Advancing the genetic engineering toolbox by combining AsCas12a knock-in mice with ultra-compact screening.

Cas12a is a next-generation gene editing tool that enables multiplexed gene targeting. Here, we present a mouse model that constitutively expresses enhanced Acidaminococcus sp. Cas12a (enAsCas12a) linked to an mCherry fluorescent reporter.

Cullin-5 controls the number of megakaryocyte-committed stem cells to prevent thrombocytosis in mice.

Cullin-5 (Cul5) coordinates assembly of cullin-RING-E3 ubiquitin (Ub) ligase (CRL) complexes that include Suppressor of Cytokine Signaling (SOCS)-box-containing proteins. The SOCS-box proteins function to recruit specific substrates to the complex for ubiquitination and degradation. In hematopoiesis, SOCS-box proteins are best known for regulating the actions of cytokines that utilize the JAK-STAT signaling pathway.

Altering phosphorylation of dystrophin S3059 to attenuate cancer cachexia.

Aims: Cancer cachexia affects up to 80 % of patients with advanced cancer and accounts for >20 % of all cancer-related deaths. Sarcolemmal localization of dystrophin, a key protein within the dystrophin-glycoprotein complex (DGC), is perturbed in multiple muscle wasting conditions, including cancer cachexia, indicating a potential role for dystrophin in the maintenance of muscle mass. Strategies to preserve dystrophin expression at the sarcolemma might therefore combat muscle wasting.

Dichotomous outcomes of TNFR1 and TNFR2 signaling in NK cell-mediated immune responses during inflammation.

Natural killer (NK) cell function is regulated by a balance of activating and inhibitory signals. Tumor necrosis factor (TNF) is an inflammatory cytokine ubiquitous across homeostasis and disease, yet its role in regulation of NK cells remains unclear. Here, we find upregulation of the immune checkpoint protein, T cell immunoglobulin and mucin domain 3 (Tim3), is a biomarker of TNF signaling in NK cells during Salmonella Typhimurium infection.

Intergovernmental Panel on Climate Change (IPCC) Tier 1 forest biomass estimates from Earth Observation.

Aboveground biomass density (AGBD) estimates from Earth Observation (EO) can be presented with the consistency standards mandated by United Nations Framework Convention on Climate Change (UNFCCC). This article delivers AGBD estimates, in the format of Intergovernmental Panel on Climate Change (IPCC) Tier 1 values for natural forests, sourced from National Aeronautics and Space Administration's (NASA's) Global Ecosystem Dynamics Investigation (GEDI) and Ice, Cloud and land Elevation Satellite (ICESat-2), and European Space Agency's (ESA's) Climate Change Initiative (CCI). It also provides the underlying classification used by the IPCC as geospatial layers, delineating global forests by ecozones, continents and status (primary, young (≤20 years) and old secondary (>20 years)).

Reflecting on a decade of the international consensus on ANA patterns (ICAP): Accomplishments and challenges from the perspective of the 7th ICAP workshop.

The International Consensus on ANA Patterns (ICAP) is an ongoing international initiative dedicated to harmonizing technical and interpretation aspects of the HEp-2 IFA test. Comprised of internationally recognized experts in autoimmunity and HEp-2 IFA testing, ICAP has operated for the last 10 years by promoting accurate reading, interpretation, and reporting of HEp-2 IFA images by professionals involved in various areas related to autoimmune diseases, such as clinical diagnostic laboratories, academic research, IVD industry, and patient care. ICAP operates through continuous information exchange with the international community and encourages the participation of younger experts from all over the world.

Mouse models to investigate in situ cell fate decisions induced by p53.

Investigating how transcription factors control complex cellular processes requires tools that enable responses to be visualised at the single-cell level and their cell fate to be followed over time. For example, the tumour suppressor p53 (also called TP53 in humans and TRP53 in mice) can initiate diverse cellular responses by transcriptional activation of its target genes: Puma to induce apoptotic cell death and p21 to induce cell cycle arrest/cell senescence. However, it is not known how these processes are regulated and initiated in different cell types.

High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases.

Respiratory infections cause significant morbidity and mortality, yet it is unclear why some individuals succumb to severe disease. In patients hospitalized with avian A(H7N9) influenza, we investigated early drivers underpinning fatal disease. Transcriptomics strongly linked oleoyl-acyl-carrier-protein (ACP) hydrolase (OLAH), an enzyme mediating fatty acid production, with fatal A(H7N9) early after hospital admission, persisting until death.

Global biomass maps can increase the precision of (sub)national aboveground biomass estimates: A comparison across tropical countries.

Countries within the tropics face ongoing challenges in completing or updating their national forest inventories (NFIs), critical for estimating aboveground biomass (AGB) and for forest-related greenhouse gas (GHG) accounting. While previous studies have explored the integration of map information with local reference data to fill in data gaps, limited attention has been given to the specific challenges presented by the clustered plot designs frequently employed by NFIs when combined with remote sensing-based biomass map units. This research addresses these complexities by conducting four country case-studies, encompassing a variety of NFI characteristics within a range of AGB densities.

Dystrophin S3059 phosphorylation partially attenuates denervation atrophy in mouse tibialis anterior muscles.

