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Background: Emergency laparotomy, a critical surgery for acute abdominal emergencies, presents significant risks of complications and mortality. Accurately predicting outcomes remains challenging, impacting resource allocation and tailored post-operative care. This study investigates serum albumin, a key blood protein, as a potential predictive marker in emergency laparotomy patients. Methods: This prospective observational study enrolled 62 emergency laparotomy patients at IGOT hospital Bengaluru between May and August 2023. Data on demographics, surgical indications, procedures, pre-operative, post operative albumin levels, and post-operative complications were collected. Complications were categorized using the Clavien-Dindo classification. Statistical analysis assessed the relationship between albumin levels and outcomes. Results:Patients averaged 46.67 years old, predominantly male (64%). Gastric perforation was the most common surgical indication (24%), followed by ileal perforation and intestinal obstruction (16% each). Pre-operative hypoalbuminemia (albumin < 3.5 g/dL) was associated with a higher complication rate (58%) compared to normal levels (38%). Severity of complications correlated with post-surgery albumin decrease. Pre-operative albumin inversely correlated with hospital stay duration, while post-operative albumin drop positively correlated with stay length. Discussion: This study underscores serum albumin's potential as a predictor of post-operative outcomes in emergency laparotomy. High hypoalbuminemia prevalence (62%) and its complication association emphasize nutritional status's critical role. Lower pre-operative albumin and greater post-operative decrease were linked to increased complication risk and severity, suggesting albumin's value in risk stratification and targeted post-operative care for potentially improved outcomes. Conclusion: This study provides compelling evidence for serum albumin's potential as a predictor of post-operative complications in emergency laparotomy. Optimizing pre-operative albumin levels may be crucial for reducing complications and enhancing patient recovery. Further research is warranted to explore albumin level monitoring's clinical utility and interventions to improve albumin status for better surgical outcomes. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder caused by persistent measles virus infection. SSPE predominantly affects children and adolescents. The symptoms usually develop 6-15 years after measles infection and ultimately leading to death in many cases. Patient 1 presented with cognitive decline and myoclonus and the Patient 2 presented with diminution of vision with myoclonic jerks. Based on the clinical features with a characteristic electroencephalogram pattern and the presence of a high titer of anti-measles IgG in serum and cerebrospinal fluid, these patients were diagnosed as SSPE. Antiepileptics were started for controlling myoclonus along with supportive treatment. Both patients were discharged on antiepileptics and supportive care. Whenever there are unusual clinical manifestations with unknown vaccination status, SSPE can be suspected and the cerebrospinal fluid should be examined for anti-measles antibodies. Our case study also highlights the importance of universal coverage of measles vaccination. To reduce the incidence of measles and associated deaths, it is important to maintain a high level of immunization coverage for the measles vaccine and to strengthen all the integral components of the national immunization program.

The process of drying agricultural products for food preservation is a difficult task that requires a significant amount of energy. The increasing cost and depletion of fossil fuels have led to the development of a food dryer that utilizes renewable energy sources. This research paper proposes the design and performance evaluation of an indirectly forced convection desiccant integrated solar dryer (IFCDISD) at the Solar Energy Research Lab at USPCAS-E, NUST Pakistan. Tomatoes were chosen as the test product due to their importance and widespread consumption. The drying process involves slicing the tomatoes and placing them on the IFCDISD rack, where a desiccant called calcium chloride (CaCl2) is integrated into the dryer. The experiments were conducted during both sunshine (SS) hours and Off-sunshine (OSS) hours. The IFCDISD operates using sunlight during SS hours and utilizes the absorbed heat of CaCl2 in OSS hours via a forced DC brushless fan powered by battery charged thro solar panel. The tomatoes were weighed before and after each drying mode, and the moisture removal was calculated. The results show that the dryer efficiency was 50.14 % on day 1, 66 % on day 2, and an overall efficiency of 58.07 %. The moisture content removal was 42.858 % on day 1, 22.9979 % on day 2, and an overall moisture content removal of 58.07 %. Moreover, the payback period is 5.1396 and the carbon mitigation was recorded as 2.0335, and the earned carbon credit was recorded as 11559.6.

