Conjugated Linoleic Acid (CLA) inhibits new vessel growth in the mammalian brain.
Conjugated Linoleic Acid (CLA) is fatty acid found endogenously in food sources that prevents new tumor development and reduces the growth of existing tumors in laboratory animals. CLA exerts its anti-carcinogenic effect by reducing VEGF and bFGF serum levels and by blocking flk-1 receptors, thereby inhibiting vascular growth critical to tumor growth and survival. Although the ability of CLA to inhibit angiogenesis in the peripheral nervous system is well characterized, it remains unknown whether CLA also affects vascular morphology in the central nervous system. Therefore, in the present study, exercising and sedentary animals received either standard rat chow or a specially formulated diet consisting of 0.5% CLA for 24 days. The brains were then examined to determine the extent of vascular growth in the cerebellum, a region known to exhibit robust exercise-induced angiogenesis. Our results indicate that CLA administration significantly reduces angiogenesis in the cerebellum. This study is the first to demonstrate the anti-angiogenic effect of CLA in the brain, and suggests that CLA be explored as a therapeutic treatment for cancer and tumors in the brain.


Suicide in frontotemporal dementia and Huntington disease: analysis of family-reported pedigree data and implications for genetic healthcare for asymptomatic relatives.
Genomic testing for early-onset dementia is becoming more accessible, along with predictive testing for at-risk relatives; however, complex counselling issues are important to address. The topic of suicide often has stigma associated, and thoughts or experiences may not be volunteered without prompting. Little has been published with consideration to suicide rates in the context of family experiences and their significance in genetic counselling for relatives of people with Huntington disease and frontotemporal dementia. This study included pedigree information for 267 symptomatic individuals with frontotemporal dementia or Huntington disease, provided via genetic counselling clinics. Descriptive statistics and suicide rate calculations based on family reported pedigree data. The suicide rate was 2996 per 100,000 compared with the population rate of 10 per 100,000. Approximately one in 15 families reported suicide of an affected family member, and file notes indicated that one in five families had experienced suicide, suicidal thoughts or suicide attempts in one or more affected, unaffected or pre-symptomatic relative. Health professional awareness of family experiences, including suicide of a relative, is vital in facilitating client decisions about genetic testing, and in providing adequate psychosocial support during the process of genetic testing and adaption to results.


Tumor-derived immunoglobulin like transcript 5 induces suppressive immunocyte infiltration in colorectal cancer.
Infiltration of immunosuppressive cells in the tumor microenvironment (TME) induced colorectal cancer (CRC) progression and its resistance to immunotherapy. Identification of tumor-specific factors to modulate inhibitory immunocyte infiltration would provide alternative and novel targets for CRC immunotherapy. Immunoglobulin-like transcript (ILT) 5 is a negative regulator of myeloid cell activation. However, its expression and functional role in solid tumors is still unknown. Using human CRC tissues and cell lines, we found that ILT5 was highly expressed in CRC cells compared with normal colorectal epithelial cells. Enriched ILT5 in tumor cells was correlated with advanced tumor stages and poor patient survival. Our subsequent in vitro and in vivo studies revealed that tumor-derived ILT5 inhibited the infiltration of T cells, especially that of CD8+ T cells in the TME, creating suppressive T-cell contexture. Furthermore, ILT5 directed M2-like polarization of tumor-associated macrophages (TAMs). Inhibition of tumor-derived ILT5 restored the immunosuppressive T-cell and TAM contexture, and restricted CRC progression. Our findings identified ILT5 expression in solid tumor cells for the first time and raised ILT5 as a potential immunotarget and prognostic predictor in CRC.


A new flavin enzyme catalyzing the reduction of dihydrodipicolinate in sporulating Bacillus subtilis. II. Kinetics and regulatory function.
Dihydrodipicolinate reductase in Bacillus subtilis PCI 219 had FMN as a prosthetic group, and the hydrogen transfer pathway is considered to be NADPH yields FMN yields dihydrodipicolinate. Linewaver-Burk plots of the reciprocal of the activity against the reciprocal of the concentration of either of the two substrates, dihydrodipocolinate and NADPH, are consistent with a reaction mechanism involving interconversion of two free forms of the enzyme by the two substrates. The Km values obtained from the secondary plots are 0.77 mM for dihydrodipicolinate and 72 muM for NADPH. Inhibition by dipicolinate is competitive with NADPH and noncompetitive with dihydrodipicolinate, and shows positive cooperativity. The possible metabolic role of the reductase in sporulating Bacillus subtilis is discussed in connection with regulation of the biosyntheses of dipicolinate and diaminopimelate.


3Shape Digital Design Software in Splints Creation-A Pilot Study.
Digital technologies have widened their horizons into the world of dental medicine and now further expanding to cover all branches. This new modern technology replaces traditional laboratory techniques allowing effective patient care. Patients who suffer from bruxism-the act of involuntary habitual grinding of teeth-have widely been benefited by splint treatments. The aim of this article is to display the variety of occlusal splints that can be created by the 3Shape Digital Design Software and their application in specific clinical situations. Six variations in the splints were created digitally-three with uncombined designs and the remaining three with a combination of two of the main options available. During this study, 36 splints were made for patients aged 24 to 55 inclusively. The largest number of splints according to the clinical picture were made of "raise to antagonist cusp tips" (14 pieces) and the remaining were of combined type "raise to antagonist cusp tips + raise to antagonist plane" (12 pieces). There thickness was within the range of 1.5 and 5 mm. 3Shape Digital Design Software-Splint Studio is a suitable system for designing and creating occlusal splints with respect to certain clinical situations. It is possible to combine the three main types in a separate section of the dental arch according to the case.


Nucleotide binding and affinity labelling support the existence of the phosphate-binding subsite p2 in bovine pancreatic ribonuclease A.
When the reaction of bovine pancreatic ribonuclease A with 6-chloropurine riboside 5'-monophosphate was carried out in the presence of several natural mononucleotides, a decrease of 25-75% was found in the amount of the reaction product derivative II (the main product of the reaction which has the nucleotide label at the alpha-NH2 group of Lys-1). The efficiency of inhibition followed the order 3'-AMP greater than 5'CMP approximately equal to 5'AMP greater than 3'CMP. Previous studies indicate that this order reflects the extent of occupancy of p2, a phosphate-binding subsite adjacent to the catalytic centre. This finding suggests that derivative II is the result of affinity labelling and that the phosphate group of the halogenated nucleotide binds to p2 before the reaction takes place. The dissociation constants and stoichiometry of the interaction between native enzyme, derivative II and derivative E (homologous to derivative II, but labelled with a nucleoside instead of a nucleotide) with 3'AMP and 5'AMP at several pH values were also determined. Although in general one strong binding site was found, no strong binding occurs between 3'AMP and derivative II. It is concluded that the phosphate of the label occupies the same site p2, as the phosphate of 3'AMP. Finally, the pH dependence for the binding of 3'AMP and 5'AMP to RNAase A indicates that they bind to different protein groups. The results presented support the structure of the active site of ribonuclease A postulated previously (Parés, X., Llorens, R., Arús, C. and Cuchillo, C.M. (1980) Eur. J. Biochem. 105, 571-579).