Australian surveys on incidence and control of blowfly strike in sheep between 2003 and 2019 reveal increased use of breeding for resistance, treatment with preventative chemicals and pain relief around mulesing.

Blowfly strike or cutaneous myiasis, caused principally by the Australian sheep blowfly Lucilia cuprina is endemic to Australian sheep producing areas and is a major cause of suffering and economic loss. This article reports incidence and control practices as determined by three cross-sectional surveys of Australian sheep farmers covering the years 2003 (n = 1365), 2011 (n = 575) and 2018 (n = 354) with more questions relating to blowfly strike in the latter two surveys. Breech strike was reported at a higher rate than body strike in all survey years. Reported annual incidence of breech strike ranged from 2.2 to 4.7% of sheep nationally with minor differences between ewes and lambs. The incidence of body strike ranged from 1.0 to 7.1% with higher incidence in younger sheep in all years. The use of fixed time routine preventative chemical treatments increased during the survey period (43%, 46% and 66%, in 2003, 2011 and 2018 respectively) with dicyclanil (54%-58%) and cyromazine (23-36%) the main insecticides used for control since 2011. The use of the Mules operation (mulesing) to remove skin wrinkles from the breech area as a preventative modification did not change between 2011 and 2018 (47% in both), however, the use of pain relief at mulesing of replacement ewe lambs increased substantially between 2011 (59%) and 2018 (87%). The most commonly used methods to assist with flystrike control were timing of crutching (clipping of wool from susceptible areas) and shearing, with few respondents destroying maggots from treated sheep (21-26%) and very low use of fly traps (5-8%). Phenotypic selection of ewes for reduced susceptibility to flystrike based on visual traits was practiced by 61% of respondents in 2011 and 56% in 2018. Selection of rams for reduced susceptibility using estimated breeding values increased from 10% in 2011 to 17% in 2018. Breeding for resistance was the most commonly nominated (21%) most important change made to flystrike management in 2018. The results indicate that concern for sheep welfare has increased with almost universal use of pain relief at mulesing. Increased use of selection for blowfly resistance indicates farmer commitment to planning for a future without mulesing, although the practice remains prevalent. An increase in the reliance on preventative chemical treatments increases the risk of insecticide resistance.

Prevalence of sheep lice and trends in control practices across Australia - Australian sheep parasite control surveys from 2003 to 2019.

The sheep body louse (Bovicola ovis) is a parasite of major economic concern in Australia. This article reports lice incidence and control practices on Australian sheep farms as determined by three cross-sectional surveys of the years 2003, 2011 and 2018. The incidence of live lice detected within a flock was similar across the survey years with a slight decline in 2018 (2003: 20%, 2011: 18.6% and 2018: 13.9%). In an average year, most farmers did not see any direct or indirect evidence of lice infestation (2011: 59.3% and 2018: 69.5%), however, over a five-year period 38.9% (2003), 66.3% (in 2011) and 55.8% (in 2018) reported seeing evidence of lice infestation at least once with significant variation between sheep producing regions in 2011. In an average year, nearly three quarters of respondents treated for lice (2011:73.5% and 2018: 73.3%) with the majority treating immediately following shearing and very few treating sheep with long wool. Even higher percentages treated for lice at least once in the preceding five-year period (2011: 86.2% and 2018: 87.5%). Backliner was the most popular method of chemical application for lice control in sheep off-shears or with short wool (2003: 77%, 2011: 73% and 2018: 74.3%). For long wool treatments, hand jetting declined in popularity from 2003 (64%) to 2011 (54%) and 2018 (8.6%) as backliners became more popular (2003: 36%, 2011: 51% and 2018: 60%). The use of benzoylphenyl urea insect growth regulators (IGR) for off-shears/short wool treatment declined from 2003 (92.8%) to 2011 (51%) and 2018 (2.9%) and were largely replaced by neonicotinoids and spinosad for backliner/spray-on products. The use of organophosphates declined for plunge dipping (2003: 83.8%, 2011: 83% and 2018: 7.7%). Spinosad use for plunge dipping off-shears/short wool increased over the survey years (2003, 0%, 2011: 9% and 2018:46.2%). The use of IGRs declined for backliner application on long wool and were mainly replaced by spinosad in 2011 and 2018. Fewer respondents reported suspected resistance to lice control products in 2018 (8%) compared with 2003 (26%) and 2011 (13%) with most reporting suspected resistance to IGR and synthetic pyrethroids and emerging suspicions of resistance to neonicotinoids in 2018. Resistance to lice control products also reduced in importance as a reason for recurring lice infestations between 2011 (ranked 2nd) and 2018 (ranked 6th). Biosecurity was important to sheep producers with the highest ranked reason for recurring lice infestations being from stray or purchased sheep.

