Outbreak.info Research Library: a standardized, searchable platform to discover and explore COVID-19 resources.

Outbreak.info Research Library is a standardized, searchable interface of coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) publications, clinical trials, datasets, protocols and other resources, built with a reusable framework. We developed a rigorous schema to enforce consistency across different sources and resource types and linked related resources. Researchers can quickly search the latest research across data repositories, regardless of resource type or repository location, via a search interface, public application programming interface (API) and R package.

Metastasizing aneurysmal dermatofibroma initially diagnosed as angiosarcoma confirmed by CD63::PRKCD fusion gene detection with nanopore sequencing.

Dermatofibroma (DF) is a benign tumor that forms pedunculated lesions ranging in size from a few millimeters to 2 cm, usually affecting the extremities and trunks of young adults. Histopathologically, DF is characterized by the storiform proliferation of monomorphic fibroblast-like spindle cells. In addition to neoplastic cells, secondary elements such as foamy histiocytes, Touton-type giant cells, lymphoplasmacytes, and epidermal hyperplasia are characteristic histological features. Several histological variants, including atypical, cellular, aneurysmal, and lipidized variants, have been reported; cases with variant histologies are sometimes misdiagnosed as sarcomas. We present a case of metastasizing aneurysmal DF that was initially diagnosed as an angiosarcoma on biopsy. A 26-year-old woman was referred to our hospital with a gradually enlarging subcutaneous mass in her lower left leg. Positron emission tomography-computed tomography revealed high fluorodeoxyglucose uptake not only in the tumor but also in the left inguinal region. On biopsy, ERG and CD31-positive atypical spindle cells proliferated in slit-like spaces with extravasation, leading to the diagnosis of angiosarcoma. Histology of the wide-resection specimen was consistent with DF, and lymph node metastasis was also observed. Nanopore DNA sequencing detected CD63::PRKCD fusion and copy number gain, although CD63 was not included in the target region of adaptive sampling. This report highlights the importance of recognizing the unusual clinical, radiological, and pathological features of DF to avoid misdiagnosis, and the potential diagnostic utility of nanopore sequencer.

Structures, Mechanisms, and Functions of His-Me Finger Nucleases.

His-Me finger (also called HNH or ßßα-me) nucleases, are a large superfamily of nucleases that share limited sequence homology, but all members carry a highly similar catalytic motif exhibiting a ßßα topology. This review represents a structural comparison of His-Me finger nucleases, summarizing their substrate-binding and recognition strategies, mechanisms of enzymatic hydrolysis, cellular functions, and the various means of activity regulation. His-Me finger nucleases usually function as monomers, making a single nick in nucleic acids to degrade foreign or host genomes, or as homodimers that introduce double-stranded DNA breaks for DNA restriction, integration, recombination, and repair. Various cellular neutralizing machineries have evolved to regulate the activity of His-Me finger nucleases, thereby maintaining genome integrity and cellular functionality.

Lipid-Binding Regions within PKC-Related Serine/Threonine Protein Kinase N1 (PKN1) Required for Its Regulation.

PKC-related serine/threonine protein kinase N1 (PKN1) is a protease/lipid-activated protein kinase that acts downstream of the RhoA and Rac1 pathways. PKN1 comprises unique regulatory, hinge region, and PKC homologous catalytic domains. The regulatory domain harbors two homologous regions, i.e., HR1 and C2-like. HR1 consists of three heptad repeats (HR1a, HR1b, and HR1c), with PKN1-(HR1a) hosting an amphipathic high-affinity cardiolipin-binding site for phospholipid interactions. Cardiolipin and C18:1 oleic acid are the most potent lipid activators of PKN1. PKN1-(C2) contains a pseudosubstrate sequence overlapping that of C20:4 arachidonic acid. However, the cardiolipin-binding site(s) within PKN1-(C2) and the respective binding properties remain unclear. Herein, we reveal (i) that the primary PKN1-(C2) sequence contains conserved amphipathic cardiolipin-binding motif(s); (ii) that trimeric PKN1-(C2) predominantly adopts a ß-stranded conformation; (iii) that two distinct types of cardiolipin (or phosphatidic acid) binding occur, with the hydrophobic component playing a key role at higher salt levels; (iv) the multiplicity of C18 fatty acid binding to PKN1-(C2); and (v) the relevance of our lipid-binding parameters for PKN1-(C2) in terms of kinetic parameters previously determined for the full-length PKN1 enzyme. Thus, our discoveries create opportunities to design specific mammalian cell inhibitors that disrupt the localization of membrane-associated PKN1 signaling molecules.

