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In the fertility clinic setting, a negative DNA paternity test result usually suggests a sample mix-up likely occurred at the testing company or in the clinic. However, we report a case where, despite repeat negative paternity test results, the alleged father (referred to as “the proband”) was confirmed to be the baby’s father. The proband, a 34 year-old male, contacted our research group when routine blood testing revealed discrepant blood types between the parents and the baby, repeat paternity tests were negative (excluding the proband as the baby’s father), and the fertility clinic found no evidence of any wrongdoing. Microarray technology was utilized to confirm biological relatedness, which revealed an avuncular (uncle/nephew) relationship. Additional tissue samples were analyzed and family studies were conducted at paternity and forensic laboratories using STR-based DNA tests to elucidate the proband’s condition of congenital tetragametic chimerism. His paternity was subsequently affirmed and the fertility clinic exonerated of claims of a semen sample mix-up. This case underscores the possibility that some allegations of fertility clinic missteps may be explained by undiagnosed chimerism, a condition where an individual harbors two distinct genomes. We offer specific suggestions for improving laboratory reporting and creating clinical guidelines to aid in identifying and rectifying future cases of false exclusions of paternity due to chimerism.

ObjectivesThe enormous toll of the COVID-19 pandemic has heightened the urgency of collecting and analysing population-scale datasets in real time to monitor and better understand the evolving pandemic. The objectives of this study were to examine the relationship of risk factors to COVID-19 susceptibility and severity and to develop risk models to accurately predict COVID-19 outcomes using rapidly obtained self-reported data.DesignA cross-sectional study.SettingAncestryDNA customers in the USA who consented to research.ParticipantsThe AncestryDNA COVID-19 Study collected self-reported survey data on symptoms, outcomes, risk factors and exposures for over 563 000 adult individuals in the USA in just under 4 months, including over 4700 COVID-19 cases as measured by a self-reported positive test.ResultsWe replicated previously reported associations between several risk factors and COVID-19 susceptibility and severity outcomes, and additionally found that differences in known exposures accounted for many of the susceptibility associations. A notable exception was elevated susceptibility for men even after adjusting for known exposures and age (adjusted OR=1.36, 95% CI=1.19 to 1.55). We also demonstrated that self-reported data can be used to build accurate risk models to predict individualised COVID-19 susceptibility (area under the curve (AUC)=0.84) and severity outcomes including hospitalisation and critical illness (AUC=0.87 and 0.90, respectively). The risk models achieved robust discriminative performance across different age, sex and genetic ancestry groups within the study.ConclusionsThe results highlight the value of self-reported epidemiological data to rapidly provide public health insights into the evolving COVID-19 pandemic.

The National Optical Astronomical Observatory (NOAO) has an ambitious long-range plan to support US astronomical research efforts. This plan includes large-scale new facilities such as LSST, GSMT, and NVO, as well as instrumentation development programs, and continuing efforts in detector research and development. This paper serves to provide a brief overview of the NOAO observatory plans.

Initiation of transcription of messenger RNA in the nucleus of eukaryotic cells is accomplished by the enzyme RNA polymerase II and a host of general transcription factors. I have studied the interaction of the general RNA polymerase II transcription factors, TATA-Binding Protein (TBP), TFIIA and TFIIB with a consensus TATA box (TATAAAA). TBP recognizes and binds the TATA box sequence in the absence of other proteins whereas TFIIA and TFIIB interact with bound TBP. Here I show that TBP recognizes the TATA box through the minor groove of the DNA and that the deformation of the TATA box sequence in the complex correlates with the strength of TBP binding. These findings raise interesting questions concerning the mechanism by which TBP recognizes the TATA box. It may be that TBP recognizes its binding site through a combination of a lack of sterically interfering groups in the minor groove and the deformability of the DNA binding site. This model would explain how TBP is able to recognize AT-rich sequences through the minor groove where the array of H-bond donors and acceptors are not distinctive. This new paradigm of DNA recognition by a protein is important because of the discovery of other proteins which apparently bind in a similar manner. I have also studied the effects of the general transcription factors, TFIIA and TFIIB, upon TBP binding to the TATA box. Upon binding, TFIIA alters the conformation of TBP such that the major groove of the TATA box, which is protected from chemical methylation in the TBP-TATA box complex, becomes solvent accessible. This finding raises the possibility that some factor which binds subsequent to TFIIA may recognize the TATA box through the major groove. My studies have also shown that bound and unbound TFIIB are in rapid equilibrium in either TBP-TATA box or TBP-TFIIA-TATA box complexes. TFIIB eliminates the effects of TATA box mutations upon the TBP-induced DNA bend, perhaps by selectively binding to those complexes which are bent to the proper angle for subsequent preinitiation complex assembly. These properties make TFIIB an excellent target for transcriptional activators.

The MONSOON Image Acquisition System is a scalable, multichannel, high-speed data acquisition system designed for the next-generation optical/infrared detectors and mosaic projects currently under development at NOAO. MONSOON is more than a controller; rather it is new image acquisition architecture, providing a total solution to “detector-limited” image acquisition for all astronomical detectors, scientific and technical, OUV to IR. MONSOON addresses detector-interface as well as the significant data flow and processing issues large-scale imaging systems require. The Monsoon effort is a full-disclosure “open-source” development effort by NOAO in collaboration with the CARA ASTEROID project for the benefit of the astronomical community.

