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Little is known of the properties of the sarsen stones (or silcretes) that comprise the main architecture of Stonehenge. The only studies of rock struck from the monument date from the 19th century, while 20th century investigations have focussed on excavated debris without demonstrating a link to specific megaliths. Here, we present the first comprehensive analysis of sarsen samples taken directly from a Stonehenge megalith (Stone 58, in the centrally placed trilithon horseshoe). We apply state-of-the-art petrographic, mineralogical and geochemical techniques to two cores drilled from the stone during conservation work in 1958. Petrographic analyses demonstrate that Stone 58 is a highly indurated, grain-supported, structureless and texturally mature groundwater silcrete, comprising fine-to-medium grained quartz sand cemented by optically-continuous syntaxial quartz overgrowths. In addition to detrital quartz, trace quantities of silica-rich rock fragments, Fe-oxides/hydroxides and other minerals are present. Cathodoluminescence analyses show that the quartz cement developed as an initial <10 μm thick zone of non-luminescing quartz followed by ~16 separate quartz cement growth zones. Late-stage Fe-oxides/hydroxides and Ti-oxides line and/or infill some pores. Automated mineralogical analyses indicate that the sarsen preserves 7.2 to 9.2 area % porosity as a moderately-connected intergranular network. Geochemical data show that the sarsen is chemically pure, comprising 99.7 wt. % SiO2. The major and trace element chemistry is highly consistent within the stone, with the only magnitude variations being observed in Fe content. Non-quartz accessory minerals within the silcrete host sediments impart a trace element signature distinct from standard sedimentary and other crustal materials. 143Nd/144Nd isotope analyses suggest that these host sediments were likely derived from eroded Mesozoic rocks, and that these Mesozoic rocks incorporated much older Mesoproterozoic material. The chemistry of Stone 58 has been identified recently as representative of 50 of the 52 remaining sarsens at Stonehenge. These results are therefore representative of the main stone type used to build what is arguably the most important Late Neolithic monument in Europe., Competing Interests: Three of the authors (JMH, MRP and NW) are employed by commercial companies (Petroclays Ltd, Vidence Inc. and Gatan UK, respectively). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The sources of the stone used to construct Stonehenge around 2500 BCE have been debated for over four centuries. The smaller "bluestones" near the center of the monument have been traced to Wales, but the origins of the sarsen (silcrete) megaliths that form the primary architecture of Stonehenge remain unknown. Here, we use geochemical data to show that 50 of the 52 sarsens at the monument share a consistent chemistry and, by inference, originated from a common source area. We then compare the geochemical signature of a core extracted from Stone 58 at Stonehenge with equivalent data for sarsens from across southern Britain. From this, we identify West Woods, Wiltshire, 25 km north of Stonehenge, as the most probable source area for the majority of sarsens at the monument., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Managed realignment (MR) schemes are being implemented to compensate for the loss of intertidal saltmarsh habitats by breaching flood defences and inundating the formerly defended coastal hinterland. However, studies have shown that MR sites have lower biodiversity than anticipated, which has been linked with anoxia and poor drainage resulting from compaction and the collapse of sediment pore space caused by the site's former terrestrial land use. Despite this proposed link between biodiversity and soil structure, the evolution of the sediment sub-surface following site inundation has rarely been examined, particularly over the early stages of the terrestrial to marine or estuarine transition. This paper presents a novel combination of broad- and intensive-scale analysis of the sub-surface evolution of the Medmerry Managed Realignment Site (West Sussex, UK) in the three years following site inundation. Repeated broad-scale sediment physiochemical datasets are analysed to assess the early changes in the sediment subsurface and the preservation of the former terrestrial surface, comparing four locations of different former land uses. Additionally, for two of these locations, high-intensity 3D-computed X-ray microtomography and Itrax micro-X-ray fluorescence spectrometry analyses are presented. Results provide new data on differences in sediment properties and structure related to the former land use, indicating that increased agricultural activity leads to increased compaction and reduced porosity. The presence of anoxic conditions, indicative of poor hydrological connectivity between the terrestrial and post-inundation intertidal sediment facies, was only detected at one site. This site has experienced the highest rate of accretion over the terrestrial surface (ca. 7 cm over 36 months), suggesting that poor drainage is caused by the interaction (or lack of) between sediment facies rather than the former land use. This has significant implications for the design of future MR sites in terms of preparing sites, their anticipated evolution, and the delivery of ecosystem services., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Heat treatment was one of the first transformative technologies in the southern African Middle Stone Age (MSA), with many studies in the Cape coastal zone of South Africa identifying it as an essential step in the preparation of silcrete prior to its use in stone tool manufacture. To date, however, no studies have investigated whether heat treatment is necessary for all silcrete types, and how geographically widespread heat treatment was in the subcontinent. The aim of this study is to investigate experimentally whether heat treatment continued further north into the Kalahari Desert of Botswana and northernmost South Africa, the closest area with major silcrete outcrops to the Cape. For this we analyse the thermal transformations of silcrete from both regions, proposing a comprehensive model of the chemical, crystallographic and 'water'-related processes taking place upon heat treatment. For the first time, we also explore the mobility of minor and trace elements during heat treatment and introduce a previously undescribed mechanism-steam leaching-causing depletion of a limited number of elements. The results of this comparative study reveal the Cape and Kalahari silcrete to respond fundamentally differently to heat treatment. While the former can be significantly improved by heat, the latter is deteriorated in terms of knapping quality. These findings have important implications for our understanding of the role of fire as a technical solution in MSA stone tool knapping, and for the extension of its use in southern Africa. Silcrete heat treatment-at least in the form we understand it today-may have been a strictly regional phenomenon, confined to a narrow zone along the west and south coast of the Cape. On the basis of our findings, silcrete heat treatment should not be added as a new trait on the list of behaviours that characterise the MSA of the southern African subcontinent.

