Our study shows that inflamed monocyte migration, through CCR2- and CX3CR1- dependent mechanisms, plays a critical role in kidney injury following ischemia reperfusion.”
“Oxidative stress and inflammation contribute to the pathogenesis of cisplatin-induced nephrotoxicity. We found that genistein, a tyrosine kinase inhibitor with broad specificities, and which also has estrogen-like activity, had protective effects on cisplatin-induced renal

injury in mice. Genistein significantly decreased reactive oxygen species production, the expression of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 proteins, as well as the translocation check details of the p65 subunit of nuclear factor-jB into the nucleus and the infiltration of macrophages, all of which were increased in the kidney by cisplatin treatment. Genistein also decreased cisplatininduced apoptosis by regulating p53 induction in kidney. Genistein significantly reduced reactive oxygen species production in cisplatin-treated

normal human kidney HK-2 cells. These studies show that genistein or similar compounds Torin 2 might be useful in prevention of cisplatin-induced renal injury.”
“The calcium-sensing receptor regulates various parathyroid gland functions, including hormone secretion, gene transcription, and chief cell hyperplasia through G alpha q-and G alpha i-dependent signaling pathways. To determine the specific function of G alpha q in these processes, we generated transgenic mice using the human parathyroid hormone promoter to drive overexpression of a dominant negative G alpha qloop minigene to selectively disrupt Gaq function in the parathyroid gland. The Gaqloop mRNA was highly expressed in the parathyroid gland but not in other tissues of these transgenic mice. Gross appearance, body weight, bone mineral density, and survival of the transgenic mice were indistinguishable

from those of their wild-type littermates. Adult transgenic mice, however, exhibited an increase in parathyroid hormone mRNA and in its basal serum level as well as in gland size. The response of the parathyroid gland to hypocalcemia was found to be reduced in sensitivity in the transgenic mice when compared to their wild-type controls. Abnormalities of the parathyroid gland function Ubiquitin inhibitor in these transgenic mice were similar to those of heterozygous G alpha q(+/-) and calcium sensing receptor(+/-) mice. These studies demonstrate the feasibility of selectively targeting the parathyroid gland to investigate signaling mechanisms downstream of the calcium receptor.”
“The kidney has a cortico-medullary interstitial gradient of decreasing pH and increasing concentrations of sodium chloride and urea, but the influence of these gradients on receptor signaling is largely unknown. Here, we measured G-protein coupled receptor function in LLC-PK1 cells acutely exposed to conditions mimicking different kidney regions.

Both events depended on the expression of Env and CD4 in donor and target cells, respectively, whereas the HIV-1 internalization required clathrin activity in target cells. Importantly, both phenomena were also observed in cocultures of primary CD4(+) lymphocytes, while primary macrophages supported only HIV-1 endocytosis. By investigating the virological consequences of these events, we noticed that while fused cells released infectious HIV-1 particles, albeit with reduced efficiency compared with donor cells, no virus expression was

PI3K inhibitor detectable upon HIV-1 endocytosis in target cells. In sum, the HIV-1 transmission following contact between an HfV-1-infected and an uninfected CD4(+) cell can occur through different mechanisms, leading to distinguishable virological outcomes.”
“In rodents, where chemical signals play a particularly important role in determining intraspecies interactions including social dominance and intersexual relationships, various studies have shown that behavior is sensitive to conspecific odor cues. Mice use urinary scent marks for communication with individual Torin 2 mouse conspecifics in many social contexts. Urinary scent involves genetic information about individuals such as species, sex, and individual identity

as well as metabolic information such as social dominance, and reproductive and health status, which are mediated by chemical proteins in scent marks including the major histocompatibility complex and the major urinary proteins. The odor of the predator which can be considered to be a threatening signal for the prey also modulate mouse behavior in which scent marking Selleckchem RGFP966 is suppressed in response to the cat odor exposure in mice. These odorant chemicals are detected and recognized through two olfactory bulbs, the role of which in detection of chemosignals with biological relevant appears to be differential, but partly overlapped. Mice deposit scent marks toward conspecifics

to maintain their social relationships, and inhibit scent marking in a context where natural predator, cat odor is contained. This Suppression of scent marking is long-lasting (for at least 7 days) and context-dependent, while the odorant signaling to conspecifics tends to appear frequently (over 24 h but less than 7 days intervals) depending on the familiarity of each signal-recipient. It has been discussed that scent marking is a communicative behavior associated with territoriality toward conspecifics, indicating that the social signaling within species are sensitive to predator odor cues in terms of vulnerability to predation risk. (C) 2008 Elsevier Ltd. All rights reserved.”
“Human immunodeficiency virus (HIV)-positive persons are predisposed to pulmonary infections, even after receiving effective highly active antiretroviral therapy.

