SARS-CoV-2 is a zoonotic betacoronavirus that was first reported at the dawn of 2019 in Wuhan, China and has since spread globally, causing an ongoing pandemic. Anthroponotic transmission was ...reported early, with confirmed infections reported in 26 species to date, including dogs and cats. However, there is a paucity of reports on the transmission of SARS-CoV-2 to companion animals, and thus, we aimed to estimate the seroprevalence of SARS-CoV-2 in dogs and cats in Sarawak, Malaysia. From August 2022 to 2023, we screened plasma samples of 172 companion animals in Sarawak, Malaysia, using a species-independent surrogate virus neutralization test. Our findings revealed the presence of neutralizing antibodies of SARS-CoV-2 in 24.5% (27/110) of dogs and 24.2% (15/62) of cats. To the best of our knowledge, this is the first report of the seroprevalence of SARS-CoV-2 in companion animals in Malaysia. Our findings emphasize the need for pet owners to distance themselves from their pets when unwell, and a strategy must be in place to monitor SARS-CoV-2 in companion animals to assess the potential impact of the virus on companion animals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metastasis is the major cause of breast cancer mortality. Phosphoinositide 3-kinase (PI3K) generated PtdIns(3,4,5)P3 activates AKT, which promotes breast cancer cell proliferation and regulates ...migration. To date, none of the inositol polyphosphate 5-phosphatases that inhibit PI3K/AKT signaling have been reported as tumor suppressors in breast cancer. Here, we show depletion of the inositol polyphosphate 5-phosphatase PIPP (INPP5J) increases breast cancer cell transformation, but reduces cell migration and invasion. Pipp ablation accelerates oncogene-driven breast cancer tumor growth in vivo, but paradoxically reduces metastasis by regulating AKT1-dependent tumor cell migration. PIPP mRNA expression is reduced in human ER-negative breast cancers associated with reduced long-term outcome. Collectively, our findings identify PIPP as a suppressor of oncogenic PI3K/AKT signaling in breast cancer.
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•Pipp knockout promotes oncogene-driven breast cancer initiation and growth•Ablation of Pipp impairs metastasis in a mouse model of breast cancer•PIPP regulates AKT1-dependent cell migration and invasion•Low PIPP expression is associated with ER-negative breast cancer and poor prognosis
Ooms et al. identify the inositol polyphosphate 5-phosphatase PIPP as a suppressor of oncogenic PI3K/AKT signaling in breast cancer. PIPP depletion increases transformation and accelerates oncogene-driven tumor growth in vivo, while paradoxically reducing cell migration, invasion, and metastasis.
Phosphoinositides are membrane-bound signalling molecules that regulate cell proliferation and survival, cytoskeletal reorganization and vesicular trafficking by recruiting effector proteins to ...cellular membranes. Growth factor or insulin stimulation induces a canonical cascade resulting in the transient phosphorylation of PtdIns(4,5)P(2) by PI3K (phosphoinositide 3-kinase) to form PtdIns(3,4,5)P(3), which is rapidly dephosphorylated either by PTEN (phosphatase and tensin homologue deleted on chromosome 10) back to PtdIns(4,5)P(2), or by the 5-ptases (inositol polyphosphate 5-phosphatases), generating PtdIns(3,4)P(2). The 5-ptases also hydrolyse PtdIns(4,5)P(2), forming PtdIns4P. Ten mammalian 5-ptases have been identified, which share a catalytic mechanism similar to that of the apurinic/apyrimidinic endonucleases. Gene-targeted deletion of 5-ptases in mice has revealed that these enzymes regulate haemopoietic cell proliferation, synaptic vesicle recycling, insulin signalling, endocytosis, vesicular trafficking and actin polymerization. Several studies have revealed that the molecular basis of Lowe's syndrome is due to mutations in the 5-ptase OCRL (oculocerebrorenal syndrome of Lowe). Futhermore, the 5-ptases SHIP SH2 (Src homology 2)-domain-containing inositol phosphatase 2, SKIP (skeletal muscle- and kidney-enriched inositol phosphatase) and 72-5ptase (72 kDa 5-ptase)/Type IV/Inpp5e (inositol polyphosphate 5-phosphatase E) are implicated in negatively regulating insulin signalling and glucose homoeostasis in specific tissues. SHIP2 polymorphisms are associated with a predisposition to insulin resistance. Gene profiling studies have identified changes in the expression of various 5-ptases in specific cancers. In addition, 5-ptases such as SHIP1, SHIP2 and 72-5ptase/Type IV/Inpp5e regulate macrophage phagocytosis, and SHIP1 also controls haemopoietic cell proliferation. Therefore the 5-ptases are a significant family of signal-modulating enzymes that govern a plethora of cellular functions by regulating the levels of specific phosphoinositides. Emerging studies have implicated their loss or gain of function in human disease.
