Rare Case of Monozygotic Twins Diagnosed With Klinefelter Syndrome During Evaluation for Infertility

Although neither Klinefelter syndrome nor monozygotic twins are particularly rare (1/667 male births and 3–4/1000 live births, respectively), the occurrence of both in the same pregnancy (ie, identical twins with Klinefelter syndrome) is exceedingly rare and has only been reported three times previously in the literature. This report describes the fourth ever reported case of monozygotic twins with Klinefelter syndrome (who presented to our male fertility clinic with failure to conceive) and sheds interesting light on the reproductive concordance observed with this rare clinical entity. To our knowledge, this is the first reported case of monozygotic twins with Klinefelter syndrome that describes the infertility workup and outcomes of microsurgical testicular sperm extraction.Key words: Klinefelter syndrome, Microsurgical testicular sperm extraction, Azoospermia, Sertoli only syndrome, Germ cell aplasiaKlinefelter syndrome, the most common sex chromosome disorder in men, is the clinical result of an additional X chromosome in human males. This syndrome, which affects an estimated 1 in 667 live male births, most commonly manifests as 47,XXY, but may also take the form of 46,XY/47,XXY (Klinefelter mosaicism), 48,XXXY, or 49,XXXXY.¹ Typical clinical manifestations of the syndrome include primary infertility, atrophic testes, hypergonadotropic hypogonadism, gynecomastia, eunuchoidism, and decreased facial and body hair.¹ This condition often goes undiagnosed in prepubertal boys, and even in adult men, despite the physical hallmarks of the syndrome; many cases come to light only during the evaluation of primary male factor infertility. The andrologist, therefore, plays a central role in the diagnosis, work-up, and management of men with Klinefelter syndrome.With an incidence approximately twice that of Klinefelter (3–4 per 1000 live births worldwide),² monozygotic (identical) twinning occurs when one fertilized egg splits and divides into two embryos. Monozygotic twins have been observed with various karyotypic abnormalities, including trisomy 21,³ trisomy 18,⁴ and trisomy 13.⁵ However, the presentation of monozygotic twins with Klinefelter syndrome (a fertilized egg with a 47, XXY karyotype splitting to produce identical embryos with Klinefelter syndrome) is exceedingly rare. In this report, we discuss one case of identical twin brothers diagnosed with Klinefelter syndrome at our fertility clinic (Glickman Urological & Kidney Institute, Cleveland, OH) as part of a work-up for inability to conceive.     

Long W tracts are over-represented in the Escherichia coli and Haemophilus influenzae genomes.

The occurrence of DNA tracts of the three binary base combinations: R.Y, K.M and W;S has been mapped in the complete genomes of Haemophilus influenzae and Escherichia coli. A highly significant over-representation of W tracts is observed in both bacteria. The excess of W tracts is particularly striking in the 10% intercoding regions. Subdivision of intercoding regions into divergent (promoting), convergent (terminating) and sequential subregions shows that the excess of W tracts is most concentrated in the promoter regions. A particularly high excess of W tracts is observed in the first 200 bases 5' upstream of coding start sites. The data suggest that W tracts have a role in promoter function. A function as unwinding centers, analogous to the role of R.Y tracts in eukaryotes, is proposed. R.Y and K.M tracts are only modestly over-represented in the two bacteria.     

Chi Mutation in a Transposon and the Orientation-Dependence of Chi Phenotype

Chi, an element that stimulates recombination via the E. coli RecBC pathway, can arise by spontaneous mutation in the transposon Tn5. When in phage lambda in one orientation, the mutant transposon confers Chi+ phenotype (large plaque and a high rate of exchange near the transposon). In the other orientation, however, the transposon does not confer Chi+ phenotype. The mobility of the transposon allows us to show that the Chi+ orientation of the mutant Tn5 is the same at different locations in lambda. These include a site near gene J, one in gam at 69, one to the right of gam at 73 and several to the right of R between 95.7 and 99.5. To the right of R, the mutant transposon could be found in only one orientation, that which confers Chi+ phenotype. We speculate that the other orientation of Tn5 in that locale is lethal to lambda. The orientation-dependence of Chi+ phenotype also revealed that Tn5 flip-flops in lambda.     

Seasonal fires shape the germinable soil seed bank community in eastern Mediterranean woodlands

季节性火烧塑造了东地中海地区林地的可萌发种子库群落 本研究探索了在典型东地中海林地中，季节性火烧是否以及如何与微生境类型(即黄连木属(Pistacia)灌木下、岩蔷薇属(Cistus)灌木下或林冠间隙)相互作用，从而影响可萌发种子库(germinable soil seed bank, GSSB)群落的组成。我们进行了一项野外实验，其中包括预定的春秋火烧，然后利用从火烧地块和相邻未火烧对照地收集的土壤样本对种子萌发的模式进行定量。研究结果表明，秋烧期间，土壤温度比春烧的要高，而春烧期间土壤温度则比秋烧的变化更大。火烧导致可萌发种子库整体的密度、丰富性和多样性降低。秋烧地块内黄连木属和岩蔷薇属灌木的可萌发种子库丰富性和多样性显著降低，这些模式主要表现在一年生植物中。在火烧样地收集的样本中，低矮灌木的可萌发种子库密度更高，在黄连木属和岩蔷薇属灌木下采集的样品中，这种模式更为明显。在季节性火烧与出现的独特物种会共同导致可萌发种子库的群落组成发生显著的变化。这些结果表明，季节性火烧与空间异质性互相作用，主要通过对一年生植物和低矮灌木的可萌发密度的差异效应来影响可萌发种子库群落的组成。这些研究发现意味着，过去几十年东地中海盆地的季节性火烧频率上升，可能转化为进化生态选择压力的变化，并对这一独特生态系统内的植物产生影响。     

