An in silico map of the SARS-CoV-2 RNA Structurome

SARS-CoV-2 is a positive-sense single-stranded RNA virus that has exploded throughout the global human population. This pandemic coronavirus strain has taken scientists and public health researchers by surprise and knowledge of its basic biology (e.g. structure/function relationships in its genomic, messenger and template RNAs) and modes for therapeutic intervention lag behind that of other human pathogens. In this report we used a recently-developed bioinformatics approach, ScanFold, to deduce the RNA structural landscape of the SARS-CoV-2 transcriptome. We recapitulate known elements of RNA structure and provide a model for the folding of an essential frameshift signal. Our results find that the SARS-CoV-2 is greatly enriched in unusually stable and likely evolutionarily ordered RNA structure, which provides a huge reservoir of potential drug targets for RNA-binding small molecules. Our results also predict regions that are accessible for intermolecular interactions, which can aid in the design of antisense therapeutics. All results are made available via a public database (the RNAStructuromeDB) where they may hopefully drive drug discovery efforts to inhibit SARS-CoV-2 pathogenesis.

Genetic barcoding and phylogenetic analysis of dusky cotton bug (Oxycarenus hyalinipennis) using mitochondrial cytochrome c oxidase I gene.

Cotton dusky bug (Oxycarenus spp.) mostly attack on cash crops such as Gossypium, Cola and Hibiscus which affect the national economy therefore sustainable pest management is needed. Cytochrome c oxidase I (COI) gene is utilized as marker gene for DNA barcoding, genetic and ecological study of insects. In present study insect (cotton dusky bug) samples were collected from cotton fields in Faisalabad. COI gene was amplified from genomic DNA of bug and cloned into pTZ57R/T vector (Fermentas). The clone was sent to Macrogen (South Korea) for Sanger sequencing. The phylogenetic analysis and pairwise multiple sequence alignment showed that our cotton dusky bug grouped with two species of Oxycarenus genus and highest sequence identity was 91.1% with Oxycarenus hylinipennis. This is the first report of genetic barcode of Oxycarenus hylinipennis from cotton from Pakistan.

Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients.

Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04-2.88; p = 0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02-1.04; p < 0.001). Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34-0.72; p < 0.001), but we were underpowered to detect risk reduction for invasive aspergillosis. Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13-0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients.

Single-nucleotide polymorphisms in pigment genes and nonmelanoma skin cancer predisposition: a systematic review.

Nonmelanoma skin cancer (NMSC) is the most common cancer in the U.S.A. The two most common NMSCs are basal cell carcinoma and squamous cell carcinoma. The associations of single-nucleotide polymorphisms (SNPs) in pigmentation pathway genes with NMSC are not well characterized. There is a series of epidemiological studies that have tested these relationships, but there is no recent summary of these findings. To explain overarching trends, we undertook a systematic review of published studies. The summarized data support the concept that specific SNPs in the pigmentation pathway are of importance for the pathogenesis of NMSC. The SNPs with the most promising evidence include MC1R rs1805007(T) (Arg151Cys) and rs1805008(T) (Arg160Trp), and ASIP AH haplotype [rs4911414(T) and rs1015362(G)]. There are a few other SNPs found in TYR, OCA2 and SLC45A2 that may show additional correlation after future research. With additional research there is potential for the translation of future findings to the clinic in the form of SNP screenings, where patients at high risk for NMSC can be identified beyond their phenotype by genotypically screening for predisposing SNPs.

Ochrobactrum ciceri sp. nov., isolated from nodules of Cicer arietinum.

A Gram-staining-negative, aerobic, rod-shaped, non-spore-forming bacterial strain, Ca-34(T), was isolated from nodules of chickpea (Cicer arietinum) in Pakistan and studied for its taxonomic affiliation. The almost full-length 16S rRNA gene sequence showed highest similarities to those of strains of the genus Ochrobactrum. Based on results of MALDI-TOF MS and 16S rRNA gene sequence similarity (98.6 %), strain Ca-34(T) and Ochrobactrum intermedium LMG 3301(T) are phylogenetic neighbours; the two strains shared DNA-DNA relatedness of 64 %. The fatty acid profile [predominantly C(18 : 1)omega7c (67.7 %) and C(19 : 0) cyclo omega8c (19.6 %)] also supported the genus affiliation. Metabolically, strain Ca-34(T) differed from other type strains of Ochrobactrum in many reactions and from all type strains in testing positive for gelatin hydrolysis and in testing negative for assimilation of alaninamide and l-threonine. Based on phenotypic and genotypic data, we conclude that strain Ca-34(T) represents a novel species, for which we propose the name Ochrobactrum ciceri sp. nov. (type strain Ca-34(T) =DSM 22292(T) =CCUG 57879(T)).

History of childhood maltreatment is associated with comorbid depression in women with migraine.

