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Supplementary Figure 2 from Reactive Oxygen Species Regulate Angiogenesis and Tumor Growth through Vascular Endothelial Growth Factor

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Reactive oxygen species (ROS) are associated with multiple cellular functions such as cell proliferation, differentiation, and apoptosis. However, the direct roles of endogenous ROS production still remain to be elucidated. In this study, we found that high levels of ROS were spontaneously produced by ovarian and prostate cancer cells. This elevated ROS production was inhibited by NADPH oxidase inhibitor diphenylene iodonium (DPI) and mitochondria electron chain inhibitor rotenone in the cells. To further analyze the source of ROS production, we found that ovarian cancer cells have much higher expression of NOX4 NADPH oxidase, and that specific inhibition of NADPH oxidase subunit p47phox diminished ROS production. To analyze the functional relevance of ROS production, we showed that ROS regulated hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF) expression in ovarian cancer cells. Elevated levels of endogenous ROS were required for inducing angiogenesis and tumor growth. NOX4 knockdown in ovarian cancer cells decreased the levels of VEGF and HIF-1α and tumor angiogenesis. This study suggests a new mechanism of higher ROS production in ovarian cancer cells and provides strong evidence that endogenous ROS play an important role for cancer cells to induce angiogenesis and tumor growth. This information may be useful to understand the new mechanism of cancer cells in inducing tumorigenesis and to develop new therapeutic strategy by targeting ROS signaling in human cancer in the future. [Cancer Res 2007;67(22):10823–30]

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Rickettsioses are caused by a broad range of obligate intracellular bacteria belonging to the genus Rickettsia that can be transmitted to vertebrate hosts through the bite of infected arthropod vectors. To date, emerging or re-emerging epidemic rickettsioses remain a public health risk due to the difficulty in diagnosis, as diagnostic methods are limited and not standardized or universally accessible. Misdiagnosis resulting from a lack of recognition of the signs and symptoms may result in delayed antibiotic treatment and poor health outcomes. A comprehensive understanding of Rickettsia characteristics would ultimately improve clinical diagnosis, assessment, and treatment with improved control and prevention of the disease. Functional studies of rickettsial genes are crucial for understanding their role in pathogenesis. This paper describes a procedure for the electroporation of the Rickettsia parkeri strain Tate's Hell with the shuttle vector pRAM18dSFA and the selection of transformed R. parkeri in tick cell culture with antibiotics (spectinomycin and streptomycin). A method is also described for the localization of transformed R. parkeri in tick cells using confocal immunofluorescence microscopy, a useful technique for checking transformation in vector cell lines. Similar approaches are also suitable for the transformation of other rickettsiae.

To investigate the age distribution of Mongolian patients with cerebral infarction caused by thrombosis and the correlation and consistency between thromboelastography (TEG) and four parameters of coagulation.The age distribution of 298 Mongolian patients with cerebral infarction treated in Affiliated Hospital of Inner Mongolia Minzu University from January 2020 to December 2021 and their TEG, four items of routin coagulation and platelet count were analyzed retrospectively. The correlation and consistency of above-mentioned two detection methods were statistically analyzed.The onset age of 298 Mongolian patients with cerebral infarction was mainly 61-70 years old, accounting for 38.3%, followed by 51-60 years old, accounting for 26.8%. The R time detected by TEG was linearly correlated with PT and APTT（r=0.186，r=0.152）. K value, MA value and α-Angle measured by TEG was linearly correlated with Fib (r=-0.364，r=0.616，r=0.359), K value, MA value and α-Angle measured by TEG was linearly correlated with Plt (r=0.318，r=0.519，r=0.301). The R time detected by TEG was consistent with PT and APTT, and the Kappa values were 0.252 (P0.001), 0.336 (P0.001). K, MA, and α-Angle measured by TEG was consistent with Fib, the Kappa values were 0.265 (P0.001), 0.289 (P0.001) and 0.290 (P0.001), respectively; K、MA and α-Angle measured by TEG was consistent with Plt, the Kappa values were 0.276 (P0.001), 0.285 (P0.001) and 0.302 (P0.001), respectively.The onset age of Mongolian patients with cerebral infarction caused by thrombosis is mainly 61-70 years old, followed by 51-60 years old. The onset age shows a younger trend. There is a significant correlation between TEG and coagulation, but the consistency is weak, therefore, the two methods can not be replaced each other.蒙古族血栓患者血栓弹力图和凝血项目的对比分析.探讨蒙古族血栓病所致脑梗死患者年龄分布情况及血栓弹力图（TEG）与凝血四项各参数间的相关性和一致性.回顾性分析2020年1月-2021年12 月内蒙古民族大学附属医院收治的298例蒙古族血栓病所致脑梗死患者的年龄分布及TEG、常规凝血四项和血常规中血小板计数的结果，统计分析两种检测方法的相关性和一致性.298例蒙古族血栓病所致脑梗死患者发病年龄主要集中在61-70岁，占比最高，为38.3%，其次为51-60岁，占26.8%。TEG检测的R时间与PT、APTT呈线性相关（r=0.186，r=0.152），TEG测出的K值、MA值、α-Angle与Fib呈明显的线性相关 （r=-0.364，r=0.616，r=0.359），TEG测出的K值、MA值、α-Angle与P1t呈明显的线性相关（r=0.318，r=0.519，r=0.301）；TEG检测的R时间与PT、APTT 的Kappa值分别为0.252（P0.001）和0.336（P0.001）；K值、MA值、α-Angle和Fib的Kappa值分别为0.265（P0.001）、0.289（P0.001）和0.290（P0.001）；K值、MA值、α-Angle和P1t的Kappa值分别为0.276（P0.001）、0.285（P0.001）和0.302（P0.001）.蒙古族血栓病所致脑梗死患者发病年龄主要集中在61-70岁，其次是51-60岁，发病年龄具有年轻化趋势；TEG与凝血四项之间呈显著相关，但一致性弱，两种方法不能互相替代.

