Enhanced near infrared optical access to the brain with a transparent cranial implant and scalp optical clearing.

We report on the enhanced optical transmittance in the NIR wavelength range (900 to 2400 nm) offered by a transparent Yttria-stabilized zirconia (YSZ) implant coupled with optical clearing agents (OCAs). The enhancement in optical access to the brain is evaluated upon comparing ex-vivo transmittance measurements of mice native skull and the YSZ cranial implant with scalp and OCAs. An increase in transmittance of up to 50% and attenuation lengths of up to 2.4 mm (i.e., a five-fold increase in light penetration) are obtained with the YSZ implant and the OCAs. The use of this ceramic implant and the biocompatible optical clearing agents offer attractive features for NIR optical techniques for brain theranostics

Regulation of the volume-regulated anion channel pore-forming subunit LRRC8A in the intrahippocampal kainic acid model of mesial temporal lobe epilepsy

Volume-regulated anion channels (VRACs) are a group of ubiquitously expressed outwardly-rectifying anion channels that sense increases in cell volume and act to return cells to baseline volume through an efflux of anions and organic osmolytes, including glutamate. Because cell swelling, increased extracellular glutamate levels, and reduction of the brain extracellular space (ECS) all occur during seizure generation, we set out to determine whether VRACs are dysregulated throughout mesial temporal lobe epilepsy (MTLE), the most common form of adult epilepsy. To accomplish this, we employed the IHKA experimental model of MTLE, and probed for the expression of LRRC8A, the essential pore-forming VRAC subunit, at acute, early-, mid-, and late-epileptogenic time points (1-, 7-, 14-, and 30-days post-IHKA, respectively). Western blot analysis revealed the upregulation of total dorsal hippocampal LRRC8A 14-days post-IHKA in both the ipsilateral and contralateral hippocampus. Immunohistochemical analyses showed an increased LRRC8A signal 7-days post-IHKA in both the ipsilateral and contralateral hippocampus, along with layer-specific changes 1-, 7-, and 30-days post-IHKA bilaterally. LRRC8A upregulation 1 day post-IHKA was observed primarily in astrocytes; however, some upregulation was also observed in neurons. Glutamate-GABA/glutamine cycle enzymes glutamic acid decarboxylase, glutaminase, and glutamine synthetase were also dysregulated at the 7-day timepoint post status epilepticus. The timepoint-dependent upregulation of total hippocampal LRRC8A and the possible subsequent increased efflux of glutamate in the epileptic hippocampus suggest that the dysregulation of astrocytic VRAC may play an important role in the development of epilepsy

The Spo13/Meikin pathway confines the onset of gamete differentiation to meiosis II in yeast

Sexual reproduction requires genome haploidization by the two divisions of meiosis and a differentiation program to generate gametes. Here, we have investigated how sporulation, the yeast equivalent of gamete differentiation, is coordinated with progression through meiosis. Spore differentiation is initiated at metaphase II when a membrane-nucleating structure, called the meiotic plaque, is assembled at the centrosome. While all components of this structure accumulate already at entry into meiosis I, they cannot assemble because centrosomes are occupied by Spc72, the receptor of the gamma-tubulin complex. Spc72 is removed from centrosomes by a pathway that depends on the polo-like kinase Cdc5 and the meiosis-specific kinase Ime2, which is unleashed by the degradation of Spo13/Meikin upon activation of the anaphase-promoting complex at anaphase I. Meiotic plaques are finally assembled upon reactivation of Cdk1 at entry into metaphase II. This unblocking-activation mechanism ensures that only single-copy genomes are packaged into spores and might serve as a paradigm for the regulation of other meiosis II-specific processes

The potential of integrative phenomics to harness underutilized crops for improving stress resilience

The current agricultural and food system faces diverse and increasing challenges. These include feeding an ever-growing human population, expected to reach about 10 billion by 2050 combined with societal disruption, and the need to cope with the impact of climate change (FAO, 2022). Given that future environmental conditions will limit crop productivity (Zhao et al., 2017; Cooper et al., 2021) and the limited potential to continually increase the performance of staple crops by conventional breeding (Hickey et al., 2019), there is an urgent need to transform agricultural systems. Central to this transformation is the application of alternative, accelerated, and sustainable approaches for the improvement and development of underutilized crops (Hickey et al., 2019). Modern breeding strategies for major crops have widely integrated novel technologies, such as advanced phenotyping or genome-wide interactions, and even epigenomics within “beyond the gene” strategies (Crisp et al., 2022) to speed up crop/genotype selection (Hickey et al., 2019; Kumar et al., 2023). Deploying phenotyping at different scales has the potential to identify novel trait(s) components that can be targeted to accelerate crop improvement (Araus and Cairns, 2014; Großkinsky et al., 2015b; Zhao et al., 2019; Varshney et al., 2021). There is even greater potential for these technologies when used to improve underutilized crops and support the agricultural transformation, as underutilized crops typically lack a biased breeding/selection history, i.e., they often exhibit a high genetic diversity and potential, and are usually better adapted to challenging environments (Kumar et al., 2021; Kumar et al., 2023). To illustrate the application of an integrative phenomics approach we discuss how combining multi-omics and advanced phenotyping is being applied to the underutilized oilseed crop Camelina sativa (camelina, gold-of-pleasure, false flax) to facilitate the generation of climate-smart crops for future agricultural systems

Deprotection of centromeric cohesin at meiosis II requires APC/C activity but not kinetochore tension

