The antibody loci of the domestic goat (Capra hircus)

The domestic goat (Capra hircus) is an important ruminant species both as a source of antibody-based reagents for research and biomedical applications and as an economically important animal for agriculture, particularly for developing nations that maintain most of the global goat population. Characterization of the loci encoding the goat immune repertoire would be highly beneficial for both vaccine and immune reagent development. However, in goat and other species whose reference genomes were generated using short-read sequencing technologies, the immune loci are poorly assembled as a result of their repetitive nature. Our recent construction of a long-read goat genome assembly (ARS1) has facilitated characterization of all three antibody loci with high confidence and comparative analysis to cattle. We observed broad similarity of goat and cattle antibody-encoding loci but with notable differences that likely influence formation of the functional antibody repertoire. The goat heavy-chain locus is restricted to only four functional and nearly identical IGHV genes, in contrast to the ten observed in cattle. Repertoire analysis indicates that light-chain usage is more balanced in goats, with greater representation of kappa light chains (~ 20-30%) compared to that in cattle (~ 5%). The present study represents the first characterization of the goat antibody loci and will help inform future investigations of their antibody responses to disease and vaccination

Direct and indirect excitons in semiconductor coupled quantum wells in an applied electric field

An accurate calculation of the exciton ground and excited states in AlGaAs and InGaAs coupled quantum wells (CQWs) in an external electric field is presented. An efficient and straightforward algorithm of solving the Schrodinger equation in real space has been developed and exciton binding energies, oscillator strengths, lifetimes, and absorption spectra are calculated for applied electric fields up to 100 kV/cm. It is found that in symmetric 8-4-8 nm GaAs/Al(0.33)Ga(0.67)As CQW structure, the ground state of the system switches from direct to indirect exciton at approximately 5 kV/cm with dramatic changes of its binding energy and oscillator strength while the bright excited direct-exciton state remains almost unaffected. It is shown that the excitonic lifetime is dominated either by the radiative recombination or by tunneling processes at small/large values of the electric field, respectively. The calculated lifetime of the exciton ground state as a function of the bias voltage is in a quantitative agreement with low-temperature photoluminescence measurements. We have also made freely available a numerical code for calculation of the optical properties of direct and indirect excitons in CQWs in an electric field.Comment: 12 pages, 11 figure

The polyclonal antibody response to FMDV in cattle and African buffalo

Protection against the highly contagious foot and mouth disease virus (FMDV) coincides with neutralising antibody titres. Infection in cattle is characterised by 100% morbidity of an acute vesicular disease whilst infection of their closest relative, the African buffalo, is sub-clinical despite having diverged only 5.7 – 9.3 million years ago (Glanzmann et al., 2016; 1). The germline and antibody repertoire in African buffalo has not previously been characterised and so the cause of their differential disease response may be the production of a more specific and / or avid antibody response to FMDV than cattle. The cattle and African buffalo antibody germline was sought to characterise the recombinatorial potential of the antibody loci and their subsequent primary antibody repertoire. Expression of the antibody heavy chain (IGH) and antibody lambda light chain (IGL) was investigated with qPCR and RNA-seq. The antibody repertoire in response to FMDV infection was interrogated in African buffalo infected with SAT1 FMDV and compared to the cattle IGH repertoire inoculated with highly purified SAT1 FMDV antigen. The recombinatorial potential of the cattle and African buffalo IGH and IGL is severely limited compared to other species such as mice and human. The characterisation of the cattle IGH and IGL is the most accurate to date and reveals internal duplications of the IGH, disrupting the expected IGHV-IGHD-IGHJ-IGHC ordering seen in mammalian immune loci and resulting in four IGHD regions, containing long and ultra-long IGHD. These IGHD provide a novel diversification mechanism that can compensate for limited germline diversity by forming long and ultra-long CDR3H loops that are highly diverse in their length and amino acid composition. The African buffalo antibody repertoire also forms highly diverse long and ultra-long CDR3H, despite lack of evidence for the existence of the duplications in their IGH. Limited variability is seen in the length and amino acid composition of the IGL in both species, suggesting they are playing a structural role to support these unusual long and ultra-long CDR3H. In response to FMDV infection in African buffalo, a dramatic increase in specific long and ultra-long CDR3H sequence abundance occurs but this change in frequency of specific transcripts is absent in cattle. The differential antibody response may account for the protection of African buffalo against FMD

