A Pleiotropic Drug Resistance Family Protein Gene Is Required for Rice Growth, Seed Development and Zinc Homeostasis

Zinc(Zn) is an essential mineral element for plant growth and development. Zn deficiency in crops frequently occurs in many types of soils. It is therefore crucial to identify genetic resources linking Zn acquisition traits and development of crops with improved Zn-use efficiency for sustainable crop production. In this study, we functionally identified a rice uncharacterized ABCG(ATP-binding cassette G-subfamily) gene encoding a PDR20(pleiotropic drug resistance 20) metal transporter for mediation of rice growth, seed development and Zn accumulation. OsPDR20 was localized to the plasma membrane, but it was not transcriptionally induced under Zn deficiency, rather was sufficiently up-regulated under high level of Zn stress. Yeast(Saccharomyces cerevisiae) transformed with OsPDR20 displayed a relatively lower Zn accumulation with attenuated cellular growth, suggesting that OsPDR20 had an activity for Zn transport. Knocking-down OsPDR20 by RNA interference(RNAi) compromised rice growth with shorter plant height and decreased biomass in rice plantlets grown under hydroponic media. Zn concentration in the roots of OsPDR20 knocked-down rice lines declined under Zn deficiency, while they remained unchanged compared with the wild type under normal Zn supply. A rice lifelong field trial demonstrated that OsPDR20 mutation impaired the capacity of seed development, with shortened panicle and seed length, compromised spikelet fertility, and reduced grain number per plant or grain weight per unit area. Interestingly, OsPDR20 mutation elevated the accumulation of Zn in husk and brown rice over the wild type. Overall, this study pointed out that OsPDR20 is fundamentally required for rice growth and seed development through Zn transport and homeostasis.

Complementary research in mammals and fish indicates MMP-2 as a pleiotropic contributor to optic nerve regeneration

Matrix metalloproteinases（MMPs）are members of the metzincin superfamily named after the zinc ion and the conserved methionine residue at the active site.In addition to their role in extracellular matrix（ECM）remodeling,these proteinases（in）activate many signaling molecules such as growth factors.

The pleiotropic effects of tissue plasminogen activator in the brain:implications for stroke recovery

Tissue plasminogen activator （tPA） use in the treatment of isch- emic stroke： tPA is a serine protease that catalyzes the breakdown of blood dots. Because of its thrombolytic properties, tPA is used to treat specific types of stroke, including ischemia, but is contra- indicated for treatment of hemorrhagic stroke or head trauma. Although a life saving and powerful ＇dot buster＇, tPA has a short therapeutic window. When administered outside of this prescribed timeframe, research suggests that tPA can produce neurotoxic ef- fects in the brain, due in part to activation of several signalling pro- cesses associated with cell apoptosis, degradation of the extracel- lular matrix, and increase in the permeability of the neurovascular unit （Yepes et al., 2009）. Concerted research has been dedicated to- ward understanding the mechanisms mediating the impact of tPA on the brain, using both in vivo and in vitro animal models.

AMPylation Signaling Participates in Diverse Processes with Pleiotropic Actions

Truttmann MC et al.[1] recently reported that AMPylation of heat shock protein 70 (HSP70) family of chaperones participates in altering the aggregation properties and maintaining protein homeostasis (proteostasis), thereby playing a vital role in the development of neurodegenerative diseases (NDs). NDs are commonly manifested by protein aggregates, which exert harmful effects on proteostasis. Interestingly, it has been observed that AMPylation of heat shock proteins (HSPs) can maintain proteostasis by inhibiting the formation of protein aggregates. As previous studies only indicate that HSPs could regulate proteostasis, such a novel discovery further demonstrates the involvement of HSP70 AMPylation in the regulation of protein aggregation and the maintenance of proteostasis. Therefore, AMPylation can be considered to possess a therapeutic potential to target certain physiological processes related to proteostasis, such as age-related diseases.