Arm site independence of coliphage HK022 integrase in human cells

The integrase encoded by the lambdoid phage HK022 (Int-HK022) resembles its coliphage λ counterpart (Int-λ) in the roles of the cognate DNA arm binding sites and in controlling the direction of the reaction. We show here that within mammalian cells, Int-HK022 does not exhibit such a control. Rather, Int-HK022 recombined between all ten possible pairwise att site combinations, including attB × attB that was more effective than the conventional integrative attP × attB reaction. We further show that Int-HK022 depends on the accessory integration host factor (IHF) protein considerably less than Int-λ and exhibits stronger binding affinity to the att core. These differences explain why wild-type Int-HK022 is active in mammalian cells whereas Int-λ is active there only as an IHF-independent mutant.     

Expression and Functional Characterization of Smyd1a in Myofibril Organization of Skeletal Muscles

Background

Smyd1, the founding member of the Smyd family including Smyd-1, 2, 3, 4 and 5, is a SET and MYND domain containing protein that plays a key role in myofibril assembly in skeletal and cardiac muscles. Bioinformatic analysis revealed that zebrafish genome contains two highly related smyd1 genes, smyd1a and smyd1b. Although Smyd1b function is well characterized in skeletal and cardiac muscles, the function of Smyd1a is, however, unknown.

Methodology/Principal Findings

To investigate the function of Smyd1a in muscle development, we isolated smyd1a from zebrafish, and characterized its expression and function during muscle development via gene knockdown and transgenic expression approaches. The results showed that smyd1a was strongly expressed in skeletal muscles of zebrafish embryos. Functional analysis revealed that knockdown of smyd1a alone had no significant effect on myofibril assembly in zebrafish skeletal muscles. However, knockdown of smyd1a and smyd1b together resulted in a complete disruption of myofibril organization in skeletal muscles, a phenotype stronger than knockdown of smyd1a or smyd1b alone. Moreover, ectopic expression of zebrafish smyd1a or mouse Smyd1 transgene could rescue the myofibril defects from the smyd1b knockdown in zebrafish embryos.

Conclusion/Significance

Collectively, these data indicate that Smyd1a and Smyd1b share similar biological activity in myofibril assembly in zebrafish embryos. However, Smyd1b appears to play a major role in this process.     

ACE2 expression and activity are enhanced during pregnancy

In the current study, we investigated the expression and activity of ACE2 during pregnancy in normotensive and hypertensive rats, focusing on the relative contribution of the uterus and the placentas, the kidney serving as a reference. We used the Sabra rat model of salt-sensitive hypertension. We confirmed a systemic vasodilatory state during the third trimester of pregnancy, as evidenced by a reduction in blood pressure, both in normotensive and hypertensive rats. At the time that blood pressure was reduced, ACE2 was expressed abundantly in the reproductive organs. The relative levels of ACE2 mRNA in the pregnant animal were placenta > kidneys > or = uterus and of ACE2 activity kidney > placenta > uterus. In the uterus and the placenta, ACE2 expression was unaffected by strain, salt-loading, or the level of blood pressure. ACE2 activity in the uterus of the nonpregnant rat was not affected by any of these variables either, but during pregnancy increased in salt-loaded animals. When estimating the total contribution of the uterus to ACE2 mRNA and activity during pregnancy, we found that the amount of ACE2 mRNA increased in both strains irrespective of diet, but that ACE2 activity increased only in salt-loaded animals. We further estimated the relative total contribution of the uterus, placentas, and kidneys to ACE2 expression and activity during pregnancy by adjusting for mass and number of organs and found that the placentas were the major contributors, followed by the kidney and the uterus. We conclude that during pregnancy, the placentas, in particular, but also the uterus, constitute important sources of ACE2, in addition to its normal production in the kidney, leading to an estimated twofold increase in total ACE2 activity. These data are consistent the hypothesis that transient ACE2 overexpression and increased activity during pregnancy may be important in modulating systemic, as well as local hemodynamics in the uteroplacental unit.     

Site-specific recombination in human cells catalyzed by the wild-type integrase protein of coliphage HK022

The activity of the Integrase (Int) protein encoded by coliphage HK022 was tested in a human cell culture. Plasmids were constructed as substrates that carry the sites of the integration reaction (attP and attB) or the sites of excision (attL and attR). The site-specific recombination reactions were monitored in cis and in trans configurations by the expression of the green fluorescent protein (GFP) as a reporter. Cells cotransfected with the substrate plasmid(s) and with a plasmid that expresses the wild-type Int show efficient integration as well as excision in both configurations. The wild-type Int was active in the human cells without the need to supply the accessory proteins integration host factor (IHF) and excisionase (Xis) that are indispensable for the reaction in the bacterial host.