June 10, 2008 ͉ vol. 105 ͉ no. 23 ͉ 7895–8162 In This Issue Proceedings of the National Academy ofPNAS Sciences of the United States of America www.pnas.org 7913 An inverted pyramid scheme 7947 minimizes joint stress 8026 provides support to blood cell membranes 8114 A sure shot to cure alcoholism

surgery, limiting movement for many patients. Kristen Moffat et APPLIED PHYSICAL SCIENCES al. examined the interface between the knee and the anterior cruciate ligament (ACL), which is the joint most often injured An inverted pyramid scheme by athletes. The ACL joins the A plastic bottle, a can, and a stiff torus pose rich problems in femur (thigh ) to the geometry and mechanics to anyone who pokes them with a tibia (shin bone) by means of pencil. The applied pressure forms indentations in these fibrocartilage connective tis- rounded objects, producing a sue. The authors used a com- variety of faceted structures, bination of energy-dispersive either localized or extensive. x-ray analysis and backscat- Ashkan Vaziri and L. tered scanning electron mi- Mahadevan analyze these croscopy, which helps resolve problems and show that the small tissue regions, to exam- Compression of the ligament-to- response of the system de- ine the makeup of this fibro- bone insertion site (red, 5% strain; pends on the Gaussian (G) cartilage. They found that the blue, 10%; green, 20%). curvature of the original sur- varies in cal- face. Although a simplified cium content and has both mineralized and nonmineralized re- A pyramidal dent grows facets un- linear model predicts the gions, with the former oriented toward bone and the latter to- der pressure. qualitative response in individ- ward the ACL. In microcompression experiments, the ual cases, a detailed model nonmineralized regions compressed more than the mineralized requires a numerical solution of the governing equations. For ones, and the ACL’s tibial insertion site exhibited greater com- example, a sphere forms an inverted pyramidal structure of pressive properties than its femoral counterpart. This mechani- three-, then four-, then fivefold rotational symmetry, with cal inhomogeneity minimizes stress on joints, especially between strongly localized deformations at the vertices of the pyramid. soft and hard tissues, the authors say. They suggest that their New facets appear in the indentation as the surface alters to work may aid in the development of better treatment for joint minimize stretching. A simple geometric argument gives ap- injuries and may give rise to engineered tissue systems that can proximate expressions for the size of the pyramid and the force integrate seamlessly into the body. — F.A. required to form it. A torus responds very differently depend- ing on whether force is applied from the inside (where the G ‘‘Characterization of the structure–function relationship at the curvature is negative) or outside (where the G curvature is pos- ligament-to-bone interface’’ by Kristen L. Moffat, Wan-Hsuan S. itive). Different multifaceted states can coexist under certain Sun, Paul E. Pena, Nadeen O. Chahine, Stephen B. Doty, Gerard A. Ateshian, Clark T. Hung, and Helen H. Lu (see pages 7947– conditions, the authors say. — K.M. 7952)

‘‘Localized and extended deformations of elastic shells’’ by Ashkan Vaziri and L. Mahadevan (see pages 7913–7918) CELL BIOLOGY

APPLIED BIOLOGICAL SCIENCES Protein provides support to blood cell membranes Cartilage minimizes joint stress The pliability of the membrane allows the cells In the knee and other joints, soft tissues such as ligaments and to squeeze through narrow capillaries while maintaining their tendons integrate into hard tissue or bone to facilitate smooth structural integrity. The source of this resilience is a mesh- motion. Joints, however, are prone to injury, and the junctions like network of fibrous spectrin molecules anchored to the between hard and soft tissues there often go unrepaired after lipid bilayer through interactions with such as 4.1R.

www.pnas.org͞cgi͞doi͞10.1073͞iti2308105 PNAS ͉ June 10, 2008 ͉ vol. 105 ͉ no. 23 ͉ 7895–7896 Downloaded by guest on September 28, 2021 Marcela Salomao et al. offer NEUROSCIENCE insight into the involvement of protein 4.1R in molecular interactions that contribute A sure shot to cure alcoholism to red blood cell membrane Breaking the cycle of addiction is an impossible task for many pa- structure and stability. The tients because a single lapse can lead to a spiral of abuse. Untan- authors found that deletion gling the biochemical pathways that lead to long-term substance of 4.1R in mouse red blood abuse and relapse could yield cells leads to a large reduc- targets for treatment and, ulti- tion in actin, an important mately, relief for sufferers of structural protein that, in addiction. Sebastien Carnicella Membrane of 4.1R- conjunction with spectrin, et al. found that when the deficient cells. bestows structural integrity growth factor glial cell line- on the red cell membrane. derived neurotrophic factor ERK1/2 phosphorylation in the Because a number of transmembrane proteins, including (GDNF) was administered into midbrain after VTA infusion. GPC, XK, Duffy, and Rh, were also greatly reduced in 4.1R- the ventral tegmental area deficient red blood cells, Salomao et al. proposed that these (VTA)—an area of the brain highly implicated in drug-seeking proteins associate with 4.1R. The results place protein 4.1R behavior—cravings for alcohol were greatly reduced in as little as at the hub of a macromolecular complex of cytoskeletal and 10 minutes from the time of injection, and the effect lasted at least transmembrane proteins. The authors suggest that disruption 3 hours. In rats that had developed alcoholism, the authors show of this complex is responsible for the instability and remodel- that GDNF had a similar effect in blocking consumption and, ing of 4.1R-deficient red cell membranes. — M.M. after 2 weeks without drinking, rats given GDNF avoided relapse even when they had easy access to alcohol rewards. In addition, ‘‘Protein 4.1R-dependent multiprotein complex: New insights into the Carnicella et al. found that GDNF is very specific, having no ef- structural organization of the red blood cell membrane’’ by Marcela fect on sugar consumption and only staunching alcohol cravings Salomao, Xihui Zhang, Yang Yang, Soohee Lee, John H. Hartwig, if administered to the VTA. The authors say that GDNF directly Joel Anne Chasis, Narla Mohandas, and Xiuli An (see pages affects the MAPK biochemical pathway, and that its rapid 8026–8031) effects—extremely fast for a growth factor—likely occur because it is acting directly on neurons. — C.E. ‘‘GDNF is a fast-acting potent inhibitor of alcohol consumption and relapse’’ by Sebastien Carnicella, Viktor Kharazia, Jerome Jeanblanc, Patricia H. Janak, and Dorit Ron (see pages 8114–8119)

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