Collegiate Programs for Secondary Students: Meeting the Needs of the Talented

The concept meeting the needs of the individual student has been paid lip service for years within educational circles. Whether this has in fact been carried out to any appreciable extent is still open to question. Since the inception of the Secondary Science Training Programs (SSTP) by the National Science Foundation in 1959, hundreds of colleges and universities have sponsored special science programs for high-ability students. However, the Department of Health, Education, and Welfare stated in November, 1973, that fewer than four percent of this country\u27s talented secondary students were being exposed to programs commensurate with their needs (Williams, 1973). An even more awakening statement in the report was that 57 percent of school administrators surveyed were unaware of having any gifted students in their schools! The question which remains to be asked is, Who is responsible for identifying and informing students of opportunities available to them beyond the high school program

Iowa Science and Humanities Symposium: An Educational Vehicle

On March 21, approximately 225 secondary students and their teachers will gather at The University of Iowa for the twelfth annual Iowa Science and Humanities Symposium. The theme for the three-day symposium is Research in the Service of Man. The annual event is held in conjunction with the annual meeting of the Iowa Academy of Science, and is sponsored by the U.S. Army Research Office

Dietary enrichment with fish oil prevents high fat-induced metabolic dysfunction in skeletal muscle in mice

High saturated fat (HF-S) diets increase intramyocellular lipid, an effect ameliorated by omega-3 fatty acids in vitro and in vivo, though little is known about sex- and muscle fiber type-specific effects. We compared effects of standard chow, HF-S, and 7.5% HF-S replaced with fish oil (HF-FO) diets on the metabolic profile and lipid metabolism gene and protein content in red (soleus) and white (extensor digitorum longus) muscles of male and female C57BL/6 mice (n = 9-12/group). Weight gain was similar in HF-S- and HF-FO-fed groups. HF-S feeding increased mesenteric fat mass and lipid marker, Oil Red O, in red and mixed muscle; HF-FO increased interscapular brown fat mass. Compared to chow, HF-S and HF-FO increased expression of genes regulating triacylglycerol synthesis and fatty acid transport, HF-S suppressed genes and proteins regulating fatty acid oxidation, whereas HF-FO increased oxidative genes, proteins and enzymes and lipolytic gene content, whilst suppressing lipogenic genes. In comparison to HF-S, HF-FO further increased fat transporters, markers of fatty acid oxidation and mitochondrial content, and reduced lipogenic genes. No diet-by-sex interactions were observed. Neither diet influenced fiber type composition. However, some interactions between muscle type and diet were observed. HF-S induced changes in triacylglycerol synthesis and lipogenic genes in red, but not white, muscle, and mitochondrial biogenesis and oxidative genes were suppressed by HF-S and increased by HF-FO in red muscle only. In conclusion, HF-S feeding promotes lipid storage in red muscle, an effect abrogated by the fish oil, which increases mediators of lipolysis, oxidation and thermogenesis while inhibiting lipogenic genes. Greater storage and synthesis, and lower oxidative genes in red, but not white, muscle likely contribute to lipid accretion encountered in red muscle. Despite several gender-dimorphic genes, both sexes exhibited a similar HF-S-induced metabolic and gene expression profile; likewise fish oil was similarly protective in both sexes.Lisa K. Philp, Leonie K. Heilbronn, Alena Janovska, Gary A. Witter

Anatomy Nights: An international public engagement event increases audience knowledge of brain anatomy

Anatomy Nights is an international public engagement event created to bring anatomy and anatomists back to public spaces with the goal of increasing the public's understanding of their own anatomy by comparison with non-human tissues. The event consists of a 30-minute mini-lecture on the anatomy of a specific anatomical organ followed by a dissection of animal tissues to demonstrate the same organ anatomy. Before and after the lecture and dissection, participants complete research surveys designed to assess prior knowledge and knowledge gained as a result of participation in the event, respectively. This study reports the results of Anatomy Nights brain events held at four different venues in the UK and USA in 2018 and 2019. Two general questions were asked of the data: 1) Do participant postevent test scores differ from pre-event scores; and 2) Are there differences in participant scores based on location, educational background, and career. We addressed these questions using a combination of generalized linear models (R's glm function; R version 4.1.0 [R Core Team, 2014]) that assumed a binomial distribution and implemented a logit link function, as well as likelihood estimates to compare models. Survey data from 91 participants indicate that scores improve on post-event tests compared to pre-event tests, and these results hold irrespective of location, educational background, and career. In the pre-event tests, participants performed well on naming structures with an English name (frontal lobe and brainstem), and showed signs of improvement on other anatomical names in the posttest. Despite this improvement in knowledge, we found no evidence that participation in Anatomy Nights improved participants' ability to apply this knowledge to neuroanatomical contexts (e.g., stroke)

