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1.
Planta ; 260(1): 13, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38809276

RESUMEN

MAIN CONCLUSION: PM3 and PM8 alleles carried by two CIMMYT wheat lines confer powdery mildew resistance in seedlings and/or adult plants. A stage-specific epistatic interaction was observed between PM3 and PM8. Powdery mildew is an important foliar disease of wheat. Major genes for resistance, which have been widely used in wheat breeding programs, are typically effective against only limited numbers of virulence genes of the pathogen. The main aim of this study was to map resistance loci in wheat lines 7HRWSN58 and ZWW09-149 from the International Maize and Wheat Improvement Center (CIMMYT). Doubled haploid populations (Magenta/7HRWSN58 and Emu Rock/ZWW09-149) were developed and grown in controlled environment experiments and inoculated with a composite of Blumeria graminis f.sp. tritici isolates that had been collected at various locations in Western Australia. Plants were assessed for powdery mildew symptoms (percentage leaf area diseased) on seedlings and adult plants. Populations were subjected to genotyping-by-sequencing and assayed for known SNPs in the resistance gene PM3. Linkage maps were constructed, and markers were anchored to the wheat reference genome sequence. In both populations, there were asymptomatic lines that exhibited no symptoms. Among symptomatic lines, disease severity varied widely. In the Magenta/7HRWSN58 population, most of the observed variation was attributed to the PM3 region of chromosome 1A, with the allele from 7HRWSN58 conferring resistance in seedlings and adult plants. In the Emu Rock/ZWW09-149 population, two interacting quantitative trait loci were mapped: one at PM3 and the other on chromosome 1B. The Emu Rock/ZWW09-149 population was confirmed to segregate for a 1BL·1RS translocation that carries the PM8 powdery mildew resistance gene from rye. Consistent with previous reports that PM8-derived resistance can be suppressed by PM3 alleles, the observed interaction between the quantitative trait loci on chromosomes 1A and 1B indicated that the PM3 allele carried by ZWW09-149 suppresses PM8-derived resistance from ZWW09-149, but only at the seedling stage. In adult plants, the PM8 region conferred resistance regardless of the PM3 genotype. The resistance sources and molecular markers that were investigated here could be useful in wheat breeding.


Asunto(s)
Ascomicetos , Mapeo Cromosómico , Resistencia a la Enfermedad , Enfermedades de las Plantas , Plantones , Triticum , Triticum/genética , Triticum/microbiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Ascomicetos/fisiología , Ascomicetos/patogenicidad , Plantones/genética , Plantones/microbiología , Resistencia a la Enfermedad/genética , Alelos , Sitios de Carácter Cuantitativo/genética , Polimorfismo de Nucleótido Simple/genética , Ligamiento Genético , Genes de Plantas , Fitomejoramiento , Genotipo
2.
PLoS Biol ; 22(5): e3002519, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38787858

RESUMEN

When males compete, sexual selection favors reproductive traits that increase their mating or fertilization success (pre- and postcopulatory sexual selection). It is assumed that males face a trade-off between these 2 types of sexual traits because they both draw from the same pool of resources. Consequently, allocation into mate acquisition or ejaculation should create similar trade-offs with other key life history traits. Tests of these assumptions are exceedingly rare. Males only ejaculate after they mate, and the costs of ejaculation are therefore highly confounded with those of mating effort. Consequently, little is known about how each component of reproductive allocation affects a male's future performance. Here, we ran an experiment using a novel technique to distinguish the life history costs of mating effort and ejaculation for mosquitofish (Gambusia holbrooki). We compared manipulated males (mate without ejaculation), control males (mate and ejaculate), and naïve males (neither mate nor ejaculate) continuously housed with a female and 2 rival males. We assessed their growth, somatic maintenance, mating and fighting behavior, and sperm traits after 8 and 16 weeks. Past mating effort significantly lowered a male's future mating effort and growth, but not his sperm production, while past sperm release significantly lowered a male's future ejaculate quantity, but not his mating effort. Immune response was the only trait impacted by both past mating effort and past ejaculation. These findings challenge the assumption that male reproductive allocation draws from a common pool of resources to generate similar life history costs later in life. Instead, we provide clear evidence that allocation into traits under pre- and postcopulatory sexual selection have different trait-specific effects on subsequent male reproductive performance.