Catalytic hydrogenation is an important process used for the production of everything from foods to fuels. Current heterogeneous implementations of this process utilize metals as the active species. Until recently, catalytic heterogeneous hydrogenation over a metal-free solid was unknown; implementation of such a system would eliminate the health, environmental, and economic concerns associated with metal-based catalysts. Here, we report good hydrogenation rates and yields for a metal-free heterogeneous hydrogenation catalyst as well as its unique hydrogenation mechanism. Catalytic hydrogenation of olefins was achieved over defect-laden h- BN ( dh -BN) in a reactor designed to maximize the defects in h- BN sheets. Good yields (>90%) and turnover frequencies (6 × 10 -5 -4 × 10 -3 ) were obtained for the hydrogenation of propene, cyclohexene, 1,1-diphenylethene, ( E )- and ( Z )-1,2-diphenylethene, octadecene, and benzylideneacetophenone. Temperature-programmed desorption of ethene over processed h -BN indicates the formation of a highly defective structure. Solid-state NMR (SSNMR) measurements of dh -BN with high and low propene surface coverages show four different binding modes. The introduction of defects into h- BN creates regions of electronic deficiency and excess. Density functional theory calculations show that both the alkene and hydrogen-bond order are reduced over four specific defects: boron substitution for nitrogen (B N ), vacancies (V B and V N ), and Stone-Wales defects. SSNMR and binding-energy calculations show that V N are most likely the catalytically active sites. This work shows that catalytic sites can be introduced into a material previously thought to be catalytically inactive through the production of defects., Competing Interests: The authors declare no competing financial interest.

