Molecular Biology

Inherited thrombophilia has recently been identified as a major cause of thrombembolism, but it may also contribute to adverse pregnancy outcomes and recurrent pregnancy loss. Three gene mutations namely leiden (FV G1691A), prothrombin (FII G20210A), and methylenetetrahydrofolate reductase (MTHFR C677T) are the most common types of hereditary thrombophilias in women with RPL, which in turn can result in placentation. These are usually undiagnosed, because most carriers are asymptomatic. The aim of this study was to determine the association of specific inherited thrombophilias and recurrent pregnant loss (RPL) among Saudi women. The study included 142 females were 72 had a history of 2 or more events of fetal loss in any of the 3 trimesters of pregnancy. The remaining 70 were clinically healthy women with a good obstetric history and have designated as a control group. Detection of inherited thrombophilia genes mutations was confirmed using different PCR screening protocols. The frequencies of FV & FII mutations related to the pregnancy loss stages showed that FV mutation ratio was similar among cases with early or late stage pregnancy loss (25%-26%) but significantly higher than that of controls (1.4%). On the other hand FII mutation ratio was high among cases with late pregnancy loss (50%) followed by early pregnancy loss (38%) and was significant higher than that of controls (1.4%). MTHFR C677T mutation was more common in group of women with fetal loss in first trimester compared to the controls. We have reported that the combinations of two or more thrombophilic polymorphism risk factors were observed in 10.8% healthy Saudi women with unexplained RPL while no more than one risk factor was observed in any of the controls. We concluded that there is a strong association between the combined inherited thrombophilic mutations related to FV G1691A, FII G20210A, and MTHFR C677T genes among Saudi women. Our data confirm the hypothesis that inherited thrombophilia is indeed a significant abnormality in the RPL subjects.

Highlights d The spike protein of SARS-CoV-2 harbors a multibasic S1/ S2 site d The host cell protease furin cleaves the SARS-CoV-2 spike protein at the S1/S2 site d Cleavage at the S1/S2 site is essential for spike-driven viral entry into lung cells Correspondence mhoffmann@dpz.eu (M.H.), spoehlmann@dpz.eu (S.P.) In Brief Coronavirus spike proteins are activated by host cell proteases. Hoffmann and colleagues show that the pandemic SARS-CoV-2 harbors a highly cleavable S1/S2 cleavage site not found in closely related coronaviruses. Cleavage at this site is mediated by furin and is required for viral entry into human lung cells.

The diastereoselective intramolecular 1,3-dipolar cycloaddition reaction of unsaturated nitrones, derived from methyl alpha-D-glucopyranoside with 2-furaldehyde and 2-(benzyloxy)acetaldehyde has been studied In our pevious studies with 2-furaldehyde, the cycloaddition resulted 3 diastereoisomers in a 3:1:1 ratio. In this article, how the number of the possible isomers generated by 1,3-cycloaddition could be reduced from 4 to 1 when 2-(benzyloxy)acetaldehyde was employed as an aldehyde is shown.

A method was developed for the synthesis of oligonucleotide-cationic peptide conjugates in solution phase by disulfide bond formation. Precipitation was avoided by the easily removable triethylammonium trifluoroacetate (TEATFAc) salt which served at the same time as a buffer of the reaction mixture. The fast and high yielding disulfide bond formation was due to the Npys thio protecting and activating group of Cys. A solution of the free 5-thiol modified oligonucleotide obtained from Poly-Pak purification was used for conjugation.

All possible dimers of the title modified bases with native nucleobases [10 dimers from 3-methylated 6-aminouracils (3sau) and 20 from 5-methyled 6-aminouracils (5sau), respectively have been calculated by ab initio method (Hartree-Fock method, 3 21G basis set). We have found two potential duplexes of 5sau and three possible duplexes of 3sau. Altogether seven dimers containing one or two bifurcating H-bonds have been found. Later on, five triplexes from ten possible calculated dimers have been found. In two of them the amino group of 6-aminouracil moiety takes part in H-bonding and there are H-bonds, too, between the first and third base of the triplexes causing an extra stabilization.

Inhibitors of apoptotic proteins (IAPs) can play an important role in inhibiting apoptosis by exerting their negative action on caspases (apoptotic proteins). There are eight proteins in this family: NAIP/BIRC1/NLRB, cellular IAP1 (cIAP1)/human IAP2/BIRC2, cellular IAP2 (cIAP2)/human IAP1/BIRC3, X-linked IAP (XIAP)/BIRC4, survivin/BIRC5, baculoviral IAP repeat (BIR)-containing ubiquitin-conjugating enzyme/apollon/BIRC6, livin/melanoma-IAP (ML-IAP)/BIRC7/KIAP, and testis-specific IAP (Ts-IAP)/hILP-2/BIRC8. Deregulation of these inhibitors of apoptotic proteins (IAPs) may push cell toward cancer and neurodegenerative disorders. Inhibitors of apoptotic proteins (IAPs) may provide new target for anticancer therapy. Drugs may be developed that are inhibiting these IAPs to induce apoptosis in cancerous cells.

see expanded revised and updated version (above) dated May 6

https://www.academia.edu/42955978/CORONA_VIRUS_JUST_a_MATTER_of_TIME_The_Disease_is_US_and_not_the_Virus_-_CHLOROQUINE_TRUMP_Fake_News_and_Clinical_Trials_by_BRAZILIAN_BUFFOONs

The BRAZILIAN BUFFOONs” Pretend
to Conduct a TRIAL of HYDROXY-CHLOROQUINE

How fake News Can Kill Thousands and Fan the Flames of Holocaust Throughout a Society

Yet we all remain paralyzed silent and simply waiting for doom to strike....harder yet...

The Mantra of today is "there's nothing we can do"?

Bacteria can survive on the surface of the microscopic grooves and cracks and will go unnoticed, hence the presence
of pathogenic bacteria on the user interface of microphone possesses a potential risk to vulnerable, immune
compromised individuals. The aim of this study was to study the antibiotics patterns of bacteria isolated from
microphones used at different churches in Umuahia, Abia State, Nigeria. 100 samples were collected from the
mouthpiece and handles of the various microphones from 22 different churches in Umuahia with sterile swab sticks
moistened with normal saline. A total of 85 isolates comprising of eight (8) genera were characterized from the
samples. These organisms included Staphylococcus sp, Coagulase negative Staphyococcus (CoNS), Streptococcus
sp, Micrococcus sp, Bacillus sp, Proteus sp, Escherichia coli and Pseudomonas sp. Frequency distribution of the
isolates was as follows Staphylococcus sp. (5.88% of total), Coagulase negative Staphylococcus (CoNS) were
(11.76%), Streptococcus sp. (9.41%), Micrococcus sp. (1.18%), Bacillus sp. (3.53%), Proteus sp. (17.65%),
Escherichia coli (36.47%) and Pseudomonas sp. (14.12%). The sensitivity and resistance testing of the bacteria to
different antibiotics showed that all the isolates were 100% sensitive to Peflacine, Ciprofloxacin and Gentamicin.
The highest percentage resistance of 42.85% was recorded for Ampicillin while the least percentage resistant of
14.28% was recorded for Ofloxacin, Streptomycin and Cefalexin each. This study showed that microphones can aid
in the spread of pathogenic microorganisms between individuals and among groups at large.

Quorum sensing is a cell-cell communication mechanism that bacteria use to collectively regulate gene expression and, at a higher level, to coordinate group behavior. .

In bacteria, sRNAs post-transcriptionally regulate genes involved in responses to conditions such as limited iron, sugar–phosphate stress, cell surface stress, and oxidative stress 

This research proposes that, in  the bioluminescent marine bacterium Vibrio harveyi, the multiple sRNAs function to translate increasing AI concentrations into a precise gradient of LuxR protein. LuxR, in turn, induces a gradient of expression of quorum-sensing target genes

Sensory information from three independent quorum-sensing systems converges on the shared response regulator LuxO.  Surprisingly, unlike in V. cholerae where the sRNAs act redundantly, in V. harveyi, the Qrr sRNAs function additively to control quorum sensing. This latter mechanism produces a gradient of LuxR that, in turn, enables differential regulation of quorum-sensing target genes.


This behavior, seemingly sophisticated, for a single celled organism, is related to mitochondrion microRNAS from thousands of mitochondrial genomes in the same cell and in relation to the genomes in neighboring cells

Many bacterial sRNAs require Hfq, an RNA chaperone similar in sequence and structure to eukaryotic Sm proteins involved in RNA splicing  When LuxO is phosphorylated, it activates the expression of a putative repressor that destabilizes the mRNA encoding the master quorum-sensing transcriptional regulator LuxR.

In V. harveyi, each of the three AI signals is detected by a distinct membrane-bound autophosphorylating histidine sensor kinase protein.  All three sensors deliver phosphate to the histidine-containing phosphotransfer protein, LuxU, which in turn transfers the phosphoryl group to the conserved

Under conditions of low cell density (i.e., when AIs are at negligible concentrations), the three sensors act as kinases, and phosphate is transferred to LuxO. LuxO∼P, in conjunction with σ54, indirectly represses expression of the genes encoding luciferase (lux), so no light is produced under this condition

At high cell densities (i.e., when AIs are at detectable concentrations), the interactions of the sensors with their cognate AIs cause the sensors to switch from kinase mode to phosphatase mode, leading to dephosphorylation of LuxO  .
This sequence of events inactivates LuxO, leading to expression of the lux operon, and light is produced 

LuxO functions by indirectly regulating the expression of luxR. LuxR directly activates the lux operon and directly or indirectly controls all other known quorum-sensing target genes

They further propose that the multiple sRNAs serve as the focal point through which additional metabolic cues feed into the quorum-sensing circuit to regulate global gene expression.