Genome haploidization involves sequential loss of cohesin from chromosome arms and centromeres during two meiotic divisions. At centromeres, cohesin's Rec8 subunit is protected from separase cleavage at meiosis I and then deprotected to allow its cleavage at meiosis II. Protection of centromeric cohesin by shugoshin-PP2A seems evolutionarily conserved. However, deprotection has been proposed to rely on spindle forces separating the Rec8 protector from cohesin at metaphase II in mammalian oocytes and on APC/C-dependent destruction of the protector at anaphase II in yeast. Here, we have activated APC/C in the absence of sister kinetochore biorientation at meiosis II in yeast and mouse oocytes, and find that bipolar spindle forces are dispensable for sister centromere separation in both systems. Furthermore, we show that at least in yeast, protection of Rec8 by shugoshin and inhibition of separase by securin are both required for the stability of centromeric cohesin at metaphase II. Our data imply that related mechanisms preserve the integrity of dyad chromosomes during the short metaphase II of yeast and the prolonged metaphase II arrest of mammalian oocytes

Monoclonal antibodies against human astrocytomas and their reactivity pattern

The establishment of hybridomas after fusion of X63-Ag8.653 mouse myeloma cells and splenocytes from mice hyperimmunized against human astrocytomas is presented. The animals were primed with 5 × 106 chemically modified uncultured or cultured glioma cells. Six weeks after the last immunization step an intrasplenal booster injection was administrated and 3 days later the spleen cells were prepared for fusion experiments. According to the specificity analysis of the generated antibodies 7 hybridoma products (MUC 7-22, MUC 8-22, MUC 10-22, MUC 11-22, MUC 14-22, MUC 15-22 and MUC 2-63) react with gliomas, neuroblastomas and melanomas as well as with embryonic and fetal cells but do not recognize non-neurogenic tumors. The selected monoclonal antibodies (McAbs) of IgG1 and IgG2a isotypes are not extensively characterized but these antibodies have been demonstrated to be reactive with a panel of glioma cell lines with varying patterns of antigen distribution. Using the McAbs described above and a series of cryosections of glioma biopsies and paraffin sections of the same material as well as glioma cultures established from these, variable antigenic profiles among glioma cell populations could be demonstrated. From these results it is evident that there is not only a distinct degree of antigenic heterogeneity among and within brain tumors, but also that the pattern of antigenic expression can change continuously. Some of the glioma associated antigens recognized by the selected antibodies persist after fixation with methanol/acetone and Karnovsky's fixative and probably are oncoembryonic/oncofetal antigen(s). The data suggest that the use of McAbs recognizing tumor associated oncofetal antigens in immunohistochemistry facilitates objective typing of intracranial malignancies and precise analysis of fine needle brain/tumor biopsies in a sensitive and reproducible manner

Searching for life with rovers: exploration methods and science results from the 2004 field campaign of the “Life in the Atacama” project and applications to future Mars Missions

LITA develops and field tests a long-range automated rover and a science payload to search for microbial life in the Atacama. The Atacama's evolution provides a unique training ground for designing and testing exploration strategies and life detection methods for the search for life on Mars

Nonsense-Mediated mRNA Decay Modulates Immune Receptor Levels to Regulate Plant Antibacterial Defense

SummaryNonsense-mediated mRNA decay (NMD) is a conserved eukaryotic RNA surveillance mechanism that degrades aberrant mRNAs. NMD impairment in Arabidopsis is linked to constitutive immune response activation and enhanced antibacterial resistance, but the underlying mechanisms are unknown. Here we show that NMD contributes to innate immunity in Arabidopsis by controlling the turnover of numerous TIR domain-containing, nucleotide-binding, leucine-rich repeat (TNL) immune receptor-encoding mRNAs. Autoimmunity resulting from NMD impairment depends on TNL signaling pathway components and can be triggered through deregulation of a single TNL gene, RPS6. Bacterial infection of plants causes host-programmed inhibition of NMD, leading to stabilization of NMD-regulated TNL transcripts. Conversely, constitutive NMD activity prevents TNL stabilization and impairs plant defense, demonstrating that host-regulated NMD contributes to disease resistance. Thus, NMD shapes plant innate immunity by controlling the threshold for activation of TNL resistance pathways

Correlation between Macular Neovascularization (MNV) Type and Druse Type in Neovascular Age-Related Macular Degeneration (AMD) Based on the CONAN Classification

To investigate associations and predictive factors between macular neovascularization (MNV) lesion variants and drusen types in patients with treatment-naïve neovascular age-related macular degeneration (AMD). Methods: Multimodal imaging was retrospectively reviewed for druse type (soft drusen, subretinal drusenoid deposits (SDDs) or mixed) and MNV type (MNV 1, MNV 2, MNV 1/2 or MNV 3). The Consensus on Neovascular AMD Nomenclature (CONAN) classification was used for characterizing MNV at baseline. Results: One eye of each eligible patient was included (n = 191). Patients with predominant SDDs had an increased adjusted odds ratio (aOR) for MNV 2 (23.4453, p = 0.0025) and any type of MNV 3 (8.7374, p < 0.0001). Patients with MNV 1/2 had an aOR for predominant SDDs (0.3284, p = 0.0084). Patients with MNV1 showed an aOR for SDDs (0.0357, p < 0.0001). Eyes with SDDs only without other drusen types showed an aOR for MNV 2 (9.2945, p < 0.0001). Conclusions: SDDs represent a common phenotypic characteristic in AMD eyes with treatment-naïve MNV. The aOR for eyes with predominant SDDs to develop MNV 2 and MNV 3 was much higher, possibly due to their location in the subretinal space. The predominant druse type may help to predict which type of MNV will develop during the course of AMD