Overall, the present results underscore that other routes, aside from the well-established CeA projections to the periaqueductal gray, may contribute to the acquisition/consolidation of the freezing response associated to a TFC task. It is suggested that CeA may presumably influence DS processing via a synaptic relay on dopaminergic neurons of the substantia nigra compacta and retrorubral

nucleus. The present observations are also in line with other studies showing that TFC and CFC responses are mediated by different anatomical networks. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The transcription BAY 1895344 in vitro factor C/EBP alpha (CEBPA) is a key player in granulopoiesis and leukemogenesis. 3-Methyladenine supplier We have previously reported the interaction of C/EBPa with other proteins ( utilizing mass spectrometry) in transcriptional regulation.

In the present study, we characterized the association of the MYST domain histone acetyltransferase Tat-interactive protein (TIP) 60 (HTA-TIP) with C/EBP alpha. We show in pull-down and co-precipitation experiments that C/EBP alpha and HTATIP interact. A chromatin immunoprecipitation (ChlP) and a confirmatory Re-ChlP assay revealed in vivo occupancy of the C/EBP alpha and GCSF-R promoter by HTATIP. Reporter gene assays showed that HTATIP is a coactivator of C/EBP alpha. The co-activator function of HTATIP is dependent on its intact histone acetyltransferase (HAT) domain and on the C/EBP alpha DNA-binding domain. The resulting balance between histone acetylation and deacetylation at the C/EBP alpha promoter might represent an important mechanism of C/EBP alpha action. We observed a lower expression of HTATIP mRNA in undifferentiated U937 cells compared ABT-737 cell line to retinoic acid-induced differentiated U937 cells, and correlated

expression of CEBPA and HTATIP mRNA levels were observed in leukemia samples. These findings point to a functional synergism between C/EBP alpha and HTATIP in myeloid differentiation and suggest that HTATIP might be an important player in leukemogenesis.”
“Raf/MEK/Erk signaling is activated in the majority of acute myeloid leukemias (AMLs), providing rationale for targeting this pathway with therapeutic intent. We investigated growth-inhibitory and proapoptotic effects of sorafenib in AML. Our studies demonstrated that sorafenib significantly inhibited the phosphorylation levels of Raf downstream target proteins MEK1/2 and Erk, induced apoptosis and inhibited colony formation in AML cell lines and in primary AML samples. Mechanistically, treatment with sorafenib resulted in upregulation of proapoptotic Bim, accompanied by an increase in Bad, Bax and Bak protein levels and decreased Mcl-1, X-linked inhibitor of apoptosis and surviving levels, which mainly led to the activation of the intrinsic apoptotic pathway.

Extended kindling also led to an increase in the number of ectopic granule cells in the hilus. In addition, although the width of the granule cell layer was not generally

affected by kindling, decreased levels of DISC1 in the subgranular zone and granule cell layer were associated with an expansion of the upper blade and crest of the dentate click here gyrus in both normal and kindled rats. These novel findings suggest that seizure activity affects DISC1 signaling in the dentate gyrus and that DISC1 expression may regulate the cytoarchitectural organization of the granule cell layer. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“The introduction of thalidomide, bortezomib and lenalidomide has dramatically changed the treatment paradigm

of multiple myeloma (MM). In patients eligible for autologous stem cell transplant (ASCT), combinations including thalidomide/dexamethasone (Thal/Dex) or bortezomib/dexamethasone (Bort/Dex) or lenalidomide/dexamethasone (Rev/Dex) have been introduced as induction regimens in patients eligible for ASCT. New induction regimens have significantly increased complete response rate before and after ASCT with a positive impact on progression-free survival. Maintenance GDC-0449 concentration therapy with thalidomide, under investigation with lenalidomide, may further prolong remission duration. In patients not eligible for ASCT, randomized studies have shown that melphalan, prednisone, thalidomide (MPT) and melphalan, prednisone and bortezomib (MPV) are both superior to melphalan and prednisone (MP), and are now considered

