Investigating the association between COVID-19 vaccination and care home outbreak frequency and duration.

OBJECTIVES: At the end of 2020, many countries commenced a vaccination programme against SARS-CoV-2. Public health authorities aim to prevent and interrupt outbreaks of infectious disease in social care settings. We aimed to investigate the association between the introduction of the vaccination programme and the frequency and duration of COVID-19 outbreaks in Northern Ireland (NI). STUDY DESIGN: We undertook an ecological study using routinely available national data. METHODS: We used Poisson regression to measure the relationship between the number of RT-PCR confirmed COVID-19 outbreaks in care homes, and as a measure of community COVID-19 prevalence, the Office for National Statistics COVID-19 Infection Survey estimated the number of people testing positive for COVID-19 in NI. We estimated the change in this relationship and estimated the expected number of care home outbreaks in the absence of the vaccination programme. A Cox proportional hazards model estimated the hazard ratio of a confirmed COVID-19 care home outbreak closure. RESULTS: Care home outbreaks reduced by two-thirds compared to expected following the introduction of the vaccination programme, from a projected 1625 COVID-19 outbreaks (95% prediction interval 1553-1694) between 7 December 2020 and 28 October 2021 to an observed 501. We estimated an adjusted hazard ratio of 2.53 of the outbreak closure assuming a 21-day lag for immunity. CONCLUSIONS: These findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate the effectiveness of the vaccines and the duration of their effects.

First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland.

Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02). For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.

Pair Correlations and Photoassociation Dynamics of Two Atoms in an Optical Tweezer.

We investigate the photoassociation dynamics of exactly two laser-cooled ^{85}Rb atoms in an optical tweezer and reveal fundamentally different behavior to photoassociation in many-atom ensembles. We observe nonexponential decay in our two-atom experiment that cannot be described by a single rate coefficient and find its origin in our system's pair correlation. This is in stark contrast to many-atom photoassociation dynamics, which are governed by decay with a single rate coefficient. We also investigate photoassociation in a three-atom system, thereby probing the transition from two-atom dynamics to many-atom dynamics. Our experiments reveal additional reaction dynamics that are only accessible through the control of single atoms and suggest photoassociation could measure pair correlations in few-atom systems. It further showcases our complete control over the quantum state of individual atoms and molecules, which provides information unobtainable from many-atom experiments.

Bioturbation by a reintroduced digging mammal reduces fuel loads in an urban reserve.

Digging animals may alter many characteristics of their environment as they disrupt and modify the ground's surface by creating foraging pits or burrows. Extensive disturbance to the soil and litter layer changes litter distribution and availability, potentially altering fuel loads. In many landscapes, including peri-urban areas, fire management to reduce fuel loads is complex and challenging. The reintroduction of previously common digging animals, many of which are now threatened, may have the added benefit of reducing fuel loads. We experimentally examined how the reintroduction of a marsupial bandicoot, quenda (Isoodon fusciventer), altered surface fuel loads in an urban bush reserve in Perth, Western Australia. Foraging activities of quenda (where they dig for subterranean food) were substantial throughout the reserve, creating a visibly patchy distribution in surface litter. Further, in open plots where quenda had access, compared to fenced plots where quenda were excluded, quenda foraging significantly reduced litter cover and litter depth. Similarly, estimated surface fuel loads were nearly halved in open plots where quenda foraged compared to fenced plots where quenda were absent (3.6 cf. 6.4 Mg/ha). Fire behavior modeling, using the estimated surface fuel loads, indicated the predicted rate of spread of fire were significantly lower for open plots where quenda foraged compared to fenced plots under both low (29.2 cf. 51.4 m/h; total fuels) and high (74.3 cf. 130.4 m/h; total fuels) fire conditions. Although many environments require fire, including the bushland where this study occurred, fire management can be a considerable challenge in many landscapes, including urban bushland reserves, which are usually small and close to human infrastructure. The reintroduction of previously common digging species may have potential value as a complimentary tool for reducing fuel loads, and potentially, fire risk.

A fast radio burst localized to a massive galaxy.

