Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine.

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SUMMARY: Cephalometry or measurement of human head is used in identification, forensic medicine, plastic surgery, orthodontics, archeology and examine the differences between races and ethnicities.This descriptive investigation was undertaken on 198 young Turkman males to determine the cephalic index and head phenotype among them in Gorgan, North of Iran. In this study cephalic index was determined by classic cephalometric method. Mean and standard deviation of cephalic index was 80.4 ± 4. Based on the cephalic index, the head shape of 42.4% of individuals were brachycephalic, 7.6% hyperbrachycephalic, 40.9% mesocephalic and 8.1% dolicocephalic.This research showed that Turkman individuals have typical brachycephalic phenotype. In comparison to other studies, we can conclude that the ethnic factor has an effective role on head phenotype in North of Iran.

It is natural that there is close relationship between cranial capacity, and the size of brain, several studies have estimated the cranial capacity which indirectly reflects the brain volume in different countries. In the present study cranial capacity has been estimated in Turkmans and native Fars17-20 years old groups in North of Iran.This study was carried out on 808 normal 17-20 years old (male 398, female 410) in Turkman and native Fars groups in South-East of Caspian Sea border (North of IRAN). By using linear dimensions of the head.The mean and SD of cranial capacity in Turkmans males and females were 1420.6±85 ml and 1227.2±120 ml, respectively. The mean and SD of cranial capacity in native Fars male and females were 1369±142ml, 1215.8±125ml, respectively, this difference was significant (P<0.05).This investigation was shown that the cranial capacity is higher in male than female, also racial factor can affect on cranial capacity.

The immunomodulatory and self-renewable features of human adipose mesenchymal stem cells (hAD-MSCs) mark their importance in regenerative medicine. Interleukin 23 (IL- 23) as a proinflammatory cytokine suppresses T regulatory cells (Treg) and promotes the response of T helper 17 (Th17) and T helper 1 (Th1) cells. This pathway starts inflammation and immunosuppression in several autoimmune diseases. The current study for producing recombinant IL- 23 decoy receptor (RIL- 23R) using hAD-MSCs as a good candidate for ex vivo cell-based gene therapy purposes reducing inflammation in autoimmune diseases. hAD-MSCs was isolated from lipoaspirate and then characterized by differentiation. RIL- 23R was designed and cloned into a pCDH-813A- 1 lentiviral vector. The transduction of hAD-MSCs was performed at MOI (multiplicity of infection) = 50 with pCDH- EFI α- RIL- 23R- PGK copGFP. Expressions of RIL- 23R and octamer-binding transcription factor 4 (OCT- 4) were determined by real-time polymerase chain reaction (real time-PCR). Self-renewing properties were assayed with OCT- 4. Bioactivity of the designed RIL- 23R was evaluated by IL- 17 and IL- 10 expression of mouse splenocytes. Cell differentiation confirmed the true isolation of hAD-MSCs from lipoaspirate. Restriction of the enzyme digestion and sequencing verified the successful cloning of RIL- 23R in the CD813A-1 lentiviral vector. The green fluorescent protein (GFP) positive transduction rate was up to 90%, and real-time PCR showed the expression level of RIL-23R. Oct-4 had a similar expression pattern with nontransduced hAD-MSCs and transduced hAD-MSCs/ RIL-23R indicating that lentiviral vector did not affect hAD-MSCs characteristics. Downregulation of IL-17 and upregulation of IL-10 showed the correct activity of the engineered hAD-MSCs. The results showed that the transduced hAD-MSCs/ RIL- 23R, expressing IL-23 decoy receptor, can give a useful approach for a basic research on cell-based gene therapy for autoimmune disorders.

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