This study utilises geochemical provenancing of silcrete raw materials, in combination with chaîne opératoire analyses, to explore lithic procurement and behavioural patterns in the northern Kalahari Desert during the Middle Stone Age (MSA). New data from the sites of Rhino Cave, Corner Cave, and ≠Gi in northwest Botswana, combined with earlier results from White Paintings Shelter, reveal that the long distance transport of silcrete for stone tool manufacture was a repeated and extensively used behaviour in this region. Silcrete was imported over distances of up to 295 km to all four sites, from locations along the Boteti River and around Lake Ngami. Significantly, closer known sources of silcrete of equivalent quality were largely bypassed. Silcrete artefacts were transported at various stages of production (as partially and fully prepared cores, blanks, and finished tools) and, with the exception of ≠Gi, in large volumes. The import occurred despite the abundance of locally available raw materials, which were also used to manufacture the same tool types. On the basis of regional palaeoenvironmental data, the timing of the majority of silcrete import from the Boteti River and Lake Ngami is constrained to regionally drier periods of the MSA. The results of our investigation challenge key assumptions underlying predictive models of human mobility that use distance-decay curves and drop-off rates. Middle Stone Age peoples in the Kalahari appear to have been more mobile than anticipated, and repeatedly made costly choices with regard to both raw material selection and items to be transported. We conclude that (i) base transport cost has been overemphasised as a restrictive factor in predictive models, and (ii) factors such as source availability and preference, raw material quality, and potential sociocultural influences significantly shaped prehistoric landscape use choices., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Lithic artifacts from the African Middle Stone Age (MSA) offer an avenue to explore a range of human behaviors, including mobility, raw material acquisition, trade and exchange. However, to date, in southern Africa it has not been possible to provenance the locations from which commonly used stone materials were acquired prior to transport to archaeological sites. Here we present results of the first investigation to geochemically fingerprint silcrete, a material widely used for tool manufacture across the subcontinent. The study focuses on the provenancing of silcrete artifacts from the MSA of White Paintings Shelter (WPS), Tsodilo Hills, in the Kalahari Desert of northwest Botswana. Our results suggest that: (i) despite having access to local quartz and quartzite at Tsodilo Hills, MSA peoples chose to transport silcrete over 220 km to WPS from sites south of the Okavango Delta; (ii) these sites were preferred to silcrete sources much closer to Tsodilo Hills; (iii) the same source areas were repeatedly used for silcrete supply throughout the 3 m MSA sequence; (iv) during periods of colder, wetter climate, silcrete may have been sourced from unknown, more distant, sites. Our results offer a new provenancing approach for exploring prehistoric behavior at other sites where silcrete is present in the archaeological record., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Before the Inca reigned, two empires held sway over the central Andes from anno Domini 600 to 1000: the Wari empire to the north ruled much of Peru, and Tiwanaku to the south reigned in Bolivia. Face-to-face contact came when both colonized the Moquegua Valley sierra in southern Peru. The state-sponsored Wari incursion, described here, entailed large-scale agrarian reclamation to sustain the occupation of two hills and the adjacent high mesa of Cerro Baúl. Monumental buildings were erected atop the mesa to serve an embassy-like delegation of nobles and attendant personnel that endured for centuries. Final evacuation of the Baúl enclave was accompanied by elaborate ceremonies with brewing, drinking, feasting, vessel smashing, and building burning.

At their clinical doses, current antipsychotic agents share the property of both dopamine D(2) and D(3) receptor blockade. However, a major disadvantage of many current medications are the observed extrapyramidal side-effects (EPS), postulated to arise from D(2) receptor antagonism. Consequently, a selective dopamine D(3) receptor antagonist could offer an attractive antipsychotic therapy, devoid of the unwanted EPS. Using SAR information gained in two previously reported series of potent and selective D(3) receptor antagonists, as exemplified by the 2,3,4,5-tetrahydro-1H-3-benzazepine 10 and the 2,3-dihydro-1H-isoindoline 11, a range of 7-sulfonyloxy- and 7-sulfonylbenzazepines has been prepared. Compounds of this type combined a high level of D(3) affinity and selectivity vs D(2) with an excellent pharmacokinetic profile in the rat. Subsequent optimization of this series to improve selectivity over a range of receptors and reduce cytochrome P450 inhibitory potential gave trans-3-(2-(4-((3-(3-(5-methyl-1,2,4-oxidiazolyl))phenyl)carboxamido)cyclohexyl)ethyl)-7-methylsulfonyl-2,3,4,5-tetrahydro-1H-3-benzazepine (58, SB-414796). This compound is a potent and selective dopamine D(3) receptor antagonist with high oral bioavailability and is CNS penetrant in the rat. Subsequent evaluation in the rat has shown that 58 preferentially reduces firing of dopaminergic cells in the ventral tegmental area (A10) compared to the substantia nigra (A9), an observation consistent with a prediction for atypical antipsychotic efficacy. In a separate study, 58 has been shown to block expression of the conditioned place preference (CPP) response to cocaine in male rats, suggesting that it may also have a role in the treatment of cue-induced relapse in drug-free cocaine addicts.