Sodium Bicarbonate Decreases Alcohol Consumption in Mice.

We previously reported that mice with low neuronal pH drink more alcohol, demonstrating the importance of pH for alcohol reward and motivation. In this study, we tested whether systemic pH affects alcohol consumption and if so, whether it occurs by changing the alcohol reward. C57BL/6J mice were given NaHCO3 to raise their blood pH, and the animals' alcohol consumption was measured in the drinking-in-the-dark and two-bottle free choice paradigms. Alcohol consumption was also assessed after suppressing the bitterness of NaHCO3 with sucrose. Alcohol reward was evaluated using a conditioned place preference. In addition, taste sensitivity was assessed by determining quinine and sucrose preference. The results revealed that a pH increase by NaHCO3 caused mice to decrease their alcohol consumption. The decrease in high alcohol contents (20%) was significant and observed at different ages, as well as in both males and females. Alcohol consumption was also decreased after suppressing NaHCO3 bitterness. Oral gavage of NaHCO3 did not alter quinine and sucrose preference. In the conditioned place preference, NaHCO3-treated mice spent less time in the alcohol-injected chamber. Conclusively, the results show that raising systemic pH with NaHCO3 decreases alcohol consumption, as it decreases the alcohol reward value.

Liraglutide pretreatment attenuates sepsis-induced acute lung injury.

There are no effective targeted therapies to treat acute respiratory distress syndrome (ARDS). Recently, the commonly used diabetes and obesity medications, glucagon-like peptide-1 (GLP-1) receptor agonists, have been found to have anti-inflammatory properties. We, therefore, hypothesized that liraglutide pretreatment would attenuate murine sepsis-induced acute lung injury (ALI). We used a two-hit model of ALI (sepsis+hyperoxia). Sepsis was induced by intraperitoneal injection of cecal slurry (CS; 2.4 mg/g) or 5% dextrose (control) followed by hyperoxia [HO; fraction of inspired oxygen ([Formula: see text]) = 0.95] or room air (control; [Formula: see text] = 0.21). Mice were pretreated twice daily with subcutaneous injections of liraglutide (0.1 mg/kg) or saline for 3 days before initiation of CS+HO. At 24-h post CS+HO, physiological dysfunction was measured by weight loss, severity of illness score, and survival. Animals were euthanized, and bronchoalveolar lavage (BAL) fluid, lung, and spleen tissues were collected. Bacterial burden was assessed in the lung and spleen. Lung inflammation was assessed by BAL inflammatory cell numbers, cytokine concentrations, lung tissue myeloperoxidase activity, and cytokine expression. Disruption of the alveolar-capillary barrier was measured by lung wet-to-dry weight ratios, BAL protein, and epithelial injury markers (receptor for advanced glycation end products and sulfated glycosaminoglycans). Histological evidence of lung injury was quantified using a five-point score with four parameters: inflammation, edema, septal thickening, and red blood cells (RBCs) in the alveolar space. Compared with saline treatment, liraglutide improved sepsis-induced physiological dysfunction and reduced lung inflammation, alveolar-capillary barrier disruption, and lung injury. GLP-1 receptor activation may hold promise as a novel treatment strategy for sepsis-induced ARDS. Additional studies are needed to better elucidate its mechanism of action.NEW & NOTEWORTHY In this study, pretreatment with liraglutide, a commonly used diabetes medication and glucagon-like peptide-1 (GLP-1) receptor agonist, attenuated sepsis-induced acute lung injury in a two-hit mouse model (sepsis + hyperoxia). Septic mice who received the drug were less sick, lived longer, and displayed reduced lung inflammation, edema, and injury. These therapeutic effects were not dependent on weight loss. GLP-1 receptor activation may hold promise as a new treatment strategy for sepsis-induced acute respiratory distress syndrome.

Anticancer effect of a pyrrole-imidazole polyamide-triphenylphosphonium conjugate selectively targeting a common mitochondrial DNA cancer risk variant in cervical cancer cells.