standard of care. Ongoing trials will soon assess if MP plus lenalidomide may be considered an attractive option. More complex regimens combining thalidomide or bortezomib or lenalidomide with cyclophosphamide or doxorubicin have been also tested. In small cohorts of patients bortezomib or lenalidomide may overcome the poor prognosis induced by deletion 13 or translocation t(4; 14) or deletion 17p13. If these data will be confirmed, a cytogenetically risk-adapted strategy might become the most appropriate strategy.”
“It has been suggested that pilocarpine-induced seizures is mediated by increases in oxidative stress. NU7026 clinical trial Current researches have suggested that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the neuroprotective effects of lipoic acid (LA) in rats, against the observed oxidative stress during seizures induced by pilocarpine. Wistar rats were treated with 0.9% saline (i.p., control group), LA (10 mg/kg, i.p., LA group), pilocarpine (400 mglkg, i.p., pilocarpine group), and the association of LA (10 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before of administration of LA (LA plus pilocarpine group). After the treatments all groups were observed for 6 h.

Further studies may clarify the significance of and mechanisms underlying individual differences in awake rcSO(2) and the changes that occur in rcSO(2) while asleep.”
“Late-phase long-term depression (L-LTD) in middle-aged mice has been difficult to achieve

and maintain. Here we report an electrically induced, homosynaptic, input-specific form of LTD that could be stably maintained for at least 4 h in the CA1 area of hippocampal slices of 10-14 months old mice. This form of L-LTD was similar in magnitude in aged, middle-aged and young mice and was blocked by high concentrations of broad-spectrum N-methyl-D-aspartate receptor (NMDAR) antagonists such as D(-)-2-amino-5-phospho-pentanoic check details acid (D-AP5) and (R)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). Extracellular and whole cell recordings revealed a decreased sensitivity to D-AP5 with age, without any differences in NMDAR conductance between the age groups tested. This L-LTD could be inhibited neither by common doses of NMDA-subunit specific antagonists like zinc, ifenprodil and Ro-25-6981, nor by various co-applications of these compounds. In addition to the lack of any GluN2 subunit bias, L-LTD did not show any discernible involvement of L-type voltage-gated calcium channels. In conclusion, our results

do not support any specific role of NMDAR subunits in LTD. (C) Torin 1 molecular weight 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Objectives. We aimed to examine the effects of 2 factors of familism (Familial Obligations and Expected Support from the Family) and Cultural Justification on caregivers’ mental and physical health as mediated by coping style.

Methods. We used a probability sample of 95 African American and 65 White family caregivers for people with dementia to test hypotheses based on the updated sociocultural stress and coping model using path analysis. Main outcome measures however included depressive symptomatology, various psychological symptoms, and subjective physical health.

Results. Both Familial Obligations and Cultural Justification had an indirect effect on poor mental health and subjective physical health via avoidant coping. Expected Support

from the Family had no effect on caregivers’ health outcomes.

Discussion. These findings suggest that feelings of obligation may be accounting for a significant proportion of the negative effects of familism on caregivers’ mental and subjective physical health. Expectations of familial social support may be relatively inconsequential in this process.”
“Objectives. Implicit skill learning underlies not only motor but also cognitive and social skills; ills therefore an important aspect of life from infancy to old age. We studied aging effects on the time course of implicit skill consolidation.

Methods. Young and elderly adults performed a probabilistic implicit sequence-learning task before and after a 12-. a 24-hr, and a 1-week interval.

Relative change in IS motion was expressed as percent change compared with initial presentation. Maximum IS extension (true lumen [TL] expansion) and contraction (TL compression), IS fraction in phase with aortic flow and correlation of IS motion with aortic flow (IS compliance) were quantified.