Sarawak has one of the highest diversity of fruit bats species (family Pteropodidae) in Malaysia, with 19 species described. Most coronavirus (CoV) studies have mainly focused on insectivorous bats, ...resulting in a lack of information on CoVs present in frugivorous bats. In addition, bat CoV surveillance activities are lacking in Malaysia.
Our study focuses on determining the presence of bat CoVs in dusky fruit bat (Penthetor lucasi).
Guano samples belonging to P. lucasi were collected from Wind Cave Nature Reserve. The samples were screened for the presence of CoVs using validated hemi-nested consensus RNA-dependent RNA polymerase consensus primers.
The bat CoV positivity rate was 38.5% (n = 15/39), with the viruses belonging to two subgenera: Alphacoronavirus (α-CoV) and Betacoronavirus (β-CoV). Phylogenetic analysis revealed that CoVs from 14 samples of P. lucasi belong to the genus α-CoV and may represent previously described genetic lineages in insectivorous bats in Wind Cave. However, only one sample of P. lucasi was detected with β-CoV which is closely related to subgenus Nobecovirus, which is commonly seen in frugivorous bats.
This study provides the first available data on CoVs circulating in P. lucasi.
Phosphatidylinositol 3-phosphate PtdIns(3)P regulates endocytic trafficking and the sorting of receptors through early endosomes, including the rapid recycling of transferrin (Tfn). However, the ...phosphoinositide phosphatase that selectively opposes this function is unknown. The myotubularins are a family of eight catalytically active and six inactive enzymes that hydrolyse PtdIns(3)P to form PtdIns. However, the role each myotubularin family member plays in regulating endosomal PtdIns(3)P and thereby endocytic trafficking is not well established. Here, we identify the myotubularin family member MTMR4, which localizes to early endosomes and also to Rab11- and Sec15-positive recycling endosomes. In cells with MTMR4 knockdown, or following expression of the catalytically inactive MTMR4, MTMR4C⁴⁰⁷A, the number of PtdIns(3)P-decorated endosomes significantly increased. MTMR4 overexpression delayed the exit of Tfn from early endosomes and its recycling to the plasma membrane. By contrast, expression of MTMR4C⁴⁰⁷A, which acts as a dominant-negative construct, significantly accelerated Tfn recycling. However, in MTMR4 knockdown cells Tfn recycling was unchanged, suggesting that other MTMs might also contribute to recycling. MTMR4 regulated the subcellular distribution of Rab11 and, in cells with RNAi-mediated knockdown of MTMR4, Rab11 was directed away from the pericentriolar recycling compartment. The subcellular distribution of VAMP3, a v-SNARE protein that resides in recycling endosomes and endosome-derived transport vesicles, was also regulated by MTMR4. Therefore, MTMR4 localizes at the interface of early and recycling endosomes to regulate trafficking through this pathway.
Phosphoinositide 3-kinase (PI3K) regulates cell polarity and migration by generating phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) at the leading edge of migrating cells. The ...serine-threonine protein kinase Akt binds to PI(3,4,5)P3, resulting in its activation. Active Akt promotes spatially regulated actin cytoskeletal remodeling and thereby directed cell migration. The inositol polyphosphate 5-phosphatases (5-ptases) degrade PI(3,4,5)P3 to form PI(3,4)P2, which leads to diminished Akt activation. Several 5-ptases, including SKIP and SHIP2, inhibit actin cytoskeletal reorganization by opposing PI3K/Akt signaling. In this current study, we identify a molecular co-chaperone termed silencer of death domains (SODD/BAG4) that forms a complex with several 5-ptase family members, including SKIP, SHIP1, and SHIP2. The interaction between SODD and SKIP exerts an inhibitory effect on SKIP PI(3,4,5)P3 5-ptase catalytic activity and consequently enhances the recruitment of PI(3,4,5)P3-effectors to the plasma membrane. In contrast, SODD−/− mouse embryonic fibroblasts exhibit reduced Akt-Ser473 and -Thr308 phosphorylation following EGF stimulation, associated with increased SKIP PI(3,4,5)P3-5-ptase activity. SODD−/− mouse embryonic fibroblasts exhibit decreased EGF-stimulated F-actin stress fibers, lamellipodia, and focal adhesion complexity, a phenotype that is rescued by the expression of constitutively active Akt1. Furthermore, reduced cell migration was observed in SODD−/− macrophages, which express the three 5-ptases shown to interact with SODD (SKIP, SHIP1, and SHIP2). Therefore, this study identifies SODD as a novel regulator of PI3K/Akt signaling to the actin cytoskeleton.
SARS-CoV-2 is believed to have originated from a spillover event, where the virus jumped from bats to humans, leading to an epidemic that quickly escalated into a pandemic by early 2020. Despite the ...implementation of various public health measures, such as lockdowns and widespread vaccination efforts, the virus continues to spread. This is primarily attributed to the rapid emergence of immune escape variants and the inadequacy of protection against reinfection. Spillback events were reported early in animals with frequent contact with humans, especially companion, captive, and farmed animals. Unfortunately, surveillance of spillback events is generally lacking in Malaysia. Therefore, this study aims to address this gap by investigating the presence of SARS-CoV-2 neutralising antibodies in wild rodents in Sarawak, Malaysia.