Intense, millisecond-duration bursts of radio waves (named fast radio bursts) have been detected from beyond the Milky Way1. Their dispersion measures-which are greater than would be expected if they had propagated only through the interstellar medium of the Milky Way-indicate extragalactic origins and imply contributions from the intergalactic medium and perhaps from other galaxies2. Although several theories exist regarding the sources of these fast radio bursts, their intensities, durations and temporal structures suggest coherent emission from highly magnetized plasma3,4. Two of these bursts have been observed to repeat5,6, and one repeater (FRB 121102) has been localized to the largest star-forming region of a dwarf galaxy at a cosmological redshift of 0.19 (refs. 7-9). However, the host galaxies and distances of the hitherto non-repeating fast radio bursts are yet to be identified. Unlike repeating sources, these events must be observed with an interferometer that has sufficient spatial resolution for arcsecond localization at the time of discovery. Here we report the localization of a fast radio burst (FRB 190523) to a few-arcsecond region containing a single massive galaxy at a redshift of 0.66. This galaxy is different from the host of FRB 121102, as it is a thousand times more massive, with a specific star-formation rate (the star-formation rate divided by the mass) a hundred times smaller.

Cryopreservation of saltwater crocodile (Crocodylus porosus) spermatozoa.

The aim of the present study was to develop a protocol for the successful cryopreservation of Saltwater crocodile spermatozoa. Sperm cells were frozen above liquid nitrogen vapour in phosphate-buffered saline (PBS) containing either 0.3M trehalose, 0.3M raffinose or 0.3M sucrose and compared with glycerol (0.3-2.7M). Although the highest levels of mean post-thaw motility were observed following cryopreservation in 0.3M trehalose (7.6%) and 0.3M sucrose (7.3%), plasma membrane integrity (PI) was best following cryopreservation in 2.7M glycerol (52.5%). A pilot study then assessed the cytotoxicity of glycerol and sucrose prior to cryopreservation and revealed no loss of survival when spermatozoa were diluted in 0.68M glycerol or 0.2-0.3M sucrose once cryoprotectants were washed out with PBS or Biggers, Whitten and Whittingham medium containing sperm capacitation agents (BWWCAP). A final study refined the combined use of permeating (0.68 or 1.35M glycerol) and non-permeating (0.2 or 0.3M sucrose) cryoprotectants. Spermatozoa were cryopreserved in liquid nitrogen vapour at rates of approximately -21°Cmin-1 (fast freeze) or -6.0°Cmin-1 (slow freeze). Post-thaw survival was highest with a combination of 0.2M sucrose and 0.68M glycerol and when these cryoprotectants were washed out with BWWCAP, regardless of whether spermatozoa were frozen using a fast (motility 14.2±4.7%; PI 20.7±2.0%) or slow (motility 12.0±2.7%; PI 22±4%) cryopreservation rate.

Loss of Keratin 17 induces tissue-specific cytokine polarization and cellular differentiation in HPV16-driven cervical tumorigenesis in vivo.

Despite preventive human papilloma virus (HPV) vaccination efforts, cervical cancer remains a leading cause of death in women worldwide. Development of therapeutic approaches for cervical cancer are hampered by a lack of mechanistic insight during tumorigenesis. The cytoskeletal protein Keratin 17 (KRT17;K17) is robustly expressed in a broad array of carcinomas, including in cervical tumors, where it has both diagnostic and prognostic value. In this study, we have established multiple functional roles for K17 in the promotion of cervical tumorigenesis in vivo using the established HPV16tg mouse model for cervical squamous cell carcinoma. In HPV16tg/+;Krt17-/-relative to HPV16tg/+ reference female mice, onset of cervical lesions is delayed and closely paralleled by marked reductions in hyperplasia, dysplasia and vascularization. In addition, loss of Krt17 is associated with a cytokine polarization and recruitment of effector immune cells to lesion-prone cervical epithelia. Further, we observed marked enhancement of terminal differentiation in HPV16tg/+;Krt17-/-cervical epithelium accompanied by a stimulation and expansion in the expression of p63, a known basal/reserve cell marker in this tissue. Altogether, the data suggest that the loss of Krt17 may foster an overall protective environment for lesion-prone cervical tissue. In addition to providing new insights into the immunomodulatory and cellular mechanisms of cervical tumorigenesis, these findings may help guide the development of future therapies including vaccines.