Benchmarking Australian sheep parasite control: Changes in gastrointestinal nematode control practices reported from surveys between 2003 and 2019.

Cross-sectional surveys of sheep parasite control practices in Australia were conducted in 2004, 2012 and 2019 to document parasite problems, control practices and measure change over time. This article reports the results pertaining to gastrointestinal nematode infection; comparisons between years are mostly descriptive and not based on statistical inference. There was a general increase in the use of grazing management to prepare clean pastures for sheep to control gastrointestinal nematode infections with the largest increases in the use of: cropping, long acting anthelmintics to prepare clean pastures, feeding strategies, selecting rams for resistance to nematodes, and leaving some sheep untreated. The proportion of respondents using faecal worm egg count monitoring (WEC) and the number of WEC monitors per year were similar in 2003 (weaners: 3.0 WEC/year, adult ewes: 2.6 WEC/year) and 2018 (lambs and weaners and adult ewes both 3.1 WEC/year) but lower in 2011(lambs and weaners: 2.0 WEC/year, adult ewes: 2.9 WEC/year), whilst there was a higher number of anthelmintic treatments given in 2011 than 2003 and 2018 which were similar. There was an increase in the proportion of respondents carrying out WEC monitors themselves from 2011 (21%) to 2018 (30%) and a corresponding reduction in the use of private laboratories, government laboratories and veterinarians with regional differences in who carried out WECs. The top three anthelmintic groups used did not differ between the three survey years with macrocyclic lactones the most used followed by benzimidazoles (BZ) and levamisole (LEV) although the percentage of MLs used in 2011 and 2018 was lower than in 2003 with higher proportions of respondents using BZ and LEV groups in the latter two survey years. Moxidectin was in the most commonly used active in all survey years. There was an increase in the use of combination of anthelmintics from different groups, especially for a combination of three anthelmintics (2003: 4.4%, 2011: 19.1%, 2018: 21.5%), with lower use of single anthelmintics in 2011 (57.0%) and 2018 (55.4%) compared with 2003 (74.5%). The use of testing for anthelmintic resistance was generally low across the survey years with a lower proportion of respondents using tests in 2011 and 2018 than in 2003 (2003:48%, 2011: 29%, 2018: 37%). Time of year, results from WEC and seasonal weather condition were the most important factors when deciding when to apply anthelmintic treatment.

Predicting aortic complications after endovascular aneurysm repair.

BACKGROUND: Lifelong surveillance is standard after endovascular repair of abdominal aortic aneurysm (EVAR), but remains costly, heterogeneous and poorly calibrated. This study aimed to develop and validate a scoring system for aortic complications after EVAR, informing rationalized surveillance. METHODS: Patients undergoing EVAR at two centres were studied from 2004 to 2010. Preoperative morphology was quantified using three-dimensional computed tomography according to a validated protocol, by investigators blinded to outcomes. Proportional hazards modelling was used to identify factors predicting aortic complications at the first centre, and thereby derive a risk score. Sidak tests between risk quartiles dichotomized patients to low- or high-risk groups. Aortic complications were reported by Kaplan-Meier analysis and risk groups were compared by log rank test. External validation was by comparison of aortic complications between risk groups at the second centre. RESULTS: Some 761 patients, with a median age of 75 (interquartile range 70-80) years, underwent EVAR. Median follow-up was 36 (range 11-94) months. Physiological variables were not associated with aortic complications. A morphological risk score incorporating maximum aneurysm diameter (P < 0·001) and largest common iliac diameter (measured 10 mm from the internal iliac origin; P = 0·004) allocated 75 per cent of patients to a low-risk group, with excellent discrimination between 5-year rates of aortic complication in low- and high-risk groups at both centres (centre 1: 12 versus 31 per cent, P < 0·001; centre 2: 12 versus 45 per cent, P = 0·002). CONCLUSION: The risk score uses commonly available morphological data to stratify the rate of complications after EVAR. The proposals for rationalized surveillance could provide clinical and economic benefits.

In situ TEM studies of local transport and structure in nanoscale multilayer films.