Asunto(s)
Eyaculación , Reproducción , Conducta Sexual Animal , Masculino , Animales , Eyaculación/fisiología , Femenino , Conducta Sexual Animal/fisiología , Reproducción/fisiología , Preferencia en el Apareamiento Animal/fisiología , Espermatozoides/fisiología , Selección Sexual
3.
Front Pediatr ; 12: 1371776, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38571701

RESUMEN

Aim: Retinopathy of prematurity is a significant global cause of childhood blindness. This study aims to identify serum biomarkers that are associated with the development of ROP. Methods: A systematic review and meta-analysis was conducted using PRISMA guidelines. Three databases were searched (Pubmed, Scopus and Web of Science) from 2003 to March 2023. Only studies investigating serum biomarker levels in preterm infants (<37 weeks gestation) were included. Results: Meta-analysis suggests that low serum IGF-1 levels have a strong association with the development of ROP [SMD (95% CI) of -.46 [-.63, -.30], p < .001]. Meta-analysis suggests that higher serum glucose levels were associated with the development of ROP [SMD (95% CI) of 1.25 [.94, 1.55], p < .001]. Meta-analysis suggests that thrombocytopenia is associated with the development of ROP [SMD (95% CI) of -.62 [-.86, -.37], p < .001]. Conclusion: Low levels of serum IGF-1, high levels of serum glucose and thrombocytopenia all appear to have the strongest association with the development of ROP out of the 63 biomarkers investigated in this review. These associations highlight their potential use as diagnostic biomarkers in ROP, though further research is needed to establish the exact relationship between these biomarkers and disease pathogenesis.

4.
Behav Ecol ; 35(2): arae002, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38273897

RESUMEN

Past reproductive effort allows males to assess their ability to acquire mates, but it also consumes resources that can reduce their future competitive ability. Few studies have examined how a male's reproductive history affects his subsequent mate choice, and, to date, no study has determined the relative contribution of past mating behavior and past ejaculate production because these two forms of investment are naturally highly correlated. Here, we disentangled the relative effects of past mating behavior and past ejaculate production in mosquitofish (Gambusia holbrooki) by experimentally preventing some males from ejaculating when trying to mate. We assessed the effect of mating behavior on mate choice by comparing males that had previously been with or without access to females and male rivals for 8 and 16 weeks and assessed the effect of ejaculation on mate choice by comparing males that either could or could not ejaculate when they had access to females for 16 weeks. Reproductive treatment did not affect male attractiveness, but it did affect male mate choice. Somewhat surprisingly, in five of the six treatment-by-age at testing combinations, males preferred a female in the vicinity of a male rival over a solitary female. This preference was marginally stronger for males that had previously engaged in mating behavior but were unaffected by past ejaculate production. We discuss the potential benefits to males of associating with another male when seeking mates. This is the first study to quantify the relative influence of pre- and post-copulatory reproductive investment on male mate choice.

5.
JAMA Cardiol ; 8(4): 366-375, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36884247

RESUMEN

Importance: Pre-heart failure with preserved ejection fraction (pre-HFpEF) is common and has no specific therapy aside from cardiovascular risk factor management. Objective: To investigate the hypothesis that sacubitril/valsartan vs valsartan would reduce left atrial volume index using volumetric cardiac magnetic resonance imaging in patients with pre-HFpEF. Design, Setting, and Participants: The Personalized Prospective Comparison of ARNI [angiotensin receptor/neprilysin inhibitor] With ARB [angiotensin-receptor blocker] in Patients With Natriuretic Peptide Elevation (PARABLE) trial was a prospective, double-blind, double-dummy, randomized clinical trial carried out over 18 months between April 2015 and June 2021. The study was conducted at a single outpatient cardiology center in Dublin, Ireland. Of 1460 patients in the STOP-HF program or outpatient cardiology clinics, 461 met initial criteria and were approached for inclusion. Of these, 323 were screened and 250 asymptomatic patients 40 years and older with hypertension or diabetes, elevated B-type natriuretic peptide (BNP) greater than 20 pg/mL or N-terminal pro-b-type natriuretic peptide greater than 100 pg/mL, left atrial volume index greater than 28 mL/m2, and preserved ejection fraction greater than 50% were included. Interventions: Patients were randomized to angiotensin receptor neprilysin inhibitor sacubitril/valsartan titrated to 200 mg twice daily or matching angiotensin receptor blocker valsartan titrated to 160 mg twice daily. Main Outcomes and Measures: Maximal left atrial volume index and left ventricular end diastolic volume index, ambulatory pulse pressure, N-terminal pro-BNP, and adverse cardiovascular events. Results: Among the 250 participants in this study, the median (IQR) age was 72.0 (68.0-77.0) years; 154 participants (61.6%) were men and 96 (38.4%) were women. Most (n = 245 [98.0%]) had hypertension and 60 (24.0%) had type 2 diabetes. Maximal left atrial volume index was increased in patients assigned to receive sacubitril/valsartan (6.9 mL/m2; 95% CI, 0.0 to 13.7) vs valsartan (0.7 mL/m2; 95% CI, -6.3 to 7.7; P < .001) despite reduced markers of filling pressure in both groups. Changes in pulse pressure and N-terminal pro-BNP were lower in the sacubitril/valsartan group (-4.2 mm Hg; 95% CI, -7.2 to -1.21 and -17.7%; 95% CI, -36.9 to 7.4, respectively; P < .001) than the valsartan group (-1.2 mm Hg; 95% CI, -4.1 to 1.7 and 9.4%; 95% CI, -15.6 to 4.9, respectively; P < .001). Major adverse cardiovascular events occurred in 6 patients (4.9%) assigned to sacubitril/valsartan and 17 (13.3%) assigned to receive valsartan (adjusted hazard ratio, 0.38; 95% CI, 0.17 to 0.89; adjusted P = .04). Conclusions and Relevance: In this trial of patients with pre-HFpEF, sacubitril/valsartan treatment was associated with a greater increase in left atrial volume index and improved markers of cardiovascular risk compared to valsartan. More work is needed to understand the observed increased cardiac volumes and long-term effects of sacubitril/valsartan in patients with pre-HFpEF. Trial Registration: ClinicalTrials.gov Identifier: NCT04687111.


