A conserved Plasmodium structural integrity maintenance protein (SIMP) is associated with sporozoite membrane and is essential for maintaining shape and infectivity.

Plasmodium sporozoites are extracellular forms introduced during mosquito bite that selectively invade mammalian hepatocytes. Sporozoites are delimited by a cell membrane that is linked to the underlying acto-myosin molecular motor. While membrane proteins with roles in motility and invasion have been well studied, very little is known about proteins that maintain the sporozoite shape. We demonstrate that in Plasmodium berghei (Pb) a conserved hypothetical gene, PBANKA_1422900 specifies sporozoite structural integrity maintenance protein (SIMP) required for maintaining the sporozoite shape and motility. Sporozoites lacking SIMP exhibited loss of regular shape, extensive membrane blebbing at multiple foci, and membrane detachment. The mutant sporozoites failed to infect hepatocytes, though the altered shape did not affect the organization of cytoskeleton or inner membrane complex (IMC). Interestingly, the components of IMC failed to extend under the membrane blebs likely suggesting that SIMP may assist in anchoring the membrane to IMC. Endogenous C-terminal HA tagging localized SIMP to membrane and revealed the C-terminus of the protein to be extracellular. Since SIMP is highly conserved among Plasmodium species, these findings have important implications for utilizing it as a novel sporozoite-specific vaccine candidate.

Biochemical and physiological investigations on adenosine 5' monophosphate deaminase from Plasmodium spp.

The interplay between ATP generating and utilizing pathways in a cell is responsible for maintaining cellular ATP/energy homeostasis that is reflected by Adenylate Energy Charge (AEC) ratio. Adenylate kinase (AK), that catalyzes inter-conversion of ADP, ATP and AMP, plays a major role in maintaining AEC and is regulated by cellular AMP levels. Hence, the enzymes AMP deaminase (AMPD) and nucleotidases, which catabolize AMP, indirectly regulate AK activity and in-turn affect AEC. Here, we present the first report on AMPD from Plasmodium, the causative agent of malaria. The recombinant enzyme expressed in Saccharomyces cerevisiae was studied using functional complementation assay and residues vital for enzyme activity have been identified. Similarities and differences between Plasmodium falciparum AMPD (PfAMPD) and its homologs from yeast, Arabidopsis and humans are also discussed. The AMPD gene was deleted in the murine malaria parasite P. berghei and was found to be dispensable during all stages of the parasite life cycle. However, when episomal expression was attempted, viable parasites were not obtained, suggesting that perturbing AMP homeostasis by over-expressing AMPD might be lethal. As AMPD is known to be allosterically modulated by ATP, GTP and phosphate, allosteric activators of PfAMPD could be developed as anti-parasitic agents.

Acute Neurological Emergency With Varied Challenges: An Unusual Occurrence and Multimodal Team Approach.

Subarachnoid hemorrhage (SAH) is a devastating condition associated with high mortality and morbidity. Vascular malformations are the most common cause of non-traumatic SAH in patients less than 40 years old. We present a case of a 37-year-old male who presented on the second day of ictus with left-sided hemiparesis and a low Glasgow Coma Scale score (E1VTM5). Non-contrast computed tomography (NCCT) scan of the head was suggestive of right basi-frontal hematoma, SAH, and hydrocephalus (HCP). Given SAH with HCP, the neurosurgical team initially placed a left frontal Ommaya. Cerebral digital subtraction angiography suggested an arteriovenous malformation (AVM) and two anterior cerebral artery aneurysms. Endovascular coiling of the ruptured A2-A3 junction aneurysm was done initially, followed by decompressive craniectomy and evacuation of hematoma and clipping of the still leaky A2-A3 junction aneurysm, also on the same day. The patient recovered in the intensive care unit and was discharged home in good health on the 18th postoperative day. Our case report presents the unique challenge of neuroprotection and maintaining intra-cerebral dynamics in a patient with cerebral aneurysms, AVM, SAH, and hematoma between coagulation (to prevent intra-cerebral hemorrhage) versus anti-coagulation (to prevent emboli during coiling), hypertensive therapy (to prevent cerebral vasospasm) versus relative normotension (to prevent rebleed), and early intervention (surgery and coiling) versus staged procedure. Our multimodal team approach was highly effective in successfully managing the patient and thus highlights its role in managing such critically ill patients.