This paper describes a novel technique for studying structure-transport correlations in nanoscale multilayer thin films. Here, local current-voltage characteristics from simplified magnetic tunnel junctions are measured in situ on cross-sectional transmission electron microscopy (TEM) samples and correlated directly with TEM images of the microstructure at the tunneling site. It is found that local variations in barrier properties can be detected by a point probe method, and that the tunneling barrier height and width can be extracted.

Carbon : nitrogen : phosphorus ratios influence biofilm formation by Enterobacter cloacae and Citrobacter freundii.

AIMS: To test the effects of C : N : P ratio modification of a well-known nutrient medium formulation, the Endo formulation on biofilm formation by Enterobacter cloacae Ecl and Citrobacter freundii Cf1 in both single-species and binary species biofilms. METHODS AND RESULTS: The C : N : P atom : atom ratio of a well-known nutrient medium formulation, the Endo formulation, that has been applied in fermentative biohydrogen studies, was modified to include two different C concentrations, one containing 17.65 g l(-1) and the other 8.84 g l(-1) sucrose, each containing four different C : N : P ratios, two at higher C : N : P ratios (334 : 84 : 16.8 and 334 : 84 : 3) and two at lower C : N : P ratios (334 : 28 : 5.6 and 334 : 28 : 1). Attached cells were enumerated after dislodging the biofilms that had formed on granular activated carbon (GAC). The modified medium containing 17.65 g l(-1) sucrose and having a C : N : P ratio of 334 : 28 : 5.6 resulted in significantly (P < 0.05) higher counts of attached cells for both single-species biofilms at 7.73 log(10) CFU g(-1) GAC and 9.3 log(10)CFU g(-1) GAC for Ent. cloacae Ecl and Cit. freundii Cf1, respectively, and binary species biofilms at 8.2 log(10) CFU g(-1) GAC and 6.34 log(10) CFU g(-1) GAC for Ent. cloacae Ecl and Cit. freundii Cf1, respectively. Scanning electron micrographs showed qualitative evidence that the 334 : 28 : 5.6 ratio encouraged more complex and extensive biofilm growth for both single-species and binary species biofilms. CONCLUSIONS: The differences in the attachment numbers between the different ratios were found not to be a result of the individual actions of the bacterial isolates involved but rather because of the effects of the various C : N : P ratios. The 334 : 28 : 5.6 ratio showed significantly (P < 0.05) higher counts of attached cells for both single-species and binary species biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: This study indicates that C : N : P ratios should be a key consideration with regard to maximizing biofilm formation in shake flask and fluidized bed bioreactor studies as well as understanding fundamental factors affecting biofilm growth in natural environments.

Brodifacoum toxicosis in two neonatal puppies.

Eight out of a litter of 13 puppies were either born dead or died within 48 hours of birth. Three puppies that died shortly after birth were necropsied. Two puppies had hemorrhage in the thoracic and peritoneal cavities, intestinal serosa, and meninges. The third puppy was smaller than the other two puppies but did not have detectable hemorrhage. Brodifacoum, a second-generation coumarin anticoagulant, was detected in livers from the two puppies with hemorrhage. The dam did not have clinical signs of coagulopathy before or subsequent to whelping. The owners were confident that the dog had not been exposed to rodenticide for at least 4 weeks before whelping. A presumptive diagnosis of in utero brodifacoum toxicity was made. To the authors' knowledge this is the first time a second-generation coumarin anticoagulant has been detected in the liver of a newborn animal. This case is also unique because the dam was unaffected, suggesting that fetuses are more susceptible to brodifacoum toxicity than adult animals.

Collective effects in grain boundary migration.

In situ high-resolution transmission electron microscopy is used to study grain boundary structure and kinetics in bicrystalline Au films at elevated temperature. We report the first direct evidence for the existence of cooperative atomic motion in grain boundary migration. Certain nanoregions at grain boundaries, typically involving up to several hundred atoms, are found to switch back and forth between neighboring grains. Reversible structural fluctuations at temperatures near 0.5T(m) and above have been discovered in [110] and [001] tilt, as well as in general grain boundaries.

Post-immunisation gastritis and Helicobacter infection in the mouse: a long term study.

