Monday, March 4, 2019

Determinants Of Back Squat Strength

By Passat25 (talk) - Own work (Original text: I (Passat25 (talk)) created this work entirely by myself.), Public Domain, https://commons.wikimedia.org/w/index.php?curid=58010663

Not surprisingly, physical rather than psychological variables are greater determinants of barbell back squat strength.  Abstract:

Previous investigations of strength have only focused on biomechanical or psychological determinants, while ignoring the potential interplay and relative contributions of these variables. The purpose of this study was to investigate the relative contributions of biomechanical, anthropometric, and psychological variables to the prediction of maximum parallel barbell back squat strength. Twenty-one college-aged participants (male = 14; female = 7; age = 23 ± 3 years) reported to the laboratory for two visits. The first visit consisted of anthropometric, psychometric, and parallel barbell back squat one-repetition maximum (1RM) testing. On the second visit, participants performed isometric dynamometry testing for the knee, hip, and spinal extensors in a sticking point position-specific manner. Multiple linear regression and correlations were used to investigate the combined and individual relationships between biomechanical, anthropometric, and psychological variables and squat 1RM. Multiple regression revealed only one statistically predictive determinant: fat free mass normalized to height (standardized estimate ± SE = 0.6 ± 0.3; t(16) = 2.28; p = 0.037). Correlation coefficients for individual variables and squat 1RM ranged from r = -0.79-0.83, with biomechanical, anthropometric, experiential, and sex predictors showing the strongest relationships, and psychological variables displaying the weakest relationships. These data suggest that back squat strength in a heterogeneous population is multifactorial and more related to physical rather than psychological variables.

Saturday, March 2, 2019

Bread and pizza every weekend




I love pizza and warm, crusty bread. But we have no bakery close by that caters to healthy food choices. Also, no bakery would customize my pizza toppings the way I want them.

Therefore, for the past two months I have been making my own bread and pizza every weekend. I went through several recipe variations from online sources and simplified until I settled on a short and cheap routine. I do not even have a Dutch oven, which seems to be a prerequisite for all recipes on Internet! I use two cookie sheets instead.

The recipe is for one thin pizza that may or may not feed three people and two small loaves of bread. If you would like to feed more people, scale accordingly or bake bread more frequently. 


I have time to cook only on weekends. Therefore, I prepare the dough on Friday evening, let it rise overnight and bake on Saturday. When I retire, I can bake twice a week. Why? Because the bread and pizza baked at home are superior to any products from the supermarket. They are also cheaper, especially if you buy the ingredients on sale.






As you can see on the picture above, even the "healthy" 100% whole wheat bread is prepared with sugar and honey, plus a ton of "preservatives". 

So, roll up the sleeves and open your own personal bakery. Happy baking!


Ingredients for the dough
6 cups of flour (I use any ratio of white to wheat flour, depending on what I have)*
3 cups warm water
1 packet yeast
1 tsp salt
2-3 Tbsp olive oil



*I recently switched to a different brand of flour and it seems that a ratio of 6.5-7 cups of flour to 3 cups of water is better for some flour brands.  You will establish if you need more flour if the dough cannot be handled at all due to its moisture. To resolve the problem, simply add another 0.5-1 cup of flour.


For the pizza topping
crushed tomatoes (a can of 28 oz)
any seasonings you like; I use lots of hot red pepper flakes, crushed garlic, salt 

any cheese(s) you like, in any quantity

Directions for the dough prep
In a huge bowl, mix the flours and salt. Make a well in the middle and in it, mix the yeast and water. After dissolving the yeast in the water, incorporate all ingredients with your hands. It takes only 2 to 3 minutes. The dough is messy and sticky, and this is normal! Pour some olive oil around the dough ball, roll the ball in the oil and smear the oil on the walls of the bowl. Cover with Saran wrap. I use two pieces of the wrap since the dough size triples overnight. On top, I add a kitchen towel.




