A Baby Step: The Status of Surrogacy Law in Wisconsin Following \u3ci\u3eRosecky v. Schissel\u3c/i\u3e

Surrogacy is an ancient and rapidly expanding industry in the United States and abroad. Despite this, the legal landscape governing surrogacy contracts remains tenuous in a majority of states—including Wisconsin. In 2013, the Wisconsin Supreme Court took the first step in developing surrogacy contract law in Wisconsin. Absent legislative guidance, the court fashioned a reasonable foundation for surrogacy contracts. However, its decision does little to ensure that intending parents and surrogate mothers who enter into such agreements fully understand their responsibilities and have assurances that their expectations will be met. This Comment does not seek to argue, as many others have, the merits of surrogacy or the limitations the law should place on the practice. Rather, it seeks to illustrate the Rosecky decision’s place within the legal landscape and suggest one provision that could form a foundation for much needed legislative guidance

A Baby Step: The Status of Surrogacy Law in Wisconsin Following \u3ci\u3eRosecky v. Schissel\u3c/i\u3e

Surrogacy is an ancient and rapidly expanding industry in the United States and abroad. Despite this, the legal landscape governing surrogacy contracts remains tenuous in a majority of states—including Wisconsin. In 2013, the Wisconsin Supreme Court took the first step in developing surrogacy contract law in Wisconsin. Absent legislative guidance, the court fashioned a reasonable foundation for surrogacy contracts. However, its decision does little to ensure that intending parents and surrogate mothers who enter into such agreements fully understand their responsibilities and have assurances that their expectations will be met. This Comment does not seek to argue, as many others have, the merits of surrogacy or the limitations the law should place on the practice. Rather, it seeks to illustrate the Rosecky decision’s place within the legal landscape and suggest one provision that could form a foundation for much needed legislative guidance

The Use of Natural Product Substrates for the Synthesis of Libraries of Biologically Active, New Chemical Entities

Since Alexander Fleming first noted the killing of a bacterial culture by a mold, antibiotics have revolutionized medicine, being able to treat, and often cure life-threatening illnesses and making surgical procedures possible by eliminating the possibility of opportunistic infection. However, during the past 30 years many of the infections that were once easily cured by the proper antibiotic are no longer so due to a precipitous rise in multi-drug resistant organisms. This rise in multi-drug resistant organisms poses a grave threat to the medical advances that have been made in the past century and underscores the need for new antibiotics. We have developed two promising candidates for pharmaceutical applications, compounds 72 and 71, which are derived from nonactin, a biologically active natural product. Nonactin 40, an ionophore macrotetrolide antibiotic that is produced by Streptomyces griseus ETH A7796, is an ideal candidate for the synthesis of new antimicrobial drugs. This secondary metabolite is composed of two units of (+)-nonactic acid 49 and two units of (-)-nonactic acid 50. Whereas nonactin does not possess a synthetically useful chemical `handle\u27, the nonactic acid subunits do. Through methanolysis of this structure and the separation of the two enantiomers, followed by a series of transformations, easily diversifiable scaffolds have been synthesized, which allows for the relatively rapid synthesis of chemically diverse libraries. From a small library of compounds that were synthesized, the compounds, 72 and 71 were found to show promising activities against vancomycin-resistant Enterococcus faecalis (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). Compounds 88 and 90 were shown to be the active enantiomers. It was also shown by making the 1,4-substituted triazoles and the 1,5-substituted triazoles 91, 92 that only the 1,4-substituted triazoles gave the aforementioned activities. These results illustrate the vital importance of stereochemistry and regiochemistry. To establish the importance of the nonactic acid moiety itself in the triazoloester compounds, analogues of these compounds were made by replacing the nonactic acid moiety with a cyclohexane moiety, specifically starting with both trans and cis 4-cyclohexanol-carboxylic acid. Neither the cis nor the trans analogues 131, 132, 142, 143, 151, 152, 160, 161 of either of the regioisomers of the compounds made to mimic 72 and 71 gave the activities of their nonactate-containing counterparts. As an alternative to chemical synthesis we investigated biotransformation of nonactic acid analogs by Streptomyces griseus. While we were unable to generate new nonactin analogues we did discover an inhibitor of nonactin biosynthesis 186 and we were able to set limits on precursor directed biosynthesis in S. griseus