Theory of pleiotropic action of biologically active compounds and medicines—Basic principles and practical application

This article represents the main positions of the theory of pleiotropic action of biologically active compounds (BACs) and medicines, which has been designed by the author based on her own experimental researches. The term “pleiotropy” means the ability of the BACs and medicines to implement more than one mechanism of action resulting in the specific biological (pharmacological) effect. The interaction of these mechanisms forms a distinct pattern of biological response (pleiotropic pattern), which reflects the change in his character with the increased dose (concentration)-dependent efficacy of BACs and medicines. The article consists of description of different pleiotropic patterns established in experiments on the model of reactive oxygen species (ROS) generation by macrophages dependent on activity of specialized enzyme called Nox2-NAD(P)H oxidase (Nox2, EC 1.6.3.1). Moreover, it consists of explanation of pharmacodynamic nature of pleiotropic patterns by means of application Chou-Talalay median effect equalization and combination index (CI) theory. The novel theory explains unsolved until now universal aspects of activity BACs and medicines, such as slope angles of “dose-effect” dependences in the conditions relevant in vivo, and it is of fundamental interest. However, it has applications in experimental pharmacology, as it allows defining the choice of the individual compounds and combinations, modulating the trust effect selectively and efficiently. This knowledge opens up new approaches to medicines discovery and evaluation, their rational dosing and combining.

Natural variation in the SVP contributes to the pleiotropic adaption of Arabidopsis thaliana across contrasted habitats

Coordinated plant adaptation involves the interplay of multiple traits driven by habitat-specific selection pressures. Pleiotropic effects, wherein genetic variants of a single gene control multiple traits, can expedite such adaptations. Until present, only a limited number of genes have been reported to exhibit pleiotropy. Here, we create a recombinant inbred line (RIL) population derived from two Arabidopsis thaliana (A. thaliana) ecotypes originating from divergent habitats. Using this RIL population, we identify an allelic variation in a MADS-box transcription factor, SHORT VEGETATIVE PHASE (SVP), which exerts a pleiotropic effect on leaf size and drought-versus-humidity tolerance. Further investigation reveals that a natural null variant of the SVP protein disrupts its normal regulatory interactions with target genes, including GRF3, CYP707A1/3, and AtBG1, leading to increased leaf size, enhanced tolerance to humid conditions, and changes in flowering time of humid conditions in A. thaliana. Remarkably, polymorphic variations in this gene have been traced back to early A. thaliana populations, providing a genetic foundation and plasticity for subsequent colonization of diverse habitats by influencing multiple traits. These findings advance our understanding of how plants rapidly adapt to changing environments by virtue of the pleiotropic effects of individual genes on multiple trait alterations.

The domestication-associated L1 gene encodes a eucomic acid synthase pleiotropically modulating pod pigmentation and shattering in soybean

Pod coloration is a domestication-related trait in soybean,with modern cultivars typically displaying brown or tan pods,while their wild relative,Glycine soja,possesses black pods.However,the factors regulating this color variation remain unknown.In this study,we cloned and characterized L1,the classical locus responsible for black pods in soybean.By using map-based cloning and genetic analyses,we identified the causal gene of L1 and revealed that it encodes a hydroxymethylglutaryl-coenzyme A(CoA)lyase-like(HMGL-like)domain protein.Biochemical assays showed that L1 functions as a eucomic acid synthase and facilitates the synthesis of eucomic acid and piscidic acid,both of which contribute to coloration of pods and seed coats in soybean.Interestingly,we found that L1 plants are more prone to pod shattering under light exposure than l1 null mutants because dark pigmentation increases photothermal efficiency.Hence,pleiotropic effects of L1 on pod color and shattering,as well as seed pigmentation,likely contributed to the preference forl1 alleles during soybean domestication and improvement.Collectively,our study provides new insights into the mechanism of pod coloration and identifies a new target for future de novo domestication oflegume crops.