The bowl goes on top of the refrigerator and stays there overnight. On the next day, two hours before the pizza is to be served, divide the dough into three equal size balls. Spray two cookie sheets with PAM (this is very important). On one of the cookie sheets, shape one of the balls into a thin layer and spread olive oil on top (the oil will help you press down the dough into a thin layer). The layer should occupy the entire cookie sheet.  On the second cookie sheet, shape the two remaining balls into two rolls to form two loaves of bread. Cover the loaves with Saran wrap again and leave on the kitchen counter for another 30 - 40 minutes. To bake, preheat the oven to 400°F.

Pizza sauce prep
Warm up the crushed tomatoes in a pot, add crushed garlic and spices to taste. Let it simmer for maximum of five minutes under a cover. I use a can of 28 oz tomatoes for two pizzas; one half of the amount is used one week, and the second half is frozen in a jar for the next week’s pizza. 


Baking directions
Before baking the pizza, spread the tomato sauce and arrange the cheese on top of the dough.   Cut diagonal slits on the loaves with a sharp knife (see picture below).





Bake the bread and pizza together. I have two shelves in the oven. On the top shelve, I bake the two loaves, on the middle shelf (under the bread) I bake the pizza. The pizza is done in 15-20 minutes. The loaves take longer (approximately 25-30 minutes). One can leave the loaves in the oven after turning off the heat for another 10 minutes (this allows for a better crust to form).

Friday, March 1, 2019

An Anti-Cancer Antibiotic

An antibiotic, Nigericin, has anti-cancer activity, and one mechanism is through targeted suppression of Wnt signaling.  Abstract:

Nigericin, an antibiotic derived from Streptomyces hygroscopicus that works by acting as an H+, K+ and Pb2+ ionophore, has exhibited promising anticancer activity. The main purpose of this study is to investigate its inhibitory effects on Wnt/β-catenin signaling pathway in colorectal cancer (CRC) cells and clarify the underlying mechanism. We exposed two CRC lines (SW620 and KM12) to increasing concentrations of nigericin for different time periods and the 50% inhibiting concentration (IC50) values were evaluated. Our data showed that nigericin treatment significantly reduced tumor cell proliferation in dose- and time-dependent manners in CRC cells. The subsequent experiments in vitro and in vivo implied that nigericin could significantly suppress the tumor growth, migration and invasion, and induce the apoptosis of CRC cells. Our results of western blot and immunofluorescence assay showed that nigericin could suppress the Wnt/β-catenin signaling pathway in CRC cells with dose-dependent increased expressions of downstream effectors and target proteins. To further elucidate the inhibitory effects of nigericin via a β-catenin-dependent signaling mechanism, we established the stably β-catenin over-expression CRC cells. Western blot, SuperTOPflash luciferase reporter and immunoprecipitation assays all confirmed β-catenin as a critical intermediary and player in Wnt/β-catenin pathway, and nigericin exerted anti-cancer effects on CRC cells by directly targeting the β-catenin destruction complex. These results suggested that Wnt/β-catenin signaling might have an essential role in CRC progression. Nigericin targeting Wnt/β-catenin signaling might provide new insight into the molecular mechanism of nigericin towards cancer cells, and suggest possible clinical application in CRC

Tuesday, February 26, 2019

Clock And Cycle: Wnt Signaling

The circadian clock controls daily life activities; the cell cycle is what allows cells to proliferate.  The two are linked via cell signaling, and in the intestines Wnt signaling is, unsurprisingly, important.  This has applications for modulation of the cell cycle for therapeutics.  Abstract:

Like two dancers, the circadian clock and cell cycle are biological oscillators engaged in bidirectional communication, resulting in circadian clock-gated cell division cycles in species ranging from cyanobacteria to mammals. The identified mechanisms for this phenomenon have expanded beyond intracellular molecular coupling components to include intercellular connections. However, detailed molecular mechanisms, dynamics, and physiological functions of the circadian clock and cell cycle as coupled oscillators remain largely unknown. In this review, we discuss current understanding of this connection in light of recent findings that have uncovered intercellular coupling between the circadian clock in Paneth cells and the cell cycle in intestinal stem cells via WNT signaling. This extends the impact of circadian rhythms regulating the timing of cell divisions beyond the intracellular domain of homogenous cell populations into dynamic, multicellular systems. In-depth understanding of the molecular links and dynamics of these two oscillators will identify potential targets and temporal regimens for effective chronotherapy.

Wnt Inhibitor And Small Cell Lung Cancer

A Wnt signaling inhibitor has some activity against small cell lung cancer.  Abstract:

Small cell lung cancer (SCLC) is the most aggressive type of lung cancer due to a fast tumor doubling time and early hematogenous spread. Advances in the treatment of non-small cell lung cancer using targeted therapies having been made, but no targeted drugs for SCLC have been approved. The Wnt signaling pathway is associated with tumor progression and metastasis; therefore, the inhibition of Wnt/β-catenin signaling is a strategy for anticancer drugs. Tankyrase 1 (TNKS1) is overexpressed in a number of types of cancer and XAV939 is a small molecule inhibitor of TNKS1 which may inhibit tumor growth. The present study aimed to investigate the potential molecular mechanisms underlying XAV939-induced suppression of the viability of SCLC cells. MTT assays were used to determine the viability-inhibition rate of cells and to identify the drug concentration which optimally inhibited cell viability. Flow cytometry was used to determine whether XAV939 induced apoptosis of SCLC cells, and to analyze the effect of the drug on the cell cycle. The results of the present study identified that XAV939 inhibited the viability of NCI-H446 cells in a dose-dependent manner, but cisplatin inhibited NCI-H446 cell viability in a time- and dose-dependent manner. The combination of XAV939 and cisplatin exhibited a slightly more pronounced inhibition of cell viability at an increased dose of XAV939. In addition, XAV939 markedly induced cell apoptosis of the SCLC cell line H446 by increasing the proportion of cells in the G0/G1 phase, leading to inhibition of the cell cycle. The results of the present study indicated that XAV939 inhibited the viability of the NCI-H446 SCLC cell line by inducing cell apoptosis through the Wnt signaling pathway. Therefore, XAV939 may be useful for the treatment of SCLC.

Saturday, February 23, 2019

Mushroom soup




Hello, everyone!

Today's weekend cooking ended up being an easy mushroom soup. Why? Because I had made a salad of beans and corn that no one was eating and the mushrooms in the supermarket were on sale.

 

Mushroom soup

Ingredients:
1 sweet red pepper, cut into small cubes
1 15-oz can of corn (buy the one without added sugar)
1 15-oz black beans
1 medium size sweet onion, cut into small cubes
20-30 oz any mushrooms, washed and cut into small cubes
salt, turmeric, black pepper, cayenne pepper to taste
2 Tbsp olive oil
1-2 Tbsp wheat flour


Directions:
In a pan, heat 2 Tbsp of olive oil and add the mushrooms. Cover with a lid and let the mushrooms simmer in their own liquid. Stir from time to time; the mushrooms should be ready in about 10 minutes. In a soup pot, combined the pepper, onion, corn, beans and onion. Boil these in 4 cups of water. Once the onion is soft, add the flour and stir well. Add the mushrooms and more water to the desired density. Bring to boil and simmer for 10 minutes. Before turning off the heat, season with salt, turmeric, black pepper and cayenne pepper (optional).

Friday, February 22, 2019

Protein Glycosylation Targeting Immunotherapy

Another approach for anti-cancer immunotherapy, abstract:

Protein glycosylation provides proteomic diversity in regulating protein localization, stability, and activity; it remains largely unknown whether the sugar moiety contributes to immunosuppression. In the study of immune receptor glycosylation, we showed that EGF induces programmed death ligand 1 (PD-L1) and receptor programmed cell death protein 1 (PD-1) interaction, requiring β-1,3-N-acetylglucosaminyl transferase (B3GNT3) expression in triple-negative breast cancer. Downregulation of B3GNT3 enhances cytotoxic T cell-mediated anti-tumor immunity. A monoclonal antibody targeting glycosylated PD-L1 (gPD-L1) blocks PD-L1/PD-1 interaction and promotes PD-L1 internalization and degradation. In addition to immune reactivation, drug-conjugated gPD-L1 antibody induces a potent cell-killing effect as well as a bystander-killing effect on adjacent cancer cells lacking PD-L1 expression without any detectable toxicity. Our work suggests targeting protein glycosylation as a potential strategy to enhance immune checkpoint therapy.

Thursday, February 21, 2019

Minoclonal Antibodies Against Clostridium Difficile

While probiotics may be a good choice for Clostridium difficile prevention, antibiotics may be required for infection.  Antibiotic resistance is becoming a problem.  Here is an interesting study on monoclonal antibody therapy for this difficult infection.  Abstract:

Background Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. Methods We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. Results In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, -10.1 percentage points; 95% confidence interval [CI], -15.9 to -4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, -9.9 percentage points; 95% CI, -15.5 to -4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, -11.6 percentage points; 95% CI, -17.4 to -5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, -10.7 percentage points; 95% CI, -16.4 to -5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. Conclusions Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239 .).

Bezlotoxumab seems to be a promising therapeutic agent against this problem infection.

Wednesday, February 20, 2019

Modeling Chemical Communication

Metabolite-protein interactions can be used to model chemical communication in the body. Abstract:

Metabolite-protein interactions control a variety of cellular processes, thereby playing a major role in maintaining cellular homeostasis. Metabolites comprise the largest fraction of molecules in cells, but our knowledge of the metabolite-protein interactome lags behind our understanding of protein-protein or protein-DNA interactomes. Here, we present a chemoproteomic workflow for the systematic identification of metabolite-protein interactions directly in their native environment. The approach identified a network of known and novel interactions and binding sites in Escherichia coli, and we demonstrated the functional relevance of a number of newly identified interactions. Our data enabled identification of new enzyme-substrate relationships and cases of metabolite-induced remodeling of protein complexes. Our metabolite-protein interactome consists of 1,678 interactions and 7,345 putative binding sites. Our data reveal functional and structural principles of chemical communication, shed light on the prevalence and mechanisms of enzyme promiscuity, and enable extraction of quantitative parameters of metabolite binding on a proteome-wide scale.

Saturday, February 16, 2019

Zesty salad for everyday



Hello, everyone!

I have been experimenting with my work lunches and decided that I needed as much spice and flavor as possible (to counteract the dullness of the work environment :)).

I love spicy-hot, check out this hot-hot walnut recipe. Therefore, I concocted a new salad mix that pleases my taste buds. I hope it pleases yours as well!
 

All major ingredients come from a can; therefore, the salad can be made in any season.

The salad is also fiber-rich, with no added sugar!



Zesty everyday salad

Ingredients
15.5-oz can corn kernels (make sure sugar is not added)
15.5-oz can black beans
20 oz pineapple chinks (no added sugar)
1 small sweet onion
hot pepper flakes (to taste)
hot sauce (to taste)
salt (to taste)


Directions
Dice the onion into small cubes (as small as possible). "Massage" (squeeze) the diced onion with some salt until the onion starts releasing its juice and it is less pungent. Drain the pineapple from its juice and cut the chunks into smaller pieces. Drain the beans and corn kernels, and combine these with the squeezed onion and pineapple. Mix with as much hot sauce and hot red pepper flakes as you like. Serve!


I keep my salad in a glass jar in the refrigerator for up to five days.