The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

/pdf/initial-sequencing-and-analysis-of-the-human-genome-5dapk1rsx1.pdf

Initial sequencing and analysis of the human genome.

Pregnancy has commonly been viewed as a cooperative interaction between a mother and her fetus. The effects of natural selection on genes expressed in fetuses, however, may be opposed by the effects of natural selection on genes expressed in mothers. In this sense, a genetic conflict can be said to exist between maternal and fetal genes. Fetal genes will be selected to increase the transfer of nutrients to their fetus, and maternal genes will be selected to limit transfers in excess of some maternal optimum. Thus a process of evolutionary escalation is predicted in which fetal actions are opposed by maternal countermeasures. The phenomenon of genomic imprinting means that a similar conflict exists within fetal cells between genes that are expressed when maternally derived, and genes that are expressed when paternally derived. During implantation, fetally derived cells (trophoblast) invade the maternal endometrium and remodel the endometrial spiral arteries into low-resistance vessels that are unable to constrict. This invasion has three consequences. First, the fetus gains direct access to its mother's arterial blood. Therefore, a mother cannot reduce the nutrient content of blood reaching the placenta without reducing the nutrient supply to her own tissues. Second, the volume of blood reaching the placenta becomes largely independent of control by the local maternal vasculature. Third, the placenta is able to release hormones and other substances directly into the maternal circulation. Placental hormones, including human chorionic gonadotropin (hCG) and human placental lactogen (hPL), are predicted to manipulate maternal physiology for fetal benefit. For example, hPL is proposed to act on maternal prolactin receptors to increase maternal resistance to insulin. If unopposed, the effect of hPL would be to maintain higher blood glucose levels for longer periods after meals. This action, however, is countered by increased maternal production of insulin. Gestational diabetes develops if the mother is unable to mount an adequate response to fetal manipulation. Similarly, fetal genes are predicted to enhance the flow of maternal blood through the placenta by increasing maternal blood pressure. Preeclampsia can be interpreted as an attempt by a poorly nourished fetus to increase its supply of nutrients by increasing the resistance of its mother's peripheral circulation.

/pdf/genetic-conflicts-in-human-pregnancy-4ip4vrvtau.pdf

Genetic conflicts in human pregnancy.

ALPHA atrial natriuretic peptide (α-ANP) and brain natriuretic peptide are homologous polypeptide hormones involved in the regulation of fluid and electrolyte homeostasis1,2. These two natriuretic peptides apparently share common receptors and stimulate the intracellular production of cyclic GMP as a second messenger1. Molecular cloning has defined two types of natriuretic peptide receptors: the ANP-C receptor of relative molecular mass (Mr) 60–70,000 (60–70 K), which is not coupled to cGMP production and may function in the clearance of ANP (refs 3,4) and the ANP-A receptor of Mr 120–140 K, which is a membrane form of guanylate cyclase in which ligand binding to the extracellular domain activates the cytoplasmic domain of the enzyme5,6. Here we report the cloning and expression of a second human natriuretic peptide-receptor guanylate cyclase, the ANP-B receptor. The ANP-B receptor is preferentially activated by porcine brain natriuretic peptide rather than human α-ANP, whereas the ANP-A receptor responds similarly to both natriuretic peptides. These observations may have important implications for our understanding of the central and peripheral control of cardiovascular homeostasis.

Differential activation by atrial and brain natriuretic peptides of two different receptor guanylate cyclases

Despite the high prevalence of performance-enhancing drug (PED) use, media attention has focused almost entirely on PED use by elite athletes to illicitly gain a competitive advantage in sports, and not on the health risks of PEDs. There is a widespread misperception that PED use is safe or that adverse effects are manageable. In reality, the vast majority of PED users are not athletes but rather nonathlete weightlifters, and the adverse health effects of PED use are greatly underappreciated. This scientific statement synthesizes available information on the medical consequences of PED use, identifies gaps in knowledge, and aims to focus the attention of the medical community and policymakers on PED use as an important public health problem. PED users frequently consume highly supraphysiologic doses of PEDs, combine them with other PEDs and/or other classical drugs of abuse, and display additional associated risk factors. PED use has been linked to an increased risk of death and a wide variety of cardiova...

/pdf/adverse-health-consequences-of-performance-enhancing-drugs-jxjzoexzjp.pdf

Adverse Health Consequences of Performance-Enhancing Drugs: An Endocrine Society Scientific Statement

The angiotensin converting enzyme (ACE) is a key component of the renin angiotensin system that contributes to the regulation of blood pressure (BP). Recent demonstration of linkage between the ACE locus and elevated BP in a rat model of hypertension has further emphasized ACE as a candidate gene in human hypertension. We report the localization of the ACE gene on the genetic map of chromosome 17, and identify an extremely polymorphic marker at the human growth hormone (hGH) locus which shows no recombination with ACE. We have found no evidence to support linkage between the ACE locus and hypertension, which suggests that mutations at the ACE locus do not commonly contribute to the pathogenesis of hypertension in our test population.

Absence of linkage between the angiotensin converting enzyme locus and human essential hypertension.

The human growth hormone locus: nucleotide sequence, biology, and evolution

In recent years, the piano education industry has occupied a huge market. However, the automatic evaluation function of piano performance has shortcomings in existing piano education products. Deep learning (DL) algorithm and the recurrent neural network (RNN) structure can help in automatics evaluation function of the piano performance. This paper proposes a Musical Instrument Digital Interface (MIDI) piano evaluation scheme based on the RNN structure and the Spark computing engine using the Deeplearning4J DL framework. The Deeplearning4J framework can run on the Java Virtual Machine; therefore, the entire system does not require cross-platform development. The Spark distributed computing engine realizes parallelization in music data preprocessing, feature extraction, and model training. Combined with the training user interface (UI) provided by the Deeplearning4J, it can improve developmental efficiency. Additionally, the RNN parameters are analyzed. The results demonstrate that the error value of the three-layer RNN structure is smaller than other closest rivals’ techniques. In particular, few piano training institutions and MIDI website datasets are used as the basis, and the experimental samples are collected. The neural network is trained, and the performance of the evaluation model is tested. The results show that the evaluation outcomes of the designed performance evaluation model for the piano are fundamentally consistent with the real levels of the players with assured feasibility; after 3k times of the training periods, the error of the RNN model is close to 0.01 and the network converges.

/pdf/educational-evaluation-of-piano-performance-by-the-deep-3q6bah1h.pdf

Yu-Cheng Liao

Papers

The human growth hormone locus: nucleotide sequence, biology, and evolution

Educational Evaluation of Piano Performance by the Deep Learning Neural Network Model