Lactotransferrin in Asian Elephant (Elephas maximus) Seminal Plasma Correlates with Semen Quality

Asian elephants (Elephas maximus) have highly variable ejaculate quality within individuals, greatly reducing the efficacy of artificial insemination and making it difficult to devise a sperm cryopreservation protocol for this endangered species. Because seminal plasma influences sperm function and physiology, including sperm motility, the objectives of this study were to characterize the chemistry and protein profiles of Asian elephant seminal plasma and to determine the relationships between seminal plasma components and semen quality. Ejaculates exhibiting good sperm motility (≥65%) expressed higher percentages of spermatozoa with normal morphology (80.3+-13.0 vs. 44.9+-30.8%) and positive Spermac staining (51.9+-14.5 vs. 7.5+-14.4%), in addition to higher total volume (135.1+-89.6 vs. 88.8+-73.1 ml) and lower sperm concentration (473.0+-511.2 vs. 1313.8+-764.7 x 106 cells ml-1) compared to ejaculates exhibiting poor sperm motility (≤10%; P\u3c0.05). Comparison of seminal plasma from ejaculates with good versus poor sperm motility revealed significant differences in concentrations of creatine phosphokinase, alanine aminotransferase, phosphorus, sodium, chloride, magnesium, and glucose. These observations suggest seminal plasma influences semen quality in elephants. One- and two-dimensional (2D) gel electrophoresis revealed largely similar compositional profiles of seminal plasma proteins between good and poor motility ejaculates. However, a protein of ~80 kDa was abundant in 85% of ejaculates with good motility, and was absent in 90% of poor motility ejaculates (P\u3c0.05). We used mass spectrometry to identify this protein as lactotransferrin, and immunoblot analysis to confirm this identification. Together, these findings lay a functional foundation for understanding the contributions of seminal plasma in the regulation of Asian elephant sperm motility, and for improving semen collection and storage in this endangered species

Practice effects in a longitudinal, multi-center Alzheimer\u27s disease prevention clinical trial

BACKGROUND: Practice effects are a known threat to reliability and validity in clinical trials. Few studies have investigated the potential influence of practice on repeated screening measures in longitudinal clinical trials with a focus on dementia prevention. The current study investigates whether practice effects exist on a screening measure commonly used in aging research, the Memory Impairment Screen (MIS). METHODS: The PREADViSE trial is a clinical intervention study evaluating the efficacy of vitamin E and selenium for Alzheimer\u27s disease prevention. Participants are screened annually for incident dementia with the MIS. Participants with baseline and three consecutive follow-ups who made less than a perfect score at one or more assessments were included in the current analyses (N=1,803). An additional subset of participants with four consecutive assessments but who received the same version of the MIS at baseline and first follow-up (N=301) was also assessed to determine the effects of alternate forms on mitigating practice. We hypothesized that despite efforts to mitigate practice effects with alternate versions, MIS scores would improve with repeated screening. Linear mixed models were used to estimate mean MIS scores over time. RESULTS: Among men with four visits and alternating MIS versions, although there is little evidence of a significant practice effect at the first follow-up, mean scores clearly improve at the second and third follow-ups for all but the oldest participants. Unlike those who received alternate versions, men given the same version at first follow-up show significant practice effects. CONCLUSION: While increases in the overall means were small, they represent a significant number of men whose scores improved with repeated testing. Such improvements could bias case ascertainment if not taken into account

Evaluation of the Geothermal Potential of the Western Snake River Plain Based on a Deep Corehole on the Mountain Home AFB Near Mountain Home, Idaho

A geothermal exploration corehole was drilled to a total depth of 1821.5 m on the Mountain Home Air Force Base near Mountain Home, Idaho. The corehole was used to collect an unusually large amount of data, including uniaxial compressive stress (UCS) experiments on core samples, to evaluate the geothermal potential of the western Snake River Plain. In addition, unlike many exploration holes in this region, a fluid entry was encountered at 1745.3 m and flowed artesian to the surface. A maximum temperature of 149.4 °C was calculated for the entry. A temperature log run on the corehole from 3 to 1675 m is nearly linear with little variation. The average geothermal gradient is 73 °C/km, and the average heat flow between 200 and 1500 m is 102 ± 15 mW/m2. Chemical analyses of a sample from the fluid entry suggest that a significant proportion of the water is not meteoric. Five geothermometers show equilibrium temperature in the range of 133–157 °C. Furthermore, based on the unconfined UCS experiments on basalt core samples, a brittle unit was found to comprise the fractured reservoir that the geothermal water flows from, while an overlying ductile unit acts as a hydrothermal caprock. This implies that the reservoir/caprock pair may be a target for future exploration wells drilled to delineate the extent of the potential resource and the boundaries of the connected fracture network

Experimental Search for Neutron to Mirror Neutron Oscillations as an Explanation of the Neutron Lifetime Anomaly

