A Highlights from MBoC Selection: Srv2/cyclase-associated protein forms hexameric shurikens that directly catalyze actin filament severing by cofilin

Actin filament severing is critical for the dynamic turnover of cellular actin networks. Cofilin severs filaments, but additional factors may be required to increase severing efficiency in vivo. Srv2/cyclase-associated protein (CAP) is a widely expressed protein with a role in binding and recycling actin monomers ascribed to domains in its C-terminus (C-Srv2). In this paper, we report a new biochemical and cellular function for Srv2/CAP in directly catalyzing cofilin-mediated severing of filaments. This function is mediated by its N-terminal half (N-Srv2), and is physically and genetically separable from C-Srv2 activities. Using dual-color total internal reflection fluorescence microscopy, we determined that N-Srv2 stimulates filament disassembly by increasing the frequency of cofilin-mediated severing without affecting cofilin binding to filaments. Structural analysis shows that N-Srv2 forms novel hexameric star-shaped structures, and disrupting oligomerization impairs N-Srv2 activities and in vivo function. Further, genetic analysis shows that the combined activities of N-Srv2 and Aip1 are essential in vivo. These observations define a novel mechanism by which the combined activities of cofilin and Srv2/CAP lead to enhanced filament severing and support an emerging view that actin disassembly is controlled not by cofilin alone, but by a more complex set of factors working in concert.     

Size-biased allocation of prey from male to offspring via female: family conflicts, prey selection, and evolution of sexual size dimorphism in raptors

In birds with bi-parental care, the provisioning link between prey capture and delivery to dependent offspring is regarded as often symmetric between the mates. However, in raptors, the larger female usually broods and feeds the nestlings, while the smaller male provides food for the family, assisted by the female in the latter part of the nestling period, if at all. Prey items are relatively large and often impossible for nestlings to handle without extended maternal assistance. We video-recorded prey delivery and handling in nests of a raptor with a wide diet, the Eurasian kestrel Falco tinnunculus, and simultaneously observed prey transfer from male to female outside the nest. The male selectively allocated larger items, in particular birds and larger mammals, to the female for further processing and feeding of nestlings, and smaller items, in particular lizards and smaller mammals, directly to the nestlings for unassisted feeding. Hence, from the video, the female appeared to have captured larger prey than the male, while in reality no difference existed. The female’s size-biased interception of the male’s prey provisioning line would maximize the male’s foraging time, and maximize the female’s control of the allocation of food between her own need and that of the offspring. The male would maximize his control of food allocation by capturing smaller prey. This conflict would select for larger dominant females and smaller energy-efficient males, and induce stronger selection the longer the female depends on the male for self-feeding, as a proportion of the offspring dependence period.     

Calcium and Dairy Acceleration of Weight and Fat Loss during Energy Restriction in Obese Adults

Objective: Increasing 1, 25‐dihydroxyvitamin D in response to low‐calcium diets stimulates adipocyte Ca²⁺ influx and, as a consequence, stimulates lipogenesis, suppresses lipolysis, and increases lipid accumulation, whereas increasing dietary calcium inhibits these effects and markedly accelerates fat loss in mice subjected to caloric restriction. Our objective was to determine the effects of increasing dietary calcium in the face of caloric restriction in humans. Research Methods and Procedures: We performed a randomized, placebo‐controlled trial in 32 obese adults. Patients were maintained for 24 weeks on balanced deficit diets (500 kcal/d deficit) and randomized to a standard diet (400 to 500 mg of dietary calcium/d supplemented with placebo), a high‐calcium diet (standard diet supplemented with 800 mg of calcium/d), or high‐dairy diet (1200 to 1300 mg of dietary calcium/d supplemented with placebo). Results: Patients assigned to the standard diet lost 6.4 ± 2.5% of their body weight, which was increased by 26% (to 8.6 ± 1.1%) on the high‐calcium diet and 70% (to 10.9 ± 1.6% of body weight) on the high‐dairy diet (p < 0.01). Fat loss was similarly augmented by the high‐calcium and high‐dairy diets, by 38% and 64%, respectively (p < 0.01). Moreover, fat loss from the trunk region represented 19.0 ± 7.9% of total fat loss on the low‐calcium diet, and this fraction was increased to 50.1 ± 6.4% and 66.2 ± 3.0% on the high‐calcium and high‐dairy diets, respectively (p < 0.001). Discussion: Increasing dietary calcium significantly augmented weight and fat loss secondary to caloric restriction and increased the percentage of fat lost from the trunk region, whereas dairy products exerted a substantially greater effect.     

Origin of the invasive Arundo donax (Poaceae): a trans-Asian expedition in herbaria

Background and Aims

The hypothesis of an ancient introduction, i.e. archaeophyte origin, is one of the most challenging questions in phylogeography. Arundo donax (Poaceae) is currently considered to be one of the worst invasive species globally, but it has also been widely utilzed by man across Eurasia for millennia. Despite a lack of phylogenetic data, recent literature has often speculated on its introduction to the Mediterranean region.

Methods

This study tests the hypothesis of its ancient introduction from Asia to the Mediterranean by using plastid DNA sequencing and morphometric analysis on 127 herbarium specimens collected across sub-tropical Eurasia. In addition, a bioclimatic species distribution model calibrated on 1221 Mediterranean localities was used to identify similar ecological niches in Asia.

Key Results

Despite analysis of several plastid DNA hypervariable sites and the identification of 13 haplotypes, A. donax was represented by a single haplotype from the Mediterranean to the Middle East. This haplotype is shared with invasive samples worldwide, and its nearest phylogenetic relatives are located in the Middle East. Morphometric data characterized this invasive clone by a robust morphotype distinguishable from all other Asian samples. The ecological niche modelling designated the southern Caspian Sea, southern Iran and the Indus Valley as the most suitable regions of origin in Asia for the invasive clone of A. donax.