BACKGROUND: A bidirectional relationship between migraine and depression suggests a neurobiological link. Adverse experiences, particularly childhood maltreatment, may alter neurobiological systems, and predispose to a multiplicity of adult chronic disorders. Our objective is to determine, within a headache clinic population of women, if depression moderates the abuse-migraine relationship. METHODS: At six headache specialty clinics, women with migraine were diagnosed using ICHD-II criteria, and frequency was recorded. A questionnaire regarding maltreatment history, headache characteristics, current depression, and somatic symptoms was completed. RESULTS: A total of 949 women with migraine completed the survey: 40% had chronic headache (> or =15 headache days/month) and 72% had "very severe" headache-related disability. Major depression was recorded in 18%. Physical or sexual abuse was reported in 38%, and 12% reported both physical and sexual abuse in the past. Migraineurs with current major depression reported physical (p < 0.001) and sexual (p < 0.001) abuse in higher frequencies compared to those without depression. Women with major depression were more likely to report sexual abuse occurring before age 12 years (OR = 2.30, 95% CI: 1.14 to 4.77), and the relationship was stronger when abuse occurred both before and after age 12 years (OR = 5.08, 95% CI: 2.15 to 11.99). Women with major depression were also twice as likely to report multiple types of maltreatment (OR = 2.07, 95% CI: 1.27 to 3.35) compared to those without depression. CONCLUSIONS: Childhood maltreatment was more common in women with migraine and concomitant major depression than in those with migraine alone. The association of childhood sexual abuse with migraine and depression is amplified if abuse also occurs at a later age.

High prevalence of somatic symptoms and depression in women with disabling chronic headache.

OBJECTIVE: To better define, in women with headache, the relationship of depression and somatic symptoms to headache, characterized by diagnoses, frequency, and disability. METHODS: At six headache specialty clinics, women with headache were classified using ICHD-II criteria, and frequency was recorded. A questionnaire addressing demographics, age at onset of headache, headache-related disability, somatic symptom, and depression severity was completed. Logistic regression was performed to measure the associations of headache frequency and headache-related disability with somatic symptom and depression severity. RESULTS: A total of 1,032 women with headache completed the survey, 593 with episodic (96% with migraine) and 439 with chronic headache (87% with migraine). Low education and household income was more common in chronic headache sufferers and in persons with severe headache disability. Somatic symptom prevalence and severity was greater in persons with chronic headache and with severe headache-related disability. Significant correlation was observed between PHQ-9 and PHQ-15 scores (r = 0.62). Chronic headache, severe disability, and high somatic symptom severity were associated with major depressive disorder (OR = 25.1, 95% CI: 10.9 to 57.9), and this relationship was stronger in the subgroup with a diagnosis of migraine (OR = 31.8, 95% CI: 12.9 to 78.5). CONCLUSIONS: High somatic symptom severity is prevalent in women with chronic and severely disabling headaches. Synergistic relationship to major depression exists for high somatic symptom severity, chronic headache, and disabling headache, suggesting a psychobiological underpinning of these associations.

Isolated petrous carotid stenosis and transient ischemic attack.

Although anterior circulation transient ischemic attacks (TIAs) tend to be more common in patients with extra- cranial carotid arterial disease than in those with intracranial carotid or middle cerebral arterial disease, the authors recently encountered 4 patients with both recurrent, stereotypical TIAs as well as isolated stenosis of their petrous internal carotid artery (ICA). While the gold standard for establishing the diagnosis of intracranial large-artery disease has always been conventional angiography, magnetic resonance angiography changes, confirmed with intra-arterial digital subtraction angiography in 2 of these patients, were quite sufficient to define the occlusive disease in each of the cases. Petrous ICA stenosis is not uncommon, but it has often been overshadowed by the search for extracranial ICA disease that might be amenable to surgical reconstruction.

Pulsatile tinnitus in cerebrovascular arterial diseases.

In a prospective study of 100 patients evaluated at the University of Wisconsin Stroke Program, we sought to document cases of incidental pulsatile tinnitus that could be ascribed to stenotic, occluded, ectatic, tortuous, or dissected craniocerebral arteries. Angiographic detail, magnetic resonance angiography, catheter-generated x-ray angiography, or both were necessary for inclusion into either Group 1 (n=29), those with pulsatile tinnitus, or Group 2 (n=71), those without pulsatile tinnitus. Patients did not appear to have head/neck tumors, aneurysms, arteriovenous malformations, transmitted cardiac murmurs, or venous etiologies for their tinnitus. Age, sex, and stroke risk factor profiles did not separate the two groups. Factors that were significantly more common in Group 1 included (1) severe, > or =70% stenosis through complete occlusion, internal carotid artery disease (59% for Group 1 v 21% for Group 2, P<.05); (2) severe, > or =50% stenosis through occlusion, vertebral or basilar disease (38% v 18%, P<.05); (3) tortuosity of at least one carotid, vertebral, or basilar artery (31% v 18%, P<.05); and (4) basilar artery dolichoectasia (14% v 0%, P=.006). We also noted when pulsatile tinnitus was either "objective" (11 of 100, 11%) or "subjective" (18 of 100, 18%), duration of tinnitus, transient versus permanent nature of tinnitus, and reasons seen in consultation by one of us.