Designs for a quantum electron microscope.

One of the astounding consequences of quantum mechanics is that it allows the detection of a target using an incident probe, with only a low probability of interaction of the probe and the target. This 'quantum weirdness' could be applied in the field of electron microscopy to generate images of beam-sensitive specimens with substantially reduced damage to the specimen. A reduction of beam-induced damage to specimens is especially of great importance if it can enable imaging of biological specimens with atomic resolution. Following a recent suggestion that interaction-free measurements are possible with electrons, we now analyze the difficulties of actually building an atomic resolution interaction-free electron microscope, or "quantum electron microscope". A quantum electron microscope would require a number of unique components not found in conventional transmission electron microscopes. These components include a coherent electron beam-splitter or two-state-coupler, and a resonator structure to allow each electron to interrogate the specimen multiple times, thus supporting high success probabilities for interaction-free detection of the specimen. Different system designs are presented here, which are based on four different choices of two-state-couplers: a thin crystal, a grating mirror, a standing light wave and an electro-dynamical pseudopotential. Challenges for the detailed electron optical design are identified as future directions for development. While it is concluded that it should be possible to build an atomic resolution quantum electron microscope, we have also identified a number of hurdles to the development of such a microscope and further theoretical investigations that will be required to enable a complete interpretation of the images produced by such a microscope.

AXSIS: Exploring the frontiers in attosecond X-ray science, imaging and spectroscopy.

X-ray crystallography is one of the main methods to determine atomic-resolution 3D images of the whole spectrum of molecules ranging from small inorganic clusters to large protein complexes consisting of hundred-thousands of atoms that constitute the macromolecular machinery of life. Life is not static, and unravelling the structure and dynamics of the most important reactions in chemistry and biology is essential to uncover their mechanism. Many of these reactions, including photosynthesis which drives our biosphere, are light induced and occur on ultrafast timescales. These have been studied with high time resolution primarily by optical spectroscopy, enabled by ultrafast laser technology, but they reduce the vast complexity of the process to a few reaction coordinates. In the AXSIS project at CFEL in Hamburg, funded by the European Research Council, we develop the new method of attosecond serial X-ray crystallography and spectroscopy, to give a full description of ultrafast processes atomically resolved in real space and on the electronic energy landscape, from co-measurement of X-ray and optical spectra, and X-ray diffraction. This technique will revolutionize our understanding of structure and function at the atomic and molecular level and thereby unravel fundamental processes in chemistry and biology like energy conversion processes. For that purpose, we develop a compact, fully coherent, THz-driven atto-second X-ray source based on coherent inverse Compton scattering off a free-electron crystal, to outrun radiation damage effects due to the necessary high X-ray irradiance required to acquire diffraction signals. This highly synergistic project starts from a completely clean slate rather than conforming to the specifications of a large free-electron laser (FEL) user facility, to optimize the entire instrumentation towards fundamental measurements of the mechanism of light absorption and excitation energy transfer. A multidisciplinary team formed by laser-, accelerator,- X-ray scientists as well as spectroscopists and biochemists optimizes X-ray pulse parameters, in tandem with sample delivery, crystal size, and advanced X-ray detectors. Ultimately, the new capability, attosecond serial X-ray crystallography and spectroscopy, will be applied to one of the most important problems in structural biology, which is to elucidate the dynamics of light reactions, electron transfer and protein structure in photosynthesis.

High-density Au nanorod optical field-emitter arrays.