Photonic and electronic properties exist inherently in ferroelectric barium titanate (BaTiO3); severe luminescence quenching also exists due to the insufficient confinement of excitons. In this sense, high optical emission can only be achieved by its chemical and structural modification. Thin BaTiO3 and Er:BaTiO3 films were grown by the spin coating method on a glass substrate at room temperature. Self-trapping of excitons in the thin BaTiO3 film and its structural modification due to the doping with Er3+ ions (Er:BaTiO3) are verified using scanning confocal fluorescence microscopy (SCFM), where self-trapping excitons never occured in its pure state. By thermal treatment and doping (BaTiO3 and Er:BaTiO3) we obtained localization of the excitons, which would further induce lattice strain around the surface defects, to accommodate the self-trapped excitons. With such a self-trapped state, the structure of BaTiO3 generates broadband emission of several overlapping bands between 1.95 and 2.65 eV at room temperature, while the structure Er:BaTiO3 showed defined emission bands at 2.24 and 2.35 eV, with very weak contributions of the emission due to the self-trapping state. The influence of the variation of the excitation wavelength using 1PE and 2PE on the emission bands of BaTiO3 and Er:BaTiO3 is also investigated. The results of enhanced emission bands suggest a clear dependence of the emission intensity on the excitation energy, where a ∼3 fold enhancement in emission has been demonstrated under Er3+ (1.55 eV) excitation, which can be attributed to effective energy transfer between the Er3+ ions. As a result, it is concluded that the developed BaTiO3 and Er:BaTiO3 can pave the way for future photonic devices. [ABSTRACT FROM AUTHOR]

Abstract Background Segmentation of nuclei in cervical cytology pap smear images is a crucial stage in automated cervical cancer screening. The task itself is challenging due to the presence of cervical cells with spurious edges, overlapping cells, neutrophils, and artifacts. Methods After the initial preprocessing steps of adaptive thresholding, in our approach, the image passes through a convolution filter to filter out some noise. Then, contours from the resultant image are filtered by their distinctive contour properties followed by a nucleus size recovery procedure based on contour average intensity value. Results We evaluate our method on a public (benchmark) dataset collected from ISBI and also a private real dataset. The results show that our algorithm outperforms other state-of-the-art methods in nucleus segmentation on the ISBI dataset with a precision of 0.978 and recall of 0.933. A promising precision of 0.770 and a formidable recall of 0.886 on the private real dataset indicate that our algorithm can effectively detect and segment nuclei on real cervical cytology images. Tuning various parameters, the precision could be increased to as high as 0.949 with an acceptable decrease of recall to 0.759. Our method also managed an Aggregated Jaccard Index of 0.681 outperforming other state-of-the-art methods on the real dataset. Conclusion We have proposed a contour property-based approach for segmentation of nuclei. Our algorithm has several tunable parameters and is flexible enough to adapt to real practical scenarios and requirements.

Diffuse reflectance spectroscopy in near infrared region was used as a fast laboratory method for quantitative assessment of the calorific value and the moisture content of Estonian oil shale. Samples of different caloricity were collected from Narva open-cast mine and from beneficiation plant of Estonia underground mine, Estonia. The set of crushed oil shale samples, which moisture content was varied were tested by the help of a commercial multipurpose analyser, where Fourier-transform spectrometer recorded spectra in near infrared region and the software used partial least squares regression method. Results were related to the values of caloricity and moisture content, obtained by the bomb calorimeter and weighing methods, respectively. Bands characterizing organic and inorganic parts of the samples as well as the presence of the free water were ascertained by the infrared spectroscopy. Using the software provided by the analyser, the calorific value and the moisture content of samples were predicted. The prediction error of the lower caloricity was 1 MJkg–1 and prediction error of the weight percent of the moisture content was 1.35%. The comparison between achieved results and the values obtained from earlier laser-induced breakdown spectroscopy (LIBS) measurements shows that in laboratory conditions more precise prediction can be made by diffuse reflectance measurements. Further improvement of the prediction accuracy could be achieved by modified software which considers observed nonlinear effects in spectra.