Conclusions

Using an integrative approach, an ancient dispersion of this robust, polyploid and non-fruiting clone is hypothesized from the Middle East to the west, leading to its invasion throughout the Mediterranean Basin.     

Neural Correlates of Post-Conventional Moral Reasoning: A Voxel-Based Morphometry Study

Going back to Kohlberg, moral development research affirms that people progress through different stages of moral reasoning as cognitive abilities mature. Individuals at a lower level of moral reasoning judge moral issues mainly based on self-interest (personal interests schema) or based on adherence to laws and rules (maintaining norms schema), whereas individuals at the post-conventional level judge moral issues based on deeper principles and shared ideals. However, the extent to which moral development is reflected in structural brain architecture remains unknown. To investigate this question, we used voxel-based morphometry and examined the brain structure in a sample of 67 Master of Business Administration (MBA) students. Subjects completed the Defining Issues Test (DIT-2) which measures moral development in terms of cognitive schema preference. Results demonstrate that subjects at the post-conventional level of moral reasoning were characterized by increased gray matter volume in the ventromedial prefrontal cortex and subgenual anterior cingulate cortex, compared with subjects at a lower level of moral reasoning. Our findings support an important role for both cognitive and emotional processes in moral reasoning and provide first evidence for individual differences in brain structure according to the stages of moral reasoning first proposed by Kohlberg decades ago.     

Trans-Endplate Pedicle Pillar System in Unstable Spinal Burst Fractures: Design,Technique, and Mechanical Evaluation

Background

Short-segment pedicle screw instrumentation (SSPI) is used for unstable burst fractures to correct deformity and stabilize the spine for fusion. However, pedicle screw loosening, pullout, or breakage often occurs due to the large moment applied during spine motion, leading to poor outcomes. The purpose of this study was to test the ability of a newly designed device, the Trans-Endplate Pedicle Pillar System (TEPPS), to enhance SSPI rigidity and decrease the screw bending moment with a simple posterior approach.

Methods

Six human cadaveric spines (T11-L3) were harvested. A burst fracture was created at L1, and the SSPI (Moss Miami System) was used for SSPI fixation. Strain gauge sensors were mounted on upper pedicle screws to measure screw load bearing. Segmental motion (T12-L2) was measured under pure moment of 7.5 Nm. The spine was tested sequentially under 4 conditions: intact; first SSPI alone (SSPI-1); SSPI+TEPPS; and second SSPI alone (SSPI-2).

Results

SSPI+TEPPS increased fixation rigidity by 41% in flexion/extension, 28% in lateral bending, and 37% in axial rotation compared with SSPI-1 (P<0.001), and it performed even better compared to SSPI-2 (P<0.001 for all). Importantly, the bending moment on the pedicle screws for SSPI+TEPPS was significantly decreased 63% during spine flexion and 47% in lateral bending (p<0.001).

Conclusion

TEPPS provided strong anterior support, enhanced SSPI fixation rigidity, and dramatically decreased the load on the pedicle screws. Its biomechanical benefits could potentially improve fusion rates and decrease SSPI instrumentation failure.     

Positional behavior and substrate use in wild adult bearded capuchin monkeys (Sapajus libidinosus)

Natural selection for positional behavior (posture and locomotion) has at least partially driven the evolution of anatomical form and function in the order Primates. Examination of bipedal behaviors associated with daily activity patterns, foraging, and terrestrial habitat use in nonhuman primates, particularly those that adopt bipedal postures and use bipedal locomotion, allows us to refine hypotheses concerning the evolution of bipedalism in humans. This study describes the positional behavior of wild bearded capuchins (Sapajus libidinosus), a species that is known for its use of terrestrial substrates and its habitual use of stones as tools. Here, we test the association of terrestrial substrate use with bipedal posture and locomotion, and the influence of sex (which co‐varies with body mass in adults of this species) on positional behavior and substrate use. Behavior and location of 16 wild adult bearded capuchins from two groups were sampled systematically at 15 s intervals for 2 min periods for 1 year (10,244 samples). Despite their different body masses, adult males (average 3.5 kg) and females (average 2.1 kg) in this study did not differ substantially in their positional behaviors, postures, or use of substrates for particular activities. The monkeys used terrestrial substrates in 27% of samples. Bipedal postures and behaviors, while not a prominent feature of their behavior, occurred in different forms on the two substrates. The monkeys crouched bipedally in trees, but did not use other bipedal postures in trees. While on terrestrial substrates, they also crouched bipedally but occasionally stood upright and moved bipedally with orthograde posture. Bearded capuchin monkeys' behavior supports the suggestion from anatomical analysis that S. libidinosus is morphologically better adapted than its congeners to adopt orthograde postures.     

The human genome puzzle - the role of copy number variation in somatic mosaicism

The discovery of copy number variations (CNV) in the human genome opened new perspectives in the study of the genetic causes of inherited disorders and the etiology of common diseases. Differently patterned instances of somatic mosaicism in CNV regions have been shown to be present in monozygotic twins and throughout different tissues within an individual. A single-cell-level investigation of CNV in different human cell types led us to uncover mitotically derived genomic mosaicism, which is stable in different cell types of one individual. A unique study of immortalized B-lymphoblastoid cell lines obtained with 20 year interval from the same two subjects shows that mitotic changes in CNV regions may happen early during embryonic development and seem to occur only once, as levels of mosaicism remained stable. This finding has the potential to change our concept of dynamic human genome variation. We propose that further genomic studies should focus on the single-cell level, to understand better the etiology and physiology of aging and diseases mediated by somatic variations.