C. elegans spermatocyte divisions show a weak spindle checkpoint response.

Male meiotic division exhibits two consecutive chromosome separation events without apparent pausing. Several studies have shown that spermatocyte divisions are not stringently regulated as in mitotic cells. In this study, we investigated the role of the canonical spindle assembly (SAC) pathway in Caenorhabditis elegans spermatogenesis.

Recapitulating the immune system of hemophilia A patients with inhibitors using immunodeficient mice.

Background And Aim: Treating hemophilia A patients who develop inhibitors remains a clinical challenge. A mouse model of hemophilia A can be used to test the efficacy of strategies for inhibitor suppression, but the differences in the immune systems of mice and humans limit its utility. To address this shortcoming, we established a humanized NOD/SCID-IL2rγ hemophilia A (hu-NSG-HA) mouse model with a severely deficient mouse immune system presenting a patient's adapted immune cells.

Volume holographic illuminator for Airy light-sheet microscopy.

Airy light sheets combined with the deconvolution approach can provide multiple benefits, including large field of view (FOV), thin optical sectioning, and high axial resolution. The efficient design of an Airy light-sheet fluorescence microscope requires a compact illumination system. Here, we show that an Airy light sheet can be conveniently implemented in microscopy using a volume holographic grating (VHG).

Apoptotic biliary epithelial cells and gut dysbiosis in the induction of murine primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a female-predominant liver autoimmune disease characterized by the specific immune-mediated destruction of the intrahepatic small bile duct. Although apoptosis of biliary epithelial cells (BECs) and alterations in gut microbiota are observed in patients with PBC, it is still unclear whether these events happen in the early stage and cause the breakdown of tolerance in PBC. In this study, we examined the early events in the loss of tolerance in our well-defined 2-OA-OVA-induced murine autoimmune cholangitis (AIC) model.

Meta-lens light-sheet fluorescence microscopy for imaging.

Light-sheet fluorescent microscopy has become the leading technique for imaging in the fields of disease, medicine, and cell biology research. However, designing proper illumination for high image resolution and optical sectioning is challenging. Another issue is geometric constraints arising from the multiple bulky components for illumination and detection.

BLMP-1 promotes developmental cell death in C. elegans by timely repression of ced-9 transcription.

Programmed cell death (PCD) is a common cell fate in metazoan development. PCD effectors are extensively studied, but how they are temporally regulated is less understood. Here, we report a mechanism controlling tail-spike cell death onset during Caenorhabditis elegans development.

SC5005 dissipates the membrane potential to kill Staphylococcus aureus persisters without detectable resistance.

Objectives: In the past few decades, multiple-antibiotic-resistant Staphylococcus aureus has emerged and quickly spread in hospitals and communities worldwide. Additionally, the formation of antibiotic-tolerant persisters and biofilms further reduces treatment efficacy. Previously, we identified a sorafenib derivative, SC5005, with bactericidal activity against MRSA in vitro and in vivo.

Volume holographic optical element for light sheet fluorescence microscopy.

Three-dimensional (3D) imaging of living organisms requires fine optical sectioning and high-speed image acquisition, which can be achieved by light sheet fluorescence microscopy (LSFM). However, orthogonal illumination and detection arms in the LSFM system make it bulky. Here, we propose and demonstrate the application of a volume holographic optical element (photopolymer-based volume holographic grating) for designing a compact LSFM system, called a volume holographic LSFM (VHLSFM).

Loss of the seipin gene perturbs eggshell formation in .

Seipin, an evolutionary conserved protein, plays pivotal roles during lipid droplet (LD) biogenesis and is associated with various human diseases with unclear mechanisms. Here, we analyzed mutants deleted of the sole gene, Homozygous mutants displayed penetrant embryonic lethality, which is caused by the disruption of the lipid-rich permeability barrier, the innermost layer of the embryonic eggshell. In oocytes and embryos, SEIP-1 is associated with LDs and is crucial for controlling LD size and lipid homeostasis.

The 14-3-3 protein PAR-5 regulates the asymmetric localization of the LET-99 spindle positioning protein.

PAR proteins play important roles in establishing cytoplasmic polarity as well as regulating spindle positioning during asymmetric division. However, the molecular mechanisms by which the PAR proteins generate asymmetry in different cell types are still being elucidated. Previous studies in Caenorhabditis elegans revealed that PAR-3 and PAR-1 regulate the asymmetric localization of LET-99, which in turn controls spindle positioning by affecting the distribution of the conserved force generating complex.

Human X-linked Intellectual Disability Factor CUL4B Is Required for Post-meiotic Sperm Development and Male Fertility.

In this study, we demonstrate that an E3-ubiquitin ligase associated with human X-linked intellectual disability, CUL4B, plays a crucial role in post-meiotic sperm development. Initially, Cul4b(Δ)/Y male mice were found to be sterile and exhibited a progressive loss in germ cells, thereby leading to oligoasthenospermia. Adult Cul4b mutant epididymides also contained very low numbers of mature spermatozoa, and these spermatazoa exhibited pronounced morphological abnormalities.

Sperm development and motility are regulated by PP1 phosphatases in Caenorhabditis elegans.

Sperm from different species have evolved distinctive motility structures, including tubulin-based flagella in mammals and major sperm protein (MSP)-based pseudopods in nematodes. Despite such divergence, we show that sperm-specific PP1 phosphatases, which are required for male fertility in mouse, function in multiple processes in the development and motility of Caenorhabditis elegans amoeboid sperm. We used live-imaging analysis to show the PP1 phosphatases GSP-3 and GSP-4 (GSP-3/4) are required to partition chromosomes during sperm meiosis.

LET-99 inhibits lateral posterior pulling forces during asymmetric spindle elongation in C. elegans embryos.

Cortical pulling on astral microtubules positions the mitotic spindle in response to PAR polarity cues and G protein signaling in many systems. In Caenorhabditis elegans single-cell embryos, posterior spindle displacement depends on Galpha and its regulators GPR-1/2 and LIN-5. GPR-1/2 and LIN-5 are necessary for cortical pulling forces and become enriched at the posterior cortex, which suggests that higher forces act on the posterior spindle pole compared with the anterior pole.

Spermatogenesis-specific features of the meiotic program in Caenorhabditis elegans.

In most sexually reproducing organisms, the fundamental process of meiosis is implemented concurrently with two differentiation programs that occur at different rates and generate distinct cell types, sperm and oocytes. However, little is known about how the meiotic program is influenced by such contrasting developmental programs. Here we present a detailed timeline of late meiotic prophase during spermatogenesis in Caenorhabditis elegans using cytological and molecular landmarks to interrelate changes in chromosome dynamics with germ cell cellularization, spindle formation, and cell cycle transitions.

Centrosome attachment to the C. elegans male pronucleus is dependent on the surface area of the nuclear envelope.

A close association must be maintained between the male pronucleus and the centrosomes during pronuclear migration. In C. elegans, simultaneous depletion of inner nuclear membrane LEM proteins EMR-1 and LEM-2, depletion of the nuclear lamina proteins LMN-1 or BAF-1, or the depletion of nuclear import components leads to embryonic lethality with small pronuclei.

PAR-3 and PAR-1 inhibit LET-99 localization to generate a cortical band important for spindle positioning in Caenorhabditis elegans embryos.

The conserved PAR proteins are localized in asymmetric cortical domains and are required for the polarized localization of cell fate determinants in many organisms. In Caenorhabditis elegans embryos, LET-99 and G protein signaling act downstream of the PARs to regulate spindle positioning and ensure asymmetric division. PAR-3 and PAR-2 localize LET-99 to a posterior cortical band through an unknown mechanism.