We demonstrate the design, fabrication, characterization, and operation of high-density arrays of Au nanorod electron emitters, fabricated by high-resolution electron beam lithography, and excited by ultrafast femtosecond near-infrared radiation. Electron emission characteristic of multiphoton absorption has been observed at low laser fluence, as indicated by the power-law scaling of emission current with applied optical power. The onset of space-charge-limited current and strong optical field emission has been investigated so as to determine the mechanism of electron emission at high incident laser fluence. Laser-induced structural damage has been observed at applied optical fields above 5 GV m(-1), and energy spectra of emitted electrons have been measured using an electron time-of-flight spectrometer.

Use of the FLUKA Monte Carlo code for 3D patient-specific dosimetry on PET-CT and SPECT-CT images.

Patient-specific absorbed dose calculation for nuclear medicine therapy is a topic of increasing interest. 3D dosimetry at the voxel level is one of the major improvements for the development of more accurate calculation techniques, as compared to the standard dosimetry at the organ level. This study aims to use the FLUKA Monte Carlo code to perform patient-specific 3D dosimetry through direct Monte Carlo simulation on PET-CT and SPECT-CT images. To this aim, dedicated routines were developed in the FLUKA environment. Two sets of simulations were performed on model and phantom images. Firstly, the correct handling of PET and SPECT images was tested under the assumption of homogeneous water medium by comparing FLUKA results with those obtained with the voxel kernel convolution method and with other Monte Carlo-based tools developed to the same purpose (the EGS-based 3D-RD software and the MCNP5-based MCID). Afterwards, the correct integration of the PET/SPECT and CT information was tested, performing direct simulations on PET/CT images for both homogeneous (water) and non-homogeneous (water with air, lung and bone inserts) phantoms. Comparison was performed with the other Monte Carlo tools performing direct simulation as well. The absorbed dose maps were compared at the voxel level. In the case of homogeneous water, by simulating 10(8) primary particles a 2% average difference with respect to the kernel convolution method was achieved; such difference was lower than the statistical uncertainty affecting the FLUKA results. The agreement with the other tools was within 3­4%, partially ascribable to the differences among the simulation algorithms. Including the CT-based density map, the average difference was always within 4% irrespective of the medium (water, air, bone), except for a maximum 6% value when comparing FLUKA and 3D-RD in air. The results confirmed that the routines were properly developed, opening the way for the use of FLUKA for patient-specific, image-based dosimetry in nuclear medicine.

Monte Carlo-based 3-dimensional dosimetry of salivary glands in radioiodine treatment of differentiated thyroid cancer estimated using 124I PET.

AIM: Salivary gland toxicity is of concern in radioiodine treatment of thyroid cancer. Toxicity is often observed while the estimated radiation absorbed dose (AD) values are below expected toxicity thresholds. Monte Carlo-based voxelized 3-dimensional radiobiological dosimetry (3D-RD) calculations of the salivary glands from eight metastatic thyroid cancer patients treated with 131I are presented with the objective of resolving this discrepancy. METHODS: GEANT4 Monte Carlo simulations were performed for 131I, based on pretherapeutic 124I PET/CT imaging corrected for partial volume effect, and the results scaled to the therapeutic administered activities. For patients with external regions of high uptake proximal to the salivary glands, such as thyroid remnants or lymph node metastases, separate simulations were run to quantify the AD contributions from both (A) the salivary glands themselves, and (B) the external proximal region of high uptake (present for five patients). The contribution from the whole body outside the field of view was also estimated using modeling. Voxelized and average ADs and biological effective doses (BEDs) were calculated. RESULTS: The estimated average therapeutic ADs were 2.26 Gy considering all contributions and 1.94 Gy from the self-dose component only. The average contribution from the external region of high uptake was 0.54 Gy. This difference was more pronounced for the submandibular glands (2.64 versus 2.10 Gy) compared to the parotid glands (1.88 Gy versus 1.78 Gy). The BED values were on average only 6.6 % higher than (2.41 Gy) the ADs. CONCLUSION: The external sources of activity contribute significantly to the salivary gland AD, however neither this contribution, nor the radiobiological effect quantified by the BED are in themselves sufficient to explain the clinically observed toxicity.

A new Eimeria species parasitic in Isoodon obesulus (Marsupialia: Peramelidae) in Western Australia.

