Postmenopausal osteoporosis is the most common bone disease, associated with low bone mineral density (BMD) and pathological fractures which lead to significant morbidity. It is defined clinically by a BMD of 2.5 standard deviations or more below the young female adult mean (T-score =−2.5). Osteoporosis was a huge global problem both socially and economically – in the UK alone, in 2011 £6 million per day was spent on treatment and social care of the 230,000 osteoporotic fracture patients – and therefore viable preventative and therapeutic approaches are key to managing this problem within the aging population of today. One of the main issues surrounding the potential of osteoporosis management is diagnosing patients at risk before they develop a fracture. We discuss the current and future possibilities for identifying susceptible patients, from fracture risk assessment to shape modeling and in relation to the high heritability of osteoporosis now that a plethora of genes have been associated with low BMD and osteoporotic fracture. This review highlights the current therapeutics in clinical use (including bisphosphonates, anti-RANKL [receptor activator of NF-κB ligand], intermittent low dose parathyroid hormone, and strontium ranelate) and some of those in development (anti-sclerostin antibodies and cathepsin K inhibitors). By highlighting the intimate relationship between the activities of bone forming (osteoblasts) and bone-resorbing (osteoclasts) cells, we include an overview and comparison of the molecular mechanisms exploited in each therapy.

Very little is understood about genetic mechanisms underlying the onset of spring migration in latitudinal avian migrants. To gain insight into the genetic architecture of the hypothalamus and liver tissues of a long-distance migrant, we examined and compared the transcriptome profile of captive night-migratory black-headed buntings (Emberiza melanocephala) between photoperiod-induced winter non-migratory (WnM) and spring migratory (SM) life-history states under short and long days, respectively. High-throughput 454 pyrosequenced transcripts were mapped initially with reference to the genome of two phylogenetically close species, Taeniopygia guttata and Ficedula albicollis. The F. albicollis genome gave higher annotation results and was used for further analysis. A total of 216 (78 in hypothalamus; 138 in liver) genes were found to be expressed differentially between the WnM and SM life-history states. These genes were enriched for physiological pathways that might be involved in the regulation of seasonal migrations in birds. For example, genes for the ATP binding pathway in the hypothalamus were expressed at a significantly higher level in SM than in the WnM life-history state. Likewise, upregulated genes associated with the myelin sheath and focal adhesion were enriched in the hypothalamus, and those with cell-to-cell junction, intracellular protein transport, calcium ion transport and small GTPase-mediated signal transduction were enriched in the liver. Many of these genes are a part of physiological pathways potentially involved in the regulation of seasonal migration in birds. These results show molecular changes at the regulatory and metabolic levels associated with seasonal transitions in a long-distance migrant and provide the basis for future studies aimed at unravelling the genetic control of migration in birds.

No abstract

No abstract

A study was performed to establish the optimal concentration of traditional preservatives or fixatives such as formaldehyde and acidic Lugol's iodine, in order to preserve phytoplankton samples for long-term storage without the introduction of artifacts or other physical aberrations. The goal of the study was to avoid any visible morphological changes to the preserved cells, minimizing the errors induced by traditional preservative concentrations, and ensuring better accuracy of ecological analyses. We found that both formaldehyde and acidic Lugol's iodine have adverse effects on the preservation of samples. Trichodesmium erythraeum was found to be most susceptible to the effects of acidic Lugol's iodine, since it displayed the highest degree of chain fragmentation when this preservative was used. However, we found that 2.0% (v/v) formaldehyde, 2.5% (v/v) acidic Lugol's iodine, and 2.0% (v/v) formaldehyde+2.5%(v/v) acidic Lugol's iodine combined were most promising, with the latter the most effective even after 3 weeks of preservation. This study also revealed that, in general, the centric diatom species were more sensitive to long-term preservation than their pennate counterparts. The present study is significant as it sheds light on the damage endured by phytoplankton cells during long-term preservation, which can lead to erroneous and biased results upon analyses. The optimal concentration of preservative established experimentally from a wide variety of concentrations caused comparatively moderate changes to the cell dimensions as well as effectively prevented microbial contamination.

No abstract

We investigated the molecular basis of seasonal testicular states in black‐headed buntings (Emberiza melanocephala), in which seasonal migrations limit reproduction to a narrow time‐window during the year. We examined testicular gene expressions in buntings during short day‐induced photosensitive nonreproductive state (SDSE), and during long day‐induced early (LDES) and late (LDLS) gonadal maturation and regressed photorefractory (LDRF) seasonal states. Using Kallisto, we pseudoaligned the RNA‐Seq transcripts and calculated the transcript abundance. We found 1,799 differentially expressed genes (DEGs) between the four photoperiod‐induced seasonal states. Further pairwise comparison with SDSE revealed 1,187, 1,224, and 1,238 DEGs in LDES, LDLS, and LDRF, respectively; 852 genes were common to three comparisons. We then identified genetic pathways putatively involved in seasonal testicular cycle. DEGs that enriched calcium ion binding were highly expressed in testicular maturation states. Similarly, DEGs that enriched glycolytic pathway were highly expressed in LDES and LDRF states. More specifically, quantitative polymerase chain reaction showed significant differences between the photoperiod‐induced states in testicular expression of genes (HOOK1, RGS2, PRDX4, BCL6, CYFIP2, PDCD4, P2RX4, and GABRA1) involved in gametogenesis and associated pathways. Overall, these results show significant transcriptional differences, and provide insights into the molecular basis of seasonal changes in the reproductive life‐history states in a photoperiodic species.

No abstract