Background: The disorders of glucolipid metabolism are prevalent in patients with type-2 diabetes mellitus (T2DM). Palmitic-Acid-Hydroxy-Stearic Acid (PAHSA) had been reported to benefit glucolipid metabolism in diabetic mice. Given the importance of autophagy in T2DM, the aim of the present study was to investigate whether S-9-PAHSA has specific therapeutic effects on diabetics, particularly with regards to autophagy. Methods: 19-week-old male C57BL6 mice were fed with high-fat-diet for 4 months, and administered with 22.5 mg/kg/d or 5.5 mg/kg/d fatty acids or an equivalent volume of vehicle for 35 days. Glucose levels and weight were determined. Insulin, glycosylated serum protein (GSP), glucagon-like peptide-1(GLP-1) and oxidized modified low-density lipoprotein (ox-LDL) were assessed by ELISA kit. Autophagy-related proteins P62 and Beclin-1in cerebral cortex were detected by western blot. SH-SY 5Y cells were incubated under diabetic environment (glucose 100mmol/L, fatty acid 200μmol/L), and then treated with S-9-PAHSA, R-9-PAHSA and 9-PAHSA. Cell viability, cell proliferation, lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) production were detected by respective kits. Apoptosis was assessed by the TUNEL assay. The protein levels of apoptosis (Cleaved caspase-3, BAX/Bcl-2), autophagy (Beclin1, p62 and LC3II/I) and PI3K/AKT pathway were determined by western blot. Results: Although S-9-PAHSA did not alter glucose levels, weight, GLP-1 and GSP in mice, high-does S-9-PAHSA improved insulin resistance and lowered ox-LDL. Compared with control group, the up-regulated expression of P62 and down-regulated expression of Beclin1 in diabetic mice were found, and the S-9-PAHSA administration reduced P62. In vitro, S-9-PAHSA increased cell viability and proliferation while reduced LDH release and ROS production, which were better than R-9-PAHSA and 9-PAHSA. S-9-PAHSA could lower the levels of Cleaved caspase-3 and percentage of TUNEL-positive cells. S-9-PAHSA enhanced the expression of LC3II/I under high glucose and fatty acid stimulation. PI3K and p-AKT/AKT ratio under diabetic environment had a downward trend, and S-9-PAHSA might enhance their expression, but there was no statistical difference. Conclusions: S-9-PAHSA could regulate glycolipid metabolism in HFD-induced T2DM mice through autophagy-associated protein, and exerted protective effects on diabetes by the regulation of autophagy, reducing oxidative stress, partially activating PI3K/AKT signaling pathway.

