We report on two prenatal ultrasound diagnoses of left ventricular non‐compaction cardiomyopathy (LVNC) associated with mutation of the cardiac β‐myosin heavy chain gene (MYH7). LVNC is characterized ...by a trabecular meshwork and deep intertrabecular myocardial recesses communicating with the left ventricular cavity. Clinical features range from non‐penetrant disease in adult carriers to heart failure, arrhythmia and thromboembolism. Both cases showed cardiomegaly on prenatal ultrasound examinations, with features indicating non‐compaction of the myocardium apparent in the third trimester. Mutations in the MYH7 gene were identified postnatally in each case in both the proband and the father. One infant underwent surgical mitral valvuloplasty and a mechanical valve implant later; in the other, left ventricular function was unimpaired at birth. Cardiac function in both cases remained stable at last follow‐up. These cases highlight the importance of prenatal ultrasound diagnosis of LVNC and the need for cardiologic and molecular testing of first‐degree relatives who may be unknown carriers of an MYH7 mutation.
The Evolution of Language Nowak, Martin A.; Krakauer, David C.
Proceedings of the National Academy of Sciences - PNAS,
07/1999, Letnik:
96, Številka:
14
Journal Article
Recenzirano
Odprti dostop
The emergence of language was a defining moment in the evolution of modern humans. It was an innovation that changed radically the character of human society. Here, we provide an approach to language ...evolution based on evolutionary game theory. We explore the ways in which protolanguages can evolve in a nonlinguistic society and how specific signals can become associated with specific objects. We assume that early in the evolution of language, errors in signaling and perception would be common. We model the probability of misunderstanding a signal and show that this limits the number of objects that can be described by a protolanguage. This "error limit" is not overcome by employing more sounds but by combining a small set of more easily distinguishable sounds into words. The process of "word formation" enables a language to encode an essentially unlimited number of objects. Next, we analyze how words can be combined into sentences and specify the conditions for the evolution of very simple grammatical rules. We argue that grammar originated as a simplified rule system that evolved by natural selection to reduce mistakes in communication. Our theory provides a systematic approach for thinking about the origin and evolution of human language.
Cardiac involvement has been reported in carriers of dystrophin mutations giving rise to Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). The progress of these abnormalities ...during long-term follow-up is unknown. We describe the long-term follow-up of dilated cardiomyopathy (DCM) in DMD/BMD carriers.
A long-term follow-up study was performed among Dutch DMD/BMD carriers first analyzed in 1995. A cardiac history was taken, and all carriers were assigned a functional score to assess skeletal muscle involvement. Electrocardiography and M-mode and 2-D echocardiography were performed. DCM was defined as an enlarged left ventricle with a global left ventricle dysfunction or fractional shortening less than 28%. Slow vital capacity of the lung was measured by a hand-held spirometer.
Ninety-nine carriers were monitored with a median follow-up of 9 years (range 7.0-10.6 years). Eleven carriers with DCM (10 DMD, 1 BMD) were identified. Nine of them developed DCM in the follow-up period. One of the patients with DCM reported in the 1995 study died of cardiac failure at age 57 years. DCM was more frequently found in carriers who were functionally symptomatic.
Cardiac abnormalities in DMD/BMD carriers are progressive, as in patients with DMD/BMD.
To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a ...genotype-phenotype relationship for mutations in the ATM gene.
Retrospective analysis of the clinical characteristics and course of disease in 13 adult patients with variant A-T of 9 families and 6 unrelated adults with classic A-T and mutation analysis of the ATM gene and measurements of ATM protein expression and kinase activity.
Patients with variant A-T were only correctly diagnosed in adulthood. They often presented with extrapyramidal symptoms in childhood, whereas cerebellar ataxia appeared later. Four patients with variant A-T developed a malignancy. Patients with classic and variant A-T had elevated serum alpha-fetoprotein levels and chromosome 7/14 rearrangements. The mildest variant A-T phenotype was associated with missense mutations in the ATM gene that resulted in expression of some residual ATM protein with kinase activity. Two splicing mutations, c.331 + 5G>A and c.496 + 5G>A, caused a more severe variant A-T phenotype. The splicing mutation c.331 + 5G>A resulted in less ATM protein and kinase activity than the missense mutations.
Ataxia-telangiectasia (A-T) should be considered in patients with unexplained extrapyramidal symptoms. Early diagnosis is important given the increased risk of malignancies and the higher risk for side effects of subsequent cancer treatment. Measurement of serum alpha-fetoprotein and chromosomal instability precipitates the correct diagnosis. There is a clear genotype-phenotype relation for A-T, since the severity of the phenotype depends on the amount of residual kinase activity as determined by the genotype.