Cashew is an important cash crop in India but the incidence of diseases incur considerable losses in cashew plantations leading to reduction both in terms of quality and quantity. The present investigation was to study the fungi associated with cashew plant in Odisha in view of the warm and humid climate. Isolation, identification, pathogenicity test and nutritional study of the test fungi as well as the control was undertaken in vitro. The result of the study revealed that seven species of fungi namely Pestalotiopsis palmarum, Phyllosticta sp., Colletotrichum gloeosporioides, Botryodiplodia theobromae, Fusarium oxysporum, Rhizoctonia solani and Chaetomium brassiliense were responsible for various diseases. Pestalotiopsis palmarum and Phyllosticta sp. were found to cause leaf spots; Colletotrichum gloeosporioides causing leaf spot, die back and gummosis of stem; Botryodiplodia theobromae causing inflorescence blight, die-back of twigs and stem gummosis; Fusarium oxysporum and Rhizoctonia solani causing seedling blight and root rot and Chaetomium brassiliense being responsible for causing storage rots in cashew nuts. Pathogenicity test revealed that all the test fungi were pathogenic to their respective host parts except stem gummosis. The results of the nutritional study on different solid media indicated that Malt Extract Agar medium supported the maximum mycelial growth of all the test fungi except Chaetomium brassiliense and Phyllosticta sp. In-vitro antifungal activity of some selected fungicides indicated that Bavistin could control all the pathogenic fungi by 100 %. Further studies can recommend suitable control measures for the farmers and commercial growers.

Although the aetiology of Behçet's disease is still poorly understood, viral infection has long been postulated as one of the factors. To investigate the relationship between herpes viruses and Behçet's disease, we used polymerase chain reaction to detect herpes simplex virus 1 (HSV-1) and 2 (HSV-2), and human herpes virus 6 (HHV-6) and 7 (HHV-7) DNA in samples of lesional tissues from patients with Behçet's disease and other related inflammatory disorders. Four cases were positive for HSV-1; 1 of 11 Behçet's disease cases, 2 of 3 Sweet's disease cases and 1 of 3 erythema nodosum cases. Two cases were positive for both HSV-1 and HSV-2; one Behçet's disease and one erythema nodosum. All cases were negative for HHV-6 and HHV-7. These findings indicate that there might be some relationship between Behçet's disease and the presence of HSV-1 and/or HSV-2 DNA and that HHV-6 and HHV-7 do not seem to be involved in the pathogenesis of Behçet's disease. However, HSV-1 and HSV-2 DNAs were also detected in non-Behçet's disease lesions, suggesting that HSV-1/2 is not correlated to the direct pathogenesis of Behçet's disease.

Crystallins, the highly abundant proteins of the ocular lens, are essential determinants of the transparency and refractivity required for lens function. Initially thought to be lens-specific and to have evolved as lens proteins, it is now clear that crystallins were recruited to the lens from proteins that existed before lenses evolved.

Crystallins are expressed outside of the lens and most have been shown to have cellular functions distinct from their roles as structural elements in the lens.

For one major crystallin group, the β/γ-crystallin superfamily, no such functions have yet been established. We have explored possible functions for the polypeptides (βA3-and βA1-crystallins) encoded by Cryba1, one of the 6 β-crystallin genes,

. βA3-and βA1-crystallins are expressed in astrocytes and retinal pigment epithelial (RPE) cells.

In both cell types, these proteins appear to be required for the proper acidification of the lysosomes. In RPE cells, elevated pH in the lysosomes is shown to impair the critical processes of phagocytosis and autophagy, leading to accumulation of undigested cargo in (auto) phagolysosomes.

We provide evidence that the cellular function of βA3/A1-crystallin involves its interaction with V-ATPase, the proton pump responsible for acidification of the endolysosomal system.

We postulate that this accumulation may cause pathological changes in the cells resembling some of those characteristic of age-related macular degeneration (AMD). Our studies also suggest an important regulatory function of βA3/A1-crystallin in astrocytes.

Focal adhesion kinase (FAK) is an essential nonreceptor tyrosine kinase regulating cell migration, adhesive signaling, and mechanosensing. Using FAK-null cells expressing FAK under an inducible promoter, we demonstrate that FAK regulates the time-dependent generation of adhesive forces. During the early stages of adhesion, FAK expression in FAK-null cells enhances integrin activation to promote integrin binding and, hence, the adhesion strengthening rate. Importantly, FAK expression regulated integrin activation, and talin was required for the FAK-dependent effects. A role for FAK in integrin activation was confirmed in human fibroblasts with knocked-down FAK expression. The FAK autophosphorylation Y397 site was required for the enhancements in adhesion strengthening and integrin-binding responses. This work demonstrates a novel role for FAK in integrin activation and the time-dependent generation of cell–ECM forces.