DNA fragmentation index (DFI) as a measure of sperm quality and fertility in mice.

Although thousands of genetically modified mouse strains have been cryopreserved by sperm freezing, the likelihood of cryorecovery success cannot be accurately predicted using conventional sperm parameters. The objective of the present study was to assess the extent to which measurement of a sperm DNA fragmentation index (DFI) can predict sperm quality and fertility after cryopreservation. Using a modified TUNEL assay, we measured and correlated the DFI of frozen-thawed sperm from 83 unique mutant mouse strains with sperm count, motility and morphology. We observed a linear inverse correlation between sperm DFI and sperm morphology and motility. Further, sperm DFI was significantly higher from males with low sperm counts compared to males with normal sperm counts (P < 0.0001). Additionally, we found that viable embryos derived using sperm from males with high DFI (62.7 ± 7.2% for IVF and 73.3 ± 8.1% for ICSI) failed to litter after embryo transfer compared to embryos from males with low DFI (20.4 ± 7.9% for IVF and 28.1 ± 10.7 for ICSI). This study reveals that measurement of DFI provides a simple, informative and reliable measure of sperm quality and can accurately predict male mouse fertility

Development of outbred CD1 mouse colonies with distinct standardized gut microbiota profiles for use in complex microbiota targeted studies.

Studies indicate that the gut microbiota (GM) can significantly influence both local and systemic host physiologic processes. With rising concern for optimization of experimental reproducibility and translatability, it is essential to consider the GM in study design. However, GM profiles can vary between rodent producers making consistency between models challenging. To circumvent this, we developed outbred CD1 mouse colonies with stable, complex GM profiles that can be used as donors for a variety of GM transfer techniques including rederivation, co-housing, cross-foster, and fecal microbiota transfer (FMT). CD1 embryos were surgically transferred into CD1 or C57BL/6 surrogate dams that varied by GM composition and complexity to establish four separate mouse colonies harboring GM profiles representative of contemporary mouse producers. Using targeted 16S rRNA amplicon sequencing, subsequent female offspring were found to have similar GM profiles to surrogate dams. Furthermore, breeding colonies of CD1 mice with distinct GM profiles were maintained for nine generations, demonstrating GM stability within these colonies. To confirm GM stability, we shipped cohorts of these four colonies to collaborating institutions and found no significant variation in GM composition. These mice are an invaluable experimental resource that can be used to investigate GM effects on mouse model phenotype

Genome-wide screening of mouse knockouts reveals novel genes required for normal integumentary and oculocutaneous structure and function.

Oculocutaneous syndromes are often due to mutations in single genes. In some cases, mouse models for these diseases exist in spontaneously occurring mutations, or in mice resulting from forward mutatagenesis screens. Here we present novel genes that may be causative for oculocutaneous disease in humans, discovered as part of a genome-wide screen of knockout-mice in a targeted single-gene deletion project. The International Mouse Phenotyping Consortium (IMPC) database (data release 10.0) was interrogated for all mouse strains with integument abnormalities, which were then cross-referenced individually to identify knockouts with concomitant ocular abnormalities attributed to the same targeted gene deletion. The search yielded 307 knockout strains from unique genes with integument abnormalities, 226 of which have not been previously associated with oculocutaneous conditions. Of the 307 knockout strains with integument abnormalities, 52 were determined to have ocular changes attributed to the targeted deletion, 35 of which represent novel oculocutaneous genes. Some examples of various integument abnormalities are shown, as well as two examples of knockout strains with oculocutaneous phenotypes. Each of the novel genes provided here are potentially relevant to the pathophysiology of human integumentary, or oculocutaneous conditions, such as albinism, phakomatoses, or other multi-system syndromes. The novel genes reported here may implicate molecular pathways relevant to these human diseases and may contribute to the discovery of novel therapeutic targets

The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

Vaccination against SARS-CoV-2 protects from infection and improves clinical outcomes in breakthrough infections, likely reflecting residual vaccine-elicited immunity and recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and cellular immunity after vaccination of seropositive individuals and after Delta or Omicron breakthrough infection in vaccinated individuals. Early longitudinal sampling revealed the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titers. While vaccination of seropositive individuals resulted in robust recall of humoral and T cell immunity, recall of vaccine-elicited responses was delayed and variable in magnitude during breakthrough infections and depended on the infecting variant of concern. While the delayed kinetics of immune recall provides a potential mechanism for the lack of early control of viral replication, the recall of antibodies coincided with viral clearance and likely underpins the protective effects of vaccination against severe COVID-19

Urban energy exchanges monitoring from space

One important challenge facing the urbanization and global environmental change community is to understand the relation between urban form, energy use and carbon emissions. Missing from the current literature are scientific assessments that evaluate the impacts of different urban spatial units on energy fluxes; yet, this type of analysis is needed by urban planners, who recognize that local scale zoning affects energy consumption and local climate. However, satellite-based estimation of urban energy fluxes at neighbourhood scale is still a challenge. Here we show the potential of the current satellite missions to retrieve urban energy budget, supported by meteorological observations and evaluated by direct flux measurements. We found an agreement within 5% between satellite and in-situ derived net all-wave radiation; and identified that wall facet fraction and urban materials type are the most important parameters for estimating heat storage of the urban canopy. The satellite approaches were found to underestimate measured turbulent heat fluxes, with sensible heat flux being most sensitive to surface temperature variation (-64.1, +69.3 W m-2 for ±2 K perturbation); and also underestimate anthropogenic heat flux. However, reasonable spatial patterns are obtained for the latter allowing hot-spots to be identified, therefore supporting both urban planning and urban climate modelling

Lower respiratory tract infection and rapid expansion of an abdominal aortic aneurysm: a case report

<p>Abstract</p> <p>Introduction</p> <p>The rate of abdominal aortic aneurysm expansion is related to multiple factors. There is some evidence that inflammation can accelerate aneurysm expansion. However, the association between pulmonary sepsis and rapid abdominal aortic aneurysm expansion is rarely reported.</p> <p>Case presentation</p> <p>Here we present a case of a rapidly expanding abdominal aortic aneurysm in a 68-year-old Caucasian man with a concomitant lower respiratory tract infection and systemic sepsis requiring intensive monitoring and urgent endovascular intervention. Our patient had an uncomplicated post-operative recovery and a follow-up computed tomography scan at one month demonstrated no evidence of an endoleak.</p> <p>Conclusion</p> <p>This case highlights the potential association between pulmonary sepsis and rapid abdominal aortic aneurysm expansion. In such cases, a policy of frequent monitoring should be adopted to identify those patients requiring definitive management.</p