We analysed 208 archived plasma from rodents collected between from 2018 to 2022 to detect neutralising antibodies against SARS-CoV-2 using a surrogate virus neutralisation test, and discovered two seropositive rodents (Sundamys muelleri and Rattus rattus), which were sampled in 2021 and 2022, respectively.
Our findings suggest that Sundamys muelleri and Rattus rattus may be susceptible to natural SARS-CoV-2 infections. However, there is currently no evidence supporting sustainable rodent-to-rodent transmission.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Eclampsia is a serious pregnancy complication that can lead to seizures and potentially fatal outcomes for both mother and baby. It is most common in developing countries but improved ...antenatal care and early intervention have significantly decreased its incidence in developed countries. Risk factors for eclampsia include pre-eclampsia, hypertension, obesity, and renal disease, and early detection and management are crucial for preventing adverse outcomes. Magnesium sulfate is the preferred treatment for seizures, and delivery timing depends on disease severity, gestational age, and fetal well-being. Maternal and perinatal mortality rates vary by country, highlighting the need for continued efforts to improve outcomes for those affected by eclampsia. The study aimed to observe the maternal and perinatal complications in eclampsia patients. Material & Methods: This observational study was conducted at the Department of Gynecology, Gonoshasthaya Nagar Hospital, Dhaka, Bangladesh during the period of January 2020 to June 2020. We included a total of 270 patients with eclampsia who were admitted to a tertiary care hospital. A Purposive consecutive sampling method was followed for the selection of the participants. Results: This study analyzed the demographic and clinical characteristics, maternal and perinatal complications, and risk factors of 270 patients with eclampsia. The majority of patients were aged between 20-34 years (77.8%), and 61.1% were multiparous. Over half of the cases (55.6%) presented with eclampsia between 28-36 weeks of gestation, and 38.9% had a history of preeclampsia in a previous pregnancy. The most common symptoms reported were headaches (88.9%). All cases involved hypertensive disorders, and maternal death was reported in 1.9% of cases. Perinatal complications included low birth weight (44.4%), preterm delivery (36.3%), NICU admission (34.8%), stillbirth (4.4%), and early neonatal death (3.0%). Maternal mortality rates were highest among women aged 20-34 years (56.5%), while perinatal mortality rates were highest among women aged under 20 years (20.0%). The highest maternal mortality rate was observed among women with severe eclampsia (91.4%), and time to treatment was a crucial factor in maternal mortality rates. These findings underscore the need for timely and appropriate care to improve maternal and perinatal outcomes, particularly in high-risk populations. Conclusion: Eclampsia is a serious complication of pregnancy that can result in significant maternal and perinatal morbidity and mortality. Early detection, prompt management, and close monitoring of high-risk pregnancies are crucial in preventing adverse outcomes. Further research is needed to identify effective interventions for preventing and managing eclampsia.
Phosphoinositide signaling molecules control cellular growth, proliferation and differentiation, intracellular vesicle trafficking, and cytoskeletal rearrangement. The inositol polyphosphate ...5‐phosphatase family remove the D‐5 position phosphate from PtdIns(3,4,5)P3, PtdIns(4,5)P2 and PtdIns(3,5)P2 forming PtdIns(3,4)P2, PtdIns(4)P and PtdIns(3)P respectively. This enzyme family, comprising ten mammalian members, exhibit seemingly non‐redundant functions including the regulation of synaptic vesicle recycling, hematopoietic cell function and insulin signaling. Here we highlight recently established insights into the functions of two well characterized 5‐phosphatases OCRL and SHIP2, which have been the subject of extensive functional studies, and the characterization of recently identified members, SKIP and PIPP, in order to highlight the diverse and complex functions of this enzyme family.
iubmb Life, 58: 451 ‐ 456, 2006
Small mammal surveys were conducted at Niah National Park, Lambir Hills National Park and Gunung Mulu National Park, Miri Division, in the northeastern region of Sarawak, using ground-level and ...canopy mist-nets, harp traps, and cage traps. The main objective of these surveys was to assess small mammal diversity in the northeastern region of Sarawak. Gunung Mulu National Park recorded the highest diversity of small mammals with 29 species, followed by Niah National Park with 19 species, and Lambir Hills National Park, 17 species. These surveys revealed nine new locality records for Miri, including eight bat species (Dyacopterus spadiceus, Megaerops wetmorei, Nycteris tragata, Hipposideros cineraceus, Hesperoptenus blanfordi, Kerivoula pellucida, Murina suilla and Myotis muricola)and a squirrel (Sundasciurus brookei). Megaerops wetmorei is also reported for the first time in Sarawak.
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