Starting from the tetrahydroisoquinoline SB-277011 1, a novel series of 5-substituted-2,3-dihydro-1H-isoindoles has been designed. Subsequent optimisation resulted in identification of 19, which has high affinity for the dopamine D3 receptor (pKi 8.3) and > or = 100-fold selectivity over other aminergic receptors. In rat studies 19 was brain penetrant with an excellent pharmacokinetic profile (oral bioavailability 77%, t1/2 5.2h).

Starting from the dopamine D3 receptor antagonist SB-277011 1, a series of 2,3,4,5-tetrahydro-1H-3-benzazepines has been identified with high affinity for the dopamine D3 receptor and selectivity over the D2 receptor. The 3-acetamido-2-fluorocinnamide derivative 20 gave high D3 receptor affinity (pKi 8.4) with 130-fold selectivity over the 2, receptor.

The dopaminergic system has long been implicated in the mechanisms of reward and addiction. 1-(4-(2-Naphthoylamino)butyl)-4-(2-methoxyphenyl)-1A-piperazine HCl (BP 897) has been claimed to be a selective dopamine D3 receptor partial agonist and has recently been shown to inhibit cocaine-seeking behaviour, suggesting a role for dopamine D3 receptor agonists in the treatment of addiction. We have previously characterised the pharmacological profile of the human dopamine D3 and D2(long) receptors using microphysiometry and radioligand binding and we have now studied the interaction of BP 897 with the dopamine D2 and D3 receptors using these methods. At both human dopamine D3 and D2 receptors, BP 897 lacked agonist activity but was a potent and selective antagonist with pK(b) values of 8.05+/-0.16 (4) and 9.43+/-0.22 (4) at human dopamine D2 and D3 receptors, respectively. These results, therefore, suggest that it may be the dopamine D3 receptor antagonist properties of BP 897 which have potential in the treatment of addiction and withdrawal.

This study utilizes the GM/KM immunoglobulin allotype system to elucidate the phylogenetic relationships of sub-Saharan Africans. The importance of understanding the relatedness of these peoples stems from the sub-Saharan region being the possible birthplace of humans. Haplotype distributions were determined for 19 populations and compared using chi-square analysis. Published data of other sub-Saharan Africans and representative populations worldwide were also added for comparison. Genetic distances between populations were calculated based on haplotype frequencies, and genetic relationships were observed through principal components analysis. Data from the GM/KM system showed a genetic homogeneity of the Bantu populations, with some exceptions, supporting the possibility of a common origin of these peoples. The Malagasy appeared as a divergent population, most likely due to Southeast Asian/Austronesian admixture, as indicated by the presence of the GM*AF B haplotype. The Cape Coloured also showed a divergence, with their genetic structures containing Caucasoid and Khoisan contributions. Finally, the Mbuti Pygmies appeared genetically isolated and had the highest frequency of the GM*A B haplotype out of all studied populations.