The genus Rickettsia encompasses a diverse group of obligate intracellular bacteria that are highly virulent disease agents of mankind as well as symbionts of arthropods. Native plasmids of Rickettsia amblyommatis (AaR/SC) have been used as models to construct shuttle vectors for genetic manipulation of several Rickettsia species. Here we report on the isolation of the complete plasmid (pRM658B) from Rickettsia monacensis (IrR/Munich) mutant Rmona658B and the construction of shuttle vectors based on pRM. To identify regions essential for replication, we made vectors containing the dnaA and parA genes of pRM with varying portions of the region surrounding these genes and a selection-reporter cassette conferring resistance to spectinomycin and expression of green fluorescent protein. Rickettsia amblyommatis (AaR/SC), R. monacensis (IrR/Munich), Rickettsia bellii (RML 369-C), Rickettsia parkeri (Tate’s Hell), and Rickettsia montanensis (M5/6) were successfully transformed with shuttle vectors containing pRM parA and dnaA. PCR assays targeting pRM regions not included in the vectors revealed that native pRM was retained in R. monacensis transformants. Determination of native pRM copy number using a plasmid-encoded gene (RM_p5) in comparison to chromosomal encoded gltA indicated reduced copy numbers in R. monacensis transformants. In transformed R. monacensis, native pRM and shuttle vectors with homologous parA and dnaA formed native plasmid-shuttle vector complexes. These studies provide insight on the maintenance of plasmids and shuttle vectors in rickettsiae.IMPORTANCEThis paper describes a new series of plasmid shuttle vectors for the transformation of rickettsiae.Shuttle vectors based on parA and dnaA sequences of the plasmid pRM can be used to transform diverse rickettsia as well as its native host Rickettsia monacensis.Our results provide insight into the maintenance of rickettsial-based shuttle vectors in rickettsiae.

Valuable high-precision data are often published in the form of tables in both scientific and business documents. While humans can easily identify, interpret and contextualize tables, developing general-purpose automated techniques for extraction of information from tables is difficult due to the wide variety of table formats employed across corpora. To extract useful data from tables, data cells must be correctly extracted and linked to all relevant headers, units of measure and in-text references. Table extraction involves identifying the border and cell structure for each document table, while table understanding provides context by linking cells with semantic information inside and outside the table, such as row and column headers, footnotes, titles, and references in surrounding text. The objective of this tutorial is to provide a detailed synopsis of existing approaches for table extraction and understanding, highlight open research problems, and provide an overview of potential applications.

Pneumonia is a serious pediatric lung injury disease caused by Mycoplasma pneumoniae (M. pneumoniae) with increasing global prevalence every year. The WHO has reported that nearly 19% of children die due to pneumonia worldwide.The present research was conducted to discover the ameliorative properties of geraniol against M. pneumoniae-provoked pneumonia in mice through the modulation of inflammatory responses.The pneumonia was provoked in the male Swiss albino mice via infecting animals with 100 µl of M. pneumoniae for 2 days and supplemented concurrently with 20 mg/kg of geraniol for 3 days. 100 mg/kg of azithromycin was used as a standard drug. The nitric oxide (NO) level and MPO activity were measured using kits. The SOD activity, GSH, and MDA levels were studied using standard methods. The polymerase chain reaction (PCR) study was performed to examine the M. pneumoniae DNA load. The inflammatory cytokines status was assessed by assay kits. The ERK1/2, JNK1/2, and NF-κB expressions were studied by reverse-transcription (RT-PCR). The lung tissues were analyzed microscopically to investigate the histological alterations.Geraniol treatment effectively reduced lung weight, NO level, and MPO activity in the pneumonia mice. The total cells and M. pneumoniae DNA load were also decreased by the geraniol. The SOD activity and GSH level were improved and MDA was decreased by the geraniol treatment. The IL-1, IL-6, IL-8, TNF-α, and TGF status were appreciably depleted by the geraniol in the pneumonia mice. Geraniol also suppressed the ERK1/2 and NF-κB expressions in the lung tissues. Histological findings also suggest the therapeutic roles of geraniol against pneumonia in mice.In summary, our results proved the beneficial roles of geraniol against the M. pneumoniae-provoked pneumonia. Geraniol could be a hopeful therapeutic agent to treat pneumonia in the future.

