Evolution of the lumbosacral angle

The lumbosacral angle (LSA) was studied in 131 children ranging in age from birth to 5 years. This angle increases from an average of 20 degrees at birth to an average of 70 degrees at the age of 5 years; it remains at that level thereafter. This study demonstrates that the formation of the LSA is not related to increasing age, height, or weight. Nor do obstetrical requirements seems to play any major role in the formation of the lumbosacral angle. Rather, it appears that the development of the LSA is related to the progressive acquisition of erect posture and the ontogeny of bipedal locomotion. This angle is almost nil in the nonprimate mammals (who only infrequently stand erect). It is minimal in monkeys who occasionally assume bipedal postures and increases somewhat in living apes who engage in facultative bipedal positional behavior. In the early australopithecines, the LSA is increased over that in apes, and it reaches its maximum in Homo sapiens. Deviations from normal and healthy erect posture in Homo sapiens result in corresponding changes in the lumbosacral angle. Lumbar and sacral angles (both forming the lumbosacral angle) are almost equal in all mammalian species. Since the sacral angle of Australopithecus afarensis is approximately 15 degrees, it can be implied that its lumbosacral angle was small, thus attesting to its "imperfect" erect posture and "primitive" form of bipedal locomotion.     

Sacral curvature and supine posture

Sacral curvature (SC), represented by the angle between the first and the last sacral vertebrae, is a feature that differentiates the human pelvis from that of other animals. The sacral curvature was measured and studied in 14 cebids, 31 cercopithecids, 17 hylobatids, 85 pongids, 23 normal human children, 15 children with orthopedic handicaps, 49 normal adult human males, and 64 normal adult human females. Sacral curvature was minimal to nil in monkeys (mean 11.5 +/- 6 SD degrees), and moderate in apes (hylobatids, mean 16 +/- 10 SD degrees; pongids, mean 27.2 +/- 16 SD degrees). In human newborns SC is minimal, increasing progressively until adolescence, reaching a mean of 64.7 +/- 29 SD degrees in adult humans. This study investigates the different factors contributing to the formation of the sacral curvature. These factors include 1) the effect of erect posture, which tilts the upper part of the sacrum dorsally and the lower part of the sacrum ventrally, and 2) the influence of supine posture, which affects the development of the lower part of the sacrum. In addition to supine posture the levator ani, which is well developed in Homo sapiens, also affects the lower part of the sacrum and coccyx and influences its ventral orientation. Variation in SC can result from differences in onset and frequency of supine posture. This is the first time that supine posture has been shown to play a role in shaping the human pelvis, although it is as characteristic of H. sapiens as is erect posture.     

Reconstruction of the STS 14 (Australopithecus africanus) pelvis

The study reports a reconstruction of the sacrum in STS 14 based on extrapolation from the measurements of the first two sacral vertebrae of STS 14 and of the angle formed by the anterior surfaces of their vertebral bodies. Reconstruction is based on comparisons of, and extrapolation from, sacra of Pan troglodytes, Homo sapiens, and Australopithecus afarensis. The reconstructed sacrum has an anterior sacral curvature of 39°. The two ossa coxae were also completed by mirror imaging of one side by the other. With the pelvis completely reconstructed, the pelvic dimensions for the antero-posterior (AP) diameters of the pelvic inlet, midpelvis, and pelvic outlet are 85, 68, and 69 mm and the corresponding transverse (TR) diameters are 109, 88, and 103 mm, respectively. The posterior sagittal diameters in the three pelvic planes are small compared to the anterior sagittal diameters. This analysis indicates that the STS 14 pelvis is platypelloid in the three pelvic planes; i.e., all the AP diameters are smaller than the corresponding TR diameters. This makes the STS 14 pelvis similar to that to Al 288-1, save for a less pronounced degree of platypelloidy at the inlet in the former. © 1995 Wiley-Liss, Inc.     