Asunto(s)
Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Hipertensión , Masculino , Humanos , Femenino , Anciano , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/inducido químicamente , Péptido Natriurético Encefálico , Antagonistas de Receptores de Angiotensina , Neprilisina , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Tetrazoles/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Volumen Sistólico , Valsartán/uso terapéutico , Atrios Cardíacos , Hipertensión/tratamiento farmacológico
6.
Theor Appl Genet ; 136(3): 61, 2023 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-36912976

RESUMEN

KEY MESSAGE: Novel sources of genetic resistance to tan spot in Australia have been discovered using one-step GWAS and genomic prediction models that accounts for additive and non-additive genetic variation. Tan spot is a foliar disease in wheat caused by the fungal pathogen Pyrenophora tritici-repentis (Ptr) and has been reported to generate up to 50% yield losses under favourable disease conditions. Although farming management practices are available to reduce disease, the most economically sustainable approach is establishing genetic resistance through plant breeding. To further understand the genetic basis for disease resistance, we conducted a phenotypic and genetic analysis study using an international diversity panel of 192 wheat lines from the Maize and Wheat Improvement Centre (CIMMYT), the International Centre for Agriculture in the Dry Areas (ICARDA) and Australian (AUS) wheat research programmes. The panel was evaluated using Australian Ptr isolates in 12 experiments conducted in three Australian locations over two years, with assessment for tan spot symptoms at various plant development stages. Phenotypic modelling indicated high heritability for nearly all tan spot traits with ICARDA lines displaying the greatest average resistance. We then conducted a one-step whole-genome analysis of each trait using a high-density SNP array, revealing a large number of highly significant QTL exhibiting a distinct lack of repeatability across the traits. To better summarise the genetic resistance of the lines, a one-step genomic prediction of each tan spot trait was conducted by combining the additive and non-additive predicted genetic effects of the lines. This revealed multiple CIMMYT lines with broad genetic resistance across the developmental stages of the plant which can be utilised in Australian wheat breeding programmes to improve tan spot disease resistance.


Asunto(s)
Sitios de Carácter Cuantitativo , Triticum , Triticum/genética , Triticum/microbiología , Mapeo Cromosómico , Resistencia a la Enfermedad/genética , Fitomejoramiento , Australia , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología
7.
Nutrients ; 15(6)2023 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-36986233