A Rare Case of Bradycardia and Hypotension Following Administration of Ondansetron to a Patient During Spinal Fixation Surgery.

Ondansetron is commonly used during the peri-operative period for the prophylaxis of postoperative nausea and vomiting (PONV). It is a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist. Although relatively safe, few cases of ondansetron-induced bradycardia are described in the literature. Here, we present the case of a 41-year-old female with a burst fracture of the lumbar (L2) vertebrae following a fall from height. The patient underwent spinal fixation in the prone position. The intra-operative period was otherwise uneventful, except for an unprecedented incidence of bradycardia and hypotension following administration of intravenous (IV) ondansetron, at the time of closure of the surgical wound site. It was managed with IV atropine and fluid bolus. The patient was shifted to a intensive care unit (ICU) postoperatively. The postoperative period was uneventful, and the patient was discharged in good health on postoperative day three.

Anion-exchange facilitated selective extraction of sulfate and phosphate by overcoming the Hofmeister bias.

Selective recognition and removal of sulfate and phosphates from aqueous media in the presence of highly competing anions is very demanding because of their biological and environmental implications. In this paper, we present the anion recognition approach for the selective and efficient extraction of sulfate by nitrophenyl-functionalized tris-urea receptors (L1-L2) from highly competitive aqueous media with an equivalent concentration of nitrate and other anions. Tetrabutylammonium hydroxide has been used for the first time as a phase transfer anionic extractant for sulfate-exchange from the aqueous phase to the organic phase (dichloromethane) containing a tris-urea receptor (L1-L3). The sulfate extraction efficacy of L2 (≈84-90%) was observed to be higher than those of L1 (≈76-82%) and L3 (≈68-75%) in competitive extraction experiments. In contrast, an analogous nitrophenyl-functionalized tris-thiourea receptor (L4) has been recognized for the selective and efficient extraction of phosphates from aqueous media in the presence of several competing anions including sulfate and nitrate, with ≈85-92% extraction efficiency. In this case, tetrabutylammonium acetate has been used as a phase transfer anionic extractant for phosphate exchange between the two immiscible phases. Due to the higher acidity of tris-thiourea -NH groups in comparison to the analogous tris-urea, tetrabutylammonium hydroxide could deprotonate a hydrogen bond donating -NH group of the thiourea receptor and phosphate extraction was observed to be inefficient in such a case. Several liquid-liquid extraction (LLE) experiments have been carried out to establish the selective removal of sulfate and phosphates by the tripodal receptors from competitive aqueous media having different combinations of two or more anions. The LLE products obtained from organic phases were characterized by NMR (1H, 13C, 31P, and 19F) spectroscopy to affirm the oxoanion selectivity of the receptors and purity of the complexes. The tripodal receptors can easily be recycled for successive extraction cycles by simply washing the LLE products (oxoanion complexes) with a methanol-water (1 : 1, v/v) solvent system followed by filtration.

Intercalation vs Adsorption Strategies of Myo-Inositol Hexakisphosphate into Zn-Fe Layered Double Hydroxide: A Tiff between Anion Exchange and Coprecipitation.

Myo-inositol hexakisphosphates (IHPs) or phytates are the most abundant organic phosphates having the potential to serve as a phosphorus reserve in soil. Understanding the fate of IHP interaction with soil minerals tends to be crucial for its efficient storage and utilization as a slow-release organic phosphate fertilizer. We have systematically compared the effective intercalation strategy of a phytate onto Zn-Fe layered double hydroxide (LDH) acting as storage/carrier material through coprecipitation and anion exchange. Powder X-ray diffraction, X-ray photoelectron spectroscopy, elemental analysis, thermogravimetric analysis, FTIR spectra, and molecular modeling demonstrated the formation of phytate-intercalated Zn-Fe LDH through coprecipitation with a maximum loading of 41.34% (w/w) in the pH range of ∼9-10 in a vertical alignment through monolayer formation. No intercalation product was obtained from the anion exchange method, which was concluded based on the absence of shifting in the XRD (003) peak. A change in the zeta potential values from positive to negative and subsequent increase in solution pH, with decreasing phytate concentration, are suggestive of adsorption of IHP onto the LDH surface. The batch adsorption data were best fitted with Langmuir isotherm equation and followed the pseudo-second-order kinetic model. The maximum adsorption capacity was found to be 45.87 mg g-1 at a temperature of 25 ± 0.5 °C and pH 5.63.