Habitat characteristics and species interference influence space use and nest‐site occupancy: implications for social variation in two sister species

Nest‐site selection is an important component of species socio‐ecology, being a crucial factor in establishment of group living. Consequently, nest‐site characteristics together with space‐use proxies may reveal the social organization of species, which is critical when direct observation of social interactions is hindered in nature. Importantly, nest‐site choice is expected to be under strong selective pressures and the object of intra‐ and interspecific competition. Although the bulk of research on sociality focuses on its ecological drivers, our study introduces interspecific competition as a potential factor that could influence social evolution. We investigated the influence of habitat and interspecific competition on the social organization of two sister species of the African four striped mouse, Rhabdomys dilectus dilectus and Rhabdomys bechuanae, in a similar macroenvironment. These species diverged in allopatry and occupy distinct environmental niches. We radiotracked 140 adults to identify their nest‐sites, determine nest characteristics and record groups that shared nest‐sites. Group cohesion was estimated from nest‐site fidelity, group association strength, and home range overlap within versus between group members. We compared the two species in sympatry versus parapatry to determine the impact of species interference on sociality. In parapatry, the two species selected distinct nest‐site types, interpreted as different anti‐predator strategies: R. bechuanae selected fewer, spaced, less concealed nest‐sites whereas R. d. dilectus selected clumped and less visible nest‐sites. Rhabdomys bechuanae also showed more cohesive and stable social groups than R. d. dilectus. In sympatry, compared to R. bechuanae, R. d. dilectus occupied similar nest‐sites, however slightly more exposed and clumped, and displayed similar nest‐site fidelity and group association strength. We conclude that although habitat selection may be an important driver of social divergence in Rhabdomys, species interference, by limiting R. d. dilectus movements and forcing nest‐site sharing may induce new ecological pressures that could influence its social evolution.     

Applications of congenic strains in the mouse

The sequencing of the human and the mouse genomes has shown that the chromosomes of these two species contain approximately 30,000 genes. The biological systems that can be studied in an individual or in a tissue result from complex interactions within this multitude of genes. Before describing these interactions, it is necessary to understand the function of each gene. In the mouse, congenic strains are developed to introduce a chromosomal segment in a given inbred genetic background. One can then compare the biological effects of different alleles at the same locus in the same genetic background or the effect of a given allele in different genetic backgrounds. One can also introduce into different congenic strains with the same genetic background genes which control a complex genetic trait, then combine these genes by appropriate crosses to study their interactions. Although the chromosomal segment transferred into a congenic strain usually contains up to several hundreds of genes, molecular markers can be used to reduce this number as well as the number of crosses required for the development of congenic strains.     

Expression of SR-BI receptor and StAR protein in rat ocular tissues

The class-B type-I scavenger receptor (SR-BI) plays a key role in cholesterol homeostasis; it mediates the selective uptake of lipoprotein cholesterol to steroidogenic tissues. We show by RT-PCR, western blot, in situ hybridization and immunohistochemistry analysis that SR-BI is highly expressed in different neuro-retinal and non-neuronal cells types on rat eye. Immunohistochemistry of the steroidogenic acute regulatory protein (StAR) involved in neurosteroid production showed the same expression pattern than SR-BI in rat eye. Our results may suggest a key role of these genes in the ocular cholesterol metabolism for membranes biosynthesis and neurosteroidogenesis.     

A recessive C-terminal Jervell and Lange-Nielsen mutation of the KCNQ1 channel impairs subunit assembly

The LQT1 locus (KCNQ1) has been correlated with the most common form of inherited long QT (LQT) syndrome. LQT patients suffer from syncopal episodes and high risk of sudden death. The KCNQ1 gene encodes KvLQT1 alpha-subunits, which together with auxiliary IsK (KCNE1, minK) subunits form IK(s) K(+) channels. Mutant KvLQT1 subunits may be associated either with an autosomal dominant form of inherited LQT, Romano-Ward syndrome, or an autosomal recessive form, Jervell and Lange-Nielsen syndrome (JLNS). We have identified a small domain between residues 589 and 620 in the KvLQT1 C-terminus, which may function as an assembly domain for KvLQT1 subunits. KvLQT1 C-termini do not assemble and KvLQT1 subunits do not express functional K(+) channels without this domain. We showed that a JLN deletion-insertion mutation at KvLQT1 residue 544 eliminates important parts of the C-terminal assembly domain. Therefore, JLN mutants may be defective in KvLQT1 subunit assembly. The results provide a molecular basis for the clinical observation that heterozygous JLN carriers show slight cardiac dysfunctions and that the severe JLNS phenotype is characterized by the absence of KvLQT1 channel.     

