The physical characteristics and usage patterns of stone axe and pounding hammers used by long‐tailed macaques in the Andaman Sea region of Thailand

Stone hammering in natural conditions has been extensively investigated in chimpanzees and bearded capuchins. In contrast, knowledge of stone tool use in wild Old World monkeys has been limited to anecdotal reports, despite having known for over 120 years that Macaca fascicularis aurea use stone tools to process shelled foods from intertidal zones on islands in the Andaman Sea. Our report is the first scientific investigation to look at the stone tools used by these macaques. We observed they were skilled tool users and used stone tools daily. They selected tools with differing qualities for differing food items, and appeared to use at least two types of stone tools. Pounding hammers were used to crush shellfish and nuts on anvils and axe hammers were used to pick or chip at oysters attached to boulders or trees. We found significant physical differences between these two tools. Tools at oyster beds were smaller and exhibited scarring patterns focused more often on the points, whereas tools found at anvils were larger and showed more scarring on the broader surfaces. We also observed grip differences between the two tool types. Lastly, macaques struck targets with axe hammers more rapidly and over a wider range of motion than with pounding hammers. Both our behavioral and lithic data support that axe hammers might be used with greater control and precision than pounding hammers. Hand‐sized axe hammers were used for controlled chipping to crack attached oysters, and larger pounding hammers were used to crush nuts and unattached shellfish on anvils. In addition to stones, they also used hand‐sized auger shells (Turritella attenuata) as picks to axe attached oysters. Pound hammering appears similar to the stone tools used by chimpanzees and capuchins, but axe hammering has not yet been documented in other nonhuman primates in natural conditions. Am. J. Primatol. 71:594–608, 2009. © 2009 Wiley‐Liss, Inc.     

Hemostasis During Urologic Surgery: Fibrin Sealant Compared With Absorbable Hemostat

In the United States, fibrin sealants have been used to achieve hemostasis for nearly two decades. Although their clinical utility was first demonstrated in cardiac surgery, their effectiveness and safety have since been demonstrated to extend to a wide array of procedures. Fibrin sealants typically contain two components—fibrinogen and thrombin—that are combined and delivered simultaneously to a target bleeding site in order to achieve hemostasis. However, many commercial formulations contain other additional components, such as antifibrinolytic agents, that have been associated with adverse outcomes. This subanalysis compares the safety and effectiveness of a fibrin sealant versus an absorbable hemostat for achieving hemostasis during urologic procedures with mild to moderate bleeding.Key words: Hemostasis, Hemostatics, Fibrin tissue adhesive, Urologic surgical procedures, Surgical techniqueIn the United States, fibrin sealants have been used to achieve hemostasis for nearly two decades. Although their clinical utility was first demonstrated in cardiac surgery,¹ their effectiveness and safety have since been demonstrated to extend to a wide array of procedures, including cardiovascular, gastrointestinal, pneumothoracic, neurologic, urologic, otolaryngologic, dental, and reconstructive surgeries.^2,3 Within the field of urology, fibrin sealants have been used to manage bleeding from renal trauma,⁴ as well as to facilitate hemostasis during renal surgeries, including partial nephrectomies.^5–7Fibrin sealants typically contain two components—fibrinogen and thrombin—that are combined and delivered simultaneously to a target bleeding site (TBS) in order to achieve hemostasis.³ Many commercial formulations contain other additional components, such as antifibrinolytic agents, that have been associated with adverse outcomes. For example, in an observational study (N = 4374), the antifibrinolytic aprotinin was associated with an increased risk of long-term mortality within 5 years following coronary artery bypass graft surgery.⁸ Furthermore, repeated exposure to aprotinin may lead to allergic or potentially fatal anaphylactic reactions.^9–11 For this reason, the US Food and Drug Administration (FDA) issued an alert in 2006 indicating that caution should be used when using aprotinin in patients with a history of previous exposure to the product.¹² Tranexamic acid, another antifibrinolytic present in some commercial fibrin sealants, has been associated with alterations in neural tissue growth and adherence.¹³ Because of the risk of cerebral neurologic toxicity, fibrin sealants containing tranexamic acid are contraindicated for use in neurosurgery or in surgical procedures during which contact with cerebrospinal fluid or dura mater may occur.¹⁴In a phase III, randomized, single-blind, parallel-group, multicenter study,¹⁵ the fibrin sealant CROSSEAL™ (Ethicon, Inc., Somerville, NJ) significantly reduced the time to hemostasis during liver resection surgery compared with conventional hemostatic techniques. EVICEL® Fibrin Sealant (Human) (Ethicon, Inc.), the successor of CROSSEAL, requires no antifibrinolytic additive and is therefore both aprotinin and tranexamic acid free, and achieves hemostasis using exclusively human components.¹⁶ The effectiveness and safety of this fibrin sealant for hemostasis in soft tissue during elective retroperitoneal or intra-abdominal surgery were compared with an absorbable hemostat (SURGICEL® Absorbable Hemostat; Ethicon, Inc.) in a randomized, active-controlled, multicenter study.¹⁷ This article describes a subanalysis of data from the largest patient subgroup from that study, and evaluates the effectiveness and safety of a fibrin sealant versus an absorbable hemostat for patients who underwent urologic surgical procedures.     

