Babylonian solar theory on the Antikythera mechanism

This article analyzes the angular spacing of the degree marks on the zodiac scale of the Antikythera mechanism and demonstrates that over the entire preserved 88° of the zodiac, the marks are systematically placed too close together to be consistent with a uniform distribution over 360°. Thus, in some other part of the zodiac scale (not preserved), the degree marks have been spaced farther apart. By contrast, the day marks on the Egyptian calendar scale are spaced uniformly, apart from minor errors. A solar equation of center is apparent which rises by nearly 2.7° over the preserved portion of the zodiac. The placement of the degree marks indicates that, in the preserved portion of the zodiac, the Sun was considered to run at a uniform pace of about 30° per synodic month, which is consistent with the Sun’s speed in the fast zone of the Babylonian solar theory of System A.

     

Britton’s theory of the creation of Column $$\varPhi $$ in Babylonian System A lunar theory

The following article has two parts. The first part recounts the history of a series of discoveries by Otto Neugebauer, Bartel van der Waerden, and Asger Aaboe which step by step uncovered the meaning of Column \(\varPhi \), the mysterious leading column in Babylonian System A lunar tables. Their research revealed that Column \(\varPhi \) gives the length in days of the 223-month Saros eclipse cycle and explained the remarkable algebraic relations connecting Column \(\varPhi \) to other columns of the lunar tables describing the duration of 1, 6, or 12 synodic months. Part two presents John Britton’s theory of the genesis of Column \(\varPhi \) and the System A lunar theory starting from a fundamental equation relating the columns discovered by Asger Aaboe. This article is intended to explain and, hopefully, to clarify Britton’s original articles which many readers found difficult to follow.     

A Study of Babylonian Observations of Planets Near Normal Stars

The present paper is an attempt to describe the observational practices behind a large and homogeneous body of Babylonian observation reports involving planets and certain bright stars near the ecliptic (Normal Stars). The reports in question are the only precise positional observations of planets in the Babylonian texts, and while we do not know their original purpose, they may have had a part in the development of predictive models for planetary phenomena in the second half of the first millennium B.C. The paper is organized according to the following topics: (I) Sections 1–3 review the format of the observations and the texts in which they are found; (II) Sections 4–6 discuss the composition of the Normal Star list; (III) Sections 7–8 concern the orientation of the reported celestial directions from star to planet; (IV) Sect. 9 concerns the relationship between the reported distances and the actual angular distances between planet and star; and (V) Sect. 10 discusses the reports of planetary stations, which are the most common reports giving precise locations of planets when they are not near their closest approach to stars, and draws some brief general conclusions about the utility of the Babylonian observations for estimating planetary longitudes and calibrating models in antiquity.I wish to thank Lis Brack-Bernsen, John Britton, Peter Huber, Hermann Hunger, Teije de Jong, Norbert Roughton, John Steele, and Noel Swerdlow for comments on drafts of the paper, for access to work before publication, and for help in various forms.     

Greek angles from Babylonian numbers

Models of planetary motion as observed from Earth must account for two principal anomalies: the nonuniform speed of the planet as it circles the zodiac, and the correlation of the planet’s position with the position of the Sun. In the context of the geometrical models used by the Greeks, the practical difficulty is to somehow isolate the motion of the epicycle center on the deferent from the motion of the planet on its epicycle. One way to isolate the motion of the epicycle center is to determine the longitude and time of oppositions of the planet with the mean Sun. A Greek astronomer might have realized that the predictions of mean oppositions by Babylonian models could serve as useful proxies for real empirical observations. It is shown that a Greek astronomer with a reasonable understanding of Babylonian System A models for the outer planets and the Sun–Moon could have used those models to estimate approximate values for the eccentricity e and longitude of apogee A required for geometrical models. The same method would work for the inner planets if conjunctions were observable, but they are not, and the variation of the observable synodic events—first and last morning and evening visibilities—is dominated more by the motion of the planet in latitude than the nonuniform motion of the epicycle center.     