RESUMEN

(1) Background/Objectives: The relationship between body mass index (BMI) and probable sarcopenia, a precursor to sarcopenia diagnosis, is unclear. While low BMI has been associated with sarcopenia risk, some evidence suggests that obesity may confer protection. We aimed to investigate the association between probable sarcopenia and BMI and, furthermore, to explore associations with waist circumference (WC). (2) Methods: This cross-sectional study included 5783 community-dwelling adults (mean age 70.4 ± 7.5 years) from Wave 6 of the English Longitudinal Study of Ageing (ELSA). Probable sarcopenia was defined using the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria for low hand grip strength and/or slow chair rise. Associations between BMI and probable sarcopenia were examined using multivariable regression analysis and were similarly performed for WC. (3) Results: Our overall findings show that an underweight BMI was significantly associated with an increased likelihood of probable sarcopenia [OR (CI) 2.25 (1.17, 4.33), p = 0.015]. For higher BMI categories, the findings were conflicting. Overweight and obesity were associated with an increased likelihood of probable sarcopenia when defined by lower limb strength alone, [OR (CI), 2.32 (1.15, 4.70), p = 0.019; 1.23 (1.02, 1.49), p = 0.35, and 1.49 (1.21, 1.83), p < 0.001, respectively]. In contrast, overweight and obesity appeared protective when probable sarcopenia was assessed by low hand grip strength alone [OR (CI) 0.72 (0.60, 0.88), p = 0.001, and 0.64 (0.52, 0.79), p < 0.001, respectively]. WC was not significantly associated with probable sarcopenia on multivariable regression analysis. (4) Conclusion: This study supports the evidence that low BMI is associated with an increased likelihood of probable sarcopenia, highlighting an important at-risk group. The findings for overweight and obesity were inconsistent and may be measurement dependent. It seems prudent that all older adults at risk of probable sarcopenia, including those with overweight/obesity, are assessed to prevent underdetection of probable sarcopenia alone or with the double burden of obesity.


Asunto(s)
Sarcopenia , Humanos , Anciano , Persona de Mediana Edad , Sarcopenia/complicaciones , Sarcopenia/epidemiología , Sarcopenia/diagnóstico , Índice de Masa Corporal , Vida Independiente , Fuerza de la Mano , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Estudios Longitudinales , Estudios Transversales , Obesidad/complicaciones , Obesidad/epidemiología , Pérdida de Peso
8.
Anal Biochem ; 647: 114581, 2022 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-35134388

RESUMEN

Sarcopenia, characterized by a loss of muscle strength, quantity/quality, and physical performance is associated with increased mortality and poor clinical outcomes in concomitant presentation with liver cirrhosis (LC). A number of mechanisms are involved in sarcopenia development in LC, many of which are secondary to liver dysfunction and/or iatrogenic involvement in treating LC. Sarcopenia severity in this population appears to be affected by patient gender, as well as the primary aetiology of LC (alcohol, non-alcoholic fatty liver disease etc.) with patient demographics shifting in recent years. Clinical detection of sarcopenia in this population may involve a combination of assessment tools, in addition to measuring muscle mass and strength separately. Muscle mass may be assessed using radiography, bioelectric impedance, ultrasound, or anthropometrics. Hand-grip strength, on the other hand, may be a useful tool for evaluating muscle strength. The role of malnutrition in sarcopenia is also a relevant factor, and screening tools such as MELD and SARC-F may be clinically useful tools for more complete diagnosis of sarcopenia in these patients. Myostatin and titin-N may represent potential diagnostic biomarkers. Lastly, physical activity and nutrition remain key elements of treatment. Further research is being conducted regarding the role of resistance vs aerobic exercise as well as the function of complementary nutrition. Continued study into the role of nutrition, physical activity and other complementary therapies will be important future endeavours in the treatment of sarcopenia in LC.


Asunto(s)
Sarcopenia , Fuerza de la Mano , Humanos , Cirrosis Hepática/complicaciones , Prevalencia , Sarcopenia/diagnóstico , Sarcopenia/epidemiología , Sarcopenia/terapia
9.
Evol Lett ; 5(4): 315-327, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34367658

RESUMEN

Although it is widely stated that both mating behavior and sperm traits are energetically costly for males, we currently lack empirical estimates of the relative costs to males of pre- versus postcopulatory investments. Such estimates require the experimental separation of the act of mating from that of ejaculation, which is a nontrivial logistical challenge. Here, we overcome this challenge using a novel morphological manipulation (gonopodium tip ablation) in the eastern mosquitofish (Gambusia holbrooki) to tease apart investment in mating effort from that in sperm replenishment following ejaculation. We quantified the relative cumulative costs of investing in mating effort and ejaculation by comparing somatic traits and reproductive performance among three types of males: ablated males that could attempt to mate but not ejaculate; unablated males that could both mate and ejaculate; and control males that had no access to females. We show that, after eight weeks, mating investment significantly reduces both body growth and immunocompetence and results in a significant decline in mating effort. In contrast, cumulative investment into sperm replenishment following ejaculation has few detectable effects that are only apparent in smaller males. These minor costs occur despite the fact that G. holbrooki has very high levels of sperm competition and multiple mating by both sexes, which is usually associated with elevated levels of sperm production. Crucially, our study is the first, to our knowledge, to experimentally compare the relative costs of pre- and postcopulatory investment on components of male fitness in a vertebrate.

