl, which is required to prevent more cells from adopting the cardioblast fate. In embryos lacking Dl function, all cells of the cardiogenic clusters become cardioblasts, and blood progenitors are lacking. Concomitant activation of the Mitogen Activated Protein Kinase (MAPK) pathway by Epidermal Growth Factor Receptor (EGFR) and Fibroblast Growth Factor Receptor (FGFR) is required for the specification and maintenance of the cardiogenic mesoderm; in addition, the spatially restricted localization of some of the FGFR ligands may be instrumental in controlling the spatial restriction of the Dl ligand to presumptive cardioblasts.     

Trophic ecology of tadpoles in floodplain wetlands: combining gut contents,selectivity, and stable isotopes to study feeding segregation of syntopic species

Hydrobiologia - Little consensus exists on the role of food partitioning in the organization of tadpole assemblages. We studied trophic ecology of syntopic tadpoles through the analysis of gut...     

Prevalence and predictors of exclusive breastfeeding among women in Kilimanjaro region,Northern Tanzania: a population based cross-sectional study

Background

Exclusive breastfeeding (EBF) is a simple and cost-effective intervention to improve child health and survival. Effective EBF has been estimated to avert 13% - 15% of under-five mortality and contribute to reduce mother to child transmission of HIV. The prevalence of EBF for infant less than six months is low in most developing countries, including Tanzania (50%). While the Tanzania Demographic Health Survey collects information on overall EBF prevalence, it does not evaluate factors influencing EBF. The aim of this paper was to determine the prevalence and predictors of exclusive breastfeeding in urban and rural areas in Kilimanjaro region.

Methods

A population-based cross-sectional study was conducted between June 2010 to March 2011 among women with infants aged 6–12 months in Kilimanjaro. Multi-stage proportionate to size sampling was used to select participants from all the seven districts of the region. A standardized questionnaire was used to collect socio-demographic, reproductive, alcohol intake, breastfeeding patterns and nutritional data during the interviews. Estimation on EBF was based on recall since birth. Multivariable logistic regression was used to obtain independent predictors of EBF.

Results

A total of 624 women participated, 77% (483) from rural areas. The prevalence of EBF up to six months in Kilimanjaro region was 20.7%, without significant differences in the prevalence of EBF up to six months between urban (22.7%) and rural areas (20.1%); (OR?=?0.7, 95% CI 0.5,1.4).In multivariable analysis, advice on breastfeeding after delivery (Adjusted odds ratio, AOR?=?2.6, 95% CI 1.5, 4.6) was positively associated with EBF up to six months. Compared to married/cohabiting and those who do not take alcohol, single mothers (AOR?=?0.4, 95% CI 0.2, 0.9) and mothers who drank alcohol (AOR?=?0.4, 95% CI 0.3, 0.7) had less odds to practice EBF up to six months.

Conclusion

Prevalence of EBF up to six months is still low in Kilimanjaro, lower than the national coverage of 50%. Strengthening of EBF counseling in all reproductive and child health clinics especially during antenatal and postnatal periods may help to improve EBF rates.