Results: IS motion

at initial presentation was 0.68 +/- 0.2 mm and was reduced at short-term (0.48 +/- 0.3 mm; P = .07) and midterm (0.5 +/- 0.2 mm; P = .1) follow-up. Trend in relative change of IS motion was variable during short-term follow-up: reduced in three subjects (-75% +/- 6%) and elevated in four subjects (48% +/- 23%). During midterm follow-up, relative change in IS motion was reduced AZD3965 price in four subjects (28% +/- 19%) and slightly elevated in one (6.2%). IS contraction decreased with follow-up while IS extension slightly increased. Fraction of IS moving in phase with aortic flow increased but IS compliance decreased, Trichostatin A in vitro suggesting increasing

IS stiffness.

Conclusions: Reduction of IS motion in AD is seen with short-term and midterm follow-up. Intersubject variability of this trend is high at short-term follow-up but low at midterm follow-up. Detailed analysis of IS motion parameters indicate reduction of IS contraction and IS compliance with time. This has potential implications for endovascular management of type B aortic dissections, as expansion of aortic stent grafts can be limited by a stiff IS. (J Vasc Surg 2012;55:1419-26.)”
“Although

the measurement of fetal proteins in maternal serum is part of standard prenatal screening for aneuploidy and neural tube defects, attempts to better understand the extent of feto-maternal protein trafficking and its clinical and biological significance have been hindered by MK-2206 supplier the presence of abundant maternal proteins. The objective of this study was to circumvent maternal protein interference by using a computational predictive approach for the development of a noninvasive, comprehensive, protein network analysis of the developing fetus in maternal whole blood. From a set of 157 previously identified fetal gene transcripts, 46 were classified into known protein networks, and 222 downstream proteins were predicted. Statistically significantly over-represented pathways were diverse and included T-cell biology, neurodevelopment and cancer biology. Western blot analyses validated the computational predictive model and confirmed the presence of specific downstream fetal proteins in the whole blood of pregnant women and their newborns, with absence or reduced detection of the protein in the maternal postpartum samples. This work demonstrates that extensive feto-maternal protein trafficking occurs during pregnancy, and can be predicted and verified to develop novel noninvasive biomarkers. This study raises important questions regarding the biological effects of fetal proteins on the pregnant woman.

Our results suggest that satsiR-12 targeting the 3′ UTR of CMV RNAs triggered RDR6-dependent antiviral silencing. Competition experiments with wild-type CMV RNAs and anti-satsiR-12 mutant RNA1 in the JQ-EZ-05 research buy presence of 2b and satRNA demonstrate the inhibitory effect of the 2b protein on the satsiR-12-related degradation of CMV RNAs, revealing a substantial suppressor function of the 2b protein in native CMV infection. Our data provide evidence for the important biological functions

of satsiRNAs in homeostatic interactions among the host, virus, and satRNA in the final outcome of viral infection.”
“The Arabidopsis thaliana somatic embryogenesis receptor-like kinase (SERK) family consists of five leucine-rich repeat receptor-like kinases (LRR-RLKs) with diverse functions such as brassinosteroid insensitive 1 (BRI1)-mediated brassinosteroid perception, development and innate immunity. The autophosphorylation activity of the kinase domains of the five SERK proteins was compared and the phosphorylated residues were identified by LC-MS/MS. Differences in autophosphorylation that ranged from high

activity of SERK1, intermediate activities for SERK2 and SERK3 to low activity for SERK5 were noted. In the SERK1 kinase the C-terminally located residue Ser-562 controls full autophosphorylation activity. Activation loop phosphorylation, Selleck IPI145 including that of residue Thr-462 previously shown to be required for SERK1 kinase activity, was not affected. In vivo SERK1. phosphorylation was induced by brassinosteroids. Immunoprecipitation of CFP-tagged SERK1 from plant extracts followed by MS/MS identified Ser-303, Thr-337, Thr-459, Thr-462, Thr-463, Thr-468, and Ser-612 or Thr-613

