Systems-level analysis reveals multiple modulators of epithelial-mesenchymal transition and identifies DNAJB4 and CD81 as novel metastasis inducers in breast cancer

Epithelial-mesenchymal transition (EMT) is driven by complex signaling events that induce dramatic biochemical and morphological changes whereby epithelial cells are converted into cancer cells. However, the underlying molecular mechanisms remain elusive. Here, we used mass spectrometry based quantitative proteomics approach to systematically analyze the post-translational biochemical changes that drive differentiation of human mammary epithelial (HMLE) cells into mesenchymal. We identified 314 proteins out of more than 6,000 unique proteins and 871 phosphopeptides out of more than 7,000 unique phosphopeptides as differentially regulated. We found that phosphoproteome is more unstable and prone to changes during EMT compared with the proteome and multiple alterations at proteome level are not thoroughly represented by transcriptional data highlighting the necessity of proteome level analysis. We discovered cell state specific signaling pathways, such as Hippo, sphingolipid signaling, and unfolded protein response (UPR) by modeling the networks of regulated proteins and potential kinase-substrate groups. We identified two novel factors for EMT whose expression increased on EMT induction: DnaJ heat shock protein family (Hsp40) member B4 (DNAJB4) and cluster of differentiation 81 (CD81). Suppression of DNAJB4 or CD81 in mesenchymal breast cancer cells resulted in decreased cell migration in vitro and led to reduced primary tumor growth, extravasation, and lung metastasis in vivo. Overall, we performed the global proteomic and phosphoproteomic analyses of EMT, identified and validated new mRNA and/ or protein level modulators of EMT. This work also provides a unique platform and resource for future studies focusing on metastasis and drug resistanceTurkiye Cumhuriyeti Kalkinma Bakanlig

Association of recurrent pregnancy loss with chromosomal abnormalities and hereditary thrombophilias

Background: Recurrent pregnancy loss (RPL) which is generally known as >3 consecutive pregnancy losses before 20 weeks’ gestation is seen in 0.5-2% of women Objective: To evaluate the association of parental and fetal chromosomal abnormalities with recurrent pregnancy loss in our area and to analyze the frequency of three types of hereditary thrombophilia’s; (MTHFR C677T polymorphisms, FV Leiden G1691A mutation and Prothrombin (factor II) G20210A mutation) in these female patients. Methods: The present case-control retrospective study was performed between February 2007 and December 2011 on 495 couples, who had two or more consecutive pregnancy losses before 20 weeks’ gestation. We used conventional cytogenetic analysis and polymerase chain reaction–restriction fragment length polymorphism. Results: Parental chromosomal abnormality was detected in 28 cases (2.8% of all cases, 5.7% of the couples) most of which (92.9%) were structural abnormalities. All of the structural abnormalities were balanced chromosomal translocations. Chromosomal analysis performed from the abortion materials detected a major chromosomal abnormality in 31.9% of the cases. The most frequently observed alteration in the hereditary thrombophilia genes was heterozygote mutation for the MTHFR C677T polymorphisms (n=55). Conclusion: Balanced translocations are the most commonly detected chromosomal abnormalities in couples being evaluated for recurrent pregnancy loss and these patients are the best candidates for offering prenatal genetic diagnosis by the help of which there is a possibility of obtaining a better reproductive outcome

Neuroenteric cyst with both thoracic and spinal component: A neonatal case report [Yenidogan döneminde torasik ve spinal kanal komponentli olan nöroenterik kist: Bir vaka takdimi]

Neuroenteric cysts are rare congenital lesions and they appear due to defect in leaving of notocord from foregut. A definitive diagnosis is made by histopathological examination. Here is a case of a neonate with neuroenteric cyst that is presented by both the thoracic and spinal canal component. Spinal canal component of the neuroenteric cysts must not be forgotten, if there is a suspicion of posterior mediastinal neuroenteric cysts in prenatal ultrasonographic examination. In the diagnosis and treatment of neuroenteric cyst, radiology, surgery, pathology, and neonatology disciplines have to work together

Psychiatric symptoms and disorders among Yazidi children and adolescents immediately after forced migration following ISIS attacks | Psychiatrische Symptome und Störungen bei jesidischen Kindern und Jugendlichen unmittelbar nach erzwungener Migration infolge von IS-Angriffen

Background The aim of the present study was to evaluate psychiatric problems and disorders among Yazidi Kurd refugee children and adolescents, who were assessed immediately after their forced migration following life-threatening attacks by ISIS terrorists. Methods We retrospectively analyzed the psychiatric assessments of 38 Yazidi children and adolescents (age 218, mean 12 years, m:f = 16:22), which were performed upon their arrival at the refugee camp. Results All children and adolescents exhibited psychiatric problems and disorders, 50% had one, and 50% had more than one. The most relevant problems were disturbed sleeping (71% of children), followed by depression (36.8%), conversion disorders (28.9%), adjustment (21.8%), acute (18.4%) and posttraumatic stress (PTSD, 10.5%) disorders, and non-organic enuresis (18.4%). Conclusion Our study confirms the results of previous studies, asserting that refugee children and adolescents do not just suffer from PTSD but from various other problems that are already present in the first days of resettlement. Children and adolescents living in refugee camps urgently need psychosocial support.(VLID)348262

The importance of the mean platelet volume in the diagnosis of supraventricular tachycardia

Background: This retrospective study aimed to investigate the diagnostic relation between the mean platelet volume (MPV) and supraventricular tachyarrhythmia (SVT) in patient with documented atrial tachyarrhythmia in the emergency department (ED). Methods: Two study groups were compared; a SVT group with arrive at the ED with documented SVT (n=122) and 100 healthy adult without any palpitation symptom, arrhythmic disease, and with normal physical examination results that were brought for checkups to the cardiology polyclinic were classified as control group. Blood samples were obtained from all patients for determining the hematologic counts and MPV during first hour in ED period. Results: In terms of the focus of the study, hemoglobin, neutrophil count, mean cell volume (MCV), red cell distribution width (RDW), platelet, white blood cell (WBC), and lymphocyte counts were similar in both group (p>0.05). MPV in the SVT group was significantly higher than in the control group (9.12±1.22 flvs 8.64±0.89 fl, p<0.001). Multivariate logistic regression analysis showed that just MPV was independent predictor of SVT in patients with palpitation in ED (odds ratio [OR] 8.497, 95% confidence interval (6.181 to 12.325), p=0.012). Conclusions: The present study described that MPV is helpful parameter for the diagnosis of SVT in emergency department, for the first time in the literature

Generation of integration-free induced pluripotent stem cells from a patient with Familial Mediterranean Fever (FMF)

Fibroblasts from a Familial Mediterranean Fever (FMF) patient were reprogrammed with episomal vectors by using the Neon Transfection System for the generation of integration-free induced pluripotent stem cells (iPSCs). The resulting iPSC line was characterized to determine the expression of pluripotency markers, proper differentiation into three germ layers, the presence of normal chromosomal structures as well as the lack of genomic integration. A homozygous missense mutation in the MEFV gene (p.Met694Val), which lead to typical FMF phenotype, was shown to be present in the generated iPSC line

Real life profile of asthma and chronic obstructive pulmonary disease patients in Turkey

Despite the presentation of similar symptoms, the airway diseases have different underlying pathophysiological processes and must be distinguished to enable the administration of appropriate treatment. In several studies the clinician- and patient-related causes of poor compliance to treatment in asthma/chronic obstructive pulmonary disease (COPD) patients have been evaluated. This study aimed to determine the clinical and sociodemographic characteristics of newly diagnosed treatment-naïve asthma and COPD patients in Turkey