Development and Evaluation of New Microemulsion-Based Hydrogel Formulations for Topical Delivery of Fluconazole

The aim of the present investigation was to develop and evaluate microemulsion-loaded hydrogels (MEHs) for the topical delivery of fluconazole (FZ). The solubility of FZ in oils, surfactants and cosurfactants was evaluated to identify the components of the microemulsion. The pseudo-ternary phase diagrams were constructed using the novel phase diagram by micro-plate dilution method. Carbopol EDT 2020 was used to convert FZ-loaded microemulsions into gel form without affecting their structure. The selected microemulsions were assessed for globule size, zeta potential and polidispersity index. Besides this, the microemulsion-loaded hydrogel (MEH) formulations were evaluated for drug content, pH, rheological properties and in vitro drug release through synthetic membrane and excised pig ear skin in comparison with a conventional hydrogel. The optimised MEH FZ formulations consisting of FZ 2%, Transcutol P 11.5% and 11%, respectively, as oil phase, Lansurf SML 20-propyleneglycol 52% and 50%, respectively, as surfactant–cosurfactant (2:1), Carbopol EDT 2020 1.5% as gelling agent and water 34.5% and 37%, respectively, showed highest flux values and high release rate values, and furthermore, they had low surfactant content. The in vitro FZ permeation through synthetic membrane and excised pig ear skin from the studied MEHs was best described by the zero-order and first-order models. Finally, the optimised MEH FZ formulations showed similar or slightly higher antifungal activity as compared to that of conventional hydrogel and Nizoral® cream, respectively. The results suggest the potential use of developed MEHs as vehicles for topical delivery of FZ, encouraging further in vitro and in vivo evaluation.KEY WORDS: fluconazole, in vitro skin permeation, microemulsion, microemulsion-loaded hydrogel, topical     

The Ciliopathy Protein CC2D2A Associates with NINL and Functions in RAB8-MICAL3-Regulated Vesicle Trafficking

Ciliopathies are a group of human disorders caused by dysfunction of primary cilia, ubiquitous microtubule-based organelles involved in transduction of extra-cellular signals to the cell. This function requires the concentration of receptors and channels in the ciliary membrane, which is achieved by complex trafficking mechanisms, in part controlled by the small GTPase RAB8, and by sorting at the transition zone located at the entrance of the ciliary compartment. Mutations in the transition zone gene CC2D2A cause the related Joubert and Meckel syndromes, two typical ciliopathies characterized by central nervous system malformations, and result in loss of ciliary localization of multiple proteins in various models. The precise mechanisms by which CC2D2A and other transition zone proteins control protein entrance into the cilium and how they are linked to vesicular trafficking of incoming cargo remain largely unknown. In this work, we identify the centrosomal protein NINL as a physical interaction partner of CC2D2A. NINL partially co-localizes with CC2D2A at the base of cilia and ninl knockdown in zebrafish leads to photoreceptor outer segment loss, mislocalization of opsins and vesicle accumulation, similar to cc2d2a-/- phenotypes. Moreover, partial ninl knockdown in cc2d2a-/- embryos enhances the retinal phenotype of the mutants, indicating a genetic interaction in vivo, for which an illustration is found in patients from a Joubert Syndrome cohort. Similar to zebrafish cc2d2a mutants, ninl morphants display altered Rab8a localization. Further exploration of the NINL-associated interactome identifies MICAL3, a protein known to interact with Rab8 and to play an important role in vesicle docking and fusion. Together, these data support a model where CC2D2A associates with NINL to provide a docking point for cilia-directed cargo vesicles, suggesting a mechanism by which transition zone proteins can control the protein content of the ciliary compartment.     

Infant Growth after Preterm Birth and Mental Health in Young Adulthood

Objectives

Faster growth after preterm birth benefits long-term cognitive functioning. Whether these benefits extend to mental health remains largely unknown. We examined if faster growth in infancy is associated with better self-reported mental health in young adults born preterm at very low birth weight (VLBW) (<1500g).

Study Design

As young adults, participants of the Helsinki Study of Very Low Birth Weight Adults self-reported symptoms of depression and attention deficit/hyperactivity disorder (ADHD) (n = 157) and other psychiatric problems (n = 104). As main predictors of mental health outcomes in linear regression models, we used infant weight, length, and head circumference at birth, term, and 12 months of corrected age, and growth between these time points. Growth data were collected from records and measures at term and at 12 months of corrected age were interpolated. Additionally, we examined the moderating effects of intrauterine growth restriction.