Plasmodium Topoisomerase VIB and Spo11 Constitute Functional Type IIB Topoisomerase in Malaria Parasite: Its Possible Role in Mitochondrial DNA Segregation.

The human malaria parasite undergoes a noncanonical cell division, namely, endoreduplication, where several rounds of nuclear, mitochondrial, and apicoplast replication occur without cytoplasmic division. Despite its importance in Plasmodium biology, the topoisomerases essential for decatenation of replicated chromosome during endoreduplication remain elusive. We hypothesize that the topoisomerase VI complex, containing Plasmodium falciparum topiosomerase VIB (PfTopoVIB) and catalytic P. falciparum Spo11 (PfSpo11), might be involved in the segregation of the Plasmodium mitochondrial genome. Here, we demonstrate that the putative PfSpo11 is the functional ortholog of yeast Spo11 that can complement the sporulation defects of the yeast Δspo11 strain, and the catalytic mutant Pfspo11Y65F cannot complement such defects. PfTopoVIB and PfSpo11 display a distinct expression pattern compared to the other type II topoisomerases of Plasmodium and are induced specifically at the late schizont stage of the parasite, when the mitochondrial genome segregation occurs. Furthermore, PfTopoVIB and PfSpo11 are physically associated with each other at the late schizont stage, and both subunits are localized in the mitochondria. Using PfTopoVIB- and PfSpo11-specific antibodies, we immunoprecipitated the chromatin of tightly synchronous early, mid-, and late schizont stage-specific parasites and found that both the subunits are associated with the mitochondrial genome during the late schizont stage of the parasite. Furthermore, PfTopoVIB inhibitor radicicol and atovaquone show synergistic interaction. Accordingly, atovaquone-mediated disruption of mitochondrial membrane potential reduces the import and recruitment of both subunits of PfTopoVI to mitochondrial DNA (mtDNA) in a dose-dependent manner. The structural differences between PfTopoVIB and human TopoVIB-like protein could be exploited for development of a novel antimalarial agent. IMPORTANCE This study demonstrates a likely role of topoisomerase VI in the mitochondrial genome segregation of Plasmodium falciparum during endoreduplication. We show that PfTopoVIB and PfSpo11 remain associated and form the functional holoenzyme within the parasite. The spatiotemporal expression of both subunits of PfTopoVI correlates well with their recruitment to the mitochondrial DNA at the late schizont stage of the parasite. Additionally, the synergistic interaction between PfTopoVI inhibitor and the disruptor of mitochondrial membrane potential, atovaquone, supports that topoisomerase VI is the mitochondrial topoisomerase of the malaria parasite. We propose that topoisomerase VI may act as a novel target against malaria.

Oxyanion-encapsulated caged supramolecular frameworks of a tris(urea) receptor: evidence of hydroxide- and fluoride-ion-induced fixation of atmospheric CO2 as a trapped CO3(2-) anion.

A tris(2-aminoethyl)amine-based tris(urea) receptor, L, with electron-withdrawing m-nitrophenyl terminals has been established as a potential system that can efficiently capture and fix atmospheric CO(2) as air-stable crystals of a CO(3)(2-)-encapsulated molecular capsule (complex 1), triggered by the presence of n-tetrabutylammonium hydroxide/fluoride in a dimethyl sulfoxide solution of L. Additionally, L in the presence of excess HSO(4)(-) has been found to encapsulate a divalent sulfate anion (SO(4)(2-)) within a dimeric capsular assembly of the receptor (complex 2) via hydrogen-bonding-activated proton transfer between the free and bound HSO(4)(-) anions. Crystallographic results show proof of oxyanion encapsulation within the centrosymmetric cage of L via multiple N-H···O hydrogen bonds to the six urea functions of two inversion-symmetric molecules. The solution-state binding and encapsulation of oxyanions by N-H···O hydrogen bonding has also been confirmed by quantitative (1)H NMR titration experiments, 2D NOESY NMR experiments, and Fourier transform IR analyses of the isolated crystals of the complexes that show huge spectral changes relative to the free receptor.