Accurate detection of butyrylcholinesterase (BChE) activity is imperative to understand its biological function and diagnose related disease. Far-red (FR)/Near-Infrared (NIR) fluorescent probe with large Stokes shift for BChE detection is extremely important. In this study, we reported a new "off-on" FR/NIR fluorescent probe (DX-2) with large Stokes shift (110 nm). DX-2 was constructed through cyclopropionate to pull-push the optical tuable hydroxyl group of chloro-substituted dicyanoisophorone fluorophore. DX-2 (λ

Tomato yellow leaf curl virus (TYLCV), a plant DNA virus of the genus Begomovirus, is transmitted by whiteflies of the Bemisia tabaci species complex in a persistent manner. Our previous study indicated that activation of the apoptosis pathway in whiteflies could facilitate TYLCV accumulation and transmission. Considering that temperature change can influence the spread of insect-borne plant viruses, we focused on plant virus induced-apoptosis to investigate the underlying mechanism of temperature regulation on plant virus transmission via an insect vector. We found that heat stress (40°C) on whiteflies could facilitate TYLCV accumulation and increase transmission to tomato plants. Despite upregulation of caspase-1 and caspase-3 gene expression, heat stress failed to induce an increase in the activation of cleaved caspase-3 and DNA fragmentation in TYLCV-infected whiteflies. However, our data failed to determine the role of heat stress in apoptosis modulation of insect-plant virus interplay while still providing clues to understand insect vectors and their transmitted plant viruses.

The blacklegged tick, Ixodes scapularis, a species of significant importance to human and animal health, harbors an endosymbiont Rickettsia buchneri sensu stricto. The symbiont is largely restricted to the ovaries, but all life stages can harbor various quantities or lack R. buchneri entirely. The endosymbiont is cultivable in cell lines isolated from embryos of Ixodes ticks. Rickettsia buchneri most readily grows and is maintained in the cell line IRE11 from the European tick, Ixodes ricinus. The line was characterized by light and electron microscopy and used to analyze the growth dynamics of wildtype and GFPuv-expressing R. buchneri. qPCR indicated that the genome copy doubling time in IRE11 was &gt, 7 days. Measurements of fluorescence using a plate reader indicated that the amount of green fluorescent protein doubled every 11 days. Two 23S rRNA probes were tested via RNA FISH on rickettsiae grown in vitro and adapted to evaluate the tissue tropism of R. buchneri in field-collected female I. scapularis. We observed strong positive signals of R. buchneri in the ovaries and surrounding the nucleus of the developing oocytes. Tissue tropism in I. scapularis and in vitro growth dynamics strengthen the contemporary understanding of R. buchneri as a transovarially transmitted, non-pathogenic endosymbiont.

Motor behaviors are central to many functions and dysfunctions of the brain, and understanding their neural basis has consequently been a major focus in neuroscience. However, most studies of motor behaviors have been restricted to artificial, repetitive paradigms, far removed from natural movements performed “in the wild.” Here, we leveraged recent advances in machine learning and computer vision to analyze intracranial recordings from 12 human subjects during thousands of spontaneous, unstructured arm reach movements, observed over several days for each subject. These naturalistic movements elicited cortical spectral power patterns consistent with findings from controlled paradigms, but with considerable neural variability across subjects and events. We modeled interevent variability using 10 behavioral and environmental features; the most important features explaining this variability were reach angle and day of recording. Our work is among the first studies connecting behavioral and neural variability across cortex in humans during unstructured movements and contributes to our understanding of long-term naturalistic behavior. Significance Statement Understanding the neural basis of human movement has long been a key focus in neuroscience. However, researchers often study constrained, monotonous tasks that differ greatly from the rich and diverse natural movements we actually make. Here, we use data-intensive computational approaches to reveal patterns in neural activity underlying naturalistic human arm movements. While such movements match previous experimental findings on average, there is substantial neural variability from one movement to the next. We partially explain this variability by aspects of the movement observed, though much variability remains unaccounted for. Our study sheds light on how the brain generates natural arm movements and emphasizes the critical need to study brain activity in more unstructured settings that mimic daily life.

Diabetic kidney disease (DKD) is one of the major chronic complications of diabetes mellitus (DM), as well as a main cause of end-stage renal disease. Over the last few years, substantial research studies have revealed a contributory role of gut microbiota in the process of DM and DKD. Metabolites of gut microbiota like lipopolysaccharide, short-chain fatty acids, and trimethylamine N-oxide are key mediators of microbial-host crosstalk. However, the underlying mechanisms of how gut microbiota influences the onset and progression of DKD are relatively unknown. Besides, strategies to remodel the composition of gut microbiota or to reduce the metabolites of microbiota have been found recently, representing a new potential remedial target for DKD. In this mini-review, we will address the possible contribution of the gut microbiota in the pathogenesis of DKD and its role as a therapeutic target.