Results

Size at birth, term, or 12 months of corrected age, or growth between these time points were not associated with mental health outcomes (p-values >0.05). Intrauterine growth restriction did not systematically moderate any associations.

Conclusions

Despite the high variability in early growth of VLBW infants, the previously described association between slow growth in infancy and poorer cognitive functioning in later life is not reflected in symptoms of depression, ADHD, and other psychiatric problems. This suggests that the development of cognitive and psychiatric problems may have dissimilar critical periods in VLBW infants.     

Microsatellite and Mitochondrial DNA Study of Native Eastern European Cattle Populations: The Case of the Romanian Grey

The Eastern European Grey cattle are regarded as the direct descendants of the aurochs (Bos taurus primigenius). Nowadays in Romania, less than 100 Grey animals are being reared and included in the national gene reserve. We examined the genetic diversity among Romanian Grey, Brown, Spotted and Black and White cattle breeds, with a particular focus on Romanian Grey through the use of (i) 11 bovine specific microsatellite markers on 83 animals and (ii) 638 bp length of mitochondrial DNA (mtDNA) D-loop region sequence data from a total of 81 animals. Both microsatellite and mtDNA analysis revealed a high level of genetic variation in the studied breeds. In Romanian Grey a total of 100 alleles were found, the mean number of observed alleles per locus was 9.091; the average observed heterozygosity was 0.940; the Wright’s fixation index (F_IS) was negative (-0.189) and indicates that there is no inbreeding and no selection pressure. MtDNA analysis revealed 52 haplotypes with 67 variable sites among the Romanian cattle breeds without any insertion or deletion. Haplotype diversity was 0.980 ± 0.007 and ranged from 0.883 ± 0.056 (Brown) to 0.990 ± 0.028 (Spotted and Black and White). The highest genetic variability of the mtDNA was recorded in the Grey breed, where 18 haplotypes were identified. The most frequent mtDNA D-loop region belonged to T3 haplogroup (80.247%), which was found across all studied breeds, while T2 haplotypes (16.049%) was only found in Grey, Spotted and Black and White genotypes. The T1 haplotypes (3.704%) were found in the Grey and Spotted. The current results contribute to the general knowledge on genetic diversity found in Eastern European cattle breeds and could prove a valuable tool for the conservation efforts of animal genetic resources (FAnGR).     

YAP/TAZ as mechanosensors and mechanotransducers in regulating organ size and tumor growth

Organ size is controlled by the concerted action of biochemical and physical processes. Although mechanical forces are known to regulate cell and tissue behavior, as well as organogenesis, the precise molecular events that integrate mechanical and biochemical signals to control these processes are not fully known. The recently delineated Hippo-tumor suppressor network and its two nuclear effectors, YAP and TAZ, shed light on these mechanisms. YAP and TAZ are proto-oncogene proteins that respond to complex physical milieu represented by the rigidity of the extracellular matrix, cell geometry, cell density, cell polarity and the status of the actin cytoskeleton. Here, we review the current knowledge of how YAP and TAZ function as mechanosensors and mechanotransducers. We also suggest that by deciphering the mechanical and biochemical signals controlling YAP/TAZ function, we will gain insights into new strategies for cancer treatment and organ regeneration.     

Scanning X-Ray Nanodiffraction on Dictyostelium discoideum

We have performed scanning x-ray nanobeam diffraction experiments on single cells of the amoeba Dictyostelium discoideum. Cells have been investigated in 1), freeze-dried, 2), frozen-hydrated (vitrified), and 3), initially alive states. The spatially resolved small-angle x-ray scattering signal shows characteristic streaklike patterns in reciprocal space, which we attribute to fiber bundles of the actomyosin network. From the intensity distributions, an anisotropy parameter can be derived that indicates pronounced local variations within the cell. In addition to nanobeam small-angle x-ray scattering, we have evaluated the x-ray differential phase contrast in view of the projected electron density. Different experimental aspects of the x-ray experiment, sample preparation, and data analysis are discussed. Finally, the x-ray results are correlated with optical microscopy (differential phase contrast and confocal microscopy of mutant strains with fluorescently labeled actin and myosin II), which have been carried out in live and fixed states, including optical microscopy under cryogenic conditions.     

Environmental Stochasticity and Long-Term Livestock Viability—Herd-Accumulation as a Risk Reducing Strategy

This study tests the hypothesis that herd accumulation can be a risk reducing strategy aimed at increasing security in an unpredictable environment. Saami reindeer husbandry in Norway is characterized by environmental unpredictability and occasionally harsh winters can have dramatic negative effects on reindeer population densities. While herd accumulation has been found to be an adaptive risk reducing strategy in stochastic environments (i.e., individually rational), the accumulation of large herds may also result in collectively negative density dependent effects, which may negatively affect individual herders (i.e., collectively irrational). We found that individual husbandry units’ strategies, such as accumulating reindeer, have a larger effect on individual husbandry units’ herd size than a negative density-dependent effect.