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Cell permeable, small molecule inhibitors are powerful tools for interrogating kinase function and validating drug targets. In this issue of Cell Chemical Biology, Liu and colleagues (2020) describe the development of a toolkit containing a highly selective DCLK1 inhibitor and complementary DCLK1 mutants for interrogating DCLK1-dependent cellular processes.

In early 2020, during the COVID-19 pandemic, New Zealand implemented graduated, risk-informed national COVID-19 suppression measures aimed at disease elimination. We investigated their impacts on the epidemiology of the first wave of COVID-19 in the country and response performance measures.

We did a descriptive epidemiological study of all laboratory-confirmed and probable cases of COVID-19 and all patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in New Zealand from Feb 2 to May 13, 2020, after which time community transmission ceased. We extracted data from the national notifiable diseases database and the national SARS-CoV-2 test results repository. Demographic features and disease outcomes, transmission patterns (source of infection, outbreaks, household transmission), time-to-event intervals, and testing coverage were described over five phases of the response, capturing different levels of non-pharmaceutical interventions. click here Risk factors for severe outcomes (hospitalisare residency (adjusted OR 3·86 [1·59-9·35]), and Pacific peoples (adjusted OR 2·76 [1·14-6·68]) and Asian (2·15 [1·10-4·20]) ethnicities relative to European or other. Times from illness onset to notification and isolation progressively decreased and testing increased over the study period, with few disparities and increasing coverage of females, Māori, Pacific peoples, and lower socioeconomic groups.

New Zealand's response resulted in low relative burden of disease, low levels of population disease disparities, and the initial achievement of COVID-19 elimination.

Ministry of Business Innovation and Employment Strategic Scientific Investment Fund, and Ministry of Health, New Zealand.

Ministry of Business Innovation and Employment Strategic Scientific Investment Fund, and Ministry of Health, New Zealand.

Preterm birth is the leading cause of child mortality globally, with many survivors experiencing long-term adverse consequences. Preliminary evidence suggests that numbers of preterm births greatly reduced following implementation of policy measures aimed at mitigating the effects of the COVID-19 pandemic. We aimed to study the impact of the COVID-19 mitigation measures implemented in the Netherlands in a stepwise fashion on March 9, March 15, and March 23, 2020, on the incidence of preterm birth.

We used a national quasi-experimental difference-in-regression-discontinuity approach. We used data from the neonatal dried blood spot screening programme (2010-20) cross-validated against national perinatal registry data. Stratified analyses were done according to gestational age subgroups, and sensitivity analyses were done to assess robustness of the findings. We explored potential effect modification by neighbourhood socioeconomic status, sex, and small-for-gestational-age status.

Data on 1 599 547 singletcidence of preterm births in the following months, in agreement with preliminary observations elsewhere. Integration of comparable data from across the globe is needed to further substantiate these findings and start exploring underlying mechanisms.

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None.The PTEN tumor suppressor controls cell death and survival by regulating functions of various molecular targets. While the role of PTEN lipid-phosphatase activity on PtdIns(3,4,5)P3 and inhibition of PI3K pathway is well characterized, the biological relevance of PTEN protein-phosphatase activity remains undefined. Here, using knockin (KI) mice harboring cancer-associated and functionally relevant missense mutations, we show that although loss of PTEN lipid-phosphatase function cooperates with oncogenic PI3K to promote rapid mammary tumorigenesis, the additional loss of PTEN protein-phosphatase activity triggered an extensive cell death response evident in early and advanced mammary tumors. Omics and drug-targeting studies revealed that PI3Ks act to reduce glucocorticoid receptor (GR) levels, which are rescued by loss of PTEN protein-phosphatase activity to restrain cell survival. Thus, we find that the dual regulation of GR by PI3K and PTEN functions as a rheostat that can be exploited for the treatment of PTEN loss-driven cancers.Some prion-like domains and low-complexity regions provide the multivalency required to facilitate protein phase separation to regulate protein function. Jung et al. (2020) demonstrate how natural selection of the ELF3 prion-like domain gives rise to an intuitive biological switch that directly responds to temperature.In this issue of Molecular Cell, Kim et al., 2020 report that PCAF is a fork-associated histone acetyltransferase (HAT) that regulates the stability of stalled forks and the response to PARP inhibition in BRCA1/2-deficient cells.Eisenbart et al. (2020) find an SSR-associated sRNA, NikS, that is subject to variable repeat-controlled expression. NikS regulates H. pylori virulence by post-transcriptionally repressing pathogenicity factors, including CagA and VacA, via base-pairing to their mRNAs.Faecalibacterium is prevalent in the human gut and a promising microbe for the development of next-generation probiotics (NGPs) or biotherapeutics. Analyzing reference Faecalibacterium genomes and almost 3,000 Faecalibacterium-like metagenome-assembled genomes (MAGs) reconstructed from 7,907 human and 203 non-human primate gut metagenomes, we identified the presence of 22 different Faecalibacterium-like species-level genome bins (SGBs), some further divided in different strains according to the subject geographical origin. Twelve SGBs are globally spread in the human gut and show different genomic potential in the utilization of complex polysaccharides, suggesting that higher SGB diversity may be related with increased utilization of plant-based foods. Moreover, up to 11 different species may co-occur in the same subject, with lower diversity in Western populations, as well as intestinal inflammatory states and obesity. The newly explored Faecalibacterium diversity will be able to support the choice of strains suitable as NGPs, guided by the consideration of the differences existing in their functional potential.