Miracle-dz/UniFAR-FTUs huggingface dataset:
Kanamycin uptake into Escherichia coli is facilitated by OmpF and OmpC porin channels located in the outer membrane.

Despite decades of therapeutic application of aminoglycosides, it is still a matter of debate if porins contribute to the translocation of the antibiotics across the bacterial outer membrane. Here, we quantified the uptake of kanamycin across the major porin channels OmpF and OmpC present in the outer membrane of Escherichia coli. Our analysis revealed that, despite its relatively large size, about 10 - 20 kanamycin molecules per second permeate through OmpF and OmpC under a 10 μM concentration gradient, whereas OmpN does not allow the passage. Molecular simulations elucidate the uptake mechanism of kanamycin through these porins. Whole-cell studies with a decisive set of E. coli porin mutants provide evidence that translocation of kanamycin via porins is relevant for antibiotic potency.
Virus-mediated total release of dimethylsulfoniopropionate from marine phytoplankton: a potential climate process

Growing, axenic cultures of the eukaryohc marine microalga Micromonas pusilla (Prasinophyceae) were inoculated with 0.7 infectious particles cell-' of the vlral pathogen MPV (Micromonas pusilla virus). Starting 11 to 14 h after the inoculation, rapid release of intracellular dimethylsulfoniopropionate (DMSP) to the dissolved pool occurred along with cell lysis. DMSP release was total. Release facilitates bacterial degradation of DMSP to dimethylsulfide, a gas that affects cloud cover over the oceans. Viruses of eukaryotic manne phytoplankton may thus participate in the biological shaping of global climate.
A Novel 4-gene Score to Predict Survival, Distant Metastasis and Response to Neoadjuvant Therapy in Breast Cancer

We generated a 4-gene score with genes upregulated in LM2-4, a metastatic variant of MDA-MB-231 (DOK 4, HCCS, PGF, and SHCBP1) that was strongly associated with disease-free survival (DFS) in TCGA cohort (hazard ratio [HR]>1.2, p < 0.02). The 4-gene score correlated with overall survival of TCGA (HR = 1.44, p < 0.001), which was validated with DFS and disease-specific survival of METABRIC cohort. The 4-gene score was able to predict worse survival or clinically aggressive tumors, such as high Nottingham pathological grade and advanced cancer staging. High score was associated with worse survival in the hormonal receptor (HR)-positive/Her2-negative subtype. High score enriched cell proliferation-related gene sets in GSEA. The score was high in primary tumors that originated, in and metastasized to, brain and lung, and it predicted worse progression-free survival for metastatic tumors. Good tumor response to neoadjuvant chemotherapy or hormonal therapy was accompanied by score reduction. High scores were also predictive of response to neoadjuvant chemotherapy for HR-positive/Her2-negative subtype. High score tumors had increased expression of T cell exhaustion marker genes, suggesting that the score may also be a biomarker for immunotherapy response. Our novel 4-gene score with both prognostic and predictive values may, therefore, be clinically useful particularly in HR-positive breast cancer.
Hyphenation of strong cation exchange chromatography to native mass spectrometry for high throughput online characterization of charge heterogeneity of therapeutic monoclonal antibodies

ABSTRACT Characterization of charge heterogeneity in monoclonal antibodies (mAbs) is needed during developability assessment and downstream development of drug candidates. Charge heterogeneity can come from post-translational modifications like deamidation, isomerization, and sialylation. Elucidation of charge variants with mass spectrometry (MS) has historically been challenging. Due to the nonvolatility and high ionic strength of conventional buffer systems, labor-intensive offline fractionation followed by MS analysis is routinely used. Here, we describe an alternative strategy that directly couples strong cation exchange (SCX) chromatography to high-resolution Orbitrap MS for online native MS analysis (SCX-MS). A combined pH and salt gradient was used for universal separation of mAbs from a wide range of pI values (6.38 ~ 9.2), including infliximab (Remicade®, chimeric IgG1/kappa), NISTmab (humanized IgG1/kappa) and trastuzumab (Herceptin®, humanized IgG1/kappa), without tailoring of chromatographic profiles. Liquid chromatography and MS parameters were optimized to achieve high-quality spectra and enhanced detection of low abundant species under high flow rate conditions. Genedata Expressionist, a vendor agnostic software, was used for data processing. This integrated strategy allows unbiased characterization of numerous charge variant species and low molecular weight fragments (<0.05%) without post-column flow splitting. The application was further expanded with middle-up approaches for subdomain analysis, which demonstrated the versatility of the strategy for analysis of various construct types. With our analysis of mAbs during developability assessment and forced degradation studies, which aimed at assessing potential critical quality attributes in antibody drug molecules, we provide, for the first time, direct visualization of molecular alterations of mAbs at intact level. Furthermore, strong correlation was observed between this novel MS approach and analysis by capillary isoelectric focusing.
Efficaciousness of Low Affinity Compared to High Affinity TSPO Ligands in the Inhibition of Hypoxic Mitochondrial Cellular Damage Induced by Cobalt Chloride in Human Lung H1299 Cells

The 18 kDa translocator protein (TSPO) plays an important role in apoptotic cell death, including apoptosis induced by the hypoxia mimicking agent cobalt chloride (CoCl2). In this study, the protective effects of a high (CB86; Ki = 1.6 nM) and a low (CB204; Ki = 117.7 nM) affinity TSPO ligands were investigated in H1299 lung cancer cell line exposed to CoCl2. The lung cell line H1299 was chosen in the present study since they express TSPO and able to undergo programmed cell death. The examined cell death markers included: ATP synthase reversal, reactive oxygen species (ROS) generation, mitochondrial membrane potential (Δψm) depolarization, cellular toxicity, and cellular viability. Pretreatment of the cells with the low affinity ligand CB204 at a concentration of 100 µM suppressed significantly (p < 0.05 for all) CoCl2-induced cellular cytotoxicity (100%), ATP synthase reversal (67%), ROS generation (82%), Δψm depolarization (100%), reduction in cellular density (97%), and also increased cell viability (85%). Furthermore, the low affinity TSPO ligand CB204, was harmless when given by itself at 100 µM. In contrast, the high affinity ligand (CB86) was significantly effective only in the prevention of CoCl2–induced ROS generation (39%, p < 0.001), and showed significant cytotoxic effects when given alone at 100 µM, as reflected in alterations in ADP/ATP ratio, oxidative stress, mitochondrial membrane potential depolarization and cell death. It appears that similar to previous studies on brain-derived cells, the relatively low affinity for the TSPO target enhances the potency of TSPO ligands in the protection from hypoxic cell death. Moreover, the high affinity TSPO ligand CB86, but not the low affinity ligand CB204, was lethal to the lung cells at high concentration (100 µM). The low affinity TSPO ligand CB204 may be a candidate for the treatment of pulmonary diseases related to hypoxia, such as pulmonary ischemia and chronic obstructive pulmonary disease COPD.
Lack of Flvcr2 impairs brain angiogenesis without affecting the blood-brain barrier.

Fowler syndrome is a rare autosomal recessive brain vascular disorder caused by mutation in FLVCR2 in humans. The disease occurs during a critical period of brain vascular development, is characterized by glomeruloid vasculopathy and hydrocephalus, and is almost invariably prenatally fatal. Here, we sought to gain insights into the process of brain vascularization and the pathogenesis of Fowler Syndrome by inactivating Flvcr2 in mice. We show that Flvcr2 is necessary for angiogenic sprouting in the brain, but surprisingly dispensable for maintaining the blood brain barrier. Endothelial cells lacking Flvcr2 have altered expression of angiogenic factors, fail to adopt tip-cell properties and display reduced sprouting leading to vascular malformations similar to those seen in humans with Fowler Syndrome. Brain hypo-vascularization is associated with hypoxia and tissue infarction, ultimately causing hydrocephalus and death of mutant animals. Strikingly, despite severe vascular anomalies and brain tissue infarction, the blood-brain barrier is maintained in Flvcr2 mutant mice. Our new Fowler syndrome models therefore define the pathobiology of this disease, and provide new insights into brain angiogenesis by showing uncoupling of vessel morphogenesis and blood-brain barrier formation.
Knowledge, attitude and preventive practices of sexually transmitted infections among unmarried youths in an urban community in Lagos State, Nigeria

Background Sexually transmitted infections (STIs) are of public health importance as over 1 million STIs are acquired daily worldwide. One-third of the new cases of curable STIs affect younger persons aged less than 25 years. Sexually transmitted infections can lead to severe complications beyond the immediate impact of infections as such. Aim This study assessed knowledge of, attitude towards and preventive practices of STI among young unmarried persons in Surulere local government area (LGA) of Lagos State, Nigeria. Setting The study was conducted among young unmarried persons in Surulere LGA, Lagos State, Nigeria, between June and November 2018. Methods A descriptive cross-sectional study was conducted among 450 young unmarried persons selected using a multistage sampling technique. An interviewer-administered questionnaire was used to obtain data. Analysis was carried out with Epi-Info 7.2.2. 2 software. Chi-square was used to test for associations. Level of significance was at p ≤ 0.05. Results The mean age was 19.9 + 2.5 years. Majority of the respondents (84.7%) had heard of STIs. About two-third (65.6%) had good knowledge, while majority (98.6%) had good attitude towards the prevention of STIs, but less than half (34.0%) had good preventive practices. Knowledge of STI was statistically significantly associated with age, level of education, attitude and preventive practices of the respondents. Conclusion Most of the respondents were aware and had good attitude towards prevention of STI, but gaps exist in knowledge and preventive practices. Hence, targeted education to improve the knowledge and preventive practices against STI among young unmarried persons is recommended.
Relationship between the Ionization Degree and the Inter-Polymeric Aggregation of the Poly(maleic acid-alt-octadecene) Salts Regarding Time

Alternating amphiphilic copolymers are macromolecular systems with a polarity duality in their structure, since they are generally formed by alternating segments corresponding to a potential electrolyte group and an alkyl (aliphatic or aromatic) group. These systems, depending on the ionization degree, as well as the time, may form different types of intra and interpolymeric aggregates in aqueous media. Therefore, this study, which in fact is the continuation of a previously reported work, is focused on establishing how the ionization degree of the sodium and potassium salts of the poly(maleic acid-alt-octadecene) affect zeta potential, pH, electrical conductivity, particle size, polydispersity index, and surface tension over time. The results showed that polymeric salts with a high ionization degree in aqueous media formed homogeneous systems with bimodal sizes and high zeta potential values, which tended to quickly become less negative, lowering the pH and slightly increasing the electrical conductivity; while systems with low ionization degree lead to the opposite, forming heterodispersed systems with several populations of particle sizes, high polydispersity, low zeta potential values, neutral and invariable pH values, and high electrical conductivity values. Consequently, these results suggest that the values of particle size, polydispersity index, zeta potential, pH, and electrical conductivity change regarding the polymeric ionization degree, as well as the time. Therefore, such variables should be considered and controlled when working with this kind of polymeric materials.
Oxidative Stress Modulation by Cameroonian Spice Extracts in HepG2 Cells: Involvement of Nrf2 and Improvement of Glucose Uptake

Oxidative stress plays a relevant role in the progression of chronic conditions, including cardiometabolic diseases. Several Cameroonian plants, including spices, are traditionally used as herbal medicines for the treatment of diseases where oxidative stress contributes to insulin resistance, like type 2 diabetes mellitus. This study evaluated the antioxidant capacity and the effects on oxidative-stress-induced impairment of glucose uptake of 11 Cameroonian spice extracts. H2O2-induced reactive oxygen species (ROS) production by human HepG2 cells was significantly reduced by 8/11 extracts. The most effective extracts, Xylopia parviflora, Echinops giganteus, and Dichrostachys glomerata, showed a concentration-dependent ROS-scavenging activity, which involved Nrf2 translocation into the nucleus. Xylopia parviflora, Tetrapleura tetraptera, Dichrostachys glomerata, Aframomum melegueta, and Aframomum citratum extracts showed the highest antioxidant capacity, according to oxygen radical absorbance capacity (ORAC) (2.52–88 μM Trolox Eq/g of extract), ferric-reducing antioxidant power (FRAP) (40.23–233.84 mg gallic acid Eq/g of extract), and total phenol (8.96–32.96% mg gallic acid Eq/g of extract) assays. In HepG2 cells, glucose uptake was stimulated by 4/11 extracts, similarly to insulin and metformin. H2O2-induced oxidative stress reduced glucose uptake, which was rescued by pretreatment with Xylopia aethiopica, Xylopia parviflora, Scorodophloeus zenkeri, Monodora myristica, and Dichrostachys glomerata extracts. The ROS-scavenging ability of the spice extracts may reside in some secondary metabolites observed by phytochemical profiling (reverse-phase high-performance liquid chromatography coupled to a diode array detector (HPLC-UV-DAD)). Further studies are needed to better clarify their biological activities and potential use to control oxidative stress and promote insulin sensitivity.
SARS‐CoV‐2 infection anxieties and general population restrictions delay diagnosis and treatment of acute haematological malignancies