Objective: To investigate the experience of timely thesis completion by the graduates of the Master of Health Professions Education (MHPE) program in Pakistan. Study Design: Qualitative interpretative study design. Settings: Riphah University Islamabad and HITEC-IMS Taxila. Duration: May 2018 to June 2019. Materials and Methods: Data was collected by semi-structured interviews. All interviews were carried out in person. Detailed notes were taken, and conversations were audio-recorded. Three authors analyzed data independently using iterative thematic analysis. Inconsistencies were resolved through discussion. Results: Two major themes out of five were identified: Intrinsic attributes of the graduates and the role of the supervisor. including sub-themes of intrinsic motivation, self-regulation, age of the participant, supervisor-trainee relationship, supervisor’s availability, supervisor’s commitment, personality traits of the supervisor. Periods of face-to-face contact sessions were considered to increase internal motivation during which participants believe to have greater self-regulation. Positive relationship with a committed supervisor who was readily available and had a friendly, yet professional attitude aided in the completion of the thesis on time while a supervisor lacking these traits posed challenges for the graduates. Conclusion: Several factors were identified which influenced thesis completion among the graduates of MHPE in Pakistan. The five major ones consisted of the following, 1) Research Project-Related Problems; 2) Support System; 3) Supervisor Guidance; 4) Attributes of the Researcher; 5) Conducive Research Environment. These results can help influence policies to evaluate and improve this program.

Background: To assess the role of ascorbic acid in portal triaditis caused by Rifampicin. Methods: In this experimental study, thirty adult BALB/c mice weighing 35-50 grams were taken. They were kept under standard laboratory conditions of temperature and humidity and light/dark cycle. Animals were given diet pellets. Mice were randomized and divided into three groups (n=10 animals in each group).Group A was given rifampicin in a dose of 100 mg/kg, Group B was given rifampicin 100 mg/kg along with Ascorbic acid 500 mg/kg orally for 6 weeks.Group C was the control group Results: Histological examination of animals revealed significant change in portal triaditis in experimental group having Ascorbic Acid along with Rifampicin. Conclusion: Ascorbic acid has a protective role against Portal Inflammation caused by Rifampicin

Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)-a transcription factor known to regulate expression of actin and actin regulators in other cell types-as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the mechanistic role of SRF in oligodendrocyte lineage cells. Here, we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in oligodendrocyte precursor cells and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Surprisingly, oligodendrocyte-restricted loss of SRF results in upregulation of gene signatures associated with aging and neurodegenerative diseases. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies an essential pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease., Competing Interests: Competing interests statement:The authors declare no competing interest.

Here, we provide a step-by-step protocol for the collection and intracerebroventricular infusion of cerebrospinal fluid (CSF) in mice. We describe steps to withdraw CSF quickly and abundantly while avoiding blood contamination. Using the Lynch coil technique, we gain functional insights into the collected CSF by slowly infusing minimal amounts of CSF directly to the lateral ventricles of aged mice. This protocol is versatile and can be used to infuse drugs, antibodies, or scarce biological compounds. For complete details on the use and execution of this protocol, please refer to Iram et al. (2022). 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing 1-3 . Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds 4,5 . We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Lysosome dysfunction is a shared feature of rare lysosomal storage diseases and common age-related neurodegenerative diseases. Microglia, the brain-resident macrophages, are particularly vulnerable to lysosome dysfunction because of the phagocytic stress of clearing dying neurons, myelin, and debris. CD22 is a negative regulator of microglial homeostasis in the aging mouse brain, and soluble CD22 (sCD22) is increased in the cerebrospinal fluid of patients with Niemann-Pick type C disease (NPC). However, the role of CD22 in the human brain remains unknown. In contrast to previous findings in mice, here, we show that CD22 is expressed by oligodendrocytes in the human brain and binds to sialic acid–dependent ligands on microglia. Using unbiased genetic and proteomic screens, we identify insulin-like growth factor 2 receptor (IGF2R) as the binding partner of sCD22 on human myeloid cells. Targeted truncation of IGF2R revealed that sCD22 docks near critical mannose 6-phosphate–binding domains, where it disrupts lysosomal protein trafficking. Interfering with the sCD22-IGF2R interaction using CD22 blocking antibodies ameliorated lysosome dysfunction in human NPC1 mutant induced pluripotent stem cell–derived microglia-like cells without harming oligodendrocytes in vitro. These findings reinforce the differences between mouse and human microglia and provide a candidate microglia-directed immunotherapeutic to treat NPC.

Activity-dependent neuroprotective protein (ADNP) mutations are linked with cognitive dysfunctions characterizing the autistic-like ADNP syndrome patients, who also suffer from delayed motor maturation. We thus hypothesized that ADNP is deregulated in versatile myopathies and that local ADNP muscle deficiency results in myopathy, treatable by the ADNP fragment NAP. Here, single-cell transcriptomics identified ADNP as a major constituent of the developing human muscle. ADNP transcript concentrations further predicted multiple human muscle diseases, with concentrations negatively correlated with the ADNP target interacting protein, microtubule end protein 1 (EB1). Reverting back to modeling at the single-cell level of the male mouse transcriptome, Adnp mRNA concentrations age-dependently correlated with motor disease as well as with sexual maturation gene transcripts, while Adnp expressing limb muscle cells significantly decreased with aging. Mouse Adnp heterozygous deficiency exhibited muscle microtubule reduction and myosin light chain ( Myl2 ) deregulation coupled with motor dysfunction. CRISPR knockdown of adult gastrocnemius muscle Adnp in a Cas9 mouse resulted in treadmill (male) and gait (female) dysfunctions that were specifically ameliorated by treatment with the ADNP snippet, microtubule interacting, Myl2 -regulating, NAP (CP201). Taken together, our studies provide new hope for personalized diagnosis/therapeutics in versatile myopathies.

Photonic and electronic properties exist inherently in ferroelectric barium titanate (BaTiO3); severe luminescence quenching also exists due to the insufficient confinement of excitons. In this sense, high optical emission can only be achieved by its chemical and structural modification. Thin BaTiO3 and Er:BaTiO3 films were grown by the spin coating method on a glass substrate at room temperature. Self-trapping of excitons in the thin BaTiO3 film and its structural modification due to the doping with Er3+ ions (Er:BaTiO3) are verified using scanning confocal fluorescence microscopy (SCFM), where self-trapping excitons never occured in its pure state. By thermal treatment and doping (BaTiO3 and Er:BaTiO3) we obtained localization of the excitons, which would further induce lattice strain around the surface defects, to accommodate the self-trapped excitons. With such a self-trapped state, the structure of BaTiO3 generates broadband emission of several overlapping bands between 1.95 and 2.65 eV at room temperature, while the structure Er:BaTiO3 showed defined emission bands at 2.24 and 2.35 eV, with very weak contributions of the emission due to the self-trapping state. The influence of the variation of the excitation wavelength using 1PE and 2PE on the emission bands of BaTiO3 and Er:BaTiO3 is also investigated. The results of enhanced emission bands suggest a clear dependence of the emission intensity on the excitation energy, where a ∼3 fold enhancement in emission has been demonstrated under Er3+ (1.55 eV) excitation, which can be attributed to effective energy transfer between the Er3+ ions. As a result, it is concluded that the developed BaTiO3 and Er:BaTiO3 can pave the way for future photonic devices.

The vascular interface of the brain, known as the blood-brain barrier (BBB), is understood to maintain brain function in part via its low transcellular permeability 1-3 . Yet, recent studies have demonstrated that brain ageing is sensitive to circulatory proteins 4,5 . Thus, it is unclear whether permeability to individually injected exogenous tracers-as is standard in BBB studies-fully represents blood-to-brain transport. Here we label hundreds of proteins constituting the mouse blood plasma proteome, and upon their systemic administration, study the BBB with its physiological ligand. We find that plasma proteins readily permeate the healthy brain parenchyma, with transport maintained by BBB-specific transcriptional programmes. Unlike IgG antibody, plasma protein uptake diminishes in the aged brain, driven by an age-related shift in transport from ligand-specific receptor-mediated to non-specific caveolar transcytosis. This age-related shift occurs alongside a specific loss of pericyte coverage. Pharmacological inhibition of the age-upregulated phosphatase ALPL, a predicted negative regulator of transport, enhances brain uptake of therapeutically relevant transferrin, transferrin receptor antibody and plasma. These findings reveal the extent of physiological protein transcytosis to the healthy brain, a mechanism of widespread BBB dysfunction with age and a strategy for enhanced drug delivery.

Microglia become progressively activated and seemingly dysfunctional with age, and genetic studies have linked these cells to the pathogenesis of a growing number of neurodegenerative diseases. Here we report a striking buildup of lipid droplets in microglia with aging in mouse and human brains. These cells, which we call 'lipid-droplet-accumulating microglia' (LDAM), are defective in phagocytosis, produce high levels of reactive oxygen species and secrete proinflammatory cytokines. RNA-sequencing analysis of LDAM revealed a transcriptional profile driven by innate inflammation that is distinct from previously reported microglial states. An unbiased CRISPR-Cas9 screen identified genetic modifiers of lipid droplet formation; surprisingly, variants of several of these genes, including progranulin (GRN), are causes of autosomal-dominant forms of human neurodegenerative diseases. We therefore propose that LDAM contribute to age-related and genetic forms of neurodegeneration.

Focusing on microtubule heterogeneity and brain specificity allowed for initial discoveries of multiple tubulin isotypes four decades ago. Methods evolved from using radioactive labelling and single cell cultures to monoclonal antibodies recognizing discrete forms of tubulin in single neurons. With the advantage of molecular cloning and fluorescent protein tagging, essential components for microtubule dynamics/stability and function were identified, including activity-dependent neuroprotective protein, ADNP and its peptide snippet, NAP (drug candidate, davunetide/CP201). ADNP/NAP through the SxIP motif interact with microtubule end binding proteins EB1 and EB3 to increase microtubule dynamics, axonal transport and dendritic spine formation. Recent transcriptomic analysis of the young mouse brain at the single cell level enabled characterization of cell-type specific cytoskeleton related gene signatures (e.g., tubulin transcripts, microtubule-associated protein Tau, Mapt and microtubule end binding protein, EB3, Mapre3) at unprecedented detail. Here, we review these findings with a methodological perspective to highlight how cutting-edge techniques have allowed us to disentangle cytoskeleton dynamics in health and disease., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To gain unfettered insight into one of the scourges of our aging societies, Mathys and colleagues in Nature (Mathys et al., 2019) illuminate the brain transcriptome of Alzheimer's disease at single-cell resolution. Their findings implicate oligodendrocytes, a cell type largely neglected in Alzheimer's disease research, and sex in the disease in intriguing ways., (Published by Elsevier Inc.)

Microglia maintain homeostasis in the central nervous system through phagocytic clearance of protein aggregates and cellular debris. This function deteriorates during ageing and neurodegenerative disease, concomitant with cognitive decline. However, the mechanisms of impaired microglial homeostatic function and the cognitive effects of restoring this function remain unknown. We combined CRISPR-Cas9 knockout screens with RNA sequencing analysis to discover age-related genetic modifiers of microglial phagocytosis. These screens identified CD22, a canonical B cell receptor, as a negative regulator of phagocytosis that is upregulated on aged microglia. CD22 mediates the anti-phagocytic effect of α2,6-linked sialic acid, and inhibition of CD22 promotes the clearance of myelin debris, amyloid-β oligomers and α-synuclein fibrils in vivo. Long-term central nervous system delivery of an antibody that blocks CD22 function reprograms microglia towards a homeostatic transcriptional state and improves cognitive function in aged mice. These findings elucidate a mechanism of age-related microglial impairment and a strategy to restore homeostasis in the ageing brain.

In Alzheimer's disease (AD), astrocytes undergo morphological changes ranging from atrophy to hypertrophy, but the effect of such changes at the functional level is still largely unknown. Here, we aimed to investigate whether alterations in astrocyte activity in AD are transient and depend on their microenvironment, or whether they are irreversible. We established and characterized a new protocol for the isolation of adult astrocytes and discovered that astrocytes isolated from old 5xFAD mice have higher GFAP expression than astrocytes derived from WT mice, as observed in vivo. We found high C1q levels in brain sections from old 5xFAD mice in close vicinity to amyloid plaques and astrocyte processes. Interestingly, while old 5xFAD astrocytes are impaired in uptake of soluble Aβ42, this effect was reversed upon an addition of exogenous C1q, suggesting a potential role for C1q in astrocyte-mediated Aβ clearance. Our results suggest that scavenger receptor B1 plays a role in C1q-facilitated Aβ uptake by astrocytes and that expression of scavenger receptor B1 is reduced in adult old 5xFAD astrocytes. Furthermore, old 5xFAD astrocytes show impairment in support of neuronal growth in co-culture and neurotoxicity concomitant with an elevation in IL-6 expression. Further understanding of the impact of astrocyte impairment on AD pathology may provide insights into the etiology of AD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Glial scarring, formed by reactive astrocytes, is one of the major impediments for regeneration after spinal cord injury (SCI). Reactive astrocytes become hypertrophic, proliferate and secrete chondroitin sulphate proteoglycans into the extracellular matrix (ECM). Many studies have demonstrated that epidermal growth factor receptors (EGFR) can mediate astrocyte reactivity after neurotrauma. Previously we showed that there is crosstalk between nucleolin and EGFR that leads to increased EGFR activation followed by increased cell proliferation. Treatment with the nucleolin inhibitor GroA (AS1411) prevented these effects in vitro and in vivo. In this study, we hypothesized that similar interactions may mediate astrogliosis after SCI. Our results demonstrate that nucleolin and EGFR interaction may play a pivotal role in mediating astrocyte proliferation and reactivity after SCI. Moreover, we demonstrate that treatment with GroA reduces EGFR activation, astrocyte proliferation and chondroitin sulphate proteoglycans secretion, therefore promoting axonal regeneration and sprouting into the lesion site. Our results identify, for the first time, a role for the interaction between nucleolin and EGFR in astrocytes after SCI, indicating that nucleolin inhibitor GroA may be used as a novel treatment after neurotrauma. A major barrier for axonal regeneration after spinal cord injury is glial scar created by reactive and proliferating astrocytes. EGFR mediate astrocyte reactivity. We showed that inhibition of nucleolin by GroA, reduces EGFR activation, which results in attenuation of astrocyte reactivity and proliferation in vivo and in vitro. EGFR, epidermal growth factor receptor., (© 2016 International Society for Neurochemistry.)