or Tyr-614 as in vivo phosphorylation sites of SERK1. Transphosphorylation of SERK1 OICR-9429 mw by the kinase domain of the main brassinosteroid receptor BRI1. occurred only on Ser-299 and Thr-462. This suggests both intra- and intermolecular control of SERK1 kinase activity Conversely, BRI1 was transphosphorylated by the kinase domain of SERK1 on Ser-887. BRI1 kinase activity was not required for interaction with the SERK1 receptor in a pull down assay.”
“This review critically examines an emerging tool to measure viral clearance from biomanufacturing streams, monitor assembly of viruses and virus-like particles, rapidly identify viruses from biological milieu, assay virus neutralization, and prepare bionanoconjugates for bacterial detection. Electrospray differential mobility analysis (ES-DMA) is a tool of choice to simultaneously determine viral size and concentration because it provides full multimodal size distributions with subnanometer precision from individual capsid proteins to intact viral particles. The review contrasts ES-DMA to similar tools and highlights expected growth areas including at-line process sensing as a process analytical technology (PAT), bioseparating as a distinct unit operation, monitoring viral reactions, and interrogating virus host protein interactions.

The RRV Delta LANA/GFP virus displayed AS1842856 cell line increased lytic gene transcription at all time points post-infection compared to RRV-GFP. Moreover, we also examined several cellular genes that are known to be repressed by KSHV LANA and report that these genes are derepressed during de novo lytic infection with the RRV Delta LANA/GFP virus compared to RRV-GFP. Finally, we also demonstrate that the RRV Delta LANA/GFP virus fails to establish latency in B cells, as measured by the loss of GFP-positive cells and intracellular viral genomes.”
“In the present study we investigated the alterations on choline

acetyltransferase (ChAT) and acetylcholinesterase (ACH) activities in rat striatum and frontal cortex

caused by pilocarpine-induced seizures. Wistar rats were treated MCC-950 with 0.9% saline (i.p., control group), with the association of 0.9% saline (i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before of administration of saline (pilocarpine group). After the treatments all groups were observed for 1 h. The ChAT and AChE activities were measured using spectrophotometric methods and the results compared to values obtained from saline-treated animals. In pilocarpine group was observed a significantly decreases in ChAT and AChE activities in striatum and frontal cortex of adult rats, when compared to control group. Results showed that during acute phase of seizures striatal and frontal cortex ChAT and AChE activities are diminished. Our findings suggest that seizures caused cognitive dysfunction and decreases of ChAT and AChE activities that might be related. at least in part, to the neurological problems presented by epileptic patients. (C) 2009 Elsevier Ireland Ltd. All rights reserved”
“An ideal human immunodeficiency virus type 1 (HIV-1) vaccine would elicit potent cellular and humoral immune responses

that recognize diverse strains of the virus. In the present study, combined methodologies (flow cytometry, V beta repertoire analysis, and complementarity-determining region 3 sequencing) were used to determine the clonality of CD8(+) T lymphocytes taking part in the recognition selleck inhibitor of variant epitope peptides elicited in Mamu-A*01-positive rhesus monkeys immunized with vaccines encoding diverse HIV-1 envelopes (Envs). Monkeys immunized with clade B Envs generated CD8(+) T lymphocytes that cross-recognized both clade B-and clade C-p41A epitope peptides using a large degree of diversity in V beta gene usage. However, with two monkeys immunized with clade C Env, one monkey exhibited p41A-specific cytotoxic T-lymphocytes (CTL) with the capacity for cross-recognition of variant epitopes, while the other monkey did not.

Tumor volume reduction (. 50%) was associated with a single metastasis (P =.012), no previous WBRT (P =.002), selleck chemicals llc and a tumor volume, 16 cm 3 (P =.002). The better peritumoral edema volume reduction (. 50%) was associated with a single metastasis (P =.024), no previous WBRT (P =.05), and breast cancer histology (P =.044).

CONCLUSION: Surgical resection remains the primary approach for larger brain metastases if feasible. Tumor volume is a better indicator than maximum diameter. Tumor volume and edema responded better in patients who underwent SRS alone.”
“The 9-aminoacridine (9AA) derivative quinacrine (QC)

has a long history of safe human use as an anti-protozoal and antirheumatic agent. QC intercalates into DNA and RNA and can inhibit DNA replication, RNA transcription, and protein synthesis. The extent of QC intercalation into RNA depends on the complexity of its secondary and tertiary structure. Internal ribosome entry sites (IRESs) that are required for initiation of translation of some viral and cellular mRNAs typically

have complex structures. Recent work has shown that some intercalating drugs, including QC, are capable of inhibiting hepatitis C virus IRES-mediated translation click here in a cell-free system. Here, we show that QC suppresses translation directed by the encephalomyocarditis virus (EMCV) and poliovirus IRESs in a cell-free system and in virus-infected HeLa cells. In contrast, IRESs present in the mammalian p53 transcript that are predicted to have less-complex structures were not sensitive to QC. Inhibition of IRES-mediated translation by QC correlated with the affinity of binding between QC and the particular IRES. Expression of viral capsid proteins, replication of viral RNAs, and production of virus were all strongly inhibited by QC (and 9AA). These results suggest that QC and similar intercalating drugs could potentially be used for treatment of viral infections.”
“BACKGROUND: Intracerebral hemorrhage (ICH) represents at least 15% of

all strokes in the Western population and a considerably higher proportion at 50% to 60% in the Oriental population.

OBJECTIVE: To investigate selleck compound whether administration of bone marrow stem cells (BMSCs) overexpressing glial cell line-derived neurotrophic factor (GDNF) provides more efficient neuroprotection for rats with ICH and neurons exposed to hypoxia/reoxygenation.

METHODS: Primary rat BMSCs were transfected with rat GDNF gene using virus vector (GDNF/BMSCs) and blank virus plasmid (BVP/BMSCs). Primary rat cortical neurons of rats were exposed to hypoxia and then reoxygenated with GDNF/BMSCs (GDNF/BMSCs group) or BVP/BMSCs (BMSCs group) treatment for 12 hours and 1, 2, 3, and 5 days. Hoechst 33258 staining was used to evaluate apoptosis. GDNF/BMSCs, BVP/BMSCs, and saline (GDNF/BMSCs, BMSCs, and control groups) were injected into the right striatum 3 days after rat ICH induced by injecting collagenase.

After 12 weeks of escitalopram treatment, treatment responders showed metabolic increases in global neocortical areas as well as limbic areas whereas non-responders did not. Conclusion: Abnormal neocortical function appears to be associated with the pathophysiology of PD and escitalopram exerts its therapeutic

action by modulating brain activity at the level of the neocortex and limbic system, notably the amygdala and parahippocam pal gyrus. Copyright selleck chemicals llc (c) 2012 S. Karger AG, Basel”
“Bacillus subtilis is a remarkably diverse bacterial species that is capable of growth within many environments. Recent microarray-based comparative genomic analyses have revealed that members of this species also exhibit considerable genomic diversity. The identification of strain-specific genes might explain how B. subtilis has become so broadly adapted. The goal of identifying ecologically adaptive genes could soon FG-4592 cost be realized with the imminent release of several new B. subtilis genome sequences. As we

embark upon this exciting new era of B. subtilis comparative genomics we review what is currently known about the ecology and evolution of this species.”
“Noroviruses are the dominant cause of outbreaks of gastroenteritis worldwide, and interactions with human histo-blood group antigens (HBGAs) are thought to play a critical role in their entry mechanism. Structures of noroviruses from genogroups GI and GII in complex with HBGAs, however, reveal different modes LY2874455 datasheet of interaction. To gain insight into norovirus recognition of HBGAs, we determined crystal structures of norovirus protruding domains from two rarely

detected GII genotypes, GII.10 and GII.12, alone and in complex with a panel of HBGAs, and analyzed structure-function implications related to conservation of the HBGA binding pocket. The GII.10- and GII.12-apo structures as well as the previously solved GII.4-apo structure resembled each other more closely than the GI.1-derived structure, and all three GII structures showed similar modes of HBGA recognition. The primary GII norovirus-HBGA interaction involved six hydrogen bonds between a terminal alpha fucose1-2 of the HBGAs and a dimeric capsid interface, which was composed of elements from two protruding subdomains. Norovirus interactions with other saccharide units of the HBGAs were variable and involved fewer hydrogen bonds. Sequence analysis revealed a site of GII norovirus sequence conservation to reside under the critical alpha fucose1-2 and to be one of the few patches of conserved residues on the outer virion-capsid surface. The site was smaller than that involved in full HBGA recognition, a consequence of variable recognition of peripheral saccharides. Despite this evasion tactic, the HBGA site of viral vulnerability may provide a viable target for small molecule- and antibody-mediated neutralization of GII norovirus.