BACKGROUND AND AIMS: Helicobacter pylori is a major cause of peptic ulcers and gastric cancer. Vaccine development is progressing but there is concern that immunisation may exacerbate Helicobacter induced gastritis: prophylactic immunisation followed by challenge with H felis or H pylori can induce a more severe gastritis in mice than seen with infection alone. The aim of this study was to investigate the relationship between immunity to Helicobacter infection and post-immunisation gastritis. METHODS: (1) C57BL/6 mice were prophylactically immunised before challenge with either H felis or H pylori. Histopathology and colonisation were assessed one month post-challenge. (2) C57BL/6 mice were prophylactically immunised against H felis infection and gastritis assessed up to 18 months post-challenge. RESULTS: Prophylactic immunisation induced a reduction in bacterial colonisation following H felis challenge which was associated with increased severity of active gastritis with neutrophil infiltration and atrophy. However, immunised mice challenged with H pylori SS1 had little evidence of pathology. Long term follow up showed that post-immunisation gastritis was evident at three months. However, from six months onwards, although immunised/challenged mice still developed gastritis, there was no significant difference between inflammation in these mice and infected controls. Post-immunisation gastritis was not associated with the serum antibody response. Immunisation prevented the formation of secondary lymphoid aggregates in the gastric tissue. CONCLUSION: The H felis mouse model of post-immunisation gastritis is the most extreme example of this type of pathology. We have shown in this model that post-immunisation gastritis is a transient event which does not produce long term exacerbation of pathology.

The potential toxicity of Ilex myrtifolia in beef cattle.

Spatial and temporal patterns of death loss in a beef cowherd indicated a possible relationship between the loss of 11 cows and the consumption of Ilex myrtifolia (myrtle leaf holly). To investigate this relationship, plant material from Ilex myrtifolia was harvested and 2 feeding trials were performed. The 1st trial involved intermittent feeding of plant material to 4-mo-o calves for 2 w, and the 2nd trial was continuous plant feeding to 2-mo-o calves for 35 d. No significant clinical pathology, histological or gross lesions resulted and no clinical signs consistent with the original herd problem were observed, suggesting that berries, leaves and stems from Ilex myrtifolia were not sufficiently toxic to induce clinical effects under these experimental conditions.

PTP-epsilon, a tyrosine phosphatase expressed in endothelium, negatively regulates endothelial cell proliferation.

The vascular endothelium is a dynamic interface between the blood vessel and circulating factors and, as such, plays a critical role in vascular events like inflammation, angiogenesis, and hemostasis. Whereas specific protein tyrosine kinases have been identified in these processes, less is known about their protein tyrosine phosphatase (PTP) counterparts. We utilized a RT-PCR/differential hybridization assay to identify PTP-epsilon as a highly abundant endothelial cell PTP. PTP-epsilon mRNA expression is growth factor responsive, suggesting a role for this enzyme in endothelial cell proliferation. Overexpression of PTP-epsilon decreases proliferation by 60% in human umbilical vein endothelial cells (HUVEC) but not in smooth muscle cells or fibroblasts. In contrast, overexpression of PTP-epsilon (D284A), a catalytically inactive mutant, has no significant effect on HUVEC proliferation. These data provide the first functional characterization of PTP-epsilon in endothelial cells and identify a novel pathway that negatively regulates endothelial cell growth. Such a pathway may have important implications in vascular development and angiogenesis.

Aging, oxidative responses, and proliferative capacity in cultured mouse aortic smooth muscle cells.

The cellular mechanisms that contribute to the acceleration of atherosclerosis in aging populations are poorly understood, although it is hypothesized that changes in the proliferative capacity of vascular smooth muscle cells is contributory. We addressed the relationship among aging, generation of reactive oxygen species (ROS), and proliferation in primary culture smooth muscle cells (SMC) derived from the aortas of young (4 mo old) and aged (16 mo old) mice to understand the phenotypic modulation of these cells as aging occurs. SMC from aged mice had decreased proliferative capacity in response to alpha-thrombin stimulation, yet generated higher levels of ROS and had constitutively increased mitogen-activated protein kinase activity, in comparison with cells from younger mice. These effects may be explained by dysregulation of cell cycle-associated proteins such as cyclin D1 and p27Kip1 in SMC from aged mice. Increased ROS generation was associated with decreased endogenous antioxidant activity, increased lipid peroxidation, and mitochondrial DNA damage. Accrual of oxidant-induced damage and decreased proliferative capacity in SMC may explain, in part, the age-associated transition to plaque instability in humans with atherosclerosis.

The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins.

