Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.06.29.177154v1?rss=1

Authors: Suresh, V., Parida, D., Minz, A. P., Senapati, S.

Abstract:

Recently, the Syrian golden hamster (Mesocricetus auratus) has been demonstrated as a clinically relevant animal model for SARS-CoV-2 infection. However, lack of knowledge about the tissue-specific expression pattern of various proteins in these animals and the unavailability of reagents like antibodies against this species hampers optimal use of these models. The major objective of our current study was to analyze the tissue-specific expression pattern of angiotensin{square}converting enzyme 2 (ACE2), a proven functional receptor for SARS-CoV-2 in different organs of the hamster. We have adapted immunoblot analysis, immunohistochemistry, and immunofluorescence analysis techniques to evaluate the ACE2 expression pattern in different tissues of the Syrian golden hamster. We found that kidney, small intestine, esophagus, tongue, brain, and liver express ACE2. Epithelium of proximal tubules of kidney and surface epithelium of ileum expresses a very high amount of this protein. Surprisingly, analysis of stained tissue sections for ACE2 showed no detectable expression of ACE2 in the lung or tracheal epithelial cells. Similarly, all parts of the large intestine (caecum, colon, and rectum) were negative for ACE2 expression. Together, our findings corroborate some of the earlier reports related to ACE2 expression pattern in human tissues and also contradicts some others. We believe that the findings of this study will enable the appropriate use of the Syrian golden hamster to carryout SARS-CoV-2 related studies.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.06.27.175273v1?rss=1

Authors: mehboob, r., Gilani, S. A., Hassan, A., Tirmazi, A. H., Ahmad, F., Akram, J.

Abstract:

BackgroundMiscarriage is a common complication of early pregnancy, mostly occurring in first trimester. However, the etiological factors, prognostic and diagnostic biomarkers are not well known. Neurokinin-1 Receptor (NK-1R) is a receptor of tachykinin peptide, Substance P (SP) and has a role in various pathological conditions, cancers but its association with miscarriages and significance as a clinicopathological parameter is not studied. Accordingly, the present study aimed to clarify the localization and expression for NK-1R in human retained products of conception. Role of NK-1R is not known in miscarriages.

Materials and MethodsNK-1R expression was assessed in products of conception by immunohistochemistry. Protein expression was evaluated using the nuclear labelling index (%).

ResultsTen human products of conception tissues were studied by immunohistochemistry to demonstrate the localization of NK-1R. The expression of NK-1R protein was high in all the cases of POCs. NK-1R expression showed no notable differences among different cases of miscarriages irrespective of the mothers age and gestational age at which the event occurred.

ConclusionsExpression of NK-1R was similar in all the cases and it was intense. It shows that dysregulation of NK-1R along with its ligand Substance P might be involved in miscarriages. Our results provide fundamental data regarding this anti-NK-1R strategy. Thus, the present study recommends that SP/NK1R system might, therefore, be considered as an emerging and promising diagnostic and therapeutic strategy against miscarriages. Hence, we report for the first time, the expression and localization of NK-1R in products of conception. We suggest NK-1R antagonist in addition to the Immunoglobulins and Human chorionic gonadotropin, to diagnose and treat spontaneous miscarriages.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.06.27.175570v1?rss=1

Authors: Mehta, U., Diep, A., Nguyen, K., Le, B., Yuh, C., Frambach, C., Doan, J., Wei, A., Palma, A. M., Farid, M., Garg, S., Kedhar, S., Wade, M., Marshall, K. A., Jameson, K. A., Kenney, M. C., Browne, A. W.

Abstract:

PurposeThe cone contrast threshold (CCT) test quantified color vision changes in subjects of all ages and those undergoing cataract surgery.

MethodsTwenty-four healthy volunteers from two cohort studies performed CCT using best corrected visual acuity, filters, mydriasis, and pinhole correction. Retrospective cross-sectional study of patients seen in eye clinics evaluated the relationship between age and color vision, and age and lens status in 355 eyes. Lastly, 25 subjects performed CCT before and after cataract surgery.

ResultsCCT scores were most reliable in the non-mydriatic condition without pinhole correction. Progressively dense brown filters produced small but significant reductions in S-cone sensitivity. Linear regression analysis of phakic subjects showed a decline for all cone classes with age. Rate of decline was greater for S-cones (slope (95% CI) = -1.09 (-1.23, 0.94)) than M-cones (slope (95% CI) = -0.80 (-0.95, -0.66)) and L-cones (slope (95% CI) = -0.66 (-0.81, - 0.52)). CCT scores increased for S-cones but reduced for L- and M-cones in pseudophakic subjects compared to phakic patients. CCT scores after cataract surgery increased for S-cones, M-cones, and L-cones by 33.0 (p<0.001), 24.9 (p=0.001), and 22.0 (p=0.008).

ConclusionsCCT assessment allows for clinically practical quantitation of color and contrast vision improvement after cataract surgery and aging patients who note poor vision despite good visual acuity.

Translational RelevanceCCT testing, historically used in research, is now a clinically practical tool to evaluate age and cataract related changes in color and contrast vision and routinely quantify vision beyond black and white visual acuity testing.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.06.27.175083v1?rss=1

Authors: mehboob, r., Gilani, S. A., Hassan, a., Tanvir, I., Khan, R., Babar, M. E., Akram, J., Ahmad, F., Munoz, M., Shahi, s.

Abstract:

To evaluate the expression and Immunolocalization of Substance P (SP)/ Neurokinin-1 Receptor (NK-1R) in Breast Carcinoma (BC) patients and its association with routine proliferative markers (ER, PR, HER2/ neu and Ki-67).

MethodsA cross-sectional study was performed on 34 cases of BC. There were 23 cases of group A (Grade III), 8 of group B (Grade II) and only 3 cases of group C (Grade I). Age range comprised of patients from 20-80 years and the mean age of patients was 45.74 years. HE, ER, PR, HER2 and Ki-67 staining was performed as routine biomarkers. Samples were then processed for immunomarkers study of Substance P and NK-1R immunohistochemistry was performed for few cases.

Results14/23 cases (61%) of group A, 7/8 cases (88%) of group B and 2/3 (67%) cases of group C were SP positive. Overall, strong staining ([≥] 10% tumors cells), labeled as "3+", was observed in 9/14 (64.2%) cases of group A and 1/8 (12.5%) case of group B. Moderate staining labelled as "2+" (in [≥] 10% tumor cells) was observed in 3/14 (21.4%) cases of group A, 4/8 (50%) cases of group B. weak positive staining "1+" was observed in only 2/14 (14.28%) cases of group A, 2/8 (25%) cases of group B and all 2/2 (100%) cases of group C.

ConclusionsSP and NK-1R is overexpressed in breast carcinomas and there is significant association between grade of tumor and their overexpression. It may serve as a novel biomarker for grading of BC. We also suggest that NK-1R antagonists as a potential therapeutic strategy to inhibit and manage BC.

Key PointsO_LIImmunohistochemical expression of Substance P and Neurokinin 1 Receptor in breast carcinoma tissue was evaluated

C_LIO_LIIt was strongly expressed in grade III, with maximum intensity

C_LIO_LIIt may be investigated further for its role as prognostic and diagnostic marker

C_LIO_LITherapeutic potential of Neurokinin-1 Receptor antagonists must be explored

C_LI

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.06.27.175026v1?rss=1

Authors: mehboob, r., Hassan, a., Perveen, S., Gilani, S. A., Waseem, H., Ahmad, f. J., Akram, J.

Abstract:

I+ntroductionSubstance P (SP)/ Neurokinin-1 Receptor (NK-1R), induces inflammatory reactions in peripheral tissues but its regulatory effects in target tissues are dependent on receptor signaling. SP has a high affinity for the NK-1 receptor, to which it binds preferentially. SP/NK-1R complex plays a key role in the interaction in the onset of pain and inflammation.

ObjectiveThe aim of this study was to investigate the expression of NK-1R in Urotheilial carcinoma and its association with cancer progression.

MethodThe study included ten biopsy samples of Urinary bladder, obtained retrospectively from a tertiary care hospital of Lahore. An Immunohistochemical study was performed using monoclonal antibodies against NK-1R. The presence or absence of staining and the intensity of the immunoreactivity were noted, as well as the number and type of cells. Evaluation of the Immunohistochemical expression was determined by the semi-quantitative method and scored.

ResultNK-1 receptor was intensely expressed in patients with higher grade Urotheilial carcinoma. The cases clinically diagnosed as High Grade Urotheilial Carcinoma showed intense expression of NK-1R. However, the cases clinically diagnosed as low grade Urotheilial carcinoma showed very weak staining with NK-1R. However, the normal margins of the same tissue showed negative expression.

ConclusionsElevated expression of NK-1R was associated with advanced stage of urothelial carcinoma. It is the first study to our knowledge to report this association. It may serve as a good diagnostic as well as prognostic marker and therapeutic strategy.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.06.26.171033v1?rss=1

Authors: Moreau, G. B., Burgess, S. L., Sturek, J. M., Donlan, A. N., Petri, W. A., Mann, B. J.

Abstract:

Abstract/SummaryMurine models of SARS-CoV-2 infection are critical for elucidating the biological pathways underlying COVID-19 disease. Because human ACE2 is the receptor for SARS-CoV-2, mice expressing the human ACE2 gene have shown promise as a potential model for COVID-19. Five mice from the transgenic mouse strain K18-hACE2 were intranasally inoculated with SARS-CoV-2 Hong Kong/VM20001061/2020. Mice were followed twice daily for five days and scored for weight loss and clinical symptoms. Infected mice did not exhibit any signs of infection until day four, when weight loss, but no other obvious clinical symptoms were observed. By day five all infected mice had lost around 10% of their original body weight, but exhibited variable clinical symptoms. All infected mice showed high viral titers in the lungs as well as altered lung histology associated with proteinaceous debris in the alveolar space, interstitial inflammatory cell infiltration and alveolar septal thickening. Overall, these results show that symptomatic SARS-CoV-2 infection can be established in the K18-hACE2 transgenic background and should be a useful mouse model for COVID-19 disease.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.06.24.168302v1?rss=1

Authors: Ellouze, W., Mishra, V., Howard, R. J., Ling, K.-S., Zhang, W.

Abstract:

Cucumber green mottle mosaic virus (CGMMV) is a re-emerging threat to greenhouse cucumber and other Cucurbitaceae crop productions worldwide. This seed-borne virus can easily spread from a contaminated seed to seedlings and to adjacent plants through mechanical contact of the foliage of diseased and healthy plants causing extensive yield losses. Additionally, infection may not be limited to the current crop but may also affect subsequent crops due to the long-term persistence of the virus on contaminated crop residues, greenhouse hard surfaces and soil or soil-less greenhouse substrates. In the present work, three greenhouse trials were conducted to develop an integrated pest management strategy towards controlling CGMMV in commercial cucumber greenhouses, by implementing an effective sanitization program and using resistant and grafted cucumber varieties. Results of sanitization trial highlighted that pressure washing and cleansing with an alkaline foam cleanser has eliminated CGMMV on some of the most heavily infested areas. However, three successive applications of cleanser and disinfectants were essential to completely eliminate CGMMV on porous and uneven surfaces, such as cement alleyway, tray gutter and floor mats. The varietal trial revealed that out of 15 cucumber varieties evaluated, two Mini ( Katrina and Khassib) and three Long English ( Sepire, Bomber and LC13900) had reduced or delayed CGMMV infection spread in the greenhouse but were intermediate in yield. The varieties Sunniwell and Bonbon were the most tolerant to CGMMV. They showed a high CGMMV infection level without compromising yield. These results proved the need for new productive cucumber varieties with CGMMV resistance. Grafting experiment showed only yield increase in case of grafted Picowell over Bonbon and not marked CGMMV resistance, which is a much desirable result when the grafting experiments are evaluated for their economic potential. In all, the current experimental trials unfold unique methodologies on CGMMV management in commercial greenhouses that are recommended to the growers to be followed for reducing crop losses and get benefitted on revenue compromise.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.06.23.166421v1?rss=1

Authors: Regazzoni, F., Vergara, C., Dede', L., Zunino, P., Guglielmo, M., Scrofani, R., Fusini, L., Cogliati, C., Pontone, G., Quarteroni, A.

Abstract:

BackgroundThe effect of COVID-19 on the cardiac function and on the vascular system increases the morbidity and mortality of infected subjects with cardiovascular diseases.

ObjectivesTo provide preliminary results on cardiac global outcomes (such as cardiac output, ventricular pressures) obtained by means of computational models in plausible scenarios characterized by COVID-19.

MethodsWe considered a lumped parameters computational model of the cardiovascular system, which models, from the mechanical point of view, the systemic and pulmonary circulations, the four cardiac valves and the four heart chambers, through mathematical equations of the underlying physical processes. To study the effect of COVID-19, we varied the heart rate, the contractility and the pulmonary resistances in suitable ranges.

ResultsOur computations on individuals with both otherwise normal and impaired cardiac functions revealed that COVID-19 worsen cardiac function, as shown by a decrease of some cardiac biomarkers values such as cardiac output and ejection fraction. In the case of existing impaired cardiac function, the presence of COVID-19 lead to values outside the normal ranges.

ConclusionsComputational models revealed to be an effective tool to study the effect of COVID-19 on the cardiovascular system. Such effect could be significant for patients with impaired cardiac function. This is especially useful to perform a sensitivity analysis of the hemodynamics for different conditions.

CONDENSED ABSTRACTEmerging studies address how COVID-19 infection might impact the cardiovascular system. This relates particularly to the development of myocardial injury, acute coronary syndrome, myocarditis, arrhythmia, and heart failure. Prospective treatment approach is advised for these patients. By the assessment of conventional important biomarkers obtained with new sources as a 0-dimentional computational model, we propose a new study protocol as an effective method to evaluate short-term prognosis. The clinical protocol proposed will help to rapidly identify which patients require intensive monitoring, diagnostic strategy and most adequate therapy.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.06.22.164921v1?rss=1

Authors: Yue, X., Huang, L., Ma, Y., Chen, L., Chang, J., Zhong, M., Wang, Z., Sun, Y., Chen, X., Sun, F., Xiao, L., Chen, J., Lai, Y., Yan, C., Yu, Y.

Abstract:

Preeclampsia (PE) is a life-threatening hypertensive disorder in pregnancy. Mitochondrial-mediated oxidative stress has been implicated in the etiology of PE with unknown underlying mechanism. We identified the downregulation of Rnd3 in the placental tissues and the primary trophoblasts from PE patients, associated with increased ROS generation and damaged mitochondrial integrity. Knockdown of Rnd3 in trophoblastic cells resulted in mitochondrial injury with membrane potential depolarization and proton leakage. Mechanistic studies indicated that Rnd3 stimulated the mitochondrial uncoupling protein 2 (UCP2) signaling, via its physical interaction with peroxisome proliferators-activated receptor {gamma} (PPAR{gamma}). Rnd3 deficiency-mediated mitochondrial dysfunction was attenuated by overexpression of PPAR{gamma}. Finally, Rnd3 overexpression in human PE primary trophoblasts partially rescued the mitochondrial defect and oxidative stress. We conclude that Rnd3 acts as a novel protective factor in placental mitochondria through PPAR{gamma}-UCP2 signaling. Downregulation of Rnd3 in PE patients may explain the mitochondrial stress involved in the pathogenesis of PE.

Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.06.18.156869v1?rss=1

Authors: Getahun, M. N., Villinger, J., Bargul, J. L., Orone, A., Ngiela, J., Ahuya, P. O., Muema, J. M., Saini, R. K., Torto, B., Masiga, D. K.

Abstract:

BackgroundAfrican animal trypanosomosis is becoming prevalent beyond its traditionally defined geographical boundaries and is a threat to animals beyond the tsetse belts in and outside Africa. However, knowledge of infections with clinically important trypanosome species and their diversity among field-collected hematophagous biting flies and domestic animals is limited mainly to tsetse and their mammalian hosts in tsetse-infested areas. This study aimed to examine the presence of trypanosomes in both biting flies and domestic animals outside the tsetse belt in northern Kenya, potential mechanical vector species, and their host-feeding profiles.

MethodsWe screened for pathogenic African trypanosomes in blood samples from domestic animals and field-trapped flies by microscopy and sequencing of internal transcribed spacer (ITS1) gene PCR products. We sequenced kinetoplast maxicircle genes to confirm Trypanosoma brucei detection and the RoTat 1.2 and kinetoplast minicircle genes to differentiate type-A and type-B Trypanosoma evansi, respectively. Further, we identified the hosts that field-trapped flies fed on by PCR-HRM and sequencing of 16S rRNA genes.

ResultsHippobosca camelina, Stomoxys calcitrans, Tabanus spp., and Pangonia rueppellii are potential vectors of trypanosomes outside the tsetse belt in Marsabit County, northern Kenya. We identified Trypanosoma spp., including Trypanosoma vivax, T. evansi, T. brucei, and T. congolense in these biting flies as well as in camels (Camelus dromedarius). Trypanosomes detected varied from single up to three trypanosome species in H. camelina and camels in areas where no tsetse flies were trapped. Similar trypanosomes were detected in Glossina pallidipes collected from a tsetse-infested area in Shimba Hills, coastal Kenya, showing the wide geographic distribution of trypanosomes. Furthermore, we show that these biting flies acquired blood meals from camels, cattle, goats, and sheep. Phylogenetic analysis revealed diverse Trypanosoma spp. associated with variations in virulence and epidemiology in camels, which suggests that camel trypanosomosis may be due to mixed trypanosome infections rather than only surra (T. evansi), as previously thought.

Copy rights belong to original authors. Visit the link for more info