Cervical cancer remains a major threat to women's health, especially in countries with limited medical resources, and new drugs are needed to improve patient survival and minimize adverse effects. Here, we examine the effects of a triphenylphosphonium (TPP)-conjugated pyrrole-imidazole polyamide (CCC-h1005) targeting the common homoplasmic mitochondrial DNA (mtDNA) cancer risk variant (ATP6 8860A>G) on the survival of cervical cancer cell lines, cisplatin-resistant HeLa cells and patient-derived cervical clear cell carcinoma cells as models of cervical cancer treatment. We found that CCC-h1005 induced death in these cells and suppressed the growth of xenografted HeLa tumors with no severe adverse effects. These results suggest that PIP-TPP designed to target mtDNA cancer risk variants can be used to treat many cervical cancers harboring high copies of the target variant, providing a foundation for clinical trials of this class of molecules for treating cervical cancer and other types of cancers.

Encapsulation of ZnO and Ho:ZnO Nanoparticles in the Core of Wrinkled Mesoporous Silica.

Wrinkled mesoporous silica (WMS) has a flower- or dendritic-like morphology, tunable pore size, and highly ordered and accessible three-dimensional (3D) pore structures. In this research, a method to encapsulate semiconductor nanoparticles in the core of the wrinkled mesoporous silica during synthesis is described. Highly uniform zinc oxide and holmium-doped zinc oxide nanoparticles have been synthesized by a sonochemical method. Zinc oxide and holmium-doped zinc oxide nanoparticles have been encapsulated in wrinkled mesoporous silica during synthesis. The ZnO@WMS and Ho:ZnO@WMS particles have been characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), UV-vis spectroscopy, fluorescence, dynamic light scattering (DLS), confocal microscopy, and X-ray diffraction (XRD).

How Brow Rotation Affects Emotional Expression Utilizing Artificial Intelligence.

BACKGROUND: It is well known that brow position affects emotional expression. However, there is little literature on how and to what degree this change in emotional expression happens. Previous studies on this topic have utilized manual rating; this method of study remains small and labor intensive. Our objective is to correlate manual brow rotations with emotional outcomes using artificial intelligence to objectively determine how specific brow manipulations affected human expression. METHODS: We included 53 brow-lift patients in this study. Pre-operative patients' brows were rotated to - 20, - 10, +10, and +20 degrees in respect to the central axis of their existing brow using PIXLR, a cloud-based set of image editing tools and utilities. These images were analyzed using FaceReader, a validated software package that uses computer vision technology for facial expression recognition. The primary facial emotion and intensity of facial action units (0 = no action unit detected to 4 = most intense action unit detected) generated by the software were recorded. RESULTS: 265 total images [5 images (pre-operative, - 20 degree brow rotation, - 10, +10, and +20) per patient] were analyzed using FaceReader. The primary emotion detected in the majority of images was neutral. The percentage of disgust in patients' expressions, as detected by FaceReader, increased with increased positive brow rotation (1.76% disgust detected at - 20 degrees, 2.09% at - 10 degrees, 2.65% at neutral, 2.61% at +10 degrees, and 2.95% at +20 degrees). In contrast, the percentage of sadness in patients' expressions decreased with increased positive brow rotation (29.92% sadness detected at - 20 degrees, 21.5% at - 10 degrees, 11.42% at neutral, 15.75% at +10 degrees, and 12.86% at +20 degrees). Our facial action unit analysis corresponded with primary emotion analysis. The intensity of the inner brow raiser decreased with increased positive brow rotation 8.54% at - 20 degrees, 4.21% at - 10 degrees, 1.48% at neutral, 0.84% at +10 degrees, and 0.76% at +20 degrees). The intensity of the outer brow raiser increased with increased positive brow rotation (0.97% at - 20 degrees, 0.45% at - 10 degrees, 1.12% at neutral, 5.45% at +10 degrees, and 11.19% at +20 degrees). CONCLUSION: We demonstrated that increasing the degree of brow rotation correlated positively with the percentage of disgust and inversely with the percentage of sadness detected by FaceReader. This study demonstrated how different manipulated brow positions affected emotional outcomes using artificial intelligence. Physicians can use these findings to better understand how brow-lifts can affect the perceived emotion of their patients. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effect of Omega-3 Rich High-Fat Diet on Markers of Tissue Lipid Metabolism in Glucocorticoid-Treated Mice.