Studies on Babylonian goal-year astronomy II: the Babylonian calendar and goal-year methods of prediction

This paper is the second part of an investigation into Babylonian non-mathematical astronomical texts and the relationships between Babylonian observational and predicted astronomical data. Part I (Gray and Steele 2008) showed that the predictions found in the Almanacs and Normal Star Almanacs were almost certainly made by applying Goal-Year periods to observations recorded in the Goal-Year Texts. The paper showed that the differences in dates of records between the Goal-Year Texts and the Almanacs or Normal Star Almanacs were consistent with the date corrections of a few days which, according to theoretical calculations, should be added to allow for the inexactness of Goal-Year periods. The current paper follows on from our earlier study to consider the effect of the Babylonian calendar on Goal-Year methods of prediction. Due to the fact that the Babylonian calendar year can contain either 12 or 13 months, a Goal-Year period can occasionally be month longer or shorter than usual. This suggests that there should in theory be certain points in the Metonic intercalation cycle where a predicted event occurs one Babylonian month earlier or later than the corresponding event a Goal-Year period later. By comparing dates of lunar and planetary records in the Astronomical Diaries, Goal-Year Texts, Almanacs and Normal Star Almanacs, we show that these month differences between the observational records and the predictions occur in the expected years. This lends further support to the theory that the Almanacs’ and Normal Star Almanacs’ predictions originated from records in the Goal-Year Texts, and clarifies how the Goal-Year periods were used in practice.     

Muḥyī al-Dīn al-Maghribī’s lunar measurements at the Maragha observatory

This paper is a technical study of the systematic observations and computations made by Mu?yī al-Dīn al-Maghribī (d. 1283) at the Maragha observatory (north-western Iran, c. 1259–1320) in order to newly determine the parameters of the Ptolemaic lunar model, as explained in his Talkhī? al-majis?ī, “Compendium of the Almagest.” He used three lunar eclipses on March 7, 1262, April 7, 1270, and January 24, 1274, in order to measure the lunar epicycle radius and mean motions; an observation on April 20, 1264, to determine the lunar eccentricity; an observation on August 29, 1264, to test the model; and another on March 15, 1262, for measuring the lunar parallax. In the second period of activity at the Maragha observatory, Shams al-Dīn Mu?ammad al-Wābkanawī (c. 1254–1320) adopted all of al-Maghribī’s parameter values in his Zīj, but decreased his value for the mean longitude of the moon at epoch by 0;13,11 $^{\circ }$ . By comparing the times of the new moons and lunar eclipses in the period of 1270–1320 as computed from the astronomical tables of the Maragha tradition with the true modern ones, it is argued that this correction was very probably the result of actual observations.     

Greek astronomical calendars I. The parapegma of Euctemon

Summary In view of the striking similarities noted in the subsection A, B, C we are bound to conclude that Euctemon was influenced by Babylonian astronomy. However, his parapegma was not just a translation of a Babylonian text: it was an improvement in many respects. His dates of annual risings and settings were more accurate than the Babylonian dates. In most cases he recorded true risings, or he recorded both the true and the visible phaenomena. This distinction is not made in the text MUL APIN.     

Diffusion of d-glucose measured in the cytosol of a single astrocyte

Astrocytes interact with neurons and endothelial cells and may mediate exchange of metabolites between capillaries and nerve terminals. In the present study, we investigated intracellular glucose diffusion in purified astrocytes after local glucose uptake. We used a fluorescence resonance energy transfer (FRET)-based nano sensor to monitor the time dependence of the intracellular glucose concentration at specific positions within the cell. We observed a delay in onset and kinetics in regions away from the glucose uptake compared with the region where we locally super-fused astrocytes with the d-glucose-rich solution. We propose a mathematical model of glucose diffusion in astrocytes. The analysis showed that after gradual uptake of glucose, the locally increased intracellular glucose concentration is rapidly spread throughout the cytosol with an apparent diffusion coefficient (D _app) of (2.38 ± 0.41) × 10^?10 m² s^?1 (at 22–24 °C). Considering that the diffusion coefficient of d-glucose in water is D = 6.7 × 10^?10 m² s^?1 (at 24 °C), D _app determined in astrocytes indicates that the cytosolic tortuosity, which hinders glucose molecules, is approximately three times higher than in aqueous solution. We conclude that the value of D _app for glucose measured in purified rat astrocytes is consistent with the view that cytosolic diffusion may allow glucose and glucose metabolites to traverse from the endothelial cells at the blood–brain barrier to neurons and neighboring astrocytes.     