Apoptosis is an innate immune response induced by infection in eukaryotes that contributes significantly to protection from pathogens. However, little is known about the role of apoptosis in the interactions of arthropod vectors with the rickettsiae that they transmit. Rickettsia spp. are vector-borne obligately intracellular bacteria and display different degrees of virulence in their eukaryotic hosts. In this study, we found that infection with Rickettsia parkeri (Rp) activated the apoptosis pathway in an Amblyomma americanum tick cell line (AAE2), as evidenced by the loss of phospholipid membrane asymmetry and DNA fragmentations. Additionally, infection with Rp also led to apoptosis activation in cell lines of different tick species. Interestingly, suppressing apoptosis decreased Rp infection and replication, while the activation of apoptosis increased Rp accumulation at the early stage of infection. Moreover, mitochondrion-dependent apoptosis was essential for Rp infection and replication in vector cells, and apoptosis induction required intracellular rickettsia replication. We further showed that Rp utilizes two different survival strategies to modulate apoptosis in the arthropod vectors and mammalian host cells. There was no direct correlation between apoptosis activation in vector cells and rickettsial pathogenicity. These novel findings indicate a possible mechanism whereby apoptosis facilitates infection and replication of a Rickettsia sp. in an arthropod vector. These results contribute to our understanding of how the vector's responses to pathogen infection affect pathogen replication and therefore transmission. IMPORTANCE Rickettsioses, infections caused by the genus Rickettsia, are among the oldest known infectious diseases. Ticks are essential arthropod vectors for rickettsiae, and knowledge about the interactions between ticks, their hosts, and pathogens is fundamental for identifying drivers of tick-borne rickettsioses. Despite the rapid development in apoptosis research with rickettsiae, little is known regarding the role of apoptosis in the interactions between Rickettsia spp., vertebrate hosts, and arthropod vectors. Here, we demonstrated that mitochondrion-dependent apoptosis is essential for rickettsial infection and replication in vector cells and that apoptosis induction requires intracellular rickettsial replication. However, rickettsial pathogenicity is not linked with apoptosis activation in tick cells. Our findings improve understanding of the apoptosis mechanism in arthropods exploited by rickettsiae and also the potential to discover specific targets for new vaccines and drugs to prevent or treat rickettsial infections.

Alkaline phosphatases (ALPs: EC 3.1.3.1) are ubiquitous enzymes and play crucial roles in the fundamental phosphate uptake and secretory processes. Although insects are regarded as the most diverse group of organisms, the current understanding of ALP roles in insects is limited. As one type of destructive agricultural pest, whitefly Bemisia tabaci, a phloem feeder and invasive species, can cause extensive crop damage through feeding and transmitting plant diseases. In this study, we retrieved five ALP genes in MEAM1 whitefly, nine ALP genes in MED whitefly via comparative genomics approaches. Compared with nine other insects, whiteflies’ ALP gene family members did not undergo significant expansion during insect evolution, and whiteflies’ ALP genes were dispersed. Moreover, whiteflies’ ALP gene family was conserved among insects and emerged before speciation via phylogenetic analysis. Whiteflies’ ALP gene expression profiles presented that most ALP genes have different expression patterns after feeding on cotton or tobacco plants. Female/male MED whiteflies possessed higher ALP activities on both cotton and tobacco plants irrespective of sex, relative to MEAM1 whiteflies. Meanwhile, adult MED whiteflies possessed higher ALP activity in both whole insect and salivary samples, relative to MEAM1 whiteflies. We also found that both MED and MEAM1 whiteflies could upregulate ALP activities after feeding on cotton compared with feeding on tobacco plants. These findings demonstrated the functions of whiteflies ALPs and will assist the further study of the genomic evolution of insect ALPs.

Alkaline phosphatases (ALPs: EC 3.1.3.1) are ubiquitous enzymes and play crucial roles in the fundamental phosphate uptake and secretory processes. Although insects are regarded as the most diverse group of organisms, the current understanding of ALP roles in insects is limited. As one type of destructive agricultural pest, whitefly Bemisia tabaci, a phloem feeder and invasive species, can cause extensive crop damage through feeding and transmitting plant diseases. In this study, we retrieved five ALP genes in MEAM1 whitefly, nine ALP genes in MED whitefly via comparative genomics approaches. Compared with nine other insects, whiteflies’ ALP gene family members did not undergo significant expansion during insect evolution, and whiteflies’ ALP genes were dispersed. Moreover, whiteflies’ ALP gene family was conserved among insects and emerged before speciation via phylogenetic analysis. Whiteflies’ ALP gene expression profiles presented that most ALP genes have different expression patterns after feeding on cotton or tobacco plants. Female/male MED whiteflies possessed higher ALP activities on both cotton and tobacco plants irrespective of sex, relative to MEAM1 whiteflies. Meanwhile, adult MED whiteflies possessed higher ALP activity in both whole insect and salivary samples, relative to MEAM1 whiteflies. We also found that both MED and MEAM1 whiteflies could upregulate ALP activities after feeding on cotton compared with feeding on tobacco plants. These findings demonstrated the functions of whiteflies ALPs and will assist the further study of the genomic evolution of insect ALPs.