To maintain quality control in cells, mechanisms distinguish among improperly folded peptides, mature and functional proteins, and proteins to be targeted for degradation. The molecular chaperones, including heat-shock protein Hsp90, have the ability to recognize misfolded proteins and assist in their conversion to a functional conformation. Disruption of Hsp90 heterocomplexes by the Hsp90 inhibitor geldanamycin leads to substrate degradation through the ubiquitin-proteasome pathway, implicating this system in protein triage decisions. We previously identified CHIP (carboxyl terminus of Hsc70-interacting protein) to be an interaction partner of Hsc70 (ref. 4). CHIP also interacts directly with a tetratricopeptide repeat acceptor site of Hsp90, incorporating into Hsp90 heterocomplexes and eliciting release of the regulatory cofactor p23. Here we show that CHIP abolishes the steroid-binding activity and transactivation potential of the glucocorticoid receptor, a well-characterized Hsp90 substrate, even though it has little effect on its synthesis. Instead, CHIP induces ubiquitylation of the glucocorticoid receptor and degradation through the proteasome. By remodelling Hsp90 heterocomplexes to favour substrate degradation, CHIP modulates protein triage decisions that regulate the balance between protein folding and degradation for chaperone substrates.

Custer, selenium and swainsonine.

The Battle of Little Bighorn was fought over 100 y ago but many controversies remain. Some feel the defeat of Custer could have been avoided if Benteen and Reno had united with Custer. A slow-moving pack train may have hindered the troops of Benteen and Reno from joining up with Custer. One report indicated the horses and mules in the pack train were lame and behaved crazily. It has been previously suggested that the animals had selenium toxicosis. We propose the lameness could have been caused by selenium, but that the behavioral problems may have been caused by the ingestion of plants containing swainsonine.

Hemorrhagic diathesis, mesenteric hematoma, and colic associated with ingestion of sweet vernal grass in a cow.

A 4-year-old Holstein cow from a farm where 2 cows had recently died suddenly was referred for evaluation of acute severe colic. Right flank laparotomy revealed a large mesenteric hematoma. Within 14 layer chromatographic analyses of the moldy hay and blood from the necropsied cow and the hospitalized cow were positive for dicumarol. A diagnosis of sweet vernal poisoning was confirmed on the basis of clinical and toxicologic findings. The cow was treated with supportive therapy, blood transfusions, and vitamin K1 and recovered without complications. Because sweet vernal grass is becoming common in certain areas and the use of round bales is commonplace, practitioners should be aware of the potential for this toxicosis.

Unique and recurrent WAS gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia.

Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) are allelic phenotypes caused by defects of the WAS gene. Fourteen distinct mutations including seven novel gene defects in 16 WAS and four XLT patients were identified by single strand conformation polymorphism analysis and DNA sequencing of the WAS gene. Eleven (79%) of these mutations are located within exons 1 to 4 with clustering in exon 2. Carrier detection in 33 at-risk females and prenatal diagnosis at 12 weeks gestation in one family with a novel WAS mutation was performed by direct mutation analysis. A remarkably high frequency (72%) of point mutations involved CpG dinucleotides. C-->T or G-->A transitions at CpG sites were identified in all isolated WAS cases (n = 7). Allele frequencies for the dinucleotide repeat at locus DXS6940 were determined in Northern European, African and Asian populations. Mutation screening alone or in combination with analysis of polymorphic loci DXS6940 and DXS255 delineated the germline origin of a unique insertion mutation and four recurrent CpG mutations, three of which arose spontaneously during maternal gametogenesis.

Flavopiridol inhibits smooth muscle cell proliferation in vitro and neointimal formation In vivo after carotid injury in the rat.

BACKGROUND: Smooth muscle cell (SMC) proliferation is a critical component of neointimal formation in many models of vascular injury and in human lesions as well. Cell-cycle inhibition by gene transfer techniques can block SMC proliferation and lesion formation in animal models, although these methods are not yet applicable to the treatment of human disease. Flavopiridol is a recently identified, potent, orally available cyclin-dependent kinase inhibitor. METHODS AND RESULTS: Using human aortic SMCs, we found that flavopiridol in concentrations as low as 75 nmol/L resulted in nearly complete inhibition of basic fibroblast growth factor-induced and thrombin-induced proliferation. At this dose, flavopiridol inhibited cyclin-dependent kinase activity, as measured by histone H1 phosphorylation, but had no effect on mitogen-activated protein kinase activation. Induction of the cell cycle-related proteins cyclin D1, proliferating cell nuclear antigen, and phosphorylated retinoblastoma protein was also blocked by flavopiridol. Flavopiridol had no effect on cellular viability. To test whether flavopiridol had a similar activity in vivo when administered orally, we examined neointimal formation in rat carotid arteries after balloon injury. Flavopiridol 5 mg/kg reduced neointimal area by 35% and 39% at 7 and 14 days, respectively, after injury. CONCLUSIONS: Flavopiridol inhibits SMC growth in vitro and in vivo. Its oral availability and selectivity for cyclin-dependent kinases make it a potential therapeutic tool in the treatment of SMC-rich vascular lesions.

