Publications by authors named "James W Larrick"

Article Synopsis
  • * A study in northeastern Ethiopia's Amibara and Haruka districts found a seroprevalence of 22.0% in domestic livestock, indicating that goats had the highest infection rate at 42.2%, significantly more than cattle, sheep, or camels.
  • * The study highlighted the need for increased monitoring of RVF in animals and humans, community education for high-risk groups, and quarantine measures to help prevent the disease's spread.
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Objective: Chikungunya is a disease caused by mosquito-borne chikungunya virus infection. This disease is becoming one of the emerging/re-emerging viral diseases in tropical and subtropical countries but is neglected by public health systems. This study assessed the seroprevalence of chikungunya virus infection among patients with acute febrile illness seeking healthcare in a malaria-endemic area in the Afar Region, Northeast Ethiopia.

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The distribution, epidemiology, and socioeconomic impact of Rift Valley fever (RVF) and West Nile (WN) viruses are poorly known in areas of sub-Saharan countries like Ethiopian pastoral region. The human and livestock density in the area has increased greatly in recent years, but little work has been done on arboviral diseases and their potential impact on human and livestock health. The aim of this study was to detect the circulation of zoonotic arboviruses such as Rift Valley fever virus and West Nile viruses in the livestock population and to estimate seroprevalence in Afar pastoral area northeast Ethiopia.

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Status epilepticus (SE) is a medical emergency associated with high mortality and morbidity. Na, K-ATPase, is a promising therapeutic target for SE, given its critical role in regulation of neuron excitability and cellular homeostasis. We investigated the effects of a Na, K-ATPase-activating antibody (DRRSAb) on short-term electrophysiological and behavioral consequences of pilocarpine-induced SE.

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Enduring occurrence of severe COVID-19 for unvaccinated, aged, or immunocompromised individuals remains an urgent need. Soluble human angiotensin-converting enzyme 2 (ACE2) has been used as a decoy receptor to inhibit SARS-CoV-2 infection, which is limited by moderate affinity. We describe an engineered, high-affinity ACE2 that is consistently effective in tissue cultures in neutralizing all strains tested, including Delta and Omicron.

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Background: Bdelloid rotifers are micro-invertebrates distributed worldwide, from temperate latitudes to the most extreme areas of the planet like Antarctica or the Atacama Desert. They have colonized any habitat where liquid water is temporarily available, including terrestrial environments such as soils, mosses, and lichens, tolerating desiccation and other types of stress such as high doses of ionizing radiation (IR). It was hypothesized that bdelloid desiccation and radiation resistance may be attributed to their potential ability to repair DNA double-strand breaks (DSBs).

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Bispecific antibody (BiAb)-armed activated T cells (BATs) comprise an adoptive T cell therapy platform for treating cancer. Arming activated T cells (ATC) with anti-CD3 x anti-tumour associated antigen (TAA) BiAbs converts ATC into non-major histocompatibility complex (MHC)-restricted anti-tumour cytotoxic T lymphocytes (CTLs). Binding of target antigens via the BiAb bridge enables specific anti-tumour cytotoxicity, Th1 cytokines release, and T cell proliferation.

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Boosting anticancer immunity by blocking immune checkpoints such as the programmed death-1 (PD-1) or its ligand (PD-L1) is a breakthrough anticancer therapy. However, many cancer patients do not respond well to immune checkpoint blockades (ICBs) alone. Here we show that low-dose pharmacological immunoactivators (e.

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Article Synopsis
  • - The B cell receptor (BCR) is made up of a membrane-bound immunoglobulin (Ig) partnered with CD79A and CD79B proteins, which are crucial for B cell signaling and activation in response to antigens.
  • - Researchers created knockin mice with humanized CD79 proteins to evaluate anti-human CD79 therapies, overcoming challenges with using standard mice due to differences in protein reactivity.
  • - The study found that targeting human CD79 can successfully reduce B cell activation and prevent autoimmune diseases in mouse models, while also potentially inhibiting antibody production in certain B cell types.
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The development of senomorphic drugs to attenuate the senescent phenotype and senolytics to clear pro-inflammatory senescent cells (SCs) to treat aging-associated disorders is being hotly pursued. The effort is complicated by the fact that SCs play a constructive role in some cellular processes such as tissue repair and wound healing. However, concerns about efficacy, which SCs to target, and unwanted side effects have created potential roadblocks.

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Background: Stimulating antitumor immunity by blocking programmed death-1 (PD-1) or its ligand (programmed death-ligand 1 (PD-L1) is a promising antitumor therapy. However, numerous patients respond poorly to PD-1/PD-L1 blockade. Unresponsiveness to immune-checkpoint blockade (ICB) can cast significant challenges to the therapeutic options for patients with hard-to-treat tumors.

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Stem cell dysfunction is a hallmark of aging. Much recent study suggests that epigenetic changes play a critical role in the loss of stem cell function with age. However, the underlying mechanisms require elucidation.

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Numerous studies demonstrate a global decrease in nicotinamide adenine dinucleotide (NAD+) with aging. This decline is associated with the development of several of the hallmarks of aging such as reduced mitophagy and neuroinflammation, processes thought to play a significant role in the progression of Alzheimer's disease (AD). Augmentation of NAD+ by oral administration of a precursor, nicotinamide riboside (NR), reduces senescence of affected cells, attenuates DNA damage and neuroinflammation in the transgenic APP/PS1 murine model of AD.