Solar and lunar observations at Istanbul in the 1570s

From the early ninth century until about eight centuries later, the Middle East witnessed a series of both simple and systematic astronomical observations for the purpose of testing contemporary astronomical tables and deriving the fundamental solar, lunar, and planetary parameters. Of them, the extensive observations of lunar eclipses available before 1000 AD for testing the ephemeredes computed from the astronomical tables are in a relatively sharp contrast to the twelve lunar observations that are pertained to the four extant accounts of the measurements of the basic parameters of Ptolemaic lunar model. The last of them are Taqī al-Dīn Mu?ammad b. Ma‘rūf’s (1526–1585) trio of lunar eclipses observed from Istanbul, Cairo, and Thessalonica in 1576–1577 and documented in chapter 2 of book 5 of his famous work, Sidrat muntaha al-afkar fī malakūt al-falak al-dawwār (The Lotus Tree in the Seventh Heaven of Reflection). In this article, we provide a detailed analysis of the accuracy of his solar (1577–1579) and lunar observations.     

Protein levels of clusterin and glutathione synthetase in platelets allow for early detection of colorectal cancer

Colorectal cancer (CRC) is one of the most frequent malignancies in the Western world. Early tumor detection and intervention are important determinants on CRC patient survival. During early tumor proliferation, dissemination and angiogenesis, platelets store and segregate proteins actively and selectively. Hence, the platelet proteome is a potential source of biomarkers denoting early malignancy. By comparing protein profiles of platelets between healthy volunteers (n = 12) and patients with early- (n = 7) and late-stage (n = 5) CRCs using multiplex fluorescence two-dimensional gel electrophoresis (2D-DIGE), we aimed at identifying differentially regulated proteins within platelets. By inter-group comparisons, 94 differentially expressed protein spots were detected (p < 0.05) between healthy controls and patients with early- and late-stage CRCs and revealed distinct separations between all three groups in principal component analyses. 54 proteins of interest were identified by mass spectrometry and resulted in high-ranked Ingenuity Pathway Analysis networks associated with Cellular function and maintenance, Cellular assembly and organization, Developmental disorder and Organismal injury and abnormalities (p < 0.0001 to p = 0.0495). Target proteins were validated by multiplex fluorescence-based Western blot analyses using an additional, independent cohort of platelet protein samples [healthy controls (n = 15), early-stage CRCs (n = 15), late-stage CRCs (n = 15)]. Two proteins—clusterin and glutathione synthetase (GSH-S)—featured high impact and were subsequently validated in this independent clinical cohort distinguishing healthy controls from patients with early- and late-stage CRCs. Thus, the potential of clusterin and GSH-S as platelet biomarkers for early detection of CRC could improve existing screening modalities in clinical application and should be confirmed in a prospective multicenter trial.     

Micromanaging freeze tolerance: the biogenesis and regulation of neuroprotective microRNAs in frozen brains

When temperatures plummet below 0 °C, wood frogs (Rana sylvatica) can endure the freezing of up to?~?65% of their body water in extracellular ice masses, displaying no measurable brain activity, no breathing, no movement, and a flat-lined heart. To aid survival, frogs retreat into a state of suspended animation characterized by global suppression of metabolic functions and reprioritization of energy usage to essential survival processes that is elicited, in part, by the regulatory controls of microRNAs. The present study is the first to investigate miRNA biogenesis and regulation in the brain of a freeze tolerant vertebrate. Indeed, proper brain function and adaptations to environmental stimuli play a crucial role in coordinating stress responses. Immunoblotting of miRNA biogenesis factors illustrated an overall reduction in the majority of these processing proteins suggesting a potential suppression of miRNA maturation over the freeze–thaw cycle. This was coupled with a large-scale RT-qPCR analysis of relative expression levels of 113 microRNA species in the brains of control, 24 h frozen, and 8 h thawed R. sylvatica. Of the 41 microRNAs differentially regulated during freezing and thawing, only two were significantly upregulated. Bioinformatic target enrichment of the downregulated miRNAs, performed at the low temperatures experienced during freezing and thawing, predicted their involvement in the potential activation of various neuroprotective processes such as synaptic signaling, intracellular signal transduction, and anoxia/ischemia injury protection. The predominantly downregulated microRNA fingerprint identified herein suggests a microRNA-mediated cryoprotective mechanism responsible for maintaining neuronal functions and facilitating successful whole brain freezing and thawing.     