10.
Proc Biol Sci ; 288(1955): 20210979, 2021 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-34315259

RESUMEN

Older males often perform poorly under post-copulatory sexual selection. It is unclear, however, whether reproductive senescence is because of male age itself or the accumulated costs of the higher lifetime mating effort that is usually associated with male age. To date, very few studies have accounted for mating history and sperm storage when testing the effect of male age on sperm traits, and none test how age and past mating history influence paternity success under sperm competition. Here, we experimentally manipulate male mating history to tease apart its effects from that of age on ejaculate traits and paternity in the mosquitofish, Gambusia holbrooki. We found that old, naive males had more sperm than old, experienced males, while the reverse was true for young males. By contrast, neither male age nor mating history affected sperm velocity. Finally, using artificial insemination to experimentally control the number of sperm per male, we found that old males sired significantly more offspring than young males independently of their mating history. Our results highlight that the general pattern of male reproductive senescence described in many taxa may often be affected by two naturally confounding factors, male mating history and sperm age, rather than male age itself.


Asunto(s)
Ciprinodontiformes , Paternidad , Animales , Copulación , Masculino , Reproducción , Conducta Sexual Animal , Espermatozoides
11.
Anim Cogn ; 24(4): 765-775, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33471228

RESUMEN

Akin to handedness in humans, some animals show a preference for moving to the left or right. This is often attributed to lateralised cognitive functions and eye dominance, which, in turn, influences their behaviour. In fishes, behavioural lateralisation has been tested using detour mazes for over 20 years. Studies report that certain individuals are more likely to approach predators or potential mates from one direction. These findings imply that the lateralisation behaviour of individuals is repeatable, but this is rarely confirmed through multiple testing of each individual over time. Here we quantify the repeatability of turning behaviour by female mosquitofish (Gambusia holbrooki) in a double sided T-maze. Each female was tested three times in each of six treatments: when approaching other females, males, or an empty space; and when able to swim freely or when forced to choose by being herded from behind with a net. Although there was no turning bias based on the mean population response, we detected significant repeatability of lateralisation in five of the six treatments (R = 0.251-0.625). This is noteworthy as we also found that individuals tended to alternate between left and right turns, meaning that they tend to move back and forth along one wall of the double-sided T-maze. Furthermore, we found evidence for this wall following when re-analysing data from a previous study. We discuss potential explanations for this phenomenon, and its implications for study design.


Asunto(s)
Ciprinodontiformes , Animales , Femenino , Lateralidad Funcional , Natación
12.
Planta ; 253(1): 5, 2021 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-33387045

RESUMEN

MAIN CONCLUSION: Dormancy in white-grained wheat is conditioned by the cumulative effects of several QTL that delay the onset of the capacity to germinate during ripening and after-ripening. Grain dormancy at harvest-ripeness is a major component of resistance to preharvest sprouting in wheat (Triticum aestivum L.) and an important trait in regions where rain is common during the harvest period. Breeding lines developed in Australia maintained their dormancy phenotype over multiple seasons and during grain ripening, the time between anthesis and the acquisition of the capacity to germinate, dormancy release, increased in line with the strength of dormancy. Genetic dissection of two dormant lines indicated that dormancy was due to the cumulative action of between one and three major genetic loci and several minor loci. This presents a significant challenge for breeders targeting environments with a high risk of sprouting where strong dormancy is desirable. Only around half of the difference in dormancy between the dormant lines and a non-dormant variety could be attributed to the major genetic loci on chromosomes 4A and 3A. A QTL that was mapped on chromosome 5A may be an orthologue of a minor QTL for dormancy in barley. At each locus, the dormancy allele increased the time to dormancy release during ripening. In combination, these alleles had cumulative effects. Embryo sensitivity to abscisic acid was related to the dormancy phenotype of the whole caryopsis, however, changes in concentrations of abscisic acid and gibberellins in embryo sections and de-embryonated grains during ripening and after-ripening could not be linked to the timing of dormancy release.


