Post-Dobbs legal conundrums surrounding preimplantation in vitro fertilization embryo dispositions.

The legal issues surrounding in vitro fertilization from its beginnings have found their way into courtrooms and legislatures, with disposition of cryopreserved in vitro fertilization preimplantation embryos presenting legal and policy conundrum for patients, providers, and lawmakers in a myriad of contexts. This article examines the legal aspects of selected embryo disposition issues and the potential impact of laws enacted following the US Supreme Court's recent removal of Constitutional protections for reproductive choice and autonomy in Dobbs v. Jackson Women's Health Organization.

Legal principles and essential surrogacy cases every practitioner should know.

Gestational surrogacy, made possible with the introduction of in vitro fertilization, has expanded family building options while introducing novel challenges to established legal principles involving constitutional, contract, and family law as well as duty of care and negligence. Both legislatures and courts have grappled with how to apply these sometimes-competing areas of law to protect participants and professionals, and to create legally secure families. This article explores the following: the Constitutionally protected rights of privacy and reproductive autonomy of gestational surrogates; Contract Law principles that govern surrogacy contracts; the varied ways states have extended Family Law to establish legally recognized parent-child relationships between intended parents and children born to gestational surrogates; and the legal duties of care medical professionals owe to their patients.

A multinational study distinguishing Alzheimer's and healthy patients using cerebrospinal fluid tau/Aß42 cutoff with concordance to amyloid positron emission tomography imaging.

INTRODUCTION: Changes in cerebrospinal fluid (CSF) tau and amyloid ß (Aß)42 accompany development of Alzheimer's brain pathology. Robust tau and Aß42 immunoassays were developed to establish a tau/Aß42 cutoff distinguishing mild-to-moderate Alzheimer's disease (AD) subjects from healthy elderly control (HC) subjects. METHODS: A CSF tau/Aß42 cutoff criteria was chosen, which distinguished the groups and maximized concordance with amyloid PET. Performance was assessed using an independent validation cohort. RESULTS: A tau/Aß42 = 0.215 cutoff provided 94.8% sensitivity and 77.7% specificity. Concordance with PET visual reads was estimated at 86.9% in a ∼50% PET positive population. In the validation cohort, the cutoff demonstrated 78.4% sensitivity and 84.9% specificity to distinguish the AD and HC populations. DISCUSSION: A tau/Aß42 cutoff with acceptable sensitivity and specificity distinguished HC from mild-to-moderate AD subjects and maximized concordance to brain amyloidosis. The defined cutoff demonstrated that CSF analysis may be useful as a surrogate to imaging assessment of AD pathology.

Facile Discovery of a Diverse Panel of Anti-Ebola Virus Antibodies by Immune Repertoire Mining.

The ongoing evolution of Ebolaviruses poses significant challenges to the development of immunodiagnostics for detecting emergent viral variants. There is a critical need for the discovery of monoclonal antibodies with distinct affinities and specificities for different Ebolaviruses. We developed an efficient technology for the rapid discovery of a plethora of antigen-specific monoclonal antibodies from immunized animals by mining the VH:VL paired antibody repertoire encoded by highly expanded B cells in the draining popliteal lymph node (PLN). This approach requires neither screening nor selection for antigen-binding. Specifically we show that mouse immunization with Ebola VLPs gives rise to a highly polarized antibody repertoire in CD138(+) antibody-secreting cells within the PLN. All highly expanded antibody clones (7/7 distinct clones/animal) were expressed recombinantly, and shown to recognize the VLPs used for immunization. Using this approach we obtained diverse panels of antibodies including: (i) antibodies with high affinity towards GP; (ii) antibodies which bound Ebola VLP Kissidougou-C15, the strain circulating in the recent West African outbreak; (iii) non-GP binding antibodies that recognize wild type Sudan or Bundibugyo viruses that have 39% and 37% sequence divergence from Ebola virus, respectively and (iv) antibodies to the Reston virus GP for which no antibodies have been reported.

Discrete functional elements required for initiation activity of the Chinese hamster dihydrofolate reductase origin beta at ectopic chromosomal sites.

The Chinese hamster dihydrofolate reductase (DHFR) DNA replication initiation region, the 5.8 kb ori-beta, can function as a DNA replicator at random ectopic chromosomal sites in hamster cells. We report a detailed genetic analysis of the DiNucleotide Repeat (DNR) element, one of several sequence elements necessary for ectopic ori-beta activity. Deletions within ori-beta identified a 132 bp core region within the DNR element, consisting mainly of dinucleotide repeats, and a downstream region that are required for ori-beta initiation activity at non-specific ectopic sites in hamster cells. Replacement of the DNR element with Xenopus or mouse transcriptional elements from rDNA genes restored full levels of initiation activity, but replacement with a nucleosome positioning element or a viral intron sequence did not. The requirement for the DNR element and three other ori-beta sequence elements was conserved when ori-beta activity was tested at either random sites or at a single specific ectopic chromosomal site in human cells. These results confirm the importance of specific cis-acting elements in directing the initiation of DNA replication in mammalian cells, and provide new evidence that transcriptional elements can functionally substitute for one of these elements in ori-beta.

Defined sequence modules and an architectural element cooperate to promote initiation at an ectopic mammalian chromosomal replication origin.

A small DNA fragment containing the high-frequency initiation region (IR) ori-beta from the hamster dihydrofolate reductase locus functions as an independent replicator in ectopic locations in both hamster and human cells. Conversely, a fragment of the human lamin B2 locus containing the previously mapped IR serves as an independent replicator at ectopic chromosomal sites in hamster cells. At least four defined sequence elements are specifically required for full activity of ectopic ori-beta in hamster cells. These include an AT-rich element, a 4-bp sequence located within the mapped IR, a region of intrinsically bent DNA located between these two elements, and a RIP60 protein binding site adjacent to the bent region. The ori-beta AT-rich element is critical for initiation activity in human, as well as hamster, cells and can be functionally substituted for by an AT-rich region from the human lamin B2 IR that differs in nucleotide sequence and length. Taken together, the results demonstrate that two mammalian replicators can be activated at ectopic sites in chromosomes of another mammal and lead us to speculate that they may share functionally related elements.