Higher rates of liana regeneration after canopy fall drives species abundance patterns in central Amazonia

In tropical rainforest, most vascular plants have some capacity to resprout, and lianas are often effective resprouters after canopy fall. However, the diversity of resprouting responses of liana species and the consequence for plant persistence are poorly understood. We hypothesized that variation in regeneration among liana species causes differences in liana species abundance in tropical rainforest through differential resprouting capacity, such that liana species with higher densities produce more resprouts after canopy falls.We applied a manipulative field experiment investigating the effect of different levels of disturbance on the production of resprouts and adventitious roots in 10 liana species of the tribe Bignonieae (Bignoniaceae) with contrasting abundances in central Amazonia. We selected 15 individuals of each species and assigned the lianas to three distinct conditions: (a) total canopy fall with lianas severely damaged and detached from trees; (b) partial fall of lianas, without visible damage; and (c) intact lianas (control). We tested whether liana species regeneration patterns were related to species density. Liana species density was calculated using previous research on liana species distribution in 30 1‐ha plots systematically distributed in a 6 × 6 km2 grid at the Ducke Reserve.The number of aerial resprouts produced by lianas under the total canopy fall treatment was twice that of plants under lower levels of disturbance, while the production of adventitious roots did not differ among treatments. Liana species showed different intensities of resprouting, and species with higher average densities on the forest landscape had more resprouts after the total canopy fall treatment.Synthesis. Our results shed new light on the factors that influence liana species abundance, highlighting the role of resprouting after canopy fall and its variation among liana species. Resprouting mitigates the negative effects of canopy damage, suggesting that the impact of increased tree fall disturbances over time, which has been attributed to Amazonian forests in the literature, may increase already abundant liana species with effective resprouting capacity. We identify liana species that are more resilient to disturbance and may alter forest dynamics during climatic change.Our results shed new light on the factors that influence liana species abundance, highlighting the role of resprouting after canopy fall and its variation among liana species. Resprouting mitigates the negative effects of canopy damage, suggesting that the impact of increased tree fall disturbances over time, which has been attributed to Amazonian forests in the literature, may increase already abundant liana species with effective resprouting capacity. We identify liana species that are more resilient to disturbance and may alter forest dynamics during climatic change.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155931/1/jec13345_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155931/2/jec13345.pd

Deciphering the interaction of lactoferrin with V-ATPase towardsa deeper understanding of its mechanisms of action

Lactoferrin (Lf), a bioactive milk protein, exhibits strong anticancer and antifungal activities. The search for Lf targets and mechanisms of action is of utmost importance to enhance its effective applications. A common feature among Lf-treated cancer and fungal cells is the inhibition of a proton pump called V-ATPase. Lf-driven V-ATPase inhibition leads to cytosolic acidification, ultimately causing cell death of cancer and fungal cells. Given that a detailed elucidation of how Lf and V-ATPase interact is still missing, in this work we aimed to fill this gap by employing a multilevel computational approach. Molecular dynamics (MD) simulations of both proteins were performed to obtain a robust sampling of their conformational landscape, followed by clustering and protein-protein docking. Subsequently, MD simulations of the docked complexes and free binding energy calculations were carried out to evaluate the dynamic binding process and build the final ranking. This computational pipeline allowed the unraveling of the putative mechanism by which Lf inhibits V-ATPase and the identification of key binding residues that will certainly aid in the rational design of follow-up experimental studies, bridging in this way computational and experimental biochemistry.info:eu-repo/semantics/publishedVersio