Predictive validity of a two-step tool to map frailty in primary care

Background EASY-Care Two step Older people Screening (EASY-Care TOS) is a stepped approach to identify frail older people at risk for negative health outcomes in primary care, and makes use of General Practitioners’ (GPs) readily-available information. We aimed to determine the predictive value of EASY-Care TOS for negative health outcomes within the year from assessment. Methods A total of 587 patients of four GP practices in and around Nijmegen (The Netherlands) consented to participate in a longitudinal primary care registry based cohort study. Participants’ frailty was judged by their GP following the EASY-Care TOS procedure and by a Comprehensive Geriatric Assessment (CGA) at baseline. After one year health outcomes of the participants were measured by reassessment with the EASY-Care TOS procedure. Results Follow up information was available for 520 of 587 participants. In the non-frail group 9 % showed any negative health outcomes (death, ADL decline, institutionalisation, too ill to undergo assessment), against 30 % in the frail group (95 % confidence interval of the difference (CI): 14 %–28 %). Area under the receiver operating curve (AUC) of the EASY-Care TOS frailty judgement for a composite of negative health outcomes mentioned was 0.67 (95 % CI: 0.62-0.73). Compared with discrimination on the basis of age, sex and GP practice (AUC 0.70), adding EASY-Care TOS frailty judgement increased the AUC to 0.75 (+0.05, p = 0.02). The AUC on the basis of a full CGA is almost comparable to the AUC of the model with age, sex, and frailty judgement with EASY-Care TOS: 0.76 (+0.07, p = 0.005). Conclusions GPs applying the EASY-Care TOS procedure, where they only perform additional assessment when they judge this as necessary, can predict negative health outcomes in their older populations efficiently and almost as accurately as a complete specialist CGA

Targeting valine catabolism to inhibit metabolic reprogramming in prostate cancer.

Metabolic reprogramming and energetic rewiring are hallmarks of cancer that fuel disease progression and facilitate therapy evasion. The remodelling of oxidative phosphorylation and enhanced lipogenesis have previously been characterised as key metabolic features of prostate cancer (PCa). Recently, succinate-dependent mitochondrial reprogramming was identified in high-grade prostate tumours, as well as upregulation of the enzymes associated with branched-chain amino acid (BCAA) catabolism. In this study, we hypothesised that the degradation of the BCAAs, particularly valine, may play a critical role in anapleurotic refuelling of the mitochondrial succinate pool, as well as the maintenance of intracellular lipid metabolism. Through the suppression of BCAA availability, we report significantly reduced lipid content, strongly indicating that BCAAs are important lipogenic fuels in PCa. This work also uncovered a novel compensatory mechanism, whereby fatty acid uptake is increased in response to extracellular valine deprivation. Inhibition of valine degradation via suppression of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) resulted in a selective reduction of malignant prostate cell proliferation, decreased intracellular succinate and impaired cellular respiration. In combination with a comprehensive multi-omic investigation that incorporates next-generation sequencing, metabolomics, and high-content quantitative single-cell imaging, our work highlights a novel therapeutic target for selective inhibition of metabolic reprogramming in PCa

Peroxisome Turnover and Diurnal Modulation of Antioxidant Activity in Retinal Pigment Epithelia Utilizes Microtubule-Associated Protein 1 Light Chain 3B (LC3B)

The retinal pigment epithelium (RPE) supports the outer retina through essential roles in the retinoid cycle, nutrient supply, ion exchange, and waste removal. Each day the RPE removes the oldest ∼10% of photoreceptor outer segment (OS) disk membranes through phagocytic uptake, which peaks following light onset. Impaired degradation of phagocytosed OS material by the RPE can lead to toxic accumulation of lipids, oxidative tissue damage, inflammation, and cell death. OSs are rich in very long chain fatty acids, which are preferentially catabolized in peroxisomes. Despite the importance of lipid degradation in RPE function, the regulation of peroxisome number and activity relative to diurnal OS ingestion is relatively unexplored. Using immunohistochemistry, immunoblot analysis, and catalase activity assays, we investigated peroxisome abundance and activity at 6 AM, 7 AM (light onset), 8 AM, and 3 PM, in wild-type (WT) mice and mice lacking microtubule-associated protein 1 light chain 3B (Lc3b), which have impaired phagosome degradation. We found that catalase activity, but not the amount of catalase protein, is 50% higher in the morning compared with 3 PM, in RPE of WT, but not Lc3b-/-, mice. Surprisingly, we found that peroxisome abundance was stable during the day in RPE of WT mice; however, numbers were elevated overall in Lc3b-/- mice, implicating LC3B in autophagic organelle turnover in RPE. Our data suggest that RPE peroxisome function is regulated in coordination with phagocytosis, possibly through direct enzyme regulation, and may serve to prepare RPE peroxisomes for daily surges in ingested lipid-rich OS. Copyright © 2019 the American Physiological Society