Feces from southern brown bandicoots, Isoodon obesulus, inhabiting the Perth metropolitan area were examined using fecal flotation and light microscopy, and were frequently found to contain oocysts (10/24; 42%). To enable formal description of the proposed new Eimeria species, i.e., Eimeria quenda n. sp., fecal oocysts from 1 juvenile male I. obesulus were allowed to sporulate in 2% potassium dichromate (K(2)Cr(2)O(7)) at room temperature. Sporulated oocysts are spheroidal to subspheroidal 24.5 × 23.6 (22.5-26.0 × 22.5-24.8) µm, with L/W ratio of 1.04 (1.00-1.13), lack a micropyle and oocyst residuum, and are contained within a smooth trilaminate oocyst wall 1.8 (1.6-2.0) µm thick. Sporocysts are ovoid, 12.6 × 9.2 (12.0-13.8 × 8.5-10.0) µm, with L/W ratio of 1.37 (1.20-1.53), have a sporocyst residuum, and 2 comma-shaped sporozoites, each containing 2 spheroidal refractile bodies. Sporulation takes 1-3 days at room temperature. This is the second formal description of an Eimeria species parasitic in the order Peramelemorphia.

Iron deficiency anaemia and delayed diagnosis of colorectal cancer: a retrospective cohort study.

AIM: The extent to which different referral pathways following a primary care diagnosis of iron deficiency anaemia (IDA) are associated with delay in diagnosis of colorectal cancer (CRC) was determined. METHOD: Eligible patients aged 40 or more years, with IDA diagnosed in primary care, and a subsequent diagnosis of CRC, were studied retrospectively. Referral pathways were identified using the specialty of first recorded GP referral following IDA diagnosis. Differences in time to diagnosis of CRC were assessed by referral specialty. Differences in the proportion of cases referred before and after the re-issue of the NICE urgent referral guidelines for suspected lower gastrointestinal (GI) cancer were also assessed. RESULTS: Of 628,882 eligible patients, 3.1% (n = 19,349) were diagnosed with IDA during the study period; 3.0% (n = 578) were subsequently diagnosed with CRC. Two hundred and fifty-nine (44.8%) patients had no recorded referral or a referral unrelated to anaemia or the GI tract. Only 35% (n = 201) of patients were referred to a relevant specialty. Median time to CRC diagnosis ranged from 2.5 months (referral to a relevant surgical specialty) to 31.9 months (haematology). Time to diagnosis was longer in patients referred to a medical compared with a relevant surgical specialty (P = 0.024). There was no significant difference in time to CRC diagnosis before and after the NICE guidelines were re-issued in 2005. CONCLUSION: Significant differences exist between referral specialties in time to CRC diagnosis following a primary care diagnosis of IDA. Despite NICE referral recommendations, a significant proportion of patients are still not managed within recommended care pathways to CRC diagnosis.

Improved probability of detection of ecological "surprises".

Ecological "surprises" are defined as unexpected findings about the natural environment. They are critically important in ecology because they are catalysts for questioning and reformulating views of the natural world, help shape assessments of the veracity of a priori predictions about ecological trends and phenomena, and underpin questioning of effectiveness of resource management. Despite the importance of ecological surprises, major gaps in understanding remain about how studies might be done differently or done better to improve the ability to identify them. We outline the kinds of ecological surprises that have arisen from long-term research programs that we lead in markedly different ecosystems around the world. Based on these case studies, we identify important lessons to guide both existing studies and new investigations to detect ecological surprises more readily, better anticipate unusual ecological phenomena, and take proactive steps to plan for and alleviate "undesirable" ecological surprises. Some of these lessons include: (i) maintain existing, and instigate new, long-term studies; (ii) conduct a range of kinds of parallel and concurrent research in a given target area; (iii) better use past literature and conceptual models of the target ecosystem in posing good questions and developing hypotheses and alternative hypotheses; and (iv) increase the capacity for ecological research to take advantage of opportunities arising from major natural disturbances. We argue that the increased anticipatory capability resulting from these lessons is critical given that ecological surprises may become more prevalent because of climate change and multiple and interacting environmental stressors.