Asunto(s)
Latencia en las Plantas , Sitios de Carácter Cuantitativo , Triticum , Mapeo Cromosómico , Germinación/genética , Hordeum/genética , Hordeum/crecimiento & desarrollo , Latencia en las Plantas/genética , Sitios de Carácter Cuantitativo/genética , Triticum/genética , Triticum/crecimiento & desarrollo
13.
Traffic ; 21(9): 560-577, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32613751

RESUMEN

Specialization of many cells, including the acinar cells of the salivary glands and pancreas, milk-producing cells of mammary glands, mucus-secreting goblet cells, antibody-producing plasma cells, and cells that generate the dense extracellular matrices of bone and cartilage, requires scaling up both secretory machinery and cell-type specific secretory cargo. Using tissue-specific genome-scale analyses, we determine how increases in secretory capacity are coordinated with increases in secretory load in the Drosophila salivary gland (SG), an ideal model for gaining mechanistic insight into the functional specialization of secretory organs. Our findings show that CrebA, a bZIP transcription factor, directly binds genes encoding the core secretory machinery, including protein components of the signal recognition particle and receptor, ER cargo translocators, Cop I and Cop II vesicles, as well as the structural proteins and enzymes of these organelles. CrebA directly binds a subset of SG cargo genes and CrebA binds and boosts expression of Sage, a SG-specific transcription factor essential for cargo expression. To further enhance secretory output, CrebA binds and activates Xbp1 and Tudor-SN. Thus, CrebA directly upregulates the machinery of secretion and additional factors to increase overall secretory capacity in professional secretory cells; concomitant increases in cargo are achieved both directly and indirectly.


Asunto(s)
Proteínas de Drosophila , Animales , Proteína de Unión al Elemento de Respuesta al AMP Cíclico , Drosophila , Proteínas de Drosophila/genética , Glándulas Salivales , Factores de Transcripción
14.
Scand J Clin Lab Invest ; 80(6): 508-514, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32706999

RESUMEN

Familial hypercholesterolemia (FH) is a monogenic disease characterized by a lifelong exposure to high LDL-C levels that can lead to early onset coronary heart disease (CHD). The main causes of FH identified to date include loss-of-function mutations in LDLR or APOB, or gain-of-function mutations in PCSK9. Early diagnosis and genetic testing of FH suspects is critical for improved prognosis of affected individuals as lipid lowering treatments are effective in preventing CHD related morbidity and mortality. In the present study, we carried out a comprehensive screening, using a next-generation sequencing (NGS) panel, for FH culprit mutations in two Icelandic studies representative of either FH families or the general population. We confirmed all previously known mutations in the FH families, and identified two subjects that had been misdiagnosed clinically at young age. We identified six new mutations in the Icelandic FH families and detected three pathogenic mutations in the general population-based study. The application of the NGS panel revealed substantial diagnostic yields in identifying pathogenic mutations, or 68.2% of those with definite clinical diagnosis of FH in the family material and 5.6-fold enrichment in the population-based genetic testing.


Asunto(s)
Pruebas Genéticas/métodos , Hiperlipoproteinemia Tipo II/diagnóstico , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hiperlipoproteinemia Tipo II/genética , Islandia , Mutación con Pérdida de Función , Mutación , Estudios Prospectivos
15.
Biol Lett ; 16(6): 20200251, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32574532

RESUMEN

The evolution of male genital traits is usually ascribed to advantages that arise when there is sperm competition, cryptic female choice or sexual conflict. However, when male-female contact is brief and sperm production is costly, genital structures that ensure the appropriate timing of sperm release should also be under intense selection. Few studies have examined the role of individual structures in triggering ejaculation. We therefore conducted a series of anatomical manipulations of fine-scale features of the complex intromittent organ (gonopodium) of a freshwater fish with internal fertilization (Gambusia holbrooki) to determine their effects on sperm release. Mating in G. holbrooki is fleeting (less than 50 ms), so there should be strong selection for control over the timing of sperm release. We surgically removed three features at the tip of the gonopodium (claws, spines, awl-shape) to test for their potential role in triggering ejaculation. We show that the 'awl-shape' of the tip affects sperm release when a male makes contact with a female, but neither gonopodial claws nor spines had a detectable effect. We suggest that the claws and spines may instead function to increase the precision of sperm deposition (facilitating anchorage and contact time with the female's gonopore), rather than the initiation of ejaculation.