The current clinical diagnosis of Von Hippel‐Lindau (VHL) disease demands at least one specific a sporadic VHL manifestation in a patient with familial VHL disease, or, in asporadic patient, at least ...two or more hemangioblastomas or a single hemangioblastoma in combination with a typical visceral lesion. To evaluate this definition, we studied the frequency of germline VHL mutation in three patients groups: (i) multi‐organ involvement (classic VHL), (ii) limited VHL manifestations meeting criteria (non‐classic VHL) and (iii) patients with VHL‐associated tumors not meeting current diagnostic VHL criteria. In addition, we validated multiplex ligation‐dependent probe amplification (MLPA) as a rapid and reliable quantitative method for the identification of germline VHL deletions. The frequency of germline VHL mutations was very high in classic VHL cases with multi‐organ involvement (95%), lower in non‐classic cases that meet current diagnostic criteria but have limited VHL manifestations or single‐organ involvement (24%) and low (3.3%), but tangible in cases not meeting current diagnostic VHL criteria. The detection of germline VHL mutations in patients or families with limited VHL manifestations, or single‐organ involvement is relevant for follow‐up of probands and early identification of at‐risk relatives.
In animal societies, conflicts can be resolved by combatants or through third‐party intervention. In gregarious species, conflicts among pairs can spread to involve multiple individuals. In the case ...of large conflicts, containment and termination of aggression by third parties is important. Successful intervention relies on consensus among combatants about the intervener’s capacity to use force. We refer to this consensus as power. We measure it and study how it arises, using as our model system a pigtailed macaque (Macaca nemestrina)society. In macaques, the degree to which one individual perceives another as capable of using force is communicated using a special dominance signal. Group consensus about an individual’s capacity to use force arises from the network of signaling interactions. We derive a formalism to quantify consensus in the network. We find that the power distribution is fat tailed and power is a strong predictor of social variables including request for support, intervention cost, and intensity. We develop models to show how dominance‐signaling strategies promote robust power distributions despite individual signaling errors. We suggest that when considering correlated interactions among many individuals it can be more useful to emphasize coarse‐grained information stored at the group level—behavioral macrostates—over detailed information at the individual level.
Mitochondria and germ-cell death Krakauer, David C; Mira, Alex
Nature (London),
07/1999, Letnik:
400, Številka:
6740
Journal Article
Recenzirano
In birds and mammals, most of the female germ cells are destroyed before fertilization in a process known as atresia, reducing the population of cells to a small fraction of that present in early ...fetal life. We suggest that this death of germ cells can be interpreted as a developmental solution to the accumulation of mutations (Müller's ratchet) in mitochondria, an idea that is supported by comparative analysis. Atresia in effect therefore removes oocytes carrying mutant mitochondria.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Conflict management is one of the primary requirements for social complexity. Of the many forms of conflict management, one of the rarest and most interesting is third‐party policing, or intervening ...impartially to control conflict. Third‐party policing should be hard to evolve because policers personally pay a cost for intervening, while the benefits are diffused over the whole group. In this study we investigate the incidence and costs of policing in a primate society. We report quantitative evidence of non–kin policing in the nonhuman primate, the pigtailed macaque. We find that policing is effective at reducing the intensity of or terminating conflict when performed by the most powerful individuals. We define a measure, social power consensus, that predicts effective low‐cost interventions by powerful individuals and ineffective, relatively costly interventions by low‐power individuals. Finally, we develop a simple probabilistic model to explore whether the degree to which policing can effectively reduce the societal cost of conflict is dependent on variance in the distribution of power. Our data and simple model suggest that third‐party policing effectiveness and cost are dependent on power structure and might emerge only in societies with high variance in power.
Abdominal aortic aneurysms (AAA), are usually asymptomatic until rupture causes fatal bleeding, posing a major vascular health problem. AAAs are associated with advanced age, male gender, and ...cardiovascular risk factors (e.g. hypertension and smoking). Strikingly, AAA and AOD (arterial occlusive disease) patients have a similar atherosclerotic burden, yet develop either arterial dilatation or occlusion, respectively. The molecular mechanisms underlying this diversion are yet unknown. As this knowledge could improve AAA treatment strategies, we aimed to identify genes and signaling pathways involved. We compared RNA expression profiles of abdominal aortic AAA and AOD patient samples. Based on differential gene expression profiles, we selected a gene set that could serve as blood biomarker or as pharmacological intervention target for AAA. In this AAA gene list we identified previously AAA-associated genes COL11A1, ADIPOQ, and LPL, thus validating our approach as well as novel genes; CXCL13, SLC7A5, FDC-SP not previously linked to aneurysmal disease. Pathway analysis revealed overrepresentation of significantly altered immune-related pathways between AAA and AOD. Additionally, we found bone morphogenetic protein (BMP) signaling inhibition simultaneous with activation of transforming growth factor β (TGF-β) signaling associated with AAA. Concluding our gene expression profiling approach identifies novel genes and an interplay between BMP and TGF-β signaling regulation specifically for AAA.
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