If I Knew You Then As I Know You Now

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Transient domain walls and lepton asymmetry in the Left-Right symmetric model

It is shown that the dynamics of domain walls in Left-Right symmetric models, separating respective regions of unbroken SU(2)_L and SU(2)_R in the early universe, can give rise to baryogenesis via leptogenesis. Neutrinos have a spatially varying complex mass matrix due to CP-violating scalar condensates in the domain wall. The motion of the wall through the plasma generates a flux of lepton number across the wall which is converted to a lepton asymmetry by helicity-flipping scatterings. Subsequent processing of the lepton excess by sphalerons results in the observed baryon asymmetry, for a range of parameters in Left-Right symmetric models.Comment: v2 version accepted for publication in Phys. Rev. D. Discussion in Introduction and Conclusion sharpened. Equation (12) corrected. 16 pages, 3 figure files, RevTeX4 styl

DNA Display III. Solid-Phase Organic Synthesis on Unprotected DNA

DNA-directed synthesis represents a powerful new tool for molecular discovery. Its ultimate utility, however, hinges upon the diversity of chemical reactions that can be executed in the presence of unprotected DNA. We present a solid-phase reaction format that makes possible the use of standard organic reaction conditions and common reagents to facilitate chemical transformations on unprotected DNA supports. We demonstrate the feasibility of this strategy by comprehensively adapting solid-phase 9-fluorenylmethyoxycarbonyl–based peptide synthesis to be DNA-compatible, and we describe a set of tools for the adaptation of other chemistries. Efficient peptide coupling to DNA was observed for all 33 amino acids tested, and polypeptides as long as 12 amino acids were synthesized on DNA supports. Beyond the direct implications for synthesis of peptide–DNA conjugates, the methods described offer a general strategy for organic synthesis on unprotected DNA. Their employment can facilitate the generation of chemically diverse DNA-encoded molecular populations amenable to in vitro evolution and genetic manipulation

Effect of pre-existing baryon inhomogeneities on the dynamics of quark-hadron transition

Baryon number inhomogeneities may be generated during the epoch when the baryon asymmetry of the universe is produced, e.g. at the electroweak phase transition. The regions with excess baryon number will have a lower temperature than the background temperature of the universe. Also the value of the quark hadron transition temperature $T_c$ will be different in these regions as compared to the background region. Since a first-order quark hadron transition is very susceptible to small changes in temperature, we investigate the effect of the presence of such baryonic lumps on the dynamics of quark-hadron transition. We find that the phase transition is delayed in these lumps for significant overdensities. Consequently, we argue that baryon concentration in these regions grows by the end of the transition. We briefly discuss some models which may give rise to such high overdensities at the onset of the quark-hadron transition.Comment: 16 pages, no figures, minor changes, version to appear in Phys. Rev.

Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum

Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs.To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria.This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment

Six Action Steps to Address Global Disparities in Parkinson Disease: A World Health Organization Priority

Importance: The Global Burden of Disease study conducted between 1990 and 2016, based on a global study of 195 countries and territories, identified Parkinson disease (PD) as the fastest growing neurological disorder when measured using death and disability. Most people affected by PD live in low- and middle-income countries (LMICs) and experience large inequalities in access to neurological care and essential medicines. This Special Communication describes 6 actions steps that are urgently needed to address global disparities in PD. Observations: The adoption by the 73rd World Health Assembly (WHA) of resolution 73.10 to develop an intersectoral global action plan on epilepsy and other neurological disorders in consultation with member states was the stimulus to coordinate efforts and leverage momentum to advance the agenda of neurological conditions, such as PD. In April 2021, the Brain Health Unit at the World Health Organization convened a multidisciplinary, sex-balanced, international consultation workshop, which identified 6 workable avenues for action within the domains of disease burden; advocacy and awareness; prevention and risk reduction; diagnosis, treatment, and care; caregiver support; and research. Conclusions and Relevance: The dramatic increase of PD cases in many world regions and the potential costs of PD-associated treatment will need to be addressed to prevent possible health service strain. Across the board, governments, multilateral agencies, donors, public health organizations, and health care professionals constitute potential stakeholders who are urged to make this a priority

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Expressão gênica no parênquima mamário de novilhas leiteiras

Dietas com níveis energéticos elevados e suplementação com bST a novilhas pré-púberes diminuem a idade ao primeiro mas podem causar alterações de móleculas envolvidas no processo de desenvolvimento mamário. No presente trabalho objetivou-se examinar a expressão diferencial de genes relacionados ao desenvolvimento parenquimal de novilhas em crescimento acelerado e suplementadas com bST. Conduziu-se dois experimentos em fatorial 2x2, com 32 amostras de tecidos coletados de novilhas abatidas na fase pós-púbere inicial. Num experimento, aplicou-se a técnica de microarranjos com uma biblioteca de cDNA específica para bovinos (NBFGC) aonde avaliou-se simultaneamente a expressão de 18.263 diferentes ESTs. O segundo experimento analisou a expressão gênica de leptina e seu receptor no parênquima com a técnica de PCR em tempo real (qRT-PCR). Adicionalmente, foi realizado um experimento in vitro com linhagem de células mamárias MAC-T para verificação de possíveis interações entre a IL-6 e IGF-1 na proliferação celular. A administração de bST estimulou a expressão de diversos genes positivamente relacionados ao desenvolvimento parenquimal e inibiu a expressão de genes negativamente relacionados a esse processo, inclusive da leptina. A dieta causou poucas alterações nesses genes, mas aumentou a expressão de leptina no parênquima. A IL-6 diminuiu a proliferação celular induzida pelo IGF-1. Os resultados obtidos demonstraram alterações na expressão de genes relacionados ao desenvolvimento tecidual em ambos os tratamentos, sendo que o bST atenuou os efeitos da dieta em genes negativamente relacionados a esse processo.High-energy diet and bST administration during pre-pubertal phase decrease age at first calving. However, these managements modify mammary development altering the expression of several genes related to parenchyma development. The objective of the present study was to analyze the effects of a highenergy diet and bST administration in the expression of genes related to tissue development in heifer mammary parenchyma. Two experiments were conducted in a 2X2 factorial, with 32 samples collected from animals killed during early post-pubertal phase. In the first experiment, the microarray technique was performed with a bovine specific cDNA library containing 18.263 ESTs. The second experiment focused in the expression of leptin and leptin-receptor in mammary parenchyma, using the qRT-PCR technique. Additionally, an in vitro experiment was conducted using an immortalized mammary epithelial cell line (MAC-T) to check possible interactions between IL-6 and IGF-1 in cell proliferation. bST administration stimulated the expression of several genes positive related to tissue development and inhibited the expression of genes negative related to this process, including leptin. High-energy diet altered the expression of few genes, but increased the expression of leptin in mammary parenchyma. IL-6 decreased IGF-1 induced cell-proliferation. The results point to alteration in expression of genes related to tissue development in both treatments and suggest that bST administration attenuates the effects of high-energy diet in genes negative related to tissue development.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES