Coronavirus disease (COVID-19), caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a worldwide challenge effecting millions of people in more than 210 countries, including the Sultanate of Oman (Oman). Spatiotemporal analysis was adopted to explore the spatial patterns of the spread of COVID-19 during the period from 29th April to 30th June 2020. Our assessment was made using five geospatial techniques within a Geographical Information System (GIS) context, including a weighted mean centre (WMC), standard deviational ellipses, Moran’s I autocorrelation coefficient, Getis-Ord General-G high/low clustering, and Getis-Ord $$G_{i}^{*}$$ G i ∗ statistic. The Moran’s I-/G- statistics proved that COVID-19 cases in datasets (numbers of cases) were clustered throughout the study period. The Moran’s I and Z scores were above the 2.25 threshold (a confidence level above 95%), ranging from 2274 cases on 29th April to 40,070 cases on 30th June 2020. The results of $$G_{i}^{*}$$ G i ∗ showed varying rates of infections, with a large spatial variability between the different wilayats (district). The epidemic situation in some wilayats, such as Mutrah, As-Seeb, and Bowsher in the Muscat Governorate, was more severe, with Z score higher than 5, and the current transmission still presents an increasing trend. This study indicated that the directional pattern of COVID-19 cases has moved from northeast to northwest and southwest, with the total impacted region increasing over time. Also, the results indicate that the rate of COVID-19 infections is higher in the most populated areas. The findings of this paper provide a solid basis for future study by investigating the most resolute hotspots in more detail and may help decision-makers identify targeted zones for alleviation plans.

SOCS2 is a pleiotropic E3 ligase. Its deficiency is associated with gigantism and organismal lethality upon inflammatory challenge. However, mechanistic understanding of SOCS2 function is dismal due to our unawareness of its protein substrates. We performed a mass spectrometry based proteomic profiling upon SOCS2 depletion and yield quantitative data for ~4200 proteins. Through this screen we identify a novel target of SOCS2, the serine-threonine kinase NDR1. Over-expression of SOCS2 accelerates turnover, while its knockdown stabilizes, endogenous NDR1 protein. SOCS2 interacts with NDR1 and promotes its degradation through K48-linked ubiquitination. Functionally, over-expression of SOCS2 antagonizes NDR1-induced TNFα-stimulated NF-κB activity. Conversely, depletion of NDR1 rescues the effect of SOCS2-deficiency on TNFα-induced NF-κB transactivation. Using a SOCS2−/− mice model of colitis we show that SOCS2-deficiency is pro-inflammatory and negatively correlates with NDR1 and nuclear p65 levels. Lastly, we provide evidence to suggest that NDR1 acts as an oncogene in prostate cancer. To the best of our knowledge, this is the first report of an identified E3 ligase for NDR1. These results might explain how SOCS2-deficiency leads to hyper-activation of NF-κB and downstream pathological implications and posits that SOCS2 induced degradation of NDR1 may act as a switch in restricting TNFα-NF-κB pathway.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in humans and is characterized with poor outcome. In this study, we investigated components of prolactin (Prl) system in cell models of GBM and in histological tissue sections obtained from GBM patients. Expression of Prolactin receptor (PrlR) was detected at high levels in U251-MG, at low levels in U87-MG and barely detectable in U373 cell lines and in 66% of brain tumor tissues from 32 GBM patients by immunohistochemical technique. In addition, stimulation of U251-MG and U87-MG cells but not U373 with Prl resulted in increased STAT5 phosphorylation and only in U251-MG cells with increased cellular invasion. Furthermore, STAT5 phosphorylation and cellular invasion induced in Prl stimulated cells were significantly reduced by using a Prl receptor antagonist that consists of Prl with four amino acid replacements. We conclude that Prl receptor is expressed at different levels in the majority of GBM tumors and that blocking of PrlR in U251-MG cells significantly reduce cellular invasion.

Increasing evidence suggests that signaling through the prolactin/prolactin receptor axis is important for stimulation the growth of many cancers including glioblastoma multiforme, breast and ovarian carcinoma. Efficient inhibitors of signaling have previously been developed but their applicability as cancer drugs is limited by the short in vivo half-life. In this study, we show that a fusion protein, consisting of the prolactin receptor antagonist PrlRA and an albumin binding domain for half-life extension can be expressed as inclusion bodies in Escherichia coli and efficiently refolded and purified to homogeneity. The fusion protein was found to have strong affinity for the two intended targets: the prolactin receptor (K D = 2.3±0.2 nM) and mouse serum albumin (K D = 0.38±0.01 nM). Further investigation showed that it could efficiently prevent prolactin mediated phosphorylation of STAT5 at 100 nM concentration and above, similar to the PrlRA itself, suggesting a potential as drug for cancer therapy in the future. Complexion with HSA weakened the affinity for the receptor to 21±3 nM, however the ability to prevent phosphorylation of STAT5 was still prominent. Injection into rats showed a 100-fold higher concentration in blood after 24 h compared to PrlRA itself.