Unraveling the regulatory network of flower coloration in soybean:Insights into roles of GmMYBA3 and GmMYBR1

Anthocyanins play crucial roles in pollen protection and pollinator attraction in flowering plants.However,the mechanisms underlying flower color determination and whether floral anthocyanin regulators participate in other processes remain largely unresolved in soybeans(Glycine max).In this study,we investigated the genetic components and mechanisms governing anthocyanin biosynthesis in soybean flowers.Molecular and genetic studies have characterized two antagonistic regulators,the positive activator GmMYBA3 and the negative repressor GmMYBR1,that modulate the gene expression of anthocyanin biosynthesis in soybean flowers.Further findings revealed a regulatory interplay between GmMYBA3 and GmMYBR1 bridged by GmTT8a,highlighting the complexity of anthocyanin regulation in different soybean organs.Exploration of additional soybean cultivars demonstrated the universality of GmMYBA3 and GmMYBR1 in regulating floral anthocyanin biosynthesis-related genes,with GmF3’5’H identified as a crucial determinant of white flower color.This study provides a molecular mechanism underlying soybean flower color determination,paving the way for the molecular modification of soybean flowers to probably enhance their resistance to abiotic stresses and attractiveness to pollinators.

Validation and Characterization of Ghd7.1, a Major Quantitative Trait Locus with Pleiotropic Effects on Spikelets per Panicle, Plant Height, and Heading Date in Rice (Oryza sativa L.)

A quantitative trait locus （QTL） that affects heading date （HD） and the number of spikelets per panicle （SPP） was previously identified in a small region on chromosome 7 in rice （Oryza sativa L.）. In order to further characterize the QTL region, near isogenic lines （NILs） were quickly obtained by self-crossing recombinant inbred line 189, which is heterozygous in the vicinity of the target region. The pleiotropic effects of QTL Ghd7.1 on plant height （PH）, SPP, and HD, were validated using an NIL-F2 population. Ghd7.1 explained 50.2%, 45.3%, and 76.9% of phenotypic variation in PH, SPP, and HD, respectively. Ghd7.1 was precisely mapped to a 357-kb region on the basis of analysis of the progeny of the NIL-F2 population. Day-length treatment confirmed that Ghd7.1 is sensitive to photoperiod, with long days delaying heading up to 12.5 d. Identification of panicle initiation and development for the pair of NILs showed that Ghd7.1 elongated the photoperiod-sensitive phase more than 10 d, but did not change the basic vegetative phase and the reproductive growth phase. These findings indicated that Ghd7.1 regulates SPP by controlling the rate of panicle differentiation rather than the duration of panicle development.

Plant pleiotropic drug resistance transporters:Transport mechanism, gene expression,and function

Pleiotropic drug resistance （PDR） transporters belonging to the ABCG subfamily of ATP-binding cassette （ABC） transporters are identified only in fungi and plants. Members of this family are expressed in plants in response to various biotic and abiotic stresses and transport a diverse array of moleculesacross membranes, Although their detailed transport mechanism is largely unknown, they play important roles in detoxification processes, preventing water loss, transport of phytohormones, and secondary metabolites. This review provides insights into transport mechanisms of plant PDR transporters, their expression profiles, and multitude functions in plants.

Novel pleiotropic loci controlling panicle architecture across environments in japonica rice (Oryza sativa L.)