Glucocorticoids (GCs) are some of the most widely prescribed therapies for treating numerous inflammatory diseases and multiple cancer types. With chronic use, GCs' therapeutic benefits are concurrent with deleterious metabolic side effects, which worsen when combined with a high-fat diet (HFD). One characteristic of the common Western HFD is the presence of high omega-6 polyunsaturated fatty acids (PUFAs) and a deficiency in omega-3 PUFAs. The aim of this experiment was to determine whether fat composition resulting from HFD affects glucocorticoid-induced alterations in lipid-handling by the liver and skeletal muscle. Male wild-type C57BL/6 mice were randomized into two groups: n-6 (45% fat 177.5 g lard) and n-3 (45% fat 177.5 g Menhaden oil). After 4 weeks on their diets, groups were divided to receive either daily injections of dexamethasone (3 mg/kg/day) or sterile PBS for 1 week while continuing diets. The n-3 HFD diet attenuated adipose and hepatic fatty accumulation and prevented GC-induced increases in liver lipid metabolism markers Cd36 and Fabp. N-3 HFD had little effect on markers of lipid metabolism in oxidative and glycolytic skeletal muscle and was unable to attenuate GC-induced gene expression in the muscle. The present study's result demonstrated that the change of fat composition in HFD could beneficially alter the fatty acid accumulation and associated lipid metabolism markers in mice treated with dexamethasone.

Diffusiophoresis of a Weakly Charged Liquid Metal Droplet.

Diffusiophoresis of a weakly charged liquid metal droplet (LMD) is investigated theoretically, motivated by its potential application in drug delivery. A general analytical formula valid for weakly charged condition is adopted to explore the droplet phoretic behavior. We determined that a liquid metal droplet, which is a special category of the conducting droplet in general, always moves up along the chemical gradient in sole chemiphoresis, contrary to a dielectric droplet where the droplet tends to move down the chemical gradient most of the time. This suggests a therapeutic nanomedicine such as a gallium LMD is inherently superior to a corresponding dielectric liposome droplet in drug delivery in terms of self-guiding to its desired destination. The droplet moving direction can still be manipulated via the polarity dependence; however, there should be an induced diffusion potential present in the electrolyte solution under consideration, which spontaneously generates an extra electrophoresis component. Moreover, the smaller the conducting liquid metal droplet is, the faster it moves in general, which means a smaller LMD nanomedicine is preferred. These findings demonstrate the superior features of an LMD nanomedicine in drug delivery.

Barriers and motivators to specializing in geriatrics and strategies for recruitment: Scoping review.

While the barriers to specializing in geriatrics are known, motivators behind why medical trainees choose geriatrics are not as well understood. It is also unknown if recruitment strategies in the literature address these barriers and motivators. The aim of this systematic scoping review is to examine the current literature on recruitment strategies alongside motivators and barriers for specializing in geriatrics. Eligible articles for this scoping review either focused on motivators or barriers among trainees (medical students, resident-physicians, fellows) or recruitment strategies. A scoping search was conducted in MEDLINE, Embase, CINAHL, and PsychINFO. Data was extracted on article characteristics and themes. 88 of 2064 articles were eligible and included. Personal fulfillment emerged as the most common theme for motivators, contrary to prior studies that cite positive role modeling. Financial disincentive remained the most common barrier, followed by limited exposure and "futile" practice. Promising interventions beyond financial compensation include defining geriatrics better, emphasizing the high job satisfaction rates, increasing clinical exposure for medical students, and additional funding for academic centers to recruit academic geriatricians. Policymakers and medical educators should consider multiple strategies that target the motivators, as well as the barriers to pursuing geriatrics.

Technical considerations for replantation: from bony fixation to soft tissue coverage.

Digital replantation is a challenging and at-time tedious operation, but if approached thoughtfully and with reasonable expectations can be a reliable and rewarding undertaking. This article summarizes technical considerations for digital replantations involving flexor tendon zone II. The article has been ordered according to the recommended sequence of a structure-by-structure repair in a non-thumb digit. Special considerations are described for thumb, multiple digits, and heterotopic replantation.

Suppression of non-small-cell lung cancer A549 tumor growth by an mtDNA mutation-targeting pyrrole-imidazole polyamide-triphenylphosphonium and a senolytic drug.