Governments worldwide have responded to the SARS-CoV-2 pandemic by officially imposing or unofficially encouraging social distancing measures. These measures have had a positive impact on the spread of the virus, however the "stay at home" formula and the lack of specific scientific information about SARS-CoV-2 has understandably resulted in increased anxiety and fear. One unforeseen consequence has been an enhanced risk of underestimating the symptoms and clinical signs of others pathologies even more severe than the viral infection. In the last 35 days, we have observed 8 patients who delayed coming to our hospital emergency room despite unmistakable clinical symptoms and signs of acute haematological disease, putting themselves at risk of compromising their entire therapeutic plan. The similarities between viral symptoms and initial clinical signs of haematological pathologies and the anxiety of contracting SARS-CoV-2 infection were the main causes of this delay.
Postoperative Functional and Cosmetic Satisfaction among Subjects Undergoing Open Versus Endonasal Septorhinoplasty: Five Years’ Experience from an Open-label Study at a Tertiary Care Center in Oman

Objectives We sought to compare functional and cosmetic satisfaction among male and female patients undergoing open and closed septorhinoplasty within sub-groups of indications for the surgery at a tertiary care hospital in Oman. Methods We conducted a prospective study in the ear, nose, and throat surgery department at Sultan Qaboos University Hospital from 2010 to 2015. All patients aged above 17 years, without dysmorphic pathologies, and due to be operated through open or endonasal septorhinoplasty based on the appropriate indications (functional or cosmetic or functional and cosmetic), were included in the study. Results Out of 215 patients who underwent septorhinoplasty, 30 were lost to follow-up. One-hundred and eighty-five patients (124 males and 61 females) available for postoperative assessment had been allocated to septorhinoplasty by the endonasal approach (n = 89; 59 males and 30 females) or open approach (n = 96; 65 males and 31 females) based on their indications for surgery: functional (n = 98; 64 males and 34 females); cosmetic (n = 39; 23 males and 16 females); and both functional and cosmetic (n = 48; 37 males and 11 females). Sex-wise distribution across different age groups for the specific surgical technique based on indication for surgery did not show any significant differences within any of the respective sub-groups. Both sexes reported no significant difference in satisfaction per their scores on the functional satisfaction scale post open or endonasal intervention. However, in their cosmetic satisfaction scale scores, a significantly higher proportion of males within the functional indication for surgery subgroup (90.9%) expressed satisfaction with the open surgical approach than the 71.0% males operated by the endonasal approach (p = 0.041). Conclusions Males undergoing septorhinoplasty for functional indications expressed significant satisfaction with the open surgical approach compared with the endonasal approach on the cosmetic satisfaction scale. This study could accrue only 185 patients during the five-year study period and hence was unable to generate any significant evidence to prove any differences in postoperative functional and cosmetic satisfaction outcomes within sub-groups based on other indications for surgery for males and females separately.
Pparg may Promote Chemosensitivity of Hypopharyngeal Squamous Cell Carcinoma

The upregulation of peroxisome proliferator-activated receptor gamma (PPARG) has been shown to increase the chemosensitivity of several human cancers. This study is aimed at studying if PPARG sensitizes hypopharyngeal squamous cell carcinoma (HSCC) in chemotherapeutic treatments and at dissecting possible mechanisms of observed effects. We integrated large-scale literature data and HSCC gene expression data to identify regulatory pathways that link PPARG and chemosensitivity in HSCC. Expression levels of molecules within the PPARG regulatory pathways were compared in 21 patients that underwent chemotherapy for primary HSCC, including 12 chemotherapy-sensitive patients (CSP) and 9 chemotherapy-nonsensitive patients (CNSP). In the CPS group, expression levels of PPARG were higher than that in the CNSP group (log‐fold‐change = 0.50). Structured text mining identified two chemosensitivity-related regulatory pathways driven by PPARG. In the CSP group, expression levels for 7 chemosensitivity-promoting genes were increased, while for 13 chemosensitivity suppressing the gene expression levels were decreased. Our results support the chemosensitivity-promoting role of PPARG in HSCC tumor cells, most likely by affecting both cell proliferation and cell motility pathways.
Effect of treading by dairy cattle on topsoil physical conditions for six contrasting soil types in Waikato and Northland, New Zealand, with implications for monitoring