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Inflammaging, the increase of proinflammatory processes with increasing age, has multiple mechanisms from increasing numbers of senescent cells secreting cytokines to changes in metabolic processes. Alterations of oxygen metabolism with aging, especially decreased levels of O with age resulting from endocrine and cardiovascular dysfunction as well as desensitization of cellular response to hypoxia, may exacerbate inflammaging, which in turn creates further oxygen metabolic dysfunction. During aging, decline in levels of erythrocyte 2,3-bisphosphoglycerate (2,3-BPG), BPG mutase, and adenosine A2B receptor, a key adenosine signaling receptor that can augment 2,3-BPG expression, may fail to protect sensitive brain tissue from subtly reduced O levels, in turn resulting in increased numbers of activated microglia and secretion of proinflammatory cytokines, ultimately promoting inflammaging and senescence of endothelial cells.

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Yellow fever (YF), Chikungunya (CHIK), and Zika(ZIK) are among re-emerging arboviral diseases of major public health concern. Despite the proximity of the Gambella Region to South Sudan where arboviral cases have been recorded repeatedly the current epidemiological situation is unclear in this part of southwest Ethiopia. Therefore, we conducted a community-based seroprevalence survey of YF virus (YFV), CHIK virus (CHIKV), and ZIK virus (ZIKV) infections in two selected districts.

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Intermittent fasting (IF) is the practice of restricting food intake for 12-48 hours per fasting cycle over a prolonged period of time. Previous study shows beneficial health effects such as weight loss and lower risk for cardiometabolic diseases. Although reduced calorie intake may account for some of the observed benefits of IF, exact mechanisms are still unclear.

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Modest modulation of oxygen intake, either by inducing mild intermittent hypoxia or hyperoxia appears to induce modest rejuvenative changes in mammals, in part, by activating key regulator hypoxia-induced factor 1a (HIF-1a). Interestingly both lower oxygen and transient higher oxygen levels induce this hypoxia regulator. Hyperbaric oxygen induces HIF-1a by the hyperoxic-hypoxic paradox that results from an overinduction of protective factors under intermittent hyperoxic conditions, leading to a state somewhat similar to that induced by hypoxia.

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Article Synopsis
  • - Inflammaging contributes to cognitive decline and neurodegeneration as people age, with NSAIDs showing some promise in reducing Alzheimer's disease risk but falling short in effective treatments.
  • - Prostaglandin E2 (PGE2), which is influenced by NSAID activity through COX-2, negatively impacts metabolism and promotes inflammation in aging by activating specific receptors like EP2.
  • - Targeting EP2 with small molecule drugs can shift immune cells to an anti-inflammatory state, enhance metabolism and mitochondrial function, and potentially improve memory, suggesting it may be a better focus for developing therapies for age-related cognitive impairments.
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West Nile fever (WNF) and Rift Valley fever (RVF) are emerging and re-emerging zoonotic diseases of veterinary and public health importance in Africa. Despite the existence of potential vectors and a wide range of hosts, the transmission of these diseases in domestic animals has not been well documented in the South Omo area of Ethiopia. This study aimed to estimate the sero-prevalence of IgG antibodies produced against West Nile virus (WNV) and Rift Valley fever virus (RVFV) infections among cattle in the South Omo area.

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SUMOylation, a conserved protein post-translational modification that performs multiple functions including regulation of nuclear transport and transcription, is implicated in numerous biological processes including aging. RNAi knockdown of the sole Small Ubiquitin-like MOdifier (SUMO) gene, smo-1, in shortened lifespan, whereas overexpression in the intestine modestly increased lifespan. Smo-1 is required for mitochondrial fission in a tissue-specific manner.

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Introduction: Rift Valley fever (RVF) and West Nile fever (WNF) are re-emerging mosquito-borne zoonotic diseases that cause public health and economic crises. Ethiopia shares borders with South Sudan and Kenya, where these diseases are often documented. The free movement of animals and humans across these borders expects to increase the spread of these diseases.

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Ferroptosis is a recently characterized cell death phenotype resulting from iron-catalyzed peroxidation of polyunsaturated fatty acid phospholipids. Increased dysfunctional iron metabolism is thought to lead to increased levels of iron and ferroptosis, which in turn leads to cell and organismal death at least in the nematode . Drugs that block lipid peroxidation or scavenge intracellular iron extend healthspan and lifespan in independently of other mechanisms such as the (insulin/insulin-like growth factor 1 [IGF-1]) pathway, but unlike many aging mechanisms do not alter temporal scaling across the life cycle of , but rather act at specific late points in the organism's life history, temporarily blocking execution of critical dysfunction that results in listless worms.

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Background: Chikungunya (CHIK) and yellow fever (YF) are becoming major public health threats in East African countries including Ethiopia. In Ethiopia, there is no reliable information about the epidemiology of CHIK. This study aimed to assess a community-based sero-prevalence of CHIK and YF in the South Omo Valley, an endemic area for YF.

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Proinflammatory alterations of white adipose tissue (WAT) with increasing age play an important role in mammalian aging. WAT produced eotaxin-1 (CCL11-C-C motif chemokine ligand 11) and monocyte chemoattractant protein 1 (MCP-1) (CCL2) are elevated in old mammals. Obese and old adipose tissues produce excessive proinflammatory cytokines such as interleukin (IL)-6, CCL2, and IL-1-beta that contribute to inflammaging.

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Article Synopsis
  • * The restoration process is linked to increased levels of cyclin D1, which helps maintain MuSC regenerative ability by interfering with the age-related TGF-beta signaling pathway.
  • * While exercise has rejuvenating effects on MuSCs, these benefits are temporary, lasting about two weeks after stopping exercise, and some aging indicators like Notch signaling do not fully return to youthful levels.
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