A new 4-(2-methylquinolin-4-ylmethyl)phenyl P1' group for the beta-amino hydroxamic acid derived TACE inhibitors

A new P1' group for TACE inhibitors was identified by eliminating the oxygen atom in the linker of the original 4-(2-methylquinolin-4-ylmethoxy)phenyl P1' group. Incorporation of this 4-(2-methylquinolin-4-ylmethyl)phenyl group onto different beta-aminohydroxamic acid cores provided compound 18, which demonstrated potent porcine TACE (p-TACE) and human whole blood activity, excellent PK properties, and good selectivity against a variety of MMPs.     

Potential antigen candidates for subunit vaccine development against Helicobacter pylori infection

Helicobacter pylori (H. pylori) is a resident bacterium in the stomach that accounts for 75% cases of gastric cancer. In this review, we comprehensively studied published papers on H. pylori vaccines using Google Scholar and NCBI databases to gather information about vaccines against H. pylori. Considering the pivotal roles of the enzyme urease (in production of NH₃ and neutralization of the acidic medium of the stomach), cytotoxin-associated gene A, and vacuolating cytotoxin A proteins in H. pylori infection, they could be the best candidates for the construction of recombinant vaccines. The outer membrane porins (Hop), blood group antigen-binding adhesin (BabA), sialic acid-binding adhesin (SabA), and outer inflammatory protein A, play significant roles in binding of bacterium to human gastric tissues, and because binding is the first step in bacterial fixation and colonization, these antigens also can be considered as suitable candidates for designing vaccines. Likely, other significant bacterial antigens, such as NapA (chemotactic factor for recruitment of human neutrophils and monocytes to the site of infection), duodenal ulcer promoting protein A (to promote duodenal ulcer), and Hsp60 (as a molecular chaperon for activation of urease enzyme), can be used in the construction of subunit vaccines. New vaccines in use currently, such as DNA vaccines and subunit vaccines, can efficiently replace the dead and attenuated vaccines. Nonetheless, the results show that urease enzyme is most used compared with bacterial components in the designing and construction of recombinant vaccines. The BabA and SabA antigens belong to the outer membrane porins family in H. pylori and are required for binding and fixation of the bacterium to the human gastric tissues.     

Kinematics and spatiotemporal parameters of infant‐carrying in olive baboons

In the field of biomechanics of quadrupedal locomotion in primates, infant‐carrying has received little attention. This study presents the first biomechanical study of infant‐carrying in captive female olive baboons (Papio anubis). We test whether females carrying infants conform 1) to the Support Polygon Model (Rollinson and Martin: Symp Zool Soc Lond 48 (1981) 377–427) of gait selection, according to which diagonality should decrease when the infant is carried cranially and increase when the infant is carried dorsally and caudally; 2) to Biewener's (Biewener: Science 245 ( 1989 ) 45–48) theory of limb postures, according to which females should extend their hind limbs more due to infant load, especially in the later stages when the infant is not fully autonomous but relatively heavy. This study focuses on the sagittal kinematics of quadrupedal gaits (joint angles and spatiotemporal parameters) of four females with and without infant loads at the CNRS Primatology Station (France). High‐speed video recordings were made using the technical platform “Motion Analysis of Primates” available in the animals' place of life. Regarding diagonality, our results do not fully conform to those predicted by the Support Polygon Model of gait selection; however, the model cannot be rejected at this stage in experiment. With regard to limb posture, our results do not support Biewener's (Biewener: Science 245 ( 1989 ) 45–48) theory: loaded females do not extend their hind limbs more as predicted; on the contrary, the hind limbs tend to be more flexed when the infant they carry is relatively heavy. Am J Phys Anthropol 155:392–404, 2014. © 2014 Wiley Periodicals, Inc.     

Synthesis and characterization of bovine serum albumin-coated nanocapsules loaded with indocyanine green as potential multifunctional nanoconstructs

We have synthesized and characterized bovine serum albumin (BSA)-coated polymeric nanocapsules (NCs) loaded with indocyanine green (ICG), an FDA-approved near infrared chromophore. Poly(allylamine) hydrochloride was electrostatically crosslinked with phosphate anions to form nanoconstructs encapsulating ICG. BSA was conjugated onto the polymeric NCs via glutaraldehyde. BSA-coated ICG-containing nanocapsules (BSA-ICG NCs) were characterized by FTIR and optical spectroscopy, SEM, and zeta-potential measurements. Using normal human endocervical epithelial cells, we demonstrate the effectiveness of BSA-ICG NCs for intracellular optical imaging in vitro. These nanoconstructs may potentially serve as a multifunctional platform for combined optical imaging, phototherapy, and drug delivery.     

Predictive Modeling and Mapping of Malayan Sun Bear (Helarctos malayanus) Distribution Using Maximum Entropy

One of the available tools for mapping the geographical distribution and potential suitable habitats is species distribution models. These techniques are very helpful for finding poorly known distributions of species in poorly sampled areas, such as the tropics. Maximum Entropy (MaxEnt) is a recently developed modeling method that can be successfully calibrated using a relatively small number of records. In this research, the MaxEnt model was applied to describe the distribution and identify the key factors shaping the potential distribution of the vulnerable Malayan Sun Bear (Helarctos malayanus) in one of the main remaining habitats in Peninsular Malaysia. MaxEnt results showed that even though Malaysian sun bear habitat is tied with tropical evergreen forests, it lives in a marginal threshold of bio-climatic variables. On the other hand, current protected area networks within Peninsular Malaysia do not cover most of the sun bears potential suitable habitats. Assuming that the predicted suitability map covers sun bears actual distribution, future climate change, forest degradation and illegal hunting could potentially severely affect the sun bear’s population.     

Inhibition of GSK‐3β enhances neural differentiation in unrestricted somatic stem cells

GSK‐3β is a key molecule in several signalling pathways, including the Wnt/β‐catenin signalling pathway. There is increasing evidence suggesting Wnt/β‐catenin signalling is involved in the neural differentiation of embryonic, somatic and neural stem cells. However, a large body of evidence indicates that this pathway maintains stem cells in a proliferative state. To address this controversy, we have investigated whether the Wnt/β‐catenin pathway is present and involved in the neural differentiation of newly introduced USSCs (unrestricted somatic stem cells). Our results indicate that the components of Wnt/β‐catenin signalling are present in undifferentiated USSCs. We also show that the treatment of neurally induced USSCs with BIO (6‐bromoindirubin‐3′‐oxime), a specific GSK‐3β inhibitor and Wnt activator, for 5 and 10 days results in increased expression of a general neuronal marker (β‐tubulin III). Moreover, the expression of pGSK‐3β and stabilized β‐catenin increased by BIO in neurally induced USSCs, indicates that the Wnt pathway is activated and functional in these cells. Thus, inhibition of GSK‐3β in USSCs enhances their neural differentiation, which suggests a positive role of the Wnt/β‐catenin signalling pathway towards neural fate.