A frame-shift mutation in MATRILINEAL, a pollen-specific phospholipase, triggers haploid induction in maize, which may be useful in developing improved haploid induction systems for crop breeding. Haploid induction in maize Haploid inbred lines are a valuable tool for genetic research and the hybrid breeding of crop plants. Timothy Kelliher et al . now examine the genetic basis of haploid induction in maize, and find that a frame-shift mutation in MATRILINEAL , a pollen-specific phospholipase, triggers haploid induction in these lines. This finding may be useful for the development of improved haploid induction systems for crop breeding. Sexual reproduction in flowering plants involves double fertilization, the union of two sperm from pollen with two sex cells in the female embryo sac. Modern plant breeders increasingly seek to circumvent this process to produce doubled haploid individuals, which derive from the chromosome-doubled cells of the haploid gametophyte. Doubled haploid production fixes recombinant haploid genomes in inbred lines, shaving years off the breeding process 1 . Costly, genotype-dependent tissue culture methods are used in many crops 2 , while seed-based in vivo doubled haploid systems are rare in nature 3 and difficult to manage in breeding programmes 4 . The multi-billion-dollar maize hybrid seed business, however, is supported by industrial doubled haploid pipelines using intraspecific crosses to in vivo haploid inducer males derived from Stock 6, first reported in 1959 (ref. 5 ), followed by colchicine treatment. Despite decades of use, the mode of action remains controversial 6 , 7 , 8 , 9 , 10 . Here we establish, through fine mapping, genome sequencing, genetic complementation, and gene editing, that haploid induction in maize ( Zea mays ) is triggered by a frame-shift mutation in MATRILINEAL ( MTL ), a pollen-specific phospholipase, and that novel edits in MTL lead to a 6.7% haploid induction rate (the percentage of haploid progeny versus total progeny). Wild-type MTL protein localizes exclusively to sperm cytoplasm, and pollen RNA-sequence profiling identifies a suite of pollen-specific genes overexpressed during haploid induction, some of which may mediate the formation of haploid seed 11 , 12 , 13 , 14 , 15 . These findings highlight the importance of male gamete cytoplasmic components to reproductive success and male genome transmittance. Given the conservation of MTL in the cereals, this discovery may enable development of in vivo haploid induction systems to accelerate breeding in crop plants.

Doubled haploid plants are invaluable breeding tools but many crop species are recalcitrant to available haploid induction techniques. To test if haploid inducer lines can be engineered into crops, CENH3 (-∕-) and CENH3:RNAi lines were complemented by AcGREEN-tailswap-CENH3 or AcGREEN-CENH3 transgenes. Haploid induction rates were determined following testcrosses to wild-type plants after independently controlling for inducer parent sex and transgene zygosity. CENH3 fusion proteins were localized to centromeres and did not cause vegetative defects or male sterility. CENH3:RNAi lines did not demonstrate consistent knockdown and rarely produced haploids. In contrast, many of the complemented CENH3 (-∕-) lines produced haploids at low frequencies. The rate of gynogenic haploid induction reached a maximum of 3.6% in several hemizygous individuals when backcrossed as males. These results demonstrate that CENH3-tailswap transgenes can be used to engineer in vivo haploid induction systems into maize plants.

Abstract Background In dogs, antiepileptic drugs (AED) cause lethargy but quantitative data regarding the effects of AED on activity levels are not available, and little is known about how AEDs affect sleep quality. Objective To quantitatively compare activity levels and nocturnal activity in dogs previously diagnosed with idiopathic epilepsy (IE) receiving AEDs compared to age- and breed-matched control dogs. Animals Sixty-two dogs with IE and 310 control dogs. Methods This is a 3-month prospective parallel observational study. An activity monitoring device for dogs was used to measure daily activity levels and sleep scores in all dogs. Results Dogs with IE treated with AEDs had an 18% average lower baseline activity level compared to control dogs (P = .005; point estimate = 0.82, 95% confidence interval [CI], 0.75-0.90). The combination of phenobarbital and potassium bromide (KBr) was associated with an average 28% decrease in activity in dogs with IE compared to control dogs (P = .03; point estimate = 0.72; CI, 0.62-0.82). Mean sleep scores were not significantly different in dogs with IE receiving AEDs compared to control dogs (P = .43). However, higher dosages of KBr were associated with lower sleep scores (P = .01). Conclusions Dogs with IE receiving AEDs have lower activity levels, but no difference in sleep scores, compared to controls. The combination of phenobarbital and KBr had the largest decrease in activity between groups. Higher doses of KBr may affect nocturnal activity in epileptic dogs.

Background Epigenetic age acceleration (an older methylation age compared to chronological age) correlates strongly with various age-related morbidities and mortality. Chronic systemic inflammation is thought to be a hallmark of ageing, but the relationship between an increased epigenetic age and this likely key phenotype of ageing has not yet been extensively investigated. Methods We modelled the trajectories of the inflammatory biomarkers C-reactive protein (CRP; measured using both a high- and low-sensitivity assay) and interleukin-6 (IL-6) over the eighth decade in the Lothian Birth Cohort 1936. Using linear mixed models, we investigated the association between CRP and immune cell profiles imputed from the methylation data and examined the cross-sectional and longitudinal association between the inflammatory biomarkers and two measures of epigenetic age acceleration, derived from the Horvath and Hannum epigenetic clocks. Results We found that low-sensitivity CRP declined, high-sensitivity CRP did not change, and IL-6 increased over time within the cohort. CRP levels inversely associated with CD8+T cells and CD4+T cells and positively associated with senescent CD8+T cells, plasmablasts and granulocytes. Cross-sectionally, the Hannum, but not the Horvath, measure of age acceleration was positively associated with each of the inflammatory biomarkers, including a restricted measure of CRP (≤ 10 mg/L) likely reflecting levels relevant to chronic inflammation. Conclusions We found a divergent relationship between inflammation and immune system parameters in older age. We additionally report the Hannum measure of epigenetic age acceleration associated with an elevated inflammatory profile cross-sectionally, but not longitudinally.