Certain somatic mutations in mtDNA were associated with tumor progression and frequently found in a homoplasmic state. We recently reported that pyrrole-imidazole polyamide conjugated with the mitochondria-delivering moiety triphenylphosphonium (PIP-TPP) targeting an mtDNA mutation efficiently induced apoptosis in cancer cells with the mutation but not normal cells. Here, we synthesized the novel PIP-TPP, CCC-021-TPP, targeting ND6 14582A > G homoplasmic missense mutation that is suggested to enhance metastasis of non-small-cell lung cancer A549 cells. CCC-021-TPP did not induce apoptosis but caused cellular senescence in the cells, accompanied by a significant induction of antiapoptotic BCL-XL. Simultaneous treatment of A549 cells with CCC-021-TPP and the BCL-XL selective inhibitor A-1155463 resulted in apoptosis induction. Importantly, the combination induced apoptosis and suppressed tumor growth in an A549 xenografted model. These results highlight the potential of anticancer therapy with PIP-TPPs targeting mtDNA mutations to induce cell death even in apoptosis-resistant cancer cells when combined with senolytics.

Electrophoresis of a highly charged fluid droplet in dilute electrolyte solutions: Analytical Hückel-type solution.

An analytical formula is presented here for the electrophoresis of a dielectric or perfectly conducting fluid droplet with arbitrary surface potentials suspended in a very dilute electrolyte solution. In other words, when the Debye length (κ-1 ) is very large, or κa ≪ $\ll $ 1, where κ is the electrolyte strength and a stands for the droplet radius. This formula can be regarded as an extension of the famous Hückel solution valid for weakly charged rigid particles to arbitrarily charged fluid droplets. The formula reduces successfully to the ones obtained by Booth for a dielectric droplet, and Ohshima for a perfectly conducting droplet, both under Debye-Hückel approximation valid for weakly charged droplets. Moreover, the formula is valid for a gas bubble and a rigid solid particle as well. Classic results obtained by Hückel for a rigid particle are reproduced as well. We found that for a dielectric droplet, the more viscous the droplet is, the faster it moves regardless of its surface potential, contrary to the intuition based on the purely hydrodynamic consideration. For a perfectly conducting liquid droplet, on the other hand, the situation is reversed: The less viscous the droplet is, the faster it moves. The presence or absence of the spinning electric driving force tangent to the droplet surface is found to be responsible for it. As a result, an axisymmetric exterior vortex flow surrounding the droplet is always present for a dielectric liquid droplet, and never there for a conducting liquid droplet.

Diffusiophoresis in suspensions of highly charged soft particles.

Diffusiophoresis phenomenon of aoft particles suspended in binary electrolyte solutions is explored theoretically in this study based on the spherical cell model, focusing on the chemiphoresis component in absence of diffusion potential. Both the electrostatic and hydrodynamic aspects of the boundary confinement, or steric effect, due to the presence of neighboring particles are examined extensively under various electrokinetic conditions. Significant local extrema are found in mobility profiles expressed as functions of the Debye length in general, synchronized with the strength of the motion-inducing double layer polarization. Moreover, a seemingly peculiar phenomenon is observed that the soft particles may move faster in more concentrated suspensions. The competition between the simultaneous enhancement of the motion-inducing electric driving force and the motion-retarding hydrodynamic drag force from the boundary confinement effect of the neighboring particles is found to be responsible for it. The above findings are also demonstrated experimentally in a very recent study on the diffusiophoretic motion of soft particles through porous collagen hydrogels. The results presented here are useful in various practical applications of soft particles like drug delivery.

Analytical solution to dielectric droplet diffusiophoresis under Debye-Hückel approximation.

A simple analytical formula is obtained for the diffusiophoresis of a dielectric fluid droplet in symmetric binary electrolyte solutions under Debye-Hückel approximation valid for weakly charged droplets. The chemiphoresis is found to yield negative mobilities most of the time for droplets of constant surface charge density, which implies that the droplets tend to move away from the source releasing ionic chemicals. This is undesirable in some practical applications like drug delivery with liposomes in terms of conveying the drug-carrying liposomes to the desired area in the human body releasing specific ionic chemicals utilizing the self-guiding nature of diffusiophoresis. The further involvement of the electrophoresis component, however, may change the scenario via the oriented electric field generated by the induced diffusion potential. The lesson here is that while the impact of the chemiphoresis component is determined by nature and uncontrollable, the electrophoresis component serves as an artificially adjustable factor via choosing droplets with the surface charge of appropriate sign in practical applications. The results here have potential use in practical applications such as drug delivery. The portable simple analytical formula is a powerful asset to experimental researchers and design engineers in colloid science and technology to facilitate their works.