Extracellular vesicles regulate the human osteoclastogenesis: divergent roles in discrete inflammatory arthropathies

Objective

Extracellular vesicles (EVs) are subcellular signalosomes. Although characteristic EV production is associated with numerous physiological and pathological conditions, the effect of blood-derived EVs on bone homeostasis is unknown. Herein we evaluated the role of circulating EVs on human osteoclastogenesis.

Methods

Blood samples from healthy volunteers, rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients were collected. Size-based EV sub-fractions were isolated by gravity-driven filtration and differential centrifugation. To investigate the properties of EV samples, resistive pulse sensing technique, transmission electron microscopy, flow cytometry and western blot were performed. CD14⁺ monocytes were separated from PBMCs, and stimulated with recombinant human M-CSF, RANKL and blood-derived EV sub-fractions. After 7 days, the cells were fixed and stained for tartrate-resistant acid phosphatase and counted.

Results

EVs isolated by size-based sub-fractions were characterized as either microvesicles or exosomes (EXO). Healthy (n = 11) and RA-derived (n = 12) EXOs profoundly inhibited osteoclast differentiation (70%, p < 0.01; 65%, p < 0.01, respectively). In contrast, PsA-derived (n = 10) EXOs had a stimulatory effect (75%, p < 0.05). In cross-treatment experiments where EXOs and CD14⁺ cells were interchanged between the three groups, only healthy (n = 5) and RA (n = 5)-derived EXOs inhibited (p < 0.01, respectively) the generation of osteoclasts in all groups, whereas PsA (n = 7)-derived EXOs were unable to mediate this effect.

Conclusions

Our data suggest that blood-derived EXOs are novel regulators of the human osteoclastogenesis and may offer discrete effector function in distinct inflammatory arthropathies.

     

Geometric division problems, quadratic equations, and recursive geometric algorithms in Mesopotamian mathematics

Most of what is told in this paper has been told before by the same author, in a number of publications of various kinds, but this is the first time that all this material has been brought together and treated in a uniform way. Smaller errors in the earlier publications are corrected here without comment. It has been known since the 1920s that quadratic equations played a prominent role in Babylonian mathematics. See, most recently, Høyrup (Hist Sci 34:1–32, 1996, and Lengths, widths, surfaces: a portrait of old Babylonian algebra and its kin. Springer, New York, 2002). What has not been known, however, is how quadratic equations came to play that role, since it is difficult to think of any practical use for quadratic equations in the life and work of a Babylonian scribe. One goal of the present paper is to show how the need to find solutions to quadratic equations actually arose in Mesopotamia not later than in the second half of the third millennium BC, and probably before that in connection with certain geometric division of property problems. This issue was brought up for the first time in Friberg (Cuneiform Digit Lib J 2009:3, 2009). In this connection, it is argued that the tool used for the first exact solution of a quadratic equation was either a clever use of the “conjugate rule” or a “completion of the square,” but that both methods ultimately depend on a certain division of a square, the same in both cases. Another, closely related goal of the paper is to discuss briefly certain of the most impressive achievements of anonymous Babylonian mathematicians in the first half of the second millennium BC, namely recursive geometric algorithms for the solution of various problems related to division of figures, more specifically trapezoidal fields. For an earlier, comprehensive (but less accessible) treatment of these issues, see Friberg (Amazing traces of a Babylonian origin in Greek mathematics. WorldScientific, Singapore 2007b, Ch. 11 and App. 1).     