To identify quantitative trait loci （QTLs） controlling panicle architecture in japonica rice, a genetic map was constructed based on simple sequence repeat （SSR） markers and 254 recombinant inbred lines （RILs） derived from a cross between cultivars Xiushui 79 and C Ban. Seven panicle traits were investigated under three environments. Single marker analysis indicated that a total of 27 SSR markers were highly associated with panicle traits in all the three environments. Percentage of phenotypic variation explained by single locus varied from 2% to 35%. Based on the mixed linear model, a total of 40 additive QTLs for seven panicle traits were detected by composite interval mapping, explaining 1.2%--35% ofphenotypic variation. Among the 9 QTLs with more than 10% of explained phenotypic variation, two QTLs were for the number of primary branches per panicle （NPB）, two for panicle length （PL）, two for spikelet density （SD）, one for the number of secondary branches per panicle （NSB）, one for secondary branch distribution density （SBD）, and one for the num- ber of spikelets per panicle （NS）, respectively, qPLSD-9-1 and qPLSD-9-2 were novel pleiotropic loci, showing effects on PL and SD simultaneously, qPLSD-9-1 explained 34.7% of the phenotypic variation for PL and 25.4% of the phenotypic variation for SD, respec- tively, qPLSD-9-2 explained 34.9% and 24.4% of the phenotypic variation for PL and SD, respectively. The C Bao alleles at the both QTLs showed positive effects on PL, and the Xiushui 79 alleles at the both QTLs showed positive effects on SD. Genetic variation of panicle traits are mainly attributed to additive effects. QTLx environment interactions were not significant for additive QTLs and additive x additive QTL pairs.

Genetic architecture of quantitative trait loci(QTL)for FHB resistance and agronomic traits in a hard winter wheat population

Wheat resistance to Fusarium head blight(FHB)has often been associated with some undesirable agronomic traits.To study the relationship between wheat FHB resistance and agronomic traits,we constructed a linkage map of single nucleotide polymorphisms(SNPs)using an F6:8 population from G97252WG97380A.The two hard winter wheat parents showed contrasts in FHB resistance,plant height(HT),heading date(HD),spike length(SL),spike compactness(SC),kernel number per spike(KNS),spikelet number per spike(SNS),thousand-grain weight(TGW)and grain size(length and width).Quantitative trait locus(QTL)mapping identified one major QTL(QFhb.hwwg-2DS)on chromosome arm 2DS for the percentage of symptomatic spikelets(PSS)in the spike,deoxynivalenol(DON)content and Fusarium damaged kernel(FDK).This QTL explained up to 71.8%of the phenotypic variation for the three FHB-related traits and overlapped with the major QTL for HT,HD,SL,KNS,SNS,TGW,and grain size.QTL on chromosome arms 2AL,2DS,3AL and 4BS were significant for the spike and grain traits measured.G97252W contributed FHB resistance and high SNS alleles at QFhb.hwwg-2DS,high KNS alleles at the QTL on 2AL and 2DS,and high TGW and grain size alleles at QTL on 3AL;whereas G97380A contributed high TGW and grain size alleles at the QTL on 2AL and 2DS,respectively,and the high KNS allele at the 4BS QTL.Combining QFhb.hwwg-2DS with positive alleles for spike and grain traits from other chromosomes may simultaneously improve FHB resistance and grain yield in new cultivars.

Potential therapeutic effects of pigment epithelium-derived factor for treatment of diabetic retinopathy

Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among working adults in the worldwide. The pathobiology of DR involves multiple molecular pathways and is characterized chronic neurovascular degeneration. Current approaches to prevent or to treat DR are still far from satisfactory. Therefore, it is important to develop new therapeutic strategies for the prevention and treatment to DR. Pigment epithelium-derived factor (PEDF), a 50-kDa secreted glycoprotein, has been described as a multi-functional protein. Some emerging evidences indicate that PEDF are able to target multiple pathways exerting neurotropic, neuroprotective, anti-angiogenic, antivasopermeability, anti-inflammation, anti-thrombogenic and anti-oxidative effects in DR. In this review, we addressed the functions of PEDF in different pathways, which could lead to potential therapeutics on the treatment to DR.