Unlabelled: Multiple EGF-like domains 10 (Megf10) is a class F scavenger receptor (SR-F3) expressed on astrocytes and myosatellite cells, and recessive mutations in humans result in early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD). Here we report that Megf10-deficient mice have increased apoptotic cells in the developing cerebellum and have impaired phagocytosis of apoptotic cells by astrocytes ex vivo We also report that cells transfected with Megf10 gain the ability to phagocytose apoptotic neurons and that Megf10 binds with high affinity to C1q, an eat-me signal for apoptotic cells. In contrast, cells expressing Megf10 with EMARDD mutations have impaired apoptotic cell clearance and impaired binding to C1q. Our studies reveal that Megf10 is a receptor for C1q and identify a novel role for Megf10 in clearance of apoptotic cells in the mammalian developing brain with potential relevance to EMARDD patients and other CNS disorders., Significance Statement: Apoptosis is a universal homeostatic process and occurs in many disease conditions. Multiple EGF-like domains 10 (Megf10) is emerging as an essential receptor for synaptic pruning, clearance of neuronal debris, and for muscle differentiation. Here we define a novel Megf10-dependent pathway for apoptotic cell clearance and show that Megf10 is a receptor for C1q, an eat-me signal, that binds phosphatidylserine expressed on the surface of apoptotic cells. Understanding the pathways by which apoptotic cells are cleared in the CNS is relevant to many physiological and pathological conditions of the CNS., (Copyright © 2016 the authors 0270-6474/16/365185-08$15.00/0.)

Alzheimer's disease (AD) is the most prevalent form of dementia in elderly. Genetic studies revealed allelic segregation of the apolipoprotein E (ApoE) gene in sporadic AD and in families with higher risk of AD. The mechanisms underlying the pathological effects of ApoE4 are not yet entirely clear. Several studies indicate that autophagy, which plays an important role in degradation pathways of proteins, organelles and protein aggregates, may be impaired in AD. In the present study, we investigated the effects of ApoE4 versus the ApoE3 isoform on the process of autophagy in mouse-derived astrocytes. The results obtained reveal that under several autophagy-inducing conditions, astrocytes expressing ApoE4 exhibit lower autophagic flux compared to astrocytes expressing ApoE3. Using an in situ model, we examined the role of autophagy and the effects thereon of ApoE4 in the elimination of Aβ plaques from isolated brain sections of transgenic 5xFAD mice. This revealed that ApoE4 astrocytes eliminate Aβ plaques less effectively than the corresponding ApoE3 astrocytes. Additional experiments showed that the autophagy inducer, rapamycin, enhances Aβ plaque degradation by ApoE4 astrocytes whereas the autophagy inhibitor, chloroquine, blocks Aβ plaque degradation by ApoE3 astrocytes. Taken together, these findings show that ApoE4 impairs autophagy in astrocyte cultures and that this effect is associated with reduced capacity to clear Aβ plaques. This suggests that impaired autophagy may play a role in mediating the pathological effects of ApoE4 in AD.