Factors affecting attitudes toward colorectal cancer screening in the primary care population.

BACKGROUND: Colorectal cancer (CRC) is a major cause of death in the United Kingdom. Regular screening could significantly reduce CRC-related morbidity and mortality. However, screening programmes in the United Kingdom have to date seen uptake rates of less than 60%. Attitudes towards screening are the primary factors determining patient uptake. METHODS: A questionnaire was sent to people aged 50-69 years who were registered with general practices in the West Midlands. A total of 11 355 people (53%) completed the questionnaire. Multivariable logistic regression analyses were performed to identify those factors (gender, age, ethnicity, deprivation, number of symptoms, and their duration) that most strongly contributed to negative/positive attitudes in the primary care population. RESULTS: Fourteen percent of respondents had a negative attitude towards screening. Men, older people, and those with Indian ethnic backgrounds were more likely to have negative attitudes toward screening, whereas people with Black-Caribbean ethnic background, people with multiple symptoms and those reporting abdominal pain, bleeding, and tiredness were more likely to have a positive attitude. CONCLUSION: Culturally relevant screening strategies should aim to increase knowledge of the symptoms and signs related to bowel cancer among South Asian ethnic groups in the United Kingdom. It is also important to find ways to increase the acceptability of screening among asymptomatic patients.

The benefits of male ejaculate sex peptide transfer in Drosophila melanogaster.

The accessory gland protein (Acp) ejaculate molecules of male Drosophila melanogaster mediate sexual selection and sexual conflict at the molecular level. However, to date no studies have comprehensively measured the timing and magnitude of fitness benefits to males of transferring specific Acps. This is an important omission because without this information it is not possible to fully understand the strength and form of selection acting on adaptations such as Acps. Here, we measured the fitness benefits to males of ejaculate sex peptide (SP) transfer. SP is of interest because it is a candidate for mediating sexual conflict: its frequent receipt reduces female fitness. In single matings with virgin females SP is known to increase egg laying and decrease receptivity. Hence, we predicted that SP could: (i) boost a male's absolute paternity by increasing offspring production and delaying female remating and/or (ii) boost relative paternity share. We tested these predictions using two different lines of SP-lacking males, in both two-mating and free-mating assay conditions. SP transfer conferred higher absolute, but not relative, male reproductive success. In matings with virgin females, SP transfer increased mating productivity and delayed remating and hence the onset of sperm competition. In already mated females, SP transfer did not elevate absolute progeny production, but did increase intermating intervals and hence the period over which a male could gain paternity. Consistent with this, under free-mating conditions over an extended period, we detected a 'per-mating' fitness benefit for males transferring SP. These benefits are consistent with a role for SP in mediating conflict, with SP acting to maximize short-term fitness benefits for males.

Cyclin-dependent kinase antagonizes promyelocytic leukemia zinc-finger through phosphorylation.

Acute promyelocytic leukemia is associated with chromosomal translocations that involve the RARalpha gene and several distinct loci producing a variety of fusion proteins. One such fusion partner is promyelocytic leukemia zinc-finger gene (PLZF), a member of the POK (POZ and Krüppel) family of transcriptional repressors that is a key developmental regulator, stem cell maintenance factor and tumor suppressor. Overexpression of PLZF has been shown to induce cell cycle arrest at the G(1) to S transition and repress the expression of key pro-proliferative genes such as CCNA2 and MYC. However, given this data suggesting an important growth inhibitory role for PLZF, relatively little is known regarding regulation of its activity. Here we show that the main cyclin-dependent kinase involved at the G(1) to S transition (CDK2) phosphorylates PLZF at two consensus sites found within PEST domains present in the hinge region of the protein. This phosphorylation triggers the ubiquitination and subsequent degradation of PLZF, which impairs PLZF transcriptional repression ability and antagonizes its growth inhibitory effects. This critical mechanism of PLZF regulation may thus be relevant for cell cycle progression during the development and the pathogenesis of human cancer.