The primary motor and premotor areas of the human cerebral cortex.

Brodmann's cytoarchitectonic map of the human cortex designates area 4 as cortex in the anterior bank of the precentral sulcus and area 6 as cortex encompassing the precentral gyrus and the posterior portion of the superior frontal gyrus on both the lateral and medial surfaces of the brain. More than 70 years ago, Fulton proposed a functional distinction between these two areas, coining the terms primary motor area for cortex in Brodmann area 4 and premotor area for cortex in Brodmann area 6. The parcellation of the cortical motor system has subsequently become more complex. Several nonprimary motor areas have been identified in the brain of the macaque monkey, and associations between anatomy and function in the human brain are being tested continuously using brain mapping techniques. In the present review, the authors discuss the unique properties of the primary motor area (M1), the dorsal portion of the premotor cortex (PMd), and the ventral portion of the premotor cortex (PMv). They end this review by discussing how the premotor areas influence M1.     

Activin controls skin morphogenesis and wound repair predominantly via stromal cells and in a concentration-dependent manner via keratinocytes

The transforming growth factor-beta family member activin is a potent regulator of skin morphogenesis and repair. Transgenic mice overexpressing activin in keratinocytes display epidermal hyper-thickening and dermal fibrosis in normal skin and enhanced granulation tissue formation after wounding. Mice overexpressing the secreted activin antagonist follistatin, however, have the opposite wound-healing phenotype. To determine whether activin affects skin morphogenesis and repair via activation of keratinocytes and/or stromal cells, we generated transgenic mice expressing a dominant-negative activin receptor IB mutant (dnActRIB) in keratinocytes. The architecture of adult skin was unaltered in these mice, but delays were observed in postnatal pelage hair follicle morphogenesis and in the first catagen-telogen transformation of hair follicles. Although dnActRIB-transgenic mice showed slightly delayed wound re-epithelialization after skin injury, the strong inhibition of granulation tissue formation seen in follistatin-transgenic mice was not observed. Therefore, although endogenous activin appeared to affect skin morphogenesis and repair predominantly via stromal cells, overexpressed activin strongly affected the epidermis. The epidermal phenotype of activin-overexpressing mice was partially rescued by breeding these animals with dnActRIB-transgenic mice. These results demonstrate that activin affects both stromal cells and keratinocytes in normal and wounded skin and that the effect on keratinocytes is dose-dependent in vivo.     

Bomirski melanomas - a versatile and powerful model for pigment cell and melanoma research (review)

Models of animal melanoma are still indispensable tools in oncological research because they can be studied in syngeneic hosts while human melanomas cannot. One such model is a family of melanomas which originated in 1959 from a spontaneous melanotic melanoma of the skin in Syrian hamster, the Bomirski melanomas. Currently, it consists of 5 transplantable in vivo-variants (Ma, Ab, MI, MI-B and Ab455) and several cell lines derived from Ab amelanotic and Ma melanotic tumors. Here we present the Bomirski family of melanomas as an excellent model to study regulatory mechanisms governing melanogenesis, differentiation and intermediary metabolism in melanocytes, and as a good animal model for developing and testing potential melanoma vaccines.     

Reversible binding of heparin to the loop peptide of endotoxin neutralizing protein

Endotoxin neutralizing protein (ENP) from Limulus polyphemus is an amphipathic, 11.8 kDa protein with an isoelectric point of 10.2. ENP neutralizes lipopolysaccharide (LPS) and possesses antibacterial activity against Gram-negative bacteria. Heparin binds to ENP and blocks its LPS-neutralizing activity. The relative blocking activity of heparin is equal to low molecular weight heparin and polyanetholsulfonic acid > heparan sulfate > chondroitin sulfate A > chondroitin sulfate C. Endoproteinase Glu-C hydrolysis of recombinant ENP results in four major peptides, three of which are seen following separation on reversed phase HPLC. Heparin binds to the loop peptide (31-72), which includes the heparin binding consensus sequence XBBXBX between the two cysteine residues of ENP. When heparin is added to the digest and then applied to a C18 column, the loop peptide is bound; however, it dissociates and elutes with either 5 M NaCl or 0.1 M sodium phosphate, demonstrating reversible binding to heparin. LPS and lipid A both bind to the loop peptide and remove it from digests of ENP; however, neither complex could be dissociated by salt or sodium phosphate. Heparin, LPS, and lipid A individually bind to the same site on ENP.     

Plasma total homocysteine levels and prognosis in patients with previous premature myocardial infarction: a 10-year follow-up study

OBJECTIVES: To explore plasma total homocysteine (tHcy) as a predictor of long-term prognosis after premature myocardial infarction (MI). DESIGN: Prospective cohort study. SETTINGS: Akershus University Hospital. SUBJECTS: A total of 247 patients (193 men and 54 women) in stable clinical phase after premature MI (males: first MI at age < or =55; females < or =60). MAIN OUTCOME MEASURES: The primary end-point was total mortality and the secondary end-point was cardiac death. The third end-point was major cardiac events: a combination of cardiac death, MI and cardiac arrest. RESULTS: After 10 years, 44 patients had died, 36 from cardiac causes. Major cardiac event occurred in 70 patients. The relative risk for death of all causes increased 1.43 (95% CI, 1.08-1.88) per tHcy quartile (P for trend = 0.01), and was only modestly reduced after adjustment for age, ejection fraction, total cholesterol, C-reactive protein, fibrinogen, smoking and hypertension to 1.37 (95% CI, 1.04-1.80) (P for trend = 0.03). Similar results were observed when cardiac death was used as the end-point, but we observed no association between tHcy and the end-point major cardiac event. CONCLUSIONS: Total homocysteine was an independent predictor of total and cardiac mortality in stable patients following premature MI. tHcy had no effect on major cardiac event in contrast to most other risk factors in this study. Thus, the mechanism(s) underlying the effects of homocysteine on coronary heart disease may differ from other risk factors.     

Syntaxin 11 is required for NK and CD8+ T‐cell cytotoxicity and neutrophil degranulation

Syntaxin 11 (STX11) controls vesicular trafficking and is a key player in exocytosis. Since Stx11 mutations are causally associated with a familial hemophagocytic lymphohistio‐cytosis, we wanted to clarify whether STX11 is functionally important for key immune cell populations. This was studied in primary cells obtained from newly generated Stx11^?/? mice. Our data revealed that STX11 is not only widely expressed in different immune cells, but also induced upon LPS or IFN‐γ treatment. However, Stx11 deficiency does not affect macrophage phagocytic function and cytokine secretion, mast cell activation, or antigen presentation by DCs. Instead, STX11 selectively controls lymphocyte cytotoxicity in NK and activated CD8⁺ T cells and degranulation in neutrophils. Stx11^?/? NK cells and CTLs show impaired degranulation, despite a comparable activation, maturation and expression of the complex‐forming partners MUNC18–2 and VTI1B. In addition, Stx11^?/? CTLs and NK cells produce abnormal levels of IFN‐γ. Since functional reconstitution rescues the defective phenotype of Stx11^?/? CTLs, we suggest a direct, specific and key role of STX11 in controlling lymphocyte cytotoxicity, cytokine production and secretion. Finally, we show that these mice are a very useful tool for dissecting the role of STX11 in vesicular trafficking and secretion.