A COLQ Missense Mutation in Sphynx and Devon Rex Cats with Congenital Myasthenic Syndrome

An autosomal recessive neuromuscular disorder characterized by skeletal muscle weakness, fatigability and variable electromyographic or muscular histopathological features has been described in the two related Sphynx and Devon Rex cat breeds (Felis catus). Collection of data from two affected Sphynx cats and their relatives pointed out a single disease candidate region on feline chromosome C2, identified following a genome-wide SNP-based homozygosity mapping strategy. In that region, we further identified COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase) as a good candidate gene, since COLQ mutations were identified in affected humans and dogs with endplate acetylcholinesterase deficiency leading to a synaptic form of congenital myasthenic syndrome (CMS). A homozygous c.1190G>A missense variant located in exon 15 of COLQ, leading to a C397Y substitution, was identified in the two affected cats. C397 is a highly-conserved residue from the C-terminal domain of the protein; its mutation was previously shown to produce CMS in humans, and here we confirmed in an affected Sphynx cat that it induces a loss of acetylcholinesterase clustering at the neuromuscular junction. Segregation of the c.1190G>A variant was 100% consistent with the autosomal recessive mode of inheritance of the disorder in our cat pedigree; in addition, an affected, unrelated Devon Rex cat recruited thereafter was also homozygous for the variant. Genotyping of a panel of 333 cats from 14 breeds failed to identify a single carrier in non-Sphynx and non-Devon Rex cats. Finally, the percentage of healthy carriers in a European subpanel of 81 genotyped Sphynx cats was estimated to be low (3.7%) and 14 control Devon Rex cats were genotyped as wild-type individuals. Altogether, these results strongly support that the neuromuscular disorder reported in Sphynx and Devon Rex breeds is a CMS caused by a unique c.1190G>A missense mutation, presumably transmitted through a founder effect, which strictly and slightly disseminated in these two breeds. The presently available DNA test will help owners avoid matings at risk.     

A missense mutation in the agouti signaling protein gene (ASIP) is associated with the no light points coat phenotype in donkeys

Background

Seven donkey breeds are recognized by the French studbook and are characterized by a black, bay or grey coat colour including light cream-to-white points (LP). Occasionally, Normand bay donkeys give birth to dark foals that lack LP and display the no light points (NLP) pattern. This pattern is more frequent and officially recognized in American miniature donkeys. The LP (or pangare) phenotype resembles that of the light bellied agouti pattern in mouse, while the NLP pattern resembles that of the mammalian recessive black phenotype; both phenotypes are associated with the agouti signaling protein gene (ASIP).

Findings

We used a panel of 127 donkeys to identify a recessive missense c.349 T > C variant in ASIP that was shown to be in complete association with the NLP phenotype. This variant results in a cysteine to arginine substitution at position 117 in the ASIP protein. This cysteine is highly-conserved among vertebrate ASIP proteins and was previously shown by mutagenesis experiments to lie within a functional site. Altogether, our results strongly support that the identified mutation is causative of the NLP phenotype.

Conclusions

Thus, we propose to name the c.[349 T > C] allele in donkeys, the a^nlp allele, which enlarges the panel of coat colour alleles in donkeys and ASIP recessive loss-of-function alleles in animals.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-015-0112-x) contains supplementary material, which is available to authorized users.     

The importance of an exponential prostate-specific antigen decline after external beam radiotherapy for intermediate risk prostate cancer

Background: To study the influence of an exponential prostate-specific antigen (PSA) decline on biochemical failure after external-beam radiotherapy (EBRT). Methods: We analyzed 114 patients with intermediate risk prostate cancer (Gleason ≤ 6 and PSA 10–20 or Gleason 7 and PSA <10). Patients were randomized between EBRT doses of either 70.2 Gy or 79.2 Gy (1.8 Gy per day). All patients had a follow up of at least six PSA measurements post-EBRT. Exponential decline and PSA half life were included in a Cox regression analysis for factors associated with biochemical failure. Results: A total of 80/114 (70.2%) patterns were classified as having an exponential PSA decline. Both exponential decline (HR 0.115, 95%CI 0.03–0.44, p = 0.0016) and PSA half life ratio were statistically significant predictors (HR 1.03 (95% CI 1.01–1.06)) of biochemical failure. In the model predicting for exponential decline, none of the factors were significant. Conclusion: Patients with an exponential PSA decline show a better biochemical outcome in the long term.