Fentanyl Versus Dexmedetomidine for the Prevention of Emergence Agitation in Children After Sevoflurane Anaesthesia: A Comparative Clinical Study.

Introduction Sevoflurane is widely used in pediatric anesthesia due to its rapid onset and offset of action, smooth induction, and less hepatotoxicity. However, it is associated with emergence agitation, which can be frightening and harm the patient or the caregiver. While a definite preventive measure of emergence agitation is in search, the use of some drugs is associated with a lesser incidence of emergence related to sevoflurane.  Aims and objective This study aimed to compare the efficacy of fentanyl with dexmedetomidine in preventing emergence agitation in children undergoing surgery with sevoflurane anesthesia. Also, we assessed the perioperative hemodynamic and postoperative recovery characteristics and side effects, if any, between children receiving the two groups of drugs. Material and method We conducted a prospective, double-blinded, randomized controlled trial after getting approval from the institutional ethical committee. A total of 120 patients were recruited into the study and divided into two groups, F and D, of 60 patients each. Patients in group F received an infusion of injection fentanyl at 1 mcg/kg and patients in group D received infusions of injection dexmedetomidine at 0.15 mcg/kg, respectively, after induction of general anaesthesia. Additionally, all patients received a caudal epidural block with 0.125% isobaric levobupivacaine. After the conclusion of surgery, we transferred the patients to the post-anaesthesia care unit for further observation and assessment. Result The Pediatric Anesthesia Emergence Delirium (PAED) score for emergence agitation was significantly greater in the fentanyl group compared to the dexmedetomidine group at 0 minutes (7.08 ± 1.03 vs. 6.43 ± 1.33, p = 0.003) and 15 minutes (5.51 ± 1.7 vs. 4.01 ± 1.08, p = 0.0001) postoperative period. The mean time to eye-opening was significantly earlier amongst children receiving fentanyl than those receiving dexmedetomidine (9.3 ± 1.1 min vs. 10.12 ±1.05 min, p = 0.0001). The modified Aldrete Score for adequacy of recovery was statistically insignificant initially, but as the duration progressed to 15 minutes, the children in the fentanyl group had significantly higher scores than those in the dexmedetomidine group (8.05 ± 0.67 vs. 7.76 ± 0.62, p = 0.01). Conclusion Prophylactic administration of dexmedetomidine (0.15 mcg/kg) or fentanyl (1 mcg/kg) administered is effective in preventing emergence agitation. Although we found emergence agitation was higher amongst children receiving fentanyl than those receiving dexmedetomidine during the early recovery period, this difference became insignificant as the postoperative period increased to 30 minutes.

Addition of Clonidine or Dexmedetomidine With Bupivacaine to Prolong Caudal Analgesia in Children Undergoing Infraumbilical Surgery.

Introduction Clonidine, a selective α2 adrenergic receptor agonist, combined with caudally administered bupivacaine, is frequently used in children to prolong the duration of postoperative analgesia following infraumbilical surgery. On the other hand, dexmedetomidine is highly selective and has a greater affinity toward α2 adrenergic receptors, especially toward its α2a subtype, accountable for more analgesic and hypnotic effects than clonidine. Aims and objectives We designed a prospective, double-blinded, randomized controlled trial to compare the analgesic efficacy and adverse effects of clonidine and dexmedetomidine when combined with bupivacaine for caudal analgesia in children undergoing infraumbilical surgeries. Materials and methods A total of 60 children aged one to eight years were randomly assigned into two different groups in a double-blinded manner. Following induction of general anesthesia, every patient received a single dose of caudal bupivacaine 0.25% (0.75 ml/kg) mixed with either clonidine (1 µ/kg) in normal saline or dexmedetomidine (1 µ/kg) in normal saline. We noted the hemodynamic variables and postoperative sedation scores. Duration and quality of postoperative analgesia and the number of rescue analgesic drug doses required were recorded during the first 24 hours postoperatively. We also observed the patients for any adverse effects to the study drugs. Result Adding dexmedetomidine to caudally administered bupivacaine significantly increased the duration of analgesia (15 ± 0.78 hours) and decreased the need for rescue drug doses than the addition of clonidine to bupivacaine (9.63 ± 1.95 hours) in children undergoing infraumbilical surgeries. Incidences of hemodynamic changes or other side effects were comparable between patients of two groups. Conclusion The addition of dexmedetomidine to caudally administered bupivacaine in children undergoing infraumbilical surgeries may provide a longer duration of analgesia than the addition of clonidine, with less requirement of rescue analgesic doses and without any significant differences in the hemodynamic parameters or other side effects.