The dystrophin protein has well-characterized roles in force transmission and maintaining membrane integrity during muscle contraction. Studies have reported decreased expression of dystrophin in atrophying muscles during wasting conditions, and that restoration of dystrophin can attenuate atrophy, suggesting a role in maintaining muscle mass. Phosphorylation of S3059 within the cysteine-rich region of dystrophin enhances binding between dystrophin and β-dystroglycan, and mimicking phosphorylation at this site by site-directed mutagenesis attenuates myotube atrophy in vitro.

Survival Difference of Endometrial Cancer Patients with Peritoneal Metastasis Receiving Cytoreductive Surgery (CRS) with and without Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Systematic Review and Meta-Analysis.

Although several studies have been completed to investigate the effect of cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in endometrial cancer with peritoneal metastasis (ECPM), a direct comparison was not performed previously. A meta-analysis was performed to investigate the suspected additional survival benefits of CRS plus HIPEC over CRS only. Twenty-one and ten studies with a total number of 1116 and 152 cases investigating CRS only and CRS plus HIPEC were identified, respectively.

Cariprazine maintenance treatment during pregnancy - a case report.

Data on reproductive safety of recently approved newer antipsychotics are limited. Here, we report a case vignette of a patient with schizophrenia treated with cariprazine during pregnancy. The patient became pregnant unexpectedly while taking medication.

Uncovering young people's situational construction of sexual consent.

To investigate how young Danes construct sexual consent generally, but also specifically in relation to heavy alcohol intoxication. Drawing on 30 qualitative in-depth interviews with young people, aged 19-25 years, and adopting a critical discursive psychological framework, we explored the interpretative repertoires that the participants made use of to construct sexual consent and the subject positions those repertoires enabled. The participants made use of three interpretative repertoires that we named as follows: (1) sexual consent as an agreement between rational individuals; (2) sexual consent as a heteronormative practice; and (3) intoxicated sexual consent.

Immunofluorescence Imaging of Vital Human Pancreatic Tissue Using Fiber-Optic Microscopy.

Purpose: Surgical resection is the only curative option for pancreatic carcinoma, but disease-free and overall survival times after surgery are limited due to early tumor recurrence, most often originating from local microscopic tumor residues (R1 resection). The intraoperative identification of microscopic tumor residues within the resection margin could improve surgical performance. The aim of this study was to evaluate the effectiveness of fiber-optic microscopy for detecting microscopic residues in vital pancreatic cancer tissues.

The BALB/c.mdx62 mouse exhibits a dystrophic muscle pathology and is a model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a devastating monogenic skeletal muscle-wasting disorder. Although many pharmacological and genetic interventions have been reported in preclinical studies, few have progressed to clinical trials with meaningful benefit. Identifying therapeutic potential can be limited by availability of suitable preclinical mouse models.

StrucNet: a global network for automated vegetation structure monitoring.

Climate change and increasing human activities are impacting ecosystems and their biodiversity. Quantitative measurements of essential biodiversity variables (EBV) and essential climate variables are used to monitor biodiversity and carbon dynamics and evaluate policy and management interventions. Ecosystem structure is at the core of EBVs and carbon stock estimation and can help to inform assessments of species and species diversity.

Land potential assessment and trend-analysis using 2000-2021 FAPAR monthly time-series at 250 m spatial resolution.

The article presents results of using remote sensing images and machine learning to map and assess land potential based on time-series of potential Fraction of Absorbed Photosynthetically Active Radiation (FAPAR) composites. Land potential here refers to the potential vegetation productivity in the hypothetical absence of short-term anthropogenic influence, such as intensive agriculture and urbanization. Knowledge on this ecological land potential could support the assessment of levels of land degradation as well as restoration potentials.

Differential in vivo roles of Mpl cytoplasmic tyrosine residues in murine hematopoiesis and myeloproliferative disease.

Thrombopoietin (Tpo), which binds to its specific receptor, the Mpl protein, is the major cytokine regulator of megakaryopoiesis and circulating platelet number. Tpo binding to Mpl triggers activation of Janus kinase 2 (Jak2) and phosphorylation of the receptor, as well as activation of several intracellular signalling cascades that mediate cellular responses. Three tyrosine (Y) residues in the C-terminal region of the Mpl intracellular domain have been implicated as sites of phosphorylation required for regulation of major Tpo-stimulated signalling pathways: Mpl-Y565, Mpl-Y599 and Mpl-Y604.

[Electromagnetic procedures in the treatment of pancreatic cancer: eminent or resentful?].

The treatment of advanced-stage pancreatic cancers is limited. Previous studies have found that the use of modulated electro-hyperthermia (mEHT) is beneficial in this patient population. However, there is no data on the optimal treatment number and initiation period.

Demonstrating the reliability of in vivo metabolomics based chemical grouping: towards best practice.

While grouping/read-across is widely used to fill data gaps, chemical registration dossiers are often rejected due to weak category justifications based on structural similarity only. Metabolomics provides a route to robust chemical categories via evidence of shared molecular effects across source and target substances. To gain international acceptance, this approach must demonstrate high reliability, and best-practice guidance is required.