Tortuosity of carotid and vertebral arteries: a magnetic resonance angiographic study.

Nine patients (group A) were found on magnetic resonance angiography (MRA) to have excessive carotid artery, vertebral artery, and vertebrobasilar junction tortuosity. A control group (group B) were age- and sex-matched to group A patients, were selected randomly from our MRA or stroke data banks, and had not undergone MRA for evaluation of migraine, "carotidynia," or pulsatile tinnitus. Factors more prevalent in group A patients included migraine, chronic daily headache, carotidynia, pulsatile tinnitus, and a positive family history of headache. Factors more prevalent in group B patients included a positive family history of stroke, large-vessel atherosclerosis, and scan evidence of ischemic infarctions; many group B patients had undergone MRA for stroke or transient ischemic attack evaluation. Men were slightly underrepresented at 44%, and were younger than women (34 +/- 6 years vs. 43 +/- 3 years; p = 0.01). Relationships in this preliminary study between arterial tortuosity and migraine seem evident.

Recurrent ischemic strokes in a patient with Medtronic-Hall prosthetic aortic valve and valve strands.

Fine strands associated with prosthetic heart valves have been demonstrated with transesophageal echocardiography, but the pathologic identity of these strands is unclear. A case of a man with a prosthetic aortic Medtronic-Hall valve with prominent valve strands and recurrent strokes is discussed. The patient underwent valve replacement surgery, and histopathologic examination of the strands identified them as Lambl's excrescences.

Differing mechanisms between posterior and middle cerebral artery infarctions.

Cardiac embolism has been thought to be one of the principal causes of posterior cerebral artery territory infarction. To determine stroke mechanisms and stroke risk factors in patients with posterior cerebral artery infarction, we studied 23 consecutive patients with recent infarcts in the posterior cerebral artery distribution (PCA infarcts) and compared these with a case-control group of 46 patients with recent infarcts in the middle cerebral artery distribution (MCA infarcts). All patients were similarly studied, including angiography and echocardiography. Case controls were age- and sex-matched and were randomly chosen from the most recent MCA infarcts seen at our institutions. All subjects were white. PCA infarcts had significantly more cardiac-source emboli (P=.01), less evident atherothrombosis (P=.003), multiplicity of infarctions (P=.05), and documented branch occlusions in the vessel involved (P=.05). MCA infarcts had more preinfarction transient ischemic attacks (P=.03) and evident occlusion of the appropriate extracranial vessel (P=.03). Different stroke mechanisms should lead to different diagnostic and therapeutic decisions.

Kanerocin: A New Triterpene from the Leaves of Nerium oleander.

From the fresh, undried, and uncrushed leaves of NERIUM OLEANDER a new triterpenoid, kanerocin, has been isolated along with known ursolic and oleanolic acids and its structure established through chemical and spectroscopic methods as 3alpha-hydroxy-urs-18,20-dien-28-oic acid.

Oleanderoic Acid and Oleanderen from the Leaves of Nerium oleander.

A new labdane diterpene, oleanderoic acid and a new triterpene, oleanderen have been isolated from the fresh, undried and uncrushed leaves of NERIUM OLEANDER. Their structures have been established as 8alpha-methoxylabdan-18-oic acid, and 12-ursene, respectively, through chemical and spectral studies, including 2D-NMR (COSY-45, NOESY and 2D- J resolved) and (13)C-NMR data.

Isolation and Structure of Neriucoumaric and Isoneriucoumaric Acids from the Leaves of Nerium oleander.

Two new coumaryloxy triterpenoids, neriucoumaric and isoneriucoumaric acids, have been isolated from fresh, undried and uncrushed leaves of NERIUM OLEANDER and their structures established as 3beta-hydroxy-2alpha-cis- P-coumaryloxy-urs-12-en-28-oic acid and 3beta-hydroxy-2alpha- TRANS- P-coumaryloxy-urs-12-en-28-oic acid respectively, through chemical and spectroscopic methods.

Isolation and Structure of Neriumol and Nerifol from the Leaves of Nerium odorum.

From the fresh, undried, uncrushed leaves of NERIUM ODORUM, two hydroxy acid methyl esters, neriumol and nerifol, have been isolated and their structures established as methyl (7 S,16)-dihydroxyhexadeca-8 Z-enoate and methyl (8,16)-dihydroxyhexadecanoate, through chemical and spectroscopic methods.