Intraoperative Dental Injury in a Neurosurgical Patient: Concerns for the Anesthesiologist.

Anesthesia-related oropharyngeal injuries are known to occur. Risk factors for intraoperative dental injuries include difficult intubation, use of transesophageal echocardiography (TEE) probe, motor-evoked potential (MEP) monitoring, poor dental hygiene, etc. Our patient was a case of a thalamic cavernoma who underwent craniotomy in a sitting position with the neck flexed along with MEP and TEE monitoring. At the end of the surgery, the lower three incisors were found to be subluxated. The subluxated teeth were stabilized using a 2-0 Ethilon suture in the operation room. Immediate dental consultation was sought postoperatively. Sitting position surgeries with associated neck flexion, simultaneous, advanced monitoring techniques like TEE and MEP, poor dental condition, and the use of hard bite blocks can predispose patients to dental injury. Preoperative dental evaluation and explanation of neuromonitoring-associated injuries can be beneficial.

A Rare Case of Urachal Cyst in a Patient With Uterine Fibroids.

A 41-year-old woman presented to the emergency department with pain in her abdomen during menstruation. On examination, we detected a cystic lump in the midline, just below the umbilicus. Ultrasonography of the whole abdomen was suggestive of uterine fibroids with a probable mesenteric cyst. Computed tomography of the abdomen confirmed an otherwise asymptomatic, silent, urachal cyst connected to the umbilicus and urinary bladder by obliterated bands. The cyst was explored and removed surgically under combined spinal-epidural anesthesia, following a single-staged approach. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was subsequently performed. Urachal cysts are rare congenital anomalies. Any unexpected finding on clinical examination should alert clinicians for further evaluation and treatment.

DNA damage-induced nuclear import of HSP90α is promoted by Aha1.

The interplay between yHSP90α (Hsp82) and Rad51 has been implicated in the DNA double-strand break repair (DSB) pathway in yeast. Here we report that nuclear translocation of yHSP90α and its recruitment to the DSB end are essential for homologous recombination (HR)-mediated DNA repair in yeast. The HsHSP90α possesses an amino-terminal extension which is phosphorylated upon DNA damage. We find that the absence of the amino-terminal extension in yHSP90α does not compromise its nuclear import, and the nonphosphorylatable-mutant HsHSP90αT7A could be imported to the yeast nucleus upon DNA damage. Interestingly, the flexible charged-linker (CL) domains of both yHSP90α and HsHSP90α play a critical role during their nuclear translocation. The conformational restricted CL mutant yHSP90α∆(211-259), but not a shorter deletion version yHSP90α∆(211-242), fails to reach the nucleus. As the CL domain of yHSP90α is critical for its interaction with Aha1, we investigated whether Aha1 promotes the nuclear import of yHSP90α. We found that the nuclear import of yHSP90α is severely affected in ∆aha1 strain. Moreover, Aha1 is accumulated in the nucleus during DNA damage. Hence Aha1 may serve as a potential target for inhibiting nuclear function of yHSP90α. The increased sensitivity of ∆aha1 strain to genotoxic agents strengthens this notion.

An Incidental Finding of Congenital Complete Heart Block Presenting in Active Labor: A Multidisciplinary Approach.

Congenital complete heart block is a rare occurrence. In some cases, it remains asymptomatic until adulthood or in the case of women until pregnancy. It is usually secondary to placental transfer of maternal antibodies and is associated with high mortality and morbidity. We present a case of a parturient who presented in active labor with premature rupture of membranes and decreased fetal movements. We found that the patient had a complete heart block with mild effort intolerance on evaluation. Markers for metabolic and ischemic causes were negative, and we made a provisional diagnosis of congenital complete heart block. The patient underwent a lower section cesarian section under spinal anesthesia with temporary pacemaker backup. Postoperatively, the patient underwent permanent pacemaker implantation. This case report underlines the importance of standard American Society of Anesthesiologists (ASA) monitoring, including a 12-lead electrocardiogram (ECG), which could prove decisive and life-saving in dire circumstances.

