THE BIG TREK. FLEEING AND MIGRATIONS IN 20TH CENTURY

Autor govori o jednom od najvećih problema dvadesetog stoljeća – problemu migracija. Rad je podijeljen u četiri dijela: u prvom, pažnju posvećuje empirijskim nalazima; u drugom govori o uzrocima unutarnjih i međunarodnih migracija; treći dio je skiciranje mogućih perspektiva i, četvrti, označavanje mogućih prijedloga kao protumjera. Dvadeseto stoljeće razlikuje se po premještanju regionalnih težišta migracija. U prvoj polovici stoljeća međunarodna kretanja izbjeglica uglavnom se događaju na europskom prostoru. U drugoj polovici stoljeća, težište migracija pomaknuto je sa sjeverne na južnu Zemljinu polutku. Jedan od glavnih uzroka migracijama je rat i nasilje koje ga prati. Teška gospodarska situacija, nagli porast stanovništva, ekološke katastrofe i erozija tradicijskih svjetonazora, također su važni uzroci. S obzirom na obilježja glavnih uzroka migracija, teško je vjerovati da će se situacija početkom 21. stoljeća značajnije poboljšati. Međunarodnim organizacijama i državama ostaje jedino ublažavanje toga problema kroz kreiranja dugoročnih strategija kojima bi se pokušalo djelovati na uzroke migracija.The author deals with one of the most pressing problems of the 20th century – the problem of migrations. The essay is divided into four parts. In the first, the author presents empirical findings; in the second, he deals with the causes of the intra- and inter-national migrations; the third part is an outline of feasible perspectives, while the fourth offers possible options as countermeasures. The 20th century is characterized by the shift of the regional focal points of migrations. In the first half of the century, the inter-national migrations of refugees largely took place in Europe. However, in the second half of the century, the hub of the migrations shifted from the northern to the southern hemisphere. One of the major causes of migrations are wars and the accompanying violence. Other important causes are economic hardships, population boom, ecological disasters and the erosion of traditional values. Judging by the characteristics of the major causes of migrations, it is very unlikely that the situation at the turn of the millennium is going to change significantly. The only thing international organizations and states can do is to alleviate this problem by creating long-term strategies that might strike at the roots of the migration issue

Transcriptome profiles of latently- and reactivated HIV-1 infected primary CD4+ T cells: A pooled data-analysis

The main obstacle to cure HIV-1 is the latent reservoir. Antiretroviral therapy effectively controls viral replication, however, it does not eradicate the latent reservoir. Latent CD4+ T cells are extremely rare in HIV-1 infected patients, making primary CD4+ T cell models of HIV-1 latency key to understanding latency and thus finding a cure. In recent years several primary CD4+ T cell models of HIV-1 latency were developed to study the underlying mechanism of establishing, maintaining and reversing HIV-1 latency. In the search of biomarkers, primary CD4+ T cell models of HIV-1 latency were used for bulk and single-cell transcriptomics. A wealth of information was generated from transcriptome analyses of different primary CD4+ T cell models of HIV-1 latency using latently- and reactivated HIV-1 infected primary CD4+ T cells. Here, we performed a pooled data-analysis comparing the transcriptome profiles of latently- and reactivated HIV-1 infected cells of 5 in vitro primary CD4+ T cell models of HIV-1 latency and 2 ex vivo studies of reactivated HIV-1 infected primary CD4+ T cells from HIV-1 infected individuals. Identifying genes that are differentially expressed between latently- and reactivated HIV-1 infected primary CD4+ T cells could be a more successful strategy to better understand and characterize HIV-1 latency and reactivation. We observed that natural ligands and coreceptors were predominantly downregulated in latently HIV-1 infected primary CD4+ T cells, whereas genes associated with apoptosis, cell cycle and HLA class II were upregulated in reactivated HIV-1 infected primary CD4+ T cells. In addition, we observed 5 differentially expressed genes that co-occurred in latently- and reactivated HIV-1 infected primary CD4+ T cells, one of which, MSRB2, was found to be differentially expressed between latently- and reactivated HIV-1 infected cells. Investigation of primary CD4+ T cell models of HIV-1 latency that mimic the in vivo state remains essential for the study of HIV-1 latency and thus providing the opportunity to compare the transcriptome profile of latently- and reactivated HIV-1 infected cells to gain insights into differentially expressed genes, which might contribute to HIV-1 latency. Keywords: HIV-1 latency reversal agents; latently HIV-1 infected primary CD4+ T cells; pooled data-analysis; pooled data-analysis differentially expressed genes (pdaDEGs); primary CD4+ T cell models of HIV-1 latency; reactivated HIV-1 infected primary CD4+ T cells; transcriptome profil

Deletions of CDKN2A and MTAP Detected by Copy-Number Variation Array Are Associated with Loss of p16 and MTAP Protein in Pleural Mesothelioma

CDKN2A deletion is a common alteration in pleural mesothelioma (PM) and frequently associated with co-deletion of MTAP. Since the standard detection method for CDKN2A deletion and FISH analysis is relatively expensive, we here investigated the suitability of inexpensive p16 and MTAP IHC by comparing concordance between IHC and OncoScan CNV arrays on samples from 52 PM patients. Concordance was determined using Cohen's kappa statistics. Loss of CDKN2A was associated with co-deletion of MTAP in 71% of cases. CDKN2A-MTAP copy-number normal cases were also IHC positive in 93% of cases for p16 and 100% for MTAP, while homozygous deletion of CDKN2A-MTAP was always associated with negative IHC for both proteins. In cases with heterozygous CDKN2A-MTAP loss, IHC expression of p16 and MTAP was negative in 100% and 71%, respectively. MTAP and p16 IHC showed high sensitivity (MTAP 86.5%, p16 100%) and specificity (MTAP 100%, p16 93.3%) for the detection of any gene loss. Loss of MTAP expression occurred exclusively in conjunction with loss of p16 labeling. Both p16 and MTAP IHC showed high concordance with Oncoscan CNV arrays (kappa = 0.952, p < 0.0001, and kappa = 0.787, p < 0.0001 respectively). We recommend combined MTAP and p16 immunohistochemistry to confirm the diagnosis of PM

Systemic sclerosis-associated pulmonary hypertension: why disease-specific composite endpoints are needed

Pulmonary arterial hypertension (PAH) is a serious complication of systemic sclerosis (SSc). In clinical trials PAH-SSc has been grouped with other forms, including idiopathic PAH. The primary endpoint for most pivotal studies was improvement in exercise capacity. However, composite clinical endpoints that better reflect long-term outcome may be more meaningful. We discuss potential endpoints and consider why the same measures may not be appropriate for both idiopathic PAH and PAH-SSc due to inherent differences in clinical outcome and management strategies of these two forms of PAH. Failure to take this into account may compromise progress in managing PAH in SSc

Solar wind ion trends and signatures: STEREO PLASTIC observations approaching solar minimum

STEREO has now completed the first two years of its mission, moving from close proximity to Earth in 2006/2007 to more than 50 degrees longitudinal separation from Earth in 2009. During this time, several large-scale structures have been observed in situ. Given the prevailing solar minimum conditions, these structures have been predominantly coronal hole-associated solar wind, slow solar wind, their interfaces, and the occasional transient event. In this paper, we extend earlier solar wind composition studies into the current solar minimum using high-resolution (1-h) sampling times for the charge state analysis. We examine 2-year trends for iron charge states and solar wind proton speeds, and present a case study of Carrington Rotation 2064 (December 2007) which includes minor ion (He, Fe, O) kinetic and Fe composition parameters in comparison with proton and magnetic field signatures at large-scale structures observed during this interval