Genome wide association study identifies SNPs associated with fatty acid composition in Chinese Wagyu cattle

Background: Fatty acids are important traits that affect meat quality and nutritive values in beef cattle. Detection of genetic variants for fatty acid composition can help to elucidate the genetic mechanism underpinning these traits and promote the improvement of fatty acid profiles. In this study, we performed a genome-wide association study(GWAS) on fatty acid composition using high-density single nucleotide polymorphism(SNP) arrays in Chinese Wagyu cattle.Results: In total, we detected 15 and 8 significant genome-wide SNPs for individual fatty acids and fatty acid groups in Chinese Wagyu cattle, respectively. Also, we identified nine candidate genes based on 100 kb regions around associated SNPs. Four SNPs significantly associated with C14:1 cis-9 were embedded with stearoyl-CoA desaturase(SCD), while three SNPs in total were identified for C22:6 n-3 within Phospholipid scramblase family member 5(PLSCR5), Cytoplasmic linker associated protein 1(CLASP1), and Chymosin(CYM). Notably, we found the top candidate SNP within SCD can explain ~ 7.37% of phenotypic variance for C14:1 cis-9.Moreover, we detected several blocks with high LD in the 100 kb region around SCD. In addition, we found three significant SNPs within a 100 kb region showing pleiotropic effects related to multiple FA groups(PUFA,n-6, and PUFA/SFA), which contains BAI1 associated protein 2 like 2(BAIAP2 L2), MAF bZIP transcription factor F(MAFF),and transmembrane protein 184 B(TMEM184 B).Conclusions: Our study identified several significant SNPs and candidate genes for individual fatty acids and fatty acid groups in Chinese Wagyu cattle, and these findings will further assist the design of breeding programs for meat quality in cattle.

Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure

Three major cardiovascular outcome trials(CVOTs)with a new class of antidiabetic drugs-sodium-glucose cotransporter 2(SGLT2)inhibitors(EMPAREG OUTCOME trial with empagliflozin,CANVAS Program with canagliflozin,DECLARE-TIMI 58 with dapagliflozin)unexpectedly showed that cardiovascular outcomes could be improved possibly due to a reduction in heart failure risk,which seems to be the most sensitive outcome of SGLT2 inhibition.No other CVOT to date has shown any significant benefit on heart failure events.Even more impressive findings came recently from the DAPA-HF trial in patients with confirmed and well-treated heart failure:Dapagliflozin was shown to reduce heart failure risk for patients with heart failure with reduced ejection fraction regardless of diabetes status.Nevertheless,despite their possible wide clinical implications,there is much doubt about the mechanisms of action and a lot of questions to unravel,especially now when their benefits translated to nondiabetic patients,rising doubts about the validity of some current mechanistic assumptions.The time frame of their cardiovascular benefits excludes glucoselowering and antiatherosclerotic-mediated effects and multiple other mechanisms,direct cardiac as well as systemic,are suggested to explain their early cardiorenal benefits.These are:Anti-inflammatory,antifibrotic,antioxidative,antiapoptotic properties,then renoprotective and hemodynamic effects,attenuation of glucotoxicity,reduction of uric acid levels and epicardial adipose tissue,modification of neurohumoral system and cardiac fuel energetics,sodiumhydrogen exchange inhibition.The most logic explanation seems that SGLT2 inhibitors timely target various mechanisms underpinning heart failure pathogenesis.All the proposed mechanisms of their action could interfere with evolution of heart failure and are discussed separately within the main text.

Characterization of QTL for unique agronomic traits of new-plant-type rice varieties using introgression lines of IR64