Neuroprotective and Proneurogenic Effects of Glucosamine in an Internal Carotid Artery Occlusion Model of Ischemia.

Neuroprotective, antineuroinflammatory, and proneurogenic effects of glucosamine, a naturally occurring amino sugar, have been reported in various animal models of brain injury including cerebral ischemia and hypoxic brain damage. Given that clinical translation of therapeutic candidates identified in animal models of ischemic stroke has remained unsatisfactory in general, possibly due to inadequacy of existing models, we sought to study the effects of glucosamine in a recently developed, clinical condition mimicking mouse model of internal cerebral artery occlusion. In this model of mild to moderate striatal damage, glucosamine ameliorated behavioral dysfunction, rescued ischemia-induced striatal damage, and suppressed ischemia-induced upregulation of proinflammatory genes in striatal tissue. Further, in ex vivo neurosphere assay involving neural stem cells/neural progenitor cells from subventricular zone, glucosamine increased the number of large neurospheres, along with enhancing mRNA levels of the proliferation markers Nestin, NeuroD1, and Sox2. Lastly, coronal brain sections containing the striatal region with subventricular zone showed increased number of BrdU positive cells and DCX positive cells, a marker for newly differentiating and immature neurons, in glucosamine-treated ischemic mice. Cumulatively, the results confirming neuroprotective, antineuroinflammatory, and proneurogenic effects of glucosamine enhance drug repurposing potential of glucosamine in cerebral ischemia.

Selective recognition and extraction of arsenate by a urea-functionalized tripodal receptor from competitive aqueous media.

A second-generation hydrogen bond donor (HBD) anion receptor with an inner amide cavity and an outer urea cavity can selectively and efficiently extract arsenate (AsO43-) from water in the presence of competitive oxoanions and halides. The X-ray structure showed encapsulation of AsO43- in a π-stacked dimeric capsular assembly of the receptor, the first crystallography-based example of pentavalent AsO43- trianion recognition by a HBD receptor.

Evaluation of Electrolyte Imbalance in Patients With Traumatic Brain Injury Admitted in the Central ICU of a Tertiary Care Centre: A Prospective Observational Study.

Introduction Electrolyte imbalance is a salient finding in traumatic brain injury which can derail their clinical course of recovery in physical and cognitive health while prolonging the hospital stay. Objective This study aims to understand the variation in electrolyte profile that occurs in traumatic brain injury patients which can help in better patient management. Materials and method 50 trauma patients with head injury (Group A) and 50 patients without head injury (Group B) admitted in Central ICU (CICU) under the Department of Anaesthesiology, Assam Medical College and Hospital (AMCH) were selected and analysed with regard to their electrolyte variability. Result All trauma patients with head injury developed an imbalance to one or more electrolytes. Then mean electrolyte level in trauma patients with a head injury and in trauma patients without head injury were 139.3±7.45 vs 143.65±8.89, p<0.05 (sodium), 3.49±0.44 vs 3.88±0.49, p<0.05 (potassium), 7.81±0.5 vs 8.9± 0.35, p<0.05 (calcium) and 2±0.33 vs 2.47±0.41, p<0.05 (magnesium) respectively. Also, patients in the head injury group had a higher incidence of hypoalbuminemia than patients without head injury 2.47±0.67 vs 2.83±0.74 (p<0.05). Conclusion We conclude that traumatic brain injury patients have a greater risk of electrolyte imbalance, viz. hyponatremia, hypokalaemia, hypocalcaemia as well as hypomagnesemia, and hypophosphatemia along with hypoalbuminemia.

A Rare Case of Partial Volvulus of the Gall Bladder Detected Preoperatively.

A middle-aged woman with uterine fibroids presented with menorrhagia and diffuse abdominal pain. The patient was anemic, afebrile, anicteric, and had a palpable tender gall bladder. Initial whole abdomen ultrasonography was inconclusive, and computed tomography of her abdomen revealed partial volvulus of the gall bladder. Following optimization, the patient had undergone open cholecystectomy under general anesthesia. Intraoperatively, the gall bladder was distended, with edematous walls and rotated clockwise (270°) along the long axis to the cystic duct. We noted no gangrenous changes, and we performed detorsion of the gall bladder and cholecystectomy. Volvulus of the gall bladder can be associated with high mortality and morbidity. Good clinical examination, a high degree of suspicion given the presentation of the case, proper investigation, and timely management prevented poor outcomes in our case.

