Fetal Medial Habenula Transplants: Innervation of the Rat Interpeduncular Nucleus

The effects of donor age and site of placement on the survival of fetal medial habenula (MH) transplants into adult rats hosts were examined. The innervation of the interpeduncular nucleus (IPN) in such cases was also examined. Explants of MH consisting of the medial-dorsal lip of the third ventricle were held in vitro for 1—2 days. Colloidal gold conjugated to wheat germ agglutinin was added for the last 18 hours to label the cells. Four of 16 cases with E19 derived transplants contained donor neurons. Markedly larger transplants were present in 95% of 20 cases with E16 derived transplants. Sites in the ventral midbrain were successful, while limited or no survival occurred at sites more remote from IPN. Retrograde labeling of transplant neurons was present in each case studied with HRP injection into host IPN. Colloidal gold-labeled macrophages, some oriented capillaries and GFAP-positive processes marked the donor-host interface. In EM the interface was evident only by the difference in tissue elements in the transplant versus host. Numerous synapses of Gray types I and II were present in the transplant. Excellent survival of MH neurons, donor/host interfaces, innervation of IPN by the transplant and fine structure in and around the transplants, all suggest that such preparations are suitable for further experimental analysis of the habenulo-interpeduncular system

Eddies and the distribution of Eddy Kinetic Energy in the Arctic Ocean

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in von Appen, W.-J., Baumann, T. M., Janout, M., Koldunov, N., Lenn, Y.-D., Pickart, R. S., Scott, R. B., & Wang, Q. Eddies and the distribution of eddy kinetic energy in the Arctic Ocean. Oceanography, 35(2), (2022), https://doi.org/10.5670/oceanog.2022.122.Mesoscale eddies are important to many aspects of the dynamics of the Arctic Ocean. Among others, they maintain the halocline and interact with the Atlantic Water circumpolar boundary current through lateral eddy fluxes and shelf-basin exchanges. Mesoscale eddies are also important for transporting biological material and for modifying sea ice distribution. Here, we review what is known about eddies and their impacts in the Arctic Ocean in the context of rapid climate change. Eddy kinetic energy (EKE) is a proxy for mesoscale variability in the ocean due to eddies. We present the first quantification of EKE from moored observations across the entire Arctic Ocean and compare those results to output from an eddy resolving numerical model. We show that EKE is largest in the northern Nordic Seas/Fram Strait and it is also elevated along the shelf break of the Arctic Circumpolar Boundary Current, especially in the Beaufort Sea. In the central basins, EKE is 100–1,000 times lower. Generally, EKE is stronger when sea ice concentration is low versus times of dense ice cover. As sea ice declines, we anticipate that areas in the Arctic Ocean where conditions typical of the North Atlantic and North Pacific prevail will increase. We conclude that the future Arctic Ocean will feature more energetic mesoscale variability

Cytoplasmic cleavage of IMPA1 3' UTR is necessary for maintaining axon integrity

The 3′ untranslated regions (3′ UTRs) of messenger RNAs (mRNAs) are non-coding sequences involved in many aspects of mRNA metabolism, including intracellular localization and translation. Incorrect processing and delivery of mRNA cause severe developmental defects and have been implicated in many neurological disorders. Here, we use deep sequencing to show that in sympathetic neuron axons, the 3′ UTRs of many transcripts undergo cleavage, generating isoforms that express the coding sequence with a short 3′ UTR and stable 3′ UTR-derived fragments of unknown function. Cleavage of the long 3′ UTR of Inositol Monophosphatase 1 (IMPA1) mediated by a protein complex containing the endonuclease argonaute 2 (Ago2) generates a translatable isoform that is necessary for maintaining the integrity of sympathetic neuron axons. Thus, our study provides a mechanism of mRNA metabolism that simultaneously regulates local protein synthesis and generates an additional class of 3′ UTR-derived RNAs

Using Fluorescence Recovery After Photobleaching (FRAP) to study dynamics of the Structural Maintenance of Chromosome (SMC) complex in vivo

The SMC complex, MukBEF, is important for chromosome organization and segregation in Escherichia coli. Fluorescently tagged MukBEF forms distinct spots (or 'foci') in the cell, where it is thought to carry out most of its chromosome associated activities. This chapter outlines the technique of Fluorescence Recovery After Photobleaching (FRAP) as a method to study the properties of YFP-tagged MukB in fluorescent foci. This method can provide important insight into the dynamics of MukB on DNA and be used to study its biochemical properties in vivo

The Mare Reproductive Loss Syndrome and the Eastern Tent Caterpillar: A Toxicokinetic/Statistical Analysis With Clinical, Epidemiologic, and Mechanistic Implications