The safety of newly approved medicines: do recent market removals mean there is a problem?

The removal of 5 pharmaceuticals from the market in a 12-month period because of unexpected adverse events raised concerns about the adequacy of the drug review process at the US Food and Drug Administration (FDA). Specifically, concerns were raised about improvements in drug review efficiency that significantly reduced FDA review times. We have reviewed the circumstances of the 5 removals to determine whether there was any relationship to the increased efficiencies in the drug review process. When the removed drugs were analyzed by date of approval, no increase in the number of drugs taken off the market was seen, demonstrating that reduced review processing time was not the reason for the cluster of removals. We conclude that the agency's drug review procedures and postmarketing surveillance system after a drug has been marketed are currently adequate but must continually adjust to future challenges.

Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions.

The chaperone function of the mammalian 70-kDa heat shock proteins Hsc70 and Hsp70 is modulated by physical interactions with four previously identified chaperone cofactors: Hsp40, BAG-1, the Hsc70-interacting protein Hip, and the Hsc70-Hsp90-organizing protein Hop. Hip and Hop interact with Hsc70 via a tetratricopeptide repeat domain. In a search for additional tetratricopeptide repeat-containing proteins, we have identified a novel 35-kDa cytoplasmic protein, carboxyl terminus of Hsc70-interacting protein (CHIP). CHIP is highly expressed in adult striated muscle in vivo and is expressed broadly in vitro in tissue culture. Hsc70 and Hsp70 were identified as potential interaction partners for this protein in a yeast two-hybrid screen. In vitro binding assays demonstrated direct interactions between CHIP and both Hsc70 and Hsp70, and complexes containing CHIP and Hsc70 were identified in immunoprecipitates of human skeletal muscle cells in vivo. Using glutathione S-transferase fusions, we found that CHIP interacted with the carboxy-terminal residues 540 to 650 of Hsc70, whereas Hsc70 interacted with the amino-terminal residues 1 to 197 (containing the tetratricopeptide domain and an adjacent charged domain) of CHIP. Recombinant CHIP inhibited Hsp40-stimulated ATPase activity of Hsc70 and Hsp70, suggesting that CHIP blocks the forward reaction of the Hsc70-Hsp70 substrate-binding cycle. Consistent with this observation, both luciferase refolding and substrate binding in the presence of Hsp40 and Hsp70 were inhibited by CHIP. Taken together, these results indicate that CHIP decreases net ATPase activity and reduces chaperone efficiency, and they implicate CHIP in the negative regulation of the forward reaction of the Hsc70-Hsp70 substrate-binding cycle.

Identification of protein phosphatase 1 as a mitotic lamin phosphatase.

At the onset of mitosis, the nuclear lamins are hyperphosphorylated leading to nuclear lamina disassembly, a process required for nuclear envelope breakdown and entry into mitosis. Multiple lamin kinases have been identified, including protein kinase C, that mediate mitotic lamin phosphorylation and mitotic nuclear lamina disassembly. Conversely, lamin dephosphorylation is required for nuclear lamina reassembly at the completion of mitosis. However, the protein phosphatase(s) responsible for the removal of mitotic phosphates from the lamins is unknown. In this study, we use human lamin B phosphorylated at mitosis-specific sites as a substrate to identify and characterize a lamin phosphatase activity from mitotic human cells. Several lines of evidence demonstrate that the mitotic lamin phosphatase corresponds to type 1 protein phosphatase (PP1). First, mitotic lamin phosphatase activity is inhibited by high nanomolar concentrations of okadaic acid and the specific PP1 peptide inhibitor, inhibitor-2. Second, mitotic lamin phosphatase activity cofractionates with PP1 after ion exchange chromatography. Third, microcystin-agarose depletes mitotic extracts of both PP1 and lamin phosphatase activity. Our results demonstrate that PP1 is the major mitotic lamin phosphatase responsible for removal of mitotic phosphates from lamin B, a process required for nuclear lamina reassembly.