Revisiting salicylidene-based anion receptors.

Several salicylidene-based colorimetric and fluorimetric anion sensors are known in the literature. However, our 1H-NMR experimental results (in DMSO-d6) showed hydrolysis of imine (-N[double bond, length as m-dash]CH-) bonds in salicylidene-based receptors (SL, CL1 and CL2) in the presence of quaternary ammonium salts (n-Bu4N+) of halides (Cl- and Br-) and oxo-anions (H2PO4 -, HSO4 - and CH3COO-). The mono-salicylidene compound CL1 showed the most extensive -N[double bond, length as m-dash]CH- bond hydrolysis in the presence of anions. In contrast, the di-salicylidene compound CL2 and the tris-salicylidene compound SL showed comparatively slow hydrolysis of -N[double bond, length as m-dash]CH- bonds in the presence of anions. Anion-induced imine bond cleavage in salicylidene compounds could easily be detected in 1H-NMR due to the appearance of the salicylaldehyde -CHO peak at 10.3 ppm which eventually became more intense over time, and the -N[double bond, length as m-dash]CH- peak at 8.9-9.0 ppm became considerably weaker. Furthermore, the formation of the salicylidene O-H⋯X- (X- = Cl-/Br-) hydrogen-bonded complex, peak broadening due to proton-exchange processes and keto-enol tautomerism have also been clearly observed in the 1H-NMR experiments. Control 1H-NMR experiments revealed that the presence of moisture in the organic solvents could result in gradual hydrolysis of the salicylidene compounds, and the rate of hydrolysis has further been enhanced significantly in the presence of an anion. Based on 1H-NMR results, we have proposed a general mechanism for the anion-induced hydrolysis of imine bonds in salicylidene-based receptors.

Bloom Helicase Along with Recombinase Rad51 Repairs the Mitochondrial Genome of the Malaria Parasite.

The homologous recombination (HR) pathway has been implicated as the predominant mechanism for the repair of chromosomal DNA double-strand breaks (DSBs) of the malarial parasite. Although the extrachromosomal mitochondrial genome of this parasite experiences a greater number of DSBs due to its close proximity to the electron transport chain, nothing is known about the proteins involved in the repair of the mitochondrial genome. We investigated the involvement of nucleus-encoded HR proteins in the repair of the mitochondrial genome, as this genome does not code for any DNA repair proteins. Here, we provide evidence that the nucleus-encoded "recombinosome" of the parasite is also involved in mitochondrial genome repair. First, two crucial HR proteins, namely, Plasmodium falciparum Rad51 (PfRad51) and P. falciparum Bloom helicase (PfBlm) are located in the mitochondria. They are recruited to the mitochondrial genome at the schizont stage, a stage that is prone to DSBs due to exposure to various endogenous and physiologic DNA-damaging agents. Second, the recruitment of these two proteins to the damaged mitochondrial genome coincides with the DNA repair kinetics. Moreover, both the proteins exit the mitochondrial DNA (mtDNA) once the genome is repaired. Most importantly, the specific chemical inhibitors of PfRad51 and PfBlm block the repair of UV-induced DSBs of the mitochondrial genome. Additionally, overexpression of these two proteins resulted in a kinetically faster repair. Given the essentiality of the mitochondrial genome, blocking its repair by inhibiting the HR pathway could offer a novel strategy for curbing malaria. IMPORTANCE The impact of malaria on global public health and the world economy continues to surge despite decades of vaccine research and drug development efforts. An alarming rise in resistance toward all the commercially available antimalarial drugs and the lack of an effective malaria vaccine brings us to the urge to identify novel intervention strategies for curbing malaria. Here, we uncover the molecular mechanism behind the repair of the most deleterious form of DNA lesions on the parasitic mitochondrial genome. Given that the single-copy mitochondrion is an indispensable organelle of the malaria parasite, we propose that targeting the mitochondrial DNA repair pathways should be exploited as a potential malaria control strategy. The establishment of the parasitic homologous recombination machinery as the predominant repair mechanism of the mitochondrial DNA double-strand breaks underscores the importance of this pathway as a novel druggable target.