SB-277011-A (trans-N-[4-[2-(6-cyano-1,2,3, 4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolininecarboxamide), is a brain-penetrant, high-affinity, and selective dopamine D(3) receptor antagonist. Radioligand-binding experiments in Chinese hamster ovary (CHO) cells transfected with human dopamine D(3) or D(2 long) (hD(3), hD(2)) receptors showed SB-277011-A to have high affinity for the hD(3) receptor (pK(i) = 7.95) with 100-fold selectivity over the hD(2) receptor and over 66 other receptors, enzymes, and ion channels. Similar radioligand-binding data for SB-277011-A were obtained from CHO cells transfected with rat dopamine D(3) or D(2). In the microphysiometer functional assay, SB-277011-A antagonized quinpirole-induced increases in acidification in CHO cells overexpressing the hD(3) receptor (pK(b) = 8.3) and was 80-fold selective over hD(2) receptors. Central nervous system penetration studies showed that SB-277011-A readily entered the brain. In in vivo microdialysis studies, SB-277011-A (2. 8 mg/kg p.o.) reversed the quinelorane-induced reduction of dopamine efflux in the nucleus accumbens but not striatum, a regional selectivity consistent with the distribution of the dopamine D(3) receptor in rat brain. SB-277011-A (2-42.3 mg/kg p.o.) did not affect spontaneous locomotion, or stimulant-induced hyperlocomotion. SB-277011-A (4.1-42.2 mg/kg p.o.) did not reverse prepulse inhibition deficits in apomorphine- or quinpirole-treated rats, but did significantly reverse the prepulse inhibition deficit in isolation-reared rats at a dose of 3 mg/kg p.o. SB-277011-A (2.5-78. 8 mg/kg p.o.) was noncataleptogenic and did not raise plasma prolactin levels. Thus, dopamine D(3) receptor blockade produces few of the behavioral effects characteristic of nonselective dopamine receptor antagonists. The effect of SB-277011-A on isolation-induced prepulse inhibition deficit suggests that blockade of dopamine D(3) receptors may benefit the treatment of schizophrenia.

A selective dopamine D(3) receptor antagonist offers the potential for an effective antipsychotic therapy, free of the serious side effects of currently available drugs. Using clearance and brain penetration studies as a screen, a series of 1,2,3, 4-tetrahydroisoquinolines, exemplified by 13, was identified with high D(3) affinity and selectivity against the D(2) receptor. Following examination of molecular models, the flexible butyl linker present in 13 was replaced by a more conformationally constrained cyclohexylethyl linker, leading to compounds with improved oral bioavailability and selectivity over other receptors. Subsequent optimization of this new series to improve the cytochrome P450 inhibitory profile and CNS penetration gave trans-N-[4-[2-(6-cyano-1, 2,3, 4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarbo xamide (24, SB-277011). This compound is a potent and selective dopamine D(3) receptor antagonist with high oral bioavailability and brain penetration in the rat and represents an excellent new chemical tool for the investigation of the role of the dopamine D(3) receptor in the CNS.

A novel series of 5,6,7,8-tetrahydroquinazolines, 4,5,6,7-tetrahydroindazoles and 4,5,6,7-tetrahydrobenzothiazoles has been prepared, having high affinity and selectivity for the dopamine D3 receptor. The 4-methoxy-5,6,7,8-tetrahydroquinazoline 6i and 2-amino-4,5,6,7-tetrahydrobenzothiazole 8 proved to be agonists with among the highest D3 receptor affinities and selectivities reported to date.

Using clearance and brain penetration studies as a screen, tetrahydroisoquinoline 3 was identified as a lead having low clearance in rats (CLb 20 ml/min/kg). Introduction of a 7-CF3SO2O- substituent into the tetrahydroisoquinoline, followed by replacement of the biphenylamido group of 3 by a 3-indolylpropenamido group gave 31, having high D3 receptor affinity (pKi 8.4) and 150 fold selectivity over the D2 receptor.

Starting from a series of 2-aminotetralins 1, a novel series of N-[4-(4-phenylbenzoylamino)butyl]-octahydrobenzoquinolines and hexahydrobenzoindoles with high potency and selectivity for the dopamine D3 receptor has been designed. The effect of ligand chirality on binding affinity has been established. Selected derivatives (e.g. 2o, 2p) show high functional selectivity and enhanced in vivo properties compared to 1.