Effect of zeolite nanomaterials in methanogenic communities

Recently, the application of zeolite structures in methanogenic communities has attracted significant attention, since they may enhance the anaerobic digestion process, by affecting specifically the methanogenic activity of the sludges1. Zeolites are solid inorganic crystalline materials comprised of silicon, aluminum and oxygen in the three-dimensional structure. The building blocks become arranged in a periodic way to form channels and cages on a nano- and subnanometer scale of strictly regular dimensions, named micropores. The presence of the aluminum in the zeolite framework create a negative charge in the lattice, which can be balanced by the exchangeable cations, as sodium or metal ions.2 In this study, commercial zeolite structures (ZSM5, USY, NaX and NaY) with different particle sizes and different exchangeable cations (Co, Cu, Zn, Fe) were used in order to investigate their effect towards the specific methanogenic activity, both acetoclastic and hydrogenotrophic, of anaerobic sludge. In the acetoclastic methanogenic activity, NaY modified with Cobalt (CoY) decreased the activity in comparison with the control (without zeolite). The remaining zeolites (ZSM5, USY, NaX and NaY), even when modified with metal ions (Zn, Fe, Cu), seems to have no effect on this methanogenic pathway. On the other hand, the hydrogenotrophic methanogenesis was improved by the presence of NaY (109 %), which did not happen in the presence of ZSM5 and USY zeolites. Additionally, the effect of different zeolite concentration was accessed. Overall, the increase of zeolite concentration from 1 g/L to 5 g/L resulted in a higher inhibition towards the methanogenic activity. In addition, the application of these nanomaterials can be evaluated in pure cultures of methanogens, in order to understand and fine-tune the best zeolite nanomaterial concentration that may improve the specific methanogenic activity.We thank the Fundação para a Ciência e Tecnologia (FCT) for financial support through Centre of Chemistry (UID/QUI/00686/2013 and UID/QUI/0686/2016) and BioTecNorte (operation NORTE-01-0145-FEDER-000004), and through Centre of Biological -engineering (UIDB/04469/2020 unit). Cátia S. N. Braga holds a grant SFRH/BD/132003/2017 funded by FCT and European Union (EU), through the Portuguese State Budget and the European Social Fund under the scope of Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Embryonal rhabdomyosarcoma of the uterine cervix: a rare case report

Embryonal rhabdomyosarcoma of the female genital tract is a rare tumour. It tends to occur during childhood in the vagina and, rarely, it can arise in the uterine cervix, with a peak incidence in the second decade. We report a case of a 18-year-old female with an embryonal rhabdomyosarcoma (sarcoma botryoides) presenting himself as a cervical polyp. This tumour consisted of rhabdomyoblasts with miscellaneous differentiation surrounded by a loose, myxoid stroma. The patient was successfully treated with cervical conization and adjuvant chemotherapy. She is now disease-free at the 28th month follow-up. Awareness of this uncommon lesion in the cervix and its clinical implications is important to prevent misdiagnosis. Therapy has recently inclined to conservative and fertility-sparing treatment

The role of interleukin 17-mediated immune response in Chagas disease:High level is correlated with better left ventricular function

Interleukin 17A (IL-17A) has been associated with protective rather than pathogenic response in Chagas disease (ChD). However, it is not established whether or not IL-17A-mediated immune response is correlated with patient's left ventricular (LV) function in ChD. To address this question we have gathered cardiac functional parameters from ChD patients and analysed the possible relationship between their plasma IL-17A levels and LV function. Plasma IL-17A levels were measured by BD Cytometric Bead Array (CBA) in 240 patients with positive specific serology for Trypanosoma cruzi (T. cruzi) grouped as indeterminate (IND) and Chagas cardiomyopathy (CARD) forms. The levels of IL-17A in ChD patients were compared with 32 healthy individuals, mean age of 39 years, 50% male, that were also included as a control group (non-infected [NI]). The overall mean age of ChD patients was 46 years and 52% were male. The IND group included 95 asymptomatic patients, with ages ranging from 27 to 69 years (mean of 43 years), and 42.1% of them were male. The CARD group included 145 patients, which 58.6% were male, with ages ranging from 23 to 67 years (mean of 49). The IND group presented substantially higher levels of IL-17A, median of 26.16 (3.66-48.33) as compared to both the CARD group, median of 13.89 (3.87-34.54) (P <0.0001), and the NI group, median of 10.78 (6.23-22.26) (P <0.0001). The data analysis demonstrated that the IND group comprises a significantly greater proportion (P <0.001) of high IL-17A producers (52.6%, 50 of 95 subjects) than do the other groups. A significant direct correlation was verified between IL-17A levels and cardiac function expressed by LV ejection fraction (LVEF), LV diastolic diameter (LVDd), and body surface area (BSA)-indexed LVDd as well as ratio of the early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e') in both groups. We demonstrated that plasma IL-17A levels has an accurate sensitivity and specificity to predict heart failure in serology-positive patients and might be a useful parameter to distinguish patients with or without cardiac impairment. This study indicates a consistent relationship between high expression of IL-17A and better LV in human chronic ChD. Our data raise the possibility that IL-17A plays an important immunomodulatory role in the chronic phase of ChD and might be involved in protection against myocardial damage