TINDAK PIDANA PREKURSOR NARKOTIKA DI WILAYAH NEGARA REPUBLIK INDONESIA

Penelitian ini dilakukan dengan tujuan untuk mengetahui bagaimana tindak pidana prekursor narkotika di wilayah negara Republik Indonesia dan bagaimana ketentuan pidana terhadap pelaku di wilayah negara Republik   Indonesia. Dengan menggunakan metode peneltian yuridis normatif, disimpulkan: 1. Pengaturan hukum prekursor narkotika diperlukan agar tujuan pengaturannya dapat melindungi masyarakat dari bahaya penyalahgunaan Prekursor Narkotika, mencegah dan memberantas peredaran gelap Prekursor Narkotika dan mencegah terjadinya kebocoran dan penyimpangan prekursor narkotika. Pemerintah menyusun rencana kebutuhan tahunan prekursor narkotika untuk kepentingan industri farmasi, industri nonfarmasi, dan ilmu pengetahuan dan teknologi. Rencana kebutuhan tahunan disusun berdasarkan jumlah persediaan, perkiraan kebutuhan, dan penggunaan Prekursor Narkotika secara nasional. Pengadaan Prekursor Narkotika dilakukan melalui produksi dan impor dan hanya dapat digunakan untuk tujuan industri farmasi, industri nonfarmasi, dan ilmu pengetahuan dan teknologi. 2. Pemberlakuan ketentuan pidana terhadap pelaku tindak pidana prekursor narkotika di wilayah negara Republik Indonesia yang telah memenuhi unsur-unsur tindak pidana dalam Undang-Undang Nomor 35 Tahun 2009 Tentang Narkotika, khususnya Pasal 111 sampai dengan Pasal 126, Pasal 127 ayat (1), Pasal 128 ayat (1), dan Pasal 129. Ketentuan pidana meliputi pidana mati, pidana penjara seumur hidup, pidana penjara dan pidana denda sesuai dengan perbuatan pidana yang dilakukan dan telah terbukti secara sah berdasarkan peraturan perundang-undangan yang berlaku dilakukan oleh pelaku tindak pidana.Kata kunci:  Tindak Pidana, Prekursor, Narkotika

Keep it Between You and Me and the Neighbors

I use the domestic as a locale to consider the function of a queer body within the “American Dream.” I frequently remove the objects from their intended uses through various methods of alterations. Breaking things down to queer identity, objects, space, and community, I consider each object as a stand-in for individuals liberated from the pressure of preconceptions and mastery. Each lends itself towards the community identity, serving individually as separate functions within the experience, but also collectively serving as an invitation for on-lookers to join this community that we would define together

Characterization of MTHFD2L expression and alternative splicing and loss of MTHFD1L activity in murine embryos and adults