Significant hearing loss and external pinna malformations are two of the most common defects evident in Down's syndrome. The external and middle ears are linked embryologically, both arising from the first and second branchial arches. Evidence indicates that the majority of hearing loss in Down's syndrome is conductive in nature, originating from malformations of the middle ear ossicles and/or the eustachian tube. Recent studies also have indicated that hearing loss is a contributing factor to the IQ and learning deficits that afflict most individuals with Down's syndrome. Therefore, an early, external diagnostic feature for predicting conductive hearing loss would be desirable. In the current study, people with Down's syndrome, people with non-Down's mental retardation and control subjects were examined in a clinical environment for the presence of hearing loss and pinna defects. It was found that 90% of the Down's syndrome population had significant hearing loss, compared to slightly more than 50% in the non-Down's group and no hearing loss in the controls. Also, the majority of hearing loss among individuals with Down's syndrome was conductive, while all hearing loss in the non-Down's group was sensorineural. The Down's syndrome population exhibited nearly 3.5 pinna defects per ear, with malformations of the helix being very evident. The non-Down's population exhibited 2.5 pinna defects per ear, with concha defects being the most common.

Mice that were homozygous recessive for the single-gene mutation, hotfoot, showed profound and progressive motor disturbances in an open field after approximately the 4th postnatal week. Studies were undertaken to examine the role of the monoaminergic system in the behavioral and developmental expression of this neurological mutation. Relative to controls, 10-and 30-day-old hotfoot mice demonstrated a significantly attenuated response to the stimulating locomotor effects of amphetamine while adult hotfoot mice were motorically unaffected by amphetamine administration. 30-day-old and adult hotfoot mice also were hypothermic relative to phenotypically normal mice after amphetamine administration. Examination of monoamine levels and turnover revealed that hotfoot mice had significantly greater concentrations of norepinephrine associated with lower turnover in cerebellum and greater levels of serotonin in cerebellum and striatum, relative to phenotypic controls. In addition, mice born and raised by hotfoot dams demonstrated neurochemical alterations regardless of genotype. Both the neurochemical data and the developmental response to the general catecholamine agonist, amphetamine, suggest that the monaminergic neurotransmitter system may be altered as a consequence of the hotfoot mutation.

We analyzed prospective data from 19,889 elderly residents of 51 nursing homes from 1984 to 1985 to determine the prevalence, incidence, and natural history of pressure ulcers. Among all residents admitted to nursing homes, 11.3% possessed a stage II through stage IV pressure ulcer. For those residents admitted to the nursing home without pressure ulcers during the study period, the 1-year incidence was 13.2%. This increased to 21.6% by 2 years of nursing home stay. People already residing in a nursing home at the start of the study had a 1-year incidence of 9.5%, which increased to 20.4% by 2 years. Pressure ulcers were associated with an increased rate of mortality, but not hospitalization. Longitudinal follow-up of residents with pressure ulcers demonstrated that a majority of their lesions were healed by 1 year. Most of the improvement occurred early in a person's nursing home stay. Although nursing home residents with pressure ulcers have a higher mortality, with good medical care pressure ulcers can be expected to heal.

Audiogenic seizure susceptibility was studied in mice segregating for the microphthalmic white gene (Miwh). Previous work by Deol had indicated that mice with either one or two Miwh alleles had severe inner ear defects. A congenic inbred strain provided mice that were identical in genetic background except for single-gene substitutions at the microphthalmia locus. The three genotypes tested were Miwh/Miwh, Miwh/+, and +/+. Mice were exposed to the sound stimulus once for a 1-min period between the ages of 17 and 30 days. Heterozygous Miwh/+ mice had more seizures and were more reactant than either type of homozygote at all ages tested. Responses were low at 17 days of age, peaked sharply by 23 days, and declined markedly by 30 days.

Development of 13 reflex responses and behavioral components of mice from the Goodale Giant inbred strain (G/Gw) was compared to that of a sample of 61 pups from a random-bred strain. Significant differences were observed between groups for several responses, but the direction of these differences was not consistent. Effects of rapid growth and increased size in G/Gw mice did not directly affect behavioral maturation.