Asunto(s)
Ciprinodontiformes , Eyaculación , Animales , Femenino , Genitales Masculinos , Masculino , Reproducción , Conducta Sexual Animal , Espermatozoides
16.
Am J Physiol Renal Physiol ; 319(1): F63-F75, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32463726

RESUMEN

Diuretics and renin-angiotensin system blockers are often insufficient to control the blood pressure (BP) in salt-sensitive (SS) subjects. Abundant data support the proposal that the level of atrial natriuretic peptide may correlate with the pathogenesis of SS hypertension. We hypothesized here that increasing atrial natriuretic peptide levels with sacubitril, combined with renin-angiotensin system blockage by valsartan, can be beneficial for alleviation of renal damage in a model of SS hypertension, the Dahl SS rat. To induce a BP increase, rats were challenged with a high-salt 4% NaCl diet for 21 days, and chronic administration of vehicle or low-dose sacubitril and/or valsartan (75 µg/day each) was performed. Urine flow, Na+ excretion, and water consumption were increased on the high-salt diet compared with the starting point (0.4% NaCl) in all groups but remained similar among the groups at the end of the protocol. Upon salt challenge, we observed a mild decrease in systolic BP and urinary neutrophil gelatinase-associated lipocalin levels (indicative of alleviated tubular damage) in the valsartan-treated groups. Sacubitril, as well as sacubitril/valsartan, attenuated the glomerular filtration rate decline induced by salt. Alleviation of protein cast formation and lower renal medullary fibrosis were observed in the sacubitril/valsartan- and valsartan-treated groups, but not when sacubitril alone was administered. Interestingly, proteinuria was mildly mitigated only in rats that received sacubitril/valsartan. Further studies of the effects of sacubitril/valsartan in the setting of SS hypertension, perhaps involving a higher dose of the drug, are warranted to determine if it can interfere with the progression of the disease.


Asunto(s)
Aminobutiratos/administración & dosificación , Antagonistas de Receptores de Angiotensina/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Enfermedades Renales/tratamiento farmacológico , Tetrazoles/administración & dosificación , Valsartán/administración & dosificación , Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Animales , Compuestos de Bifenilo , Combinación de Medicamentos , Hipertensión/fisiopatología , Enfermedades Renales/fisiopatología , Masculino , Ratas , Ratas Endogámicas Dahl , Cloruro de Sodio Dietético , Tetrazoles/uso terapéutico , Valsartán/uso terapéutico
17.
Biol Lett ; 16(2): 20190945, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32097600

RESUMEN

Studies often show that paternal age affects offspring fitness. However, such effects could be due either to age, or to a male's previous mating effort (which is necessarily confounded with age). We experimentally tested whether differences in the mating history of old males affect offspring performance in the mosquitofish Gambusia holbrooki. Upon maturation, males were housed for a duration of the natural field-breeding season (23 weeks) either with mating access to females (lifetime-mating), or with visual but no physical access to females (no-mating). We then paired these males with a female to test whether male mating history had a significant effect on their mate's breeding success or offspring performance. The daughters, but not the sons, of 'no-mating' treatment males matured significantly sooner, and at a significantly smaller size, than those of 'lifetime-mating' treatment males. There was, however, no effect of male mating history on their daughters' initial fecundity, or on proxy measures of their sons' reproductive success. These results, when combined with earlier studies showing effects of male mating history on sperm quality, growth and immunity, suggest that variation in paternal effects currently attributed to male age could partly arise because older males have usually mated more often than younger males.


Asunto(s)
Ciprinodontiformes , Conducta Sexual Animal , Animales , Femenino , Fertilidad , Masculino , Herencia Paterna , Reproducción
18.
J Evol Biol ; 32(11): 1262-1273, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31444811

RESUMEN

Many studies investigate the benefits of polyandry, but repeated interactions with males can lower female reproductive success. Interacting with males might even decrease offspring performance if it reduces a female's ability to transfer maternal resources. Male presence can be detrimental for females in two ways: by forcing females to mate at a higher rate and through costs associated with resisting male mating attempts. Teasing apart the relative costs of elevated mating rates from those of greater male harassment is critical to understand the evolution of mating strategies. Furthermore, it is important to test whether a male's phenotype, notably body size, has differential effects on female reproductive success versus the performance of offspring, and whether this is due to male body size affecting the costs of harassment or the actual mating rate. In the eastern mosquitofish Gambusia holbrooki, males vary greatly in body size and continually attempt to inseminate females. We experimentally manipulated male presence (i.e., harassment), male body size and whether males could copulate. Exposure to males had strong detrimental effects on female reproductive output, growth and immune response, independent of male size or whether males could copulate. In contrast, there was a little evidence of a cross-generational effect of male harassment or mating rate on offspring performance. Our results suggest that females housed with males pay direct costs due to reduced condition and offspring production and that these costs are not a consequence of increased mating rates. Furthermore, exposure to males does not affect offspring reproductive traits.