During 2001, central Kentucky experienced acute transient epidemics of early and late fetal losses, pericarditis, and unilateral endophthalmitis, collectively referred to as mare reproductive loss syndrome (MRLS). A toxicokinetic/statistical analysis of experimental and field MRLS data was conducted using accelerated failure time (AFT) analysis of abortions following administration of Eastern tent caterpillars (ETCs; 100 or 50 g/day or 100 g of irradiated caterpillars/day) to late-term pregnant mares. In addition, 2001 late-term fetal loss field data were used in the analysis. Experimental data were fitted by AFT analysis at a high (P \u3c .0001) significance. Times to first abortion (“lag time”) and abortion rates were dose dependent. Lag times decreased and abortion rates increased exponentially with dose. Calculated dose × response data curves allow interpretation of abortion data in terms of “intubated ETC equivalents.” Analysis suggested that field exposure to ETCs in 2001 in central Kentucky commenced on approximately April 27, was initially equivalent to approximately 5 g of intubated ETCs/day, and increased to approximately 30 g/day at the outbreak peak. This analysis accounts for many aspects of the epidemiology, clinical presentations, and manifestations of MRLS. It allows quantitative interpretation of experimental and field MRLS data and has implications for the basic mechanisms underlying MRLS. The results support suggestions that MRLS is caused by exposure to or ingestion of ETCs. The results also show that high levels of ETC exposure produce intense, focused outbreaks of MRLS, closely linked in time and place to dispersing ETCs, as occurred in central Kentucky in 2001. With less intense exposure, lag time is longer and abortions tend to spread out over time and may occur out of phase with ETC exposure, obscuring both diagnosis of this syndrome and the role of the caterpillars

Exploring the facilitators and barriers to using an online infertility risk prediction tool (FoRECAsT) for young women with breast cancer: A qualitative study protocol

INTRODUCTION: As cancer treatments may impact on fertility, a high priority for young patients with breast cancer is access to evidence-based, personalised information for them and their healthcare providers to guide treatment and fertility-related decisions prior to cancer treatment. Current tools to predict fertility outcomes after breast cancer treatments are imprecise and do not offer individualised prediction. To address the gap, we are developing a novel personalised infertility risk prediction tool (FoRECAsT) for premenopausal patients with breast cancer that considers current reproductive status, planned chemotherapy and adjuvant endocrine therapy to determine likely post-treatment infertility. The aim of this study is to explore the feasibility of implementing this FoRECAsT tool into clinical practice by exploring the barriers and facilitators of its use among patients and healthcare providers. METHODS AND ANALYSIS: A cross-sectional exploratory study is being conducted using semistructured in-depth telephone interviews with 15-20 participants each from the following groups: (1) premenopausal patients with breast cancer younger than 40, diagnosed within last 5 years, (2) breast surgeons, (3) breast medical oncologists, (4) breast care nurses (5) fertility specialists and (6) fertility preservation nurses. Patients with breast cancer are being recruited from the joint Breast Service of three affiliated institutions of Victorian Comprehensive Cancer Centre in Melbourne, Australia-Peter MacCallum Cancer Centre, Royal Melbourne Hospital and Royal Women's Hospital, and clinicians are being recruited from across Australia. Interviews are being audio recorded, transcribed verbatim and imported into qualitative data analysis software to facilitate data management and analyses. ETHICS AND DISSEMINATION: The study protocol has been approved by Melbourne Health Human Research Ethics Committee, Australia (HREC number: 2017.163). Confidentiality and privacy are maintained at every stage of the study. Findings will be disseminated through peer-reviewed scholarly and scientific journals, national and international conference presentations, social media, broadcast media, print media, internet and various community/stakeholder engagement activities

RNA aptamer delivery through intact human skin

It is generally recognised that only relatively small molecular weight (typically 100,000-fold) and aptamer integrity was confirmed using an oligonucleotide precipitation assay. A Th17 response was stimulated in freshly excised human skin resulting in significantly upregulated IL-17f, and 22; topical application of the IL-23 aptamer decreased both IL-17f and IL-22 by approximately 45% but did not result in significant changes to IL-23 mRNA levels, confirming that the aptamer did not globally suppress mRNA levels. This study demonstrates that very large molecular weight RNA aptamers can permeate across the intact human skin barrier to therapeutically relevant levels into both the epidermis and dermis and that the skin penetrating aptamer retains its biologically active conformational structure capable of binding to endogenous IL-23

Abuse and Diversion of Buprenorphine Sublingual Tablets and Film

Buprenorphine abuse is common worldwide. Rates of abuse and diversion of three sublingual buprenorphine formulations (single ingredient tablets; naloxone combination tablets and film) were compared. Data were obtained from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System Poison Center, Drug Diversion, Opioid Treatment (OTP), Survey of Key Informants\u27 Patients (SKIP), and College Survey Programs through December 2012. To control for drug availability, event ratios (rates) were calculated quarterly, based on the number of patients filling prescriptions for each formulation ( unique recipients of a dispensed drug, URDD) and averaged and compared using negative binomial regression. Abuse rates in the OTP, SKIP, and College Survey Programs were greatest for single ingredient tablets, and abuse rates in the Poison Center Program and illicit diversion rates were greatest for the combination tablets. Combination film rates were significantly less than rates for either tablet formulation in all programs. No geographic pattern could be discerned