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5–20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of d-glucose was lower than d-fructose. However, uptake of d-glucose was higher than d-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection.     

miR-124-3p is a chronic regulator of gene expression after brain injury

Traumatic brain injury (TBI) initiates molecular and cellular pathologies that underlie post-injury morbidities, including hippocampus-related memory decline and epileptogenesis. Non-coding small RNAs are master regulators of gene expression with the potential to affect multiple molecular pathways. To evaluate whether hippocampal gene expression networks are chronically regulated by microRNAs after TBI, we sampled the dentate gyrus of rats with severe TBI induced by lateral fluid-percussion injury 3 months earlier. Ingenuity pathway analysis revealed 30 upregulated miR-124-3p targets, suggesting that miR-124-3p is downregulated post-TBI (z-score?=?? 5.146, p?<?0.05). Droplet digital polymerase chain reaction (ddPCR) and in situ hybridization confirmed the chronic downregulation of miR-124-3p (p?<?0.05). Quantitative PCR analysis of two targets, Plp2 and Stat3, indicated that their upregulation correlated with the miR-124-3p downregulation (r?=?? 0.647, p?<?0.05; r?=?? 0.629, p?<?0.05, respectively). Immunohistochemical staining of STAT3 confirmed the increased protein expression. STRING analysis showed that 9 of the 30 miR-124-3p targets belonged to a STAT3 network. Reactome analysis and data mining connected the targets especially to inflammation and signal transduction. L1000CDS2 software revealed drugs (e.g., importazole, trichostatin A, and IKK-16) that could reverse the observed molecular changes. The translational value of our data was emphasized by in situ hybridization showing chronic post-traumatic downregulation of miR-124-3p in the dentate gyrus of TBI patients. Analysis of another brain injury model, status epilepticus, highlighted the fact that chronic downregulation of miR-124 is a common phenomenon after brain injury. Together, our findings indicate that miR-124-3p is a chronic modulator of molecular networks relevant to post-injury hippocampal pathologies in experimental models and in humans.     

Insulin can induce the expression of a memory-related synaptic protein through facilitating AMPA receptor endocytosis in rat cortical neurons

Learning and memory depend on long-term synaptic plasticity including long-term potentiation (LTP) and depression (LTD). Activity-regulated cytoskeleton-associated protein (Arc) plays versatile roles in synaptic plasticity mainly through inducing F-actin formation, underlying consolidation of LTP, and promoting AMPA receptor (AMPAR) endocytosis, underlying LTD. Insulin can also induce LTD by facilitating the internalization of AMPARs. In neuroblastoma cells, insulin induced a dramatic increase in Arc mRNA and Arc protein levels, which may underlie the memory-enhancing action of insulin. Thus, a hypothesis was made that, in response to insulin, increased AMPAR endocytosis leads to enhanced Arc expression, and vice versa. Primary cultures of neonatal Sprague–Dawley rat cortical neurons were used. Using Western-blot analysis and immunofluorescent staining, our results reveal that inhibiting AMPAR-mediated responses with AMPAR antagonists significantly enhanced whereas blocking AMPAR endocytosis with various reagents significantly prevented insulin (200 nM, 2 h)-induced Arc expression. Furthermore, via surface biotinylation assay, we demonstrate that acute blockade of new Arc synthesis after insulin stimulation using Arc antisense oligodeoxynucleotide prevented insulin-stimulated AMPAR endocytosis. These findings suggest for the first time that an interaction exists between insulin-stimulated AMPAR endocytosis and insulin-induced Arc expression.     

Two types of muscarinic acetylcholine receptors in Drosophila and other arthropods

Muscarinic acetylcholine receptors (mAChRs) play a central role in the mammalian nervous system. These receptors are G protein-coupled receptors (GPCRs), which are activated by the agonists acetylcholine and muscarine, and blocked by a variety of antagonists. Mammals have five mAChRs (m1–m5). In this study, we cloned two structurally related GPCRs from the fruit fly Drosophila melanogaster, which, after expression in Chinese hamster ovary cells, proved to be muscarinic acetylcholine receptors. One mAChR (the A-type; encoded by gene CG4356) is activated by acetylcholine (EC₅₀, 5 × 10^?8 M) and muscarine (EC₅₀, 6 × 10^?8 M) and blocked by the classical mAChR antagonists atropine, scopolamine, and 3-quinuclidinyl-benzilate (QNB), while the other (the B-type; encoded by gene CG7918) is also activated by acetylcholine, but has a 1,000-fold lower sensitivity to muscarine, and is not blocked by the antagonists. A- and B-type mAChRs were also cloned and functionally characterized from the red flour beetle Tribolium castaneum. Recently, Haga et al. (Nature 2012, 482: 547–551) published the crystal structure of the human m2 mAChR, revealing 14 amino acid residues forming the binding pocket for QNB. These residues are identical between the human m2 and the D. melanogaster and T. castaneum A-type mAChRs, while many of them are different between the human m2 and the B-type receptors. Using bioinformatics, one orthologue of the A-type and one of the B-type mAChRs could also be found in all other arthropods with a sequenced genome. Protostomes, such as arthropods, and deuterostomes, such as mammals and other vertebrates, belong to two evolutionarily distinct lineages of animal evolution that split about 700 million years ago. We found that animals that originated before this split, such as cnidarians (Hydra), had two A-type mAChRs. From these data we propose a model for the evolution of mAChRs.     