Asunto(s)
Tamaño Corporal , Ciprinodontiformes/fisiología , Fertilidad/fisiología , Conducta Sexual Animal , Agresión , Animales , Copulación , Femenino , Inmunidad Celular/efectos de los fármacos , Inmunidad Celular/fisiología , Masculino , Fitohemaglutininas/farmacología
19.
Philos Trans R Soc Lond B Biol Sci ; 374(1768): 20180174, 2019 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-30966962

RESUMEN

How populations and species respond to modified environmental conditions is critical to their persistence both now and into the future, particularly given the increasing pace of environmental change. The process of adaptation to novel environmental conditions can occur via two mechanisms: (1) the expression of phenotypic plasticity (the ability of one genotype to express varying phenotypes when exposed to different environmental conditions), and (2) evolution via selection for particular phenotypes, resulting in the modification of genetic variation in the population. Plasticity, because it acts at the level of the individual, is often hailed as a rapid-response mechanism that will enable organisms to adapt and survive in our rapidly changing world. But plasticity can also retard adaptation by shifting the distribution of phenotypes in the population, shielding it from natural selection. In addition to which, not all plastic responses are adaptive-now well-documented in cases of ecological traps. In this theme issue, we aim to present a considered view of plasticity and the role it could play in facilitating or hindering adaption to environmental change. This introduction provides a re-examination of our current understanding of the role of phenotypic plasticity in adaptation and sets the theme issue's contributions in their broader context. Four key themes emerge: the need to measure plasticity across both space and time; the importance of the past in predicting the future; the importance of the link between plasticity and sexual selection; and the need to understand more about the nature of selection on plasticity itself. We conclude by advocating the need for cross-disciplinary collaborations to settle the question of whether plasticity will promote or retard species' rates of adaptation to ever-more stressful environmental conditions. This article is part of the theme issue 'The role of plasticity in phenotypic adaptation to rapid environmental change'.


Asunto(s)
Adaptación Fisiológica , Evolución Biológica , Cambio Climático , Ambiente , Selección Genética , Genotipo
20.
Philos Trans R Soc Lond B Biol Sci ; 374(1768): 20180184, 2019 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-30966965

RESUMEN

In a rapidly changing environment, does sexual selection on males elevate a population's reproductive output? If so, does phenotypic plasticity enhance or diminish any such effect? We outline two routes by which sexual selection can influence the reproductive output of a population: a genetic correlation between male sexual competitiveness and female lifetime reproductive success; and direct effects of males on females' breeding success. We then discuss how phenotypic plasticity of sexually selected male traits and/or female responses (e.g. plasticity in mate choice), as the environment changes, might influence how sexual selection affects a population's reproductive output. Two key points emerge. First, condition-dependent expression of male sexual traits makes it likely that sexual selection increases female fitness if reproductively successful males disproportionately transfer genes that are under natural selection in both sexes, such as genes for foraging efficiency. Condition-dependence is a form of phenotypic plasticity if some of the variation in net resource acquisition and assimilation is attributable to the environment rather than solely genetic in origin. Second, the optimal allocation of resources into different condition-dependent traits depends on their marginal fitness gains. As male condition improves, this can therefore increase or, though rarely highlighted, actually decrease the expression of sexually selected traits. It is therefore crucial to understand how condition determines male allocation of resources to different sexually selected traits that vary in their immediate effects on female reproductive output (e.g. ornaments versus coercive behaviour). In addition, changes in the distribution of condition among males as the environment shifts could reduce phenotypic variance in certain male traits, thereby reducing the strength of sexual selection imposed by females. Studies of adaptive evolution under rapid environmental change should consider the possibility that phenotypic plasticity of sexually selected male traits, even if it elevates male fitness, could have a negative effect on female reproductive output, thereby increasing the risk of population extinction. This article is part of the theme issue 'The role of plasticity in phenotypic adaptation to rapid environmental change'.


Asunto(s)
Adaptación Fisiológica , Preferencia en el Apareamiento Animal , Fenotipo , Reproducción , Animales , Evolución Biológica , Femenino , Masculino , Modelos Biológicos , Selección Genética
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