Presentations are critical for communication in all areas of our lives, yet the creation of slide decks is often tedious and time-consuming. There has been limited research aiming to automate the document-to-slides generation process and all face a critical challenge: no publicly available dataset for training and benchmarking. In this work, we first contribute a new dataset, SciDuet, consisting of pairs of papers and their corresponding slides decks from recent years' NLP and ML conferences (e.g., ACL). Secondly, we present D2S, a novel system that tackles the document-to-slides task with a two-step approach: 1) Use slide titles to retrieve relevant and engaging text, figures, and tables; 2) Summarize the retrieved context into bullet points with long-form question answering. Our evaluation suggests that long-form QA outperforms state-of-the-art summarization baselines on both automated ROUGE metrics and qualitative human evaluation., Comment: accepted at NAACL 2021

Adding lead-carbon composite materials to the negative plate of lead-acid batteries can effectively improve the electrochemical performance of the battery. In this paper, a novel quasi-solid method is used to in-situ synthesize the nano-Pb/C composite as additives in the negative active material of lead-acid cells, which can greatly increase the utilization rate of negative active material and the initial discharge capacity of the lead-acid cell. Compared with the N C material, the nano-Pb/C composite effectively inhibits the hydrogen evolution reaction. In addition, since the nano-Pb/C composite and the negative active material in the negative plate form a porous framework, the diffusion of the electrolyte and the dissolution of PbSO4 are accelerated. The cell containing 1 wt.% nano-Pb/C composite has the best cycle performance (18,154 cycles) under high-rate partial-state-of-charge condition. All in all, the nano-Pb/C composite prepared via a new quasi-solid method has the advantages of improving the initial capacity and lifespan of lead-acid batteries, and it is a promising candidate material for lead-acid battery additives.

The incidence of human diseases caused by tick-borne pathogens is increasing but little is known about the molecular interactions between the agents and their vectors and hosts. Anaplasma phagocytophilum (Ap) is an obligate intracellular, tick-borne bacterium that causes granulocytic anaplasmosis in humans, dogs, sheep, and horses. In mammals, neutrophil granulocytes are a primary target of infection, and in ticks, Ap has been found in gut and salivary gland cells. To identify bacterial genes that enable Ap to invade and proliferate in human and tick cells, labeled mRNA from Ap bound to or replicating within human and tick cells (lines HL-60 and ISE6), and replicating in primary human granulocytes ex vivo, was hybridized to a custom tiling microarray containing probes representing the entire Ap genome. Probe signal values plotted over a map of the Ap genome revealed antisense transcripts and unannotated genes. Comparisons of transcript levels from each annotated gene between test conditions (e.g., Ap replicating in HL-60 vs. ISE6) identified those that were differentially transcribed, thereby highlighting genes associated with each condition. Bacteria replicating in HL-60 cells upregulated 122 genes compared to those in ISE6, including numerous p44 paralogs, five HGE-14 paralogs, and 32 hypothetical protein genes, of which 47% were predicted to be secreted or localized to the membrane. By comparison, 60% of genes upregulated in ISE6 encoded hypothetical proteins, 60% of which were predicted to be secreted or membrane associated. In granulocytes, Ap upregulated 120 genes compared to HL-60, 33% of them hypothetical and 43% of those predicted to encode secreted or membrane associated proteins. HL-60-grown bacteria binding to HL-60 cells barely responded transcriptionally, while ISE6-grown bacteria binding to ISE6 cells upregulated 48 genes. HL-60-grown bacteria, when incubated with ISE6 cells, upregulated the same genes that were upregulated by ISE6-grown bacteria exposed to uninfected ISE6. Hypothetical genes (constituting about 29% of Ap genes) played a disproportionate role in most infection scenarios, and particular sets of them were consistently upregulated in bacteria binding/entering both ISE6 and HL-60 cells. This suggested that the encoded proteins played central roles in establishing infection in ticks and humans.