LICHENS AS INDICATORS OF AIR QUALITY IN BALNEOLOGICAL CENTER PROLOM BANJA (SOUTHERN SERBIA)

This paper deals with using lichens as a bioindicators of the air quality and it was conducted on the territory of balneological center Prolom Banja (Southern Serbia). The exploration was conducted in the year 2019. The analysis of the sample from 15 investigated points indicates the presence of 72 lichen taxa, which shows that this area is rich in lichen species. For each investigated point, the index values of atmospheric purity (IAP) and index of human impact (IHI) were calculated. The IAP values varied in range from 40 to 56, while IHI values ranged between 8 and 24. Therefore, the map showing the air quality of the investigated area was made. There is a presence of “normal lichen zone” on the map which indicates that the air quality in this area is quite good. There are no significant air pollution sources in this area, so the level of pollution is considered low or very low. In the investigated area there are not stations for the monitoring of physico-chemical parameters of air quality. The investigation of air quality on the territory of Prolom Banja has not been done until now.

Engineered Hyperactive Integrase for Concerted HIV-1 DNA Integration

The DNA cutting and joining reactions of HIV-1 integration are catalyzed by integrase (IN), a viral protein that functions as a tetramer bridging the two viral DNA ends (intasome). Two major obstacles for biochemical and structural studies of HIV-1 intasomes are 1) the low efficiency of assembly with oligonucleotide DNA substrates, and 2) the non-specific aggregation of both intasomes and free IN in the reaction mixture. By fusing IN with a small non-specific DNA binding protein, Sulfolobus solfataricus chromosomal protein Sso7d (PDB: 1BNZ), we have engineered a highly soluble and hyperactive IN. Unlike wild-type IN, it efficiently catalyzes intasome assembly and concerted integration with oligonucleotide DNA substrates. The fusion IN protein also functions to integrate viral reverse transcripts during HIV-infection. The hyperactive HIV-1 IN may assist in facilitating future biochemical and structural studies of HIV-1 intasomes. Understanding the mechanistic basis of the Sso7d-IN fusion protein could provide insight into the factors that have hindered biophysical studies of wild-type HIV-1 IN and intasomes

The global burden of scabies: a cross-sectional analysis from the Global Burden of Disease Study 2015.

Background Numerous population-based studies have documented high prevalence of scabies in overcrowded settings, particularly among children and in tropical regions. We provide an estimate of the global burden of scabies using data from the Global Burden of Disease (GBD) Study 2015. Methods We identified scabies epidemiological data sources from an extensive literature search and hospital insurance data and analysed data sources with a Bayesian meta-regression modelling tool, DisMod-MR 2·1, to yield prevalence estimates. We combined prevalence estimates with a disability weight, measuring disfigurement, itch, and pain caused by scabies, to produce years lived with disability (YLDs). With an assumed zero mortality from scabies, YLDs were equivalent to disability-adjusted life-years (DALYs). We estimated DALYs for 195 countries divided into 21 world regions, in both sexes and 20 age groups, between 1990 and 2015. Findings Scabies was responsible for 0·21% of DALYs from all conditions studied by GBD 2015 worldwide. The world regions of east Asia (age-standardised DALYs 136·32), southeast Asia (134·57), Oceania (120·34), tropical Latin America (99·94), and south Asia (69·41) had the greatest burden of DALYs from scabies. Mean percent change of DALY rate from 1990 to 2015 was less than 8% in all world regions, except North America, which had a 23·9% increase. The five individual countries with greatest scabies burden were Indonesia (age-standardised DALYs 153·86), China (138·25), Timor-Leste (136·67), Vanuatu (131·59), and Fiji (130·91). The largest standard deviations of age-standardised DALYs between the 20 age groups were observed in southeast Asia (60·1), Oceania (58·3), and east Asia (56·5), with the greatest DALY burdens in children, adolescents, and the elderly. Interpretation The burden of scabies is greater in tropical regions, especially in children, adolescents, and elderly people. As a worldwide epidemiological assessment, GBD 2015 provides broad and frequently updated measures of scabies burden in terms of skin effects. These global data might help guide research protocols and prioritisation efforts and focus scabies treatment and control measures. Funding Bill & Melinda Gates Foundation

Scabies prevalence after ivermectin-based mass drug administration for lymphatic filariasis, Samoa 2018–2019

Background: Scabies is a common skin infestation caused by the Sarcoptes scabei mite. Ivermectin, one of three drugs used in mass drug administration (MDA) for lymphatic filariasis, is also effec-tive for treating scabies. Ivermectin-based MDA was first conducted in Samoa in August 2018, with ivermectin being offered to those aged ≥5 years. Here, we report scabies prevalence in Samoa after MDA. Methods: We conducted household surveys 1.5–3.5 months (Survey 1) and 6–8 months (Survey 2) after the 2018 MDA in 35 primary sampling units. We conducted clinical examination for sca-bies-like rash and used International Alliance for the Control of Scabies classification crite-ria. We estimated scabies prevalence by age, gender and region. Multivariable logistic regression was used to assess factors associated with prevalence. Results: We surveyed 2868 people (499 households) and 2796 people (544 households) aged 0–75 years in Surveys 1 and 2, respectively. Scabies prevalence increased from 2.4% (95% CI 2.1–2.7%) to 4.4% (95% CI 4.0–4.9%) between surveys. Scabies was associated with younger age (0–4 years: aOR 3.5 [2.9–4.2]; 5–15 years: aOR 1.6 [1.4–1.8] compared to ≥16 years), female gender (aOR 1.2 [95% CI 1.1–1.4]; region (aOR range from 1.4 [1.1– 1.7] to 2.5 [2.1–3.1] between regions), large households (aOR 2.6 [2.0–3.4] households ≥13), and not taking MDA in 2018 (aOR 1.3 [95% CI 1.1–1.6]). Conclusions: We found moderate prevalence of scabies in two population-representative surveys conducted within 8 months of the 2018 MDA for lymphatic filariasis. Prevalence appeared to increase between the surveys, and ongoing surveillance is recommended, particularly in young children

Ack1 Mediated AKT/PKB Tyrosine 176 Phosphorylation Regulates Its Activation

The AKT/PKB kinase is a key signaling component of one of the most frequently activated pathways in cancer and is a major target of cancer drug development. Most studies have focused on its activation by Receptor Tyrosine Kinase (RTK) mediated Phosphatidylinositol-3-OH kinase (PI3K) activation or loss of Phosphatase and Tensin homolog (PTEN). We have uncovered that growth factors binding to RTKs lead to activation of a non-receptor tyrosine kinase, Ack1 (also known as ACK or TNK2), which directly phosphorylates AKT at an evolutionarily conserved tyrosine 176 in the kinase domain. Tyr176-phosphorylated AKT localizes to the plasma membrane and promotes Thr308/Ser473-phosphorylation leading to AKT activation. Mice expressing activated Ack1 specifically in the prostate exhibit AKT Tyr176-phosphorylation and develop murine prostatic intraepithelial neoplasia (mPINs). Further, expression levels of Tyr176-phosphorylated-AKT and Tyr284-phosphorylated-Ack1 were positively correlated with the severity of disease progression, and inversely correlated with the survival of breast cancer patients. Thus, RTK/Ack1/AKT pathway provides a novel target for drug discovery

Humanized Mice Are Instrumental to the Study of Plasmodium falciparum Infection

Research using humanized mice has advanced our knowledge and understanding of human haematopoiesis, non-adaptive and adaptive immunity, autoimmunity, infectious disease, cancer biology, and regenerative medicine. Challenges posed by the human-malaria parasite Plasmodium falciparum include its complex life cycle, the evolution of drug resistance against anti-malarials, poor diagnosis, and a lack of effective vaccines. Advancements in genetically engineered and immunodeficient mouse strains, have allowed for studies of the asexual blood stage, exoerythrocytic stage and the transition from liver-to-blood stage infection, in a single vertebrate host. This review discusses the process of “humanization” of various immunodeficient/transgenic strains and their contribution to translational biomedical research. Our work reviews the strategies employed to overcome the remaining-limitations of the developed human-mouse chimera(s)

Challenges of drug resistance in the management of pancreatic cancer

The current treatment of choice for metastatic pancreatic cancer involves single agent gemcitabine or combination of gemcitabine with capecitabine and erlotinib (tyrosine kinase inhibitor). Only 25-30% of patients respond to this treatment and patients who do respond initially ultimately exhibit disease progression. Median survival for pancreatic cancer patients has reached a plateau due to inherent and acquired resistance to these agents. Key molecular factors implicated in this resistance include: deficiencies in drug uptake, alteration of drug targets, activations of DNA repair pathways, resistance to apoptosis, and the contribution of the tumor microenvironment. Moreover, for newer agents including tyrosine kinase inhibitors, over expression of signaling proteins, mutations in kinase domains, activation of alternative pathways, mutations of genes downstream of the target, and/or amplification of the target represent key challenges for treatment efficacy. Here we will review the contribution of known mechanisms and markers of resistance to key pancreatic cancer drug treatments