The ether lipid precursor hexadecylglycerol protects against Shiga toxins

Shiga toxin-producing Escherichia coli bacteria cause hemorrhagic colitis and hemolytic uremic syndrome in humans. Currently, only supportive treatment is available for diagnosed patients. We show here that 24-h pretreatment with an ether lipid precursor, the alkylglycerol sn-1-O-hexadecylglycerol (HG), protects HEp-2 cells against Shiga toxin and Shiga toxin 2. Also the endothelial cell lines HMEC-1 and HBMEC are protected against Shiga toxins after HG pretreatment. In contrast, the corresponding acylglycerol, dl-α-palmitin, has no effect on Shiga toxicity. Although HG treatment provides a strong protection (~30 times higher IC₅₀) against Shiga toxin, only a moderate reduction in toxin binding was observed, suggesting that retrograde transport of the toxin from the plasma membrane to the cytosol is perturbed. Furthermore, endocytosis of Shiga toxin and retrograde sorting from endosomes to the Golgi apparatus remain intact, but transport from the Golgi to the endoplasmic reticulum is inhibited by HG treatment. As previously described, HG reduces the total level of all quantified glycosphingolipids to 50–70 % of control, including the Shiga toxin receptor globotriaosylceramide (Gb3), in HEp-2 cells. In accordance with this, we find that interfering with Gb3 biosynthesis by siRNA-mediated knockdown of Gb3 synthase for 24 h causes a similar cytotoxic protection and only a moderate reduction in toxin binding (to 70 % of control cells). Alkylglycerols, including HG, have been administered to humans for investigation of therapeutic roles in disorders where ether lipid biosynthesis is deficient, as well as in cancer therapy. Further studies may reveal if HG can also have a therapeutic potential in Shiga toxin-producing E. coli infections.     

Induction of recombination between diverged sequences in a mammalian genome by a double-strand break

To investigate whether mammalian cells can carry out recombinational double-strand break (DSB) repair between highly diverged sequences, mouse fibroblasts were transfected with DNA substrates that contained a “recipient” thymidine kinase (tk) gene disrupted by the recognition site for endonuclease I-SceI. Substrates also contained a linked “donor” tk gene sequence. Following DSB induction by I-SceI, selection for tk-expressing clones allowed recovery of repair events occurring by nonhomologous end-joining or recombination with the donor sequence. Although recombinational repair was most efficient when donor and recipient shared near-perfect homology, we recovered recombination events between recipient and donor sequences displaying 20 % nucleotide mismatch. Recombination between such imperfectly matched (“homeologous”) sequences occurred at a frequency of 1.7 × 10^?7 events per cell and constituted 3 % of the DSB repair events recovered with the pair of homeologous sequences. Additional experiments were done with a substrate containing a donor sequence comprised of a region sharing high homology with the recipient and an adjacent region homeologous to the recipient. Recombinational DSB repair tracts initiating within high homology propagated into homeology in 11 of 112 repair events. These collective results contrasted with our earlier work in which spontaneous recombination (not intentionally induced by a DSB) between homeologous sequences occurred at an undetectable frequency of less than 10^?9 events per cell, and in which events initiating within high homology propagated into adjoining homeology in one of 81 events examined. Our current work suggests that homology requirements for recombination are effectively relaxed in proximity to a DSB in a mammalian genome.