In Eukaryotes, folate-dependent one-carbon (1C) metabolism is a highly compartmentalized process in which mitochondria play a central role. Defects in folate metabolism are associated with diseases such as cancer, Alzheimer's disease, and neural tube defects (NTDs). 1C units are attached to tetrahydrofolate (THF) and carried in various oxidation states between folate-dependent enzymes. There is an exchange of 1C units across the mitochondrial membrane, with 1C donors such as serine and glycine being oxidized to formate in the mitochondria, which is then released into the cytoplasm. 1C units in the cytoplasm can be used for the synthesis of purines, thymidylate, and methionine for the methyl cycle. The core of the pathway in both compartments is catalyzed by the methylene-tetrahydrofolate (MTHFD) gene family. These enzymes catalyze the reversible interconversion between CH₂-THF, CH⁺-THF, CHO-THF, and formate. The cytoplasmic protein MTHFD1 is trifunctional and carries the CH₂-THF dehydrogenase, CH⁺-THF cyclohydrolase, and 10-CHO-THF synthetase activities necessary to carry out these interconversions. In the mitochondria, two bifunctional isozymes, MTHFD2 and MTHFD2L, carry the dehydrogenase/cyclohydrolase (D/C) activities. The monofunctional enzyme MTHFD1L is responsible for the synthetase activity. MTHFD2 is only expressed in embryos and transformed cells, and the enzyme responsible for the D/C activity in adults was unknown until the recent discovery of MTHFD2L. In this work, characterization of the expression of MTHFD2L in mouse embryos and adults is described. Expression of MTHFD2L in embryos was found to be switched on between embryonic days 8.5-10.5, and remains high throughout development. MTHFD2L is also widely expressed in adults, with highest expression in brain and lung. A splice variant of MTHFD2L lacking exon 8 was found to be abundant in embryos but was not catalytically active in vitro or in vivo. MTHFD1L is an essential protein, and SNPs in MTHFD1L are associated with increased risk for Alzheimer's disease and NTDs in humans. Loss of MTHFD1L activity in adult mice with and without a folate deficient diet was investigated. Indications of sex-dependent behavioral anomalies were found, with evidence for genotype-dependent hyperactivity in male mice and diet-dependent anxiety in female mice, but further investigation of these findings is warranted. Finally, metabolic defects associated with NTDs and growth restriction in MTHFD1L-null (Mthfd1l [superscript z/z]) embryos were identified. Glycolysis, the TCA cycle, and the metabolism of methionine, purines, and multiple amino acids were found to be disrupted in Mthfd1l [superscript z/z] embryos. These altered metabolic pathways suggest potential future therapies for preventing NTDs in humans.Biochemistr

Cas9 interrogates DNA in discrete steps modulated by mismatches and supercoiling.

The CRISPR-Cas9 nuclease has been widely repurposed as a molecular and cell biology tool for its ability to programmably target and cleave DNA. Cas9 recognizes its target site by unwinding the DNA double helix and hybridizing a 20-nucleotide section of its associated guide RNA to one DNA strand, forming an R-loop structure. A dynamic and mechanical description of R-loop formation is needed to understand the biophysics of target searching and develop rational approaches for mitigating off-target activity while accounting for the influence of torsional strain in the genome. Here we investigate the dynamics of Cas9 R-loop formation and collapse using rotor bead tracking (RBT), a single-molecule technique that can simultaneously monitor DNA unwinding with base-pair resolution and binding of fluorescently labeled macromolecules in real time. By measuring changes in torque upon unwinding of the double helix, we find that R-loop formation and collapse proceed via a transient discrete intermediate, consistent with DNA:RNA hybridization within an initial seed region. Using systematic measurements of target and off-target sequences under controlled mechanical perturbations, we characterize position-dependent effects of sequence mismatches and show how DNA supercoiling modulates the energy landscape of R-loop formation and dictates access to states competent for stable binding and cleavage. Consistent with this energy landscape model, in bulk experiments we observe promiscuous cleavage under physiological negative supercoiling. The detailed description of DNA interrogation presented here suggests strategies for improving the specificity and kinetics of Cas9 as a genome engineering tool and may inspire expanded applications that exploit sensitivity to DNA supercoiling

Population Growth Characteristics of Incipient Colonies of the Eastern Subterranean Termite, Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae)

Growth of Reticulitermes flavipes (Kollar) incipient colonies during their first year was documented via a monthly destructive sampling census of 15 unique colonies, each headed by an inbred primary pair, for a total of 180 colonies. King and queen biomass greatly decreased during the first 2 months, coinciding with egg production and colony foundation, but their biomass remained relatively constant thereafter. Three cohorts of eggs were produced, with the greatest number of eggs (mean = 14.5) during the first month. Larvae were present at 1 month, and workers were first observed at 2 months. The survival rate of the initial brood was less than 100%, most likely due to cannibalism. A single soldier was first noted in some colonies at 6 months. Offspring biomass was equal to that of the reproductive pair at the 2-month census, double at 3 months, and quadruple at 11 months. One-year-old colonies ranged in size from 20 to 40 individuals, with an average of 28.9 individuals; total colony biomass was 39.8 mg. The growth rate of these R. flavipes colonies was much slower than was reported in other studies, but our observations are consistent with previous models and suggestions regarding colony growth