Abstract A study of the physical condition of soils under dairying in the Waikato and Northland regions was undertaken to determine the physical condition of the soil, possible changes from pugging damage, and the most appropriate measurements and sampling regimes for monitoring change. Sites were selected on widespread soil types (Allophanic and Gley Soils in the Waikato; Allophanic, Ultic, and Podzol Soils in Northland) and corresponded to never trodden, usual usage or conditions, and previously pugged (>18 months ago) pasture. Soil cores were collected at 50‐mm depth increments for determination of bulk density, total porosity, saturated and unsaturated hydraulic conductivity, proportion of pores greater than 30 and 60 μm, and aggregate size class. The 0–100‐mm depth was best for showing differences between treading regimes. Within this depth, hydraulic conductivity and aggregate size showed the greatest differences between regimes. All measurements were useful for showing differences in the Waikato data. However, for Northland, bulk density, total porosity, and proportion of pores were not always indicators of change. Approximately 20 cores were needed per regime to show differences. Soil properties on most soil types were still affected 18 months after a pugging event. Measurements selected for showing change varied depending on whether data were for geographic regions, a single region, or a particular soil type.
2020 International Society of Hypertension Global Hypertension Practice Guidelines.

Document reviewers: Hind Beheiry (Sudan), Irina Chazova (Russia), Albertino Damasceno (Mozambique), Anna Dominiczak (UK), Anastase Dzudie (Cameroon), Stephen Harrap (Australia), Hiroshi Itoh (Japan), Tazeen Jafar (Singapore), Marc Jaffe (USA), Patricio Jaramillo-Lopez (Colombia), Kazuomi Kario (Japan), Giuseppe Mancia (Italy), Ana Mocumbi (Mozambique), Sanjeevi N.Narasingan (India), Elijah Ogola (Kenya), Srinath Reddy (India), Ernesto Schiffrin (Canada), Ann Soenarta (Indonesia), Rhian Touyz (UK), Yudah Turana (Indonesia), Michael Weber (USA), Paul Whelton (USA), Xin Hua Zhang, (Australia), Yuqing Zhang (China).
Symptomatic Internal Carotid Agenesis in Children

Carotid artery agenesis is a rare congenital anomaly, and there are controversies in the leading cause for it. We present a 6-year-old girl with resolved focal neurological ischemic stroke that showed bilateral internal carotid artery (ICA) agenesis. Through this paper, we highlight the carotid canal congenital obliteration hypothesis as it may be a risk for such finding.
Regeneration of the urodele forelimb after reversal of its proximo‐distal axis

Much of the rcsearch which over the years has dealt with the phenomenon of limb regeneration in urodeles has been concerned with the mechanics of the establishment of the regeneration blastema and the manner in which it undergoes morpliogenesis in giving rise to a new limb. Amputation of a urodele limb ordinarily serves as the primary stimulus for initiating the mobilization of cells to form a blastema. As the blastema develops it acquires moi-phogenetic potencies and gradually, through an integrated succession of clevelopmental events, is transformed into the definitive structures of the new limb. Although the regencration blastema usually is established at the level of amputation, under certain esperimental conditions a blastema can arise long after amputation and at a level far proximal to the point of amputation. Such a situation prevails, for example, when a limb is rendered nerveless at the time it is amputated. On a nerveless limb no blastema is ever established and consequently no regeneration takes place ; rather, the limb undergoes regression, -tt.hich may be so extensive as to result in the loss of a considerable portion of the limb proximal to the amputation. If reinnervation of such a regressed limb takes place, then a regmeration blastema will be established at the level at which the tips of the outgrowing nerve fibers reach thc area of regression. Such