Non-peptidic Cruzain Inhibitors with Trypanocidal Activity Discovered by Virtual Screening and in Vitro Assay

A multi-step cascade strategy using integrated ligand-and target-based virtual screening methods was developed to select a small number of compounds from the ZINC database to be evaluated for trypanocidal activity. Winnowing the database to 23 selected compounds, 12 non-covalent binding cruzain inhibitors with affinity values (K-i) in the low micromolar range (3-60 mu M) acting through a competitive inhibition mechanism were identified. This mechanism has been confirmed by determining the binding mode of the cruzain inhibitor Nequimed176 through X-ray crystallographic studies. Cruzain, a validated therapeutic target for new chemotherapy for Chagas disease, also shares high similarity with the mammalian homolog cathepsin L. Because increased activity of cathepsin L is related to invasive properties and has been linked to metastatic cancer cells, cruzain inhibitors from the same library were assayed against it. Affinity values were in a similar range (4-80 mu M), yielding poor selectivity towards cruzain but raising the possibility of investigating such inhibitors for their effect on cell proliferation. in order to select the most promising enzyme inhibitors retaining trypanocidal activity for structure-activity relationship (SAR) studies, the most potent cruzain inhibitors were assayed against T. cruzi-infected cells. Two compounds were found to have trypanocidal activity. Using compound Nequimed42 as precursor, an SAR was established in which the 2-acetamidothiophene-3-carboxamide group was identified as essential for enzyme and parasite inhibition activities. the IC50 value for compound Nequimed42 acting against the trypomastigote form of the Tulahuen lacZ strain was found to be 10.6 +/- 0.1 mu M, tenfold lower than that obtained for benznidazole, which was taken as positive control. in addition, by employing the strategy of molecular simplification, a smaller compound derived from Nequimed42 with a ligand efficiency (LE) of 0.33 kcal mol(-1) atom(-1) (compound Nequimed176) is highlighted as a novel non-peptidic, non-covalent cruzain inhibitor as a trypanocidal agent candidate for optimization.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Sao Carlos, Dept Quim, BR-13560 Sao Carlos, SP, BrazilUniv São Paulo, Inst Quim Sao Carlos, Grp Quim Med IQSC USP, Sao Carlos, SP, BrazilUniv Calif San Francisco, Dept Pathol, Ctr Discovery & Innovat Parasit Dis, San Francisco, CA 94140 USAUniv São Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, BR-14049 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, São Paulo, BrazilFAPESP: 2011/01893-3,CNPq: 301614/2010-5CAPES: 5985/11-0Web of Scienc

The cause of urinary symptoms among Human T Lymphotropic Virus Type I (HLTV-I) infected patients: a cross sectional study

BACKGROUND: HTLV-I infected patients often complain of urinary symptomatology. Epidemiological studies have suggested that these individuals have a higher prevalence and incidence of urinary tract infection (UTI) than seronegative controls. However, the diagnosis of UTI in these studies relied only on patient information and did not require confirmation by urine culture. The purpose of this study was to investigate the role of urinary tract infection (UTI) as the cause of urinary symptoms in HTLV-I infected patients. METHODS: In this cross sectional study we interviewed, and cultured urine from, 157 HTLV-I seropositive individuals followed regularly at a specialized clinic. All patients were evaluated by a neurologist and classified according to the Expanded Disability Status Scale (EDSS). Urodynamic studies were performed at the discretion of the treating physician. RESULTS: Sixty-four patients complained of at least one active urinary symptom but UTI was confirmed by a positive urine culture in only 12 of these patients (19%); the majority of symptomatic patients (81%) had negative urine cultures. To investigate the mechanism behind the urinary complaints in symptomatic individuals with negative urine cultures, we reviewed the results of urodynamic studies performed in 21 of these patients. Most of them (90.5%) had abnormal findings. The predominant abnormalities were detrusor sphincter hyperreflexia and dyssynergia, findings consistent with HTLV-I-induced neurogenic bladder. On a multivariate logistic regression, an abnormal EDSS score was the strongest predictor of urinary symptomatology (OR 9.87, 95% CI 3.465 to 28.116, P < 0.0001). CONCLUSION: Urinary symptomatology suggestive of UTI is highly prevalent among HTLV-I seropositive individuals but true UTI is responsible for the minority of cases. We posit that the main cause of urinary symptoms in this population is neurogenic bladder. Our data imply that HLTV-I infected patients with urinary symptomatology should not be empirically treated for UTI but rather undergo urine culture; if a UTI is excluded, further investigation with urodynamic studies should be considered

Índice elevado de CPOD em pacientes com doença inflamatória intestinal

The aim of this study was to appraise the presence of decayed, filled, missed teeth (DFMT) and the oral conditions about the oral mucosa in patients with inflammatory bowel disease (IBD) and compare them with healthy patients. Ninety nine patients with Crohn’s disease (CD), eighty with Ulcerative Colitis (UC) and seventy four control patients (C) were examinated. The intra-oral examination registered the DMFT index, the plaque index and the oral soft tissue lesions. The average age, in years, was 38,99 (± 12,90); 43,33 (± 13,21) and 40,28 (± 12,87) for CD, UC and C, respectively. A high prevalence of DMFT was showed in DC (p= 0.016) and UC ( < 0,0001) groups compared to C group. The mean percentage of plaque was smaller in CD group 44,04 (DP± 30,49) than in C group 54,10 (DP ±26,4), p= 0,017; but there weren´t differences at percentage of plaque between UC and C groups. In relation to the total oral lesions, there was significant difference in CD (p= 0.041) and UC (p= < 0.0001) towards C group, being pyostomatitis vegetans the significant difference lesion between the groups. It was concluded that when the inflammatory bowel disease (DC and UC) are considered separately, a high DMFT index is observed in relation to control group; and patients with intestinal involvement show more oral lesions than the control groups patients, thus when the lesions are observed separated, the pyostomatitis vegetans is the only one that shows significant prevalence in those groups.O objetivo deste estudo foi o de avaliar a presença de lesões cariosas, restauradas, elementos perdidos por cárie (CPOD) e a condição da mucosa oral em pacientes com Doença Inflamatória Intestinal e compará-los com pacientes saudáveis sistemicamente. Foram examinados 99 pacientes com Doença de Crohn (DC), 80 com Colite Ulcerativa (UC) e 74 controles (C). No exame clínico, foram registrados o índice CPOD, o índice de placa e a presença de lesões no tecido mole oral. A idade média, em anos, foi de 38,99 (DP± 12,90); 43,33 (DP ± 13,21) e 40,28 (DP ± 12,87) para os grupos DC, UC e C, respectivamente. Houve aumento significante na prevalência do índice de CPOD no grupo DC (p = 0,016) e UC ( < 0,0001), quando comparado ao C. A porcentagem de placa foi menor no grupo DC 44,04 (DP± 30,49) que no C 54,10 (DP ±26,4), p= 0,017, mas não houve diferença entre UC e C. Com relação ao número total de lesões orais, foi observada diferença significante entre os grupos DC (p= 0.041) e UC (p= < 0.0001) e o grupo C, sendo a pioestomatite a lesão significantemente diferente entre esses grupos. Assim, conclui-se que, quando as doenças inflamatórias intestinais (DC e UC) são avaliadas separadamente, elevado índice de CPOD foi observado em relação ao grupo de controle; e pacientes com comprometimento intestinal apresentam mais lesões bucais que os pacientes do grupo de controle, sendo que, quando as lesões são observadas separadamente, a pioestomatite vegetante é a única que se mostra significantemente prevalente naqueles grupos

RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness

Rank signaling enhances stemness in mouse and human mammary epithelial cells (MECs) and mediates mammary tumor initiation. Mammary tumors initiated by oncogenes or carcinogen exposure display high levels of Rank and Rank pathway inhibitors have emerged as a new strategy for breast cancer prevention and treatment. Here, we show that ectopic Rank expression in the mammary epithelia unexpectedly delays tumor onset and reduces tumor incidence in the oncogene-driven Neu and PyMT models. Mechanistically, we have found that ectopic expression of Rank or exposure to Rankl induces senescence, even in the absence of other oncogenic mutations. Rank leads to DNA damage and senescence through p16/p19. Moreover, RANK-induced senescence is essential for Rank-driven stemness, and although initially translates into delayed tumor growth, eventually promotes tumor progression and metastasis. We uncover a dual role for Rank in the mammary epithelia: Rank induces senescence and stemness, delaying tumor initiation but increasing tumor aggressiveness