Endoscopic Browlift in Patients With Receding Hairlines.

ABSTRACT: Patients with receding or high hairlines have traditionally been considered unfavorable candidates for endoscopic brow lift as this can further lengthen the hairline. We analyzed outcomes in patients that underwent a novel endoscopic brow lift technique with placement of incisions and anchoring Endotine Forehead Devices (CoApt Systems Inc, Palo Alto, CA, USA) directly at the natural forehead crease lines, in an effort to minimize elevation of the hairline, whereas providing well-hidden scars. We retrospectively reviewed all patients who underwent this new Endotine and incision placement between 2016 and 2020. Preoperative and postoperative photographs of all patients were analyzed to determine the postoperative changes in brow elevation and forehead length proportion (defined as length from cranium to chin).The forehead length proportion was unchanged pre- and post-operatively, with no statistically significant differences noted (P = 0.48). The average brow position elevation ranged from 2.78 mm in the medial location to 5.05 mm in the lateral location. All patients were happy with their appearance and had improved visual fields postoperatively. The forehead scars healed well and were well hidden in forehead rhytids at long term follow-up.This novel endoscopic brow lift technique provides an option to utilize a minimally invasive approach in patients with receding hairline. With this technique, visible scars were minimized, whereas still being able to achieve reasonable brow elevation. Thus, our approach enables long term maintenance of brow elevation with inconspicuous scars in the forehead.

Authenticated Semi-Quantum Key Distribution Protocol Based on W States.

In 2019, Wen et al. proposed authenticated semi-quantum key distribution (ASQKD) for identity and message using the teleportation of W states and GHZ-like states without pre-shared keys. However, the ASQKD protocol presents a vital issue in the teleportation of W states owing to its inappropriate design. Bob recovers the teleported W states without obtaining the position of the corresponding photons and then returns the recovered photons back to Alice. Hence, the teleportation of W states in Wen et al.'s ASQKD protocol was malfunctioning. Moreover, Wen et al.'s ASQKD protocol requires quantum memory, which strongly disobeys the definition of semi-quantum proposed by Boyer et al. Therefore, in this study, we discover the flaws of Wen et al.'s ASQKD protocol and propose an authenticated semi-quantum key distribution protocol. When compared to Wen et al.'s ASQKD protocol, the proposed ASQKD protocol has the following advantages: legal semi-quantum environment (i.e., does not require quantum memory), reduced quantum hardware requirement (i.e., based only on W states), does not involve classical cryptography (i.e., the hash function), and provided 1.6 times higher qubit efficiency.

Lack of Charge Interaction in the Ion Binding Site Determines Anion Selectivity in the Sodium Bicarbonate Cotransporter NBCe1.

The Na/HCO3 cotransporter NBCe1 is a member of SLC4A transporters that move HCO3- across cell membranes and regulate intracellular pH or transepithelial HCO3 transport. NBCe1 is highly selective to HCO3- and does not transport other anions; the molecular mechanism of anion selectivity is presently unclear. We previously reported that replacing Asp555 with a Glu (D555E) in NBCe1 induces increased selectivity to other anions, including Cl-. This finding is unexpected because all SLC4A transporters contain either Asp or Glu at the corresponding position and maintain a high selectivity to HCO3-. In this study, we tested whether the Cl- transport in D555E is mediated by an interaction between residues in the ion binding site. Human NBCe1 and mutant transporters were expressed in Xenopus oocytes, and their ability to transport Cl- was assessed by two-electrode voltage clamp. The results show that the Cl- transport is induced by a charge interaction between Glu555 and Lys558. The bond length between the two residues is within the distance for a salt bridge, and the ionic strength experiments confirm an interaction. This finding indicates that the HCO3- selectivity in NBCe1 is established by avoiding a specific charge interaction in the ion binding site, rather than maintaining such an interaction.