An unexplained $>4\,\sigma$ discrepancy persists between "beam" and "bottle" measurements of the neutron lifetime. A new model proposed that conversions of neutrons $n$ into mirror neutrons $n'$, part of a dark mirror sector, can increase the apparent neutron lifetime by $1\%$ via a small mass splitting $\Delta{m}$ between $n$ and $n'$ inside the 4.6 T magnetic field of the National Institute of Standards and Technology Beam Lifetime experiment. A search for neutron conversions in a 6.6 T magnetic field was performed at the Spallation Neutron Source which excludes this explanation for the neutron lifetime discrepancy

Elaborating the potential of Artificial Intelligence in automated CAR-T cell manufacturing

This paper discusses the challenges of producing CAR-T cells for cancer treatment and the potential for Artificial Intelligence (AI) for its improvement. CAR-T cell therapy was approved in 2018 as the first Advanced Therapy Medicinal Product (ATMP) for treating acute leukemia and lymphoma. ATMPs are cell- and gene-based therapies that show great promise for treating various cancers and hereditary diseases. While some new ATMPs have been approved, ongoing clinical trials are expected to lead to the approval of many more. However, the production of CAR-T cells presents a significant challenge due to the high costs associated with the manufacturing process, making the therapy very expensive (approx. $400,000). Furthermore, autologous CAR-T therapy is limited to a make-to-order approach, which makes scaling economical production difficult. First attempts are being made to automate this multi-step manufacturing process, which will not only directly reduce the high manufacturing costs but will also enable comprehensive data collection. AI technologies have the ability to analyze this data and convert it into knowledge and insights. In order to exploit these opportunities, this paper analyses the data potential in the automated CAR-T production process and creates a mapping to the capabilities of AI applications. The paper explores the possible use of AI in analyzing the data generated during the automated process and its capabilities to further improve the efficiency and cost-effectiveness of CAR-T cell production

Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans

Importance: Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. Objective: To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). Design, Setting, and Participants: A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. Exposures: Ionizing radiation and doxorubicin. Main Outcomes and Measures: Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. Results: Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95% CI, 0%-5%]; African wild dog, 8% [95% CI, 0%-16%]; lion, 2% [95% CI, 0%-7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95% CI, 3.14%-6.49%), compared with humans, who have 11% to 25% cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95% CI, 1.93%-3.48%] vs human controls, 7.17% [95% CI, 5.91%-8.44%] vs elephants, 14.64% [95% CI, 10.91%-18.37%]; P \u3c .001; doxorubicin exposure: human controls, 8.10% [95% CI, 6.55%-9.66%] vs elephants, 24.77% [95% CI, 23.0%-26.53%]; P \u3c .001). Conclusions and Relevance: Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression

From Africa to Europe and back: refugia and range shifts cause high genetic differentiation in the Marbled White butterfly Melanargia galathea

<p>Abstract</p> <p>Background</p> <p>The glacial-interglacial oscillations caused severe range modifications of biota. Thermophilic species became extinct in the North and survived in southern retreats, e.g. the Mediterranean Basin. These repeated extinction and (re)colonisation events led to long-term isolation and intermixing of populations and thus resulted in strong genetic imprints in many European species therefore being composed of several genetic lineages. To better understand these cycles of repeated expansion and retraction, we selected the Marbled White butterfly <it>Melanargia galathea</it>. Fourty-one populations scattered over Europe and the Maghreb and one population of the sibling taxon <it>M. lachesis </it>were analysed using allozyme electrophoresis.</p> <p>Results</p> <p>We obtained seven distinct lineages applying neighbour joining and STRUCTURE analyses: (i) Morocco, (ii) Tunisia, (iii) Sicily, (iv) Italy and southern France, (v) eastern Balkans extending to Central Europe, (vi) western Balkans with western Carpathian Basin as well as (vii) south-western Alps. The hierarchy of these splits is well matching the chronology of glacial and interglacial cycles since the Günz ice age starting with an initial split between the <it>galathea </it>group in North Africa and the <it>lachesis </it>group in Iberia. These genetic structures were compared with past distribution patterns during the last glacial stage calculated with distribution models.</p> <p>Conclusions</p> <p>Both methods suggest climatically suitable areas in the Maghreb and the southern European peninsulas with distinct refugia during the last glacial period and underpin strong range expansions to the North during the Postglacial. However, the allozyme patterns reveal biogeographical structures not detected by distribution modelling as two distinct refugia in the Maghreb, two or more distinct refugia at the Balkans and a close link between the eastern Maghreb and Sicily. Furthermore, the genetically highly diverse western Maghreb might have acted as source or speciation centre of this taxon, while the eastern, genetically impoverished Maghreb population might result from a relatively recent recolonisation from Europe via Sicily.</p

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag