Early Appearance Research Articles

Environmental temperature influences ophidiomycosis progression and survival in experimentally challenged prairie rattlesnakes (Crotalus viridis).

Ophidiomycosis is a prevalent and intermittently pervasive disease of snakes globally caused by the opportunistic fungal pathogen, Ophidiomyces ophidiicola. Host response has yet to be fully explored, including the role of temperature in disease progression and hematologic changes. This study enrolled twelve adult prairie rattlesnakes (Crotalus viridis) in an experimental challenge with O. ophidiicola at two temperatures, 26°C (n = 6) and 20°C (n = 6). Each temperature cohort included four inoculated and two control snakes. Assessments involving physical exams, lesion swabbing, and hematology were performed weekly. Differences were observed between inoculated and control snakes in survival, behavior, clinical signs, ultraviolet (UV) fluorescence, hematologic response, and histologic lesions. All inoculated snakes held at 20°C were euthanized prior to study end date due to severity of clinical signs while only one inoculated animal in the 26°C trial met this outcome. In both groups, qPCR positive detection preceded clinical signs with regards to days post inoculation (dpi). However, the earliest appearance of gross lesions occurred later in the 20°C snakes (20 dpi) than the 26°C snakes (13 dpi). Relative leukocytosis was observed in all inoculated snakes and driven by heterophilia in the 20°C snakes, and azurophilia in the 26°C group. Histologically, 20°C snakes had more severe lesions, a lack of appropriate inflammatory response, and unencumbered fungal proliferation and invasion. In contrast, 26°C snakes had marked granulomatous inflammation with encapsulation of fungi and less invasion and dissemination. The results of this study identified that O. ophidiicola-infected rattlesnakes exposed to lower temperatures have decreased survival and more robust hematologic change, though minimal and ineffective inflammatory response at site of infection. Ophidiomycosis is a complex disease with host, pathogen, and environmental factors influencing disease presentation, progression, and ultimately, survival. This study highlighted the importance of temperature as an element impacting the host response to O. ophidiicola.

Effects of co-inoculation of Bioformulates (PGPR's) on germination percentage and growth promotion in papaya (Carica papaya L.) seedlings

Dormancy is a blockage to germination and represents an adaptive mechanism that allows papaya seed to delay its emergence. Rhizobacteria improve plant growth in several ways, phytohormone production, nitrogen fixation, phosphate solubilization and increase root morphology. The present investigation was conducted to determine the efficiency of rhizobacteria (PGPR's) Pseudomona protegens (CHA0) and Pseudomona putida (BMR 2-4) inoculated within three bioformulates to be evaluated within the percentage of germination, increase of absorbing hairs using rhizotrons and seedlings under consortia or in combination of phosphorus fertilizers. Under in-vitro conditions, BIOIMPULSE co-inoculation was very effective in increasing germination percentage with an average of 80%. In rhizotrons, a greater increase in absorbing hairs of 5.67 mm and root area of 0.86 mm2 per BIOIMPULSE was exhibited, comparable to the treatment with AIA (25 mg/mL). In seedlings, BIOIMPULSE is highly effective in improving root morphology and height by emendando 5 g/L phosphorus was observed Ø hypocotyl dimensions between (5.12 to 4.62 mm) and functional leaves (9.75 to 11.75). BIOIMPULSE modifies root functioning, improves plant nutrition, and influences vegetative physiology, being versatile over all other bioformulates by increasing the germination percentage, early appearance of root hairs and root growth in the presence of phosphorus fertilizers. This means that they can be useful to reduce the cost of chemical fertilizers.

Natufian Hunter-Gatherers Fishing Strategies: The Early Appearance of the Fishhooks in the Near East and Their Significance

Natufian Hunter-Gatherers Fishing Strategies: The Early Appearance of the Fishhooks in the Near East and Their Significance

A history of thalidomide in India.

In contrast to the well-known stories of the embryotoxic drug, thalidomide, in countries where it was responsible for large numbers of birth defects, there is limited information on its history in India. Its presence before 2002, when the country issued the first marketing licence for a thalidomide-containing preparation, is assumed to be negligible. This article challenges this view by showing that the drug entered the Indian subcontinent through the former Portuguese territory of Goa around 1960. We examine the subsequent development of its distribution, use and regulation in India from the mid-1960s up to the present situation. Colonial legacies are a crucial explanation for the early appearance of thalidomide on the Indian subcontinent. They also influenced its re-emergence as drug for treating leprosy reactions in India after 1965. We identify key actors in this process: the original German producer that delivered thalidomide free of charge, European doctors who worked for international non-governmental organizations, the World Health Organization (WHO), which supported clinical trials and later discouraged the use of the drug, and finally the Indian state institutions that limited its distribution and later quickly opened the way for the private sector to produce and market thalidomide and its analogues. Finally, we discuss the risk of thalidomide-induced birth defects by casting a critical look on the present state of regulatory provisions and the monitoring of birth defects in India.

CLINICAL FUNCTIONAL CHARACTERISTICS OF SICK CHILDREN WITH GLOMERULONEPHRITIS WITH INCREASED THYROID FUNCTION

Abstract: To date, there have been few works on a comprehensive study of the functional state of the thyroid gland in glomerulo- and pyelonephritis in children, but there is no consensus on the nature of these relationships (12,13,14). Purpose of the work: to study the clinical and functional characteristics of sick children with glomerulonephritis with increased thyroid function. Material and methods of research: The work is based on clinical observations, examination and treatment of 22 children with glomerulonephritis with hyperfunction of the thyroid gland aged 5 to 17 years, who were hospitalized in the neurological department. Conclusions: characterizing the features of the clinical course of glomerulonephritis in children with increased activity of the thyroid system, one should first of all note the presence of 2 clinical variants of the disease: acute glomerulonephritis with nephritic syndrome, which was characterized by an acute onset with symptoms of general intoxication, early appearance of renal symptoms, and the presence of mixed polymorphic urinary syndrome , pronounced edema, a variety of extrarenal changes.

Acute acrylamide poisoning with severe symptoms in a short time: a case report

BackgroundAcrylamide poisoning is often reported as chronic poisoning presenting with peripheral neuropathy or carcinogenic action due to long-term exposure to low concentrations. However, there have been few reports of acute poisoning due to oral ingestion of acrylamide, where the symptoms appear a few hours after ingestion. Here, we report a case of acute acrylamide poisoning where a high concentration was ingested in a short time, resulting in a fatal outcome due to the rapid course of events.Case presentationThe patient was an adolescent female who ingested 150 ml (148 g) of acrylamide with suicidal intent. A disorder of consciousness was observed when the emergency medical team arrived 36 min later. An hour later, tracheal intubation and intravenous access were performed at a hospital, and 2 h after that, she was transported to our hospital. After she arrived at the hospital, circulatory dynamics could not be maintained despite vasopressor and colloid osmotic infusion, and hemodialysis could not be introduced. Subsequently, cardiopulmonary arrest occurred, and the patient passed away 7 h after ingestion.In the present case, severe symptoms appeared shortly after acrylamide ingestion, unlike other reported cases. In previous report summarizing animal studies, there was a relationship among the symptoms of acute poisoning, the dose, and onset time. The data from this case were compared to those from previous reports, and we were able to predict the early appearance of severe symptoms based on this comparison.ConclusionThe severity of acute acrylamide poisoning by oral ingestion was primarily dependent on the amount and rate of ingestion.

Comparison of Evaporite-Related Source Rocks and Implications for Petroleum Exploration: A Case Study of the Dongying Depression, Bohai Bay Basin, Eastern China

The Dongying Depression (Bohai Bay Basin, eastern China) was widely filled with evaporite (anhydrite and halite) layers during the Paleogene period, especially the middle of the fourth member of the Shahejie Formation (Es4). Most evaporite layers are interbedded with mudstone strata. The strata of Es4 are divided into three sections, referred to as the upper layers, evaporite layers, and lower layers, respectively. The analysis of elemental concentrations, elemental ratios, and Pr/Ph suggests that the lower layers were deposited in an intermittent saline lake environment within a relatively dry climate. The evaporite layers were formed in a highly saline lake environment, whereas the upper layers were formed in a brackish-saline to fresh-water environment. Organic matter (OM) abundance indices, including total organic carbon (TOC), chloroform extracts, total hydrocarbon content (HC), hydrocarbon generation potential (S1 + S2), and OM type, show that the source rock potential for petroleum generation in the upper layers is best, that in the evaporite layers is fair, and in the lower layers it is poor. Carbon isotopes (δ13C) of hydrocarbons in the evaporite and lower layers were heavier than those in the upper layers. Thermal maturity parameters show that the thermal evolution process of OM in the upper layers was faster where evaporite were present compared with evaporite-free areas, while the thermal evolution of OM in the lower layers was slower in these regions. The high thermal conductivity of evaporites may have accelerated the thermal evolution of source rocks in upper layers and allowed hydrocarbon generation at a shallower burial depth. This resulted in the earlier appearance of the petroleum generation window compared to in evaporite-free areas. Meanwhile, the thermal evolution of OM in the lower layers was restrained, and consequently the hydrocarbon generation window was widened, which implies the potential for petroleum exploration in deep strata under the evaporite sequence. This is a common phenomenon in evaporite-bearing basins, according to previous and present studies.

Autonomous fracture flow tunning to enhance efficiency of fractured geothermal systems

To avoid any shortcuts that may “short-circuit” the fluid flow between the injection and production wells in an enhanced geothermal system (EGS), we explore the idea of autonomous in-situ tunning of fracture hydraulic conductivity (FCTT) and its potential benefits. The new technique is expected to provide variable fracture hydraulic conductivity depending on the surrounding temperature. Through FCTT, we can effectively manage the fluid flow in the reservoir and promote a uniform thermal gradient along the flow paths. A numerical finite element model is established to assess the impact of tunning magnitude and fracture network geometries on the production efficiency of EGSs. Results show that utilizing this technique could prevent an early appearance of fluid flow shortcut between injector and producer in an EGS. After 50 years of production, the output thermal power with the technique could be increased by 67.51%. Furthermore, we found that fracture density and fracture network connectivity in the reservoir could affect performance improvement reached by FCTT in production. We also present a field case with a realistic fracture network. After 50 years of production, applying this technique increases heat extraction by 101.78% in fracture networks that are expected in EGS. Since other flow-control systems in geothermal production are mainly focused on the wellbore and near-wellbore areas, this technique can provide a more effective enhancement in heat extraction by controlling flow deep inside the reservoir.

Gonadal morphogenesis in the South American toad Rhinella Arenarum (Anura, Bufonidae) unveils an extremely delayed rate of sex differentiation.

Among anurans, Bufonids are recognized for their retarded sex differentiation. However, few studies have addressed gonadal morphogenesis in this family. Here, we analyzed the early gonadogenesis in laboratory-reared Rhinella arenarum. Few germ cells were identified in the genital ridge at Gosner stage 26. At metamorphosis, somatic cells and germ cells were observed in the outer region of the undifferentiated gonad, whereas the central region was occupied by stromal tissue. A cortico-medullary organization was first recognized on Day 7 postmetamorphosis. The cortex was composed of germ cells and encompassing epithelial cells, whereas the medulla contained cells presumptively derived from the coelomic epithelium. Medullary somatic cells formed metameric knots along the length of the undifferentiated gonad. Consequently, a series of 12-14 gonomeres became recognizable externally. The first sign of ovarian differentiation was observed on Day 15 postmetamorphosis, when a cavity was formed within each gonomere. In contrast, testes were recognized by a uniform distribution of germ cells and intermingled somatic cells, as the division into cortex and medulla was lost. By Day 50 postmetamorphosis, the gonadal metameric organization was still apparent both in the ovaries and testes. Follicles containing diplotene oocytes were observed within the ovary. In the testis, an incipient lobular architecture was recognized without initiation of meiosis within the seminiferous cords. These observations reveal an extremely delayed gonadal development in R. arenarum, not reported previously for other anuran species. In addition, the late differentiation of the gonads contrasted with the early appearance of follicles in the Bidder's organ. Lastly, we observed that delayed metamorphs exhibited an undifferentiated gonad, demonstrating that gonadogenesis in this species is more dependent on somatic development than on age.

Early appearance of radiolucent lines around total knee arthroplasty in rheumatoid arthritis patients. How does it impact the aseptic failure rate and functional outcomes at 13 years of follow-up?

IntroductionAseptic total knee arthroplasty (TKA) failure has been associated with radiolucent lines. This study aimed to determine the impact of the early appearance of radiolucent lines (linear images of 1, 2, or >2mm at the cement–bone interface) around the TKA on prosthetic survival and functional outcomes in rheumatoid arthritis (RA) patients during a 2–20 years follow-up. MethodsWe retrospectively analyzed a consecutive series of RA patients treated with TKA between 2000 and 2011. We comparatively analyzed patients with and without radiolucent lines around implants. Clinical outcomes were assessed with the knee society score (KSS) collected before surgery, at years 2, 5, and 10, and at the last postoperative follow-up. The knee society roentgenographic evaluation system was used to analyze the impact of radiolucent lines around the implants at 1, 2, 5, and more than ten years of follow-up. The reoperation and prosthetic survival rates were calculated at the end of the follow-up. ResultsThe study series included 72 TKAs with a median follow-up of 13.2 years (range: 4.0–21.0), of which 16 (22.2%) had radiolucent lines. We did not observe aseptic failure, and prosthetic survival at the end of the study was 94.4% (n=68). The KSS improved significantly (p<0.001) between preoperative values at 2, 5, and 10 years and the end of follow-up, with no differences between patients with and without radiolucent lines. ConclusionsOur study demonstrates that the early appearance of radiolucent lines around a TKA in RA patients does not significantly impact prosthetic survival or long-term functional outcomes at 13 years of follow-up.

Danian-Ypresian dinocyst biostratigraphy, fish fauna and depositional environment of the Akli Formation, Barmer Basin, western India

ABSTRACT Herein, we present a diverse record of dinoflagellate cysts from the lignite-associated sedimentary succession (belonging to the Akli Formation) at Sonari Lignite Mine, Barmer Basin, Rajasthan State, western India. The dinoflagellate cyst assemblage implies a Danian to Ypresian age for the investigated succession and argues that the deposition of lignitic sequences along India’s western margin is not coeval. We also identify two vertebrate (dominantly fish-yielding) units within the studied Akli Formation succession. The Ypresian fish genera (mainly represented by dental remains) include Ginglymostoma, Jaekelotodus, Brachycarcharias, Pycnodus and Myliobatis while the Selandian-Thanetian fish dental remains include Dasyatis. A discontinuous distribution of fish fauna during the early Paleogene (based on the temporal and spatial data) within the lignite-associated sedimentary successions of western and north India allows us to infer the prevalence of separated realms with variably restricted palaeoenvironmental conditions. Overall, the faunal evidence is indicative of dominantly estuarine to shallow marine conditions with enhanced freshwater influence during the Thanetian as compared to the Danian. Our study also argues in favour of the earliest appearance of dinoflagellate cyst Apectodinium in the near-equatorial region of the Tethys Ocean during the early Paleocene. (within Danian).

Growth mechanism of oxide layer on Ti-6Al-4 V substrate with different surface topographies during the early stage of micro-arc oxidation

The aim of this work was to explore the effect of microscopic surface topographies of the Ti-6Al-4 V alloy on the coating growth behaviour during the initial stages of micro-arc oxidation (MAO). Firstly, MAO treatments were carried out on the surfaces of Ti-6Al-4 V alloys with different surface morphologies for 5, 10 and 15 min respectively. Second, the effects of substrate topographies on the roughness, porosity, thickness, and microstructure of the coatings were studied. Then, the corrosion resistance of the MAO-treated titanium alloys was assessed by electrochemical analysis. Finally, the formation mechanisms and morphological results of the oxide layer were discussed and illustrated graphically. The results showed that the surface morphologies of the substrate affected the micro-arc discharge behaviour during the process of oxidation. Notably, rough areas on the substrate surface facilitated the breakdown of the passivation film, which was evidenced by the early appearance of plasma discharges in these areas. However, surface morphology with uneven distribution of pores observed in the oxide layer formed by the rough substrate. The coatings grown on the grooves were more porous than those grown in other areas, due to the non-uniformity of the micro-discharge on the rough substrate surface.

Abdominal Penetrating Aortic Ulcer and Endovascular Treatments: A Systematic Review and Meta-Analysis.

Abdominal penetrating aortic ulcer (aPAU) is defined as an ulceration of the aortic intima and media lamina, even with rupture of the internal elastic lamina. Recently, there have been an increasing number of publications on endovascular treatment for aPAU. This review aimed to assess the efficacy and safety of endovascular treatment and provide clinicians with the latest evidence-based medical data. 3 academic databases (Embase, PubMed, and Scopus) were systematically searched for literature reporting on aPAU from 1986 (the earliest appearance of the concept of aPAU) to September 1, 2021, and related data were collected and evaluated. A fixed/random effects model was used to construct the forest plots. Funnel plots and linear regression tests were used to assess the publication bias. 6 articles including 121 patients were included in the analysis. The average age was 71.4years, with 72.7% of males and 85.6% with hypertension. Saccular aneurysms (SA) were the most prevalent complication (35.5%). Endovascular treatment had a perioperative mortality rate of .24% (95% CI, .00-2.70). The technical success rate was 99.15% (95% CI, 96.49-100). The type-II endoleak rate was 5.69% (95% CI, .00-12.13). The 1-year survival rate was 95.69% (95% CI, 90.49-100). The revascularization rate was 7.20% (95% CI, .07-14.32). Endovascular treatments for aPAU would lead to a high rate of technical success, few complications, and satisfactory 1-year survival. aPAU are a common disease that mainly affects elderly males with hypertension and hyperlipidemia. Endovascular treatment is required when an ulcer progresses rapidly or manifests symptoms. Endovascular treatment is associated with high technical success, low complication, and satisfactory 1-year survival. Further investigation into the long-term results of endovascular treatment is necessary.

Evo-Devo in Ophiuroids: The Switch from Planktotrophy to Lecithotrophy in Ophionereis.

AbstractUnderstanding the evolution of development (evo-devo) in the Ophiuroidea and the pathways in the switch from a feeding to a nonfeeding larva is complicated by the variability in the phenotype of the metamorphic larva, being a reduced yolky ophiopluteus in some species (type I development) and a vitellaria larva in others (type II development). We investigated evo-devo in the family Ophionereididae, a group dominated by lecithotrophic development through a vitellaria larva. We reared the planktotrophic larvae of Ophionereis fasciata to settlement to determine the metamorphic phenotype. Counter to expectations, O. fasciata did not exhibit type II metamorphosis through a vitellaria, although it did exhibit transient vitellaria-like features. Resorption of the larval arms in the same interradial positions where the ciliary bands form in vitellariae gave them a fleeting vitellaria-like appearance. Development of O. fasciata exhibits heterochronic features in early formation of the skeletal primordium of the third pair (postoral) of larval arms and in the presettlement juvenile early appearance of the juvenile terminal arm plates on external view in parallel with larval arm resorption. Development of the fourth pair (posterodorsal) of larval arms, the last pair to be formed, is plastic, with 44% of larvae exhibiting partial arm growth. Heterochronic traits in development, as seen in O. fasciata, may have facilitated evolution of a lecithotrophic mode of development in Ophionereis. Comparison of the ophiopluteus of O. fasciata and the vestigial pluteus of O. schayeri provided insights into the simplification of larval form from the ancestral (feeding larva) state in Ophionereis. The diverse metamorphic phenotypes in ophiuroids indicate that type I and type II development may not be completely divergent lines of evo-devo and point to selective pressure in the pelagic-benthic transition in the evolution of ophiuroid development.

Bacterial Microorganisms in Definitive Neonatal Sepsis

Background The proper diagnosis and treatment of neonatal sepsis is done depends on the understanding of its causative organisms. Objective The present study aimed to investigate the types of microorganisms in definitive neonatal sepsis. Methods Neonatal sepsis is a serious infectious disease with high mortality. And its diagnosed by blood culture. It includes early (appearance of clinical symptoms from birth to the third-seventh day) and late (from the third day to the twenty-eighth day) types with specific and sometimes common clinical symptoms. This cross-sectional study was performed on 266 neonates hospitalized with definitive sepsis in Ghaem Hospital in Mashhad from 2010 to 2020 using available sampling method. Infants suspected of bacterial infection who had positive blood cultures were included in the study. Type of bacterial organism, time of sepsis, main causes of death and need for mechanical ventilation were evaluated. Results Eighty eight neonates had early sepsis and 197 neonates had late sepsis. The bacterial organism of early sepsis was gram negative as 70.1% and in late sepsis was gram negative as 77.1%. The most common causes of early sepsis were Klebsiella pneumonia 21 cases (23.9%), Staphylococcus epidermis 16 cases (18.2%) and 10 cases (11.4%) E. coli . And the most common causes of late sepsis were K. pneumonia 35 cases (25.4%), Enterobacter aeroginosa 25(18.1%), S. epidermis 12(8.7%) and E. coli 11(8%). Conclusion K. pneumonia, S. epidermis and E. coli were three most common organisms in early neonatal sepsis and K. pneumonia, S. epidermis and Enterobacter were the most common organisms in late neonatal sepsis.

Early appearance of functional plasma cells (CD138+CD98+) in non-immunized neonate mice

Plasma cells (PCs) are terminally differentiated antibody-secreting cells, derived from activated B-lymphocytes in response to either T-independent or T-dependent antigens. The plasma cell population is scarce in circulation in non-immunized individuals. It is established that neonates are incapable of mounting an efficient immune response due to the immaturity of the immune system. However, this disadvantage is well overcome through the antibodies neonates receive from breastmilk. This implies that neonates will be only protected against antigens the mother had previously encountered. Thus, the child might be potentially susceptible to new antigens. This issue prompted us to seek for the presence of PCs in non-immunized neonate mice. We found a PC population identified as CD138+/CD98+ cells since day one after birth. These PCs were positive for Ki67 and expressed Blimp-1, B220, and CD19, which suggests the populations are plasmablasts and PCs with heterogeneous phenotype. These PCs were also determined to secrete antibodies, although mainly isotype IgM. Altogether, the results indicated that neonate PCs can produce antibodies against antigens they encounter in the first weeks of life, most likely coming from food, colonizing microbiota, or the environment.

Study on the Effect of External Air Supply and Temperature Control on Coal Spontaneous Combustion Characteristics

Coal spontaneous combustion in underground mine goaf has a great impact on coal mining. The temperature-programmed experiment is a commonly used and effective method for studying the characteristics of coal spontaneous combustion. Aiming at the problem that the numerical simulation of coal spontaneous combustion characteristics under the condition of external air supply and temperature control in a temperature-programmed experiment is insufficient, a multi-physical field coupling numerical model of coal spontaneous combustion in the temperature-programmed experiment is established. The variation characteristics of coal temperature, oxygen, and oxidation products under external air supply and temperature control were studied. The results show that the numerical simulation results are consistent with the experimental results. With the increase in temperature, the volume fractions of oxygen and carbon dioxide decrease and increase, respectively. As the air supply volume increases, the oxygen volume fraction at the outlet increases, and the peak value of the oxygen volume fraction change rate exhibits a “hysteresis” feature, and the time corresponding to the peak value increases. Moreover, the temperature change rate increases. With the increase in the heating rate, the peak value of the oxygen volume fraction change rate increases and shows an “early appearance” characteristic, at the same time, the maximum coal temperature displays a linear increase trend.