The synthesis and antihypertensive activity of a series of novel 4-(cyclic amido)-2H-1-benzopyran-3-ols, administered orally to conscious spontaneously hypertensive rats, are described. The effects of lactam ring size, the presence of heteroatoms in the lactam ring, substitution at C(2) and C(3), relative stereochemistry at C(3) and C(4), and aromatic substitution pattern on the blood pressure lowering activity of this series have been determined. The key compound 2 from this work [BRL 34915; (+/-)-6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxopyrrolidin-1- yl)-2H-1-benzopyran-3-ol] has been resolved, and antihypertensive activity was found to reside primarily in the (-) enantiomer. The key step in the preparation of this class of compounds is the action of a cyclo amidic anion on an appropriate epoxide. Another approach, involving a cyclization step to the lactam was found to be more convenient in certain cases, particularly in forming the cis analogue of compound 2. Compound 2 has been shown to possess a novel mechanism of action, and it has been selected for progression to the clinic.

A malformation that resulted in the formation of 2 complete tails is described in a mouse that was heterozygous for the sex-linked gene Bent-tail (Bn). One of the tails appeared normal and contained 29 vertebrae, whereas the other tail consisted of 27 vertebrae and had several bends or kinks in it and also had malformed vertebrae similar to those described for the Bn gene. A comparison of the malformation with previously described bifurcated tail conditions in the mouse is presented. It is possible that this 2-tailed mouse represents a special case of X-chromosome inactivation.

1. The blood serum proteins of five species of Nearctic squirrels were electrophoretically examined. 2. Protein polymorphism was detected in all the species described. 3. The use of the mean relative mobility of specific proteins was shown to be a valuable aid in distinguishing species.

Ontogenetic and adult behavioral tests were conducted on an extreme non-agouti strain of mice carrying the Miwh mutation. Except for startle response, no significant differences were seen in any aspect of the preweaning reflex and neuromuscular tests. The lack of startle response seen in Miwh/Miwh and Miwh/+ mice can be attributed to abnormalities found in the inner ear of these genotypes. Among adult mice, significant differences were found in the open field and visual cliff tests.

Paddle is a lethal, single recessive gene mutation in the mouse which results in a large median cleft palate and chondrodystrophy. Comparative cephalometric measurements on the growth of the normal and paddle fetal craniofacial complexes were made to determine the cause of cleft palate in paddle. Two methods of cephalometric measurements were used with 20 parameters analyzed. Both methods revealed a reduction in maxillary and mandibular growth, and a reduced cranial base angle which did not allow forward movement of the tongue under the primary palate, and hence obstructed shelf movement.

Effects of abnormal neural tube development were studied in immature and adult mice. The behavior of affected adult mice was found to resemble that of mice that exhibit the "waltzer syndrome." Behavioral ontogenetic studies indicate that effected mice are deficient in labyrinthine responses as shown by the late development or lack of negative geotaxic behaviors and the delayed loss of pivoting behavior. Retarded maturation of neural responses was indicated by a delay in the appearance of the startle response. Evidence that circling behavior in adult mice of the "waltzer syndrome" may be a result of central nervous system disorders alone, or in concert with abnormalities of the inner ear, was provided by the fact that open field activity was increased in affected mice that exhibit circling behavior as adults.

We examined susceptibility of several strains of mice to Eimeria separata. Mice of the following coat-color genotypes were inoculated with 2 X 10(4) sporulated oocysts of E. separata isolated from Rattus norvegicus: random-bred (aabbCC and A-bbCC), Balb/C (AAbbcc), Balb/Gw (AABBcc), Z/Gw (aaBBcc), and Swiss NLW (cc). Allele designations are A = agouti, a = nonagouti, B = black, b = brown, C, c = albino. Eimeria separata completed its life cycle with oocyst production in all male and female random-bred (aabbCC), Balb/Gw and G/Gw mice. The reproductive index of E. separata in Balb/Gw mice was significantly lower (P less than or equal to 0.05) than that of the other mouse strains. Among the random-bred mice, E. separata had a significantly lower (P less than or equal to 0.05) mean reproductive index in male than in female hosts. Patent period and oocyst length/width indices remained constant irrespective of host genus. This is the first documentation that genetic factors play a role in susceptibility of mice to the rat coccidium, E. separata.