To enhance the yield potential of an elite indica rice cultivar,an introgression(BC_3-derived) line of IR64,YTH288,was developed using a new-plant-type cultivar,IR66215-44-2-3,as a donor parent.YTH288 has agronomically valuable characteristics such as large panicles,few unproductive tillers,and large leaves inherited from NPT.To identify the genetic basis of these traits,we used 167 F_2 plants derived from a cross between IR64 and YTH288 to conduct QTL analysis for five agronomic traits:days to heading(DTH),culm length(CL),flag leaf length(FLL),flag leaf width(FLW),and filled spikelet number per panicle(FSN).Six putative QTL were detected:four on chromosome4(for CL,FLL,FLW,and FSN) and two on chromosome 2(for DTH and FLL).All QTL with the IR66215-44-2-3 allele,except that for FLL on chromosome 2,had positive effects on each trait.To confirm the effects of these putative QTL,we developed NILs with the IR64 genetic background by marker-assisted selection.We observed significant differences in several agronomic traits between IR64 and NILs that carried these QTL on chromosomes2 and 4.Additionally,four IR64-NILs carrying chromosomal segments derived from different NPT varieties on the long arm of chromosome 4 exhibited similar pleiotropic To enhance the yield potential of an elite indica rice cultivar, an introgression(BC3-derived) line of IR64, YTH288, was developed using a new-plant-type cultivar,IR66215-44-2-3, as a donor parent. YTH288 has agronomically valuable characteristics such as large panicles, few unproductive tillers, and large leaves inherited from NPT.To identify the genetic basis of these traits, we used 167 F2 plants derived from a cross between IR64 and YTH288 to conduct QTL analysis for five agronomic traits: days to heading(DTH), culm length(CL), flag leaf length(FLL), flag leaf width(FLW), and filled spikelet number per panicle(FSN). Six putative QTL were detected: four on chromosome4(for CL, FLL, FLW, and FSN) and two on chromosome 2(for DTH and FLL). All QTL with the IR66215-44-2-3 allele, except that for FLL on chromosome 2, had positive effects on each trait. To confirm the effects of these putative QTL, we developed NILs with the IR64 genetic background by marker-assisted selection. We observed significant differences in several agronomic traits between IR64 and NILs that carried these QTL on chromosomes2 and 4. Additionally, four IR64-NILs carrying chromosomal segments derived from different NPT varieties on the long arm of chromosome 4 exhibited similar pleiotropiceffects for unique agronomic traits. These NILs can be used as research materials for studying each trait and as breeding materials for yield improvement of indica rice cultivars.

NaPDR1 and NaPDR1-like are essential for the resistance of Nicotiana attenuata against fungal pathogen Alternaria alternata

Pleiotropic drug resistance(PDR) transporters are widely distributed membrane proteins catalyzing the export or import of a diverse array of molecules, and are involved in many plant responses to biotic and abiotic stresses. However, it is unclear whether PDRs are involved in Nicotiana attenuata resistance to the necrotic fungal pathogen Alternaria alternata. In this study, transcriptional levels of both NaPDR1 and NaPDR1-like were highly induced in N. attenuata leaves after A. alternata inoculation. Interestingly,silencing NaPDR1 or NaPDR1-like individually had little effect on N. attenuata resistance to A. alternata;however, when both genes were co-silenced plants became highly susceptible to the fungus, which was associated with elevated JA and ethylene responses. Neither NaPDR1 nor NaPDR1-like was significantly elicited by exogenous treatment with methyl jasmonate(MeJA), whereas both were highly induced by ethylene. The elicitation levels of both genes by A. alternata were significantly reduced in plants with impaired JA or ethylene signaling pathways. Thus, we conclude that both NaPDR1 and NaPDR1-like function redundantly to confer resistance against A. alternata in N. attenuata, and the elicitation of the transcripts of both genes by the fungus is partially dependent on ethylene and jasmonate signaling.