Abdominal visceral tuberculosis: a malignancy mimic.

The purpose is to discuss abdominal tuberculosis mimicking malignancy involving the abdominal viscera. TB of the abdominal viscera is common, especially in countries where tuberculosis is endemic and in pockets of non-endemic countries. Diagnosis is challenging as clinical presentations are often non-specific. Tissue sampling may be necessary for definitive diagnosis. Awareness of the early and late disease imaging appearances of abdominal tuberculosis involving the viscera that can mimic malignancy can aid detecting TB, providing a differential diagnosis, assessing extent of spread, guiding biopsy, and evaluating response.

Triplication of HSA21-encoded genes modulates Alzheimer’s Disease-related phenotypes in vivo

Abstract People with Down syndrome (DS), the genetic condition caused by Trisomy 21 (T21), exhibit early appearance of Alzheimer’s disease (AD), likely due to the triplication of the Amyloid Precursor Protein (APP) gene. However, the impact of many chromosome 21 (HSA21) genes on AD phenotypes in the context of DS remains unknown. To test this, we conducted a detailed phenotypic characterization of how AD-related neuropathology is modulated by an extra copy of genes orthologous to HSA21 by creating a novel DS-AD mouse strain, by crossing Dp16 with 5xFAD mice (models for DS and AD, respectively), generating: WT, Dp16, 5xFAD, and 5xFAD-Dp16 mice. Here, we performed a battery of behavioral assessments longitudinally and paired these analyses with endpoint transcriptional profiling and high-content imaging. We identified that DS-AD mice exacerbate cognitive deficits and show increased neuronal cell loss in multiple brain regions compared to DS and AD mice. Although, DS-AD mice do not present altered amyloid-β (Aβ) pathology compared to AD mice at 9-months of age, an increased number of activated microglia associated to Aβ plaques are present with a distinct transcriptional signature indicative of disease associated and interferon-activated microglia cells in these animals. These results indicate that DS contributes to the neuroinflammation network of AD, causing changes in cellular states consistent with alterations in memory and cognitive decline. However, deeper characterization is needed to understand the mechanisms by which T21 contributes to AD-pathogenesis to determine potential therapeutic intervention to significantly improve neurological health in people with DS. Supported by grants from NIH (R01AI145988 and R01AI150305). Supported by grants from NIH (R01AI145988 and R01AI150305)

B cell apoptosis and inflammation conspire to promote lupus in mice

Abstract The pathogenesis of Systemic lupus erythematosus (SLE) is driven by autoreactive B and T cells and autoinflammation. Impaired apoptosis in T and B cells has been shown to result in autoimmune disease, and we recently demonstrated that reducing apoptosis in B cells alone, by B cell-specific deletion of Bim (B.Bim f/f) could lead to SLE with prominent features of Sjogren’s Syndrome in C57BL/6 mice. Consistently, B cell targeting therapies are successful in reducing SLE pathogenesis in mouse models, however, their clinical success requires a better understanding of the contributions of B cells and the mechanisms that drive inflammation to autoimmunity. To address the role of inflammation in the development and progression of autoimmunity we generated a novel mouse model that lacks ZFAND6 (Zfand6 −/−) and crossed with the B.Bim f/fmice. ZFAND6 is an A-20 like ZF domain-containing protein with a potential role in the negative regulation of NF-kB activation, however, its physiological function is unknown. The compound mutant mice displayed accelerated and exacerbated overlapping lupus and Sjogren’s autoimmune symptoms with a higher incidence of splenomegaly and kidney pathology than either single mutant alone including the early appearance of anti-SSA, anti-SSB, and anti-RNP autoantibodies. The compound mutant mice displayed increased spontaneous and TLR-induced TNFa and IL-6 and B cells from these mice produced much greater levels of these cytokines in response to TLR7 and TLR9. These results suggest that inappropriate B cell survival and persistent inflammation cooperate in the initiation and severity of lupus pathogenesis. Sylvester Comprehensive Cancer Center, University of Miami, Miami FL