Teneligliptin: Heralding Change in Type 2 Diabetes

“Sweet is Sweet but until it is not too Sweet”. As the sweet spoon of diabetes challenges the global population, diabetic organizations across the globe call for unanimous resonance of Diabetes Voice to tackle diabetes with healthy living. With the discovery of new pathophysiology associated with diabetes, patients are gaining access to the newer therapeutic classes. Teneligliptin, a third generation DPP-4 inhibitor exhibits unique “J-shaped” structure with “anchor-lock domain” mechanism which provides potent & long duration of action. It acts like an insulin/glucagon modulator controlling blood glucose over 24 hours. It is effective in tackling short-term glycemic fluctuations and improvement in β-cell parameters is observed soon after treatment. Half-life of 26.9 hours ensures once a day administration. Because the metabolites of this drug are eliminated via renal and hepatic excretion, no dose adjustment is necessary in patients with renal impairment. Improvement in lipid profile, LV function, adiponectin levels & natriuretic effect is among the added pleiotropic benefits. With the effective glycemic control & capability for improvement in β-cell function, Teneligliptin promises to be a preferable antidiabetic agent with long-term efficacy & safety in patients with type 2 diabetes. The objective of this paper is to provide a comprehensive datum analysis of Teneligliptin in the management of type 2 diabetes. It summarizes the unique pharmacodynamic & pharmacokinetic advantages of Teneligliptin and additionally its pleiotropic benefits of cardioprotection. It provides a comprehensive comparison of Teneligliptin vis-à-vis other gliptins in the class & provides a concise summary of all clinical trials till the date with Teneligliptin monotherapy & combination with other antidiabetic drugs.

A Capra hircus chromosome 19 locus linked to milk production influences mammary conformation

Background:Economically important milk production traits including milk volume,milk fat and protein yield vary considerably across dairy goats in New Zealand.A significant portion of the variation is attributable to genetic variation.Discovery of genetic markers linked to milk production traits can be utilised to drive selection of highperformance animals.A previously reported genome wide association study across dairy goats in New Zealand identified a quantitative trait locus(QTL)located on chromosome 19.The most significantly associated single nucleotide polymorphism(SNP)marker for this locus is located at position 26,610,610(SNP marker rs268292132).This locus is associated with multiple milk production traits including fat,protein and volume.The predicted effect of selection for the beneficial haplotype would result in an average production increase of 2.2 kg fat,1.9 kg protein and 73.6 kg milk yield.An outstanding question was whether selection for the beneficial allele would co-select for any negative pleiotropic effects.An adverse relationship between milk production and udder health traits has been reported at this locus.Therefore,a genome wide association study was undertaken looking for loci associated with udder traits.Results:The QTL and production associated marker rs268292132 was identified in this study to also be associated with several goat udder traits including udder depth(UD),fore udder attachment(FUA)and rear udder attachment(RUA).Our study replicates the negative relationship between production and udder traits with the high production allele at position 19:26,610,610(SNP marker rs268292132)associated with an adverse change in UD,FUA and RUA.Conclusions:Our study has confirmed the negative relationship between udder traits and production traits in the NZ goat population.We have found that the frequency of the high production allele is relatively high in the NZ goat population,indicating that its effect on udder conformation is not significantly detrimental on animal health.It will however be important to monitor udder conformation as the chromosome 19 locus is progressively implemented for marker assisted selection.It will also be of interest to determine if the gene underlying the production QTL has a direct effect on mammary gland morphology or whether the changes observed are a consequence of the increased milk volume.

Statins in risk-reduction and treatment of cancer

Statins,which are competitive inhibitors of 3-hydroxy-3-methyl-glutarylcoenzyme A reductase,reduce cholesterol blood levels and the risk of developing cardiovascular diseases and their related complications.In addition to this main activity,statins show pleiotropic effects such as antioxidant,anti-inflammatory and antiproliferative properties,with applications in many pathologies.Based on their antiproliferative properties,in vitro and in vivo studies have investigated their effects on various types of cancer(i.e.,breast cancer,prostate cancer,colorectal cancer,ovarian cancer,lung cancer)with different genetic and molecular characteristics.Many positive results were obtained,but they were highly dependent on the physiochemical properties of the statins,their dose and treatment period.Combined therapies of statins and cytotoxic drugs have also been tested,and synergistic or additive effects were observed.Moreover,observational studies performed on patients who used statins for different pathologies,revealed that statins reduced the risk of developing various cancers,and improved the outcomes for cancer patients.Currently,there are many ongoing clinical trials aimed at exploring the potential of statins to lower the mortality and the disease-recurrence risk.All these results are the foundation of new treatment directions in cancer therapy.